firenze university press www.fupress.com/substantia doi: 10.13128/substantia-15 substantia. an international journal of the history of chemistry 1(1): 99, 2017 acknowledgments our first thanks is for you, who are reading this page and this first issue of substantia. we do rely on you, on your interest and on your patience, on your approval and also on your sincere criticism. substantia is the product of a great effort, of a great pleasure and of a renewed hope in the human capability to wonder about the beauty and complexity of reality and matter, and to inspect their features with the strength of reason.. without this hope or better without this certainty any attempt to uncover and understand the world would be nosense and we would be pulled back to darkness. we sincerely thank the authors of this first issue: they granted us the strength of their knowledge and wisdom, and gladly accepted the challenge of a new journal. thank you to the members of the international scientific board, who offered their prestige and reliability for the benefit of the scientific level of the journal and to our colleagues in the department of chemistry, who welcomed the birth of substantia. finally i want to express my deepest loyal gratitude to moira ambrosi, antonella capperucci, laura colli, marco fontani, romeo perrotta and alessandro pierno for sharing with me this challenging and tantalizing adventure. their enthusiastic and tireless commitment was the first nourishment for our journal. we tried to do our best, it has been and will be a great struggle. and for sure we could have done it better. we apologize for any mistake and we thank you the reader of these articles for your invaluable support and for all the suggestions that you may want to share with us in the future. firenze, 25 january 2017 pierandrea lo nostro editor-in-chief the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments firenze university press www.fupress.com/substantia preface it is a great honour for me to write these few lines of preface to the special issues of substantia dedicated to the 150th anniversary of the periodic table by dmitrij mendeleev. in 2019 there are other important anniversaries besides that of the periodic table. one of these is the centenary of primo levi’s birth. i believe these two anniversaries are strictly related, in fact the periodic table by levi has been considered by the royal institution of great britain as the “best book of science ever written”. it would be sufficient to recall an impressive excerpt from “iron”, a tale of the the periodic table, to acknowledge the uniqueness of this literary work: “we began studying physics together, and sandro was surprised when i tried to explain to him some of the ideas that at that time i was confusedly cultivating. that the nobility of man, acquired in a hundred centuries of trial and error, lay in making himself the conqueror of matter, and that i had enrolled in chemistry because i wanted to remain faithful to this nobility. that conquering matter is to understand it, and understanding matter is necessary to understand the universe and ourselves: and that therefore mendeleev’s periodic table […] was poetry …”. when we designed the project related to these special issues, we had in mind levi’s work and in particular his wonderful tales that belong to the periodic table. i like to recall this homage to a chemist-writer-witness to introduce the six topics that are associated to the special volumes of substantia. as president of the university of florence which is the owner of the publisher firenze university press, i am truly grateful to the editors – marc henry, vincenzo balzani, seth rasmussen, luigi campanella, mary virginia orna with marco fontani, and brigitte van tiggelen with annette lykknes and luis moreno-martinez – for accepting the invitation made by the editorin-chief pierandrea lo nostro and for the extraordinary work for the preparation of these special issues. of course the choice of the six subjects was not accidental: we tried to identify some features of the chemistry realm, related for several reasons to the periodic table. they are strikingly associated to the great challenges for our future: these are water, sustainability, energy, open chemistry, the history and the educational perspectives of the periodic table. during its long path of progress and civilisation mankind has strongly modified nature to make our planet more comfortable, but at present we must be very careful with some dramatic changes that are occurring in our earth. science and technology, and chemistry primarily, can help mankind to solve most of the environmental and energy problems that emerge, to build a radically different approach from that that has prevailed in the last 8 scientific board two centuries. it is a fantastic challenge, since for the first time we can consider nature not as a system to simply exploit, but a perfect ally for improving life conditions in the whole planet. chemistry has already engaged and won a similar challenge when, understanding the pollution problems generated by a chaotic and rapid development, succeeded in setting up a new branch, green chemistry, that turned upside down several research topics. now is the time to develop sustainable chemistry: the occurring events demand that chemists propose new routes and innovative approaches. in the last two centuries we have transformed immense amounts of matter from nature into waste without thinking that we were using non renewable energy sources. we have been acting as our natural resources were unlimited, but knowing that they are instead limited. now we are realizing that it is not possible to continue along this road. our planet and our atmosphere are made of finite materials and their consumption during the last two centuries has been impressive. some elements that are crucial for current and future industrial countries are known to be present on earth crust in very small amounts and their recycling from waste cannot be a choice anymore, but it is rather an obligation. climate is another big problem associated to the terrific changes occurring in some equilibria, both as a consequence of the violent industrial development and energy consumption. we need, and we will always need more and more, an immense amount of energy. the only solution to secure wellness to future generations is the conversion to renewable energy sources. in this view, food and water, due to the strong increment in the demographic indices, could become the true emergencies for billions of individuals. looking at the picture i tried to draw in this short preface it becomes more clear why we selected those topics for our special issues. i am optimistic, and i have the strong confidence that chemistry, that studies matter and its transformations, will give mankind the picklock to overcome those challenges. we will definitely need insightful minds, creativity, knowledge and wisdom. luigi dei president of the university of florence firenze university press www.fupress.com/substantia substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 6 2019 firenze university press where does chemistry go? from mendeelev table of elements to the big data era luigi campanella1, laura teodori2,* visualizing solubilization by a realistic particle model in chemistry education antonella di vincenzo, michele a. floriano* chemistry as building block for a new knowledge and participation stefano cinti tissue engineering between click chemistry and green chemistry alessandra costaa#, bogdan walkowiakb, luigi campanellac, bhuvanesh guptad, maria cristina albertinie* and laura teodori a, f* chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity. sara tortorella,1,2,* alberto zanelli,2,3 valentina domenici2,4 substantia. an international journal of the history of chemistry 6(1): 5-6, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1570 to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro department of chemistry “ugo schiff ” and csgi, university of florence, 50019 sesto fiorentino (firenze), italy email: pierandrea.lonostro@unifi.it an interesting paper recently published in peer j. by enrique teran and coworkers casts light on a peculiar side effect of the covid-19 pandemic that concerns the quality of articles that appeared as preprints in archives or as regular papers in peer-reviewed scholarly journals.1 the authors report a detailed perusal of the scientific publications related to research on covid-19 in a portion of the year 2020. what emerges from the study is that over the total number of preprints uploaded in the archives’ servers, that are not subjected to a formal peer-review process, only about 5.7% were later converted into regular articles and published in scholarly journals after a regular peer-review process. the statistics is based on a global sample of 5,061 preprints uploaded in three different archives. the fast, almost immediate dissemination of experimental studies has certainly played an important role during the pandemic. in fact it was promoted by the international committee of medical journal editors.2 moreover, the world health organization3 and some journals require that manuscripts be shared as preprints before being sent to reviewers. in this way preprints are exposed to a public form of peer-review in real time. fast publication as preprints certainly helped different research groups to exchange data and interpretations, hypothesis and proposals for public health guidelines to secure a powerful response to the virus attacks. however, a conversion of 5.7% from preprints to regular articles seems to be too low. this may be due to the emergence of more accurate studies, to repeated verifications of the presented data on different samples, and to the very fast communications of results that made fresh data look like old and outdated findings. but on the other hand, covid-19 related topics are very delicate matters for their social and political consequences. no doubt they must be treated with extra care. so many fake news, accusations of conspiracies, distrust in official authorities’ statements have filled newspapers and websites, including the social networks that in this specific case have probably shown the dreadful and terrific power of some people’s madness and ignorance. peer-review requires time. reviewers are often reminded and urged to return their comments within few days. we know that a “short lapse between submission and acceptance” is a very appreciated feature of scholarly journals. authors are anxious to see their work published, and sometimes do not appreciate enough the benefit of an accurate review. teran’s article also reports that between february and may 2020 about 17,500 articles have been published in peer-review journals indexed in pubmed, suggesting that even during the covid-19 emergency, scholarly journals kept pace with an enormous pressure from the scientific community and publish their articles after a formal peer-review process.1 another interesting point is that articles published in scholarly journals received more attention and a higher citation rate than preprints. the citation count is one of the quantitative indicators of the scientific relevance of a publication (although not all citations may be positive).4 in conclusion, while the scientific communities have all the tools to confirm or reject the findings published in open access preprints, the same does not hold http://www.fupress.com/substantia 6 pierandrea lo nostro for average non-specialized readers that sometimes take advantage of partial or limited results to discredit the conclusions of serious studies. and in our democracies the recent events have proved that these differences between scientists and selfproclaimed “experts” do matter. references 1. añazco, d.; nicolalde, b.; espinosa, i.; camacho, j.; mushtaq, m.; gimenez, j.; teran, e. publication rate and citation counts for preprints released during the covid-19 pandemic: the good, the bad and the ugly. peer j. 2021, 9, e10927. doi: 10.7717/ peerj.10927 2. icmje. overlapping publications 2020, http://icmje. org/recommendations/browse/publishing-and-editorial-issues/overlapping-publications.html. last accessed feb 07, 2022. 3. moorthy, v.; henao restrepo, a. m.; preziosi, m.-p.; swaminathan, s. data sharing for novel coronavirus (covid-19). bulletin of the world health organization 2020, 98(3), 150. doi: 10.2471/blt.20.251561. 4. aksnes d. w.; langfeldt, l.; wouters, p. citations, citation indicators, and research quality: an overview of basic concepts and theories. sage open 2019, 9(1), 2158244019829575. doi: 10.1177/2158244019829575. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 1(2): 5-6, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-22 editorial how do we recognize a good scientist? on june 11, 2010 before actually starting its activities, anvur agenzia nazionale per la valutazione del sistema universitario e della ricerca (national agency for the evaluation of the university and research system) had raised positive expectations in italy. it was quite clear to everyone, inside and outside the academic community, that it was useful to carefully check the quality of both teaching and research activities, respectively in all italian universities and research institutes. in these seven years, anvur has released several reports, and has often expressed its assessments of the quality of both university education and scientific research. however, there is no longer a general support of evalutation. anvur’s practical activity has aroused consensus, as well as criticism, both inside and outside the academic world. several people criticized the way in which assessments have been used. indeed, the italian governments of the last seven years, have allocated remarkable “reward shares” out of the scarce ffo (fondo di finanziamento ordinario – ongoing financing fund) to those universities which had been the best, according to anvur’s judgement. this has meant a flow of funds from the universities of southern italy up to those of the centre and north of the country. as a consequence, the university system of the most economically depressed area of italy has been further weakened, whereas the richer northern areas have taken advantage of it. in turn, fewer young people have enrolled in the south. also, many boys and girls from the south moved towards the universities of central and northern italy. many other youth did not enroll at all. however, anvur cannot be blamed for this usage of the evalutation of university system. nor the idea of evalutation itself can be blamed. in fact, this is a political responsability. this choice does not concern ita ly only: it is actually a general problem. the idea is spreading all around europe and the whole world, that research is an enterprise like any other, and that human and financial resources should be concentrated in a few centres and universities of excellence, which can “compete and win” on the international market for the production of knowledge and education. from this perspective, most research institutes and universities only fulfil residual tasks. this choice is a direct attack against both democracy and knowledge, as well as against the effectiveness of scientific research. it is indeed an attack against the democracy of knowledge, since it involves the fact that only a chosen few can get access – as researchers, lecturers or students – to universities and centres of excellence. in the case of students, there is a clear inequality. in several countries – from the united states to the united kingdom – the tuition fees for universities of excellence are so expensive (tens of thousands euros a year for foreign students in some british universities) that only the children of very rich families can enrol. on the other hand, education is not a “rival” good, which diminishes as it is used. quite the opposite: the more it is used, the more it grows. this was clear to the editorial that introduces this second issue of substantia focusses on a critical issue, the assessment of the quality of scientific research. an everlasting question that is currently debated in several institutions is: how can we measure and evaluate the performance of individual researchers? this is a terrifically concrete and overwhelming process that affects and afflicts most of scientists in their career, and ultimately the progress of science. the outputs of science are not manufacturing industrial products. we need to speak out about the use of more or less obscure algorithms whose final result becomes a judgment on the quality of research. the use of algorithms does not guarantee impartial neutrality, as claimed. it is typical of those who cannot really and deeply evaluate, and therefore must rely on numbers: impact factors, h indexes, citations, etc. this editorial tries to contribute to the current international debate by presenting the case of the italian national agency anvur. i also recommend you to read a nicely acute and amusing paper written by gregory a. petsko for genome biology in 2008, entitled "having an impact (factor)". not only for fun, but for your thoughtful consideration. 24/09/2017 pierandrea lo nostro 6 pietro greco vannevar bush, as he wrote his report to the us president in 1945 – science, the endless frontier, the “manifesto” of modern science policy. in it, bush stated the need to enlarge the recruitment of “brains” necessary for the scientific development, by opening the university doors to the children of all us families, because intelligence does not belong to one social class only, but is rather transversal by definition. during the second world war, the u.s. were planning to take – thanks to scientific research too – the economic and cultural leadership of the planet. in the same way, the whole world needs the intelligence of everyone. another kind of criticism has been made by a section of the italian accademic community, and concerns anvur’s method of evalutation. indeed, they say anvur uses in an excessively overriding and rigorous way the typical parameters of bibliometry when assessing the research quality of a university: namely, the number of published papers; the impact factor of journals in which they are published; and, finally, the number of quotations of each paper. this type of criticism has a wider significance. indeed, many people all over the world are wondering whether the bibliometric method may indeed be considered the best evalutation method for research, or even for researchers. it is true that, in a world where several millions people devote their lives to science, in the framework of a growing number of international projects, it is convenient to find a universal evalutation method for research activity. however, it is also true that, if we reduce evalutation to the mere analysis of bibliometric parameters, this may produce misleading results. indeed, bibliometric analysis has its own inherent limits, as pointed out by an endless scientific literature. we cannot analyze them in detail here. we’ll just consider its main limits, since they can steer the evolution of the international research and higher education system in undesiderable directions. in bibliometric analysis, research quality and quantity tend to match. normally, quality is assessed by measuring quantity. now, the number of papers published in international scientific journals, as well as quotations obtained, are significant indicators of a researcher’s talent. however, they are not the only indicators, and probably not the main ones. in any case, the evalutation of quality as based esclusively on bibliometry is not only incomplete: it is also misleading. young people, in particular, pay a high price for this evaluation system. first of all, even geniuses are penalised, because they have had no time as yet to publish a lot of papers and get quotations. secondly, this leads to a vision of scientific activity as based upon the “publish or perish” principle, rather than upon good ideas. bibliometric evaluation, when used in the wrong way, may become a levelling-out power in the research community, for more than one motive. first of all, the “publish or perish” principle tends to eat away at scientific creativity, in favour of thomas kuhn’s “normal science”. even the search for a high number of quotations may become a levelling-out element, because it leads to join “fashionable” schools of thought, rather than look for originality, which is one of the five values considered by robert merton as the bases of scientific enterprise. the exclusively quantitative pressure becomes a levelling-out power, not only for individual researchers, and for small groups of researchers, but also for large institutes and broad areas of science. indeed, both financial and human resources tend to be concentrated in those institutes and areas which are better assessed. as a consequence, small – but promising – institutes and areas suffer from a worse assessment – as in the case of the flow of students from southern to northern universities in italy. as a result, we may get a world scientific system constituted by a sea of mediocrity and a few islands of excellence, where many papers are published and lots of quotes are made, where as kuhn’s “dominating paradigms” are not challenged. it would be something of a paradox that an age so rich in scientists – the world has never had so many of them – also becomes an age poor in groundbreaking scientific ideas. hence the need, which is also felt ouside academia, to get past the bibliometric method and look for a satisfying answer to the difficult question, which the german physicist reinhard werner recently posed in nature: «how do we recognize a good scientist?» however, the pooling of human and financial resources in few “knowledge firms” competing on the international market, together with the wrong method of evaluation of research quality can lead to the end of science itself. this has already happened in the past: hellenistic science, for instance, was “forgotten” with the romans conquering the mediterranean area. it took europe a millennium and a half in order to go back to its own true nature. in the same way, if science resorts to seeking – like any other firm – immediate results which may increase its competitiveness; if it entrenches itself smugly in a few fortresses; if it promotes uniformity rather than innovation, it risks dying out. therefore, the urgent question now is: “how do we recognize and save a good science? pietro greco substantia. an international journal of the history of chemistry 6(1): 145-147, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1498 obituary professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 1 vavilov institute for the history of science and technology of the russian academy of sciences, russia 2 kotel’nikov institute of radio engineering and electronics of the russian academy of sciences, russia 3 department of chemistry “ugo schiff ”, university of florence, italy; 4 belozersky institute of physico-chemical biology of the lomonosov moscow state university, russia 5 emanuel institute of biochemical physics of the russian academy of sciences, russia on september 15, 2021, professor alexander v. kessenikh had passed away. he was known for his works on nuclear magnetic resonance (nmr) and history of science (figure 1). alexander v. kessenikh was born on february 13, 1932 in tomsk, a scientific capital of siberia at that time, where his parents-physicists worked. due to the work on military subjects of his father, vladimir n. kessenikh, the family moved to moscow region in 1943. in 1949-1953, alexander kessenikh studied at the faculty of physics of the lomonosov moscow state university (msu). it was a momentous time for both soviet physics and soviet student community, and alexander kessenikh took an active part in the events of that moment. in late 1940s-early 1950s, science in the ussr has been subjected to the strongest ideological press or even (in some scientific fields) to almost complete destruction. in physics, the relativity theory and quantum mechanics were declared “idealistic and hostile” branches of sciences. fortunately, the burning need of the ussr for atomic weapons prevented the defeat of physics, but in msu and many other universities of the country, modern physics education was practically destroyed. in the msu faculty of physics, students rebelled with the demand to return them to a full-fledged physics education, although this was an unprecedented and threatened danger for the initiators. this resulted in a revolution in physics education at msu (and hence in other universities) and in students’ self-awareness bringing a breath of freedom to the student community. alexander kessenikh was one of the organizers of that revolution[1]. another manifestation of freedom in the student community was the flourishing of student amateur art. in this area, alexander kessenikh was also one of the most popular student leaders due to his poetic talent (later, he authored several published books of poetry, e.g.[2]) that he applied not only to writing poetry: together with his like-minded friends, he wrote several humorous operas on the themes of student life and created a student festival, archimedes day. one of the first archimedes days was visited by niels bohr, who was delighted and said that if students were capable of the same figure 1. alexander v. kessenikh (1932-2021). source: personal archive of a.v. kessenikh. http://www.fupress.com/substantia 146 andrey v. andreev et al. ingenuity and wit in physics, he would feel secure about the future of physics. the physics faculty operas and archimedes days became a model for students and catalyzed the emergence of similar student festivals across the country, and not only among physicists[3,4] (figure 2). from his first steps in science, alexander kessenikh linked his scientific fate with the recently discovered nmr. his research interests included dynamically and chemically induced polarization of nuclear spins, double nuclear-nuclear resonances, paramagnetic relaxation mechanisms, and structural and chemical applications of nuclear magnetic resonance. among his most cited works are works on the dynamic polarization of protons[5]. in this area, alexander kessenikh made an outstanding scientific discovery: a new (three-spin) mechanism of dynamic nuclear polarization (dnp) in solids was proposed theoretically and confirmed experimentally[5-7]. this mechanism (named “cross effect”) is currently recognized as one of the main dnp methods and is successfully used in nuclear physics, nmr tomography, and other fields[8]. the priority of the kessenikh group in this discovery is now generally recognized. since the late 1990s, alexander kessenikh started his research in the history of physics. he made a truly huge contribution to the creation of the history of research in the field of nmr in the ussr. in fact, his works constitute an encyclopedia of this history. he desired also to compose a database of literature in the field of magnetic resonance. fortunately, he managed to publish the results of this work[9,10]. studying the interaction of physics and chemistry in the history of nmr research allowed him to contribute to the analysis of interdisciplinarity in physics research. he also studied the social history of soviet science focusing on the golden age of the soviet science (mid-1950s-1960s) which had previously been poorly studied. the other focus was on scientific schools in physics, and his research gave a fruitful example of considering the soviet physics history as the history of formation and development of scientific schools in physics. along with his own scientific research in the field, he did a lot of editorial work[11-14]. unfortunately, most of his research on history of science remained published only in russian (e.g., in [11-14] and other collections of articles). despite his poor health, he did not stop working until the very last days. thus, in recent years, he developed a fruitful cooperation with the journal substantia, for which he wrote two articles[15,16]. alexander kessenikh did not live a few months to be 90. references 1. gaponov yu.v., kovaleva s.k., kessenikh a.v. student protests in 1953 at the physics faculty of moscow state university as a social echo of the atomic weapon project (in russian) // the history of the soviet atomic project: documents, memoirs, research. vol. 2. ed. v.p. vizgin. comp. v.p. vizgin and i.s. drovenikov. — st. petersburg: publishing house of the russian academy of sciences. 2002. pp. 519 544. 2. kessenikh a.v. dibs on for all and for myself ! (in russian: chur za vsekh i za sebia). verses of various years and excerpts from the poems. — moscow: print-express, 1998. 3. kessenikh a.v. operas of the physics faculty (in russian) / soviet physicist, 2013, №6(103). h t t p s : / / w w w. p hy s . m s u . r u / r u s / a b o u t / s o v p hy s / issues-2013/06(103)-2013/19658/ 4. gaponov yu.v. traditions of “art of the physicists” in the russian scientific physical community of the 1950s -1990s (in russian) / studies in the history of science and technology, 2003, №12. http://vivovoco. ibmh.msk.su/vv/journal/viet/physlit.htm 5. kessenikh a.v., lushchikov v.i., manenkov a.a., taran y.v. proton polarization in irradiated polyethylenes / soviet physics — solid state, 1963, vol.5, №2, pp. 321-329. 6. kessenikh a.v., manenkov a.a. dynamic polarization of nuclei during saturation of nonuniformly broadened electron paramagnetic resonance lines / soviet physics — solid state, 1963, vol.5, №4, pp. 835-837. figure 2. alexander kessenikh among the other authors of the first physics faculty opera and the archimedes day festival. left to right: yu. gaponov, s. soluyan, a.v. kessenikh, v. pismenny, yu. dnestrovsky. around 1980. source: personal archive of a.v. kessenikh. 147professor alexander kessenikh (1932-2021) 7. kessenikh a.v., manenkov a.a., pyatnitskii g.i. on explanation of experimental data on dynamic polarization of protons in irradiated polyethylenes / soviet physics — solid state, 1964, vol.6, №3, pp. 641-643. 8. wenckebach w.t. essentials of dynamic nuclear polarization. — the netherlands: spindrift publications, 2016. 9. kessenikh a.v. on the historiography and bibliography of magnetic resonance (in russian) // historical studies in physics and mechanics 2005. — moscow: nauka, 2005. pp. 217-291. 10. kessenikh a.v., ptushenko v.v. magnetic resonance in the interior of the century: biographies and publications. — moscow: fizmatlit, 2019. www.rfbr.ru/rffi/ ru/books/o_2092940. 11. soviet physicists scientific community. 1950-1960s and other years. issue 1 (in russian) / kessenikh a.v., vizgin v.p. (eds. and comp.). — saint petersburg.: russian christian humanitarian academy publishing, 2005. 12. soviet physicists scientific community. 1950-1960s and other years. issue 2 (in russian) / vizgin v.p., kessenikh a.v. (eds. and comp.). — saint petersburg.: russian christian humanitarian academy publishing, 2007. 13. to study the phenomenon of soviet physics. 1950– 1960s years. socio-cultural and interdisciplinary aspects (in russian) // vizgin v.p., kessenikh a.v., tomilin k.a. (eds. and comp.) — saint petersburg: russian christian humanitarian academy publishing, 2014. 14. historical studies in physics and mechanics. 20142015 (in russian) // vizgin v.p., vdovichenko n.v., tomilin k.a., kessenikh a.v. (eds. and comp.) — moscow: yanus-k, 2016. 15. kessenikh a. estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) / substantia, 2020, vol.4, №2; https://doi.org/10.13128/ substantia-851. 16. kessenikh a. spin temperature and dynamic nuclear polarization. from the history of researches (1953 – 1983) / substantia, 2021 vol.5, №2, 19 34. https://doi.org/10.36253/substantia-1224. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 4(2): 119-123, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-813 citation: m. alloisio, a. basso, m.m. carnasciali, m. grotti, s. vicini (2020) the strange case of professor promezio: a cold case in the chemistry museum. substantia 4(2): 119-123. doi: 10.13128/substantia-813 received: jan 13, 2020 revised: mar 25, 2020 just accepted online: apr 21, 2020 published: sep 12, 2020 copyright: © 2020 m. alloisio, a. basso, m.m. carnasciali, m. grotti, s. vicini. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini university of genova, department of chemistry and industrial chemistry, via dodecaneso 31, 16146 genova, italy *corresponding authors: andrea.basso@unige.it; marco.grotti@unige.it abstract. promezio is a famous italian chemistry professor who is searching for missing element n. 61. in 1924 his laboratory is partially destroyed by a fire and he disappears. almost one hundred years later high school students are recruited to investigate this strange case. “the strange case of professor promezio” represents a unicum in the panorama of laboratory activities for high school students: it is a cold case in which students are asked to investigate a fact that took place almost a century ago. through the chemical analysis of different findings, the connection with historical events of that period, the study of the suspects’ interrogation reports, the reproduction of the experiments conducted by professor promezio, the students will identify the possible culprit. a complex scientific problem is solved exploring different areas of chemistry and, in addition, interconnections with history, geography, ethics and other school subjects are deepened. keywords: high school introductory chemistry, inquiry-based learing, problem solving, forensic chemistry, history of chemistry. introduction in the last few decades, a significant decrease in the interest and attitudes in science of high-school students was observed, with strong differences between gender and across countries.1,2 the awareness of the impact of science on society and economy in an increasingly complex technological world, stimulated several initiatives to improve science education, at both national and european scale. in particular, a large number of projects have been set up to motivate students to study science more efficiently by stimulating their interest.3 in italy, the ministerial program asl, an acronym of “alternanza scuola-lavoro” (school-work alternation), is an innovative teaching method which, through practical experiences, helps to consolidate the knowledge acquired at school and tests the attitudes of students, enriching their education and orienting their study path.4 school-work alternation, compulsory for students in the last three years of high school, is one of the most significant innovations of the italian law 107 of 2015 (la buona scuhttp://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia mailto:andrea.basso@unige.it mailto:marco.grotti@unige.it 120 marina alloisio, andrea basso, maria maddalena carnasciali, marco grotti, silvia vicini ola) in line with the principle of open school. a cultural change for the construction of an italian way to the dual system, which incorporates good european practices, combining them with the specificities of the italian socio-cultural context. in this frame, “the strange case of professor promezio” is a practical experience able to combine laboratory activities with historical events which took place in the 20s of the last century, involving third parties like the chemistry museum of genova5 and the forensic police. the link between schools and museums has been recently demonstrated to play an important role in the context of chemical education.6 according to the tetrahedral model7 and the “context-based science teaching” approach,8 learning chemistry can be facilitated if chemistry is not taught in an abstract way, but by connecting it to human beings, everyday life, and society problems. in particular, the promotion of the interest toward chemistry by exploiting the great attraction of teenagers for crime scene investigation has been reported.9,10,11,12,13,14,15,16 however, most of these activities dealt with specific subjects, offering a narrow view of the chemistry world. in order to overcome this problem, we recently reported a practical activity in which students were involved in various interconnected laboratory experiences, able to provide a general overview of chemistry and its many subdisciplines.17 a detailed and rigorous evaluation of this activity led to the conclusion that the interest of high-school students towards chemistry could be improved by this multidisciplinary approach. now we wish to report a new project, “the strange case of professor promezio”, that, to the best of our knowledge, represents a unicum in the panorama of laboratory activities for high school students. in fact, it does not only lead the students through six interconnected laboratories, but, in order to solve a cold case, it induces them to deepen historical aspects such as the discovery of element 61, the advent of nationalisms at the beginning of the last century and the spread of malaria in italy in those years. the effectiveness of teaching science using case histories dates back to the work of conant.18,19 history of science can be used to celebrate landmark discoveries as well as great scientists: by connecting scientific knowledge to names, faces and places, science can reach a “human” dimension and can be perceived by the students as something that can be achieved not only by “geniuses”. historical context, on the other hand, allows to highlight how scientific discoveries are the result of the contribution of many factors, often interconnected.20 more recently it has been demonstrated that a better comprehension of scientific concepts and methods can be achieved including historical components in science classrooms21,22 and by highlighting how chemistry knowledge has developed over time.23 so, scientific, forensic and historical aspects are synergistically involved in capturing and inspiring the students. the activity illustrated below has been organized in 2018 and 2019 and has involved about 100 students every year. the students, equally distributed between males and females, were aged 17-18 years and were coming from high schools of liguria and southern piemonte and had different backgrounds: 72% came from scientific high schools, 18% came from technical institutes and 10% were specializing in classical studies. discussion “the strange case of professor promezio” is a cold case in which students are asked to investigate an event that took place almost a century ago and that involved a famous professor, promezio in fact, who was looking for the chemical element number 61 and mysteriously disappeared during the fire of his laboratory. the case was closed by the police of that time because no corpse was found and evidence against possible suspects was not strong enough; meanwhile the laboratory has been transformed into a chemistry museum. the case was unexpectedly reopened after a skeleton was brought to light by the collapse of a wall in that museum. students are involved at this stage of the story, to analyze the findings collected at the time of the facts and others recently found next to the skeleton, to reproduce the experiments described in prof. promezio’s notebook and identify who, among the possible suspects, could have killed the professor and set fire to the laboratory. the history of professor promezio is a re-adaptation of an event that really happened around 1920: the dispute between prof. rolla and prof. noyes on the paternity of the discovery of the element number 61 and on the name, florentium or illinium, to be given to it.24,25 history tells that neither of the two contenders was right, and indeed element 61 was named promethium, by the researchers of clinton laboratories (oak ridge, tennessee, usa) who isolated it by nuclear fission.26 the students, during their investigations, will discover that professor promezio, an imaginative representation of prof. rolla, mistakenly attributed experimental evidence to the new element. going into the details of the activities, the students are involved in: 1. visit to the chemistry museum with illustration of the original equipment used to purify and characterize rare earth elements in the 20s. 121the strange case of professor promezio: a cold case in the chemistry museum 2. detection of latent fingerprints on the semi-burned notebook of prof. promezio, using the ninhydrin stain. 3. detection of genetic material on a metal tube found close to the skeleton, using the luminol test. 4. qualitative and quantitative analysis of a white powder, presumably used to set the fire, employing flame and magneson tests and atomic absorption spectrometry. 5. replication of the experiments described in the notebook of prof. promezio, aimed at the isolation of a lanthanide element and at its recognition. 6. analysis of some fabrics by visual inspection and solubility tests. 7. identification of an organic molecule through the determination of physical properties and the comparison of analytical data with those found in a database. details on each experiment are available in the supporting information. from a chronological point of view, upon arrival, the students are gathered in a classroom, where a short presentation of objectives and conditions of the activity is given. then, the students are guided through the chemistry museum and introduced to the work of stanislao cannizzaro during his stay in genova, with focus on his influence on the mendeleev periodic table of the elements and on how the latter led to the discovery and classification of most of the rare earth elements, between the end of 1800 and the beginning of 1900. subsequently, the students are divided into teams of five people and each group participates in six half-day experiments, according to a specific workplan. the order of the activities is not relevant for the case study, as information deriving from each experiment is independent and not conclusive itself. students are directly involved in the practical work and supervised by young m.sci or phd students (tutors) in order to encourage their active participation. experiments cover the main branches of chemistry and are designed to stimulate the discussion on both specific and general aspects. in detail, preliminary tests on the crime scene lead the students to discover the chemistry behind the routine techniques used by the scientific police, as well as to discuss the general issue of false positives during the analysis. the experience in the analytical chemistry laboratory introduces the students to the concept of qualitative and quantitative analysis, and more in details to sensitivity and reproducibility. qualitative analysis of fabrics, on the other hand, stimulates the discussion on comparative properties of natural and synthetic tissues, structure-property relationships in polymers and on the evolution of synthetic tissues throughout the last century. the organic chemistry experience is aimed at identifying the nature of an unknown substance, highlighting the relationship between structure and properties of molecules. finally, the evolution of the procedures in the inorganic/physical chemistry field is experienced by performing the isolation of a rare earth element from the mineral monazite according to classical procedures (fractional crystallization and calcination), followed by its identification through a modern instrumental technique (x-ray diffraction). results from each experiment are relevant for the solution of the murder case, but never conclusive, suggesting one or more suspects or exonerating others. finally, the activity ends with a presentation of results by the different groups, where students are asked to critically discuss the collected data and the scientific evidences in order to come to a sound conclusion of the murder case. this final task is an opportunity to highlight the remarkable creativity and imagination of the students, as well as their enthusiasm and involvement in the investigation. during the conclusive day of the activity, some representatives of the forensic police are invited to deliver a lecture on how crime scene surveys really take place. in addition, they assist to the presentations of the students and evaluate them, selecting the best one and assigning to the authors a very coveted prize: a one-day visit to the laboratories of the forensic police. conclusion in conclusion, the key features of this activity can be summarized in the following points: 1. hands-on: students are not spectators but actors in performing the laboratory experiences, collecting data and analyzing results. 2. tutoring: students are guided in all activities by young tutors (graduates from the chemistry department), able to establish a fruitful and friendly relationship. 3. team working: students are divided into groups of five people (“teams”), selected in order to be heterogeneous in scholastic background and gender. 4. multidisciplinary and interdisciplinary: a complex scientific problem is solved exploiting different areas of chemistry; in addition, interconnections with history, geography, ethics and other school subjects are deepened. 5. evaluation: asl provides a cross-evaluation of the activity by the students and of the students by the university staff, making it available on-line through the italian ministry portal. 122 marina alloisio, andrea basso, maria maddalena carnasciali, marco grotti, silvia vicini according to the student evaluation, the activity was greatly appreciated; in particular, the topic was judged very stimulating, able to efficiently introduce different chemistry disciplines and to involve the students in proficuous team working. due to the acquisition of technical and practical skills, several students declared interest for the study of chemistry. besides these qualitative statements of general satisfaction, possible changes in the situational interest raised by the activity have been assessed through an entrance and exit test, performed and elaborated as previously reported.17 it was confirmed that the activity significantly increased interest and attitude toward chemistry, mainly for students with lower scores in pleasure for the study of chemistry (e.g. high-school students compared to students from technical institutes), self-efficacy and self-concept in chemistry. the students also observed that working under the supervision of young tutors, competent and close for age to them, allowed to communicate easily and to carry out the experiments independently but with the correct procedures. the final presentation of the results and of the solution of the case was also considered very useful and captivating. moreover, all high-school teachers involved in the asl project were invited to the final presentation of their students and, through the above mentioned italian ministry portal, they inserted a feedback regarding the students’ experience. their evaluation was enthusiastic (showing always five stars as the score) not only for the positive feedback of the students, but also for the scientific content of the project and for the practical activities, able to fill the gap with the more abstract way of teaching that is typical of high school. supporting information general organization and detailed experiments for laboratory activities are available as supplementary material. acknowledgements the project has been financially supported by the italian national project “scientific degrees plan”. references 1. science education for responsible citizenship, report to the european commission by the expert group on science education. http://ec.europa.eu/research/swafs/ pdf/pub_science_education/ki-na-26-893-en-n. pdf, last accessed on 10/01/2020 2. the rose project: an overview and key findings, report to the european commission. http://www. 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nature, 1927, 120, 14. 26. j. a.marinsky, l. e. glendenin, c. d. coryell, j. am. chem. soc. 1947, 69, 2781. substantia an international journal of the history of chemistry vol. 4, n. 2 2020 firenze university press some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy, ph.d., j.d. …and all the world a dream: memory outlining the mysterious temperature-dependency of crystallization of water, a.k.a. the mpemba effect evangelina uskoković1, theo uskoković1, victoria wu1,2, vuk uskoković1,3,* the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries aleksander sztejnberg communicating science: a modern event antonio di meo substantia. an international journal of the history of chemistry 6(1): 7-12, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1528 citation: hyde s.t. (2022) faraday’s dogma. substantia 6(1): 7-12. doi: 10.36253/substantia-1528 received: nov 21, 2021 revised: jan 10, 2022 just accepted online: jan 11, 2022 published: mar 07, 2022 copyright: adapted from faraday’s dogma, published by stephen t. hyde on jot down cultural magazine (https://www.jotdown.es/). copyright © 2021, by stephen t. hyde. used with permission of the publisher. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature articles faraday’s dogma stephen t. hyde department of applied mathematics, australian national university, australia email: stephen.hyde@anu.edu.au abstract. contemporary scientific research is competitive, costly and coupled to the parallel universe of commerce. a faustian bargain between scientists and politicians allows the funding to flow. there is another path: to slow down, think and experiment without the pressure of competition and frequent publication. that path will come at a cost: reduced funding for people and equipment. the article compares and contrasts the most creative musical and visual artists with the current scientific model. i suggest that science requires acceptance that true creativity can only come by decoupling from current commercial and political imperatives. keywords: science and art; scientific creativity. when asked the secret of doing science, the great chemist michael faraday, replied in the early 1800s work, finish, publish no-nonsense common sense from a humble autodidact, who rose from working class obscurity to being offered (and refusing) the presidency of the royal society in his maturity. faraday’s extraordinary experiments exploring electromagnetism are legion. given his status, his words are treasured to this day by scientists. surely, those words have been drummed into countless young postgraduate researchers by well-meaning seniors for generations. his vision of experimental science remains de rigeur to this day: i am no poet, but if you think for yourselves, as i proceed, the facts will form a poem in your minds. that quote hints that science may be an ethereal enterprise, less focussed than a take-no-prisoners voyage of discovery. science is poetry? alternatively, faraday’s insistence on ”facts” as the stuff of his poetry is to many reassuringly grounding, bringing the practice back to earth. the brevity and subliminal appeal to common-sense of both quotes seems to me a hallmark of british science. i see a direct line, for example, from no-nonsense faraday to (in my mind) the most british scientist of all, the (new zealander!) ernest rutherford, who classified all science as physics or stamp-collecting, and http://www.fupress.com/substantia 8 stephen t. hyde reckoned the odds of betting against science at 1012 to 1. so it came as a surprise to me to come across the following words, also from rutherford… i think a strong claim can be made that the process of scientific discovery may be regarded as a form of art. this is best seen in the theoretical aspects of physical science. the mathematical theorist builds up on certain assumptions and according to well understood logical rules, step by step, a stately edifice, while his imaginative power brings out clearly the hidden relations between its parts. a well constructed theory is in some respects undoubtedly an artistic production. a fine example is the famous kinetic theory of maxwell. … the theory of relativity by einstein, quite apart from any question of its validity, cannot but be regarded as a magnificent work of art. those words can be parsed to imply that creativity resides in science, just as in art. that claim is no threat to modern science, but what if it were taken more literally? it is somewhat startling to a card-carrying scientist (including this one) to read rutherford’s words once more...”scientific discovery may be regarded as a form of art”! is science another domain of artistic practice, alongside sculpture, film-making, etc.? that reading is perhaps overblown; after all, rutherford explicitly invokes the notion of a logical progression to scientific ”discovery”, an implicit credo dear to the hearts of many practising scientists. yet he also allows for the creation of scientific theories as works of pure art, regardless of their validity. hmmm. do scientists ”create” rather than ”discover”? and, for that matter, do artists ”discover” or ”create”? these conundrums are age-old, but largely forgotten in the day-to-day hustle and busyness of the massive production line of science, whether from a crowded lab in some unprepossessing rural university, or the fabled cern scientific complex, so extensive that its ”lab” sprawls across a national border, straddling france and switzerland. perhaps they are forgotten for a simple reason: science is expensive. in fact, science is far more costly than even the most costly art productions, including the bloated budgets of hollywood productions. after all, hollywood films are deemed to have failed unless they recoup their production costs, and (far) more. value is no more, or less, than a balance of expenditure over costs. ask a film producer, or a crusading journalist, or the imaginary taxpayer, summoned into the mind of any politician as he or she weighs up a country’s annual budget. science too is likewise constrained. its triumphs, such as the extraordinarily rapid development of covid vaccinations are sure indicators of its value. likewise, the current crowd of ”scientific experts” quizzed by the media on the covid epidemic: a daily parade of epidemiologists from all corners, whose variety of models will surely explain any eventuality. despite the public swagger of science, it remains at heart a fragile construction. even at its most strident, its ”facts” are unclear. to give one current example, the debates over effective quarantine measures in australia gloss over the ”fact” that aspects of the fundamental science of viral transmission, from fluid mechanics[4] to soft-matter science[7], remain unknown. despite an apparent consensus, science remains a human activity, far more complex than a well-equipped voyage of discovery. any reckoning of the (financial) value of science is messy and ultimately hopeless. the conscientious accountant must include the price of microplastics in the environment, of fossil fuel extraction, as well as the benefits of vaccinations. it seems to me that in the midst of covid and the apparent triumph of scientific research, we would do figure 1. michael faraday posing with a tool of trade (a magnet?). photograph by maull & polyblank. wikimedia commons. photo from the wellcome library (icv no 26801). photo number: v0026348. 9faraday’s dogma well to sit quietly, and reflect on the the nature of science itself. my own thoughts were triggered by a recent visit to the heide museum of modern art in melbourne, where i spent a few hours at a retrospective exhibition of the australian modernist robert owen, ”blue over time”, featuring sculptures, paintings, and assorted other pieces[5]. owen is a deep thinker and profound artist, whom i have been fortunate to occasionally spend time with. (a recommended introduction to his work is the beautifully produced recent monograph ”robert owen a book of encounters”[6].) he’s worth knowing for his own sake: he spent a few years in the early 1960s on the greek island of hydra together with an extraordinary community of writers, musicians and scholars, including leonard cohen and (lesser known globally, but equally influential to australians) charmian clift and george johnston. the f lavour of that community is beautifully captured by a couple of exhibits at heide: a pair of reed flutes, hand-crafted by owen and exchanged with cohen. in return, owen was given a copy of cohen’s latest book of poetry, ”flowers for hitler” (1964), inscribed with the poet’s dedication: for bob like your reeds there is a special way to blow on these all good things leonard, hydra, winter 1965 figure 2. (l to r:) models for florentia (2006). robert owen. cadence no. 1 (a short span of time), 2003. 10 stephen t. hyde the practical advice of faraday and the dreamy lyrics of cohen are so different, both in intent and content, that visiting aliens could be excused were they to suggest the existence of multiple distinct life-forms on earth. it seems that scientists and artists have evolved entirely distinct ways of thinking and doing on the same planet. or perhaps faraday, maxwell, einstein, even rutherford, were poets, like cohen? on the other hand, my heide visit rekindled the converse thought: perhaps (good) artists are in fact scientists? i find owen’s works scientific as well as artistic. so much so that after being shown his sculptures a few years ago, i began researching the concept of ”tangled polyhedra” from the perspective of topology and graph theory, a subject which continues to preoccupy me and other scientific colleagues, more than a decade later. (owen and i described those connections elsewhere[3].) my interest was triggered by nothing more (or less) than owen’s artworks, yet i – in all honesty, dishonestly – continue to justify my research on these tangled forms in technical papers by its relevance to things of ”value”, such as interwoven molecular frameworks in modern synthetic materials. the ”value” of that field of fundamental scientific research is in turn routinely justified to the broader science community (in less specialised science publications and grant applications) via its relevance to really useful stuff, such as ”designer materials” tuned to store hydrogen for green energy, or capture carbon dioxide to mitigate global warming. all scientists know the game well, for those who will not or cannot play rarely survive beyond their first post-doctoral post or grant round. one more confession: (nearly?) all the scientists i know admit to the essential dishonesty of that game, playing along to keep the funds and publications flowing. the game is an ingrained aspect of contemporary science, tolerated as an obligatory distraction from the real business of scientific research. but just what is that real business? it may come a surprise to many non-scientists to learn that the deeper one looks into the practice of scientific research, the closer the practice of fundamental science resembles the art of owen and cohen than the well-paved path from the lab to the publisher, chronicled by faraday. faraday claimed his ”poems” were built with ”facts”. and so they were: his magnets and galvanometers did not lie. neither do the reams of data thrown up by cern’s accelerator, or the the microwave map of the sky. but the spinning and weaving of that data into a scientific fabric, offered to the otherwise uneducated masses as the signature of the elusive higgs particle, or an echo of the big bang reverberating around the cosmos, is neither a truth nor a lie. it is a story, spun by human creativity. there is no single road from ”work” to ”publish”. conversely, it is not too far-fetched to associate visual art, or literature, with ”facts”, though those facts are not readily detected by a scientific instrument. conjunctions of colours, which lie at the heart of owen’s abstract pixellated paintings, and words, which fizz within cohen’s lyrics, catalyse common, unquantifiable, emotional responses in very different people. in the current climate of usefulness and value, the intrinsic slipperiness of science, as opposed to the incremental and essentially phenomenological nature of engineering, is too often denied. art is an essential reminder. artists explicitly embrace the irrational: the essential source of creative ideas. we scientists, on the other hand, flee from such flakiness, preferring to shelter within more politically-acceptable quarters, whose admission price is alignment with the prevailing notion (not notions) of ”value”: economic growth. our adherence to the ”value” of science, measured and funded in terms of economic value, has cost us dearly. i was reminded of that cost reading an essay by the eminent quantum theorist, david bohm, ”on the relationships of art and science” (available in a collection of essays by bohm, ”on creativity”[1]), recommended to me by owen. in his essay, bohm discusses the new artistic languages in the twentieth century, from cézanne to cubism, constructivism and mondrian and their common feature: the emergence of an entirely new form of art, which involves new structural elements which in themselves have no meaning, but which combine to form structures whose meanings arise from the imagination of the artist alone. the value of such art, bohm argued, lies in its possibility to shed light on how structure itself is perceived by the senses, potentially opening new ways of seeing the external environment. the artist who wrestles with forms, reveals, at his or her best, ”new general understanding of structure at the perceptual level… from this, the scientist can form new abstract ideas of space, time and the organization of matter.” his argument can be interpreted as one of peripheral relevance to most scientific researchers: after all, how many of us are looking at new ideas of space or time? that response is comforting, but too easy. for surely all physicists, chemists and molecular biologists are looking deeply into ”the organization of matter”? like rutherford’s comparison of scientific theory with art, bohm’s argument seems astonishing today. both quotes betray a proud indifference to the conventional practice of scientific research, articulated so clearly by faraday. in contrast, today’s science can be de scribed as faraday-lite: obsessed with continuous reinforcement of the fiction of ”values”, thereby sidestepping deeper sources of thought. 11faraday’s dogma can scientific culture value deep thinking? thankfully, yes. witness, for example the recognition of its importance by rutherford and bohm (and numerous other ”great” scientists, including einstein, poincaré,…). if so, how can scientists recover the practice of deep thinking? first, we must abandon current obsessions guiding ”good science”. the fiction that scientists work better in a hurry must be laid to rest, with apologies to mr. faraday. like slow food, whose origins lay in rejection of fast food by italian consumers and growers, slow science is healthy. second, the cult of collaboration must be exposed for what it is: an empty belief. though group-research is important to some, larger groups are also prone to group-think mediocrity – science by committee – rather than creative ideas. worse, the very idea of a scientist working alone remains acceptable in mathematics, but anathema in the other sciences. perhaps, most painfully but most importantly, we must abandon the credo that binds us to the political and sociological ”system” whose measures of value allow only shortto medium-term productivity and utility. that will happen anyway, it’s called engineering. (at this point, i hear murmurs of disapproval from many quarters: acceptance of a basic distinction between science and engineering is an implicit nod to elitism. in fact, both practices require their own elites.) like artists, scientists must accept that true creativity is unlikely to be funded to the level required to sustain another cern or a (wo)manned mission to mars, even with elon musk’s purse. more to the point, the time has surely come for science to definitively break the yoke that binds science to ”value”. within my own time in science since the 1980’s, i have seen the wholesale reassignment of scientists as de-facto engineers. giant industrial labs, such as ibm and xerox in the us, have disappeared, their (engineering) research now funded by the taxpayer, being done in physics and chemistry labs in academia. more recently, covid has induced extreme financial hardship on universities in australia, dependent on fee-paying by non-australian students to sustain a large body of selfidentifying science researchers, all claiming to conduct ground-breaking and world-beating (and expensive) research. sadly, it is not too far-fetched to argue that unfettered scientific research is all but gone, except in the most privileged of academies around the world. if it is to revive, perhaps reversion to fewer, modestly-funded (dare i say ”elite”!) scientists is essential in any case. i was reminded of these uncomfortable prescriptions for the future of science most recently, and forcefully, by a fascinating article by the genoese art critic germano celant, first published in 1967. celant’s article is devoted to the philosophy of a group of italian artists, whom he associated with a new philosophy of art-making, which he famously called ”arte povera” (poor art, or perhaps better translated as impoverished art). like bohm, the text is recognisably of another era. celant argued that the ”true” artist, exemplified by marcel duchamp, is obliged to remain outside the system. if not, ”the artist, the new apprentice jester, is … called upon to produce fine commercial merchandise, offering satisfaction to sophisticated palates.” his articulation of arte povera includes the declaration: so on the one hand, we have an attitude to be defined as ’rich’ since it is osmotically connected to the enormous instrumental and informational possibilities that the system offers; an attitude that imitates and mediates the real creates the dichotomy between art and life, public behavior and private life. and on the other hand, we have ’poor’ research … this is a way of being that asks only for essential information, that refuses dialogue with both the social and the cultural systems, and that aspires to present itself as something sudden and unforeseen with respect to conventional expectations: an asystematic way of living in a world where the system is everything. such an attitude … is intent upon retrieving the factual significance of the emerging meaning of human life. it’s a question of an identification between man and nature, but with none of the theological purposes of the medieval narrator-narratum; the intention, quite to the contrary, is pragmatic, and the goal is liberation, rather than any addition of ideas or objects to the world as it presents itself today. celant’s vision of art, shorn of the coat of 1960s polemic, is strikingly parallel to a conventional philosophical vision of science, which seeks identification between ”man and nature”, driven to understand the ”factual” significance of our existence. arte povera, like slow food, was a radical rejection of the ”system”. if science is to revive, perhaps an equally radical stance is required. i am struck by the notion that whereas (some) artists have wrestled with the importance of new ways of seeing, analogous discussions are (to my knowledge) nowhere to be found among scientists. indeed, it is thanks to robert owen that i came across celant’s essay, recently reprinted to commemorate his death last year[2]. whereas science and art will always have their differences, often communicated by different languages, both professions have something to learn from each other. viewed from the scientific side of the linguistic border, art-speak is often obscure, with a propensity to purloin scientific concepts and reissue them in a half-garbled form, thereby gilding the work with an aura of the other. (interestingly, the converse practice: art-speak in scientific publications, is hard to find, save 12 stephen t. hyde some celebrated cases; another story worth telling elsewhere). however, a deeper dive, into celant, or owen (or cohen) reveals a humility and dedication to the primacy of deep, creative thought over the ”valuable”. it is time for scientists to abandon the widely-held view that art is secondary to science, forever hobbled by its fondness for imaginative thought over the empirical and its explicit admission of the irrational. it is time to rekindle the association between art and science which was openly acknowledged by scientists in earlier times. bring on slow science and scienza povera. for even the most unfettered scientific poems may hit paydirt eventually. when asked by gladstone what his new-fangled concept of electricity could offer society, faraday famously answered why sir, there is every possibility that you will soon be able to tax it. his wit is undeniable, but has proven to be all-too prophetic in recent years. despite his own well-documented integrity and humility, he crystallised a dangerous idea: science is money. given the exorbitant prices exchanged on the international art market in recent years, so too is art. but that’s not the point. references [1] d. bohm. on creativity. routledge classics. routledge, 2004. [2] g. celant. in memory of germano celant: arte povera. notes on a guerrilla war. flash art april 20, 2020. [3] s. hyde and r. owen. sculpting entanglement. australian physics, 52(6), 2015. [4] r. mittal, r. ni, and j.-h. seo. the flow physics of covid-19. journal of fluid mechanics, 894, 2020. [5] h. museum of modern art. blue over time. https:// www.heide.com.au/exhibitions/blue-over-time-robert-owen [6] r. owen and etc. robert owen—a book of encounters. perimeter book, 2021. [7] w. c. poon, a. t. brown, s. o. direito, d. j. hodgson, l. le nagard, a. lips, c. e. macphee, d. marenduzzo, j. r. royer, a. f. silva, et al. soft matter science and the covid-19 pandemic. soft matter, 16(36):8310–8324, 2020. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 5(2): 35-39, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1287 citation: campanella l., suffritti g. b. (2021) can non-recyclable plastic waste be made environmentally sustainable?. substantia 5(2): 35-39. doi: 10.36253/ substantia-1287 received: apr 12, 2021 revised: jul 19, 2021 just accepted online: jul 20, 2021 published: sep 10, 2021 copyright: © 2021 campanella l., suffritti g. b. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature articles can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 1 dipartimento chimica, sapienza, università di roma, roma, italy 2 dipartimento di chimica e farmacia, università degli studi di sassari, sassari, italy e-mail: luigi.campanella@uniroma1.it; pino.suffritti@gmail.com abstract. after death the fraction of living matter which is not biodegraded (shells, bones, corals, carbonaceous deposits) becomes environmentally sustainable. this is not the case for plastics so that these wastes should be either recycled or made environmentally inert and stored in secure repositories as a resource for future generations. chemistry has offered different solutions to this problem, and each brings about advantages and disadvantages when compared to other options. one further possible route could consist in the enrichment of the plastics waste in carbon content (“carbonization”), in analogy with the production of charcoal from wood, but we hope to stimulate a debate about all the other possible routes among scientists and engineers in the involved fields. keywords: plastics waste accumulation and dispersion, circular economy, carbonization of plastics waste. 1. introduction there is a growing concern about the accumulation and dispersion of plastics waste.1-4 plastics have become indispensable for human life and for industry, but their high chemical stability makes most of them not completely degradable when dispersed in soil, fresh and sea water, and in air, unless it was properly designed to be biodegradable. most plastics are obtained from fossil oil,up to about 10-12 % of the global production, according to an iea report published in 2018.3 even using the best plastic waste management practices,5-9 models predict that an important fraction of plastics waste (more than 22% in 2050) will accumulate,10 especially in surface water and oceans, reaching a mass of 500±100 mt in 2050.3 in oceans these wastes are able to create true plastic islands, that reached in 2018 an overall surface of 1.6·106 km2, corresponding to about 6 times the surface of france, in the pacific ocean only.3 plastics waste degradation is accelerated by irradiation from the uv component of sunlight and by some mechanical wearing, with the continuous production of smaller and smaller debris, maintaining a substantial chemical integrity.11-17 energy recovery as heat, steam, or electricity by burning plastics wastes, that in 2016 represented http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 36 luigi campanella, giuseppe b. suffritti the fate of as much as 40% of plastics waste,3 is strongly discouraged because of the production of greenhouse gases and pollutants.1-3,13 as it will be better detailed below, different strategies have been proposed for reusing and recycling plastics waste,18 but its large fraction that accumulates in landfills and, what is much more dismaying, in surface waters and oceans, is generally not adequately considered. although we are not pure specialists in the field, general common sense considerations led us to give our little contribution to drive the attention of the scientific community of chemists to this important problem in order to be allowed to say “i do my part of the job” 2. circular economy and plastics waste there are several different ways to define circular economy. according to the european commission’s implementation of the circular economy action plan, approved in 2019, circular economy is: a system aimed at eliminating waste, circulating and recycling products, and saving resources and the environment.19 in a recent review focused on the plastics waste, it is stated that:9 [the] concept of “circular economy” (ce) commonly refers to the “take-make-use-break-make” concept, where the main goal is to create economic impetus from the waste. it also enables the close-looping of product – waste – building block cycle. however, as remarked for instance by kümmerer et al.,5 a complete recycling of plastics waste is practically impossible, unless plastics materials are purposely designed, and in fact a huge amount of wasted plastic residues is actually dispersed in the environment. a closer look at natural living systems action to maintain environmental sustainable cycles can give some further insight in extending the concept of circular economy. indeed, after completing their vital cycle, the fate of living matter “waste”, besides a small quantity of volatile compounds, which are dispersed in the atmosphere, water or in soil, is mostly bio-recycled. only a negligible fraction of it is burned as a consequence of natural events, such as fires caused by lightning, or by volcanic eruptions. however, a more or less important fraction of living matter waste is made of mineralized remnants. for instance, bones buried in soil last nearly unchanged for centuries, shells of aquatic animals are accumulated in lakes, seas, oceans floors and eventually become rocks, and coral colonies are able to build up entire islands. finally, fossil carbonaceous deposits (coal, oil and natural gas) were originated by large amounts of living matter deeply sunk in soil. all these long-lasting living matter wastes share the important property to be environmentally sustainable, or inert. in conclusion, the natural ecology is not strictly circular, but the produced “waste”, which is not recyclable is environmentally sustainable. therefore, it is reasonable to ask ourselves why we cannot follow a similar route for the management of plastics waste, by proposing that all what cannot be biodegraded or used as feedstock for recycling18 shall be treated to become environmentally inert and stocked in secure repositories, for future use as matter and energy resource. 3. overall management of the plastics waste plastics often consist in one or more co-polymers along with several additives such as plasticizers, flame retardants, coloured agents, ultraviolet-light stabilizers, antioxidants that are difficult to separate during the recycle process leading to waste of time, money and material. the bottleneck of recycling is the preliminary separation and fractionation of the present compounds. therefore recycling is often considered only at the atomic or molecular level with possible loss of the intrinsic properties of the products compared to those of the same products in the original waste. in january 2018 the european commission announced a vision for europe’s new plastics economy substantially based on a new model of economy: from linear to circular economy. so the following commitments are considered to be implemented: – all plastic packaging used in europe must be reused or recycled by 2030; – more than half of the plastic wastes must be recycled; – plastic sorting and recycling capacity must be extended fourfold by 2030: – some 10 million tons of recycled plastics are to be used for new products by 2025. mechanical recycling consists in transforming the plastic waste in raw material without any substantially modification of its chemical structure. it is the largely most adopted method in europe but due to the presence of additives the process cannot recover more than 60-70% of the original wastes. the recycled materials find the same application as the original plastic wastes, in any sector of our today common life. 37can non-recyclable plastic waste be made environmentally sustainable? if separation and filtration of additives is omitted to save time and money, the obtained products are mainly used in mixed formulations applied to building works such as streets, bridges and other infrastructures. an alternative way is based on a selective dissolution of the plastic waste followed by filtration and evaporation of the solvent, but the real innovative process of recycle is based on chemical and biotechnological processes especially applied in the case of wastes of polyethylene terephthalate (pet), nylon and polyurethane. among the chemical processes, pyrolysis consists in heating under vacuum which will result in a final product that contains a mixture of liquid and gaseous hydrocarbons.4,20-23 de-polymerization can be obtained, at least for pet by means of microwave radiation.24 hydrogenation is a degradation that involves a treatment with hydrogen followed by heating, and in this case the products are olefinic hydrocarbons (ethylene, propylene, butadiene). gasification is obtained by heating at high temperature (800-1600 °c) in the absence of air that results in a mixture of hydrogen and carbon monoxide. chemolysis, glycolysis, methanolysis, amminolysis are all de-polymerisation processes that produce low molecular weight products, which can be used as reagents of multiple synthetic reactions and represent an alternative route, that results in the formation of chars (solid carbonaceous materials) and gaseous hydrocarbons. however, these solutions do not contribute to the “decarbonisation” of our society: the products are intended to be used as fossil fuels so contributing to further increase the anthropogenic greenhouse effect. an innovative way of recycling is the enrichment of plastics wastes in c content. this process leads also to the recover of hydrogen and other heteroelements. the final products can be stored in the same sites where the raw material was extracted, such as exhausted carbon mines and fuel deposits, reproducing a stock of inert raw material to be used in the future.25 the main problem of this option is to have the proper catalyst able for the extraction of hydrogen and other elements similarly to what was obtained with the charcoal from the thermal treatment of wood. as recently reported, a catalyst based on mixed iron and aluminum oxides acting under a microwave field of 1000 w seems to be able to extract hydrogen from plastics. also biotechnological methods were successfully applied to the recycling of plastics.6 the discovery made by a group of researchers of carbios and of the toulouse institute of biotechnology26 of an enzyme present in the leaves’ compost has opened a new way to recycle pet with very promising results as the recycled material has the quite same properties of the original waste. in the 25th august 2020 issue of the chemistry world weekly kyra welter reports that an international group of research was successful in obtaining a polymer able to be recycled in principle for an infinite number of times, during which it was depolymerized and the obtained monomer was re-polymerized and so on.27,28 contrary to mechanical recycling that changes the properties of the material after few cycles, monomerization can potentially bring to materials that can be recycled whenever needed without any limit and keeping the same properties of the raw starting material. the problem in this case is that monomerization, if not purposely designed for plastic materials is not an available chemical process. the chemical modification of the existing hardly recyclable plastics can increase their lifetime and face three different problems: first, in general polymers easily decomposed do not present good properties; second, the obtained products behave better in many common applications; and, third, if one wants to have good mechanical properties for the new product it is necessary to control the stereochemistry of the polymerization. the integration of this option in the actual recycling systems could be difficult because of the multifarious variety of the plastic waste, increasing the number of the possible components. this point can only be solved by a very responsible behavior of citizens and of local institutions. in general, plastics waste treatment can entail a net cost, which is to be supported in view of the unbearable environmental damage of accumulation and dispersion of plastics waste.4 in line with a recent proposal about carbon taxes, this cost should be recovered from special ad hoc taxes “similar to a value added tax (vat) [...] such that end users pay the full costs.”.29 indeed general taxation usually is not equally charged and distributed among taxpayers.30 note that actually many megatons per year of plastics waste are exported from europe, australia and north america to china and other countries,3,4 entailing transport costs that could be avoided if sustainable domestic treatments are properly implemented. 4. discussion and conclusions in this paper we shortly outlined some dismaying problems connected with the management of plastics wastes, and particularly, of the large fraction of this waste which is accumulated untreated in landfills as well as in surface and sea waters, even if an increasing commitment is advanced to reuse and recycle plastics waste by the various available procedures.1 any effort and strategy should be performed to avoid the dispersion of 38 luigi campanella, giuseppe b. suffritti plastics waste in air, waters and soil, by securing and controlling any phase of deposit, and especially in the long-lasting landfills. as remarked, in view of the global warming problems, it should also avoided and restricted any treatment of plastics waste releasing co2 and other greenhouse gases into the atmosphere. in addition, the products of plastics waste recycling suitable as fuels should be preferably if not mandatorily used as feedstock for the chemical industry, so sparing mineral oil resources, or stored in secure repository. a general strategy for the plastics waste management was proposed in the conclusions of a recent review about microplastics (tiny specks of plastics of micrometer size) by hale et al.:13 most plastics are inexpensive to manufacture. hence, there is little financial incentive to reuse them. to support a circular lifecycle, the upfront price of plastics must incorporate end of life costs. currently, low volume plastic users and associated ecosystems bear a disproportionate burden (e.g., remote islands are now being littered with plastic debris). this environmental injustice echoes that of climate change and sea level rise. landfills may be mined by future generations as resources become scarce and technologies improve. optimization of such “dumps” into “repositories” is worthy of consideration. political initiatives across borders should seek to accomplish these goals. however, by considering the amounts and the rate of accumulation in landfills, in our opinion it is urgent to find also sustainable technical routes to transform the untreated or not recyclable plastics waste into “inert” matter which should be stored in secure repositories, such as exhausted mines of coal and other minerals, or impermeable quarries, as a resource for future generations. it could be objected that a large fraction of plastic waste is already environmentally “inert”, as it lasts almost unchanged for hundreds or even thousands of years,14 if properly saved. there are at least two reasons to propose a further treatment of plastic waste. first, the chemical nature of plastic materials makes their use as a feedstock in the future rather difficult and expensive, so that saving more homogenous materials would be preferable. the second reason is that the recovery of hydrogen, fluorine and other elements could help in reducing or even offset the cost of the treatment. in addition, the danger of a dispersion of degraded plastics in air and waters (especially as microplastics) would be contrasted, and the amount of the final waste could be reduced. all this can be obtained by the enrichment of the plastics waste in c content (“carbonization”). examples of chemical processes that can achieve this result are discussed by chen et al.25 if this proposal is considered unpractical or too expensive, we wonder whether there are there other ways to obtain environmentally sustainable materials from plastics waste. in conclusion, on one hand, we urge scientists and engineers working in the field of plastics materials to think and propose practical solutions to this problem, and on the other hand we hope that a fruitful discussion about the ways to avoid accumulation and dispersion of plastics wastes will involve a larger scientific, technological, political and especially social public. references 1. united nations environment programme, converting waste plastics into a resource. compendium of technologies. assessment guidelines, division of technology, industry and economic international environmental, technology centre osaka/shiga, united nations environment programme (unep), 2009. https://wedo cs.unep.org/bitstream/handle/20.500.11822/8638/wasteplasticsest_compendium_full.pdf ?sequence=3&isallowed=y. 2. oecd background report: improving plastics management: trends, policy responses, and the role of international co-operation and trade, environment policy paper no. 12, oecd, 2018, https://www.oecd. org/environment/waste/policy-highlights-improvingplastics-management.pdf. 3. iea, the future of petrochemicals. towards more sustainable plastics and fertilizers, iea, 2018, https:// www.iea.org/reports/the-future-of-petrochemicals. 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22-26. doi: 10.1038/ d41586-021-01143-3. 16. n. h. m. nor, m. kooi, n. j. diepens, a. a. koelmans, environ. sci. technol. 2021, 55, 5084. doi: 10.1021/acs.est.0c07384. 17. y. picó, d. barceló, acs omega 2019, 4, 6709−6719. doi: 10.1021/acsomega.9b00222. 18. iso 15270:2008(en) plastics guidelines for the recovery and recycling of plastics waste, 2008. https://www. iso.org/obp/ui/#iso:std:iso:15270:ed-2:v1:en 19. european commission, implementation of the circular economy action plan, brussels, 2019. https://eurlex.europa.eu/legal-content/en/txt/pdf/?uri=cel ex:52020dc0098&from=en. 20. g. lopez, m. artetxe, m. amutio, j. bilbao, m. olazar, renew. sustain. energy rev. 2017, 73, 346 –368. doi: 10.1016/j.rser.2017.01.142. 21. h. rubel, u. jung, c. follette, a. meyer zum felde,. s. appathurai, m. b. díaz, a circular solution to plastic waste, boston consulting group, boston, 2019. https://image-src.bcg.com/images/bcg-acircular-solution-to-plastic-waste-july-2019_tcm9223960.pdf. 22. a. 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www.chemistryworld.com/news/designer-plastic-canbe-recycled-over-and-over-again/4012317.article. 29. s. tagliapietra, g. b. wolff, nature 2021, 591, 526528. doi: 10.1038/d41586-021-00736-2. 30. t. piketty, capital et idéologie, éditions du seuil, paris, 2019 [engl. ed.: t. piketty, capital and ideology, harvard university press, cambridge, usa, 2020] substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 3(1): 113-118, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-161 citation: j.-p. gerbaulet, pr. marc henry (2019) the ‘consciousnessbrain’ relationship. substantia 3(1): 113-118. doi: 10.13128/substantia-161 copyright: © 2019 j.-p. gerbaulet, pr. marc henry. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 1 n-light endowment fund, 30 rue de cronstadt, paris 2 université de strasbourg, umr 7140, 4 rue blaise pascal, 67000 strasbourg e-mail: jpg@n-light.org abstract. from a thought experiment on the observation of a human intellect by itself, we will attempt to demonstrate that, unlike what many neuroscientists postulate, assemblies of neurons do not generate consciousness: consciousness pre-exists any material system. keywords. consciousness, meaning, information, activity, neurons. introduction understanding that the nature of consciousness is a real challenge for western cultures which heavily focus on the scientific method for understanding natural phenomena, one usually refers in this case to the “hard problem”.1 by contrast, eastern cultures traditionally adopt philosophical approaches to the problem, such as hinduism2 or buddhism3, with a notable western exception (eckhart tolle).4 in a nutshell, three main visions are fighting each other over tackling the “hard problem” from the western side.5 a first position is physicalism, a kind of monism stating that physical laws are perfectly valid for explaining the existence of both mind and body. such a vision (thales, leucippus, democritus, epicurus) is a broader version of materialism taking for granted that there exists in the universe, in addition to matter, energetic phenomena such as electromagnetism, that are physical and real. in this view, physical states (size, mass, shape, energy, etc.) and mental states (beliefs, desire, emotions, etc.) are made of the same “stuff ”. a second position is dualism (plato, descartes), stating that mental and physical states are both real and made of two different materials that cannot be assimilated to one another. finally, a third position is illusionism, stating that consciousness simply does not exist and involves some sort of introspective illusion. according to d.j. chalmers, this illusion is a close relative to the meta-problem of consciousness, i.e. the problem of explaining why we think that there is a problem of consciousness. in fact, illusionism states that distinguishing between 114 jean-pierre gerbaulet, marc henry easy problems and the hard problem distracts our attention from the hard question which is: “and then what happens”?6-8 in contrast with the above approaches, we would like to draw your attention to an einstein’s remark made in the context of “how to deal with the threat of the atom bomb”: “a new type of thinking is essential if mankind is to survive and move toward higher levels”.9 owing to the generality of this statement, such a remark has been widely diffused out of its context in several versions, among which we shall retain this one: “no problem can be solved from the level of consciousness that created it”. such a formulation is quite reminiscent of gödel’s incompleteness theorems.10 applied to the ‘hard problem’ or the ‘hard question’ of consciousness, it means that the bottom-up logic, typical of western thinking, in which consciousness is the result of long-range coherence in neural activity11, may be considered as a deadend. if a theoretical model has recently been proposed for decoding brain wave information,12 it remains that it does not address subtle aspects of consciousness. it is thus our deep conviction that a “new” approach (as far as western minds are concerned) is to consider a top-down logical process inspired by eastern thinking where consciousness pre-exists any material system such as neurons or brain. in other words, we plan to demonstrate that consciousness cannot be an emergent property of neural activity. owing to the importance of such an assertion for western minds, the demonstration proposed in this paper is concise and readable by non-scientists. a more technical and scientific demonstration is published as a separate paper showing how this top-down approach fits into current scientific knowledge.13 definitions our aim in this paper is to give a wide audience access to the concise demonstration of the logical necessity to consider consciousness as the source of reality. the presentation has thus necessarily many gaps that will be addressed in a forthcoming article. among the gaps, the very first one is a good definition of consciousness. we sincerely think that the best way of handling the consciousness concept is to assign it an “ identity card” in order to recognize it by its manifestations in space and time.14 on this ground, we state that consciousness is the tool that allows us to find a meaning in information, either analyzed by intelligence or coming directly from feelings and intuition (qualia). it a priori applies to most living beings. our demonstration below thus necessarily implies the existence of two other dimensions (one space-like, the other one time-like) located outside a 4d space-time framework.15 with such two extra-dimensions, consciousness would acquire an extra-human value and it would then be designated by consciousness. it has as real (probably more real) features than our so-called “objectivity” attached to our manifest 4-d space-time horizon. we will assume that the extra time dimension is the ordering element that generates different attributes within itself as illusions16 as developed elsewhere13. our line of thought in this matter is inspired by chemistry, a science where thermodynamics uses static general concepts putting constraints on dynamical aspects, which allows selecting among all possible paths the most favorable to evolution. consequently, we shall now focus on the framework rather than on what may happen within the framework, a problem which will be addressed later.13 concerning dynamics, we will be considering time as an emanation of consciousness, the question of its topology (linear, curved or fractal) being thus irrelevant to our demonstration. similarly, we have introduced the conceptof activity, which is generally used in thermodynamics to combine energy and entropy within a single entity. we therefore recommend reading “energy/entropy” whenever you come across the word “activity”, unless you are familiar with thermodynamics.17 and if you are reluctant to the concept of entropy, just think “energy”. it is close enough to make laypeople understand the idea. scientific bases, postulate to demonstrate the priority of consciousness over neurons, we will use principles of computer science,18,19 information theory,20 gödel’s incompleteness theorems10 and the laws of thermodynamics.17 and we will refer to the following postulate: any phenomenon preexisting another one is able to participate in the creation of the latter, whereas the contrary is impossible.  this postulate, which conditions the possibility to create a principle from another one, should clearly explain how a space-time-matter framework used by conventional science is able to emerge from a non-local consciousness following a hierarchical cascade, hereafter named “the thought experiment”, where a person observes the functioning of his/her own intellect. 115the ‘consciousness-brain’ relationship context and description of the thought experiment the thought experiment that we will propose relates to what is called in psychology: metacognition. some evolutionary psychologists hypothesize that humans use metacognition as a survival tool, which would make metacognition the same across cultures. writings on metacognition date back as far as two works by the greek philosopher aristotle (384-322 bc): “on the soul”21 and the “parva naturalia”.22 today, metacognition is studied in the domain of artificial intelligence and modelling. therefore, it is the main domain of interest of emergent systemics. in such an experiment, the subject and the object are the same since the person observes his/her intellect by means of the latter. although all the parameters of the subject and the object are identical, they operate in the self-observation process at different chronological and hierarchical levels. the result is that the situation can be summarized by the relationship between five protagonists: consciousness, meaning, information, activity and neurons. organized in couples, their specific relationship allows for the proper functioning of the whole: • consciousness and meaning, • meaning and information, • information and activity, • activity and neurons. consciousness-meaning the intellect is a system comprising, by analogy with a computer23, a hardware (material device) and several types of software (immaterial devices). the difference with a computer is that the physical entity is able to repair itself by creating de novo material components (cells) necessary to its proper functioning. in the software-hardware couple composing a computer, hardware without software would only be a set of ‘dumb’ electronic circuits: central unit, memories, i/o interfaces, peripherals. even if artificial intelligence equipped computers are able to write software, to self-educate and self-duplicate themselves, even to selfimprove their level of performance, they have initially been fitted with software designed by conscious beings, without which they would be unable to operate. moreover, electronic components are designed and manufactured by conscious beings, not by the computers themselves using 3d-printers for instance, owing to difficulties in implementing evolutionary processes and to the “salt contingency problem” raised by alex ellery in 2017.24 in a computer, since software gives life to hardware, it has a functional anteriority over hardware. now, in a computer, the process of cognition and memorization is based on the manipulation of binary digits, the so-called “bits” (with just two possible values 0 and 1), a succession of such bits being called “information”. an important aspect is that, at computer level, such information has no meaning, even if bits are combined and manipulated according to logical rules inferred from the existence of consciousness. meaning only appears as soon as information is combined with consciousness.25 thus, it is consciousness that gives a meaning to information, and thereby possesses a functional anteriority over meaning. meaning-information the way consciousness gives meaning to information is by considering pieces of information which, once compared to memorized other pieces of information, are placed in a context which gives them a meaning. we typically find ourselves in the framework of the information theory, where meaning is defined as information in a context.26 although of a similar nature to the point to be often confused in everyday’s language, information and meaning are not identical. at the end of his life, the great physicist john wheeler considered that, in the universe, all could be made of information.27 in our thought experiment this basically means that, within a field of information, consciousness has the ability to select pools of information of varying sizes thus defining “objects” or “things” that could be differentiated by their respective information content. obviously, as evidenced by the fluidity of thought, such pools of information should not be considered as static entities, but rather as dynamic systems exchanging information. since it is the meaning that gives its value to a given amount of information it chronologically anteriorizes information and is, therefore, hierarchically superior to it. information-activity based on the above considerations, it follows that, in our thought experiment, characterizing pools of information solely by their number of bits is not enough. one may assume that within a given pool of information, some groups of bits that are considered by consciousness as having a high meaning will not be easily transferred 116 jean-pierre gerbaulet, marc henry to another pool of information, since such groups of bits give an identity to the information pool. thus, transferring them, would inevitably make the pool lose its identity. here appears, in a logical way, the conscious “i” which holds a number of bits sufficient to give itself an identity within the whole information field. this means that besides the information content, one should also introduce an information availability that could be low or high depending on its importance for the definition of the identity of the pool. as soon as two pools have not the same information availability, information is expected to flow from the pool having the higher availability towards the pool having the lower availability. by such information transfers, the information availability of the emitter decreases, whereas the information ability of the receiver increases, allowing pools of information to undergo evolution on two levels. at a first level, pools may just change their information content by exchanging non-meaningful bits that are readily available. at a second level, pools may also change their identity by exchanging meaningful bits that are not readily available. it suggests introducing a new concept, information activity, defined as the product of information content by information availability.13 consequently, one may meet pools having small information content that are not readily available, corresponding to a low activity pool. conversely, pools characterized by high information content that is readily available for information transfers would be qualified as high activity pools. such a definition of information activity has also the consequence to make duality appear within a non-dual information field. accordingly, a given activity value may be associated either to a low information availability within a large pool of information or to a highly available information coming from a small pool of information. in the first case, activity may be associated to “moving” information allowing evolution and change in “time”, while in the second case it becomes associated to “structural” information defining conservation and identity in “space”. a space-time frame thus emerges quite naturally by the action of consciousness giving meaning to various pools of the information field. from this analysis, it follows that information is unique in the information field, whereas activity characterizing the intensity of information transfers has a dual character responsible for an energy/entropy duality in the physical world. such a duality is reflected by the existence of two universal constants: boltzmann’s constant kb ruling the minimum information content viewed as an entropy (statistical physics) planck’s constant h ruling the minimum information activity for observing an energy change viewed as a frequency (quantum physics) or as a temperature (thermodynamics). consequently, one can assert that information chronologically anteriorizes activity, and is therefore, hierarchically superior to it. activity-neurons having given birth to concepts of entropy s and energy w through the concept of vibration f (w = h·f ) and temperature t (w = kb·t), it remains introducing the “matter” concept through a third universal constant intimately associating space to time. the reason for it clearly stems from the fact that it is the same consciousness acting on a unique information field that creates time as moving information, and space as structural information. the two concepts referring to the same amount of information should thus necessarily be linked as two different viewpoints about the same parameter depending on information availability. the basic postulate of equivalence between space and time stemming from the theory of relativity, another most important physical theory in science, is thus logically introduced. by this definition, the third universal constant should be a speed c imposing an upper limit to the transfer of moving structural information between information pools. from the above considerations, it follows that two kinds of elements should exist in a physical universe: those able to propagate with the maximum allowed speed c, known as “photons”, and those that propagate at speeds v < c, known as “matter”. in the second case, one may assign to a material object with an energy e, an inertial coefficient m or “mass”, linked to it by m = e/c2. adding the two other universal constants, we may write the fundamental identity of our physical world: e = m·c2 = h·f = kb·t, meaning that our reality is made of a combination of inertia (mass m), spontaneous vibration (frequency f) and spontaneous movement (temperature t). going back to our computer analogy, it should now be clear that neurons are likened to hardware since they are the cells dedicated to information processing. each neuron is an information-processing unit linked to other neurons to form a network with various crucial physical nodes at the levels of brain, heart and intestines. the nodes of the network are linked together to form an intranet-like physical body which behaves in an 117the ‘consciousness-brain’ relationship autonomous way and can be likened to a set of circuits: network nodes (brain, heart, intestines), input interfaces (the five senses plus a sixth one relaying feelings and intuitions), output interfaces (limbs, voice, ...), associated to neuronal, and possibly non-local, memories. the physiological complexity of the whole allows it to perform processing functions, but not interpretations. in a nutshell, even if the intranet-body possesses a certain processing autonomy, the directions of its actions are given, at each stage of the process, by the meaning of the intermediate results interpreted by our consciousness. it then appears that neurons, which are in the physical world the material interface for manipulating information, are located at the very end of the hierarchy described in our thought experiment. this analysis shows that activity plays a role chronologically anterior hence hierarchically superior to the one of matter, making it impossible to state that consciousness emerges from the physical activity of neurons. it is the opposite. synthesis: we have hereby demonstrated that consciousness anteriorizes meaning, which anteriorizes information, which anteriorizes activity, which anteriorizes neurons. consequently, the relationship between consciousness acting on a unique information field, and brain acting in a four-dimensional space-time, acquires in this environment the status of a law: law: consciousness preexists neurons and cannot be an emergent property of them. we shall deduct from it 5 corollaries, some of them remaining to be confirmed. corollary 1: consciousness exists independently from the neurons. corollary 2: matter originates in consciousness (spirit). we posit that consciousness preexists not only neurons but matter in general. by likening consciousness to spirit, one could, subject to further confirmation, deduct that matter originates in spirit. corollary 3: extension to non-local consciousness: subject to similar confirmation, matter, activity, information, meaning and consciousness would be states of decreasing vibratory levels of a same principle, the ground state of which would be pure consciousness, and the forms closer to this fundamental level would be subtler or less material. we might then postulate that this fundamental state being without precursor, it would be at the origin of all that exists. there may then be a high probability that the primordial consciousness be located outside space-time, since being at the origin of it, it could hardly belong to it (gödel’s theorem). this primordial consciousness could be named non-local consciousness. corollary 4:  generalization • non-local consciousness would preexist all that exists in the observable universe or manifest world. • its expressions would be of a decreasing level when coherence diminishes: meaning, information, activity, and finally inert matter. • they would be of an increasing level when coherence grows: structured matter (crystals), unconscious life, life conscious of the world, then of itself, and, at last, of the fact to be conscious of being conscious, this most advanced state being the one of humanity. by analogy with the geometrical fractalisation, this cascade of levels could be named conceptual fractalisation. corollary 5: practical consequences in our thought experiment, the energy considered is a mix of chemical energy, well known by biologists (mass m and temperature t), and of electromagnetic energy (frequency f ), tolerated by them. since these energies are the ones concerning the object-oriented language, as defined in our companion paper,13 nothing prevents from having more subtle energies working at the meta-language level, such as vital energy or psi energy, largely ignored by mainstream neuroscientists. using the brain computer metaphor, it may be time to update our own software.28 by contrast, traditional medicines commonly use these energies and the ‘informational function’ of consciousness to cure patients, with track records of several millennia. this contradiction is the main subject of interest  of the experiments, underway or in project, by the n-light research institute, its members and its partners. references 1. d. j. chalmers, j. consciousness stud. 1995, 2, 200. 2. g. sri aurobindo gose, the life divine vol. 21 & 22, sri aurobindo ashram publication department, pondicherry, 2005. 3. h. h. dalaï lama, consciousness at the crossroad, conversation with the dalaï lama on brain science and 118 jean-pierre gerbaulet, marc henry buddhism, snow lion publications, ithaca, new york, 1999. 4. e. tolle, oneness with all life: inspirational selections from a new earth, dutton, penguin group, new york, 2008. 5. d. j. chalmers, j. consciousness stud. 2018, 25, 6. 6. d. c. dennett, phil. trans. r. soc. b 2018, 373, 20170342. 7. n. block, behavorial and brain sci. 1995, 18, 227. 8. j. e. bogen, s. bringsjord, d. brown, d. j. chalmers, d. gamble, d. gilman, g. güseldere, a. murat, b. mangan, a. alva; e. pöppel, d. m. rosenthal, a. h. c. van der hejiden ; p. t. w. hudson, a. g. kurvink, n. block, ned, behavorial and brain sci.1997, 20, 144. 9. a. einstein, m. amrine, the new york times magazine 1946, june, 23, p.7. 10. k. gödel, kurt, monatsh. math. phys. 1931, 38, 173. 11. s. dehaene, j.-p. changeux, l. naccache, lionel (2011), in research and perspectives in neurosciences, (eds.: s. dehaene, y. christen), springer-verlag, berlin, 2011, pp. 55-84. 12. s. sen, siddhartha, j. consciousness stud. 2018, 25, 228. 13. m. henry, j.-p. gerbaulet, substantia (submitted). 14. j.-f. houssais, md, les 3 niveaux de la conscience, guy trédaniel, paris, 2016. 15. m. henry, inference : int. rev. sci., vol. 2, issue 4; http://inference-review.com/article/super-saturatedchemistry 16. many thanks to referee #1 for drawing our attention to this point. 17. w. j. gibbs, the scientific papers of j. willard j. gibbs, vol. 1, longmans green and co, london, 1906. 18. a. m. turing, proc. london math. soc. 1937, 42, 230. 19. a. m. turing, proc. london math. soc. 1937, 43, 544. 20. c. e. shannon, bell syst. tech. j. 1948, 27, 379. 21. aristotle, “de anima (on the soul)”, translated by hugh lawson-tancred, penguin classics, 1986. 22. aristotle, “parva naturalia (short treatises on nature)”, translated by j. i. beare & g. r. t. ross, oxford, 1931. 23. r. m. biron, j. comput. higher educ. 1993, 5, 111. 24. a. ellery, in proceedings of the ecal 2017, (eds.: c. knibbe et al.), the mit press, cambridge ma, 2017, pp. 146-153 25. r. mukhopadhyay, j. consciousness stud. 2018, 25, 184. 26. m. burgin, r. feistel, information 2017, 8, 139. 27. j. a. wheeler, k. ford, geons, black holes and quantum foam. a life in physics, w.w. norton & co., new york, 1998, pp. 63-64. 28. g. weber, evolving beyond thought: updating your own software, createspace independent publishing platform, 2018. substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 1(1): 61-67, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-13 citation: s. gottardo (2017) new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection. substantia 1(1): 61-67. doi: 10.13128/substantia-13 copyright: © 2017 s. gottardo.this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declares no competing interests. historical article new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo european laboratory for nonlinear spectroscopy (lens), 50019 sesto fiorentino (florence), italy e-mail: gottardo.stefano@gmail.com abstract. joseph weber, form maryland university, was a pioneer in the experimental research of gravitational waves and neutrinos. today these two techniques are very promising for astronomical observation, since will allow to observe astrophysical phenomena under a new light. we review here almost 30 years of weber’s career spent on gravity waves and neutrinos; weber’s experimental results were strongly criticized by the international community, but his research, despite critics, boosted the brand new (in mid-sixties of last century) research field of gravity waves to become one of the most important in xxi century. on neutrino side, he found an unorthodox way to reduce the size of detectors typically huge and he claimed to observe neutrinos flux with a small pure crystal of sapphire. keywords. gravitational wave, neutrino, joseph weber, bar detector, torsion balance. introduction the astronomic observations will grow rich, in the next few years, two new methods of investigation. today the sky is observed and measured almost exclusively by electromagnetic radiation. until 1950 the available radiation was only the visible or near-infrared. then in the second half of the last century, thanks to enormous technological advances, we added x-ray radiation, microwaves, radio-waves that almost complete the electromagnetic spectrum. these frequencies allowed to discover objects like pulsars, quasars, neutron stars and cosmic background radiation. many things are still hidden to electromagnetic radiation. an example is the photons (the quanta of electromagnetic field) that come from the sun. the earth is illuminated by a “old” radiation, about 100,000 years old. the photons are created in the center of the sun, but employ about 100,000 years to arrive on earth surface. the reason is the very high temperature inside our star. matter is not what we know at such temperature. the core of the sun has a density 150 times larger than water and a temperature of 1,5x107 °c. the core is formed by a plasma of ions and electrons, which traps the light. photons cannot escape from the core, except after a long time, this is because the plasma of ions and electrons is opaque to 62 stefano gottardo electromagnetic radiation (the scattering cross section of photons with plasma is much higher with respects to the ordinary matter, where nuclei and electrons form atoms). one type of particles, however, manages to escape quickly from the solar core and to get on the earth after only 8 minutes, with a velocity very close to the speed of light. these particles are neutrinos. hypothesized by austrian physicist wolfgang pauli  and structured theoretically by enrico fermi in the 1920s, neutrinos are elusive particles that do not interact electromagnetically, but only through the weak interaction. they are produced during the nuclear fusion process that occurs in the sun and tell us the types of nuclear reaction that is occurring inside our star. the typical decay that involves neutrino is the so called β-decay, where a free neutron n decays into a proton p, an electron eand an electronic antineutrino  νe .1 n→ p+e− +νe neutrinos can also reveal hidden features in supernovae explosions. the huge flow of neutrinos will invest the earth when a supernova explodes. the neutrino detectors on the earth will alert telescopes and radio telescopes on supernova position. in fact, the neutrinos emitted by the explosion will travel undisturbed towards us, while the electromagnetic radiation will need a bit of time, as it will encounter in its path the hot plasma of ions and electrons. there is a worldwide alert on neutrinos called snews (supernova early warning system), active since 2005 with the participation of seven detectors around the world including the two italian lvd and borexino. neutrino detection can give very precious information on neutron stars’ structure and on the merger process between two neutron stars in a binary system. the very new second method of astronomical investigation is the detection of gravitational waves. according to the present theories, such types of waves are emitted by nearly all astrophysical objects and the most violent ones give off gravity radiations in copious amounts. supernova explosion observed via gravitational waves can reveal how the star collapse is going on, what happens to star core and how the final explosion takes place. the internal part of supernova will be accessible only to gravitational waves or neutrinos. another violent astrophysical event is the black holes merging. two black holes, orbiting one on each other (binary system), release gravitational waves when they become more and more close and at the end an enormous amount of gravity radiation will be emitted when they will merge into a more massive black hole. black holes are the only massive astrophysical object that cannot be observed directly with electromagnetic waves detectors or neutrinos. nothing can escape from black hole, neither light. but an exception are gravitational waves that can be observed during the merging of black holes binary systems. gravitational waves were predicted in 1916 by einstein, by finding that they are the carrier of the energy of the gravitational field, as electromagnetic waves transport the energy of electromagnetic field. in 1915 einstein developed, after seven years, the theory of general relativity2 that fixed a lot of paradoxes present in the old newtonian gravitational theory (see ref. 3 for an introduction to general relativity). the gravity force in general relativity is due to the curvature of the spacetime that is generated by masses (as in newtonian theory) but also by any form of energy and momentum. einstein field equation in tensorial notation has a simple form of: gµν = 8πg c4 tµν (1) where g is the gravitational constant, c the speed of light in vacuum. a part from the constants, the equation tells that gμv called the einstein tensor that contains the spacetime curvature, is equal to stress-energy tensor tμv. in other words, the stress-energy tensor modifies the spacetime form flat (tμv = 0) to curved (tμv ≠ 0). the indexes μ,v = 0,1,2,3 (the spacetime has 4 dimensions, 3 space type, 1 time type and the index 0 is usually the time component), so the eq. 1 are in practice 16 equations. it is interesting to see how gravitational waves emerge from einstein field equation (1), to estimate the order of magnitude of such space time ripples that can be detected on the earth. the einstein tensor depends in a complicated way by the spacetime metric gμv if the space is flat, called the euclidian space, the spacetime metric is identified by the tensor ημv that is: ηµν = −1 0 0 0 0 1 0 0 0 0 1 0 0 0 0 1 ⎛ ⎝ ⎜ ⎜ ⎜ ⎜ ⎞ ⎠ ⎟ ⎟ ⎟ ⎟   (2) we can suppose for the moment that extreme astrophysical events, like binary black holes merging, happen very distant form our observation point, and that we are in a place where the stress-energy tensor tμv = 0 (no gravity at all). the flat space will become nearly flat when spacetime ripples, caused by some event, will hit our detector. in this weak field hypothesis, the metric tensor gμv becomes gμv = ημv + hμv, where hμv is the correction to flat space and we can consider |hμv|<<1. with the latter two hypothesis einstein field equation eq. (1) becomes: ∂2hµν ∂2 xµ =− 16πg c4 tµν =0 (3) 63new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection eq. (3) are now 4 equations since only the index v survived the index contraction. eq (3) can be expressed in a more familiar way: − ∂2 ∂2t +∇2 ⎛ ⎝ ⎜ ⎞ ⎠ ⎟hµν =0 (4) that is the standard wave equation. the solution of eq. (4) is: aµν exp iωt+ik1x+ik2y+ik3z( ) (5) where k is the three-dimensional wave vector and ω is the frequency of the wave; so, the spacetime oscillates with an amplitude aμv, after some distant astrophysical event. eq. (5) is the gravitational wave. the first step to detect gravitational waves is to estimate their strength for a detector on earth. the order of magnitude of the wave amplitude depends on the phenomena, for example one of the most violent one could be a supernova explosion and a formation of a black hole of 10 solar masses 10m⊙( ).  genearally the upper limit for a≤m/r where r is the distance from the event and m is the mass of the object; if it happens in andromeda galaxy, that is the closest galaxy to our milky way, distant from earth roughly 2,5 million of light-years, a≤10-17. the probability to observe such close and violent event is very rare and the wave amplitude typical for events that can happen two-three times per year is 10-21. so, the target for detector sensitivity should be 10-22. the first who claimed to observe gravitational waves in 1969 was joseph weber.4 he worked in his carrier on both gravitational waves and neutrino, mainly giving an enormous and unique boost to the first one. results and discussion in the history of gravitational waves a prominent place belongs to joseph weber, american physicist of maryland university. early in his career he has proposed a mechanism that explained the proper operation of the laser,5 but without funds to experimentally prove his idea, has been overtaken by others who have demonstrated the laser mechanism and got nobel prizes and glory. forced to change the research field, he went to princeton university under the supervision of john archibald wheeler. wheeler in the decades 1950-1970 was considered the main expert of general relativity.6 weber learned of the existence of gravitational waves and chose them as a research field. he was an experimental physicist, so he decided to design a detector for gravitational waves. after years of study to understand the best way to measure gravitational waves, he decided to use a bar detector, a resonant mass detector that responds to incident gravitational waves by vibrating.7 the detector was a simple aluminum cylinder, 2 m long and with diameter of 96 cm. gravitational waves, ripples of spacetime, would compress and then tend the bar. weber chose the size of the bar to reveal the gravitational wave frequency of about 1600 hz. he based the choice on very rough estimate. in the early 1960s a clear picture of which astronomical events could emit gravitational waves around 1 khz was not clear. this frequency is typical of black holes and neutron stars binary systems that with a spiral motion merge and release a large part of their mass via gravitational waves. to measure the deformation of the bar detector, he adopted piezoelectric crystals, which property is that under mechanical deformation respond with an electric voltage, see figure 1. in measuring this voltage, weber could understand how his bar has been deformed from a gravitational wave. in the early sixties of last century, weber was the only experimental physicist who developed a detector and tried to observe gravitational waves, while today there are four operating gravity waves observatories and other under construction or design. in the late sixties,4,8 weber began to publish data on the possible extent of gravitational waves. at that point, several research groups started gravitational waves search and adopted bar detectors to try to reveal the ripples of spacetime. no group in the early 1970s, however, was neither able to replicate weber result’s, nor confirm his results.9 weber continued to publish results of gravitational waves detection10 and in the meanwhile he added a new bar detector placed about 1000 km away from the previous one. this method based on the coincidence figure 1. weber’s bar detector. joseph weber with his bar detector. the small metallic squares on the aluminum cylinder (the bar) are the piezoelectric crystals that were used to quantify the bar deformation. image credit: university of maryland libraries special collections and university archives. 64 stefano gottardo between the two detectors, allowed to identify more easily spurious signals that come from any source but gravitational waves. since weber was the only one to detect gravitational, while all other experiments around the world failed, the physics community discredited weber and his measurements were decreed not reproducible. for many physicists weber made mistakes or manipulated data in identifying the threshold for gravity waves event detection. as a general rule an experiment must be repeated by anyone under the same conditions in different places and at different times, otherwise it is labeled not reproducible and it means that the original experiment is suffering from some weird error that alters the results. we will not enter here into the dispute between weber and the physics community, but a very interesting problem that plagues bar detectors is the uncertainty principle. quantum mechanics, the theory in physics that very precisely describes the behavior of the infinitely small as atoms and elementary particles, includes the uncertainty principle. if we take an electron and, for instance, we want to measure at a given instant of time its position and its velocity very precisely, we would be disappointed. if we measure its position very precisely its speed will be almost completely indeterminate, and vice versa. so, nature does it on microscopic scales, but what does it happen in the macroscopic world to bar detectors that are two meters long? in 1978 the russian physicist braginsky showed that resonant bar detectors were affected by the uncertainty principle.11 more accurately was the measurement of the position of one end of the bar, more unpredictable was the force that caused the vibration. by making calculations of the intensity of spacetime deformation due to the passage of gravitational waves, one get that powerful gravity waves were about 10 times weaker than the quantum limit of braginsky for bar type detectors, meaning that the quantum fluctuations were much larger than gravitational wave signal; in other words, the wave amplitude limit of weber’s bar was 10-16, accordingly to uncertainty principle. this could be the main reason for which none, except weber, detected gravitational wave with bar detectors. the quantum limit will be always present any system, but different detectors have different quantum noise threshold. instead of bar detectors, one possible way to measure the deformation of space is to send light back and forth and measure how light travelling time changes. to do this, one can use a michelson-type interferometer. the light from a laser crosses a beam splitter, which send half to one arm and half to the other interferometer arm (perpendicular to the first). the phase difference of photons in the two arms of the interferometer is correlated. when light comes back from the two arms an interference pattern is visible in the detector. this pattern will change if a gravitational wave will cross the interferometer and stretches and squeezes the spacetime. interferometers have two main advantage with respect to bar detector, one is that they operate in range of frequency of about 1000 hz and their sensitivity can reach very large value. ligo (laser interferometer gravitational wave observatory) is formed by 2 interferometers with 4 km long arms. proposed in 1976 by kip thorne,6 40 years later in 2016 ligo observed for the first time directly the ripples of spacetime.12 to date there are two direct observations of gravitational waves by ligo that occurred in 2016.13 the first observation was caused by two black holes orbiting one around each other, with masses respectively 36 and 29 solar masses.14 after the merge, a black hole of 62 solar masses has been created, while 3 solar masses instead have been converted into gravifigure 2. first gravity wave measured. the gravitational-wave event gw150914 observed by the ligo hanford (h1, left column panels) and livingston (l1, right column panels) detectors. image credit: ligo, picture taken from ref. 13. 65new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection tational waves that were measured by ligo detectors. the event was distant from earth 1,3 billion light-years and generated a wave amplitude (called also strain) of 2 10-21. in figure 2 the measurements from the two ligo interferometers were depicted, around 0.4 s the two black holes were merged (courtesy of ligo, ref. 13). there are other detectors similar to ligo, the more similar is virgo, located in italy, an interferometer of 3 km long arms (see figure 3). virgo was upgraded during ligo observation and will be in operation early in 2017. the japanese observatory called kagra is under construction in kamioka observatory, near the neutrino detector super-kamiokande, and it should be ready to run in 2018. the interferometric detectors work on frequency range from 10 hz to 2000 hz roughly. as for electromagnetic waves, gravitational waves exist in a very broad frequency window. very challenging for european space agency is the project elisa (evolved laser interferometer space antenna), where 3 satellites (distant 1 million km one from each other) will form a giant michelson interferometer. elisa will work in a frequency range form few hz to 10-5 hz (complementary to observatories on earth) allowing to observe gravitational signals from many astrophysical interesting sources such as binary stars within our galaxy and binary  supermassive black holes  in other galaxies. elisa proposed launch date is 2034. joseph weber’s work inspired and boosted the research in gravitational waves detection. kip thorne, one of the founder of ligo project, was inspired by weber’s research in mid-sixties of the last century and after a conference, where weber showed his preliminary experimental work, he decided to investigated theoretically the gravitational waves.6 perhaps, without weber pioneering work, we wouldn’t have had any detection of gravity waves in 2016. he used very simple and cheap detector; nowadays we have very expensive observatories and the others planned will be more and more expensive, e.g. elisa estimated cost is 2,4 billion of usd. on the other side, some research is still running on “alternative” detectors, based on resonant mass detectors. the bar type detector is replaced by spherical mass detector, that use the same working principle of the bar but with the advantage of having a larger frequency range. two experiments are quite active, mario schenberg brazialian graviton project14 and minigrail of leiden university in the netherlands.15 at the current time, no direct gravitational waves observation was reported from these two experiments, due to their quantum limit around ≈4x1021, higher than ligo measured signal in the first direct observation (see figure 2). the interest of weber for gravitational waves weakened after the debate with physics community and his discredit on this research field. he continued to receive founding on gravitational wave detection, but he published most of his research on not peer review journals.16 his interest moved towards another fundamental research line, the neutrino detection. in 1984 weber proposed a new mechanism to detect neutrinos with a very simple apparatus.17 weber theoretical claim involved scattering of low energy neutrinos on an infinite stiff crystal. the weak interaction theory of lee and yang predicts a scattering cross section for low energy neutrinos by a quark, that depends on n, where n is the number of nuclei of the medium.18 weber coherent scattering theory applied to infinite stiff crystal predicts a scattering cross section that depended on n2.19 the major experiments around the world that detect neutrinos from various sources, as for instance ice cube,20 superkamiokande,21 borexino,22 have detectors formed by enormous amount of liquid-solid material (south pole ice, ultra-pure water, peculiar scintillator respectively). neutrinos cross section is proportional to the number of molecules n of the detectors, for this reason to increase the probability of detection many experiments use very large amount of matter. the proposal of weber for low energy neutrinos, applicable for example to radioactive source or to solar neutrinos could enhance instruments sensitivity by a factor of 1023 ! the theoretical work of weber of 1985 was criticized by two papers of 1986 and 1987. the conclusion of both papers is,23,24 as reported by butler in ref. 25: “weber’s derivation of large total cross section is wrong on the basis of elementary physical arguments and that is a result of an incorrect mathematical derivation”. weber in 1988 published a detailed paper where he showed experfigure 3. ego observatory. view of ego (european gravitational observatory) that guest the experiment virgo. ego is a frenchitalian consortium and the observatory is located near pisa (italy). image credit: virgo collaboration. 66 stefano gottardo imentally how “coherent scattering of neutrinos can give measurable force due to coherent momentum transfer to crystal of cm of dimensions”.26 weber used a torsion balance equipped with single crystal sapphire target. he had three different torsion balances for three different experiments. the low defect sapphire crystal used mimicked the infinite stiff crystal for low energy neutrinos predicted by weber's theory.19 in the first experiment, where neutrino energy was 12 kev, the balance was equipped with two identical mass bars. one made of lead, and the second made of titanium tritide, acting as antineutrino source, with an activity of roughly 3000 ci). the β-decay from tritium created electrons and electronic antineutrinos. such neutrinos flux is enough to move the balance of a measurable quantity. the measured force per antineutrino was (1,05±0,12)x10-23 n cm-2 s-1. in the second experiment weber used the balance to measure the antineutrino flux from a nuclear reactor. in the third experiment weber measured the solar antineutrino flux (neutrino energy from 0 kev to 430 kev). the scheme of the torsion balance used for solar antineutrinos is shown in figure 4. as reported by weber in ref. 25: “a diurnal effect is predicted as the position of the sun changes, relative to the balance. we have been observing the diurnal effect during the past two years, with a peak, when the sun is in the direction of the line normal to the line joining the two masses”. in all three experiments the torsion balance of weber succeeded to measure the antineutrino flux. weber experimental paper, even though the theory of neutrino coherent scattering was considered wrong, were taken seriously by other research groups. the giant effect on solar antineutrinos observed by weber inspired james franson and bryan jacobs to replicate in a more precise and sophisticated way weber’s observations.26 they used two torsion balances suspended in a vacuum chamber. the expected different angle between the two balances was measured trough a mach-zender interferometer. weber in his paper in 1988 obtained a value of 0,86 for the efficiency of momentum transfer from antineutrinos to sapphire crystal. the very precise experiment of franson and jacobs gave an efficiency of 0,0033. in practice this value represented the lower limit of their apparatus; they measured nothing but apparatus noise. they concluded that their experiment was in strongly disagreement with weber’s one. after that, other three experiments with similar torsion balance were conducted by other teams. all of them concluded that weber’s observation of momentum transfer form solar antineutrinos to torsion balance was incorrect. no team measured any torque from neutrino scattering.27-29 but in 2011 a team succeed to confirm weber’s experiment on solar antineutrinos.30 they used a torsion balance under vacuum, with one target of low defect sapphire and the other made of lead. they observed the diurnal effect, with intensity similar to weber’s one. but except from the latter paper, where only preliminary results were reported, no detail study has been published yet. weber unorthodox theory and experimental proof on neutrino scattering was considered not correct by scientific community, as happened for gravitational waves detection. conclusion we reviewed here joseph weber’s scientific career in gravitational waves and neutrinos detection. these two research fields are today considered the future of astrophysical observation. this demonstrated the intuition of joseph weber in working in fields of physics with great prospects. weber was mainly a solitary researcher; in the majority of his papers he was the only contributing author. this fact was also confirmed by kip thorne in ref. 6, where he reported the affinity between him and weber in working in loneliness and in unexplored research fields. in the 1970s and 1980s the debate between weber and scientific community was very harsh. the experimental results of weber were almost considered not valid. this does not diminish the impulse that weber’s work has given and will give to both research figure 4. solar antineutrino detector. schematic view of torsion balance used by weber in solar antineutrino experiment, where neutrino coherent scattering from sapphire crystal produced a measurable torque. picture taken form ref. 24. image credit: american physical society. 67new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection fields. today neutrino and gravity waves researches are what is called big science fields, in the sense of large projects involving large research groups for decades. the challenge is that neutrino and gravitational waves should become small science, in the sense to have more compact and cheaper detectors. weber with his experimental intuition performed experiments on both fields with a reasonable 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2006, 23, 2052. 30. m. crucero et al., inter. jour. mod. phys. a, 2011, 16, 2773. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments \documentclass{rinton-p9x6} 1 equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the 𝝅𝟎 meson, its mass and lifetime barry w. ninham1,*, iver brevik2,* and mathias boström3,* 1 department of materials physics , research school of physics , australian national university, canberra, australia, 0200. 2 department of energy and process engineering, norwegian university of science and technology, no-7491 trondheim, norway. 3centre for materials science and nanotechnology, department of physics, university of oslo, p. o. box 1048 blindern, no-0316 oslo, norway. * e-mail addresses: barry.ninham@anu.edu.au; iver.h.brevik@ntnu.no; mathias.bostrom@smn.uio.no received: sep 09, 2022 revised: dec 03, 2022 just accepted online: dec 05, 2022 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: ninham b.w., brevik i., boström m. (2022) equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the π0 meson, its mass and lifetime. substantia. just accepted. doi: 10.36253/substantia-1807 mailto:barry.ninham@anu.edu.au mailto:iver.h.brevik@ntnu.no mailto:mathias.bostrom@smn.uio.no 2 abstract it is shown how maxwell’s equations for the electromagnetic field with planck quantisation of allowed modes appears to provide a semiclassical account of nuclear interactions. the mesons emerge as plasmons, collective excitations in an electron positron pair sea. the lifetime and mass of 𝜋0 mesons are predicted. keywords: casimir-effect, meson-theory, positron-electron-plasma, lifetime 1. electrodynamic fluctuation forces. feynman is reported to have believed that there had to be a connection between electromagnetic theory and nuclear forces. [1]. he never found such a link. it is shown how such a connection might come about. historical background: where do mesons come from?? a hundred years ago rutherford’s team at cambridge had shown that the atomic nucleus was comprised of protons and neutrons. the particles had a mass, 2000 times that of an electron ; protons were positively charged. a neutron could transform into a proton and a negatively charged electron. electrostatic forces played a role in the interactions between nucleons. but whatever other forces held them together remained a mystery [2]. quantum mechanics in its various manifestations, from planck, sommerfeld and bohr, schroedinger, heisenberg, dirac; and later quantum electrodynamics 3 promised insights. in 1935 yukawa had came up with a characterisation of this so called “weak nuclear interaction” that worked. the force was mediated by “particles” called mesons, mass 273 times that of an electron and variously charged. they were detected from cosmic ray decay by powell in 1937. there were 𝜇 and 𝜋 and later bigger 𝐾 mesons. particle physics developed subsequently culminating in the prediction of higgs unifying boson. but the fundamental physics embodied in maxwell’s equations for the electromagnetic field and quantum mechanics seemed to have nothing much to do with it. somehow something was apparently missing. the electromagnetic forces seemed too small. but protons and electrons were charged. the mystery and disjunction remained. theory in words without equations the classic paper of casimir in 1948 [3] on relativistic effects on the attractive forces between colloidal particles was motivated by, and applied to the newly developed deryaguin-overbeek theory of colloid stability. overbeek had posed the problem of these ”retardation” effects to his friend casimir in utrecht (bwn private communication with overbeek). casimir derived the forces due to quantisation of zero temperature electromagnetic fluctuations in the vacuum between two ideal metal plates. it stimulated a huge literature that still flourishes. it seemed to bear on our problem. but it could not due to its limitation to zero temperature. this and the term retardation are incorrect and unphysical [4-6]. further insights into the nature of the electromagnetic vacuum had to wait on the development of lifshitz theory for interactions between and across dielectric media [7] and included temperature. this theory at time appeared to be the culmination and triumph of quantum electrodynamics. it had been foreshadowed by p. n. lebedev who discovered light radiation 4 pressure. he was a friend of j. clerk maxwell and the stepfather of deryaguin. deryaguin had asked lifshitz to work on the problem. in 1894 lebedev wrote: ”if the solution of this problem ever becomes possible we shall be able, from the results of spectral analysis, to calculate in advance the values of the intermolecular forces due to molecular inter-radiation, deduce the laws of their temperature dependence, and, by comparing the values obtained with experimental results, solve the fundamental problem of molecular physics whether all the so-called ’molecular forces’ are confined to the already known mechanical action flight radiation mentioned above, to electromagnetic forces, or whether some forces of hitherto unknown origin are involved” as quoted by deryaguin [8]. however the triumph was illusory. the generalisation of the casimir effect involved some sleight of hand that approximated a non linear problem by a linear one [9]. this theory applied to casimir’s two plate problem gives out automatically: the binding energy of two nucleons in nucleus in equilibrium and automatically replaces the problem by one with a virtual intervening electron positron pair sea with known density and therefore plasma frequency of excitations. the renormalisation is identical to the klein gordon equation for scalar mesons with mass identified from the plasma frequency. the implication is that positive and negatively charged 𝜋 mesons are identifiable with bound electron-plasma and positron-plasma excitations. and what used to be called k mesons are higher order double plasma excitations known from solid state physics. what is quite new is that the identification of the scalar 𝜋0 meson with a collective excitation in the electron positron sea allows us to calculate its lifetime , correctly. taken together, binding energy, scalar meson mass , and lifetime all seem to add plausibility to our case. the simplified version of lifshitz theory we have used is the same lifshitz theory at the foundations of physical chemistry, molecular and colloidal particle interactions in the dlvo 5 theory. there the limitations due to the linearisation approximation are very clear. if the equivalence we have drawn is correct so too must present theories of particle physics. we first outline what we mean by electromagnetic forces. a 1961 paper of dzyaloshinski, lifshitz and pitaevski [7] applied quantum electrodynamics to the problem of molecular forces. it extended earlier work on electromagnetic fluctuation forces between molecules and colloidal particles of casimir and lifshitz to include effects of an intervening medium between the interacting particles. this impressive advance turned out later to be flawed. an approximation made in the derivation meant that the formidable mathematical formalism collapsed to a semi-classical theory. by this we mean maxwell’s equations with boundary conditions and quantisation of allowed modes [6,9,10]. technically the reason for this is that in the development of the theoretical formalism there occurs an integral equation for the polarisation operator that involves a non-linear coupling constant integration. an approximate solution can be found by linearising. the true polarization operator is then replaced by the macroscopic dielectric susceptibility. a detailed exposition can be found in eq. 2.9 and eq. 3.1 in ref. [7]. 2. theory 2.1 model assumptions and the casmir energy we assume that the nucleons have a structure which involves electromagnetic forces somehow as protons have a positive charge and a magnetic moment. then, how much of a role could electromagnetic forces play in nuclear interactions? consider two nucleons. if the nucleons were 6 perfectly reflecting spheres, calculation of the electromagnetic fluctuation forces would require an analytic solution of the helmholtz equation. this is complicated [11,12]. so we simplify the model and approximate the nucleons by perfectly reflecting planes with the same cross sectional area as the (spherical) nucleons. then the attractive electromagnetic fluctuation energy of interaction (all energies in this work are given per unit area) across a vacuum at zero temperature is [3] 𝐸 = − 𝜋2 720 ℏ𝑐 𝑑3 . (1) here d is the distance between the plates, ℏ is planck’s constant and c the velocity of light. we take d to be the distance between surfaces of the protons. the effective surface area is 𝐴 = 𝜋r2, r=proton radius~0.8 fermi. a typical nucleon-nucleon surface to surface distance is of the order of one fermi. then the available two nucleon-nucleon energy for binding in a nucleus from vacuum fluctuations is about 5 mev. the implication is that there is enough electromagnetic energy available in the zero-point casimir energy to account for nuclear interactions. the binding energy per nucleon varies in different atomic nuclei but is typically in the range from 1.1 mev to 8.8 mev. 2.2 temperature dependence of electromagnetic forces the observation that the zero temperature casimir vacuum fluctuation energy is enough to provide the binding energy of nucleons in a nucleus is suggestive. to take matters further we need to consider the effects of temperature. the gibbs free energy extension of casimir’s result that does so is due to lifshitz, it is [7,9,10,13], 7 𝐺(𝑑, 𝑇) = 𝑘𝑇 𝜋 ∑ ′ ∫ 𝑑𝑞𝑞𝑙𝑛 [1 − 𝑒 −2𝑑√𝑞2+𝜉𝑛 2 /𝑐2 ] ∞ 0 ∞ 𝑛=0 , (2) where k is boltzmann’s constant, t is temperature, q is the wavevector, and 𝜉𝑛 = 2𝜋𝑛𝑘𝑇/ℏ . the prime indicates that the zero frequency term carries a factor of one half. explicitly, at small distances, or high temperatures, this has the expansion [14], g(d, t) ≈  − π2 ℏ𝑐 720d3  −    ζ(3) k3 t3  2 πℏ2 c2  +   π2 d k4 t4  45ℏ3 c3  +.., (3) ζ(3) ≈ 1.202 is a zeta function. here the first term is the attractive (zero temperature) casimir result. the third term is the equilibrium black body radiation energy in the vacuum between the plates. it opposes the attractive casimir term. additional exponentially decaying terms are negligible in the regime of interest and have been omitted. leaving aside the second term for the moment, we suppose that the first and third terms are equal at equilbrium. this then provides us with a temperature determined by the distance d between the two plates, t= ℏc 2kd , at which the attractive and repulsive forces balance. the electron—positron sea the second term, is a chemical potential term in the gibbs free energy. we can recognise it explicitly as due to an electron positron pair sea formed from the photons in the gap by the reaction 𝑒 ++𝑒− ↔ γ [11]. from the temperature at distance d we can calculate the density for this electron 8 positron pair sea. as discussed by landau and lifshitz [15] the number of electrons and positrons are very nearly identical and both very large, even at temperatures of the order of 𝑚𝑐 2. (an electron-positron plasma becomes more nearly perfect with increasing density so we can use perfect gas formulae and ignore correlations .) the second term can then be re-written as  ζ(3) k3 t3  2 πℏ2 c2  = π(ρ− +ρ+)ℏ𝑐 6 , (4) where we use the expression for the density (𝜌 = ρ− + ρ+ = 3ζ(3)(kt)3 π2ℏ3 c3 ) of the electron-positron plasma [15]. the interpretation of the chemical potential term (the second term in eq. (3)) is the key to the equivalence we seek. 2.3 reformulation: the klein gordon equation and meson mass the imposition of a balance between the vacuum fluctuation and black body radiation forces has reformulated the problem to be that of an electromagnetic fluctuation force in which there are two metal plates separated by a medium. this medium, an electron-positron plasma, has the permittivity 𝜀(ω) = 1 − 𝜔𝑝 2 𝜔2 ; 𝜔𝑝 2 = 4𝜋(ρ−+ρ+)𝑒 2 𝑚𝑒 , (5) 9 where e is the unit electric charge and 𝑚𝑒 is the mass of the electron. the electromagnetic fluctuation interaction energy between two perfectly conducting plates across a plasma can be derived from the equation for the scalar potential, in maxwell’s equations [9], which after a fourier transform reduces to, ∇2∅ + 𝜔2 𝑐2 (1 − 𝜔𝑝 2 𝜔2 ) ∅ = 0, (6) yukawa [16] proposed that the nuclear interaction could be derived from the klein-gordon equation, ( 1 𝑐2 𝜕2 𝜕𝑡2 − ∇2 + 𝜇2 )∅𝜋 = 0. (7) this equation has the solution ∅𝜋~ ± 𝑔2𝑒 −𝜇𝑑 𝑑 [16]. the range of the yukawa potential is inversely proportional to the meson mass (𝑚𝜋 ): 𝑑𝜋 = 1 𝜇 = ℏ/(𝑚𝜋𝑐). one can proceed from this known relationship between 𝑑𝜋 and 𝑚𝜋 [2]. but, for later work on the lifetime it is useful to recall first the very basic physical assumptions used to relate the meson mass to the yukawa decay length. as discussed by wick [2], mesons act via emission and absorption processes of virtual excitations, and the time required for the excitation to travel between a pair of nucleons is of the order ∆𝑡~ 𝑑𝜋 𝑐 . the relativistic energy, ∆𝐸 ≥ 𝑚𝜋 𝑐 2, obeys the heisenberg uncertainty principle for energy [17]: ∆𝐸∆𝑡 ≥ ℏ. these expressions for energy and time lead us to the required relationship: 𝑑𝜋 ≅ ℏ/(𝑚𝜋𝑐). 10 the klein-gordon equation for yukawa potential (∅) after a fourier transform may be cast into the form [16], ∇2∅𝜋 + 𝜔2 𝑐2 (1 − 1 𝜔2 ( 𝑚𝜋𝑐 2 ℏ ) 2 ) ∅𝜋 = 0. (8) we identify this equation with equation (6). thus, we obtain after identification of eq. (6) with eq. (8) 𝜔𝑝 2 = 4𝜋𝜌𝑒2 𝑚𝑒 = 𝑐2 𝑑𝜋 2 = ( 𝑚𝜋𝑐 2 ℏ ) 2 . the meson mass follows as 𝑚𝜋 = 2𝑒ℏ 𝑐 √ 𝜋𝜌 𝑚𝑒𝑐 2 . (9) this gives 𝑚𝜋 = 267𝑚𝑒 in surprising agreement with the experimental result (264𝑚𝑒). we discuss this result further in section 3. in this scenario the charged 𝝅− and 𝝅+mesons would emerge as electron-plasmon and positron-plasmon bound states. 2.4 binding energy of nucleons casimir-lifshitz theory returning to the model of sec. 2.1, we have for the interaction of two perfectly conducting plates across an intervening plasma [14,18], the gibbs free energy 𝐺(𝑑, 𝑇) = 𝑘𝑇 𝜋 ∑ ′ ∫ 𝑑𝑞𝑞𝑙𝑛 [1 − 𝑒 −2𝑑√𝑞2+𝜅2+𝜉𝑛 2 /𝑐2 ] ∞ 0 ∞ 𝑛=0 , (10) 11 where 𝜅 = 𝜔𝑝/𝑐. for high temperatures at fixed separation, or large separation at fixed temperature, it follows [19,20] it has an expansion of the form: 𝐺(𝑑, 𝑇) = − 𝑘𝑇𝜅 4𝜋 𝑒 −2𝜅𝑑 𝑑 [1 + 1 2𝑑𝜅 ] − (𝑘𝑇)2𝑒 −2η𝑑 ℏ𝑐 𝑒−𝜌 ∗η𝑑 𝑑 + 𝑂(𝑒 −4η𝑑 ), (11) where 𝜌∗ = 𝜌𝑒 2ℏ2/(𝜋𝑚𝑒𝑘 2 𝑇 2), η = 2𝑘𝑇 ℏ𝑐 and 𝜅 is defined above. both the n=0 and n>0 terms behave similarly to the yukawa potential [16]. both provide a contribution to our model nuclear binding energy that agrees very well with the experimentally observed binding energy per nucleon. we will compare our theoretical results with the typical experimental results in sec. 3. 2.5 lifetime of plasmons and mesons our assumption is that at equilibrium the zero point fluctuation energies of the vacuum and the black body radiation energy cancel out. what is left are collective excitations, plasmons in the remaining electron -positron sea. these can be identified as pions. this allows us to estimate the lifetime of the 𝜋0 meson. the lifetime is that for the decay of a plasmon into two electron-positron pairs [21]. these can decay to produce two photons. the theory of collective electron excitations plasmons is known. the broadening (δ𝐸) of the plasmon peak and its lifetime (𝜏 ≥ 1/∆𝐸) is known analytically and measured [22], δ𝐸~ 6𝜋𝜀𝐹 5ℏ ( 𝑞𝜋 𝑞𝐹 ) 2 ( ℏ𝜔𝑝 2𝜀𝐹 ) 3 [10 ln(2) + 2 − 4.5 ℏ𝜔𝑝 2𝜀𝐹 + 𝑂 ( ℏ𝜔𝑝 2𝜀𝐹 ) 2 . . ], (12) 12 the entities involved are the fermi energy (𝜀𝐹 ∝ 𝜌 2/3), plasma frequency (𝜔𝑝 ∝ 𝜌 1/2), and fermi wavevector (𝑞𝐹 ∝ 𝜌 1/3). these depend on density and (in our case) on the distance between the nucleons. the lifetime dependence upon the electron-positron plasma density can be deduced once we have a model for the neutral pi meson (plasmon) wave vector. in order to calculate the lifetime of the plasmon we need an estimate for the 𝑞𝜋-vector. we use the relationship between q-vector and energy. the relativistic energy of the plasmon excitation (meson with mass 𝑚𝜋), 𝐸 ∼ 𝑚𝜋𝑐 2, [2], is assumed spread into kinetic energy ( ℏ2𝑞𝜋 2 2𝑚𝑒 ) for each particle of two electron-positron pairs (in general not all energy turns into the kinetic energy of these particles). this leads to an order of magnitude estimate for the wave vector of the plasmon: 𝑞𝜋 ≤ 𝑐√ 𝑚𝜋𝑚𝑒 2 ℏ⁄ . as we have shown in eq. (9) that 𝑚𝜋 ∝ 𝜌 1/2, the broadening and lifetime is apparently independent of electron-positron density (and independent of separation between nucleon pairs). a possibly better estimate subtracts off the relativistic energy for each of the particles created in the two electron-positron pairs from the relativistic energy of the plasmon. this leads to: 𝑞𝜋 ≤ 𝑐√ (𝑚𝜋−4𝑚𝑒)𝑚𝑒 2 ℏ⁄ , with only a slight density dependence for the lifetime. the estimate will be seen to lead to the same numerical value (to the first decimal place) as the “naive” (weinberg’s word [23]), qft (quantum field theory) approximation for the uncharged pion lifetime. both our result for lifetime and the “naive” one have the same order of magnitude (~0.2 × 10−16s). this can be compared with the state-ofthe-art qft result (0.80-0.85 × 10−16s) which agrees with the experimental value (0.834 × 10−16s), cf. sec. 3. 13 3. results 3.1 numerical, experimental and selected qft results for 𝝅𝟎 mesons meson mass the equivalent black box at a nucleon pair separation of 1 fermi or closer contains very nearly the maximum number of electron positron pairs. if we take d~1.5 fermi, the equivalent temperature is 𝑘𝑇~128𝑚𝑒𝑐 2. this leads via eq. (9) to a meson mass of 267𝑚𝑒 which compares remarkably favorably with the experimental results [24,25], 𝑚𝑒 ≈ 0.511 𝑀𝑒𝑉 and 𝑚𝜋 ≈ 134.97 𝑀𝑒𝑉 ≈ 264𝑚𝑒. the dependence of the estimated meson mass on nucleon separation will be shown in table 1. meson lifetime using this distance for the lifetime in the equation given by ninham [22], we obtain the 𝜋0 lifetime ≥ 0.16 × 10−16s. noteworthy, as we mentioned earlier the predicted lifetime is stable for different nucleon-nucleon separations unlike binding energy (which increases with decreasing separations). this is a curious consequence of the density dependence of the plasmon wavevector. this is applicable only at the very high temperatures we predict (corresponding to a plasmon with energy high enough to create particles). the experimental textbook result [24] is around 0.83 × 10−16s. our result is of the right order of magnitude. a “simple” qft approximation [23] leads to an estimate for the lifetime around 0.22 × 10−16s. (a theoretically plausible improvement of the “simple” qft result discussed by weinberg [23] leads to 0.52 × 10−13s which is different by a factor 1000 from the experimental result). a better theoretical approximation, assuming among other 14 things the number of colors for the quarks, leads to an estimated qft lifetime for the neutral pion of ~0.9 × 10−16s [23]. the decay of the neutral pion into two photons has its basis in the explicit breaking of the axial symmetry by quantum fluctuations of quark and gluon fields. the first four decay pathways [21] are: (1) 𝜋0 → 𝛾𝛾, (2) 𝜋0 → 𝛾 + 𝑒 ++𝑒−, (3) 𝜋0 → 𝛾 +positronium; (4) 𝜋0 → 𝑒 ++𝑒− + 𝑒 ++𝑒−. our theory, taken with the reactions 𝑒 ++𝑒− ↔ γ and 𝑒 ++𝑒 − → positronium → γ, could account for the 𝜋0 particle being able to produce these four decay pathways. precise measurements of the decay width of the 𝜋0 → 𝛾𝛾 process give an average of 7.80 ev. this gives a lifetime of 0.834 × 10−16s [26,27]. this is in good agreement with previous theoretical results and with its estimated 1.5% accuracy offers a benchmark test for the most sophisticated theoretical estimates including the prediction 0.804 × 10−16s by kampf and moussallam [28]. high accuracy calculations of the lifetime also include those discussed by larin et al. [26] and by bernstein and holstein [29]. these authors [26,29] discuss how the axial, chiral, anomaly originating from quantum fluctuations of quark and gluon field, and exploiting the number of qcd quark colors, drives the 𝜋0 meson decay with a lifetime around 0.849 × 10−16s. nuclear binding energy furthermore, the lifshitz-yukawa binding energy at this separation receives -0.9 mev from the n=0 term and -3.6 mev from the n>0 term leading to a total binding energy from electromagnetic fluctuation interaction of 4.5 mev. the binding energy increases with decreasing nucleon-nucleon separation in line with the fact that binding energies of nucleons are different in different nuclei [30-32], and also in line with the fact that local surroundings influence the local structure of the 15 nucleons [30-32]. the binding energy per nucleon varies in different atomic nuclei from 1.1 mev for deuterium to 8.8 mev for nickel-62. also, the structure of neutrons and protons within different nuclei depends on the local environment (for references see the work by feldman [31]). (note also in passing the experimental data on nucleon binding energies in ref. [33]. in that (controversial) paper the authors infer that neutron-neutron, just as proton-proton interactions are repulsive, whereas the neutron-proton interaction is attractive.) summary of numerical results we summarize our numerical results in table 1. the equivalent temperatures (note that: 𝑚𝑒 𝑐 2/𝑘 ≈ 5.9 × 109𝐾) are high enough to generate the electron-positron plasma. the effective surface area is taken to be 𝐴 = 𝜋r2 with r=proton radius~0.8 fermi. improved estimates would, for example, require an expansion of our planar estimate to consider a pair of perfectly conducting spheres in a high-density electron-positron plasma. table 1: the lifetime, meson mass and binding energy versus separation between a pair of neutrons (or protons). recall the approximations in our model (sec. 2.1), implying the nucleons to be replaced by conducting plates. separation lifetime meson mass binding energy kt 1.0 fermi 1.61 × 10−17s 491𝑚𝑒 13.6 mev 193 𝑚𝑒𝑐 2 1.5 fermi 1.62× 10−17s 267𝑚𝑒 4.5 mev 128 𝑚𝑒 𝑐 2 16 2.0 fermi 1.64× 10−17s 173𝑚𝑒 2.0 mev 97 𝑚𝑒𝑐 2 4. summary and conclusion we began this enquiry with the idea that if feynman believed there ought to be a link between electromagnetic theory and nuclear forces, there might be something in it. it seems there is. from our semi-classical theory we have been able to predict better than order of magnitude estimates for the basic properties of the neutral pion, namely its decay length, mass, and lifetime. in the picture a high-density electron-positron plasma emerges quantitatively and naturally as a key player in nuclear interactions. a defect is the modelling of nucleon interactions by planar perfectly reflecting surfaces. there are two free length parameters, area and distance between the model ”nucleons”. but they are close to actual distance scales. it would be more convincing if the theory also predicted the various decay modes for 𝜋0, in terms of 𝑒 +𝑒− pairs and photons. further, in such a theory the charged mesons, 𝝅−/𝝅+, would emerge as an electron/positron bound to a plasmon. one thing is clear. there is certainly enough energy available to account for nucleon interactions. and if the claim that our theory is not equivalent to the canonical theory, where has that energy gone? it is possible to push matters further by including magnetic suceptibilities in the formalism for interactions using a fully relativistic electron-positron plasma. there is a useful analytic framework available in the work of daicic, kowalenko, frankel and co-workers [34-36]. in 17 connection with this we observe that larin et al. [26] performed some of the most precise measurements of the lifetime of the 𝜋0 meson. their weighted average final result for the 𝜋0 → 𝛾𝛾 decay width defines the new lifetime to be 8.337 × 10−17s. such surprisingly short lifetimes can in the qcd framework be obtained once axial anomaly is accounted for. the axial anomaly, which historically provided strong evidence in favor of the color-charge concept in qcd, seems to present us with state of the art knowledge about some of most fundamental aspects of nature—for example, by constraining the fundamental physics beyond the standard model and presenting opportunity to, e.g., measure the light quark mass ratio [26,27]. however, using a much simpler semi-classical theory we have found results that turn out to have exactly the right order of magnitude. this suggests an as yet unexplored link between our theory (expanded to magnetic anisotropic media) and one of the most profound theories in physical science. there are wider implications: if the equivalence we seek can be firmed up, the consequences would be significant. the full qft of interactions of dlp involves a nonlinear coupling constant integral equation for the polarisation operator. that awkward difficulty was resolved by replacing that by a linear integral, and the whole formalism collapsed to a semi classical theory. the consequences of these mathematical simplifications have been a serious obstacle to progress in the biological and engineering sciences that depend on molecular forces in the disciplines of physical, colloid and surface chemistry [37-40]. the theories inconsistently treat electrostatic forces in a nonlinear theory and quantum fluctuation (dispersion) forces in a linear theory [37,41]. so central specific ion (hofmeister) effects, and hydration effects are lost. the problem is being partially rectified [40]. but a proper fundamental theory requires the complete non linear theory to go further. 18 the same would be true for the theory of nuclear interactions. it should also be a non linear theory and not linear as it is now. a partial version of this mss (bwn and colin pask, unpublished) was written in 1969. a brief version was published by two of us (bwn and mb) in 2003, but it omitted the meson lifetime. this version is more detailed and includes this important result. in the following 55 years what is new has been the application of lifshitz theory to the foundations of physical chemistry. the literature is extensive. classical theories ignore all important hofmeister (specific ion effects). the problem can be traced to the same linearization approximation and rectified. the equivalence established between lifshitz theory and pi zero mesons implies that particle physics suffers the same difficulties. references [1] freeman dyson, communicated to bwn. see also: f. j. dyson, ”feynman’s proof of the maxwell’s equations”, am. j. phys. 58, 209 (1990). a related observation was made by r. p. feynman, phys. rev. 80, 440 (1950): ‘‘high energy potentials could excite states corresponding to other eigenvalues, possibly thereby corresponding to other masses”. [2] g. c. wick, “range of nuclear forces in yukawa's theory”, nature 142, 293-294 (1937). [3] h. b. g. casimir, “on the attraction between two perfectly conducting plates”, proc. k. ned. akad. wet. 51, 793 (1948). [4] b. w. ninham and v. a. parsegian, “van der waals forces: special characteristics in lipid-water systems and a general method of calculation based on the lifshitz theory”, biophys. j. 10, 646 (1970). [5] v. a. parsegian and b. w. ninham , “temperature-dependent van der waals forces.”, biophys. j. 10, 664 (1970). 19 [6] d. j. mitchell, b. w. ninham and p. richmond, “on black body radiation and the attractive force between two metal plates”, am. j. phys. 40, 674 (1972). [7] i. e. dzyaloshinskii, e. m. lifshitz, and p. p. pitaevskii, ”the general theory of van der waals forces”, advan. phys. 10, 165 (1961). 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[14] b. w. ninham, and j. daicic, “lifshitz theory of casimir forces at finite temperature”, phys. rev. a 57, 1870 (1998). [15] l. d. landau, e. m. lifshitz, statistical physics, part 1, 3rd edition (butterworth-heinemann, oxford, 1999). [16] h. yukawa, “on the interaction of elementary particles. i”, proc. phys. math. soc. japan 17, 48 (1935). 20 [17] l. d. landau, e. m. lifshitz, quantum mechanics (non-relativistic theory), 3rd edition (butterworth-heinemann, oxford, 1997). [18] j. mahanty and b. w. ninham, dispersion forces, (academic press, london, 1976). [19] b. w. ninham and m. boström, “screened casimir force at finite temperatures: a possible role for nuclear interactions”, phys. rev. a 67, 030701 (2003). [20] b. w. ninham, m. boström, c. persson, i. brevik, s. y. buhmann, and bo e. sernelius, ”casimir forces in a plasma: possible connections to yukawa potentials”, eur. phys. j. d 68, 328 (2014). [21] p. a. zyla et al. (particle data group), ”review of particle physics”, prog. theor. exp. phys. 2020, 083c01 (2020); page 1212. [22] b. w. ninham, c. j. powell, and n. swanson, “plasmon damping in metals”, phys. rev. 145, 209 (1966). [23] s. weinberg, the quantum theory of fields, volume ii modern applications (cambridge university press, cambridge, 2016). [24] w. e. burcham and m. jobes, nuclear and particle physics, (longman scientific & technical, essex, 1995). [25] j. d. jackson, the physics of elementary particles (princeton legacy library, london, 1958). [26] i. larin et al., ”precision measurement of the neutral pion lifetime”, science 368, 505 (2020). [27] h. b. meyer, ”𝜋0 decay precision-tests the chiral anomaly”, science 368, 469 (2020). [28] k. kampf and b. moussallam, ” chiral expansions of the 𝜋0 lifetime”, phys. rev. d 79, 076005 (2009). [29] a. m. bernstein and b. r. holstein, ”neutral pion lifetime measurements and the qcd chiral anomaly”, rev. mod. phys. 85, 49 (2013). 21 [30] j. j. aubert, et al., ”the ratio of the nucleon structure functions f2n for iron and deuterium”, phys. lett. b 123, 275–278 (1983). [31] g. feldman, “origin of neutron and proton changes in nuclei”, nature 566, 332 (2019). [232] the clas collaboration, ”modified structure of protons and neutrons in correlated pairs” nature 566, 354 (2019). [33] o. mauel, c. bolon, a. katragada, and m. insall, ”attraction and repulsion of nucleons: sources of stellar energy”, j. fusion energy 19, 93 (2000). [34] v. kowalenko, n. e. frankel, and k. c. hines, ”response theory of particle-anti-particle plasmas”, phys. rep. 126, 109 (1985). [35] j. daicic, n. e. frankel, and v. kowalenko, ”magnetized pair bose gas: relativistic superconductor”, phys. rev. lett. 71, 1779 (1993). [36] j. daicic, n. e. frankel, r. m. gailis, and v. kowalenko, ”statistical mechanics of the magnetized pair quantum gases”, phys. rep. 237, 128 (1993). [37] b. w. ninham and v. v. yaminsky, “ion binding and ion specificity: the hofmeister effect onsager and lifschitz theories”, langmuir 13, 2097 (1997). [38] b. d. hughes and b. w. ninham, ”a correspondence theory”, physica a 443, 495 (2016). [this publication promotes modern analysis as the fundamental language of quantum physics. a corrected version of this work was published in substanta 2, 51 (2018)]. [39] d. parsons, m. boström, p. lo nostro, b. w. ninham, “hofmeister effects: interplay of hydration, non-electrostatic potentials, and ion size”, phys. chem. chem. phys. 13, 12352 (2011). [40] b. w. ninham and p. lo nostro, molecular forces and self assembly in colloid, in nano sciences and biology, (cambridge university press, cambridge, 2010). 22 [41] m. boström, d. r. m. williams, and b. w. ninham, “specific ion effects: why dlvo theory fails for biology and colloid systems”, phys. rev. lett. 87, 168103 1-4 (2001). equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the ,𝝅-𝟎. meson, its mass and lifetime 2.1 model assumptions and the casmir energy 2.2 temperature dependence of electromagnetic forces substantia. an international journal of the history of chemistry 4(2) suppl.: 109-117, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-821 citation: m. taseidifar, j. antony, r.m. pashley (2020) prevention of cavitation in propellers. substantia 4(2) suppl.: 109-117. doi: 10.36253/substantia-821 copyright: © 2020 m. taseidifar, j. antony, r.m. pashley. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. prevention of cavitation in propellers mojtaba taseidifar1, john antony2, richard m. pashley1,* 1 school of science, unsw canberra, northcott drive, canberra, australia 2 dynamikx pty ltd, 169 hampton road, south fremantle, wa, australia *corresponding author: r.pashley@adfa.edu.au abstract. it is well known that cavitation phenomena affect the efficiency of propellers. it is a major worldwide economic problem for the transport industry. the speed of fast, ocean going vessels is limited by cavitation effects on hydrofoils and propulsion systems. the main approaches by industry to mitigate the detrimental effects of cavitation on propellers is restricted to varying operating conditions, geometric design and employing wear resistant materials. we here develop a simple solution to the problem. it has been known for over a century that dissolved gases reduce the tensile strength of liquids by orders of magnitude. degassing a liquid dramatically reduces its ability to cavitate. propeller cavitation in ships and submarines is typically controlled by reducing rotation rate and/or blade pitch. we here demonstrate the astonishing fact that cavitation can be completely prevented by releasing degassed water adjacent to the low pressure side of a rotating propeller, without varying blade speed or pitch. practical implementation is simple and cheap. keywords: cavitation, degassing, hollow fibre membrane, propeller. 1. introduction at the end of the 19th century it was realised that ships were not attaining their projected design speed. this was eventually found to be due to cavitation.1 the effects of the collapse of a spherical cavity within a fluid were first considered by besant in 1859.2 cavitation in fluids has been studied for over a century since this pioneering work and that of reynolds in 1886 and lord rayleigh in 1917.3 there are two main types: inertial cavitation, created by differences between boundary and bulk fluid flow in pumps, valves and propellers; and non-inertial cavitation, created by oscillatory processes such as simple shaking and sonication.1 cavitation also occurs in fine cavities between solid surfaces.4 in many diverse processes, cavitation not only reduces the efficiency of fluid systems but the collapse of the created bubbles near surfaces creates shock waves. shock waves create microjets which impinge upon a surface and create wear. the temperatures produced by the rapid collapse of a bubble can reach 20,000 degrees k, and can cause transient light emission or sonoluminescence, and initiate undesirable reactions in fluid components. the cavitation index c (σ or sometimes k) is used as a measure of cavitation potential and is defined as:5 110 mojtaba taseidifar, john antony, richard m. pashley (1) where pr–pv is the pressure difference due to dynamic effects of the fluid flow; pr is the local (reduced reference pressure) and pv the vapour pressure of the fluid (at that temperature). ρ is the density of the fluid and v the fluid velocity. in effect, the cavitation index is the ratio of the work done by the pressure to the work done by the fluid kinetic energy. the critical value of the index ci is when cavitation inception occurs, and c < ci corresponds to conditions of advanced cavitation. the ability of a particular fluid to cavitate depends on the tensile strength of the fluid under the operating conditions. in general, c >> 1 makes cavitation increasingly unlikely.6 in fluid cavitation, it is generally assumed that local suction pressures just below the vapour pressure of a fluid, at a given temperature, will nucleate bubbles which then implode once local hydrostatic pressure returns. in practice, there is a significant additional barrier to the formation of cavities in the absence of suitable nucleation sites, and it is actually very difficult to cavitate pure liquids in clean, smooth vessels. nano-sized cavities are usually the smallest structures which can be considered as a separate phase, and their growth or collapse controls the extent of cavitation.4 the presence of dissolved atmospheric gases facilitates fluid cavitation. for example, water can dissolve close to 20 ml of atmospheric gases per litre and hydrocarbons typically absorb ten times more. the removal of these dissolved gases inhibits fluid cavitation. in 1982, israelachv i li and pashley 7 made t he rema rk able d iscover y t hat hyd rophobic su r faces immersed in water were attracted to each other with a long-range (~10 nm) force much stronger than expected for van der waals forces. they called this the ‘longrange hydrophobic interaction’. since that discovery, there have been many reports extending the range of the force, depending on surfaces and conditions, in some cases to a range of 300 nm. these observations created a problem for theoretical interpretation simply because the local effect of a hydrophobic, nonhydrogen bonding surface on water should only extend a few water molecules, at most. in 1985, pashley et al.4 noticed that a bridging cavity was formed when two solid hydrophobic surfaces were pulled apart in water, and later christenson et al.8 reported cavitation as two hydrophobic surfaces approached within a few nm, but before making contact. these observations led to the suggestion that the long-range hydrophobic interaction may be caused by the formation of bridging cavities between hydrophobic surfaces, giving a more reasonable explanation for the extraordinarily long range of the force. craig et al.9 have given a thorough review of bulk and surface cavitation and its link to nanobubbles. two recent studies10, 11 have also considered the formation and applications of bulk nanobubbles. if cavitation held hydrophobic surfaces together, then it follows that the inhibition of cavitation by removing dissolved atmospheric gases may indeed allow oil and water to mix. this idea was tested by pashley (in 2003)12 by studying the effects of degassing on the dispersion of oil droplets in water. hydrocarbon oils such as decane immediately phase separated after shaking with water but, upon degassing, a fine stable dispersion was easily produced. this work demonstrated that cavitation also plays a central role in the dispersion of oil in water. we note in passing that with colloidal systems involving electrolytes (dlvo) forces and hofmeister effects change dramatically with removal of dissolved gas, a fundamental matter attracting much interest. the presence of dissolved, non-polar gas molecules in a surrounding fluid, in equilibrium with the atmosphere, produces nucleation sites throughout this fluid. both aqueous and non-aqueous fluids show similar effects, and, in addition, non-polar fluids have an increased capacity to dissolve non-polar gases relative to water. it has been demonstrated13, and is elucidated upon in this work, that degassing a separate quantity of the fluid, and releasing it such that it flows directly onto a moving surface can completely prevent cavitation by providing a boundary layer of degassed fluid on the surface. 2. materials and methods 2.1. materials hollow fibre membranes were purchased from membrana, charlotte, usa (model 2×6 radial flow superphobic). a vacuum pump, fossa fo 0015 a (busch sydney, australia) was used for de-gassing. a diaphragm water pump (model: flojet-d3732-e5011) was purchased from creativepumps australia. a mettler-toledo m700 process analysis system fitted with a type o2 4700 ppb module to detect dissolved oxygen levels in liquids in ppb, and fitted with a corresponding inpro 6900 dissolved oxygen electrode was obtained from mettlertoledo ltd., melbourne, australia. tap water with and without added salt (nacl with 0.17 m) was used in all the experiments. 111prevention of cavitation in propellers 2.2. methods 2.2.1. membrane degassing for water and aqueous solutions hollow fibre hydrophobic membrane systems offer the most efficient commercial process for large scale degassing due to providing high surface area of contact per unit volume of fluid.14 a photograph of the experimental setup used in this study is given in figure 1. a strong vacuum is applied to the outside of a hollow fibre hydrophobic membrane or membrane array where the dissolved gases emerge, while the aqueous solution flows around a core of hollow fibres. the hollow fibre membranes are strongly hydrophobic (teflon or polypropylene), and have small pores designed to prevent liquid water passing through them due to the high laplace pressure of small diameter water/air interfaces. only water vapour can exist in the pores and the high surface area membrane efficiently transfers water vapour and atmospheric gases out of aqueous solutions. this technique has been used to produce a continuous flow of water more than 99.5% degassed. in these experiments, tap water was used to determine the effect of degassing on cavitation, and gases were removed from the tap water by pumping it through the membrane using a small diaphragm water pump while applying a vacuum to the inside of the hollow fibres in the membrane. the vacuum pump, with ultimate pressure ≤ 2.5×10-2 mbar was protected from exposure to water vapour by two 5 l pyrex glass tanks connected in series filled with pre-dried granular silica gel. the dissolved oxygen content, and thereby the level of degassing, was measured using an inpro 6900 oxygen electrode with a detection limit of 1ppb in these studies. cavitation was monitored visually using a pentax k-5 ii s camera aimed at an observation cell, shown in figure 1. the observation cell (5) was a perspex housing (l: 300 mm, w: 65 mm and h: 65 mm) for a three-blade propeller (5 cm diameter) inside and two metal tubes sealed to the box – one to provide normal gassed water (tap water or salt water) and another one to provide degassed water. 3. results and discussion 3.1. theoretical prediction of the link between degassing and cavitation pressure in fluid cavitation, it is generally assumed that local suction pressures just below the vapour pressure of the fluid, at a given temperature, will nucleate bubbles which then implode once local hydrostatic pressure returns. in practice, there is a significant additional barrier to the formation of cavities in the absence of suitable nucleation sites, and it is actually very difficult to cavitate pure liquids in clean, smooth vessels. nano-sized cavities are usually the smallest structures which can be considered as a separate phase, and their growth or collapse controls the extent of cavitation.12 both homogeneous cavitation and heterogeneous nucleation cavitation in water are considered here, caused by the presence of inert dissolved atmospheric gas molecules throughout the bulk liquid phase. the barrier to ‘ideal’ homogeneous cavitation can be estimated from a simple analysis of the formation of a nano-sized spherical cavity. the total energy et of a cavity of radius r is given by the sum of the negative work done by the suction pressure -∆p on the cavity volume and the surface tension work done on creating the surface of the cavity. thus, the total cavity energy is given by: et= πr3(∆p)+4πr2γ (2) a diagram of the behaviour expected for water is shown in figure 2. assuming that nm-sized cavities must form within pure water, the barrier to their formation is very high, of the order of 80 kt, which makes their formation difficult. if we make the assumption that 1 nm is the critical radius of cavity formation, i.e. when det/dr = 0, we can estimate the critical suction pressure from the laplace equation: figure 1. photograph of the system used to study the effect of degassing on cavitation. (1) m700 process analysis system (to monitor do levels); (2) hollow fibre membrane; (3) water pump; (4) silica gel tanks; (5) observation cell; (6) vacuum pump; (7) variable motor; (8) do electrode; (9) degassed water reservoir. 112 mojtaba taseidifar, john antony, richard m. pashley ∆p=– (3) th is gives a critical suction pressure of about -1,440 atm for pure water or -493 atm for a typical hydrocarbon liquid. th e largest suction pressure observed experimentally for degassed water was -1400 atm, which is close to theoretical predictions.16 in most practical situations, contaminants and ‘real’, rough surfaces facilitate the heterogeneous nucleation of cavities in water at much lower suction pressures than this. th e presence of dissolved gases and hydrophobic groups also substantially reduce the cavitation pressure. experimental cavitation pressures are typically about -1 atm for distilled water, saturated with air, since this is eff ectively the vapour pressure of water at room temperature. however, a suction pressure of -200 atm is required when the water is 99.98% de gassed according to17; see figure 3. from these experimental results, it is clear that degassing water strongly inhibits cavitation, especially when degassed to greater than 99%. th e disruptive presence of dissolved, non-polar gas molecules in the liquid water phase produces nucleation sites throughout the liquid.4 from solid state physics it is well known from studies of lattice dynamics in the harmonic approximation isotopes or impurities attract each other, a collective eff ective van der waals interaction and associate into aggregates. th e same happens in liquids. it is these that act as nucleation sites that connect adjoining nano sites. an equivalent result occurs with non-aqueous fl uids, which also have an increased capacity to dissolve non polar gases relative to water. a theoretical model has been developed to estimate the cavitation pressure pc required to cause (heterogeneous) cavitation in water at a wide range of dissolved gas levels. th e basic principle used is that the pressure required can be estimated from the change in activation energy δμ required to transfer a dissolved gas molecule (e.g. n2) from the aqueous phase to the gas phase. since μ(g,w) will change with concentration of the dissolved gas in water xg, i.e.: μ(g,w)=μ0(g,w)+ktlnxg (4) and since the gas-phase chemical potential will stay constant, the activation energy for the transfer from solution to gas phase will vary with concentration in the aqueous solution as: ∆μ=ktln (5) where xgs is the mole fraction of gas in water under standard atmospheric conditions (1 atm). th e cavitation pressure can then be estimated from the activation-energy equation: pc=p0exp (6) where p0 is the standard, i.e. saturated gas cavitation value, of 1 atm. hence, it follows that: pc=p0 (7) note that for air-equilibrated water, xgs is about 1.53 × 10-5. also, note that this result reduces simply to: figure 2. theoretical calculation of the energy (in kt units) required to form a spherical cavity of radius r in pure water under ideal, de-gassed conditions, in the absence of nucleation sites, with an applied suction pressure of -1400 atm. figure 3. experimental data showing the eff ect of de-gassed levels on the suction pressures required to produce cavitation in water and benzene. reprinted with permission from ref 16. copyright 1954, acoustic society of america. 113prevention of cavitation in propellers pc(atm)= (8) this cavitation-pressure model will work for any liquid, since it is based entirely on gas solubility relative to a standard state. a graphical representation of this result is given in figure 4 and figure 5. for the case of water, the model predicts that when the dissolved gas level is reduced to about 0.07% (or about 0.6 μm), the gas cavitation pressure equals that of pure water (note that at 20 ºc, water in equilibrium with the atmosphere has 0.85 mm of dissolved gases: n2, o2, co2 and ar). the pure water cavitation pressure is at its maximum and can be estimated using the laplace equation with an estimated, critical cavity radius of 1 nm (eq. 3). this gives a calculated (homogeneous) cavitation pressure of -1440 atm. this value agrees with the reported experimental value for pure (i.e. completely degassed) water of -1400 atm. these high suction pressures are also consistent with the basic (kinetic) model of condensed liquids, in which the repulsive ideal-gas pressure (p = nrt/v) is more than balanced by the cohesive molecular forces. for water at 20 °c, the ‘ideal’ repulsive molecular pressure p is 1353 atm. cohesive pressures in liquid water must be higher than this. thus, there is strong evidence for this high value for pure, completely degassed water. this analysis strongly suggests that the galloway data (1954)17, shown in figure 3, is correct at relatively low degassing levels (less than 99%) but that the cavitation pressures expected, for pure liquids, at higher levels of degassing was most likely not achieved in these experiments, probably due to the ubiquitous presence of contamination particles, which offer nucleation sites for cavity formation. thus, the reported maximum of about -200 atm is much less than the theoretical prediction. 3.2. experimental study of the prevention of propeller cavitation in degassed water the cavitation created by a three-blade propeller with a maximum speed of 2960 rpm can be observed inside a water-filled perspex observation cell (figure 6 and figure 7). tap water was pumped at 600 ml/min through the hollow fibre membrane whilst vacuum was applied to its outer housing. the m700 oxygen analysis system displayed the measured oxygen content in the water tank, which continuously decreased. when seawater was subjected to compressive pressures in the 10–55 atm range, we found in earlier studies18 that on release of this pressure through a needle valve, cavitation of dissolved gases occurred. it was found that degassing the seawater to above 99% completely prevented this cavitation and this was used20 to improve the desalinated water product flow rate through a high pressure reverse osmosis system. in these studies, it was found that by increasing the degassed level of the water, the speed of the propeller could be increased before cavitation was observed, as illustrated in figure 8. the results of these rotation ate/degassing measurements are summarised in table 1, which clearly shows that higher degassing levels produced higher cavitation pressures in the system (this data was obtained from the theoretical values for water cavitation in figure 4). the experiments summarised in table 1 were reproduced using a 0.5 m nacl solution to simulate seawater. as an example, 70% degassing was found to be sufficient to prevent cavitation even at the maximum rotation rate of 2960 rpm. this degree of degassing corresponds to a cavitation pressure of about 3 atm, according to eq. (8). figure 4. calculated cavitation pressures for water obtained using equation (8). figure 5. effect of de-gassing on cavitation in water. 1 10 100 1000 10000 0,01 0,1 1 10 100 c av it at io n p re ss u re / a tm % air concentration theoretical water cavitation values pure water cavitation pressure -250 -200 -150 -100 -50 0 0 20 40 60 80 100 120 ca vi ta ti on p re ss ur e in a tm de-gassing level in % theoretical water cavitation values 114 mojtaba taseidifar, john antony, richard m. pashley 3.3. prevention of cavitation using a local degassed aqueous environment in these experiments, degassed water was introduced locally, close to the low pressure side of rotating propeller blades immersed in gas-equilibrated water. inside the perspex observation cell, gassed tap water flowed at a rate of 8l/min through a bent metallic pipe (10mm diameter), and 80% degassed water was released through a vertical metallic pipe with suitable holes (4.4 mm diameter and with six holes on the side and one at the end of the pipe) at a flow rate of about 1/10th the background water flow-rate, as shown in figure 9. with only gassed tap water flowing within the cell, visible cavitation occurred (figure 9), but when a local flow of degassed water was released adjacent to the propeller blades, all cavitation ceased (figure 10). these experiments were carried out at high rotation rates of 2300 rpm using a three-blade propeller. the cessation of the sound accompanying cavitation on starting the degassed water flow was also obvious and immediate. acoustic measurements also show that the noise level was reduced from 75 db to 65 db after releasing the degassed water behind the propeller, despite having another, additional, noise involved which was from the water pump releasing the degassed water. the observed drop in db level, even with the additional pump noise, corresponds to a sound intensity decrease on releasing the degassed fluid, of 10x. similar results were also obtained using a 0.5 m nacl aqueous solution to simulate seawater. figure 6. photograph of the propeller used to study cavitation at the laboratory scale. figure 7. cavitation occurring in air-equilibrated water at atmospheric pressure at a propeller rotation rate of 2960 rpm. table 1. experimental results of the de-gassing effects on cavitation observed for a rotating propeller completely immersed in de-gassed water. time (min) de-gassing (%) cavitation pressure (atm) minimum rpm to start cavitation 0 0 1 ‒ 5 19.7 1.3 148 10 27.8 1.5 592 15 36.9 1.6 1628 20 45.4 1.8 2072 30 56.0 2.8 2500 60 76.7 4 not even with 2960 90 84.4 7 not even with 2960 120 87.0 8 not even with 2960 figure 8. complete cavitation prevention after gassed water was replaced with 70% de-gassed tap water (at 2960 rpm propeller). 115prevention of cavitation in propellers 3.4. effects of degassed boundary layer films on a rotating propeller blade when the flow of degassed water was terminated, it was observed that the cavitation effects remained absent for several seconds or 100-200 rotations of the propeller. this is consistent with the observation (shown in figure 10) that release of degassed water onto the upper rotating propeller blade prevented cavitation effects through a full cycle of the blade. these observations support the view that coating a rotating propeller with a film of degassed fluid is sufficient to give protection against cavitation. the lowest pressure regions on the low pressure side of a rotating propeller blade are at the edge and the tip of the blade. for zero-slip conditions, water flow across a plate of length x (i.e. the propeller blade), will slow down to zero at the surface, as shown in figure 11. the experimental boundary layer equation can be used to calculate the thickness δ of the water layer next to the plate at which the incident flow velocity reaches 99% of the bulk water flow velocity:19,20 δ=5x/√(re) (9) where re is the reynolds number. this situation is shown in figure 11, illustrating the ‘zero-slip’ condition, in which the fluid velocity slows to zero on the surface. the reynolds number of the fluid depends on the distance x the fluid has moved over the surface and these two parameters (re, x) determine the thickness δ of the boundary layer.20 the reynolds number in this case is given by re=(ρv∞x)/μ (10) where ρ is the density of water, v∞ the bulk fluid velocity (i.e. the incident fluid velocity beyond the boundary layer), μ is the dynamic viscosity of water and x is the position on the surface. typically, re corresponding to laminar flow will be in the range 1000 to 5 × 105. for example, if re = 50,000, the boundary-layer water thickness d will be about 1.1 cm for an x value of 0.5 m. much closer to the surface, say within 1% of the boundary layer thickness, the water moves only slowly relative to the solid surface: in a water layer of 110 µm thickness, the water flow velocity is about 10 cm/s. cavitation occurs when dissolved gas is present in a fluid such as water. for the diffusion of gas in one direction (x), the appropriate equation is fick’s second law in the form:21 (11) figure 9. cavitation occurring in flowing tap water at atmospheric pressure, i.e. in fully gassed water (at 2300 rpm). figure 10. cavitation completely prevented in gassed tap water after flowing 80% de-gassed water directly onto the rotating propeller blades (at 2300 rpm). figure 11. schematic diagram of stationary or boundary-layer formation as a fluid flows over a flat solid surface (adapted from david weybourne (https://en.wikipedia.org/wiki/boundary_layer_thick). 116 mojtaba taseidifar, john antony, richard m. pashley where c is the solute concentration and d the diffusion coefficient. when completely degassed water is exposed to air at atmospheric pressure, a very thin layer will form rapidly at the surface which will be at the atmospheric dissolved gas concentration (of 0.85 mm). this layer will maintain its saturated concentration from then onwards (in equilibrium with the atmosphere), and the dissolved gas will subsequently diffuse further into the water beyond this layer. thus, fick’s law must be solved for the boundary conditions c = c0, when x = 0 for any value of t and cx = 0 for x > 0 when t = 0. also, cx = c0 for any value of x as t becomes very large. the solution to fick’s law under these conditions is:21 (12) where the error function can be calculated using either tables or, as for the present calculation, using the series:21 (13) for oxygen and nitrogen gases in water the value of the diffusion coefficient d at 20 oc is about 2 × 10-5 cm2/s and the saturated gas concentration, c0 is about 0.85 mm. using these values, the calculated results obtained show that for quiescent water that is in the almost stationary part of the boundary layer, closest to the solid surface, significant re-gassing of a degassed water film of about 100 µm thickness would take several seconds. thus, a transient coating of a boundary layer of degassed water on a rapidly rotating blade can be used to prevent cavitation effects for many subsequent rotations. this means that the amount of degassed water required to prevent or minimise cavitation can be substantially reduced, and the effect of cavitation minimisation can persist for a significant period of time e.g. a few or more seconds. the effect of reducing the occurrence of cavitation will persist until the stationary film drains as the blade rotates or until diffusion from the bulk fluid re-gasses the degassed film. the effects of having a transient film of degassed fluid could be further optimised by having a periodic, controlled release of a positive, relatively high pressure flow of degassed fluid, released close to the rotating blades and timed to strike the leading edge on the negative pressure side. once the de-gassed fluid strikes the blade, it would coat the face with degassed fluid (e.g. water) and form a boundary layer. the zeroslip boundary condition will ensure the retention of a degassed film on the rotating surface. put another way, the degassed fluid could be periodically directed onto the surface using a pulsed flow to form the boundary layer. use of a pulsed flow of degassed fluid may mean degassed fluid only needs to be released in a periodic fashion, such as every 1 in 100 rotations of the blade, or for only 1% of the time. the leading edge of the rotating blade divides the incident flow into a high pressure stream on the nearly flat ‘lower’ face and a low pressure stream on the upper side of the blade. as the blade rotates, the film of degassed water will drain from the leading edge to the trailing edge of the blade, and suppress cavitation across the low pressure face. at the same time, dissolved gases within the flowing fluid (e.g. water) begin to diffuse into the degassed boundary layer. however, gas diffusion under effectively quiescent conditions next to the solid surface is relatively slow; for a 0.1 mm film, this re-gassing will take several seconds. in addition to these effects, the centrifugal forces generated by the rotating blade will force the degassed boundary layer to flow towards the tip of the rotating blade, which will also help to prevent cavitation at this point, where it is often observed. 4. conclusions this study has demonstrated a new method for preventing cavitation at a surface that moves relative to a fluid. the method comprises directing a second fluid that is at least partially degassed towards the surface, where it will form a boundary layer. the boundary layer at least partially increases the negative pressure required to initiate cavitation at the surface, reducing the occurrence of cavitation during the relative movement. collapse of the cavities formed during cavitation creates shockwaves, and hence microjets, which impinge upon surfaces, creating noise and causing wear, for example, on propeller blades. in these experiments, noise generation was completely suppressed, which suggests that wear could also be substantially reduced. therefore, this process may help to reduce cavitation noise and wear and improve the efficiency of propeller-driven boats, ships and submarines. 5. acknowledgements the authors would like to acknowledge mechanical workshop staff at the school of science at unsw canberra. 117prevention of cavitation in propellers references 1. h. kato, cavitation, in advances in marine hydrodynamics, computational mechanics publications, 1996. 2. c.e. brennen, cavitation and bubble dynamics, oxford university press, 1995. 3. l. rayleigh, viii. on the pressure developed in a liquid during the collapse of a spherical cavity, the london, edinburgh, and dublin philosophical magazine and journal of science, 1917, 34 (200), 94-98. 4. r. m. pashley, p. m. mcguiggan, b. w. ninham, d. f. evans, attractive forces between uncharged hydrophobic surfaces: direct measurements in aqueous solution, sci., 1985, 229(4718), 1088-1089. 5. r. w. johnson, handbook 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19. j.h. arakeri, p.n. shankar, ludwig prandtl and boundary layers in fluid flow. resonance, 2000, 5(12) 48-63. 20. h. schlichting, k. gersten, fundamentals of boundary–layer theory, in boundary-layer theory, springer berlin heidelberg: berlin, heidelberg, 2017, 29-49. 21. r. m. pashley, m. rzechowicz, l. r. pashley, m. j. francis, de-gassed water is a better cleaning agent, j. phys. chem. b, 2005, 109(3) 1231-1238. substantia. an international journal of the history of chemistry 3(1): 119-129, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-173 citation: d. pushcharovsky (2019) dmitry i. mendeleev and his time. substantia 3(1): 119-129. doi: 10.13128/ substantia-173 copyright: © 2019 d. pushcharovsky. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article dmitry i. mendeleev and his time dmitry pushcharovsky lomonosov moscow state university, department of geology, vorob’evy gori, 1, 119899 moscow, russia e-mail: dmitp@geol.msu.ru abstract. the history of the creation of periodic table and of the mendeleev’s discovery of periodic law is considered. the different approaches used by mendeleev’s colleagues are discussed. the contribution of the periodic system to the extension of the scientific ideas in geology and best of all in geochemistry and mineralogy is illustrated by the discovery of new chemical elements and by the isomorphic replacements in minerals. the details of uneasy history of mendeleev’s nomination to the st. petersburg academy and for the nobel prize are given. keywords. periodic table, isomorphism, nobel prize, electronic structure of atom. periodic table of chemical elements on the front of the main building of the central board of weights and measures in st. petersburg; height – 9 m, area – 69 m2; red colour elements, known in the mendeleev lifetime, blue colour – elements discovered after 1907 (public domain) 120 dmitry pushcharovsky introduction the united nations declared 2019 as the international year of the periodic table. this decision is related to the 150th anniversary since its first version elaborated by the prominent russian chemist dmitry ivanovich mendeleev (1834-1907, fig. 1) was published on the 17th of february 1869. on this date he sent his table to the publisher and simultaneously distributed it among his colleagues in russia and abroad. in connection with un resolution it is necessary to address the question whether it is really urgent to discuss the events related to mendeleev’s discovery. researchers all over the world consider that as before it contributes the further development of many scientific branches. on the basis of the periodic table they search the answers to the many mysteries which nature still hides. besides that the history of its creation clearly justifies the absolutely non-linear process which usually accompanies the scientific progress [1]. these aspects are the focus of the present paper which is devoted to some applications of the periodic table, to its author and to the time when he made his historical discovery. biography mendeleev was born on the 27th of january (8th of february) 1834 in tobolsk – the first siberian town established in 1587, located between ural and western siberia (fig. 2). he was the last among 17 children in the family of his father ivan mendeleev, the director of local gymnasium, and his mother maria kornil’eva, a daughter of the “middle class” landowner. in the gymnasium dmitry was not a brilliant student and had very modest marks in latin and scripture, however showing an evident interest in mathematics and physics. he was 10 years old when his father passed away. his mother inherited a small glass factory and she managed it until dmitry finished gymnasium in 1849. the same year the factory was burned down and the family moved first to moscow and then to st. petersburg. mendeleev was unable to continue his education immediately. finally one year later, in 1850, he was admitted to the faculty of mathematics and physics of the main teacher’s training institute in st. petersburg. here he also had some problems with his studies. when he was a first year student he failed all the exams except for mathematics. however the turning point occurred at the end in 1855, when he graduated in the institute with the excellent certificate and with the golden medal. as a result he obtained the position of senior teacher in the crimean town simferopol. it was the critical period of the crimean war and it was the reason why mendeleev moved to odessa where he continued to teach in the richelieu gymnasium. in 1856 mendeleev returned to st. petersburg where he defended his thesis for the master degree in chemistry. at that time he began to deliver lectures in organic chemistry. in 1864 he was elected professor of chemistry in the petersburg technological university and one year later, in 1865, he defended his thesis for the doctor’s degree. two years later he became the chair of inorganic chemistry in st. petersburg university. private life in the spring of 1862 in st. petersburg mendeleev married feozva leshcheva, who was 6 years older. she was a stepdaughter of the russian poet piotr ershov, figure 1. d.i mendeleev (photo from public domain). 121dmitry i. mendeleev and his time who was mendeleev’s teacher of russian literature in the tobolsk gymnasium (fig. 3a). however the relations within the family didn’t get on and in 1881 the spouses divorced. mendeleev’s second wife, anna i. popova, was 26 years younger than him (fig. 3b). during 1876-1880 she studied at the academy of art in st. petersburg. omitting many details of their love story, i can only mention that in december 1880 her father sent anna to italy to put distance between her and mendeleev. she stayed in rome for 4 months. at that time her main supervisor was alessandro rizzoni, a russian painter of portraits and genre scenes. she also attended the classes in the academy gigi (l’accademia gigi – l’accademia libera del nudo). on the 14th of march 1881 mendeleev arrived to rome to meet anna and on the 5th of may they came back to st. petersburg. the same year the orthodox church accepted mendeleev’s divorce. however he was condemned to penance for the following six years and during that period he could not be married. however in april 1882 in spite of this verdict the priest of the admiralty church in st. petersburg, whose name was kuntsevich, received 10 thousand rubles and married mendeleev with his sweetheart anna popova. as a result the breach of inhibit led to the deprivation of kuntsevich’s holy orders. mendeleev had seven children with his wives. his and anna popova’s eldest daughter lyubov (lyuba – fig. 3c) was married to alexander blok, the prominent rusfigure 2. tobolsk at the end of xix century: left the bogoyavlensky church were mendeleev was baptized; right the gymnasium where mendeleev studied (permission of museum and archives of dmitri mendeleev in st. petersburg). figure 3. ladies of mendeleev’s family: mendeleev with his first wife feozva leshcheva (a); anna popova – his second wife (b); c – mendeleev’s daughter lyubov (permission of the museum and archives of dmitri mendeleev in st. petersburg). a b c 122 dmitry pushcharovsky sian poet of silver age (period from the last decade of the 19th century up to first two or three decades of the 20th century). he dedicated to lyuba his first cycle of poetry stikhi o prekrasnoi dame (verses about the beautiful lady, 1905). work on the periodic table mendeleev worked in st. petersburg university until 1890, and it is just here he made his most significant discovery – the creation of periodic table of chemical elements. he began to give a lecture course “fundamentals of chemistry” in october 1867. during 1868-1871 he summarized it in 5 issues with the same name. during the composition of this edition mendeleev noticed that the properties of chemical elements definitively obey some periodicity. this regularity became specifically clear when he arranged the elements according to their atomic weights, even though some of their values needed a correction. later on this approach justified the prediction of some chemical elements which were unknown at that time. the history does not give an unambiguous answer to some questions related to the events when the first version of the periodic table was completed. it is known [2] that on monday 17th of february 1869 mendeleev prepared the manuscript with the title written by him in french: “essai d’une systeme des elements d’après leur poids atomiques et fonctions chimiques”. it is curious, because mendeleev’s gymnasium mark for foreign languages was far from excellent. in the last decade of february he also finished the work on the corresponding paper with the additional information which was published the same year in the journal of the russian chemical society – the first chemical journal in russia [3] (fig. 4). figure 4. mendeleev’s manuscript “essay of the system of elements according to their atomic weights and chemical properties”, 17th of february 1869 (a). the first version of the mendeleev’s periodic system distributed before his report among the members of russian chemical society and published in the beginning of the first two issues of “fundamentals of chemistry” in march 1869 (b) (permission of museum and archives of dmitri mendeleev in st, petersburg). a b 123dmitry i. mendeleev and his time from the very beginning mendeleev understood that his discovery needed international recognition. therefore immediately, already in february, he sent his table to his colleagues in western europe. apart from that, on the 6th of march his famous report with the same title of his paper was presented by professor n.a.menshutkin – the first editor of the journal rcs – during the meeting of the russian chemical society. in 1906 mendeleev remembered these events [4]: “in 1869 i sent to many chemists the separate page “essai d’une systeme des elements d’après leur poids atomiques et fonctions chimiques” – “essay of the system of elements according to their atomic weights and chemical properties” and provided this information to the russian chemical society during its meeting in march 1869 “on the correlation between properties and atomic weights of the elements”. from that it is unclear whether the author gave the presentation or not. according to some data just on the 17th of february he had to leave st. petersburg for an inspection of the cooperative cheese dairy in tver province. but because this day became the day of discovery of periodic table the departure was postponed until the beginning of march. during this trip mendeleev also planned to visit his homestead boblovo, where his house had been restored at that time. however, other records of that time show that mendeleev personally gave a presentation during the meeting of chemical society on the 6th of march. anyway all these details deviate back in comparison with the very essence of mendeleev’s discovery. step by step improving the first version of the periodic system mendeleev continued his work until 1871, when the table gained the perfect well-known form [5] (fig. 5). that year he visited several well-known chemical centers where he gave lectures devoted to his periodic table of chemical elements and the same year he presented his famous article “periodic validity for chemical elements”. according to [6], perhaps this discovery inspired us physicist eugene wigner, the nobel laureate in 1963, who in his lecture on this occasion at the stockholm city hall, formulated the philosophy of scientific research work: “… science begins when a body of phenomena is available which shows some coherence and regularities, that science consists in assimilating these regularities and in creating concepts which permit expressing these regularities in a natural way” [7]. mendeleev’s colleagues as it often happens with important discoveries, which correspond to the challenges related to the scientific ideas about nature, several researchers in different countries at the same time were thinking about the periodicity in the system of the chemical elements. julius lothar meyer (1830-1895), who worked in germany, and british chemist john alexander newlands (18371898), contributed in a significant way to the development of the ideas concerning the periodicity of elements [6]. their main results will be reviewed below, however initially in connection with mendeleev’s discovery it is worth mentioning the italian chemist stanislao cannizzaro (1826 –1910, fig. 6a), whose fate had been complicated. he studied medicine and chemistry at the universities of palermo, naples and pisa. in 1849 he took an active role in the popular revolt in sicily. it was suppressed and cannizzaro was condemned to death. he fled to paris and since 1855 he began to work in different italian universities. in 1871 he was elected as a member of the italian senate and later on he became its vicechairman. as a member of senate, cannizzaro supervised the scientific education in italy. cannizzaro brought the attention to the concepts already present in literature between atom and molecule. in this respect it is worthy to mention the fundamental paper by a.avogadro [8], published approximately half a century earlier. moreover, cannizzaro elaborated and revised the system of the crucial chemical notions: definition of chemical formula, differences between atom and molecule, atomic and molecular figure 5. two of the world’s oldest periodic table charts: a printed in 1876 and exposed in st. petersburg university (public domain); b found at university of st. andrews in scotland by dr. a.aitken and printed in 1885 in vienna (public domain, photo st. andres university) a b 124 dmitry pushcharovsky weights. j. berzelius published the first data of atomic weights (consequent to the definition of isomorphism by mitscherlich) as early as 1828 [9]. however cannizzaro provided their most accurate values. his historical significance is connected primarily to these results. he expressed his theory and the distinction between atomic and molecular weights in the pamphlet [10,11] which he distributed among the participants of the international chemistry congress in karlsruhe in september 1860. mendeleev and julius lothar meyer were among the attendees and together with the leading european chemists they highly appreciated cannizzaro’s contribution to general chemistry. many years later mendeleev said: “i consider him (cannizzaro) as my real predecessor”, because he determined by himself the values of atomic weights and created a necessary fulcrum”. lothar meyer (fig. 6b), who never used his first given name, was a german chemist and a foreign member of st. petersburg academy (1890). in the beginning of their careers both mendeleev and meyer worked in heidelberg with r.bunsen, who elaborated the spectral analysis. meyer is one of the pioneers in developing the first periodic table of chemical elements. in meyer’s birthplace varel (lower saxony, germany) there is a memorial with three sculptural portraits of meyer, mendeleev, and cannizzaro. in 1864 meyer composed a table with 28 elements allocated in six columns according to their valences. obviously such arrangement of limited number of chemical elements revealed the similarity of their chemical properties within the same vertical column. in connection to this approach mendeleev argued that this system is just a simple comparison of some elements on the basis of their valences. such values are even not constant for the same element and therefore should not be considered as its crucial characteristic. consequently, meyer’s table could not pretend for the full description of elements and did not reflect their inherent periodic law. only half a year after the first version of mendeleev’s periodic table was printed in 1869, meyer published a revised and expanded version of his 1864 table, which was similar to that published by mendeleev. this paper “die natur der chemischen elemente als function ihrer atomgewichte” (“the nature of the chemical elements as a function of their atomic weight” annalen der chemie (1870)) [12], contained the table and the plot with the correlation between atomic volumes and atomic weights for the known chemical elements at that time. it is worthy to recall that meyer unjustly reproached mendeleev for the correction of some atomic weights in the periodic table. however several years later he wrote: “i confess frankly that i lacked the courage for far-sighted assumptions which mendeleev expressed with certitude” [2, 13]. approximately at the same time the british chemist newlands (fig. 6c) suggested his own version of the periodic system of the chemical elements. in the beginning of 1864 newlands was impressed by the paper, which claimed that for most of the chemical elements the values of atomic weights are multiple of 8. obviously the author’s opinion was erroneous, however newlands figure 6. mendeleev’s colleagues: stanislao cannizzaro (a); julius lothar meyer (b); john alexander newlands (c) (photos from public domain). a b c 125dmitry i. mendeleev and his time decided to continue his research in this direction. he composed the table where the elements were ordered according their atomic weights. in his paper dated 20th of august 1864 he emphasized the periodicity in the arrangement of chemical elements [14]. after he numbered the elements and compared their properties he noticed the repeating pattern of elements where every 8 each element had similar chemical properties as the first one in common with the eighth note in musical octave. this mysterious musical harmony finally compromised the whole concept which exhibited similarity with mendeleev’s periodic table only externally. one year later, on the 18th of august 1865, newlands published the new table which he called “law of octaves” [15]. on the 1st of march 1866 in the chemical society he gave a talk “law of octaves and the causes of numerical relations among the atomic weights”, which received the hostile reception on behalf of the audience. in particular, g. c. foster, professor of physics at the university college of london, humorously inquired whether the speaker had ever examined the elements according to the order of their initial letters [16]. according to [6], in 1884 newlands collected his various papers on the discovery of the periodic law in [17]. in 1887 the london royal society awarded newlands with the davy medal “for his discovery of the periodic law of the chemical elements”. this medal is given annually since 1877 to an outstanding researcher in the field of chemistry. five years earlier dmitry mendeleev and lothar meyer received the davy medal from royal society “for their discovery of the periodic relations of the atomic weights”. newlands rewarding seemed rather ambiguous, however he primarily revealed the periodic variation of the chemical properties of the elements which is reflected in his law of octaves, and it is obviously his merit. mendeleev emphasized that “…due to his works it was possible to perceive periodic law in its first stages” [18, 19]. periodic table and mineralogy the periodic system contributed to the progress in many natural sciences. it significantly extended the scientific ideas in geology and best of all in geochemistry and mineralogy [20]. the discovery of new minerals and consequently of the chemical elements in their composition contributed to the creation of the periodic table. at the same time the periodic table indicated some shortcomings in the scientific ideas about these elements. one of the first results of its use was the revision of the atomic weights of uranium and rare earth elements as well as the transfer of the latter from the divalent calcium analogues to the group of trivalent elements. the significance of this correction becomes more important nowadays when the use of the rare earth elements is estimated at 2000 tons per year only in russia [21]. electronics and photonics use about 70% of this quantity and thus the hunt for rare earth elements is expanding all over the world. besides atomic weights mendeleev composed his periodic table on the basis of the chemical properties of the elements. thanks to that he predicted the analogues of aluminum (gallium) and of silicon (germanium). both elements were discovered in 1876 [22] and in 1886 [23], respectively. they are widely used in semiconductor technology and thus, the industrial demand for them is growing up. finally it is worthy to note that when mendeleev was still alive, the noble gas group was discovered. this discovery definitively indicated that the periods include octets of chemical elements where the 9th element is similar to the 1st one, and have no analogy with the musical octaves. these elements are also of geochemical interest, namely he and ne are important constituents of the gas giants jupiter and saturn. during several decades after the publication of the periodic table researchers in different countries continued to think over the question whether a more fundamental property of the chemical element than its atomic weight exists. thus in 1913, six years after d.mendeleev passed away, the young british physist henry moseley introduced a new characteristic “atomic number” which is equal to the number of positive charges in the atomic nucleus and consequently to the number of electrons in the neutral atom [24]. the electronic model of atoms enlarged the ideas related to their behavior in the geochemical processes. in particular, in 1958 the german mineralogist hugo strunz discovered gallite cugas2 the first ga-mineral with a crystal structure identical to the widespread chalcopyrite cufes2. thus everybody began to think that gallium, which is a rare chemical element, can be hidden in chalcopyrite. however all attempts to find gallium in chalcopyrite failed because it and iron have different electronic structure: there are 18 electrons in the outer shell of ga whereas fe contains only 13 electrons and thus there is no isomorphic replacement between these minerals. professor vladimir vernadsky at moscow university highly appreciated the important contribution of the periodic law to mineralogy [20]. in the end of xix century he composed the table of isomorphic elements with emphasis on so-called vernadsky’s rows. the atomic radii were not known at that time and thus the isomor126 dmitry pushcharovsky phic replacements were examined only within the vertical groups of the periodic table. therefore vernadsky’s rows did not receive an acknowledgement on behalf of mineralogists and geochemists and as a result for some time the periodic table was shifted back in their mind. this situation radically changed when in 1926 victor goldsmith, a norwegian mineralogist, on the basis of the interatomic distances and the experimentally determined values of radii for o2= 1.32 å and f= 1.33 å, composed the system of ionic radii and formulated the rule for isomorphic replacements [25]. he indicated that the size difference for the ions involved in such substitution cannot exceed 10-15%. thus three parameters, namely atomic weight, atomic number and ionic radius were used to characterize each element in the periodic table. after that the diagonal rows of elements which correspond to the directions of possible isomorphic replacements were revealed within the periodic table. the following examples illustrate goldsmith’s rule: li+ mg2+ sc3+; na+ ca2+ y3+ th4+; al3+ ti4+ nb5+ w6+. this idea allowed to explain the complete substitution between na+ and ca2+ in feldspars – the main rock forming minerals in the earth crust, according the scheme na+ + si4+ = ca2+ + al3+ [26]. this diagonal also contains yttrium and in association with it the whole group of rare earth elements. they always replace calcium in the minerals and that’s the reason why these elements were considered primarily as bivalent. the recent theoretical calculations and experimental results indicate a dramatic transformation of electronic structure in some atoms at high pressures. it leads to some changes in their chemical properties and consequently the formation of several new materials with the unexpected stoichiometry. for example, the cubic nacl3 was synthesized at the pressure 55-60 gpa and at the temperature >2000 k [27]. similarly such exotic compounds were found in some other systems, namely mg – o and al – o. obviously these phenomena still require an appropriate explication, however the periodic table is a starting point for such works. in general the mineralogical observations and conclusions extend the ideas related to the periodic variations of electronic structure at no ambient conditions, of ionic radii, ionization potential and some other notion of energetic crystal chemistry. mendeleev after his discovery mendeleev’s lifeline shows that he had many interests and hobbies. he was friends of many artists (fig. 7), knew painting, he liked to play chess and producing suitcases was among his unusual hobbies. these items were of exceptional quality because mendeleev invented a completely unique glue. therefore all the merchants in st. petersburg tried to get just these suitcases directly “from mendeleev”. during his last years mendeleev promoted the establishment of the first siberian university in tomsk and the polytechnic institute in kiev. in 1866 he initiated the foundation of the first chemical society in russia. in 1890 mendeleev had to leave st. petersburg university due to his support to the student’s movement related to the displeasure of life and studies conditions. in 1892 the minister of finance s.j. vitte suggested mendeleev to be the head of the new central board of weights and measures in russia. being on this position mendeleev insisted on the implementation in russia of the metric system which was essentially accepted in 1899 (fig. 8). in the beginning of january 1907 he fell ill with pneumonia and on the 20th of january he passed away. his tomb is in volkov’s cemetery in st. petersburg (fig. 9). at his funeral in st. petersburg, his students carried a large figure 7. repin i.e (1885). mendeleev in the mantle of edinbourgh university honorable professor (permission of tretyakov gallery, moscow). 127dmitry i. mendeleev and his time copy of the periodic table of the elements as a tribute to his work. final remarks mendeleev’s priority in the discovery of the periodic law and in the creation of periodic table of the chemical elements was definitively recognized by the international scientific community. in 1905 he was decorated with the copley medal – the highest award from the royal society of london established in 1731 “for his contributions to chemical and physical science”. mendeleev was elected as a member of the london royal society, the united states national academy of science and the royal swedish academy of sciences (fig. 10). in 1876 he was also elected as a corresponding member of the st. petersburg academy of science. the academician a.m. butlerov, one of the principal creators of the theory of the chemical structure, nominated mendeleev as a candidate for the full member vacancy in march 1980. two other well-known russian chemists friedrich konrad beilstein and nikolai n. beketov were also considered as challengers for the same vacancy. it is really touching that the relations between all of them were full of respect and estimation. however there was no doubt that mendeleev should have been elected assuming his exceptional contribution to the science. nevertheless the results of the voting in the academy meeting on the 11th of november 1880 were really shocking: 10 votes – black, 9 votes – white [2, 28]. there were a lot of protests against this result but mendeleev accepted it rather quietly and in his autobiographic notes he marked the events of 1880 with the single phrase: ‘… travelled with volodia (his son) along volga”. perhaps it is worthy to add that anna popova (later on she became his second wife) accompanied them… three times in 1905, in 1906 and in 1907 mendeleev was nominated to nobel prize, however all the times it was done by 1 or 2 his foreign colleagues, whereas his opponents were supported by 20-30 scientists [6]. it is known that the nobel prize is conferred for the recently obtained outstanding results and therefore every time there was a controversy whether the creation of periodic table could be considered as a state-of-the-art work. the discovery of the noble gas group and their very logic placement within the periodic table were among the most convincing arguments to its urgency. in 1905 apart from mendeleev the nobel committee considered the works by two other chemists: a. von bayer (organic chemistry, germany) and h. moissan (inorganic chemistry, france). as a result the voting was in favor of von bayer. next year the nobel committee in chemistry recommended d.mendeleev to the generfigure 8. mendeleev in his office: russia’s new central board of weights and measures (permission of museum and archives of dmitri mendeleev in st, petersburg). figure 9. the tomb of mendeleev in volkov’s cemetery in st petersburg (permission of museum and archives of dmitri mendeleev in st, petersburg). 128 dmitry pushcharovsky al assembly of the royal swedish academy. the voting results for mendeleev at the committee meeting was 4:1. the only vote was for h. moissan, who was again mendeleev’s competitor. the swedish chemist peter klason, who was the member of nobel committee, supported him very actively. he positively estimated mendeleev’s contribution but emphasized that the creation of periodic table could be impossible without the accurate values of atomic weights which were obtained by cannizzaro. that is him who suggested considering both mendeleev and cannizzaro as the candidates for the nobel prize. at a first glance this suggestion seemed reasonable. however the inclusion of cannizzaro into the list of candidates for the prize in 1906 was already impossible because the dead line for nomination was terminated on the 31st of january. thus the h. moissan received the prize in 1906. in 1907 both mendeleev and cannizzaro were nominated for the noble prize. however that year mendeleev passed away and according the statute of nobel prize it cannot be conferred posthumously. obviously the lack of mendeleev’s name in the list of nobel prize laureates is a great historical mistake. his name is well-known all over the world and the periodic table is in each classroom and auditorium where people study chemistry. on the 10th of june 1905 mendeleev wrote in his diary: “apparently the future does not threaten the periodic law by its destruction and on the contrary it promises the superstructure and its further development” [29, 30]. the last 150 years completely justified this prediction. acknowledgement the author is grateful to mrs. j. angelett for improving the english in the manuscript and to three anonymous referees for their valuable comments. a special gratitude is addressed to professor dmitriev i.s., the director of museum and archives of dmitri mendeleev in st, petersburg. this study was supported by the russian foundation for basic research (grant no. 18-05-00332). references 1. pushcharovsky d.yu. dmitry ivanovich mendeleev and his discovery. nauka i zhizn’, 2019, 2, 19-25 (in russian). 2. smirnov g.v. mendeleev. moscow, “molodaya gvardiya”, 1974, 382 p. (in russian). 3. mendeleev d.i. the correlation between properties and atomic weights of the elements. journal of russian chemical society, 1869, 1, 60-77 (in russian). 4. mendeleev d.i. fundamentals of chemistry. 8th edition, corrected and completed. spb: frolova m.p. printing office and lithography, 1906, 816 p. (p. 612). (in russian). 5. mendeleev d.i. the natural system of the elements and its application for the evidence to the properties of undiscovered elements. journal of russian chemical society, 1871, 3, 25-56 (in russian). 6. hargittai b. and hargittai i. year of the periodic table: mendeleev and the others. structural chemistry, 2019, 30(1), 1-7. 7. wigner e.p. city hall speech – stockholm, 1963. reproduced in wigner ep (1967) symmetries and reflections: scientific essays. indiana university press, bloomington and london, 1963, pp. 262-263. 8. avogadro a. essai d’une manière de déterminer les masses relatives des molécules élémentaires des corps, et les proportions selon lesquelles elles entrent dans ces combinaisons. journal de physique de chimie et d’histoire naturelle 1811, 73, 58-76. 9. berzelius j. table des poids atomistiques des corps simples et de leurs oxides,d’après les analyses les plus exactes et les plus récentes. paris 1828. annales de chimie et de physique, 1828, 38. s.426-432. 10. cannizzaro s. lettera del prof. stanislao cannizzaro al prof.s. de luca; sunto di un corso di filosofia chimica, fatto nella r. universita’ di genova. (1858). il nuovo cimento, 7(1), 321-368. 11. cannizzaro s. sunto di un corso di filosofia chimica. nota sulle condensazioni di vapore dell autore stesso. pisa, tipografia pieraccini, 1858, 62 p. figure 10. the participants of the 52nd meeting of british association for the advancement of science, manchester, 1887. 1st rank (from left to the right): menshutkin n.a., mendeleev d.i., roscoe h.e.; 2nd rank: outside left joule j.p., president of association, shorlemmer c. (second from the right side), thompson w., outside right (permission of museum and archives of dmitri mendeleev in st, petersburg). 129dmitry i. mendeleev and his time 12. meyer l. die natur der chemischen elemente als function ihrer atomgewichte. annalen der chemie und pharmacie, supplementband vii, 1870. s. 354-364. 13. paneth f. die entwicklung und der heutige stand unserer kenntnisse iber das natiirliche system der elemente (zum 100-jährigen jubilaum von lothar meyer’s geburtstag). die naturwissenschaften, 1930, bd. 18. heft 47, s. 964-976 (s. 968). 14. newlands j. a. r. on relations among the equivalents. chemical news, 1864 (20 aug.), vol. 10, 94-95. 15. newlands j. a. r. on the law of octaves. chemical news, 1865 (aug. 18, 1865). vol. 12, 83. 16. newlands. extract from the report of the meeting of the chemical society, march 1st, 1866. chemical news (march 9, 1866) 13, 113. 17. newlands j.a.r. (1884) on the discovery of the periodic law, and on the relations among the atomic weights. e and fn spon, london (it is a reprint collection). 18. kedrov b.m. (ed.) (1958) d. i. mendeleev: the periodic law (in russian, d. i. mendeleev: periodicheskii zakon). izd. akad. nauk sssr, moscow p. 314. 19. mendeleev d.i. fundamentals of chemistry. 8th edition, corrected and completed. spb: frolova m.p. printing office and lithography, 1906, 816 p. (p. 613). (in russian). 20. belov n.v. essays on structural mineralogy. moscow, nedra, 1976, 344 p. (in russian). 21. state and usage of mineral resources of russian federation in 2016 and 2017. state report. the ministry of natural resources and environment of russian federation. moscow 2018, pp. 370. 22. de boisbaudran lecoq. caractères chimiques et spectroscopiques d’un nouveau métal, le gallium, découvert dans une blende de la mine de pierrefitte, vallée d’argelès (pyrénées). comptes rendus hebdomadaires des séances de l’académie des sciences, 1875, 81, 493495. 23. winkler c. germanium, ge, ein neues, nichtmetallisches element. berichte der deutschen chemischen gesellschaft, 1886, 19, s. 210-211 24. moseley, h.g.j. the high-frequency spectra of the elements. philosophical magazine, 6th series. 1913, 26, 1024-1034. 25. goldschmidt v. m. die gesetze der krystallochemie. die naturwissenschaften 1926, 14, 21, 477-485. doi: 10.1007/bf01507527 26. zambonini f. the isomorphism of albite and anorthite. american mineralogist, 1923, 8, 81-85. 27. zhang w., oganov a.r., goncharov a.f., zhu q., boulfelfel s.e., lyakhov a.o., stavrou e., somayazulu m., prakapenka v.b., konôpková z. unexpected stable stoichiometries of sodium chlorides. science 20 dec 2013, 342, 6165, 1502-1505. doi: 10.1126/science.1244989 28. dmitriev i.s. boring story. in: dmitriev i.s. a man of alternation epoch. (essays of d.i.mendeleev and his time). st. petersburg, chimizdat, 2004, p. 397-458 29. mendeleev d.i. – archive, vol. 1, autobiographic materials, collected articles, compilers mendeleeva m.d., kudryavtseva t.s. editors: shchukareva s.a. and valka s.n. leningrad, 1951, 34 p. (in russian) 30. evdokimov yu. on the history of the periodic law. nauka i zhizn’, 2009, 5, 12-15 (in russian). substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 3(2) suppl. 6: 49-57, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-765 citation: m. bellardita, r. ceccato, s. dirè, v. loddo, l. palmisano, f. parrino (2019) energy transfer in heterogeneous photocatalysis. substantia 3(2) suppl. 6: 49-57. doi: 10.13128/ substantia-765 copyright: © 2019 m. bellardita, r. ceccato, s. dirè, v. loddo, l. palmisano, f. parrino. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. energy transfer in heterogeneous photocatalysis marianna bellardita1, riccardo ceccato2, sandra dirè2, vittorio loddo1, leonardo palmisano1,*, francesco parrino2,* 1 dipartimento di ingegneria, università di palermo, viale delle scienze ed. 6, 90128 palermo, italy 2 dipartimento di ingegneria industriale, università di trento, via sommarive 9, 38123 trento, italy *corresponding authors: l.p: e-mail: leonardo.palmisano@unipa.it; f.p: e-mail: francesco.parrino@unitn.it. abstract. electron transfer reactions constitute one of the main pillars of chemistry and numerous examples can be found in nature and in technological applications. energy transfer induced reactions are more elusive but equally important in phenomena related with natural photosynthesis and in general when light-matter interactions are relevant. heterogeneous photocatalysis is generally considered based on electron transfer reactions. in fact, absorption of photons of suitable energy induces formation of photogenerated charges (electron and holes) which in turn initiate redox reactions through interfacial electron transfer to (or from) surface species. however, rare examples of photocatalytic reactions induced by prevailing energy transfer have been recently reported in literature. investigation in this field may be still defined at a nascent level, and the mechanistic aspects of energy transfer, widely investigated in photochemistry of homogeneous or colloidal systems should be clarified in heterogeneous photocatalysis. in the manuscript the basic principles of energy transfer will be presented along with some known examples. these concepts will be inferred in the field of heterogeneous photocatalysis, by considering the excited solid semiconductor as the energy donor. some rare examples of energy transfer induced heterogeneous photocatalytic reactions will be presented along with some tentative mechanistic hypotheses. keywords. energy transfer; heterogeneous photocatalysis; green chemistry. 1. introduction processes based on energy transfer are nowadays of great actuality. even if the theoretical description of these phenomena has been clarified last century,1,2 these basic processes find application in innovative technologies connecting chemistry, biology and physics in interdisciplinary approaches. for instance, techniques based on energy transfer processes have been used to monitor dna hybridization and sequencing, protein conformation, enzyme activity, and cellular dynamics.3-5 other applications concern photonic logic 50 marianna bellardita et al. gates6,7 and energy harvesting.8,9 the reason for this widespread interest in energy transfer based technologies lies on the extremely high sensitivity to conformational changes in the distance and orientation between energy donors and acceptors. the distance changes observable in this way range from 0.5 to 10 nm so, for this reason, energy transfer based techniques are also referred to as “molecular rulers”.10 moreover, energy transfer mechanisms have been found to be fundamental for the capture and transmission of light in natural photosynthesis.11 in fact, photosynthetic organisms use specialized complexes which are able to transfer the captured light energy through an efficiently distributed hierarchy of proteins. this energetic cascade efficiently proceeding in precise time and distance scales, eventually reaches the reaction centres where solar energy is fixed into chemical bonds. the energy transfer process12 can be summarized through eq. 1: d* + a → d + a* (1) in which the excited donor (d*) is quenched to its ground state (d) and the released energy is absorbed by an acceptor (a) which in turn is promoted to its excited state (a*). the simplest energy transfer mechanism is radiative and is known with the name of “trivial”. in this case, the emission spectrum of *d must overlap the absorption spectrum of a in order to make possible the absorption of the photon emitted by d* by the acceptor a. this process depends on the extent of overlapping of the spectra, on the emission efficiency of d* (i.e. its quantum yield of emission) and on the concentration of a in the path of photons emitted by d*. energ y transfer can also occur non-radiatively through förster or dexter mechanisms. förster resonance energy transfer (fret) occurs from a fluorescent donor to a lower energy acceptor via long-range dipole-dipole interactions. therefore, fret mechanism is favoured at a specific geometric orientation and it is highly sensitive to donor-acceptor distances. the efficiency (e) of fret can be described by eq. 2: e r r r 0 6 0 6 6 (2) where r is the distance between donor and acceptor, and r0, typical for each donor-acceptor couple, is the distance at which the efficiency decreases of 50% (forster distance). the fret efficiency can be also expressed in terms of life time (τ) of the donor or of the fluorescence intensity (f) according to eq. 3: e f f da d da d 1 1 (3) where the subscripts d and da refer to as the donor and the donor in the presence of the acceptor, respectively. according to eq. 3, the decrease of the lifetime (or of the fluorescence intensity) of the donor in the presence of an acceptor indicates the existence of fret. finally, the rate (kt) of fret is described by eq. 4: k r rt d 1 0 6 6 (4) fr et mechanism requires a large overlapping between donor emission and acceptor absorption spectra. energy transfer can also proceed through a “collision” mechanism which is often referred to as “dexter” mechanism. in other words, the orbitals of the excited donor and of the acceptor in its ground state can overlap giving rise to a double electron transfer which does not modify the total charge of the system, but only its electronic configuration. in this case, the initial steps of the interaction are the same giving rise to electron transfer, but the system evolves differently along with the reaction coordinate and no net charge separation is obtained. the rate (k) of dexter energ y transfer can be described by eq. 5: k kj r l � � � � � � � �exp 2 (5) where k is a constant related to the specific donor-acceptor couple, j is the normalized spectral overlap integral, r is the distance between donor and acceptor relative to their radii of van der waals (l). by comparing eqs. 4 and 5 it is evident that the rate of energy transfer decreases with increasing r but with different dependence laws. in particular, unlike fret, dexter energy transfer becomes negligible when the distance between donor and acceptor increases of few angstroms. this is quite obvious by considering that dexter mechanism requires orbital (not only spectral) overlap. any fluorescent species such as organic dyes, fluorescent proteins, or nanoparticles can be potentially an energy donor.13 in particular, semiconductor nanoparticles of few nanometres (quantum dots) have been deeply investigated due to their excellent photo-physical features, stability and versatility.14-16 however, the donor behaviour of larger semiconductor nanoparticles in 51energy transfer in heterogeneous photocatalysis energy transfer processes is poorly understood as discussed throughout the text. demonstrating and opportunely exploiting the presence of energy transfer mechanisms in heterogeneous systems is relevant, for instance, in the fields of photocatalysis and photoelectrocatalysis. these applications are generally based on electron transfer processes occurring on the surface of irradiated semiconductor nanoparticles suspended in a reacting medium or immobilized onto a support.17,18 both technologies can be performed in mild conditions of temperature and pressure, with water as the solvent, solar light as the driving force, and by using cheap, abundant and robust semiconductor nanoparticles. these technologies found traditional application in the field of environmental remediation for both water and gaseous effluents.19 however, applications for the synthesis of high value added compounds are gaining increasing attention due to the appealing features of these processes in terms of conversions, selectivity and sustainability.20 the product distribution of this traditionally “electron transfer driven” processes can be significantly different when energy transfer processes become the prevailing mechanisms. for these reasons, understanding these mechanisms in heterogeneous photocatalytic systems and developing the technological tools to control and switch them from electron to energy transfer driven processes is highly desired and could open the route to unexplored and exciting novel organic syntheses as green alternative to the traditional ones. 2. electron and energy transfer in heterogeneous photocatalysis charge recombination is generally seen as detrimental in photocataly tic reactions as the absorbed energ y does not induce interfacia l electron transfer but is radiatively or not radiatively emitted. this energy could be in principle transferred to other species in the reacting mixture similarly to colloidal or homogeneous systems. however, even if the formal similarity with energy transfer processes in homogeneous systems is plausible, in heterogeneous systems such as photocatalytic suspensions, it is often difficult to discriminate between electron and energy transfer, mainly due to the presence of solid particles. first of all, light scattering phenomena limit the use of spectroscopic techniques and the consequent achievement of the parameters required for a rigorous characterization of the energy transfer process. for these reasons, up to now energy transfer mechanisms have been highlighted indirectly by considering the product distribution of particular (and rare) reactions. the radiant field distribution in an irradiated slurry suspension is intrinsically not homogeneous and depends on features of the light absorbing species, reactor geometry and configuration, type of radiation and physico-chemical and optic characteristics of the photocatalyst.21 indeed, unlike reactants which can be mechanically mixed within the system, photons do not possess mass and their “concentration” decreases with the distance from the radiation source.22 in these systems it is challenging to retrieve the local value of the rate of photon absorption (rpa) which in turn determines the intrinsic reaction rate.23 in fact, only the average value of rpa is experimentally accessible while the local one, describing the intrinsic kinetics, i.e. the events occurring at a molecular level not depending on mass and energy transport phenomena, can be retrieved rigorously only by the laborious and time demanding solution of the radiation transfer equation (rte) by means of numerical methods. monte carlo simulations24 and discrete ordinate methods (dom) are usually used.25 this problem has been recently approached by demonstrating that the average values satisfactorily approximate the local ones at sufficiently low optical thickness of the suspension.23 however, even if rpa could be approximatively retrieved, it is impossible to attribute it to the sole energ y transfer events because the macroscopic chemical transformation observed in a photocatalytic reactor is the result of various processes differently interacting in a complex way. only in few cases it has been possible to unequivocally attribute the formation of an intermediate product to energy transfer mechanisms. as a matter of fact, these cases are rare because the product distribution of electron and energy transfer reactions is often similar. moreover, even if specific energy transfer derived products could be produced, they must be selectively obtained. this is not trivial, as the hydroxyl radicals photocatalytically produced oxidize almost any organic species with only few exception, and the selective formation of a specific compound is the result of the complex interaction between light, reactants, products, and the irradiated surface of the photocatalyst. even if the specific compound is selectively obtained, consecutive reactions and adsorption phenomena could mask the identification of the prevailing mechanism. for these reasons, energy transfer mechanisms in heterogeneous photocatalysis have been often vaguely invoked but up to now never directly evidenced. the extent and the nature of the energy transfer processes, deeply clarified in the photochemistry of homogeneous systems, need to be investigated in heterogeneous photocatalysis. 52 marianna bellardita et al. in principle it is possible to hypothesize that the energy transfer mechanisms occurring in homogeneous systems also hold when an energy acceptor locally interact with the excited semiconductor acting as the energy donor. only some mechanistic details for the formation of singlet oxygen in heterogeneous photocatalysis have been tentatively proposed while less is known when more complex systems are under investigation.26 upon absorption of a photon of suitable energy, an electron (e-cb) and a hole (h+vb) are localized respectively in the conduction and valence band of a semiconductor (sc) according to eq. 6:27 sc + hν → sc*(e-cb, h+vb) (6) the photogenerated charges migrate to the surface of the semiconductor where they undergo interfacial electron transfer (eq. 7). in fact, they can reduce or oxidise electron donors (d) or acceptors (a) to the corresponding radical cation (d+∙) and anion (a-∙): sc*(e-cb, h+vb) + a + d → sc + a-∙ + d+∙ (7) the interfacial electron transfer is thermodynamically feasible if the redox potentials of the couples a/a-∙ and d+∙/d lie within those of the photogenerated charges. however, kinetic limitations or the absence of suitable a and d species in the reacting medium can favour quenching of sc* and, possibly, consequent energy transfer to a generic species b (eq. 8): sc*(e-cb, h+vb) + b → sc + b* (8) it is worth to note that the difference between the redox potentials of the sc bands and those of d and a species is the driving force of electron transfer while the downhill character of the process in terms of energy (e(sc*) > e(b*)) mainly determines the rate of energy transfer. moreover, while the electron transfer process creates a large charge re-distribution by generating charged species (a-∙ and d+∙), energy transfer generates a neutral excited state (b*). as a consequence, for instance the polarity of the solvent affects more the electron than the energy transfer processes. the quenching of the excited semiconductor can occur radiatively by emission of a photon. in this case the energy transfer to the species b occurs by absorption of the emitted photon similarly to the trivial mechanism expressed in homogeneous systems. this process is summarized in eqs. 9-10 and in figure 1: sc*(e-cb, h+vb) → sc + hν (9) b + hν → b* (10) this mechanism does not require electronic interaction or even contact between the irradiated semiconductor and the energy acceptor. the efficiency of this type of energy transfer does not depend on the distance between b and the surface of the semiconductor, but mainly on its concentration in the suspension. in fact, at higher b concentrations it increases the number of b molecules in the path of the emitted photons. other factors influencing the efficiency of the trivial mechanism are the charge recombination rate and the probability to emit photons rather than heat. moreover, it is required that the emission spectrum of the semiconductor and the absorption spectrum of b overlap in order to avoid mismatch between the excited semiconductor and the acceptor. unlike the trivial mechanism, förster and dexter energy transfer are radiationless processes and depend on the distance of the acceptor from the semiconductor (even if with different dependence laws, see eqs. 4-5). no electron exchange between acceptor and donor occurs when förster mechanism takes place (figure 2). indeed, the oscillating electric field locally produced by the separated charges behaves as a virtual photon which excites the acceptor through dipole-dipole interactions. notably, the oscillating field can be generated both by charges localized in the valence and conduction bands upon band to band transitions, or within the conduction band by vibrational states transitions. on the other hand, dexter energy transfer mechanism occurs when simultaneously two electrons move in opposite directions (from donor to acceptor and viceversa) without net charge exchange (figure 3). it is generally accepted that in heterogeneous photocatalysis electronic interaction occurs through surface adsorption of a substrate, which generally gives rise to surface metal coordination compounds. adsorption perturbates the electronic structure of both semiconductor and adsorbate at different extents.28 this situation is hν b* tio2* b eh+ figure 1. trivial energy transfer mechanism. 53energy transfer in heterogeneous photocatalysis similar to what occurs in dexter processes at the initial stage of interaction but, as below detailed, generally it results in interfacial electron transfer. strong electronic coupling between adsorbate and semiconductors generates new energy levels.29 combination of the homo level of the adsorbate with conduction band surface states creates a surface hybrid homolumo system between the adsorbate and the semiconductor which can extend deeply into the semiconductor due to its band structure. the resulting electronic system is generally characterized by novel ligand to metal electronic transitions, usually in the visible light region, which can be classified as optical electron transfer (oet). in this case, neither the semiconductor nor the adsorbate alone are able to absorb visible light, while the resulting charge transfer complex does. various organic and some inorganic compounds present this behaviour when adsorbed onto a semiconductor such as aromatic 1,2 diols, some lignin components and so2. the extent of this electronic interaction is evident when considering the effects of the adsorption of these compounds onto colloidal semiconductor nanoparticles (ca. 3 nm sized). in fact, in this cases the electronic alteration of the band structure is extended to the whole particle and a significant red shift of the band gap is obtained rather than novel absorption bands. notably, similar behaviour is reported also for other strongly interacting electronic systems such as solid solutions of semiconductors.30 weaker electronic coupling generally favours electron transfer from the adsorbate to the semiconductor or, in rare cases, viceversa. this mechanism, also known as photoinduced electron transfer (pet), usually takes place when chromophore species such as dyes are adsorbed on a semiconductor.31 visible light radiation absorption promotes the dye to its excited state which in turn injects an electron in the conduction band of the semiconductor. this weak electronic coupling determines high electron transfer efficiency and low charge recombination and, therefore, these systems are often used in dye sensitized solar cells. notably, these considerations justify the necessity to avoid the use of dyes as model compounds when one needs to estimate the visible light photocatalytic efficiency of novel semiconductors. in fact, the dye degradation rate expresses the efficiency of electron injection from the excited dye to the conduction band of the semiconductor rather than the activity of the semiconductor. it is generally accepted that the above reported electronic interactions favour optical or photoinduced electron transfer. on the other hand, as far as the energy transfer in photocatalysis is concerned, indirect observations suggest that energy transfer is prevailing when the surface of the semiconductor is grafted with species which block or substitute the surface hydroxyl groups, as in the examples reported in the next section. therefore, it seems that the direct contact between semiconductor and substrate favours electron transfer, while a mediated contact or a certain distance between them could favour energy transfer. for this reason, it seems plausible that some energy transfer processes observed by blocking the surface of the semiconductor could be of trivial or förster nature. even if, up to now, the few examples of energy transfer driven photocatalytic reactions reported do not allow to further discriminate between them, it is possible to conclude that surface grafting can be proposed as a tool to switch between energy and electron transfer processes. hydroxyl groups mainly origin from dissociative adsorption of water at the surface of the semiconductor.32 they determine the acidity and basicity of the surface, are responsible for the hydrophilicity (and superhydrophilicity) of the surface and influence the water dynamics and the competition between different substrates, greatly affecting the selectivity of photocatalytic reactions. in some cases, the hydroxylation density favours the photocatalytic activity even if not all of the surface hydroxyl groups are able to generate hydroxyl radicals. however, for the purpose of this paper, it is worth to stress the role of hydroxyl radicals in determining the electronic features of the semiconductor. first of all, protonation or deprotonation of hydroxyl groups changes the charge of the surface. therefore, ph changes can shift the potentials of the valence and conduction band and influence the redox ability of the irradiated semiconductor. moretio2* b tio2 b* eeh+ eeh+ figure 2. förster energy transfer mechanism. figure 3. dexter energy transfer mechanism. 54 marianna bellardita et al. over, hydroxyl groups can act as traps for the photogenerated charges which thus prolong their life time and facilitate interfacial electron transfer. moreover, as mentioned above, they act as anchoring sites for organic species and mediate the electronic modifications induced by the interaction. as a consequence, blocking these sites may favour charge recombination thus reducing the probability of efficient charge transfer.26 3. examples of energy transfer driven photocatalytic reactions some significant examples of energy transfer driven processes have been obtained in plasmonic photocatalytic composites used as sensors or as oxygen getters, but only rarely energy transfer driven processes have been invoked in classical heterogeneous photocatalysis for degradation or synthetic applications. one of the first examples of energy transfer process in heterogeneous photocatalysis has been reported by wang et al.33 authors hypothesized, without providing conclusive demonstration, that an array of vicinal tio2 nanoparticles could enable energy transfer through an antenna mechanism similar to the natural photosynthetic process of the same name (figure 4). an interesting case of photocatalytic mechanism which can be possibly interpreted as an energy transfer process is the hole induced oxidation of alcohols.34 this reaction generally occurs through abstraction of a hydrogen atom from the α position, giving rise to α-hydroxyalkyl radicals (eq. 11): r−ch2 –oh + h+ →r−ċh−oh + h+ (11) these radicals are generally powerful reducing species which can then inject an electron into the conduction band of the semiconductor according to a photoelectrochemical process often referred to as “current doubling effect” which eventually produce the carbonyl compound.35 this example is paradigmatic for at least two reasons. firstly, by considering that the spatial charge separation of the photogenerated electrons and holes is only some angstroms across the surface of the excited semiconductor, it is highly probable that the current doubling effect occurs in a concerted way rather than as a two-steps process. in this case it could be tentatively seen as a dexter energy transfer. secondly, the sole presence of the carbonyl product is not an evidence of an energy transfer mechanism, as the same product can be obtained also through other mechanisms. in fact, evidences of current doubling effects have been obtained by photocurrent measurement rather than by simple photocatalytic experiments. this example highlights the difficulties faced in trying to evidence energy transfer mechanisms in photocatalytic reactions. direct or indirect detection of singlet oxygen in aqueous photocatalytic suspensions is an indirect demonstration of the existence of energy transfer triggered process in heterogeneous photocatalysis. molecular oxygen exists in its ground state as a triplet. two excited states of molecular oxygen can be obtained upon excitation. the energy of these two singlet states, denoted as 1σg+ and 1δg lie 158 and 95 kj∙mol-1 above the energy of the ground state, respectively. the 1δg state, commonly denoted as 1o2, is the more stable of the two excited states and is enough long living to induce chemical transformation under mild conditions. formation of singlet oxygen in the presence of irradiated tio2 as the semiconductor has been explained by nosaka et al.36 in terms of double electron transfer in opposite direction. in fact, molecular oxygen can be first reduced by a photogenerated electron at the surface of tio2 to superoxide anion radical which in turn can be oxidized by a photogenerated hole giving rise to singlet oxygen. it is evident that the result of this mechanism is a neutral species (singlet oxygen) and no net charge exchange occurs. to the best of our knowledge, there are no clear evidences that this double electron transfer occurs in a consecutive or in a concerted way. in the second case, similarly to the current doubling effect mentioned above, the formation of singlet oxygen could resemble a dexter type energy transfer mechanism. other authors hypothesized that trivial mechanism could be responsible for the formation of singlet oxygen, i.e. that the radiative emission occurring upon charge recombination in the semiconductor could afford triplet to singlet excitation of molecular oxygen.37 however, daimon et al. pointed out the energetic mismatch between the band gap of the considered semiconductor (tio2) and the energy difference between triplet and singlet oxygen states.38 by taking into account this observation, recently macyk et al.39 proposed the formation of singlet oxygen in the presence of surface modified a a-∙ d d+∙ eeeeeh+ h+ h+ h+ h+ tio2 tio2 tio2 tio2 tio2 figure 4. photocatalytic antenna mechanism. 55energy transfer in heterogeneous photocatalysis tio2, through energy transfer from excited ti3+ species to molecular oxygen. in this case the energetic differences between the states in the donor (semiconductor) and acceptor (molecular o2) are compatible. the semiconductor quenching responsible for the transfer, in this case, is an intra-band transition (within the conduction band) rather than band to band recombination (figure 5). unfortunately, the nature of this energy transfer has not been highlighted. also in this case surface modifications performed by substituting hydroxyl with fluoride groups or by anchoring organosilanes, organic molecules or platinum complexes are reported to enhance the production of singlet oxygen. for instance, janczyk et al.37 observed efficient photocatalytic degradation of cyanuric acid only in the presence of surface modified tio2. in fact, cyanuric acid is one of the few compounds which cannot be photocatalytically degraded by bare tio2, due to its stability even in the presence of hydroxyl radicals, superoxide anions and peroxides, but it can be oxidized in the presence of singlet oxygen. these reports elegantly demonstrate that (i) singlet oxygen can be produced in aqueous irradiated suspensions of tio2, and that (ii) modification of the surface of tio2 promotes the production of singlet oxygen. a similar indirect demonstration of significant singlet oxygen formation in the presence of surface modified tio2 has been recently reported by ciriminna et al. [40,41] in this case a synthetic approach has been used. the considered reaction is the epoxidation of limonene (see figure 6). this natural terpene is gaining increasing attention because it can be used as a raw material for the production of a promising biopolymer, i.e. polylimonene carbonate (plc). plc is biodegradable, presents high thermal resistance (transition temperature up to 180°c), high transparency, and exceptional gas permeation ability. these features make plc a green alternative to the petrochemical derived polycarbonates with applications in the field of breathing glasses and food safe plastics. moreover, the presence of an exocyclic c=c double bond, easy to functionalize, makes the properties of plc extremely tunable for innovative applications such as sea water soluble polymers and antibacterial polymers. the bottle neck of the plc production is its starting material, i.e. limonene epoxide (le). le is obtained industrially from limonene in low yields and harsh operative conditions (prileshayew reaction). recently, limonene epoxide has been obtained with high conversion and selectivity (up to 90%) in the presence of surface modified commercial tio2 (evonik) under simulated solar light and in acetonitrile as the solvent. while oh radicals formed in the presence of bare tio2 mainly induced overoxidation of limonene, alkyl silane modification of tio2 favoured formation of singlet oxygen which selectively oxidizes limonene to 1,2 limonene epoxide. another example of energy transfer driven process is the photocatalytic isomerization of caffeic acid in aqueous tio2 suspensions and under nitrogen atmosphere42 (figure 7). uv irradiation of aqueous solutions of trans-caffeic acid in the absence of the semiconductor induces photochemical formation of the cis isomer until a photio2* eh+ 3o2 o2-∙ 1o2 tio2* eh+ tio2* h+ ti 3+ ti3+* 3o2 1o2 ir uv light d+∙ d ea b figure 5. mechanisms of singlet oxygen formation. a: nosaka mechanism; b: macyk mechanism. notably, the tio2 surface has been functionalized in the experiments carried out by macyk et al. 39 figure 6. limonene epoxidation. trans-caffeic acid cis-caffeic acid figure 7. isomerization of caffeic acid. 56 marianna bellardita et al. tostationary cis/trans ratio is achieved. in the presence of tio2 a higher cis/trans ratio has been observed. this finding suggests that photocatalysis contributes to isomerization along with the photochemical process. various tests have been performed in order to highlight this result. photocatalytic degradation of caffeic acid is suppressed being the reaction carried out under nitrogen atmosphere. this factor supports the hypothesis of energy transfer due to the high recombination probability in deoxygenated suspensions. moreover, in the presence of 2-propanol as the hole scavenger, isomerization was totally inhibited and again surface modification of tio2 further enhanced the cis/trans ratio. 4. conclusion and perspectives heterogeneous photocatalysis has been generally considered as the result of electron transfer reactions mainly occurring at the surface of the irradiated semiconductor. the possibility of addressing the product distribution of photocatalytic reactions and of obtaining selectively some reaction intermediates as high value added compounds, recently moved the attention of the scientific community towards photocatalytic syntheses rather than photocatalytic degradation. as a matter of fact, after ca. 50 years of scientific investigations on photocatalytic water purification, the gap between laboratory solutions and the needs of the water purification industry is evident. a change of direction is required in this field. it makes sense to use photocatalysis, possibly coupled with other advanced oxidation processes, to get rid of compounds harmful at low concentrations but only as a final treatment, after the application of technologies capable to efficiently treat high volumes of effluents. robust and reusable photocatalysts should be used rather than elegant and complex composites and applicative and engineering issues must be faced rather than basic research. the situation is different when considering photocatalysis as a green alternative to traditional organic synthesis methods. in this case basic research is still needed to develop tools to control and address the selectivity of the process and to propose novel and sustainable synthetic solutions. from the few examples summarized hereby it is possible to conclude that when the substrate electronically interacts with the surface of the semiconductor, electron transfer is generally the prevailing process, even if dexter-like double electron transfer processes cannot be excluded. on the other hand, trivial or forster energy transfer processes likely occur at the surface of modified semiconductors where orbital overlapping is less probable. these preliminary results, however, require further efforts to understand the energy 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open learning and activities in non-formal environments to inspire passion and curiosity. sara tortorella,1,2,* alberto zanelli,2,3 valentina domenici2,4 substantia. an international journal of the history of chemistry 3(2) suppl. 2: 17-26, 2019 firenze university press www.fupress.com/substantia citation: s. fuzzi (2019) energy in a changing climate. substantia 3(2) suppl. 2: 17-26. doi: 10.13128/substantia-213 copyright: © 2019 s. fuzzi. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-213 energy in a changing climate sandro fuzzi istituto di scienze dell’atmosfera e del clima,consiglio nazionale delle ricerche, bologna, italy e-mail: s.fuzzi@isac.cnr.it abstract. warming of the earth’s climate represents the “great challenge” of our times that may even undermine the subsistence of humankind on the planet. this paper reviews the causes and effects of climate change due to the anthropogenic activities. since energy production constitutes the main source of climate-forcing anthropogenic emissions, a particular emphasis is given in the paper to the energy system transition to meet the objectives of the paris agreement, the international treaty signed in 2015 under the auspices of the united nations framework convention on climate change, aimed at reducing the risks and effects of climate change on the global society. keywords. climate change, anthropogenic emissions, energy system transition, ipcc, paris agreement. 1. the earth’s climate system the term “climate” (from the ancient greek word klima: inclination) refers to the meteorological and environmental conditions in a given geographical area averaged over a long period of time, typically 30 years or more, as defined by the world meteorological organisation (wmo). the earth’s climate system includes different components, sometimes referred to as “compartments”, which interact dynamically with each other: atmosphere, ocean, earth surface, cryosphere and biosphere, the life on the planet, including mankind. the system evolves with time, influenced both by an internal dynamics and by external factors called climate forcings. climate forcing can either be due to natural phenomena (natural forcing) or to anthropogenic activities, in the latter case defined as anthropogenic forcing. the “engine” of the earth’s climate is the sun. the earth’s surface, in fact, receives energy from the sun, 50% of which in the visible part of the electromagnetic spectrum. part of the incident radiation is reflected back to space by the earth’s surface and by the clouds. the fraction of reflected energy is defined “albedo”. the earth’s albedo is on average approximately 0.3 (30% of the solar energy is reflected back to space), but varies considerably in different areas of the globe depending on the nature of the surface: snow and ice, sea surface, vegetation, desert, urban areas, etc. to balance the absorbed incoming energy, the earth must radiate the same amount of energy back to 18 sandro fuzzi space. because the earth is much colder than the sun, it radiates at much longer wavelengths, primarily in the infrared part of the spectrum. the earth reaches therefore an equilibrium temperature where absorption and emission are balanced (fig. 1). but in the atmosphere are naturally present certain atmospheric constituents such as water vapour, carbon dioxide (co2), methane (ch4) nitrous oxide (n2o) and other compounds that absorb a significant fraction of the infrared radiation emitted by the earth. the absorbed energy is then re-emitted in all directions thus contributing to the warming of the lower levels of the atmosphere causing the so-called (natural) greenhouse effect, in analogy with the heat trapping effect of the glass walls in a greenhouse illuminated by the sun that increases the temperature of the air inside (fig. 1). these absorbing species are therefore cumulatively called greenhouse gases (ghgs). in the absence of an atmosphere the radiative equilibrium temperature of the earth would be purely a function of the distance of the earth from the sun and of the surface albedo that is -18°c. but, as a consequence of the natural greenhouse effect, the average surface temperature of the earth is ca. 15°c, 33°c higher than the radiative equilibrium temperature. it is easy to understand that, in the absence of the natural greenhouse effect, the life on the planet would not have developed, at least not in the way we now experience. 2. the anthropocene after the end of the last glaciation, ca. 12.000 years ago, the warmer temperatures caused by the natural greenhouse effect favoured, with the development of agriculture, the emergence of our civilization. since the onset of civilisation, man has modified the natural environment to make it more suitable to his needs, e.g. clearing large forested areas transformed into agricultural land. until recent times, however, the world population was quite limited in number and the technologies available were relatively primitive, therefore the impact of humans on the environment had been quite limited both quantitatively and spatially. but for the past two centuries or so the effects of humans on the global environment have increased dramatically. during the past two centuries, the human population has increased tenfold to more than 7 billion and is expected to reach 10 billions in this century. humans exploit about 30 to 50% of the planet’s land surface and use more than half of all accessible fresh water. energy use has grown 16-fold during the twentieth century, causing 160 million tonnes of atmospheric sulphur dioxide (so2) emissions per year, more than twice the sum of its natural emissions. more nitrogen fertilizer is applied in agriculture than is fixed naturally in all terrestrial ecosystems; nitric oxide (no) production by the burning of fossil fuel and biomass also overrides natural emissions. fossil fuel burning and agriculture have caused substantial increases in the concentrations of ghg, co2 by 40% and ch4 by more than 150%, reaching their highest levels over the past 800 millennia (crutzen, 2002). for all these reasons the nobel laureate paul crutzen and the biologist eugene stoermer suggested that the holocene, the geologic epoch initiated with the end of the last glaciation has come to an end and that it seems appropriate to assign the term anthropocene to the present geological epoch in many ways dominated by human activities (crutzen and stoermer, 2000). there are different views concerning the beginning of the anthropocene. while crutzen and stoermer had dated the beginning of the anthropocene with the beginning of the industrial revolution in mid-18th century, ruddimann (2013) has put forward the idea that mankind has started modifying the natural environment at least 9,000 years ago with the large deforestations to get cultivable land. finally, more recent discussions have determined that the beginning of the anthropocene as a geological epoch should be dated to the early 1950s, corresponding to the “great acceleration” after the 2nd world war, marked by a major expansion in human population, large changes in natural processes, the development of new materials and of the international trade (lewis and maslin, 2015). figure 1. schematic representation of the earth’s climate system and the greenhouse effect (from le treut et al., 2007). 19energy in a changing climate 3. climate change in the anthropocene human activities contribute to climate change by causing changes in the atmosphere of the amounts of greenhouse gases and other gaseous and particulate components, with the largest contribution deriving from the burning of fossil fuels. since the beginning of the industrial era, the overall effect of human activities on climate has been a warming influence and the human impact now greatly exceeds that due to natural processes, such as solar changes and volcanic eruptions (forster et al., 2007). the 5th assessment report of the intergovernmental panel on climate change (ipcc), published in 2014, reports that more than half of the observed increase in global average surface temperature from 1951 to 2010 was caused by the anthropogenic increase in ghg concentrations and other anthropogenic forcing agents together. in fact, the best estimate of the human-induced contribution to warming is similar to the observed warming over the same period (fig. 2). the observed surface temperature change in fig. 2 is shown in black; the attributed warming ranges (colours) are based on observations combined with climate model simulations, in order to estimate the contribution of an individual external forcing to the observed warming. the 5 to 95% uncertainty range is superimposed to the bars. human-induced warming has now reached on average 1°c above pre-industrial levels in 2017, increasing at a rate of 0.2°c per decade, but warming greater than the global average has already been experienced in many regions and seasons (allen et al., 2018). 3.1. anthropogenic ghg emission the main ghgs deriving from human activities are the above-mentioned co2, ch4 and n2o. these gases accumulate in the atmosphere, causing concentrations to increase with time. significant increases of all these components have occurred in the industrial era (fig. 3), with an even higher increase staring from the 1950s (the great acceleration). all of these increases are attributable to human activities (ipcc 2014). between 1750 and 2011, the cumulative anthropogenic co2 emissions to the atmosphere were 2040 ± 310 gtco2. about 40% of these emissions have remained in the atmosphere (880 ± 35 gtco2), the rest was removed from the atmosphere and stored on land (in plants and soils) and in the ocean that has absorbed about 30% of the emitted anthropogenic co2. what is more important, about half of the anthropogenic co2 emissions between 1750 and 2011 have occurred over the last 40 years. co2 is not, as previously mentioned, the only ghg emitted by human activities, and fig. 4 reports the globfigure 2. comparison between the observed increase of global mean temperature (gmst) over the period 1951-2010 and the estimated anthropogenic contribution. the black bar is the observed gmst over the period, while the green and yellow bars represent the modelled contribution of ghgs and other climate forcers (mainly atmospheric aerosols that exert a cooling effect on climate; fuzzi et al., 2015), respectively. the orange bar is the sum of the two (green + yellow) representing the total modelled temperature increase due to anthropogenic emissions. as can easily be seen, the modelled and observed gmst increase are very close to each other, taking into account the uncertainty ranges of the different quantities (the 5 to 95% uncertainty range is reported on top of each bar). the natural contributions to gmst increase and the internal variability of the earth’s climate system are minimal, if not negligible (from ipcc 2014). figure 3. atmospheric concentrations of the most important ghgs over the last 2,000 years. increases since about 1750 are attributed to human activities in the industrial era. concentration units are parts per million (ppm) or parts per billion (ppb) (from forster et al., 2007). present ghg concentrations (2017) are: co2 = 406 ppm, ch4 = 1859 ppb, n2o = 330 ppb (wmo, 2018). 20 sandro fuzzi al annual anthropogenic ghg emissions expressed as co2-equivalent (co2-eq). the global ghg emission in 2010 amounted to 49 gt co2-eq. the main drivers of anthropogenic ghg emissions are the population increase and the increasing energy needs of our society. some figures illustrate the combined effects of the evolution of these two parameters. at the time when agriculture emerged, about 10,000 b.c., the population of the world was estimated a few millions, growing to a couple of hundred millions by year 1 a.d.. around 1800 the world population had reached one billion, with the second billion achieved in only 130 years (1930), the third billion in 30 years (1960), the fourth billion in 15 years (1974), and the fifth billion in only 13 years (1987). during the 20th century alone, the population in the world has grown from 1.65 billion to over 6 billions.  on the other hand, the world per-capita energy consumption, that amounted to some 20 gj per year at the beginning of the 19th century has now reached ca. 80 gj per year (tverberg, 2012). 3.2. anthropogenic ghg emissions by economic sector all human activities cause the emission in the atmosphere of ghgs, and fig. 5 reports the global anthropogenic ghg emissions from different economic sectors in 2010 (ipcc, 2014). as can be seen from the figure, energy production constitutes the anthropogenic activity with the highest share of ghg emission (35%). 4. the effects of climate warming in recent decades, changes in climate have caused impacts on natural and human systems on all continents and across the oceans. the 5th ipcc assessment report has described in great detail the observed effects on the basis of some main climatic parameters (ipcc, 2014). 4.1. temperature increase global warming (presently +1°c gmst with respect to the preindustrial period) is already negatively influencing the agricultural yields, thus affecting food security (zhao et al., 2017). at the same time, the increase of seawater temperature is influencing the marine ecosystems and biodiversity. at present, the worldwide effect on human health of climate warming has been relatively small, although an increased heat-related mortality has been reported (e.g. the 2003 heat wave in central-southern europe). climate warming is also altering the precipitation regimes of several regions with effects on water availability and agricultural yields (steffen et al., 2015). 4.2. sea level rise over the period 1901–2010, global mean sea level rose by 0.19 m (0.17 to 0.21). this is mainly due to glafigure 4. total annual anthropogenic ghg emissions in gigatonnes of co2-equivalent per year (gtco2-eq/yr) for the period 1970 to 2010 by gases: co2 from fossil fuel combustion and industrial processes; co2 from forestry and other land use (folu); ch4; n2o; gases covered under the kyoto protocol (f-gases) (from ipcc, 2014). figure 5. total anthropogenic ghg emissions in gtco2-eq/ yr) from different economic sectors in 2010. the circle shows the shares of direct ghg emissions in percentage of total emissions form the five main economic sectors. the pullout shows how shares of indirect co2 emissions from electricity and heat production are attributed to sectors of final energy use (ipcc, 2014). 21energy in a changing climate cier mass loss and ocean thermal expansion (ipcc, 2014). the rate of sea level rise since the mid-19th century has been larger than the mean rate during the previous two millennia. sea level rise is threatening all coastal areas with risk of flooding and the need of relocating the affected population (nicholls et al., 2011). 4.3. melting of glaciers over the last two decades, the greenland and antarctic ice sheets have been loosing mass and glaciers have continued to shrink almost worldwide, contributing on the one side to sea level rise, and on the other threatening freshwater availability in many regions of the world (ipcc, 2014). 4.4. extreme events the impact of recent climate-related extremes, such as heat waves, droughts, floods, cyclones and wildfires reveal significant vulnerability of some ecosystems and many human systems to current climate variability. impacts of such climate-related extremes include alteration of ecosystems, disruption of food production and water supply, damage to infrastructures and other consequences for human wellbeing (ipcc, 2014). 5. the paris agreement and the means for the implementation the policy actions to be implemented in order to limit the effects on the human society of the climate warming that is already happening fall under two broad categories: • mitigation – measures aimed at reducing the emission of ghgs and other climate forcers (energy efficiency, decarbonisation, more efficient agricultural practices, etc.); • adaptation – technological and infrastructural measures that allow contrasting the effects of climate change in progress. since more than 25 years the united nations framework convention on climate change (unfccc) has been working on a global treaty that could reduce the ghgs emissions to contrast climate change. finally, on december 12, 2015, within the 21st unfccc session, 196 countries, responsible for 95% of global ghg emission, approved the so called “paris agreement” that deals with ghg emissions mitigation, adaptation, and finance and that will formally start in the year 2020. the long-term overall goal of the paris agreement is to keep the increase in global average temperature to well below 2  °c above pre-industrial levels, and pursuing efforts to limit the temperature increase to 1.5 °c above pre-industrial levels, since this would substantially reduce the risks and effects of climate change. ipcc was then invited by the unfccc to provide a special report on the impacts of global warming of 1.5°c above pre-industrial levels and related global greenhouse gas emission pathways contained in the paris agreement. this report was actually prepared and presented in october 2018 (ipcc, 2018). the headline statements reported below from the summary for policymakers highlight some of the main conclusions of the report (ipcc, 2018). for a guide to the treatment of uncertainty within the ipcc reports, reference is made to mastrandrea et al., (2010). 5.1. understanding global warming of 1.5°c human activities are estimated to have caused approximately 1.0°c of global warming above pre-industrial levels, with a likely range of 0.8°c to 1.2°c. global warming is likely to reach 1.5°c between 2030 and 2052 if it continues to increase at the current rate. (high confidence). warming from anthropogenic emissions from the pre-industrial period to the present will persist for centuries to millennia and will continue to cause further long-term changes in the climate system, such as sea level rise, with associated impacts (high confidence), but these emissions alone are unlikely to cause global warming of 1.5°c (medium confidence). figure 6. human-induced warming reached approximately 1°c above pre-industrial levels in 2017. at the present rate, global temperatures would reach 1.5°c around 2040. stylized 1.5°c pathway shown here involves emission reductions beginning immediately, and co2 emissions reaching zero by 2055 (from allen et al., 2018). 22 sandro fuzzi climate-related risks for natural and human systems are higher for global warming of 1.5°c than at present, but lower than at 2°c (high confidence). these risks depend on the magnitude and rate of warming, geographic location, levels of development and vulnerability, and on the choices and implementation of adaptation and mitigation options (high confidence). 5.2. projected climate change, potential impacts and associated risks climate models project robust differences in regional climate characteristics between present-day and global warming of 1.5°c, and between 1.5°c and 2°c. these differences include increases in: mean temperature in most land and ocean regions (high confidence), hot extremes in most inhabited regions (high confidence), heavy precipitation in several regions (medium confidence), and the probability of drought and precipitation deficits in some regions (medium confidence). by 2100, global mean sea level rise is projected to be around 0.1 metre lower with global warming of 1.5°c compared to 2°c (medium confidence). sea level will continue to rise well beyond 2100 (high confidence), and the magnitude and rate of this rise depend on future emission pathways. a slower rate of sea level rise enables greater opportunities for adaptation in the human and ecological systems of small islands, low-lying coastal areas and deltas (medium confidence). on land, impacts on biodiversity and ecosystems, including species loss and extinction, are projected to be lower at 1.5°c of global warming compared to 2°c. limiting global warming to 1.5°c compared to 2°c is projected to lower the impacts on terrestrial, freshwater and coastal ecosystems and to retain more of their services to humans (high confidence). limiting global warming to 1.5°c compared to 2°c is projected to reduce increases in ocean temperature as well as associated increases in ocean acidity and decreases in ocean oxygen levels (high confidence). consequently, limiting global warming to 1.5°c is projected figure 7. the dependence of risks and/or impacts associated with selected elements of human and natural systems on the level of climate change, highlighting the nature of this dependence between 0°c and 2°c warming above pre-industrial level (from hoegh-guldberg et al., 2018). 23energy in a changing climate to reduce risks to marine biodiversity, fisheries, and ecosystems, and their functions and services to humans, as illustrated by recent changes to arctic sea ice and warmwater coral reef ecosystems (high confidence). climate-related risks to health, livelihoods, food security, water supply, human security, and economic growth are projected to increase with global warming of 1.5°c and increase further with 2°c. most adaptation needs will be lower for global warming of 1.5°c compared to 2°c (high confidence). there is a wide range of adaptation options that can reduce the risks of climate change (high confidence). there are limits to adaptation and adaptive capacity for some human and natural systems at global warming of 1.5°c, with associated losses (medium confidence). the number and availability of adaptation options vary by sector (medium confidence). 5.3. emission pathways and system transitions consistent with 1.5°c global warming two main pathways can be followed for limiting global temperature rise to 1.5°c above pre-industrial levels: i) stabilizing global temperature at 1.5°c or ii) global temperature temporarily exceeding 1.5°c before coming back down later in the century. in model pathways with no or limited overshoot of 1.5°c, global net anthropogenic co2 emissions decline by about 45% from 2010 levels by 2030 (40–60% interquartile range), reaching net zero around 2050 (2045–2055 interquartile range). for limiting global warming to below 2°c, co2 emissions are projected to decline by about 25% by 2030 in most pathways (10–30% interquartile range) and reach net zero around 2070 (2065–2080 interquartile range). nonco2 emissions in pathways that limit global warming to 1.5°c show deep reductions that are similar to those in pathways limiting warming to 2°c (high confidence). pathways limiting global warming to 1.5°c with no or limited overshoot would require rapid and far-reaching transitions in energy, land, urban and infrastructure (including transport and buildings), and industrial systems (high confidence). these systems transitions are unprecedented in terms of scale, but not necessarily in terms of speed, and imply deep emissions reductions in all sectors, a wide portfolio of mitigation options and a significant up-scaling of investments in those options (medium confidence). all pathways that limit global warming to 1.5°c with limited or no overshoot project the use of carbon dioxide removal (cdr) on the order of 100–1000 gtco2 over the 21st century. cdr would be used to compensate for residual emissions and, in most cases, achieve net negative emissions to return global warming to 1.5°c following a peak (high confidence). cdr deployment of several hundreds of gtco2 is subject to multiple feasibility and sustainability constraints (high confidence). significant near-term emissions reductions and measures to lower energy and land demand can limit cdr deployment to a few hundred gtco2 without reliance on bioenergy with carbon capture and storage (beccs) (high confidence). 6. energy system transition to meet the objectives of the paris agreements realizing a 1.5°c-consistent pathway would require rapid and systemic changes on unprecedented scales in: i) the energy system, ii) land and ecosystem management, iii) urban and infrastructure planning, iv) the industrial system. as previously stated, the energy system constitutes the anthropogenic activity with the highest share of ghg emission and in this section mitigation and adaptation options related to the energy system transition will be reported, derived from the ipcc 1.5°c report (de coninck et al., 2018). to limit warming to 1.5°c, mitigation would have to be large-scale and rapid. transformative change can arise from grow th in demand for a new product or market, such that it displaces an existing one. this is sometimes called “disruptive innovation”. for example, high demand for led lighting is now making more energy-intensive, incandescent lighting near obsolete, with the support of policy action that spurred rapid industr y innovation. similarly, smart phones have become global in use within ten years. but electric cars, which were released around the same time, have not been adopted so quickly because the bigger, more connected transport and energy systems are harder to change. renewable energy, especially solar and wind, is considered to be disruptive by some as it is rapidly being adopted and is transitioning faster than predicted. but its demand is not yet uniform. urban systems that are moving towards transformation are coupling solar and wind with battery storage and electric vehicles in a more incremental transition, though this would still require changes in regulations, tax incentives, new standards, demonstration projects and education programmes to enable markets for this system to work (de coninck et al., 2018). different types of transitions carry with them different associated costs and requirements for institutional or governmental support. some are also easier to scale up than others, and some need more government support than others. the feasibility of adaptation and mitigation 24 sandro fuzzi options requires careful consideration of multiple different factors. these factors include: • whether sufficient natural systems and resources are available to support the various options (environmental feasibility); • the degree to which the required technologies are developed and available (technological feasibility); • the economic conditions and implications (economic feasibility); • what are the implications for human behaviour and health (social/cultural feasibility); • what type of institutional support would be needed, such as governance, institutional capacity and political support (institutional feasibility). an additiona l factor (geophysica l feasibi lit y) addresses the capacity of physical systems to carry the option, for example, whether it is geophysically possible to implement large-scale afforestation consistent with the 1.5°c requirements (de coninck et al., 2018). 6.1. renewable energy the largest growth driver for renewable energy has been the dramatic reduction in the cost of solar photovoltaic (pv). solar pv with batteries has been cost effective in many rural and developing areas and smallscale distributed energy projects are being implemented in developed and developing cities where residential and commercial rooftops offer potential for consumers becoming producers (prosumers). the feasibility of renewable energy options depends to a large extent on geophysical characteristics of the area considered. however, technological advances and policy instruments make renewable energ y options increasingly attractive in most regions of the globe. another important factor affecting feasibility is public acceptance, in particular for wind energ y and other large-scale renewable facilities that raise landscape management challenges, but financial participation and community engagement can be effective in mitigating resistance (de coninck et al., 2018). 6.2. bioenergy and biofuels bioenergy is renewable energy from biomass, while biofuel is biomass-based energy used in transport. there is high agreement that the sustainable bioenergy potential in 2050 would be restricted to around 100 ej/yr. sustainable deployment at higher levels, in fact, may put significant pressure on available land, food production and prices, preservation of ecosystems and biodiversity, and potential water and nutrient constraints. some of the disagreement on the sustainable capacity for bioenergy stems from global versus local assessments. global assessments may mask local dynamics that exacerbate negative impacts and shortages while, at the same time, niche contexts for deployment may avoid trade-offs and exploit co-benefits more effectively. the carbon intensity of bioenergy is still a matter of debate and depends on several factors such as management, direct and indirect land-use change emissions, feedstock considered and time frame, as well as the availability of coordinated policies and management to minimize negative side effects and trade-offs, particularly those around food security (de coninck et al., 2018). 6.3. nuclear energy the current deployment pace of nuclear energy is constrained by social acceptability in many countries due to concerns over risks of accidents and radioactive waste management. though comparative risk assessment shows health risks are low per unit of electricity production and land requirement is lower than that of other power sources, the political processes triggered by societal concerns depend on the country-specific means of managing the political debates around technological choices and their environmental impacts. on the other hand, costs of nuclear power have increased over time and the current time lag between the decision date and the commissioning of plants is presently between 10 and 19 years (de coninck et al., 2018). 6.4. energy storage the growth in electricity storage for renewables has been around grid flexibility resources. battery storage has been the main growth feature in energy storage over the last few years mainly as a result of significant cost reductions due to mass production for electric vehicles. although costs and technical maturity look increasingly positive, the feasibility of battery storage is challenged by concerns over the availability of resources and the environmental impacts of its production. research and demonstration of energy storage in the form of thermal and chemical systems continues, but large-scale commercial systems are still rare. renewably derived synthetic liquid (like methanol and ammonia) and gas (like methane and hydrogen) are increasingly seen as a feasible storage options for renewable energy, producing fuel for use in industry during times when solar and wind are abundant. the use of electric vehicles as a form of storage has 25energy in a changing climate also been evaluated as an opportunity, and demonstrations are emerging, but challenges to up-scaling remain (de coninck et al., 2018). 7. conclusion warming of the earth’s climate is a scientifically proven reality and represents the “great challenge” of our times that may even undermine the subsistence of our specie on the planet. scientists have proven unequivocally that climate warming is already taking place and that human influence has been the dominant cause of the observed warming since the mid-20th century (ipcc 2014). it is then up to the policy makers to undertake the appropriate and timely actions for the mitigation of and the adaptation to climate warming that is already underway. in addition to political actions, citizen’s behavioural attitudes are also important for mitigation of global warming: mobility choices, dietary habits, waste management, household management, etc.. it is also certain that several aspects of climate change will persist for centuries and that an effective endeavour for contrasting this phenomenon involves a commitment for many generations to come: higher emissions today imply the need of a higher decrease tomorrow, with higher economic and social costs. today, the global society has already available the scientific knowledge and most of the technologies needed to effectively contrast climate change, and the strategies to be put in place depend solely on political and economic choices. in any case, it should be considered that the social and economic costs of inaction towards climate change mitigation and adaptation are definitely higher than those for implementing the necessary mitigation and adaptation measures (stern, 2007; ricke et al., 2018). acknowledgements this review paper builds largely on various reports of the intergovernmental panel of climate change, to some of which i have contributed. these reports have analysed and assessed several tens of 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on global observations through 2017; available online. zhao c., liu b., piao s., wanga x., lobelli d.b., huangj y., huanga m., yaoa y., bassuk s., ciais p., durand j-l., elliott j., ewert f., janssens i.a., lis t., lint e., liu q., martreu p., müller c., penga s., peñuelas j., ruaney a.c., wallachz d., wang t., wu d., liu z., zhu y., zhua z., asseng s., 2017. temperature increase reduces global yields of major crops in four independent estimates. pnas, 114, 9623-9631. http://www.ipcc.ch https://ourfiniteworld.com/2012/03/12/world-energy-consumption-since-1820-in-charts/ https://library.wmo.int/doc_num.php?explnum_id=5455 substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 4(2) suppl.: 79-88, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-830 citation: m. ziaee, m. taseidifar, r.m. pashley, b.w. ninham (2020) selective removal of toxic ions from water/ wastewater: using a novel surfactant. substantia 4(2) suppl.: 79-88. doi: 10.36253/substantia-830 copyright: © 2020 m. ziaee, m. taseidifar, r.m. pashley, b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. selective removal of toxic ions from water/ wastewater: using a novel surfactant mohammad ziaee1, mojtaba taseidifar1, richard m. pashley1, barry w. ninham2,* 1 school of science, university of new south wales, northcott drive, canberra, australia 2 department of applied mathematics, research school of physical sciences, the australian national university, canberra, australia *corresponding author: barry.ninham@anu.edu.au abstract. pollution of drinking water by toxic heavy-metal ions is a matter of concern worldwide. these ions occur naturally, and also from environmental spills, radioactive wastes and other industrial waste. arsenic and lead are typical examples. a novel green surfactant, purpose designed, and environmentally friendly is shown to be extremely effective and specific for heavy metal ion removal. this is a considerable step forward on previous technologies. surfactants have been used universally to remove organic and inorganic contaminants from water. but little selectivity has been achieved. after usage, the residual surfactants are discharged into surface waters or sewage systems. this causes environmental pollution. in this review, three surfactants from different classes (novel green surfactant, synthetic chemical surfactant and biosurfactant) are compared in terms of their efficiency in flotation, removal of different heavy-metal ions, biodegradability, and toxicity level, including their advantages and disadvantages. keywords: ion flotation, green surfactant, chemical synthetic surfactant, biosurfactant, water treatment, toxic heavy metals. 1. introduction low but toxic amounts of heavy metal ions like arsenic occur naturally in drinking water. it is a long-standing problem. it affects millions of people. there has been little progress towards its solution. similar environmental issues of increasing concern are: wastewater from mining operations, battery and electronic manufacturing, the paper industry, radioactive waste disposal, which all pose massive challenges. the discharge of such waste waters into rivers and lakes affect aquifers, discharge into the ocean and can cause serious problems to marine life and to public health.1,2 heavy metals such as chromium (cr), cobalt (co), lead (pb), cadmium (cd), mercury (hg), nickel (ni), zinc (zn) and copper (cu) are not biodegradable and they can accumulate in human tissues. cobalt and chromium are a big problem with joint replacement surgery, and horse racing! another 80 mohammad ziaee, mojtaba taseidifar, richard m. pashley, barry w. ninham example: although zinc is essential for normal function of both eukaryotic and prokaryotic cells and other different human tissues, excessive amounts of zinc cause skin irritation and vomiting.3 another ion, copper is an important element in human metabolism; however, excessive ingestion of copper can lead to spasms, vomiting, and even death.4 heav y-metal ions like radioactive strontium and radium in low concentration are among the most damaging in nuclear waste. so new techniques that allow removal, and especially selective removal of contaminating heavy metal ions, wherever they occur, is a matter of highest importance. the urgent need for separation technologies for rare earth metals for the computer industry reinforce this. in the medical field, a large amount of research has focused on establishing critical heavy metal levels in the human body. for instance, nickel, lead, mercury, cadmium, and chromium can be carcinogenic and cause serious problems for normal human organ function.5-7 the existence of heav y metal ions in industrial wastewater, a matter of global concern, has led to stricter environmental regulations. much research on the removal of heavy metal ions from water has been aimed at several different methods: membrane technology, adsorption, ion exchange, chemical precipitation, and flotation. of these, flotation is a technique of much promise. this method is able to remove heavy metal ions using bubbles and a ‘collector’ in the aqueous phase. in the context of minerals beneficiation, collectors are usually surfactant molecules. they are used in froth flotation of particulates, metal rich minerals that attach to surfactant coated air bubbles. they typically leave unwanted substances like silica and clays behind in the flotation process. there are several processes that use this technique: froth flotation, dissolved air flotation, precipitation flotation, and ion flotation that are well described in references.8,9 ion f lotation derives from the mineral separation industry. it is a technique also capable of removing organic and inorganic contaminants either in anionic or cationic forms from wastewaters.10 currently, ion flotation is in use for the recovery of precious metals, ion separation, and wastewater treatment because of its low energy consumption, inexpensive ancillary devices, flexibility, and a negligible amount of sludge.11,12 a simple schematic of a laboratory scale ion flotation process is depicted in figure 1 and shown in the graphical abstract. the conventional picture of how froth flotation separation of mineral particles works has it that surfactants adsorb onto finely ground hydrophilic mineral particles, selectively converting the required mineral to possess a hydrophobic surface. the continuous flow of a high density of bubbles captures the coated hydrophobic particles and carries them off into the collected foam. naturally hydrophobic particles, such as talc and some mineral sulphides, float naturally, whereas most minerals are hydrophilic and will not float unless coated with an adsorbed layer of surfactant. the selective and controlled hydrophobicity of the mineral particles in a mixture, facilitates the successful selectivity of the froth flotation separation process. our interest is in ion flotation for which the simplest explanation is different but closely related to froth flotation. the important process is that surfactants adsorb to bubbles below the cmc, to provide a monolayer to which the heavy metal ions to be collected adsorb specifically and as the bubbles rise, the surfactant-ion complex can be collected in the froth. at the same time, ions in solution may selectively bind to the surfactant head-group(s) and then be adsorbed at the bubble surface. whichever process dominates, it works and our aim here is to make the process as specific as possible. in this study, the effectiveness of a novel kind of surfactant designed for specificity in the removal of heavy metal ions has been explored and compared with two other standard surfactants. 2. green synthetic surfactants. hints from biology the promise of flotation techniques has not been matched by expectation so far. the goal of selectivity, of specificity, in harvesting heavy metal ions has remained figure 1. schematic diagram of the column setup for ion flotation process. 81selective removal of toxic ions from water/wastewater: using a novel surfactant an elusive eldorado. taking a lesson from biology, from enzymes, we have synthesised novel surfactants that go some way to achieving improved specificity. there are double pluses in this. the most widely used surfactants are made from petroleum compounds. these surfactants are made by a wide range of industries, which themselves produce toxic products for the environment. remediation methods of these surfactants include ozonation, uv radiation and catalyst-coupled auto-oxidations, which are of economic concern. in addition, the levels of co2 liberated by petrochemical processes for the synthesis of the surfactants was found to be as high as 37% in the eu. further, cationic surfactants with quaternary ammonium and pyridinium headgroups widely used in many household and pharmaceutical/ medical applications are potent immunosuppressants (see section 3 below). these difficulties have led to the idea of going green, that is, through the search for a new class of surfactants which are to be obtained from raw renewable materials.13 environmentally friendly, or “green surfactants” can be obtained from natural and renewable ingredients. they should be biodegradable with low toxicity. there are evolving stricter environmental regulations due to increasing concern about traditional surfactants which create health and environmental /water pollution issues. our goal in this search for green surfactants that are ion specific is made easier in that nature has already shown the way. the shape, folding and hydrophobicity that determines structure and function of proteins and enzymes all depend on binding of specific ions to sites with specific dispersion forces and hydration compatibility. there are myriad examples of active sites within enzymes that bind specific, usually divalent, ions that can serve as guides to templates that suggest prototypes for novel synthesised surfactant head groups. 2.1. l-cysteine an exemplar l-cysteine is an amino acid that is biosynthesised in the human body, mostly in keratin-rich tissues, such as nails, hair, and skin which have the highest level of cysteine.14 different cysteine-based green surfactants with suitable hydrocarbon chain lengths can be synthesized by reacting octanoyl chloride and dodecanoyl chloride with cysteine.15,16 such surfactants have many useful properties. they are edible! so, their potential as a soap in industry is immense. for our present problem of heavy metal contamination, then if a slight amount of this surfactant remains in treated water after a flotation process, it will not be harmful for human beings compared to traditional chemical synthetic surfactants. it might even put hair on our chests! 2.2. reaction synthesis below is the standard reaction synthesis method which can be used to obtain different cysteine-based surfactants.15,16 the obtained surfactant was recrystallised in a mixture of ethanol:water (v:v 50:50) twice before using in the ion flotation experiments. 2.3. green surfactant properties these surfactants can be naturally decomposed by enzymes known as peptidases and proteases, a process that takes place in the intestine. the process produces octanoic acid and cysteine, which are both natural and have health benefits. octanoic acid is an organic carboxylic acid, which is found naturally in the milk of various mammals and is a minor component of kernel oil, palm, and coconut oil. octanoic acid (caprylic acid), can also be taken as a  dietary supplement due to its anti-inflammatory and antimicrobial properties. as a consequence, both of the products of this decomposition reaction are compatible with the human body. 2.4. an application to arsenic removal cysteine-based surfactants with different chain lengths were developed and used for removal of low level of arsenic from drinking water.16 single chain octanoylcysteine (s-octanoyl-cys) and single chain dodecanoylcysteine (s-dodecanoyl-cys) have been applied as the collectors in a single stage batch ion flotation process. the o cl hs o oh nh2 in acetone in water 6 ph=8-10, t=10-15 oc 6 o nh cooh sh n-octanoyl-cys (product) figure 2. schematic for the synthesis of octanoyl-cysteine surfactant from octanoyl chloride, in acetone, and l-cysteine in water.16 82 mohammad ziaee, mojtaba taseidifar, richard m. pashley, barry w. ninham results obtained are given in table 1. the single-chain octanoyl-cysteine surfactant was found to have a relatively high cmc value of 0.1 mol/l and showed significant foaming ability. the corresponding values for dodecanoyl cysteine surfactant were found to be 0.009 mol/l. the dodecanoyl-cysteine surfactant, with the lowest cmc value, also showed the lowest solubility in water and the weakest foaming ability. it is necessary to avoid forming micelles, in which the surfactant spontaneously forms surfactant aggregates that make the flotation process less efficient. during the ion flotation experiments here , the initial concentrations of these surfactants were used at about 0.1 of their cmc(s), i.e. at levels of 0.01 m and 0.0009 m, respectively. these experiments were performed at ph = 8 (using naoh 10% w/w), and an initial concentration of 5 mg/l (ppm) for arsenic, as (v) ions. based on table 1, s-octanoyl-cys shows superior affinity with as (v) rather than s-dodecanoyl-cys surfactant. as a consequence, after 60 minutes ion flotation, s-octanoyl-cys was able to remove 97.6% of as (v), while s-dodecanoyl-cys was capable of removing only 53% of the initial arsenic ions from solution. most of the research on the binding process of heav y metals to cysteine is limited to computational studies, however there are few experimental studies based on nmr analyses. it has been reported17 that three cysteine molecules are needed to make the as(cys)3 complex, coordinated with thiolates. this coordination, resulting in a pyramid trigonal site, makes the interaction between as (iii) (arsenite) and sulfhydryl in cysteine group more stabilized; and this demonstrates a possible cause of the toxicity mechanism for arsenic in causing structural distortion of cysteine-based biopolymers. 18 binding of cd ions with cysteine was also studied using 113cd nmr spectrum, which displayed 9 resonances where 8 of them were at the range of 600700ppm, related to s-thiolate coordination for the cd ions. while one resonance occurred at 516ppm, which is destabilised and can be interrupted. this resonance relates to c-terminal cluster of cd ions to the cysteine molecule.19 2.5. the effects of the input gas type the effect of different gases on the efficiency of heavy metal ion removal in the ion flotation process was also examined.15 pure nitrogen and dry air were introduced separately to the bubble column to produce bubbles with an average of about 2 mm diameter. the results presented in table 2 show that air gas was slightly better for ion flotation than nitrogen, removing 99.9% of the arsenic compared with 99.4% for nitrogen (see table 2). mercury was found to have the highest removal rate in the presence of nitrogen gas, at 99.9%; with air, 99.6% was removed. table 2 indicates the results of removing arsenic, lead, and mercury from water using s-octanoylcys as the collector and n2 and air as the inlet gases to produce bubbles. the results presented in table 2, illustrate that the green s-octanoyl-cys surfactant is entirely able to remove lead, mercury, and arsenic ions from aqueous solutions, at levels more than 99%. according to the table, this green surfactant almost gives the same efficiency either using table 1. ion flotation results for the removal of arsenic ions (5 mg/l or ppm) at ph = 8 using different cysteine-based surfactants (reproduced from15). c(surfactant) = 0.01m. surfactant as (ppm) after 30 mins removal (%) after 30 mins as (ppm) after 60 mins removal (%) after 60 mins s-octanoyl-cys 1st crystallized 0.442 91.2 0.120 97.6 s-octanoyl-cys 2nd crystallized 0.135 97.3 0.025 99.5 s-dodecanoyl-cys 2nd crystallized 3.310 33.8 2.34 53.2 table 2. flotation results for of 5 mg/ l (ppm) of different heavy-metals ions using s-octanoyl-cys, c(surfactant) = 0.01m and ph = 8. (reproduced from15). contaminant inlet gas as (ppm) after 30 mins removal (%) after 30 mins as (ppm) after 60 mins removal (%) after 60 mins ref. lead air 0.399 92.0 0.0467 99.1 15 lead nitrogen 0.257 94.9 0.032 99.4 15 mercury air 0.024 99.5 0.020 99.6 15 mercury nitrogen 0.022 99.6 0.002 99.9 15 arsenic air 0.137 97.3 0.006 99.9 20 arsenic nitrogen 0.032 99.4 0.029 99.4 20 83selective removal of toxic ions from water/wastewater: using a novel surfactant air or nitrogen gas. th is high effi ciency is remarkable and suggests that the process could be used to treat water contaminated with heavy metal ions like arsenic (as), which is a naturally occuring toxic element and human carcinogen in countries such as bangladesh, india, brazil and china. its concentration has oft en been increased in ground water due to industrial waste from mining, metallurgy and also the use of toxic substances such as pesticides, in some parts of the world, leading to even greater levels of contamination of ground water and crops.21,22 from these results, it appears that air could be used instead of the relatively expensive pure nitrogen gas to reduce the operation costs of a commercial ion fl otation plant. it is notable that according to world health organisation (who), the acceptable level of heav ymetal ions in drinking water is less than 0.5 mg/l. aft er 60 minutes ion fl otation using the green s-octanoyl-cys surfactant, the concentrations of lead, mercury, and arsenic ions in water are 0.046, 0.02, and 0.029 mg/l, respectively, which are 10 to 25 times lower than the who standard level. following the excellent results for removal of heavy metal ions by using s-octanoyl-cys as the collector, a wide range of heavy metals were examined in a single batch stage fl otation process. removal of eight common heavy metals: cadmium, chromium, strontium, calcium, gold, mercury, lead, and arsenic were determined aft er sixty minutes bubbling.12,15,20 th e initial concentration of each single metal ion was 5 mg/l and the initial concentration of used s-octanoyl-cys surfactant was adjusted to 0.01 m. th ese experiments were carried out at ph = 8 (using naoh 10% w/w) and the results obtained for each single heavy-metal ion are reported in table 3. as the table shows, there is an excellent affinity between the surfactant and various metal ions in the aqueous solutions. th is green biodegradable surfactant is able to adsorb sr, cr, as, hg, cd, pb, and ca ions through a physico-chemical process and remove them from drinking water with high removal rates (%) of 99.8, 99.7, 99.6, 99.4, 99.2, 99.1, and 97.3, respectively. according to table 3, this natural surfactant has less affi nity to bind with gold ions in comparison with other metals examined. it shows a moderate removal rate of 42.4%. gold ions were used in the form of aucl4ions. we have also found12 that the ion fl otation system using s-octanoyl-cys surfactant at an initial concentration of 0.01 m and at ph 8, can successfully remove copper ions at 50 mg/l in aqueous solutions. th e results show a high removal rate for copper ions using this surfactant and in the hydrated form of copper ions, in the sulphate salt, even visual observation shows a noticeable visible blue colour at concentrations higher than about 200 mg/l of cu2+. th e results observed for ion fl otation of copper ions at 500 mg/l indicates that using the s-octanoyl-cys causes this colour to rapidly disappear, which confi rms that the ion-fl otation process should be directed towards the development of novel treatment methods for the removal of heavy-metal ions, such as cu, from mining wastewater. 2.6. selectivity in mixtures of ions extending these results, we have illustrated the removal effi ciency and the selectivity of s-octanoyl-cys to remove several ions in a mixed aqueous solution with initial concentrations of 5 mg/l.12 th ese experiments were undertaken in the presence of an initial concentration of 0.01 m of the surfactant and ph = 8. aft er 60 minutes samples were taken. although this green surfactant showed excellent removal rates for single metal ions in aqueous solution, aft er icp-ms analysis for a table 3. ion fl otation results of diff erent single heavy metals in aqueous solution using s-octanoyl-cys (c(surfactant, initial) = 0.01m, c(heavy metal ion, initial) = 5 mg/l (ppm), and ph = 8). (reproduced from12, 20). single pollutant c (ppm) aft er 30 min removal (%) aft er 30 mins c (ppm) aft er 60 min removal (%) aft er 60 mins cd (іі) 0.27 94.6 0.04 99.2 cr (ііі) 0.33 93.4 0.001 99.7 sr (іі) 0.03 99.4 0.009 99.8 ca (іі) 0.72 85.6 0.13 97.3 au (ііі) 3.12 37.6 3.38 42.4 hg (іі) 0.02 98.5 0.02 99.4 pb (іі) 0.40 92.02 0.05 99.1 as (v) 1.37 72.6 0.02 99.6 figure 3. removal rate of diff erent heavy-metal ions in a mixed aqueous solution using s-octanoyl-cysteine surfactant through a batch stage ion fl otation process (reprinted from ref. 12, with permission from elsevier). 83,6 78,5 43,8 34,6 25,6 16,3 6,3 r em ov al % heavy metal ions 84 mohammad ziaee, mojtaba taseidifar, richard m. pashley, barry w. ninham mixture of metal ions, the results indicated that some of the metal ions were clearly bound more strongly. the removal rate results for an aqueous solution containing seven heavy-metal ions (cu, cr, cd, la, pb, mg, and fe) are depicted in figure 3. based on the data from icp-ms analysis, copper and chromium ions also show strong binding affinity to the surfactant with removal rates of 83% and 78%, respectively. however, in comparison with other heavy-metal ions, iron and magnesium ions exhibited less bonding. the removal rates were 16% and 6% for mg and fe ions, respectively. 2.7. other applications in addition to removal of pollutants from water, there is another significant application for ion flotation. this technique has found its way as a promising separation process with especial interest in heavy metal ions recovery. therefore, further research on the effectiveness of the green s-octanoyl-cys surfactant has been conducted for separation of iron and lanthanum ions in an aqueous solution. for this purpose, a mixed solution of 5 mg/l of lanthanum and iron ions was studied and ion flotation was undertaken using an initial concentration of 0.01 m of s-octanoyl-cys surfactant at ph = 8. after 60 minutes bubbling, samples of solution remaining in the column were taken and the results are reported in table 4. it is evident that besides excellent heav y metal removal capacity of this surfactant, it also can be used to separate or produce specific recovery of some metal ions from a mixed aqueous solution. the table indicates s-octanoyl-cys surfactant has a stronger binding affinity with lanthanum ions rather than iron ions. as a result, la recovery is almost 12 times more than fe removal. 3. chemical synthetic surfactants chemical synthetic surfactants were initially used by sebba23 in a flotation process to concentrate inorganic ions from aqueous solutions. this type of surfactant is widely used in industry since the molecular structures could be designed as they are required. alkane sulfonate, alkylamine, disodiumalkyl malonate, xanthate, sodium oleate, and sodium dodecyl sulfate (sds) have been widely applied in ion flotation.24 besides the advantage of using chemical synthetic surfactants, there are a number of drawbacks to applying them in industry. chemical synthetic surfactants demonstrate considerable biological activity. for instance, anionic chemical synthetic surfactants are able to form bonds with macromolecules such as enzymes, peptides, and dna which might alter their surface charge and vary the folding of the polypeptide chain. this binding can interfere their normal biological functions.25,26 furthermore, quaternary ammonium compounds are the most common type of cationic surfactants. they are known to bind with the inner membrane of bacteria. as a result, this type of chemical synthetic surfactant can disorganise them and affect their normal functions27-32 cationic surfactants are potent immunosuppressants, a fact as widely known as it is ignored. the fact that our cysteine-based surfactants are not toxic and actually edible is highly significant. in addition, non-ionic surfactants demonstrate the ability of binding with phospholipid membranes and different proteins. this binding raises permeability of cellular membranes which can cause cell damage or death due to loss of amino acids and ions.33 it is notable that sodium dodecyl sulfate (sds) is one of the most well-known chemical synthetic surfactant that is used widely in industries. this surfactant is also known as sodium lauryl sulfate. figure 4 illustrates the molecular structure of this anionic surfactant. the effectiveness this surfactant in removing heavymetal ions has been assessed in a number of reports. for example, yenidünya34 applied sds as the collector in an ion flotation process for removing mn2+, cu2+, and zn2+ from water. after 60 minutes flotation, 99.8%, 90.5%, and 73.4% of magnesium, copper, and zinc were removed from the aqueous solution. table 5 shows the results obtained from various studies using sds for removal of heavy-metal ions through ion flotation. according to table 5, although a frother and axillary ligand have been used, the achieved removal rates are table 4. flotation results for a mixed solution of iron and lanthanum, using s-octanoyl-cys surfactant in a batch process. initial concentration of la and fe are 5 mg/l. initial surfactant concentration = 0.01m and ph=8. (reproduced from12). mixed ions c (mg/l) after 30 min removal (%) after 30 min c (mg/l) after 60 min removal (%) after 60 min iron 4.78 4.4 4.6 8.0 lanthanum 1.00 80 0.27 94.6 figure 4. the molecular structure of sodium dodecyl sulfate (sds) as an anionic chemical synthetic surfactant.34 85selective removal of toxic ions from water/wastewater: using a novel surfactant relatively lower than those obtained by s-octanoyl-cys surfactant. tea saponin is uncharged with a cmc value of about 0.72 mm.33 in a recent study,34 tea saponin was used for removing cadmium, lead and copper ions in aqueous solutions. the highest efficiencies were achieved when the tea saponin ratio to heavy metal was 3:1 at ph = 6. the removal efficiency decreased slightly with increasing in ionic strength obtained by adding nacl solutions (in the range 0.001-0.004 m). 4. biosurfactant biosurfactants are known as ecosystem friendly compounds, which are found in plants, animals, and microbes etc. most biosurfactants are found either in anionic or non-ionic form and only a few of them are cationic.42,43 the lipophilic part of these biosurfactants is usually based on long-chain fatty acids. 4 the hydrophilic sector can be an amino acid, cyclic peptide, carbohydrate, alcohol, or carboxylic acid.45 biosurfactants are widely applied as additives in food industry, adsorbents for environmental treatment, and flocculants because of their properties such as biodegradability, low toxicity, and biocompatibility.46 due to stricter environmental regulations, biosurfactants would be the promising alternatives to the traditional chemical synthetic surfactants. the tea saponin molecule, found in camellia plants, is a non-ionic surfactant which has been used in soil and water treatments.47 the molecular structure of this surfactant is depicted in figure 5. a very small number of studies have been conducted to ascertain the effectiveness of heavy metal ion removal using tea saponin biosurfactant in the ion flotation technique. table 5 shows the results obtained for heavy metal removal from water using tea saponin as the collector in an ion flotation process. the removal rates of cu2+, cd2+, and pb2+ from water using this surfactant were found to be 81%, 8%, and 12%, respectively. although tea saponin is a relatively ecosystem friendly biosurfactant, it does not show a satisfactory removal rate for cadmium and lead ions. it is notable that long flotation times and low removal efficiency are the main limits of applying biosurfactants in large-scale water treatment plants. therefore, more research is required on developing biosurfactants to make them of greater practical value in the water treatment industry. 5. summary the na-octanoyl amino acid-based single-chain cysteine surfactant shows a high-water solubility and high foaming ability over a wide ph range. in a batch ion flotation process, this surfactant was able to remove table 5. using sodium dodecyl sulfate and tea saponin surfactants in the process of ion flotation for removing heavy metal ions from water. surfactant pollutants condition removal (%) ref. sodium dodecyl sulphate (sds) zn (іі), mn (іі), cu (іі) cmetal:csds:c axillary ligand =1:5:5, ph = 4 90.5, 99.8, 73.4 35 sodium dodecyl sulphate (sds) cr (ііі) csds : cmetal = 2, ph = 8 91.6 36 sodium dodecyl sulphate (sds) cu (іі), pb (іі), ni (іі), cd (іі), zn (іі) cmetal:csds = 1, ph = 9 97.5, 87.5, 87, 83, 92.5 37 sodium dodecyl sulphate (sds) cd (іі) csds : ccd =3, ph = 4 94 38 sodium dodecyl sulphate (sds) ni (іі), zn (іі) csds : cmetal = 13.5, ph = 9.7 99.8, 90.4 39 sodium dodecyl sulphate (sds) cd (іі) csds : cmetal = 2, ph = 10 99.8 38 tea saponin cu (іі) csurfactant : cmetal = 3, ph = 4 81 40 tea saponin cd (іі) csurfactant : cmetal = 11, ph = 7.5 8 41 tea saponin pb (іі) csurfactant : cmetal = 11, ph = 4.8 12 41 figure 5. the molecular structure of tea saponin molecule as an example of a non-ionic biosurfactant.47 86 mohammad ziaee, mojtaba taseidifar, richard m. pashley, barry w. ninham 97‒99% of the initial 5 ppm level of strontium, lanthanum, arsenic and different heavy metal ions at levels typically present in contaminated water, in a simple, single-stage physiochemical process. the surfactant showed significantly lower efficiency for the removal of iron, selenium and gold ions. in a solution mixed with heavy-metal ions, including arsenic, copper, cadmium, magnesium, lanthanum, chromium, lead and iron, the surfactant shows a higher affinity to bind with arsenic, copper and chromium compared with the others. moreover, the effectiveness of this surfactant for removal of gold ions from aqueous binary mixtures in the presence of iron and mercury ions has been explored. this new surfactant is highly efficient compared with commercial surfactants (e.g., sds and ctab) for ion flotation. importantly, it is also an environmentally acceptable compound. it can be decomposed into cysteine (amino acid) and octanoic acid (caprylic acid), which is taken as a dietary supplement. the surfactant has the potential for wide usage in ion flotation and in froth flotation.48 in the ion flotation experiments reported here, the cysteine surfactant concentration was in the range 10 mm (initially) to 5 mm, whereas the initial metal ion concentrations were in the range: 0.1 mm (for light elements ions such as ca) and 0.025 mm (for the heavy elements, au, hg and pb). hence, in all cases, the surfactant was always present in the batch column process in excess, relative to the metal ion concentrations. it should be noted that in this protocol the surfactant, unlike the ions, was not fully depleted from the column during 60 minutes of bubbling time. that is, the surfactant concentration was approximately halved in the column during the bubbling experiments. hence, the surfactant was always present in the column at a much higher concentration level than the metal ions, during these experiments. these conditions were used to illustrate the relative selectivity of the surfactant for a range of different ions, as shown in the results, from a series of single and mixed ion flotation experiments presented here. by comparison, in a commercial process much longer ion flotation columns would be used to increase the efficiency of ion collection relative to the surfactant concentration, since the surfactant coated rising bubbles will continue to remove ions from the solution until they have reached saturated adsorption densities. 6. conclusions and future prospects we have shown that ion f lotation can be used for the treatment of contaminated waters containing toxic metallic ions. the example given is that of the s-octanoyl-cys surfactant, which can remove a range of low level toxic ions from water. the significant selectivity of this surfactant for some of the ions studied is also most encouraging. it suggests that the ion flotation process could be used to completely separate some specific ion mixtures that pose problems, like rare earth ions. more research and methodological work is needed on how to harvest other valuable ions, such as gold, to reduce the significant costs of current refining processes. the surfactant also showed high efficiency for the removal of relatively high concentrations of copper ions, which could be used as a promising alternative for the treatment of different industrial and mining wastewater. from a sustainability view-point, the surfactant collected in the foam can be released from the bound ion and then re-used to enable recycling of the surfactant. this surfactant also readily decomposes into products which are acceptable for human ingestion. it is also worth mentioning that the commercial development of this process would have a wide variety of applications and can address the global issue of heavy metal ion presence in drinking water. a final observation: many enzymes have an active site, a hydrophobic pocket, centred around a specific ion which is generally divalent. the binding is highly specific and the ion sets the required structure of the hydrophobic pocket that allows the enzyme-substrate lock and key process. for example, with the restriction enzyme hindi 2, the specific ion, e.g magnesium, can be replaced by suboptimal calcium, manganese, copper or nickel. 48 with the suboptimal replacements, the enzyme can still “work”, but not so efficiently and the chain of subsequent reactions is affected. this explains why trace elements are necessary, for both plants and animals, and why small amounts of ions like arsenic are so toxic. that different enzymes bind different trace ions so selectively may provide an entry into a wide range of other novel surfactants. 7. acknowledgments the authors would like to gratefully acknowledge ms. rabeya akter for icp-ms analysis support within the mark wainwright analytical at the university of new south wales. the authors also thank dr fatemeh makavipour for her assistance with the arsenic flotation experiments. the 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taseidifar, a.g. sanchis, r.m. pashley, b.w. ninham, novel water treatment processes, substantia, 2019, 3(2), 11-17. 49. h. k. kim, e. tuite, b. nordén, b. w. ninham, coion dependence of dna nuclease activity suggests hydrophobic cavitation as a potential source of activation energy, eur. phys. j., 2001, 4, 411-417. substantia. an international journal of the history of chemistry 5(1) suppl.: 89-97, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1280 citation: a.h. cutler (2021) steno and the rock cycle. substantia 5(1) suppl.: 89-97. doi: 10.36253/substantia-1280 copyright: © 2021 a.h. cutler. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. steno and the rock cycle alan h. cutler department of engineering, physical and computer sciences, montgomery college, 51 mannakee street, rockville, md 20850 usa e-mail: alan.cutler@montgomerycollege.edu abstract. geologists categorize the basic types of rock according to their origin – igneous, sedimentary, or metamorphic – rather than by their physical properties. this is expressed dynamically by the fundamental concept of the rock cycle, which describes how the basic rock types are derived from one another within the earth system as a result of ongoing cyclic geologic processes. in nicolaus steno’s published geological work, particularly de solido, he takes a similar approach, outlining how a substance can be examined “to disclose the place and manner of its production”. steno also recognizes the roles of erosion, transport, and deposition in the production of sedimentary strata from pre-existing earth materials. his description and diagrams of the geological evolution of tuscany also show a clear cyclicity of process. while the modern concept of the rock cycle did not emerge until the 19th century, steno’s work contains key elements of this important concept. keywords: geology, rock cycle, rock classification, earth processes, nicolaus steno. introduction in his short scientific career, nicolaus steno produced two major works on geology. the first was an addendum to a 1667 report, canis carchariae dissectum caput1, on the dissection of a shark head that he performed in florence for the court of grand duke ferdinand ii. in the addendum steno argued for the organic origin of fossil shark’s teeth and other marine fossils (a contentious issue at the time) and for the sedimentary origin of the enclosing rock. he followed canis two years later with a more expansive work, de solido intra solidum naturaliter content dissertationis prodromus2, which was intended to be an abstract, or prodromus, for a much longer and more detailed study, but this full version never appeared. both canis and de solido include many acute observations on minerals, rocks, and fossils, but de solido in particular is widely regarded as one of 1 n. steno, canis carchariae dissectum caput in steno, n. elementorum myologiae specimen: florence, stella, 1667, p. 90-110. (english translation in steno geological papers (ed: g. scherz) copenhagen, odense university press, 1969, pp. 66-131. 2 n. steno, de solido intra solidum naturaliter content dissertationis prodromus, florence, stella, 1669, 78p. english translation in steno geological papers (ed: g. scherz) copenhagen, odense university press, 1969, pp. 134-234. 90 alan h. cutler the founding documents of the science of geology. it is best known for what geologists today refer to as his principles of crystallography and stratigraphy. both are staples of introductory geology classes and reflect the view shared by steno and modern geologists that mineral crystals and the earth as a whole are not static objects, but dynamic entities with a history of growth and development. in fact, his stratigraphic principles of superposition, original horizontality, and lateral continuity laid the logical foundation for historical geology and the exploration of deep time. my purpose here is to explore how another key concept in modern geology also appears in de solido, albeit in a rudimentary form. this is the so-called rock cycle, which describes how the materials of the earth’s crust are continuously being created, destroyed, transformed, and recycled by geologic processes operating within the earth and on its surface. some elements of this idea have a long history, extending back as far as classical times, and it did not fully take shape until the 19th century with the work of lyell and his contemporaries, so i make no claim here that steno should be seen as the author of the rock cycle concept. rather, this is an attempt to discern what elements of this important geological concept are present, and what are missing, in steno’s work, and the extent to which his conception of earth processes can be considered a coherent rock cycle. the rock cycle the cyclic view of earth processes described by the rock cycle has deep historical roots. aristotle and other classical writers observed marine fossils on land and in the rocks of mountains and proposed that there was a periodic interchange of land and sea3. the idea of cycles in earth’s history appears in the writings of medieval writers in europe and the islamic world, as well as renaissance thinkers such as dante alighieri, and leonardo da vinci4. cyclicity was also a feature of several 17th and 18th century theories of the earth5. these early “rock cycles” were primarily sedimentary. that is, they mostly considered cycles of erosion and deposition of sediment. hutton is generally credited for giving igneous activity a significant role in his version of the cycle6. metamor3 a. cutler, the seashell on the mountaintop, dutton, new york 2003, pp. 8-9.; d. oldroyd, thinking about the earth: a history of ideas in geology, harvard, cambridge, 1996, pp. 7-28 4 pp. 24, 27 in ref. 3, (oldroyd). 5 see s.j. gould, time’s arrow, time’s cycle, harvard university, cambridge, 1987, pp. 21-59 and f. ellenberger, history of geology, v. 2, balkema, rotterdam, 1999, pp. 209-231 for examples. 6 j. hutton, theory of the earth with proofs and illustrations, william creech, phism was later introduced by lyell in his principles of geology 1833.7 figure 1 shows a simplified diagram of the rock cycle, as generally conceived today. the main points of reference are three basic classes of rock: igneous, sedimentary, and metamorphic. each type of rock represents not just the material itself but the geological context and processes that produced it. igneous rock forms as magma or lava cools and solidifies. igneous rock formed from magma that solidifies in the earth’s interior is plutonic rock. igneous rock formed from lava that solidifies on the earth’s surface after an eruption is called volcanic rock. sedimentary rock forms from the raw material of its source rock, which undergoes weathering, transportation, deposition, and ultimately lithification. metamorphic rock forms as pre-existing rock – igneous, sedimentary, or other metamorphic – in the earth’s interior is altered by heat and extreme pressure to create altered rock with new mineralogy and/or texture. as will be discussed in more detail below, the modern rock cycle is far more complex than what steno could have imagined in 1669. accordingly, the following discussion will focus on three underlying aspects of the cycle that are implicit in steno’s work: 1) the classification of rock by its mode of origin (generative classification), 2) derivation of rock from pre-existing earth materials, and 3) cyclicity of earth processes. steno and generative classification classifying materials by their history or origin is a hallmark of geologic thought and has been called “generative classification” by hansen.8 it is different from the approach generally taken by ahistorical physical sciences such as chemistry or physics. a crystal of silicon dioxide (quartz) is silicon dioxide regardless of how, when, or where it formed, but geologists distinguish between a quartzose sandstone (sedimentary rock) and quartzite (metamorphic rock), even though their chemical makeup may be precisely the same. steno makes no attempt in de solido to construct any system for describing or classifying rock, but he lays the foundation for the generative classification approach at the beginning of his de solido as he lays out the general problem he aims to address: edinburgh, 1795. see ref 5 (gould) for discussion of hutton’s cycle. 7 c. lyell, principles of geology, v. 3, facsimile of first edition (1833), university of chicago press, 1991, pp. 374-379. 8 j.m. hansen, on the origin of natural history: steno’s modern, but forgotten philosophy of science, in the revolution in geology from the renaissance to the enlightenment (ed: g.d. rosenberg) geological society of america memoir 23, boulder, 2009, pp. 159-178. 91steno and the rock cycle given a substance endowed with a certain shape, and produced according to the laws of nature, to find in the substance itself clues disclosing the place and manner of its production.9 gould10 argued that one of steno’s most momentous insights in de solido was his decision, as gould put it, “to arrange solids within solids according to the causes 9 p. 141 in ref 2 (scherz). steno’s reasoning here applies a method now termed “abduction”, in which the most likely explanation is sought for a given set of observations. see j.e.h.smith, thinking from traces: nicolas steno’s palaeontology and the method of science, in steno and the philosophers (eds.: r. andrault, r., m. lærke m.), brill, leiden, 2018, pp. 177-200. 10 s.j. gould, hen’s teeth and horses toes, norton, new york, 1984, pp. 69-78. that fashioned them”. gould saw steno’s “great taxonomic insight” as the key to the long-standing puzzle of fossils: were they the true remains of ancient organisms or merely simulacra created by vegetative forces within the earth? steno recognized that organic and inorganic bodies in rock necessarily differed in their place and manner of production. to discern the different origins of solids, steno offered two propositions: i. if a solid body is enclosed on all sides by another solid body, the first of the two to harden was that one which, when both touch, transferred its own surface characteristics to the surface of the other.11 11 p. 151 in ref 2 (scherz) figure 1. typical depiction of the rock cycle. arrows indicate processes and stages in the cycling between igneous, sedimentary, and metamorphic rock. see text for further explanation. adapted from several sources by the author. 92 alan h. cutler and ii. if a solid body resembles another solid body in all respects, not only in the state of its surface but also in the internal arrangement of the parts and particles, it will resemble it also in the method and place of production.12 the first is often referred to as the principle of molding13 and the second as the principle of sufficient similarity14 or the recognition criterion.15 for organic bodies such as mollusk shells, their place of production was outside of the rock matrix that entombed them, or within the matrix, but while it was still soft and unlithified. because their growth was unimpeded by a solid matrix, they invariably showed their characteristic shapes and ornaments without regard to the enclosing material. for inorganic bodies such as mineral crystals and metallic ore deposits, their place of production was within the solid rock matrix, or within fractures and voids within the rock. growing in situ, their shapes were often constrained by the space available, and so did not show the same consistency as organic bodies.16 as for manner of production, steno added a third proposition: iii. if a solid body was produced according to the laws of nature, it was produced from a fluid.17 steno applied this principle to distinguish organic fossils from inorganic mineral growths,18 but he applied it with even more force to rocks and rock strata. in canis he discusses the aqueous origin of sedimentary deposits at length.19 in de solido, steno follows his proposition of the principle of sufficient similarity with this declaration: the strata of the earth agree, in location and manner of production, with those strata that are deposited from turbid water.20 12 p. 151 in ref 2 (scherz) 13 ref 5 (gould) 14 ref 5 (gould) 15 ref 3 (hansen) 16 pp. 111-113 in ref 1 (scherz) 17 p. 153 in ref 2 (scherz) 18 in de solido he argued that organic solids such as mollusk shells grow by addition of material from internal fluids delivered to growing surfaces through pores. in contrast, mineral crystals and other inorganic substances grow by addition of material to their external surfaces from external fluids. steno rejects the idea that crystals grow “vegetatively,” as others had speculated. 19 pp. 99-109 in ref 1 (scherz) 20 p. 151 in ref 2 (scherz) this relates, of course, to the origin of sedimentary rock, which is the type of rock steno primarily observed in tuscany and is the type that most commonly contains fossils. in both canis and de solido he describes graded bedding, the arrangement of sedimentary grains resulting from rapid settling from turbid water, in which larger particles (the first to settle out) are overlain by increasingly fine particles (which settle out more slowly). his description in canis of the depositional process is particularly lucid: if we believe that the water under discussion could receive muddy water, either from the ocean or from torrents, it is certain that the bodies which make the water muddy ought to sink to the bottom when the violent motion ceases. nor do we need to seek diligently for examples of this type, since both the beds of rivers and their estuaries give sure proof of it. one thing should be noted here, – the bodies that make the water muddy are not all the same weight; thus it follows that, as the water gradually calms down, first the heavier particles then the less heavy ones settle out; the lightest particles, however, float longer in the vicinity of the bottom before becoming attached to it. it is clear, in consequence, that frequently different layers will be found in the same sediment.21 he also mentions it in de solido: the larger bodies constrained in these same strata obey for the most part the laws of gravity, not only with respect to the position of any individual body but also the relative positions of different bodies to each other.22 steno also applies the principle of sufficient similarity to sedimentary rock strata in recognizing “place” of production in the sense of sedimentary environment. a marine environment would be indicated by “traces of sea salt, the remains of marine animals, timbers of ships and substances similar to the sea bed”.23 on the other hand, strata containing terrestrial bodies such as pine cones and tree branches would have been laid down by “a river in flood or by a torrential outbreak”, that is, in a fluvial environment.24 steno recognizes another aspect of the place of production, that is, whether a sedimentary particle con21 p. 105 in ref 1 (scherz) 22 p. 161 in ref 2 (scherz). geologists frequently use graded bedding within sedimentary rock strata to interpret tectonically tilted and overturned rock units, as it indicates the original “up” direction in contorted beds. given steno’s invocation of gravity, it is possible that his observations of graded bedding in tuscan strata were instrumental in his formulation of the stratigraphic principle of original horizontality. any graded bedding he observed in inclined strata would have required him to mentally rotate the strata to a horizontal orientation. 23 p. 163 in ref 2 (scherz) 24 p. 163 in ref 2 (scherz) 93steno and the rock cycle tained within sedimentary rock was produced elsewhere and transported to the site of deposition or produced in situ (allochthonous or autochthonous, respectively, in modern terminology). sediments are then formed when the contents of a fluid sink under their own weight regardless of whether these contents have been conveyed there from elsewhere or have been secreted gradually from particles of the fluid itself, either in its upper surface or from all the particles of fluid”.25 in effect, steno appears to recognize the distinction between detrital and chemical sediments. he further notes that autochthonous chemically deposited bodies can be eroded and deposited elsewhere as allochthonous detrital grains. referring to agates, he writes “incrustations of this kind are often found away from the place of production because the material of the place has been scattered by the bursting of the strata”,26 the abraded surfaces of these clasts in deposits being the clue to their allochthonous origin. the principle of molding is applied by modern geologists when determining the allochthony or autochthony of sedimentary grains. allochthonous mineral grains, such as sand grains or pebbles and other larger clasts in detrital rocks, are solid before deposition, so they commonly retain their original shape and do not interlock as the sediment is compacted and lithified. but autochthonous cement minerals that form in situ after deposition during lithification fill in the pore spaces between the allochthonous grains, creating an interlocking crystalline mass that binds the rock together and conforms to the shape of the pre-existing grains. this clastic texture in detrital sedimentary rock, with allochthonous clasts bound together by autochthonous cement, is distinct from the crystalline texture of chemical sedimentary rock such as rock salt or igneous rock such as granite, in which the mineral crystals are dominantly autochthonous and intergrow with one another as the minerals either precipitate from aqueous solution or crystallize from cooling magma. the principle of molding applies here as well: later-growing crystals fill in the spaces between earlier-growing crystals and take their shape from these spaces, allowing the sequence of crystal growth to be determined. geologists apply all three of steno’s principles in describing and classifying rock according to its origin, but nearly missing from steno’s discussion is rock that could be described as metamorphic or igneous. the absence of metamorphic rock from steno’s geology is not surprising; 25 p. 161 in ref 2 (scherz) 26 p. 161 in ref 2 (scherz) it was not recognized as a distinct form of rock until the 19th century. further, metamorphic rock does not form from a fluid, the transformations that create it occur in the solid state. but igneous rock does form from a fluid – magma. though steno makes a brief allusion to volcanoes in his discussion of the origin of mountains, where he writes that mountains can form from “the eruption of fires that belch forth ashes and stones together with sulphur and bitumen”27, nowhere does he mention rock or any solids forming from molten fluids. this is somewhat surprising, given that as a goldsmith’s son he would have been familiar with molten metals. he was certainly aware of writing on volcanoes by kircher and others, and he traveled to elba where he would have had the opportunity to observe granite in outcrop. we can only speculate whether his planned dissertation to follow up de solido would have included a discussion of igneous rock. derivation of rock from pre-existing materials according to the rock cycle, all rock in the earth’s crust is derived from pre-existing materials which have a history that extends backward in time to the formation of the earth. this is an idea implicit in much of de solido, where steno discusses the origins of detrital sedimentary rock and attempts in its last section to lay out a geological history of tuscany, going back to the primordial strata at the time of creation. he makes it explicit in a later sermon: this holds for diamonds and all precious stones whose matter certainly was created at the beginning of time with the other material of the universe, and was mixed with the other particles of solid and fluid bodies until, after the destruction of the earth it was secreted in old subterranean caves and took shape now to be used by human toil to be used for its own purposes.28 in the sermon, steno’s intention is not scientific, but theological – he attributes minerals “not created by god, but after the malediction of earth” to the curse on adam after the fall.29 the concept of a history of recycling behind geological materials is clear enough, however. in de solido steno describes a fossil shell he recognized as having been reworked from a deposit older than the deposit where it was found: 27 p. 167 in ref 2 (scherz) 28 steno, n. “ornaments, monuments, signs, arguments” in steno geological papers (ed: g. scherz) copenhagen, odense university press, 1969, p. 251. 29 p. 251 in ref 23 (scherz) 94 alan h. cutler a shell, partly destroyed internally, in which a marble incrustation, covered by various balanoids, had replaced the substance eaten away; thus it is possible to conclude with certainty that the shell had been left upon the land by the sea, then carried down to the sea, covered again by a new deposit and abandoned by the sea.30 he bases this conclusion on his taphonomic observations that the shell had diagenetic features (the marble encrustation, which implied previous burial and lithification) that were overlain by marine barnacles (balanoids), implying a second exposure in a marine environment before ultimate burial in the sedimentary stratum in which it was found. not only are fossils recycled and preserved, but rock particles can be as well. steno notes that “fragments of another stratum” can be found in a stratum, making it “certain that the said stratum must not be counted among the strata that settled out of the first fluid at the time of creation”. cyclicity of earth processes two aspects of the cyclicity of earth processes as described in the modern rock cycle deserve mention. the first is that the rock cycle has no set time frame. that is, the stages or transitions described in the cycle can occur over time scales ranging from very short (days, or even less) to very long (billions of years). erupted volcanic ash can become “sediment” virtually instantly upon eruption, whereas plutonic igneous rock can remain uneroded and unmetamorphosed for billions of years. this lack of a regular time frame distinguishes it from many familiar cycles in science, such as astronomical and seasonal biological cycles. more to the point for the discussion here, though, is that this lack of a set time frame distinguishes the question of the cyclicity of earth processes from the question of the cyclicity of time itself. the conflict between cyclic models of time (as conceived by aristotle, for example) and linear models of time (as laid out in the bible) has been discussed a length elsewhere.31 while a cyclic model of time necessarily implies a cyclicity of processes, linear models of time can also easily accommodate subordinate cyclicity. for this reason, steno’s religious faith and commitment to the biblical narrative of creation would have posed no necessary impediment to his acceptance of cyclic processes. 30 pp. 195-197 in ref 2 (scherz) 31 s. toulmin and j. goodfield, the discovery of time, university of chicago, chicago, 1982, 280 p.; s.j. gould, time’s arrow, time’s cycle, harvard university, cambridge, 1987, 222 p.; and many others. a second aspect of the rock cycle is that it does not necessarily follow the set sequence shown by the outer circle of arrows in the figure 1. igneous rock is not inevitably eroded to create sediments and sedimentary rock, sedimentary rock is not inevitably altered to become metamorphic rock, and, finally, metamorphic rock is not inevitably melted to create magma and igneous rock. as the arrows passing through the circle illustrate, rock of any type at any stage of the cycle can be uplifted and weathered to produce sediments, and igneous rock can be altered to become metamorphic rock without any intermediate conversion to sediment or sedimentary rock. finally, though not shown on the diagram, igneous rock can be re-melted to create magma which then crystallizes into new igneous rock, and, similarly, metamorphic rock can be “re-metamorphosed” by changing conditions to make new metamorphic rock. as discussed above, steno makes no mention of the igneous and metamorphic elements of the rock cycle, aside from some passing references to fire and heat. for this reason, the kinds of transformations and cycleswithin-cycles possible within the modern cycle do not appear in steno’s version of the cycle. it is essentially a sedimentary rock cycle. the part of the sedimentary rock cycle that steno devotes most of his attention to in de solido is sedimentation, including the formation of graded bedding, as discussed above. oddly, despite his emphasis on the hardening of sediments into rock in his principle of molding, steno offers no account of lithification, besides a few scattered hints. in canis he describes precipitation of dissolved bodies from transparent liquids to produce solids and observes that lime and gypsum can bind together fossil shells.32 in de solido, following his proposition that all solids are produced from fluids, he discusses at length the growth of mineral crystals, incrustations and organic tissues but makes no clear reference to either the compaction of sediments or the cementation of sedimentary grains. the next stage of the rock cycle, in which rock buried within the crust becomes exposed to surface weathering and erosion, gets more attention from steno. this stage happens either by uplift, raising marine strata above sea level, for example, or by a drop in sea level, exposing the former sea bottom to subaerial weathering and erosion. either way, whether it is the land that rises or the water level that drops, this is a key step in the rock cycle. it makes the rock available to become broken down to become sediment and ultimately new sedimentary rock. steno describes both uplift and sea level change in de solido. 32 pp. 105-109; p. 97 in ref 1 (scherz) 95steno and the rock cycle steno states that “mountain peaks can be raised and lowered”33, attributing their formation mainly to the “alteration in the position of strata”.34 how does this happen? steno proposes two mechanisms: the first way is the violent upheaval of strata, whether this be due mainly to a sudden flare of subterranean gases or to a violent explosion of air caused by other great subsidences nearby. this upward thrust of strata is followed by the dispersal of earthy material as dust and the shattering of rock material into pebbles and rough fragments.35 and the second way is a spontaneous slipping or subsidence of the upper strata after they have begun to crack because of the withdrawal of the underlying substance of foundation; in consequence the broken strata take up different positions according to the variety of cavities and cracks.36 in his second mechanism, the relative uplift and tilting of rock strata can be the result of collapse of cavities within the earth37. this would not in itself raise the overall elevation of the rock strata, but it would create a more irregular land surface, with local highs creating mountains. steno suggests that progressive internal collapse over time has made land surface more irregular: it is completely uncertain what the depth of the valleys was at the beginning of the deluge; but reason persuades us that, in the first centuries of the world’s existence, cavities were gnawn [sic] out by water and by fire, so that slight collapse of strata followed from this; however, the highest mountains, of which scripture mentions, were the highest mountains then found, not the highest of those observed in the present day.38 as for sea level fall, the collapse of caverns described above could also open passageways into the earth for surface water to drain, thus lowering sea level. this is the hypothesis steno favors. who has investigated the structure of the interior of the 33 p. 169 in ref 2 (scherz) 34 p. 167 in ref 2 (scherz) 35 p. 165-167 in ref 2 (scherz) 36 p. 167 in ref 2 (scherz) 37 descartes also invoked crustal collapse as mechanism for producing relief on the earth’s surface in his principia philosophiae, amsterdam. apud ludovicum elzerverium, 1644. see ref 3 pp. 45-47 (oldroyd) for a description of descartes’ model. 38 p. 207 in ref 2 (scherz). steno illustrates these inferred caverns de solido in his depiction of the evolution of tuscany (21 and 24 in figure 2), discussed below. earth and will dare deny the possible existence of huge spaces there, at times filled with aqueous fluid, at other times filled with aerial fluid? 39 as for a subsequent rise in sea level that precedes the next cycle of sedimentation, steno’s mechanism is more complex. he proposes that volumes of water in the earth’s subterranean chambers could be heated by internal fires, causing it to be expelled to the atmosphere and fall as rain, which would then presumably cause the oceans to overflow onto the land. he also suggests that the bottom of the sea could be “raised up by the expansion of subterranean caverns.”40 this may be reference to the hypothesis of the greek geographer strabo, who in an effort to explain marine shells found on land suggested that periodic upward flexing of the sea floor could displace ocean water and thus raise sea level.41 rock strata uplifted and exposed, by whatever mechanism, are then weathered to produce sediment, which is eroded and transported to its site of deposition. the first step, the slow breakdown of rock by weathering, is not directly addressed by steno. in de solido, he attributes the “dispersal of earthy material as dust and the shattering of rock into pebbles and rough fragments” to the “violent upheaval” and “upward thrust” of rock strata.42 sediment transportation is described by steno in de solido in several passages, emphasizing the “great quantity of earth” carried to the sea every year by rivers and “innumerable torrents.43 steno sees this as an ongoing process, with new sediment “added daily” to coastal deposits. this completes steno’s cycle, with these deposits potentially forming new rock strata. cycles in the geological evolution of tuscany figure 2 shows steno’s conception of the geological evolution of tuscany, which represents two cycles of sedimentation in six “aspects”. two aspects (22 and 25) represent marine deposition, two (21 and 24) represent the hollowing out of subterranean caverns (perhaps associated with the draining away of surface waters and the drop in sea level), and two (20 and 23) represent the collapse and shifting of strata to produce an uneven landscape. steno describes the first episode of deposition (25 in figure 2) as occurring when “everything was cov39 p.207 in ref 2 (scherz) 40 p.209 in ref 2 (scherz) 41 f. ellenberger, history of geology, v1, balkema, rotterdam, 1996, p.22 42 p.165-167 in ref2 (scherz) 43 p.209-211 in ref 2 (scherz) 96 alan h. cutler ered by water”44, as described in genesis. these strata were deposited by the first fluid “devoid of plants, animals, and other solids.” he does allow the possibility that younger strata containing “various bodies” might in some places lie unconformably above the primal strata laid down by the first fluid, but these younger strata are not shown in the diagram. also not shown in the diagram is any indication of a source for the sediments in these original strata. in a time when the entire world was covered by water, there would have been no exposed land to supply detrital sediments. it may be that steno conceived these sediments as being chemical sediments derived from materials dissolved in the first fluid at creation. in fact, the actual strata corresponding to those in the diagram are detrital turbidite sediments, consisting of well-sorted, fine-grained sands, which steno likely saw in his travels around tuscany.45 the uniformity and fine size of the sediments, and the lack of visible fossils, convinced steno of their primordial origin. earlier in de solido he writes: if all particles in a stony stratum are observed to be of the same nature and of fine size, it cannot reasonably be denied that this stratum was produced at the time of creation from a fluid that then covered all things: descartes, too, accounts for the origin of the earth’s strata in this way.46 the second episode of deposition (22 in figure 2) steno attributes to the deluge. steno notes that mountains existed at that time, according to scripture. the diagram shows first-cycle rock strata (f-g in figure 2) at higher elevations than strata (b-a-c) deposited 44 p. 205 in ref 2 (scherz) 45 s. dominici, journal of mediterranean earth sciences, 2009, 1, 101110. 46 p. 163 in ref 2 (scherz). steno’s mention of descartes refers to the model presented in ref 33 (descartes). in descartes’ model the solid particles producing the earth’s strata are “corpuscles” of matter, rather than sedimentary grains. during the second cycle, so these presumably provided the source for these sediments. it is less clear, however, if steno intends that all these strata formed during that single event, because in several places in de solido he explicitly considers multiple marine incursions into tuscany. marine strata containing the “timbers of ships”47 are clearly post-diluvial, and steno cites approvingly the ancient accounts of “earth movements, eruptions of fires from the earth, flooding by rivers and seas” as demonstrating that “many and various changes have occurred in four thousand years” since the deluge.48 it would appear then, that while steno is careful to reconcile his scenario with scripture, he conceives his rock cycle as not only a natural, but an ongoing process. conclusion in steno’s geological works, canis and de solido, he lays out the elements of a functional, if in modern terms incomplete, rock cycle. missing, of course, are igneous and metamorphic rocks, and he also gives little attention to the processes of lithification and weathering. however, the three key aspects of the rock cycle mentioned above are well-represented in steno’s work, especially in de solido: 1. classification of rock by its mode of origin (generative classification). steno introduces this idea at the outset of de solido, and he applies it in both works to argue for the sedimentary origin of rock strata, as well as to make the distinction between chemical and detrital sediments, and to discern sedimentary environments of strata. his principles of molding and sufficient similarity, which form the basis of generative classification, would later find application to other rock types as well, such as plutonic igneous and metamorphic, of which steno was unaware but are fundamental parts of the modern rock cycle. 2. derivation of rock from pre-existing earth materials. steno is clear that sedimentary strata can be composed of recycled material eroded from older rock. moreover, his principles of reasoning allowed him to recognize this material in strata. in contrast with modern understanding, however, he considers the oldest exposed rocks in tuscany to be primordial and therefore a product of the original creation. 3. cyclicity of process. in de solido steno proposes natural mechanisms for uplift and sea level change. he also describes ongoing processes of erosion, transport, 47 p. 163 in ref 2 (scherz) 48 p. 211 in ref 2 (scherz) figure 2. steno’s diagram of the geologic history of tuscany in de solido, showing two cycles of sedimentation and mountain-building. time sequence goes from lower right (25) to upper left (20) in reverse numeric sequence. from reference 2 (steno). 97steno and the rock cycle and sedimentation. further, in his outline of tuscany’s geologic history, he recognizes two major cycles of sedimentation, and hints at later, smaller-scale cycles. steno’s stated purpose in de solido was to account for the existence of solid bodies, such as fossils and mineral crystals, inside of solid rock, not to create an overarching theory of the earth. still, despite some gaps and inaccuracies, steno’s rock cycle as it appears in his work, supported by his principles of molding and sufficient similarity, constituted a forerunner of the modern rock cycle concept. acknowledgements i want to thank stefano dominici for organizing the 2019 symposium, “galilean foundation for a solid earth 1669-2019: 350th anniversary of nicolaus steno’s prodromus”, where an early version of this paper was presented. my participation in that event was made possible by montgomery college eap funds. i am grateful to stefano dominici, gary rosenberg, and victor baker for their insightful comments and suggestions, which substantially improved the manuscript. thanks also to amy cutler for preparing figure 1. references cited cutler, a. (2003) the seashell on the mountaintop, dutton, new york, 228 p. descartes, r. (1644) principia philosophiae, amsterdam. apud ludovicum elzerverium. dominici,s. (2009) steno, targioni, and the two forerunners. journal of mediterranean earth sciences, 1: 101110. ellenberger, f. (1996) history of geology, v. 1, balkema, rotterdam, 299 p. ellenberger, f. (1999) history of geology, v. 2, balkema, rotterdam, 404 p. gould, s.j. (1984) the titular bishop of titiopolis, in hen’s teeth and horses toes, norton, new york, pp. 69-78. gould, s.j. (1987) time’s arrow, time’s cycle, harvard university, cambridge, p. 222. hansen, j.m. (2009) on the origin of natural history: steno’s modern, but forgotten philosophy of science, in the revolution in geology from the renaissance to the enlightenment (ed: g.d. rosenberg) geological society of america memoir 23, boulder, pp. 159-178. hutton, j. (1795) theory of the earth with proofs and illustrations, william creech, edinburgh, p. 567.. lyell, c. (1833) principles of geology, v. 3, facsimile of first edition, university of chicago press, 1991, 398 p. oldroyd, d. (1996) thinking about the earth: a history of ideas in geology, harvard, cambridge, 410 p. smith, j. (2018) thinking from traces: nicolas steno’s palaeontology and the method of science, in steno and the philosophers (eds.: r. andrault, r., m. lærke m.), brill, leiden, 2018, pp. 177-200. steno, n. (1667) canis carchariae dissectum caput in steno, n. elementorum myologiae specimen, florence, stella, p. 90-110. (english translation in steno geological papers (ed: g. scherz) copenhagen, o dense university press, 1969, pp. 66-131. steno, n. (1669) de solido intra solidum naturaliter content dissertationis prodromus, florence, stella, 78p. english translation in steno geological papers (ed: g. scherz) copenhagen, odense university press, 1969, pp. 134-234. steno, n. (1675-1677) ornaments, monuments, signs, arguments in steno geological papers (ed: g. scherz) copenhagen, odense university press, 1969, pp. 249-267. toulmin, s. and j. goodfield, the discovery of time, university of chicago, chicago, 1982, 280 p. substantia. an international journal of the history of chemistry 4(1): 5-6, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-816 editorial peer review – critical feedback or necessary evil? seth c. rasmussen department of chemistry and biochemistry, north dakota state university, fargo, nd 58108 usa email: seth.rasmussen@ndsu.edu anyone who has participated in scientific publishing, either as author or editor, has dealt with the process of peer review. of course, individual opinions on peer review vary, with viewpoints ranging from it being an important part of ensuring the quality and reliability of scientific publications, to thoughts that the process as a whole is completely broken. unfortunately, it also seems that authors often look at peer review as being a painful exercise forced upon them by journals, while those serving as reviewers too often see it as something expected of them, but not important enough to spend considerable effort performing. before discussing various points of the peer review process, however, it is worth considering where this process began. current historical studies generally suggest that the modern process of formalized peer review developed in the 19th century and grew slowly and haphazardly, encountering skepticism and criticism along the way. one such recent study by melinda baldwin1 suggests that the practice of soliciting written reviews by specialists found its origins in 1831, when william whewell (1794-1866) proposed that two fellows of the royal society should write their views on submissions to the journal philosophical transactions, after which the written reports would be published in the new journal proceedings of the royal society of london.2 while the plan to publish the reviews was abandoned, the practice of sending submitted papers out for refereeing endured and by the mid-19th century, coordinating refereeing was one of the chief responsibilities of the secretaries of the royal society. in germany and france, however, refereeing remained relatively uncommon throughout the 19th and early 20th centuries. although it had been originally 1 m. baldwin. isis 2018, 109, 538. 2 a. csiszar. nature, 2016, 532, 306. intended for the referees’ identities to be known to both the author and the journal’s readers, the royal society quickly decided that referees would give more candid advice if they remained anonymous. thus, the modern practice of referee anonymity has been part of peer review since very early in its history, with the most common form referred to as single blind peer review (i.e, only the reviewer’s identities are anonymous). prior to this modern form of peer review, other practices had sought to fulfill some of the same goals. one common practice by some scientific societies was that papers were required to first be orally presented at the meeting of the corresponding society, at which it could be vetted through discussion among the meeting participants. this practice, however, resulted in a number of famously long delays in the publication of critical works. some societies had other internal practices for evaluating the work of their members before it was circulated,3 but those systems have not been viewed to be ones that led to the modern form of systematic external refereeing. in germany, some of the most prominent journals were controlled by powerful editors who preferred to make decisions without relying on the opinions of others, although they would sometimes add their own personal critical comments as editorials after select papers, thus providing review in some form. of course, many have voiced dissatisfaction with modern peer review, citing problems with bias,3,4 problems of objectivity and the ability to gauge reliability or importance, and the opinion that traditional refereeing is antiquated. such views have led to the conclusion by some that the system has broken down and has become 3 c. j. lee, c. r. sugimoto, g. zhang, b. cronin. j. am. soc. inf. sci. technol. 2013, 64, 2. 4 c. j. lee. philosophy of science, 2015, 82, 1272. 6 seth c. rasmussen an obstacle to scientific progress.2 as a response, some publishers have attempted to introduce new forms and variants of peer review, including double blind review,3 open review, and post-publication peer review.5 double blind review, in particular, aims to remove the author’s identity and thus protect the author against forms of social bias.3 however, even without knowledge of the author names, all too often it is easy to discern the identity of more established authors in your field and thus bias favoring established authors and hindering newer authors still remains. personally, as an author, i am always disappointed with negative reviews. still, i try to view the overall review exercise as a positive process. i have always realized that my published work is a permanent record and the last thing i would ever want is to include a stupid mistake that will never go away. as such, i always pray that reviewers catch any such possible errors. even when reviewers fail to understand the point of the work submitted, or i view the reviewer’s comments to be in error, this usually leads to a stronger publication. as i always strive to make my publications clear and approachable to the lay reader, such misunderstandings on the part of reviewers result in additional efforts on my part to focus the message or further improve the clarity of my arguments. in that respect, i will always view peer review as a critical part of the publication process, despite its potential flaws. as a reviewer, i think that my experience as the recipient of peer review influences the way that i provide criticism, as does my decades as an educator. in that respect, i have come to regard peer review as much more than just pointing out errors in the experimental methods or in the interpretation of results. that is, i have come to approach each review as a teachable moment and present my comments in nearly the same way as when i am revising the writing of my graduate students. the goal too is really the same, helping the authors to improve their paper and make it the best it can be. this, of course, includes ensuring that the methodology and analysis is sound, but also includes things like ensuring that prior work on the topic has been properly credited and acknowledged, correcting misconceptions that have crept into the literature, and ensuring that the paper is written in a clear fashion, such that it can be understood by others less familiar with the subject. along the way, i will suggest alternate wording to improve clarity or remove errors in terminology, and i always try to back up more significant criticisms with specific references for 5 e. stoye. chemistry world 2015, january 12th, https://www.chemistryworld.com/news/post-publication-peer-review-comes-of-age/8138.article (accessed sept. 19, 2019). the authors to consult. furthermore, i try to approach every review the same, whether the manuscript is from one of the top researchers in my field or from those that have little to no prior experience with the topic. to write a good review, however, takes both effort and time. in addition, it necessitates a sound understanding of the fundamental concepts dealt with in the paper under review. unfortunately, as an editor, i find that many reviewers are either unwilling to contribute the time and effort required to provide a quality review, or simply lack the ability to do so. because of this, journals that want to ensure high quality peer review really need to actively cultivate a pool of reviewers that are committed to taking peer review seriously, rather than just a task to be completed as quickly and effortlessly as possible. of course, this too requires time and effort, and it means keeping track of both reviewers and the quality of their reviews, both good and bad, and then finding ways to encourage the better reviewers to keep accepting future reviews for their journals. in this respect, a number of journals and publishers have done a much better job at recognizing top reviewers for their efforts in recent years.6 lastly, it is important to remember that the value of peer review goes beyond the scientific community and impacts everyone, both the expert and the public at large. we are at a point where public trust in science is diminishing7,8 and traditions that instill confidence in science are critical. as the process of peer review developed, the referee was gradually reimagined as a sort of universal gatekeeper, with peer review emerging as a mighty public symbol that scientists had a structured process for regulating themselves and for producing consensus in science.2 thus, while it may have its flaws, peer review is still the best way to ensure that scientific literature is sound, correct, and presented without bias. if we want the public to feel that they can depend on scientific studies and presented results, then we need to do everything we can to make sure that the scientific literature is as absolutely strong as it can be. 6 a. meadows. recognition for review: who’s doing what? https:// orcid.org/blog/2016/09/20/recognition-review-who%e2%80%99s-doingwhat (accessed sept. 22, 2019). 7 g. tsipursky. (dis)trust in science. sci. am. 2018, https://blogs.scientificamerican.com/observations/dis-trust-in-science/ (accessed sept. 22, 2019). 8 g. c. kabat. embo rep. 2017, 18(7), 1052 (doi: 10.15252/ embr.201744294). https://www.chemistryworld.com/news/post-publication-peer-review-comes-of-age/8138.article https://www.chemistryworld.com/news/post-publication-peer-review-comes-of-age/8138.article https://www.chemistryworld.com/news/post-publication-peer-review-comes-of-age/8138.article https://orcid.org/blog/2016/09/20/recognition-review-who%e2%80%99s-doing-what https://orcid.org/blog/2016/09/20/recognition-review-who%e2%80%99s-doing-what https://orcid.org/blog/2016/09/20/recognition-review-who%e2%80%99s-doing-what https://blogs.scientificamerican.com/observations/dis-trust-in-science/ https://blogs.scientificamerican.com/observations/dis-trust-in-science/ substantia an international journal of the history of chemistry vol. 4, n. 1 2020 firenze university press peer review – critical feedback or necessary evil? seth c. rasmussen particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 consciousness, information, electromagnetism and water marc henry leonardo and the florence canal. sheets 126-127 of the codex atlanticus filippo camerota the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí astatine – the elusive one keith kostecka vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of xx century aleksander sztejnberg article training of future chemistry teachers by a historical / steam approach starting from the visit to an historical science museum valentina domenici1 1 department of chemistry and industrial chemistry, university of pisa, via moruzzi 13, 56124 pisa, italy. * corresponding author: valentina.domenici@unipi.it web-site: http://smslab.dcci.unipi.it/ & https://smslab.dcci.unipi.it/progetti-stem.html received: jul 20, 2022 revised: nov 06, 2022 just accepted online: nov 08, 2022 published: xxx this article has been accepted for publication and undergone full peer review but hasnot been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: domenici v. (2022) training of future chemistry teachers by a historical / steam approach starting from the visit to an historical science museum. substantia. just accepted. doi: 10.36253/substantia1755 keywords high order thinking skills, education, history of chemistry, stem, steam, historical teaching approach, inquiry-based learning, hands-on activities. mailto:valentina.domenici@unipi.it http://smslab.dcci.unipi.it/ https://smslab.dcci.unipi.it/progetti-stem.html abstract the visit to a scientific historical museum represents a great opportunity for future science teachers to develop educational activities and effective laboratories for high school and first year undergraduate students. in this paper, a pilot educational project experimented in the frame of the course of ‘fundaments and methods of chemistry education’ held at the university of pisa (italy) during the academic year 2019-2020, aimed to train future chemistry teachers, is described. the main steps of the project, from the visit to the museum ‘galileo’ in florence (italy) to the design of educational hands-on activities by the undergraduate students, are discussed. emphasis will be given to the role of historical scientific collections, such as the galilean thermoscopes and other historical thermometers’ collection, in stimulating the creativity and higher order thinking skills. 1. introduction non-formal learning and teaching are considered important aspects in science education as well as in chemistry education.1-4 since the european community has recognized the role of life-long learning and its impact on the education of aware citizens,1,2 non-formal contexts started deserving the attention of scientists dealing with education and in particular science education. among non-formal contexts, science museums5-8 and scientific festivals, as typical example of contexts hosting openscience and outreach activities,9-11 were the object of several research studies focusing on their role in increasing the scientific literacy and the engagement of students toward science.5-13 several papers, published in the recent years, show that out-of-school programs and outreach activities designed for children, families and/or for school students are effective in terms of acquired knowledges and skills in specific topics about science and technology.14-18 traditional science museums, historical collections linked to high schools or universities and interactive science centres are nowadays strongly connected with schools of any levels, from primary to high schools, and they have developed numerous activities, mainly laboratorial and interactive ones, where science is presented in its relationship with society and with other disciplines.5,7,8,18 this approach is an effective alternative to the more traditional and scholastic ways of teaching science through its concepts, laws and more formal aspects. on the other hand, science teachers’ training is now focused on a more multidisciplinary and interdisciplinary approach,18 which is also referred to as the so-called stem (science, technology, engineering, and mathematics) teaching and learning philosophy.19 according to this idea, students are encouraged to ‘think as a scientist’, developing high order thinking skills, such as the ability to solve complex problems by using knowledges and competences typical of different disciplines. in the recent years, this teaching method evolved towards the steam approach, which includes ‘arts’ to the stem.20-23 however, the letter ‘a’ in the steam acronym has a more general meaning: it can be extended to all human disciplines, such as music, history and languages. the basic idea of this teaching and learning method is that a multidisciplinary approach, combining scientific and logical thinking with creativity and multiple intelligences,21-23 can help students to understand the complexity of the real world and possibly find new solutions to everyday life problems. this teaching approach has influenced chemistry education, too. the role of human disciplines, such as history and philosophy, as well as the multidisciplinary approach and the use of contextual or situated educational methods24 to teach chemistry at high school and undergraduate levels can be related to well-known chemistry education models, such the tetrahedral model proposed first by peter mahaffy25 and then structured and reinterpreted by talanquer26 and sjostrom,27,28 who added relevance dimensions and explained different levels of chemistry understanding and implications in chemistry education. within the tetrahedral chemistry education model and its variants,25-28 teachers are invited to analyse different facets of chemistry education, such as the pedagogical, sociological, ethical, historical and philosophical ones,29 when working with their students. in line with this model,25-28 the use of historical approaches to teach chemistry at different school and university levels30,31 and the introduction of specific courses of ‘history of chemistry’ and ‘chemistry, ethics and society’32-35 in the curriculum of future chemists represent additional elements of novelty in chemistry education. based on these premises, historical science museums and collections of historical objects, such as glassware, scientific instruments, historical books and reactants, as well as ancient artifacts,6-8,18,30-39 acquire novel roles and values for chemistry teachers who can take advantage of such contexts to teach specific chemical topics and try to engage them with more interactive teaching methods. in this paper, a pilot educational project40 experimented upon in the frame of the course of ‘fundaments and methods of chemistry education’ held at the university of pisa (italy) during the academic year 2019-2020, and aimed to train future chemistry teachers, is reported.41,42 the details of the methodology optimized and experimented within this course of chemistry education are reported and discussed in a previous paper.18 here, the main steps of the teaching method and the pilot educational project, from the visit to the museum ‘galileo’ in florence (italy)43 to the design of educational laboratorial activities by the undergraduate students, are described and commented on. emphasis will be given to the role of historical scientific collections, such as the galilean thermoscopes and other historical thermometers,44-47 in stimulating the creativity48 and higher order thinking skills in future chemistry teachers. 2. the teaching method 2.1 the course of chemistry education to train future chemistry teachers the course of ‘fundaments and methods of chemistry education’ of the degree in chemistry at the university of pisa41,42 has been active since 2013 and it is included in the national training program and ‘public national competitions’ for chemistry teachers to be employed in the secondary schools. as reported in ref. 18, the course is an optional one (3 cfu; total of 24 hours of lessons in the first semester of the third year of the degree course in chemistry) and it is structured with initial 10-12 hours of lessons aimed to introduce students to the main pedagogical theories and the fundaments of the most used active teaching strategies applied to chemistry education. emphasis is given on the inquiry-based education and problem-solving methods, different kinds of laboratorial strategies, the basis of the cooperative learning and peer education, and, among the structured knowledge approaches, the ‘conceptual maps’ method. during these first introductory lessons, students are asked to master these interactive teaching strategies, to read the materials provided during the lessons, through the e-learning platform,42 to answer some on-going (in itinere) interactive quiz and to prepare short presentations. the second part of the course (about 12-14 hours of lessons plus additional extrahours of activities) is focused on examples of interactive activities aiming to show the best practices in teaching chemistry at intermediate and high schools (from k6 to k12 levels, corresponding to students of the age from 11 to 18 years old). in this second part of the course, a teaching methodology, developed in the last ten years to train future chemistry teachers, called ‘steam project-based learning’,18 is applied, as will be discussed in the following paragraph. at the end of the course, students are required to present and discuss a didactic sequence or an educational project, designed and discussed during the second part of the course, in extra-time hours. to prepare the educational activities, students are encouraged to work in group of three-four units according to the cooperative learning method. moreover, students are invited to follow an instruction scheme, which refers to a hierarchic instructional model,2,18 which is usually discussed during the progress of the course. finally, the educational projects designed by students can be put into practice with real school students or with children or families in non-formal contexts, such as science museums, or during open days organized at the dipartimento di chimica e chimica industriale, or they can be presented at festivals of sciences, such as the one organized in genova.9,18,49-52 2.2 scheme of the ‘steam project-based learning’ teaching methodology the scheme of the ‘steam project-based learning’ methodology18 adopted within the course to train future chemistry teachers is structured in nine steps: 1) visit at the science museum. a visit at a natural or historical science museum, is organized at the beginning of the course in order to get inspiration and to know all key-aspects of a typical non-formal context. 2) brain storming and collective discussion. during the visit, students are stimulated to observe the collections and activities carried out at the museum. some guided questions are given in order to stimulate students’ thinking. thereafter, a brain storming followed by a collective discussion is performed with the aim of allowing discussion on specific topics related to chemistry to emerge. 3) selection of the main topics of the project. students usually select few key topics from the previous collective discussion, such as ‘mixture among chemical substances’, ‘the history of the separation techniques’, ‘colorimetric chemical reactions’, ‘the chemistry of pigments’, and so on. the selected topics are usually strongly related to the museum and to the scientific collections. 4) design of the educational activities. once the topics have been selected, students start designing the educational activities, which are normally structured following a general hierarchical scheme provided and discussed during the lessons. it is important that the students decide first what the target is (children, families, high school students, …), the context (formal, like a school class, or non-formal, like a laboratory at the science museum) and the main objectives of their educational project. this is the core of the ‘steam project-based method’, where students’ knowledges and creativity combine giving rise to the development of higher-order thinking skills. 5) preparation of the materials. the design of the educational activities encourages the students to ask themselves how to put the project into practice, estimate the timing of activities, search for the best materials, such as reagents, bearing in mind safety and environmental issues. 6) simulation in class. when the educational activities are ready, an important step of the methodology is the ‘simulation’. this means that students can test their activities during the extracurricular hours, with their mates, and eventually propose some changes or discuss critical aspects. 7) activities with students (at school or at the museum). the most exciting part of the project is the carrying out of the projects with students in a real class or with the more heterogenous attendants of activities in the frame of open days, science festivals of laboratories organized at the science museum. 8) analysis of the students’ feedback and discussion. at the end of the educational pathway, students should be able to evaluate their activities, the efficacy of the project and the achievement of the educational objectives. this part of the methodology concerns the metacognition level, namely, the developed ability to make self-evaluation and to critically analyse their works. the use of initial and final surveys, as well as the design of specific evaluation tests related to the topics of the project are encouraged. 9) conclusion and final report. at the end, students usually present their work during the final exam or at an event, and discuss all aspects of the project, underlining positive and negative aspects and possible developments. within this last step of the project, communication skills are also evaluated. 3. the context of the science museum and the participants to the project 3.1 museum of science ‘galileo’ the non-formal context chosen to put into practice the ‘steam project-based learning’ method in the academic year 2019-2020, was the historical museum of science ‘galileo’ in florence (italy).43 the museum ‘galileo’ has a long tradition: some of the scientific collections, such as the medicean collection of scientific instruments, were first collected in 1562 by cosimo i de’ medici (1519-1574), who was the ‘duke’ of florence from the 1537, and then the ‘grand duke of tuscany’ until his death in 1574. the first location of the historical geographic maps, celestial and terrestrial globes and other scientific objects was palazzo vecchio; then they were transferred in uffizi gallery, together with other historical scientific instruments. among them, after the foundation of the ‘accademia del cimento’ in 1657, inaugurated by ferdinand ii (1610-1670) and leopoldo de' medici (1617-1675), the collection was enriched with thermometric, barometric and pneumatic instruments used mainly for research. additional instruments of mathematics, physics, meteorology and electricity, were added to the scientific collection in the xix century. some microscopes, telescopes, micrometers and spectroscopes were specifically built to be hosted in the museum, which became managed by the institute of the history of science during the first part of the xx century and finally moved to the actual location, the palazzo castellani in the centre of florence. after 1930, the historic and scientific collections were opened to the public. in the recent decades the museum ‘galileo’ has been largely renovated with the inclusion of didactic interactive expositions and the addition of an increasing number of temporary activities specifically devoted to school students and families. as it will be discussed in section 4, the museum ‘galileo’ offers several occasions to be in close contact with historically relevant objects and instruments related to chemistry. the famous table of affinities (tabula affinitatum) realized by franz huber hoefer, around the year 1766, is one of the examples of very inspiring historical scientific object conserved at the museum ‘galileo’.53 this table, in fact, is a first tentative to organize in a systematic way the known elements on the basis of their ‘affinities’, which are actually connected with elements’ chemical reactivity, as reported in ref. 54, and for the analogy with the systematic work done almost one century later by several scientists, as dimitri mendeleev, it can be considered a sort of precursor of the table of elements. another example is represented by the historical glassware, containing artifacts such as retorts, alembics, chemical apparatus, eudiometers, precision balances, thermoscopes and thermometers. 3.2 the participants to the project the education activities here described refer to the academic year 2019-2020, with 23 students attending lessons during the first semester. among them, 15 students participated in the integrated activities and in almost all steps of the ‘steam project-based learning’ project, including the visit to the museum ‘galileo’ in florence, and the design of educational activities for high school students. at the end of the course, 22 of 23 students passed the final exam, with an average grade 28.23 / 30 and their feedback about the project was eccellent.18 as will be described in the main part of the paper, students attending the 2019-2020 academic year designed their educational activities, stimulated by the visit to the science museum, and in particular their focus was the history of thermoscopes and thermometers. this activity was integrated with the usual lessons of the course of ‘fundaments and methods of chemistry education’ and the project was supported by the university of pisa with a specific didactic project.40 unfortunately, due to the covid-19 pandemic, the final part of the project, namely the carrying out of the activities designed by the undergraduate students with real school students, was not carried out in-person. 4. putting the educational project into practice with future chemistry teachers 4.1 from the visit at the science museum… the first step of the educational project was the visit to the science museum ‘galileo’ in florence the 26th of october 2019. the visit was planned in advance with the collaboration of dr. andrea gori who is the responsible of the education activities carried out at the science museum. a special guided tour was organized to let students know and enjoy the scientific and historic collections starting from the medici’s and lorenese collections of historical instruments and maps, and the large collection of instruments of mathematics, physics and astronomy (see figure 1).43 the visit to the scientific museum was enriched by an interactive lesson, of about one hour, held in the historical library of the museum (see figure 1). here, dr. andrea gori talked with undergraduate students about the educational projects and activities typically organized in the science museum, involving children and school students. figure 1. pictures taken during the visit at the museum ‘galileo’ under the guide of the curator of the educational activities at the science museum, dr. andrea gori. (photo credit: valentina domenici) students had the opportunity to receive a detailed explanation of the history and scientific relevance of the objects and instruments hosted in the room dedicated to ‘chemistry and the public usefulness of science’ and of the glassware collection in ‘the accademia del cimento: art and experimental science’ room (see figure 2).53,55-57 figure 2. pictures of historical objects present in the museum ’galileo’ related to chemistry. on the left: collection of thermoscopes and thermometers designed by ferdinando ii de' medici in the middle of the xvii century in florence. on the right: original of the ‘tabula affinitatum’ made by franz huber hoefer in 1766.56-59 (photo credit: valentina domenici) before visiting the museum, students received an ‘observation guided template’ with some guided questions aimed at giving them some non-formal instructions on how to better observe the collections and to visit the museum with a critical attitude (see table 1). moreover, students were invited to prepare some questions concerning the laboratorial activities designed for students and for children by the museum ‘galileo’. thanks to the competence and availability of the curator, dr. andrea gori, students could have a concrete idea how laboratorial activities for school students are designed and performed in a science museum. table 1. ‘guided questions’ given to the students before visiting the museum. observe the ‘texts’ are there written captions close to the scientific objects? are there texts in different languages? how long are the captions? do you think they contain all important information? how big and readable are the texts? other comments… observe the ‘collections’ what is the criterion of exposition? how are the expositions and the collections organized? describe how the museum is structured and choose a room as an example. how are the scientific instruments and historical objects exhibited? observe the ‘digital and media tools’ are there digital tools in the museum? what are they like? are there video projections? are they used by the visitors? describe one of these tools. observe the ‘didactic laboratory’ and ‘educational activity’ room is there a room or a space dedicated to the laboratorial activities with school students? how are the permanent exhibits specific for school students and children organized? find all details about the planning and design of activities and ask to the guide relevant information, such as: how many students visit the museum every year? what is the main target? are the laboratorial activities related to some specific objects or instruments present in the collection? what are the typical approaches used during the laboratorial activities? … observe the ‘catalogues’ examine the catalogues. are there in print and / or digital ones? are there informative materials for children? what is the language used? are there photographs or pictures in the catalogue? are the catalogues complete/ non complete / …? are there brochures, posters and so on? observe the ‘accessibility’ of the museum comment on the accessibility of the museum to people with different disabilities. do you think that all people can easily access to the museum? what are the limitations, if any? after the visit to the museum, a lesson was dedicated to a collective discussion (step 2 of the project) concerning the experience at the science museum and an interactive activity was organized to put together students’ impressions and observations during the guided tour. some posters were prepared hosting their answers to the questions reported in table 1 and other comments made by students (see some details of the posters in figure 3). (a) (b) (c) figure 3. observations and comments made by the students during the visit at the science museum concerning several aspects as indicated in table 1: comments about (a) the presence of catalogue, captions and brochures; (b) the language used, the type of communication, the presence of a website, eventual videos and animations; (c) the presence of interactive and digital tools, educational exhibits. step 3 of the ‘steam project-based learning’ methodology, namely the selection of chemistryrelated topics inspired by the visit to the science museum, was an interesting part of the students’ work. students were very impressed by some historical objects, such as the antonio santucci's armillary sphere60 and other mathematical instruments, and as a first activity, they tried to make some analogies between these historical models of the universe and the models of the atom developed at the end of the xix and beginning of the xx centuries. despite of the stimulating discussions, students moved their focus on ‘more-chemical’ objects, such as the ‘tabula affinitatum’ and the glassware collections of the museum ‘galileo’. at the end of this collective work, students decided to choose the historical thermoscopes and thermometers59 for their further activities. among them, it is worth noticing some particular thermoscopes, such as the cluster thermometer, consisting of six phials clustered on a column and resting on a round pedestal. each phial contains a small glass sphere having a different density: density is the physical property at the basis of the motion of these spheres in the six phials when temperature changes. a series of fifty-degree thermometers with coloured liquids and a set of thermometers with snail stems also attracted the undergraduate students. as most of the thermometers collected at the museum ‘galileo’, the invention of these thermometers is attributed to grand duke ferdinand ii de' medici and they were used by the members of the accademia del cimento mainly for meteorological applications. in addition, the historic collection at the museum ‘galileo’ contains several thermoscopes, as the so-called ‘galilei’s thermoscope, which was invented by galileo during his stay in padua in 1597.61 these thermoscopes and thermometers were the object of educational activities devised by students, as will be described in the following paragraphs. 4.2 … to the design of the educational activities the step 4 of the project is the design of educational activities to be carried out at school (formal context) or at the science museum or during open days at the university (non-formal context). undergraduate students who participated to the visit to the museum ‘galileo’ in florence were divided in three groups of five students; then each group started working on some sub-topics related to the more general theme of ‘thermoscopes and the thermometers’. students decided to focus on the history of the thermoscopes and thermometers present in the science museum ‘galileo’, such as the history of the discovery of the thermoscope by galileo galilei. one group decided to design a laboratorial activity concerning the construction of a thermoscope and the calibration of a thermometer. all activities were planned for high school students following a general hierarchic scheme of educational instruction (see table 3 in ref. 18). some educational aspects of the activities are reported in scheme 1 for the three projects designed and proposed by the undergraduate students and in figure 4 some photographs and drafts of the thermometers and thermoscopes object of investigation by the students during their educational project are reported. scheme 1. main aspects of the three educational projects designed by the undergraduate students who visited the science museum ‘galileo’ in florence. activity n. 1 (first group of students) relevant aspects description scientific topics the thermoscopes. history of the thermoscopes of the scientific collection at the museum ‘galileo’ target high school students (first year) main chemical-related topics glassware, liquid and gas states of matter, expansion of gases and liquids and temperature effect, density of liquids, temperature. guided questions / inspiring questions to start the activity what is a thermoscope and what is its use? who invented the first thermoscopes? look at these objects (real ones or photographs, as the ones reported in figure 4a) and search for information about their history, inventors, functioning (guided activities on the web). methodology inquiry-based activities; historical approach. timing 2 hours notes this activity is particularly useful to introduce the topic of ‘temperature’ and how different chemical substances behave by changing the temperature, and how liquids and gases behave at different temperatures. main educational objectives search for information about the history of an instrument by using materials provided by the teacher and on the web. understand the principles of functioning of a ‘thermoscope’. understand the phenomenon of gas expansion by changing the temperature. understand the role of the shape of glass components of a thermoscope. know the role of the first thermoscopes and their first applications. activity n. 2 (second group of students) relevant aspects description scientific topics the ‘galilei’s thermometer: the real history and inventors. how does it work? target high school students (second year) main chemical-related topics glassware, liquid and gas states of matters, expansion of gas and liquid, density of liquids, miscibility / immiscibility among liquids, solutions, concentrations, temperature-dependence of some chemical-physical properties. guided questions / inspiring questions to start the activity how does the so called ‘galilei’s thermometer’ work? what are the principles of functioning? do you know the history of this thermometer? who were the real inventors of this thermometer? what are the uses of this thermometer? what is the sensitivity and what are the applications of this thermometer? methodology inquiry-based learning; cooperative learning; historical approach. timing 3 hours notes this activity consists in three parts. first, students are divided in groups according to the cooperative learning method, some groups are invited to search for information about the so-called modern ‘galilei’s thermometer’ (see figure 4b) and the principles of functioning. other groups have a different task: search for the historical origin of this thermometer: why it is referred to galileo galilei and who are the real inventors? the second part of the activity is a collective discussion aimed at sharing the relevant information obtained by the groups. the third part is the preparation of a poster and some educational materials (i.e. brochures) about the history, scientific principles and main applications of this thermometer. main educational objectives understand the differences between thermoscopes and thermometers; understand the working principles of the galilei’s thermometer; understand the temperature-dependence of the density in liquids; search for scientific and historic information on resources on-line and read a scientific paper provided by the teacher concerning thermoscopes and thermometers. activity n. 3 (third group of students) relevant aspects description scientific topics from the thermoscopes to the thermometers. let’s build our own instruments. target high school students (second year) main chemical-related topics glassware, liquid and gas states of matter, expansion of gas and liquid, density of liquids, miscibility / immiscibility among liquids, solutions, concentrations, temperature-dependence of some chemical-physical properties. guided questions / inspiring questions to start the activity what is the difference between a thermoscope and a thermometer? what are the basic principles of an alcohol thermometer? how is the graduate scale on a thermometer determined? what are the main uses of a thermoscope? and of a thermometer? methodology inquiry based and laboratorial activity timing 3 hours notes this is a laboratorial activity made of two steps. the first step is the building of a thermoscope and the second step is the calibration of a thermoscope to be used as a thermometer. these activities are relatively simple and the materials to be used are usually available (see for instance refs. 55 and 63). main educational objectives understand the differences between thermoscopes and thermometers; put into practice the scientific knowledge and design of a simple thermoscope; use common materials to build a thermoscope and a thermometer; acquire some practical skills related to the building of an instrument; estimate the sensitivity of the instrument; apply the instruments to measure the temperature of different systems. during this activity (step 4 of the project), undergraduate students were very much interested in the stories around the attribution to galileo galilei of the discovery of thermoscopes and thermometers. in fact, they knew about the galileo’s thermometer, which was not actually discovered by him, and they didn’t know about the galilei’s thermoscope. this last one, as that reported in figure 4a, was invented by galileo galilei to measure temperature when he was professor in padua in 1597.61 (a) (b) (c) figure 4. some of the thermoscopes and thermometers as object of the investigation and educational activities planned by the students. (a) an historical thermoscope similar to the ones contained in the collection of the science museum ‘galileo’ (photo credit: wikipedia: https://commons.wikimedia.org/);55-57,62 (b) an example of a modern and commercial version of the so-called ‘galilei’s thermometer’ (photo credit: wikipedia: https://commons.wikimedia.org/);46,47 (c) draw of a thermoscope made by a student during the educational activities. this thermoscope consists of a small ampule with a long neck. the ampule is heated by the hands and then it is reversed and partially immersed in a container filled with water. when the hands are removed, the air in the ampule becomes colder and contracts, so that the water rises in the neck. the changes in air density due to the change of temperature are easily visualized by the increase or decrease of the level of water in the neck. it seems that the first liquid used by galileo was the spirit of wine and later still the grand duke ferdinand ii of florence, a former pupil of galileo, used coloured spirit of wine and reduced the dimension of the tube to get a more precise instrument. the so-called galilei thermometer, as that shown in figure 4b, was actually invented by members of the ‘accademia del cimento’ in florence, between 1657 and 1667, and for this reason is also called ‘florentine thermometer’.46,47 it consists of a sealed glass cylinder containing a transparent liquid with suspended small glass spheres, called floaters, containing a coloured liquid. each floater contains a liquid with a slightly different density, associated to a temperature tag. the principle of working is based on the temperature-dependence of the density of liquids. the liquid in the cylinder is in contact with the external air through the glass and it is supposed to be in thermal equilibrium. when the temperature increases the liquid in the cylinder decreases its density due to volume expansion, and floaters containing a liquid with lower density start moving up, while floaters with higher density go down. the temperature of the liquid of the cylinder is something in between the two floaters closer to the centre of the cylinder (such as the green and yellow floaters in figure 4b). during steps 5 and 6 of the project, which are focused on the preparation of materials and the simulation of the designed activities, undergraduate students were very much interested in the historical part. for instance, they realized that the motivation at the basis of the invention of the thermoscopes and thermometers, mainly related to meteorology (i.e. knowing the air temperature, and the changes during the day or during a period of time) are very important from the educational point of view. another aspect which merits some attention by the teachers is the counterintuitive functioning of the galilei’s thermoscopes with respect to modern bulb thermometers. in fact, the increase of temperature of the air contained in the ampule corresponds to a decrease of the level of the water (or alcohol or other coloured liquids) in the thick neck. it’s worth noticing that during the preparation of the educational materials of the three projects students used their creativity and skills related to their ability to draw, organize the materials and use interactive tools and resources. in this respect, several steps of the project allowed me to note the potentialities of a steam approach, combined with the effectiveness of the cooperative learning methodology. as previously stated, undergraduate students could not put their projects into practice (step 7), which were planned during the second semester when the covid-19 pandemic started. the project concluded with the presentation of their cooperative works during the final exam of the course and the efficacy of the methodology was verified by analysing their feedbacks and final evaluation tests.18 5. conclusions and future perspectives the pilot study here reported concerns a structured method for training future chemistry teachers, called ‘steam project-based learning’, which is centred on the role of science museums and historical scientific collections on learning science and, in particular, chemistry. as reported in this paper, the visit to a science museum represents a great stimulus for students and teachers, since a simple object in a collection can instil original ideas of how to approach a specific scientific topic or to build a non-formal activity related to a chemical concept. this methodology has been optimized within a course of ‘chemistry education’, as reported in refs. 2 and 18, and the feasibility of this approach at undergraduate level has been discussed. in the literature, other examples of activities about chemistry with educational approaches typical of science museums have been also reported at high school level.2,5,7,64,65 all these experiences and research works demonstrated that non-formal hands-on activities centred on scientific museum or historical collections are very be effective in engaging students, improving their interest toward scientific topics and developing communication skills. as in the case reported here, where students decided to focus their attention on historical thermoscopes and thermometers held by the science museum ‘galileo’ in florence (italy), the educational activities can be designed to include history of science in an interactive and constructive way,30 with the aim to develop skills, which are usually indicated as higher order thinking skills, typically reached at the high school educational level. the steam philosophical approach is particularly suited for non-formal contexts, such as the science museum, and in this work, it is one of the key aspects of the methodology adopted during the course of ‘fundaments and methods of chemistry education’. in the educational activities designed by the undergraduate students, the interdisciplinarity aspect is related to the main scientific disciplines, chemistry and physics, and to history of science, among humanistic disciplines. a key part of the project is the hands-on activity, since laboratorial activities need to have a high level of active participation in all steps, from the planning to the putting into practice, as also reported in other cases.7,18,66 the only limitation of this project and in general of this educational approach is that it needs much more time than normal lessons, and it require a very good preparation by the teachers, who need to visit the museum in advance, prepare the materials and dedicate extra-curricular hours to let students work to their project. in the case study reported in this paper, it is important to underline that the undergraduate students who participated were able to explore some scientific concepts, such as the temperature, the temperature-dependence of density, the miscibility among liquids, the density as chemical-physical property of a chemical substance, by using non-formal educational methodologies starting from the investigation of the history of some objects collected in the science museum. among the active methodologies at the basis of the activities designed by future chemistry teachers, the inquiry-based, cooperative and laboratorial learning methods were used in combination with the historical approach, which underlines the role of the ‘humanistic’ level in chemistry education teaching and learning models. from the evaluation of the project done by the students at the end of the course and from their final exam, i can conclude that this pilot project merits to be continued and implemented with the hope to be able in the next years to put into practice the activities planned by the students at the end of the project. acknowledgments i’d like to thank students of the course “fundaments and methodology of chemistry education” (academic year 2019-2020), dr. andrea gori from the ‘museo galilei’ in florence (italy) and the university of pisa for the special educational project 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https://catalogo.museogalileo.it/sezione/termometridellaccademiavetridartescienza.html https://catalogue.museogalileo.it/section/antoniosantuccisarmillarysphere.html 62. one of the copies of the ‘galilei’s thermoscope’ of the museum: https://catalogue.museogalileo.it/object/thermoscope.html (accessed on 16th july 2022). 63. activities on the web on ‘how to calibrate a thermometer’: https://www.physicsclassroom.com/class/thermalp/lesson-1/temperature-and-thermometers (accessed on 19th july 2022). 64. a. a. gallitto, v. pace, r. zingales, museologia scientifica, 2017, 11, 103-107. 65. p.l. daubenmire, m.t. van opstal, n.j. hall, b. wunar, n. kowrach, int. j. sci. edu. – part b, 2017, 7, 60-75. 66. a. francescangeli, j. chem. educ. 2020, 97, 12, 4400-4405. https://catalogue.museogalileo.it/object/thermoscope.html https://www.physicsclassroom.com/class/thermalp/lesson-1/temperature-and-thermometers article training of future chemistry teachers by a historical / steam approach starting from the visit to an historical science museum substantia. an international journal of the history of chemistry 4(1): 37-50, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-817 citation: f. camerota (2020) leonardo and the florence canal. sheets 126127 of the codex atlanticus. substantia 4(1): 37-50. doi: 10.13128/substantia-817 received: aug 08, 2019 revised: nov 20, 2019 just accepted online: nov 21, 2019 published: mar 11, 2020 copyright: © 2020 f. camerota. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature articles leonardo and the florence canal. sheets 126127 of the codex atlanticus filippo camerota museo galileo – istituto e museo di storia della scienza, piazza dei giudici 1, 50122 firenze, italy e-mail: f.camerota@museogalileo.it abstract. the folios 126 r-v and 127 r-v of the codex atlanticus represent the most exhaustive account of a project developed by leonardo over many years: the construction of a waterway between florence and the sea. this navigable canal was supposed to restore the country from the arno floods and encourage commercial traffic, bringing wealth to the entire region. its length of no less than 72 km, the system of automatic locks designed to overcome the total height difference of 34 meters between florence and pisa, and the idea of feeding it with a water reserve located in valdichiana would have made it one of the most imposing and technologically advanced hydraulic works of the time. keywords. hydraulic engineering, river navigation, locks, siphons, cartography. the “florence canal” is one of the most famous ‘technological dreams’ of leonardo da vinci. it was conceived as a navigable canal from florence to the sea; a waterway that was supposed to restore the country from the arno floods and encourage commercial traffic, bringing wealth to the entire region1. the project was developed on several occasions over many years but it never reached a final stage because, in fact, there was never an official appointment for its drafting. leonardo worked on it with the hope of sensitizing the floren1 according to giorgio vasari (lives 1568), leonardo “was the first who, as a young man, talked about the arno river to put it in a canal from pisa to florence” (g. vasari, vite de’ più eccellenti pittori scultori e architettori, 1550 e 1568, ed. by r. bettarini and p. barocchi, firenze 1966-1987, vol. 4, p. 17). on the florence canal project, see mario baratta, leonardo da vinci negli studi per la navigazione dell’arno, “bollettino della società geografica italiana”,  fasc. 10-12 (1905), p. 739761; girolamo calvi, i manoscritti di leonardo da vinci: dal punto di vista cronologico, storico e bibliografico, zanichelli, bologna 1925, pp. 225-232; william barclay parsons, engineers and engineering in the renaissance, the mit press, cambridge (mass.) 1975, pp. 323-334; carlo pedretti, in jean paul richter, the literary works of leonardo da vinci / commentary by c. pedretti, commentary to fol. 127r-v, phaidon, oxford 1977, pp. 174-175; carlo zammattio, acqua e pietre: loro meccanica, in carlo zammattio, augusto marinoni, anna maria brizio, leonardo scienziato, firenze 1980, pp. 10-67; sara taglialagamba, il canale di firenze. foglio 126v, in leonardo e firenze. fogli scelti dal codice atlantico, catalogue of the exhibition, firenze, palazzo vecchio (march 24th – june 24th 2019), ed. by cristina acidini, giunti, firenze 2019, pp. 52-53; alessandro vezzosi, il canale di firenze. scienza, utopia e land art, in leonardo e firenze, cit., pp. 55-63. 38 filippo camerota tine republic, especially after the assignment obtained in the summer of 1503 to divert the arno at the gates of pisa during the siege of the florentine troops. the failure of that enterprise, however, soon quenched the enthusiasm, and put a limit also to the ambitions of its main supporter, niccolò machiavelli, the strategist of the pisan siege. the two men had met at the court of cesare borgia, when leonardo held the office of “architect and military engineer” of the prince, and machiavelli that of ambassador of the florentine republic2. when leonardo was dismissed, machiavelli called him to supervise the fortress of verruca at the gates of pisa, newly conquered by the florentines, and to present a project for the deviation of the arno towards stagno, next to livorno3. it was in the year that elapsed between the presentation of the project and its implementation that leonardo seems to have devoted himself more assiduously to the ambitious project of the florence canal. the folios 126r-v and 127r-v of the codex atlanticus represent the most exhaustive account of the project. even in their extreme textual and graphic synthesis, the sheets contain all the elements necessary to understand the scope of the project which, for technological innovations and impact on the territory, far exceeded the expectations of the possible clients. most likely, the sheets derive from a bifolio that leonardo began to write from the last page, as usual for his left-handed writing. the last page (the first for leonardo) was folio 127r, followed by 127v, then by 126v and then by 126r (fig. 1). the double 2 permission letter issued to leonardo by cesare borgia on august 18 1502, melzi d’eril archives, belgioso (pavia): vaprio d’adda 1993. 3 see emanuela ferretti, fra leonardo, machiavelli e soderini. ercole i d’este e biagio rossetti nell’impresa “del volgere l’arno” da pisa, “archivio storico italiano”, 2019, 2, a. 177, n. 660, pp. 235-272. sheet was presumably part of a series of “notebooks” on water engineering, mentioned by leonardo on sheet 26r of the codex leicester, the treatise that he dedicated to the nature of water and its cosmological implications4. sheet 127r opens with a cartographic sketch of the area affected by the construction of the canal, namely the plain of florence and the lower valdarno, up to the mouth of the arno river (fig. 2). it is a very summary sketch that, however, we are able to read thanks to the much more accurate maps, now kept in the royal collection of windsor castle and in the codex madrid ii5. the names of the cities of florence, prato and pistoia, of the serravalle pass, and of the lake of sesto (or, of bientina), mark the route of the canal that, once deviating from the arno at the gates of florence, would once again have entered the river next to vicopisano. above the drawing, the title “canale di firenze” can be read, and below it there is a text that immediately indicates the essential condition for the realization of the work: facciasi alle chiane d’arezzo tali cateratte che, mancando acqua la state in arno, il canale non rimanga arido. let’s construct sluices in the chiane of arezzo so that, lacking water in the arno in summer, the canal would not dry out. (f. 127r) 4 the hypothesis is supported by g. calvi, op. cit., pp. 224, 229. for the codex leicester, see leonardo da vinci’s codex leicester: a new edition, ed. by domenico laurenza and martin kemp, oxford university press, oxford 2019; paolo galluzzi, ed., l’acqua microscopio della natura : il codice leicester di leonardo da vinci, catalogue of the exhibition (florence, uffizi gallery, october 30th 2018 – january 20th 2019), giunti, firenze 2018. 5 the topographical drawings of the lower valdarno are kept at the royal library of windsor, inv. 12279 and 12685, and in the codex madrid ii, cc. 22v-23r. figure 1. recomposition of sheets 126r-v and 127r-v of the codex atlanticus. 39leonardo and the florence canal. sheets 126-127 of the codex atlanticus in order to make the canal navigable throughout the year it was necessary to guarantee a water reserve sufficient to ensure navigability even when the arno had a limited water flow, that is, in the summer months. the water reserve was located in valdichiana where the large swamp existing at that time could be transformed into a huge reservoir suitable for the purpose. leonardo does not specify how, but the valdichiana map drawn up between 1502 and 1503, and the map of tuscany, presumably of the same period, allow us to identify some elements of this project6. the swamp of the “chiane d’arezzo” was formed in the middle ages perhaps due to a phenomenon of bradyseism that had caused the raising of the ground in the middle of the valley, breaking in two branches the chiane master canal, once a commercial waterway between the arno and the tiber7. one of the two branches underwent a reversal of flow, beginning to flow towards the arno; the other continued to flow towards the tiber. the lack of maintenance of the water courses, due to the interruption of commercial activities in the period of the barbarian invasions, contributed to provoking the swamping of the valley that already at the time of dante was known for its unhealthy air8. 6 the map of the valdichiana and the general map of tuscany are both kept at the royal library of windsor, respectively with the inventory numbers 12278 and 12277. 7 see, vittorio fossombroni, memorie idraulico-storiche sopra la val-dichiana, firenze 1789; a. bigazzi, la bonifica della val di chiana (secoli xvi-xx): gli aspetti tecnici, “atti e memorie della accademia petrarca di lettere, arti e scienze”, nuova serie, lxix, 2007, pp. 267-298. 8 dante recalls the summer miasmas of the chiane in the 29th canto of inferno (vv. 46-48, “qual dolor fora, se de li spedali / di valdichiana tra ‘l luglio e ‘l settembre / e di maremma e di sardigna i mali” ), while a little later fazio degli uberti attributes to the unhealthy air of the region the cause of the dropsy or anasarca: dittamondo, book iii, chapt. x, vv. 23-24, “quivi son volti pallidi e confusi / perché l’aire e le chiane li in leonardo’s drawing, one of the most refined cartographic products of the time, the two branches of the chiane’s master canal are traced with a darker blue inside the large swampy expanse that crosses the valley from north to south (fig. 3). the map was drawn up for military purposes in the aftermath of the arezzo uprising but it is likely that it was also conceived for a reclamation project necessary to restore the region that cesare borgia had just annexed to his conquests in central italy9. to betray the possibility of a hydrographic project in the mind of leonardo is the presence of a dry ditch not indicated in the other maps of the region, and insignificant for military purposes. the ditch is also reported in the general map of tuscany accompanied by a significant note: “braccio da montona closed it, thence it has disappeared” (fig. 4). this specific note reveals an attention to the issue of waters that goes beyond the mere cartographic recording. the dried-out canal, is called “trasumeno” (fig. 5). it was an emissary of the lake trasimeno that poured the floods of the lake in the chiane’s master canal, periodically aggravating the swamping of the valley. braccio da montone, the lord of perugia, closed it around 1420 in an attempt perhaps to reclaim the valley. the floods of the lake were then poured into the tiber through the opening of a new emissary towards the south that in the map of leonardo, as well as in other contemporary maps, is recognizable by the characteristic graphic interruption due to the tunnel path under the hills in proxnemica / sì che li fa idropichi e rinfusi”. 9 the revolt of arezzo against the florentine domination broke out in june 1502 and was strongly supported by vitellozzo vitelli, captain of fortune in the service of cesare borgia and friend of leonardo to whom he lent a book of the works of archimedes. arezzo came back under florentine rule already in august thanks to the intervention of the king of france who ordered cesare borgia to renounce the city. figure 2. c.a., fol. 127r: detail of the topographic map with the plain of florence and the lower valdarno. figure 3. map of valdichiana, windsor, royal library, 12278r 40 filippo camerota imity of the lake (fig. 6). at the point where the southern emissary enters the tiber leonardo writes “here is the outflow of the lake”. this note, together with the actual height difference between the lake and the tiber, which is here much lower, rules out the hypothesis that leonardo may have considered to convey tibeŕ s water to the trasimeno in order to create a compensation basin in the chiane that fed into the arno in the summer months10. it is possible instead that for that purpose he planned to reopen the northern emissary which had been closed by braccio da montone, a hypothesis still put forward in the sixteenth century by the savant priest 10 this hypothesis is put forward by carlo zammattio, acqua e pietre: loro meccanica, in c. zammattio, a. marinoni, a.m. brizio, leonardo scienziato, firenze 1980, p. 23. baldassarre nardi11. if duke of valentinoiś intent was to acquire riches from a potentially productive area, by reclaiming the whole swampland, then leonardo seems to have conceived a more elaborate regional water system that connected the large valleys of tuscany to one another, in order to ensure the feasibility of the great project for the “canale di firenze” (fig. 7). e facciasi esso canale largo in fondo braccia 20 e 30 in bocca, e braccia 2 sempre [ac]qua o 4, perché dua d’esse braccia serva[n] alli mulini e li prati. 11 the hypothesis to convey water from lake trasimeno into the canale maestro of the chiana was resumed at the end of the 16th century by baldassarre nardi (discourse on the reclamation of the chiane, ms., 17th century, florence, biblioteca riccardiana, ricc. 2575), who seems to have dreamt of the possibility to make the entire stretch a navigable canal that would have connected “livorno to rome through the arno, the chiane, the paglia and the tiber”; see v. fossombroni, op. cit., p. 312, note 11. figure 4. detail of the dried-out canal, called “trasumeno”, from the map of tuscany, windsor, royal library, 12277. figure 5. detail of the “trasumeno” from the map of valdichiana, windsor, royal library, 12278r. figure 6. detail of the southern emissary of the lake trasimeno from the map of valdichiana, windsor, royal library, 12278r. figure 7. scheme of leonardo’s hydrographic project (traced on the map of tuscany, windsor, royal library, 12277). water reserve florence canal 41leonardo and the florence canal. sheets 126-127 of the codex atlanticus and make the canal wide at the bottom, braccia 20 and 30 in the mouth, and deep braccia 2 always or 4, so that two braccia will serve the mills and the fields. (f. 127r) the canal would have had such a width to allow the comfortable passage of two boats in the opposite direction. considering that the major boats used at that time had a maximum width of 7.5 braccia (about 4.5 meters) so we read in sheet 1007r of the codex atlanticus12 leonardo fixed the width of the canal at 20 braccia on the bottom and 30 on the surface, and established a depth of 4 braccia that could contain a sufficient amount of water to operate the mills, irrigate the fields and allow navigation. the minimum depth for navigation was set at 2 braccia, or just over one meter, sufficient to guarantee the floating of the large flat-bottomed boats of the river waterways. the canal measurements indicate a trapezoidal section that leonardo draws in other notes of the codex atlanticus. in the third page of this bifolio, instead (fol. 126v) the canal has a rectangular section. the banks are formed by thick palisades with a robust plank that holds the ground to form two “3 or 4 braccia” docks before the gravel embankment that protects the surrounding lands from possible flooding. questo [canale] bonificherà il paese; e prato, pistoia e pisa insieme con firenze fia l’anno di meglio dugento mila ducati, e porgeranno le mani a spesa a esso aiutorio, e i lucchesi il simile. this [canal] will reclaim the country; and prato, pistoia and pisa, together with florence, will make the year better than two hundred thousand ducats, and they will help with the expenses, and the lucchesi the like. (f. 127r) in addition to the aforementioned functions, the canal would also have served to absorb the overflows of the arno avoiding the periodic floods that always represented a danger for the city of florence and the surrounding countryside. instructions “for the canalisation of the arno” along the urban stretch were issued from 1458 to 1477, while, before 1469, luca fancelli had elaborated a project for piero de’ medici for making the river navigable from mulino di ognissanti to signa. the difficulties arisen in that plan, which fancelli still discussed in a letter to lorenzo the magnificent in 1487, were due to the torrential nature of this river13. for slow12 codex atlanticus, fol. 1107r: «le maggiori barche che si faccino, sono larghe 7 braccia e 1/2 [4,5 m] e lunghe 42 braccia [24 m] e alte di sponde uno braccio e ½ [0,9 m]» (the major boats that are built are 7 braccia and 1/2 wide[4.5 m] and 42 braccia long [24 m] and one braccio and ½ high at the sides[0.9 m]). 13 luca fancelli to lorenzo de’ medici, milan, august 12 1487; in corinna vasić vatovec, ed. by, luca fancelli architetto. epistolario gonzagheing the flow of the arno down, it was necessary to block its course by a series of kiddles, which, however, turned out to be a barrier during floods; but it was not possible without kiddles, since in the canalised stretch the stream would have been even more impetuous, therefore it would have brought about the erosion of the riverbed and the consequent breakage of the river banks. in order to find a solution to this problem leonardo thought to build a canal alternative to the natural course of the arno which, by its nature, was not suitable for this plan: “this arno floods – leonardo explains – because it does not let its water run off with the same promptness as waters flow into it from the upper arno valley. and the golfolina obstructs the passage of them through its valley filled with trees” (fig. 8)14. the alternative way was a navigable canal with a very slight slope, then without kiddles, which would have reached prato and pistoia from mulino di ognissanti and would have passed through the marshes of fucecchio for flowing into the arno near cascina. prato, pistoia and pisa are indicated as the main cities that, together with florence, would have benefited from the construction of the canal and should therefore have contributed financially to its construction. but leonardo also indicates lucca that having small commercial landings on lake of bientina, could have benefited equally from that important infrastructure, if the canal had been in communication with that lake. perché il lago di sesto sia navigabile, falli fare la via di prato e pistoia e tagliare serravalle e uscire nel lago. sco, firenze 1979, pp. 60-62. 14 codex atlanticus, fol. 785ii r. figure 8. c.a., fol. 785ii r: detail of a study for the arno canal. 42 filippo camerota for lake of sesto to be navigable, let it [the canal] pass through prato and pistoia and cut serravalle and exit into the lake. (f. 127r) the “lake of sesto” or lake of bientina was partly marshy (fig. 9); it dried up during the dry season but only in the outlying areas. a large central area always remained navigable and had an emissary, the ditch of serezza, which conveyed the excess waters into the arno near vicopisano. the lake was half in the lucca territory and half in the florentine dominion. two of the maps drawn by leonardo to trace its route windsor 12685 and madrid ii (figg. 10-11) – show the canal that grazes the southern shore of lake of bientina, crossing a slightly hilly area that would have required a work of excavation certainly excessive. only the windsor map 12279 (fig. 12) shows a sinuous path that seems to bring the canal slightly further north, where it would have crossed a totally flat area to enter the lake at altopascio. keeping the slopes minimal was a necessary condition to avoid the construction of locks whose maintenance would have represented an important burden. perché non bisogni di conche o sostegni, i quali non sono etterni, anzi sempre si sta in esercizio a operarli e mantenerli figure 12. map of the lower valdarno, windsor, royal library, 12279. figure 9. lake of sesto, or “of bientina”, carta orografica e idrografica del ducato di lucca, in a. zuccagni orlandini, atlante geografico degli stati italiani, firenze 1844, ii. figure 10. map of the lower valdarno, windsor, royal library, 12685. figure 11. map of the lower valdarno, codex madrid ii, cc. 22v-23r. florence canal 43leonardo and the florence canal. sheets 126-127 of the codex atlanticus so that it does not need chambers or locks, which are not eternal, rather it is always necessary to operate and maintain them. (f. 127r) the technology of ‘chambers’, ‘bulkheads’ or ‘locks’ was known to leonardo for having experimented and perhaps perfected it during the milanese years. the gates system fully illustrated by him in the codex atlanticus, for example in sheet 935r, is known today as “porte vinciane” or ‘da vinci gates’ (fig. 13). two large doors close the canal forming an angle of about 120° in upstream direction so as to resist the thrust of the water better than any transverse plane barrier. the doors remained tight thanks to the push of the water, and they were secured to the ground by a stone step that served as a ‘doorstop’. two gates of this type delimited the chamber where the boat was let in to reach the upper or lower level of the canal. in lombardy canals, locks of this type allowed to overcome up to four meters in altitude. when a boat entered the chamber and the gates from which it had passed were closed, two small shutters hinged to the doors of the second gates were opened to let water enter the chamber itself, or to let it out in the event of a passage to the lowest level. the operation was risky, especially uphill, since the introduction of water into the chamber caused vortices that could push the boat too close to the inlet with consequent danger of sinking, as leonardo explains in the verse of sheet 127 (fig. 14): pericolosa cosa è da fondare i navili nella conca e di fori d’essa conca; e questo accade quando s’aprano le portelle. bisogna legare i navili in modo indirieto che non abbiano cagione di correre innanzi in verso il loco basso, dove cade l’acqua del portello, che giugnendo lì l’acqua, che cade d’esso portello infra l’altra acqua, poi caderebbe nella barca e subito la empierebbe, e sommergerebbela. sicché legala in m. dangerous thing is the risk of sinking the boats in the chamber and outside, and this happens when the doors open. we have to tie the boats behind, so that they have no way of running forward towards the low place, where the water falls from the doors, because arriving there, the water that falls from the doors into the other water, then it would fall into the boat and immediately would fill it and submerge it. then tie it in m. (f. 127v) the water level between the two doors went up to that of the upper section of the canal and only then could the second door be opened to let the boat pass. this system made it possible to overcome considerable differences in height but required high construction costs and, according to leonardo’s concerns, even more significant maintenance costs. leonardo does not say it but we should consider that having to periodically absorb the floods of the arno, the sluices would have represented a problem to the gradual outflow of the waters. however, even without the flood problem, the florence canal could not have been built without water supports. even if his path could have had a constant slope, we would still have an inclination that would generate too much stream for a comfortable navigation. in its total extension of approximately 72 km between florence and vicopisano, the canal would have had to overcome a drop of 34 m, developing a slope of about one meter every 2 km. in the lombardy canals, the average slope is about one meter every 3 km, a limit beyond which it was not advisable to proceed15. but the ques15 on water engineering in the lombardy area see, cesare s. maffioli, i contributi di leonardo da vinci e degli ingegneri milanesi : misura delle figure 13. c.a., fol. 935r: chamber, or navigation basin, with the kind of locks called “porte vinciane”. figure 14. c.a., fol. 127v, detail: filling of the navigation basin through the door of the lock. 44 filippo camerota tion did not arise even in these terms because at least as far as pistoia the canal should have had a minimum slope, finding itself having to overcome a difference in height of 14 m in the short stretch that separates pistoia from the val di nievole, beyond the relief of serravalle (fig. 15). the stretch in question measures about 14 km, impossible to navigate without water supports. between florence and pistoia the ground has a minimal slope and in that stretch the canal would have had to exceed four tributaries of the arno, two of which, the bisenzio and the ombrone, particularly dangerous during the autumn floods (fig. 16). leonardo intended to use the water of the tributaries to feed the canal through special aqueducts with controlled access, but the torrents themselves could not enter the canal; they had to be crossed with a bridge of the type illustrated in the third page of the bifolio (126v) (fig. 17). the bridge is on three arches, the central one corresponding to the usual width of the watercourse, the other two necessary to cover the acque e navigazione dell’adda tra fine xv e xvi secolo, “archivio storico lombardo”, anno 142 (2016), pp. 97-127. riverbed to absorb the floods: “if this river usually occupies the width of an arch, let it the bridge having 3 arches, and this is for the causes of floods ”. above the bridge runs the navigable canal whose depth here is reduced to the bare minimum. and beyond the bridge we can see a navigation basin with corner gates. in the cross section drawing it is clear that the canal proceeds from a higher level than that of the river that is crossed (fig. 18). in this case the filling of the navigation basin occurred by fall, as in the case of the ivrea canal that leonardo mentions on the sheet 563r of the codex atlanticus. in the section between florence and pistoia, on the other hand, the canal runs at the same altitude as the rivers it must pass. the bridge therefore required a navigation basin that was necessarily higher than both sections of the canal that it connected and its filling took place from below. the only technology that leonardo could have entrusted with this artifice was that of the siphon, or “cicognola” as it was called at that time; a tube of adequate dimensions which, by exploiting the figure 15. topographic section between the ombrone river and the val di nievole. figure 16. satellite view of the plain between florence and pistoia with the route of the canal and the crossing of the tributaries of the arno. figure 17. c.a., fol. 126v, detail: perspective view of the canal bridge. figure 18. c.a., fol. 126v, detail: cross section of the canal bridge. 45leonardo and the florence canal. sheets 126-127 of the codex atlanticus phenomenon of communicating vessels, would have put the two canal sections separated from the bridge into communication, ensuring the continuous feeding of the canal itself and, when necessary, filling the navigation basin to allow the boats to pass from side to side. this problem probably refers to the singular siphon drawn in the last page of the bifolio (126r) (fig. 19). the siphon technolog y applied to the aqueduct bridges is illustrated by mariano di jacopo, known as “il taccola”, and by francesco di giorgio martini (fig. 20)16. in their writings the solution contemplated by leonardo is clearly prefigured, namely a siphon bridge that crosses a river bringing the water of a canal from one bank to the other. leonardo certainly considered this technological solution, taking into account, however, the possibility of adapting it to the navigability of the canal. the greater length of the exit pipe that characterizes the siphon technology, here seems to be obtained with the help of a double curve with a gooseneck joint whose function was to increase the flow velocity. once the siphon was filled from the mouths placed at the top of the two curves keeping both mouths closed at the bottom of the canal and the filling of the upstream channel was ensured, the mouthpieces could be opened to let the water flow into the section of canal downstream. the continuous flow of the canal would keep the siphon in constant operation. to guarantee the simultaneous opening of the mouthpieces, leonardo studied a mechanical system with balance and coun16 see mariano di jacopo, called il taccola, de ingeneis, ed. by gustina scaglia, frank prager, ulrich montag, dr. ludwig reichert verlag, wiesbaden 1984, fols. 73v, 83r, 94v, 105r, 115r, 134r; and francesco di giorgio martini, trattati di architettura, ingegneria e arte militare, ed. by corrado maltese and livia maltese degrassi, il polifilo, milano 1967, fols. 40r, 42v, 45r. terweights that is activated by cutting a rope stretched between the two ends of the siphon. the drawing does not explain how the navigation basin was to be filled, but if this was to be the second function of the siphon necessary to guarantee the navigability of the canal we should imagine an opening at the top of one of the two curves; an opening of such dimensions as to allow the introduction of water into the basin without interrupting the flow in the siphon. this solution is indicated by leonardo in sheet 301r of the codex atlanticus, where it is applied to an extremely ambitious case, that of bringing the boats to the top of the hills (fig. 21): “ogni grosso fiume si conducerà in su l’altissime montagne per la ragion de la cicognola (every big river will lead up the very high mountains for the reason of the siphon)”. the siphon figure 20. francesco di giorgio martini, trattati di architettura, ingegneria e arte militare, firenze, biblioteca medicea laurenziana, cod. ashb. 361, c. 38r, detail: bridge with siphon to carry the water of a canal from one bank to the other of a river. figure 19. c.a., fol. 126r, detail: double siphon. 46 filippo camerota is used to feed the highest of a system of navigation basins which, proceeding in a zig-zag fashion, would have allowed for “condurre delle navi in sulle montagne (carrying ships on the mountains)”. the idea would have found application in france in the seventeenth century with the construction of the canal du midi which connects the mediterranean see with the atlantic ocean, overcoming an intermediate relief of 190 m (fig. 22). in this case, however, the supply of the highest basin occurs through a water reserve located further upstream. if the canal had not also served as a spillway, and if it had been possible to guarantee a water supply in the pistoia mountains, this solution would have been applicable also to the serravalle problem. but the conditions were different. the mountainous relief that separates the plain of florence-pistoia from the val di nievole is today crossed in a tunnel by a stretch of motorway and by the railway line, and it has been repeatedly suggested by scholars that this could be one of the solutions meditated by leonardo. to support the hypothesis is usually the 111r sheet of the codex madrid i where leonardo illustrates a new “way to drill a mountain” (fig. 23). the excavation of tunnels for canals and aqueducts is illustrated in the works of taccola (fig. 24) and a real case well-known to leonardo was the tunnel of the southern emissary of the trasimeno. however, unlike the approximately 900 meters covered in tunnel by the trasimeno emissary, overcoming the relief of serravalle required a dig of several kilometers. if the excavation had been done horizontally, as leonardo shows and before him taccola, the exit of the tunnel towards pieve a nievole would have been found 14 meters higher than the valley that it was supposed to reach. in conclusion of his description, leonardo states that by tilting the level the excavation figure 21. c.a., fol. 301 r, detail: big siphon to feed the highest navigation basin of a system of locks to bring boats up to the mountains. figure 22. map of the nouveau canal de languedoc, paris 1677. figure 23. codex madrid i, c. 111r: level used to guide the excavation of a tunnel. 47leonardo and the florence canal. sheets 126-127 of the codex atlanticus could follow an inclined plane, but there is no evidence that this excavation technique was related to the passage of the canal to serravalle. in the first page of the bifolio, leonardo clearly writes “cut serravalle” and it seems clear that his solution foresaw a passage in trench, or the cutting of an artificial gorge that would have allowed to proceed gradually downwards with a series of “steps” interrupted by weirs of the type illustrated in sheet 90v of the codex atlanticus (fig. 25). this drawing shows navigation basins with a system of locks simpler than the one with corner gates. these are sluice gates raised like a drawbridge that certainly required lower construction and maintenance costs. for this part of the florence canal, and for the following stretch as far as lake bientina, leonardo seems to have thought of even simpler water supports that we see illustrated in the second page of the bifolio (127v). these are counterweight systems designed to support just one braccio of water, the minimum allowed for river navigation, which could be operated by the boats themselves (fig. 26). ques[t]o sostegno sta levato dinanz[i] braccia uno, e le barche nel salire e dismontare lo cacciano in ba[sso], e per questo modo le barche camminano in poco fondo. this support rises on the front one braccio, and as the boats go up and down they drive it down, and in this way the boats walk in little depth. (f. 127v) two similar supports had to be located at the two ends of the navigation basin (fig. 27). arriving from figure 26. c.a., fol. 127v, detail: counterweight water support. figure 24. mariano di iacopo, called il taccola, de ingeneis, biblioteca nazionale centrale di firenze, ms. palat. 762, c. 34r: method for digging a tunnel for the passage of canals and aqueducts. figure 25. c.a., fol. 90v: canal with kiddles and locks. 48 filippo camerota the top of the canal (right, in the drawing), and tapping lightly on the sloping sluice of the support, the boat would have caused the lowering of the sluice itself which the water, pouring inside the basin, would have helped to push even more down. the opposite gate would have blocked the passage of water allowing the basin to fill up to the upper level of the canal. at that point the boat could enter the basin and proceed until it touched the second support which, by lowering, would allow the basin to empty itself until it reached the lower level of the canal. the emptying took place after the first support, brought back in position by the counterweight, had blocked the access of the water from the upper part of the canal. alternatively, the two supports could be connected like a rocker arm, as in the drawing at the bottom of the sheet (fig. 28). questo strumento di sotto è un sostegno d’acqua, il quale è di grande utilità per li navili che contro all’acqua vanno carichi; imperò che, quando il navilio tocca in s, s s’abbassa, e k si leva e chiude l’acqua che era da s in su. la quale acqua s’ ingorga, e s’alza subito in modo che con facil[i]tà esso navilio monta contro all’aperta bocca dell’acqua. this instrument below is a water support, which is very useful for loaded ships sailing upstream; so that when the ship touches in s, s is lowered, and k rises and closes the water that was from s upwards. which water is engorged, and immediately rises so that with ease the boat gets in the open mouth of the water. (f. 127v) here leonardo imagines a boat that sails upstream (fig. 29). the navigation basin has the same level of the lower part of the channel; the boat enters the basin and knocks against the sluice gate which blocks water access to the upper level. this is lowered causing at the same time the raising of the downstream sluice gate which closes the access to the water in the meantime poured into the basin from the highest part of the canal. the water level in the basin then rises up to that of the upstream channel, and at this point the boat proceeds in its navigation. here it is not clear if the system should remain in this position until the passage of another boat or if the difference in weight between the two parts of the rocker arm would have gradually brought the basin back to the initial condition. it is clear, however, that in both cases the height difference exceeded by the boats had to be minimal, no more than one braccio, and although numerous, these water supports would have been less expensive than the traditional locks. to overcome the 14-meter difference in height between pistoia and the val di nievole, the section of the canal in serravalle would have required about 23 water supports of this type located at a distance of about 600 meters from each other. the next stretch, up to lake of bientina, would have required as many supports. then the canal would have figure 29. operation of the rocker arm system designed to support one braccio of water. figure 27. operation of the counterweight system designed to support one braccio of water. figure 28. c.a., fol. 127v, detail: rocker water support. 49leonardo and the florence canal. sheets 126-127 of the codex atlanticus continued with a minimal slope until it re-entered the arno at a point where the river itself, having no more tributaries, would have become navigable up to the mouth. the final part of the text we are examining contains an estimate of the costs for the excavation of the canal, a decisive and unavoidable aspect that leonardo methodically tackles in other sheets of the codex atlanticus. e sappi che se cavando il canale dove esso è profondo 4 braccia, si dà 4 dinari per braccio quadro, in doppia profondità si dà 6 dinari. and know that if you dig the canal where it is 4 braccia deep, you give 4 dinari per square braccio, in double depth you give 6 dinari. (f. 127r) leonardo carries out the calculation of costs in milanese dinari probably because that was the unit value of reference most familiar to him for hydraulic works of such a scale. it was an estimate of the costs which he maintains in this form because the annotations on these sheets are still entirely personal. if the project had been translated into an official document, the costs would certainly have been converted into florentine currency. se fai 4 braccia, e’ sono solamente 2 banchi, cioè uno dal fondo del fosso alla superfizie de’ labri del fosso, e l’altro da essi labri alla sommità del monte della terra che d’ in sulla riva dell’argine si leva. if you make 4 arms, they are only 2 banks, that is, one from the bottom of the ditch to the surface of the laps of the ditch, and the other from them to the top of the pile of earth that rises on the shore. (f. 127r) leonardo divides the ground into layers, or “banks,” of four arms in height and considers that the ground excavated for the depth of the canal would have been used for the construction of the embankments. e se fussi di doppia profondità esso argine cres[c]e solo uno banco, cioè braccia 4, che cresce la metà della prima spesa; cioè che dove prima in due banchi si dava dinari 4, in 3 si viene dinari 6, a 2 dinari per banco, essendo il fosso in fondo braccia 16. ancora se ‘ l fosso fussi largo braccia 16 e profondo 4, venendo a 4 soldi per opera[io], dinari 4 milanesi il braccio quadro, il fosso che in fondo sarà braccia 32, verrà dinari 8 il braccio quadro. (f. 127r) and if it were of double depth, it would only grow of one bank, that is 4 braccia, which grows half of the first expenditure; that is, where 4 dinari were given first for two banks, for 3 banks is 6 dinari, 2 dinari per bank, the ditch being at the bottom 16 braccia. still if the ditch was 16 braccia wide and 4 braccia deep, costing 4 soldi per worker, 4 milanese dinari per square braccio, the ditch that at the bottom will be 32 braccia, will coast 8 dinari per square braccio. (f. 127r) sheet 126r replicates the cost per worker and suggests the best period for carrying out the work between march and june, when farmers cost less because they are free from work in the fields, the days are longer, and the heat is not excessive. e sappi che questo canale non si po cavare per manco di 4 dinari il braccio [quadro], dando a ciascun operatore 4 soldi il dì, e questo canale si de’ fare da mezzo marzo insino a mezzo giugno, perché i villani, sendo fori del loro ordinario esercizio, s’ hanno per buono mercato, e dì sono grandi e ‘ l caldo nolli stanca. and know that this canal cannot be excavated for less than 4 dinari per square braccio, giving each worker 4 soldi per day, and this canal must be made from mid-march until mid-june, because the villains, being free from their ordinary exercise, they are cheap, and the days are long and the heat does not tire them. to reduce labor costs and accelerate excavation times, leonardo devised specific excavation and earth moving machines (fig. 30). the design commitment that transpires also from the conception of these machines betrays a deep involvement and perhaps the real conviction of being one step away from the official assignment which, however, does not appear to have ever been conferred. the 126 and 127 sheets of the codex atlanticus are usually referred to the milanese period. calvi dates them to 1490 while pedretti proposes a date around figure 30. c.a., fol. 4r: earthmoving machine. 50 filippo camerota 149517. only heydernreich is pronounced for a later date, referring to the second florentine period, around 150318. the first two datings are based on critical considerations relating to the style and ductus of the writing, and could find support in the cost estimation that leonardo carries out in milanese currency. however, as anticipated, leonardo’s estimate could simply refer to a unit value familiar to him, and would not necessarily indicate the place where he made those calculations. to raise doubts about the dating of the milanese period is the fact that there is no strong motivation to justify the drafting of a project so detailed in economic as well as technological terms. the eventual creative stimulus produced by the frequentation of luca fancelli when he was in milan to deal with the tiburio of the cathedral, is not sufficient to explain the level of application found in these sheets. the estimate betrays a feasibility study that implies the presence of a client, or at least the occurrence of circumstances that would have favored a specific interest. there were no such circumstances except after leonardo’s involvement in the arno deviation project of 1503, a period in which it seems reasonable to trace the resumption of the navigable canal project (fig. 31). however, the project was not followed. the failure of the deviation of the arno was presumably the most immediate cause but, perhaps, we should also consider the fact that, in view of the important economic commitment required by the grandeur of the work, lacked the political stability necessary to ensure that such an infrastructure could actually work. pisa was still out of control and the recent revolt in arezzo did not play 17 for calvi and pedretti see the bibliographical references at note 1. 18 ludwig h. heydernreich, leonardo da vinci, new york 1954, pl. 218. in favor of such an important investment in valdichiana. for such a project a unitary state was needed that would guarantee political stability and total control over the territory. it is no coincidence that the project was resumed in the middle of the century by cosimo i de ‘medici, when tuscany was almost entirely under the rule of the medici19. but even in that case the idea remained only an ambitious desire, a technological dream evidently still too far from the possibility of being realized. 19 the project is described in a letter of bartolomeo concini to vincenzo borghini, march 26 1572, in l. cantini, vita di cosimo de’ medici primo gran duca di toscana, firenze 1805, pp. 228, 477-478, 668-669. figure 31. codex madrid ii, c. 52v-53r: map of the surroundings of pisa. the place where the deviation of the arno was carried out is marked as “rotta d’arno”. substantia an international journal of the history of chemistry vol. 4, n. 1 2020 firenze university press peer review – critical feedback or necessary evil? seth c. rasmussen particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 consciousness, information, electromagnetism and water marc henry leonardo and the florence canal. sheets 126-127 of the codex atlanticus filippo camerota the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí astatine – the elusive one keith kostecka vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of xx century aleksander sztejnberg substantia. an international journal of the history of chemistry 6(1): 129-131, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1529 citation: rasmussen s.c. (2022) comments on shirakawa’s response. substantia 6(1): 129-131. doi: 10.36253/ substantia-1529 received: dec 20, 2021 revised: jan 16, 2022 just accepted online: jan 17, 2022 published: mar 07, 2022 copyright: © 2022 rasmussen s.c. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article comments on shirakawa’s response seth c. rasmussen department of chemistry and biochemistry, north dakota state university, fargo, nd 58108 usa email: seth.rasmussen@ndsu.edu as both an active researcher in the synthesis of conjugated materials and a chemist-historian that has spent the last decade attempting to detail and clarify the history of conjugated and conducting polymers,1,2 i am overjoyed that prof. shirakawa has elected to provide additional personal details relating to the discovery and development of polyacetylene films. shirakawa has provided this material in response to my most recent substantia paper that details newly revealed accounts by hyung chick pyun (1926-2018), who was a visiting korean scientist that carried out the initial experiment that led to these films.3 this material is critical to advance our understanding of this important historical event. at the same time, however, i was quite disappointed to find that shirakawa viewed my paper as biased, particularly as this puts me in the unpleasant position of having to defend my integrity as a chemist-historian. i approach my historical efforts with great care and the integrity of these efforts is something that i take quite seriously. according to merriam-webster, when used as a verb (as the case here), bias means “to give a settled and often prejudiced outlook to”. in a more general way, bias typical refers to an emphasis in favor of or against an idea or entity, usually in a manner that is closed-minded, prejudicial, or unfair. of course, the goal and expectation within history is that descriptions of historical subjects, general interpretations of the past, and historical explanations are fair and not misleading. this does not mean that bias does not occur within history and the historian c. behan mccullagh describes four common ways in which historical writing can be biased.4 still, mccullagh goes on to explain that such cases are only biased if they occur because the historian wants a particular outcome, normally to further certain personal interests. of course, one can describe pyun’s account as biased, which would be valid. after all, it is a personal account with significant self-interest, as are many such personal accounts, and was written by a man who felt grievously wronged. still, the use of such sources does not necessarily make the resulting historical analysis biased. historians have long been aware that written documents reflect the concepts and interests of their authors.4 this issue is generally dealt with by not taking material at its face value, but to construct explanations of its origins that will account for its features as much as possible, after which efforts are made to find coherence among the various explahttp://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 130 seth c. rasmussen nations to decide what really happened. this is precisely the approach taken in the analysis of pyun’s account and its incorporation into a larger view of the discovery of polyacetylene films, including highlighting aspects that were known to be inaccurate. shirakawa is also critical of the sources used in the analysis and presentation of the discovery of polyacetylene films, stating “most descriptions in the article are based on pyun’s accounts and third-party records, such as press reports by the nobel foundation and royal swedish academy of sciences at the time of the nobel prize announcement and award. the article lacks any of my own input, except for my printed nobel lecture and scientific papers.” this, however, is a misrepresentation of the sources used. while third-party sources were indeed used, this was only in discussion of how the event has been commonly portrayed by others, as well as highlighting errors in many of those descriptions of the event. in terms of constructing a more accurate narrative of the discovery of polyacetylene films, the primary sources beyond pyun’s account were shirakawa’s scientific publications, his published nobel lecture,5 his nobel autobiography,6 and a reflection by shirakawa on the polyacetylene film synthesis that was published in the journal of polymer science: part a. polymer chemistry in 1996.7 all of these sources were written by shirakawa and include his personal descriptions of various aspects of the event. as such, the published narrative included all available sources at the time. of course, as i pointed out in the substantia paper:3 “the truth is shirakawa has actually said very little on the subject and what has been said is somewhat vague.” while shirakawa is now sharing additional material that will further add to our understanding of these events, the previous work cannot be criticized for not including details that had never been communicated. i look forward to a deeper study of this new account from shirakawa, which will likely change our view of the details of this event. the addition of new sources is a common aspect of historical study, which can often result in refinement, correction, or even drastic re-evaluation of historical events. as with the previous account of pyun, this will require analysis of shirakawa’s newly presented account and renewed efforts to find consistency between all of the available sources to decide what really happened. clearly, this will require more significant time and effort than what i have been able to dedicate for the preparation of this short commentary. however, initial review seems that shirakawa is now implying that pyun’s initial experiment did not produce polyacetylene films, but only “a black flappy or spongy matter”. this failed experiment then served as motivation for further experiments by shirakawa and his students, which ultimately resulted in the successful generation of polyacetylene films. as emphasized by shirakawa, pyun was not involved with these additional experiments and stated that “pyun’s contribution was minimal ”. this new narrative, however, does not seem to be consistent with multiple statements shirakawa has made in the past. such statements include an acknowledgement “to messrs. h. c. pyun and t. ito for the preparation of poly(acetylene) films” in his 1971 paper,8 as well as the following statement from his autobiography that describes pyun’s initial product as a film:6 “when a visiting scientist tried to make polyacetylene in the usual way, he only produced some ragged pieces of a film.” and then, there is of course the acknowledgement to pyun made in his nobel lecture:5 “...and to dr. hyung chick pyun with whom i encountered the discovery of polyacetylene film by the fortuitous error.” finally, i must point out that shirakawa makes various statements concerning the history of organic semiconducting materials that are not supported by our current understanding of the historical record. rather than enumerate these specific points, i will just encourage the reader to consult my extensive work on this topic for the most current analysis of this history, as well as discussion of the associated historical record.1,2 references 1. for the most recent review of this historical work, please see: s. c. rasmussen, conjugated and conducting organic polymers: the first 150 years. chempluschem 2020, 85, 1412–1429. 2. for the specific history of acetylene polymers, please see: s. c. rasmussen. acetylene and its polymers. 150+ years of history. springer briefs in molecular science: history of chemistry; springer: heidelberg, 2018. 3. s. c. rasmussen, new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry. substantia 2021, 5, 91-97. 4. c. b. mccullagh, bias in historical description, interpretation, and explanation. history and theory, 2000, 39, 39-66. 5. h. shirakawa, the discovery of polyacetylene film: the dawning of an era of conducting polymers (nobel lecture). angew. chem. int. ed. 2001, 40, 2574-2580. 6. h. shirakawa, hideki shirakawa. in les prix nobel, the nobel prizes 2000 (ed: t. frängsmyr) nobel foundation: stockholm, 2000, pp. 213-216. 131comments on shirakawa’s response 7. h. shirakawa, reflections on “simultaneous polymerization and formation of polyacetylene film on the surface of concentrated soluble ziegler-type catalyst solution,” by takeo ito, hideki shirakawa, and sakuji ikeda, j. polym. sci.: polym. chem. ed., 12, 11 (1974). j. polym. sci. a polym. chem. 1996, 34, 25292530. 8. h. shirakawa, s. ikeda, infrared spectra of poly(acetylene). polym. j. 1971, 2, 231-244. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 1(1): 49-53, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-7 citation: l. caruana sj (2017) from water to the stars: a reinterpretation of galileo’s style. substantia 1(1): 49-53. doi: 10.13128/substantia-7 copyright: © 2017 l. caruana sj.this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declares no competing interests. research article from water to the stars: a reinterpretation of galileo’s style* louis caruana sj faculty of philosophy, pontificia università gregoriana, 00187 rome, italy e-mail: caruana@unigre.it abstract. galileo galilei’s contribution during the early stages of the scientific revolution and his clash with the catholic church have been discussed, studied, and written about for many decades. there are indications however that recent work in this area has tended to underestimate the fact that galileo had a particular style. by style here i mean a particular combination of behavioural features that are specific to a person or a historical period. style of course can be related to behaviour in general, but what is relevant in this paper is the combination of dispositions that determine a particular way of engaging in science, as discussed by scholars like a.c. crombie.1 galileo, i will argue, had a scientific style marked by overconfidence. he tended to downplay the importance of obvious contradictory evidence that undermined his claims, and he did this by producing auxiliary hypotheses that sometimes verged on the extravagant. if we focus on this somewhat neglected aspect of his style, some interesting new questions emerge: to what extent did galileo depend on such auxiliary hypotheses? how insecure did they render his position? and how ad hoc were they? in this paper, i explore these questions by comparing two important debates: one about the nature of water and buoyancy, the other about cosmology. since the main features of the cosmology debate, the one involving galileo’s defence of heliocentrism, are well known, i will dedicate more time to the water debate, before proceeding to highlight the elements of style that are common to both debates, and to evaluate the relevance of these elements for current understanding of scientific practice. keywords. galileo, auxiliary hypotheses, ice, buoyancy 1. the buoyancy debate1 first, a word about galileo’s social and cultural situation. the way empirical inquiry used to be motivated and propagated at that time, when what we now call the scientific revolution was at its infancy, differed considerably from the way it is today. in that context, the driving force used to originate mainly not from scientific questioning as such but from what the major patrons of individual scholars regarded as marvels and curiosities, from what these patrons * republished from "aqua incognita. why ice floats on water and galileo 400 years on". p. lo nostro and b.w. ninham, eds., connor court publishing pty ltd., ballarat (australia), 2014. isbn: 978-19-2513-821-4. 50 louis caruana sj considered worthy of exciting debates and controversy. the question “why does ice float on water?” was one clear example of an exciting question because we all know that ice is in fact nothing more than water. the overall social, political, and cultural context in the seventeenth century was such that science was dependent to a very large extent on what patrons wanted, and this meant that natural philosophers, or anyone we would now recognize as a scientist, could never be fully in control of their research. patron-dependence was crucial: through financial support, it made the scientist’s work possible. but it produced a number of difficulties as well, mainly because the general habitat for science, where science happened, was not the isolated laboratory but pubic disputation, and this mode of scientific practice usually drew attention not to careful and technical understanding but to quick, publicly accessible answers. moreover, during the period when galileo flourished, mathematics was still considered a discipline that was less important than aristotelian philosophy within the overall hierarchy of knowledge. galileo had to struggle hard against this mindset. the only way he could gain a hearing was to make himself philosophically versatile enough to engage with the aristotelians on the same level.2 with this background in mind, we can now appreciate better the various forces at work during the debate that concerns us here, the one concerning water and buoyancy. this was launched in the summer of 1611, a session that took three days. it started with a dispute about the nature of cold as a quality, but then shifted into one about buoyancy. the major contention arose when the aristotelians among those present were shocked to learn that, for galileo, ice was not condensed water, as they had always assumed. they had to admit that the issue was not completely clear in the classic texts. although aristotle had indeed indicated that ice was condensed water, his reflections on this point were rather sketchy. for instance, in his metaphysics he discussed the different senses in which the word “is” can be used, and the examples he offers include ice. he writes: “[the word] ‘is’ has [a] number of senses; for a thing ‘is’ a threshold because it is situated in a particular way, and ‘to be a threshold’ means to be situated in this particular way, and ‘to be ice’ means to be condensed in this particular way. some things have their being defined in all these ways: by being partly mixed, partly blended, partly bound, partly condensed.”7,8 aristotle here takes the idea that ice is condensed water as obvious. why? we find no clear answer in aristotle’s own works, but his followers filled up the reasoning behind this in the following way. he must have started not from the fact that ice floats on water but from the fact that it is colder than water. since ice is colder than water, it must be water minus something, minus some amount of heat, and this lack leads to a condensation. it is water with a deficiency, as it were, not with something extra. and as regards the question why ice floats, aristotelians considered this fact as just one example of buoyancy in general. for them, buoyancy is a matter of shape only. it had nothing to do with density. on this issue, they were certainly following their master who had explained this point quite carefully. in his book de caelo, he argued that shape matters because the determining factor in buoyancy is the difference that the various materials we consider show as regards penetrability. for instance, air is more penetrable than water, and water is more penetrable than earth. he adds: “the reason why broad things keep their place [e.g. a plank of wood afloat on water] is because they cover so wide a surface, and the greater quantity [i.e. the water] is less easily disrupted. bodies of the opposite shape sink down because they occupy so little of the surface, which is therefore easily parted.”9 it is good for us to recall here that, in galileo’s times, aristotelians used to feel obliged to defend aristotle, be it on buoyancy or geocentrism, or any other issue, not only because his positions were justified, as indeed they thought they were, but also because they considered these various positions important individual bricks that held an entire worldview in place. for them, removing one brick could have devastating consequences that would destabilize the entire conceptual scheme. what was galileo’s reaction to this? for him, aristotelians were seeing the entire issue the wrong way round. they had started from the observation that ice is colder than water and had sidelined the fact that ice floats on water. what they should have done was to start from the fact that ice floats on water. for galileo, since ice floats on water, it must be rarified water, not condensed water. and as regards buoyancy, galileo resorted to another ancient source: archimedes. while aristotle had developed a shape-theory of buoyancy, archimedes had developed a density-theory, according to which a thing in water experiences a buoyant force equal to the weight of water displaced. galileo did not deny that shape matters. he conceded that the shape of a body affected the speed with which it sinks or rises, but was convinced that shape does not affect whether it sinks or rises. up to this point, the debate seemed well balanced. both sides presented interesting insights, and both had a heavyweight from ancient greece as support. the decisive factor came when galileo’s main opponent, lodovico delle colombe, devised a simple but spectacular and decisive experiment. he did not want to resort to aristotelian deductive reasoning or anything like that. he appealed instead to direct evidence, just like galileo. he made all the participants gather round the demonstrating table and he showed them how a sphere of ebony, whose 51from water to the stars: a reinterpretation of galileo’s style density is higher than that of water, sinks when placed on water, while a thin piece of the same material remains afloat even with some weights on it. so the determining factor was shape, not density – full stop. galileo must have been quite astounded by this, but he did not give up. he tried to come up with some way of explaining this experiment in his own terms. this was not easy at all, because according to his worldview there should not be any special effect at the surface of a liquid which does not arise elsewhere within liquid. in other words, his view of liquids ruled out what we now call surface tension. he took therefore another line of argument and tried to bring in the relevance of wetness, but this lead to no convincing conclusion. since the dispute itself became noisy and inconclusive, the meeting was brought to a close, and the main protagonists left with the intention of producing a full written version of their position. galileo, encouraged to proceed with this by his patron, duke cosimo ii, took his task seriously, and produced his written text within a year. for him, maintaining the duke’s favour was obviously important. we notice once again how science was dependent on patronage to an extent that is hard for us to accept today. galileo’s written version, entitled discourse on bodies in water and published in 1612, was based on archimedes’s classic work on floating bodies, which had emphasized hydrostatics. archimedes had offered an account of buoyancy that had been intended to explain the situation once equilibrium is reached. in other words, he had described the state of affairs when a body is stationary and floating, or when it has sunk and lies at the bottom. he had said nothing about the process of rising to the surface or of sinking; his view had been limited to statics as opposed to dynamics. galileo therefore saw a way of breaking new ground by delving into hydrodynamics. this was a risky business, because in claiming the right to give an account of motion, he was encroaching into the philosophers’ domain – yet again. resorting to the model of the lever, he wanted to explain the downward motion of a sinking body and the corresponding upward rise of the water surface, two motions with different speeds. and he did this by resorting to the model of a lever with different arm-lengths, a lever that makes a short swing on the short side and a quick swing on the long side. he adopts therefore a mechanical view of the world – and this was seriously at odds with the aristotelian worldview, at least in two senses. first of all, aristotelians had always believed that each of the four elements had its own specific motion: for instance earthly bodies move down because they have heaviness, while fiery ones move up, because they have lightness. heaviness and lightness were for them real attributes belonging to things according to their nature. each object or material will therefore have its share of overall heaviness or lightness in proportion to its constitution from the elements. from these fundamental, elemental motions, therefore aristotelians offered the explanation of all motion. as regards the specific case we are dealing with here, the case of sinking or floating, the shape of the body, they used to say, was not the determining factor but only a causa per accidens, an explanation of secondary importance. the floating object needs to be understood in terms of its own inherent constitution in terms of the elements, the proportion of which determines the object’s intrinsic quantity of heaviness and of lightness. galileo was dissociating himself entirely from this kind of explanation. he was proposing a worldview in which buoyancy was the result neither of an innate upward trend (lightness as an attribute) nor of an effect of shape. for him, it was the result of the body’s downward motion being counterbalanced by a counterforce. the implication here was that bodies, be they predominantly earthy or predominantly fiery, have only one type of motion: downwards. the aristotelians were not amused. secondly, the fact that water shows a kind of skin at its surface was perfectly in line with the aristotelians’ broad view of liquids in general. for them, water, being a continuum, has a tendency to preserve its cohesion and integrity, as their master had expressed quite clearly in his work de caelo: “since there are two factors, the force responsible for the downward motion of the heavy body and the disruption-resisting force of the continuous surface, there must be some ratio between the two. for in proportion as the force applied by the heavy thing towards disruption and division exceeds that which resides in the continuum, the quicker will it force its way down; only if the force of the heavy thing is the weaker, will it ride upon the surface.”10 on this issue, galileo had a problem. for him, water was made up of corpuscles with no intrinsic difference between them. it did not matter whether these corpuscles were at the surface or within the interior of the liquid. this view therefore, as mentioned above, ruled out any idea of surface-tension. how could galileo then account for the impressive demonstration of his opponent delle colombe? to account for the intriguing floating chip of ebony, he had no choice but to resort to an explanation that was considerably extravagant. he proposed that, as the chip is lowered onto the surface, the observable slight depression of the water surface as it floats makes the chip associate itself with a layer of air above it. in this way, the composite object, layer of air and layer of ebony, will have a specific weight less than that of water. was he introducing, through the back door, some occult forces here, some “magnetic virtue of air” as his opponents were quick to remark? these are his words: 52 louis caruana sj but if it [the ebony chip as it presses down onto the water surface] has already penetrated and is, by its nature, denser than water, then why does it not proceed to sink but stops and remains suspended within that small cavity that had been produced by its weight? i would say: because, as it moves down until its [upper] surface arrives at the water level, it loses a part of its own weight, and it then proceeds to lose the rest of its weight as well by descending deeper even below the water surface, which produces a ridge and a bank around it. it loses weight as it descends in such a way that it drags down to itself the air above it, by adherent contact. this air proceeds to fill up the cavity produced by the little water ridges, in such a way that, in this case, what really descends and is located in water is not just the ebony chip, or the iron chip, but the composite of ebony and air, from which there results a solid [solido]which does not exceed water in density as does ebony on its own, or gold on its own.11,12 this is the best galileo could come up with as he tried to reason things out from within his system. i think it is fair to say that, as an explanation, it looks farfetched and ad hoc. what it shows is a strong determination on his part to save his overall worldview at all costs. he was ready to go even that far. so, all in all, we can say that debate on water and buoyancy that had started viva voce in 1611 and then dragged on in writing for more than four years had no clear winner.13 as historians now recognize, one important thing we see in this debate is the emergence of a growing gap between two very different professional identities: on the one side, we have professional philosophers, the aristotelians, whose principles are derived from acknowledged philosophers; on the other side, we have a specimen of a new species of intellectual, a mathematician-philosopher, who seemed to violate the disciplinary boundaries that had been well established and respected for hundreds of years. 2. comparing with the astronomy debate let us draw a quick comparison now between this debate and the one on the solar system. as is well known, the main story of the solar-system debate, in short, was this. with the use of the telescope, galileo discovered new evidence in favour of the heliocentric view that had been promoted mathematically by nicholas copernicus about fifty years beforehand. galileo therefore started to defend the idea that copernicus’s view was not a mere mathematical shortcut to obtain quick predictions of planetary positions, but was a true description of how things are. in the ensuing debate, which involved aristotelians yet again, galileo was challenged to explain some pretty glaring instances of counterevidence to his proposals. and this is the crucial point where this solar-system debate shows some remarkable similarity with the buoyancy debate. in both cases, galileo had to deal with counterevidence that seemed obvious and convincing. in both cases, he made proposals that were unconventional and therefore somewhat suspicious. instead of going into all the intricate detail of the solar-system debate, let us consider the crucial points only. one obvious element of counterevidence for the proposal that the earth is in motion is direct experience. we simply have no sensation of movement. in line with this, as common sense suggests, if the earth were in motion, there should be some detectable displacement during the falling of an object, because, by the time the object hits the ground, the earth would have moved a little. but nothing of the kind is observed. here we have, therefore, a serious challenge to anyone who wants to argue that the earth moves. for galileo, however, this kind of argument was not the most worrying. he rose to this challenge in a spectacular way by establishing the basic principles of relativity. he proved that, for two reference frames in uniform motion, no such displacement should be expected.14 the real worrying element of counterevidence was the lack of stellar parallax. if the earth were really in motion through space, then the nearby stars should show some displacement with respect to the distant stars. our view of the night sky would be somewhat like what we see from a moving train: nearby trees shifting across the distant background. but no such effect is evident in the night sky. so again, galileo had a problem. he tried to use his telescope, but it was all in vain.15 the only way he could respond to this problem was to adopt what had already been suggested by some commentators before him, namely that the absence of stellar parallax was due to the fact that all stars were infinitely far out in space.16,17 this suggestion, of course, did solve the problem. it was however ad hoc and embarrassing – embarrassing because it went against galileo’s own idea that aristotle had made a mistake in assuming that there is an essential difference between the sub-lunar universe and the rest. for galileo, the entire universe should be homogenous with a uniform distribution of stars throughout. so here we see a clear common feature with the previous debate, a common stylistic feature involving the way science was engaged in. in both cases, galileo faces an insurmountable problem but sticks to his guns; he does not shy away from defending himself by walking on stilts, as it were: by producing auxiliary hypotheses that, because of their ad hoc nature, apparently drain his position of its convincing power. 53from water to the stars: a reinterpretation of galileo’s style 3. conclusion what conclusion can be drawn? there is of course much more that can be said about all the major points highlighted above. the little that has been mentioned however is enough to justify the following three points. first, we need to accept that the practice of science rarely involves clear-cut crucial experiments that decide an issue at one go. what has been highlighted in both debates confirms the idea, proposed by philosopher imre lakatos, that science does not develop according to naïve falsificationism but according to a more complex process involving auxiliary hypotheses.18 these auxiliary hypotheses can have various degrees of plausibility or acceptability, depending on how they fit in with background beliefs that are shared by both the proponent and the opponent of the theory. the early stages of the new scientific paradigm inaugurated by galileo were vulnerable. there was no knock-down argument on either side. it is true that, in both debates, galileo’s view did eventually turn out to be correct. at that time, however, his case had some obvious weaknesses, even on his own terms. secondly, a few words about the church. although the way the church handled galileo during the solar-system debate remains an embarrassment, especially because of its official declaration that heliocentrism was heretical, which it certainly is not since it is not even theological, the arguments mentioned above can nevertheless help us understand why the case was so intriguing, and why some aristotelians and theologians were not immediately won over by galileo’s arguments.19,20 and finally, a word about galileo’s genius: as we know, time proved galileo right in both debates. this shows that he was a man of genius: he had a way of seeing ahead, a way of seeing beyond what can be expressed by reasoned argument and experiment. we see him sometimes groping in the dark, especially in formulating auxiliary hypotheses, but in fact he was groping in the right direction. references 1. a.c. crombie, styles of scientific thinking in the european tradition: the history of argument and explanation especially in the mathematical and biomedical sciences and arts, gerald duckworth & company, london, 1995. 2. this is discussed in ref. 3, chapter 3; the following paragraphs owe a lot to biagioli’s excellent study. other useful sources are refs. 4-6. 3. m. biagioli, galileo courtier, university of chicago press, 1993. 4. s. drake, cause, experiment and science: a galilean dialogue incorporating a new english translation of galileo’s “bodies that stay atop water, or move in it”, university of chicago press, 1981. 5. p. palmieri, arch. hist. exact sci. 2005, 59, 189. 6. s. straulino, c.m.c. gambi, a. righini, am. j. phys. 2011, 79, 32. 7. metaphysics 1042b 25-28 (my translation). the crucial greek word here is πεπυκνῶσθαι; this is derived from πυκνόω, which means to make close, to condense. some translators, like w.d. ross (see ref. 8), miss the important nuances by translating πεπυκνῶσθαι as ‘solidified’ instead of ‘condensed’. 8. the basic works of aristotle, (ed.: r. mckeon), random house, new york, 1941. 9. aristotle, de caelo, 313b 14-16, see ref. 8. 10. aristotle, de caelo 313b 16-22, see ref. 8. 11. g. galilei 1612, p. 98 (my translation), see ref. 12. 12. g. galilei, discorso intorno alle cose che stanno in su l’acqua o che in quella si muovono (1612), http://www. ousia.it/sitoousia/sitoousia/testidifilosofia/testipdf/ galilei/discorsoinsul’acqua.pdf, last accessed on jan 03, 2017. 13. the other main texts directly related to this debate include the following. on the side of the aristotelians: lodovico delle colombe, discorso apologetico d’intorno al discorso di galileo galilei (1612); and vincenzo di grazia, considerazioni sopra ’l discorso di galileo galilei (1613); on the side of galileo: benedetto castelli, risposta alle opposizioni del s. lodovico delle colombe e del s. vincenzo di grazia contro al trattato del sig. galileo delle cose che stanno in su l’acqua (1615). this latter author was a friend of galileo’s, but we have now clear indications that this book had been written by galileo himself. 14. he shows this in “day two” of his dialogue concerning the two chief world systems. 15. c.m. graney, phys. persp. 2008, 10/3, 258. 16. this had been proposed by thomas digges (c. 15461595) in his translation of copernicus’s book de revolutionibus; see ref. 17, p. 207. 17. j.r. ravetz in a companion to the history of modern science, (eds.: r.c. olby, g.n. cantor, j.r.r. christie, m.j.s. hodge), routledge, 1996, pp. 201. 18. i. lakatos in criticism and the growth of knowledge, (eds.: i. lakatos, a. musgrave),  cambridge university press, 1970, pp. 91. 19. for more on how galileo’s ideas where incorporated slowly within the school curriculum during the century following his death, see ref. 20. 20. l. caruana in the cambridge companion to the jesuits, (ed.: t. worcester sj), cambridge university press, 2008, pp. 243-260. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments substantia. an international journal of the history of chemistry 6(1): 107-119, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1425 citation: rasmussen s.c. (2022) the early history of polyaniline ii: elucidation of structure and redox states. substantia 6(1): 107-119. doi: 10.36253/ substantia-1425 received: oct 05, 2021 revised: nov 16, 2021 just accepted online: nov 18, 2021 published: mar 07, 2022 copyright: © 2022 rasmussen s.c. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen department of chemistry and biochemistry, north dakota state university, ndsu dept. 2735, p.o. box 6050, fargo, nd 58108-6050, usa email: seth.rasmussen@ndsu.edu abstract. polyaniline, one of the primary parent conducting polymers, is a quite old material with a history dating back to 1834. with the distinction of being the oldest known fully synthetic polymer and successfully commercialized as several popular cotton dyes in the 1860s, this material was originally known by the name of its black dye, aniline black. of course, throughout this early history, the chemical identity and structure of these early polyaniline products were completely unknown, and it was not until the 1870s that initial attempts began to reveal various structural aspects. the current report will present a detailed historical account of the efforts to determine the structures of these early aniline oxidation products over the time period of ca. 1870-1915. in addition to the identity and structure of specific products, studies revealing the interconversion of one species to another via both redox and acid-based processes will also be discussed, with these collective efforts resulting in a comprehensive model of these materials that has remained essentially unchanged to this day. keywords: polyaniline, aniline black, emeraldine, nigraniline, structure elucidation. introduction1 polyaniline is one of the most commonly studied parent conjugated polymers (figure 1),1-8 with its oxidized emeraldine form (figure 2) representing one of the earliest examples of a conducting organic polymer. while such conducting polymers generated from the oxidation (p-doping) or reduction (n-doping) of conjugated polymers are generally viewed to be quite modern materials,1,3-7 electrically conductive polymers actually date back to the early 1960s. conjugated polymers as a whole are even older, with a history dating back to the early 19th century.9-14 within this long historical record, polyaniline holds the distinction of being the earliest known conjugated polymer and dates back to 1834 with the work of the german chemist f. ferdinand runge (1794-1867), who treated protonated aniline salts with various oxidants to generate green and † part i was previously reported as s. c. rasmussen, the early history of polyaniline: discovery and origins. substantia 2017, 1(2), 99-109. http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 108 seth c. rasmussen black materials.15 as such, it predates the 1839 report of eduard simon (1789-1856) detailing the generation of the material now identified as polystyrene,16 making polyaniline also the oldest known fully synthetic organic polymer.12,17 of course, the modern name polyaniline was not introduced until the 1960s,18-20 prior to which it was referred to by various color-based names, the most common of which was aniline black. this emphasis on color was largely due to the fact that the primary application of early polyaniline was as green, blue, and black dyes for cotton, with the commercialization of these dyes dating back to 1860.10-13 at the same time, it is important to note that the chemical identity and structure of these early polyaniline products were unknown at the time and it was not until the beginning of the 20th century that deeper knowledge of the material’s composition began to take shape. the structural details of polyaniline are complicated by the fact that it is the only member of the common conjugated polymers to exhibit both protonated and free-base forms (figure 2). in addition, while conjugated polymers are all redox active materials, thus leading to conducting polymers in their non-neutral redox states, polyaniline exhibits multiple known oxidative states, each with distinct properties and characteristics. although previous reports have presented an in-depth early history of polyaniline up to ca. 1870,13,14 the current report will present a detailed historical account of the efforts to determine the structures of these early aniline oxidation products, beginning with attempts in the 1870s to reveal the mechanistic processes involved in their synthesis. in addition to the identity and structure of specific products, studies revealing the interconversion of one species to another via both redox and acidbased processes will be discussed, with these collective efforts of ca. 1870-1915 resulting in a comprehensive model of these materials that has remained essentially unchanged to this day. the beginnings of these efforts can be traced to a particularly noteworthy report by heinrich rheineck in 1872.21 rheineck and nigraniline although heinrich rheineck played an important role in the history of polyaniline, very little is actually known about him. originally from neckarsulm, germany (near stuttgart), he enrolled in the study of pharmacy at the university of tübingen in the fall of 1860.22 at tübingen, he carried out research under adolph strecker (1822-1871) on the action of sodium on allantoin, resulting in a single paper published in 1865.23 he then worked in hohenheim as an assistant chemist in agricultural chemistry for several years,24 but had moved to hagen, germany in north rhine-westphalia (near dusseldorf ) by 1871.24-26 here he studied aspects of inorganic dyes such as prussian blue.26 his time in hagen was short, however, and by 1872, he had moved to nearby elberfeld (ca. 30 km to the southwest),21,27 most likely employed by one of the smaller aniline dye companies located there. it was at elberfeld that rheineck then published his seminal work on aniline black.21 this paper attracted a fair amount of interest and it was republished a number of times.27-29 rheineck began the discussion of his study by stating that like other aniline dyes, aniline black is produced by the oxidation of aniline, thus resulting in the molecular condensation of repeated aniline units. furthermore, these oxidation products are still of a basic nature, with aniline black a definite base. he then proposed that this base be called nigraniline (latin nigrum “black” + aniline) in analogy to the name rosaniline for aniline red.21 in order to support these conclusions, he produced samples of aniline black following common conditions for its production on fabrics (aniline hydrochloride, potassium chlorate, and copper chloride). this aqueous figure 1. common parent conjugated organic polymers. figure 2. various common forms of polyaniline. 109the early history of polyaniline ii: elucidation of structure and redox states mixture was allowed to evaporate in a porcelain dish and repeatedly moistened until a dry, velvety black powder was produced, after which the product was washed with hot water. as it was well known that this material appeared dark green on fabric and turned dark blueviolet after treatment with alkalis, rheineck proposed that the blue-violet material was a free base, with the initial green material the corresponding hydrochloride salt. to confirm this, he treated the initially produced aniline black with either soda or ammonia to remove hydrochloric acid and generate what he viewed to be the free base.21 this base could then be successfully used to remove acid from aniline salts. that is, if the isolated free base was produced on a piece of cotton, and then treated with aniline salts in the absence of oxidant, the fabric immediately turned green. treating this again with alkali then returned the fabric to the original blue-violet color. in addition, he showed that the green hydrochloride salt could also be treated with sulfuric acid to release hydrochloride fumes and give a violet solution. when diluted, this solution again gives a black-green precipitate, which he was confident was the sulfuric acid salt.21 rheineck felt that these results confirmed his view that the blue-violet material was a free base (nigraniline), which generated green salts when treated with acid. however, he decided not to follow through with more detailed studies, stating:21 for lack of opportunity and facilities, i have to refrain from further elaboration on this interesting subject in scientific terms, and make other chemists aware of it, to which a well-established laboratory is available. as such, this remained his only publication on aniline black and he left it to others to expand upon his initial efforts. one such to carry out further efforts was the german chemist rudolf nietzki (1847-1917), who reported various studies on aniline black starting in 1876.30,31 nietzki and oxidative degradation rudolf hugo nietzki was born on march 9, 1847, in heilsberg, prussia (now lidzbark warmiński, poland) to a protestant family.32-35 his father, karl johann emil nietzki, was a pastor, rector and writer.32,33 in 1854, the family moved to the prussian town of zinten (now kornevo, russia), where his father served as pastor to the small town.35 initially educated by his father, nietzki was sent to complete his studies at the gymnasium in königsberg (now kaliningrad, russia), as kinten was too small to have schools for higher education.32,33,35 unhappy with his gymnasium education, he left before completion32,35 and began the study of pharmacy, beginning with an apprenticeship in zinten, followed by an internship in kreuzburg, prussia (now kluczbork, poland).33,35 after passing the assistant examination in 1865,32,33 he then worked in a pharmacy in nearby hirschberg (now jelenia góra, poland),33,35 before additional studies at the university of berlin in 1867.32,33,35 in 1870, he passed the state pharmacy examination35 and soon after was called to serve as a military pharmacist in the franco-prussian war,32,33,35 during which he was captured by the french and held as a prisoner of war.33,35 following the end of the war in 1871, he was offered a position as private assistant to august wilhelm hofmann (1818-1892) at the university of berlin.32,33,35 during his spare time, he also carried out some research in plant chemistry,35 such that he was able to obtain his dr. phil. at the university of göttingen in 1874.32-35 as he did not have a certificate of maturity from a gymnasium, he could not take the degree in berlin.35 after obtaining his doctorate, he worked as a chemist for matthes & weber in duisberg,32,33,35 but then moved to the university of leiden in 1876 to became first assistant in the laboratory there,35 working under antoine paul nicolas franchimont (1844–1919)32,33,35 and jacob maarten van bemmelen (1830-1911).35 in 1879, he began working as a research chemist in the laboratory of kalle & co. in biebrich, rhineland-palatinate,32,33,35 but left in 1883 to rent a place in the laboratory of dr. schmidt, in wiesbaden, with the desire to carry out independent industrial and scientific studies.35 in the spring of 1884, he moved to basel, switzerland, to introduce processes he had developed to the dyestuffs company j. r. geigy33,35 and at the same time obtained space in the laboratory at the university of basel. at the university, jules piccard (1840-1933) quickly recognized the value of having a specialist in dye chemistry at basel and offered to establish nietzki as a privatdozent.35 nietzki completed his habilitation at the university of basel on june 30, 1884, after which he was appointed professor extraordinarius in 1887.32,33,35 he was made professor of chemistry in 189532-35 and as the university laboratory did not have enough spaces to meet the demand of students, nietzki established an organic chemistry laboratory at his own expense, in a private house located in the rue du rhin. the lab initially accommodated 20 students, but was later expanded to allow 36 students. during his third decade at basel, rapidly developing arteriosclerosis hampered his ability to work and ultimately made laboratory manipulations very difficult.35 as a result, he resigned as professor in march of 1911,32,33,35 retiring to freiburg im breisgau, in 110 seth c. rasmussen southern germany, the following year.35 after a long illness, he died at the neckargemund sanatorium on september 28, 1917.32-35 it was while at leiden that nietzki began reports of his investigations into the nature of aniline black in 1876, beginning with efforts to produce high purity samples for study.30 once satisfied with the quality of the samples of aniline black, he then began efforts to analyze its chemical composition. such efforts resulted in the empirical formula c18h15n3∙hcl. it should be noted that this formula is very similar to that previously reported by carl julius fritzsche (1808-1871) in 1843, although with lower cl content.13,14,36 as nietzki had extensively purified his aniline black samples, it is quite possible that he had partially reduced his sample, thus inadvertently reducing the cationic content and thus the amount of clcounterions. two additional analysis papers then followed in 187631 and 187837, but these efforts focused primarily on the blue material generated by boiling isolated aniline black in excess aniline, which nietzki viewed to be a form of phenylated aniline black. in the 1878 paper, he does conclude that the amount of cl found during analysis is dependent on the methods of purification and drying of the sample.37 it was during the period between the second and third of these papers on the analysis, however, that nietzki reported a discovery that would have far more impact on the eventual elucidation of the structural nature of aniline black. thus, in an 1877 report,38 he found that if aniline black is heated with potassium dichromate (k 2cr2o7) in sulfuric acid, copious amounts of quinone was produced. to study the nature of this reaction, he suspended aniline black in dilute sulfuric acid and gradually added potassium dichromate. in the process, the black material was consumed, giving rise to a strong odor of quinone. the brown, liquid mixture was then separated by steam distillation to give a considerable amount of quinone, although not enough to correspond to the initial amount of aniline black. the residual content of the still was then evaporated to give a colorless crystalline material identified as hydroquinone. thus, nietzki concluded that aniline black was initially converted to hydroquinone, which was then oxidized to quinone (figure 3). as aniline black is itself produced via the oxidation of aniline, nietzki proposed that hydroquinone or quinone could be produced in this way from aniline, in which aniline black was then just an intermediate oxidation product. treatment of aniline with dichromate in dilute sulfuric acid confirmed this view to be correct, with the ratio of hydroquinone to quinone dictated by the amount of oxidant applied. nietzki then followed this initial report with a second paper in 1878, here focusing on optimizing the isolated yield of quinone.39 while he had previously found that hydroquinone could be produced in good yield, efforts to generate the final quinone always occurred in significantly lower yields, with the exception of attempts carried out at very small scale. as this led him to suspect that the quinone was undergoing further reactivity under heat and oxidation, he steam distilled samples of pure quinone in the presence of oxidant, which resulted in the generation of hydroquinone and a resinous product. he then repeated the process without the oxidant, again getting similar results, which led to the belief that quinone was undergoing condensation under heat. thus, rather than the application of steam distillation, he found that near quantitative amounts could be generated by the slow addition of potassium dichromate to cooled sulfuric acid solutions of aniline, after which the quinone was isolated by ether extraction. of course, the generation of quinone and hydroquinone via the oxidative degradation of aniline black provided some clues as to structural aspects of the initial aniline material. however, this did not seem to be a significant focus for nietzki, who seemed much more interested in this process as an easy and effective method for the generation of quinone. the next significant step towards an understanding of the structures involved then came from one of the original developers of commercial black aniline dyes, heinrich caro (1834-1910). caro and critical intermediates heinrich caro (figure 4) was born in posen, prussia (now poznań, poland) on february 13, 1834.13,40 the family moved to berlin in 1842, at which point caro entered the köllnische realgymnasium there.40 he continued his studies at the köllnische realgymnasium until 1852, after which he attended the königliches gewerbeinstitut (royal technical institute), which trained students for industry.13,40-42 at the same time, he was also attending lectures at berlin’s friedrich-wilhelms-universität (now the humboldt university of berlin).13,40-42 towards the end of his studies, caro was encouraged to focus on subjects related to printing and dyeing, figure 3. nietzki’s proposed oxidative degradation of aniline black. 111the early history of polyaniline ii: elucidation of structure and redox states as discussion had begun about setting up a state school for the training of technicians in this field, which would thus require teachers.40 thus, in april of 1855, caro took a modest appointment with c. &. f. troost, a calico printing company in mülheim an der ruhr, where he mainly performed analytical work.13,40,42 in march of 1857, caro was then sent on a study trip to england, where he was instructed to visit a large number of printing and dyeing factories.13,40-42 in particular, he visited roberts, dale & co, having previously met the owner john dale in 1854 during a trip to germany.40,41 after caro’s return to germany, the decision was made to build a larger factory and to transform c. &. f. troost into a corporation, becoming luisenthaler aktiengesellschaft of mülheim.40 during this same period, caro carried out his military service in 1857-1858.40 the following year, caro decided to try his luck in england, moving there in november of 1859. although his initial efforts were unsuccessful, he was ultimately able to obtain a position with john dale at the cornbrook chemical works of roberts, dale & co. in manchester.40-43 it was during this time that caro developed a process for making aniline purple in 1860, from which a black residue was isolated as a byproduct. this residue provided an excellent fast black dye for printing on cotton, with this aniline black then commercialized by roberts, dale & co. in 1862.13,41,42 at least partially due to declining health, caro dissolved his partnership with roberts, dale & co. in october of 1866, after which he returned to germany.41,42 once back in germany, caro took a post in the laboratory of robert bunsen (1811-1899) at the university of heidelberg, and began private consultancy work, primarily for the newly formed badische anilin und soda fabrik (basf).41 his work with basf grew to the point that he was hired as a technical director by the end of 1868.40-43 at basf, he oversaw the development of various new dyes, including artificial alizarin, eosin, methylene blue, and azo dyes, as well as the initial stages of the indigo synthesis.41,42 his various contributions to the dye industry resulted in caro being awarded an honorary doctorate by the university of munich in 1877.42 it was also during this time period that caro started to become involved in the development of german patent law, which had only been recently introduced.42,43 caro was then appointed to the company’s board of directors in 1884.43 by the end of 1889, however, the strain of his activities in the fields of both chemistry and patent law, as well as his duties as director, lead to an end of his direct involvement in the work at basf,42 although he remained active on the company’s supervisory board.42,43 after a short illness, caro died on september 11, 1910 in dresden.13,40,43 it was towards the end of his career, in 1896, that caro published studies that followed up on a previous statement by nietzki concerning the production of a yellow species from the oxidation of aniline in cold, aqueous alkaline solutions.44,45 initial efforts showed that the addition of a permanganate solution to alkaline, aqueous aniline solution resulted in the production of a green solution coupled with precipitation.44 filtration isolated a solid mixture of mno2 and azobenzene (figure 5), leaving a yellow solution. optimized methods utilized a 2% solution of potassium permanganate to an naoh solution of aniline with vigorous stirring.45 the yellow filtrate was then treated with iron sulfite to give a colorless solution, which was then filtered, and evaporated to remove unreacted aniline.44,45 on cooling, a black tar separated, which was then boiled with dilute sulfuric acid to result in the crystallization of a colorless sulfate salt which was insoluble in cold water. the corfigure 4. heinrich caro (1834-1910) (edgar fahs smith memorial collection. kislak center for special collections, rare books and manuscripts. university of pennsylvania). 112 seth c. rasmussen responding base was then crystallized from ligroin as colorless, flat needles which were found to be the known species p-amidodiphenylamine (figure 5).44,45 oxidation of this base with pbo2 in cold water then resulted in the isolation of yellow crystals, which were ultimately determined to be n-phenylquinonediimine.45 this final product was believed to be the identity of the original yellow species. caro recognized that n-phenyl-quinonediimine and azobenzene were isomeric species, with both isomers formed during the alkaline oxidation of aniline. the exact mechanism of their formation, however, still remained unknown.45 further efforts were then continued in 1906 by the german chemist richard willstätter (1872-1942).46 willstätter and linear oligoaniline structures richard willstätter (figure 6) was born on august 13, 1872, in karlsruhe, germany to jewish parents.47-49 after two years in the gymnasium at karlsruhe, the family moved to nürnberg in 1883, where he entered the realgymnasium with the goal of a commercial career.48 he then moved to munich in october 1890, where he studied at the university of munich while also attending lectures at the technische hochschule.48,49 although adolf baeyer (1835–1917) was chair at munich, the bulk of willstatter’s studies were under eduard buchner (1860–1917), johan rupe (1866-1951) and eugen bamberger (1857–1932). he took the pre-doctorate examination in 1893 and was assigned to alfred einhorn (18561917) as a research student.48,49 willstätter started his independent work in 1894, after which he became privatdozent in 1896.48-50 he was then made professor extraordinarius and head of the organic section in 1902.48,50 in 1905, he accepted the chair of chemistry at the eidgenössische polytechnische schule in zurich (now eth zurich).47-51 he was then appointed director of the new kaiser-wilhelminstitut for chemistry in dahlem (now the max planck institute for chemistry), moving to berlin in 1912.47-51 he then returned to munich in 1915 to succeed baeyer, becoming professor and director of the state chemical laboratory. that same year, he was also awarded the nobel prize for chemistry for his work on chlorophyll and plant pigments.47-51 unfortunately, rising antisemitic views in germany ultimately led to his resignation on june 24, 1924,48,49 after which he retained a room to continue some limited research.48,50 a spate of attractive offers from other institutions followed, but all were declined.49,51 recognition for his contributions also continued, including the davy medal of the royal society of london in 1932 and the willard gibbs medal of the chicago section of the american chemical society in 1933.48,50 in late 1938, the gestapo searched his house and he was later ordered to leave the country, resulting figure 5. caro’s synthesis and identification of the intermediate oxidation product n-phenylquinonediimine. figure 6. richard willstätter (1872-1942) (edgar fahs smith memorial collection. kislak center for special collections, rare books and manuscripts. university of pennsylvania). 113the early history of polyaniline ii: elucidation of structure and redox states in his move to muralto-locarno in southern switzerland in 1939.48-51 there, he died of a heart attack on august 3, 1942.49-51 willstätter began his investigation of aniline black and aniline oxidation by revisiting caro’s oxidation of p-amidodiphenylamine by lead oxide as discussed above (figure 5). in analyzing the isolated oxidation product, he found the nitrogen content to be lower than expected for the n-phenylquinonediimine proposed by caro, ultimately concluding that carrying out the reaction in water resulted in a portion of the oxidation product to be hydrolyzed to the corresponding n-phenylquinone monoimine (figure 7), which co-crystallizes with the diimide.46 in contrast, he found that if the oxidation was carried out in an ether solution using dry silver oxide, pure n-phenylquinonediimine could be obtained. willstätter then continued with polymerization studies of n-phenylquinonediimine via treatment with acid.46 the yellow material first turned red-brown upon protonation, after which it eventually turned into a dark green product. this green product was referred to as emeraldine in reference to the commercial name of the green aniline-based dye developed by frederick cracecalvert (1819-1873) and coworkers in 1860.13 based on a suggestion from nietzki, it was found that the same material could be produced more easily by oxidizing p-amidodiphenylamine with iron chloride in acidic media. similar results were also achieved using hydrogen peroxide and a catalytic amount of feso4.46 from these products, a blue species was isolated that was viewed to be the emeraldine base, also known as the blue aniline-based dye azurine. analysis of the crystallized compound led to a formula of c24h20n4, which was concluded to have been formed from the polymerization of two molecules of n-phenylquinonediimine.46,52 benzene solutions of the blue base were then oxidized with pbo2 to give a red product with two less hydrogens (c24h18n4). both the blue and red products could be reduced to give the colorless leuco base (c24h22n4), which could not be reduced any further.46 as in the case of the oxidation of p-amidodiphenylamine in water (figure 7), oxygen-terminated byproducts were also found in the blue, red, and leuco base species here. efforts were then made to determine the structures of the blue, red, and leuco base species, beginning with consideration of what type of bond might link the two n-phenylquinonediimine units. of the various new linkages considered, the only option that was viewed to be consistent with the observed results was the formation of a new c-n bond between a terminal nitrogen of one unit and a phenyl unit of the other. with the nature of the linkage limited to a simple c-n bond, there still remained various possible structural motifs as illustrated in figure 8.46 of the three possible structures given, it was viewed that the two branched structures (ii and iii) should be easily converted into azine species (iib and iiib) and thus efforts to find evidence of azine content in the blue species was pursued. as no indication of azine content could be found, it was determined that the linear structure (i) was the most reasonable structure for the blue species,46,52 which was also consistent with the initial formation of p-amidodiphenylamine from aniline. from this determination, the structures of the three species and their transformations via oxidation or reduction can be summarized as shown in figure 9.46 figure 7. oxidation of p-amidodiphenylamine. figure 8. possible structural motifs for the isolated blue product. figure 9. structures and interconversions of isolated species. 114 seth c. rasmussen willstätter viewed his various emeraldine products as intermediates in the formation of aniline black. however, it was found that of the three species given in figure 9, only the isolated red species could be converted directly to an insoluble black material.46 in this way, it was found that the red product underwent further polymerization upon heating or treatment with dilute acids to give a black product referred to by willstätter as polymerization black. he acknowledged that the properties of the aniline black prepared from the red intermediate did depend on the exact conditions applied, but examples that produced aniline black without byproducts gave a composition of (c6h4.5n)x. thus, he concluded that this composition best represented that of aniline black. as his aniline black was produced from the red intermediate consisting of four units (i.e. x = 4), he concluded that the smallest possible structure for aniline black was where x equaled a minimum of 8, with the simplest possible formula being c48h36n8.46 willstätter recognized that this was not a definitive determination of the structure of aniline black, admitting in a second paper published in 1909:52 “the way in which the aniline residues are linked in [aniline] black has not yet been determined.” in fact, the german chemist hans theodor bucherer (1869-1949) had published a paper in 1907 that refuted the proposed structures in willstätter’s initial report, stating that only azine-type structures could explain the significant stability of the aniline black.53 to further support the linear structures given in figure 9, willstätter subjected samples of aniline black to strong oxidation, which had previously been shown by nietzki to decompose the black material to quinone.44,45 various methods were thus studied in order to maximize the experimental yield of quinone from aniline black.52 the resulting experimental yields were then compared to the theoretical yields of quinone possible from the various proposed structures for aniline black at the time, which showed that the experimental values were ca. 95% of the theoretical value expected for the linear structure proposed by willstätter, but much higher than that expected for the alternate branched or azine-based structures. in the same study, a more detailed elemental analysis was also performed, resulting in a more precise average composition of c5.97h4.55n. based on this composition, it was thus proposed that aniline black had a composition consisting of units of the three-fold quinoid derivative given in figure 10. in a second 1909 paper,54 willstätter continued the study of aniline black to determine the presence and interconversion of two different quinoid species, both of which were derived from the same leuco base (figure 10). in addition to the three-fold quinoid derivative previously proposed, he now added the fully oxidized four-fold quinoid unit, which could be produced from the three-fold species via further oxidation with hydrogen peroxide. this fully oxidized species was described as blue-black, with salts giving a dark green color. the content of these two oxidized species in aniline black was viewed to be dependent on the oxidation conditions applied. the three-fold quinoid species, which gave a blue-colored base and green materials as the protonated salts, was viewed to represent the traditional material emeraldine. in contrast, the polymerization black previous generated from the heating of his red intermediate (figure 9) was viewed to be closer to the four-fold quinoid species. this was then followed up with a 1910 paper in which the gradual reduction of aniline black was studied via treatment with phenylhydrazine carbamate.55 in this way, the initial aniline black (viewed to be primarily the three-fold quinoid species) was found to progress through three phases. the initial reduction was observed at 30-45 °c, resulting in a transition from a dark blue base to light blue color. further heating resulted in another transition at ca. 80 °c to give a gray material. finally, a colorless product was obtained at temperatures above 120 °c. the leuco base produced in this manner converted back to the black material under atmospheric oxygen in the presence of a small amount of ferrous salt. concurrent with the publication of willstätter’s study on the reduction of aniline black, the english industrial chemists arthur g. green (1864-1941) and arthur e. woodhead began reporting competing studies. while the first of these papers was reported in 1910,56 two solo works by green had also been reported the previous year.57,58 at least initially, green had very different ideas concerning the structure of aniline blacks. figure 10. proposed oxidative states representative of aniline black (quinoid units highlighted in blue). 115the early history of polyaniline ii: elucidation of structure and redox states green, woodhead, and further refinement arthur george green (figure 11) was born in 1864, in the town of ealing, located in west london, and was educated at lancing college, sussex. after matriculating in 1880, he entered university college, london.59,60 in his first year there, he won the gold medal in the junior practical chemistry class and the clothworkers’ exhibition in chemistry; the next year he won the gold medal for chemical analysis, and in 1883 the tuffnel scholarship.59,61 at the college, green carried out research under lecturers henry forster morley (1855-1943) and richard john friswell (1849-1908),60,61 and worked as a volunteer during college vacations in the laboratory of messrs. williams bros., aniline dye manufacturers of hounslow.60 green commenced his industrial career in june 1885, as research chemist with messrs. brooke, simpson & spiller, ltd.59-61 at the atlas aniline dye works in the east london neighborhood of hackney wick, where he had previously carried out his research with friswell.62 his initial career was successful and he was awarded the silver medal of the royal society of arts in 1891.59 he then left in 1894 to became manager at the clayton aniline company, in manchester.59,60 in 1901, he decided to become independent and setup in london as a consultant, but accepted an invitation in 1903 to the chair of chemistry and dyeing at the university of leeds, a position made vacant by the death of john james hummel (1850–1902).59 green was later elected to the royal society in 1915. his time at leeds was ultimately finite and he resigned the chair in march 1916 to became director of research at levinstein ltd. in manchester.59 he also gave part of his time during 1916-1918 to the college of technology, manchester, where he established the dyestuffs research laboratory, with the assistance of frederick maurice rowe (1891-1947), one of his past students.59,60,63 during this period, green continued to receive various accolades. he was elected to the livery of the worshipful company of dyers in 1918 and he received the dyers’ company gold medal three times, in 1909, 1914 (with w. johnson), and 1923. he was the society’s perkin medalist in 1917 and received an honorary m.sc. from the university of leeds.59 in 1919, levinstein, ltd. merged with british dyes to become the british dyestuffs corporation, ltd, after which green resigned his position as director of research in 1923. at this time, green returned to his private practice which was considerable both in europe and america.59 in 1936, he returned to became consultant to the dyestuffs group of imperial chemical industries ltd., which was established in december 1926 from the merger of british dyestuffs corporation with three other british companies: brunner mond, nobel explosives, and the united alkali company. five years later, green died peacefully in his sleep at his home at walton-on-thames on september 12, 1941 at the age of 78.59,60 green’s earliest report on the structure of aniline black consisted of a short paper that presented proposed structures for both the emeraldine and nigraniline materials,57 along with brief comments on the early report by willstätter and moore.46 this was then followed up with a second report covering much of the same material in a bit more detail.58 as shown in figure 12, both of green’s structures were cyclic species consisting of three aniline repeat units. it is also important to note that he never designates what the substitution geometry is on various bridging phenyl rings (i.e. ortho, meta, or para). in terms of the report of willstätter and moore, green agrees with the empirical formula of (c6h4.5n)x. but does not accept any of the rest. as stated by green:58 figure 11. arthur george green (1864-1941) (obit. notices fellows r. soc. 1943, 4, 251–270; courtesy of jstor). 116 seth c. rasmussen the view expressed by these authors that the product of this so-called “polymerisation” must have a molecule in which x = at least 8, and is to be represented as a complex indamine with a long open chain, appears to me to be very difficult to reconcile with its properties (stability to acids, etc.). by the publication of the first paper coauthored with arthur edmund woodhead in 1910,56 however, this stance seems to be somewhat moderated, stating that the work of willstätter and his coworkers has added much to the knowledge of the complex oxidation products of aniline. still, they point out that the results of willstätter can really only apply to the primary oxidation products of aniline (emeraldine or nigraniline), while the most stable form of aniline black, commonly known as ungreenable aniline-black, must be an azine. based on this view, it was then proposed:56 that the term “aniline-black ” should be restricted to the higher condensation products (ungreenable black), whilst the original names “emeraldine” and “nigraniline” should be retained for the primary oxidation products. green and woodhead then went on to reinterpret some of willstätter’s previous results and attempted to provide additional data to present a more detailed model of the primary oxidation products of aniline. in the process, they retained the general linear octameric structures of willstätter, even though they felt the question of linear chains vs. ring structures was still undecided. on this point, they state:56 assuming the correctness of the eight-nucleal structure for the primary oxidation products, it still remains an undecided question whether the aniline residues are to be regarded as united in an open or in a closed chain, but without attempting to decide this point we shall make use of the open-chain formulae to express provisionally the analytical results. these efforts started with the preparation of emeraldine via multiple methods, converted to the corresponding base, and carefully purified to produce an initial material for study. this material was then dissolved in aqueous solutions of either acetic (80%) or formic acid (60%) to give yellowish-green solutions. the addition of a very dilute solution of chromic acid then resulted in the color of the solution changing first from green to pure blue, and then to violet with the further addition of oxidant, which ultimately gave a violet precipitate.56 if a very weak solution of sodium hydrogen sulfite was added to the violet solution, these color changes would occur in the opposite direction, from violet to blue to green. stronger reducing agents (phenylhydrazine, sodium hyposulfite, or titanium trichloride) would convert the green solution to the colorless leuco base. as the initial solution began with the emeraldine, the next sequential colored solution via oxidation was designated nigraniline, with the name pernigraniline (latin per “through, entirely, utterly” + nigraniline) proposed for the final violet solution. it should be noted here that the prefix per is commonly used in chemistry to denote the highest known oxidation state of various species (i.e. persulfate or permanganate) and thus is added to nigraniline here to denote the fully oxidized form. in a similar fashion, the parent leuco base was given the name leucoemeraldine (i.e. the leuco base of the original emeraldine). their analysis then continued with efforts to determine the quantity of hydrogen required for conversion of emeraldine into leucoemeraldine via titration of the initial acetic acid solution with titanium trichloride.56 from these measurements, it was determined that the emeraldine corresponded to a diquinoid species. in a similar manner, the quantity of oxygen consumed in the conversion of emeraldine into nigraniline was then studied by titration of the initial acetic acid solution with a standard solution of chromic acid. in this way, it was concluded that the conversion of emeraldine to nigraniline was the introduction of one additional quinonoid group. this then led to the series as outlined in figure 13.56 as the difference between emeraldine and leucoemeraldine was two quinoid units, the additional proposed single quinoid containing species was added between these in the series, which green gave the name protoemeraldine (greek prōtos “first” + emeraldine) to denote the first oxidized form. willstatter’s response and green’s rebuttal willstätter then responded to the work of green and woodhead in an additional 1911 paper.64 while he felt that the proposed renaming of the structures provided no improvement over his previous descriptive nomenclature, it was the contradicting views on the quinoid content of emeraldine that dominated his response. the prifigure 12. green’s initially proposed structures of emeraldine and nigraniline. 117the early history of polyaniline ii: elucidation of structure and redox states mary point raised by willstätter was that from their previous attempts at reducing materials to the leuco base, the titanium trichloride required higher temperatures for full reduction than that applied by green and woodhead. as such, he felt that the leucoemeraldine reported by green was actually the monoquinoid product, which he felt was also supported by their description of a “pale brown amorphous powder”, when it should be completely colorless. such an assignment would then remove any differences between the studies of the two groups. green and woodhead then provided their own response to willstätter in 1912.65,66 here, they refute willstätter’s claim that full reduction to the leucoemeraldine cannot be accomplished with titanium trichloride at lower temperatures and highlight various points in willstätter’s work that they view as problematic. “in order to place the matter beyond doubt”, attempts were made to further reduce their leucoemeraldine samples with titanium trichloride at high temperature. here, leucoemeraldine was prepared from the reduction of emeraldine by phenylhydrazine at a low temperature, after which the leucoemeraldine was treated with boiling titanium trichloride. as the results were not consistent with the further reduction of a mono quinoid species to the full leuco base, it was concluded that their original conclusions were fully supported. it does not seem that willstätter had anything further to say on the subject, at least not in the chemical literature. as such, the debate was generally considered decided. this is further supported by the fact that no further modifications to these structural models have been reported since. conclusions other than the modern understanding of the macromolecular nature of polyaniline, the final oxidative series as presented by green and woodhead still remain the currently accepted structural forms. although the modern literature typically gives green and woodhead the credit for determining the structure and oxidative forms of polyaniline, with little to no mention of willstätter, it is clear from the historical record that the primary structure determination was really accomplished by willstätter. this is not to ignore the contributions of green and woodhead, who clearly made important corrections and additions to the oxidative series, as well as establishing the traditionally accepted nomenclature, but this was all accomplished by refinement of the previous structural models of willstätter. even at the end, green was not convinced of the linear nature of these materials and only used the linear structures as a convenient working model. in contrast, willstätter had eliminated other possible structures through careful analysis and fully believed in his linear model. in addition, although these models were presented as linear octomers, willstätter made it clear that this was the minimum length necessary to explain the presented results and the actual materials could certainly be larger, thus paving the way for the eventual understanding of these materials as macromolecules. as such, willstatter certainly deserves greater recognition for his important contributions to our modern understanding of polyaniline materials. 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j. soc. dyers colour. 1944, 60, 81-93. 62. r. j. friswell, a. g. green, on the relation of diaxobenaeneanilide to anzidoazobenzene. j. chem. soc., trans. 1909, 95, 2202-2215. 63. e. j. cross, j. b. speakman, prof. f. m. rowe, f.r.s. nature 1947, 159, 53. 64. r. willstätter, c. cramer, über anilinschwarz. v. ber. dtsch. chem. ges. 1911, 44, 2162–2171. 65. a. g. green, a. e. woodhead, anilinschwarz und seine zwischenkorper. ii. ber. dtsch. chem. ges. 1912, 45, 1955-1958. 66. a. g. green, a. e. woodhead, aniline-black and allied compounds. part ii. j. chem. soc. trans. 1912, 101, 1117-1123. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 6(1): 37-47, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1364 citation: schwartz l., benichou l., schwartz j., pontié m., henry m. (2022) is the second law of thermodynamics able to classify drugs? substantia 6(1): 37-47. doi: 10.36253/substantia-1364 received: jul 17, 2021 revised: dec 16, 2022 just accepted online: jan 25, 2022 published: mar 07, 2022 copyright: © 2022 schwartz l., benichou l., schwartz j., pontié m., henry m. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research articles is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 1 assistance publique des hôpitaux de paris, paris france 2 paris-est créteil university (upec) school of medicine. créteil, france 3 université d’angers, faculté des sciences, groupe analyses et procédés, (ga&p) 2 boulevard. lavoisier, 49045 angers cedex 01 4 institut le bel, université de strasbourg, umr 7140, 4 rue blaise pascal, 67070 strasbourg *corresponding author. email: dr.laurentschwartz@gmail.com abstract. specialization characterizes pharmacology, with the consequence of classifying the various treatments into unrelated categories. treating a specific disease usually requires the design of a specific drug. the second law of thermodynamics is the driving force both for chemical reactions and for life. it applies to diseases and treatment. in most common diseases, there is a metabolic shift toward anabolism and anaerobic glycolysis, resulting in the release of entropy in the form of biomass. in accordance with the second principle of thermodynamics, treatment should aim at decreasing the entropy flux, which stays inside the body in the form of biomass. most treatments aim at increasing the amount of entropy that is released by the cell in the form of thermal photons. as clinically different diseases often requires similar drugs, this calls for reinforcement in a quest for a single unified framework. for example, treatment of aggressive autoimmune diseases requires the same cytotoxic chemotherapy than for cancer. this strongly suggests that despite their apparent disparity, there is an underlying unity in the diseases and the treatments. the shift toward increased entropy release in the form of heat offers sound guidelines for the repurposing of drugs. keywords: pharmacology, alzheimer, psychiatry, cancer, entropy, phi, mitochondria, lactic acid, paradigm shift. 1. introduction this paper is one of a series of publications trying to merge medicine back into physics. accordingly, the combination of theory and subsequent experiments was the cause of major progress in physics. we aim at describing diseases and thus treatment as physical features. but in medicine, measurements of physical data such as calculation of entropy are missing. entropy production and dissipation has never been measured in human cells. we are, at a stage, where we can only raise hypothesis based of indirect markers of the fluctuation of entropy. http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 38 laurent schwartz et al. we have based our reasoning on data based on the metabolic flux centered by the mitochondria, the place within a cell, providing the maximum production of entropy as heat. we also have used clinical data. for example, if the patient is more active (like after treatment with thyroid hormones) one can assume that the entropy flux has increased. similarly, if the temperature decreases (like after antibiotic treatment for infection) one may deduce that there is a decrease in entropy released in the outer space. in this paper, we have tried to merge biological and medical data, focusing on their impact on entropy. the second law of thermodynamics tells us that entropy can only increase in a closed system. when discussing the second law of thermodynamics, one should always define its reference. here we consider the human body as the reference point. the entropy can be excreted from the patient and thus locally decreases. but, the entropy of the universe is always going up, as the contribution from our body, compared to the sun-earth system, is almost negligible. 2. background in the vast majority of diseases, there is a shift toward increased synthesis of biomass. in cancer, there is increase in cellular proliferation. in neurodegenerative diseases, there are protein deposits like the amyloid plaques in alzheimer’s disease or the bodies of lewy in parkinson’s disease. in inflammation, there is secretion of proteins such as lymphokines and cytokines and proliferation of inflammatory cells. the nobel prize, otto warburg (1883-1970) in the 1920s, first described this shift toward anabolism in cancer cells. the  warburg’s effect  is a modified  cellular metabolism based on aerobic fermentation, which tends to favor anaerobic glycolysis rather than oxidative phosphorylation, even in the presence of oxygen. in epithelial cells, the warburg’s effect results in cancer[1]. the warburg’s effect is a bottleneck. the cells cannot burn the glucose because the pyruvate cannot be degraded in the krebs’ cycle. evidence of the central role of the warburg’s effect comes when the researcher injects into cancer cells, with a micropipette, normal mitochondria. the growth will stop. these cells have become benign. the injection of the nuclei of cancer cells into normal cells does not increase growth. these cells can still burn glucose because the mitochondria are normal and do not form tumors [1 and references therein]. the inhibition of the oxidative phosphorylation results in the activation of the anabolic pathway, such as the pentose phosphate pathway (ppp), that is necessary for dna and rna synthesis [1 and references therein]. the warburg’s effect results in the release of lactic acid in the extracellular space, the concomitant activation of the pentose phosphate pathway, and anabolism[1]. the warburg’s effect results in the synthesis of new proliferating cells[1]. more recently, metabolic shifts have been described in alzheimer and parkinson’s diseases[2,3]. similar shifts toward anaerobic glycolysis have been described in most common disease. to name a few, among others, as published in[4]: autism[5,6] schizophrenia[7], alzheimer[3], parkinson’s disease[8,9] huntington’s disease[10], stroke[11,12], infection[13], fibrosis[14,15], cirrhosis[16,17], emphysema[18], arthritis[19], scleroderma[20], lupus[21,22]. to the difference to the warburg effect, these shifts toward glycolysis and increased lactate secretion may be transient and reversible in the presence of oxygen[4]. in biology, like in physics and chemistry, we are dealing with intertwined variables. in physics, newton’s law links forces to momenta. in chemistry, the ideal gas law links pressure, volume, temperature and the amount of matter. in biology, the release of entropy in the form of heat, oxidative phosphorylation, high mitochondrial activity and acidic intracellular phi are linked if not synonymous. it seems that there is a shift to mitochondrial impairment in almost every disease, resulting in increased lactate concentration. these diseases appear to be a consequence of impaired mitochondrial function and increased entropy release in the form of biomass. in cancer, mitochondrial impairment results in cell proliferation and tumor growth. in alzheimer disease, there is an abnormal secretion of amyloid plaques, in parkinson’s disease, there are intracellular deposits (lewy bodies) [3 and references therein]. a basic equation for cellular life taking into account that cells are open systems have been previously proposed[4,23-25]: foods (in) = biomass (in) + heat (out) + wastes (out) (1) where “in” and “out” refer to a system surrounded by a containment able to exchange heat and matter between the inside and the outside of the cell. catabolism powered by oxidative phosphorylation is another word for entropy release in the form of heat. anabolism through fermentation is another name for entropy release in the form of biomass[24]. thus, from a thermodynamic standpoint, diseases can be classified according to the second law of thermodynamics. the cell feeds on low entropy molecules such as glucose to release higher entropy molecules such as co2 and atp[23]. to comply with the second law of ther39is the second law of thermodynamics able to classify drugs? modynamics, the cell absorbs and degrades low entropy compounds into heat or biomass with a neat production of entropy[24]. differentiated cells release their entropy in the form of thermal photons[25]. proliferating cells have lower mitochondrial activity and release their entropy in the form of biomass. differentiated cells have an increased mitochondrial activity [26–29], resulting in the release of entropy in the form of heat. differentiated cells have a basal oxidative metabolism. the efficient tca cycle degrades glucose into pyruvate [1,30]. the oxidative phosphorylation of acetyl-coa into mitochondria yields large amounts of entropy-rich atp and releases carbon dioxide and water as entropy-rich waste products. this is the opposite of proliferative cells. biomass synthesis and cell growth requires a rewiring of the carbon flux. here, the ppp acts as a shunt for glycolysis, generating nucleic acid precursors for dna replication [1,30]. poorly differentiated cells release their entropy in the form of biomass[25]. undifferentiated cells have lower mitochondrial activity resulting in alkaline ph and lower transmembrane potential, and increased cell division[31]. cells oscillate between two modes of entropy production. differentiated cells release entropy in the form of heat. they have high atp production, increased transmembrane potential, increased ionic concentration, intracellular acidic ph, and low water activity. on the other hand, proliferative cells have decreased atp synthesis, diluted ionic content, low transmembrane potential, alkaline ph[26]. during adulthood, respiration is predominant[32]. childhood and aging are more anabolic than adulthood. in childhood, anabolism results mostly in growth. in aging, anabolism results in age-related diseases such as cancer and alzheimer’s disease. most drugs impact both anabolism and catabolism. for clarity, we will focus on what appears to be the main target of the drug. 3. attempt of classification diseases can be described as a perturbation of the flux of entropy[24]. most drugs should be described based on their impact on the entropy flux. drugs have been designed to target a specific receptor. as a key opens the lock, the active compound binds with its receptor and modify the fate of the targeted cell. this view of pharmacology has yielded tremendous results, most recently, with the advent of targeted therapies. our goal is to complement this approach with the necessary compliance to the second law of thermodynamics. but most drugs have multiple effects on entropy. for example, as we will discuss later, thyroid hormones increase entropy production, decrease the release of entropy in the form of biomass and shift toward the release of entropy in the form of thermal photons. a) drugs increasing the release of entropy some diseases are a consequence of a decreased metabolic activity, resulting in decreased production of entropy. a decrease in physical and psychological activity is the hallmark of these diseases. in hypothyroidism, there is constipation, somnolence and sometimes depression[33]. treatment w it h t hy roid hormones resu lts in increased heart rate, weight loss and excitability[34]. thyroid hormones result in increased entropy flux, but also in a shift toward increased release of thermal photons. overdose of thyroid hormones may result in hyperactivity, fever, mania, diarrhea and increased heart rate. these are indirect signs of increased production of entropy. the mechanism underlying the regulation of the basal metabolic rate by thyroid hormones remains unclear. it has been suggested that these hormones uncouple substrate oxidation from atp synthesis. a molecular determinant of the effects of t3 could be uncoupling protein-3 (ucp-3)[34]. such uncoupling from atp synthesis results in increased secretion of heat in the form of thermal photons[35]. amphetamines are a class of psychotropic drugs with high abuse potential, as a result of their stimulant, euphoric and hallucinogenic properties. amphetamines are synthetic drugs, of which methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine (“ecstasy”) represent well-recognized examples. resulting from their amphiphilic nature, these drugs can easily cross the blood–brain barrier and elicit their well-known psychotropic effects[36]. both cocaine and amphetamine induces the secretion of uncoupling protein, resulting in thermogenesis[37]. cardiac stents reestablishes the blood flow to the diseased heart and peripheral tissues, resulting in the restoration of the metabolism and increased entropy production. antiarrhythmic and cardio tonics increase the efficacy and improve the contraction of the heart, which leads to increased quantity of blood flow to the peripheral tissues. it results an improvement of metabolism and increase production of entropy and a better well being of the patient. the drugs aiming at treating cardiovascular diseases are numerous. they, all, aim at increasing the efficacy of 40 laurent schwartz et al. the cardiac pump. digoxin intensifies the phosphorylating activity of mitochondria[38]. digoxin stimulates the mitochondrial activity and thus decreases the amount of entropy released in the form of biomass. digoxin has been repurposed in the treatment of cancer[39]. the addition of oxygen to patients with cardiac or pulmonary failure results in better mitochondrial efficacy and enhanced synthesis of thermal photons[40]. table 1. drugs and devices increasing entropy production. thyroid hormones[34,35] amphetamines[36,37] cocaine[37] cardiac stents digoxin[39,39] oxygen[40] b) drugs decreasing the flux of entropy caloric restriction, without malnutrition, delays aging[41] and extends life span in diverse species including humans. caloric restriction delays the onset of ageassociated pathologies. specifically, caloric restriction reduces the incidence of diabetes, cancer, cardiovascular disease and alzheimer’s disease[41]. the brain has the highest energy consumption of the body (around 20% of the body oxygen and 25% of the glucose) while representing 3% of our body’s mass. biological conditions, which decrease mitochondrial energy yield, would impact brain functions, increasing vulnerability to brain disorders[42]. drugs, which decrease the metabolism, slow down the flux of entropy. anesthetics such as lidocaine, an amide local anesthetic, decreases glucose uptake through the reduction of the expression of glut1 and hk2. lidocaine inhibits the enhanced glycolysis and glycolytic capacity induced by lps in the macrophages [43,44]. similarly, halothane anesthesia decreases glucose uptake because of transient inhibition of brain phosphofructokinase[45]. intraperitoneal injections of phenobarbital decrease the concentration of glucose-6-phosphate and fructose6-phosphate and result in the depression of the motor activity. the finding of decreased hexose phosphates in the brain supports the hypothesis that central depressant drugs suppress glycolysis in the central nervous system in vivo possibly by a diminution of glucose phosphorylation[46]. propofol is another of the most commonly used sedative. this drug inhibits anaerobic glycolysis and the krebs’ cycle. consistently, propofol inhibited the expression and glycolysis proteins (glut1, hk2 and ldha)[47]. conventional medications against seizure reduce neuronal excitability through effects on ion channels or synaptic function. recently, it has become clear that metabolic factors also play a crucial role in the modulation of neuronal excitability[48]. in 1955, greengard[49] demonstrated that anticonvulsant prevents the rise in oxidation such as seen during seizures. the clinical effectiveness of a variety of diets based on metabolism, especially for children with epilepsy refractory to medication, underscores the applicability of metabolic approaches to the control of seizures and epilepsy. such diets include the ketogenic diet. a promising avenue to alter cellular metabolism, and hence excitability, is by partial inhibition of glycolysis, which has been shown to reduce seizure susceptibility in a variety of animal models as well as in cellular systems in  vitro. one such glycolytic inhibitor, 2‐deoxy‐d‐glucose (2dg), increases seizure threshold in  vivo and reduces interictal and ictal epileptiform discharges[50]. anxiety could be viewed as a shift toward the transient warburg effect. an argument for a mitochondrial explanation of anxiety is stress’s capacity to trigger the shift toward a decreased energy yield of the mitochondria. for example, catecholamines induce warburg’s effect and the secretion of lactate[51]. in times of stress,  catecholamines can bind muscle cell receptors and trigger the breakdown of glycogen to lactate, diffusing out into circulation and used as a fuel. similarly, hypoxia is a risk factor for anxiety[52]. hyperventilation is a cause for hypoxia, which leads to anxiety and panic attacks[53]. sleep apnea causes a panic attack[54]. in 1967, pitts and mcclure suggested that a raised lactate level in blood and body fluids causes all symptoms of anxiety[55]. leibowitz and hollander has confirmed their work[56,57]. since then, sajdyk demonstrated that the infusion of lactate results in anxiety in rats. significant changes in regional blood flow in panicking patients but not in the non-panicking patients occurs after lactate infusion[58]. the amygdala processes and directs inputs and outputs that are key to fear behavior. it directly senses that reduced ph and increased co2 content, inducing fear. buffering ph attenuated fear behavior[59]. anxiolytic drugs are, to a large extent, effective in ameliorating anxiety symptoms. diazepam boosts mitochondrial respiration in the nucleus accumbens[60].this change of ph may be a consequence of change in the transport mechanisms of bicarbonate ions[61]. likewise, several antidepressants with anxiolytic capacity have been reported to improve mitochondrial activity such as monoamine oxidase inhibitors[62], selective serotonin reuptake inhibitors (ssris)[63]. 41is the second law of thermodynamics able to classify drugs? table 2. drugs decreasing entropy production. caloric restriction[41] anesthetics[43-45] sedative[46,47] anxiolytics[48] antiepileptic drugs[48-50] c) drugs increasing the release of entropy in the form of biomass metabolic syndrome is the consequence of diets rich in fructose. intake of fructose causes an anabolic syndrome with increase in visceral adipose deposition and de novo lipogenesis[64]. the risk of developing cardiovascular disease and type 2 diabetes increases with the occurrence of metabolic syndrome.  in the u.s., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial minorities[65]. insulin is an anabolic hormone. in type-1 diabetes, there is weight loss and hyperglycemia, which may result in coma. to the opposite, treatment with excess insulin may cause weight gain[66-68]. long-term uses of corticosteroids have been used to increase muscle strength and performance. anabolic steroids have been used to enhance recovery after massive stress and exhaustion[69]. estrogen suppression results in anabolism. ovariectomized rats eat more and gain weight more rapidly than sham-operated rats. estradiol (e2) treatment attenuates food intake and body weight gain in ovariectomized in rats[70]. women gain weight at menopause. table 3. drugs increasing the release of entropy in the form of biomass. diet rich in sugar[64] insulin[65] long-term corticosteroids [67-69] estrogen[70] d) drugs excreting entropy as waste products from a thermodynamic standpoint, urine, and feces are waste products. their elimination relieves the body from entropy-rich products. diuretics, emetics, and laxative should be considered as lowering the entropy of the body. radiation therapy (rt) is a therapy using ionizing radiation to control or kill inflammatory and cancer cells. rt has been extensively used for the treatment of inflammation, but this indication is slowly disappearing because of the risk of radiation-induced malignancies. rt may be curative in several types of cancer if they are localized to one limited area of the body.  rt kills both cancer and normal cells. cytotoxic chemotherapy activates the concentration of radicals species, such as the ones induced by radiation therapy. this is evident by the elevation of lipid peroxidation products; the reduction in plasma levels of antioxidants such as vitamin e, vitamin c, and β-carotene; and the marked reduction of tissue glutathione levels that occurs during chemotherapy. those agents that generate high levels of reactive oxygen species (ros) include the anthracyclines (e.g., doxorubycin, epirubicin, and daunorubicin), alkylating agents, platinum complexes (e.g., cisplatin, carboplatin, and oxaliplatin), epipodophyllotoxins (e.g., etoposide and teniposide), and the camptothecins (e.g., topotecan and irinotecan)[71]. after successful radiation therapy or chemotherapy, there is a sharp decline in the number of cancer cells, resulting in decreased tumor mass. table 4. drugs excreting entropy as waste products. diuretics laxatives emetics high dose cytotoxic chemotherapy[71] radiation therapy[71] surgery (organ removal) e) drugs increasing the release of entropy in the form of heat sport increases the activity of the mitochondria, thus the release of entropy in the form of heat. increased activity has been shown to improve survival from cancer[72] and memory in alzheimer’s disease[73]. inf lammation is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, or irritants and is a protective response involving immune cells, blood vessels, and molecular mediators. the function of inflammation is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult and the inflammatory process, and initiate tissue repair. inflammation (a clinical feature) is closely related to hyperosmolarity (a physical feature)[74-76]. animal models of inflammation demonstrate that, in an inflammatory fluid, whatever its cause, there is an increased protein content resulting in increased osmolarity (oncotic pressure). on the other hand, increased osmolarity, whatever its cause, results 42 laurent schwartz et al. in inflammation[74-76]. increased extracellular osmolarity increases cytokine synthesis and secretion and results in the proliferation and activation of immune cells. there is an inflammatory component in every major disease[4]. there is a concomitant rewiring of the metabolic fluxes, with an increase in secretion of lactic acid. the increased pressure such as seen in inflammation inhibits the mitochondria and induces the secretion of lactic acid[77]. the increased secretion of lactic acid, a stigma of the metabolic shift toward anabolism, feeds on the inflammatory cells and plays a part in the immune response such as seen in all these diseases[4]. this is in line with the concomitant finding of inf lammation, mitochondrial impairment, and lactic acid secretion in most chronic diseases. intraperitoneal injections in rats of hypertonic solutions result in the secretion of lactate by the brain cells. non-steroidal anti-inflammatory drugs (nsaids) alleviate inf lammation, the cyclooxygenase (cox) enzyme. cox synthesizes prostaglandins. nsaid decreases the synthesis of pro-inflammatory molecules by enhancing the mitochondrial activity[78]. there is also increased osmotic pressure in cancer[4]. increased pressure has recently been discovered as one of the reason for the warburg’s effect[77] the warburg’s effect is present in all tumors[25]. to compensate the reduced energy yield, there is massive glucose uptake, aerobic glycolysis, with an up-regulation of the ppp resulting in increased biosynthesis leading to increased cell division. the massive extrusion of lactic acid contributes to the extracellular acidity and the activation of the immune system [4,24]. anticancer drugs have been designed to kill cancer cells, but most drugs also target the warburg effect, thus decreasing the synthesis of biomass and stimulating the excretion of entropy in the form of heat. injection of radio labeled glucose (pet scan) allows assessment of the efficacy of treatment. the decrease in uptake of glucose correlates with the efficacy of radiation therapy[79], chemotherapy and hormonotherapy[80]. accordingly, cancer treatment should aim at restoring the oxidative phosphorylation. lipoic acid targets the pyruvate dehydrogenase and increases the oxidative phosphorylation[81]. hydroxycitrate inhibits the citrate lyase and decreases the efflux of citrate into the cytoplasm, enhancing the energy yield of the mitochondria[82]. the combination of these two drugs decreases the growth of tumor and prolongs the life of the mice[82]. inhibition of cancer growth appears universal (independent of the primary site). methylene blue (mb) is an fda drug discovered in 1878. it has already been rigorously studied and used in humans for over 120 years[83]. methylene blue functions as an alternative electron carrier, which accepts electrons from nadh and transfers them to cytochrome c[84-86]. it decreases aerobic glycolysis and enhances oxidative phosphorylation. methylene blue reverses the warburg’s effect and inhibits proliferation of cancer cell[87]. antidepressants target the mitochondria at multiple levels [83, 84, 88]. bachman studied the effects of five antidepressants, two phenothiazines and one butyrophenone on respiratory functions of rat heart mitochondria[89]. all compounds increased oxygen consumption and caused uncoupling of oxidative phosphorylation. table 5. drugs increasing the export of entropy in the form of heat. sport[72,73] anti-inflammatory[78] low dose cytotoxic chemotherapy hormonotherapy drugs targeting the mitochondria/metabolism[85] antidepressants[88-89] drugs enhancing the memory[84] conclusion in conclusion, we have been able to propose a qualitative classification of drugs for a wide range of diseases. such classification derives directly from equation (1) that is based on the facts that living cells are open systems that are not at thermodynamic equilibrium. rather, living cells, through their metabolism, produce continuously a large amount of entropy. such entropy is released in part as heat, i.e. as infrared radiations having a wavelength larger than 10 µm (far-ir). in our classification, drugs do not change the entropy content of substances fueling their metabolism, which that are the three main ways of producing entropy. it should be clear that thermodynamics of irreversible processes allows derivation of equation (1). see references[23-25] for technical details. this explains why me must put focus on entropy rather than energy. the next step will be to associate to each drug its irreversibility potential (irp). this would then allow moving from a qualitative classification to a quantitative one. if the corresponding computations are not difficult, there are tedious owing to the huge amount of drugs available in medicine. it also follows from the presented approach that drugs can be repurposed. to convince the reader, we will take some examples. a first one is methylene blue (mb). this drug has a wide spectrum of action: malaria, 43is the second law of thermodynamics able to classify drugs? leprosy, depression, neurodegenerative diseases or more recently cancer[69]. in psychiatry, methylene blue has been used for over a century. it was tried successfully to treat psychotic and mood disorders and as a memory enhancer in fear-extinction training. particularly promising results have been obtained in both shortand long-term treatment of the bipolar disorder. in these studies, methylene blue produced an antidepressant and anxiolytic effect without the risk of a switch into mania. long-term use of methylene blue in bipolar disorder led to a better stabilization and a reduction in residual symptoms of the illness[83]. in addition to protect neurons, mb’s effects have been associated with improvement of memory and behavior in a network-specific and practice-dependent fashion. specifically, low-dose mb has shown cognitive-enhancing effects in a considerable number of learning and memory paradigms, including inhibitory avoidance, spatial memory, fear extinction, object recognition, open-field habituation and discrimination learning[83]. yet another example is lithium that appears both effective in bipolar and in cancer[90]. finally, it is worth noting that anticancer agents have been repurposed in the treatment of autoimmune diseases[91]. we do hope that the classification proposed here, based on physics and not on biology, will helps in repurposing old drugs. this would strongly reduce the cost of the treatments, with the additional advantage of escaping from troubles linked to patents. accordingly, most old drugs are now in the public domain and would then be easily available for emergent countries. seen from a biologist’s perspective, most metabolic pathways appear to be connected to each other. but from a physicist standpoint, they all point towards an increase in entropy flux within the body. whatever the causes (i.e., genetic defect, inflammation, or toxicity of xenobiotics), they all converge toward a shift in the type of entropy that is released in the environment. in other words, most, if not all diseases have in common a decreased activity of the mitochondria. the synthesis of thermal ir photons decreases, and there is a concomitant increase in biomass synthesis. this can be addressed by the treatment of the primary cause (for example a genetic defect) or by medication targeting the mitochondria, such as methylene blue. to proceed toward a better outcome, the treatment needs to be evaluated and integrated into more comprehensive and global theories, accounting with principles of physics. it then follows that the goal of modern pharmacology may be to address treatment able to modulate entropy input or output to the desired organ. references 1. 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(2022) johann beckmann (1739-1811) and modern chemical technology. substantia. just accepted. doi: 10.36253/substantia-1870 abstract. modern chemical technology, in the humanistic spirit of the enlightenment, begins with johann beckmann (1739-1811). it followed pre-modern technologies associated with cameralism and chemia applicata. beckmann’s holistic approach to technology, expressed in “anleitung zur technologie” (1777) and “entwurf einer allgemeinen technologie” (1806), also engages with economic, social, cultural and ethical problems, giving the term ‘technology’ a new meaning. viewed with skepticism in his time, there was a revival of beckmann’s ideas by franz exner (1840-1913) in 1878. only in recent decades his contribution to technology was more extensively studied. examples of beckmann’s ideas are presented. keywords: johann beckmann; history of chemical technology; practical chemistry before beckmann; cameralism and chemia applicata; sugar industry; refutation of criticism of technology. “i believe i am only a fragment of humanity, but yet that i must try to look at things from the point of view of the whole, and not of the fragment”. (george sarton)1 mailto:juergen.maar@gmail.com 2 introduction despite his overwhelming importance in the evolution of chemical technology, including its introduction as a university course, johann beckmann does not receive in many places the recognition he deserves. his name is frequently omitted from histories of chemistry. this omission is especially serious when we consider that his work began during the phlogiston era and continued under the aegis of lavoisier’s new oxygen theory. beckmann’s theoretical work, however, shows no break in continuity, no significant structural change, or no paradigm shift (in kuhnian terminology). on the contrary, beckmann’s work on chemical technology is an example of a subject’s linear evolution in terms of knowledge. beckmann’s oblivion in many countries is not a consequence of opinions or attitudes against beckmann himself, a typical representative of the enlightenment, but a reaction against the very idea of technology being necessary. as an example, in contemporary latin america there is a double origin for this pre-conceived idea against technology and innovation. the iberian world is contrary to the concept of “technics”, an idea succinctly expressed by miguel de unamuno (1864-1936), with his famous “… que inventen ellos!” (“let others invent!”)2 . post-modern ideas, ever so popular in the latin world, tend to minimize the role of scientific rationality and efficacy, often overemphasizing the importance of practical knowledge, and resisting “rationalization of work” – as bruno jacomy puts it3. the entry of technology in history, in the history of science regardless of the semantic issue associated with the term and, therefore, in culture in general, occurred from mid-19th century. in general, in the pioneering countries of the industrial revolution, such as great britain and france, the revolution occurred with few concerns about technique and technology. in countries of more recent industrialization, such as germany and the united states, there was a greater concern with a possible 'methodology of technological progress'. in these cases, it was part of the effort in favour of technology to awaken the interest of young people in the subject and to integrate the so-called 'technological' subjects in university curricula. obviously no theory, neither technological nor economic, caused the old method of “trial and error” to leave the scene – we are here in face of chance as cause of social and economic development. but real progress is rare. what is of importance is an efficient “methodology of technology”, similar to an efficient methodology of scientific work. 3 also johann beckmann and his enlightened spirit are important. science and technology develop and advance by means of a pre-conceived, structured methodology, from time to time revised in accordance with its own principles, allowing a reliable application of the conditions underlying scientific knowledge, as defined by sir karl popper (1902-1994) and by imre lakatos (1922-1974). evolution of some concepts some seemingly very modern concepts, like technology and “fine chemistry” are in fact not so new. such precursor periods in the ‘arts’ or ‘techniques’, of artisanal and pre-industrial production, were necessary for the emergence of a chemical technology and later of a chemical industry in a broader sense. the alchemists by no means occupied themselves solely with transmutation or with the elixir of life, but they were possessors of a wide range of knowledge about mining, metallurgy, medications and chemical processes in general (production of saltpeter and gun powder, of several acids, dyes and pigments, dyeing and tanning, and many others). this explains the presence of alchemists in the courts of kings, princes and potentates in 16th and 17th centuries4. leonhard thurneysser (1531-1596), an alchemist of paracelsian tradition, was not only the physician of prince-elector john george of brandenburg (1525-1598), but his consultant for mining and metallurgy. thurneysser set up in 1574 in the greyfriars monastery, the former convent of the franciscans in berlin (now in ruins), a manufacturing plant for diverse chemicals, employing 300 workers and producing saltpeter, mineral acids, alum, colored glass, pharmaceuticals and several essences. these expensive products were sold, and had, as we would say today, ‘high added value’, so he earned considerable wealth. i see in thurneysser the first representative of fine chemistry5. a first ‘chemical technology’ not yet methodologically or scientifically organized, but surpassing the purely practical aspects of the alchemists, arose in the 18th century, as an answer to immediate commercial necessities and availabilities, like the production of saltpeter and gun powder, or the economic reconstruction of central europe, devastated by the thirty years war (1618/1648). for the majority of historians, johann rudolf glauber (1604-1670) was the most important representative of the period which principe and newman call ‘chymistry’, a term coined to avoid the parallel use of ‘alchemy’ and ‘chemistry’, to avoid speaking simultaneously about alchemical theories and practices and of chemical theories, concepts and activities 6. however, due to his 4 knowledge of chemicals it would not be wrong to consider him a precocious inorganic chemist, and also as the first chemical technologist7. i regard him as a precursor of chemical technology, a task for which his immense knowledge of inorganic chemicals was a deciding factor. in schmauderer’s opinion8, this ‘technology’ begins in the spirit of the science of the baroque period, at first in obedience to a religious precept that states the researcher’s responsibility in applying his knowledge as well as the natural resources presented to us by god for the welfare of his brothers. in the context of the mercantilism typical of the 18th century’s economy, this ethical-religious precept changes, and allows a new ‘technology’ acting in the interest of the absolutist state, in which economic issues dictated the rules: protectionism, state monopolies, prohibition to export or import certain products. in his amsterdam laboratories, glauber began in 1650 his technological activities, surpassing the work of precedent ‘technologists’, which were specialized in metallurgy, or glass, or ceramics. glauber’s production was more widespread, ranging from fermentation to metal analyses, from preparation of acids to treatment of textiles. glauber produced according to the capitalist concept: to obtain products with the best possible quality, with the least possible number of employees, and using the minimum of resources. he analysed the costs of each step of the proposed or necessary procedure, the yields, and even calculated the minimum quantity to be produced of each compound to warrant a cost-effective process. it must be said that these frankly capitalist system was preceded by ‘pre-capitalistic’ initiatives of predecessors, like those of jakob fugger the rich (1459-1525) in banska bystrica (neusohl), slovakia, or in his mines in tyrol or carinthia in austria. the alchemist johann joachim becher (1635-1682) is best remembered in connection with his creation of the phlogiston’s theory and the chemical philosophy expressed in his physica subterranea.9 his chemical technological achievements are undervalued by most historians of chemistry. as an entrepreneur, he was in disadvantage by his boundless imagination and lack of sense of practicality, visible for instance, in his dreams of colonisation in south america, in lands inherited from the count of hanau, between suriname and the amazon. this was already the opinion of john stillman (1852-1923) a long time ago10 . today, becher’s activities are seen in a better light. his technological activities were mainly that of an organiser, in duty of the duke of bavaria (1664/1670) and the imperial court in vienna (1670/1672), where he founded the chamber of commerce, the kommerzienkolleg, and several industries (chemicals, textile goods), frequently without the expected success. sponsored by the 5 imperial government, becher founded in vienna a chemical laboratory, where he produced saltpeter, salt-ammoniac, borax, vegetable dyes, pigments (cinnabar, minium), and constructed new equipments, like experimental ovens for the glass and ceramics industry. his plant in tabor, near vienna, founded in 1667, produced pigments (cinnabar, minium, verdigris, lead white), and incorporated plants for refining sugar, produce “venetian” glass, as well as noble metals. the third alchemist precursor of modern chemical technology is johann kunckel (1630-1703), famous for his vast experience with the technology of glass production (“ars vitraria experimentalis”, 1679) and the invention of the artificial ruby, a very valuable red glass (1679)11. kunckel stood in the services of prince-electors john george ii (1613-1680) in dresden, and frederick william the “great elector” (16201688) in berlin. frederick william presented him with the peacock island (pfaueninsel), where he built not only his glass factory but also a “secret laboratory”, which allowed him to work “without being disturbed or observed”. his posthumous “laboratorium chymicum” (1716) describes a great number of chemical and metallurgical processes, showing that his importance surpasses by much the invention of the rubinglas: he describes for instance how he obtained phosphorus in dresden, and all the processes necessary to produce the artificial ruby, processes which he pretended to maintain secret. baroque science and technology had a religious origin, but gradually 18th century technology assumed a clear capitalist aspect, and almost all political economists of that time were alchemists: alchemists transform useless materials (our raw materials) in new and valuable materials (our commodities). the original intention of obtaining gold from less noble metals, turned into obtaining money and other financial resources, and in the opinion of rudolf soukup from the vienna polytechnic, it makes sense to call upon alchemists as economical consultants, and economical theory may be defined as the “alchemy of the future”12 . glauber, becher and kunckel are forerunners from the same cultural context as beckmann. there are of course many early contributions to a pre-technological activity from other contexts. the amalgamation process (beneficio de patio, patio process), developed in mexico by bartolomé de medina (1503-1585) is a very important contribution to metallurgy and technology13, ignored during centuries by european historians of science and technology. an important pioneer of technology was the 6 frenchman jean helot (1685-1766), particularly with respect to dyeing and porcelain making14 (wisniak, 2009, 111-121). the immediate origin of modern chemical technology: cameralism and chemia applicata. christoph meinel suggests that the intertwined relation of cameralism and 18th century chemistry is similar only to the intertwined relation of chemistry and medicine observed a century earlier15. cameralistics or cameralism (kameralistik, kameralwissenschaften), the science of public revenue, is typically a german university course, generally taught at law schools, addressed to future public servants; it may be viewed as a german version of mercantilism (whether cameralism is a form of mercantilism is still a matter of debate)16. this course included the study of economical and administrative problems, arts and crafts, techniques and other topics of interest for the future public servant. it included general aspects about crafts, manufactures and industries, from which slowly emerged the “chemical technology”. the first chairs of cameralism were created by the initiative of king frederick william i (1688-1740) of prussia in 1727 at the universities of halle and frankfurt-oder; they were more practical than theoretical, and still directed to an agricultural economy. the new university disciplines were agriculture, forestry and veterinary (may be a surprise, however knowledge about dairy products, wool, leather, fats and oils were lectured). for several reasons cameralism as a depositary of chemical knowledge was important for the evolution towards a chemical technology17: cameralism emphasizes the role of chemistry in modern society. cameralism included chemistry in the wider economical and administrative objectives of the state. this substantiated chemistry as an independent academic activity. cameralism highlighted the importance of a scientifically based technological and industrial activity. society learned about new perspectives of development, by means of the universities, through thoroughly trained graduate professionals. during the first decades of the 19th century cameralism as a discipline began to break down. matters related to finances and public administration were incorporated in law or economics, matters related to the arts, crafts and techniques were housed in the écoles centrales in france and in the gewerbeschulen in germany, and at university 7 level in the polytechnic schools, the first and possibly most respected the école polytechnique in paris, founded in 1794 by the commission for public works, under the leadership of lazare carnot and gaspard monge. in germany, austria, switzerland, the netherlands and the scandinavian countries were created the technische hochschulen, viewed initially with certain contempt by the traditional universities. in sweden, long before cameralism was firmly established in germany, chemistry was no more a subsidiary discipline for physicians and medicine, but a subsidiary in economic activities, like mining, metallurgy, industry. the first chemistry chairs in swedish universities were held by chemists involved with these practical activities. the dominant personality in formally organizing this “practical chemistry”, the chemia applicata, was johann gottschalk wallerius (1709-1785), professor at uppsala university (1750/1767). in a publication from 1751, wallerius distinguished between chemia pura and chemia applicata, defining them as follows: “chemia pura is a science on fundamental matter and its reactions ( mixtures). chemia applicata is operative, is an art showing how by means of mixtures or decompositions of bodies we can prepare several new substances, possibly useful in daily life”. wallerius separated theoretical from applied chemistry, but did not keep them as distinct entities, avoiding the artificial distance created by pierre joseph macquer (17181784) when he published “elements of theoretical chemistry” (1749) and “elements of practical chemistry” (1751). wallerius considered practical chemistry more important than theoretical chemistry, and classified chemia applicata in nine branches18 : (1) medical chemistry; (2) mineralogical chemistry (lithurgica); (3) chemistry of salts (halurgica); (4) chemistry of combustion (thejurgica); (5), metallurgy; (6) glass chemistry; (7) agricultural chemistry (chemia oeconomica); (8) chemistry of colours (chemia chromatica); (9) chemistry of arts and crafts (chemia technica, opificiaria). by advocating such posture, wallerius contributed to promote and value practical chemistry, so we must not downplay his importance in the synthesis of several substances during the “chemical revolution”, substances like sulphuric acid, ammonium salts and many others, as well in process improvements in the production of glass, porcelain and ceramics, sugar, beet sugar, bleaching, dyeing, among others. wallerius was criticised by his colleagues, particularly by torbern bergman (1735-1784), his successor in uppsala, for having done only a few experiments himself, using instead existing knowledge about these subjects. wallerius was the first organiser and 8 systematiser of a pre-technological chemistry, and in the opinion of b. bensaudevincent, from the university of paris, the correct proportion of theoretical and practical chemistry allowed a transition from science into art without great conflicts. wallerius theoretical chemistry was phlogistonist, the same theory advocated by countrymen bergman and scheele and the one referred to in cameralism. johann beckmann and chemical technology. the first university professor to teach technological matters (metallurgy) was probably johann conrad barchusen or barkhausen (1666-1723), at the university of utrecht, where he had been active since 169319 . the philosopher christian wolff (1679-1745) tried in 1728, with little success, to introduce a modern concept of technology (technologia), in a short philosophical essay: “it is the science of the things which man produces by using the organs of the body, especially the hands”20 . but modern chemical technology begins with the publication in 1777 of “anleitung zur technology” (introduction to technology) by johann beckmann (1739-1811). beckmann coined the term “technology” (= historia artium), contrasting with natural history, and in 1772 defined technology as: “the science which teaches how to transform natural products, or the knowledge of the arts, industries and manufactures” 21. before choosing the term “technology”, beckmann considered using “handwerkswissenschaft”, or the “science of tasks”22. beckmann was also the first formal teacher of chemical technology, as professor of philosophy (1766) and economics (1770) at göttingen university. “chemical technology” as a university discipline developed from cameralism. in 1878, centennial of the publication of beckmann’s “anleitung”, wilhelm franz exner (1840-1913), professor of general technology at the vienna polytechnic, published a biography and delivered lectures in vienna, with the aim of preserving beckmann’s memory. in exner’s words23 : “the founder of chemical technology, professor johann beckmann, has already fallen into oblivion among the public at large. specialists from several fields still value his contribution and use his works, but even they probably know nothing about beckmann’s life history”. in fact, outside the context of his profession, beckmann is now unknown or undervalued. the decay of cameralism was also the decay of technology. the johannbeckmann-gesellschaft, hoya, founded 1987, tries to preserve his memory. 9 figure 1. johann beckmann. lithography by f. e. haid. (courtesy johann-beckmanngesellschaft, hoya). johann beckmann24 was born on 4 june 1739 in hoya, a small city at the weser river, in northwestern germany, in the principality (1806-1866 kingdom) of hannover, son of nicolaus beckmann (1700-1745), tax collector and administrator of the post office, and dorothea magdalena beckmann (1718-1763). after his first school years in hoya, he went to study in stade, near hamburg; in 1759 he enrolled at göttingen university, studying theology, physics, mathematics and natural sciences; he undertook studies also in leiden (where he entered a masonic lodge), and with carl von linné (1707-1778) in uppsala in 1765. anton friedrich büsching (1724-1793), geographer and historian, professor and minister of the german community in saint petersburg, convinced beckmann, then in need of money, to establish himself in the russian capital (1763), where he stayed for only a short time. but even a short residence sufficed to turn beckmann into an intermediary between russian and german science. he travelled in russia, sweden, denmark and the netherlands, visiting mines and industries. in 1766 he was appointed extraordinary professor of weltweisheit (literally “wisdom of the world” = philosophy) in göttingen; very successful as a teacher, in 1770 he was appointed regular professor of physics and natural sciences, and later of economics. 10 figure 2. view of the city of hoya, 17th century. engraving by matthäus merian the older (1593-1650). (courtesy johann-beckmann-gesellschaft) the university of göttingen was founded in 1737, following planning by adolf baron von münchhausen (1688-1770), innovative since its establishment, offering ‘modern’ disciplines, like geography and physics, and extracurricular disciplines like modern languages and design. regular instruction in economics and technology belonged to the ‘modern’ disciplines. beckmann approached the different industrial ‘arts’ and handcrafts, from both theoretical and practical viewpoints, in accordance with the principles of enlightenment. in each case, beckmann was concerned about origin and evolution of the technique under study, including its history: in the opinion of friedrich klemm (1904-1983), from the deutsches museum in munich, beckmann is also the founder of the history of technology25. ruy gama (1928-1996) concludes that beckmann’s main interest was to bring together scholars and manufacturers, taking to the academy and to the university the production processes for different commodities, allowing the development of more rational and modern processes, a task performed also by other technologists26. the role of the university in the creation of technology and innovation can be found in this ‘meetings of savants and craftsmen’. technology entered göttingen university even before its economic importance was properly appreciated. johann beckmann lectured at göttingen for more than thirty years. he died in göttingen on 3 february 1811, aged 71, likely from pneumonia. his lectures were famous, attracting students from other universities, like alexander von humboldt 11 (1769-1859). his weekly classes on practicum camerale were renowned, and constitute perhaps the first example of interdisciplinarity, or maybe of multidisciplinarity. his classes were theoretical and practical, including visits to mines and industries, and working in the ‘modellkammer’, a kind of simulation of the processes studied27 . figure 3. stamp issued in honour of beckmann in1989 by the former german democratic republic. beckmann was a member of the academia leopoldina in halle (1771), of the göttingen (1772), munich (1809), saint petersburg, stockholm (1790), the netherlands (1809) academies. little is known about beckmann’s private life, and his biography is awaiting interested historians. in 1767, he married sophie karoline schlosser, from kassel. the couple had two children, the twins samuel johann beckmann (1771-1841) and johanna petronella sophie beckmann (1771-1831). today, beckmann’s descendants live in germany, in the united states and in brazil. beckmann’s technological work beckmann’s fundamental contribution to technology, the most important for the history of technology, the most praised (and most criticized) is doubtless his “anleitung zur technologie” (1777, göttingen, seven editions until 1823, “guide to technology”). it is not yet an exhaustive, systematic work including all branches of technology, but instead, an organized, formal, essentially qualifying and descriptive work on the diverse manufactures and handicrafts. the first edition (1777) still had as theoretical foundation the phlogiston theory; in the fourth edition (1796) beckmann 12 embraced “lavoisier’s anti-phlogistic theory”. as mentioned by otto gekeler (19121999), beckmann describes as follows the general concepts of his “anleitung”28: handcrafts should be ordered not only following the used materials and the produced objects, but also following the common parts and analogies during their processing and the principles upon which these are based. knowledge of handcraft, fabrics and manufactures is indispensable: what has been made, ordered, qualified, handled, gained, used, and performed should at least be known and understood. “when basic knowledge fails, the craftsman should be left upon his own or he will receive plans which cannot be performed”. in somewhat random fashion, beckmann mentions 324 crafts, 58 of which relating to chemistry29. in the introductory section he emphasises the economic aspects of production (beckmann was professor of economics), suggesting the use of by-products of a chemical process, or discussing costs related to labour, transportation of materials and final products, interest rates due to funding for the purchase of raw materials, which would be sold as products many months later. he describes in detail, 32 manufactures, 23 of them chemical in nature, like production of soda, potash, sulphuric acid, nitric acid, vitriols and other salts, saltpeter, common salt, sugar, distillation of tar and coal, gun powder, porcelain and glass, dyeing of wool and silk, tanning, production of pigments (lead white, prussian blue, ultramarine) and dyes (indigo, woad, litmus, india ink, carmine), fermentation processes for wine, beer, vinegar, liquors and other distillates, and many more. the themes chosen and the approach to their discussion suggest two theses accepted by historians: beckmann describes the manufactures still deficient in germany, or he presents proposals intended to solve these deficiencies. many chairs of “technology” were created at several universities after publication of beckmann’s book, and “technological” literature appeared very quickly, and, as gekeler, wrote: “it is out of doubt that the actual presence of technology in the wide range of realisations depends directly upon the publication of this technological standard book, wherein, for the first time, several products such as paper, beer and porcelain are treated and classified in the way they can be produced”30 . 13 the first german universities in which technological matters were lectured were giessen (1777), stuttgart (1781, the karlsschule), vienna (1781), ingolstadt (1782, today the university of munich), mainz (1784). outside germany, beckmann’s technology spread to a lesser extent: in france, isaac haffner (1751-1831) taught technology in strasbourg and jean henri hassenfratz (1755-1827) promoted the diffusion of technological contents in other institutions. in italy, short lived lectures (1819/1823) at the university of padua, and in scotland there was a discipline of technology in edinburgh, which did not survive the death of the lecturer, george wilson (1818-1859)31 . the case of cane sugar production captured beckmann’s attention32. in the 1777 edition, still having the phlogiston theory as theoretical foundation, “the components of sugar are water, earth, acid and a fine oily or combustible component” (in this last component should be found the “sweetness” of sugar). the 4th edition (1796) follows lavoisier’s anti-phlogistic theory, and sugar is composed by carbon, oxygen and hydrogen, and the different qualities of different sugars, of tartaric figure 4. front page of “anleitung zur technologie”, 1777 edition. acid and oxalic acid are due to different proportions of oxygen. strangely, beckmann does not mention the “sacharologia” (1637) by angelo sala (1576-1637), probably the 14 first monograph about sugar, published in german in rostock33 , and does not mention the discovery of beet sugar in 1747 in berlin by andreas sigismund marggraf (17091782) – most likely because the process was not yet exploited commercially, an exploitation which would occur in 1798 by franz karl achard (1753-1821) in a small factory in kunern, silesia (now konary, in poland). beckmann restricted his discussions and descriptions to processes used in his own time. still about sugar, beckmann presents a historical introduction, classifications based on various criteria, geographical for instance (sugar from st. thomas, guadaloupe and martinique, madeira, pernambuco, bahia), or aspect, grades of purity, among others. he mentions other plants containing sugar (maples, aceraceae like european acer campestre, or canadian acer saccharinum), and briefly describes the production of cane sugar and sugar refining, an industrial activity still done mostly in europe. although interested in joining theory and practice, beckmann describes in detail the sugar production process proper. from the many details presented, ruy gama (1928-1996), a brazilian historian of technology and authority in the history of sugar production, says “we could think these authors [beckmann and his contemporaries and successors, even marx] knew the sugar factories”, but this is obviously not the case34 . sugar refining is a perfect example of an activity in which chemical technology could offer great improvement: refining at the places of production would reduce costs and increase productivity. beckmann suggests that refining in the same place where sugar cane is produced would improve profitability. charles edward howard (1774-1816), a selfeducated english scientist, designed a new vacuum evaporator and other accessories for the sugar industry (first patented in 1812), which were used in west indian factories and elsewhere35 . gun powder is another product discussed by beckmann36: its origin, he says, is unknown, but it certainly is not an invention of bertholdus niger37. beckmann discusses the properties of powder and the desired qualities of its ingredients, he distinguishes “strong” from “weak” powder, which resulted from the different proportions of saltpeter, sulphur, and carbon. in his time, the best powder was produced in essone, france (we know about lavoisier’s efforts in improvement of powder), and its typical composition would be: 75 pounds of saltpeter, 9,5 pounds of sulphur and 15 pounds of carbon. beckmann’s observation that powder was used in mining, in rammelsberg by the year 1200, before its military use, is indeed surprising. the mines 15 of rammelsberg are located near göttingen, and he may have heard this from local miners, so that the information may be not devoid of truth. the “anleitung” knew six more editions, in 1780, 1787, 1796, 1802, 1809 and 1823. this text from 1777 is greatly responsible for beckmann’s reputation and importance, but the first of his books to draw attention was the “grundsätze der deutschen landwirtschaft” (“basics of german agriculture”, 1896), from 1769, one of the most read ‘technological’ texts of its time, responsible for introducing agriculture as a university discipline, the first economic activity to gain university status. “vorbereitung zur waarenkunde” (göttingen, 1793/1800), or “introduction to the commodity sciences”, is probably the first general treatise on what we call today the commodities (waren = marketable products). beckmann describes in detail 42 products or groups of products, qualifying them as natural products or products of “the arts”. these waren included the so called kolonialwaren, products which the europeans brought from their colonies: cotton, rubber, soy, coconuts, ivory, musk, indigo and other dyes. beckmann endeavoured to turn these raw materials into useful products, but also showed concern with the possible extinction of some of them38. alexander kraft relates that in 1772 king frederick ii the great (1712-1786) ordered andreas sigismund marggraf (1709-1782), from the berlin academy, to try to obtain artificial chocolate and vanilla aromas from small-leaved linden tree (tilia cordata) barks and fruits. cocoa and vanilla were too expensive, and frederick forbade their import39 . among many other publications by beckmann, the five volumes of “beiträge zur geschichte der erfindungen” (leipzig, 1782/1805), published in english as “history of inventions, discoveries and origins” (1798, 4th edition 1846), deserves some commentaries. it is a collection of easy-to-read texts aiming at diffusing science and technology. but it also contained detailed descriptions of the evolution of some chemical processes, like the process for obtaining alum. the collection shows the breadth of the historical knowledge of the author, dealing with a wide range of themes: italian renaissance accounting, gold refining, the origin of the names of the elements, plants, animals and minerals, street lighting, glass engraving... friedrich klemm (19041983) considers this collection the very beginning of the historiography of technology40. history of technology was restricted to the evolution of practical and productive activities in a european context, and activities or even innovations originated in peripheral countries were of no interest in face of the innovations of the industrial revolution41 . 16 a very important book, in exner’s opinion, is beckmann’s “entwurf einer allgemeinen technologie” (1806, göttingen, “draft on general technology”). a new edition in 2006, organised by bernd meier and helmut meschenmoser, calls the book “the birth certificate of general technology”. in this booklet of only 72 pages beckmann “normatizes men and machines”, establishing a systematic classification for technology, based on the systematic classification developed by carl von linné (17071778). linnean taxonomy or systematics has a ranked hierarchy, with kingdoms (mechanical processes, chemical processes), divisions (or phyla), classes, orders, families, genera, species. as an example, in the kingdom “chemical processes”, there is an order “filling of imperfections” (of the bodies), which can be done by greasing, varnishing or glazing/vitrifying (these are three “families”). “species” for greasing are bee wax, carnauba wax, candelilla wax; for varnishing, there is lacquer (shellac); for glazing, there is lead oxide. before beckmann, other technologists made use of binary classifications; johann georg krünitz (1729-1796) qualified in his “oekonomische encyclopaedie” (1790) different types of coal in accordance with a binary system: carbo anthrax ( = charcoal), carbo lithoanthrax ( = hard coal), and others42. beckmann’s publications and teachings were rich and prolific. his rational work, derived from late enlightenment, was very distant from the romantic thinking then dominant in germany. this dominance was another reason for beckmann’s oblivion in the german romantic period. otto gekeler takes this text of 1806 as an obvious complement for the text published in 1777. “it may be stated that “beckmann’s viewpoints are trivial and universal at the same time: one object can be made following different systems; one system can be used for different objects”43. he was the first to mention what chemical engineers today call ‘unit operations’, a concept introduced by arthur dehon little (1863-1935), professor at the massachusetts institute of technology. in his treatise from 1806, beckman presents his “principle of completeness” (ganzheitsprinzip), in the following words44 (beckmann, 1806): “we must obtain the material and immaterial benefit from the commodity with a minimum of nature and human substance throughout the commodity’s life with due regards to health, political, ethical and other relevant aspects”. multidisciplinarity hidden in the ganzheitsprinzip unveils beckmann’s concern in producing science and technology ‘for the people’. quoting gekeler45 , 17 “this conscious appreciation of all possible implications of technology and commodities, encountered at all stages of their existence (from production over usage and/or consumption to waste management) will be called the ‘ganzheitliche betrachtung’ or contemplation in entirety”. this is clearly in the spirit of universal enlightenment. a group of japanese researchers, leaded by tetsuo tomita, translated beckmann’s treatise from 1806 and the “history of inventions” into japanese (1976/1982), wishing to understand and better assess how technology was transferred from europe to japan46. tomita writes: “our purpose was not necessarily to learn the history of technics of europe but to compare the basic civilization and technics of europe depending upon their climate and geophysical elements with those of japan, particularly before the developments in the field of electricity and modern synthetic chemistry had been attained. such trails will make it possible for us to find suggestions for analysis and prediction of conditions and reactions of technological transfer in future”47 . sometime before, in 1786, in göttingen, and in the spirit of enlightenment, johann friedrich gmelin (1748-1804) published the first textbook on chemical technology, “grundsätze der technischen chemie” (foundations of technical chemistry); a second edition (1795) was titled “handbuch der technischen chemie”. gmelin used terminology in the sense we mentioned, saying that “technical chemistry is that part of applied chemistry which teaches the basics of factories, manufactures, arts and crafts, and the advantages of applying these principles to these activities”48 . some of these crafts existed since remote times, in gmelin’s opinion, but others are unimaginable without technical chemistry. among the oldest crafts related to chemistry, practiced since the thirteenth and fifteenth centuries, gmelin mentions in his “geschichte der chemie” (1797, “history of chemistry”) activities like metallurgy, obtention of alum and vitriol, ceramics, glass, dyeing, pharmacy. in any case, also for gmelin, chemical technology dates from the second half of the eighteenth century, the “great century” of chemistry, among other reasons because of the emergence of methodologically organised chemical technology. characteristic features of beckmann’s technologie are, as mentioned by guido frison: 18 “the object of technologie corresponds to something which may be called “industrial work”; and the subject who is interested in technologie is the ruler of the process of production. technologie is a science, or more accurately an analysis of production from a naturalistic perspective. technologie examines the productive procedures; i.e., what goes on between the social actor and his means of labour but not from a sociological point of view; the knowledge of technologie allows innovation” 49. such characteristics, according to frison, are still distant from an ideal productive procedure. at the same time beckmann creates his ‘technologie’ as a discipline, his friend and colleague in göttingen, historian august ludwig von schlözer (1735-1809), conceives a new form of presenting the universal-historie, a general and universal history, in which he considers technics and inventions (in the sense given by beckmann) as driving factors for human and cultural development50. schlözer suggests four “methods” for structuring history: the chronographic, technographic, geographic, and ethnographic methods. the chronographic method is a simple chronologic record, unable to analyse the relation between facts. the technographic method explains progress and retrogression of humankind in terms of progress and retrogression of technologie and inventions. the geographical method accounts a systematized harmony of the diverse geographical regions. in the ethnographic method, the inhabitants of the earth are brought together on the basis of behavioural similarities, in groups, “peoples” or “populations” – although it remains unclear how many “peoples” would exist. evaluation the evaluation of johann beckmann has varied much according to place and time, sometimes viewed as positive, and sometimes not so much. it is not really an evaluation of beckmann himself, but of the methods he proposes for the creation, management and improvement of technological processes or procedures. one same process can be analysed and explained in accordance with different stances: as a purely empirical sequence, disconnected from every theoretical association, as sequences of trial-anderror reactions; or, as a rigorous application of a “technological methodology”, similar to a scientific methodology. the most emblematic example is the explanation of leblanc’s process for producing soda (1791): charles gillispie (1918-2015) suggests an 19 artisanal and empirical sequence of trial-and-error reactions51; john graham smith suggests a typical case of rigorous application of a technological methodology52. beckmann intended – and for this he is often criticised – to include in university teaching all aspects related to technology: raw materials, rationalisation of technological processes, use of by-products and many others. in pioneering countries of the industrial revolution, like france and great britain, empiricism alone lead to satisfactory results with respect of quality and costs of products obtained, and theoretical concerns, as expressed by beckmann, seemed to be irrelevant. as frison observes, the notions of “technique” and “technology” are absent from the works of adam smith (1723-1790) and john stuart mill (1806-1873): terms like ‘art’, ‘trade’, industry’, ‘manufacture’ are found instead53. in fact, as ruy gama observes, beckmann does not exist in french or british technological literature, he is not cited in the monumental “history of technology” by charles singer (1876-1960), or in the famous article about mills, which marc bloch (1886-1944) published in 1935 in the annales. authors less famous today, although fundamental for the evolution of this area of knowledge, as george sarton (1884-1956), lewis mumford (1895-1990) or edmund oskar von lippmann (1857-1940) attribute minor importance to beckmann. karl marx (1818-1883) was a frequent reader of beckmann and quotes him several times in his “capital”, as a source of factual data. marx became familiar with beckmann’s works through one of the latter’s students, the technologist johann heinrich moritz von poppe (1776-1854)54. he utilized as a definition of technology that used by beckmann and j. h. poppe. marx was aware of the meaning and originality of this new discipline created by beckmann55 . a renewed interest for johann beckmann arose in the 1970s in former german democratic republic. marx’s interest in beckmann can be found in several essays and papers on techniques and technology. with the collapse of the socialist system of production in eastern europe the interest of historians and scholars even for this critical interpretation of the marx-beckmann relationship diminished. wilhelm exner, in his presentations in vienna in 1878, the centennial of the publication of “anleitung”, regretted the oblivion of beckmann in his own country, for which there is, however, a plausible reason. beckmann advocated during all his career at göttingen the inclusion of technological matters into university teaching, an initiative which brought him many opponents. for the incredulous and sceptics, beckmann wrote in the introduction of the anleitung 56: 20 to those who do not understand, and to those who do not want to admit, that agriculture, technology and commerce can be taught with good results at university, i ensure that i know the contrary based on ten years of experience, and i could mention people who now occupy high positions, whose duties require such knowledge, and who would … confirm it. it is obvious, he comments, that artisans learn their activity in workshops, merchants in their offices, but it would be ridiculous to assert they do not need any theoretical knowledge in their professional practice. exner was too pessimistic. industrialisation in germany, an unified nation only since 1871 – “the nation which arrived too late” – began in the middle of the 19th century, and the contribution of universities to the productive process would be successful only with the involvement of a third partner: the state. the chemist august wilhelm von hofmann (1818-1892) was personally engaged in establishing this conjunction of factors. the equivalence of traditional universities and technische hochschulen was recognised formally in 1900, including the privilege to grant ph.d. titles. technology is an inseparable and irreversible part of modernity. this realisation, from which one cannot escape, gave origin to philosophy of technics or philosophy of technology, dedicated to, among other purposes, identifying the limits between the rational and the irrational, the artificial and natural, mechanization or “machinization” (in the sense of replacing the work of a person with that of a machine). from the inevitability of technology in our context, good or evil, we derive the inevitability of ethical/normative questionings. to discuss these issues falls outside the scope of this paper. our aim is to discuss the role of beckmann in the history of technology and social progress. 21 figure 5. wilhelm franz exner’s essay on life and work of beckmann, 1878. a common critique of technology and of beckmann suggests that technology or technical science is still a project, a project which tries to reshape the world according to machinery principles, and dreaming in turning its principles into the basis of a unified knowledge. this proposition is a denying one, and ignores the history of science. leblanc’s process for soda production is an example that technology is not a project, but that it advanced far beyond a project. other examples are the solvay process for soda production, the contact process for producing sulphuric acid, the electrochemical and the haber-bosch processes for ammonia production, among others. artificial production of fertilizers is, as the chemist william crookes (1832-1919) puts it as a follower of malthus, a basic condition for maintenance of life in later days57. beckmann’s strategy can be seen in all of these processes, even for those who do not 22 want to admit it: maximum utilization of raw materials, search for alternative raw materials, recycling raw materials and their rejects, usage of by-products, removal of environmental damage, reduction of costs. obviously, this did not occur overnight, but is the result of a gradual ripening of a technological project. the gap between the “two cultures” – the scientific/technological and the humanist – of charles lord snow (19051980), makes it impossible, or at least very difficult, to have a full understanding of problems like the importance of beckmann. another kind of critique is presented by post-modern authors, as bruno latour (1947-2022), for whom the notion of science hold by scientists is irrelevant for scientific activity58. but without taking into account what scientists and technologists think about their activities, philosophers and sociologists of science could not explain how it was possible to technologists like beckmann, or to chemists like martin heinrich klaproth (1743-1817), to change from phlogiston theory to lavoisierian anti-phlogistic theory without any rupture in their work. philosophers and sociologist of science would not be able to work out a methodology of scientific practice, nor decide about the scientificity or not of a theory. finally, it must be said that in beckmann’s time there was no distinction between a “scientific” culture and a “humanist” culture. in other words, the “two cultures” show the comprehensiveness of all their vast knowledge: historical, philosophical, educational, practical and technical. this was a time of optimism about technology, distinct from today’s fears about possible (probable?) technological excesses damaging the fabric of society. beckmann looked at technology and its evolution in terms of his ganzheitsprinzip, or, as a unified whole, including historical, cultural, social, political, ethical, and environmental aspects. for today’s skeptics with respect to the environmental cause, let us see beckmann’s opinion on using ivory: “aesthetics associate to artworks and objects made of ivory on one side, on the other side, the irrationality of pursuing animals for sake of aesthetics”59. nil sub sole novum. but this is a paper about the past and about beckmann, for whom the advantages of technology surpass in much the risks; but nowadays risks are greater day after day, so that george sarton himself suggested caution with machines60. 23 trivia. i had the pleasure to be in correspondence, during several years, until his death, with egon max beckmann (1925-2012), descendant of johann beckmann. his grandfather adolf beckmann (1861-1934) came as an immigrant to brazil, and in 1887 founded in joinville the hotel beckmann, a meeting point for voyagers and local people. sold in 1915, it reopened later as hotel palácio. i stayed there for a few days in 1951, with my mother, during school holidays. such incredible coincidences cannot be predicted.... aknowledgements to the former johann-beckmann-gesellschaft, hoya/germany, for providing bibliography difficult to access, as well as iconography about beckmann; to detlef meyer, mayor of hoya, for permission to reproduce the images; to helga lühmannfrester, former secretary of the johann-beckmann-gesellschaft, for providing iconography. references. 1 . g. sarton, “the history of science and the new humanism”, cambridge/mass. harvard university press, 1966, p. liv. 2. unamuno, m., “del sentimiento trágico de la vida”, editorial alianza, madrid, 2008, p. 307. (original spanish edition 1912; english translation, ‘tragical sense of life, by j. crawford flitch, 1913). 3. jacomy, b.,”a era do controle remoto”, editora zahar, rio de janeiro, 2002, p. 103. 4. weyer, j., chemie an einem fürstenhof der renaissance, chemie in unserer zeit, 12, 241-249 (1992). 5 . thurneysser was a controversial figure, and his work in this field is lesser known. older historiography (e.g.stillman) considers him an adventurer, but more recent research shad a new light on his multiple interests (e.g. b. herold, história natural de portugal, ágora, nº 19, 305-334 (2017). 6. newman, w., principe, l., alchemy vs chemistry: the etymological origins of a historiographic mistake, early science and medicine, 3, 32-65 (1998), p. 32. 7. debus, a., “the chemical philosophy”, dover, new york, 2002 [1977]. 8. schmauderer, p., glaubers einfluss auf die frühformen der chemischen technik, chemie-ingenieur-technik, 42, 686-696 (1970), 9 . soukup, r., “chemie in österreich”, vienna, böhlau. 2007, pp. 443-455. 10 . stillman, j. “history of alchemy and early chemistry”, new york, dover, 1960 [1924], p. 420. 11. lärmer, k., johann kunckel der alchemist auf der pfaueninsel, berlinische monatschrift, 2000, pp.10-16. rau, h., johann kunckel, geheimer kammerdiener des grossen kurfürsten, und sein glaslaboratorium auf der pfaueninsel in berlin, medizinhistorisches journal, 11, 129-148 (1976). 12 . soukup, r., “chemie in österreich”, böhlau, vienna, 2007, p. 414. 24 13. roche, m., “early history of science in latin america,” science, 164, 806-810 (1976). 14. wisniak, j., jean hellot. a pioneer of chemical technology, revista cenic ciencias químicas, 40, 111-121 (2009). 15. meinel, c., reine und angewandte chemie. die entstehung einer neuen wissenschaftskonzeption in der chemie der aufklärung, berichte zur wissenschaftsgeschichte, 8, 25-45 (1985). 16. frison, g., the first and modern notion of technology from linnaeus to beckmann and marx, consecutio rerum, anno iii, nº 6, 147-162, (2018), p. 152. 17. meinel, c., artibus academica inserenda. chemistry’s place in eighteenth and early nineteenth centuries universities, history of universities, 8, 89-115 (1988). 18 . meinel, c., theory or practice? the eighteenth-century debate on the scientific status of chemistry, ambix, 30, 121-132 (1983). 19 . linde, r., johann conrad barkhausen (1666-1723) – der bedeutendste sohn der stadt horn in lippe, lippische mitteilungen aus geschichte und landeskunde, vol. 53 (1964). 20 . frison, g., the first and modern notion of technology from linnaeus to beckmann and marx, consecutio rerum, anno iii, nº 6, 147-162, (2018), p. 148. 21 . beckmann, j., “anleitung zur technologie”, vandenhoeck, göttingen, 1777 22. lühmann-frester, h., “europa in der frühen neuzeit”, böhlau verlag, vienna, 1999, vol. 5, (ed. e. donnert), pp. 627/628. 23. exner, w., johann beckmann, begründer der technischen wissenschaft, hoya, johann beckmann gesellschaft, 1989, introduction. this is a facsimile reprint of exner’s original edition, vienna, carl geralds, 1878. 24 . biographies of beckmann may be found e.g. in exner’s book from 1878 (reprint 1989), or in o. gekeler, johann beckmann and the consideration of commodities and technology in their entirety, sartoniana, 2, 139-171 (1989). 25 . klemm, f. “geschichte der technik”, rowohlt, hamburg, 1983. see also w. könig, h. schneider, “die technikhistorische forschung in deutschland seit 1800”, kassel, universitätsverlag, 2007. 26 . gama, r., “tecnologia e trabalho na história”, edusp, são paulo, 1986, p. 74. 27 . lühmann-frester, h., “europa in der frühen neuzeit”, böhlau verlag, vienna, 1999, p. 631. 28 . gekeler, o., johann beckmann and the consideration of commodities and technology in their entirety, sartoniana, 2, 139-171 (1989), p. 149. 29 . beckmann, j., “anleitung zur technologie”, vandenhoeck, göttingen, 1777. 30. gekeler, o., johann beckmann and the consideration of commodities and technology in their entirety, sartoniana, 2, 139-171 (1989). 31. frison, g., the first and modern notion of technology from linnaeus to beckmann and marx, consecutio rerum, anno iii, nº 6, 147-162, 2018. 32. beckmann, j., “anleitung zur technologie”, vandenhoeck, göttingen, 1777, pp 324 341. 33. gelman, z., angelo sala, an iatrochemist of the renaissance, ambix, 41, 142-160 25 (1994) (on p. 147/148), 34. gama, r., “ engenho e tecnologia”, editora duas cidades, são paulo, 1983, p. 342. 35. wisniak, j., charles edward howard – explosives, meterorites and sugar, educación química, 23, 230-239 (2012). kurzer, f., life and work of charles edward howard, annals of science, 56, 113-141 (1999). 36. beckmann, j., “anleitung zur technologie”, vandenhoeck, göttingen, 1777, pp. 342-353. 37. bertholdus niger (berthold schwarz), a legendary alchemist (14th century) from freiburg, often credited with the invention of gun powder, is not a historical character. see r. oesper, ‘berthold schwarz’, j. chem. educ., 16, 303-306 (1939). 38. reith, r., introduction to meyer, t. (ed.), “luxus und konsum – eine historische annäherung”, waxmann, münster, 2003, pp. 18-19. 39. kraft, a., chemiker in berlin – andreas sigismund marggraf (1709-1782), jahrbuch des vereins für die geschichte berlins, 2000, p. 23. 40 . klemm,, f., “geschichte der technik”, rowohlt, hamburg, 1983. 41 . saldaña, j., la historiografia de la tecnología en américa latina: contribución al estudio de su história intellectual, quipu, 15, 7-26 (2013), p. 23. 42 . krünitz, j., oekonomische encyclopaedie, tressler, brünn, 1790, part 43, p. 4. 43. gekeler, o., johann beckmann and the consideration of commodities and technology in their entirety, sartoniana, 2, 139-171 (1989), p. 154. 44 . beckmann, j, “entwurf einer allgemeinen technologie”, göttingen, 1806. 45. gekeler, o., johann beckmann and the consideration of commodities and technology in their entirety, sartoniana, 2, 139-171 (1989). 46 . tomita, t., cited by o. gekeler, op. cit., p. 146. 47. troitzsch, u. , postfacium, facsimile edition of exner, hoya, 1989. 48 . gmelin, f, “handbuch der technischen chemie”, gebauer, halle, 1795, p.1. 49 . frison, g., linnaeus, beckmann, marx and the foundation of technology between natural and social sciences; a hypothesis of an ideal type, history and technology, 10, 161-173 (1993). 50. lühmann-frester, h., europa in der frühen neuzeit, böhlau verlag, vienna, 1999, pp. 632-634. 51. gillispie, c., the discovery of the leblanc process, isis, 48, 152-170 (1957). 52. graham-smith, science and technology in early french chemistry, colloquium ‘science, technologie et industrie’, oxford, 1979. 53. frison, g., “technical and technological innovation in marx”, history and technology, 6, 299-324 (1998). 54 . müller, a., unbekannte excerpte von karl marx über johann beckmann, in g. bayerl, j. beckmann, “johann beckmann (1739-1811)”, waxmann, münster, 1999. 55 . frison, g., “technical and technological innovation in marx”, history and technology, 6, 299-324 (1998). 56. beckmann, j., anleitung zur technologie, vandenhoeck, göttingen, 1777, in the preface. 57. crookes, w., speech at the baas meeting in bristol, published in science, edition 26 from 28 october 1898, pp. 561-575. the haber-bosch process was invented only in 1908, but in 1898 there was already known the frank-caro process (1895). 58 . latour, b., woolgar, “laboratory life – the construction of scientific facts”, princeton university press, 1971. 59. gekeler, o., johann beckmann and the consideration of commodities and technology in their entirety, sartoniana, 2, 139-171 (1989), p. 148. in this sense, beckmann would welcome leo hendrick baekeland’s (1863-1944) invention of bakelite (1909). 60 . sarton, g., “history of science and the new humanism”, harvard university press, 1962, pp. 161-162. substantia. an international journal of the history of chemistry 6(1): 25-36, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1451 citation: henry m., radman m., benichou l., alfarouk k.o., schwartz l. (2022) singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy. substantia 6(1): 25-36. doi: 10.36253/substantia-1451 received: nov 08, 2021 revised: jan 22, 2022 just accepted online: jan 22, 2022 published: mar 07, 2022 copyright: © 2022 henry m., radman m., benichou l., alfarouk k.o., schwartz l. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research articles singlet dioxygen 1o2, its generation, physicochemical properties and its possible hormetic behavior in cancer therapy marc henry1,  miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* 1 institut le bel, université de strasbourg/cnrs, umr 7140, 4 rue blaise pascal, 67070 strasbourg 2 mediterranean institute for life sciences (medils), split, croatia 3 paris-est créteil university (upec) school of medicine. créteil, france 4 zamzam university college, khartoum, sudan 5 assistance publique des hôpitaux de paris, paris france *corresponding author. email: dr.laurentschwartz@gmail.com abstract. singlet dioxygen 1o2 is one excited state among the three other possible spectroscopic states of molecular oxygen. here, we first describe the use of published spectroscopic data and thermodynamic modeling based on irreversible entropy production. such concepts are further applied to the synthesis of singlet dioxygen and its reactions with crucial biological molecules. in a last section, we suggest that singlet dioxygen and ozone may be responsible for the success of radiation therapy, that has been used to treat cancer successfully for over 120 years. its precise mechanism of action remains controversial. we thus aim to clarify the role of singlet oxygen in radiotherapy and chemotherapy. a partial conversion of ionizing radiation in the body into thermal photons could be assumed. the antitumor effect may involve these thermal photons, such as the one delivered by red/infrared sources. thermal photons (wavelengths of 635 nm and 1270 nm) convert triplet dioxygen into singlet dioxygen by changing the spin of its outer electrons. despite its short half-life, singlet dioxygen is responsible for the activation of multiple free radicals (such as hydrogen peroxide), which may target proteins and dna, induce either apoptosis or oxidative phosphorylation. at moderate concentrations, thermodynamic data suggests that singlet dioxygen may readily react with water to form a potent pro-apoptotic molecule (ozone), thus decreasing cancer growth. however, at high concentration cytotoxic effects against all kind of cells occurs. this strongly suggests a non-linear hormetic behavior of singlet dioxygen. it is also proposed that cytotoxic chemotherapy induces the same free radicals that singlet dioxygen does. there are also other ways to enhance the production of singlet dioxygen, such as phototherapy using methylene blue for instance. as a source of reactive oxygen species (ros), singlet oxygen could thus be a common agent active both in radiotherapy and chemotherapy. it is probable that the activity of radiation therapy and chemotherapy may be mediated by the conversion of triplet to singlet oxygen. this may explain the oxygen effect such as described in radiotherapy and chemotherapy. keywords: cancer, phototherapy, warburg’s effect, radiation therapy, singlet oxygen, chemotherapy, oxygen effect. http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 26 marc henry et al. introduction less than two months after the discovery of x-rays by wilhelm röntgen in 1895, leopold freund treated, successfully, a child with a large nevus, a benign skin lesion[1]. in the following months, there were multiple reports of the efficacy of radiation therapy in the treatment of both benign and malignant lesions. radiation therapy (rt) is a therapy using ionizing radiation to control or kill  inflammatory and cancer cells. rt has been extensively used for the treatment of inflammation, but this indication is slowly disappearing because of the risk of radiation-induced malignancies[2]. rt may be curative in several types of cancer if they are localized to one limited area of the body. several shaped radiation beams coming from several angles of exposure intersect at the tumor to spare normal tissues (such as skin or organs that radiation must pass through to treat the tumor). this provides a much higher absorbed dose there than in the surrounding healthy tissue. rt kills normal cells, and every radiation oncologist knows the dose not to trespass to the normal tissues. ionizing radiation has been published to target the dna  leading to cell death. in the laboratory setting, the damage caused by ionizing radiation to the dna is immediate and consists of single or double-strand breaks and mutations[3]. a correlation exists between the toxicity of rt to the normal cells and the damage to the dna[4]. unlike the laboratory setting, there is no immediate sign of death for cancer cells in clinical practice. in the minutes following a cardiac infarct, there is an increased level of cardiac enzymes, such as troponin, in the blood plasma[5]. assessment of the treatment response after rt occurs, not minutes or even days but weeks after the inception of treatment[6]. recently, radman demonstrated that the prime target of radiation is not the dna as previously thought but the proteasome. the cell dies because of oxidative damage to its proteins[7]. the polymerases may repair the concomitant damage to the dna. this paper aims to suggest existence of a link between rt and production of singlet dioxygen mediated by thermal photons. radiation may also affect the activity of water around proteins or dna and change mitochondria activity. herein, we will not try reviewing the past 50 years in mechanistic, spectroscopic, computational, and biological studies of singlet oxygen. this topic is covered in great details in a recent textbook[8]. our interest is rather to work in an historical perspective with focus on rather old concepts that will be revisited through the lens of the entropy concept[9-11]. moreover, we are perfectly aware that singlet dioxygen reacts by two distinctive pathways (type i and type ii mechanisms), and causes damage to biomolecules, materials such as polymers, food, paints etc. amino acids, nucleic acids, unsaturated molecules (e.g.; membranes) also react with singlet oxygen to yield decomposed products and consequently to cause cell death. but, all these important properties, which rationalize the toxic and fatal behavior of 1o2 to organisms completely neglects the fact that many biological processes, display a biphasic or triphasic response to exposure to increasing amounts of a substance or condition such as radiation. even if this hormesis model of dose response is still vigorously debated[12], it seems worth investigating if it could apply to the biological response of singlet dioxygen. moreover, in the spirit of putting more physics in biological or medical thinking, part of the article will be devoted to a reminder of the electronic structure and spectroscopic properties of these species deriving from molecular oxygen. finally, we will focus mainly on healing cancer, even if the ideas exposed here could be extended to other diseases. thermal photons are effective against cancer and inflammation the metabolism of the cancer cells has been extensively studied since the seminal work of the german scientist otto warburg[13]. warburg’s effect is, in fact, the cause of every hallmark of cancer, such as the proliferation of cells, angiogenesis, or immortality[14]. cancer is not the only disease involving warburg’s effect, as this effect is also crucial in inflammation[15] or alzheimer’s disease[16]. alleviating warburg’s effect decreases cell proliferation[14]. non-ionizing radiation has been developed successfully in the treatment of both benign and malignant tumors. delivery of hyperthermia is possible using nonionizing radiation such as ultrasound, microwave, or most commonly infrared (thermal) photons. red and infra-red photons have also been used in the treatment of inflammation. it is a well-accepted fact that a practice does not need total mechanism clarity to operate. more than 6500 publications registered on pubmed from lllt keyword (low-level light therapies) covering cancer[17] wound healing[18], inf lammation and pain management[19], muscles and joints injuries[20] as well as nerve regeneration[21], traumatic brain injuries[22], depression and anxiety[23] and more recently neurodegenerative such as alzheimer and parkinson diseases[24] as well as age-related macular degeneration[25]. 27singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy the three forms of molecular dioxygen dioxygen is a very peculiar molecule whose chemical behavior cannot be explained using conventional octet’s rule[26]. such rule generally applies to any molecule built from atoms belonging to the second period of the periodic table of the elements. let n be the total number of atoms, e, the total number of valence electrons, q the number of atoms other than hydrogen, and c, the number of cycles. it then mathematically follows that the number of single bonds should be s = n + c – 1, the number of lone pairs should be l = e – 3×q – n, and the number of multiple bonds should be m = 3×q – e/2 – c + 1 – e%2[27]. here e%2 = 0 or 1 if e is respectively even or odd. for dioxygen o2 characterized by e = 6 + 6 = 12, n = q = 1 + 1 = 2, c = 0, the rule predicts that s = 2 + 0 – 1 = 1 (one single bond), l = 12 – 3×2 – 2 = 4 (four lone pairs) and m = 3×2 – 12/2 – 0 + 1 = 1 (one double bond). this corresponds to the classical notation :o:=:o: found in every elementary chemistry textbook. the trouble is that such a formula is utterly wrong as it predicts that dioxygen, having an even number of electrons, should be a diamagnetic molecule in its ground state. experiments, on the other hand, show that dioxygen is rather a paramagnetic molecule in its ground state, diamagnetic states corresponding to excited states. such a deep mystery could be resolved by writing lewis’s structures after the removal of two electrons (o22⊕ ion with e = 10) or the addition of two electrons (o22⊝ ion with e = 14)[28]. for the dication, langmuir’s rules predicts that the number of single bonds does not change (s = 1), but that l = 10 – 3×2 – 2 = 2 (two lone pairs) and m = 3×2 – 10/2 – 0 + 1 = 2 (one triple bond). this corresponds to the classical notation, ⊕:o≡o:⊕, meaning that the two electrons in the highest occupied energy level are of anti-bonding character, as removing them leads to the apparition of an additional chemical bond. concerning, the dianion, the same rules predicts that l = 14 – 3×2 – 2 = 6 (six lone pairs) and m = 3×2 – 14/2 – 0 + 1 = 0 (no multiple bond, i.e. ⊝:ö:–:ö:⊝). this means that the lowest unoccupied energy level is also of anti-bonding character, as adding 2 electrons there leads to the transformation of the double bond into two lone-pairs and a single bond. so, using just the wellestablished octet’s rule, it could be anticipated that the states of the highest energy (occupied and unoccupied) in dioxygen are of similar nature (anti-bonding character). this strongly suggests that these two states have the same energy (degeneracy) with a single unpaired electron in each state, •:o: —:o:•. this explains the observed paramagnetism of dioxygen in its ground state. further development of quantum mechanics and group theory has confirmed the validity of such a picture. accordingly, owing to its high symmetry (d∞h cylindrical symmetry), molecular orbital (mo) theory predicts that dioxygen has a doubly degenerated homo (highest occupied molecular orbital) or lumo (lowest unoccupied molecular orbital). in other words, writing structures obeying the octet’s rule is an easy graphical way to get good solutions for schrödinger’s equation. from mo-theory, we also learn that, owing to the phenomenon of resonance, obeying octet’s rule can be of a dynamic nature. thus, starting from the static solution (s = 1, l = 4, m = 2), we get the dynamic solution (s = 1, l = 5, m = 1), after transformation of the double bond into a delocalized lone pair: :ö:⊝—:o:⊕ ↔ ⊕:o: —:ö:⊝ here, violation of the octet’s rule occurs at a given time. however, after averaging in time, there is no possibility of distinguishing between the two oxygen atoms owing to the d∞h cylindrical symmetry. this restores octet’s rule, but in a dynamic sense. consequently, for a good understanding of dioxygen chemistry, it appears necessary to consider three main forms for this molecule: one apolar resonant paramagnetic bi-radical (triplet dioxygen): 3o2 (3σg-): •a:o: —:o:•b ↔ •b:o: —:o:•a one polar resonant diamagnetic molecule (singlet dioxygen) 1o2 (1∆g): :ö:⊝—:o:⊕ ↔ ⊕:o: —:ö:⊝ one apolar static diamagnetic molecule (singlet dioxygen) 1o2 (1σg+): :o:=:o: the greek symbols in brackets are the rigorous notation using labels derived from the symbols of the irreducible representations of d∞h point group symmetry. without such a notation, it would be impossible to distinguish between the two different forms of singlet dioxygen 1o2. this is a crucial point, as these three forms do not have the same energy. solving schrödinger’s equation thus shows that the ground state is 3o2 (3σg-) followed by the first excited state 1o2 (1∆g) located at an energy ∆e = 153 zj (1 zj = 10-21 j) above the ground state. to reach this state, the dioxy28 marc henry et al. gen molecule should absorb a photon of wavelength λ = h·c/∆e, where h is planck’s constant and c the celerity of light in the vacuum. with h·c = 198 645 nm·zj, the 1o2 (1∆g) state could be reached with a photon of wavelength λ = 198 645/153 = 1298 nm (infrared light). reaching the second state 1o2 (1σg+), located at an energy ∆e = 259 zj above the ground state, will involve a photon of wavelength λ = 198 645/259 = 767 nm (red light). it is then quite unfortunate that most biology textbooks treat dioxygen as a single species, generally written as :o:=:o: or o2 in short, which is not the ground state formulation. the fact that the spin state (upper left digit before the chemical symbol) is usually not even mentioned is also quite unfortunate. accordingly, it is worth recalling that spin conservation is one of the most fundamental laws of physics expressed by witmer-wigner for chemical transformation[29]. these rules state that if sa is the spin of reactant a and sb the spin of reactant b, a reaction will be spin-allowed if the total spin of the products is included in the series: |sa + sb|, |sa + sb 1|, |sa + sb 2|,…, |sa sb|. let us consider, for instance, one of the most exothermic reactions known in chemistry: 2 1h2 (g) + 3o2 (g) → 2 1h2o (l) ∆rg° = -2×237 = -474 kj·mol-1 as indicated by the superscripts showing spin multiplicities, such a direct reaction is spin-forbidden, as we have s(1h2) = ½(1 – 1) = 0 and s(3o2) = ½(3 – 1) = 1. it then follows that the total spin of the reactants is s = 2×0 + 1 = 1. for the products, we have s(1h2o) = ½(1 – 1) = 0, meaning that the total spin of the reactants is s = 2×0 = 0. there is thus a violation of spin conservation in water synthesis from dihydrogen and dioxygen taken in their ground state. this is the reason why nothing happens upon mixing a powerful reductant (h2) with a powerful oxidant (o2). however, it is a well-known fact that the reaction is immediate and explosive after the introduction of sparkle in the mixture. the role of sparkle is to bring enough energy to transform triplet oxygen 3o2 (3σg-) into singlet oxygen 1o2 (1∆g). the reaction then becoming: 2 1h2 (g) + 1o2 (g) → 2 1h2o (l) ∆rg° = -2×237 95 = -569 kj·mol-1 as now ∆s = 0, the reaction can proceed easily without any catalyst. it is worth recalling here that water synthesis is at the heart of complex-iv (cco). this complex of the electron transport chain (etc) in mitochondria has a catalytic site allowing direct reduction of triplet dioxygen into the water using separated fluxes of protons and electrons. the separation of protons from electrons is thus mandatory, as upon mixing them together, we would obtain singlet dihydrogen that is unable to react with triplet dioxygen to form water. this means that quantum chemistry should be at the heart of biological thinking. the fact that it does not have deleterious consequences, particularly for medicine, as prevention of water synthesis from triplet dioxygen in mitochondria leads to warburg’s effect, a common source for many kinds of diseases[14]. spectroscopic properties of singlet dioxygen as explained above, thermal photons may interact with triplet dioxygen (3o2) to form singlet dioxygen (1o2). switch from triplet to singlet state necessitates energy. the most common way to switch to the singlet form is irradiation by visible photon (red at 635 nm), allowing reaching the 1o2 (1σg+) state or infrared ones at 1270 nm, leading to the 1o2 (1∆g) state. the average lifetime of singlet oxygen is 1-50 µs in aqueous systems[30]. in the gas phase, both singlet states may relax towards the triplet state 3o2 (3σg-) by two different mechanisms. the 1o2 (1∆g) state may use collisions with other molecules m according to: 1o2(1∆g) + n m → 3o2 (3σg-) + n m* + heat the notation m* means that, after the collision, the molecules m are left in a rotating state of higher energy. the intrinsic electronic spin has thus been transformed into an extrinsic spin (rotations), ensuring spin-conservation. the generated heat corresponds to the energy difference ∆e = 153 zj existing between the first excited state and the ground state. the following relationship allows estimating the expected temperature increase ∆t after dissipation of an energy ∆w into heat: here, we have used the equipartition theorem of statistical physics ∆w = ½kb×∆t×σ(df ), where kb is boltzmann’s constant and σ(df ), the total number of degrees of freedom concerned by the relaxation process. now, for a non-linear molecule made of n atoms, one may expect three degrees for the translation of the center of mass, three degrees for the rotation around the center of mass, and 2×(3n – 6) degrees for the normal modes of 29singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy vibration. factor 2 considers that each vibration mode has two degrees, one associated with the position and the second one to speed. each non-linear molecule will then contribute 6×½kb + (3n-6)×(½kb + ½kb) = ½kb×(6n 6). for a linear molecule, the rotation around the molecular axis cannot be used to store energy and thus corresponds to a vibration mode. each linear molecule will then contribute to ½kb×(6n -5). it then follows that if nl stands for the number of linear molecules and nc for the number of non-linear ones and if n is the total number of atoms, we have σ(df) = 6×(n – nc) – 5×nl. water being the most abundant molecule in a cell, we have n = 3×nw, nl = 0 and nc = nw, leading to ∆t(k) = 12×∆w(zj)/nw. consequently, in order reaching a temperature t = 310 k (or 37°c) from a temperature t = 288 k (or 15°c, the average temperature of the earth), the total number of concerned water molecules involved in the relaxation of one 1o2(1∆g) molecule characterized by ∆w = 153 zj is estimated as nw = 1849/(310 – 288) = 84 molecules. furthermore, the average volume v of a molecule having a molecular weight m (da) in a liquid of density ρ (g·cm-3), assuming a random packing efficiency ξ = 0.6366, is given by: for water (m = 18 da, ρ ≈ 1 g·cm-3, i.e. v = 19 å3), the thermal relaxation volume around one 1o2(1∆g) molecule is about 19×84 = 1598 å3, corresponding to a sphere of radius r = 7.3 å. as the average diameter of isolated water is a molecule is d = (19×6/π)⅓ ≈ 3.3 å, this corresponds to 2 shells of water molecules. this shows how we may relate a biological number, the average body temperature, to a molecular quantum process relaxation of 1o2(1∆g) towards the 3o2 (3σg-) ground state through heating, using well-known physical laws. besides this thermal relaxation process involving water molecules, there is a radiative mechanism involving infrared photons: 1o2(1∆g) → 3o2 (3σg-) + 3γir here, nature uses the fact that a photon is a particle of spin s = 1, allowing photonic relaxation with the emission of a photon spinning in one direction (ms = +1), leaving the dioxygen molecule in its ground state with the two electrons spinning in the same direction opposite to that of the photon (ms = –1/2 – ½ = –1) to conserve the initial null spin (0 = 1 – 1). heisenberg’s uncertainty relationship drives the timescale associated with such photonic relaxation. it allows relating the intrinsic lifetime τ of the excited state having energy ∆e to the reduced planck’s constant ħ ≈ 106 zj·fs: ∆e×τ ≈ ħ. consequently, with ∆e = 153 zj, it comes that τ ≈ 106/153 = 0.7 fs. this lifetime should be compared with the average rotation time τc of a water molecule at a given temperature, needed for allowing thermal non-radiative relaxation. stokes-einstein relationship gives this correlation time that depends on absolute temperature t, viscosity η and molecular volume v: τc = η×v/(kb×t), i.e. τc(ps) = 72.4×η(mpa·s)×v(å3)/t(k)[31]. for liquid water (v = 19 å3) at t = 310 k, we have η = 0.69 mpa·s, meaning that τc ≈ 3 ps. this shows that for one molecule undergoing thermal relaxation from the excited state to the ground state, about 5,000 molecules undergo photonic relaxation in the near-ir part of the electromagnetic spectrum. as the second excited state 1o2 (1σg+) is much higher in energy (∆e = 259 zj), its thermal relaxation towards the ground state will mobilize a much more number of water molecules, typically nw = 3128/(310 – 288) = 142 molecules. this forms a relaxation volume of 2,702 å3, corresponding to a sphere of radius r = 8.6 å, i.e., nearly 3 shells of water molecules around one 1o2 (1σg+) molecule. the average lifetime of this second excited state being shorter, τ ≈ 106/259 = 0.4 fs, about 7,300 molecules undergo photonic relaxation as a characteristic, red-colored visible light when one relaxes using the thermal channel. formation of singlet dioxygen singlet dioxygen cannot be formed by direct optical excitation of triplet dioxygen by infrared or red photons. accordingly, from fermi’s golden rule and group theory, such transitions are both spin-forbidden and orbital-forbidden. this is the reason why a photosensitizer should be used[30]. another completely different way of forming singlet dioxygen is to use a chemical reaction releasing a large amount of entropy. reasons for using entropy and not gibbs’ free energies have been analyzed elsewhere[9-11]. shortly, a single criterion of spontaneous evolution in nature is that entropy of the universe should always increase in any kind of transformation, whether chemical or biological. in other words, biological systems are fully compliant with the second law of thermodynamics with no need to introduce alternate notions such as negentropy, for instance. the observed complexity of biological systems is a consequence of large entropy f lux towards the universe, in compliance with the laws of irreversible, far from equilibrium, thermodynamics. from a technical viewpoint to each 30 marc henry et al. transformation of matter corresponds to a change in the standard irreversibility potential ∆πi° (t = 25°c, p = 1 atm) that cannot be negative. rules for computing an irreversibility potential πi° for each substance involved in the transformation have been presented elsewhere[10]. for biological systems, such standard irreversibility potentials are transformed to π’i° values considering that biology occurs in water (ph = 7) in the presence of ionic species (ionic strength i ≈ 250 mm). we have used generalized legendre’s transformation, a mathematically straightforward procedure[32]. all the computational details are available as supplementary information (si). irreversibility potentials (irps) are useful for comparing two substances according to their entropy content relative to the whole universe. basically, substances that have strongly negative irps are reducing substances. they present a spontaneous tendency to be irreversibly transformed through oxidation into substances having a strongly positive irp. one may thus notice that singlet dioxygen has a significantly more negative irp than triplet dioxygen. this automatically means that combustion with 1o2 leads to larger entropy production than combustion with 3o2. moreover, the burning of a combustible substance existing in a singlet spin-state with 1o2 is spin-allowed, whereas its combustion with 3o2 is spin-forbidden, needing the presence of a catalyst. in biology, singlet dioxygen plays a key role in photosynthesis. generation of 1o2 from water molecule has been widely reported during photosynthesis in plants, using energy from the sunlight. photosensitizers are generally necessary for producing singlet through light absorption. this is particularly true in plants where 1o2 is generated by chlorophyll and other cofactors of the photosystem[33]. in plants exposed to excess light, the increased production of singlet dioxygen can result in cell death[34]. various substances such as quinones, carotenoids, and tocopherols contained in chloroplasts quench singlet dioxygen and protect against its toxic effects. in humans, transportation of the dioxygen molecule to the target cell occurs through the triplet state. it is used in the mitochondria together with electrons and protons at the level of the complex iv of the mitochondria, producing water as a non-toxic waste together with some heat and biomolecules with very negative irps such as nadh (πi’° = -6.23829 zj·k-1) or nadph (πi’° = -1.32422 zj·k-1) for instance. it is worth noticing the large difference in irreversibility potentials between nadh and nadph. however, when considering oxidized forms nad⊕ (πi’° = -5.89863 zj·k-1) and nadp⊕ (πi’° = -0.98399 zj·k-1), we get almost the same standard oxidation potential: nad⊕ + h⊕ + 2 e⊝ = nadh ⟹ ∆πi’° = -0.34534 zj·k-1 ⟺ e’° = -321 mv nadp⊕ + h⊕ + 2 e⊝ = nadph ⟹ ∆πi’° = -0.34534 zj·k1 ⟺ e’° = -321 mv therefore, irps are much more useful for biological thinking than oxidation potentials. accordingly, nadh appears in catabolism for glycolysis, for β-oxidation, by pyruvate dehydrogenase (pdh), by tricarboxylic acid cycle (tca), in the electron transport chain (etc), and by nicotinamide nucleotide transhydrogenase (nnt) (35). this simply stems from its negative irp much lower than any of the non-metallic species. accordingly, biosynthesis of nadh needs absorption of a large positive entropy flux, such as the one generated at the level of the tca or the etc. in deep contrast, nadph is used in anabolism for performing reductive biosynthesis, in the pentose phosphate pathway (ppp), by isocitrate dehydrogenase (idp), by the malic enzyme (me), by aldehyde dehydrogenase (aldh), and by nadph-oxidase (36). owing to its much lower irp, biosynthesis of nadph needs a much smaller positive entropy flux than the one required for nadh. it follows that nadph is more able to drive biosynthetic pathways and is also involved in redox sensing and as a substrate of nadph oxidases for generating reactive oxygen species. so, we have here a good example of two remarkably similar reductants having quite contrasted entropy content, explaining the observed strong compartmentalization of redox functions in a living cell. it is also worth noticing that at the mitochondrion level, there is the orientation of the positive entropy flux towards the synthesis of biomolecules displaying large positive irps. such molecules play the role of “canned entropy” for driving molecular machines, just like batteries act as “canned electricity” for driving electrical motors. the best candidates are polyphosphates such as adenosine diphosphate (adp with πi’° = +7.93486 zj·k1) or adenosine triphosphate (atp with πi’° = +12.76803 zj·k-1). accordingly, the positive entropy flux for making atp from adp appears too small relative to their entropy content: adp + pi = atp + h2o ⟹ ∆πi’° = -0.2007 zj·k-1 ⟺ pk = 6.3 at a temperature t = 298.15 k, such a pk-value corresponds to a free energy change ∆g’ = +36.0 kj·mol-1 = 60 zj. conversely, this is just the amount of heat that would be generated upon the hydrolysis of atp into adp. here, it is worth using our relationship ∆t(k) ≈ 12×w(zj)/nw allowing converting an amount of heat w into a temperature change ∆t after spreading such heat 31singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy among nw water molecules. choosing ∆t = 1 k for w = 60 zj leads to nw = 720 or rw = 1.66×nw⅓ = 14.9 å, in terms of radius of the hydration shell surrounding the spatial location of the reaction. now, on average, four shells of water molecules surround each biomolecule in a living cell[37]. this translates into a radius of hydration rh = 4×3.3 = 13.2 å, a value close to the radius of conversion of entropy into heat rw. as explained in previous papers (9,10), the main role of atp in a living cell is not to provide energy but rather to play the role of a powerful hydrotrope[35]. atp has thus the crucial double role of being both an entropy sink and avoids by its presence the irreversible coagulation of proteins. there is obviously not enough entropy liberated through hydrolysis of a single atp molecule to convert triplet dioxygen into singlet dioxygen. from the relative irps of 1o2 and 3o2 and with ∆πi’° = 0.2007 zj·k-1 for atp hydrolysis, the formation of singlet dioxygen from triplet dioxygen would require the simultaneous hydrolysis of at least n(atp) = sup(0.53256/0.2007) = 3 molecules. as this is very unlikely on the statistical ground or as it would involve a huge protein, it may seem that singlet dioxygen would have a negligible role to play in a living cell favoring triplet dioxygen. this is, of course, the conventional biological thinking putting the exclusive focus on the ground state 3o2 (3σg-) with very few references to the first excited state 1o2(1∆g). owing to its quite negative irp, very few substances can create singlet dioxygen as a waste. among them, we have, for instance, ozone 1o3. it is easy checking that water has entropy high enough to resist oxidation into hydrogen peroxide by ozone: 1o3 + 1h2o = 1o2 + 1h2o2 ∆πi’° = -0.22868 zj·k-1 ⟺ pk = 7.2 this is not the case of hydrogen peroxide that is easily reduced into the water by ozone with singlet dioxygen as a by-product: 1o3 + 1h2o2 = 2 1o2 + 1h2o ∆πi’° = +0.29663 zj·k-1 ⟺ pk = -9.3 suppose the reaction leading to triplet dioxygen is much more favorable, it is, however, spin-forbidden, allowing singlet dioxygen to be the main kinetic product in the absence of a catalyst. the trouble is that if ozone is an important compound in the atmosphere owing to its irradiation by the sun, its occurrence in a living cell is not so obvious. singlet dioxygen may also be produced in a living cell subjected to an oxidative stress upon annihilation of oxygen-based radicals: 2o2•⊝ + 2oh• = 1o2 + 1oh⊝ ∆πi’° = +0.80038 zj·k-1 ⟺ pk = -25 2ho2• + 2ho2• = 1o2 + 1h2o2 ∆πi’° = +0.03602 zj·k-1 ⟺ pk = -1.1 however, such reactions are in competition with formation of triplet dioxygen and a much larger entropy release: 2o2•⊝ + 2oh• = 3o2 + 1oh⊝ ∆πi’° = +1.33282 zj·k-1 ⟺ pk = -42 2ho2• + 2ho2• = 3o2 + 1h2o2 ∆πi’° = 0.56846 zj·k-1 ⟺ pk = -18 catalysis of this last reaction in vivo involves the well-studied enzyme superoxide dismutase (sod) that is not affected by the presence of singlet oxygen[35]. as triplet dioxygen has higher irreversibility potential than singlet dioxygen, it will always play the role of the thermodynamically favored species. this means that the production of singlet dioxygen using the annihilation of inorganic radicals is, as a rule, quite difficult to control. this is no more the case by using singlet species, as even if the formation of triplet dioxygen is still more favorable, it becomes slow as the reaction is now spinforbidden. here is a good example that readily occurs in neutrophils, for instance: 1clo⊝ + 1clo⊝ = 1o2 + 2 1cl⊝ ∆πi’° = +0.39840 zj·k-1 ⟺ pk = -12.5 however, such a reaction requires a high concentration of the rather unstable hypochlorous ion. this is the reason for the extensive use of phagosomes by neutrophils. under diluted conditions, there is the possibility of using hydrogen peroxide, forming as by-products water and chloride ions: 1h2o2 + 1clo⊝ = 1o2 + 1cl⊝ + 1h2o ∆πi’° = +0.46186 zj·k-1 ⟺ pk = -14.5 it is worth noting that use of the hypochlorous ion is mandatory, as the entropy difference between the chlorous and hypochlorous species is not high enough for allowing the production of singlet dioxygen: 1h2o2 + 1clo3⊝ = 1o2 + 1clo2⊝ + 1h2o ∆πi’° = -0.09802 zj·k-1 ⟺ pk = 3.1 32 marc henry et al. trapping of singlet dioxygen singlet dioxygen could be very harmful to normal cells. the first reason stems from the fact that there is no spin restriction for reacting with other singlet molecules. a second reason is that it has a quite negative irp. it is worth recalling here its lewis’ structure: :ö:⊝—:o:⊕ ↔ ⊕:o: —:ö:⊝ a most prominent feature is the formal positive charge on one of the two oxygen atoms, meaning that singlet dioxygen has a high affinity for any electron-rich centers. among them, carbon atoms engaged in a c=c double bond are sites for preferential attack owing to their complementary dynamic lewis’ structure: >c=c< ↔ >c:⊝—c⊕< ↔ >⊕c —c:⊝< the reaction of singlet dioxygen with c=c double bonds often leads to the formation of endoperoxides (figure 1). for a single c=c double bond, the resulting endoperoxides have a quite strained four-membered ring, leading to a highly unstable addition compound. this is not the case when oxidation leads to a rather stable sixmembered ring, a situation encountered in any molecule containing at least two conjugated c=c double bonds. singlet dioxygen may react rapidly with other singlet molecules forming species such as hydroxyl radical (•oh), hydrogen peroxide (h2o2) or superoxide radical (•o2−). these reactive oxygen species will oxidize dna (mutation and dna breaks), proteins and lipids. here is a list of favorable reactions with ubiquinol (h2coq10), ascorbic acid (vitamin c, asch2), reduced cytochrome-c, dihydrolipoic acid (dhla), reduced glutathione (gsh) and free iron (ii): 1o2 + 1h2coq10 = 1h2o2 + 1coq10 ∆πi’° = +0.850 zj·k-1 ⟺ pk = -27 1o2 + 1asch2 = 2 2ho• + 1dha ∆πi’° = +0.680 zj·k-1 ⟺ pk = -21 1o2 + 1asch2 = 1h2o2 + 1dha ∆πi’° = +1.719 zj·k-1 ⟺ pk = -54 1o2 + cytc-1fe2⊕ = 2o2•⊝ + cytc-2fe3⊕ ∆πi’° = +0.326 zj·k-1 ⟺ pk = -10 1o2 + 1dhla = 2 2ho• + 1ala ∆πi’° = +0.195 zj·k-1 ⟺ pk = -6 1o2 + 2 1gsh = 2 2ho• + 1gssg ∆πi’° = +0.173 zj·k-1 ⟺ pk = -5 1o2 + fe2⊕ + = 2o2•⊝ + 2fe3⊕ ∆πi’° = +0.049 zj·k-1 ⟺ pk = -2 it is worth noticing the mandatory generation of hydrogen peroxide with ubiquinol, as there is, in this case, not enough entropy for generating two hydroxyl radicals: 1o2 + 1h2coq10 = 2 2ho• + 1coq10 ∆πi’° = -0.190 zj·k-1 ⟺ pk = 6 singlet dioxygen, ozone, and radiation therapy the above reactions explain why singlet oxygen (1o2) is widely used in photodynamic therapy of cancer.  during photodynamic therapy, photosensitizers excited by light react with ground state oxygen  3o2, which leads to the generation of this major cytotoxic agent. after generation, singlet dioxygen oxidizes all the molecules responsible for the redox homeostasis of the cell rapidly, killing the surrounding tissues and cells[38]. it has been more than 60 years since the discovery of the  oxygen effect  that empirically demonstrates the direct association between cell radiosensitivity and oxygen tension, important parameters in radiotherapy. however, no real understanding of the mechanisms underlying this principle tenet of radiobiology is yet available[39]. figure 1. affinity of singlet dioxygen for conjugated double bonds leading to the formation of an endoperoxide bridge. endoperoxides may also be formed from triplet dioxygen in the presence of a photosensitizer. one may speak of endoperoxides as “canned singlet dioxygen” owing to their ability to release 1o2 upon heating. 33singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy photons react with water to form free radicals, including singlet oxygen. singlet oxygen interacts with the mitochondria to cause the permeabilization of the mitochondrial outer membrane, leading to the cytosolic release of pro-apoptotic proteins and to the impairment of the bioenergetic functions of mitochondria and resulting apoptosis[40]. about twenty years ago, it was shown by wentworth et al. that antibodies catalyze the generation of ozone by a water oxidation pathway[41]. it was first postulated that dihydrogen trioxide [h2o3] was a key intermediate. however the direct formation of this intermediate is not thermodynamically favorable: 1o2 + 1h2o = 1h2o3 ∆πi’° = -0.509 zj·k-1 ⟺ pk = 16 it is worth noticing that adding another singlet dioxygen cannot oxidize water into ozone o3 according to: 2 1o2 + 1h2o = 1o3 + 1h2o2 ∆πi’° = -0.297 zj·k-1 ⟺ pk = 9 however, upon generation of at least three singlet dioxygen molecules, water oxidation becomes possible with the release of triplet dioxygen as waste: 3 1o2 + 1h2o = 1o3 + 1h2o2 + 3o2(aq) ∆πi’° = +0.236 zj·k-1 ⟺ pk = -7 however, such a reaction is spin-forbidden. hence, we propose this final scheme, which is spin-allowed: 4 1o2 + 1h2o = 1o3 + 1h2o2 + 2 3o2(aq) ∆πi’° = +0.768 zj·k-1 ⟺ pk = -24 owing to the liberation of ozone, any tumor would be burnt with the generation of only gases as wastes. moreover, one of the reactants is the water molecule, the most abundant chemical species in a living cell. the crucial point is that water no more acts here as a solvent whose activity is equal to one, owing to its huge abundance. it is a well-established fact that the status of water in tumors is quite different from that of water in a normal cell. in thermodynamics language, this translates into the fact that water activity cannot be the same in a tumor and in a normal cell[42–46]. as the above equilibrium is sensitive to water activity, one may expect different yields of ozone according to the status of water in the cell exposed to radiations able to generate singlet dioxygen in the large amount. in other words, there is a possibility of targeting any 1o2-treatment towards cancer cells, leaving normal cells relatively unaffected. the radiation therapist knows that soft tumors like lymphomas and seminoma are more sensitive to radiation than harder ones. accordingly, doses needed to eradicate seminoma and lymphoma is smaller, and the treatment is shorter than the treatment of squamous cell carcinoma or adenocarcinoma. the earlier sign of tumor response during radiation therapy is the change of consistency (harshness) of the tumor. this is in line with a change in the activity of water (see above). conclusion it is possible that ionizing radiation such as produced by modern linear accelerators act at the cellular level by the mean of thermal photons. these photons will induce, in turn, the synthesis of singlet dioxygen. in such a scheme of thought, high-energy photons are just a way to deliver thermal photons to deep-seated tumors. infrared photons are not powerful enough to reach these lesions. absorption of over 90% of the dose occurs in the first cm[47]. cytotoxic chemotherapy activates the concentration of free radicals such as the ones induced by singlet dioxygen or radiation therapy. this is evident by the elevation of lipid peroxidation products; the reduction in plasma levels of antioxidants such as vitamin e, vitamin c, and β-carotene; and the marked reduction of tissue glutathione levels that occurs during chemotherapy. those agents that generate high levels of ros include the anthracyclines (e.g., doxorubicin, epirubicin, and daunorubicin), alkylating agents, platinum coordination complexes (e.g., cisplatin, carboplatin, and oxaliplatin), epipodophyllotoxins (e.g., etoposide and teniposide), and the camptothecins (e.g., topotecan and irinotecan) [48]. one other option to improve the efficacy of infrared photons is to activate a photosensitizer such as methylene blue[49]. moreover, an often-overlooked fact is that water activity is higher in cancer cells than in normal cells. as demonstrated just above this could mean that in a cancer cell, singlet dioxygen may react with water yielding ozone, a powerful oxidant. such a possibility opens the road to a non-linear hormetic behavior of singlet dioxygen. typically, we expect a harmful increase of oxidative stress at low concentration, a healing effect against cancer at moderate concentration (due to selective insitu formation of ozone) and a well-documented cytotoxic effect towards any kind of cell at high concentration. future experimental research is needed to confirm 34 marc henry et al. or reject such a putative behavior suggested by available thermodynamic data. funding we acknowledge the help of the “fondation guérir du cancer”. references 1. feeund 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therapy: from basic mechanisms to clinical applications. photodiagnosis photodyn. ther. 2005; 2: 175–191. annex table 1 gives irreversibility potentials (irps or πi’°) values in ascending order for species discussed in this work. as the whole universe is by definition a closed system, this allows, in compliance with the second law, to identify three kinds of processes in nature: i) irreversible processes that are spontaneous being such that ∆π’i° > 0. ii) fully reversible processes are characterizing equilibrium situations as ∆π’i° = 0. iii) non-spontaneous processes, such that ∆π’i° < 0, thus requiring to be coupled with another spontaneous process characterized by ∆πi’° > -∆π’i° > 0. moreover, owing to their definition, irreversibility potentials changes may be related to equilibrium constants k, or to standard oxidation potentials e’°, using the following conversion relationships (t = 298.15 k): conversion into standard oxidant potentials are for transformations involving electrons and requires the knowledge of the number of electrons n that should be added to an oxidant to transform such species into its conjugated reduced form. 36 marc henry et al. let us consider for instance the two-electrons reduction of protons into dihydrogen (2 h⊕ + 2 e⊝ = h2) or the four-electrons reduction of dioxygen into water (3o2 + 4 h⊕ + 4 e⊝ = 2 h2o). from table 1, we evaluate that: this allows classifying dihydrogen as a reductant (e’° < 0) and dihydrogen as an oxidant (e’° > 0). but, one may also consider reacting dihydrogen with dioxygen in order to produce water (2 h2 + o2 = 2 h2o). electrons being eliminated, the irreversibility potential change is now expressed as equilibrium constant k: pk = -31.456 × [2 × (0.8667 + 0.55218) + 0.09135) = -92.1 as at t = 298.15k, we have ∆g’°(kj·mol-1) = rt·ln(10)×pk = 5.708×pk, the highly positive ∆πi’° = 2.92943 zj·k-1 variation responsible to the quite negative pk, corresponds to a large negative change of the so-called “gibbs’ free energy,” viz. ∆g’° = -526 kj·mol-1. with such a pk value, one may conclude that water synthesis is a spontaneous quasi-quantitative process. the reason for such a huge release of entropy is obvious after noticing that on the right of the equation, a substance with a large positive irreversibility potential appears, whereas, on the left, two substances with negative irreversibility potentials disappear. leading the left column, we find species with large negative potentials (reductants), thus providing the largest entropy production upon their transformation into species located on the right column (oxidized forms). consequently, such species are to be considered as useful low entropy “food.” reciprocally, species at the bottom of the right column are generally end products in a chemical transformation, owing to their high entropy content. consequently, they may be qualified as “waste” that will be eliminated in order to maintain the largest entropy gradient in the living organism. another crucial point is that we find in both columns radical species holding unpaired electrons. this means that some radicals should be considered as food and others as waste. moreover, some radicals may be strong reductants, such as atomic hydrogen: h⊕ + e⊝ = h•(aq) ⟹ ∆πi’° = -1.46898 zj·k-1 ⟺ e’° = -2.31 v on the other hand, the hydroxyl radical ho• behaves as a strong oxidant: ho• + h⊕ + e⊝ = h2o ⟹ ∆πi’° = +1.24046 zj·k-1 ⟺ e’° = +2.73 v table 1. irreversibility potentials πi’° and corresponding standard free energies of formation ∆fg’° for chemical species considered in this work. values computed at t = 398.15 k, ph = 7 for an ionic strength i = 0.25 m. species πi’0/zj·k-1 ∆fg’°/zj ∆fg’°/kj·mol-1 coq10 -25.28740 7539 4540.36 coq10h2 -25.22108 7520 4528.45 dhla -1.77480 529 318.67 h•(aq) -1.46898 438 263.75 ala -1.45613 434 261.45 o3 -0.96965 289 174.10 1o2 -0.62378 186 112.00 h2(aq) -0.55211 165 99.13 1o2(g) -0.52665 157 94.56 h2(g) -0.45409 135 81.53 ho• -0.37352 111 67.07 h2o3 (c2-symmetry) -0.26618 79 47.79 ho2•/o2•⊝ -0.18370 55 32.98 3o2(aq) -0.09134 27 16.40 3o2(g) -0.00000 0 0.00 cytc-[fe3⊕] 0.04059 -12 -7.29 [clo3]⊝ 0.04879 -15 -8.76 fe3⊕(aq) 0.06676 -20 -11.99 cytc-[fe3⊕] 0.15455 -46 -27.75 hocl/clo⊝ 0.22429 -67 -40.27 h2o2 0.29239 -87 -52.50 fe2⊕(aq) 0.45747 -136 -82.14 cl⊝ 0.73538 -219 -132.04 h2o 0.86694 -258 -155.66 gsh 1.52051 -453 -273.01 asch2 3.03142 -904 -544.29 gssg 3.33710 -995 -599.18 dha 3.83413 -1143 -688.42 pi 5.90080 -1759 -1059.49 nadh 6.10589 -1820 -1096.31 nad⊕ 6.44221 -1921 -1156.70 adp 7.93486 -2366 -1424.71 nadph 11.08026 -3304 -1989.46 nadp⊕ 11.40756 -3401 -2048.23 atp 12.76803 -3807 -2292.50 substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 5(1) suppl.: 19-28, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1275 citation: a. ottaviani (2021) the opposite poles of a debate lapides figurati and the accademia dei lincei. substantia 5(1) suppl.: 19-28. doi: 10.36253/substantia-1275 copyright: © 2021 a. ottaviani. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. the opposite poles of a debate lapides figurati and the accademia dei lincei1 alessandro ottaviani università di cagliari, dipartimento di pedagogia, psicologia, filosofia, via is mirrionis 1, 09123 cagliari e-mail: alessandro.ottaviani@unica.it abstract. the essay analyses the research carried out by some members of the accademia dei lincei on lapides figurati, namely by fabio colonna on animal fossils, and by federico cesi and francesco stelluti on plant fossils; the aim is to show the role played by the accademia dei lincei in establishing during the second half of the seventeenth century the opposite poles of the debate on the lapides figurati, on the one hand as chronological indices of a past world and, on the other, as sudden outcome of the vis vegetativa. keywords: accademia dei lincei, fabio colonna, federico cesi, francesco stelluti, fossils, lapides figurati, rationes seminales. 1. fabio colonna on fossils1 the research of fabio colonna (1567-1640) is fairly well known among historians of science, particularly in the fields of geology and palaeontology.2 given the links with niels steensen (1638-1686) and agostino scilla (1629-1700), these researches have concentrated on the 1616 dissertation on glossopetrae,3 at the expense of several interesting observations already ventilated in 1606. the latter deserve analysis because colonna there sets out the convictions at which he had already arrived on the basis of his initial inquiries, and which were to nourish the more accurate analyses contained ten years later in the dissertation. this early stage is represented in the long 1 english translation by peter mason. 2 on colonna and ‘palaeontological’ themes cf. n. morello, “fabio colonna e gli inizi della paleontologia”, physis, 1977, 19: 247-278; ead., la nascita della paleontologia nel seicento: colonna, stenone e scilla, milano, franco angeli, 1979; a. ottaviani, o. trabucco, theatrum naturae. la ricerca naturalistica tra erudizione e nuova scienza nell’italia del primo seicento, napoli, la città del sole, 2007; a. ottaviani, “methodus philologica e naturales quaestiones fra l’accademia dei lincei e galileo galilei” galilaeana. studies in renaissance and early modern science, 2017, 14, 2017: 39-59; id., “fra diluvio noaico e fuochi sotterranei. note sulla fortuna sei-settecentesca di fabio colonna” giornale critico della filosofia italiana, 2017, 96: 272-303. 3 cf f. colonna, de glossopetris dissertatio, in id., purpura. hoc est de purpura ab animali testaceo fusa, e hoc ipso animali, aliisque rarioribus testaceis quibusdam…, romae, apud jacobum mascardum, 1616, pp. 31-39. 20 alessandro ottaviani twenty-first chapter of the observationes, included as an appendix in the ekphrasis published in rome by guglielmo facciotti. the opening of the chapter may confuse the reader: after a series of observations on cartilaginous fish, gastropods, marine invertebrates, mammals, reptiles and insects, colonna unexpectedly introduces the bare outline of a theory on the origin of stones. without preamble, in a style reminiscent of the de lapidibus of theophrastus, colonna concisely indicates the material causes (water and earth) and efficient causes (heat and cold),4 and the effect of their various combinations. however, he continues, there are denser and purer concretions materially caused by those vapours that are drawn upwards by heat before freezing immediately in the atmosphere.5 colonna compares the process to an experience familiar to all: the concretions of the solfatara of pozzuoli, which are obtained in a similar way in chemical laboratories,6 or the stony incrustations produced by fumes. they seem to support the hypothesis that stones have a generic vegetal nature, and that their increase in size should be understood as a genuine process of growth.7 yet that would be a hasty conclusion, 4 f. colonna, de aquatilibus aliisque animalibus quibusdam libellus in id., minus cognitarum stirpium ac etiam rariorum nostro coelo orientium stirpium ἔκφρασις..., romae, apud guilielmum facciottum, 1606, p. xliii: «adeo duo haec elementa cohaerent, terra scilicet et aqua, ut ex eorum quotidiana ad invicem commixtione maxime lapides generari perpetuo pro certo compertum habeamus. nec alia est lapidis concretio, nisi terrae pars tenuior et purior aquae commixta, vel impurior aut terrestrior aqua, a solis calore exucta humiditatis parte ac etiam ab ambiente terra coire incipiens, frigore densata reliqua, sicciore deinde utrisque concurrentibus longo tempore intercedente in totum soliditatis naturam adepta, cum antea terreus liquor, vel aqueus lentus ac glutinosus esset. terra quidem solis calore concocta aquis madefacta lentescit, nec minus quam arte effecta calx vel gypsum aqua mixtum liquescit ac facile coit, et exucta aquae parte, ab illa ignea natura per coctionem acquisita, reliqua ab extranea solis et frigoris vi exiccata, lapidis naturam adipiscitur. densior vero, durior, aut fragilior lapis erit, si purior vel impurior, tenuior vel crassior terra immutata erit, magis vel minus solis ardoribus excocta, et deinde maioribus, vel minoribus frigoribus densata, longiore tempore perfecta». 5 ivi, p. xliv: «est et alia densior puriorque lapidum concretio, quae non ab ipsa terra vel aqua ad invicem imbribus commixtis efficitur ut superior, sed ab eorum vaporibus sursum elatis atque densatis, ut sunt lapides e caelo cum fulgure decidentes, durissimi atque politi». 6 ibidem: «verum, ut exemplum afferamus quod oculis subiici et ex eo coniici possit modus elevationis vaporis et congelationis, proponemus sulphureas evaporationes puteolanas,quae nobis aqueae videntur, attamen circa saxa specus e quo exeunt, sulphur adhaeret salis modo concretum, sed et ipsum artificiale sulphur: ex terra lapidibus calore vaporantibus, veluti per alembicum ex fornace fluit humor, qui sulphur est, sic et alia mineralia». 7 ibidem: «sed et fuligo in caminis nonne, praeter illam spongiosam aut lanosam, in superficie alia subest crustosa dura? et nihil aliud est nisi lignorum humiditas, tamen terream adeo magnam secum habet naturam, ac etiam lentorem quendam, ut in ligneis caminis observatur veluti pice infectis splendida vitrea crusta intectis fumo illam efferente. ex huiuscemodi vero concretione facta lapides quidem vegetabilem quandam naturam habere conspiciuntur atque crescere illos quis putare posset». colonna goes on to explain, because the increase in size of a stone can come about by the mere successive accumulation of parts according to two different modalities: augmentation from an external source or from the matrix of the stone.8 the former resembles the way that shells grow through the hardening of the secretion that the animal periodically deposits on the edge of the shell; the latter is like the way in which nails and teeth grow from their matrix.9 there is no need here to follow the successive observations. in each case the focus is confined to the data observed, rendering virtually impossible any hypothesis on colonna’s sources. we know, however, that he owed his training to frequent direct contact with the recognised expert apothecary ferrante imperato (15501631). in 1599 imperato had published the results of his researches, a large part of which was dedicated to the study of soils, metals, stones and gems. he offered several modalities for their genesis, some of them corresponding to those indicated by colonna.10 master and pupil were not in complete agreement, however: ferrante imperato discussed not only the successive augmentation but also the truly vegetal property of stones,11 a thesis from which, as we have seen, colonna 8 ibidem: «verum augmentum lapidi venit additione superveniente, ambiente vel, ut in his, ab imo succurrente, quare, veluti ab radice, alimentum et augmentum habere videtur». 9 ibidem: «exemplum in dentibus et unguibus. de his quae per additionem crescunt, ut in testaceis maritimis et terrestris cochleis, quibus non centrum, sed circumferentia ampliatur. signa rugarum testantur hoc ipsaque extremitas orae veluti cartilaginea, duritiem adhuc non habens, ex ambiente humore viscido ipsius animalis generata». 10 f. imperato, dell’historia naturale..., napoli, per costantino vitale, 1599, p. 587: «vien dunque in considerazione se le gemme da principio si apprendano nella propria grandezza come gli parpuglioni si concreano dentro delle lor cruste chiamate da alcuni aurelia, o se pigliano aumento da piccolo principio, come le creature crescono nel ventre materno e le foglie e i frutti nelle piante, o se crescono per semplice aggiunte fatte dalle radici come il capello e l’ungia, percioche si vede ciascuna delle dette manier haver propri argomenti [...]»; on imperato cf. b. accordi, “ferrante imperato (napoli 1550-1625) e il suo contributo alla storia della geologia”, geologica romana 1981, 20: 43-56; e. stendardo, ferrante imperato. collezionismo e studio della natura a napoli tra cinque e seicento, napoli, accademia pontaniana, 2001. 11 ivi, pp. 460-61, 659, 689: «e se noi consideriamo il modo del movimento et il corso delle fibre che dalle radici della marchesite si distendono, vederemo manifestamente in esse la virtù vegetale non dissimile a gli altri vegetali [...]. dall’historia del lyncurio più che da alcuna altra delle pietre narrate possiamo argomentare la virtù vegetale nella natura delle pietre qual molti hanno negato come cosa da quelle aliena; ma che la vegetazione che propriamente intendiamo essere l’accrescimento da principio interno non sia da questo geno aliena, possiamo riconoscere nelle parti dell’istessi animali percioche le corteccie degli animali marini che sono nel geno ostracino e non meno delle chiocciole terrene sono manifestamente di consistenza di pietra e si cuociono in calce non altrimenti che le pietre [...]. e si ha della sua vegetazione [del marmo] argomento molto evidente, percioche si sono ritrovate le cave già prima fatte nel successo di tempo rinchiuse dall’accrescimento della pietra». 21the opposite poles of a debate lapides figurati and the accademia dei lincei was to distance himself. this is the move that provides the implicit but decisive characterisation of the lithological framework that he uses to introduce the real subject of the chapter: the description of the substantial series of fossils found. this commences with an interesting note on changes in the process of lithification depending on environmental conditions. in this context colonna isolates two fundamental poles, that typical of arid, torrid zones, and that to be found in the cold, snowy and humid conditions of mountainous areas.12 colonna concentrates on the former, adducing a series of observations conducted in the environs of the small town of andria in apulia. inspection of this hilly terrain with its tuff slopes revealed, surprisingly, a large number of shells stuck together in a perfect state of preservation that permeated the entire area.13 as for the mountainous habitat, colonna made observations during his frequent journeys over the apennines, leading him to conclude that the fossils resulting from the process of putrefaction induced by humidity were of a very different kind, in which the lithic component had replaced the initial structure. colonna was aware that it was cases like this that had led to the thesis of chance formation (lusus naturae), but the analysis of the structure, inserted within a temporal framework that colonna vaguely defines as immemorial, suggests that they are the result of a slow decomposition of the organic remains and their successive lithification in parallel with the gradual transformation of the soil into a lithic state.14 colonna found confirmation of this 12 colonna, de aquatilibus aliisque animalibus quibusdam libellus, p. xlv: «in montibus nivosis quidem ob continuam humoris abundantiam aquarum et nivium terra magis excolatur et colligitur in alveis in quibus deinde densatur atque ob humoris frequentiam ligna, cornua, animalium ungues, dentes, ossa, testacea crustacea e similia putrefiunt, quamquam a frigore servari possent, quod minime evenit in locis calidioribus et maritimis ut observavimus. nam ibi ob humoris paucitatem et nimiam siccitatem potius servantur veluti condita ab aëre et humore tuta, quae ibi obruta inveniuntur». 13 ivi, pp. xlv-xlvi: «et ut experientia comprobari hoc videatur, nostram in hoc observationem afferemus, quam omnes veram fateri oportebit. apuliae tractus in quo civitas nobilis est andria dicta, tota collibus et clivis referta tophaceis, quibus ad aedificiorum ornamenta et structuras arte elaboratis utuntur, et per totam fere apuliam etiam similibus. quibus conspectis, nihil aliud quispiam esse dixerit, quam acervum sive potius massam testaceorum maritimorum terreno glutine confectam, atque varia cochlearum conchyliorum testaceorumque fragmenta ac etiam integra observabis nullam corruptionem adhuc temporis passa. nec in quolibet communi manuali lapide duo aut tria conspicies, sed totum ex illo confectum dices, ut vix altera fit terrae portio. nec etiam uni lapidi hoc accidere, sed toto colli, nec uni sed omnibus per totam illam regionem». 14 ivi, p. xlvi: «non autem hoc ita in apenninis montibus evenit, ut diximus, rebus humorem adversantibus et in terram putrescentibus. nam et ipsas maritimorum animalium testas putrescere ibi certum est, sicut ligna, ossa et terrestres etiam cocleas et alia de quibus dicemus. quae omnia non integra et veluti servata, sed penitus putrefacta in lapiin the exact correspondence of the delineatio of those forms transformed into stone to living creatures (see figs. 1 and 2). since that correspondence was not generic but specific, it could not be the result of a fortuitous generation.15 colonna continues with a series of descriptions of fossils, accurately drawing from them those analyses of comparative morphology required to distinguish clearly between figured stones and fossils. although he applied this morphological criterion with great precision –  in this respect he was perhaps unequalled in his own day and only later by steensen and martin lister – it had a weakness that he rapidly recognised. while ferrante imperato admitted the vegetal property, this was not incompatible with an explanation of fossil formation in terms of successive lithification. his son fran cesco imperato (1570 ca.post 1629) adopted a solution that was equally possible and more linear: in an opusculum published in 1610, he did not rule out the possibility that the fossils found in the mountains might have been transported there by the flood, but this could only be applicable to those scattered on the surface; for those buried more deeply it was necessary to appeal to the action of a vegetal faculty. he emphasised the potency of this faculty, whose mimetic property rendered morphological similarities far less conclusive: ‘so it is necessary to admit that it originates within the earth and then that it originates not fortuitously, but by an intrinsic vegetal capacity, while retaining the aspect of its counterparts’.16 the vegetabilis facultas also applied to the glossopetrae, contrary to those who ascribed their origin to the teeth of sharks. imperato considered that explanation impossible because of the quantity of glossopetrae found, which dem versa vel potium saxum, ut ad siliceam naturam parum accedere videantur ob duritiem, densitatem et levorem, cum illa in apulia servari videantur a tophacea concretione fragili admodum respecta saxorum. huius rei contemplationis causa fuerunt varia testacea aliaque naturalia intra saxorum moles inventa eadem saxorum natura, sed propria effigie servata. in quorum structura animadvertendum censuimus, illa non sic intra saxa naturam efformasse fortuito, ut aliqui putant, sed immemorabili tempore ab hominibus deiectis et casu terra obrutis, intra humum putrescentibus, illa sicut ambiens terra in lapidem deinde mutata elementorum perpetua vicissitudine, non minus ac excussores ac sculptores faciunt ex convexa cavam effigiem atque e contra convexam». 15 ibidem: «hoc testari videtur exacta admodum illorum delineatio atque cum ipsis naturalibus similitudo atque etiam copiosa eiusdem rei, eiusdem effigiei magnitudinis et structurae inventio. non enim, si casu an natura effingerentur, tam similes et exacte formarentur ut eadem prorsus res, non dicimus species, videatur». 16 cf. fr. imperato, de fossilibus opusculum..., neapoli, typis jo. dominici roncalioli, 1610, p. 69: «unde opus est fateri intra terram ortum ducere et successive, non casualiter, sed vegetabili facultate iniuncta originem ducere similium servata effigie»; on this opusculum see fr. imperato, de fossilibus opusculum (1610), (eds.: f. brattolo, f. coletta, m. pladini, c. pisaniello, c. porcaro, e. stendardo), napoli, accademia pontaniana, 2015. 22 alessandro ottaviani he regarded as incompatible with the number of sharks to have populated the seas since the beginning of the world (though he does not reveal the basis of his calculations): ‘indeed, on the island of malta we discover every day tooth-shaped stones, which are (mistakenly) taken to be the teeth of sharks; because they are extracted in such numbers all over the island that they exceed the number of teeth of all the cetaceans that ever lived from the origin of the world down to the present day’.17 colonna’s response to this implicit polemic was to concentrate on the glossopetrae, conducting not only the usual morphological comparisons but also subject17 ivi, pp. 69-70: «equidem in melita insula quotidie cernimus lapides quosdam dentium formas exprimentes, qui lamiarum dentes putantur (sed falso); nam ex qualibet dictae insulae parte adeo copiose eliciuntur, ut nec omnium cetorum dentes, qui ab origine mundi usque num vitam duxere, illorum numerum aequare possint». ing them to chemical analysis. he regarded the different products obtained from combustion of the fossil part and the lithic part as proof that the matrix and the tooth had different origins. it was an ingenious but inconclusive attempt, since the glossopetrae were derived from a ‘warm’ environment. the results obtained from lithic fossils extracted from mountainous and snow-covered terrains might be very different – an objection that was often raised in the subsequent debate.18 18 at least down to the beginning of the following century, for which cf. e. camerarius, dissertationes taurinenses epistolicae physico-medicae…, tubingae, impensis joh. georgii cottae, 1712, pp. 268-279, which reports on the chemical analyses by guillaume rivière: cf. j. gaudant. “une nouvelle contestation de la nature organique des fossiles: les dissertationes taurinenses epistolicae physico-medicae d’elias camerarius (1712) travaux du comité français d’histoire de la géologie, s. iii, 2012, 26: 235-240. figures 1 & 2. two plates from colonna, de aquatilibus aliisque animalibus quibusdam libellus (1606), representing shells of fossil and living animals. the fossil specimens are: fig. 1. pectunculus lapideus (upper left corner); concha lapidea recurva and concha lapidea nautili effigie (both on the second line from the bottom); concha lapidea gibbosa (lower left corner); fig. 2. buccinum lapideum laeve (upper left corner). colonna claims to have found them in the environs of andria, in puglia, and in the fortress of campochiaro, in molise. the other represented specimens are all from living animals. 23the opposite poles of a debate lapides figurati and the accademia dei lincei 2. cesi and stelluti on metallophytes in the years intervening between 1606 and 1616 fabio colonna was admitted to the accademia dei lincei. the de glossopetris dissertatio was an independent work, but became attached to the malacological treatise de purpura. the two works were then combined with the botanical work entitled minus cognitarum stirpium pars altera published in rome by giacomo mascardi,19 underlining the ascription to the lincei. it was during the preparation of the thesaurus mexicanus that the neapolitan, who was by now involved with the roman associates, first came into contact with prince federico cesi’s researches on lapides figurati. the occasion was the dispatch of a proof of the first pages of the tabulae phytosophicae that federico cesi (1585-1630) planned to include among the commentaries contained in the volume. in a letter of 10 november 1628 to francesco stelluti (1577-1653), who was acting as intermediary, colonna gave his first impression from naples after a hasty perusal of the tables: ‘the first sheet, the table of the whole thesaurus and the principle of division or rather distinction, gave me great pleasure. i am certain that the ingenuity of your excellency is such that i hope it will command universal admiration when parts of these things appear in print’.20 though time was pressing, colonna commented on some links in cesi’s remarkable chain and formulated some possible diagnoses of them. one of these concerned the zoolithophyton, the other the pianta metallo, which he thought might be identified with ferrante imperato’s marcasite (argento ramoso).21 in the latter case colonna was wide of the mark, but in a certain sense he was correct in assuming that the answer should be sought among the treasures of the apothecary. after all, cesi had visited imperato in 1604 in the course of his trip to naples and had observed there, as francesco stelluti recalled in 1630, a cytisus (a genus of plant) and some pieces of fossil ebony.22 co19 cf. f. colonna, minus cognitarum stirpium par altera…, romae, apud iacobum mascardum, 1616. 20 g. gabrieli, il carteggio linceo, roma, accademia nazionale dei lincei, 1996, p. 1187. 21 ivi, pp. 1187-88: «io non so per dire il vero che cosa sia la pianta animale lapidea, sotto il nome di zoolithophyton, che desidero sapere come cosa da me finhora non osservata, credo per non l’haver havuto: così anco la pianta metallo, se pur sia differente dall’argento ramoso descritto dall’imperato»; for the reference to marcasite see above, note 10. 22 cesi describes the journey in a letter to stelluti dated 17 july 1604 in ivi, pp. 40-41; cf. also f. stelluti, persio tradotto in verso sciolto e dichiarato, roma, appresso giacomo mascardo, 1630, pp. 169-170: «mi ricordo bene che in napoli il signor ferrante imperato autore di un museo così ricco e celebre, mostrò al nostro signor principe cesi […] una spezie di citiso, come parve ad esso signore, quale si potrà vedere, e qualche de gli ebani minerali dice da esso scoperti, ne suoi libri de metallofiti, che presto doveranno stamparsi»; stelluti was anticipated by faber lonna was not in naples on that occasion, but we may suppose that, even when he was, he would not have retrospectively recalled that mineralised ebony, which ferrante imperato explained simply as the remains of fossil wood.23 the extant documentation shows that cesi must have discovered his pianta metallo in the first decade,24 but there is little information about that until the beginning of the second decade, when cesi had already decided to make his contribution to the thesaurus in the form of tables and to confer a strategic role on the socalled intermediate natures in order to illustrate effectively the continuum of the divine creation. he wrote to johann faber (1574-1629) asking for information regarding ‘whether anyone has distinguished and listed fossils in an orderly fashion in their classes, particularly the metallic ones and semi-minerals; and likewise whether anyone has summarised the sciences synoptically in tree structures and tables’.25 we do not have faber’s reply, nor can we reconstruct the reading and researches leading to 1624, the year in which johann baptist winther (? – 1628 ca.), writing to faber on 18 may, mentions a double excursion with cesi in the course of which he drew the prince’s attention to a ‘certain point’ in the de metallicis libri tres by andrea cesalpino (1519-1603); cesi declared that it coincided with his own opinion.26 the passage in question is part of the forty-first chapter of the second book in the section on gemmae pellucidae. it is introduced by a premise intended to make it clear that the chapter will deal only with fossil ebony and not black coral. cesalpino knows that many authorities take them to be related, if not identical, but the only thing in common that he is prepared to concede is their colour. otherwise in his commentary in the thesaurus mexicanus, already printed in 1628, in which he reported cesi’s discovery without going into the merit of the thesis regarding its origin: see rerum medicarum novae hispaniae thesaurus seu plantarum, animalium, mineralium mexicanorum historia…, romae, ex typographeio vitalis mascardi, 1651, pp. 502-503. 23 f. imperato, dell’historia naturale, op. cit. pp. 668-669; the same opinion in fr. imperato, discorsi intorno a diverse cose naturali, napoli, nella stamperia di eg. longo, 1628, pp. 3-4. 24 a.c. scott, “federico cesi and his field studies on the origin of fossils between 1610 and 1630”, endeavour, 2001, 25(3): 93-103; also useful g. godard, “les travaux géologiques de la première accademia dei lincei (1603-1651)”, travaux de comité français d’histoire de la géologie, 2011, s. iii, 75(5): 119-137. 25 gabrieli, il carteggio linceo, p. 732. 26 ivi, p. 881: «siano stati due volte in luogo montuoso et argilloso, dove si trovano certi sodissimi legni in gran quantità, negre et odorate, con bellissime vene sotto terra, stimati dal sig.r principe minerali, sonno bene grandi argomenti del sito e della sostanza d’alcuni di loro petrificata. io, havendo letto nel cesalpino il capo del ebano, ho trovato un certo punto, il quale mostrato al sig.r principe gli confermò totalmente la sua opinione, se bene non mancano argomenti in contrarium validissimi, tanto ch’io non so che dirmi sin’hora. però mi mostro d’andare con i piedi ne la opinione del sig.r principe». 24 alessandro ottaviani they originate in different environments – black and all other corals in the sea, fossil ebony on land – and their nature remains to be determined. if black coral is undeniably vegetal, the nature of fossil ebony is inscrutable; cesalpino does not exclude the possibility that it is a root or wood that has been lithified, like coral, or that it is a stone that simply resembles wood.27 the ambiguity went back to the ancient sources such as pausanias, whom cesalpino quotes. he reports the explanation of a cypriot that ebony was a sort of subterranean vegetal lacking leaves and fruit: ‘ebony does not grow leaves or bear fruit, or even appear in the sunlight at all, but consists of underground roots which are dug up by the ethiopians, who have men skilled at finding ebony’.28 more recent discoveries, such as those made in the environs of the town of hildesheim in lower saxony, reported at length by giorgio agricola (1494-1555) in his de natura fossilium libri x, failed to resolve the question either,29 27 a. cesalpino, de metallicis libri tres…, romae, ex typographia aloysii zannetti, 1596, liber ii, cap. xli, pp. 126-127: «ad gemmas non pellucidas reduci possunt corallii, rubrum, candidum, et nigrum, quod antipathes dicitur. egimus autem de iis inter plantas. antipathi similis est ebenus fossilis, sive radix sit, lignumve ebeni in lapidem concreti, sive omnino lapis per se genitus ligno similis. differt a corallio nigro: hoc enim non nisi in mari nascitur; ebenus foditur»; gabrieli, il carteggio linceo, cit., p. 112, n. 3 assumes winther was referring to a. cesalpino, de plantis libri xvi, florentiae, apud georgium marescottum, 1583, lib. 3, cap. xxxiiii, pp. 114-115, that contains, at any rate, the same opinion on the ebenus fossilis. 28 pausanias, description of greece with an english translation by w.h.s. jones, london, william heinemann-new york, g.p. putnam’s sons, 1918, pp. 227, 229; followed by a reference to theophrastus: see cesalpino, de metallicis libri tres, p. 127: «et theophrastus tradit ebenum fossilem inveniri inclusum aliis lapidibus tamquam foetum in ventre. si igitur haec vera sunt, nec radix nec arbor dicenda est in lapidem conversa, sed lapis ebeno similis in fibris saxorum genitus». the passage, however, does not correspond to any of those in which theophrastus discusses ebony. 29 cesalpino, de metallicis libri tres, p. 127: «nec tamen absurdum etiam ebeni lignum intra terram diu conditum lapidescere, quod & aliis generibus lignorum contigisse compertum est», followed by a reference to g. agricola, de natura fossilium libri x, basileae, in officina frobeniana, 1558, pp. 324-325: «in hildesheimio quoque in terra aluminosa inventum est lignum quernum in lapidem conversum. in eodem e regione arcis marieburgi collis est plenus lapideis trabibus, quarum capita interdum eminent. sunt vero perlongae, acervatim positae, inque medio earum terra est, colore nigra, ferro aut altero lapido percussae non aliter nec marmor hildesheimium, de quo supra dixi, cornu usti virus olent, omninoque ex eadem materia sunt, quare cum natura lapides arborum similes procreet, diligenter videndum est an corticem et medullam aliaque habeant. quae si absunt non stipites in lapides conversi sunt, sed natura fecit lapides stirpium simillimos, quales sunt trabes istae hildesheimiae. trabs igitur quam iovianus pontanus invenit in promontorio pausyllipi, cum tempestas artem monte abrupuisset, qualis fuerit, non possumus scire; non enim explicatur an fuerit saxum, quod trabs speciem prae se ferebat, an lignum in saxum conversum»; cesi owned copies of the treatise of cesalpino and of agricola (in the edition of 1616): cf. m. t. biagetti, la biblioteca di federico cesi, roma, bulzoni, 2008, p. 266, n° 151 for cesalpino, and pp. 271-272, n° 2259 for agricola. leaving open the possibility of arguing for a transformation from wood to stone, while leaving open two possible scenarios of the process: that of a slow transformation, projected into the past, and that of metamorphosis by lightning. but this ambivalence is common: we can find it for example in william camden (1551-1623),30 and equally in cesalpino, who seems reluctant to come down in favour of either opinion. it is regrettable that winther did not specify the nature of that ‘certain point’ with which cesi had expressed his agreement. but we do know what his frame of reference was at the end of the year, thanks to the only extant fragment from the materials that the prince was compiling to deal with the matter in depth. this document owes its origin to the desire to address a letter to cardinal francesco barberini with a concise explanation to accompany the gift of a table made of ebony. the brief but dense letter is intended above all to underline the importance of this discovery in the eyes of the cardinal because of its capacity to increase knowledge of the so-called intermediate nature, otherwise defined as entia imperfecta. although cesi stresses the completely unparalleled way in which these metallophytes combine two or even three natures, he locates their essential characteristic in their bituminous nature. this is followed by a list of examples of naturalia: the stones gagates (jet) and aetites (eagle stones), on whose disputed identification cesi concurs with pliny;31 another jet-like stone known as acciavaccio (the neapolitan term for a dark stone known in spanish as azabache and used as a talisman), fossil ebony, lithanthracite (these are simply named), and finally agalloch, aloe wood, whose 30 agricola de natura fossilium, p. 325: «iidem autem fontes et fluvii chirotecas et ossa aliasque res in se immissas, ut forma prior maneat, ossaque dissolvens cum corpore tabificus seps, in lapidem conversus nuer ad rivum quendam montis piriferi salso dicti inventus est»; w. camden, britannia…, londini, impensis, georg. bishop, 1600, e.g. p. 542: «ubi flumen australem agri limitem attingit inter ericeta et iacentia loca, in quibus, uti etiam alibi, arbores ab inundato mundo, ut credunt, defossas saepe eruunt»; p. 622: «sub quo fons est in quem ex impendentibus rupibus aquae guttatim distillant, unde dropping well vocant, in quem quicquid ligni immittitur, lapideo cortice brevi obduci et lapidescere observatum est». 31 cited from gabrieli, il carteggio linceo, p. 966: «fra questi ho veduti i nascimenti del gagate, ancorché lontano dal gange, del aetite ad esso prossimo; nel che venga lodato plinio, e liberato dalla calunnia, che communemente se l’è data, d’haverli insieme congionti»; the reference is pliny x 12. cesi read gagaten, the accepted reading in the editions until then, while modern editors (e.g. detlefsen, mayhoff, rackham, de saint denis, könig and winkler) accept the reading gagiten; the principal ancient sources on the stone were dioscorides v 129 and pliny xxxvi 141. the latter is not free of errors, on which cfr. a. mottana, “ricerche di iconografia mineralogica: i. la pietra «gagate» nel codex medicus graecus 1 della biblioteca nazionale austriaca”, rendiconti della accademia dei lincei. classe di scienze fisiche, matematiche e naturali, 2002, s. ix, 13: 89-112. 25the opposite poles of a debate lapides figurati and the accademia dei lincei legendary origin in terrestrial paradise cesi mentions in passing.32 the list is intended to display the salient properties of the metallophyte,33 comprised within the spectrum of characters extending between the extremes of jet, which pliny describes as ‘black, smooth, porous, light, not very different from wood, and brittle, and has an unpleasant smell when rubbed’34 and of agalloch, noted for its fragrance.35 according to francesco stelluti, the detailed description of the naturalia in this list and their relation with metallophytes would have corresponded to the treatise on which cesi was working.36 stelluti regretted that cesi’s early death had prevented him from completing it and saved the most valuable part – the woods of acquasparta – from oblivion when he dedicated a brief trattato to them in 1637. stelluti presents his own thesis as the result of a laborious intellectual trajectory that involved the rejection of what he claimed as the most natural 32 presumably cesi took the legend from p.a mattioli, commentarii secundo aucti in libros sex pedacii dioscoridis anazarbei de materia medica…, venetiis, in officina valgrisiana, 1560, p. 48: «sunt qui somniantes dixerint agallochi arborem vidisse neminem, cum terrestri tantum paradiso proveniat, illudque ferri fabulantur fluminibus quae (ut sacra testantur monumenta) ex eo manant. atqui pro comperto habetur (ut paucis innuit serapio) gangem indiae amplissimum fluvium quam plurima secum agallochi fragmina vehere, quae tamen in ipsum ducuntur aliorum fluminum cursu, qui in eum confluunt. quippe cum fluvii transluant loca, ubi agallochum provenit, aquarum inundationibus turgentes, huius truncos, fragmina ac ramenta rapiunt una cum aliis varii generis lignis, et in gangem transferunt, quemadmodum in nostris etiam fluminibus saepe ac saepius visitur. cuius rei indicium affert illud quod venetiis venditur, utpote quod longo aquarum discursu omni ex parte laceratum, exesum, comminutumque spectetur»; the primary source for the agallochum is dioscorides i 22. 33 a very forced interpretation of this list is proposed by d. freedberg, the eye of the lynx. galileo, his friends, and the beginnings of modern natural history, chicago and london, the university of chicago press, 2002, pp. 327-328, though as a preliminary to an interpretation of cesi’s mineralogical researches on which serious doubts have been cast by p. galluzzi, «libertà di filosofare in naturalibus». i mondi paralleli di cesi e galileo, roma, scienze e lettere, accademia nazionale dei lincei, 2014, pp. 425-426 [= idem, the lynx and the telescope. the parallel worlds of federico cesi and galileo, trans. p. mason, brill, leiden, 2017, pp. 382383]. 34 pliny, xxxvi, 142: «niger est, planus, pumicosus, levis, non multum a ligno differens, fragilis, odore si teratur gravis». 35 confirmation that the list serves to define the spectrum of the qualities of the metallophyte can be found in stelluti’s statement that the sample can emit a distateful odour like that of gagate, or a more pleasing one closer to the extreme sweetness of the scent of aloe wood: f. stelluti, trattato del legno fossile minerale nuovamente scoperto…, in roma appresso vitale mascardi, 1637, p. 7: «se si mette al fuoco mentr’è stato cavato di fresco dalla terra, s’abbrucia, ma lentamente con gran fumo, e con odore spiacevole. quando poi il legno è secco, l’odore è più grato […]». 36 ivi, pp. 11-12: «[p]oiché non solo scriveva della generatione di dette pietre e legno, e delle pietre aquilini, che pure in detti luoghi se ne genera gran quantità, ma di tutte l’altre pietre note sin qui, e di altre ancora non più osservate, ne descritte da altri autori». hypothesis, viz. that they were the remains of trees buried a long time before that had slowly been transformed into stone.37 the absence of roots, seeds and other circumstantial evidence led him ineluctably to the idea that they originated from ‘a soil type containing a lot of chalk, which gradually converts it into wood’ (see fig. 3). 37 ivi p. 6: «ne meno si può credere, che questi legni siano tronchi o frusti d’alberi sotterrati in quei luoghi, o caduti, e dalla terra ricoperti, e formati poi con quell’onde da quell’acque minerali, che ivi scaturiscono, e da fuochi sotterranei, com’io nel principio mi persuasi, per haver trovato alcuni olmi ricoperti dalla terra in quei luoghi, dove detto legno si trova, perché la sua forma si varia, e la mole si grande mi fa credere il contrario, non trovandosi alberi mai dalla natura formati come nelle seguenti figure si vedrà […]»; on stelluti cf. francesco stelluti linceo di fabriano, fabriano, città e comune di fabriano, 1986. figure 3. plate from stelluti, trattato del legno fossile (1637). the annotation runs: “this piece of wood, ovoid from a to b, was three palms high; i say high because it was found with the part a facing downwards and the part b facing upwards; and from c to d it was thirteen palms long; from e to f it was eleven palms long; from f to g ten and a half palms. from g to h the wood was covered with earth while it was being excavated, and it was impossible to see where it ended.” although the annotation does not mention it, the fragments represented on the upper left were presumably detached during the excavation. 26 alessandro ottaviani it has been repeatedly claimed that such a thesis could not have appealed to cesi because of its excessive naïveté, but apart from the fact that comparison of the letter to barberini with the text of stelluti does not afford any positive evidence for such a difference of opinion, there is a clue that enables us to qualify stelluti’s thesis as fully compatible with the philosophical horizon of cesi enshrined in the tabulae phytosophicae. they show a clear adhesion to the paracelsian doctrine of transplantatio. this doctrine allows that, given certain conditions, the process of changing along the axis of the natural continuum that usually proceeds downwards (commonly defined as degeneratio) can operate in the reverse direction and even perform considerable leaps.38 3. from thomas bartholin to johann jakob scheuchzer however eccentric and extreme the solution suggested by cesi and stelluti, it remains anchored to the vision of nature summed up in the action of rationes seminales or spiritus metallicus.39 this vision was by no means marginal in the course of the seventeenth century, and often adopted in order to explain the origin of fossils and figured stones, from johann de laet’s de gemmis et lapidibus libri duo (1647),40 and ulisse aldrovandi’s musaeum metallicum, posthumously edited in 1648,41 to the catalogue of manfredo settala’s wunderkammer.42 this helps to understand why the trat38 on this aspect cf. ottaviani, “methodus philologica e naturales quaestiones, op. cit. 39 obviously, this notion had a long history: see h. hirai, le concept de semence dans les théories de la matière à la renaissance: de marsile ficin à pierre gassendi, turnhout, brepols, 2005, and a. clericuzio, elements, principles and corpuscles. a study of atomism and chemistry in the seventeenth century, dordrecht-boston, kluwer, 2000. 40 see johann de laet, de gemmis et lapidibus libri duo…, lugduni batavaorum, ex officina ioannis maire, 1647, p. 177: «quemadmodum spiritus metallicus a deo terrae natura inditus, in venis auri argentique mirabilia artificio efformat arbusculas et herbas, ex auro et argento, ita in lapidicinis etiam varias effigies testaceorum animantium e materia plane lapidea et quasi metallica, quod et supra vidimus in lapidibus serpentinis et cornua ammonis. quare meo iudicio frustra sunt qui opinantur has conchas aliquando testaceas fuisse et viva animantia continuisse et successi temporis in lapides esse conversas». 41 cf. u. aldrovandi, musaeum metallicum in libros iiii distributum, bononiae, typis io. baptistae ferronii 1648. 42 cf. museum septalianum manfredi septalae patritii mediolanensis industrioso labore constructum, pauli mariae terzagi physici… descriptum…, dertonae, typis filiorum qd. elisei violae 1664; museo o galeria adunata dal sapere e dallo studio del sig. canonico manfedo settala nobile milanese, descritto in latino dal sig. dott. fis. paolo maria terzago et hora in italiano dal sig. pietro francesco scarabelli dott. fis. di voghera e dal medesimo accresciuta, in tortona, per li figliuoli del qd. eliseo viola 1666. tato del legno fossile minerale was, with a few very rare exceptions,43 favorably received as, for example, by fortunio liceti (1577-1657), martin schoock (1614-1669), charles patin (1633-1693), and athanasius kircher (16021680).44 more interesting is the case of the danish physician thomas bartholin (1616-1680), who in 1643 went on a long italian tour that took him to rome, naples, sicily and malta. in the course of his journey, he wrote that, in the course of planning a treatise on this material, he had arrived at a view of the glossopetrae that in no way agreed with that of colonna.45 at the same time as he rejected the conclusions of the latter’s dissertation, bartholin, who recorded having seen ‘the spectacle of the new wood’ in rome, had no objection to the thesis of stelluti.46 bartholin thereby gave form to a duality that was destined to be repeated, although two decades later colonna’s thesis seems to be widely acknowledged, for example by johann daniel major (1634-1693) and her43 g. naudé, lettres inédites écrites d’italie à peiresc, 1632-1636, publiées et annotés par philippe tamizet de larroque, paris, léon techener, 1887, pp. 42-43, 51-52. 44 cf. f. liceti, de tertio-quaesitis per epistolas clarorum virorum, medicinalia potissimum, et aliarum disciplinarum arcana postulantium responsa…, utini, ex typographia nicolai schiratti, 1646: liceti resp. de multiplici generatione succini, eboris, ebeni et ligni, deque viribus electri, pp. 200-201; m. schoock, tractatus de turffis ceu cespitibus bituminosis…, groningae, typis johannis cöllenii, bibliopolae et typographi, 1658, pp. 72-74; c. patin, traité des tourbes combustibles…, a paris, chez jean du bray, aux espics-meurs et pierre variquet. à l’enseigne du gril, 1663, p. 45; a. kircher, mundus subterraneus in xii libros digestus, tomi 2, amstelodami, apud joannem janssonium et elizeum weyerstraten, 1664-5, especially ii, p. 65 on stelluti’s treatise. 45 t. bartholin, epistolarum medicinalium a doctis vel ad doctos scriptarum centuria i et ii, hafniae, typis matthiae godiccheni, 1663: centuria i. epistola liii. de raris naturae in insula melita observatis, pp. 223-224; epistola lvi. de glossopetris melitensibus, p. 240: «nam de glossopetris optimum agnosco iudicium tuum, quae cur ex metallorum ordine exigendae sint, basin rationum parum firmam apud f. columanm observo, de quibus incoram pluribus, si deo visum est, agemus»; epistola lvii. de glossopetris, pp. 241-242. 46 t. bartholin, de unicornu observationes novae…, patavii, typis cribellianis, 1645, pp. 283-284: «novi ligni spectaculo ex terrea lapidi mixta materie saeculum nostrum illustravit nuper natura duobus retro messibus, aquaspartae in umbria, ubi lignum fossile inventum cedro mauritanico simile, venis in longitudinem extensis, non in altitudinem, quia radice caret, cortice interdum fragili, aliquando durissima et aspera partim lignea partim cretacea, sed medulla duriore. mirum variantis naturae miraculum cum stupore apud unicum eius inter mortales authorem cassianum puteum vidi, et in rei fidem dono singulari aliquam eiusdem ligni partem rudem partim, partim tornatam, servo. resinam lignorum instar sudat candidam mastichi similem vel thuri, metallique filamenta quaedam habet et capillamenta, ut nomen metallophyti impetravit a francisco stelluti qui totam eius historiam etrusco idiomate cum depicto ligno typis romae vulgavit, ubi et terram fossilis huius materiam inde exploravit quod gleba ei adhaerens humida post aliquot menses tota evaserit lignea, a calore, ut arbitror, temperato, quem modica oleosque humiditas in sicciorem lapidem vetat indurescere». 27the opposite poles of a debate lapides figurati and the accademia dei lincei mann conring (1606-1681),47 and, with more substantial evidence, by steensen in his canis carchariae dissectum caput (1667) and prodromus (1669),48 and scilla, in his la vana speculazione disingannata dal senso, edited in 1670.49 in 1671 paolo boccone (1633-1704), when he was in paris, published a series of observations in two modest volumes.50 france was the first stage of the journey that he had reluctantly undertaken once it had become clear that he would be unable to remain in tuscany, where he had found his niche as personal botanist to the grand duke. one of the two works was on the nature of fossils. convinced like colonna that they originated from plants and animals,51 boccone crossed the alps in the knowledge that his thesis was finding confirmation by steensen with whom he was on cordial terms. as it happened, 1671 was the year in which steensen’s theses were severely criticised by martin lister (1639-1712).52 in a letter of 13 december 1673, henry oldenburg wrote to lister: i have now in my custody a boxe, left with me by a sicilian, paulo boccone, (an inquisitive person, especially as to plants and figured stones,) for the repository of the r. society; in which, amongst other curiosities, there are sev47 see j.d. major, dissertatio epistolica de cancris et serpentibus petrefactis..., jenae, typis joannis nisii, sumptu esaiae fellgiebeli, bibliop. vratislav. 1664, and h. conring, de antiquissimo statu helmestadii et viciniae coniecturae, helmestadii, typis et impensis henningi mulleri, 1665, pp. 35-36: «sunt scilicet talia dentes carchariae, aut lamiae, aliorumque cetaceorum marinorum. quod praeclare docuit singulari dissertationi fabius columna, de melitensibus eiusmodi glossopetris disputans». 48 n. steensen, canis carchariae dissectum caput et dissectus piscis ex canum genere, in id., elementorum myologiae specimen…, florentiae, ex typographia sub signo stellae, 1667; de solido intra solidum naturaliter contento dissertationis prodromus…, florentiae, ex typographia sub signo stellae, 1669. 49 a. scilla, la vana speculazione disingannata dal senso. lettera responsiva circa i corpi marini che petrificati si trovano in varii luoghi terrestri, napoli, appresso andrea colicchia, 1670. 50 p. boccone, recherches et observations naturelles and recherches et observations curieuses sur la nature du corail blanc et rouge, vray de dioscoride, both paris, chez claude barbin, 1671. 51 on boccone’s research on fossils cf. b. accordi, “contributions to the history of geological sciences; paolo boccone (1633-1704) – a practically unknown excellent geo-paleontologist of the 17th century”, geologica romana 1975, 14: 353-359. 52 m. lister, “a letter... written at york august 25 1671 confirming the observation in n° 74 about musk sented insects; adding some notes upon d. swammerdam’s book of insects, and on that of m. steno concerning petrify’d shells”, philosophical transactions, 1671, 6: 2281-2285; on which cf. n. morello, “le «conchiglie stravaganti» da colonna a lister”, in il meridione e le scienze (secoli xvi-xix) (ed.: p. nastasi) palermo, università di palermo, istituto gramsci siciliano di palermo, napoli, istituto italiano per gli studi filosofici, 1988, pp. 257-279; a.m. roos, web of nature: martin lister (1639-1712), the first arachnologist, leiden-boston, brill, 2011. eral pieces of coral, red and white, some hard and solid, others britle sticking about pieces of wood etc. which latter may much inform us about the original of coral, and teach us, that’tis of a stony, not vegetable nature.53 boccone had hardly left england, the second stage of his journey, where he had made a favourable impression. he now headed for holland, where he was to publish the parisian works in a single volume in amsterdam in 1674, taking into account the recent english and dutch discoveries. he made no mention of lister;54 we do not know the reason for this silence, but it may be supposed that the englishman’s objections, which ended up reviving the ‘plastic virtue’ hypothesis, may have had a déjàvu ring to boccone. the abovementioned scilla’s treatise was ably promoted by boccone; in that work scilla replied point by point to the letter in which the maltese physician giovan francesco buonamici (1639-1680) opposed the colonna/steensen position, based on an elaborate version of the genesis of fossils and other figured stones by the action of occult seeds.55 the successive decades, however, had more than one surprise in store for boccone. both in england and on 53 the correspondence of dr. martin lister (1639-1712). volume one: 1662-1677, (ed.: anna marie roos), leiden-boston, brill, 2015, p. 639; oldenburg is providing lister with a synthesis of the content of the “account of some of the natural things, with which the intelligent and inquisitive signor paulo boccone, of sicily hath lately presented the royal society, and enriched their repository” already published in philosophical transactions, 1673, 6158-6161. 54 p. boccone, recherches et observations naturelles…, amsterdam, chez jean jansson à waesberge, 1674, where lister is also passed over in silence, “a description of certain stones figured like plants, and by some observing men esteemed to be plants petrified…”, philosophical transactions 1673, 8: 6181-6191, although he added considerable material on the astroite: ivi, cf. pp. 118-124, 135-149. 55 buonamici’s letter was printed much later: cf. g.f. buonamici, “lettera missiva… diretta ad agostino scilla…. ove si tratta dell’origine delle glossopietre, occhi di serpi, bastoncini detti di san paolo, ed altre pietre figurate, che si cavano dall’isola di malta e del gozzo”, in opuscoli di autori siciliani, palermo, per pietro bentivenga, 1770, vol. xi: 105-195, 188: «né anco è da credere a mio parere, che solamente i semi occulti, e principi materiali di quell’animaletti minuti e stimati comunemente meno perfetti si contengono dispersi nell’acqua e nella terra, ma anco de’ maggiori e più perfetti, sicché questi potrebbono similmente generarvisi, toltone però l’uomo, la di cui produzione non fu commessa alla terra, ma riserbata alla mano dell’altissimo, come della più perfetta delle creature, ch’è composta di spirito e corpo, checché si sia sognata la pagana antichità e de’ suoi preadamiti abbia empiamente scherzato la perriera moderno scrittore, de’ suoi omicciuoli fatti per arte chimica entro una caraffa scrisse paracelso, e di non so che razza d’uomini verdi scappati dal seno della terra lasciò registrato il neobrigense»; buonamici had already stated his position in a letter to michele giustiniani, published by the latter in lettere memorabili… parte prima, roma, per nicolò angelo tinassi, 1667, pp. 389-404; on him cf. n. morello, “giovanni francesco buonamico and the fossils: a flood of problems”, in italian scientists in the low countries in the xviith and xviiith centuries, (ed. cesare s .maffioli – lodewijk c. palm), amsterdam-atlanta, ga, rodopi, 1989, pp. 131-145. 28 alessandro ottaviani the continent, the challenge of lister and buonamici was taken up in a sequel of interventions, which, irrespective of the arguments deployed to reject totally or to limit the validity of the theses of colonna and steensen, had in common a view holding that fossils originate by plastic virtue or occult seeds.56 quite eloquent was the case of the swiss physician johann jakob scheuchzer. born at zürich in 1672, graduated at the university of utrecht, schuechzer in 1697 published an essay entitled de generatione conchitarum.57 still far from wholeheartedly embracing the diluvian theory that he was soon to adopt after reading the works of john woodward,58 scheuchzer treated this complex material warily, cautiously weighing up the two major theses in open conflict, and eventually (with many reservations) came down on the side of steensen, whose works he read with great care.59 nevertheless, only a few years later scheuchzer continued to appreciate that position but restricted its scope even further as he grew inclined to accept the arguments of those who clung firmly to panspermia, the spiritus mun56 that is the case of john ray, robert plot edward lhwyd, johann jakob wagner, johann jakob reiskius, theodor geyer, elias camerarius, karl nikolaus lange, just to cite a few. 57 j.j. scheuchzer, “de generatione conchitarum”, miscellanea curiosa sive ephemeridum medico-physicarum germanicarum caesareo-leopoldinae naturae curiosorum 1697, 4, appendix: 151-166, pp. 155 and 157: «non etiam immorabor multum [...] descriptioni accuratiori figurae conchitarum [...] ut nec solutioni famosae illius apud litographos quaestionis, num sc. conchitae aliique lapides figurati fuerunt aliquando revera conchae, cochleae &c. fluviatiles vel marinae, atque adeo spolia diluvii universalis, inundationum particularium, absorbitionum terrae, quae postea in terra relicta a petrificante quodam succi il lapides transmutata vi, an non potius sint id genus lapides corpora terrigna, atque adeo mire variantes suas figuras terrae debeant, non mari; corporibus inanimatis, non incolis maris, animalibus variis. [...]»; e p. 157: «non satisfacit mihi, si verum fateor, reiskii vis κυγκχοποιητικὴ, salmasii aptitudo huius vel illius loci peculiaris, ad continendum eiusmodi succum conchiferum, geyeri succus lapidescens, et sal illud modificans wagneri et aliorum vis seminalis terrae innata»; on him cf. m. kempe, wissenschaft, theolo gie, aufklärung. johann jakob scheuchzer (1672-1733) und die sintfluttheorie, epfendorf, bibliotheca academica verlag, 2003. 58 the hesitations, still present in specimen lithographiae helveticae curiosae, tiguri, typis davidis gessneri, 1702, disappear from piscium querelae et vindiciae, tiguri, sumtibus authoris, typis gessnerianis 1708. 59 cf. scheuchzer, “de generatione conchitarum”, pp. 155 and 157: «non etiam immorabor multum [...] descriptioni accuratiori figurae conchitarum [...] ut nec solutioni famosae illius apud litographos quaestionis, num sc. conchitae aliique lapides figurati fuerunt aliquando revera conchae, cochleae &c. fluviatiles vel marinae, atque adeo spolia diluvii universalis, inundationum particularium, absorbitionum terrae, quae postea in terra relicta a petrificante quodam succi il lapides transmutata vi, an non potius sint id genus lapides corpora terrigna, atque adeo mire variantes suas figuras terrae debeant, non mari; corporibus inanimatis, non incolis maris, animalibus variis. [...]»; e p. 157: «non satisfacit mihi, si verum fateor, reiskii vis κυγκχοποιητικὴ, salmasii aptitudo huius vel illius loci peculiaris, ad continendum eiusmodi succum conchiferum, geyeri succus lapidescens, et sal illud modificans wagneri et aliorum vis seminalis terrae innata». di or the archeus espoused by van helmont.60 we do not know whether his change of attitude was also influenced by his turning attention to vegetal forms, but it is certain that, whether willingly or not, in the divergence resulting from the juxtaposition of the two sententiae, scheuchzer ended up reproducing a polarity whose dialectical tension had been taken to its limit by the accademia dei lincei. 60 cf. j.j. scheuchzer, “dissertatio epistolica acarnanis de dendritis aliisque lapidibus, qui in superficie sua plantarum, foliorum, florum figuras exprimunt”, miscellanea curiosa sive ephemeridum medico-physicarum germanicarum caesareo-leopoldinae naturae curiosorum, 1700, 5-6, appendix: 57-80, p. 67: «sic non improbaverim eorum sententiam, qui spiritui mundi, archeo sive natura universali, in globum hunc terraqueum ubique panspermia imbutum perpetuo agenti, et pro subiecti diversitate figuras varias producenti cuncta tribuunt»; on van helmont see w. pagel, joan baptista van helmont: reformer of science and medicine, cambridhe [et alibi], cambridge university press, 1982. substantia. an international journal of the history of chemistry 3(2) suppl. 1: 27-42, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-264 citation: r. m. baum sr. (2019) taking the earth’s temperature: 200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer. substantia 3(2) suppl. 1: 27-42. doi: 10.13128/substantia-264 copyright: © 2019 r. m. baum sr. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. taking the earth’s temperature: 200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer rudy m. baum sr. science writer/editor, 2738 sw patton ct, portland, or 97201, us e-mail: rudybaum589@gmail.com abstract. because of the threat of global warming due to the build-up of atmospheric carbon dioxide from burning fossil fuels, energy use is the central factor in creating a sustainable future. anthropogenic climate change is real, but climate change deniers insist that carbon pollution is not a threat and that the science behind climate change is flimsy at best and a sham at worst. in fact, efforts to understand earth’s climate and why the planet’s temperature is what it is date back to the early 19th century, and i review that history in this paper. earth’s atmosphere was first likened (inaccurately, as it turns out) to a greenhouse in the 1820s; co2 was first shown to be a greenhouse gas in the 1860s; the idea that burning fossil fuels could change the earth’s temperature was proposed in the late 19th century; the concentration of co2 in the atmosphere was first shown to be inexorably rising in the 1950s. the science of climate change has a long and distinguished pedigree. keywords. greenhouse gases, global warming, climate change, fossil fuels, carbon dioxide. introduction energy consumption is by far the most important factor in determining whether humanity can transition to a sustainable economic system in the 21st century. burning fossil fuels powered the industrial revolution and, in a mere 200 years, transformed civilization. civilization as we know it is entirely dependent on burning fossil fuels—which are, in fact, fossilized sunshine—cheaply. humans burn fossil fuels on the cheap because we treat the atmosphere as a free dumping ground for the waste products of combustion, primarily carbon dioxide (co2). for many years, economists and others thought the supply of fossil fuels would place limits on economic growth. books were written on “peak oil”— when the amount of petroleum extracted from the earth would begin an inevitable decline as oil fields were depleted.1 it turns out that that’s probably not the case. enough fossil-fuel resources—petroleum, natural gas, and coal— are left on earth for us to keep the economic engines that have powered 200 years of exponential growth going for another 200 or 300 years or so. 28 rudy m. baum sr.28 rudy m. baum sr. earth’s climate, however, will not tolerate humans continued unrestrained fossil fuel use. the buildup of atmospheric co2—from 280 ppm at the beginning of the industrial revolution to more than 400 ppm today2—is already forcing the climate to change. earth’s temperature is increasing due to the buildup of co2 and other greenhouse gases, many of them associated with fossil fuel production and use. among scientists, there is no doubt that anthropogenic climate change is real. however, a determined cadre of climate change deniers insists that carbon pollution is nothing but propaganda, that climate scientists are engaged in an elaborate conspiracy to demonize fossil fuels and line their pockets with research grants. one persistent thread in the deniers’ claims is the suggestion that climate change is a relatively new idea cooked up by left-leaning scientists and politicians bent on strangling economic growth. nothing could be further from the truth. scientists have been pondering the question of why the earth’s temperature is what it is for 200 years. that the earth’s atmosphere plays a role in regulating the planet’s temperature was first proposed in the 1820s. carbon dioxide was first shown to be a greenhouse gas—able to absorb infrared radiation—in the 1860s. the idea that burning fossil fuels could ultimately change earth’s climate was proposed in the late 19th century; the first calculation on the potential impact of co2 on climate was published in 1896. climate change has a long and distinguished scientific pedigree. it should be noted that while the terms “greenhouse gases” and “greenhouse effect” are now firmly embedded in the vernacular concerning climate change and that a number of 19th century scientists made allusions to a greenhouse or a blanket when discussing the influence of earth’s atmosphere on the planet’s surface temperature, the term “greenhouse effect” was not used until 1901 by the swedish scientist nils ekholm. perhaps unfortunately, as will be discussed further, a greenhouse is not an accurate analogy for how gases like carbon dioxide are warming the earth. energy balance why is the temperature at the surface of the earth what it is? the french mathematician and physicist joseph fourier (1768–1839) addressed the question in the early 1800s as part of his more general work on heat flow. fourier is best known for his work on discontinuous functions, work that is the foundation of what is known today as the fourier transform. he also made seminal experimental and theoretical contributions to our understanding of energy flow in various substances. fourier thought that there were three sources of energy that contributed to earth’s surface temperature: solar radiation, which is unevenly distributed across earth’s surface and gives rise to the diversity of climates; energy from interstellar space, essentially from the stars; and energy from earth’s interior, which he thought to be relatively minor.3,4,5 the most important energy source was the sun. when the light from the sun strikes the earth and warms it, why doesn’t the planet just keep getting hotter? fourier reasoned that the earth must be radiating invisible heat—infrared radiation—back into space to achieve a net energy balance. treating the earth as a black body being heated by sunlight, fourier calculated that its temperature would be significantly lower than it is. fourier thought, incorrectly, that the difference was likely made up by energy from interstellar space. however, he also speculated that the atmosphere might be transparent to sunlight impinging on the planet but that it somehow impeded the outward flow of heat from the planet back into space. in one analogy, he compared the heating of the atmosphere to the action of a heliothermometer, an instrument designed and used by horace benedict de saussure (1740–1799) in the 1770s to study the variability of the intensity of solar radiation with altitude. the device consists of a small wooden box lined by a layer of figure 1. joseph fourier (1768–1830); credit: www.bridgeman images.com. 29200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer 29taking the earth’s temperature blackened cork and fitted with three panes of glass separated by air spaces. the similarity of a heliothermometer to a greenhouse and fourier’s reference to it are what gives rise to the suggestion that fourier was the first to liken earth’s atmosphere to a greenhouse, although he never used that term. in fact, it’s a little bit tricky to unearth fourier’s precise thinking about this subject. fourier’s 1827 disquisition “mémorie sur les temperatures du globe terrestre et des espaces planétaires” (“memoir on the temperature of the earth and planetary spaces”), often cited to support the link between fourier and the greenhouse effect, may well have been a public presentation rather than a formal scientific paper. it contains no equations or formal calculations. as james r. fleming points out in “joseph fourier, the ‘greenhouse effect’, and the quest for a universal theory of terrestrial temperatures,”6 the 1827 article “has been mentioned repeatedly as being the first reference in the literature to the atmospheric ‘greenhouse effect.’ here i will review the origins of this practice and demonstrate that most of these citations are unreliable, misdirected and anachronistic. while there are indeed greenhouse analogies in fourier’s writings, they are not central to his theory of terrestrial temperatures, nor are they unambiguous precursors of today’s theory of the greenhouse effect.” nevertheless, fourier clearly stimulated others to investigate the factors that determined the earth’s temperature. one such scientist was claude s. m. pouillet (1790– 1868), who in the 1830s developed a pyrheliometer and made the first quantitative measurements of the solar constant. in his 1838 article,7,8 “mémoire sur la chaleur solaire, sur le pouvoir rayonnants et absorbants de l’air atmosphérique, et sur la temperature de l’espace” (“memoir on solar heat, on the radiating and absorbing powers of the atmospheric air, and on the temperature of space”), pouillet credits fourier as being “the first who has had the idea of regarding the unequal absorption of the atmosphere as exercising an influence on the temperature of the soil.” pouillet regarded light rays and heat rays to be fundamentally different—“the rays of heat and of light may derive their origins from the same source, be emitted at the same time, and coexist in the same pencil of rays, but they preserve a distinctive character”—and as such could be thought of differently in how they interact with matter. this allows him to view the atmosphere as being “diathermanous,” meaning that light rays can pass through the atmosphere without heating it while heat rays are absorbed by it and warm it. thus, he writes: with regard to the solar heat no doubt exists: we know that in traversing diathermanous substances it is less absorbed than the heat which is derived from different terrestrial sources, the temperature of which is not very high. it is true that we have been able to make the experiment only upon liquid or solid diathermanous screens; but we regard it as certain that the atmospheric stratum acts in the manner of screens of this kind, and that consequently it exercises a greater absorption upon the terrestrial than upon the solar rays. that is, some component of the atmosphere absorbs heat emanating from the earth’s surface resulting in an overall warming of the planet. neither fourier nor pouillet had any idea what that component of the atmosphere might be. of glaciers and ice ages questions about the earth’s temperature also were stimulated in the first half of the 19th century by the then radical idea that the earth had experienced numerous ice ages during its history. geologists had taken note of large boulders scattered across much of europe far from the mountains from which they had originated. how did they get there? one explanation was noah’s flood. another was violent volcanic activity. jean de charpentier (1786–1855), a german-swiss mining engineer and geologist who studied swiss glaciers, proposed that these so-called erratics had been carried to their locations by glaciers that had once been much more extensive than at that time.9 he did not know how the glaciers had formed, moved, or what had happened to them. credit for the idea of ice ages is somewhat controversial.10 the german botanist karl friedrich schimper (1803–1867) studied mosses growing on erratics and, like charpentier, wondered where the boulders had come from and concluded that they had been carried by ice. schimper spent the summer of 1836 in the swiss alps with his former university friend louis agassiz (1807–1873) and charpentier and together they developed the theory of successive glaciations covering much of northern europe, asia, and north america. schimper coined the term “ice age” (“eiszeit” in german) in 1837. the same year, agassiz, already renowned for his work in paleontology, presented the theory to the helvetic society. the theory was not well received as it conflicted with then current ideas about earth’s climate history. in 1840, agassiz published a two-volume work “études sur les glaciers” (“studies of glaciers”).11 the question, of course, was, if the idea of global ice ages was correct, what could possibly have caused the earth’s climate to shift so drastically to allow such mas30 rudy m. baum sr.30 rudy m. baum sr. sive ice sheets to form? it is a question that has still not been completely answered. john tyndall (1820-1893), an irish chemist and physicist, had a keen interest in glaciers and in heat flow. he was a careful and precise experimenter who had made his reputation with his studies of diamagnetism in the early 1850s.12 he was also an accomplished mountaineer who had made close studies of glaciers. in addition to a number of papers on glaciers—he coauthored “on the structure and motion of glaciers” with thomas huxley in 1857—he wrote “glaciers of the alps: being a narrative of excursions and ascents, an account of the origin and phenomena of glaciers, and an exposition of the physical principles to which they are related” in 1860. tyndall began his experiments on the absorption of heat by gases in early 1859. his biographer, roland jackson, writes: his interest had a long gestation. … he had considered the topic for several years; he read macedonio melloni’s work on the absorption of heat by liquids and solids around 1850, and frequently discussed the issue with friends. his work on glaciers rekindled that interest. he had explored the existence of air bubbles in ice, the conduction of heat through ice, and the formation of flower-shaped structures in ice by a focused beam of light. now his attention turned to the atmosphere, to examine its interaction with solar and terrestrial radiation, and to investigate the remarkable condition of temperature in mountain regions. his aim was to do for gases what melloni had done for liquids and solids. there was further motivation. he was convinced that not only the physical but also the chemical composition of substances—and specifically their molecules—played a part previously unrecognized in radiation and absorption. he would be probing the nature of molecules themselves using radiation.13 tyndall’s skill as an experimentalist allowed him to succeed where melloni had failed in measuring how different gases interacted with heat radiation. tyndall built the first differential spectrometer.14 it consisted of a long tube that he filled with the gas under study. the ends of the tube were capped with slabs of rock salt, which is transparent to infrared radiation. a precision heat source emitted radiation that traversed the tube and interacted with the gas before entering one cone of a differential thermopile. another heat source emitted exactly the same amount of radiation directly into the other cone of the thermopile. the thermopile was connected to a galvanometer, which measured small voltage differences. a voltage measurement indicated that the gas under study had attenuated the passage of radiation down the tube. tyndall quickly discovered that dry air is transparent to heat radiation and that both water vapor and carbon dioxide absorbed it. he announced his results to the royal society and followed with a “discourse” to the royal institution, “on the transmission of heat of different qualities through gases of different kinds.”15 he had demonstrated that a number of gases absorbed heat, although the only one he specified in his report was “coal gas,” a mixture of carbon monoxide and methane. he concluded: “thus the atmosphere admits of the entrance of the solar heat; but checks its exit, and the result is a tendency to accumulate heat at the surface of the planet.” tyndall continued his research on gases into the 1860s.16 he showed that water vapor, co2, and numerous hydrocarbons absorbed heat radiation and that absorption was proportional to density for small amounts of a gas. why were oxygen and nitrogen such poor absorbers of radiant heat? as jackson summarizes: tyndall thought that this might be due to their existence as single atoms—although we now know them to be diatomic—and that the far stronger power of other substances, such as water, carbon dioxide, and coal gas, was figure 2. john tyndall (1820–1893). credit: wellcome collection, cc by. 31200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer 31taking the earth’s temperature due to their molecular structure as oscillating systems of atoms. these compound molecules, tyndall imagined, ‘present broad sides to the ether,’ unlike the simple individual spherical atoms. they have more sluggish motions, so tend to bring the period of oscillation into synchrony with the slower undulations of radiant heat compared to those of visible light.17 tyndall realized that water vapor, because of its relatively high atmospheric concentration compared to other trace gases, was the most influential absorber of heat radiation in the atmosphere. in an 1863 royal institution discourse “on radiation through the earth’s atmosphere,” he stated: “this aqueous vapor is more necessary to the vegetative life of england than clothing is to man. remove for a single summer night the aqueous vapor from the air which overspreads this country and you would assuredly destroy every plant capable of being destroyed by a freezing temperature.”18 tyndall went on to probe the nature of heat radiation, which he referred to as “black” or “obscure” heat, beginning to break down the idea that visible light and heat are fundamentally different phenomena. he showed that heat radiation could be focused, that it could set paper ablaze, and that it could make metal glow with visible light, a phenomenon he referred to as “calorescence,” a counterpoint to “fluorescence.” in a presentation to the royal society in 1865, he showed that the maximum heat in the spectrum of an electric lamp was beyond the visible red.19 interestingly, although tyndall’s work has long been recognized as seminal in our understanding of the interaction of the atmosphere and solar radiation, he was not the first person to show experimentally that a trace constituent of the atmosphere could absorb infrared radiation. in 2010, raymond p. sorenson, a retired petroleum geologist, discovered the work of eunice foote (1819– 1888), an american scientist who in 1856 reported that water vapor and carbon dioxide absorbed heat radiation and in doing so warmed the atmosphere.20 foote speculated that a higher concentration of co2 could have been figure 3. 1: heat source. 2: heat screen. 3: thermopile, with conical reflectors. 4: galvanometer. 5: brass tube with rock salt plugs at each end. the tube contains the gas that is under study. 6: gas enters tube. 7: heat source. 8: manometer. 9: circulating cold water solves a heat conduction issue. 10: vacuum pump. 11: the gas or gas mixture can pass through some filtration process beforehand. 12: container of gas or gas mixture to be studied. 32 rudy m. baum sr.32 rudy m. baum sr. the cause of a much warmer climate earlier in earth’s history. foote’s paper, “circumstances affecting the heat of the sun’s rays,” was presented in august 1856 at the 10th annual meeting of the american association for the advancement of science by john henry, the founding director of the smithsonian institution. foote subsequently published a paper, “on the heat of the sun’s rays” in the november 1856 issue of the american journal of science & arts with a note that it had been presented at the aaas meeting.21 foote’s experimenta l apparatus, only vag uely described in her paper, was crude compared to tyndall’s. unlike tyndall, foote did not expose gases only to long-wavelength radiation, which is the basis of the greenhouse effect. nevertheless, in a recent paper, jackson concludes that foote “does seem to have been the first person to notice the ability of carbon dioxide and water vapour to absorb heat, and to make the direct link between the variability of these atmospheric constituents and climate change. for that she deserves proper recognition, even if she was not able to explore, and perhaps did not recognize, the distinction between solar radiation and radiated heat from the earth”.22 how cold? how warm? tyndall had concluded that earth would be a frozen wasteland without the greenhouse warming provided by water vapor, but he didn’t calculate what the earth’s temperature would, in fact, be without that cloak. nor did he try to calculate what change in atmospheric co2 levels could bring on an ice age. the swedish chemist, physicist, and mathematician svante arrhenius (1859–1927) is primarily remembered for his research on the conductivities of electrolytes, work for which he won the 1903 nobel prize in chemistry; and the concept of an activation energy, an energy barrier that must be overcome before two molecules will react. however, as with tyndall and many other 19th century natural philosophers/scientists, arrhenius’ intellect ranged widely. it was this diversity of talents and interests that led him to embark on what some now view as his greatest achievement, the mathematical analysis of the influence of co2 on the earth’s energy budget as detailed in his now-famous paper, “on the influence of carbonic acid [carbon dioxide] in the air upon the temperature on the ground.”23 while the work is now regarded as a seminal contribution to climate science, it was not recognized as such when it was published or for many years thereafter. arrhenius was a founding member of stockholm physics society, which drew a wide range of scientists to its fortnightly meetings to discuss topics ranging from physics to chemistry, meteorology, geology, and astrophysics, including the ice ages and what caused them.24 it was through meetings of the society that arrhenius formed a close collaboration with arvid högbum (1857– 1940), a geologist who studied the geochemical carbon cycle of the earth, especially how atmospheric co2 is influenced by the oceans, vegetation, and formation of carbonates. högbum believed that atmospheric co2 levels varied widely over geologic time and likely influenced climate. why focus on co2 when water vapor is much more prevalent in the atmosphere and a much more influential greenhouse gas? arrhenius realized that earth is a wet planet. water cycles in and out of the atmosphere continuously. co2, by contrast, remains in the atmosphere figure 4a. svante arrhenius (1859–1927). credit: university archives, universität würzburg. 33200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer 33taking the earth’s temperature for centuries. it acts as a “control knob” that sets the level of atmospheric water vapor. if atmospheric co2 levels dropped substantially, earth’s temperature would fall only slightly at first. but this lower temperature would result in less water vapor in the atmosphere, further lowering the earth’s temperature. arrhenius embarked on the laborious effort to develop equations to quantify how much atmospheric co2 would have to vary to bring about changes, both warmer and colder, that could explain the ice ages. as thomas r. anderson, ed hawkins, and philip d. jones point out in their paper “co2, the greenhouse effect and global warming: from the pioneering work of arrhenius and callendar to today’s earth system models”: 25 the calculations involved balancing the radiative heat budget (thereby assuming a state of equilibrium), namely solar radiation arriving at the earth’s surface (including the effects of albedo from clouds and the earth’s surface) and the subsequent absorption of re-emitted infrared radiation by the atmosphere. calculating this absorption required integration across the different wavelengths that encompass the absorption spectrum of co2 and water vapor, as well as integrating across different zenith angles … and the corresponding path lengths associated with incoming and outgoing radiation. by his own admission, the calculations were laborious, taking up a year of his time. in his 1896 paper, he wrote: “i should certainly have not undertaken these tedious calculations if an extraordinary interest had not been connected with them.” it is possible that he immersed himself in the work as an emotional escape from personal problems. that year, he went through a painful divorce after only two years of marriage from sofia rudbeck, a former student, losing not only his wife but custody of their young son. arrhenius made calculations for six scenarios, with co2 levels at 0.67, 1.0, 1.5, 2.0, 2.5, and 3.0 times the levels in the atmosphere at that time. his work showed that doubling or halving the amount of co2 would result in warming or cooling the earth by 5–6 °c. to lower the temperature the 4–5 °c needed to bring on an ice age, he wrote, would require co2 to drop to 0.62–0.55 of its 1896 level. what of global warming? arrhenius wasn’t too concerned because he thought it would require 3,000 years for humans burning coal to double the atmospheric level of co2. nor did he necessarily consider global warming such a bad outcome. in his 1908 book “worlds in the making,” which was written for a nontechnical audience, arrhenius wrote: we often hear lamentations that the coal stored up in the earth is wasted by the present generation without any thought of the future. … we may find a kind of consolation in the consideration that here, as in every other case, there is good mixed in with the evil. by the influence of the increasing percentage of carbonic acid in the atmosphere, we may hope to enjoy ages with more equable and better climates, especially as regards the colder regions of the earth, ages when the earth will bring forth much more abundant crops than at present, for the benefit of rapidly propagating mankind.26 arrhenius’ friend and collaborator, the swedish meteorologist nils ekholm (1848–1923), expressed a similar sentiment, saying that if “the present burning of pit-coal continues for some thousand years, it will undoubtedly cause a very obvious rise in the mean temperature of the earth,” and that, with this impact, coupled with humans tapping other sources of co2, figure 4b. first page of arrhenius’ groundbreaking paper. 34 rudy m. baum sr.34 rudy m. baum sr. “it seems possible that man will be able efficaciously to regulate the future climate of the earth and consequently prevent the arrival of a new ice age”.27 as it turns out, the temperature changes that arrhenius calculated are somewhat higher than the currently accepted range of 1.5–4.5 °c of warming that would result from doubling atmospheric co2.28 nevertheless, his accomplishment was remarkable given the tools and data at his disposal. one argument raised against arrhenius’ conclusions on the effects of atmospheric co2 is important because it was widely accepted at the time and because it is still raised by climate change deniers. not long after arrhenius published his results, another swedish scientist, knut ångström (1857–1910), who published the first infrared absorption spectrum of co2, argued that his work showed that the infrared absorption bands of the gas were completely saturated in the lower atmosphere. that is, the trace co2 already in the atmosphere was absorbing all of the infrared radiation that it was capable of absorbing, and that, therefore, adding more co2 could not change the earth’s energy balance.29 arrhenius strongly rejected ångström’s argument,30 but many other influential scientists of the day did not. as a result, practically no one took seriously arrhenius’ idea that burning coal and other fossil fuels could eventually result in a warmer earth, and no one paid much attention to the concentration of co2 in the atmosphere. the fallacy in ångström’s reasoning is that it treats the atmosphere with regard to infrared radiation as a single slab, much like the panes of glass in a greenhouse. in point of fact, this is where the greenhouse metaphor as an explanation of global warming breaks down. for the purposes of absorbing infrared radiation, the atmosphere must be viewed as consisting of many layers which get thinner, drier, and colder at higher and higher altitudes. earth’s temperature is controlled by these thin upper layers where radiation escapes easily into space. adding co2 to these layers does change the planet’s energy balance. as infrared radiation leaving the surface of the earth moves up through the layers of the atmosphere, some of it is absorbed at each layer. the layer of air radiates some of the energy back toward earth’s surface and some toward higher layers. in the topmost layers where heat radiation from lower layers slips easily through into space, adding co2 means the layer will absorb more radiation and warm, thus shifting to even higher layers where radiation escapes into space. adding greenhouse gases to the atmosphere effectively increases the pathlength infrared radiation takes before escaping into space, changing the equilibrium of energy arriving and departing the planet. instead of the metaphor of a greenhouse, a more accurate analogy is that adding co2 and other infrared absorbers to the atmosphere has the effect of placing a thicker blanket around the earth. (which, like all metaphors for atmospheric dynamics, isn’t entirely accurate, either.) the oceans as a co2 sink there were other substantive objections to arrhenius’ argument that co2 could influence earth’s climate. one was related, in a way, to ånström’s objection that the co2’s infrared absorption was saturated in the lower atmosphere. co2 absorbs infrared radiation in a few narrow bands while water vapor’s infrared absorption bands are broad and largely overlap those of co2. thus, this reasoning went, more co2 in the atmosphere could not affect the absorption of radiation already entirely absorbed by water vapor. this argument, although widely accepted, fails for the same reason ångström’s objection fails: what is critical is the co2 in the dry, cold upper layers of the atmosphere. moreover, in the thin upper atmosphere the absorption lines of both molecules narrow and become better defined, and here the overlap between the two spectra is not complete. yet another argument raised against arrhenius was that the oceans would absorb the vast majority of co2 released by all sources. it was known that there is 50 times more co2 dissolved in the oceans than is present in the atmosphere. however, the dynamics of the equilibrium between atmospheric co2 and co2 dissolved in ocean water are complicated and were not well understood. most scientists simply assumed that ocean water represented an essentially infinite reservoir for the co2 humans were pouring into the atmosphere from burning fossil fuels. earth’s climate, the argument went, was a selfregulating system that naturally remained at equilibrium. these objections to the notion of anthropogenic climate change mitigated against research into the field for most of the first half of the 20th century. there simply didn’t seem to be much point in probing what was an inherently complex system because the consensus was that there wasn’t anything to discover. scientists are loath to waste their time on questions that have already been answered. guy stewart callendar (1898–1964) did not subscribe to the consensus view and developed data to challenge it. a british steam engineer with a lifelong passion for a wide variety of scientific topics, callendar took up meteorology and climatology as a hobby.31 callendar compiled temperature records from the late nineteenth century through the 1930s and detected a 35200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer 35taking the earth’s temperature warming trend over a 50-year period. he also evaluated old measurements of atmospheric co2 concentrations and, although these were crude, concluded that the concentration of the gas had increased by 6% between 1880 and 1935 and that this could account for the observed warming. the increased atmospheric co2, he argued, was consistent with combustion of fossil fuels which had added about 150 billion tons of the gas to the atmosphere, about three quarters of which, he estimated, remained there. he published his findings in a 1938 paper “the artificial production of carbon dioxide and its influence on temperature”.32 the opening paragraphs of callendar’s paper neatly summarize the then-accepted consensus and his own challenge to it: few of those familiar with the natural heat exchanges of the atmosphere, which go into the making of our climate and weather, would be prepared to admit that the activities of man could have any influence upon phenomena of so vast a scale. in the following paper i hope to show that such an influence is not only possible, but is actually occurring at the present time. it is well known that the gas carbon dioxide has certain strong absorption bands in the infra-red region of the spectrum, and when this fact was discovered some 70 years ago it soon led to speculation on the effect which changes in the amount of the gas in the air could have on the temperature of the earth’s surface. in view of the much larger quantities and absorbing power of atmospheric water vapor it was concluded that the effect of carbon dioxide was probably negligible, although certain experts, notably svante arrhenius and t.c. chamberlin, dissented from this view. callendar did not accept the idea that the oceans would absorb most of the co2 being produced by burning fossil fuels. he felt that the relatively shallow surface waters of the oceans would become rapidly saturated with co2 and that it would take thousands of years for the ocean water to turn over and be fully exposed to the atmosphere. callendar published numerous papers on climate change, infrared radiation, and the carbon cycle between 1938 and his death in 1964. his ideas, however, were not taken seriously throughout much of that time by mainstream climate scientists. but his model was surprisingly accurate, given the resources he had at hand. a 2016 analysis of callendar’s work by anderson, hawkins, and jones asked, “what, then, would callendar have projected for global temperature rise during the twentieth century if he had correctly anticipated the increase in atmospheric co2, as well as taking into consideration the other greenhouse gases and aerosols?” using callendar’s equations, they showed that he would have predicted an increase in heating of “0.52 °c which is somewhat on the low side compared to the observed rise of 0.6 °c … a consequence of callendar’s model … not taking account of climate feedbacks (other than water vapour) that amplify warming. … nevertheless, we conclude that callendar’s model, in conjunction with realistic forcing, performs remarkably well when used to project climate warming during the twentieth century”. 33 as anderson, hawkins, and jones note in their paper, a source of uncertainty in callendar’s calculations was the role of the ocean as a reservoir for co2. callendar believed that the oceans did not absorb all of the co2 being produced by burning fossil fuels, but he had not demonstrated it. that task fell to one of the seminal figures of twentieth century climate science, roger revelle (1909–1991), director of the scripps institute of oceanography in san diego, and his scripps collaborator, hans seuss (1909–1993). before moving to scripps to work with revelle in 1956, seuss worked at the u.s. geological survey in washington, d.c. no one at the time knew whether co2 from burning fossil fuels was adding to the total amount figure 5. guy stewart callendar (1898–1964). credit: copyright university of east anglia, used by permission. 36 rudy m. baum sr.36 rudy m. baum sr. of co2 in the atmosphere. suess, working in collaboration with harold urey’s laboratory at the university of chicago, undertook a study of the concentration of 14c in wood harvested in the early 1950s compared to wood from the nineteenth century, prior to the advent of the industrial revolution. 14c is continuously being produced in the atmosphere by cosmic rays interacting with 14n. plants absorb the 14c and incorporate it into their tissues. because 14c has a half-life of only 5,730 years, however, fossil fuels contain an undetectable amount of the isotope. if co2 from burning fossil fuels were accumulating in the atmosphere, it should be reflected as a relative decrease in the amount of 14c in the modern wood compared to the nineteenth century wood. seuss’ work showed that this was, indeed, the case. the 14c concentrations in four nineteenth century wood samples varied only slightly, not more than 0.12%, seuss reported. by contrast, results for the modern wood “showed marked variations, always in the direction of a lower 14c content,” suggesting to seuss “relatively large local variations of co2 in the atmosphere derived from industrial coal combustion”.34 at scripps, revelle and seuss worked to determine the average lifetime of a co2 molecule in the atmosphere. their 1957 paper, “carbon dioxide exchange between the atmosphere and ocean and the question of an increase of atmospheric co2 during the past decades,” in a sense, marks the beginning of the modern age of climate science. the paper’s abstract concisely summarizes the situation humans faced: from a comparison of c14/c12 and c13/c12 ratios in wood and in marine material and from a slight decrease of the c14 concentration in terrestrial plants over the past 50 years it can be concluded that the average lifetime of a co2 molecule in the atmosphere before it is dissolved into the sea is of the order of 10 years. this means that most of the co2 released by artificial fuel combustion since the beginning of the industrial revolution must have been absorbed by the oceans. the increase in atmospheric co2 from this cause is at present small but may become significant during future decades if industrial fuel combustion continues to rise exponentially.35 revelle had studied ocean chemistry throughout his career. he realized that absorption of co2 by sea water was a complex process buffered by the various species the molecule adopts when it goes into solution—carbonate ion (co32-), bicarbonate ion (hco3-), and protonated carbonic acid (h3co3+)—and that the combination of dissociation constants limits how fast co2 can enter the ocean. revelle and seuss were very aware of the implications of their work. they pointed out in their paper that the united nations had estimated in 1955 that during the first decade of the 21st century fossil fuel combustion could produce co2 equal to 20% of that then in the atmosphere, which they estimated was something like two orders of magnitude greater than the rate of co2 production from volcanoes. the scientists famously wrote: thus human beings are now carrying out a large scale geophysical experiment of a kind that could not have happened in the past nor be reproduced in the future. within a few centuries we are returning to the atmosphere and oceans the concentrated organic carbon stored in sedimentary rocks over hundreds of millions of years. this experiment, if adequately documented may yield a far-reaching insight into the processes determining weather and climate. the keeling curve revelle and seuss concluded their paper with a focus on some of what still needed to be understood to know whether humans were changing earth’s climate: present data on the total amount of co2 in the atmosphere, on the rates and mechanisms of co2 exchange between the sea and the air and between the air and the soils, and on possible fluctuations in marine organic carbon, are insufficient to give an accurate base line for measurement of future changes in atmospheric co2. an opportunity exists during the international geophysical year to obtain much of the necessary information. the opportunity did indeed exist and revelle would set in motion a profoundly important set of measurements to answer what seemed to be a fundamental question: was the concentration of atmospheric co2 increasing because of use of fossil fuels? in fact, an even more fundamental question needed to be answered: what was the atmospheric concentration of co2? the literature stated that the concentration was about 300 ppm by volume, but published values ranged from 250 to 550 ppm. atmospheric scientists had even proposed using co2 concentrations as tags to track different air masses.36 revelle was one of the founders of the international geophysical year (igy) in 1957–58, an international effort involving 67 countries collaborating to make geophysical measurements over an 18-month period in 11 earth sciences, including meteorology and oceanography. revelle hired a young california institute of technology postdoc, charles david keeling (1928–2005), to nail down the atmospheric concentration of co2 and monitor it over time to establish whether humans were changing the composition of earth’s atmosphere. 37200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer 37taking the earth’s temperature keeling was an ideal choice for the work. he had received his ph.d. in chemistry with a minor in geology from northwestern university in 1953. his thesis had been in polymer chemistry and he had received job offers from a number of chemical companies on the east coast, which, to his thesis advisor’s consternation, he had turned down. in a charming 1994 extended autobiographical sketch,37 keeling wrote: “i had trouble seeing the future this way. i wrote letters offering my services as a ph.d. chemist exclusively to geology departments west of the north american continental divide. in general, i received back polite declining letters, but i got two offers.” he accepted one of them, an invitation from harrison brown (1917–1986) to become his first postdoctoral fellow in the newly established geochemistry department at caltech. at caltech, keeling developed instrumentation and carried out field observations to test an idea of brown’s: that the concentration of carbonate in ground water could be estimated by assuming that the water is in equilibrium with both limestone (caco3) and atmospheric co2. he did the field work in the pristine environment of big sur on the central california coast. keeling quickly discovered that the water in the stream he was monitoring was supersaturated with co2 and therefore not amenable to brown’s equilibrium hypothesis. he focused his attention on measurements of co2 in air because they showed an intriguing diurnal pattern: the air contained more co2 at night than during the day and the 13c/12c ratios in night and day air suggested that, during the day, plants at some sites reabsorbed co2 previously released into the air locally the night before. he also found that air in the afternoon always had nearly the same amount of co2, about 310 ppm, while concentrations at night were quite variable and always higher than during the day. keeling’s studies eventually resulted in job offers from the weather bureau in washington, d.c., and from revelle at scripps. once again, he chose the west and work in open spaces to the east and a cramped basement office. he moved to scripps in august 1956. in the year leading up to the advent of the igy in july 1957, keeling established co2 monitoring stations at the weather observatory on mauna loa in hawaii at an altitude of about 3,000 meters and at a u.s. weather station on the coast of antarctica. the measurements were made with a highly precise, continuously recording infrared gas analyzer. keeling had insisted on instrumentation with a precision of 0.1 ppm, which some critics thought unnecessary as they anticipated that atmospheric co2 concentrations would be highly variable. a number of issues arose at mauna loa in the fall of 1957 that prevented data from being collected. data collected in 1958 were somewhat patchy due to electrical outages and other issues, but a clear trend was evident: co2 concentration increased from january until may and then figure 6. the keeling curve through 2019. courtesy ralph keeling, scripps institute of oceanography. 38 rudy m. baum sr.38 rudy m. baum sr. began a steady decrease that lasted until late september when the trend reversed and the concentration began to increase once again. the variation was not insignificant, on the order of 6 ppm from the summer peak to the winter minimum. as keeling writes: “the maximum concentration at mauna loa occurred just before the plants in temperate and boreal regions put on new leaves. at mauna loa the regular season pattern almost exactly repeated itself during the second year of measurements. … we were witnessing for the first time nature’s withdrawing co2 from the air for plant growth during the summer and returning it each succeeding winter.” one other trend was immediately clear from the data: the atmospheric concentration of co2 was steadily increasing at a rate of 0.7 ppm per year.38 human beings, through their ravenous thirst for energy, were slowly but surely changing the chemical makeup of the atmosphere. keeling would continue measuring co2 at mauna loa for the remainder of his career, despite regular threats by various government agencies to cut his funding. since keeling’s death in 2005, the work has been supervised by ralph keeling, one of keeling’s five children, who is the principal investigator for the scripps atmospheric oxygen research group and the director of the scripps co2 program. the sawtooth, steadily rising plot of the co2 data is now known as the “keeling curve,” and has been called by many the single most important environmental data set of the twentieth century. on may 9, 2013, the co2 concentration on mauna loa passed 400 ppm for the first time, a dire milestone in human history.39 in the long quest to understand why earth’s temperature is what it is and whether human beings could affect earth’s climate, two things were now clear: co2 is a potent greenhouse gas and burning fossil fuels was inexorably increasing its concentration in earth’s atmosphere. one critical question remained: was earth’s climate heating up? the hockey stick accurate thermometer readings of earth’s temperature extend back only to the 1880s. in the 1930s, callendar believed that he had detected a slight increase in earth’s temperature over the 50-year period covered by that temperature record. many critics thought that callendar was simply wrong in this conclusion. others argued that, even if there had been an increase, it was part off the natural fluctuations one would expect of earth’s complex climate system. by the 1970s, the temperature record suggested a slight cooling trend over the previous several decades, and many observers declared that concerns about the buildup of co2 in the atmosphere were overblown. in 1975, wallace broecker (1931–2019), a distinguished climate scientist at columbia university’s lamont-doherty earth observatory, published what would come to be recognized as a groundbreaking paper in science, “climate change: are we on the brink of a pronounced global warming?” that strongly challenged this view. broecker wrote: the fact that the mean global temperature has been falling over the past several decades has led observers to discount the warming effect of co2 produced by the burning of chemical fuels. in this report i present an argument to show that this complacency may not be warranted. it is possible that we are on the brink of a several-decades-long period of rapid warming. briefly, the argument runs as follows. the 18o record in the greenland ice core strongly suggests that the present cooling is one of a long series of similar natural climatic fluctuations. this cooling has, over the last three decades, more than compensated for the warming effect produced by the co2 released into the atmosphere as a by-product of chemical fuel combustion. by analogy with similar events in the past, the present natural cooling will, however, bottom out over the next decade or so. once this happens, the co2 effect will tend to become a significant factor and by the first decade of the next century we may experience global temperatures warmer than any in the last 1000 years.40 broecker’s paper proved to be prophetic, as global temperatures almost immediately began to climb and have continued to do so ever since. as his 2019 obituary in the new york times pointed out, however, broecker based his predictions “on a simplified model of the climate system, and he later realized … that some of his analysis had been flawed. he would later write a follow-up paper stating that, as accurate as his prediction turned out to be, ‘it was dumb luck.’”41 nevertheless, broecker’s paper earned him the sobriquets “grandfather of climate science” and “father of global warming.” broecker’s analysis was theoretical. in his paper, he observed that, “meteorological records of the mean global temperatures are adequate only over the last century. … from this record alone little can be said about the causes of climatic fluctuations. it is too short and may be influenced by pollution.” but was the temperature record really so inconclusive? the national aeronautics & space administration’s goddard institute for space studies (giss) published its first global temperature analysis in 1987.42 giss scientist james hansen (1941–) and coauthor sergei lebedeff analyzed surface air temperature data from meteorological stations from 1880–1985 and found that the temperature 39200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer 39taking the earth’s temperature changes at midand high-latitude stations were highly correlated. “we find that meaningful global temperature change can be obtained for the past century, despite the fact that the meteorological stations are confined mainly to continental and island locations. the results indicate a global warming of about 0.5°–0.7 °c in the past century, with warming of similar magnitude in both hemispheres.” they continued that a strong warming trend between 1965 and 1980 “raised the global mean temperature in 1980 and 1981 to the highest level in the period of instrumental records.” hansen and lebedeff updated their analysis a year later, reporting that, “data from meteorological stations show that surface air temperatures in the 1980s are the warmest in the history of instrumental records. the four warmest years on record are all in the 1980s.”43 on june 23, 1988, hansen and other climate scientists testified on the possibility of anthropogenic climate change before the senate committee on energy & natural resources. hansen was more emphatic than any other witness, stating: i would like to draw three main conclusions. number one, the earth is warmer in 1988 than at any time in the history of instrumental measurements. number two, the global warming is now large enough that we can ascribe with a high degree of confidence a cause and effect relationship to the greenhouse effect. and number three, our computer climate simulations indicate that the greenhouse effect is already large enough to begin to affect the probability of extreme events such as summer heat waves.44 while stressing that global climate models needed improvement, hansen drew particular attention to the correlation between the observed warming in the temperature record and warming predicted by computer models of the climate. “since there is only a one percent chance of an accidental warming of this magnitude, the agreement with the expected greenhouse effect is of considerable significance,” he told the committee. although scientists had been discussing the possibility that co2 from burning fossil fuels could impact earth’s climate for decades, hansen’s senate testimony marked a turning point in the public perception of the figure 7. the hockey stick—time reconstructions (blue) and instrumental data (red) for northern hemisphere mean temperature. in both cases, the zero line corresponds to the 1902-80 calibration mean of the quantity. courtesy michael mann. 40 rudy m. baum sr.40 rudy m. baum sr. issue. nasa was 99% certain, hansen had testified, that a warming trend was occurring and that humans were responsible. the june 24, 1988, front-page story in the new york times on hansen’s testimony was entitled “global warming has begun, expert tells senate.”45 temperature records go back only about 140 years. climate change skeptics insisted that the changes hansen was seeing were not, in fact, indicative of a long-term trend. other scientists, however, were working to extend our understanding of the temperature of the earth over much longer time spans, over hundreds and even thousands of years into the past. the field of paleoclimatology uses indirect evidence provided by “proxy climate data”—oxygen isotope ratios from ice cores, tree rings, deep ocean sediments, corals, and other natural data—to estimate temperature changes in the past. in 1998, michael e. mann and raymond s. bradley of the department of geosciences at the university of massachusetts and malcolm k. hughes of the laboratory of tree-ring research at the university of arizona published “global-scale temperature patterns and climate forcing over the past six centuries,” in which they used proxy data networks to reconstruct earth’s temperature from 1400 to the present.46 a year later, they extended the analysis over the entire past millennium in “northern hemisphere temperatures during the past millennium: inferences, uncertainties, and limitations.”47 in his book “the hockey stick and the climate wars,”48 mann describes the data set that resulted from this work: despite the uncertainties, my coauthors and i were able to draw certain important conclusions. we deduced that there had been a decline in temperature from a period running from the eleventh century through the fourteenth—a period sometimes referred to as the medieval warm period—into the colder little ice age of the fifteenth to the nineteenth centuries. think of this as the shaft of a hockey stick laid on its back. this long-term gradual decline in temperature was followed by an abrupt upturn in temperatures over the past century. think of this as the blade. mann and his colleagues used actual temperature measurements to fill in the plot from 1980 through 1999 as relatively few long-term proxy records had been updated since the early 1980s. “thus was born the hockey stick—though the term itself was actually coined later by a colleague in princefigure 8. graph of average annual global temperatures since 1880 compared to the long-term average (1901-2000). the zero line represents the long-term average temperature for the whole planet; blue and red bars show the difference above or below average for each year. national oceanic & atmospheric administration. 41200 years of research has established why the earth is as warm as it is and how burning fossil fuels is making it warmer 41taking the earth’s temperature ton,” mann writes. “it didn’t take long for the hockey stick to become a central icon in the climate change debate. it told an easily understood story with a simple picture that a sharp and highly unusual rise in atmospheric warming was occurring on earth.” conclusion for 20 years, the hockey stick has drawn the scorn of climate change deniers. they insisted the blade of the hockey stick flattened in the 2000s as earth’s temperature increase seemed to pause, albeit at an elevated level. then the temperature began to increase again around 2010 and the blade still looks very much like a blade. when james hansen testified before the senate, he pointed out that the 1980s were the warmest years in the historical record. those days are long gone. according to noaa, 18 of the 19 warmest years on record have occurred in the twenty first century—the only outlier is 1998—and the past five years have been the warmest ever (figure 8).49 ocean levels are rising because the oceans are being warmed and are expanding and the greenland and antarctic icecaps are melting; oceans are also acidifying as they absorb excess co2. the large-scale geophysical experiment that revelle and seuss pointed to in 1957 is now well underway and climate change denial is both intellectually indefensible and morally reprehensible. any notion of a sustainable economy in the 21st century must center on energy, specifically weaning humanity from fossil fuels. other earth resources are under stress and must also be attended to, but earth’s climate is not just under stress. it is careening toward catastrophe. a sustainable world requires many adaptations, but chief among them is for humans to learn to power civilization with energy sources other than fossil fuels, primarily the sun. humans will have to learn how to live off the sun in real time. there is much work left to be done before earth’s climate is fully understood, but two hundred years of path-breaking research has made our dilemma clear. references the website the discovery of global warming” (available online), created by spencer weart and maintained by the american institute of physics, and wikipedia provided invaluable background information and references for this paper. 1. k. deffeyes, hubbert’s peak: the impending world oil shortage, princeton university press, princeton, 2001. 2. national oceanic & atmospheric administration. available online, last accessed on 26/02/2019. 3. j. fourier, ann. chem. phys. 1824, 27, 136. 4. j. fourier, mémoires de l’académie royale des sciences, 1827, 7, 567. 5. w. m. connolly, translation of j. fourier 1827 “memoire sur les temperatures de globe et des espaces planetaires, available online. 6. j. r. fleming, endeavour 1999, 23, 72. 7. c. pouillet, compt. rend. 1838, 7, 24. 8. english translation: c. pouillet in scientific memoirs, selected from the transactions of foreign academies of sciences and learned societies, and from foreign journals, vol. 4 (ed.: r. taylor), richard and john e. taylor, london, 1846, pp. 44–90. 9. t. r. anderson, e. hawkins, p. d. jones, endeavour, 2016, 40, 178. 10. e. p. evans, north american review, 1887, 145, 94. 11. l. agassiz, études sur les glaciers, neuchatel, 1840. 12. r. jackson, the ascent of john tyndall, oxford university press, oxford, 2018. 13. ref. 12, p. 155. 14. j. r. fleming, historical perspectives on climate change, oxford university press, oxford, 2005, pp, 68-71. 15. j. tyndall, proc. roy. inst. 1859, 3, 155. 16. j. tyndall, phil. trans. 1861, 151, 1; available online, last accessed on 08/08/2019. 17. ref. 12, p. 161. 18. ref 12, p. 174. 19. ref. 12, p. 185. 20. r. p. soresnson, search and discovery, 2018, article #70317, available online, last accessed on 24/01/2019. 21. e. foote, am. j. sci. art. 1856, 22, 382. 22. r. jackson, notes rec. 2019, doi: 10.1098/ rsnr.2018.0066, last accessed on 08/08/2019. 23. s. arrhenius, phil. mag. 1896, 41, 237. 24. e. crawford, arrhenius: from ionic theory to the greenhouse effect, science history publications, canton, ma, 1996, p. 145. 25. ref. 9, p. 181. 26. s. arrhenius, worlds in the making: the evolution of the universe, harper & row, new york, 1908, p. 63. 27. ref. 9, p. 181. 28. ref. 2 29. k. ångström, ann. physik, 1900, 4, 720, doi: 10.1002/andp.19003081208. https://history.aip.org/climate/index.htm https://www.climate.gov http://www.wmconnolley.org.uk/sci/fourier_1827/fourier_1827.html https://doi.org/10.1098/rstl.1861.0001 http://www.searchanddiscovery.com/documents/2011/70092sorenson/ndx_sorenson.pdf 42 rudy m. baum sr.42 rudy m. baum sr. 30. s. arrhenius, ann.physik, 1901, 4, 690. 31. j. r. fleming, the callendar effect: the life and work of guy stewart callendar (1898–1964), the scientist who established the carbon dioxide theory of climate change, american meteorological society, boston, 2007. 32. g. s. callendar, q. j. r. meteorol. soc. 1938, 64, 223. 33. ref. 9, p. 182. 34. h. seuss, science 1955, 122, 415. 35. r. revelle, h. seuss, tellus 1957, 9, 18. 36. d. c. harris, anal. chem. 2010, 82, 7865. 37. c. d. keeling, annu. rev. energy environ. 1998, 23, 25. 38. c. d. keeling, j. c. pales, j. geophys. res. 1965, 70, 6053. 39. r. showstack, eos, transactions american geophysical union, 2013, 94, 192. 40. w. s. broecker, science 1975, 189, 460. 41. the new york times, february 20, 2019, p. b15. 42. j. e. hansen, s. lebedeff, j. geophys. res. 1987, 92, 13345. 43. j. e. hansen, s. lebedeff, geophy. res. letters 1988, 15, 323. 44. statement of james e. hansen, director, giss, available online, last accessed on 20/02/2019. 45. the new york times archive, available online, last accessed on 22/02/2019. 46. m. e. mann, r. s. bradley, m. k. hughes, nature 1998, 392, 779. 47. m. e. mann, r. s. bradley, m. k. hughes, geophys. res. letters 1999, 26, 759. 48. m. mann, the hockey stick and the climate wars, columbia university press, new york, 2012. 49. ref. 2. https://climatechange.procon.org/sourcefiles/1988_hansen_senate_testimony.pdf https://climatechange.procon.org/sourcefiles/1988_hansen_senate_testimony.pdf https://www.nytimes.com/1988/06/24/us/global-warming-has-begun-expert-tells-senate.html substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 4(2) suppl.: 19-32, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-823 citation: b.w. ninham, m. shahid, r.m. pashley (2020) a review and update of bubble column evaporator processes. substantia 4(2) suppl.: 19-32. doi: 10.36253/substantia-823 copyright: © 2020 b.w. ninham, m. shahid, r.m. pashley. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. a review and update of bubble column evaporator processes barry w. ninham1, muhammad shahid2, richard m. pashley2,* 1 department of applied mathematics, research school of physical sciences, the australian national university, canberra, australia 2 school of science, university of new south wales, northcott drive, campbell, canberra, australia *corresponding author: r.pashley@adfa.edu.au abstract. this paper gives an updated review of the bubble column evaporator (bce) and its various new processes. these include recent work on helium gas desalination and high temperature inlet gas decomposition. the bce process offers a continuously produced source of high gas-water interface and consequently provides high overall heat and mass transfer coefficients. very different results have been obtained using nitrogen, oxygen, carbon dioxide and helium inlet gases. although the bubbling process itself is both simple to use and apply, our understanding of the fundamental physical and chemical principles involved is surprisingly limited and there are many issues yet to be explained. recently the process has been used to develop new methods for the precise determination of enthalpies of vaporisation (∆hvap) of concentrated salt solutions, as an evaporative cooling system, a sub-boiling thermal desalination unit, for sub-boiling thermal sterilization, for low temperature thermal decomposition of different solutes in aqueous solution and for the inhibition of particle precipitation in supersaturated solutions. these novel applications can be very useful in many industrial practices, such as desalination, water/wastewater treatment, thermolysis of ammonium bicarbonate (nh4hco3) for the regeneration in forward osmosis and refrigeration related industries. the background theories and models use to explain the bce process are also reviewed and this fundamental knowledge is applied to the design of bce systems and to explain recently explored applications, as well as potential improvements. many other prospective applications of the bce process are also reported in this paper. keywords: bubble column evaporator, sub-boiling, bubble inhibition, thermolysis, desalination, heat of vaporisation, supersaturation. 1. introduction to the bubble column evaporator (bce) double, double toil and trouble; fire burn: and, cauldron, bubble. the three witches of shakespeare’s play mcbeth: act 1v, scene 1 (1606) seem to be the first to have used hot bubble columns effectively. however, the witches use of various outrageous potions distilled from animals would be forbidden in our present politically correct society. nonetheless bubble column evapo20 barry w. ninham, muhammad shahid, richard m. pashley rators or bces are simple devices that have emerged as facilitators of powerful new technologies for aqueous systems in: • desalination (seawater and groundwater). • water sterilization (recycled water with no surviving pathogens including viruses). • thermolysis of solutes in aqueous solution (destruction of drugs, facilitation of high temperature reactions). • inhibition of salt precipitation in concentrated salt solutions. • evaporative air conditioning systems for buildings. the first three are now proven processes, and cheap at industrial scales. they represent encouraging progress in the search for clean water, arguably the biggest problem facing the world. 2. bubble column evaporators as conventional equipment by itself the bubble column evaporator (bce) is a good and faithful and apparently boring tool of chemical engineering. it employs gas-liquid interfaces to drive fundamental processes involving heat and mass transfer. bubble columns are devices in which a gas, often dry air, is pumped through a porous sinter disc to form gas bubbles in contact with the column solution. they are continuously replenished. dry gas bubbles in the column solution may be used simply to mix the liquid phase homogenously to attain uniform temperature distribution or to saturate dissolved gases in the column solution. substances can also be transferred from one phase to the other, for example, when liquid reaction products are stripped from a gas, where both mass and heat transfer processes can occur simultaneously.1 heat transfer using shell and tube heat exchangers is a fundamental chemical engineering process by which heat is transported between two fluids via a material having high thermal conductivity (i.e. copper, cu). heat transfer may also be accomplished directly by mixing the solution and the heating fluid (for example, water and hot air bubbles), to give so-called direct-contact evaporators. this concept of heat transfer via hot bubbles was first demonstrated by collier in a patent, published in 1887.2 the first commercial plant was installed in the usa in the early 20th century.3 there has been much attention on the industrial uses of bubbles columns in the chemicals industry, including a volume in chemical engineering technology in 2017.4 much work has also been carried out on the difficult area of numerical modelling of turbulent bubble column reactors.5 advantages of bubble columns, using direct-contact heat transfer, compared to other multiphase reactors are several: (a) less maintenance required due to the absence of moving parts, (b) higher effective interfacial areas and overall mass transfer coefficients can be achieved, (c) higher heat transfer rates per unit volume of the reactors can be attained, (d) solids can be handled without any erosion or plugging problems, (e) less floor space is occupied and bubble column reactors are less costly, (f ) slow reactions can be carried out due to high liquid residence time,6 and (g) the product can be recovered from the reaction mixture without additional separation operations.1 finally, and a glaringly obvious technology still to be exploited, high temperature reactions can be carried out at the surface of bubbles whilst maintaining a relatively low temperature in the liquid column. 3. extraordinary salt induced bubble fusion inhibition 3.1. new opportunities for the bce the bce is easy to use. but a theoretical understanding of processes involved is still embryonic. it becomes more difficult to understand when a new phenomenon is thrown into the mix. this is the phenomenon of bubble coalescence inhibition with addition of salt. this was first used experimentally by russian mineral coal flotation engineers more than 100 years ago. the addition of sufficient salt inhibits bubble-bubble fusion, produces smaller bubbles, and the efficiency of flotation was improved.7 more recently, aqueous bubble column evaporators have been used for a range of new applications based largely on the unexpected effects of many salts and sugars on inhibiting bubble-bubble coalescence in water, in combination with limited bubble rise rates and rapid water vapour uptake into the bubbles.8-13 the percentage of bubbles that fuse as a function of salt concentration as they ascend the column and the transition from 100% fusion on collision to zero fusion occurs over a narrow concentration range centered at the same 0.175 m for 1:1 salts. similarly for others like 2:1, 1:2, 3:1, 3:2 electrolytes and so on but at different concentrations. however, for other salts no such effect occurs.11,14-15 there are a set of rules that assign each ion pair to either class, and that allow prediction for outcomes with mixtures.11,14 there are no exceptions. the phenomenon occurs also for different isomers of sugars and other solutes.11 there is no theoretical explanation.14-15 classical theories of molecular forces (e.g. dlvo forces) would predict that increased salt ought to 21a review and update of bubble column evaporator processes reduce double layer forces between bubbles and enhance, not inhibit bubble fusion. with non-ionic solutes no electrostatic theory is relevant anyway. even more remarkable is that the fact that the ionic strength of blood is exactly the same critical concentration. there are good physiological reasons for this has recently been discovered.16 it is also the same concentration as that estimated for the permian ocean when land animals emerged. the absence of any theoretical explanation for the bubble coalescence phenomenon has not inhibited the development of a wide range of useful techniques. these include: • a new method for the precise determination of enthalpies of vaporisation (δhvap) of concentrated salt solutions;10,15 • evaporative cooling;10 • a new method for thermal desalination;17-19 • a novel method for sub-boiling, thermal sterilization;20-22 • a novel method for the low temperature thermal decomposition of different solutes in aqueous solution8 and • a new approach to aqueous precipitation in a controlled manner23 (see fig. 1). in addition to these methods, the thermal design of a bubble column condenser has also been studied for the production of high quality water as condensate.24-26 bubble coalescence behaviour is vital in water-based cleaning processes, ore-flotation, food processing, gas– oil separations, absorption and distillation.27 as discussed above, bubble coalescence inhibition depends critically on salt type as well as concentration.11, 28 salt solutions that do inhibit coalescence have recently been used in many applications, as illustrated in fig. 1. all attempts to explain the inhibition problem and its salt dependence with theory have failed. that is not surprising as the theories of forces in colloid science suffer from sins of omission and commission that are now as well documented as they are ignored. these are: 1. the ansatz of separability of electrostatic and dispersion forces. this violates two fundamental laws of thermodynamcs, even in the continuum solvent model, and dismisses specific ion effects. 2. hydrophobic interactions are ill defined and depend on dissolved gas.29 we can speculate that the theories fail because of the omission, not just of dissolved gas, but of the capacity of dissolved gas to self assemble into dynamic microstructures, just as do surfactants. nanobubbles seem to have critical nanobubble concentration cnc, which is salt and salt concentration dependent, just as do the cmcs of surfactants. such nanobubbles would inhibit fusion by depletion forces and adsorption at the macfigure 1. different applications of the bce process (reprinted by permission of the publisher, taylor&francis ltd, http://www.tandfonline. com, from m. shahid et al. 2015).8 22 barry w. ninham, muhammad shahid, richard m. pashley robubble surfaces. for a history of nanobubbles see ref 30. the bubble coalescence process is not obvious partly because it is also dependent on dynamic effects, since bubbles slowly forced together always coalesce in aqueous salt solution. 3.2. bubble evaporation layer model the deficiencies of the classical theories of forces does not inhibit us from applying thermodynamics to explore some important aspects of bubble column evaporators. the bubble evaporation layer model presented here is based on the estimated thickness of a heated water layer formed transiently around the surface of an initially dry, hot bubble. some of this water layer must be evaporated into the bubble to produce saturated vapour pressure, at that temperature. this surface bubble layer thickness is a function of temperature and bubble diameter. it will be useful in considering heat and mass transfer processes for desalination, sterilization and other applications. the bubble layer thickness (t bl) varies with temperature, and this model can be described by the following equation for situations where the evaporated film thickness is much less than the radius of the bubble: (1) where r is the radius of a bubble; is the water vapour density at the steady state column temperature and ρw is the liquid water density. eq. (1) shows that the bubble layer thickness is a function of steady state column temperature. as an example, for water the average evaporation layer thickness would be about 23 nm for an inlet dry air temperature of 200 °c, forming 1 mm radius bubbles. 3.3. bubble surface hot layer model water vapor is transported through the surface of a hot, dry bubble as it enters a bce. simultaneously heat will also flow to a thin water layer surrounding the bubble, as the bubble approaches steady state and cools to the temperature of the column solution. a transient hot water film will be produced around the bubbles flowing into a bce and this layer can be used to effect changes within the solution. it is therefore useful to consider the likely thickness of this heated layer as a function of inlet air temperature. these thermal effects appear to play a key role for heat transfer processes like sterilization20-22 and solute thermal decomposition.8 the maximum extent of the layer can be estimated for a given inlet air temperature. the estimate assumes that there is a linear decrease in the temperature of the surrounding water film from the bubble temperature to the column solution temperature. the thermal energy supplied to heat the water film must be supplied by cooling of the freshly released bubble. (note that the millimetre bubble surface can be considered to be flat relative to the thin, nanometre thickness of the heated water layer). in this simple model we consider the intermediate state when the inlet bubble (initially at a high temperature ti) has cooled from ti to tb (assumed to be 100 °c) and the heat transferred to the thin water film surrounding the bubble is sufficient to produce this temperature profile in the film. this amount of heat is the same as that required to heat a film of thickness δ from the column solution temperature tc to the average film temperature (tb+tc)/2. the bubble layer thickness varies with bubble radius, the temperature of the inlet gas and the steady state column solution temperature. a rough estimate of the heated layer thickness can be calculated using the thermal energy balance equation:8,20 cp∆tr=3cs∆tδ (2) where cp and cs are the air and solution (or water) specific heat capacities in j/m3k, respectively, and ∆t= – tc and ∆t=ti–tb are the transient temperature increase in the solution layer and the temperature reduction within the cooling bubbles, respectively. (note that in this approximate equation the value of cp should be taken as that at the average temperature of the cooling bubbles, i.e. at t=(ti+tb)/2 and the value of cs should be that at t=(tb+tc)/2). the volume of a layer of thickness δ around a bubble is given by 4πr2δ, when δ is much smaller than r. hence the cooling of the bubble by ∆t must determine the thickness δ. in addition, if we also assume that there is a 50% heat loss due to water vaporisation, then the thickness of the active hot region can be roughly estimated. for example, this approximate calculation indicates that for 1mm radius (dry) air bubbles, at an inlet temperature of about 200 °c, on cooling to 100 °c, forms a transient heated water film around the rising bubbles of about 50 nm thickness. this transient layer of heated water around the bubbles must be responsible for the sterilization effects20-22 and solute thermal decomposition effects8 recently reported when using inert gases, such as nitrogen. however, in addition to these thermal effects some gases also have specific properties which can also produce effects 23a review and update of bubble column evaporator processes on solutes and microorganisms in bubble columns. for example, recent results have shown that co2 inlet gas can be more effective at virus and bacterial sterilization and can even be effective at low temperatures.34 the use of hot, pure o2 inlet gas can also be used to enhance solute oxidation processes, whilst maintaining a relatively low bce solution temperature. 3.3. bubble water vapour equilibration it has been observed that fairly large air bubbles (1-3 mm) in water, which are used in the bce method, become non-spherical and oscillate both in shape and trajectory, thus enhancing the rate at which water vapour equilibrates within the bubbles.35 it is remarkable that water vapour saturation within these bubbles is attained in a few tenths of a second. it does so because of these oscillations and the circulatory f luid f low induced inside the bubbles due to shear forces generated at the surface of bubbles. this produces rapid water vapour transfer within the bubbles.36 the vapour transfer is much faster that that expected for quiescent diffusion, which would require several seconds to reach equilibrium according to fick’s law. this rapid vapour transfer must correspond to a similarly fast rate of transfer of heat to the surrounding column solution. it is these factors that form the basis for several recent applications (see fig. 1) of the bce process. 3.4. bubble rise velocity bubble rise behaviour in water, even for single isolated air bubbles, is surprisingly complex35,36 and depends on bubble diameter, sphericity and water purity.37 the presence of many other bubbles within a bce makes this situation even more complex and this has not been well studied. the rise of a bubble in a liquid is a function of many parameters viz. bubble characteristics (diameter and shape), properties of gas-liquid systems, and operating conditions, temperature, cleanliness etc. it was demonstrated by leifer et al.35 that the motion of intermediate (single, isolated) bubbles ranging from 1-3 mm diameter is produced by the combination of two oscillation types, trajectory oscillations (zig-zag or helical), and shape or deformation oscillations (ellipsoidal). these gas bubbles actually rise at a limited rate of between about 15 and 35 cm s-1 in quiescent water because they undergo trajectory and shape oscillations which reduce their rise rate.38 quinn et al.39 reported that the shape and velocity of ellipsoidal bubbles appears to oscillate in a fashion linked with increasing solute concentration. increased solute concentration creates more spherical bubbles with reduced rise velocity and a unique bubble shape. the rise velocity relationship is independent of solute type. it was also explained by gonzaleztello et al.40 that surfactants modify the surface of a bubble predominately through the adsorption of a monolayer. this produces a more rigid interface and so enhances fluid drag. the rise velocity in these solutions is less than for clean bubbles of the same diameter. luo et al.41 have studied the rise velocity of single bubbles in liquid-solid suspensions at pressures up to 17 mpa and temperatures up to 88 °c, over the bubble diameter range from 1 to 20 mm. it was found that the bubble rise velocity decreased with increasing pressure and with decreasing temperature. the decrease of bubble rise velocity was mainly due to the variations of gas density and liquid viscosity with pressure and temperature. many researchers have described several factors affecting bubble rise velocity.37 but the detailed understanding of bubble rise velocity and its associated parameters with regards to the bubble column evaporator method (bce) is yet to be thoroughly explained. stokes’ law was derived for spherical objects moving under high reynolds number and with zero slip boundary condition and gives rise rates substantially higher than those observed for air bubbles in water. unfortunately, the addition of slip boundary conditions would give even higher rise rates, such as those obtained using the hadamard-rybczynski (h-r)42 equation (see fig. 2 (a)). the levich43 formula gives results more closely resembling experimental rates and this is also given in fig. 2. eq (3) represents the general formula for the theoretical bubble rise calculation but unfortunately, none of these equations give an accurate explanation of air bubbles in the 1-3 mm diameter range of interest.35, 44 the general formula is given by the equation: (3) where u∞ is the bubble rise velocity in an infinite liquid, η is the coefficient of viscosity of the liquid, ρw is the density of the liquid, g is the gravitational constant, a is the gas bubble radius and k is a constant (2/9 for stokes equation, 1/3 for the hadamard-rybczynski equation and 1/9 for the levich equation) (see fig. 2 (a)). the three typical equations, discussed earlier, have closer agreement with the experimental results summarised by klaseboer et al. in fig. 2 (b)45 when bubble diameters are less than about 1.0 mm. 24 barry w. ninham, muhammad shahid, richard m. pashley the complex behaviour of bubble rise rates for isolated bubbles in the diameter range >1 mm will be further complicated by multiple collisions within a densely packed bubble column, where coalescence is inhibited by the presence of added salts. 3.5. thermal energy balance in the bce consideration of the steady state thermal energy balance within a bce, containing salt solutions can be used to explain the process whereby the heat supplied from the entering warm bubbles (per unit volume of gas leaving the column) is balanced by the heat required for vaporisation, to reach the equilibrium water vapour pressure within these bubbles. this principle is based on the steady state volumetric balance within a bubble column, which has been used for the determination of the enthalpy of vaporisation (∆hvap) of concentrated salt solutions,9-10,18 and is described by the following eq. (4): ∆t×cp(te)+∆p=ρv(te)×∆hvap(te) (4) where cp(te) is the specific heat per unit volume of the gas flowing into the bubble column at constant pressure; te is the steady state temperature near the top of the column; ρv is the water vapour density at te, which can be calculated from the water vapour pressure of salt solutions at the steady state temperature, using the ideal gas equation; δt is the temperature difference between the gas entering and leaving the column; δp is the hydrostatic differential pressure, between the gas inlet into the sinter and atmospheric pressure at the top of the column. this represents the work done by the gas flowing into the base of the column until it is released from the solution. this equation was first published in 2009 by francis and pashley10 for low vapour pressure aqueous solutions, that is, at low column temperatures of about 283 k. the equation’s accuracy and precision was further tested in later studies9,18 at room temperature. the units used throughout the equation are jm-3, which relates directly to the thermal energy transfer or work done per unit volume of gas flow passing through the column, at the steady state temperature of the column. once the steady state is reached, then assuming no heat losses to the environment, the cooling of each bubble entering the column exactly balances, on average, the latent heat required to vaporize water to reach the equilibrium vapour pressure with that bubble, at that steady state temperature. this thermal energy and work done per unit volume of gas, means that once the steady state temperature is reached, the balance given in equation (4) is independent of gas flow-rate. however, the time taken to reach the steady state temperature will depend on the gas flow rate. in a more recent variation of this energy balance equation, use of the heat capacity per unit volume, cp, in volume-based units was replaced by the corresponding heat capacity per unit weight of gas (i.e. 1.005 j g-1 k-1 over 270-330 k46 for dry air), which is fairly constant with temperature. this gives a new version of the thermal balance equation: [∆t× (te)×mg]+∆p=ρv(te)×∆hvap(te) (5) where mg is the mass of air (or gas) in gram per cubic meter. this can be obtained using the molar mass of air (28.96 g mol-1) where the absorbed water vapour is subtracted from the total number of moles of gas within the figure 2. the relationship between rise velocity of isolated bubbles and bubble diameter using typical equations (a) and from models results (b) published by klaseboer e. et al.45 (reprinted from ref. 45, with permission from elsevier). 25a review and update of bubble column evaporator processes bubble per unit volume, using the ideal gas equation, at te and 1 atmosphere pressure. it should be noted that the mass of air or gas within a bubble remains constant as the bubble passes through the column. this equation appears to encompass a logical and reasonable thermophysical energy balance to describe the bce process, especially at higher column solution temperatures, where the water vapour pressure will be more significant. this model assumes that while bubbles are capturing water vapour and rising in the solution from their initial dry state to 100% water vapour saturation at te, they will expand further due to the water vapour captured into the bubbles but only the initial (and constant) mass of gas can supply heat to the column, to produce this level of evaporation. in both balance equations ∆hvap includes the work done by vapour expansion. however, for high gas temperatures and short bubble residence times, removing the water vapour expansion work produces a better fit when using eq. (5) to give eq. (6), which is adapted for no work of water vapour expansion and corresponds to the following equation: [∆t× (te)×mg]+∆p=ρv(te)×[∆hvap(te)–p∆v(te)] (6) hence, it appears that high temperature bubbles in short height column solutions (~5 cm) and short residence times appear to show no expansion due to vapour uptake (see fig. 3). on the other hand, low temperature experiments appear to correspond to a steady state condition in terms of not only temperature but also the bubbles’ vapour expansion. it is interesting that at low temperatures, eq. (6) produces low errors for calculated ∆hvap values, similar to those produced from eq.(4) and eq.(5), because the p∆v term has no significant effect on the calculation. it should be noted that since bubbles reach vapour and temperature equilibrium within a few tenths of a second, the column height becomes important. in this work we define a medium height column to be one where this equilibrium is just attained. it should be noted that use of , the heat capacity of the dry air under constant volume conditions (0.718 j g-1 k-1 for 270-330 k46) in place of the corresponding values gives inaccurate ∆hvap values at both high and low column solution temperatures. this indicates that atmospheric work done on the contracting, cooling bubbles must be transferred to the column and so must be included in the energy balance equations. based on the results obtained and the analysis of energy balances in the bce, the original balance eq.(4) was found to be accurate for the determination of ∆hvap values of salt solutions over a wide range of temperatures. in comparison, eq.(5) can only be used at low temperatures and eq. (6) is applicable to the special case of high inlet gas temperatures and short bubble residence times. although the original eq. (4) was derived for low temperatures, around room temperature, we have since shown that it also works well for very hot inlet gases.18 this is because any given bubble released into the column at high temperature (ti) will contract until it reaches the column solution equilibrium temperature te. the heat supplied by the bubble (of volume vb at temperature t) to the column, as it contracts, is given by the sum of cp(t) × vb(t) over the temperature range ti to te (i.e. ∆t). however, because the mass of gas in any given bubble remains constant, the value cp(t) × vb(t) is also constant for any bubble and hence the heat transferred to the column is given by cp(te) × ∆t, per unit volume, as given in eq.(4). the results obtained using inlet air temperatures at around 275 °c and for solutions ranging from 0.5-6 m nacl indicate that the amount of water carried over varied with different nacl concentrations, relative to the expected vapour carry over, obtained from the variable theoretical column temperature (i.e. since the theoretical column temperature varies with increasing nacl concentrations) and the corresponding vapour pressure. at the highest nacl concentration, 6 m, the calculated energy utilization at 275 °c was found to be about 29 figure 3. schematic diagram of a bubble column (reprinted by permission of the publisher, taylor&francis ltd, http://www.tandfonline.com, from m. shahid et al. 2015).8 26 barry w. ninham, muhammad shahid, richard m. pashley mj m-3 which indicates that the bce process can be an energy effective method, especially at higher solution concentrations and hence could be used for industrial applications. 4. applications of the bubble column evaporator (bce) the gas-liquid direct-contact bubble column evaporator is characterized by a continuously replenished, high gas-liquid interfacial area, which subsequently offers higher mass and heat transfer coefficients due to non-isothermal3 (i.e. localized evaporation) nature of the bce. it could be applied in many large scale industrial applications. we now spell out in detail current applications of the bubble column evaporator (bce) in aqueous systems: 4.1. determination of ∆hvap values for concentrated aqueous solutions using the bce method bubble coalescence inhibition and rapid vapour transfer both offer a novel application of the bce process for the precise measurement of ∆hvap values for concentrated salt solutions 3,6,15 where the vapour pressure values of salt solutions are known. ∆hvap values can be obtained from the volumetric energy balance within the column, operating under steady state conditions, as defined by equation (4), at ambient temperatures. in recent work9,17, ∆hvap values of various salt solutions at different concentrations have been obtained with accuracies, on average, within around 0.5-1.0% compared to the literature values for several salt solutions and demonstrate a measurement precision of between 0.1% and 0.9%. for relatively low column temperature studies, around room temperature, the two balance equations, discussed earlier, give similar results, i.e. within the 0.51.0% range, on average. the accuracy and precision of these ∆hvap measurements was recently further improved using vacuum insulation (which reduced thermal transfers with the room environment) of the bubble column and an automatic data acquisition system for temperature readings.17 under the steady state of the bce system, hundreds of temperature data can be acquired by computer within 0.5-1 hour and hence a large number of ∆hvap values can be produced using these energy balance equations. these ∆hvap values17 were found to pass the kolmogorovsmirnov test47 with high probabilities after standardization of data and supported the null hypothesis, that is, the normal distribution. typical examples are shown in the frequency histograms given in fig. 6.18 narrow confidence intervals (95%), say always around ±0.02 kj mol-1, also demonstrated the high precision of the bce method for ∆hvap measurement, as well as supporting the basic physics of the energy balance equation. at relatively higher operating or steady state temperatures, around 40 to 50°c, the bce method was still found to be suitable for determining ∆hvap values of the salt solutions. 4.2. bce for evaporative cooling the steady state operating temperature of an aqueous solution in a bubble column can be calculated using the volumetric energy balance equation (4). the relation between inlet gas temperature and column top temperature using known ∆hvap values and vapour pressure values for salt solutions or pure water, can be calculated for pure water and salt solutions. the steady state column solution temperature within the bce is a function of the temperature of the inlet gas.9,10 this cooling effect has led to the suggestion that the bce process could be used as a simple evaporative cooling system for buildings. this was earlier proposed by m.j. francis and r.m. pashley and published in 2009.10 when the bce process is used with some types of salt solutions, which have coalescence inhibition effects on the bubbles,28 it will produce a high volume fraction of small bubbles which will enhance the water vapour transfer into the bubbles. the solution with dissolved salt (nacl) at 0.5 m has a more efficient evaporative cooling effect and hence halves the time for the column to reach steady state conditions. as an example, inlet dry air at a temperature of 50 °c will cool the 0.5m nacl column solution to less than 20 °c. 4.3. seawater desalination using the bubble column evaporator the dynamic bce method has higher overall mass transfer and heat transfer coefficients, compared with the quiescent system.1 in this novel bubble column desalination system, water vapour can be captured and transported using a simple bce system operated at temperatures well below the boiling point. the inhibition of bubble coalescence in salt solutions enables the design of a bubble column with a high volume fraction of small air bubbles, continuously colliding but not merging. this produces a uniform and efficient exchange of water vapour into the bubbles, which together with the high bubble rising velocity, due to its shape and trajectory based oscillations, allows water vapour to be rapidly 27a review and update of bubble column evaporator processes absorbed into bubbles, condensed and then collected as pure water.17 the bce method for seawater desalination, was examined and patented in 2013.48 the process is, of course, a reduced version of the natural phenomenon in which air is used as a carrier gas for desalting seawater through the rain cycle. however, the bce process is based on the unexpected property of seawater in stopping air bubble coalescence11,28 because this facilitates a high packing volume of air bubbles, which are persistently colliding but are prevented from coalescing by the presence of salts. in addition, the bubbles produced in the 1-3 mm diameter range are ideally suited for rapid water vapour uptake.35 these factors form the basis of this enhanced process for the desalination of seawater. in addition, the bce process offers an efficient vapour transfer mechanism in a continuous f low, with the evaporative bubble column operating below the boiling point. this method provides a very high surface area of air/water interface continuously produced and managed, naturally, by gas bubbling in salt water, such as seawater, to improve the efficiency of evaporation and transportation of the water saturated vapour producing drinking water from seawater.36 in the first reported experiments,17 seawater was first heated to 70 °c then air bubbles ranging from 1-3 mm diameter were produced via a glass sinter (porosity no.2) and was passed continuously through heated seawater. after bubbling for 60 min, the temperature of the solution in the column had fallen to about 52 °c. the starting and finishing temperatures were used to estimate the theoretical yield expected for complete collection and condensation of the water vapour, at the average temperature of the column. the electrical conductivity of the bubble column solution was reduced from 49 ms cm-1 (seawater) to 6 µs cm-1 (well below the levels required for acceptable drinking water).17 one of the advantages is that renewable sources of energy (i.e. solar energy system) could easily be coupled with a bubble column system.17 4.4. enhanced supersaturated bubble column desalination in these experiments hot, dry, air bubbles ranging from 150 to 275°c at about 23 l min-1 were first passed through an empty dry bce column and then a known mass of the solution was quickly added. however, in these experiments 200 g of 0.5 m nacl was added with and without 0.002 g of a non-ionic surfactant (c12eo8). the temperature of the solution was then measured every minute throughout the 30 min bubbling runs. after 30 min, the column and remaining solution was detached and weighed. since the dry weight of the column was also known, the total amount of water vapour removed in each experiment was easily measured.17 the results obtained show that increasing the temperature of the inlet air increases the water vapour carryover expected from the column solution vapour pressure and the air volume passed. the results obtained also showed that with added surfactant the carryover increased even more. it seems likely that the use of the non-ionic surfactant, octaethylene glycol monododecyl ether (c12eo8), provides a monolayer coating at the surface of bubbles. thus, it appears that the packed mono-layer of surfactant molecules allows water vapour transport into the bubbles but inhibits this vapour from re-condensing on the interior, now hydrophobic, walls of the bubbles. hence, the surfactant layer acts like a “surface molecular diode”, which facilitates water vapour transport in one direction. this supersaturation of the air bubbles then produces increased water vapour carryover.17 4.5. enhanced bubble column desalination using helium as a carrier gas helium as inlet gas can increase the bce performance more than 3.3 times higher compared with expected equilibrium vapour pressure, which is significant. it suggests that he as a carrier gas could be a promising solution for efficient seawater desalination. it was suggested previously48,49 that a suitable clathrate-forming carrier gas might be used to vaporize water not as individual molecules but in clusters and so remove the high thermal energy required for vapour phase desalination. a clathrate-forming gas partially dissolved in the aqueous solution would equilibrate with the gas in the bubbles and produce water clusters in the highly turbulent water. so providing conditions that favour enhanced evaporation with lower temperatures.48 helium produces different lattice structures to capture water molecules in gas form with multiple cages over a wide range of pressure and temperature. this was found by employing optimising dynamic method to determine free gibbs energy of the he clathrate hydrates produced. results showed that among different he clathrate hydrates, si hydrate and filled ice ii are relatively metastable comparing to sii hydrate form.50 another possible explanation for the high performance of helium in the bce desalination is based on the simple idea that the continuous flow of heated he sparge gas breaks down a small proportion of the hydrogen bonding network within water molecules due to its small size. this would also reduce the δhvap value. for example, a decrease in hydrogen bonding of 3.6 to 3.2, due to 28 barry w. ninham, muhammad shahid, richard m. pashley a modest increase in temperature, of 0 to 70 °c, corresponds to a decrease in ∆hvap of about 3 kj/mol.19 the effect of this reduction can be roughly estimated using fundamental thermodynamics. that is from the standard equations of equilibrium: ∆g=∆h–t∆s and (7) ∆g0=–rtlnkeq↔keq=exp(– ) (8) it can be assumed that the entropy difference of conversion water to gas (liquid↔gas) will be constant for either air or he. so, any difference in vaporization entropy change for the two gases will be insignificant, that is: d(δs)=0 and eq. (8) becomes: d(∆g)=d(∆hvap) (9) given this and the water density ratio of he comparing to air (keq= =3.3), eq. (9) becomes: keq= =3.3=exp(– ) (10) in this equation, r is the gas constant and t is the average column temperature, and average d(∆hvap) is calculated to be -3 kj mol-1. the expected δhvap values for different column temperatures is, on average, about 43.4 kj mol-1, so with he experiments, a 7% reduction of δhvap is sufficient to explain the enhanced water vapour carryover.19 4.6. comparison and benefits the main advantages of the bce desalination system are its simplicity, resilience to feed water purity and the fact that it is a continuous and controlled, nonboiling process. these are clear advantages over the two most common seawater desalination processes currently used, that is seawater reverse osmosis (swro) and thermal desalination (such as msf). there is little room left for improvement in swro but thermal desalination methods can still be substantially improved. methods such as the bce which represent low capital investment do not rely on rare materials or complex manufacturing and ready use of waste heat and sustainable energy sources, such as wind power, offer fewer constraints than the other common processes. the main advantages in the bce system for water desalination are listed below. • the bce collects water vapour throughout the entire body of the salt solution as compared to msf, which uses only the surface of the heating plates as the main water vapour transfer site. • the bce process is uniform and controlled because it does not involve boiling. • very fast vapour collection of a few tenths of a second for 1-3 mm diameter bubbles. • high rising velocity of saturated bubbles within the bce system. • air f low produces continuously renewed bubbles and high surface area of evaporating surfaces. • no requirement for feedwater pre-treatment as in swro. • system is self-cleaning via the flotation process. • sub-boiling process easier to control compared with msf and doesn’t produce scaling. • can concentrate to a much higher level, up to 6 m nacl, than either swro or msf, i.e. produces higher recovery rate. • simple design will give low capital cost compared with msf. • single stage and continuous process produces high quality water. • well suited for sustainable wind power for air flow generation and use of waste industrial hot gases. • does not need vacuum pumps to reduce pressure and boiling point, compared with msf. • use of heated gas inflow offers an ideal process for control of column temperature and hence evaporation rate. 4.7. water sterilization using the bce the high heat transfer coefficients created within the bce system can be used to thermally destroy biological organisms well below the boiling point and it has recently been established that sterilization occurs due to transitory impact of biological species with hot gas bubbles by collisions with the heated air-water interface, although the column temperature remains low and actually even favours the growth of bacterial colonies present in typical contaminated water.21-22 in the first bce sterilization study,22 hot gas bubbles up to 150 °c were used and in a more recent study bubbles up to 250 °c21 were passed into a water column via a glass sinter with 40-100 µm pores. the effects of exposure on sterilizing water were examined with different time intervals and typical results showed that only 2 min flow of 250 °c air was required to destroy almost all of the coliforms in the solution. the degree of sterilization was determined using natural lake water heavily contaminated with coliforms from waterfowl and land run-off. these coliform counts, obtained through the membrane filtration method, were used to measure the degree of sterilization using hot gas bubbling under 29a review and update of bubble column evaporator processes a range of conditions but in all cases where the column solution temperature never exceeded the optimum growing temperature for the coliforms.21-22 the presence of a salt that inhibits bubble coalescence in the solution serves to preserve finer bubbles of the heated gas, enhancing the number of bubble collisions with the biological species by ensuring a higher gas-liquid contact surface area and higher surface area per gas volume which leads to improved sterilization rates. the use of added nacl enhances the rate of water sterilization as air bubbles more t y pica lly in t he approximate size range of 1 to 3 mm diameter increase the probabilities of bubble collisions with ty pically small microorganisms ranging from 2 to 5 µm in size. it is worth mentioning that after 2 mins very few coliform colonies were still observed for columns with added nacl in the solution, which produced the smaller bubbles. 4.8. thermolysis of solutes in aqueous solution thermal sterilization studies with the bce led to the suggestion that this process could also facilitate thermal decomposition of some solutes in aqueous solutions, even at lower solution temperatures and at a faster rate than is normally produced via the direct heating of a bulk solution. studies of the use of the bce process for the thermal decomposition of solutes have recently been reported.8,52 this study examined the thermal decomposition of ammonium bicarbonate (nh4hco3) in aqueous solution. this salt has been used for important applications, such as a draw solution in forward osmosis 53 and, more recently, in the regeneration of ion exchange resins.54 a second solute in widespread use is potassium persulfate (k2s2o8) which was also studied in aqueous solutions. this salt is often used as a radical initiator for the process of emulsion polymerization.55 4.8.1. decomposition of nh4hco3 solutions typical decomposition results obtained using different solution conditions8 clearly demonstrate that the bce process is much more efficient for nh4hco3 decomposition, especially compared with the standard method, which is, using a stirred water bath at the same solution temperature, of 45 °c. for example, in the bce process, 90% thermal decomposition of nh4hco3 was obtained after 30 min of bubbling of 150 °c air through 0.5m solutions.8 the initial high (2 m) concentration of nh4hco3 used in these bce experiments was found to inhibit bubble coalescence, producing small bubbles. however, after 30 min of the bce process, the significant reduction in nh4hco3 concentration produced larger bubbles of the same diameter as those observed in pure water, which also confirms the decomposition of nh4hco3 salt into ammonia and carbon dioxide gases.8 4.8.2. proposed mechanism of bce solute pre-heated gas bubbles introduced and passed through the aqueous solution, must produce a transient hot surface layer around each rising bubble. the transient hot surface layer will have a higher temperature than the average temperature of the aqueous solution. we believe that it is the interaction of the solute with this transient hot surface layer which results in the thermal decomposition of the solute, even when the average temperature of the aqueous solution remains below the temperature at which it would normally cause thermal/ chemical decomposition of the solute. for situations where thermal decomposition is either required very quickly or at reduced temperature, the bce method offers a new approach. 4.9. inhibition of particle growth in a bce at first, it might appear that the bce process, with continuous water evaporation via the rising dry bubbles, could be used to slowly increase supersaturation levels and hence cause precipitation. however, it was discovered23 using aqueous cacl2 and k2so4 mixtures that the bce process actually has a significant inhibition effect on the precipitation process, and as these particles grow the turbidity was monitored with time during the precipitation. in this case, with no added foreign nucleating particles, turbidity values within the bce solutions were fairly constant with time over more than 300 mins, even though in quiescent solutions, at this same supersaturation level, significant particle growth was observed much earlier. these results suggest that the high density of rising bubbles might disrupt sub-nuclei or molecular clusters in the solution during precipitation and, in addition, the charged surfaces of the bubbles might have a big perturbation on interacting ions involved in nucleation and growth. a similar phenomenon was reported by j. w. mullin and k. d. raven56-57 who found that an increase in the intensity of agitation does not always lead to an increase in nucleation, which might be explained by assuming that agitation can disrupt sub-nuclei or molecular clusters in the solution. stirred systems are also 30 barry w. ninham, muhammad shahid, richard m. pashley complex in that, for example, different types of impellers can have a significant effect on other process parameters of crystallization58 and can lead to the production of different crystal shapes.59 4.10. other potential applications the bce process, in addition to its applications in wastewater concentration, could at the same time be used to inactivate different types of viruses and enzymes in the wastewater. the bce hot air system could also possibly be used for the sterilization of dairy and dairy based products and could even be used for the production of chiral compounds. in addition, the bubble column system could be effective in treating water-based foods, beverages, blood and blood related products and it might also be employed in specific stages for the treatment of pharmaceutical products. the bce could also be used for carbon capture by adding surfactant to produce a continuous flow of co2 foam from hot waste industrial gases. this foam could be transported and then buried under pressure to reduce total volume and foam cell size for long term storage. 5. conclusions this updated review article examines the theoretical background and the applicability of the bce process to several important industrial applications. the design and development of the bce are established on the two main features (1) higher overall mass transfer coefficient and (2) efficient heat transfer coefficient, which is a prerequisite for different bubble column evaporator applications. it is argued that a thorough and in-depth understanding of the bce system, when used with aqueous solutions, is critically dependent on the physical properties of water. further detailed studies would be required to develop large scale industrial applications of this technique. acknowledgement the authors would like to thank the australian research council for funding this project. list of parameters, definitions and units (∆hvap): enthalpy of vaporization (kj/mol) cmc: critical micelle concentration of a surfactant (m) t bl: bubble layer thickness (m) (tc): is the water vapour density at the steady state column temperature (tc) (in mol/m3) r: radius of the bubble (m) ρw: is the liquid water density (mol/m3) cp and cs: are the air (at constant pressure) and solution (or water) specific heat capacities (in j/m3 k) δt: estimated transient temperature increase in the solution layer surrounding the bubbles (k) δt: temperature reduction within the cooling bubbles (k) δ: estimated heated layer thickness around partially cooled hot bubble (m) ti: initial bubble temperature (k) tb: temperature of partially cooled bubbles (in k) assumed to be equal to 100 °c tc: column solution temperature (k) u∞: is the bubble rise velocity in an infinite liquid (m/s) η: is the coefficient of viscosity of the liquid (nsm-2) ρw: is the density of the liquid (kg/m3) a: is the gas bubble radius in eqn (3) (m) g: is the gravitational constant (9.81m/s2) k: in eqn (3) is a bubble rise constant cp(te); is the specific heat per unit volume of gas at constant pressure and at temperature te (j/m3 k) te: steady state temperature of the solution in a bubble column (k) ρv(te): is the water vapour density at temperature te (mol/m3) δhvap(te): is the enthalpy of vaporization of water at temperature te (j/mol) δt: is the temperature difference between the gas entering and leaving the column (k) δp: is the hydrostatic differential pressure, between the gas inlet into the sinter and atmospheric pressure at the top of the column (pa) (te): mass heat capacity of gas at temperature te (j/kg k) mg : is the mass of air (or gas) per cubic meter at te (kg/ m3) p : gas pressure (pa) δv: change in gas volume at temperature te (m3) : the heat capacity of gas under constant volume conditions (j/m3 k) : the heat capacity of gas under constant pressure conditions (j/m3 k) vb: volume of a bubble (m3) rwhe: water vapour density from helium sparged solution (mol/m3) rwair: water vapour density from air sparged solution (mol/m3) r: gas constant (j/k mol) 31a review and update of bubble column evaporator processes references 1. p. zehner, m. kraume, bubble columns, ullmann’s encyclopedia of industrial chemistry, 2000. 2. a. h. luedicke, b. hendrickson, g. m. pigott, a method 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industrial applications, weinheim: john wiley & sons, 2013. 59. i. mukhopadhyay, v. p. mohandas, g. r. desale, a. chaudhary, p. k. ghosh, crystallization of spherical common salt in the submillimeter size range without habit modifier, ind. eng. chem. res., 2010, 49(23), 12197-12203. substantia. an international journal of the history of chemistry 1(1): 69-76, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-12 citation: v. schettino (2017) isaac newton and alchemy. substantia 1(1): 69-76. doi: 10.13128/substantia-12 copyright: © 2017 v. schettino.this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declares no competing interests. historical article isaac newton and alchemy vincenzo schettino university of florence e-mail: vincenzo.schettino@unifi.it abstract. isaac newton dedicated a good part of his activity to alchemical experiments. this article tries to discuss the motivations that drove newton to spend so much of his time in the laboratory: the search for a unitary vision of the forces acting in the macrocosm and in the microcosm, the belief on a hidden prisca sapientia in the occult philosophy to be rediscovered with a scientific approach and the dispute with materialistic philosophy. keywords. newton, alchemy, transmutation, cosmology, physics. 1. the spiritual side of alchemy in the popular imagination the idea of alchemy is mostly bound to current definitions that can be found in dictionaries or encyclopedias. for instance, the webster’s new world dictionary of american language reports that alchemy is: the chemistry of middle ages, the chief aims of which were to change the baser metals into gold and to discover the elixir of perpetual youth or seemingly miraculous change of one thing into another. alternatively, one can find that metaphorically alchemy can be intended as synonymous with subtle artifice or deception. if the story were as simple as this, alchemy would be reduced to a kind of philosophy or pseudo-science definitely passed away, albeit still of interest for a historical reappraisal. however, in that case it would be quite hard to explain how alchemy could have lasted for more than two millenia.1 in like manner it is quite surprising that the novel the alchemist, written in the 1980s by paulo coelho, had such an extraordinary success to sell more that 100 million copies, with translations in 65 different languages.2 yet, the novel is about an entirely alchemical journey. the story is about santiago, an andalusian shepherd boy. after a recurring prophetic dream santiago meets melchizedek, the misterious king of salem, who reveals that a treasure is waiting for him at the feet of the pyramids in egypt and gives him two magical stones, urim and tummim, that will show him the path to reach the treasure. [at the beginning of the story we find one of the key features of alchemy, the revelation]. santiago 70 vincenzo schettino sells the flock and leaves to africa, but is soon victim of a robbery and plunges into the deepest misery, remaining with only the two magic stones; it is the black phase of the opus alchemicum. but santiago succeeds in recovering a good economic condition by hard working for a crystal merchant until he gets in the condition to resume his journey through the desert. santiago makes three important meetings, the first with fatima, an arab girl with whom he falls in love. but he must leave fatima to continue his journey in search for the treasure. the second meeting is with an englishman who has studied alchemy and is travelling to meet a famous alchemist, 200 hundred years old. santiago learns some alchemy from the englishman and finally meets the alchemist who becomes his guide for part of the remaining travel. finally, and after many adventures, santiago gets to the pyramids and finds the treasure, but this is not the philosopher’s stone that transmutes metals into gold. what santiago will discover is the world language which is in all things and, understanding the nature, with this language he will realize his personal legend. the alchemical journey is thus the attainment of knowledge and a journey of purification and self-fulfillment: also the alchemist, indeed, though understanding the world language, though knowing how to transform lead in gold, lived in the desert. without a need to demonstrate to anybody his science and his art. while continuing on the way toward his personal legend, the boy had learned all needed to know and had experienced every thing he might have dreamed of. to better investigate this point let us try to read a brief passage from a treatise on alchemy:3 it is possible to create the medicine with different compounds, however it is a single matter and does not require any other extraneous thing, apart from some white and red ferment. pure and natural, the opus has no other manifestation; at right times different colours will appear. the first days it will be necessary to get up early and see if the vineyard is in flower; the following days it is necessary to see if it has changed into raven’s head. later it will change in different colours and among them one must look for the intense white because this is what we expect without error: our king, the elixir or the simple powder, soft to the touch, which has as many names as the things of the world ... if, apart from the hermetic language typical of alchemy,4 we simply dwell on the surface of such a description of alchemical procedures, it is apparent that alchemy is an antiquated, faded practice. however, when we consider that this excerpt is taken from the tractatus in arte alchemiae (treatise in alchemical art) attributed to saint thomas aquinas, one of the saints of the church and a leading philosopher of the middle ages, a reflection is in order. in fact, in thomas’ conception: laboratorium est oratorium (the laboratory is an oratory), which means that the exploration of natural elements that can be looked after in the crucible of the alchemical laboratory is only a pathway to a more substantial knowledge of the truth that is guaranteed by religion. for thomas alchemy was a moral and religious activity rather than simply a practical or scientific activity and this has been also the attitude of many other philosophers of the middle ages and of the renaissance. outside this context it would be quite impossible to figure out that a description of the search for the philosopher stone, usually taken as a foolish attempt of charlatans and visionaries, can be found in another treatise, de lapide philosophico (on the philosopher stone),3 attributed again to thomas: i also attempted to transform in gold our red sulphur, after boiling it in aqua fortis on low flame; when this water became red, i distilled it in the alembic and at the bottom of the retort a pure rubedo of the sulphur remained which i freezed with the aforesaid white stone to make it red. then i threw part of it over much copper and i obtained very pure gold. however, about this procedure i can only speak quite generally and in obscure word, neither i will reveal it here, in order that anybody wishing to operate will do it not before a full comprehension of the methods of sublimation, distillation, freezing, and of the shapes of the containers and quantity and quality of the flames. for thomas aquinas (1225-1274) alchemy was not a prosaic search for the philosopher stone but a quest of a divine spirit that, in a unified vision, permeates all nature in its material and spiritual manifestations. 2. isaac newton, the alchemist a similar attitude toward alchemy has continued a long time after the middle ages and is expressed in the following way by isaac newton in a letter of his correspondences: for alchemy does not trade with metals as ignorant vulgars think, which error has made them distress that noble science; but she has also material veins of whose nature god created handmaidens to conceive and bring forth its creatures... this philosophy is not of that kind which tends to vanity and deceit but rather to profit and to edification inducing first the knowledge of god and secondly the way to find out true medicines in the creatures ... the scope is to glorify god in his wonderful works, to teach a man how to live well ... this philosophy both speculative and active is not only to be found in the volume of nature but also in the sacred scrip71isaac newton and alchemy tures, as in genesis, job, psalms, isaiah and others. in the knowledge of this philosophy god made solomon the greatest philosopher in the world. isaac newton has been the founder of modern science and an advocate of the scientific rigour who expressed his working method by the motto hypotheses non fingo. newton was very meticulous in his researches and rarely completely satisfied with the obtained results. speaking of himself he said: i do not know what i may appear to the world, but to myself i seem to have been only like a boy playing on the seashore, and diverting myself in now and then finding a smoother pebble or a prettier shell than ordinary, whilst the great ocean of truth lay all undiscovered before me. yet, newton dedicated his time almost exclusively to alchemy for some 25 years, in the same period when he completed his philosophiae naturalis principia mathematica.5-8 initially, and for several years, he studied with great accuracy all had been published on alchemy, and unpublished works as well, making annotations and résumés and transcribing several texts (see figure 1). then he established and equipped his own alchemical laboratory and started to carry experiments. when newton died, in his library, among others, 169 books were found, 138 on alchemy and 31 on chemistry. actually, he always tried to consider separately experiments on chemistry and on alchemy. but many other books on alchemy may have been lost when newton moved from cambridge to london and, possibly, others were lost during a fire that occurred in his laboratory. newton never published anything on alchemy but he left notes and writings on alchemy for almost one million of words, a patrimony that has remained unexplored for a long time. the absolute commitment of newton to alchemical experiments has been described by his assistant humphrey newton:9 he very rarely went to bed, till 2 or 3 of the clock, sometimes not till 5 or 6, lying about 4 or 5 hours, especially at spring & ffall of the leaf, at which times he us’d to employ about 6 weeks in his elaboratory, the ffire scarcely going out either night or day, he siting up one night, as i did another till he had finished his chymical experiments, in the performances of which he was the most accurate, strict, exact: what his aim might be, i was not able to penetrate into but his paine, his diligence at those sett times, made me think, he aim’d at something beyond the reach of humane art & industry. ... about 6 weeks at spring & 6 at the ffall the fire in the elaboratory scarcely went out, which was well furnished with chymical materials, as bodyes, receivers, ffends, crucibles &c, which was made very little use of, the crucibles excepted, in which he {fused} his metals: he would sometimes, thô very seldom, look into an old mouldy book, which lay in his elaboratory, i think it was titled, – agricola de metallis, the transmuting of metals, being his chief design, for which purpose antimony was a great ingredient. near his elaboratory was his garden, which was kept in order by a gardiner i scarcely ever saw him do any thing (as pruning &c) at it himself. when he has sometimes taken a turn or two, has made a sudden stand, turn’d himself about, run up the stairs, like another archimedes, with an ε’ύρηκα, fall to write on his desk standing, without giving himself the leasure to draw a chair to sit down in. by the end of the 1670s and again around 1690s, newton got into a deep crisis from nervous breakdown and depression touching the madness as it is evident from several letters that he wrote in those periods. the causes of these crisis are not really clear. certainly newton was a brilliant man but his family and affective events were rather poor and may have been at the origin of these crisis. for the purpose of the present discussion it is of interest that a lock of newton’s hair has been analyzed and a high concentration of mercury, in particular, and lead has been found.10,11 from this result it has been hypothesized the newton’s illness was caused by mercury poisoning. but this inference does not seem certain since the reported symptoms do not seem to correspond to mercury poisoning. the high level of metals in the hair, however, once again demonstrates that newton spent a considerable time in the alchemical laboratory. to such an extent that john maynard keynes, the famous economist which at an auction bought a good part of the alchemical writings by newton stated that: figure 1. an autograph note by newton with the alchemical symbols in the liber mercuriorum corporum. partly taken from “the chymistry of isaac newton”. reproduced by permission of the provost and scholars of king’s college. 72 vincenzo schettino newton was not the first of the age of reason. he was the last of the magicians, the last of the babylonians and sumerians, the last great mind which looked out on the visible and intellectual world with the same eyes of those who began to build our intellectual inheritance rather less than 10,000 years ago. 3. the alchemy meets the mechanics newton applied to all his alchemical experiments with the same rigour as in his scientific experiments in mathematics, mechanics and optics and, as already noted above, his writings and notes in alchemy are quite consistent. david brewster, one of the first biographers of newton, accurately examined all his alchemical writings and, to his disappointment, had to observe that these investigations looked at variance with the idealized picture of newton as a great scientist:9 in so far as newton inquiries were limited to the transmutation and multiplication of metals, and even to the discovery of the universal tincture, we may find some apology for his researches; but we cannot understand how a mind of such power, and so nobly occupied with abstractions of geometry, and the study of the material world, could stoop to be even the copyist of the most contemptible alchemical poetry, and the annotator of a work, the obvious production of a fool and a knave. although brewster was still convinced that the purpose of newton, and of his other great contemporaries interested in alchemy, was to rescue alchemy from the condition of a process commencing in fraud and terminating in mysticism: the alchemy of boyle, newton and locke cannot be thus characterized. the ambition neither of wealth nor of praise prompted their study, and we may safely say that a love of truth alone, a desire to make new discoveries in chemistry, and a wish to test the extraordinary pretensions of their predecessors and their contemporaries were the only motives by which they were actuated, in practice, the alchemical writings were finally considered not fit for publication and were not included in newton’s opera omnia, as obscuring his fame as a scientist, to remain neglected until the twentieth century. the reasons why newton never published anything on his researches on alchemy may be various. in a letter to john conduit he states that: they who search after the philosopher’s stone by their own rules [are] obliged to a strict and religious life, which complies with the common attitude of alchemists that the secrets of the great work should not be revealed to non adepts. in a letter to the president of the royal academy, henry oldenburg, newton likewise recommends that boyle should not make the results of his alchemical researches available to the vulgar because: it may be an inlet to something more noble, not to be communicated without immense damage to the world if there should be any verity in the hermetic writers, therefore i question not but the great wisdom of the noble author will sway him to high silence till he shall be resolved of what consequences the thing may be either by his own experience, or the judgment of some other ... that is of a true hermetic philosopher ... there being other things beside the transmutation of metals (if those great pretenders brag not which none but they understand). apart from this general belief in secrecy, it is more likely that newton had been unable to sort from his alchemical experiments the answers he was actually looking for and probably wanted to include in the principia. so, the real question is about the actual motivations that made newton so deeply interested in alchemy. a hint to the problem can be found in the same newtons’s writings. in the preface to one of the editions of the principia newton writes: i wish that we could derive the rest of the phenomena of nature by the same kind of reasoning from mechanical principle ... for if nature be simple and pretty comfortable to herself, causes will operate in the same kind of way in all phenomena, so that the motion of smaller bodies depend upon certain smaller forces just as the motion of larger bodies are ruled by the greater force of gravity. it remains therefore that we inquire by means of fitting experiments whether there are forces of this kind in nature, then what are their properties, quantities and effects. after discovering the laws of gravitation governing the motion of the celestial bodies and of the planets, newton conceived the idea that the principles active in the macrocosm could have an equivalent in the microcosm: so far i have explained the system of this visible world, as regards the larger movements that we can easily observe. but any reasoning is valid for larger motions must be valid also for the smaller ones. the first rely on larger forces of attraction of larger bodies, and i think that the latter are dependent on smaller forces, for now not observed, between microscopic particles. newton’s attempt was to discover this equivalent in the crucible of the alchemist. in essence, newton was interested in a synthesis of all knowledge, a unified theory of the principles governing the universe. on the one 73isaac newton and alchemy hand this interest derived from the profound religious beliefs of newton, as described by yates:12 as a deeply religious man, ... newton was profoundly occupied by the search for one, for the one god, and for the divine unity in nature. newton’s marvellous physical and mathematical exploration of nature had not entirely satisfied him. perhaps he entertained, or half-entertained, a hope that the “rosicrucian” alchemical way through nature might led him even higher. in his search for a unified theory of the universe newton may have been attracted by the central concept of alchemy of a prima materia, a concept originally attributed to the greek philosophers and to aristotle,in particular, of a starting material at the origin of all the materials of the world (a kind of anima mundi). a pictorial representation of a kind of alchemical cosmogony in the frame of the four elements (earth, water, air, fire) or alternatively of the tria prima (salt, mercury, sulphur) is shown in figure 2. according to a definition attributed to arnaldo de villanova, there is in nature a certain pure matter that art (i.e. alchemy) can discover and bring to perfection such that it can convert to itself all the imperfect bodies of nature by contact. in the emblem xxxvi of his atalanta fugiens (see figure 3) michael maier represents the first matter as cubes that pervade all the world as explained in an attached epigram: the stone that is mercury, is cast upon the earth, exalted on mountains, resides in the air, and is nourished in the waters. maier also explains how to find the materia prima: all persons that have once heard of the name or power of the stone, unless they are altogether incredulous, ask presently where it may be found, that so they may run directly to it. the philosophers answer is twofold: first adam brought it with him out of paradise, that is, in you and in me, and in every man that, birds flying, bring it with them out of far countries. secondly, it may be found in the earth, mountain, air and rivers. which path therefore must be taken? i say, both, but in a different respect, although the last pleases us best, and seems most safe. but newton’s research for a unified theory through alchemy was unsuccessful and this is likely the reason why his alchemical results were neither included in the principia, nor published in any form. however, concerning newton’s interest in alchemy there are two more points deserving a discussion. a famous sentence by newton concerning his major scientific achievements reads: if i have seen further it is by standing on the shoulders of giants. figure 2. a picture of the unitary alchemical cosmology. figure 3. michael maier, atalanta fugiens – emblem xxxvi. see ref. 13. 74 vincenzo schettino a metaphor, first used in a more elaborate form by bernard de chartres: dicebat bernardus carnotensis nos esse quasi nanos, gigantium humeris insidentes, ut possimus plura eis et remotiora videre, non utique proprii visus acumine, aut eminentia corporis, sed quia in altum subvenimur et extollimur magnitudine gigantea14 this same metaphor has later been used by several great scientists to signify that the scientific progress is not simply the achievement of a single leading scientist but is rather a collective enterprise with contributions by a series of researchers from the same and from previous times. the underlying idea in newton’s understanding was that of a prisca sapientia. newton believed that in the earliest times the truth about the natural world was revealed and was in the possession of mankind and that, dissipated in the arcane philosophy, was to be sought in the wisdom of the ancients by a correct interpretation of the occult language of alchemy and the accurate interpretation of the sacred scriptures, as we have already quoted: this philosophy, both speculative and active, is not only to be found in the volume of nature, but also in the sacred scriptures, as in genesis, job, psalms, isaiah and others. in the knowledge of this philosophy, god made solomon the greatest philosopher in the world. the concept of a primeval revelation of the truth is a characteristic feature of the alchemical philosophy that we already find in the corpus hermeticum of hermes trismegistus, the supposed founder of alchemy: hermes saw the totality of things, and, seeing it, he understood; and with the understanding gained the strength to testify and reveal. he wrote down his thoughts and hid most of his writings, sometimes wisely keeping silent, sometimes talking, so that in the future the world would continue to look for these things. to unravel the secrets of the ancient wisdom and of alchemy newton proceeded with the same rigour as in the study of mechanics and optics. a second point worth to be remarked is that the idea of a unitary universe is in harmony with the transmutation of the elements, and of the metals in particular, a transmutation in which newton definitely believed as we can argue from this statement in opticks (query 31): the changing of bodies into light, and light into bodies, is very conformable to the course of nature, which seems delighted with transmutations. the unitary concept, in fact, implied the transformation and convergence of opposites like, for instance, it can be seen from figure 2 for fixed and volatile. indeed, in newton’s transcription from hermes trismegistus we find: that which is above is like that which is below and that which is below is like that which is above, to accomplish the miracles of only one thing. this was an essential point in newton’s ideas about gravitation. in fact, he realized that, although the laws of attraction between the heavenly bodies had been laid down, thus far i have explained the phenomena of the heavens and of our sea by the force of gravity, but i have not yet assigned a cause to gravity. indeed, this force arises from some cause that penetrates as far as the centers of the sun and planets without any diminution of its power to act, and that acts not in proportion to the quantity of the surfaces of the particles on which it acts (as mechanical causes are want to do) but in proportion to the quantity of solid matter, and whose action is extended everywhere to immense distances, always decreasing as the squares of the distances, the causes that maintained the planets in motion were not clarified: it is inconceivable, that inanimate brute matter should, without the mediation of something else, which is not material, operate upon and affect other matter without mutual contact … that gravity should be innate, inherent, and essential to matter, so that one body may act upon another at a distance, through a vacuum, without the mediation of anything else, by and through which their action and force may be conveyed from one to another, is to me so great an absurdity, that i believe no man who has in philosophical matters a competent faculty of thinking, can ever fall into it. gravity must be caused by an agent, acting constantly according to certain laws; but whether this agent be material or immaterial, i have left to the consideration of my readers. the existence of attraction forces between inanimate bodies at a distance, and not in contact through something intermediate, was not conceivable in the xvii century. the prevailing ideas were rather tied to the mechanist philosophy of descartes which denied the possibility of any occult force and assumed that the action only depends on contact. the universe is packed with tiny material particles in continuous motion and colliding to form vortices that transmit the interaction. on the contrary, newton refused this purely materialistic view thinking that the attraction occurred through something immaterial and that the motion of the planets was set 75isaac newton and alchemy by a divine willing. therefore, in newton’s view, the universe relied on the convergence of opposites, material and immaterial. the dispute about the two conceptions was harsh. from one side, the exaltation of newton’s figure could lead to things like the following drinking song: the atoms of cartes sir isaac destroyed; leibniz pilfer’d our countryman’s fluxions; newton found out attraction, and proved nature’s void spite of prejudic’d plenum’s constructions. gravitation can boast, in the form of my toast, more power than all of them knew, sir and on the other side we can find expressions of distrust of newton’s ideas of interaction through the vacuum: nor does great newton’s famous system stands, on one compact foundation, simply plann’d . . . reflect how vainly is that art employed, which founds a stately fabrik on a void; can less the fair result of sober thought, who builds on vacuum, merely build on nought the discussion on the alchemy of newton has been restricted to what we have called the spiritual side. but newton heavily worked on the practical aspects of alchemy in a more properly chemical approach with the usual rigour of his method. one aspect of practical alchemy has been the pretention of fools and imposters to obtain miraculous medicines and elixirs, to transform lead in gold and other wonders. as already noted, it has been for these aspects of alchemy that the newton’s work on alchemy has been neglected for a long time. however, the role of imagination and of at first sight improbable ideas for the progress of science should not be minimized. indeed, newton writes that: no great discovery was ever made without a bold guess. claude bernard (1813-1878), the french physiologist founder of the experimental medicine, referring in particular to chemistry, writes that: even mistaken hypotheses and theories are of use in leading to discoveries. this remark is true in all the sciences. the alchemists founded chemistry by pursuing chimerical problems and theories which are false. in physical science, which is more advanced than biology, we might still cite men of science who make great discoveries by relying on false theories. it seems, indeed, a necessary weakness of our mind to be able to reach truth only across a multitude of errors and obstacles. along the same lines, august kekulé turned into a legend his discovery of the cyclic structure of benzene (see figure 4) ascribing the discovery to a dream were a serpent, the ouroboros, appeared eating its own tail, again an image of opposites that meet. in a famous conference kekulé, after recalling the metaphor of sitting on the shoulders of giants, concluded exalting the dream and the imagination for the progress of science: let’s learn to dream, gentlemen, then perhaps we shall find the truth and to those who don’t think the truth will be given they’ll have it without effort but let us beware of publishing our dreams till they have been tested by the waking understanding. finally, the old dream of the alchemists to transmute one element into another has been realized in modern science, albeit not in the form they really looked for. the realization of today’s chemistry closer the to dream of the alchemists to transform a base into a precious, valuable material has been the obtainment at high pressure of diamond, the most precious stone, from graphite or carbon, the most worthless material. references 1. s. califano, storia dell’alchimia. misticismo ed esoterismo all’origine della chimica moderna, firenze university press, firenze, 2015. figure 4. the cyclic molecular structure of benzene and the ouroboros eating its own tail. image credit: haltopub / cc by-sa. 76 vincenzo schettino 2. p. coelho, the alchemist, harpertorch, new york, 1988. 3. tommaso d’aquino, l’alchimia ovvero trattato della pietra filosofale, newton compton editori, roma, 2006. 4. for example, the vineyard in flower stands for green, one phase of the colours of the opus alchemicum (the great work of alchemy), symbolizing the life force in the leaves of the plants, and the raven’s head stands for blackening, another important phase of the great work. 5. m. white, isaac newton. the last sorcerer, perseus books group, new york, 1997. 6. b.j.t. dobbs, the foundation of newton’s alchemy, cambridge university press, 1994. 7. b.j.t. dobbs, the janus face of a genius: the role of alchemy in newton’s thought, cambridge university press 1991. 8. p. fara, newton. the making of a genius, columbia university press, new york, 2002. 9. d. brewster, memoirs of the life, writings and discoveries of sir isaac newton, th. constable & co., edinburgh, 1855. 10. l.w. johnson, m.l. wolbarsht, notes rec. r. soc. lond. 1979, 34, 1. 11. p.e. spargo, c.a. pounds, notes rec. r. soc. lond. 1979, 34, 116. 12. f. a. yates, the rosicrucian enlightenment, routledge, london, 1972. 13. m. maier, atalanta fugiens, johann theodor de bry, oppenheim, 1617. 14. bernard the chartres said that we are like dwarfs, sitting on the shoulders of giants, such that we can see more things and farther away not quite by our own better insight or ability, but because we are brought to a higher position by the gigantic greatness. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments substantia. an international journal of the history of chemistry 6(2): 79-91, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1591 citation: michálek j., podešva j., dušková-smrčková m. (2022) true story of poly(2-hydroxyethyl methacrylate)based contact lenses: how did it really happen. substantia 6(2): 79-91. doi: 10.36253/substantia-1591 received: mar 01, 2022 revised: jun 26, 2022 just accepted online: jun 27, 2022 published: september 1, 2022 copyright: © 2022 michálek j., podešva j., smrčková m. d. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. true story of poly(2-hydroxyethyl methacrylate)-based contact lenses: how did it really happen jiří michálek, jiří podešva, miroslava dušková-smrčková* institute of macromolecular chemistry, czech academy of sciences, heyrovsky sq. 2, 162 06 prague 6, czech republic e-mail: jiri@imc.cas.cz, podesva.ji@seznam.cz, m.duskova@imc.cas.cz *corresponding author abstract. soft hydrogel contact lenses represent the most famous and commercially successful application of poly(2-hydroxyethyl methacrylate). the scarcely crosslinked network of this hydrophilic polymer finds its use also in many other fields, be it in (bio)medicine or technology. moreover, the polymer itself and its crosslinked forms, discovered more or less serendipitously in the early fifties by a group of czech chemists, is extremely interesting due to its exceptional properties: it readily swells in water, is optically clear, soft, biologically compatible, sufficiently strong, stable, gas-permeable, cheap, and easy to produce. looking for its as-yet undiscovered qualities and possible utilization still continues. the story of the invention of hydrogel contact lenses was referred to many times in various literary sources which, however, contain numerous errors and misinterpretations. in the present article, we put these records straight and present the correct chronology of the hydrogel contact lenses development including the dramatic patent litigation. a brief overview of the chemical nature, properties, and applications of the constitutive substance of the lenses, i.e., the hydrophilic methacrylate, is also given. keywords: hydrogels, contact lenses, intraocular lenses, poly(2-hydroxyethyl methacrylate), otto wichterle. 1. introduction modern hydrogels are usually tailor-made for the given purpose and application, be they synthesized by radical-initiated or stepwise processes, performed in a standard way, or by 3d printing. since the times of the invention of the first hydrophilic plastic “swellable perspex”, prepared by o. wichterle’s group in the 1960s using the radical polymerization of 2-hydroxyethyl methacrylate (hema),1 much effort has been devoted to a detailed study of this polymer. this was due both to its use for pioneering hydrogel contact lenses (the so-called “swelling plastic”) and to its interesting properties. poly(2-hydroxyethyl methacrylate) (phema) is distinguished by a good swellability (primarily in hydrophilic and partially also in hydropho80 jiří michálek, jiří podešva, miroslava dušková-smrčková bic media) and by a very good compatibility with living tissues. even after swelling in aqueous media it keeps its mechanical strength and flexibility and is stable in time. that is why this material has found so many applications. besides the medicinal use in the fields of ophthalmology, implants, or systems for drug transport and releasing, there are less known but no less successful uses for sorbents with a large intrinsic surface or separation monoliths in chromatography.2-4 thus, phema remains a subject of lively scientific interest, as indicated by the number of papers with this keyword, published every year. at the same time, it represents an important model polymer both for the scientific research of synthetic hydrogels and for biomedicinal applications, including testing experiments of tissue engineering. this paper brings information on the history of the research and applications of this unique monomer and its polymers, with special regard to hydrophilic contact lenses. it is the authors’ ambition to put some erroneous historical data straight. moreover, we consider it useful to briefly outline also the classification and history of the whole phenomenon of contact lenses. 2. exciting history of contact lenses in general what is the contact lens? the basic definition reads: contact lens is a small optical system placed directly on the cornea. all the issues and problems related to the contact lenses follow therefrom. contact lenses can be categorized in various ways. however, according to m. f. refojo,5 the fundamental division is based on the nature of the material. most simply, contact lenses could be distinguished into rigid ones and soft ones, the latter then into hydrophobic and hydrophilic. further categorization, necessary in connection with the development of new materials for contact lenses, is given in more detail in the appendix (tab.  i). in current sources, this division is, regrettably, often oversimplified. the idea of contact lenses is ver y old, reaching back as far as the 16th century and leonardo da vinci concepts, and its implementation is closely connected with the development of material science. various inventors tried to use a broad spectrum of materials for contact lenses. for example, when poly(met hyl met hacr ylate) (pmma) was introduced into the market (1933) and its relatively good biocompatibility was discovered, a way was opened for new medicinal applications of this plastic. thanks to its optical properties, pmma found its main use in ophthalmology (as a material for contact lenses, later for intraocular lenses, spectacles, etc.). this was the beginning of the era of polymers or covalent polymer networks in contactology, a brief history of which is presented in a tabulated form in the appendix (tab. ii).6-9 after pmma had been tested and finally abandoned, the following development of contact lenses was carried out to improve the properties of the lenses, namely, their permeability for gases (primarily oxygen) and also for water-soluble substances and ions. although both of these requirements were met excellently by hydrogels studied by wichterle and lím,1 another branch of the research continued towards the silicone elastomers (1965) which offered a high permeability for gases and showed good softness but were hydrophobic. these properties were then responsible for problems met when removing these lenses from the eye, namely, mechanical damage to a testing person’s cornea. as a consequence of this, contact lenses based purely on silicone hydrophobic elastomers are no more accessible in the common market.10 still another route of the development resulted in rigid gas-permeable (rgp) materials (1974), usually copolymers of alkyl methacrylates and siloxane methacrylates (possibly also fluoroalkyl methacrylates) which guarantee a high permeability for oxygen11 but are hydrophobic and do not allow the transport of watersoluble substances. diverse variants of high-swelling hydrogels for contact lenses have continuously been being developed which had, in dependence on the equilibrium water content, a higher permeability for both water-soluble substances and gases. in addition to the basic sparsely crosslinked phema, other glycol methacrylates were used, such as diethylene glycol methacrylate, triethylene glycol methacrylate, dihydroxyalkyl methacrylates (e.g., glycerol methacrylate), acrylamide, and, for ionogenic materials, also methacrylic acid sodium salt. besides the acrylic acid derivatives, also 1-vinyl-2-pyrrolidone and polyvinylalcohol found their use as materials for highswelling hydrogel contact lenses.12 thus, in the sixties and seventies, the development headed toward soft contact lenses based on phema or similar hydrophilic methacrylates, as will be discussed below. later, however, silicone hydrogel lenses of the first generation were developed and introduced (1998-1999, according to the territory) and became an important milestone. based on the first experience, the second generation arrived in 2004 and soon after (2006) even the third one. interestingly, the first relevant patent dates back to 1979.13 81true story of poly(2-hydroxyethyl methacrylate)-based contact lenses: how did it really happen 3. true story of soft phema-based contact lenses 3.1. origins of the idea the story of the origin of phema-based contact lenses from the primal idea to the invention itself and its putting into practice seems to be generally known. the discovery of the synthetic hydrogel based on sparsely crosslinked phema and its successful application as a biomimetic material for soft contact lenses are often mentioned in introductory parts of scientific papers. similarly, the pioneering article by wichterle and lím1 on the unexpected hydrophilic behavior of certain plastics and future possibilities of their biological applications, as well as the corresponding patents (see, e.g.,14) are frequently cited, too. however, although the history of the development of phema, its polymerization, and properties, as well as hydrogel lenses based on it, has been published many times in various literary sources, the interpretations very often digress from reality. hence, the following chapter aims to bring a systematic survey of events that led to the worldwide known invention and to the subsequent global development of soft contact lenses. the text is based on reviewed sources, otto wichterle’s book of memoirs,15 and a personal experience of the first author, i.e., his collaboration with the famous inventor for fifteen years. the primary impulse arose from a fortuitous meeting of prof. wichterle with dr. pur, the secretary of a certain committee for the application of plastics in medicine at the czechoslovak ministry of health care. by coincidence, in 1953, they traveled together by train and looked through an ophthalmological journal with an advertisement for a tantalum prosthesis to substitute the eyeball. as he later mentioned in his memoirs,15 wichterle had expressed an opinion that it would be more suitable to prepare such implants from biocompatible polymers and suggested an idea of three-dimensional sparsely crosslinked hydrophilic gels. this idea attracted wichterle’s attention so much that he started to put it immediately into practice in the department of plastics at the then czech technical university in prague, together with his younger colleagues, especially drahoslav lím. at that time, research on methacryloyl derivatives of oligoethylene glycol was already running with the aim to get new plastics for future biomedical applications. the first hydrogel prepared and identified by d. lím was crosslinked triethylene monomethacrylate, as described in a paper by j. kopeček.16 later, as mentioned in another paper by kopeček et al.,17 in 1953 d. lím succeeded in synthesizing the first hydrogels by the copolymerization of hema with ethylene dimethacrylate. in the same year wichterle, as the only inventor, submitted a patent application for an invention, in which he claimed the whole class of sparsely crosslinked hydrophilic polymers including a description of many potential uses including even contact lenses unless he (or whoever else) had prepared this material.15, 18 of course, this was a pure fantasy at that time but, as it turned out later, also a realistic prophecy. later on, this application was withdrawn and substituted by another one19, which finally led to a patent entitled “the way of preparation of hydrophilic gels”.20 in the meantime, however, patents were granted to translated versions of the applications with differing delays in various territories. for example, in great britain and the then federal republic of germany, it was granted still to the earlier application from 1953, while in other countries already to the one from 1955. that is why various literary sources differ in dating the origin of hydrogel lenses. since 1956 the contact lenses have been being prepared in wichterle’s lab in prague but their ridges were of poor quality so testing persons were able to tolerate them on their eyes only for a few minutes at most. in the meantime, however, part of the applied research was transferred under the supervision of the ministry of health (dental laboratory, prague). several good lenses could have eventually been selected from the production of this laboratory where they were being prepared in polystyrene molds (1957). the tests on patients (performed in the 2nd ophthalmology clinic at the general university hospital in prague, mr. dreifus, m. d.) proved that the soft hydrophilic lenses, prepared on a lab-scale but using ground glass molds, can ensure a very good correction of vision and are excellently tolerated (1959). we quote here from the paper cited above (entitled „hydrophilic gels for biomedical use“):1 “promising results have also been obtained in experiments in other cases, for example, in manufacturing contact lenses, arteries, etc.” that is why some sources proclaim 1960 as the year of the origin of soft hydrophilic lenses. till today, this publication has been cited almost 1100 times. however, most authors consider 1961 to be a true year of the origin of the hydrogel lenses. at the end of december 1961, prof. wichterle, using a czech-made children’s toy building set merkur (similar to the wellknown erector kit), assembled at his home a device for the spin casting of contact lenses and named it (with his typical sense of humor) the “lens-machine” (fig.  1, left). the principle of the spin casting consists in that the starting liquid polymerization mixture, dropped into a mold with a precise inner shape, is rotated by fine-tuned 82 jiří michálek, jiří podešva, miroslava dušková-smrčková number rpm. due to a combination of the mold shape, the centrifugal force, and the surface tension, a proper lens shape is formed and, aft er the polymerization is fi nished, the solid contact lens acquires also the desired optical properties. with this improvised pilot-plant device, the fi rst hydrogel contact lenses were produced (fig. 1, right). later on, but still before the end of the same year, wichterle patented a method to produce contact lenses.21 in this way, the patents protecting the material for contact lenses were complemented by those describing the production method and the foretold use of synthetic hydrogels for contact lenses came into existence. a typical appearance of a contact lens is in fig. 1. a meeting with g. nissel, a british producer of lathes and facilities for lathe-cutting of hard contact lenses, inspired prof. wichterle to submit another patent application of the invention to produce soft hydrogel lenses by turning from xerogel blocks, i.e., from prefabricated parts constituted by hydrogel in a dry state (fig. 2), followed by fi ne polishing and swelling the lathed lenses.22 in 1964 prof. wichterle met his license partners-tobe from the national patent development corporation (npdc, usa). during the negotiations, he took out a lens from his eye, put it down to the ground, trampled it, then picked it up, removed the dirt from it fi rst by fi ngers and then in his mouth, and fi nally put it back on his eye. th is impressed his guests enormously. in 1965, the fi rst license deal was signed between the then czechoslovak academy of sciences and npdc. later on, in 1966, npdc transferred the sub-license for soft contact lenses to bausch & lomb co. which started to produce them in the usa, to prepare the distribution network and the marketing support, while waiting for approval of the production from the food and drug administration (fda). th is was granted as late as 1972 but thanks to thorough preparation, bausch & lomb quickly penetrated the market and met a considerable demand for lenses. 3.2. fascinating lawsuit on the patent priority already at the beginning of the seventies, infringements of wichterle’s patents by some producers appeared and even the bausch & lomb co. took part in the litigations to save money for license fees. th ey used a tactic of denying the validity of wichterle’s patents with an argument of alleged pre-publication of some results and an absence of clinical tests. aft er npdc had requested wichterle’s personal participation and testimony in american courts, the lawsuits began. to make the long story short, we set aside complications and obstacles laid by czech communist authorities to block wichterle’s travel to the usa. fortunately, he was allowed to testify in the end. th ese legal disputes stretched till the beginning of the 80ies, although, thanks particularly to wichterle’s unambiguous replies to questions, became increasingly obvious that the validity of the patents will be confi rmed. by the end of 1976, despite this promising course, the czech side acceded to an out-of-court settlement, figure 1. replica of the building set merkur (improvised lens-machine) for spin-casting (left ), an example of a soft hydrophilic phemabased contact lens (right). 83true story of poly(2-hydroxyethyl methacrylate)-based contact lenses: how did it really happen and, for receiving an amount equal to the license income for one year, the czechoslovak academy of sciences, controlled by the communist regime, stupidly opted out of the contractual liability for the participation in the patent lawsuits. in this way, the czech side forfeited not only the license contracts but also the share of the proceeds of the lawsuit. in 1980, a radical turnaround happened in the lawsuit which meant a full victory because all disputed issues were explained and dr. dreifus, who had been apparently manipulated by the infringers, was convicted of false testimony. still, it had taken two years of thrilling waiting before the final verdict was delivered (1982). in the meantime, still in 1981, npdc made, probably as an expression of gratefulness to o. wichterle for his contribution to the victory at the court, a new license contract regarding the preparation of contact lenses by a photopolymerization initiated by uv radiation.20-22 license fees from this contract have been coming to the czech republic till 2000. 3.3. further development simultaneously with improving the quality of the contact lenses, also the means of maintenance of them had to be adapted to the newly developed materials. thus, the physiological solution, used in the beginning, was substituted by multipurpose solutions containing, e.g., a disinfection or conservation component, a buffer system, detergents, wetting agents, and auxiliary substances, such as those with chelating effects. similarly, the regime of wearing the lenses, as well as the planning replacement of them (rate), have been developing. in this way, the development resulted in disposable lenses. in the nineties (1993) a one-time non-recurring contract was made with south korean partners who took over a new lens-making machine (“lens machine”) of the carousel type with an electronic-pneumatic control of functions and documentation for innovative technological processes including a new version of the software (fig. 3). although the koreans paid for a corresponding part of the charges, they never started to produce so the fees derived from the number of pieces produced were never received by the czech side. prof. wichterle’s decease in 1998 sy mbolica lly closed the era of the early development of phemabased hydrogel contact lenses. in the same year, the first “silicone hydrogels”, constituted partly of polysiloxane chains, were introduced into the market. the polysiloxane structure, hydrophobic by nature, is made sufficiently hydrophilic by the covalent attaching of methacryloylated segments and other hydrofigure 2. special lathe for contact lens manufacturing (left) and the lathing of the contact lens from xeroblock. 84 jiří michálek, jiří podešva, miroslava dušková-smrčková philic vinylic polymers. 23 silicone hydrogel contact lenses arrived at their 3rd generation and the “tricks” of attaining hydrophilicity differ from generation to generation. the type dailies total one, which was introduced on the market in 2012, represents a unique type of lens with a swelling gradient. however, hydrogels based on polymethacrylates or poly(vinyl alcohol) still constitute a substantial part of the world’s production of contact lenses. supposedly, for some clients, they will remain a suitable variant of the ocular refraction defect correction. innovations still appear, for instance, the product called hy pergel from bausch & lomb, which is a bio-inspired hydrogel material containing 78% of water and showing an increased oxygen permeability (dk = 42  barrer). this multicomponent polymer formulated on the basis of hema, n-vinylpyrrolidone, and 2-hydroxy-4-tert.butyl-cyclohexyl methacrylate, and crosslinked by ethylene dimethacrylate and allyl methacrylate, contains also a uv stabilizer based on benzotriazole and incorporated in the chain by a methacryloyl substituent. undesirable drying of the lens surface made of a highly swelling material is prevented by a block copolymer formed by two outer blocks of poly(ethylene oxide) and a central block of poly(propylene oxide). the copolymer is terminated on both ends by two methacrylate groups, through which it is incorporated into the structure of the whole polymer network. contact lenses made from it were introduced in the market under the trademark biotrue oneday in 2014. 4. hema and its polymers 4.1. history of hema and phema the first notices on hema and its polymers date back to the thirties, namely in the us patent no. 2,129,722 entitled esters of methacrylic acid and registered on september 13, 1938, for john c. woodhouse as the inventor and dupont de nemours co. as the applicant.24 in several claims (1-4), esters of methacrylic acid and a series of aliphatic diols, triols or pentaerythritol, etc. are generally presented; among these alcohols, also ethylene glycol is mentioned. claim 8 is devoted solely to polymeric monomethacrylate prepared by heating the monomeric ester to 60-100  oc in the presence of dibenzoyl peroxide. although the monomer, the polymer, and their preparations were thus described, a real utilization of them came as late as during the systematic study of the hydrophilic structures performed by wichterle and lím.1,15 4.2. nomenclature, structure, and properties of the hema monomer the most frequently used, non-systematic but the deep-rooted name is 2-hydroxyethyl methacrylate (usually acronymed as hema), sometimes also glycol methacrylate. names like glycol monomethacrylate, hydroxyethyl methacrylate, ethylene glycol methacrylate, or 2-(methacryloyloxy)ethanol are also used. according to iupac, the systematic name is 2-hydroxyethyl-2-methylprop-2-enoate. to preserve intelligibility and to comply with the scientific community’s common usage, the name 2-hydroxyethyl methacrylate (hema) is used throughout the text; similarly, ethylene glycol will be used instead of the systematic 1,2-ethanediol. the structure of the monomer is presented in fig.  4 together with its basic physical properties. if not stated otherwise, the values correspond to standard conditions, i.e., 25 oc and 101.325 kpa.25 4.3. preparation of the hema monomer of the procedures to produce hema, two have been used on a larger scale. the czechoslovak patent was based on the reesterification of methyl methacrylate by glycol.26 this process led to a product with a relatively high content of diester (ethylene dimethacrylate causing a crosslinking during the polymerization), the concentration of which had to be decreased by subsequent purification procedures. in addition to that, the prodfigure 3. lens machine for spin casting, the carousel type from the nineties. 85true story of poly(2-hydroxyethyl methacrylate)-based contact lenses: how did it really happen uct contained traces of diethylene glycol methacrylate and diethylene glycol dimethacrylate (the latter being a crosslinking agent, too) but was free of methacrylic acid. nowadays hema is commonly produced by a reaction of ethylene oxide with methacrylic acid. the resulting product contains a low level of the crosslinking agent and traces of methacrylic acid (see, e.g.,27). 4.4. polymerization of hema the double bond of 2-hydroxyethyl methacrylate reacts readily under normal pressure in bulk or in a solution, similarly to other methacrylates. the temperature range of the radical polymerization of hema has its upper limit at ca. 160  oc; at this and higher temperatures, depolymerization of the polymer chain takes place. practically, the lower limit corresponds to the solidification (vitrification) temperature of the polymerizing system; however, it is possible to perform a redoxinitiated polymerization under the condition of the so-called cryogelation, i.e., at sub-zero temperatures, e.g. around -20  oc and in presence of a diluent, when interesting macroporous structures are formed in the resulting gel thanks to freezing of the diluent (typically aqueous) off the system.28 a living anionic polymerization of hema with a protected hydroxyl group has also been reported, 29,30 proceeding at much lower temperatures (40 to 80  oc) and yielding an isotactic polymer. in the latest decade, papers have been published reporting on the possibility to control the hema polymerization by the raft (reversible addition-fragmentation chain transfer)31 or atrp (atom transfer radical polymerization)32 methods. it is the aim of these controlled radical polymerizations to get a polymer with the distribution of molar mass narrower than that obtained by standard (uncontrolled) free radical polymerization and to possibly attach certain functional groups onto the chain ends. interestingly, the sparsely crosslinked phema (i.e., with the level of the crosslinker below ca. 1 mol.%) significantly swells in water attaining swelling equilibrium at approx. 36-38 wt.% of water at room temperature.33 the swelling behavior of the phema macromolecular network is very interesting and shows a certain “swelling anomaly”: the equilibrium swelling degree does not depend much on the crosslink density which is also true for a linear phema of a high degree of polymerization. phema belongs to the ucst-lcst1 system exerting swelling minimum at 55°c.34 4.5. physical prerequisites for making the perfect contact lens the phema-based hydrogel suitable for lenses (phema prepared with 38–40 wt.% of water and ca. 1 mol.% crosslinker) is characterized by some key properties such as the equilibrium content of water (approx. 38 wt.%), the oxygen permeability (8-12 x 10-11 barrer), and modulus of elasticity (typically 0.5-0.6 mpa).8,28 however, these parameters strongly depend on the starting conditions and exact way of hydrogel preparation, especially on the concentration of the crosslinking agent and diluent (water) at polymerization. here we focus solely on the microstructure and porosity. the phema hydrogels can be prepared either as macroscopically homogeneous (optically transparent) or, inversely, as a heterogeneous substance, showing a loss of transparency and a formation of opalescence, thus indicating refraction of light on microscopic interphases due to the formation of pores. at this point, our report deserves a more detailed explanation of the phema hydrogel optical clarity. in the early studies, when wichterle and his coworkers observed the first crosslinked phema gels, the pieces of water-swollen material were rather transparent and colorless. their observations were truly serendipitous as the material resembled clear glass and provided an index of refractivity very close to that of the biological cornea, so the ideas about a gel-based soft contact lens could be explored ever since. but it soon became evident that not always the free radical crosslinking of the hema-based system leads to an optically clear material and that there are critical limits of composition beyond which the resulting material turns irreversibly hazy, or completely non-transparent – and thus not useful for an optical lens. these “clarity limits” for hema-based systems were subjected to thorough experimental studies in the institute of macromolecular chemistry in prague in the 1970s. it was found that when the content of water as a diluent in the polym1 ucst – upper critical solution temperature, lcst – lower critical solution temperature o o oh figure 4. the schematic formula of 2hydroxyethyl methacrylate (properties: colorless liquid, density 1.07 g·cm-3, melting point 99 oc, boiling point 213 oc, vapor pressure 0.08 hpa). 86 jiří michálek, jiří podešva, miroslava dušková-smrčková erizing system exceeds ca. 50 vol.%, an opaque or white, or even porous heterogeneous material is obtained. indeed, the limits also correlated with the amount of crosslinker. the reasons for the existence of the limits were in the meantime explained by k. dušek who put forward the analysis of the formation of thermodynamic phases leading to the porosity of the crosslinking system styrene-divinylbenzene investigated for ion exchange resins.35 deeper studies of phema and its solution and gel properties continued in the seventies.36 dušek derived a generalized thermodynamic treatment for phase separation in a three-dimensional polymer system based on the analysis of the flory-huggins swelling equation and he coined the term microsyneresis (or syneresis). this term denotes a separation of phases in the so-called quasi binary system where the phase of the swollen gel separates from that of the diluent, the latter, however, possibly containing residua such as a soluble monomer or its oligomers. this separation is a consequence of the change of miscibility within the polymerizing system with conversion, so-called c-syneresis, and/ or is induced by increasing crosslink density, so-called n-syneresis.37 whereas hema monomer is unlimitedly miscible with water (starting state), the growing chains only have limited solubility in the water-hema mixture and limited entropy of chain arrangements (crosslinked state). microsyneresis in water-hema crosslinking system proceeds through the mechanism of the nucleation and growth which leads to a typical structure of mutually connected microscopic spheres providing a heterogeneous gel well visible in fig. 5. these gels, when swollen to equilibrium volume in water, macroscopically appear white or opaque – far from the perfectly transparent appearance necessary for a contact lens. interestingly enough, even standard hydrogel of composition used for contact lenses showed, already during polymerization, the formation of nanosized inhomogeneities, supposedly pores, of several typical dimensions between 1 and 10 nm.28 such inhomogeneities do not deteriorate the optical clarity of the final product but can enhance the transport of water, oxygen, and small ions. 38 microsyneresis provides an interesting and wellexplored way nowadays leading to a formation of porous systems, predominantly with communicating pores having their size in the range of 100-101  μm. it is a systemspecific thermodynamic phenomenon that can be predicted, is perfectly reproducible, and is inevitable within a certain compositional range. as mentioned above, the hema monomer always contains a little amount of bis-methacrylic units (ethylene dimethacrylate, edma). during the polymerization, edma is gradually incorporated through its two vinyl groups into the polymer chains so that the branching and, at higher degrees of conversion, also crosslinking inevitably takes place. during the development, various methods have been used to achieve the porosity of phema:40 besides the thermodynamic demixing, also introducing washable microparticles (porogen) into the gel matrix. in this way, interesting porous structures based on phema have been prepared, including (nano)fibers.41 also composites of phema, e.g. with bacterial cellulose, 42 or interpenetrating networks,43 as well as materials with dual porosity44 have been described. 5. phema – applications other than contact lenses 5.1. medicinal applications since the seventies, within the group of younger wichterle’s colleagues, there existed a lively activity in the field of biological application of phema materials other than ophthalmology.45 due to its good compatibility with living tissue, phema was predetermined for medicinal applications. during its decades-long history, this biocompatibility was proved beyond any doubt by its long-term use in this field. some later studies then confirmed that not only the high-molar-mass polymer of hema but also its very short chains (oligomers) are well biocompatible.46 in fact, phema has become a material of the first choice for biomedicinal applications, in particular for pilot experiments; subsequently, the material can be modified in many ways according to the needs of the particular application. thanks to their transparency, homogeneous hema polymers found their first medicinal applications in ophthalmology. in addition to the already discussed soft hydrophilic contact lenses which aroused a global response, phema has its history too as a material for intraocular lenses implanted into the eye during cataract surgery,47 artificial vitreous body, 48 etc. wichterle himself proposed many medicinal applications of phema which were put in practice more or less successfully. of the other applications, known are implants for otorhinolaryngology,49,50 plastic or general surgery,51 gynecology,52 urology,53 and neurology,54 as well as carriers for cell cultivation for dermal wounds healing, burns, or bedsores.55,56 polymers of hema are still used to prepare ointments/salves57 and various gel preparations,58 drug carriers,59 tissue expanders,60 synthetic emboli61, or hemoperfusion detoxicating columns.62 3d microstructured carriers for cell cultivation, known as 87true story of poly(2-hydroxyethyl methacrylate)-based contact lenses: how did it really happen scaffolds, have since recently been used. thus, phema has become a successful reference material also in the fields of cell therapy and tissue engineering. recently, with the development of additive manufacturing methods, hema finds its use as a photopolymerizing monomer in the resin compositions in stereolithographic 3d printing and 3d writing methods. it was used to constitute photopolymerizable ink for direct writing of 3d microarrays as scaffolds for neuronal cultures.63 5.2. technical applications to this category belong, e.g., (meth)acrylate coatings. phema of technical grade is being used as a part of single-component dispersion coatings (together with figure 5. porous hydrogels prepared from poly(2hydroxyethyl methacrylate) and visualized by the methods of scanning electron microscopy. (a) macroscopic view; (b) phema hydrogel showing after the microsyneresis a structure of connected spheres, (c) phema hydrogel prepared from poly(hema-stat-ma) (fractionated nacl was used as a porogen; after washing out the porogen, the gel was visualized by the aquasem method); (d) microscopic structure of a cryogel of hema showing the dual size of pores. figs 5b and 5d were obtained by the so-called environmental sem.39 a) b) c) d) 88 jiří michálek, jiří podešva, miroslava dušková-smrčková butyl acrylate or butyl methacrylate). as a comonomer, hema carries the functional reactive oh group into the polyol component of the two-component curable and highly resistant polyurethane coatings.64 another proven application, though not yet published, was the preparation of heterogeneous membranes with incorporated ion exchangers. the high adhesivity of phema to other materials, as well as its transparency, enabled such technical applications as gluing of methacrylates or their layers. as an example, until now unpublished results of the tests (performed in 1982 and based on stress-strain curves) enabled one to assess the strength of the link formed by polymerization of 2-hydroxyethyl methacrylate in between two specimens, the latter being constituted by a common mineral glass, an organic glass, a polyamide, and steel of class 11. in all cases, very firm joints were obtained, resisting stress of about 2  mpa. the results, suitable especially for gluing glass, led to the testing of polymers based on phema, to prepare permanent microscopic preparations, mechanically resistant layered glass or antifire layered glass, or to restore various historical glass objects (fig. 6). in an interesting application, water confined in certain hydrogels (semi-interpenetrating phema/polyvinylpyrrolidone networks) was used to gently remove dirt from the surface of water-sensitive cultural artifacts.38 similarly, complex cleaning f luids confined in these hydrogels were used to remove aged varnishes.65 a highly diluted solution of phema was tested by o. wichterle as an “anti-spray” coating to prevent the creation of graffiti. regrettably, to the best of our knowledge, this method has been neither patented nor published. its advantage lies in that that the coating is cheap and can easily be removed by excess water. 6. conclusions it follows from the facts presented that the history of the origin, development, and applications of 2-hydroxyethyl methacrylate and its polymers is extremely interesting, varied, edifying, and sometimes even exciting. in this review, the development of the famous application of hydrogel based on poly(2-hydroxyethyl methacrylate) for contact lenses is presented. inventors’ effort was ideadriven rather than serendipitous: otto wichterle and his co-workers not only arrived at a technically useful product but also showed the general importance of hydrogels. the dispute over the validity of the corresponding patents became a subject of a thrilling lawsuit that ended with the victory of the inventors. the eventual success was possible thanks to inventors’ endurance and ability to overcome the obstacles, both technical and political. the whole process from idea to final product took twenty years. when inspected in more detail, the present state of the art in the field suggests a possibility of further and deeper studies and even broad projects on the subject. in this way, some new properties, behavior, and applications of poly(2-hydroxyethyl methacrylate) hydrogels, so far unexplored, could be discovered. figure 6. historical cup restored using a preparation based on phema. 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[65] m. baglioni, j. a. l. domingues, e. carretti, e. fratini, d. chelazzi, r. giorgi, p. baglioni, acs appl. mater. interfaces 2018, 10, 22, 19162-19172. https:// doi.org/10.1021/acsami.8b01841. 91true story of poly(2-hydroxyethyl methacrylate)-based contact lenses: how did it really happen appendix table i. categorization of contact lenses from the material point of view. how it changed in time original division hard soft hydrophobic hydrophilic recent division hard impermeable glass, pmma gas permeable rigid gas permeable (rgp) soft hydrophobic silicone elastomers hydrophilic standard hydrogels phema high swelling hydrogels hybrid hydrogels silicone hydrogels present day division rigid gas permeable (rgp) hydrogels silicone hydrogels table ii. important dates in global contactology (from the viewpoint of polymer materials and manufacturing methods) 1933 rohm and hass co. introduced transparent polymethyl methacrylate (pmma) into the market. 1936 william feinbloom described a scleral lens composed of a central clear part (glass) and an opaque edge (pmma). soon after that, rigid lenses have been produced by turning solely from pmma. 1948 by mistake in turning, kevin tuohy prepared a very small size lens of pmma and found that it was better tolerated than that of the original size. afterward, he patented hard corneal lenses of pmma. 1953 d. lím successfully prepared the first hydrogel following the idea of otto wichterle; application of the first o. wichterle’s patent. 1956 the first hydrogel contact lens was prepared in wichterle’s prague laboratory. 1959 tests on volunteers showed good correction of visus and excellent tolerance of hydrogel contact lenses. 1960 wichterle and lím published an article in nature, entitled “hydrophilic gels for biomedical use” where they described phema gels. 1961 priority of spin casting method of hydrogel contact lens fabrication (wichterle) 1963 priority of lathe cutting method of lens fabrication from xerogel blocks (wichterle) 1965 hydrophobic soft contact lenses made of silicone elastomers 1972 hydrophilic (hydrogel) soft contact lenses were introduced to the global market. 1974 rgp – rigid gas permeable lenses 1988 lenses with regular replacement (cast molding technology began to prevail) 1994 disposable lenses (regular replacement after one day) 1998 silicone hydrogels, 1st generation 2004 silicone hydrogels, 2nd generation 2006 silicone hydrogels, 3rd generation (till present day) 2014 new highly swollen hydrogel contact lenses (biotrue oneday) were introduced on the global market. their material (hypergeltm) contains in equilibrium 78% of water. the mixed blessings of pragmatism. jean-baptiste dumas and the (al)chemical quest for metallic transmutation by leonardo anatrini dipartimento di lettere e filosofia (dilef) università degli studi di firenze via della pergola, 60 50121 firenze – leo.anatrini@gmail.com via alessandro lazzerini, 21/1 59100 prato – (+39) 339 7972288 orcid: 0000-0001-9001-3240 received: jun 01, 2023 revised: jun 26, 2023 just accepted online: jul 03, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: l. anatrini (2023) the mixed blessings of pragmatism. jean-baptiste dumas and the (al)chemical quest for metallic transmutation. substantia. just accepted. doi: 10.36253/substantia-2169 abstract there were at least three prerequisites for the transmutability of metals to become once again a scientifically acceptable subject of research from the 1810s: new hypotheses concerning the mutual reducibility of certain elements, such as those of integer multiples and protyle put forward by the british chemist and physician william prout; the experimental confirmation that chemical compounds with the same percentage composition could be substances with very different properties, i.e. the discovery of isomerism and allotropy; the comparison between metals and compound radicals of organic chemistry. this paper aims at illustrating how these premises were exploited by jeanbaptiste dumas, one of the leading french chemists of the 19th century, to reintroduce in the chemical discourse the alchemical topic of transmutation. keywords – transmutation, jean-baptiste dumas, ammonium, jöns jacob berzelius, cyprienthéodore tiffereau introduction the experimentation conducted towards the end of the 18th century, which helped to describe the regularity and reproducibility that characterised a wide range of chemical compositions and led, for example, to the enunciation of the law of definite proportions by joseph-louis proust (1754 1826), were propaedeutic to the spread of a new idea of atomism. after all, with a simple logical step, it was possible to deduce, from the regularities observed in chemical reactions, a mailto:leo.anatrini@gmail.com necessary regularity in the composition of matter of a corpuscular nature. the atom originally theorised in democritus’ time (c. 460 c. 370 bc), however, was the minimal entity of a uniform and continuous matter understood ontologically and not instrumentally, whose essentially identical parts differed only in size, form and motion. in such a system, chemical change was generated by alterations occurring in a vacuum in the ordering of atoms into molecular structures. nevertheless, everything since the results produced by the chemical reform of georg ernst stahl (1659 1734), suggested the existence of a whole range of elements characterised by exclusive qualities. stemming from the desire and need to quantify the ultimate units of matter for calculative purposes, aiming at a consequent mathematisation of chemistry, the atomic theory of john dalton (1766 1844) was born. with it, the english scientist united quantitative speculations inspired by democritus with a qualitatively categorised matter, overcoming the very limits beyond which antoine lavoisier (1743 1794) had relegated a purely philosophical investigation of empedoclean descent. in an effort of hopeful pragmatism, dalton’s atom was no longer the omnipresent manifestation of matter, becoming instead the physical unit of measurement of lavoisier’s substances simples1. although the acceptance of the physical reality of the daltonian atom in the first half of the 19th century was certainly not extraordinarily widespread in france, the theorisations of the english scientist had emphasised the importance of the quantification guaranteed by the system of atomic weights in the elaboration of the categorisations and classifications necessary to establish the foundations of a science of chemical relationships, a prodrome to structural chemistry. and it was precisely in this field that in 1826 one of the fathers of organic chemistry, jean-baptiste dumas (1800 1884), brought his research to the attention of the international scientific community2. by experimentally applying the hypothesis of amedeo avogadro (1776 – 1856)3 which he knew and studied through andré-marie ampère (1775 1836)4 -, he proposed new methods for determining the molecular weight of gases, obtained through volume density, succeeding in optimising and even correcting the data of jöns jacob berzelius (1779 1848), who, with his calculation of the atomic weights of 45 different elements and the centesimal composition of some 2000 chemical compounds, is remembered as the greatest experimenter of the early 19th century5. in 1818, he was able to theorise a first set of atomic weights based on entirely experimental data6, disproving the possibility of a total generalisation of the hypothesis developed in 1815 by the physician and chemist william prout (1785 1850) aimed at illustrating the atomic weights of the elements as integer multiples of that of hydrogen7. then, from 1826 onwards, berzelius refounded his investigation and in this context, the desire for revenge provoked by dumas’ essay must have played no small part through the instrumental adoption of two innovations of particular importance for chemical research. in 1819, chemist pierre louis dulong (1785 1838) and physicist alexis thérèse petit (1791 1820), succeeded in calculating the specific heat of 13 different elements (11 metals, tellurium and sulphur) and discovered their similar heat capacity (between 0.3675 and 0.3830, for o = 1 and h2o having c = 1), i.e. the constant describing the product between the relative atomic weight of an element and its specific heat8. in the same year, the german eilhard mitscherlich (1794 1863), in the course of lengthy crystallographic experiments, put forward a hypothesis concerning the possibility that substances with similar chemical properties and crystalline form, called isomorphic by berzelius himself, might have similar formulae9. believing is seeing: the convictions of a scientist dumas desired to succeed in obtaining stable and experimentally consistent principles, and the opportunity that avogadro’s hypothesis offered was unrepeatable. however, from the time of his first major publication as is also evident from his 1832 doctoral thesis the young chemist had been grappling with a problem difficult to surmount, found in the measurement of the molecular volumes of the phosphorus contained in his trichloride (pcl3) and the sulphur contained in hydrogen sulphide (h2s)10. in the particular case of phosphorus and chlorine, by reacting one volume of the former with three volumes of the latter, dumas could not explain how it was possible that, if avogadro and ampère had been right, not one but two volumes of phosphorus trichloride would be generated11. the cause of the problem lay in the widespread terminological confusion linked to the atomistic lexicon, which dumas had declined from ampère’s, even going so far as to hypothesise the divisibility of the elementary molecules, although he did not realise the tetratomicity of liquid phosphorus and the diatomicity of chlorine in the gaseous state (and, more generally, not imagining that elements placed in reaction could give rise to variations in atomicity), finally resorting to expressions that were variously criticised, when not entirely oxymoronic, such as that of ‘half-atom’12. moreover, the values he calculated were based on berzelius’ 1818 atomic weights, which for phosphorus and chlorine were twice as high as they should have been. thus, he would have expected a synthesis reaction of the type p + 3cl → pcl3, whereas what he obtained was p4 + 6cl2 → 4pcl313. from 1828 onwards, dumas endeavoured to adopt the avogadrian criterion of the distinction between the physical particle and the chemical particle, constantly emphasising the material reality of the former and the purely instrumental dimension of the latter, with a methodology partly borrowed from the thought of william hyde wollaston (1766 1828)14. this latter, in fact, decided to address the shortcomings caused by an ontologically understood atomism from a decidedly more pragmatic point of view, emphasising the priority of practical effects and purposes of chemical research. in a celebrated 1814 essay entitled a synoptic scale of chemical equivalents, he introduced a stable categorisation to define the minimum quantities required for elements to enter combinations forming compounds15. dumas, however, was not satisfied with a utilitarian implementation of wollaston’s equivalents16. in fact, by the time his colleague marc antoine gaudin (1804 1880), with his recherche sur la structure intime des corps inorganiques (1833), had brought to the attention of the scientific community the importance of a stable nomenclature that provided a clear distinction between concepts such as ‘molecule’ and ‘atom’, especially in virtue of the increasingly encouraging results provided by research into atomic weights (regarding which gaudin was the first to hypothesise the polyatomicity of certain elements), dumas had become definitively convinced that the results of his experiments offered a clear refutation of avogadro’s hypothesis17. as has been persuasively illustrated by some scholars, at the basis of dumas’ rejection was surely the perception that atomism was little more than a faith and that, in the end, no experimentation would be able to account for the existence of ultimate physical entities18. therefore, faced with the results of his experiments, rather than questioning the ontological value of what he probably considered to be non-essential abstractions, he chose, while recognising the instrumental usefulness of the system developed by dalton, not to engage in theoretical elaborations concerning the physical dimension of ultimate entities. conversely, he showed an increasing interest in another hypothesis, based on experimental data which, although variously manipulated and aiming at an even more general theorisation, were plausibly preferred as they could be used to investigate the relationships between the various elements without necessarily delving into lucubrations on the nature of matter. the hypothesis in question is that of the integer multiples of hydrogen elaborated by prout, which dumas no doubt became acquainted with thanks to the french edition of an attempt to establish the first principles of chemistry by experiment (1825), by dalton’s pupil and first biographer, thomas thomson (1773 1852)19. added to this, there were two other factors which plausibly, at a time before proper research on valence and stereochemistry, led dumas to increasingly doubt the value of atomic theory. in 1828, the german chemist friedrich wöhler (1800 1882) documented the first case of isomerism, unintentionally demonstrating the convertibility between organic and inorganic compounds. trying to obtain ammonium cyanate (ch4n2o an inorganic salt), he succeeded instead in synthesising urea (co(nh2)2 an organic compound contained in the urine of almost all tetrapod organisms) by reacting purely inorganic substances such as silver cyanide (agcn) and ammonium chloride (nh4cl). this experience led to the formulation of the principle of isomerism, whereby substances with very different physical properties and chemical behaviour can have the same molecular mass and percentage composition20. something similar was observed for elementary substances (at the time mainly in carbon and sulphur), thanks to the polymorphic nature of certain corps simples, describing phenomena to which berzelius would give the name allotropy in 184121. convinced of the absolute precedence of experimental data in the elaboration of hypotheses otherwise judged arbitrary and aprioristic, dumas, perhaps due to a lack of imagination and an excess of faith in the mathematisation of scientific research, abandoned the prophetic intuitions of avogadro and ampère in favour of data useful to quantify an illusion. at this point, it would be as easy as it would be wrong to make dumas a follower also of prout’s other famous hypothesis, enunciated for the first time one year after the hypothesis of integer multiples of hydrogen, as distinct from (though superimposable to) it, defining the hypothetical unity of matter as originating from a mysterious primordial element called protyle22. as already mentioned, the former became acquainted with the latter’s work through the mediation of thomson, who was as enchanted by the hypothesis of integer multiples as he was certainly annoyed especially in virtue of the degree of probability he attributed to the daltonian theory by the possibility of discussing the unity of matter once again. dumas had shrewdly foreseen how the explanation of isomerism and the various phenomena of polymorphism, such as allotropy, passed through the investigation not only of the percentage composition of bodies but also of the structural arrangement of their constituents. however, in the absence of stable terminology and a clear distinction between atom and molecule, the constraint indicating the element as the limit of qualitative decomposability was lost. thus, faced with the apparent superimposability and proportionality between the atomic weights of inorganic elements, it must have seemed natural to dumas to ask himself whether it was not indeed possible to convert one species into another, to transmute matter. as if this were not enough, there was a whole tradition of studies revolving around the concept of transmutation of metals, which, within the elite of french scientific research came back to make its authority felt, as witnessed by one of dumas’ most famous works, the leçons sur la philosophie chimique, published in 1837. particularly interesting, and useful in clarifying how dumas’ alchemical knowledge came from a thoughtful as well as partial study of primary sources, is the attempted description in chemical terms of a supposed procedure for making the philosopher’s stone, extracted from a work by the 15th-century english alchemist george ripley (c. 1415 1490). dumas adopted a hermeneutic oblivious of the philosophical and symbolic values of his chosen writing, interpreting it in the light of his own chemical knowledge and using the visual and thermal variations described as his only compass, decoding the various entities as the signifiers of an allegory and coming to the conclusion that ripley’s philosopher’s stone was nothing more than acetone (c3h6o), obtained by repeated distillations of lead diacetate pb(ch3coo)223. it is curious to note, in such an attitude, the adoption of a mirror-image approach to written testimony by the scientists and those who were to become, in the second half of the century, the new alchemists. for if the latter could be accused of anti-scientific behaviour in their constant substitution of the experimental method for textual authority, to which they generally attributed far greater value, the former resorted to anti-historical methods, carefully selecting the only data useful for the elaboration of a tradition no less unreal than that on which the hermeticists based their hermeneutics. considering the inescapable precedence that dumas attached to experimental data, it is difficult to imagine that he could have devoted himself to such a felt study of alchemical texts before his calculations of atomic weights aroused probabilistic doubts in him. the fact remains that the motivations that led him to establish the possibility of some link between the superposition and proportionality of the atomic weights of many metals and the concept of transmutation stemmed from his inability to interpret the data of his experiments while preserving avogadro’s hypothesis. to seek an answer in the millenary tradition that glorified a process that could perhaps resolve his doubts, represented the crystallisation of a human limit, which concealed an insatiable desire for knowledge and not necessarily adherence to any form of esoteric thought. and dumas certainly believed he could overcome the incompatibility between chemistry and alchemy by quantifying the study of the latter, so as to extract data useful for his research. however, this was a dangerous process, especially from a value-based point of view. alchemy had been brought into play in order to reach a truth that chemistry, although hypothetically, was not even managing to describe comprehensively. the implicit risk was that of attributing a similar if not overlapping gnoseological value to the two disciplines, placing alchemy, which had already long since arrived at the concept of transmutation, in a privileged position, thus establishing an epistemologically null but logically consistent and easily misunderstandable parallel between textual authority and scientific authoritativeness that were no longer clearly distinct. not to mention that every alchemical theory rested on concepts of unity of matter that, in the face of possible scientific confirmation of transmutation, would have offered an opportunity for generalisation that would have been difficult to avoid. in spite of his ideals, dumas chose to believe in order to see. nonetheless, he probably never fully realised how contingent the value of the data from his experimental research was on his personal interpretation of them. furthermore, as mentioned, there was a third factor that led him to question the plausibility of the elemental nature of many of the simple substances in mineral chemistry, namely the possibility to put in relation metals and compound radicals of organic chemistry. this factor arose from the field of investigation in which he recorded some of his greatest successes, that of chemical substitutions. by 1833, dumas and his students had embarked on an intensive experimental campaign concerning the chlorination processes of organic compounds and by the following year, he had collected sufficient data concerning the action of chlorine on turpentine essence and ethanol (c2h5oh) to affirm the ability of the said element to replace hydrogen ‘atom by atom’ in these compounds, which nevertheless had almost identical chemical properties24. in doing so, he reinforced his belief that these properties depended more on the arrangement than on the nature of the particles. in the eighth of the leçons, dumas’ observations on the hypothetical transmutability of elements were based on three different principles: isomerism, allotropy and supposed direct proportionality observable according to the atomic weight of different elements (16 metals, tellurium and sulphur)25. these formulations and observations could describe the change of species produced by a transmutation but were not proof of the composite nature of metals. hence the circumspection in the choice of words with which dumas described the possibility and not the probability of a feat of alchemical memory. there was, however, at least one sensata esperienza that could have been used as evidence. nevertheless, such evidence was carefully omitted in the leçons (only a veiled allusion is made)26 by virtue of the interpretability of the phenomenon on which this datum was based and the fact that, as the only useful experimental evidence, it certainly did not meet the criteria of exhaustiveness and rigour on which a theory should be based. in 1808, berzelius, together with his friend and future court physician magnus martin de pontin (1781 1858), replicated the experiments that the previous year had led humphry davy (1778 1829) to the discovery of sodium and potassium, obtained from their hydroxides27. the two swedes extended davy’s research to another substance that resembled the so-called caustic alkalis in chemical properties, i.e. ammonia (nh3). by subjecting a negatively electrified quantity of mercury to electrolysis and placing it in contact with an aqueous ammonia solution, they produced a substance that had the appearance of an amalgam28. in this regard, the sentence at the end of the first part of berzelius and de pontin’s account of their experiments is particularly interesting, in which the two scientists, apologising for the ‘almost alchemical’ tone of their lucubrations, observe how the phenomenon they investigated could have led to the ‘decomposition of metals’ and the discovery of the processes necessary to perform chrysopoeia, as already suspected by ‘many chemists’: «and even if these discoveries do not bring us any closer to the goal [i.e. the transmutation of metals] so unsuccessfully pursued for so many centuries, they do at least give us a clearer idea of the decomposability of metals, making the possibility somewhat intelligible. we may be forgiven this almost alchemical argument; however, many chemists had already predicted [...] that one day we would discover the composition of gold and devise the means to assemble its components»29. so, how to explain such a phenomenon, considering that the composite nature of ammonia was well known? when confronted with the work of his colleagues, davy was enthusiastic and inclined to devise a classification of metals described as hydrogenated compounds at the basis of which, given its instability and discernible composite nature, was the hypothetical metallic element that together with mercury formed the amalgam, called ammonium: «the more the properties of the amalgam obtained from ammonia are considered, the more extraordinary do they appear. mercury by combination with about 1/12000 part of its weight of new matter, is rendered a solid, yet has its specific gravity diminished from 13.5 to less than 3, and it retains all its metallic characters; its colour, lustre, opacity, and conducting powers remaining unimpaired. it is scarcely possible to conceive that a substance which forms with mercury so perfect an amalgam, should not be metallic in its own nature; and on this idea to assist the discussion concerning it, it may be conveniently termed ammonium» 30. the stahlian dream of a metallising phlogistic principle seemed within reach once again, especially in light of the fact that ammonia was composed of non-metallic elements 31. from the study of the amalgam, the formula for ammonium was logically deduced, parallel to that of today’s ammonium ion (although it should be specified that the amalgam is formed after the alkaline or electrolytic reduction of the cation nh4+ into the ammonium radical nh4 . ). thus berzelius, in the first edition of the second volume of his lärbok i kemien (1812), did not hesitate to include ammonium in the list of elements that could be obtained from earths and alkalis, being all metals32. moreover, it is in this book that can be found the first clear conceptual overlap between the radicals of organic chemistry and metals, observable in the title of the relevant chapter: «alkaliernas och jordarternas metalliska radicaler» (metallic radicals of alkalis and earths)33. the problem also interested some of the leading french scientists of the time. first claudelouis berthollet (1748 1822), then ampère34 examined the potential of berzelius and de pontin’s discovery. anyway, the scientific community, faced with the impossibility of finding a solution, and building on the results of an increasing number of studies based on better-established concepts of element, atom and molecule, although remembering the ammonium amalgam phenomenon, ended up shelving it almost completely until the mid-20th century35. one of the few scientists who continued to take an interest in ammonium was exactly dumas, who on three separate occasions while writing his traité de chimie one of the most important manuals dedicated to technical-industrial applications of chemical research of the period, the editing of which kept him busy for eighteen years, between 1828 and 1846 dealt with berzelius and de pontin’s discovery and what it might entail36. seeking to establish a classification of metals on the basis of their respective chemical properties, after observing and describing the isomorphism of potassium, sodium, lithium, barium, strontium and calcium, he put forward a conjecture about the composite nature of metals (the highly speculative nature of which he himself affirmed), observing how, from the known data, it might be plausible to conclude that «ammonia is transformed into a metal when, to the three volumes of hydrogen it contains, a fourth is added»37. in the fifth volume (1835), on the other hand, building on the discoveries that led him to the substitution theory, attempting an initial classification of nitrogen and hydrogen compounds, dumas identifies ammonium as a ‘metal-like body’, with a related discussion concerning the advantage that the identification of its oxide would represent. firstly because, just as ammonium in the amalgam experiment was shown to be able to replace potassium, the hypothetical oxide would have confirmed the superposition of its chemical properties with those of sodium and potassium hydroxides. second, because an entity such as ammonium oxide would have led to the assumption of «the existence of a large number of unknown combinations, which would replace all known hydrogenated compounds in the products they form by uniting with acids»38. this statement is only apparently obscure since after a few lines it becomes clear what dumas is aiming at, namely extending his theory of ethers to inorganic chemistry. between 1827 and 1828, together with his colleague and pharmacist félix-polydore boullay (1806 1835), dumas had arrived at the enunciation of the formula for the synthesis of ethers cnh(2n + 2)o -, compounds formed, in the authors’ words, from ‘an acid combined with two volumes of ethylene c2h4, called oleophilic gas and one volume of water vapour’; a description elaborated by generalising to an entire class of compounds the values describing the components of diethyl ether, at the time known as sulphuric ether (c4h10o)39. but this generalisation, since supported by serious experimentation, had proved to be accurate, producing, as charles adolphe wurtz (1817 1884) defined it forty years later in his history of chemistry, the first occasion on which: «in organic chemistry a series of similar phenomena was grouped together by theory and [...] the facts relating to the formation, composition and metamorphoses of an entire class of bodies were given a simple interpretation, using atomic formulae and equations»40. in their account, dumas and boullay offer a term of comparison which, interpreted in the light of the mystery of ammonium, serves to clarify the curious digressions in the fifth volume of the traité. the two had in fact described in an analogical key the function of ethylene in the formation of ethers with that of ammonia in the formation of ammonia salts, by virtue of the latter’s ability to decompose diethyl ether41. the choice of comparative term stemmed from the observation of the properties of ammonia, which described capacities for the analysis of organic compounds and the synthesis of saline compounds in the presence of acids that overlapped and even exceeded those attributed to metal hydroxides used for the same purposes. years passed, and by the time dumas wrote the next passage of the traité, the constant comparison between ammonium, alkalis and earths had matured in him a definite conviction. faced with the impossibility of isolating the fabled metal, obtaining its oxide would have provided solid proof not of the existence of a metallic phase of the radical nh4 . (a concept unknown to the chemistry of the time), but of the composite nature of metals, since the properties of the new element would have fallen squarely within the casuistry described by the alkaline and alkaline-earth metals (as we have already seen with berzelius): «nevertheless, this is the place to bring out a theory already proposed by ampère, on the occasion of the singular combinations that have been described under the names of ammoniacal hydrides of mercury or potassium and mercury. according to ampère, these compounds, which have so often been compared to alloys, contain a kind of metal made up of 2 parts nitrogen to 8 parts hydrogen42. there is nothing to prevent us from classifying such a compound alongside the metals when we already classify cyanogen alongside chlorine and other similar nonmetallic bodies. if we assume this base, we would have the following series: az2 h4 a chlorine-like substance found in amines. az2 h6 ammonia. az2 h8 a metal-like substance. ammonium. az2 h8 o ammonium protoxide. az2 h8, ch2 ammonia hydrochlorate or rather ammonium chloride. az2 h8 o, s o3 ammonia sulphate or rather ammonium protoxide sulphate, and so on for the different ammonia salts known. with regard to the combination formed between anhydrous sulphuric acid, for example, and ammonia, it would necessarily be considered an amine. here are the main advantages of this theory, as far as i can appreciate them. it explains the formation of the remarkable amalgams that first gave us the idea. it eliminates hydrochlorates, hydriodates and other similar ammonia salts, whose existence embarrasses the theory of chlorides, iodides, etc. it gives perfect simplicity to the formulae of double chlorides, double iodides and other similar compounds containing ammoniacal combinations, whereas in the other theory, these formulae are complicated and of an unusual form. it gives a good idea of the basic role of ammonia since it is no longer ammonia that plays the role of base, but an oxide produced by the union of ammonia and water. this oxide is therefore completely comparable to potash or soda. this better explains the isomorphism of ammoniacal salts with similar combinations of potassium or sodium; since, for example, ammonium replaces potassium everywhere, and ammonium oxide replaces potash. now here are its disadvantages: it is based on the existence of a combination az2 h8, which has not been isolated. and on the existence of an ammonium oxide, az2 h8 o, which is completely unknown to us, although ammonia and water can produce it by combining and these two bodies have been brought together in circumstances most favourable to combination. it leads us to suppose the existence of a large number of unknown combinations, which would replace all the known hydrogenated compounds, in the products that these form by uniting with acids. it therefore forces us to admit a large number of hypothetical hydrogen carbides, playing the role of metals, which is possible, but difficult to admit without proof. thus, as has already been pointed out, the theory of ethers and that of ammoniacal combinations are so closely linked that they will probably be decided by each other. those who attribute the role of a base to the sulphuric ether will admit ammonium oxide; those who regard ammonia as a base must attribute the same role to carbonated hydrogen and its analogues. by showing that both theories are admissible, we have given a fair idea of the state of the question; by preferring the latter point of view, we have followed the general opinion. chemists who have turned their attention to the philosophy of science have all been struck by the difficulties that the history of ammonia has given rise to, and have long sought to discover some metallic radical in it, in order to bring this body back into the great family of oxides. after the useless attempts made by davy and berzelius twenty years ago, they returned to the original idea of considering ammonia as a base in itself. this discussion, almost forgotten, has been rejuvenated by its connection with the ether theory. it is impossible to ignore what is broad and great in the point of view that would bring all these so diverse combinations back to the known laws that regulate those of metal oxides […]. on the other hand, however, it is not an uncommon fact that ammonia is considered to be an alkaline base. it is a consequence of a principle that is no less extensive than the previous one, nor less worthy of attention. is it not natural to admit, in fact, that hydrogen, by uniting with simple bodies, can sometimes constitute acids, sometimes bases, depending on whether its properties predominate or succumb in the presence of the antagonistic element? if the ammonium theory had been generally accepted, sulphuric ether and its analogues would have been given the role of base. of all the known phenomena, only those relating to the theory of substitutions can be explained by a single hypothesis, the one accepted in this book […]. leaving aside these hypotheses, we shall confine ourselves here to the pure and simple expression of facts […]. we will therefore consider ammonia as a base in itself»43. before asserting the plausibility of a hypothesis, dumas considered it necessary to produce empirical proof. otherwise, claiming its veracity on a logical-consequential basis would have led beyond the limits of a scientifically provable analogical correspondence, trespassing into the domain of personal convictions to which one could arbitrarily attribute the function of principles. so much so that the problem of ammonium in the leçons, a work with historical ambitions but with a strongly programmatic slant, is only hinted at transversally through recourse to the authority of certain ‘illustrious chemists’, berzelius in the lead (and the only one to be cited by name), who had «put forward conjectures such as to make the composite nature of nitrogen conceivable»44. hence dumas’ progressive (and definitive) rejection of physical atomism, which he increasingly saw as a set of aleatory speculations about an invisible world, in favour of research with far greater classificatory potential, one that was devoted to the radicals of organic chemistry. on the strength of his successes in the elaboration of the substitution theory, in the same year of publication of the leçons, he drafted, together with another great organic chemist of the time and long-time rival, justus von liebig (1803 1873), a programmatic article, almost a manifesto, with which the quest to finally bring order to the tumultuous sea of organic compounds was inaugurated, entitled note sur l’état actuel de la chimie organique45. the historiography of chemistry has always emphasised how dumas, at least from the early 1830s onwards, set atomism aside in favour of recourse to immediately measurable quantities such as equivalents; and that is true. however, the instrumental value of atomism was never denied by him, and in order to lend solid mathematical representability to his research, in the aftermath of the leçons the scientist prepared an experimental investigation aimed once again at calculating the atomic weights of the principal agents of organic chemistry (carbon, hydrogen, oxygen and nitrogen). the results of this investigation, together with the theory of substitution and that of types, earned him the copley medal of the royal society in 1843. in the very definition of chemical type offered by dumas, in fact, the recourse to atomistic concepts remained central, while to have been partially excluded was the concept of element, instrumentally necessary but functionally replaced by that of type46. as is well known, the idyll between dumas and liebig was very short-lived due to disagreements at a theoretical level47. ironically, it was liebig’s theory of compound radicals48 that provided the rationale for hypothesising the analogy that dumas, in the absence of ammonium oxide, had refused to enunciate openly out of methodological rigour. one of the fathers of structural chemistry, alexandre-édouard baudrimont (1806 1880), who in turn adopted at least in part prout’s integer multiples hypothesis, was the one who performed the feat. epitomising his words, in inorganic chemistry, oxygen, chlorine and sulphur could be combined with a metal to produce compounds in which the latter played the role of a radical, which, on the other hand, in organic chemistry never consisted of a single element. from the juxtaposition of the relevant data, baudrimont concluded that metals not only could, but plausibly should, be corps composés: «just as a chemical element can only be analysed with its own matter, so it can only be produced with this same matter; thus, in the present state of chemistry, nothing other than gold can be found in gold, and gold can only be made with gold. this is the limit of experience; the rest is mere conjecture or supposition. it is known, however, that alchemists claim to have made gold from bodies that were not gold, but these facts, although often presented with candour and with testimonies that leave little room for doubt, will only be accepted by science when they can be proved experimentally. however, despite the deliberate obscurity that reigns in the writings of the alchemical philosophers, we can say with certainty that they did not produce gold by combinations, but by imprinting on the nature of the bodies a modification of the kind that gives rise to isomerism, under the influence of a catalytic agent. the bodies on which they worked were lead and mercury; their agent was the projection powder: this product they produced with such slow and arduous labour. to the alchemists, we can add the theoretical ideas of prout, who believes that all bodies are formed from one and the same material, the disposition of which alone causes the differences that we observe in bodies considered simple […]. liebig’s theory, at least in most if not all cases, establishes radicals that are entirely comparable to metals. the theory i have defended leads us to suspect that metals are composed, and i believe this view to be as well-founded as that of lavoisier, who thought that earths and alkalis could well be metallic oxides. let us hope that a new davy will resolve this question. hydrogen would be the link that binds the constituent parts of metals together. if this bond could be broken, they could undoubtedly take on new arrangements, and metallic transmutation would take place»49. in a period during which berzelius’ electrochemical dualism was slowly being replaced by unitary theories also thanks to the discoveries of michael faraday (1791 1867) but immediately preceding the first studies on valence and the dawn of stereochemistry yet still far from the refinement of nomenclature and atomistic conceptualisation brought about by stanislao cannizzaro (1826 1910) in the late 1850s -, the plausibility of hypotheses such as the transmutation of metals was hardly questionable. seeing is believing: the dreams of an inventor during one of the sessions devoted to chemistry at the 21st annual conference of the british association for the advancement of science, held in ipswich in july 1851, michael faraday returned to emphasise how many scholars (including himself) expected future developments that would restore a simpler view of matter to physical and chemical research. this attitude implied a strong desire to curb that multiplicative drift characterised by an increasingly crowded pool of chemical elements, still interpreted by more than one scholar in the mid-century as an illogical break from an organisation of the physical world of (albeit now distant) democritean and empedoclean ancestry. galvanised by faraday’s words, jean-baptiste dumas took the opportunity to present his own convictions concerning the plausibility of transmutation to an audience of scholars. carefully avoiding the edge case of ammonium, dumas resorted to the categorisation principles developed more than twenty years earlier by his german colleague johann wolfgang döbereiner (1780 1849). this latter, after more than a decade of experimentation, had managed in 1829 to group fifteen elements into triads characterised by physical and chemical affinities, the middle term of which had an atomic weight equal to or close to the average of the sum of the atomic weights of the two extremes50. such research, further developed after the middle of the century, sanctioned a turning point that in the following decade culminated, thanks to the work of dmitrij ivanovič mendeleev (1834 1907), in a stable theorisation of the periodicity of the elements51, while dumas chose instead to resort to such organisational criteria for the purpose of revaluation. according to a rather obvious analogical process (and arguably influenced also by baudrimont’s lucubrations concerning the transmutability of matter), the french chemist saw in the triadic organisation of certain elements the possibility of deriving numerical ratios parallel to those of compound radicals. in this way, his observations became part of a possible confirmation of prout’s ‘integer multiples’ hypothesis, by which the elements that constituted triads in inorganic chemistry were characterised by an analogical relationship with the components of organic chemistry’s homologous series52. always well aware of the highly speculative nature of this kind of hypothesis, dumas undertook further laboratory research before presenting them at the académie des sciences (where they ended up at the centre of a heated debate between 1858 and 1859)53. thus, on the occasion of the conference, he chose not to submit any paper, as indicated by the fact that the related report contains no contribution of his own, nor any mention of the matter by faraday. the only valuable, detailed account of the affair was published anonymously in the 12 july 1851 issue of the athenaeum, the leading english generalist weekly magazine devoted to art and literature as well as scientific news and dissemination. taking into account the technical knowledge required to produce such an account, we can attribute it with a fair degree of certainty to the scientist and politician lyon playfair (1818 1898), at the time co-chairman of the committee of the british association’s section dedicated to chemical research54, as well as correspondent of the athenaeum55: «[…] dr. faraday expressed an opinion that chemists had of late years viewed with regret the increase in the number of metals, and hoped that the day was not far distant when some of the metals would afford honour to chemists by new modes of investigation leading to their decomposition. […] prof. dumas gave many examples of groups of bodies, such as the alkalies, earths, &c., arranged in the order of their affinities. he called the attention in the triad groups, to the intermediate body having most of its qualities intermediate with the properties of the extremes, and also that the atomic or combining number was also of the middle term, exactly half of the extremes added together; thus, sulphur 16, selenium 40, and tellurium 64. half of the extremes give 40, the number for the middle term. chlorine 35, bromine 80, and iodine 125. or the alkalies, lithia, soda, and potassa, or earths, lime, strontia, and baryta, afford, with many others, examples of this coincidence; hence the suggestion, that in a series of bodies, if the extremes were known by some law, intermediate bodies might be discovered; and in the spirit of these remarks, if bodies are to be transformed or decomposed into others the suggestion of suspicion is thrown upon the possibility of intermediate body being composed of the extremes of the series, and transmutable changes thus hoped for. prof. dumas then showed that in the metals similar properties are found to those of non-metallic bodies; alluding to the possibility that metals that were similar in their relations, and which may be substituted one for the other in certain compounds, might also be found transmutable the one into the other. he then took up the inorganic bodies where substitutions took place which he stated much resembled the metals. after discussing groups in triads, prof. dumas alluded to the ideas of the ancients of the transmutation of metals and their desire to change lead into silver and mercury into gold; but these metals do not appear to have the requisite similar relations to render these changes possible. he then passed to the changes of other bodies, such as the transmutation of diamonds into black lead under the voltaic arc. after elaborate reasoning and offering many analogies from the stores of chemical analysis, prof. dumas expressed the idea that the law of the substitution of one body for another in groups of compounds might lead to the transformation of one group into another at will; and should endeavour to devise means to divide the molecules of one body of one of these groups into two parts, and also of a third body, and then unite them, and probably the intermediate body might be the result. in this way, if bodies of similar properties and often associated together were transmutable one into the other, then by changes portions of one might often, if not always, be associated with the other […]. dr. faraday expressed his hope that prof. dumas was setting chemists in the right path; and although conversationally acquainted with the subject, yet he had been by no means prepared for the multitude of analogies pointed out»56. at the time, dumas could not have known that a young researcher, cyprien-théodore tiffereau (1819 1909), had sent a memoir to the académie in january of the same year entitled nouveau point de vue sous lequel nous devons envisager les métaux, basé sur un fait acquis à la science par l’expérimentation (a new way of looking at metals, based on a fact acquired by science through experimentation), which stated that the theory of a metallising principle, openly borrowed from stahl’s thought, was one step away from experimental confirmation57. that young man, who by mid-century was already making a name for himself as an inventor and photographer, is today mainly remembered for his dream of succeeding in transmuting metals, which accompanied and haunted him for 60 years58. having completed a scientific education of which we know very little, tiffereau, a native of a small village in the vendée, after working as a chemical preparator at the école professionelle in nantes, embarked for mexico in 1842, eager to further his studies on the terrains in which precious metals are found and the technologies used for their mining. as can be deduced from the numerous biographical passages in the contributions he published after his return to france59, during the period between 1843 and 1845 he travelled extensively, producing a considerable amount of photographic evidence of his mining and chemical research, unfortunately lost today. it is, however, easy to see that his studies aimed at technological development in the field of photography were the occasion (if not even the pretext) to deepen chemical experimentation that was already tending towards the desire to confirm the transmutability of metals. in fact, it is impossible not to see clear points of contact between the methodologies employed at the time for the development of daguerreotypes and the particular transmuting procedures prepared by tiffereau, which, by then, retained only a vague memory of the alchemical tradition. in 1846, he decided to settle semi-permanently in guadalajara, where he earned a living as a photographer (which also allowed him to subsidise his chemical research). it was at this juncture that tiffereau became convinced, thanks to an experiment that was successfully replicated twice more over the next year, that he had achieved the synthesis of artificial gold. after subjecting nitric acid (hno3) to the direct action of sunlight for a few days, he added filings of a copper-silver alloy, leaving everything exposed to the sun again until the partial dissolution of said alloy. the next step, consisting almost of a trivial parody of the alchemical solve et coagula, involved cooking the metals until the solvent evaporated, which was again added and evaporated until the solid residue, initially blackish in colour, became progressively lighter. once a bright yellow metallic hue was reached, the assay confirmed the successful transmutation into gold: «i reduced 10 grams of silver alloyed with copper to filings and projected them into a flask 2/3 full of pure nitric acid at 36° [bè]. at first, there was a lively release of nitrous gas; a little later, the attack having diminished in intensity, the release slowed down almost all of a sudden and remained barely noticeable, but nevertheless uniform, until the end of the operation; on the other hand, the unattacked filings seemed to increase a little in volume. after 3 weeks, i boiled the liquor in the sun on my terrace. the nitrous vapours ceased to be released and the boiling, which continued until it was dry, showed me a dull matter tending towards black, aggregated into a single whole: i noted no deposit of any saline part or any impurity. i poured nitric acid at 36° [bè] over the residue thus obtained. i boiled it and pushed the operation to complete dryness: i obtained, as before, an agglomerated whole but whose black colour took on a greenish appearance. further attacks and successive boiling with concentrated acid gave me a residue that was still agglomerated but whose colour gradually changed from greenish to yellowish. finally, during the last boiling to dryness, the dry matter, which had previously always been agglomerated, separated into a number of particles, making it perfectly clear that they consisted of filings that were easily crushed under the hammer. these various particles all had a clear golden yellow colour»60. this procedure, in all likelihood at least partly borrowed from alchemical readings that tiffereau never explicitly quoted, was influenced by the traditional idea of accelerating the ripening time of metallic substances combined with a concept of photosensitivity attributed to metals and acidic materials that was nevertheless foreign to traditional literature (which spoke at most of the astrological circumstances favourable or adverse to the great work). tiffereau’s experiments recalled instead the photographic impression procedures regulated by precise exposure times, considering how the development of daguerreotypes took place through the direct action of light on silver plates. the extent of the alchemical contribution to the genesis of tiffereau’s transmutational hypotheses remains unknown to this day, so to trace them back to the cross-reading of precise alchemical texts would represent mere conjecture. shortly after the outbreak of the mexican-american war (1846-48), tiffereau was forced to leave the new world. already planning an industrialisation process to put his incredible discovery to good use, he sailed from tampico to paris in early 1848, but once back home, he came up against an obstacle he would never be able to overcome. for unknown reasons, it was impossible for him to successfully replicate his mexican experiences. in the period immediately following his return, tiffereau nevertheless managed to consolidate his position by establishing himself as a photographer and inventor. over the next twenty years, several devices of his own creation, such as hourglasses for calculating the exposure times of photosensitive materials used in photography, laboratory gasometers and hydraulic clocks, became very popular and earned him academic prizes and awards. so much so that his first contact with the académie des sciences came by way of a pli cacheté dated november 1850 in which he discussed the possibility of using special aerostatic devices to irrigate cultivated fields61. while tiffereau was privately continuing his experiments in an attempt to carry out the transmutation once again, on 31 may 1852 he sent the académie a sample of the artificial gold that had been transmuted in guadalajara in 1846, together with a second missive, in which he stated that apart from himself, the only person made aware, on 23 june 1851, of the procedure successfully used in mexico, was none other than napoleon iii (1808 1873), at the time président de la république, who on that occasion granted the ambitious researcher financial support for his investigations62. when he felt ready to divulge his discovery, in june 1853 tiffereau published a short memoir eloquently entitled les métaux ne sont pas des corps simples, mais bien des corps composés (metals are not simple bodies, they are compound bodies), of which he sent a copy to the académie clamouring for its judgement, plausibly ignoring the rule by which this institution refrained from commenting on scientific contributions already published in france. surprisingly, it was nevertheless decided to summon him and so, on 17 october, tiffereau presented the account of his mexican experiences before the french scientific gotha, showing more samples of artificial gold. the aspiring transmuter must have realised early on that presenting a hypothesis partially based on the recovery of stahl’s phlogiston, considered for decades to be a pseudoscientific device, would not have been received as a wise or inspired choice. thus, he reshaped his ideas about transmutation on more recent concepts, considered at least probable and shared by more chemists, from the comparison between the compound radicals of organic chemistry and metals dear to baudrimont and dumas to prout’s integer multiples hypothesis. the attempt at theoretical generalisation, constructed using language more in keeping with mid-century chemical research, thus revolved around the possibility that metals, defined as isomer compounds (in deference to what dumas had suspected since his leçons sur la philosophie chimique), whose unknown radical would consist of one or even more allotropic states of hydrogen (in homage to prout’s integer multiples), could be transmuted through oxidation processes regulated by the catalytic and fermentative action of nitrogen (with indirect reference to the phenomenon of ammonium). metals were thus presented as oxyhydrides, the more inert and dense the more the amount of oxygen present in them increased, thus justifying the use of nitric acid, a known oxidising agent. bearing in mind the decades-long debate about the actual ‘simplicity’ of metals, it should come as no surprise that the académie responded by setting up a commission of enquiry63, chaired by the leading expert on the subject, jean-baptiste dumas; his mentor louis-jacques thénard (1777 1857), since the 1810s accustomed to studying related topics, as we have seen in the case of ammonium64; the most knowledgeable scholar of alchemical sources available to the institution, michel-eugène chevreul (1786 1889), one of the founders of modern organic chemistry and a pioneer of fatty acid chemistry. on 7 november, the committee members informed tiffereau that they would need more technical data to reach a judgement. in essence, they were asking him to reveal his experimental protocol. it took six months to formulate a response, for a rather obvious reason. realising the magnitude of the economic and financial repercussions that would result from the confirmation of his hypothesis and, consequently, the achievement of the technical reproducibility of transmutation, tiffereau wished to protect himself as the inventor of the procedure. to this end, on 22 december he applied for a fifteen-year patent registered by imperial decree on 10 february 1855 «for transmuting metals into one another»65. the new memoir, which reached the members of the commission in may 1854, finally explained the terms and methods of the experiments conducted in mexico between 1846 and 1847, also asking for the scientific community’s help in unravelling the mystery behind the impossibility of reproducing transmutations on french soil. however, tiffereau received no further response. during the same year, he sent three more papers to the académie, after which, having obtained the patent, he broke his silence and collected the communications sent to the institute in 1853-54 in a booklet with another self-explanatory title: les métaux sont des corps composés (metals are compound bodies). the fifth of these communications (sent to the académie on 16 october 1854) is of particular interest, as it testifies to the repetition of tiffereau’s experiments at the imperial mint under the direction of the essayer and prominent metallurgist alexandre irénée françois levol (1808 1876)66. the results, although ambiguous, were deemed conclusive and tiffereau’s request for further examinations was rejected67. between the end of 1855 and 1858, he produced two more memoirs, but, faced with the indifference of the experts, he temporarily shelved the enterprise and concentrated on his career. he married and had four children, and after he retired to private life in 1884 after selling the now-famous photographic atelier located at 130 rue du théâtre to one of his employees, he resumed his research into transmutation, updating his hypotheses in the light of the latest chemical discoveries. conclusions it could be argued that it was dumas himself who indirectly took up tiffereau’s baton. the former, in fact, having long since abandoned all hope of confirmation of avogadro’s principle but constantly searching for criteria of categorisation and ordering useful in chemical research, between 1857 and 1859 produced a series of contributions of extreme interest in fully understanding the reasons for the survival of speculations concerning the transmutability of matter in the chemical field68. first with a mémoire sur les équivalents des corps simples (1857) and then with a note on the same subject published the following year, dumas, building on the successes achieved through the application of his substitutions and types theories, made explicit his strategy aimed at achieving two co-implicating aims. one was the validation of prout's hypothesis of integer multiples for as many corps simples as possible. the other, representing a crucial step towards analogical generalisations informed more by speculations typical of magical thinking than by scientifically plausible inductive inferences, involved the demonstration of the existence, between elements belonging to the same family, of relationships analogous to those of the homologous series of organic chemistry (just like speculated during the ipswich conference of 1851)69. thus, dumas implicitly repeated that comparison between radicals from organic chemistry and elements from inorganic chemistry that we found in berzelius as the conceptual overlay that later evolved into a true hypothesis with baudrimont. dumas, however, could not have known that in that same period his italian colleague stanislao cannizzaro, with his sunto di un corso di filosofia chimica (1858), was laying the foundations for one of the first turning points towards the acceptance of the physical reality of atoms. and it was cannizzaro himself who emphasised first the methodological shortcomings of dumas’ hypotheses by reiterating what had been stated in his sunto: «dumas has set out to resolve one of the most important and general questions of natural philosophy; but for this purpose, it seems to me that one should compare not the quantities of bodies that are substituted, but the weights of those last particles of theirs that always enter their molecules whole, and of their compounds, namely the atomic weights»70. regardless of cannizzaro’s remarks, the following year dumas came to a definitive systematisation of his research into the équivalents des corps simples. in a long essay, characterised by philosophical digressions and almost prophetic accents, the scientist’s arguments culminate in the hope of finally achieving the ‘decomposition of the radicals of inorganic chemistry’: «it is no more necessary to teach chemists that bodies they cannot decompose do not decompose than it would be to teach them that compound bodies decompose; these are two truths of the same order. chemists have taken their analysis as far as the power of the forces at their disposal or the energy of the reactions whose formulas they know. they have done even better, for by this analysis they have reduced all the natural bodies to certain metallic or non-metallic bodies, showing by indisputable common characteristics and by an energetic mutual affinity that they are all radicals of the same order. when, in this state of affairs, there appears to be a reason to doubt that these radicals are simple bodies and that chemistry has said its last word about them, is it necessary to repeat this series of perfectly established demonstrations which prove that it has not hitherto been possible to decompose them? i do not think so. the infinite manipulations of the laboratories of science and industry over the last century have left no clouds in people’s minds on this subject. there is no question of going back to the past; what it has left us, everyone takes to be true and sufficiently proven. it is a question of looking to the future and seeing if we can go one step further. but it is a difficult step, the most difficult, in my opinion, that human science has ever attempted, and which requires something other than the use of heat or the application of ordinary electrical forces. chemistry may be a new science, but chemical phenomena are as old as the world itself, and the radicals of inorganic chemistry that are to be subjected to further decomposition have been known to mankind for a long time. their existence is revealed from the earliest historical times when their immutability is also revealed in a way […]. decomposing the radicals of inorganic chemistry would therefore be a more difficult task than the one lavoisier had the pleasure of undertaking and accomplishing. for it would mean revealing not only new and unknown beings, as we discover from time to time, but beings of a new and unknown nature whose appearances and properties our minds cannot by any analogy imagine. this would mean taking the analysis of matter to a point that neither the most energetic natural forces nor the combinations and processes of the most powerful science have ever reached. it would mean harnessing forces that we are unaware of, or reactions that no one has imagined. it's one of those problems that human thought needs to ponder for centuries […]»71. nowadays, we can safely assume that this essay represents one of the last academic contributions to that chemical research on metallic transmutation influenced by concepts, images and speculations of alchemical derivation. moreover, when in 1888 tiffereau returned to the question of how to replicate the mexican transmutations of over forty years earlier, his interlocutor would no longer be academia, but the elite of the second generation of french occultism72. within the fin de siècle occultist milieu, constantly seeking an epistemologically impossible synthesis between science and esoteric beliefs, speculations on the unity of matter would know a new phase, aiming at a representation and study of matter understood as an epiphenomenon of ether, described in turn as the material and vital principle of the entire phenomenic reality73. by contributing to the acceptance of an atomism physically intended which, however, in france would prevail only in the early 20th century74 cannizzaro’s reform, crowned by the endorsement of the greater part of the chemistry community gathered in karlsruhe for its first international conference (3-5 september 1860)75, in all likelihood also contributed to the demise of theoretical elaborations such as those of dumas. just as alchemy did not meet its end with the birth of modern chemistry during the second half of the 18th century, it did not continue to exist, from then on, solely as an esoteric discipline governed by gnoseological paradigms irreconcilable with any modern idea of science. in this respect, the enquiry into the relationships between chemistry and alchemy during the 19th century offers an excellent chance to investigate in a more in-depth and impartial fashion not only debates on the nature and behaviour of matter on the one hand and esoteric conceptualisations on the other. such an enquiry grants also the opportunity to analyse the set of biases, convictions and personal beliefs (often part of unconscious cognitive processes) that characterised the history of both disciplines during a period of epochal transformations. the case of dumas dealt with on this occasion has been chosen both for its relevance and to illustrate how it does not represent a rare exception, but rather part of a large and multi-faceted chapter in the history of science and ideas still largely to be written. 1 w. h. brock, from protyle to proton. william prout and the nature of matter, 1785-1985, adam hilger ltd., bristolboston, 1985, pp. 83-84; m. p. banchetti-robino, in what is a chemical element? a collection of essays by chemists, philosophers, historians, and educators (eds. e. scerri, m. ghibaudi), oxford university press, oxford-new york, 2020, pp. 87-108; b. bensaude-vincent, ivi, pp. 32-52. 2 j.-b. dumas, annales de chimie et de physique, 1826, 33, 337-391; m. chaigneau, j.-b. dumas, chimiste et homme politique. sa vie, son oeuvre: 1800-1884, guy le prat, paris, 1984, pp. 81-88; m. novitski, auguste laurent and the prehistory of valence, harwood academic publishers, chur [etc.], 1992, pp. 15-16. 3 a. avogadro, journal de physique, de chimie, d’histoire naturelle et des arts, 1811, 73, 58-76. 4 a.-m. ampère, annales de chimie, ou recueil de mémoires concernant la chimie et les arts qui en dépendent, 1814, 90, 43-86. 5 j. i. solov’ev, эволюция основных теоретических проблем химии, наука, москва, 1971, p. 128. dumas certainly came to know the results of berzelius’ research on the calculation of atomic weights published both in the third volume of his lärbok i kemien and in the fifth of the journal he founded together with wilhelm hisinger, 1766 1852 (afhandlingar i fysik, kemi och mineralogi) through their french edition, the publication of which was supervised by the author himself; j. j. berzelius, lärbok i kemien, tryckt hos direct. henr. a. nordström, stockholm, 1808-18 (3 vols.), iii (1818); id., essai sur la théorie des proportions chimique et sur l’influence chimique de l’électricité […], chez méquignon-marvis, libraire pour la partie de médecine, rue de l’école de médecine, n. 3, près celle de la harpe, paris, 1819. 6 see ref. 5 (berzelius 1808-18), iii, pp. 104-130; e. m. melhado, jacob berzelius: the emergence of his chemical system, almqvist & wiksell, stockholm; university of wisconsin press, madison (wi), 1981, pp. 270-278; g. eriksson in enlightenment science in the romantic era: the chemistry of berzelius and its cultural setting (eds.: e. m. melhado, t. l. frängsmyr), cambridge university press, cambridge, 1992, pp. 56-84. 7 w. prout, annals of philosophy, 1815, 6, pp. 321-330; see ref. 1 (brock), pp. 82-89. 8 p. l. dulong, a. t. petit, annales de chimie et de physique, 1819, 19, pp. 395-413; r. fox, the british journal for the history of science, 1968, 4,1, pp. 1-22. to appreciate the degree of accuracy achieved by the two scientists in calculating the constant (equal to 6.2 cal/°c), it is only necessary to multiply the average of the values describing the heat capacity of the elements by the atomic weight unit derived from berzelius’ data (o = 100) and divide it by the correct atomic weight of the same element (o = 15.9994). the result obtained is 6.004. 9 e. mitscherlich, annales de chimie et de physique, 1820, 14, pp. 172-191; id., kongliga vetenskaps akademiens handlingar, 1821, 9, pp. 4-79; e. m. melhado, historical studies in the physical sciences, 1980, 11,1, pp. 87-123; h.-w. schütt, eilhard mitscherlich: baumeister am fundament der chemie, oldenbourg, münchen, 1992, pp. 81-90. on berzelius’ application of dulong-petit law and isomorphism to the calculation of atomic weights, see j. w. van spronsen, chymia, 1967, 12, pp. 157-169; j. i. solov’ev, v. i. kurinnoi, якоб берцелиус: жизнь и деятельность, наука, москва, 19802, pp. 78-83; h.-w. schütt in ref. 6 (e. m. melhado, t. l. frängsmyr), pp. 171-179. berzelius’ results were disseminated in france through a new translation of the lärbok and a second edition of the 1819 monograph; cf. j. j. berzelius, traité de chimie minérale, végétale et animale, firmin-didot frères, libraires-éditeurs, paris, 182933 (8 vols.); id., théorie des proportions chimiques, et table synoptique des poids atomiques des corps simples et de leurs combinaisons les plus importantes, firmin-didot frères, libraires-éditeurs, paris, 1835. 10 j.-b. dumas, dissertation sur la densité de la vapeur de quelques corps simples, imprimerie de m.e v.e thuau, paris, 1832. 11 see ref. 2 (dumas), pp. 354-355. 12 ivi, p. 339; id., traité de chimie, appliquée aux arts, chez béchet jeune, paris, 1828-46 (8 vols. and 1 atl.), i, pp. xxxviii-xxxix. 13 see ref. 5 (berzelius 1808-18), iii, pp. 106-107. cl = 221.325 (o = 100) → cl = 69.164 instead of 35.453; weight of diatomic phosphorus contained in the molecule of phosphorus pentoxide (p2o5 but described as po5 by then) = 196.15 → p = 61.71 instead of 30.973. 14 m. g. faershtein, история учения о молекуле в химии (до 1860 г.), наука, москва, 1961, pp. 70-88, 123-126. 15 w. h. wollaston, philosophical transactions of the royal society of london, 1814, 104, pp. 1-22; m. c. usselman, pure intelligence: the life of william hyde wollaston, the university of chicago press, chicago, 2015, pp. 190-239. 16 j. petrel, la négation de l’atome dans la chimie du xixème siècle: cas de jean-baptiste dumas, centre national de la recherche scientifique, centre de documentation sciences humaines, paris, 1979, pp. 19-29. 17 m. a. gaudin, annales de chimie et de physique, 1833, 52, pp. 113-133; t. m. cole, isis, 1975, 66,3, pp. 334-360; see refs. 2 (chaigneau), pp. 83-84, and 14 (faershtein), pp. 88-98. 18 see ref. 16 (petrel); l. j. klosterman, annals of science, 1985, 42,1, pp. 1-80: 73-80. 19 thomas thomson, an attempt to establish the first principles of chemistry by experiment, printed for baldwin, craddock, and joy, london, 1825 (2 vols.); id., principes de la chimie, établis par les expériences; ou essai sur les proportions définies dans la composition des corps […], crevot, libraire-éditeur, rue de l’école de médecine, n. 3, près celle de la harpe, paris, 1825 (2 vols.); m. p. crosland, in john dalton and the progress of science (ed.: d. s. l. cardwell), manchester university press, manchester, 1968, pp. 274-287. 20 r. keen, the life and work of friedrich wöhler (1800-1882), traugott bautz, nordhausen, 2005, pp. 73-102; k. c. nicolaou, angewandte chemie international edition, 2013, 52,1, pp. 131-146. 21 w. b. jensen, journal of chemical education, 2006, 83,6, pp. 838-839. 22 w. prout, annals of philosophy, 1816, 7, pp. 111-113; see ref. 1 (brock), pp. 97-108. 23 j.-b. dumas, leçons sur la philosophie chimique, bechet jeune, paris, 1837, pp. 30-32. 24 j.-b. dumas, annales de chimie et de physique, 1834, 56, pp. 113-154; a. dumon, r. luft, naissance de la chimie structurale, edp sciences, les ulis, 2008, pp. 31-38. 25 see ref. 23 (dumas), pp. 316-320. 26 ivi, p. 267. 27 r. siegfried, isis, 1963, 54,2, pp. 147-158. 28 j. j. berzelius, m. m de pontin, economiska annaler med kongl. maj:ts nådigste tillstånd utgisna af kongl. vetenskaps-academien, 1808, 6 (may), pp. 110-130; 6 (june), pp. 113-118 (maxime pp. 122-130); see ref. 9 (solov’ev, kurinnoi), pp. 59-63; see ref. 6 (melhado), pp. 203-210. the curious amalgam was independently discovered and similarly described during the same year by thomas johann seebeck (1770 1831) and johann friedrich august göttling (1753 1809); cf. t. j. seebeck, journal der chemie, physik und mineralogie, 1808, 5, pp. 482-483; j. f. a. göttling, elementarbuch der chemischen experimentirkunst, bey h. ch. w. seidler, jena, 1808-9 (2 vols.), i, pp. 247-249; j. r. partington, a history of chemistry, macmillan, london, 1961-70 (4 vols.), iv, p. 48. 29 see ref. 28 (berzelius, de pontin), p. 130. 30 h. davy, the collected works of sir humphry davy, bart. (ed.: j. davy), smith, elder and co., cornhill, london, 1839-40 (9 voll.), v, pp. 102-139 (electro-chemical researches on the decomposition of the earths 30 june 1808): 130-131. 31 r. siegfried, chymia, 1964, 9, pp. 117-124. 32 see ref. 5 (berzelius 1808-18), ii, pp. 48-65. 33 ivi, pp. v, 45-68. 34 c.-l. berthollet, nouveau bulletin des sciences, par la société philomathique de paris, 1808, 1, pp. 150-152; a.-m. ampère, annales de chimie et de physique, 1816, 2, pp. 5-32: 16. joseph louis gay-lussac (1778 1850) and louis jacques thénard dumas’ mentor for some time were even inclined to believe in the existence of a phlogistic principle whereby metals would be hydrogenated compounds: j. l. lussac, l. j. thénard, annales de chimie, ou recueil de mémoires concernant la chimie et les arts qui en dépendent, 1808, 65, pp. 325-326; idd., ivi, 1808, 66, pp. 205-217; idd., ivi, 1810, 73, pp. 197-214. 35 m. bernal, j. m. harrie, s. w. massey, monthly notices of the royal astronomical society, 1954, 114,2, pp. 172-179; d. j. stevenson, nature, 1975, 258,5532, pp. 222-223; a. baranski, w. lu, electroanalytical chemistry, 1993, 355,1/2, pp. 205-207. the solution to the problem required knowledge that would not be within the reach of physicochemical research for several decades yet. moreover, the reasons behind the behaviour of ammonium remain largely to be clarified, after stabilisation of the metallic phase of the compound. so far, it has only been theorised and plausibly believed to exist under particular conditions of temperature and pressure, such as those hypothetically detectable in the cores of planets like uranus and neptune. 36 see ref. 12 (dumas), ii, pp. 39-44; iii, pp. 634-637; v. pp. 691-692. 37 ivi, ii, p. 43. 38 ivi, v, p. 692. 39 see ref. 2 (chaigneau), pp. 96-102; j.-b. dumas, f.-p. boullay, annales de chimie et de physique, 1827, 36, pp. 294310; idd., ivi, 1828, 37, pp. 15-53; u. klein, experiments, models, paper tools: cultures of organic chemistry in the nineteenth century, stanford university press, stanford, 2003, pp. 118-129, 133-137. 40 c.-a. wurtz, histoire des doctrines chimiques depuis lavoisier jusqu'à nos jours, librairie de l. hachette et cie, boulevard saint-germain, n° 77, paris, 1869, p. 77. 41 see ref. 39 (dumas, boullay 1828), pp. 36-37. 42 see ref. 34 (ampère). 43 see ref. 12 (dumas), v, pp. 690-694. 44 see ref. 23 (dumas), p. 267. in chronological order, maybe the first of the ‘illustrious chemists’ dumas was thinking of was christoph girtanner (1760 1800), who already prophesied an alchemical vengeance ushered by the decomposition of bodies deemed elementary, starting with nitrogen: “there is no refuted opinion to which we may not recur, and again examine. philosophy acknowledges no authority which can proscribe it from admitting, or forbid it to examine. there are many other opinions, long ago refuted, to which we ought still to recur; for example, that of the transmutation of metals. what chemist at present will dare to deny the possibility of it? the change of one metal into another ought to appear less difficult than the conversion of the sweetest body (sugar) into the sourest (oxalic acid); than the change of the hardest body (the diamond) into the softest (carbonic acid gas); than the change of the most transparent (the diamond) into the most opake (charcoal). in the 19th century the transmutation of metals will be generally known and practised”; c. girtanner, the philosophical magazine, 1800, 6, pp. 335-354: 353. 45 j.-b. dumas, j. von liebig, comptes rendus de l’académie des sciences, 1837, 5, pp. 567-572; o. t. benfey, from vital force to structural formulas, houghton mifflin co., boston, 1964, pp. 36-37; see ref. 39 (klein), pp. 161-163. 46 j.-b. dumas, comptes rendus de l’académie des sciences, 1840, 10, pp. 149-178: 158; id., annales de chimie et de physique, 1840, 73, pp. 73-100; id., justus liebigs annalen der chemie, 1840, 33, pp. 259-300; see ref. 2 (chaigneau), pp. 117-131; c. gérard, l’actualité chimique, 2002, 254, pp. 38-46; see ref. 39 (klein), pp. 188-202. 47 see ref. 2 (chaigneau), pp. 78-79; w. h. brock, justus von liebig: the chemical gatekeeper, cambridge university press, cambridge, 1995, pp. 80-87; a. j. rocke, nationalizing science: adolphe wurtz and the battle for french chemistry, the mit press, cambridge (ma)-london, 2001, pp. 94-95; j. drulhon, jean-baptiste dumas (1800-1884). la vie d’un chimiste dans les allées de la science et du pouvoir, hermann, paris, 2011, pp. 84-87. 48 e. i. hjelt, sammlung chemischer und chemisch-technischer vorträge, 1908, 12, pp. 447-482 (or. ed. berzelius liebig dumas i deras förhållande till radikalteorin 1832-1840, edlundska bokhandeln, helsingfors, 1903). 49 a.-é. baudrimont, traité de chimie générale et expérimentale, avec les applications aux arts, à la médecine et à la pharmacie, chez j.-b. baillière, paris, 1844-46 (2 vols.), i, pp. 68-69, 275. 50 j. w. döbereiner, annalen der physik und chemie, 1829, 15, pp. 301-307; e. scerri, the periodic table: its story and its significance, oxford university press, oxford-new york, 20202, pp. 46-54. 51 id., foundations of chemistry, 2010, 12,1, pp. 69-83; see ref. 50 (scerri), pp. 33-135. 52 l. cerruti, in s. cannizzaro, sunto di un corso di filosofia chimica (ed.: l. cerruti), sellerio, palermo, 1991, pp. 73282: 185; l. anatrini, m. ciardi, la scienza impossibile. percorsi dell’alchimia in francia tra ottocento e novecento, carocci, roma, 2019, p. 39-41, see ref. 50 (scerri), p. 56. 53 w. v. farrar, the british journal for the history of science, 1965, 2,4, pp. 297-323: 305-306; see ref. 52 (cerruti), pp. 185-190. 54 report of the twenty-first meeting of the british association for the advancement of science; held at ipswich in july 1851, john murray, albemarle street, london, 1852, p. xxi. 55 l. a. marchand, the athenaeum: a mirror of victorian culture, the university of north carolina press, chapel hill (nc), 1941, p. 226. 56 [l. playfair], the athenaeum: journal of literature, science, and the fine arts, 12 july 1851, 1237, p. 750; see ref. 53 (farrar), p. 304. 57 this kind of papers, sent in the form of pli cacheté to be kept sealed, was used in disputes concerning discoveries and inventions, in order to establish paternity. the senders made use of them in particular, as in the case of tiffereau, when they considered the results of their research not yet definitive, and therefore not disclosable. thus, in most cases, as no dispute arose, these papers remained secret and their content known only to the authors. the académie des sciences, since the early 1980s, has adopted a new policy whereby papers dating back at least one hundred years can be opened; é. brian, c. demeulenaere-douyère, histoire et mémoire de l’académie des sciences: guide des recherches, tec & doc, paris, 1996, pp. 73-74. the contents of the memoir sent by tiffereau on 6 january 1851 only became known on 9 june 1983; archives de l’académie des sciences, pli cacheté 1070. 58 tiffereau is one of the very few protagonists of 19th century alchemical research on whose work a dedicated study has been conducted: l. m. principe, alchemy and chemistry. breaking up and making up (again and again), smithsonian libraries, washington d.c., 2017, pp. 24-53. for a detailed biographical profile of tiffereau, see p. virat, vaugirardgrenelle: bulletin de la société historique et archéologique du xve arrondissement de paris, 2015, 45, pp. 47-58. 59 c.-t. tiffereau, les métaux sont des corps composés. production artificielle de l’or […], imprimerie a. quelquejeu, rue gerbert, 10, paris, 1888, pp. 9-20, id., la science en face de la transmutation des métaux. production chimique de l’or, imprimerie billon, rue du commerce, 47, paris, 1906, pp. 4-8. 60 id., la transmutation des métaux. les métaux sont des corps composés ainsi que les gaz, preuves incontestables basées sur des faits indéniables, chez l’auteur, vaugirard; imprimerie a. quelquejeu, rue gerbert, 10, paris, 1900, pp. 4-5. of the numerous accounts of the experiment provided by tiffereau, this is arguably the most detailed one. 61 archives de l’académie des sciences, pli cacheté 1052; c.-t. tiffereau, nouveaux procédés d’irrigation, de desséchement et de drainage spécialement applicables à la grande et à la petite industrie agricole […], imprimerie de l. martinet, rue mignon, 2, paris, 1854. 62 this other pli remained sealed until 1983, while the incredible annex containing the artificial gold sample was not opened until 2015 (related chemical analyses have yet to be conducted); see ref. 58 (principe), pp. 28-33; id., l’actualité chimique, 2017, 424, pp. 68-71: 70-71. 63 comptes rendus de l’académie des sciences, 1853, 37, p. 579. 64 see ref. 34 (gay-lussac, thénard). 65 bulletin des lois de l’empire français. xie série, imprimerie impériale, paris, 1853-69 (34 voll.), v (1855), pp. 1161, 1178. 66 j. c. poggendorff, biographisch-literarisches handwörterbuch zur geschichte der exacten wissenschaften […], verlag von johann ambrosius barth, leipzig, 1863 (2 vols.), i, col. 1442; f. szabadváry, history of analytical chemistry, pergamon, oxford, 1966, p. 274. 67 c.-t. tiffereau, les métaux sont des corps composés […], imprimerie d’alfred choisnet, rue de l’église, 6 et 8, vaugirard, 1855, pp. 47-52. as carefully pointed out see ref. 58 (principe), p. 74 the experimental protocol followed by levol at the mint differed from the one originally developed by tiffereau in mexico. unfortunately, the same goes with the only known reproduction conducted in more recent times; cf. a. truman schwartz, g. b. kauffman, journal of chemical education, 1976, 53,3, pp. 136-138, 53,4, pp. 235-239: 238. 68 j.-b. dumas, comptes rendus de l’académie des sciences, 1857, 45, pp. 709-731; id., ivi, 1858, 46, pp. 951-953; 47, pp. 1026-1034 ; id., ivi, 1859, 48, pp. 139-142, 372-375; id., annales de chimie et de physique, 1859, 55, pp. 129-210. 69 see ref. 2 (chaigneau), pp. 178-183. 70 s. cannizzaro, nuovo cimento, 1858, 8, pp. 16-17: 16. 71 see refs. 68 (dumas 1859 annales), pp. 207-209, 52 (cerruti), pp. 188-189, and 52 (anatrini, ciardi), pp. 39-40. 72 see ref. 58 (principe), p. 51. 73 see ref. 52 (anatrini, ciardi), pp. 117-118, 160-161. on the role of ether physics in late 19th-century chemical research and esoteric discourse, see conceptions of ether. studies in the history of ether theories, 1740-1900 (eds.: g. n. cantor, m. j. s. hodge), cambridge university press, cambridge, 1981; h. kragh, ambix, 1989, 36,2, pp. 49-65; e. asprem, aries. journal for the study of western esotericism, 2011, 11,2, pp. 129-165. 74 p. colmant, revues des questions scientifiques, 1972, 33, pp. 493-519; a. j. rocke, chemical atomism in nineteenth century, ohio state university press, columbus (oh), 1984, pp. 321-326. 75 see refs. 14 (faershtein), pp. 342-343, 5 (solov’ev), p. 151, and 52 (cerruti), pp. 207-214; h. hartley in studies in the history of chemistry, clarendon press, oxford, 1971, pp. 185-194; m. ciardi, reazioni tricolori. aspetti della chimica italiana nell’età del risorgimento, franco angeli, milano, 2010, pp. 182-183. substantia. an international journal of the history of chemistry 1(2): 7-17, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-25 citation: h. kragh (2017) on the ontology of superheavy elements. substantia 1(2): 7-17. doi: 10.13128/ substantia-25 copyright: © 2017 h. kragh. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declared that no competing interests exist. research article on the ontology of superheavy elements helge kragh niels bohr institute, university of copenhagen, blegdamsvej 17, copenhagen, denmark e-mail: helge.kragh@nbi.ku.dk abstract. the study of so-called superheavy elements with atomic numbers z > 102 has for several decades been a major research field in nuclear physics and chemistry. presently all elements up to and including z = 118 have been discovered and assigned official names by iupac. to speak of “discovery” is however unfortunate since the elements are in reality produced, manufactured or created in the laboratory. they are not found in nature. moreover, it is not obvious that they exist in the normal sense of the term or that they can be called elements at all. apart from sketching the history of transuranic and superheavy elements, the paper focuses on some of the philosophical issues which are relevant to the synthesis of very heavy elements at the end of the periodic table. in addition, the relationship between superheavy elements and exotic atoms (such as anti-atoms and muonic atoms) are briefly considered. keywords. superheavy elements, nuclear chemistry, transuranic elements, discovery, periodic table. 1. introduction for more than half a century the synthesis and study of very heavy chemical elements have attracted much attention not only scientifically but also in the public sphere. what are known as superheavy elements, commonly abbreviated shes (she in the singular), are investigated in a few large and very expensive research facilities currently located in russia, the united states, germany, and japan. whereas the transuranic elements up to z = 100 were produced by means of neutron capture or irradiation with alpha particles, since the late 1960s the basic method of synthesis has been heavy-ion collisions where a target of a heavy element is bombarded with accelerated ions of a lighter element. for example, in 1981 a few atoms of element 107 (bohrium) were produced in the nuclear reaction + → + ncr   bi bh  24 54 83 209 107 262 0 1 in so far that she research is concerned with the formation of new atomic nuclei and relies crucially on advanced accelerator and detection technology, it is a branch of nuclear physics rather than chemistry. on the other hand, in the identification of new nuclides methods of nuclear chemistry are indispensable. 8 helge kragh more importantly, shes are about elements and there is a long historical tradition that everything concerning new elements belong to the domain of chemistry. the responsibility of recognizing new elements still belongs to iupac (the international union of pure and applied chemistry) and not to the physicists’ sister organization iupap (the international union of pure and applied physics). the distinction between physics and chemistry in modern she research is in some way artificial as workers in the field rarely consider themselves as either physicists or chemists. nonetheless, the relationship between the two sister sciences in this research area has often been characterized by controversy rather than harmony.1 while the scientific literature on the synthesis and properties of shes is dauntingly large, there is no comprehensive history of she research. what has been written is limited to reviews from the perspective of the scientists participating in the development.2 next to nothing has been written on the subject from a proper historical perspective and even less from a philosophical perspective. and yet, as eric scerri points out, the synthesis of shes “has raised some new philosophical questions regarding the status of the periodic law.”3 the subject is indeed of considerable interest from the point of view of history, philosophy and sociology of science.4 in this paper i focus on the crucial notion of what constitutes a chemical element. can one reasonably claim that superheavy elements exist in the same sense that the element oxygen exists? after all, they are created in the laboratory and not discovered in nature such as has been the case with most elements. apart from this ontological question, she research also involves the epistemic question of how knowledge of a new she is obtained and what the criteria for accepting discovery claims are. and, what is equally important, who are responsible for the criteria and for evaluating discovery claims? the latter questions are relevant to the paper, but not what it is primarily about. they deserve a fuller treatment. the synthesis and scientific study of shes, not to mention the historical development of the field, may not be well known to the majority of chemists and historians of chemistry. for this reason i start with two introductory sections offering a brief historical account of how the early attempts in the 1930s to produce transuranic elements in the post-world war ii era grew into the modern research area which may be best characterized as a hybrid between high energy physics and nuclear chemistry. 2. artificial chemical elements the periodic table consists presently of 118 elements, starting with hydrogen of atomic number z = 1 and ending with oganesson of z = 118. about a quarter of the elements does not exist in nature or only exist in miniscule amounts. twenty-six of the elements are transuranic, meaning that they have atomic numbers larger than the z = 92 for uranium, the heaviest of the naturally occurring elements. the name “transuranic” (german “transurane”) may first have been used by the german physicist and engineer richard swinne in a paper of 1926 dealing with the periodic system.5 on the basis of bohr’s atomic theory swinne proposed detailed electron configurations for elements with 92 < z < 108. although speculations concerning transuranic elements can be found as early as the late nineteenth century,6 it was only with the development of nuclear physics in the 1930s that laboratory synthesis of the elements became a realistic possibility. famously, enrico fermi and his research group in rome thought for a short while to have obtained the elements 93 and 94 by bombarding uranium with slow neutrons: β β+ → → + → +− −nu u ao hs 292 238 0 1 92 239 93 239 94 239 the supposed but premature discovery of two new elements – provisionally called ausenium (ao) and hesperium (hs) – was part of the reason for awarding fermi figure 1. a version of the history of element discoveries according to two leading dubna scientists. source: g. n. flerov, g. ter-akopian, pure appl. chem. 1981, 53, 909, on p. 910. © iupac. 9on the ontology of superheavy elements the nobel prize in physics in 1938.7 it soon turned out that the announcement was a mistake. only in 1940, when investigating fission fragments from neutron-irradiated uranium, did edwin mcmillan and philip abelson at the berkeley radiation laboratory succeed in detecting element 93, soon to be named neptunium. the more important discovery of element 94 (plutonium) made by glenn seaborg, arthur wahl and joseph kennedy followed a year later. due to the war it was only announced in public in a paper of 1946. however, the first artificial element ever produced in the laboratory was sub-uranic and a result of fermi’s group in rome. in 1937 emilio segré and his collaborator carlo perrier analyzed plates of molybdenum irradiated with deuterons and neutrons from the berkeley cyclotron. they were able to identify two isotopes of element 43, for which they proposed the name “technetium” ten years later. there had earlier been several unconfirmed claims of having detected the element in natural sources, as reflected in names such as “masurium” and “illinium,” but segré and perrier soon became recognized as discoverers.8 segré is also recognized as the co-discoverer, together with dale corson and kenneth mackenzie, of element 85 which was produced in berkeley in 1940 by bombarding bi-209 with alpha particles. in 1947 they suggested the name astatine for it. tiny amounts of astatine exist in nature, and also in this case there were previous claims of having identified the very rare element.9 the early history of transuranic elements was completely dominated by a group of californian chemists and physicists led by seaborg and albert ghiorso. elements 95 and 96 were first identified in 1944 at the metallurgical laboratory in chicago and named americium (am) and curium (cm), respectively.10 after the war followed the discovery of z = 97 (berkelium, bk) and z = 98 (californium, cf ) which were announced in 1950. in 1951, at a time when six transuranic elements had been added to the periodic system, seaborg and mcmillan were awarded the nobel prize in chemistry “for their discoveries in the chemistry of the transuranium elements.” elements 99 and 100, named einsteinium (es) and fermium (fm), were first identified in late 1952, not in a planned experiment but in the fallout from a test of the american hydrogen bomb (the discovery team led by ghiorso only published its findings in 1955, a delay caused by orders from the u.s. military). also in 1955, the discovery of element 101 (mendelevium, md) was announced by the berkeley group using its cyclotron to irradiate a tiny sample of the einsteinium isotope es-253 with alpha particles. the californian dominance in the synthesis of new transuranic elements was first challenged in connection with element 102. an isotope of this element was claimed discovered by experimenters in stockholm in 1957 and some years later also by the russian physicist georgii flerov and his group at the new joint institute for nuclear research (jinr) in dubna outside moscow. founded in 1956, the dubna institute soon became a most important centre for nuclear physics and chemistry.11 much of the later research in the synthesis of heavy transuranic elements was marked by an intense rivalry between the two research centres, one american (lbnl, lawrence berkeley national laboratory) and the other russian (jinr). although transuranic elements are artificial there is a faint possibility that some of their isotopes have a long life-time and are not exclusively the products of nuclear laboratories. since about 1970 there have been numerous searches for heavy transuranic elements in nature, but so far not a single atom has been found. the exception is neptunium and plutonium which, strictly speaking, do occur naturally. however, the trace amounts found of these two elements are not of primordial origin but owe their existence to nuclear reactions in uranium such as neutron capture followed by beta decay. the two elements exist in nature in extremely low concentrations only, such as illustrated by the amount of plutonium in the uranium mineral pitchblende (largely uo2), which is about one part to 1011. several of the transuranic elements have been made in visible quantities and a few of them, such as long-lived isotopes of curium and americium, have even found applications in science and industry (many household smoke detectors contain the americium isotope am-241). plutonium is unique by being the only synthetic element produced in very large quantities, primarily a result of its use in nuclear weapons. it is estimated that today the world stockpile of the element is about 500 tons.12 the long half-life of plutonium (2.4 × 104 years for pu-239) means that the element is not just an ephemeral visitor on earth but will remain with us for thousands of years to come. the heaviest isotope detected in nature is pu-244 with a half-life of 81 million years. 3. a brief history of superheavy elements the term “superheavy element” for the heaviest of the transuranic elements has no precise meaning but often refers to the transactinide elements with z ranging from 103 to 120. the name owes its origin to the american physicist john wheeler, who in the 1950s examined theoretically the limits of nuclear stability. however, it can be found even earlier, perhaps first in a 1938 review 10 helge kragh paper on possible transuranic elements.13 on the basis of the liquid drop model of nuclear structure wheeler suggested that atomic nuclei twice as heavy as the known nuclei might be ascribed “experimental testable reality.”14 with this phrase he implied that the nuclei should have a lifetime greater than 10-4 second. the first scientific paper with “superheavy elements” in the title appeared in 1966 and fifty years later the cumulative number of such papers had grown to approximately 2,000. much of the impetus for she research derives from theories of nuclear structure and in particular from predictions based on the shell or independent-particle model developed in the late 1940s independently by maria goeppert mayer in the united states and hans jensen and collaborators in germany.15 according to mayer, nuclei with 2, 8, 20, 50, 82, and 126 protons or neutrons were particularly stable. these were “magical numbers” representing closed shells in the nucleus, an idea which mineralogists had anticipated much earlier. the first anticipation of magical numbers dates from 1921 and was due to the swiss mineralogist paul niggli.16 the theoretical possibility of a relatively stable element of z = 126 seemed remote from laboratory physics, but in the late 1960s more sophisticated nuclear models indicated that z = 114 rather than z = 126 was a magic number. the region around (z, n) = (114, 184) – a “doubly magical” nucleus – was expected to represent nuclei with a relatively long half-life and therefore accessible to experimental study. the region became known as an “island of stability,” a term that may first have appeared in the physics literature in 1966.17 the hope of the experimenters was to reach the fabled island, if it existed, either by manufacturing the nuclides or by finding them in nature. as a leading she physicist recalled, the predictions from nuclear theory “immediately stirred up a gold-rush period of hunting for superheavy elements in natural samples.”18 indeed, from about 1970 many researchers began looking for evidence of shes in cosmic rays, meteorites, terrestrial ores, or even samples of lunar matter.19 the favoured method was to look for tracks due to spontaneous fission, a process which is exceedingly rare in nature but is the dominant decay mode for shes (the probability of spontaneous fission is roughly proportional to the parameter z2/a). the first searches for natural shes were reported in 1969 by research groups from berkeley and dubna, and a decade later the search had grown into a minor industry. the search is still going on, but without any convincing evidence of naturally occurring shes.20 interesting as this chapter in she history is, in the present context there is no need to cover it. one of the problems of reaching the island of stability is that by and large the half-lives of the longest-living nuclides decreases with the atomic number. while the half-life for sg-269 (z = 106) is 3 minutes, it is 14 seconds for ds-281 (z = 110), 2 seconds for fl-289 (z = 114), and 0.7 milliseconds for og-294 (z = 118). another problem is the very low production rate, which typically is of the order of a few atoms per day and in some cases even lower. in spite of these and other problems all shes until and including element 118 have now been discovered and are officially recognized as citizens of the periodic kingdom. the elements with z ranging from 103 to 109 were synthesized in the two decades from 1965 to 1985, in all cases by means of heavy-ion fusion reactions where a target of a heavy element is bombarded with mediumsized ions. the elements were produced in a competitive race between scientists from dubna and berkeley, and since the mid-1970s also involving a third party in the form of the gsi (gesellschaft für schwerionenforschung) figure 2. number of scientific papers including the term “superheavy elements” in the title. source: web of science. 11on the ontology of superheavy elements in darmstadt, germany, established in 1969. in the present context there is no need to go into detail or to dwell on the many controversies between the research groups concerning priority and names.21 elements with atomic numbers 110, 111 and 112 were produced by the darmstadt group in the years 1995 and 1996 and eventually named darmstadtium (ds), roentgenium (rg) and copernicium (cn). the even heavier elements 114 and 116 (flerovium and livermorium) were first synthesized in dubna by a russian-american collaboration including scientists from llnl, the lawrence livermore national laboratory. the most recent newcomers to the periodic table are the elements with atomic numbers 113, 115, 117 and 118, which all received official recognition in 2016. the first atoms of element 113, named nihonium (nh) were produced in 2003-2005 by a team at the riken nishina center for accelerator-based science in japan. elements 115 and 117 were synthesized in experiments from 2010 by the dubna-livermore collaboration extended with scientists from the oak ridge national laboratory in tennessee. while element 115 was named moscovium (mc), element 117 was assigned the name tennessine (ts). element 118 was another product of the successful dubna-livermore collaboration led by the dubna physicist yuri oganessian, a highly esteemed veteran in she research. in experiments of 2006 the team observed three decay chains arising from the fusion of ca-48 and cf-249, which was interpreted as due to the formation of the a = 294 isotope of element 118, namely + → + nca   cf og  320 48 98 249 118 294 0 1 the results obtained in 2006 were confirmed and improved in subsequent experiments, but it took until 2016 before the discovery was officially recognized and the new element was named oganesson (og) in recognition of the leader of the discovery team.22 although no atoms of oganesson have ever been studied experimentally, calculations predict that its electron shell structure is 2, 8, 18, 32, 32, 18, 8, and that it thus belongs to the group of noble gases. remarkably, this is the very same structure that bohr suggested back in 1922.23 4. criteria for discoveries the history of discoveries and discovery claims of shes differs from the earlier history of most element discoveries. the reason is that short-lived shes are produced artificially and in a small number of atoms only, sometimes one by one, and that the atoms can only be identified indirectly according to certain criteria of nuclear physics and chemistry. moreover, new shes need to have the characteristics of ordinar y elements in order to be placed in the periodic table alongside other elements. the organization responsible for accepting or dismissing discovery claims is iupac, which also authorizes the names and symbols of the elements. bureaucratically speaking, an element is only an element when it has been officially approved by the iupac council. the names of the transuranic elements were first considered at the 15th iupac conference in 1949, when the commission on nomenclature of inorganic chemistry (cnic), a branch under iupac, officially adopted the proposed names for elements 93 to 96.24 during the first decades of the twentieth century there were two basic criteria for recognizing the discovery of a new element, namely the optical spectrum and the atomic weight of the claimed element. since the mid1920s the main criterion became the element’s characteristic x-ray spectrum which directly reveals the atomic number.25 the first element identified and recognized in this way was hafnium, z = 72. however, for several of the superheavy elements none of these criteria are relevant since they have no definite atomic weight and also no spectrum based on electron transitions between different energy levels. besides, x-ray spectroscopy requires amounts of matter much greater than the few atoms often produced in she reactions. the method could only be used indirectly, to determine the characteristic x-rays emitted by atoms of the daughter nuclide after the decay of the parent she nuclide. the confusing number of discovery claims for new shes through the 1960s and 1970s inevitably caused reconsideration of the old question, what does it mean to have discovered a new element? scientists engaged in she synthesis agreed that the atomic number was the defining parameter of an element, but they shared a concern over the confusion caused by missing operational criteria for she discoveries. in 1971 flerov and his dubna colleague, the czechoslovakian nuclear chemist ivo zvára, wrote a memorandum in which they pointed out that the concept of element belonged to chemistry and atomic physics and not to nuclear physics. “if the atomic number is established by chemical means or by techniques of atomic physics (roentgen spectroscopy, etc.),” they stated, “then even without a nuclear-physics identification the work should be considered a discovery.”26 the following year 12 helge kragh two nuclear chemists at the lawrence berkeley laboratory similarly suggested that chemical methods to the identification of atomic numbers would be essential or at least complementary to methods of nuclear physics.27 on the proposal of the dubna group, in 1974 iupac in collaboration with iupap appointed an ad hoc group of nine neutral experts, three of which were from the united states and three from the soviet union. according to the american members of the group, its purpose was “to consider the claims of priority of discovery of elements 104 and 105 and to urge the laboratories at berkeley (usa) and dubna (ussr) to exchange representatives regarding these experiments.”28 however, the initiative was a failure as the committee never completed its work or issued a report. indeed, it never met as a group.29 according to roger fennell, a historian of iupac, “in 1977 iupap said it had lost interest as the existence of the two elements was doubtful anyway.”30 in a paper of 1976 a group of western she specialists pointed out that lack of definite discovery criteria “has contributed significantly to the competing claims for the discovery for these [transuranic] elements.”31 in discussing various ways of identifying new elements, some chemical and other physical, the authors emphasized proof of the atomic number as essential. the 1976 article was general in nature and did not apply the proposed discovery criteria to the ongoing priority controversies. but several years later three of the american co-authors published a detailed investigation of the discovery claims of elements 104 and 105 which was largely based on the 1976 criteria.32 the leading gsi physicist peter armbruster joined the debate in early 1985, expressing his wish of an international physics-chemistry commission taking care of the many controversies over names and discoveries. he proposed that “a name should be accepted only if the experiment claiming the discovery is reproducible.” moreover, “an isotope is defined by its mass and atomic number, its fingerprints are its decay modes and its half-life.”33 armbruster’s paper most likely inspired iupap’s president, the canadian-american nuclear physicist allan bromley, to suggest a working group of physicists to investigate priority questions related to the transfermium elements (z > 100). the result was the transfermium working group (twg) established jointly by iupap and iupac in 1985 and consisting of two scientists nominated by iupac and seven by iupap. to secure neutrality, none of the members were from usa, ussr or west germany, the three nations with she facilities. the responsibility of the group, headed by the distinguished oxford nuclear physicist denys wilkinson, was to formulate criteria for when an element was discovered and to evaluate discovery claims accordingly.34 in a report published in pure and applied chemistry in 1991 the twg investigated systematically and thoughtfully criteria for recognizing the existence of a new chemical element. of interest in the present context is the summary definition formulated by wilkinson and his fellow twg members: “discovery of a chemical element is the experimental demonstration, beyond reasonable doubt, of the existence of a nuclide with an atomic number z not identified before, existing for at least 10-14 s.”35 with regard to the requirement of a minimum lifetime of the nuclide it was introduced to make the formula more chemical and in accord with the standard view of the term element. “it is not self-evident,” the authors wrote, “that ‘element’ makes sense if no outer electrons, bearers of the chemical properties, are present.” it takes about 10-14 second for a nucleus to acquire its electron system and thus to become an atom with certain chemical properties. the same requirement was mentioned in the earlier mentioned report of 1976. “we suggest,” the authors wrote, “that composite nuclear systems that live less than about 10-14 second … shall not be considered a new element.”36 so-called quasi-atoms of very high z are formed transiently in heavy-ion collisions, but they exist only for about 10-20 second. consequently they do not qualify as nuclides of new elements. however, there seems to be no consensus among nuclear physicists of when a nucleus exists. some take the definition of an atomic nucleus to be limited by the time scale 10-12 second, and according to others “if a nucleus lives long compared to 10-22 s it should be considered a nucleus.”37 the definition of an element did not change as the atomic number z was still considered the defining property, as it had been since the early 1920s. on the other hand, the twg report of 1991 pointed out that “the exact value of z need not be determined, only that it is different from all z-values observed before, beyond reasonable doubt.” that determination of the atomic number was still important is shown by the competing claims for having found element 113. when an iupaciupap joint working party decided to attribute the discovery to the riken team and not to the dubna team, it was primarily because the first team provided solid evidence for the atomic number. the dubna measurements, on the other hand, “were not able to within reasonable doubt determine z.”38 the twg was disbanded in 1991 but later on followed by other ad hoc inter-union groups of experts, generally referred to joint working parties or groups. for example, a five-member joint working party was 13on the ontology of superheavy elements established in 2011 to examine claims of having discovered elements with z > 112 and another working party reported in 2016 on element 118. the discovery definition of twg mentioned above was adopted by all the later working parties and can thus be ascribed an authoritative status. 5. discovered or created? the various working groups established by iupac and iupap were concerned with the discoveries of new elements, a term used consistently in their reports. the press release issued by iupac on 30 december 2015 announced “the verification of the discoveries of four new elements” (namely z = 113, 115, 117, and 118).39 but although she scientists agree that their synthetic elements have been discovered, clearly this is in a different sense than the one we associate with the discoveries of, for example, gallium, argon and hafnium. whereas the latter elements were found in nature, shes and artificial elements generally were created or invented, in largely the same way that a statue is created or a technological device invented. they belong to what the ancient greeks called techne (human-made objects or imitation of nature) and not to physis (nature). to aristotle and his contemporaries, techne denoted primarily a kind of craft or skill that could bring forth an artefact from the material nature. interestingly, seaborg insisted that the transuranic elements he and others had found were created rather than discovered. “after all,” he said, “you can’t discover something that doesn’t exist in nature any more than michelangelo discovered his david inside a block of marble.”40 and yet michelangelo did not think of his famous sculpture as just imposing form onto a lifeless block of marble, but rather as releasing a form that was imprisoned in the block. he reputedly said that he just cut away everything that wasn’t david.41 by contrast, it makes no sense to say that a transuranic element is imprisoned in the nuclear reactants out of which it eventually emerges. the creation of synthetic and yet in a sense natural objects did not start with the work of segré and perrier in 1937, for at that time there already was a long tradition in organic chemistry of synthesizing chemical compounds. the first such compound without a counterpart in nature may have been william perkin’s famous discovery (or manufacture) of the aniline dye mauveine in 1856. the discovery initiated the synthetic revolution in chemistry, a revolution which has resulted in millions of man-made molecular compounds. in a sense the synthesis of transuranium elements is a continuation of the tradition in synthetic organic chemistry, only at a more fundamental level. when mendeleev and his followers predicted from the periodic table that certain missing elements actually existed, they implicitly relied on a version of the socalled principle of plenitude.42 according to this metaphysical principle as expounded by leibniz and others, what can possibly exist does exist. nature abhors unactualized possibilities. or, in its modern version, if a hypothetical object is not ruled out by laws of nature it (most likely) will exist and thus be a real object. according to leonard susskind, a physicist and cosmologist, there are planets made of pure gold, for “they are possible objects consistent with the laws of physics.”43 in this line of reasoning it is presupposed that existence refers to nature, but the situation with respect to shes is different as these elements are possible and yet not realized in nature. the potential existence is turned into actual existence not by finding a she in nature, as ordinary elements like gallium and germanium were found, but by creating it in the laboratory. the classical plenitude principle, expressing a belief in nature’s richness and continuity, does not seem applicable to the artificial world created by chemists and physicists.44 whereas plutonium may be said to be a technological product, not only because it is man-made but also in so far that technologies are always purposeful and oriented towards social practices, this is not the case with most of the shes. they have been produced in minute amounts only and serve no social or economic purposes. the business of she research is fundamental science with no aim of contributing to technological and economic progress. it is science for the sake of science. in a recent interview yuri oganessian justified his research field by saying that “it is about tackling fundamental questions in atomic physics.” foremost among the questions is the prediction of an island of stability. according to oganessian: “theorists predict that there should be some superheavy atoms, with certain combinations of protons and neutrons, that are extremely stable … but we are still far from the top of the island where atoms may have lifetimes of perhaps millions of years. we will need new machines to reach it.”45 other leading she scientists have expressed a similar l’art pour l’art attitude. the gsi veteran sigurd hofmann refers to the “sense of the excitement which has motivated workers in this field” and suggests that the motivation for study shes is “because we are curious.”46 but of course one may always fall back on the mantra, as two she nuclear chemists did in 1972, that “practical and useful applications would be forthcoming eventually, as is always the case with basic research.”47 they 14 helge kragh were referring to the possibility that long-lived shes might be discovered in nature. should this be the case, unlikely as it is, these hypothetical elements would have been discovered in the traditional sense (or perhaps in the sense that technetium was discovered). but the short-lived isotopes below the island of stability would still belong to created and not discovered elements. 6. ontological status of the heaviest elements as mentioned, she isotopes have short life-times and thus, in several cases they have been produced only to disappear again almost instantly. the elements have been produced and detected in nuclear processes and thus did exist at the time of the detection. but strictly speaking they do not exist presently any more than dinosaurs exist. the existence of shes is ephemeral or perhaps potential, which is quite different from the existence of ordinary elements whether radioactive or not. can we truly say that the element oganesson exists when there is not, in all likelihood, a single atom of it in the entire universe? sure, more atoms or rather nuclei of element 118 could be produced by replicating or modifying the dubna experiments, which makes the element different from the long-time experiment of living nature known as the dinosaurs. but within a fraction of a second the re-created oganesson atoms would disappear again. one may object that particles with even shorter lifetimes are known from high energy physics without physicists doubting that they really exist. for example, the neutral pion π0 decays into two gamma quanta with a lifetime of about 10-16 seconds. the particle was first detected in nuclear reactions in berkeley in 1950, but contrary to the nuclides of the shes it was also found in nature, namely in cosmic rays. the neutral pion thus exists and is not exclusively a laboratory product. the same is the case with the antiproton, another exotic particle first produced in accelerator experiments, in this case in 1955, and only subsequently detected in the cosmic rays. incidentally, in 1959 owen chamberlin and emilio segré – the co-discoverer of the elements technetium and astatine – were awarded the physics nobel prize for the antiproton experiment. the antiproton can be brought to combine with a positron and thus form anti-hydrogen according to + →+p e h this exotic atomic system has been produced in the laboratory and studied experimentally.48 anti-hydrogen atoms can under laboratory conditions survive for as long as 15 minutes. in 2011 an international collaboration of physicists reported observation of 18 events of artificially produced anti-helium 4 he consisting of two antiprotons and two antineutrons.49 no anti-helium atom has been detected so far. anti-hydrogen has in common with shes that it is element-like and only exists when manufactured. but contrary to the shes, there is no place for anti-hydrogen or other anti-elements in the periodic system. there is also no place in the periodic system for other exotic atoms where the constituent protons and electrons are replaced by elementary particles such as positrons and muons. positronium, a bound system of an electron and a positron, was discovered experimentally in 1951 but had been hypothesized almost twenty years earlier.50 sometimes described as a very light isotope of ordinary hydrogen or protium, the short-lived positronium has been extensively researched and its chemistry studied for more than half a century.51 the positron can be replaced by a positively charged muon (μ+) in which case one obtains muonium with an atomic mass a ≅ 0.11 between positronium and protium. first detected in 1960, muonium has a half-life of about 2 × 10-6 second. if only a historical curiosity, ideas of exotic chemical “elements” had much earlier been entertained by a few chemists suggesting that the electron was such an element. this was what janne rydberg, the swedish physicist and chemist, proposed in 1906, assigning the symbol e for the electron and placing it in the same group as oxygen.52 two years later, the nobel laureate william ramsay independently made a similar proposal, again using the symbol e.53 but nothing came out of these speculations and when the atomic number was introduced in 1913, they were relegated to the graveyard of forgotten chemical ideas. in 1970 the distinguished russian nuclear chemist vitalii goldanski wrote a paper on shes and exotic atoms in which he suggested that mendeleev’s table remained unaffected by the discovery of the latter kind of atoms. he wrote as follows: the replacement of electrons with other negative particles (for example, μ− or π− mesons) does not involve a change in the nuclear charge, which determines the position of an element in the periodic system. as to the replacement of a proton with other positive particles, for example, a positron (e+) or μ+ meson, such a replacement leads to the formation of atoms which in the chemical sense can be considered as isotopes of hydrogen. … on the basis of the value of the positive charge [positronium and hydrogen] occupy one and the same place in the periodic table.54 15on the ontology of superheavy elements goldanski’s view is remarkable but also problematic, to say the least. two widely different elements in the same box of the periodic table? although muonium does not count as an ordinary chemical element it does have chemical properties and has even been assigned a chemical symbol (mu). the analogy between muonic atoms and shes is underlined by the fact that the nomenclature of the first kind of atoms and their chemical compounds has been considered by iupac.55 a related question is whether short-lived transfermium elements really count as elements in the traditional meaning of the term. elements consist of atoms and it is the atoms and their combinations which endow elements with chemical properties. an isolated atomic nucleus has no chemistry. this is what wilkinson and his twg stated in its 1991 report and more recently two nuclear chemists elaborated as follows: “the place an element occupies in the periodic table is not only defined by its atomic number, i.e. the number of protons in the nucleus, but also by its electronic configuration, which defines its chemical properties. strictly speaking, a new element is assigned its proper place only after its chemical properties have been sufficiently investigated.”56 to phrase the point differently, although a chemical element is defined by its atomic number, not everything with an atomic number is an element. the point is worth noticing as nuclear scientists commonly refer to an atomic nucleus or a nuclide as were it an element. for example, the 1991 twg definition stated that a chemical element had been discovered when the existence of a nuclide had been identified. however, the term nuclide, coined in 1947, refers to a species of nucleus and thus emphasizes nuclear properties. by contrast, the corresponding and older term isotope denotes an atomic concept and emphasizes chemical properties. the difference between the two terms is more than just a semantic detail, but unfortunately the terms are often used indiscriminately. not only is the number of produced transfermium atoms extremely small, what are directly formed are nuclei and not atoms. under normal circumstances a bare atomic nucleus will attract electrons and form an atom, but the circumstances of she experiments are not normal and the few atoms may only exist for such a small period of time that they cannot be examined experimentally. no atoms are known for the heaviest of the shes of which only atomic nuclei have been produced and studied. to this date, some 35 nuclei of livermorium (z = 116), all with half-lives less than 50 milliseconds, have been observed.57 despite the elusive nature of shes nuclear scientists have succeeded in measuring some of their chemical and physical properties. ionization potentials have been measured up to lawrencium (z = 103) and even an element as heavy as flerovium (z = 114) has been the object of experimental study. much is known also about other shes, but for some of them the knowledge is exclusively in the form of theoretical predictions, extrapolations and estimates.58 for example, in the case of tennessine, element 117, its oxidation states have been predicted to be +1, +3, and +5; the electron structure and radius of the atom have been calculated and so have the boiling point and density of the element as well as of hypothetical compounds such as tsh and tsf3. but there are no empirical data and none are expected to come in the foreseeable future. of course, the situation is different for the less heavy transuranic elements and especially for plutonium. even some of the transactinides such as rutherfordium and dubnium have a real chemistry.59 consider again the heaviest of the elements, oganesson, which is presently known only as one nuclide with an extremely small lifetime. to repeat, very few of the nuclei have been produced and none of them exist any longer. oganesson has received official recognition from iupac and entered the periodic table alongside other and less exotic elements. and yet one may sensibly ask if oganesson is really a chemical element in the ordinary sense of the term. perhaps its proper status is better characterized as a potential element, somewhat along the line recently suggested by amihud gilead, an israeli philosopher of science.60 i am not arguing for an anti-realist position with regard to the shes at the end of the periodic table. nuclides of these elements undoubtedly exist, or rather they existed at the time of their detection, but it is questionable if they exist or existed as proper chemical elements. 7. conclusion the study of the present state and historical development of shes is not only of interest to the historian of modern chemistry and physics but also raises questions of a more philosophical nature. besides, in so far that much of the modern development of modern she research has taken place within the framework of a few competing nuclear laboratories and been evaluated by working groups established by iupac and iupap, it is also of interest from the perspective of sociology of science. as pointed out in this paper, shes are not discovered in the normal sense of the term but are man-made objects the existence of which is entirely due to artificial nuclear reactions. the short-lived nuclides of shes 16 helge kragh are ephemeral visitors to our universe, which calls into question the meaning of their existence. although they have been officially recognized as chemical elements and designated places in the periodic table, it is far from evident that they can be properly characterized as elements. the old question of what constitutes a chemical element appears in a new light when seen through the lens of she research. references 1. a. ghiorso, g. t. seaborg, prog. part. nucl. phys. 1993, 31, 233; c. jarlskog, epj web of conferences 2016, 131, 06004. 2. g. t. seaborg, w. d. loveland, the elements beyond uranium, john wiley & sons, new york, 1990; d. c. hoffman, a. ghiorso, g. t. seaborg, transuranium people: the inside story, imperial college press, london, 2000; s. hofmann, on beyond uranium: journey to the end of the periodic table, taylor & francis, london, 2002; g. herrmann in the chemistry of superheavy elements, eds. m. schädel, d. shaughnessy, springer-verlag, berlin, 2014, pp. 485-510. 3. e. scerri in philosophy of chemistry, eds. a. woody, r. hendry, p. needham, north-holland, amsterdam, 2012, pp. 329-338, on p. 336. 4. h. kragh, arxiv:1708.04064(physics.hist-ph). 5. r. swinne, zeitschrift für technische physik 1926, 7, 166. 6. h. kragh, eur. phys. j. h 2013, 38, 411. 7. see nobel presentation speech of 10 december 1938, online as https://www.nobelprize.org/nobel_prizes/ physics/laureates/1938/press.html; m. thoenessen, the discovery of isotopes, springer, berlin, 2016, pp. 39-65. 8. for the complicated discovery history of technetium, see e. scerri, a tale of 7 elements, oxford university press, oxford, 2013, pp. 116-143. 9. the discovery history of element 85 is described in b. f. thornton, s. c. burdette, bull. hist. chem. 2010, 35, 81. 10. for a lively account of the two elements’ naming history, see g. t. seaborg, terminology 1994, 1, 229. the discovery and applications of americium are examined in k. kostecka, bull. hist. chem. 2008, 33, 89. 11. d. blokhintsev, soviet atomic energy 1966, 20, 328. 12. https://en.wikipedia.org/wiki/plutonium 13. l. quill, chem. rev. 1938, 23, 87. 14. j. a. wheeler in niels bohr and the development of physics, ed. w. pauli, pergamon press, london, 1955, pp. 163-184; f. g. werner, j. a. wheeler, phys. rev. 1958, 109, 126. 15. k. e. johnson, am. j. phys. 1992, 60, 164; m. mladenović, the defining years of nuclear physics 1932-1960s, institute of physics publishing, bristol, 1998, pp. 287-305. 16. h. kragh, phys. persp. 2000, 2, 381. 17. w. myers, w. swiatecki, nucl. phys. 1966, 81, 1. 18. g. herrmann in the chemistry of superheavy elements, eds. m. schädel, d. shaughnessy, springerverlag, berlin, 2014, pp. 485-510. 19. g. herrmann, nature 1979, 280, 543; f. dellinger et al., phys. rev. c 2011, 83, 065806. 20. g. m. ter-akopian, s. n. dmitriev, nucl. phys. a 2015, 944, 177. 21. on these issues, see ref. 2 (hoffman, ghiorso, seaborg) and ref. 4 (kragh). 22. l. öhrström, j. reedijk, pure appl. chem. 2016, 88, 1225. 23 ref. 6 (kragh); c. nash, j. phys. chem. a 2005, 109, 3493. 24. c. d. coryell, n. sugarman, j. chem. educ. 1950, 27, 460; w. h. koppenol, helv. chim. acta 2005, 88, 95. 25. h. kragh, stud. hist. phil. mod. phys. 2000, 31, 435. 26. the 1971 memorandum was in russian and is here quoted from the translation in g. flerov et al., soviet journal of particles and nuclei 1991, 22, 453, on p. 454. 27. s. g. thompson, c. f. tsang, science 1972, 178, 1047. 28. e. k. hyde, d. c. hoffman, o. l. keller, radiochim. acta 1987, 42, 57. the paper was originally intended to be a contribution to the 1974 working group from the perspective of the americans. 29. a. h. wapstra et al., pure appl. chem. 1991, 63, 879, on p. 881. 30. r. fennell, history of iupac 1919-1987, blackwell science, london, 1994, p. 269. 31. b. g. harvey et al., science 1976, 193, 1271. the authors included seven americans, one german and one frenchman but none from the soviet union. 32. ref. 28 (hyde, hoffman, keller). 33. p. armbruster, ann. rev. nucl. part. sci. 1985, 35, 135. 34. m. fontani, m. costa, m. v. orna, the lost elements: the periodic table’s shadow side, oxford university press, oxford, 2015, p. 386 states mistakenly that the twg chairman was geoffrey wilkinson, the 1973 nobel laureate in chemistry. 35. ref. 29 (wapstra et al.), p. 882; r. c. barber et al., prog. part. nucl. phys. 1992, 29, 453. 36. ref. 31 (harvey et al.). 37. m. thoenessen, rep. prog. phys. 2004, 67, 1187, on p. 1195. 38. p. j. karol et al., pure appl. chem. 2016, 88, 139, on p. 146. 17on the ontology of superheavy elements 39. h t t p s : / / w w w . i u p a c . o r g / c m s / w p c o n t e n t / uploads/2016/01/iupac-press-release_30dec2015.pdf. 40. quoted in g. johnson, “at lawrence berkeley, physicists say a colleague took them for a ride,” new york times, 15 october 2002. 41. c. mitcham, thinking through technology: the path between engineering and philosophy, university of chicago press, chicago, 1994, p. 127. 42. o.t. benfey, j. chem. educ. 1965, 42, 39. for the early history of the principle of plenitude, see a. o. lovejoy, the great chain of being, harvard university press, cambridge, ma, 1976. 43. l. susskind, the cosmic landscape: string theory and the illusion of intelligent design, little, brown and co., new york, 2006, p. 177. 44. r. le poidevin, brit. j. phil. sci. 2005, 56, 117. 45. interview in r. gray, new scientist 2017, 234 (15 april), 40. 46. ref. 2 (hofmann), p. 205. 47. ref. 27 (thompson, tsang). 48. f. close, antimatter, oxford university press, oxford, 2009, pp. 80-100; m. amoretti et al., nature 2002, 419, 456. 49. h. agakishiev et al., nature 2011, 473, 353. 50. for the early history of positronium, see h. kragh, j. chem. educ. 1990, 67, 196. 51. the first monograph on the subject was j. green, j. lee, positronium chemistry, academic, new york, 1964. 52. j. r. rydberg, elektron der erste grundstoff, lund, håkon ohlsson, 1906. 53. w. ramsay, j. chem. soc. 1908, 93, 774. 54. v. i. goldanskii, j. chem. educ. 1970, 47, 406. 55. w. h. koppenol et al., pure appl. chem. 2001, 73, 377. 56. a. türler, v. pershina, chem. rev. 2013, 113, 1237, on p. 1238. see also c. e. düllmann, nucl. phys. news 2017, 27 (issue 2), 14. 57. k. day, nature chemistry 2016, 8, 896. 58. ref. 56 (türler, pershina). 59. j. v. kratz, in handbook of nuclear chemistry, eds. a. vértes et al., springer, berlin, 2011, pp. 925-1004. 60. a. gilead, found. chem. 2016, 18, 183. in the spirit of the principle of plenitude gilead suggests that shes exist as “chemical pure possibilities” whether or not they are synthesized and thus turned into actual elements amenable to experiment. apparently he endows any theoretically predicted atom, whatever its atomic number, with reality. however, gilead’s concept of “panenmentalist realism” seems far from the idea of reality adopted by most chemists and physicists. substantia. an international journal of the history of chemistry 6(2): 43-54, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1564 citation: kragh h. (2022) chemists without knowing it? computational chemistry and the møller-plesset perturbation theory. substantia 6(2): 43-54. doi: 10.36253/substantia-1564 received: feb 01, 2022 revised: apr 1, 2022 just accepted online: apr 15, 2022 published: september 1, 2022 copyright: © 2022 kragh h. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. chemists without knowing it? computational chemistry and the møller-plesset perturbation theory helge kragh niels bohr institute, university of copenhagen, blegdamsvej 17, copenhagen, denmark. e-mail: helge.kragh@nbi.ku.dk abstract. this paper considers aspects of the chemistry-physics relationship from a historical perspective and with a focus on the entrance of quantum mechanics in twentieth-century chemistry. traditionally, theoretical physics was widely regarded as epistemically superior to chemistry if also, from the chemists’ point of view, of little practical relevance. with the emergence of quantum chemistry in about 1930, the gulf widened as it seemed that the new discipline was more physics than chemistry. one way of investigating theoretically many-electron atoms was by means of the hartree-fock approximation method. the møller-plesset perturbation theory introduced in 1934 by a danish and an american physicist was a refinement to the hartree-fock method. although the møller-plesset theory was initially neglected – and is still neglected in the historiography of quantum chemistry – it came to play a most important role in later studies. indeed, it is a prime example of what in sociological studies of science is known as a “sleeping beauty.” the paper discusses the historical context of the møller-plesset theory, concluding that, in a sense, its originators were “chemists without knowing it.” keywords: quantum chemistry, chemistry-physics relations, møller-plesset theory, chemistry nobel prizes, sleeping beauties. 1. introduction much has been written on the physics-chemistry relationship from both a historical and philosophical perspective.[1] in the first part of this paper i briefly discuss how physicists have often considered chemistry a science inferior to their own (section 2). this somewhat condescending attitude was only reinforced with the advent of the so-called old quantum theory principally due to niels bohr and arnold sommerfeld (section 3). the second part is devoted to the emergence and early development of quantum chemistry based on post-1925 quantum mechanics (sections 4-5). rather than dealing with the chemical bond, a classical and well-researched area of the quantumchemical revolution, the paper looks at a theory of many-electron systems from 1934 which seems to have been forgotten in the historical literature http://www.fupress.com/substantia http://www.fupress.com/substantia mailto:helge.kragh@nbi.ku.dk 44 helge kragh (section 6). this theory, the møller-plesset perturbation theory or method, has an interesting and little-known history. it illustrates in its own way how physicists unintendedly could make important contributions to theoretical chemistry. moreover, it also illustrates the concept of a “sleeping beauty,” a term used for scientific papers which hibernate for a long time until they are called alive and become highly influential (section 7). in the final section 8 i briefly reconsider the physics-chemistry relationship in the light of the history of the nobel prizes awarded to either physicists or chemists. 2. chemistry versus physics? the early phase the relationship between the two sister sciences chemistry and physics has never been fixed but always in a state of flux. traditionally, physics was considered the big brother, a much nobler and more scientific field than the supposedly primitive and empirical chemistry. this is an old image still widely shared in the public and also, regrettably, by many scientists. as far back as 1669 bernard fontenelle, the perpetual secretary of the académie royale des sciences in paris, wrote as follows: through its visible operations, chemistry resolves bodies into a certain number of crude tangible principles; salts, sulfurs, etc. while through its delicate speculations, physics acts on the principles as chemistry acts on bodies, resolving them into other even simpler principles, small bodies fashioned and moved in an infinite number of ways. … the spirit of physics is clearer, simpler, less obstructed, and, finally, goes right to the origins of things, while the spirit of chemistry does not go to the end.[2] more than a century later, after newton’s mechanical physics had been generally accepted, immanuel kant repeated fontenelle’s message of chemistry’s lower epistemic status. not only was chemistry inferior to newtonian physics, according to kant it was not even a genuine science and could never become one. the problem was that by its very nature laboratory-based chemistry was, or was claimed to be, intractable to the mathematical method and systematic deduction from higher laws or principles. as kant expressed it in his metaphysische anfangsgründe der naturwissenschaft from 1786: chemistry can be nothing more than a systematic art or experimental doctrine, but never a proper science, because its principles are merely empirical, and allow of no a priori presentation in intuition. consequently, they do not in the least make the principles of chemical appearances conceivable with respect to their possibility, for they are not receptive to the application of mathematics.[3] at the time when kant degraded chemistry to a non-science there were already a few attempts to apply mechanical physics to chemical phenomena, indeed to subjugate the latter under the former. thus, in an ambitious work of 1758 with the characteristic title essai de chymie mécanique the swiss natural philosopher georges-louis le sage claimed to have explained chemical affinity and properties of matter purely in terms of mechanical physics. according to le sage, cohesion, affinity, and gravitation were all aspects of the same general law of mechanics.[4] later in the century, the newtonian paradigm came to be highly regarded by chemists and physicists in the french tradition mainly due to pierre-simon laplace and claude louis berthollet. however, the dream of a newtonian chemistry was more rhetoric than reality. it remained a dream and in the early part of the nineteenth century it was realized to be a dead end.[5] during the last quarter of the century the dream was shortly revived in the version of “vortex chemistry” based on the mathematically advanced theory of the vortex atom proposed by william thomson, j. j. thomson, william hicks, and other british physicists. however, to the large majority of chemists this theory was too much physics and mathematics, and too little chemistry. latest by the turn of the century vortex chemistry (and vortex atom theory generally) was abandoned.[6] still, a few chemists in britain and the united states responded favorably to j. j. thomson’s vision of a vortex chemistry. harry c. jones, a physical chemist at johns hopkins, referred positively to the theory in a textbook of 1902. and according to francis venable, professor of chemistry at the university of north carolina, the vortex theory of matter offered a future theory of everything which included all chemical phenomena.[7] when speaking about the chemistry-physics relationship over long periods of time it is important to avoid anachronisms and keep in mind that the terms “chemistry” and “physics” once had different meanings than they have today. what fontenelle and kant referred to with these terms cannot be directly translated into the sciences as known in the second half of the nineteenth century. this said, we shall first briefly consider some aspects of the relationship between chemistry and physics in the period from about 1880 and 1920. by that time kant’s claim of chemistry as a non-scientific art had long been contradicted by its explosive development. and yet the epistemic status of chemistry as compared to that of physics remained a matter of discussion. with the emergence of chemical thermodynamics, a highly abstract yet empirically powerful theory developed principally by josiah willard gibbs in the united 45chemists without knowing it? computational chemistry and the møller-plesset perturbation theory states and hermann helmholtz in germany, it seemed for a while that chemistry had been solidly founded in universal laws of nature. however, it was a foundation laid by physicists with no experience in laboratory chemistry and no high opinion of the kind of work most chemists were engaged in. as helmholtz arrogantly expressed it in a letter of 1891: “thermodynamic laws in their abstract form can only be grasped by rigorously schooled mathematicians, and are accordingly scarcely accessible to the people who want to do experiments on solutions and their vapor tensions, freezing points, heats of solution, &c.”[8] helmholtz referred somewhat condescendingly to the new school of physical chemistry established by svante arrhenius, jacobus van’ t hoff, wilhelm ostwald, and others. nevertheless, by the turn of the century a small group of chemists had become “rigorously schooled mathematicians” who mastered the abstract theory of thermodynamics. one of them was the dutch chemist johannes van laar who in a series of works cultivated thermodynamics as the royal road to what he called “mathematical chemistry.”[9] on the other hand, although thermodynamics was a major step toward integrating physics and chemistry, it was at most a partial integration. after all, thermodynamics is concerned only with the state functions and bulk matter, whereas it is not applicable to the chemical elements and compounds – or to atoms and molecules – that chemistry is first and foremost about. traditional chemists found the mathematics of physical theories to be incomprehensible as well as irrelevant for their science, and there were also other reasons why many of them resisted what they felt was an intrusion of physics into chemistry. one of the reasons was the discovery in the 1890s of radioactivity and the electron. the great dmitri mendeleev was in some respects a traditionalist who firmly believed that if the physicists’ subatomic particle (the electron) and transmutation of elements (radioactivity) were accepted, chemistry would degrade into a pre-scientific state.[10] he thought to have found an alternative to the new physics in the form of the ether, which he, contrary to the physicists, conceived as an ultralight chemical element with a place in the periodic table. referring to radioactivity and what he called the “metachemical” electron, he stated: “it is my desire to replace such vague ideas by a more real notion of the chemical nature of the ether.”[11] mendeleev wanted to establish the supremacy of chemistry over the new physics, but the large majority of scientists – whether physicists or chemists – ignored his grand project. although mendeleev’s proposal of incorporating the world ether as an essential part of chemistry failed, several contemporary chemists shared his skeptical or even hostile attitude to the new physics. one example is arthur smithells, professor of chemistry at the university of leeds, who in a presidential address to the 1907 meeting in leicester of the british association for the advancement of science (baas) warned against what he called the “invasion” of chemistry by mathematics and physics: with radioactivity, in relation to the ponderable, we seem almost to be creating a chemistry of phantoms … associated as it is with the exuberance of mathematical speculation of the most bewildering kind concerning the nature, or perhaps i should say the want of nature, of matter. … though chemistry and physics meet and blend there is an essential difference between the genius of physics and the genius of chemistry. apart from his manipulative skills, the latter is not given to elaborate theories and is usually averse to speculation; nor has he the usually an aptitude in mathematics. … chemistry should not be invaded by mathematical theorists.[12] henry armstrong, like smithells a chemical traditionalist, noted in another presidential address to the chemical section of baas two years later that “now that physicists are regular excursionists into our territory, it is essential that our methods and our criteria be understood by them.” he found it “a serious matter that chemistry should be so neglected by physicists.”[13] 3. quantum theory enters chemistry the gulf between chemistry and physics only deepened with the advent of niels bohr’s quantum atom which not only addressed physical problems but also chemical. after all, the title of his three seminal articles in the 1913 volume of philosophical magazine was “on the constitution of atoms and molecules.” bohr applied the new theory to problems which traditionally belonged to chemistry, such as the heat of formation of molecular hydrogen, the covalent bond, and the periodic system of the elements.[14] in an address of 1920 given to the royal danish academy of sciences, he cautiously suggested that in the future theoretical chemistry might become a branch of atomic physics: “since … a possibility has been opened up of interpreting chemical experiences with the aid of considerations originating in the so-called physical phenomena, a connection between physics and chemistry has been created which does not correspond to anything conceived of before.”[15] other theoretical physicists were more direct in their reductionist attitude to the physics-chemistry relationship. max born in göttingen tended to see chemis46 helge kragh try as inferior to physics because chemistry – which he, contrary to kant, after all admitted as a proper science – lacked a mathematical foundation. to illustrate his point, he made use of a military metaphor: we realize that we have not yet penetrated far into the vast territory of chemistry, yet we have travelled far enough to see before us in the distance the passes that must be traversed before physics can impose her laws upon her neighbor science.[16] for a while, several physicists thought that bohr, with his new quantum theory of atoms and molecules, might become the new newton who succeeded in basing chemistry deductively on the higher principles of physics. the british physicist oliver lodge referred implicitly to the kantian dream of a mathematized chemistry when he lyrically wrote about “the brilliant attempts at further analysis of the atoms of all the chemical elements, so as to deduce their properties – the full beauty of atomic astronomy which is now unfolding before the eyes of enthusiastic experts.” he concluded that, “we are living in the dawn of a kind of atomic astronomy which looks as if it were going to do for chemistry what newton did for the solar system.”[17] born’s colleague in göttingen, the great mathematician david hilbert, was more explicit. according to him, the desired reduction of chemistry to physics required “a newton of atomic theory, and this has been niels bohr, who on the basis of new physical ideas, namely, the quantum theory, made a deeper understanding of this area a possibility.”[18] however, not everyone, and as expected not the chemists in particular, agreed that bohr was a new newton or, for that matter, that chemistry needed to comply with the strange laws of quantum physics. in fact, bohr’s attempt to extend the quantum theory of atomic structure to the realm of chemistry was considered unconvincing by most chemists. their dissatisfaction with the semi-classical bohr atom was given voice by the american physical chemist richard tolman, who, contrary to many of his colleagues in the chemical sciences, was also an accomplished mathematician. in an address delivered in toronto in 1921, he objected to bohr’s postulates of stationary states and the mechanism of light emission in terms of quantum jumps. with respect to the bohr-sommerfeld atom he said that it was “constructed by the physicists, like a solar system … partly because they were entirely unfamiliar with the actual facts concerning the behavior of atoms in chemical combination.”[19] moreover, pretending to represent the average chemist, he stated the chemist’s point of view as … extreme hostility to the physicists, with their absurd atom, like a pan-cake of rotating electrons, an attitude which is only slightly modified by a pious wish that somehow the vitamin “ h” [planck’s constant] ought to find its way into the vital organs of their own, entirely satisfactory cubical atom. … in general i feel that the cubical atom of lewis and langmuir must be regarded as representing chemical facts better than anything proposed by the physicists. without going into further detail, molecular structure remained an unsolved problem within the framework of the old quantum theory which was unable to explain even the simplest molecules such as h2 and h+2. the result was that the majority of chemists disregarded the bohr-sommerfeld theory and instead adopted the “cubical atom” with fixed electrons such as proposed by gilbert n. lewis and irving langmuir in particular. although this kind of atomic model was pure nonsense according to the quantum physicists, from the point of view of the chemists it was useful and of great heuristic value.[20] the objections of the physicists were summarized by edward andrade, professor of physics at the artillery college, woolwich, who wrote about langmuir’s model of the atom: “it is scarcely necessary to insist on the artificiality of this picture… the electrons in langmuir’s atom have, in fact, so few of the known properties of electrons that it is not immediately clear why they are called electrons at all.”[21] 4. the emergence of quantum chemistry chemical considerations played no role in the establishment of quantum mechanics as the theory was formulated 1925-1926 principally by heisenberg, born, and jordan (matrix mechanics), dirac (q-number algebra), and schrödinger (wave mechanics). as seen in retrospect, modern quantum chemistry took its beginning with a seminal paper of 1927 written by two german physicists, 27-year-old fritz london and the four years younger walter heitler. the title of their paper in zeitschrift für physik was “wechselwirkung neutraler atome und homöopolare bindung nach der quantenmechanik ” (the interaction of neutral atoms and homopolar bond according to quantum mechanics).[22] the basic approach of the heitler-london theory of the h2 molecule was to consider separately one of the electrons in each of the combining atoms and then, by means of approximation methods and taking into regard the recently discovered resonance effect, to construct a wave function representing the paired-electron bond between them. apart 47chemists without knowing it? computational chemistry and the møller-plesset perturbation theory from explaining the formation of h2 from two hydrogen atoms, they also explained why two helium atoms cannot form a he2 molecule. without making use of any empirical data, heitler and london estimated from their ab initio calculations the dissociation energy of the molecule to be about 2.4 ev. in a more general sense the main result of the heitler-london paper was its deductive argument that the covalent bond can be explained purely in terms of spin quantum mechanics and is therefore outside the reach of classical chemistry. the pioneering work of the two physicists suggested a mathematization of chemistry more real and thorough than what had previously been dreamt of. it can be regarded as yet another example of the “invasion” of a chemical territory by theoretical physicists with basically no background in or knowledge of laboratory chemistry. in a letter to heitler from 1935, london indicated his lack of respect for the culture of chemistry: the word “valence” means for the chemist something more than simply forces of molecular formation. for him it means a substitute for these forces whose aim is to free him from the necessity to proceed, in complicated cases, by calculations deep into the model. … the chemist is made out of hard wood and he needs to have rules even if they are incomprehensible.[23] given linus pauling’s background in chemistry and later reputation as a “chemical translator,” it is noteworthy that in his younger days he subscribed to the reductionist view expressed by some quantum theorists. thus, in a lecture from 1928 to the american chemical society, he stated that chemistry was a kind of by-product of theoretical physics: we can now predict with a considerable measure of confidence the general nature of the future advances [in theoretical chemistry]. we can say, and partially vindicate the assertion, that the whole of chemistry depends essentially upon two fundamental phenomena: these are (1) the one described in the pauli exclusion principle; and (2) the heisenberg-dirac resonance phenomenon.[24] pauling’s assertion had more than a little in common with dirac’s better-known claim from the following year (see below). the approach of heitler and london formed the backbone of what came to be known as the valence bond (vb) method, which in the version developed by pauling and others dominated quantum chemistry during the 1930s. the alternative molecular orbital (mo) method can be traced back to a paper that yet another german physicist, friedrich hund, published in 1927. hund assumed that an individual electron moved in the field from all the nuclei and the other electrons in the molecule. his approach was paralleled by works done by robert mulliken, who contrary to hund had a solid chemical training and a phd in physical chemistry. at around 1931 the two methods, valence bond and molecular orbitals, reached immaturity and quantum chemistry entered as a social and scientific reality. the concept of “chemical physics” was well known in the nineteenth century, when it typically referred to chemical agents such as heat, light, and electricity.[25] it now re-emerged in a different form which indicated the growing autonomy of quantum chemistry. the journal of chemical physics was founded in 1933 with harold urey as its first managing editor. in the first issue urey reflected on the old theme of the relationship between physics and chemistry, which he thought had entered a new and fruitful phase of symbiotic cooperation: at present the boundary between the sciences of physics and chemistry has been completely bridged. men who must be classified as physicists on the basis of training and of relations to departments or institutes of physics are working on the traditional problems of chemistry; and others who must be regarded as chemists on similar grounds are working in fields which must be regarded as physics.[26] the new journal was aimed for contributions too mathematical for journal of physical chemistry, too physical for journal of the american chemical society, and too chemical for physical review. although it contained many articles on quantum chemistry, journal of chemical physics was not devoted to this branch of science. as many or more articles were on molecular spectroscopy, kinetics of reactions, materials science, and more traditional areas of physical chemistry. only in 1967 did the community of quantum chemists get its own journal, the international journal of quantum chemistry created by per-olov löwdin, the influential swedish expert and a major force in establishing quantum chemistry as a proper scientific discipline.[27] most but not all of the post-world war ii generation of chemists came to realize that theoretical chemistry is essentially based on the laws of quantum mechanics. “the whole of chemistry is one huge manifestation of quantum phenomena,” wrote carl johan ballhausen, a professor of chemistry at the university of copenhagen best known for his important contributions to so-called ligand field theory. according to ballhausen: without a background in quantum theory it is impossible to possess an “ in depth” understanding of chemistry. the elucidation of chemical phenomena by means of the quan48 helge kragh tum laws is now left to the chemists; the solid state physicists do not have the necessary chemical background and the high energy physicists are not interested in electrons. let us therefore think in deep gratitude and admiration to those pioneering physicists who opened the doors to modern chemistry.[28] ballhausen and his contemporaries had no problem with recognizing quantum chemistry as based on work done by physicists and only subsequently developed by chemists. 5. early many-electron theories although not originally recognized to belong to the domain of quantum chemistry, in the years around 1930 several physicists dealt with the problem of calculating systems with many electrons. one of them was paul dirac, who in a paper of 1929 studied the exchange interaction of several identical particles such as electrons belonging to the same atom. when dirac’s paper is still cited today it is not so much because of its scientific content but rather because of its introductory remarks concerning the hypothetical reduction of chemistry to physics: the general theory of quantum mechanics is now almost complete … the underlying physical laws necessary for the mathematical theory of a large part of physics and the whole of chemistry are thus completely known, and the difficulty is only that the exact application of these laws leads to equations much too complicated to be soluble. it therefore becomes desirable that approximate practical methods of applying quantum mechanics should be developed.[29] dirac referred in his paper not only to the heitlerlondon theory but also to an important theory by the cambridge mathematical physicist douglas r. hartree, who in a series of papers published 1928-1929 in the proceedings of the cambridge philosophical society introduced the so-called self-consistent field approximation method for calculation of many-electron atoms.[30] the general idea of this method was to reduce the many-electron problem to a one-electron problem, which was done by representing the effect of an electron on other electrons by a sort of average field corresponding to a central non-coulomb field of force. in this way hartree could obtain an approximate solution to the schrödinger equation even for fairly complicated atomic systems (such as na+ and cl-) that agreed well with observed values. however, as was realized early on by john slater and a few other physicists, the hartree method was in some respects flawed as it disregarded the spin states and the associated pauli exclusion principle.[31] in 1930 the russian physicist vladimir fock published a mathematically complex paper in zeitschrift für physik in which he improved the method by taking into consideration that the indistinguishability of electrons give rise to exchange forces.[32] the result was what soon became known as the hartree-fock approximation method, which since then has played an important role in quantum-chemical calculations. however, initially the method was applied exclusively to small and medium-sized atoms, and even in these cases calculations based on the hartree-fock theory were laborious. to extend the method to molecules required computational resources that were available only in the post-world war ii era. whereas the papers of hartree and fock attracted critical interest among physicists, as indicated by citations to them they were largely ignored by the chemists. thus, during the period 1928-1932 hartree’s first paper on the self-consistent field method received 27 citations, all of them in physical review or other physics journals (google scholar). the picture is the same with fock ’s paper, which during 1930-1934 was cited 9 times. there were no citations to either of the papers in journals of chemistry or physical chemistry. the har tree-fock met hod was not t he only approach to many-electron calculations developed in the 1930s. in calculations based on this method, the interaction between electrons of opposite spins was taken into account only by means of an average interaction. to remedy for this deficiency various so-called electron correlation methods were developed, the first and arguably most important of which was the møller-plesset perturbation theory dating from 1934. according to a review paper of 2011: in 1934, møller and plesset described in a short note of just five pages how the hartree-fock (hf) method can be corrected for electron pair correlation by using second-order perturbation theory. this approach is known today as møller–plesset perturbation theory, abbreviated as mppt or just mp in the literature. mppt, although in the beginning largely ignored, had a strong impact on the development of quantum chemical ab initio methods in the past 40 years.[33] although thousands of papers have been written on this widely used perturbation method, many of them referring to the original paper from 1934, it and its two authors are nearly invisible in the historical literature on quantum and computational chemistry.[34] most likely, very few of the modern scientists using the method and referring to the 1934 paper have any idea of whom 49chemists without knowing it? computational chemistry and the møller-plesset perturbation theory møller and plesset were. so, who were they and what was the context of their contribution to what retrospectively can be identified as the history of quantum chemistry? if the møller-plesset theory had a strong impact only from about 1970, what about the earlier history? 6. møller-plesset theory in the 1930s as christian møller and milton plesset stated in their abstract, “a perturbation theory is developed for treating a system of n electrons in which the hartreefock solution appears as the zero-order approximation.” and later in the paper: “thus, the perturbation method shows that the theory of the self-consistent field is accurate in the determination of energy to the second approximation.”[35] in other words, møller and plesset used the hartree-fock theory as a starting point but added a small perturbation given by the deviation of the hartree-fock hamiltonian (energy operator) from the exact hamiltonian. the perturbation term of the second order corresponded to the electron-electron interaction neglected in the hartree-fock theory. møller is described in a wikipedia article on him as “a danish chemist and physicist,” which is a gross mistake given that neither he nor his coauthor plesset ever worked in or published on chemistry.[36] they were quantum physicists with no interest whatsoever in chemistry or even recognizing that their short paper in physical review belonged to the new fields of chemical physics and quantum chemistry. the two authors did not offer any application or calculation, as for instance hartree did. they considered their work to be a contribution to theoretical quantum mechanics and no more than that. in fact, the words “atom” and “molecule” did not appear in the article, which also did not mention “chemistry” or related terms. nor did it refer to experimental data of any kind. christian møller (1904-1980) was a 30-year-old danish physicist at bohr’s institute of theoretical physics in copenhagen (figure 1). at the time he was best known for an important quantum theory of relativistic electron-electron scattering, a phenomenon which became known as møller scattering.[37] by 1934, when he collaborated with plesset, he had begun working on enrico fermi’s new theory of beta-radioactivity. shortly after having completed the paper with plesset, he went to rome on a rockefeller stipend to work with fermi’ group. later in his career møller turned to the meson theory of nuclear forces, to which he contributed with several papers in the period from 1939 to 1946. in 1943 he was appointed professor of mathematical physics at the university of copenhagen. since the early 1950s møller focused increasingly on the theory of general relativity on which subject he became internationally recognized as a leading expert. his authoritative and muchused textbook from 1952 titled the theory of relativity played an important role in the so-called renaissance of general relativity. milton spinoza plesset (1908-1991) earned his phd at yale university in 1932 and subsequently moved to caltech, where he worked with j. robert oppenheimer on positron theory and problems of quantum electrodynamics. in 1933 he went to bohr’s institute in copenhagen on a national research council fellowship. in september that year he participated in the annual institute conference with, among others, møller, dirac, heisenberg, and heitler (figure 2). while in copenhagen he also accompanied bohr and his wife on a visit to the soviet union in may 1934, where he met fock and other russian physicists. and then he found time to collaborate with møller on the many-electron theory which came to bear their names. figure 1. portrait photography of christian møller, 1936. credit: niels bohr archive, photo collection, copenhagen. 50 helge kragh bohr valued plesset as a very promising physicist, such as evidenced in a letter he wrote to an american colleague: surely he is one of the best of young american theoretical physicists and especially he has as you know a great insight in the relativistic quantum theory of the electron… he hopes soon to publish an account of some of his work together with [john] wheeler, and you may perhaps has seen a recent paper in the physical review on the manyelectron problem, which he published a few months ago together with møller.[38] after having worked in copenhagen and elsewhere in europe, plesset returned to caltech where he was appointed professor in engineering science in 1963. his scientific work after world war ii was mostly concerned with fluid dynamics and nuclear physics (figure 3).[39] the paper by møller and plesset was predominantly mathematical, with no indication at all of the areas of physics and chemistry to which the theory might be applied. apparently they did not care. none of the two copenhagen physicists considered their work to be important and they never returned to it or related fields of science. when plesset was interviewed in 1981, he did not even mention møller and the work he did with him.[40] as shown by the number of citations to the 1934 paper, for a long period the møller-plesset theory was ignored. during the 1930s the paper received only 5 citations, all of them in physical review except one in journal de physique et le radium written by the swedish theoretical physicist oskar klein. while two of the citing papers considered the theory in relation to nuclear structure, none of them referred to the electron structure of atoms. by 1962 the cumulative number had increased to 22, less than one citation per year in average. in other words, the møller-plesset perturbation method was scarcely visible in the scientific literature. however, the poor record changed drastically from about 1980 – the year that møller died – and today the total number of citations to the møller-plesset paper has exploded to about 16,600 according to google scholar or 13,600 according to web of science (figure 4). of course, when evaluating such citation curves one has to take into consideration the general growth in the numbers of publications in the period.[41] but even then the møller-plesset citation curve is highly anomalous. 7. a sleeping beauty the fate of the møller-plesset theory only changed when computers began to be widely used to solve problems in chemical physics and quantum chemistry. according to dieter cremer, a german specialist in computational chemistry, perturbation theory as a tool in theoretical chemistry was rediscovered in the 1960s and from the mid-1970s onwards this kind of theory developed rapidly.[42] so-called mpn methods – meaning møller-plesett theories of perturbation order n – were developed by, among others, the british-american theoretical chemist and later nobel laureate john pople.[43] due to the works of pople and his collaborators, the old copenhagen paper of 1934 became much better known. pople concluded that the original møller-plesset method carried figure 2. conference at bohr’s institute, september 1933. on the first row: n. bohr, p. dirac, w. heisenberg, p. ehrenfest, m. delbrück, l. meitner. milton plesset is on the second row, number four from the right, and christian møller seats behind him, number three from the right on the third row. credit: niels bohr archive, photo collection, copenhagen. figure 3. milton plesset (left) with n. bohr, f. kalckar, e. teller, and o. frisch at the copenhagen institute in 1934. credit: niels bohr archive, photo collection, copenhagen. 51chemists without knowing it? computational chemistry and the møller-plesset perturbation theory to second and third order (mp2, mp3) had advantages over other methods and for small atoms and molecules agreed satisfactorily with experimental data. when pople in 1998 gave his nobel lecture in stockholm, he praised the møller-plesset theory as an important step in the history of computational chemistry.[44] the growth in visibility is illustrated by the number of citations (google scholar) to the møller-plesset paper in the six decades between 1962 and 2021: 1962-1971: 91. 1972-1981: 222. 1982-1991: 1070. 1992-2001: 3570. 2002-2011: 5330. 2012-2021: 6100. by far most of the many citations to the 1934 paper are in journals devoted to chemical physics and quantum chemistry. the paper by møller and plesset is a prime example of what in the sociology of science is known as a “sleeping beauty.” this is a scientific paper whose relevance has not been recognized for a long time and then, more or less suddenly, becomes highly influential and cited. [45] such sleeping beauties are of obvious interest from a historical and sociological point of view. why were they initially ignored? why did a sleeping beauty wake up at a particular, much later date? a recent large-scale study of citation histories in all branches of natural and social sciences suggests that sleeping beauties are not exceptional and particularly not so in chemistry and physics.[46] the authors define a parameter called the “beauty coefficient” (b) which expresses the number of citations a paper has received and how long after publication it gained them. it is so constructed that a paper which accrues citations linearly over time has b = 0, whereas one which languishes for 100 years before rising to fame can have b = 10,000 or even more (for the full definition of b, see ref. 45). the study in question lists the top fifteen sleeping beauties in science since 1900, seven of which it classifies as chemistry and five as physics. one of them is the møller-plesset paper of 1934, for which b = 2,584 and the “awakening time” is found to be 1982. another and much better known sleeping beauty, but with a beauty coefficient (b = 2,258) a little less than that of the møller-plesset paper, is the famous einstein-podolsky-rosen (epr) paper of 1935 on the completeness of quantum mechanics.[47] 8. nobel perspectives it is well known that a large number of nobel chemistry prizes have been awarded to scientists who were either physicists or whose work would be normally classified as physics.[48] on the other hand, no nobel prize in physics has ever been awarded to a chemist. consider as an early example the 1908 chemistry prize to ernest rutherford for his contributions to radioactivity including “the chemistry of radioactive substances.” bemused to have transformed so quickly from a physicist to a chemist, he wrote to otto hahn: “i must confess that it was very unexpected and i am very startled at my metamorphosis into a chemist.”[49] many years later the 1951 chemistry nobel prize was awarded to glenn seaborg and edwin mcmillan for their discoveries of the first transuranic elements. while seaborg was trained in chemistry under g. n. lewis, mcmillan was a nuclear physicist, such as he pointed out in his nobel lecture. “in spite of what the nobel prize committee may think, i am not a chemist,” he said.[50] as mentioned, quantum chemistry was originally created by physicists rather than chemists and has to this day continued as an interdisciplinary field in which physicists play an important role. this is reflected in sevfigure 4. number of citations per year 1935-2020 to the møller-plesset paper according to web of science. 52 helge kragh eral of the more recent nobel prizes. thus, one-third of the 2013 prize was awarded to michael levitt, an israeli trained in physics and molecular biology but not in chemistry. when levitt was informed about the honor, he reportedly said, “i never studied chemistry, actually i’m a physicist. but that’s okay.”[51] the nobel prize awarded to john pople and walter kohn in 1998 was the first and so far only one explicitly motivated in quantum chemistry. while pople was a quantum chemist (or perhaps a chemical physicist), kohn’s background was purely in theoretical physics. he wrote his doctoral dissertation under julian schwinger, one of the founders of modern quantum electrodynamics, and later changed to theoretical condensed matter physics. it was in this context that he developed the so-called density functional theory, a very successful approach to the many-particle problem which was widely considered an alternative to møller-plesset theory.[52] much like møller and plesset, kohn was a theoretical physicist whose work unintendedly came to play a crucial role in quantum chemistry. like plesset had stayed at bohr’s institute in the 1930s, where he met møller, so 27-year-old kohn came on a fellowship to copenhagen to work in the same institute, where møller was appointed his supervisor. in a report of 1953, bohr and møller wrote that, “in all his work dr. kohn has proved himself a highly qualified theoretical physicist with great knowledge of a wide field of problems.”[53] during kohn’s stay at the bohr institute, which lasted from july 1951 to september 1952, he participated in a large conference on problems of quantum physics attended not only by møller and plesset, but also by heisenberg, bethe, pauli, and other quantum luminaries. however, he did not enter a collaboration with møller, whose research interests at the time were quite different from his. when kohn developed his density functional theory in the mid-1960s, møller and plesset had almost forgotten about their earlier work and none of them showed any interest in kohn’s new approach or any other approaches to quantum chemistry. 9. conclusion the relations between physics and chemistry have changed significantly over time, often with physicists entering the field of chemistry with theories that most chemists found to be difficult and of no relevance to what chemistry is really about. the pioneers of quantum chemistry were theoretical physicists who had but little interest in traditional chemical problems and did not at all consider themselves to be chemists. the main result of the present study is a slight reevaluation of the standard history of early quantum chemistry, or at least a supplement to it. while this standard history covers in considerable detail hartree’s work and its extension to the hartree-fock theory, it has little to say about fock’s contribution and even less about the one of møller and plesset. the two contributions, the one from 1930 and the other from 1934, had in common that they were one-time mathematical investigations not originally related to chemical problems. the møller-plesset theory exemplifies to some extent how quantum theorists acted as “chemists without knowing it” insofar that much later the theory came to be seen as an important contribution to computational chemistry. because the møller-plesset theory was a “sleeping beauty” with very little initial impact, it is perhaps understandable that it does not figure in historical writings on the early period of quantum chemistry. after all, it would be anachronistic to let our knowledge of the theory’s later development, say after the 1970s, influence the historical account of quantum chemistry in the 1930s. it is less understandable and harder to justify that the møller-plesset method has also been neglected in the writings on the more recent era, where extensions of this method have undeniably played a very significant role. references [1] for an overview of the debate citing many references, see h. chang in relocating the history of science: essays in honor of kostas gavroglu (eds.: t. arabatzis, j. renn, a. simões), springer, new york, 2015, pp. 193-210. see also h. kragh, between the earth and the heavens: historical studies in the physical sciences, world scientific, london, 2021, pp. 151-172, on which parts of the present paper rely. [2] quoted in b. bensaude-vincente, ber. wissenschaftsgesch. 2009, 32, 365-378. [3] i. kant, metaphysical foundations of natural science (ed. m. friedman), cambridge university press, cambridge, 2004, p. 6. [4] j. s. rowlinson, notes rec. roy. soc. 2003, 57, 35-45. [5] f. gregory, arch. int. h. sci. 1984, 34, 108-123; a. m. duncan, laws and order in eighteenth-century chemistry, clarendon press, oxford, 1996. [6] h. kragh, centaurus 2002, 44, 32-114, esp. pp. 60-69. [7] h. c. jones, elements of physical chemistry, macmillan, new york, 1902; f. p. venable, the study of the atom, american chemical society, easton, pa, 1904. 53chemists without knowing it? computational chemistry and the møller-plesset perturbation theory [8] quoted in h. kragh in hermann von helmholtz and the foundations of nineteenth-century science (ed. d. cahan), university of california press, berkeley, 1993, pp. 401-431, on p. 429. [9] j. j. van laar, lehrbuch der mathematischen chemie, j. a. barth, leipzig, 1901; h. a. m. snelders, centaurus 1986, 29, 53-71. [10] h. kragh, ambix 1989, 36, 49-65. m. d. gordin, a well-ordered thing: dmitrii mendeleev and the shadow of the periodic table, basic books, new york, 2004, pp. 217-224. [11] d. i. mendeleev, an attempt towards a chemical conception of the ether, longmans, green & co., london, 1904, p. 17. [12] a. smithells, proc. brit. assoc. adv. sci. 1907, 469479, and nature 1907, 78, 352-357. [13] h. e. armstrong, proc. brit. assoc. adv. sci. 1909, 420-454, on p. 477. see also a. simões, k. gavroglu in chemical sciences in the 20th century (ed. c. reinhardt), wiley-vch, weinheim, 2001, pp. 51-74. [14] h. kragh, niels bohr and the quantum atom: the bohr model of atomic structure 1913-1925, oxford university press, oxford, 2012; h. kragh, phys. today 2013, 66 (5), 36-41. [15] niels bohr: collected works, vol. 3 (ed. j. rud nielsen), north-holland, amsterdam, 1976, p. 240. [16] m. born, naturwissenschaften 1920, 8, 373-382, on p. 382. [17] o. lodge, atoms and rays: an introduction to modern views on atomic structure and radiation, george h. doran co., new york, 1924, p. 203. [18] quoted in david hilbert’s lectures on the foundations of physics 1915-1927 (eds. t. sauer, u. majer), springer, dordrecht, 2009, p. 209. [19] r. c. tolman, j. opt. soc. am. rev. sci. 1922, 6, 211228. [20] a. n. stranges, electrons and valence: development of the theory, 1900-1925, a&m university press, college station, tx, 1982. see also h. kragh, riv. storia scienza 1985, 2, 463-486. [21] e. n. de andrade, the structure of the atom, g. bell and sons, london, 1923, p. 239. see also t. arabatzis, representing electrons: a biographical approach to theoretical entities, university of chicago press, chicago, 2006. [22] quantum chemistry: classic scientific papers (ed. h. hettema), world scientific, london, 2000, pp. 140155. on the early development of quantum chemistry, see j. mehra, h. rechenberg, the historical development of quantum theory, vol. 6, springer, new york, 2001, pp. 521-571. a full history is given in k. gavroglu, a. simões, neither physics nor chemistry: a history of quantum chemistry, mit press, cambridge, ma, 2012. [23] quoted in ref. 22 (gavroglu, simões), p. 100. [24] unpublished lecture of 6 april 1928 quoted in b. s. park, brit. j. hist. sci. 1999, 32, 21-46. [25] t. pynchon, introduction to chemical physics, van nostrand, new york, 1874. [26] h. c. urey, j. chem. phys. 1933, 1, 1-2. on this journal and the disciplinary boundaries between chemical physics and physical chemistry, see m. jo nye, from chemical philosophy to theoretical chemistry: dynamics of matter and dynamics of disciplines 1800-1950, university of california press, berkeley, 1993, pp. 227-261, and j. w. servos, physical chemistry from ostwald to pauling: the making of a science in america, princeton university press, princeton, 1990, pp. 251-298. [27] a. simões, k. gavroglu, int. j. quantum chem. 2014, 114, 116-127; b. s. park, ann. sci. 2003, 60, 219-247. [28] c. j. ballhausen, j. chem. educ. 1979, 56, 357-361; c. j. ballhausen, introduction to ligand field theory, mcgraw-hill, new york, 1962. [29] p. a. m. dirac, proc. roy. soc. a 1929, 123, 714-733, emphasis added. for the response of chemists to dirac’s claim, see a. simões, phys. perspect. 2002, 4, 253-266. [30] c. f. fischer, douglas rayner hartree: his life in science and computing, world scientific, new jersey, 2003; b. s. park, hist. stud. nat. sci. 2009, 39, 32-62. [31] j. slater, phys. rev. 1928, 32, 339-348. [32] v. fock, z. phys. 1930, 61, 126-148. [33] d. cremer, comp. mol. sci. 2011, 1, 510-530. [34] møller-plesset theory is not mentioned in ref. 22 (gavroglu, simões) nor in other of the many works written on the history of quantum and computational chemistry. [35] c. møller, m. s. plesset, phys. rev. 1934, 46, 618622. received 14 july 1934 and published 1 october the same year. [36] https://en.wikipedia.org/wiki/christian_m%c3%b8ller [37] h. kragh, arch. hist. exact sci. 1992, 43, 299-328. [38] n. bohr to l. page, 23 december 1934. bohr scientific correspondence, niels bohr archive, copenhagen. [39] see the obituary by t. y. wu in memorial tributes: national academy of engineering, vol. 6, national academies press, new york, 1993, pp. 172-174. [40] interview with plesset by c. bugé of 8 december 1981, online as https://oralhistories.library.caltech. edu/127/ [41] r. sinatra, nature phys. 2015, 11, 791-796; d. b. baker, chem. eng. news 1981, 59, 29-34. https://en.wikipedia.org/wiki/christian_m%c3%b8ller https://oralhistories.library.caltech.edu/127/ https://oralhistories.library.caltech.edu/127/ 54 helge kragh [42] ref. 33. [43] ref. 22 (gavroglu, simões), pp. 224-229; l. radom in new dictionary of scientific biography, scribner’s, new york, 2008, pp. 129-133, which includes a rare reference to the møller-plesset perturbation theory. [44] j. s. binkley, j. a. pople, int. j. quantum chem. 1975, 9, 229-236; j. a. pople, j. s. binkley, r. seeger, int. j. quantum chem. 1976, 10, 1-19; j. a. pople, ang. chem. int. edit. 1999, 38, 1894-1902. [45] a. van raan, scientometrics 2004, 59, 467-472. [46] q. ke et al., p. natl. acad. sci. usa 2015, 112, 74267431. https://doi.org/10.1073/pnas.1424329112 [47] a. einstein, b. podolsky, n. rosen, phys. rev. 1935, 47, 777-780. [48] for a list of chemistry prizes awarded to physicists 1908-1977, see h. kragh, quantum generations: a history of physics in the twentieth century, princeton university press, princeton, 1999, p. 432. [49] rutherford to hahn, 29 november 1908, quoted in a. s. eve, rutherford: being the life and letters of the rt. hon. lord rutherford, cambridge university press, cambridge, 1939, p. 183. see also h. kragh, “chemical and other aspects of rutherford’s nuclear atom,” j. roy. soc. new zeal. 51 (2021): 513-527. [50] e. mcmillan, in nobel lectures, chemistry 19421962, elsevier, amsterdam, 1964, pp. 314-322, on p. 318. online: https://www.nobelprize.org/prizes/ chemistry/1951/mcmillan/lecture/ [51] tweet f rom stanford university, 9 october 2013, see https://twitter.com/stanford/status/387913130673979392 [52] a. zangwill, arch. hist. exact sci. 2014, 68, 775-848. [53] bohr to p. r. wallace, 5 march 1953 (møller papers, niels bohr archive, copenhagen). https://doi.org/10.1073/pnas.1424329112 https://www.nobelprize.org/prizes/chemistry/1951/mcmillan/lecture/ https://www.nobelprize.org/prizes/chemistry/1951/mcmillan/lecture/ https://twitter.com/stanford/status/387913130673979392 https://twitter.com/stanford/status/387913130673979392 substantia. an international journal of the history of chemistry 6(2): 93-106, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1600 citation: franza a., pratesi g. (2022) just a grand duke who loves chemistry. peter leopold of habsburg-lorraine (1747–1792) and his chemical cabinet at the imperial and royal museum of physics and natural history. substantia 6(2): 93-106. doi: 10.36253/substantia-1600 received: mar 12, 2022 revised: jun 26, 2022 just accepted online: jun 27, 2022 published: september 1, 2022 copyright: © 2022 franza a., pratesi g. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. orcid af: 0000-0003-3146-6957 gp: 0000-0001-6329-901x just a grand duke who loves chemistry. peter leopold of habsburg-lorraine (1747–1792) and his chemical cabinet at the imperial and royal museum of physics and natural history annarita franza, giovanni pratesi* department of earth sciences, university of firenze, via g. la pira 4, 50121 firenze, e-mail: annarita.franza@unifi.it; giovanni.pratesi@unifi.it *corresponding author. abstract. this article dealt with the history of the chemical cabinet established by the grand duke of tuscany, peter leopold of habsburg-lorraine (1747–1792), at the imperial and royal museum of physics and natural history in firenze during his regency. to achieve this goal, it investigated untapped archival sources (e.g., administrative and commercial documents, minutes, correspondences, inventories) concerning the museum management from its foundation in 1775 to the departure of the grand duke for vienna to be crowned as holy roman emperor leopold ii in 1790. the article analyzed the chemical cabinet’s manuscript catalog, whose entire transcription is presented in the supplementary information files. the work then examined the connections between the activities performed at the chemical laboratory and peter leopold’s interest in experimental chemistry. concerning this research question, the scientific relationship he held with the naturalist giovanni valentino mattia fabbroni (1752–1822) – vice-director and then director of the imperial and royal museum of physics and natural history – who helped the grand duke navigate all aspects of his interests in chemistry and natural sciences, was also discussed. keywords: peter leopold, history of chemistry, giovanni fabbroni, catalog, museum. introduction writing about a notable historical figure such as peter leopold of habsburg-lorraine (1747–1792) is not an easy task. so, it is not by chance that soll stated that “there is no single way to characterize peter leopold. his approach to intellectual life, philosophy, and governing were pragmatic, eclectic, and a mix of his various influences”.1 in fact, it is difficult to account for the life2 of a man who was the ninth son of francis i (1708–1755) and maria theresa of austria (1717–1780), brother of joseph ii (1741–1790) and marie antoinette (1755–1763),3 grand duke of tuscany from 1755 to 1790, and the next-to-last holy roman emperor (leopold ii) from 1790 to 1792, year in which he suddenly died from pleurisy at the age of 44 years.4 but that 94 annarita franza, giovanni pratesi is not all. peter leopold was a jansenist and an enlightened despot,5 whose concrete projects – as stated by maran, castellini, and bisman–6 reformed the administrative, managerial, organizational, judicial,7 and economic aspects of social and cultural life in the grand duchy of tuscany. in this regard, sarti found that these amendments “transformed tuscany into a model state”,8 while maran et al. underlined how the analysis of the municipalities’ reform contributed to a better understanding of today’s decentralization by governments in the context of the new public management.9 however, a complete survey of peter leopold’s reforms of tuscany is out of scope here, and the reader is referred to the literature for further details.10 th e principal aim of this study is to detail and analyze the history of the chemical cabinet peter leopold established at the imperial and royal museum of physics and natural history through the investigation of the scientifi c relationship the grand duke held with the naturalist and museum’s vice director giovanni valentino mattia fabbroni (1752–1822)11 together with the examination of the laboratory’s catalog.12 th e latter unpublished source is preserved at the museo galileo’s library, whose archival fund on the history of the imperial and royal museum of physics and natural history13 holds various documents that were investigated to achieve the goals of the present paper. th e existing literature on the imperial and royal museum of physics and natural history is extensive and focuses mainly on its collections and history.14 th e museum, established by peter leopold’s motu proprio on 22 february 1775, was not only a place to gather and preserve the naturalistic and scientifi c collections inherited by the medici family15 and the accademia del cimento16 but also acted as a research center to promote useful knowledge in the service of the public good.17 in this regard, contardi underlined how the museum collections were open to all and organized to encourage a visitor’s self-instruction through the display of explanatory labels.18 however, the collections did not comprise only the specimens and instruments belonging to the medici family and the accademia del cimento. th ey were constantly enriched by new acquisitions19 promoted by peter leopold, together with the instruments, preparations, and objects20 realized at the various museum workshops.21 among these, there was the chemistry cabinet that was established to represent, according to both felice fontana (1730–1805) and giovanni fabbroni, one of the most advanced research centers at an international level. it encompassed, in addition to the standard equipment like fl asks and bell-jars, diverse pneumatic pumps22 together with a workbench –realized by the woodcutter francesco schmidt (dates uncertain)– 23 belonging to peter leopold. it was openable with a slate working surface for experiments. one of the three cavities in the workbench is linked to a bellow operated by pedals useful for calcination and combustion operations. various shelves allowed to store glassware, tiny bottles, and chemical compounds (fig. 1). in this regard, scorrano et al. analyzed 38 samples using x-ray fl uorescence, x-ray diff raction, gas chromatography-mass spectrometry, ir spectroscopy, thermal analysis, and chemical tests. according to the authors, most of the compounds were employed in textile manufacturing, while the remaining represented both chemicals helpful in improving wine production and substances of apothecary interest.24 many historians have connected the investigation on the workbench to the work of huber franz hoefer (1728–1795) at the court apothecary, as well as to the research the grand duke patronized on water25 and hot springs26. while recent studies have linked peter leopold’s interest in chemistry to mineralogy, mining science, and mineral collecting.27 however, so far, there has been little discussion about the involvement of peter leopold in the experiments being conducted at the chemistry cabinet and the organization of the chemical laboratory. in the following pages, the analysis of untapped archival documentation will generate fresh insights into these subjects. materials and methods as mentioned in the introduction section, this study investigated the historical documentation that described figure 1. leopold’s chemistry cabinet. museo galileo, room x. 95just a grand duke who loves chemistry both peter leopold’s interest in chemistry and the chemical cabinet he established at the imperial and royal museum of physics and natural history. the documentation covers a period from the museum’s foundation in 1775 until the end of peter leopold’s regency as grand duke of tuscany in 1790. exceptions were documents about the chemical cabinet covering a period up to 1807. the materials were analyzed according to the standard archival research methods illustrated, for example, in ventresca and mohr.28 the benefit of this approach is providing access to data that would not otherwise be known. furthermore, the presentation of the archival documents according to a schematic organization facilitates their use as a resource for scholars interested in the history of chemistry in 18th-century italy. bonding in chemistry: peter leopold and giovanni fabbroni one of the first research questions that come to mind is: did peter leopold attend the imperial and royal museum of physics and natural history? or the museum’s establishment was, as stated by solomon,29 just a result of the european enlightenment ideas? if, on the one hand, it is beyond dispute that the museum foundation was a consequence of peter leopold’s reformism, i.e., the promotion of science as an instrument of public utility,30, on the other hand, it represented a place that the grand duke used to attend in person as shown by a billet his intimate secretary, giovanni tommaso mannucci (1750–1814), sent to fabbroni on 3 september 1789 forewarning his visit for the following day.31 at the imperial and royal museum of physics and natural history, peter leopold established a close scientific relationship with giovanni fabbroni. the latter also assisted him in handling the contacts with various foreign chemists and apothecaries, such as antoine baumé (1728–1804).32 through the mediation of francesco favi (1749–1823)33 –who was the secretary of the tuscan legation in paris deputed to purchase and ship diverse kinds of scientific products to firenze via marseille, livorno, and pisa–34 fabbroni got in contact with baumé and received a copy of the catalog of his preparations in july 1787. the genres du catalogue de m. de baumé encompassed 40 items, among which there were cobalt crystals useful for both nitrous and vitriolic acids, flowers of benzoin (benzoic acid), fusible salts of urine (i.e., the complex of salts present in human urine, which may indicate ammonium sodium phosphate or sodium ammonium chloride) and diverse essential oils (e.g., chamomile and cardamon).35 since then, fabbroni bought various boxes of baumé’s preparations until 1788.36 one of the last products fabbroni purchased from baumé at peter leopold’s request was a supply of pâte de guimauve, i.e., a demulcent lozenge prepared from the root of althea officinalis.37 on tuesday 19 may 1788, mannucci advised that “his royal highness ordered fabbroni to write to monsieur baumè to send him, as soon as possible, 12 pounds of pâte de guimauve within a small cup, so that it would not be broken”. the order had to be of particular urgency since mannucci sent the same note twice on friday 22 may 1788.38 at the end of june, fabbroni noticed that the box was just arrived in firenze, hoping that it would be delivered at the royal chamber soon.39 unlike the previous shipments, the pâte de guimauve was transported from paris to firenze via genova, and its delivery was in the care of the courier francesco maria vignolo (dates uncertain).40 on the same note, fabbroni gave positive news about sending 17 pounds and 2 ounces of venus crystals (copper acetate) that had been bought from bertrand pelletier’s (1761–1767) laboratory.41 the products sold by pelletier had already aroused the grand duke’s interest in the past. as an example, on 6 april 1787, during one of his stays in pisa, peter leopold charged his intimate secretary ranieri fulger (dates uncertain) writing fabbroni to inquire about the essences and essential oils sold by the parisian apothecary.42 peter leopold was then very interested in the work of another french chemist, jean antoine claude chaptal (1756–1832).43 in an undated document, mannucci referred to fabbroni that the grand duke had heard the news about a “monsieur chaptal who has a big store in montpellier selling all kinds of chemicals, acids, and drugs of excellent quality at a meager price”. mannucci then said that “his royal highness will appreciate fabbroni writing to some of his correspondents to know whether this is true or not. in case of a positive response, his royal highness will be pleased to receive a note on all the products he sells with their respective prices”.44 fabbroni wrote to chaptal45 and the latter sent back a descriptive letter46 on both the compounds he produced and the procedures he followed for realizing the crystallization of vitriol oil. in this regard, it has to be said that chaptal sent fabbroni letters like this more than once. for example, he illustrated the products he sold in montpellier and his research methods in a missive dating 24 december 1786. this document shows on the top right of its first page a fabbroni’s brief remark in which he noted that the response was sent on 15 january 1787. he also noticed to have rewritten to the french chemist on 22 february 1787 because he was waiting for a box of chemicals that was not delivered yet. later, chaptal would have informed fabbroni about his chemi96 annarita franza, giovanni pratesi cal products and his upcoming scientific publications. this is the case of a letter, partially gone missing, in which he noticed the forthcoming release of a treatise in two volumes on modern chemistry (i.e., elements de chemie, 1790).47 on 10 november 1786, fabbroni sent a request for chemicals to chaptal following a detailed list peter leopold had sent to him some days earlier.48 the content of the list is reported in table 1. it is interesting to note that, on 27 november 1786, the grand duke required that the products, once in firenze, be delivered to him in pisa. they had to be shipped via river using monti’s boat that sailed every friday with the groceries for the royal pantry.49 table 1. peter leopold’s order of chemicals purchased from jean antoine claude chaptal. 4 november 1786. substances weight vitriol oil 10 pounds alkali volatile fluor 6 pounds alkali volatile concrete 6 pounds alkali volatile caustic 6 pounds salt of tartar 8 pounds volatile salt of hart’s horn 2 pounds cinchona essential oil 1 pounds butyric antimony 1 pounds volatile salt of hart’s horn 3 pounds oil of tartar per deliquium 4 pounds diaphoretic antimony 1 pounds flowers of benzoin 1 pounds emetic tartar 1 pounds infernal stone 3 ounces marine ether 1 pounds acetic ether 1 pounds sugar-cane acid 1 pounds regulus of cobalt 10 ounces a second list, containing the request for other three chemicals (e.g., six ounces of phosphor, six ounces of pyrophorus,50 and one pounds of tartar acid) to buy from pelletier’s laboratory, was attached in a letter peter leopold sent to fabbroni from pisa on 17 january 1787.51 the delivery of the products coming from chaptal’s store in montpellier was late, so the company durand martin et c.ie wrote to fabbroni to apologize for any inconvenience it might have caused on 3 march 1787.52 when the shipment finally arrived in pisa on 26 march, peter leopold personally opened the three boxes and checked their content. after separating what he would have kept for himself from what would have been sent to the chemistry cabinet, the grand duke noted that three chemicals were missing (e.g., the essential oil of cinchona, the flowers of benzoin, and the marine ether), so he asked fabbroni to contact chaptal to send them as soon as possible. he was also informed that an unusual quantity of vitriol oil had been delivered to the imperial and royal museum of physics and natural history and asked to set aside a bottle he would have used for his experiments when back in firenze. in this regard, it has to be noted that peter leopold carried out chemical experiences outside the royal cabinet.53 for instance, on 18 december 1786, he gave instructions to the chancellor gaetano stefani (dates uncertain) to contact fabbroni asking for a supply of lute54 to be sent to pisa. the compound, mixed with boiled oil and clay, had to be like the one previously prepared by fabbroni for the experiments he conducted in the chemistry cabinet. peter leopold’s request was quite urgent. fabbroni had to prepare and deliver the lute in a day to the grand-ducal intimate secretary, so it could be placed in a suitcase that was ready to be shipped to pisa.55 coming back to the order of chemicals delivered by the french apothecary chaptal in march 1787, peter leopold gave away the butyric antimony to the chemistry cabinet. he advised fabbroni that the products’ jars were extremely fragile and had to be handled with highly caring.56 one of the last orders fabbroni commissioned to chaptal dated from mid-january to midmarch 1788.57 as mentioned before, fabbroni was not only an agent for purchasing chemicals but also a mentor who guided the grand duke through the path of chemistry. for example, while he was experiencing cinchona, peter leopold asked fabbroni if its extract could be reverted to gel in a brass pot, in a copper and silver evaporator, or if it was necessary to store the compound in an earthenware evaporator.58 fabbroni was also peter leopold’s mentor for mineral chemistry and its application to mining science. in this regard, after visiting the habsburg iron mines in 1779, peter leopold realized that the tuscan iron deposits were not adequately exploited. therefore, he asked thaddeus rauscher (dates uncertain), a mining expert in carinthia, to come to the grand dutchy of tuscany to evaluate the ore processing. fabbroni discussed the results of rauscher’s investigations in two reports in 1780. in the first document, the events concerning these inspections were summarized. fabbroni stated that two experts from carinthia arrived in september to check the quality of the iron ores and any abuses committed by the local min97just a grand duke who loves chemistry ing administrations. however, one of the two men left the country promising to return after a few days, while the other remained in firenze without continuing the work. new mining experts arrived from carinthia, and after analyzing some ores extracted in maremma, they came to different conclusions about the iron processing systems in use. the first one stated that the defects in ironworking originated from the small amount of coal used in processing the raw materials. the second expert thought that they were caused by an insufficient quantity of iron ores being processed.59 so ends the first document. in the following report on the iron mines in the grand duchy of tuscany and the sampling made by taddeo glauscher of carinthia in 1780,60 fabbroni disagreed with the opinions of the foreign mining experts, saying that “they were not aware of the progress in iron processing made outside their homeland”. as an example, he stated that the three furnaces employed in the smelting were necessary because of the samples’ size, while the iron produced in livorno, whose excessive malleability could be easily corrected, could also be used to manufacture nails and plowshares. however, at the end of his second report, fabbroni agreed with rauscher about the necessity to reorganize the wood supply for the furnaces in val di cecina. moreover, the excellent quality of the coal deposits in those areas was worthwhile for further analysis. peter leopold was no stranger to this dispute. he was pleased with the results shown in fabbroni’s reports to the point that he supported the research of new ore deposits in val di cecina in the years to come. starting from january 1789, fabbroni investigated the quality of the soil near the coal mines, their extent, and the possibility of finding other deposits nearby. the grand duke also ordered that an essay on coal mining and its processing methods be written to improve and promote this activity in the grand duchy of tuscany. one year later, fabbroni informed alessandro pontani (dates uncertain), the secretary of the state council, to have finished the book the grand duke requested. the volume was called dell’antracite o carbon di cava detto volgarmente carbon fossile (on anthracite or quarry coal, commonly called hard coal) and was printed in 250 copies by gaetano cambiagi (1725–1795), who was a typographer and the owner of the grand-ducal printing house.61 besides the investigations he carried out in val di cecina, fabbroni was also deputed to the characterization of presumed coal samples. these analyses were performed in the chemistry cabinet. for example, on 26 december 1788, he examined 20 coal samples brought to the museum by francesco henrion (dates uncertain), an archivist at the archives of the tithes of the grand duchy of tuscany.62 on peter leopold’s request, fabbroni also examined ores coming from montecerboli to ascertain the presence of borax63 and copper specimens to verify the possibility of opening a new mine near arcidosso, a project carried out some years later under the grand-ducal regency of ferdinand iii (1769–1824).64 in the following sub-section, the organization of the chemistry cabinet is described through the examination of its catalog –comprising instruments, books, and compounds, some of which belonged to and were made by peter leopold. information is also given on the destiny of the cabinet after the grand duke left firenze in the summer of 1790 to be crowned as holy roman emperor leopold ii. a grand duke at work: peter leopold’s chemistry cabinet the organization of the chemistry cabinet is illustrated in a 100-pages manuscript entitled laboratorio di chimica (chemistry laboratory), which is preserved at the museo galileo’s library.65 the volume covers a period from 1780 to 1807. it is divided into four sections, the first of which is represented by the indice delle droghe e preparazioni chimiche lasciate al reale museo da s.m.i. e collocate nella prima nuova stanza del laboratorio chimico (index of the drugs and chemical preparations left to the royal museum by h.r.h. and placed in the first new room of the chemical laboratory). on the first page was reported, in red ink, the location (room ii) where the preparations were kept, and each compound was preceded by the symbols “·” or “x”, which probably indicated its presence or lack ascertained during an inventory. the chemicals were then grouped according to the shelves where they were stored, as shown in table 2. the results and discussions section will analyze this part of the chemistry cabinet’s catalog. the following catalog’s section concerned the chemicals obtained by processing the “three kingdoms of natures” (i.e., animals, plants, and minerals), which were housed in the second of the three rooms designed to accommodate the chemical cabinet within the imperial and royal museum of physics and natural history.66 in this regard, it has to be noted that most of these compounds were in poor conservative conditions, since they were evaporated or altered, and needed to be restored. the preparations’ list has been transcribed in supplementary information files i–iv, while some information of potential interest resulting from the transcription activity is reported below. in a closet on the left of the room were substances of animal and/or human origin (e.g., cow’s milk serum, 98 annarita franza, giovanni pratesi gelatinous part of dried human blood, urine salts) for a total of 129 preparations. some of these compounds’ descriptions are followed by the letters “mb” in red ink, while the red-ink string “o-ki-ao-” is placed before the “donkey glue as prepared by chinese people” (colla d’asino come preparate dai cinesi). subsequently, there were the plant chemicals comprising 295 preparations. among them, seven samples were preserved without their containers.67 it is then interesting to note that diverse samples of honey were listed as preparations of vegetable origin, and one of these varieties (e.g., honey without phlegm, miele sfl emmato in the original text) was marked with the red-ink letters “mb”. it is also noteworthy to highlight the presence of two kinds of milk sugars (e.g., impure sugar milk, zucchero di latte impuro; white sugar milk, zucchero di latte bianco) as well as the numbers “ii” and “iii” to indicate two different samples of rectifi ed ether. numbers “2”, “2.3”, and “3” were used to show respectively a sample of turpentine essential oil (olio essenziale di terebentina), and two samples of turpentine oil (olio di terebentina). th e only compound that was cataloged as a poison was a sample of ticunas, i.e., an american poisonous substance whose eff ects were studied by felice fontana in an essay published in 1780.68 on the right side of the room, a closed kept the compounds that were realized by processing minerals for a total amount of 436 samples. two preparations (e.g., earth-based sea salt, sale marino a base terrosa; hombergy’s sedative salt, sale sedativo d’hombergio) were inventoried without containers (vase missing, manca il vaso). th e red-ink numbers “i”, “ii”, “iii”, and “iv” indicated four samples of blue enamel (azzurro di smalto), while the string “100.6” and “8.00” was reported on a cobalt sample (cobalto reputato fattizio con 100.6. e 8.00. di vienna). th e number “2” showed that a sample of berlin-blue was prepared using sheele’s method (azzurro di berlino privato della parte colorita col metodo 2: di sheele). th e letters “a.b.” were then present in the description of a crystallized fusible alloy (lega fusibile dell’a. b. cristallizzata). th e cabinet also preserved 104 chemistry and natural sciences books constituting the third catalog’s section.69 many of these volumes were written in german and french, while only two editions in italian were present.70 th e inventory did not provide information about the books’ publishing house or their year of publication with the exception of taschenbuch für scheidekünstler und apotheker auf das jahr (1789) and göttling’s almanach (1780). th e books’ titles were usually shortened as well as the names of their authors. th e number of tomes in a single work followed the title. at the end of the section, a brief note remarked that all the compounds and preparations are figure 3. frontispiece chemistry cabinet’s catalog. biblioteca del museo galileo, firenze. table 2. numbers of shelves and preparations as listed in index of the drugs and chemical preparations left to the royal museum by h.r.h. and placed in the fi rst new room of the chemical laboratory. shelf drugs and preparations nos. i 81 ii 45 iii 79 iv 63 viii 92 ix 89 x 36 v 40 vi 145 vii 85 ix 54 xii 51 xiii 75 above the shelves 15 99just a grand duke who loves chemistry usually used in experiments and other investigations. for this reason, they were not included in the general catalog. the transcription71 of the entire inventory is provided in the supplementary information files. the fourth and last catalog section described 56 scientific instruments (e.g., balances, mortars, boilers). the transcription of this section is also presented in the supplementary information files. it is interesting to note that the title of this section referred to the objects stored in all three cabinet rooms (utensili e arnesi che si conservano nelle tre stanze del laboratorio). nevertheless, ten instruments kept in a fourth room, i.e., the cabinet’s obscure hallway (androne oscuro), were also inventoried. it is then worth of mention that the descriptions presented in this section are more detailed than those given in its previous catalog parts, providing accurate data about the instruments’ physical and external characteristics, the materials they were made from, and whether accessories were present or not. by analyzing this descriptive model, it was discovered that two anvils showed the emblem of the medici family.72 after peter leopold returned to vienna to be crowned holy roman emperor leopold ii, he donated the workbench and all the objects preserved in the chemistry cabinet to the imperial and royal museum of physics and natural history. the donation happened on 27 july 1790 when all the preparations belonging to the grand duke were transferred to the purpose-built museum room together with “various tools, housewares, earthenware, and crystal vases”. fabbroni’s economic evaluation estimated the cabinet’s value at 7217 tuscan lire. in detail, the chemical preparations and the instruments were evaluated at 6235 tuscan lire; the housewares, the furniture, and the tools at 952 tuscan lire; the books at 30 tuscan lire.73 results and discussions this study aimed to assess the history of the chemical cabinet at the florentine imperial and royal museum of physics and natural history during the grand duke peter leopold’s regency. to achieve this goal, the catalog of the chemical cabinet was analyzed, and the entire manuscript text was transcribed in the supplementary information files. the investigation showed that 1534 items were kept in the cabinet between 1780 and 1807. among them, there were 1374 chemicals. what is interesting about the data is that 950 compounds belonged to peter leopold and therefore, they were inventoried and described altogether in the first part of the catalog. a closer inspection of their list transcribed in the supplementary information file i revealed as some of these preparations might have been prepared by the grand duke himself. for instance, a sample of lac martin – i.e., a mastic-based varnish used in the restoration of paintings – was described as “made by his royal highness [on] 29 december 1780”.74 one of the most intriguing aspects, besides the sample evidence of peter leopold’s genuine interest in chemistry, is that it was still preserved in the early 20th century when ugo schiff (1834–1915) noted its presence among the compounds kept in the chemical cabinet. schiff also outlined that jakob philipp hackert (1737–1807), a painter working for ferdinand i of the two sicilies (1751–1825) in napoli, had probably illustrated the method for preparing the lac martin to peter leopold during the meeting he had with the grand duke at the end of 1778.75 in this regard, it has to be noted that the sample made by peter leopold was stored on shelf no. viii, which was entirely devoted to the preservation of dyes and varnishes for painting, coating wood, gilded brass, and other minerals. among the 92 preparations, there were two samples of lac martin: the one prepared by peter leopold and a second one briefly described as “bechi’s lac martin”.76 unfortunately, the catalog provided neither further information on peter leopold’s preparation nor on the bechi’s one. nevertheless, the latter could be possibly identified with antonio bechi (dates uncertain), a member of the florentine confraternity of the misericordia and an impresario who established a theater in via di porta rossa in 1760.77 in the current state of research; it is neither possible to affirm nor deny that the bechi who prepared the second lac martin sample was antonio bechi. and if this was the case, neither had he ever met peter leopold to explain the varnish preparation. however, this is a hypothesis valuable to be explored in further studies. another striking observation emerging from comparing the chemicals’ inventory belonging to peter leopold is that various preparations were comprised in the orders the grand duke received by the diverse french apothecaries in the 1780s. as expected, not all the compounds bought through the years have been cataloged (e.g., the pâte guimauve) because they were used to perform experiments or make other preparations, such as the radical vinegar of venus, which was based on venus crystals. however, table 1 showed that most of the chemicals ordered to chaptal on 4 november 1786 (excepting the essential oil of cinchona) were cataloged in pure form (i.e., flowers of benzoin, emetic tartar, infernal stone, and sugar-cane acid) or in combination with other compounds. this is the case of the marine ether, which was used to make four different prepara100 annarita franza, giovanni pratesi tions (i.e., manganese marine ether with vitriolic oil, marine salt, and wine spirit; marine ether with libavio’s liqueur; nitrous and vitriolic marine ether). it is then worth of mention that peter leopold’s interest in mineral chemistry outlined in the previous section was confirmed by the catalog’s analysis of his preparations preserved in the chemical cabinet at the imperial and royal museum of physics and natural history. for example, diverse compounds were utilized in mineral processing, such as vitriolic oil, which was used in the distillation of manganese and the extraction of lead in association with cobalt and zinc. in this regard, it is interesting to note the presence of many preparations constituted by minerals such as ruby-sulphur (realgar)78 and various copper-, antimony-, and manganese-based compounds. about this topic, it is worth mentioning that on shelf no. v was kept 30 cobalt preparations, such as a cobalt specimen from vienna melted with nitrous acid and prepared with tartar oil, and four compounds made with zaffre (zaffra), which indicated impure cobalt arsenate.79 among them, one was used for realizing a sample of sympathetic green ink mixed with royal water (aqua regia), i.e., a 3:1 mixture of hydrochloric acid and nitric acid. in this regard, it is important to note that 13 different sympathetic cobalt-based inks were preserved, including five green and one rose samples. it can be assumed that peter leopold was genuinely interested in sympathetic inks and their chemical principles, a fondness he shared with the cultural milieu of his time. on this, macrakis highlighted that sympathetic inks gained the interest of the intellectual community at the end of the 18th century. in particular, the progress in knowing the properties of cobalt (e.g., the changing of colors from rose to green and blue when heated) in the early 1700s and the research of chemists such as jean hellot (1685–1766) and pierre joseph macquer (1718–1784) allowed the use of these writing tools to become much more advanced and fashionable throughout europe.80 the remaining parts of the catalog gathering the chemical preparations belonging to peter leopold present various compounds that could be utilized in precious metal refining as a mixture of salpeter and ammonia salt to refine gold. these preparations may help us understand the research on mineralogy, chemistry, and mining activities the grand duke performed with giovanni fabbroni’s assistance. the present results are significant in at least two major respects. broadly speaking, the compounds belonging to peter leopold that were listed in the first part of the chemical cabinet’s catalog reflected the institutional reforms he undertook to promote the development of chemical knowledge through the establishment of new research centers as the chemical cabinet at the royal museum of physics and natural history. the latter soon became a center of great importance from a european perspective, as shown by the french apothecaries with whom fabbroni was in contact. the cabinet was then equipped with the most up-to-date instruments and tools to perform experiments in pneumatic chemistry, as revealed by the analysis of its catalog. furthermore, the investigations carried out at the chemistry cabinet, such as those to improve iron processing in maremma or the research on the characterization of valuable minerals, were aimed, as stated by mokyr, at expanding the set of useful knowledge and applying natural sciences to solve technological problems and bring about economic growth.81 to this theoretical framework has to be referred to fabbroni’s publication on the coal deposits, which represented a means to promote mining sciences and activities within the grand duchy of tuscany. in this regard, it is noteworthy that the typologies of the preparations listed in the chemistry cabinet’s catalog showed how chemistry was an applied science in 18th-century italy, closely linked on the one hand with medicine and pharmacopeia and on the other hand with mineralogy and mining processes. on this subject, it is interesting to outline that peter leopold asked thaddeus rauscher to improve the working methods used in tuscan iron deposits and ordered fabbroni to observe the mining and mineral processing techniques utilized in the habsburg mines. this action followed similar resolutions taken by the rulers of other italian states that supported the educational travels to the mines of central and northern europe (e.g., to the renewed chemnitz mining school) for their naturalists, as happened to marco carburi (1731–1808) and matteo tondi (1762– 1835).82 so, it was not by chance that fabbroni, after the restoration, left his position as director of the imperial and royal museum of physics and natural history to be responsible for the mint and the mines of the grand dutchy of tuscany. it should then be noted that the measures peter leopold implemented to improve chemical knowledge, such as the establishment of a chemistry chair at the university of siena in 1771, continued the actions carried on by his father, francis i, who instituted the first tuscan chair of chemistry at the university of pisa in 1757.83 subsequently, the combination of the findings presented in this study raises the possibility that peter leopold’s interest in chemistry, although influenced by the cultural context in which he lived, could be genuine. for example, he carried out experiments on the diverse phases of matter and performed personal investigations 101just a grand duke who loves chemistry outside the chemistry cabinet, as shown by the orders of chemical products he asked to be delivered in pisa with urgency at the end of 1786. about the remaining parts that constituted the catalog of the chemical cabinet, it was considered not to explore them further than the materials presented in the previous section since these inventories are linked neither to peter leopold nor to the activities he carried out at the chemical cabinet, covering the volume a period up to 1807. regarding the inventory of the books kept in the chemistry cabinet, it is interesting to outline that on 14 may 1789, francesco favi informed fabbroni of the publication of lavoisier’s traité élémentaire de chimie and of the first volume of the annales de chimie. favi then advertised to have shipped the books by courier to fontana’s address and asked whether he was to send the ongoing annals or not.84 according to inventory, the museum acquired for the library of the chemical cabinet both the volumes of lavoisier’s traité élémentaire de chimie and the first ten issues of the annales de chimie. conclusions the present study aimed to examine the history of the chemical cabinet at the imperial and royal museum of physics and natural history up to 1790, when grand duke peter leopold, who founded the museum in 1775, returned to vienna as holy roman emperor leopold ii. the second goal of this work was to analyze peter leopold’s interest in chemistry to investigate whether he had a sincere fondness for this branch of science. thanks to the examination of the chemical cabinet’s catalog, whose transcription is presented in the supplementary information files, and the data comparison with other archival sources relative to the imperial and royal museum of physics and natural history, this study has found that the establishment of the chemical cabinet fell under the policies for promoting scientific culture peter leopold implemented in the grand dutchy of tuscany under his regency. however, one of the more significant findings to emerge from this work is that the establishment of the cabinet and its management also suited the grand duke’s interests in natural and experimental sciences, disciplines that experienced remarkable advancements in the second half of the 18th century. peter leopold’s fascination with analytical chemistry is evidenced by the collection of preparations he owned within the chemical cabinet –some of which he made– that were inventoried in the first part of the cabinet’s catalog. their analysis, together with the reconstruction of the activities he carried out with the help of giovanni fabbroni, showed the scientific and experimental interest in the chemistry of an enlightened ruler, who was fully aware of the economic, social, and cultural benefits that would result from the development of chemical knowledge for the territories under his governance. acknowledgments the authors of this work thank all the museo galileo’s library staff for their kindness and help in accessing the archival documentation. the authors then acknowledge the financial support of fondi di ricerca scientifica d’ateneo 2022 – università degli studi di firenze. references [1] j. soll in florence after the medici, (eds.: c. tazzara, p. findlen, j. soll), routledge, new york, 2020, p. 331. [2] for an overview of the biography literature on peter leopold see: m. rastrelli, memorie per servire alla vita di leopoldo ii. imperatore de’ romani già gran-duca di toscana, firenze, 1792; f. becattini, vita pubblica e privata di pietro leopoldo d’austria granduca di toscana poi imperatore leopoldo ii, all’insegna del mangia, siena, 1797; a. wandruszka, pietro leopoldo: un grande riformatore, vallecchi, firenze, 1968; g. capponi, introduzione alla istoria civile dei papi; storia di pietro leopoldo, le lettere, firenze, 1976; h. peham, pietro leopoldo granduca di toscana, bonechi, firenze, 1990; r. pasta, dizionario biografico degli italiani 2015, 83, 563–573. [3] an investigation of the relationship between peter leopold, joseph ii and marie antoinette is included in a. ritter von arneth, marie antoinette: joseph ii und leopold ii: ihr briefwechsel: joseph ii und leopold ii: ihr briefwechsel, k.f. köhler, leipzig, 1866. [4] a. wandruszka, physis 1962, 4(2), 116–124. [5] l. bellatalla, pietro leopoldo di toscana granducaeducatore: teoria e pratica di un despota illuminato, pacini fazzi editore, lucca, 1984. [6] l. maran, m. castellini, j. bisman, manag. organ. hist., doi: 10.1080/17449359.2013.826907. [7] as an example of peter leopold’s judicial reforms, it is worth mentioning that the grand duchy of tuscany was the first country to abolish torture and the death penalty on 30 november 1786. more details on this topic can be found in: l. berlinguer, f. colao, la leopoldina nel diritto e nella giustizia in toscana, giuffré, milano, 1989; d. edigati, prima della leopol102 annarita franza, giovanni pratesi dina: la giustizia criminale toscana tra prassi e riforme legislative nel xviii secolo, jovene, napoli, 2011; c.e. tavilla in il diritto come forza, la forza del diritto. le fonti in azione nel diritto europeo tra medioevo ed età contemporanea (eds.: r. braccia, a. carrera, a.a. cassi, e. fusar poli, a. marchisello, g. rossi, c.e. tavilla, a. sciumè), giappichelli, torino, 2012, pp. 151–185. [8] r. sarti, italy: a reference guide from the renaissance to the present, facts on file, new york, 2004, p. 38. [9] l. maran, w. funnell, m. castellini, a.a.a.j., doi: 10.1108/aaaj-10-2017-3180. [10] for a more extensive survey of peter leopold’s reforms see: c. mangio, la polizia toscana: organizzazione e criterio d’intervento 1765–1808, giuffré, milano, 1988; a. tacchi, medioevo e rinascimento, 1992, 6, 361–373; g. la rosa, il sigillo delle riforme. la costituzione di pietro leopoldo di toscana, vita e pensiero, firenze, 1997; m. rosa, settecento religioso. politica della ragione e religione del cuore, marsilio, venezia, 1999; v. baldacci, le riforme di pietro leopoldo e la nascita della toscana moderna, regione toscana press, firenze, 2000; a. contini in la corte di toscana dai medici ai lorena (eds.: a. bellinazzi, a. contini) ministero per i beni e le attività culturali, direzione generale per gli archivi, roma, 2002, pp. 129–220; v. perlato, studi urbinati, a scienze giuridiche, politiche ed economiche, doi: 10.14276/1825-1676.1070; r. messbarger in florence after the medici, (eds.: c. tazzara, p. findlen, j. soll), routledge, new york, 2020, pp. 116–154. [11] giovanni valentino mattia fabbroni was one of the most renewed intellectuals in the tuscan cultural circles of the late 18th century. in their review of the history of analytical chemistry in italy, burns et al. stated that fabbroni’s research interests encompassed natural sciences, mineralogical and agricultural chemistry, electrochemistry, and political economy. fabbroni was also involved in managing the imperial and royal museum of physics and natural history, where he worked since he was sixteen years old as an assistant to the director felice fontana (1730–1805). in 1780 fabbroni was appointed as museum’s vice director. he became museum director in 1825. see: t. burns, g. piccardi, l. sabbatini, microchim acta, doi: 10.1007/s00604-007-0769-0. for a more exhaustive fabbroni’s scientific biography see: r. pasta, scienza, politica e rivoluzione. l’opera di giovanni fabbroni (1752–1822) intellettuale e funzionario al servizio dei lorena, l.s. olschki, firenze, 1989; s. contardi in linnaeus in italy: the spread of a revolution in science (eds: m. beretta, a. tosi), science history publications, sagamore beach, 2007, pp. 113–128. [12] archivio museo galileo (amg), fabbroni 10, cc. 1–99. [13] the archive of the royal museum of physics and natural history preserves more than 5700 records about the administration, organization, and management of the museum from 1775 to 1872. this archival fund represents one of the most important sources of information to investigate the fascinating and complex history of this institution. [14] on the history of the collections housed at imperial and royal museum of physics and natural history see: g. barsanti, g. chelazzi (eds.), il museo di storia naturale dell’università degli studi di firenze. le collezioni della specola, firenze university press, firenze, 2009; m. raffaelli (ed.), il museo di storia naturale dell’università di firenze – le collezioni botaniche, firenze university press, firenze, 2009; s. monechi, l. rook (eds.), il museo di storia naturale dell’università degli studi di firenze. le collezioni geologiche e paleontologiche, firenze university press, firenze, 2010; g. pratesi (ed.), il museo di storia naturale dell’università degli studi di firenze. le collezioni mineralogiche e litologiche, firenze university press, firenze, 2012; j. moggi cecchi, r. stanyon (eds.), il museo di storia naturale dell’università degli studi di firenze. le collezioni antropologiche ed etnologiche, firenze university press, firenze, 2014; m. borgheresi, f. di benedetto, a. caneschi, g. pratesi, m. romanelli, l. sorace, phys. chem. miner., doi: 10.1007/s00269-007-0175-5; g. pratesi, a. franza, e. lascialfari, l. fantoni, f. malesani, a. hirata, geoheritage, doi: 10.1007/s12371-021-00624-1. [15] on 18 october 1771, felice fontana (1730–1805), who was the first director of the imperial and royal museum of physics and natural history, received the inventory concerning the scientific instruments and the naturalistic specimens kept in the royal gallery (today uffizi gallery) that had belonged to the medici family. amg, armu 001, aff. 1, cc. 331–380. on the scientific medicean collecting see: f. camerota, m. miniati, i medici e le scienze: strumenti e macchine nelle collezioni granducali, giunti, firenze, 2008. for an investigation of the medici collections that are still preserved at the florentine natural history museum see: a. re, d. angelici, a. lo giudice, j. corsi, s. allegretti, a.f. biondi, g. gariani, s. calusi, n. gelli, l. giuntini, m. massi, f. taccetti, l. la torre, v. rigato, g. pratesi, nucl. instrum. methods phys. res. b: beam interact. mater. at., doi: 10.1016/j.nimb.2014.11.060. 103just a grand duke who loves chemistry [16] the accademia del cimento, founded by leopold i de medici (1617–1675) and ferdinand ii de medici (1610–1670) in 1657, was the first scientific society in europe. it remained active until 1667 and was devoted to studying the natural philosophy’s principles in the light of the experimental method. during the accademia’s meetings, usually held at pitti palace, the participants –among which there were francesco redi (1626–1697) and giovanni alfonso borelli (1608–1679)– performed experiments on thermometry, barometry, and pneumatics using the purposebuilt instruments that were stored in the grand-ducal residence, until peter leopold transferred them to the imperial and royal museum of physics and natural history at torrigiani palace. see: p. findlen, academies, networks, and projects: the accademia del cimento and its legacy, galilaeana, 7, 2010, 277–298.    [17] in the spirit of enlightenment, useful knowledge covered many disciplines (from today’s hard sciences to humanities) that could improve a country’s education, progress, and civilization. see: t. morel, g. parolini, c. pastorino (eds.), the making of useful knowledge, max planck institut für wissenschaftsgeschichte, berlin, 2016. in this scientific, social, and cultural milieu, the establishment of the imperial and royal museum of physics and natural history can be included among the policies – such as the reforms of hospitals and libraries – peter leopold implemented for the public good. see: m.m. goggioli, la biblioteca magliabechiana. libri, uomini, idee per la prima biblioteca pubblica a firenze, l.s. olschki, firenze, 2000; e. chapron, il patrimonio ricomposto. biblioteche e soppressioni ecclesiastiche in toscana da pietro leopoldo a napoleone, archivio storico italiano, 2009, 167, 299–346; e. diana, m. geddes de filicaia, regolamento dei regi spedali di santa maria nuova e di bonifazio, polistampa, firenze, 2010; s. barchielli, l’istituto vaccinogeno all’ospedale di santa maria degli innocenti di firenze nel xviii secolo, nuncius, 1998, 13(1), 247–263. [18] s. contardi, la casa di salomone a firenze: l’imperiale e reale museo di fisica e storia naturale, 1775–1801, l.s. olschki, firenze, 2002. [19] for instance, an overview of the museum acquisitions coming from the habsburg dominions is reported in: m. benvenuti, v. moggi cecchi, l. fantoni, r. manca in collectio mineralium. the catalog of holy roman emperor leopold’s ii mineralogical collection (eds: a. franza, j. mattes, g. pratesi), firenze university press, firenze, 2022. [20] a classic example of the objects realized at the museum laboratories is the anatomical models produced at the la specola wax workshop. see: a. maerker, model experts: wax anatomies and enlightenment in florence and vienna, 1775-1815, manchester university press, manchester, 2011. [21] among the museum workshops, contardi highlighted how the physics cabinet represented one of the most renewed research centers on electrical phenomena at that time and was attended by various scholars such as angelo querini (1721–1796), antonio vallisnieri junior (1707–1777), and carlo barletti (1735–1800). the latter studied the machines that were built there. furthermore, the physics cabinet also realized mechanical and pneumatic equipment and various optical instruments. see s. contardi in il museo di storia naturale dell’università degli studi di firenze. le collezioni della specola (eds.: g. barsanti, g. chelazzi), firenze university press, firenze, pp. 18–25. [22] the surviving pneumatic pumps (ca. 13 instruments) are now preserved at the museo galileo (inventory nos. 358–359, 423, 831, 1530–1537, 3777). among these, it is worth mentioning a pear-shaped glass ampoule that was used to simulate the aurora borealis phenomenon (inv. no. 423), two vitreous globes for experiments with a bladder in a vacuum (inv. nos. 358–359), and an air pump that resembles the device described by jean antoine nollet (1770–1770) in his leçons de physique expérimentale (1743–1748) (inv. no. 1534). on the latter instrument, see: p. brenni in the art of teaching physics: the eighteenth century demonstration apparatus of jean antoine nollet (eds.: l. pyenson, j.f. gauvin), septentrion, sillery, 2002, pp. 11–27. [23] o. gori, mitteilungen des kunsthistorischen institutes in florenz, 2002, 46(2/3), 518–532. [24] see: g. scorrano, n. nicolini, i.m. masoner, j. chem. ed., doi: 10.1021/ed079p47. peter leopold’s workbench is now displayed in room x of the museo galileo’s permanent exhibition. [25] hubert franz hoefer was born in colonia in 1728. there was no news about him until 1765 when he arrived in firenze along with peter leopold’s retinue. he remained in firenze for 25 years and was appointed director of the court’s pharmacy. in 1766 he commissioned the tabula affinitatum, i.e., a table of the chemical affinities between different substances based on étienne-françois geoffroy’s table des differents rapports observés entre differentes substances (1718), for the apothecary’s shop. the tabula affinitatum is now preserved at the museo galileo (inv. no. 1899). from the early 1780s, hoefer analyzed the tuscan springs of rapolano, san quirico d’orcia, 104 annarita franza, giovanni pratesi and rio nell’elba. still, his most renewed investigation was the water analysis of lagone cerchiaio in monterotondo marittimo, during which he discovered the natural boric acid (1778). when peter leopold was crowned as holy roman emperor in 1790, hoefer returned to vienna, where he died as a court chamberlain five years later. see: g. piccardi, la farmacia granducale di firenze, l.s. olschki, firenze, 2018; g. piccardi, nuncius, 2004, 19(2), 545–568. [26] after the renovation of bagni di pisa and bagni di lucca, peter leopold oversaw the establishment of a new thermal center near montecatini. following the works of david becher (1725–1791), who was a physician and a balneologist also known as the “hippocrates of karlovy vary”, the grand duke ordered chemical analyses on both coldand hotwater springs to formulate individual hydrothermal treatments. similar investigations were performed in the siena area by giuseppe baldassarri (1705–1785). see: v. becagli in una politica per le terme: montecatini e la val di nievole nelle riforme di pietro leopoldo. atti del convegno di studi: montecatini terme, 25-26-27 ottobre 1984, periccioli, siena, 1985, pp. 174–210; g.l. corinto, geotema, 2019, 60, 44– 52; a. guarducci in chiare, fresche e dolci acque. le sorgenti nell’esperienza odeporica e nella storia del territorio (ed.: c. masetti), cisge, roma, 2020, pp. 355–370. [27] a. franza, r. fabozzi, l. vezzosi, l. fantoni, g. pratesi, earth sci. hist., doi: 10.17704/1944-617838.2.173; a. franza, j. mattes, g. pratesi, collectio mineralium. the catalog of holy roman emperor leopold’s ii mineralogical collection, firenze university press, firenze, 2022. [28] m.j. ventresca, j.w. mohr in the blackwell companion to organizations (ed.: j.a.c. baum), blackwell, maiden, 2002, pp. 805–828. [29] e. solomon, reference/representation, 105–108, 2011. [30] s. contardi in il museo di storia naturale dell’università degli studi di firenze. le collezioni mineralogiche e litologiche (ed. g. pratesi), firenze university press, firenze, p. 17. [31] “sua altezza reale fa sapere all’aiuto del direttore del real museo gio: fabbroni che domane verrà al d. museo alle ore 2 pomeridiane scendendo alla porta della strada. 3 settembre 1789.” see: amg, fabbroni 04, c. 3. [32] according to simon, although he did not enjoy the same historical recognition as other pharmacists due to his opposition to antoine lavoisier’s oxygen theory, baumé was a qualified chemist. he wrote several works on the crystallization of salts, the phenomena of freezing and fermentation, and the properties of boric acid, sulphur, and opium. baumé’s research also dealt with the practical use of chemistry. for example, he studied the characteristics of clays and other building materials and created a system for fabric dyeing and silk bleaching. baumé then proposed a new method for the purification of saltpeter and established the first ammonium salt factory in france. he also perfectioned the empirical hydrometer that today is named after him. on antoine baumé see: j. simon, osiris, doi: 10.1086/678108; c. barnard, a. fones, platin. met. rev., doi: 10.1595/147106712x650811. with regards to his studies on fermentation producers, on 9 november 1787, baumé complimented fabbroni for the essay about wine fermentation written by his brother adamo. amg, fabbroni 04, c. 34. the work dell’arte di fare il vino (1787) dealt with producing and conservating wines to be exported. on adamo fabbroni (1748–1816) see: r. pasta in dizionario biografico degli italiani, istituto della enciclopedia italiana, roma, 1993, vol. 43, pp. 669–673. [33] francesco raimondo favi was a well-known diplomat in the parisian political, economic, and cultural milieu. thanks to his intermediation, new scientific publications as well as diverse mechanical drawings, botanical specimens, and scientific instruments reached firenze in the last decades of the 1700s. see: z. ciuffoletti, parigi-firenze 1789-1794. dispacci del residente toscano nella capitale francese al governo granducale, l.s. olschki, firenze, 1994. [34] francesco favi, joseph latour (dates uncertain), and david durand (dates uncertain) oversaw the shipments on the french front, while rocco bacigalupo (dates uncertain) was responsible for the deliveries from livorno to pisa and firenze. [35] amg, fabbroni 04, cc. 69–72. another list of chemicals fabbroni asked baumé for is given in amg, fabbroni 04, c. 57. [36] amg, fabbroni 04, cc. 30–32, c. 52. [37] r.d. hoblyn, dictionary of terms used in medicine, printed for sherwood, gilbert, & piper, london, 1844, p. 228. [38] amg, fabbroni 04, c. 16. [39] amg, fabbroni 04, c. 11. [40] amg, fabbroni 04, c. 12. [41] bertrand pelletier was an apothecary conducting diverse investigations into mineral chemistry at his parisian laboratory in rue jacob 48. following jean baptiste romé de l’isle’s (1736–1790) studies, he realized salt crystals that were soluble at very slow evaporation. in 1785, he confirmed carl scheele’s (1742–1786) discovery that chlorine could be pro105just a grand duke who loves chemistry duced from hydrochloric acid and manganese. see: w.a. smeaton, platinum metals rev., 1997, 41, 86–88. [42] amg, fabbroni 04, c. 77. [43] jean antoine chaptal, count of chanteloup, was a chemist and a statesman. his studies dealt with the industrial manufacture of soda ash and sodium nitrate. with louis nicolas vauquelin (1763–1829), he determined the alum composition, promoting its industrial production by synthetic means. see: j. hoff, technology and culture, 1998, 39, 671–698. [44] amg, fabbroni 04, c. 43. this document is related to a brief note, showing no signature or date, partially written in french, reporting general information about chaptal and his well-stocked store in montpellier. a closing remark in italian says, “i would write for the prices and the kinds of products he sells”. see: amg, fabbroni 04, c. 48. [45] amg, fabbroni 04, c. 50. [46] amg, fabbroni 04, cc. 101 and 108. [47] amg, fabbroni 04, cc. 80–81. [48] amg, fabbroni 04, c. 2. the document heading reported that if fabbroni did not need to file the order note, this would be sent back to his royal highness. [49] amg, fabbroni 04, c. 104. [50] the pyrophorus hombergii was a flammable compound realized from human fecal matter created by the dutch chemistry and physician wilhelm homberg (1652–1715) in the early 18th century. see: l. principe, the transmutations of chymistry. wilhelm homberg and the académie royale des sciences, university of chicago press, chicago, 2020. [51] amg, fabbroni 04, cc. 89–90. [52] amg, fabbroni 04, c. 86. [53] amg, fabbroni 04, c. 84. [54] the lute was usually used in chemical distillation processes to seal a vessel and prevent the dispersion of the stem while protecting its surface from heat. see: s.j. linden, the alchemy reader: from hermes trismegistus to isaac newton, cambridge university press, cambridge, 2003. [55] amg, fabbroni 04, c. 126. [56] amg, fabbroni 04, cc. 96 and 98. [57] amg, affari 002, c. 355. [58] amg, fabbroni 04, c. 30. [59] amg, fabbroni 02, cc. 9–12. [60] amg, fabbroni 02, cc. 2–8. the original title was relazione sopra le miniere di ferro nel granducato di toscana e saggi sopra le medesime fatte da taddeo glauscher di carintia nel 1780. taddeo glauscher can be identified with the mining expert taddeus rauscher, since the correct spelling of his name is mentioned in the opening of fabbroni’s report. [61] amg, fabbroni 03, cc. 268–271. [62] amg, fabbroni 03, c. 253. [63] amg, fabbroni 03, c. 251. [64] amg, fabbroni 03, c. 275 and 404. [65] amg, fabbroni 10, cc. 1–99. [66] the full title of the second catalog’s section is serie di preparazioni chimiche risultanti dall’analisi dei tre regni della natura e che si conservano in piccoli saggi nella seconda stanza del laboratorio (series of chemical preparations resulting from the analysis of the three kingdoms of nature and stored in small samples in the second room of the laboratory). [67] acid and light cacao butter oil (acido e olio leggiero del burro di caccao), precipitated copal of the spirit of wine with the effusion of water (coppale precipitata dello spirito di vino con l’effusione dell’acqua), cherry-laurel spirit (spirito di lauro-ceraso), essential oil and resinous part of laurel berries separated from its fixed oil by means of wine spirit (olio essenziale e parte resinosa delle bacche di alloro separati dal suo olio fisso col mezzo dello spirito di vino), aromatic part of wine dissolved in wine spirit (parte odorante del vino disciolta nello spirito di vino), litmus tincture (tintura di tornasole), litmus starch or mold laquer (fecula del tornasole ò lacca muffa). [68] in his essay on ticunas, fontana stated that he had the opportunity to study this vegetable-origin poison at the beginning of his stay in london (approximately in the summer of 1778). the english version of the essay’s title reported the compound as belonging to the grand duke of tuscany. since no other mention of this fact was written neither in fontana’s text nor in the chemistry cabinet’s catalog, it is impossible to include this sample within the preparations peter leopold owned. see: f. fontana, philosophical transactions of the royal society of london, 1780, 70:163– 220, ix–xlv. [69] the third catalog’s section was entitled libri d’arte che si conservano nel laboratorio (arts books kept in the laboratory). [70] they were scopoli’s materie spettanti alla chimica and the italian edition of macquer’s dizionario di chimica. [71] the transcription reports as precisely as possible how the books have been inventoried; therefore, possible spelling errors have not been corrected unless they made the text unintelligible. [72] here is the original text: un tasso ed una bicornia sul medesimo coppo lustri e intagliati a bulino con vari fregi e coll’arme de medici. [73] amg, armu affari 004, c. 307. 106 annarita franza, giovanni pratesi [74] “lac martin fatta da s.a.r. 29 dicembre 1780” in the original text. [75] u. schiff, m. betti, archeion, 1928, 9:290–324. [76. “lac martin del bechi” in the text. [77] see: tomo settimo delle gazzette toscane uscite settimana per settimana nell’anno 1772, appresso anton giuseppe pagani stampatore e librajo delle scalere di badia, firenze, 1772, no. 12, unnumbered page; p. landini, istoria della venerabile compagnia di santa maria della misericordia della città di firenze con i capitoli, riforme, e catalogo di tutti i capi di guardia dal suo primo principio, nella stamperia di pietro allegrini alla croce rossa, firenze, 1786, p. cxvii; [78] t. wright, the universal pronouncing dictionary, and general expositor of the english language, the london and new york printing and publishing company, london and new york, vol. 5, p. 267. [79] f. flügel, j.g. flügel, a practical dictionary of the english and german languages: deutschenglisch, julius richter, leipzig, 1861, p. 1128. [80] on the history of sympathetic inks, their usage in the late 18th century, and chemical research about their composition, see: j. wisniak, revista cenic ciencias químicas, 2009, 40(2): 111–121; c. lehman, ambix, doi: 10.1179/174582310x12629173849881; k. macrakis, prisoners, lovers, and spies: the story of invisible ink from herodotus to al-qaeda, yale university press, new haven, 2014. [81] j. mokyr, the journal of economic history, 2005, 65(2):285–351. [82] r. vergani, quaderni storici, 1989, 24: 123–141; c. guerra, lavoisier e partenope: contributo ad una storia della chimica del regno di napoli, società napoletana di storia patria, napoli, 2017. [83] g. fochi, annali di storia delle università italiane, 2010, 14: 207–216. [84] amg, armu affari 002, aff. 94, c. 374. substantia. an international journal of the history of chemistry 6(2): 7-13, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1630 citation: lekner j. (2022) the spinning electron. substantia 6(2): 7-13. doi: 10.36253/substantia-1630 received: apr 16, 2022 revised: may 23, 2022 just accepted online: may 24, 2022 published: september 1, 2022 copyright: © 2022 lekner j. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. the spinning electron john lekner school of chemical and physical sciences, victoria university of wellington, po box 600, wellington, new zealand e-mail: john.lekner@vuw.ac.nz abstract. the notion introduced by ohanian that spin is a wave property is implemented, both in dirac and in schrödinger quantum mechanics. we find that half-integer spin is the consequence of azimuthal dependence in two of the four spinor components, relativistically and non-relativistically. in both cases the spinor components are free particle wavepackets; the total wavefunction is an eigenstate of the total angular momentum in the direction of net particle motion. in the non-relativistic case we make use of the lévy-leblond result that four coupled non-relativistic wave equations, equivalent to the pauli-schrödinger equation, represent particles of half-integer spin, with g-factor 2. an example of an exact gaussian solution of the non-relativistic equations is illustrated. keywords: electron, spin, spinor. 1. introduction in his article “what is spin” [1], ohanian argues that ‘spin may be regarded as an angular momentum generated by a circulating flow of energy in the wave field of the electron’, and that ‘the spin of the electron has a close classical analog: it is an angular momentum of exactly the same kind as carried by the wave field of a circularly polarized electromagnetic wave.’ ohanian credits belifante [2] for establishing that ‘this picture of spin is valid not only for electrons but also for photons, vector mesons, and gravitons.’ dirac [3,4] regarded his four-by four matrices as ‘new dynamical variables…describing some internal motion of the electron, which for most purposes may be taken to be the spin of the electron postulated in previous theories’ [4]. this is how the concept of spin is presented in most texts, as intrinsically relativistic, a mysterious internal angular momentum for which there is no classical analogue. for example, in his “introduction to quantum mechanics” [5] griffiths states ‘…the electron also carries another form of angular momentum, which has nothing to do with motion in space (and which is not, therefore, described by any function of the position variables r,θ,ϕ) but which is somewhat analogous to classical spin…’. we shall construct, for a general relativistic or non-relativistic wavepacket, an eigenstate of the component of total angular momentum in the net http://www.fupress.com/substantia http://www.fupress.com/substantia mailto:john.lekner@vuw.ac.nz 8 john lekner direction of propagation, with eigenvalue ℏ/2. such eigenstates are four-component spinors, of which two components have eiϕ azimuthal dependence. in these formulations the phenomenon of spin is incorporated into ordinary space-time: the twist is in the azimuthal dependence of two of the wavefunctions. to the question: what does a spinning electron look like? we answer, in brief, that spin in the spinor formulation, relativistic or nonrelativistic, resides in the azimuthal dependence of two of the spinor components. this contrasts with the usual spin-space formulation, and the decoupling of spin from space-time. in sections 2 we construct genera l relativistic wavepackets with spin half; these are four-component spinors. an important aspect of spin is that it is not purely a relativistic effect: levy-léblond [6] has proved that the galileo group has irreducible representations with non-zero spin. a reviewer has pointed out that galindo and del rio [7] show that galilean fermions are possible, with a four-component spinor linearization of the non-relativistic wave equation and a correct (to lowest order) g-factor. the galindo and del rio paper anticipates some of the work of lévy-leblond [6] and gould [14]. lev y-léblond ’s four-component nonrelativ istic spinors are implemented in section 3, to construct general angular momentum eigenstates with spin half. an explicit example of a non-relativistic spinning wavepacket is illustrated in section 4. 2. dirac spinors the wavefunction ψ(r,t) of an electron wavepacket in free space is to satisfy the dirac equation hψ(r,t)=iℏ∂tψ(r,t), h=cα∙p+βmc2, p=-iℏ∇ (2.1) the 4×4 matrices α,β are written in terms of the pauli spin matrices σx,σy,σz and the unit 2×2 matrix i as (2.2) the wave equation (2.1) thus consists of four coupled first-order partial differential equations. we consider wavepacket motion, predominantly along the z direction. in cylindrical polar coordinates is the distance from the z-axis, ϕ is the azimuthal angle, and (2.3) the four time-dependent free-space equations for the spinor ψ read, with mc/ℏ=k, (∂ct+ik)ψ1+e-iϕ(∂ρ-iρ-1∂ϕ)ψ4+∂zψ3=0 (2.4a) (∂ct+ik)ψ2+eiϕ(∂ρ+iρ-1∂ϕ)ψ3-∂zψ4=0 (2.4b) (∂ct-ik)ψ3+e-iϕ(∂ρ-iρ-1∂ϕ)ψ2+∂zψ1=0 (2.4c) (∂ct-ik)ψ4+eiϕ(∂ρ+iρ-1∂ϕ)ψ1-∂zψ2=0 (2.4d) when the spinor components ψj are independent of ϕ, solutions exist only for the ψj also independent of ρ. these are the well-known plane wave solutions ψj=ajei(qzωt), where the wavenumber q and the energy ℏω are constrained by (ω/c)2=k2+q2. to attain localized wavepacket solutions, we need to consider azimuthal dependence. the angular momentum operator l=r×p does not commute with the hamiltonian, but the combination j=l+ σ does, where σ= . the z component of the total angular momentum operator is (2.5) let the spinor components ψj have azimuthal dependence eiνjϕ; the jz eigenstate equations for ψ1,ψ2 read (2.6) this will be an eigenstate of jz if ν1+1/2=ν2-1/2, ν2-ν1=1, with eigenvalue (ν1+1/2)ℏ. similarly for ψ3,ψ4 we shall have an eigenstate of jz if ν3+1/2=ν4-1/2, ν4-ν3=1, with eigenvalue (ν3+1/2)ℏ. hence the choice ν1,3=0, ν2,4=1 makes ψ an eigenstate of jz with eigenvalue ℏ/2. (the choice ν1,3=-1, ν2,4=0 makes ψ an eigenstate of jz with eigenvalue -ℏ/2.) it is necessary to have integer νj, since the spinor components are in real space-time (not in some abstract spin space) so we must have ψj(ϕ+2π)=ψj(ϕ). the eigenvalues of jz are thus ±ℏ/2,±3ℏ/2 etc. with spinor components ψ1,3=f1,3(ρ,z,t),ψ2,4=eiϕf2,4 (ρ,z,t), the azimuthal dependence cancels out, and the equations (2.4) read (∂ct+ik)f1+(∂ρ+ρ-1)f4+∂zf3=0 (2.7a) 9the spinning electron (∂ct+ik)f2+ ∂ρf3-∂zf4=0 (2.7b) (∂ct-ik)f3+(∂ρ+ρ-1)f2+∂zf1=0 (2.7c) (∂ct-ik)f4+ ∂ρf1-∂zf2=0 (2.7d) the combination (∂ct-ik)(2.7a)-(∂ρ+ρ-1)(2.7d)-∂z(2.7c) gives (∂2ct+k2-∂2ρ-ρ-1∂ρ-∂2z)f1(ρ,z,t)=0 (2.8) likewise (∂ct-ik)(2.7b)-∂ρ(2.7c)+∂z(2.7d) gives us (∂2ct+k2-∂2ρ-ρ-1∂ρ+ρ-2-∂2z)f2(ρ,z,t)=0 (2.9) the equations (2.8) and (2.9) are solved respectively by ei(qz-ωt)j0(kρ), ei(qz-ωt)j1(kρ), k2+q2+k2=(ω/c)2 (2.10) the function f3 satisfies the same equation as f1, and f4 satisfies the same equation as f2. the transverse and longitudinal wavenumbers k and q are real, and ω≥ck, or ℏω≥mc2. the wavenumbers k≥0 and q≥0 are related to k=mc/ℏ and ω by k2+q2+k2=(ω/c)2; the maximum value of both k and q is q= . hence the general form of the spinor eigenstate of jz with eigenvalue ℏ/2 is 0 ψ1,3(ρ,z,t)= dω dk a1,3(ω,k)ei(qz-ωt)j0(kρ) (2.11) ψ2,4(ρ,ϕ,z,t)=eiϕ dω dk a2,4(ω,k)ei(qz-ωt)j1(kρ) (2.12) these are analogues of the acoustic and electromagnetic wavepackets, for which simple closed forms exist ([8], section 2.6). the author has not found amplitudes aj(ω,k) which lead to closed forms for the relativistic spinor components. bessel beam wavefunctions (not localized enough transversely to have finite energy per unit length) have been studied by bliokh et al. [9]. 3. non-relativistic spinors lévy-leblond [6] has shown that four coupled nonrelativistic wave equations, equivalent to the schrödinger equation, are spinors representing spin 1/2 particles, with g-factor 2 (see also greiner [10]). we shall again construct a general eigenstate of jz with eigenvalue ℏ/2: it is a four-component spinor. it is based on localized wavepacket solutions of the time-dependent schrödinger equation, with no restriction on the wavepacket parameters. in section 4 we shall explore some properties of exact gaussian solutions of the equations satisfied by the spinor components. let ψ(r,t) be the four-component spinor, ψ= , with ψ,χ each having two components. the lévy-leblond non-relativistic coupled spinor equations are, with e=iℏ∂t, p=-iℏ∇, eψ+σ∙pχ=0, σ∙pψ+2mχ=0 (3.1) σ are, as before, the pauli spin matrices defined in (2.2). note that the ψ,χ in (3.1) have dimension differing by a speed; we could make them the same by inserting factors e2/ℏ or c in front of χ, but choose not to do so, in order keep the lévy-leblond formulation. note also that the lower spinor component χ can be eliminated, giving the pauli-schrödinger equation eψ= (σ∙p)2ψ, with hamiltonian h= (σ∙p)2. for comparison, the dirac equations (2.1), with ψu= , ψv= , may be written in the form (e-mc2)ψu=cσ∙pψv, cσ∙pψu=(e+mc2)ψv (3.2) the non-relativistic limit is obtained from (3.2) by setting ψj(r,t)=e-imc 2t/ℏ)fj(r,t). then eψj=iℏ∂t ψj=e (mc2+iℏ∂t)fj, and the equations (3.2) have the dominant terms efu=cσ∙pfv, cσ∙pfu=2mc2fv (3.3) these are the same as (3.1) if we identify fu with ψ, and cfu with -χ. returning to solutions of the lévy-leblond equations (3.10), we write ψ= , χ= , and consider wavepacket motion, predominantly along the direction, but of course converging onto or diverging from the focal region, which we shall centre at the space-time origin. again in cylindrical polar coordinates ρ,ϕ, and with use of (2.3), the four time-dependent free-space equations (3.1) for the spinor ψ read -∂tψ1+e-iϕ(∂ρ-iρ-1∂ϕ)ψ4+∂zψ3=0 (3.4a) -∂tψ2+eiϕ(∂ρ-iρ-1∂ϕ)ψ3+∂zψ4=0 (3.4b) ψ3+e-iϕ(∂ρ-iρ-1∂ϕ)ψ2+∂zψ1=0 (3.4c) ψ4+eiϕ(∂ρ-iρ-1∂ϕ)ψ1+∂zψ2=0 (3.4d) when the spinor components ψj are independent of ϕ, solutions exist only for the ψj also independent of ρ. these are the plane wave solutions ψj=ajei(qz-ωt), where the wavenumber k and the energy ℏω are constrained by 10 john lekner ℏω=ℏ2q2/2m. to attain localized wavepacket solutions, we need to consider azimuthal dependence. the angular momentum operator l=r×p does not commute with the free-particle hamiltonian h= (σ∙p)2, but the combination j=l+ σ, σ= does, as may be verified from the commutators σ×σ=2iσ, [l,σ∙p]=iℏσ×p, [σ,σ∙p]=-2iσ×p. j satisfies the angular momentum commutation relations j×j=iℏj. the z component of the total angular momentum operator is again jz=lz+ =-iℏ diag(1,1,1,1)∂ϕ+ diag(1,-1,1,-1) (3.5) we shall now construct the non-relativistic spinor eigenstates of jz. let the spinor components ψj have azimuthal dependence eiνjϕ; the jz eigenstate equations for ψ1,ψ2 are the same as in (2.6): (3.6) the equations (3.5) and (3.6) have the same form as in the relativistic case, equations (2.5) and (2.6). hence as before the choice ν1,3=0, ν2,4=1 makes ψ an eigenstate of jz with eigenvalue ℏ/2 and the choice ν1,3=-1, ν2,4=0 makes ψ an eigenstate of jz with eigenvalue -ℏ/2. with spinor components ψ1,3=f1,3(ρ,z,t), ψ2,4=eiϕf2,4(ρ,z,t), the equations (3.4) read -∂tf1+(∂ρ+ρ-1)f4+∂zf3=0 (3.7a) -∂tf2+∂ρf3-∂zf4=0 (3.7b) f3+(∂ρ+ρ-1)f2+∂zf1=0 (3.7c) f4+∂ρf1-∂zf2=0 (3.7d) the last two equations give f3,4 in terms of derivatives of f1,2, which in turn satisf y the free-space schrödinger equation for azimuthal orbital quantum number 0 and 1: (iℏ∂t+ [∂2ρ+ρ-1∂ρ+∂2z])f1(ρ,z,t)=0 (3.8) (iℏ∂t+ [∂2ρ+ρ-1∂ρ-ρ-2+∂2z])f2(ρ,z,t)=0 (3.9) equations(3.8) and (3.9) are satisfied by jn(κρ)einϕeiqz e-iℏk2t/2m, with n=0,1 respectively, and κ2+q2=k2; jn are the regular bessel functions of order n. hence spinor components of forward-propagating wavepackets have the form einϕ dk e-iℏk2t/2m dq fn(k,q)eiqzjn(κρ) (κ2+q2=k2) (3.10) the amplitudes fn(k,q) are complex functions, subject only to the existence of the norm and of the expectation values of energy and momentum of the wave packet. a similar expression gives the wavefunctions of scalar and of electromagnetic pulses [8]. to sum up this section: a general non-relativistic eigenstate of jz with eigenvalue ℏ/2 has been found: it is a four-component spinor, of which two components have ‘twist’, with eiϕ azimuthal dependence. in this formulation the spin resides in the azimuthal dependence of two of the wavefunctions, in real space-time. any spinor based on localized wavepacket solutions of the time-dependent schrödinger equation, constructed as above, will be an eigenstate of jz with eigenvalue ℏ/2. the next section gives an explicit example. stationary states (energy eigenstates) of the hydrogen atom are briefly discussed in appendix a. 4. spinning gaussian wavepackets a free-particle wavepacket solution of schrödinger’s time-dependent equation dates back to the early days of quantum mechanics (kennard [11], darwin [12]). this is the gaussian wavepacket. it is a compact exact solution, but with a physical flaw, to be discussed below. for propagation along the axis, and with cylindrical symmetry, it has the form g(ρ,z,t)=b3/2[b+ivt]-3/2exp{iq(z)} (4.1) the gaussian wavepacket (4.1) is normalized so that g*g=1 at the space-time origin. in (4.1) the spatial origin ρ=0, z=0 is the position of maximal |g| a time t=0, q is the dominant z component wavenumber, m is the mass of the particle, u=ℏq/m is the group speed, and v=ℏ ⁄2mb is the spreading speed. the length b gives the spread of the wavepacket at t=0. earlier and later the longitudinal and lateral spread of the packet is greater, proportional to [b2+(vt)2]1/2. thus ρ=0, z=0 can be thought of as the centre of the focal region of the wavepacket, occupied at t=0. as t increases towards zero the wavepacket converges to its most compact form, reaches it at t=0, and then expands as it continues to propagate in the positive z direction. the packet used by ohanian [1] is equivalent to (4.1) evaluated at q=0 (zero momentum expectation value) and t=0. for the gaussian wavepacket g the momentum operator has the expectation values (see for example [13]) 11the spinning electron ‹pz›=-iℏ‹∂z›=ℏq, ‹px›=0=‹py›, ‹p2›= =‹-ℏ2∇2›=ℏ2 (4.2) the wavepacket g is neither an energy nor a momentum eigenstate, but it is an eigenstate of the orbital angular momentum operator lz=xpy-ypx=-iℏ(x∂y-y∂x)= -iℏ∂ϕ. the orbital angular momentum eigenvalue is zero, because g is independent of the azimuthal angle ϕ. eigenstates of the z component of orbital angular momentum, with eigenvalues which are integer multiples of ℏ, may be generated from any such g by differentiation, as shown in [13]. the probability density of the scalar wavepacket is g*g: the probability that the particle described by g(r,t) is within the volume element d3r is d3r g*g. the norm n=∫d3r g*g (integration over all of space) is independent of time. the probability density flux, or the probability current density vector s, satisfies the conservation law ∇.s+∂t(g*g)=0, s(r,t)= im(g*∇g) (4.3) what are the corresponding relations for spinors? the conservation law is now (lévy-leblond [6], section iiie, and appendix b) ∇.s+∂t(ψ+ψ)=0 (4.4) s(r,t)=-ψ+σχ-χ+σψ= im(ψ+ ∇ψ)+ ∇×(ψ+σψ) (4.5) the first term in the second expression for s corresponds to the schrödinger current in (4.3), the second is a spin current. ohanian [1] derived the relativistic analogue of last term in (4.5). he showed that it leads, in the nonrelativistic limit, to an azimuthal current. in his words, “such a circulating flow of energy will give rise to an angular momentum. this angular momentum is the spin of the electron.” we shall calculate the radial, azimuthal, and longitudinal components of the probability current density, sρ,sϕ,sz in the simplest case, in which the spinor components are ψ1=f1(ρ,z,t), ψ2=0, ψ3~∂zψ1, ψ4~eiϕ∂ρψ1. from appendix b, the components of the probability current density are given by sρ=im{ f*1∂ρf1}, sϕ=∂ρ|f1|2, sz=im{ f*1∂zf1} (4.6) with f1(ρ,z,t)=g(ρ,z,t) the probability density and current components are given by g*g=b3[b2+(vt)2] exp (4.7) sρ= g*g, sϕ= g*g, sz= g*g (4.8) the components sρ,sz are the same for the scalar wavepacket, the azimuthal component sϕ is zero in the scalar case based on g. the conservation law (4.4) is satisfied. a problem with the gaussian solution is apparent in sz: for positive z and negative t (or vice versa) the longitudinal component is negative if the magnitude of vtz exceeds that of 2qb3. the probability current then flows backward. far from the focal region (here centred on the space-time origin) there should be no backward flow for free-space propagation. note that the gaussian wavepacket cannot be put in the purely forward-propagating form (3.10). nevertheless, the gaussian packets demonstrate the azimuthal current component which arises in the spinor formulation. figures 1 and 2 show the current components in the focal plane, and at a transverse plane cutting through the wavepacket center at a later time. the azimuthal part gives the electron wavepacket its spin. figure 1. focal plane section through a gaussian spinor wavepacket, at t=0. the contours give the probability density, the arrows the transverse current density (the longitudinal current is not shown). the direction of motion is out of the page. the transverse current density is purely azimuthal at this instant. 12 john lekner 5. summary the spinning electron may be described by a fourcomponent spinor, depending on space and time coordinates, in both relativistic and non-relativistic quantum theory. the non-relativistic quantum theory and its azimuthal dependence is similar to the relativistic dirac spinor formulation of section 2. in both cases the spin is contained in the azimuthal dependence of wavefunctions in ordinary space-time. gould [14] used the hamiltonian h= (σ.p)2 to show that the magnetic moment follows (correct to lowest order), just as in the lévyleblond spinor formulation. there is thus an alternative formulation to the usual ‘spin degree of freedom’, and the total wavefunction being a product of space and spin parts, as is done in nonrelativistic quantum theory. nevertheless, the non-relativistic decoupling of space and spin is usually simpler, as is illustrated by the spinor version of the hydrogen atom, appendix a. acknowledgment constructive comments of t he referees have improved the paper, and are much appreciated. references [1] ohanian h c “what is spin?”, am. j. phys. 54, 500505 (1986). [2] belinfante f j “on the spin angular momentum of mesons”, physica 6, 887-898 (1939). [3] dirac p a m “the quantum theory of the electron”, proc. roy. soc. a 117, 610-624 (1928). [4] dirac p a m “the quantum theory of the electron. part ii”, proc. roy. soc. a 118, 351-361 (1928). [5] griffiths d j, introduction to quantum mechanics, 2ed (prentice hall, new jersey, 2005), section 4.4. [6] lévy-leblond j-m “nonrelativistic particles and wave equations”, commun. math. phys. 6, 286-311 (1967). [7] galindo a and del rio c s “intrinsic magnetic moment as a nonrelativistic phenomenon”, am. j. phys. 29, 582-584 (1961). [8] lekner j, theory of electromagnetic pulses (institute of physics publishing 2018), section 2.6. [9] bliokh k y, dennis m r and nori f “relativistic electron vortex beams: angular momentum and spin-orbit interaction”, phys. rev. lett. 107, 174802 (2011). [10] greiner w, quantum mechanics, 3ed (springer, berlin, 1994), chapter 13. [11] kennard e h “zur quantenmechanik einfacher bewegungstypen”, z. physik 44, 326-352 (1927). [12] darwin c g “free motion in wave mechanics”, proc. roy. soc. lond. a117, 258-293 (1927). [13] lekner j “rotating wavepackets”, eur. j. phys. 29, 1121-1125 (2008). [14] gould r j “the intrinsic magnetic moment of elementary particles”, am. j. phys. 64, 597-601 (1996). [15] lévy-leblond j-m “the total probability current and the quantum period”, am. j. phys. 55, 146-149 (1987). [16] mita k “virtual probability current associated with the spin”, am. j. phys. 68, 259-264 (2000). [17] landau l d and lifshitz e m, quantum mechanics, 2ed. (pergamon, oxford, 1985). figure 2. gaussian spinor wavepacket, at z=ut=2b. the transverse current density now has radial and azimuthal components. the group speed is u, so the section is through the centre of the wavepacket. the longitudinal current density is not shown. 13the spinning electron appendix a. the hydrogen atom in spinor form the equations (3.1) become, with e now an energy eigenvalue, no longer a time derivative, (e+ )ψ+σ∙pχ=0, σ∙pψ+2mχ=0 (a.1) ψ=eψ or [ ∇2-e ]ψ=eψ (a.2) considering the non-degenerate ground state, with jz eigenvalue , ψ1 and ψ2 must satisfy the same equation. this is not possible if we choose ψ2 to have azimuthal dependence eiϕ, as in section 3, unless we also take ψ2 to be zero. the ground state spinor now consists of ψ1, the hydrogenic ground state 1s, and ψ2=0, ψ3~∂zψ1, ψ4~eiϕ∂ρψ1. because the lévy-leblond probability density is defined in terms of the first two spinor components ψ1,ψ2, and the probability density current can be expressed in terms of ψ1,ψ2, the hydrogenic ground state is, at least in the probability density and the probability density current, equivalent to the scalar ground state. the azimuthal dependence is hidden in the fourth spinor component. for the first excited states we have a choice of 2s and 2p. the former is set up as above, the latter with ψ1=0, and ψ2 with e±iϕ dependence. lévy-leblond [15] and mita [16] discuss the electron probability current of the ‘stationary’ states. appendix b. probability density and flux in the dirac case (section 2), ψ+ψ is the probability density, and s=cψ+αψ, with α is defined in (2.2). in the nonrelativistic formulation of lév y-leblond we have a time derivative of ψ but not of χ: iℏ∂tψ+σ∙pχ=0, σ∙pψ+2mχ=0, or ∂tψ-σ∙∇χ=0,-iℏσ∙∇ψ+2mχ=0. to keep the norm time-independent lévy-leblond defines the probability density in terms of ψ only, as ψ+ψ. the conservation law is now (lévy-leblond [6], section iiie) ∇.s+∂t(ψ+ψ)=0 (b.1) ∂t(ψ+ψ)=ψ+(σ∙∇χ)+(∇χ+∙σ)ψ=∇∙(ψ+σχ+χ+σψ) (b.2) hence s(r,t)=-(ψ+σχ+χ+σψ). we may express this current purely in terms of the top two spinor components ψ, since χ= σ∙∇ψ. this gives s(r,t)= {ψ+σ(σ∙∇ψ)-(σ∙∇ψ)+σψ} (b.3) on using the commutation relations of the pauli matrices, σ×σ=2iσ, the probability density current becomes s(r,t)= [ψ+∇ψ-(∇ψ+)ψ]+ ∇×(ψ+σψ) (b.4) the first term in this expression for s corresponds to the schrödinger current in (3.3), the second is a spin current, which gives the correct g factor at leading order [6]. the spin term is the curl of a vector, and so does not contribute to the conservation law (b.1). see also landau and lifshitz [17] section 114, and mita [16] for the spin current term. we shall calculate the radial, azimuthal, and longitudinal components of the probability current density, sρ,sϕ,sz. the corresponding spin matrix components are σρ=σ. = , σϕ=σ. = , σz= (b.5) let f1,f2 be solutions of (3.8) and (3.9), respectively, and ψ1=f1, ψ2=eiϕf2. we can set f2=a∂ρf1 [12]; a is a length parameter. we shall first calculate ψ+σψ; this has the cylindrical components (2are{ f *1∂ρf1}, 2aim{(∂ρf *1)f1}, | f1|2-a2|∂ρf1|2). note that there is no ϕ dependence. the curl of this vector is ∇×(ψ+σψ)=(-2a∂zim{(∂ρf*1)f1}, 2a∂zre{ f*1∂ρf1}-∂ρ[|f1|2-a2|∂ρf1|2], 2a∂ρim{(∂ρf*1)f1}+2aρ-1im{(∂ρf*1)f1}) (b.6) when the length a is zero, just the azimuthal component remains, ∇×(ψ+σψ)a=0=(0,-∂ρ| f1|2,0). in that special case the schrödinger current is proportional to im{ f *1∇f1}=im{ f *1(∂ρf1,0,∂zf1)}, and the components of the probability current density are given by sρ=im{ f*1∂ρf1}, sϕ=∂ρ|f1|2, sz=im{ f*1∂zf1} (b.7) as in the hydrogen ground state, the a=0 spinor now consists of ψ1, and ψ2=0, ψ3~∂zψ1, ψ4~eiϕ∂ρψ1. the fourth component contributes to the azimuthal current, and to the angular momentum. substantia. an international journal of the history of chemistry 5(1) suppl.: 59-75, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1278 citation: s. dominici (2021) a man with a master plan: steno’s observations on earth’s history. substantia 5(1) suppl.: 59-75. doi: 10.36253/substantia-1278 copyright: © 2021 s. dominici. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. a man with a master plan: steno’s observations on earth’s history stefano dominici museo di storia naturale, università di firenze, via la pira 4, firenze, italy e-mail: stefano.dominici@unifi.it abstract. we present specific sources, including specimens of the medicean cabinet and geological outcrops in tuscany, probably used by nicolaus steno to build a theory on the origin of organic fossils, crystals and sedimentary strata, in order to construct the history of the earth based on universal geometric principles. phenomena he observed in tuscany and in preceding travels were revealing a sequence of events consistent with the biblical account. we propose that he devised his method to reconstruct a chronology of primordial events to demonstrate the historicity of the biblical creation in contrast to unorthodox thinking. this had been spreading in philosophical circles of northern europe since the 1650s, circles frequented by steno before his arrival in tuscany in 1666. steno knew in advance what places to visit to find fossils, from literature such as michele mercati’s metallotheca. this was a manuscript owned by the florentine carlo dati, whom steno probably heard about while in paris in 1664-1665. in tuscany he soon formed a tight interaction on matters regarding the interpretation of fossils with the local community of learned men. these included giovanni alfonso borelli who was asked by prince leopoldo de’ medici to provide steno with fossils from sicily and malta. steno’s theory and scale-independent, geometrical method of inquiry of geological objects found in tuscany is hinted at in his canis carchariae dissectum caput, a geological essay completed in a few months in 1666. the theory was published in its most complete form in the so-called prodromus of 1669. in both works he demonstrated that fossils in younger strata in the tuscan hills, such as shark teeth and molluscan shells, have an origin analogous to solids which living animals form. in both essays he explicitly related the deposition of strata with marine fossils to the biblical flood, an idea foreshadowed in “chaos,” his oldest known manuscript of 1659, when he was a student in copenhagen. he found no fossils in older sandstones of the apennines and understood those strata to have formed before the creation of life. these discoveries and other observations he made in tuscany were, for steno, the final proof that natural philosophy and biblical revelation disclose in synergy the mysteries of god’s creation. keywords: nicolaus steno, meaning of fossils, natural philosophy, accademia del cimento, biblical chronology, early modern science. 1. introduction the most important and lasting contribution that nicolaus steno (16381686) left to modern science is the 78-page book titled the prodromus to a 60 stefano dominici dissertation on a solid naturally contained within a solid (the prodromus in short).1 the dissertation that the title alluded to never followed, and the prodromus was the last published scientific essay of the intense and brief career of a young researcher bound to influence his generation of natural philosophers.2 most of his precedentsetting works were centered on anatomical research and the study of the animal body, but the prodromus dealt with crystals, fossils and rocks. why turning to a different subject? and why steno accepted the parallelism between the natural history revealed in the rock record and the biblical narrative? since his scientific endeavour ended in coincidence with his conversion to catholicism and the start of a vocation in theology, modern understanding has to deal with history of science and history of religion at the same time. consequently the aim behind the prodromus remains obscure unless readers are familiar with both contexts. according to biographers who emphasized steno’s role in the history of science, such as the late gustav scherz (1895-1971), the standard story is that steno turned to the study of fossils in 1666 when he realized, while casually studying the anatomy of a shark’s head, that fossils called glossopetrae (meaning “tongue stones”) were actually shark’s teeth and not, as generally supposed, sports of nature. a second widely-accepted narrative suggests that denying biblical chronology in the face of hard empirical evidence was “a losing game,”3 so that steno “continued to hesitate about the implications of his finding”4 and in the final chapter of the prodromus “took care to reassure readers that his science did not contradict the bible.”5 this emphasis implies that during those years some empirical evidence, or science in the modern sense, could undermine the credibility of biblical chronology. historians of religion know very well, however, that it was not natural philosophy, but textual criticism itself, which at that time called into question scripture. furthermore, criticism stemmed from disputatious free1 n. stensen, de solido intra solidum naturaliter contento dissertationis prodromus, florence, stella, 1669 (prodromus in following notes). english translation, pp. 621-660, in t. kardel, p. maquet, nicolaus steno, biography and original papers of a 17th century scientist, 1st edition, heidelberg, springer, 2013 (k&m in following notes). 2 a treatise on precious stones, written after the prodromus, was never published, indicating that steno left the scientific community by 1669: f. sobiech, in the revolution in geology from the renaissance to the enlightenment (ed.: g. d. rosenberg), geol. soc. am. mem., 2009, 203, 179-186. 3 a. cutler, the seashell on the mountaintop. dutton, new york, 2003, pp. 5-16, 115-122, 191-192. 4 p. findlen, possessing nature: museums, collecting and scientific culture in early modern italy university of california press, berkeley, 1994, p. 237. 5 r. rappaport, when geologists were historians, cornell university press, ithaca and london, 1997, p. 201. thinkers, such as the french isaac la peyrère (1596-1676) and richard simon (1638-1712), isaac vossius (16161689) and baruch spinoza (1632-1677) in the dutch republic, and francis lodwick (1616-1694) in england, people who had no public followers of their caliber until the second half of the eighteenth century.6 indeed, biblical chronology was understood to be a science with its worthy followers, and seventeenth-century natural philosophers did not doubt that the book of genesis was a reliable historical account of the distant past. this needed interpretation, the reason why a science of biblical chronology was necessary.7 this means that the parallelism drawn by steno in the last chapter of the prodromus between an empirical reconstruction of historical events and the biblical account, from creation to repopulation of the earth after the deluge, was not motived by fear of the authorities of the church to which he had recently converted, as instead suggested by some.8 steno, like any other natural philosopher of his time, took the bible as “obviously and predominantly historical,” an account to be carefully interpreted using all available translations.9 the evidence presented in the present paper reinforces the opinion that steno sincerely wanted to prove that he had found a limited, but relevant and additional means to reconstruct history. steno’s latest scientific production is underlain by a search for true religion and a way to reconcile natural philosophy and biblical revelation, in years when unorthodox thinking triggered debate in northern europe.10 it is suggested that steno actually had planned field work before moving from paris to tuscany. the standard point of view is therefore disputed and it is hypothesised that the young dane knew that in italy he could find evidence for a reconstruction of primordial history based on an unprecedented way to study crystals, fossils and rocks. since his student years, steno’s multifaceted general research plan to uncover the mysteries of god’s creation included aspects of his ongoing 6 r. rappaport in ref. 5, p. 76. criticism towards historicity of the biblical narrative was discussed only privately, and in small circles: see an eloquent example in w. poole, scripture and scolarship in early modern england (eds. a. hessayon, n. keene), ashgate, aldershot, hampshire, 2006, pp. 41-56 7 m. j. s. rudwick, earth’s deep history. chicago university press, chicago, 2014, pp. 9-30. 8 a. cutler in ref. 3, pp. 5-16, 192. 9 quote and emphasis from r. rappaport in ref. 5, p. 72. on the role of the different translations of the bible see e. jorink, “ “horrible and blasphemous”: isaac la peyrère, isaac vossius and the emergence of radical biblical criticism in the dutch republic,” in nature and scripture in the abrahamic religions: up to 1700 (eds. j. m. van der meer, s. mandelbrote), brill, leiden, 2016, pp. 429-450. 10 s. miniati, nicholas steno’s challenge for truth. reconciling science and faith, milan, franco angeli, 2009, 336 p. 61a man with a master plan: steno’s observations on earth’s history studies of anatomy, and other studies aimed at proving the historicity of the biblical account by geometrical means. his contemporaries understood the prodromus as such, looking forward to seeing the full dissertation published. it is questioned whether steno’s interest in the origin of fossils stemmed from a serendipitous discovery that glossopetrae were shark’s teeth (a finding already publicly demonstrated in 1616 by fabio colonna).11 instead of moving top-down from philosophical, metaphysical and theological questions that mattered to steno and his peers, this study reconsiders the timing with which he collected geological data in tuscany, what textual sources on local paleontological sites he most certainly drew from, and his relationships with a network of sources. the amount of data he swiftly collected and the conclusions he drew in the very first months after his arrival in florence imply that he had planned to do geological research, a plan that ultimately related to chronology of biblical events and had of course something to do with debates on the intepretation of scripture occurring in cultural circles that he had frequented before 1666. those circles embodied the spirit of the ‘new philosophy’, as termed by john donne in 1611,12 and at least in part coincided with ‘the republic of letters’, a transnational community that cultivated science based on observation, experiments and mathematics, not on scholastic authority. his work in tuscany, started at the age of 28, came at the climax of a series of readings and experiences traced back to 1659, when he was 21 years-old. these had made him receptive to evidence concerning the nature of fossils and sedimentary rocks and will be reviewed as such. learned men at the medici court were connected with european intellectual circles and would have offered steno plenty of knowledge on geological matters. the italian tradition dealing with re metallica, “metallic things”, or geological data in the modern sense, with studies practiced by italian renaissance and early modern writers, such as andrea cesal11 f. columnus, de glossopetris dissertatio. in fabii columnae lyncei purpura, rome, 1616, pp. 31-39. see m. j. s. rudwick, the meaning of fossils. episodes in the history of paleontology, chicago, university of chicago press, 2nd edition, 1976 [1972], pp. 42-44; a. ottaviani, “la natura senza inventario: aspetti della ricerca naturalistica del linceo fabio colonna”, physis, 1997, 34, pp. 31-70. 12 “and new philosophy calls all in doubt,/the element of fire is quite put out,/the sun is lost, and th’ earth, and no man’s wit/can well direct him where to look for it:” j. donne, conclusion from an anatomy of the world, cited in d. wootton, the invention of science: a new history of the scientific revolution, new york, harper perennial, 2015. donne writes about a ‘new philosophy’ a year after the publication of galileo galilei’s sidereus nuncius, and is thus identified by wotton as the first accountable testimony to the birth of modern science. pino (1524-1603), michele mercati (1541-1593), ferrante imperato (1550-1631) and fabio colonna (1567-1640) was famed enough to attract steno to visit cabinets of natural history and rock outcrops from which geological specimens came. the geological data he referred to have remained somewhat obscure, because none of the essays he published in italy, with few exceptions, contain clear information on location and description of specific places he visited and specimens he studied. this situation has influenced the perception of the prodromus as an abstract work that assembled an “odd array of material,”13 an opinion that the present paper will attempt to dispel. 2. a man with a plan steno’s philosophical and religious background must be recalled in order to understand the reason he searched for confirmation of scripture in nature. empiricism underlay bot h his natura l philosophy and his theolog y14 and transcended what is recognized today as a separation of physics from metaphysics. within the physical world, steno dealt jointly with ‘geological ’, chemical and anatomical obser vations. this he did in the light of the scripture since at least 1659, when he recorded in his journal, entitled “chaos”, lessons which he derived from the writing of others.15 this collection of extracts, an aid for the memory when he was a student and a sort of commonplace book,16 is steno’s oldest known manuscript. it starts with words and concepts directly referred to the christian faith and the writings of moses, the purported author of the book of genesis: in the name of jesus chaos not out of aristotle’s [elements] 13 r. rappaport in ref. 5, pp. 99-101; but see m. j. s. rudwick, the meaning of fossils. episodes in the history of paleontology, chicago, university of chicago press, 2nd edition, 1976 [1972], pp. 58-60; d. garber, steno and the philosophers (eds.: r. andrault, m. lærke), brill, leiden, 2018, (a&l in following notes), pp. 201-232. 14 f. sobiech, ethos, bioethics, and sexual ethics in work and reception of the anatomist niels stensen (1638-1686), springer, 2016, pp. 30-35. 15 a. ziggelaar in n. stensen, acta hist. sci. nat. med. (ed.: a. ziggelaar), 1997 [1659] (chaos in following notes), 44, 453 pp.; g. d. rosenberg, geol., 2006, 34, pp. 793-796; s. olden-jørgensen, in ref. 2 (rosenberg), pp. 149-157. 16 the practice of writing commonplace books, a form of text collections, emerged particularly during the late renaissance and remained in use among literate people during the early modern age: e. havens, commonplace books: a history of manuscripts and printed books from antiquity to the twentieth century. university press of new england, 2002, 99 pp. 62 stefano dominici that man is composed of the four elements is against holy scripture, where moses only mentions water and earth. for aristotle’s air nowhere appears and fire is an accident. […] bodies are only resolved into water and earth.17 the first two lines can be regarded as a synthesis of the first part of the creation seen form a christian perspective: “in the beginning was the word […] and the word was god” (meaning jesus), says the prologue according to the evangelist john. in this sense, ‘in the name of jesus’ right before ‘chaos’ becomes god’s word commanding order to raise from non-order. this last concept is confirmed in a later remark in steno’s elementorum myologiae specimen of 1667: “in holy scripture it is said that the world has come forth from ‘unseen’ matter as from chaos.”18 the other part of the opening regards the third day of the biblical creation, when god separated dry land from water. steno quoted the passage from the surgeon cornelius schylander’s practica chirurgiae brevis et facilis (1575),19 where the authority of aristotle on the number of elements is submitted to the authority of the bible: the basic elements all bodies are made of are water and earth (air and fire being secondary). furthermore, taking the point of view of a student writing not for publication, steno’s private collection of excerpts seems also to start with an auspice that his knowledge be ordered, from the chaotic form of the commonplace book into that of a mature anatomist.20 several times steno, while excerpting the books he was reading, fell into despair and doubted his ability to bring order to the many subjects he approached.21 he subtly declared an attempt to reach a unitary comprehension of nature and in the same page he confirmed that ‘the profane is not to be excluded from the sacred’ (a quote taken from jeremias drexel’s ioseph aegypti prorex descriptus of 1641).22 most of the above, written in 1659, are about medical matters, but water, earth and scripture are for the first time related with fossils in some revealing quotes taken from pierre borel’s historiarum et observationum 17 n. stensen, chaos, in ref. 15, p. 21. 18 n. stensen, elementorum myologiae specimen, seu musculi descriptio geometrica, in ref. 1 (k&m), p. 435; j. smith, in ref. 13 (a&l), pp. 177200. 19 a. ziggelaar, in ref. 15, p. 103. 20 francis bacon praised the activity of text collecting in his the advancement of learning: “there scarcely can be a thing more useful, even to ancient, and popular sciences, than a solid, and good aid to memory; that is, a substantial and learned digest of common places. […] i hold that the diligence and pains in collecting commonplaces, is of great use and certainty in studying”: quoted in e. havens, the yale university library gazette, 76, 2002, pp. 136-153. 21 f. sobiech, in ref. 14, pp. 59-61. 22 n. stensen, chaos, in ref. 15, p. 22; smith, in ref. 2, p. 197. medico-physicarum (1656). in a passage steno focused on analogies between the human body and the earth that allowed him to realize that marine fossils were evidence of an “ancient deluge”. singular stones of the bladder, shells turned into stones. therefore stones in places that lie very far from the sea, it is certain that seas change their beds. in the right kidney a grey stone was observed, in the left kidney clay. […] snails, shells, oysters, fish etc. found petrified on places far remote from the sea. either they have remained there after an ancient deluge or because the bed of the seas has slowly changed. on the change of the surface of the earth i plan a book.23 the last sentence, although taken from borel, may well allude also to steno’s program, at least denoting what he considered worthy of serious consideration when he was 21. the original borel’s text reports that: near the town of montpellier i found large petrified oysters, mussels and even fossil fishes […] all these things show that in ancient times the flood for long covered this place (as discovered also elsewhere, very far from the sea), that is to say that the sea has changed position, (which i will prove in my book ‘on the changed position of the globe’, and at other places i saw dragon’s teeth), so the sea receded from innumerable places.24 the importance of quotes taken from this contemporary french cartesian philosopher is underlined by side notes made by steno in the 1659 manuscript.25 the above passage also indicates the region around montpellier as one where marine fossils occur, suggesting why steno sojourned in that town of southern france in winter 1665-1666, before continuing his trip to tuscany. as a young student, steno approved the method of inquiry laid out by rené descartes in the discourse de le méthode (1637) and les principes de la philosophie (1644), without sharing the cartesian preference to separate natural philosophy from theology.26 in the words of historian of science justin e.h. smith, young steno appears “speculative, somewhat mystically inclined, 23 n. stensen, chaos, in ref. 15, pp. 46, 58-59. the original borel’s text relates the presence of marine fossils with the biblical flood, with writing a book on the argument. 24 p. borel, historiarum et observationum medico-physicarum, billaine, paris, 1656, p. 261. the italics are in the original text and refer to the title of the book that borel had planned to write. 25 a. ziggelaar, in ref. 2 (rosenberg), pp. 135-142. j. bek-thomson, ref. 2 (rosenberg), p. 289. 26 e. jorink, reading the book of nature in the dutch golden age, 1575– 1715, brill, leiden, 2010, p. 16. see also olden-jørgensen in ref. 2 (rosenberg), pp. 149-157. on the role of borch in directing steno’s education, see a. ziggelaar, in ref. 2 (rosenberg), pp. 135-142. 63a man with a master plan: steno’s observations on earth’s history and at the same time keen on absorbing the latest lessons from empirical natural philosophy, including those of bacon, descartes, and others, even when these come from thinkers who do not share the same mystical and theological concerns.”27 when in 1661 he went to study medicine in the low countries, he connected with the circle of dutch savants and curieux, first in the hotbed of radical thinkers that was amsterdam, then in nearby leiden. there he had relations “far from marginal” with the unorthodox philosopher baruch spinoza28 and the innovative physician johannes swammerdam.29 swammerdam and steno were fellow students and close friends in leiden from 1661-1663 and then in paris in 1664, the two sharing a motivation to search for a bridge between natural philosophy and true religion. swammerdam maintained that skilful dissections of animals, even insects, disclosed to the anatomist the immense wisdom that god had instilled in the minutest parts of creation. the two came to believe that ‘studying the intricate fabric of anatomical structures was a tribute to god, the omniscient architect’.30 they lived in a critical place at the critical time for the future of religion when, following the interventions of descartes and spinoza, ‘the relation between belief and natural science became problematic’.31 the philosophy underlying steno’s and swammerdam’s research consciously moved away from the deus sive natura principle of spinoza, a motto that denoted the identity between the infinite substance of god and the finiteness of nature. the two chose instead a religion grounded on ‘the argument from design’, the idea that god is not identical to nature, but is the great architect, whose brilliance can be deduced from the ‘great fabric of the world’.32 historiographers still discuss if, in his early twenties, steno was a genuine lutheran33 or a deist, however “sui generis”,34 yet opinions converge in depicting those years as a period during which he gradually lost faith in cartesian dogmatism and a mechanistic perspective, instead becoming more meditative and inquisitive in religious matters. in autumn 1664 he joined swammerdam in paris, where, for nearly a year, both were 27 j. e. h. smith, in ref. 13 (a&l), pp. 177-200. 28 quote from p. totaro, “ho certi amici in ollandi”, analecta romana instituti danici, 2002, suppl. 31, pp. 27–38. on the relation between steno and spinoza, see also g. scherz, in ref. 1 (k&m), pp. 91-92, and particularly s. miniati, scienza, filosofia e religione nell’opera di niels steensen (eds. m. a. vitoria, f. j. insa gómez), pagnini, firenze, 2020, pp. 29 e. jorink, in ref. 13 (a&l), p. 16. 30 e. jorink, quoted in ref. 13 (a&l), p. 29. 31 e. jorink, quoted in ref. 13 (a&l), p. 16. 32 e. jorink, quoted in ref. 13 (a&l), p. 18. 33 s. miniati, ref. 10. 34 s. olden-jørgensen, in ref. 2 (rosenberg), pp. 149-157; f. sobiech, ref. 14. hosted by melchisédec thévenot (1620-1692). thévenot had been a diplomat in italy during the 1650s, and was an experimentalist in close contact with the accademia del cimento in florence, himself hosting a sort of academy in his house. there steno met with pierre borel and admired his skills, as he recalled two years later: in paris, in the academy at the house of my great friend thévenot, i have seen borel, greatly skilled in chemistry, pour together two quite clear liquids which immediately became so solid that not even a drop left the glass container when it was inverted.35 thévenot was also a collector of travel accounts from long-distance voyagers and the owner of a cabinet of curiosities.36 among thévenot’s other connections was athanasius kircher, founder in 1651 of ‘museum kircherianum’ in rome. in the early 1660s kircher’s popularity was immense, based on his encyclopaedic interests, vast experience, and even vaster imagination regarding late renaissance visions in natural matters that often conflicted with the new philosophy. savants throughout europe, including prince leopold of medici37 in florence, had been awaiting the publication of his mundus subterraneus in 1664,38 preceded in 1641 by magnes sive de arte magnetica, extensively quoted in steno’s chaos. one of kircher’s disciples on sinology at the roman college was the jesuit missionary martino martini, author in 1658 of ‘history of china’,39 a book that pro35 n. stensen, canis carchariae dissectum caput, florence, stella, 1667 (canis carchariae in following notes). english translation in ref. 1 (k&m), p. 591. 36 n. dew, in bringing the world to early modern europe: travel accounts and their audience (ed.: mancall), brill, leiden, 2007, p. 49. the correspondence between thévenot and future members of the cimento academy dated back to 1643, continued through the years and included letters to prince leopold of medici, in florence, on experimental matters (1660-1666): ref. 38 (mg); w. e. k. middleton, the experimenters: a study of the accademia del cimento, john hopkins press, baltimore, 1971, 415 pp. 37 prince leopold of medici (1617-1675) promoted the publication of galileo galilei works (1655-1666) and the activities of the accademia del cimento (1657-1667): knowles middleton, ref. 36; a. mirto, dizionario biografico degli italiani, 2009, 73, pp. 106-12. as an erudite collector of art and antiquities, in 1662-1668 he had established a productive european network: s. dall’aglio, j. hist. collect. 12/12/2019, pp. 1-12. 38 w. c. parcell, in ref. 2 (rosenberg), p. 64-66; letter by a. kircher (15 august 1965) to prince leopold, in digital archive, museo galileo (mg in following notes), gal. 277, f. 215r: https://www.museogalileo.it/it/ biblioteca-e-istituto-di-ricerca/biblioteca-e-archivi/archivio-storico.html (accessed on 24 may 2020). 39 ‘historia’ of the title retains its traditional significance of ‘collection of facts’, not its reductive modern use as ‘chronology of events’. this is evident from martini’s address to the reader, ‘extrema asia sive sinarum imperii compendio & annorum ordine comprehensam historiam’: m. martini, sinicae historiae, blaeu, amsterdam, 1659, p. 6. for the use of ‘historia’ in steno and his contemporaries, see j. bek-thomsen, in ref. 64 stefano dominici posed a chronology different from the biblical.40 it is reasonable to suppose that steno discussed earth’s history at thévenot’s circle in 1664-1665, in the wake of debates in amsterdam circles of freethinkers, where the idea that human history is older than history told in the old testament had found sustainers41 and the universality of the noachian flood was questioned.42 a new type of anatomical observation, this time on a grand scale, so as to see the body of the earth cut open, would have pushed him to move south where he knew he could observe fossils on the field.43 thévenot formed a bridge with the liberal court of ferdinand ii, grand duke of tuscany, and his brother, prince leopold. at the medici court another international circle had gathered, including the french oriental philologist barthélemy d’herbelot (1625-1695). by moving to florence steno could hope to earn a wage to pursue his research, whether on muscles or on fossils and their context.44 the florentine carlo dati (1619-1696), one of the members of the accademia del cimento and a correspondent with learned men from paris,45 was also a correspondent of thévenot’s. steno had probably heard in advance about the paleontological heritage of tuscany, well known to carlo dati as it will be shown. from tuscany he could move further south, until eventually reaching sicily and malta and there collect other fossils. first in the dutch republic, then in paris, steno was thus in the middle of a fierce polemic on which he could hardly remain neutral, judging from his inquisitivity on religious matters. 2 (rosenberg), pp. 296-297; n. morello, niccolò stenone e la scienza in toscana alla fine del ‘600 (eds.: l. negri, n. morello, p. galluzzi), laurenziana, firenze, 1986, pp. 67-89. 40 martino martini (1614-1661) dominated european knowledge of china in the period 1654-87: n. dew, orientalism in louis xiv’s france, oxford university press, oxford, 2009, 302 p.; e. jorink, d. miert, isaac vossius (1618-1689) between science and scholarship, brill, leiden, 2012, 352 p.; see also r. rappaport, ref. 5. 41 martini’s book influenced the reception of the preadamite theory by isaac la peyrère (1596-1676), particularly in the dutch republic starting from the late 1650s: r. h. popkin, isaac la peyrère (1596-1676): his life, work, and influence, brill, leiden, 1987, pp. 85-87; j. l. morrow, three skeptics and the bible: la peyrère, hobbes, spinoza, and their reception, eugene, pickwick, 2016, pp. 83-84; a. grafton, “isaac vossius, chronologer”, in ref. 40 (e. jorink, d. miert), pp. 43-84. 42 a. ottaviani, giorn. crit. filosof. it., 2017, 13, 272-301. 43 j. bek-thomsen, in ref. 2 (rosenberg). 44 n. dew, ref. 40, pp. 62-76. ‘for many years, a prominent position inside the medici court meant an attractive lifestyle and high wages’: l. boschiero, experiment and natural philosophy in seventeenth-century tuscany. the history of the accademia del cimento, springer, dordrecht, 2007, p. 20. 45 carlo roberto dati, humanist, disciple of galileo and experimentalist, in close contact with jean-baptiste colbert, minister of the finances under louis xiv, was consulted in 1666 for the birth of the académie de sciences. see n. dew, ref. 40, p. 53, and w. e. k. middleton, ref. 36. 3. the nature of tuscany steno arrived in tuscany in april 1666. ferdinand ii and prince leopold recognized him as an outstanding natural philospher, an anatomist whose public dissection of a human brain performed in paris in october, 166546 proved descartes wrong about the manner in which this organ functions.47 by december of the same year, steno had completed the essay canis carchariae dissectum caput which ended with a “digression on bodies resembling parts of animals that are dug from the earth”, a writing where ‘tongue stones” were interpreted as sharks’ teeth.48 this essay was subsequently published in april 1667 as an appendix to his treatise on myology.49 the interpretation of the dissection as the starting point of a research on fossils is probably based on steno’s brief account of his scientific career, written in the opening pages of the prodromus (“to take me away from a detailed account of the muscles, a shark of prodigious size was thrown up by your seas”),50 a rhetorical artifice to emphasize that in his life he had been accustomed to submit to someone else’s will. instead, he could hardly collect all evidences contained in the ‘digression’ between october51 and december, so he had carried out the many observations on fossils and the sedimentary strata in which they were found before the dissection. as for the reason to carry out any field activity, canis carchariae already shows that his interest for marine fossils was related to two events narrated in the scripture, two cornerstones of earth’s history presented in the prodromus. the first event was the separation of solid matter from fluid, on the third day of creation (“and god said, ‘let the waters under the sky be gathered together into one place, and let the dry land appear’”: gen 1, 9), an interest foreshadowed by the opening quote of the chaos manuscript (see above note 17). the second event was the universal deluge (“the flood continued forty days on the earth; and the waters increased, […] and it rose high above the earth”: gen 7, 17), referred to in borel’s quote transcribed in 1659 (see above notes 23-24). both events relate to a universal fluid covering all or most of the globe. canis carchariae reports that different types of fossils were contained in two types of strata, one hardened the other soft, separated by surfaces that deviated from 46 n. stensen, discours sur l’anatomie du cerveau, paris, ninville, 1669. english translation in k&m, pp. 507-527; r. andrault in ref. 13 (a&l), pp. 87-112. 47 a. cutler in ref. 3, p. 53. 48 n. stensen, canis carchariae, in ref. 1 (k&m), pp. 571-595. 49 n. stensen, myologiae specimen, in ref. 1 (k&m), pp. 545-570. 50 n. stensen, canis carchariae, in ref. 1 (k&m), pp. 623-624. 51 a. cutler in ref. 3, p. 53. 65a man with a master plan: steno’s observations on earth’s history horizontality (a geometric character that implies tilting of strata after their deposition and that would become a central argument of the prodromus): the soil from which bodies resembling parts of aquatic animals are dug is in certain places rather hard, like tufa and other kinds of stone; in other places it is rather soft like clay or sand […]. in various places, i have seen that the said soil is composed of layers superimposed on each other at an angle to the horizon. […] in those soils that i have been able to observe up to now, bodies of different kinds have been concealed in the same soil, sometimes in the harder, and sometimes the softer sort. i have observed that the number of these bodies in clay is quite large in the surface but quite small in the soil itself .52 very many oyster shells are found in some regions, deformed and hardened into one lump; sometimes also, broken scallops and mussels are dug up; some people have seen, in the same place, many tongue stones clinging as it were to the same matrix.53 based on the comparison of ‘tongue stones’ with the teeth of the large shark he had dissected, he hypothesised in the essay that they did not grow in the earth, an opinion still held by many.54 steno had surely seen ‘tongue stones’ in copenhagen in the museum of ole worm (1588-1654),55 and learned about them through his teacher thomas bartholin (1616-1680), who had written a book on glossopetrae after travelling to malta in 1644.56 but he had never seen them in earlier travels: i do not yet have the knowledge of this matter [the tongue stones] to pass judgment on it here; and though my travels have taken me through various places of this kind, nevertheless, i do not dare to guarantee that what i shall observe in the rest of my journey will be similar to what i have observed up to now. chiefly, since i have not yet seen what my very famous teacher bartholin observed in his journey to malta.57 ‘several places of this kind’ refers to localities of outcrops where assemblages of marine animal fossils are embedded in compact or hardened rock. following borel’s indication, he had possibly seen strata with 52 n. stensen, canis carchariae, in ref. 1 (k&m), p. 585. 53 n. stensen, canis carchariae, in ref. 1 (k&m), p. 586. 54 n. morello, ref. 39. 55 for the museum wurmianum in copenhagen and its role for steno’s upbringing, see rosenberg, ref. 15 and appendix; for the significance of private museum collections for seventeenth century natural philosophers see rappaport, ref. 5, pp. 53-55. 56 bartholin’s essay on glossopetrae is now lost. scherz, in ref. 1 (k&m), p. 38; a. ziggelaar in ref. 15, pp. 466-469; i. h. porter, med. hist., 7, 1963, pp. 99-125; a. ottaviani, schede umanistiche, riv. sem. arch. um. rin. bol., 2004, 2, pp. 89-110. 57 n. stensen, canis carchariae, in ref. 1 (k&m), p. 585. marine shells around montpellier, where he had met with other savants interested in the study of fossils, such as john ray (1627-1705) and martin lister (1638-1717).58 above all, he must have been informed that tuscany was particularly suited to carry out that type of fieldwork. although ‘tongue stones’ were difficult to find, fossils they were usually associated with were a useful substitute (see comment ‘some people have seen, in the same place [of oysters, scallops and mussels], many tongue stones’ above).59 the most important influence was an unpublished ‘field guide’ by the tuscan michele mercati, a manuscript handed to him in florence.60 in the preceding century, mercati had systematically arranged the pope’s collection of minerals, stones and fossils in 19 large and expensive cabinets to form the vatican museum called metallotheca. the manuscript was owned by carlo dati, who had lent steno two of the engravings made for the metallotheca which the dane used to illustrate the canis carchariae essay,61 as well as the manuscript itself. this told about ‘instructions’ that interested steno, as he himself revealed: mercati’s manuscript [contains] much that is well worth knowing and a wealth of varied instruction about soils, salts, oily fluids, stones, bodies of idiomorphic shapes, and so on; this manuscript would have remained buried in eternal darkness, had not the very learned dati’s skill brought it out of the underworld and provided an opportunity for it to be exposed to the light of day.62 mercati revealed that at his hometown of san miniato (locality 3 in fig. 1), a place famous for marine shell beds as recorded also by leonardo da vinci (14531519),63 large tongue stones were found with oysters (fig. 2). mercati had subdivided tongue stones on the basis of size and shape and pictured them in three beautiful 58 g. scherz, in ref. 1 (k&m), pp. 137-140. 59 the association of fossil shark teeth with seashells was also described in fabio colonna’s de glossopetris dissertatio: ref. 10. m. rudwick, ref. 13, pp. 42-44; n. morello, ref. 39, p. 71. 60 michele mercati (1541-1593) and his teacher andrea cesalpino (1519-1603) were leading figures in late renaissance study of res metallica. cesalpino ordered the medicean collection of natural history and completed mercati’s systematic work in de metallicis (1596). see u. viviani, vita ed opere di andrea cesalpino, viviani, arezzo, 1917, pp. 186-187, 218-219; b. accordi, geologica romana, 1980, 19, pp. 1-50; p. findlen, in ref. 4, pp. 61, 233-235; for the medicean gallery of natural history in pisa, certainly visited by steno already during the first part of his stay, see l. tongiorgi tomasi, giardino dei semplici. l’orto botanico di pisa dal xvi al xx secolo (eds.: f. garbi, l. tongiorgi tomasi, a. tosi), pacini, ospedaletto, 1986, pp. 161-170. 61 j. bek-thomsen, in ref. 2 (a&l), pp. 233-258. 62 n. stensen, canis carchariae, in ref. 1 (k&m), p. 572 63 e. cioppi, s. dominici, in water as microscope of nature. leonardo da vinci’s leicester codex (ed.: p. galluzzi), firenze, giunti, 2018, pp. 171183. 66 stefano dominici drawings that were engraved, together with all other plates, by the german artist anton eisenhoit (15531603). one type belonged to large sharks which we now know as the great white (carcharodon carcharias), as the one dissected by steno. in the words of mercati: i received very beautiful [large tongue stones] from my father, fortuitously found in a field near san miniato. […] ostracites [fossil oysters] are found in fields near the towns of siena and san miniato.64 evidence is thus consistent with an hypothesis that steno studied fossiliferous strata of tuscany early in 1666. consequently, when he had an opportunity to dis64 m. mercati, michaelis mercati samminiatensis metallotheca: opus posthumum, auctoritate & munificentia clementis undecimi pontificis maximi e tenebris in lucem eductum: opera autem & studio joannis mariæ lancisii archiatri pontificii illustratum, roma, salvioni, 1717 [1593], p. 48. sect the head of a shark, his mind was already set. this explains the rapidity with which he published, hastening to secure a priority on the subject. at san miniato he would also observe sandy and clayey strata, some cemented, most simply compacted, crop out in the steep flanks of the hill where the town is built. these strata are slightly inclined towards nne (fig. 3), so this is one of those places, in which he would have seen ‘that the said soil is composed of layers superimposed on each other at an angle to the horizon’ (see note 52 above), meaning they had been tilted after deposition. the study of sedimentary strata allowed steno to prove that water twice covered the tuscan relief, acknowledging that observation of nature and words in scripture work in pair: nor can there be strong opposition to the belief that the said soil was once covered with water. […] [if] we assume that this piece of ground always had the same situation, figure 1. schematic map of tuscany showing localities mentioned in the present paper, in relationship with steno’s prodromus description of strata on which he based his history of the earth. these localities are: 1) monte ceceri, 2) gonfolina, 3) san miniato, 4) volterra, 5) chiana valley. original graphic by the author. 67a man with a master plan: steno’s observations on earth’s history […] we learn from holy scripture that all things, both at the beginning of creation, and at the time of the flood, were covered with water.65 tertullian writes elegantly about this: “a change occurred in the whole world when it was covered with all the waters; even now, sea shells of mussel and whelk range over the mountains seeking to prove to plato that the very peaks have been under water.66 steno’s digression in canis carchariae revolves around the demonstration of the marine origin of fossils (he explains this through “conjectures” numbered 1-4, 6) 65 n. stensen, canis carchariae, in ref. 1 (k&m), p. 587. morello, ref. 39, p. 77. 66 n. stensen, canis carchariae, in ref. 1 (k&m), p. 587. and the precipitation of solids from liquids (conjectures 4-5, indicating ‘the ways in which solid bodies hidden in water may be secreted’). judging from the subsequent development of these two topics in the prodromus, this means that in 1666 not only had steno already studied fossiliferous mudstones and sandstones at the top of the tuscan sedimentary succession (his evidence of ‘the flood’), but also older unfossiliferous strata which he thought formed at ‘the beginning of creation’ (see above, and note 65), when god separated earth from a primordial fluid. 4. the italian network in 1667 steno shared his thoughts on fossils with other learned men around him, not just on marine fossils, but also terrestrial ones. the latter were related to a ‘time of giants’ referrable to scripture, a third biblical event with which to compare the fossil record, as it will be shown. the book of genesis in fact revealed that: the giants were in the earth in those days, and also after that, when god’s sons were being entered toward the daughters of humans and they were begetting to themselves; those were the giants from the eons [greek αἰών] the humans of renown.67 67 genesis 6, 4, from the greek septuagint bible. see r. s. hendel, “of demigods and the deluge: toward an interpretation of genesis 6:1-4”, j. bibl. lit. 106, 1987, pp. 13-26. for an exploration of protestant and catholic attitudes towards the interpretation of this passage, see a. hessayon, ref. 6, pp. 5-40. figure 2. copper engraving by eisenhoit of a large oyster shell (‘ostracites’) dug up from the earth at san miniato (‘oppidi miniati’; locality 3 in fig. 1) and drawn by mercati, published posthumously in 1717, but available to steno in 1666. photograph by saulo bambi, reproduced with permission, courtesy of the botanical library of the florence university. figure 3. slightly inclined fossiliferous strata at san miniato (locality 3 in fig. 1; outcrop about 50 m-thick). rich shell beds associated with large shark teeth have been studied here since the time of leonardo da vinci (1453-1519) to the present day. photograph by the author. 68 stefano dominici in florence steno was sustained by the esteem of newly-acquired learned friends, including renowned disciples of galileo such as vincenzo viviani (1622-1703) and francesco redi (1626-1697).68 the sea of tuscan coast offered plenty of living shelled marine animals to compare with fossils that were dug up in nearby hills. bruno della molara, a member of the court, testified that in the summer of 1667 steno was studying living mussels and discussing his view with others: i am delighted by your progresses in the investigations of interesting matters, particularly of the mussels and i am even more pleased that you have made satisfactory observations which confirm your view.69 among the florentine academians was giovanni alfonso borelli (1608-1679), one of the most gifted disciples of galileo galilei.70 the least friendly among the medici courtiers, he helped steno, providing knowledge and fossils form sicily. steno had contacted him soon after his arrival in tuscany, as a suspicious borelli revealed in july 1667 in a letter to marcello malpighi (of the same galilean circle): i’m giving you the news that steno is here, and that he shall remain the whole summer, and that he told me he wants to come to visit me, and that he wants me to teach him something about geometry etc. i won’t refrain from offering him all the courtesy possible, but i’m not so gullible as to believe in the idea of modesty and good manners in which he is proclaimed, because those little epistles he has printed clearly hint at his avidity to absorb all the things, and put others in distress, and i know these foreigners come here to us well prepared, and willing to remain cautious, so that their cunning by far surpasses ours, with the result that in the end it will be us who will be submitted for long.71 the italian network of learned men interested in steno’s canis carchariae included agostino scilla in sicily,72 collaborating with borelli, malpighi and john 68 p. galluzzi, in ref. 39 (negri, morello, galluzzi), pp. 113-129. 69 for bruno della molara (1639-1685) see a. cont, dimensioni e problemi della ricerca storica, 2011, 2, pp. 231-259. letter (14 july 1667) quoted in ref. 1 (k&m), p. 187. another learned informant was francesco maria florentini (1603-1673): g. scherz, in ref. 1 (k&m), p. 182. 70 l. boschiero, in borelli’s on the movement of animals on the force of percussion (tr.: p. maquet), brill, leiden, 1989, p. i-xxi. p. galluzzi, ref. 68. 71 g. a. borelli, 17 july 1666, in m. malpighi, the correspondance of marcello malpighi (ed.: h. b. adelmann), cornell university press, ithaca-london, 1975, 1, pp. 318-319. borelli was studying animal movement, a subject dealt with by steno at exactly the same time. 72 f. giallombardo, agostino scilla (1629-1700) e la cultura visuale della historia, fra antiquaria e storia naturale, unpublished phd thesis, università di palermo, palermo, 2016, pp. 71-72. ray,73 and the physician giovanni battista capucci from crotone, in calabria.74 the authority of prince leopold, accompanied by the general enthusiastic acceptance of steno by the medici court, forced borelli to submit and provide specimens from sicily. in august he answered the prince: i send you two chunks of stone of the type produced by date shells [rock-boring mussels; …] i’ve commanded to bring you some piece of good stone, which no doubt will give the opportunity to philosophise.75 in two letters of october-december 1667, borelli communicated with prince leopold about the interpretation of marine and terrestrial fossils. these manuscripts not only testified to the whole court being involved in steno’s research, but particularly revealed that larger fossil bones were interpreted as evidence of ‘a time of giants’, as mentioned in the book of genesis: i also thought that those shells could have originated from the sea, but then i changed opinion. i will await for the fine discourses of these gentlemen to ascertain for me the truth. in the meanwhile, i have written to friends in palermo, siracusa and other places to get me the so called giants’ teeth, and those large petrified shells that are found at many places in sicily […] if your highness could send me the drawing of the skull of that african ox found in the chiane [referring to the chiana valley, locality 5 in fig. 1] to know how big it is, i would be grateful. […] i will send to livorno those teeth and shells that i am collecting.76 i have received the drawing of the buffalo skull, or ox found in the chiane, and it is indeed much larger than those that we see nowadays in italy [see fig. 4 for a similar fossil coming from the same context]. if it came from africa i couldn’t say, since i’m told that in that savage place you don’t find oxen of such an enormous size. maybe in that time in italy lived that race of a size larger than our [cattle] given that as among both dogs and horses we find some that by large exceed others, and i can assure your highness that here we find certain limestones and human teeth the size of which must relate to a man at least 2.3 m tall. for you to get the exact proportion, i send with this letter a drawing of one of those teeth. the man who owns them is too jealous of these curiosities and i didn’t dare ask, even if he is a friend. i have moreover collected a large quantity of petrified shells, some of very large size, that i will send, as you commanded me to do, with the first vessel that sails 73 p. findlen, science in the age of baroque (eds. g. gal, r. chen-morris), springer, dordrecht, 2013, p. 135. 74 g. b. capucci, 25 july 1667, in ref. 40, pp. 352-352. 75 g. a. borelli to prince leopold, 3 august 1667, in ref. 38 (mg), gal. 278, f. 42v. 76 g. a. borelli to prince leopold, 4 october 1667, in ref. 38 (mg), gal. 278, f. 73r-73v. 69a man with a master plan: steno’s observations on earth’s history to livorno. when mr. steno will pass from here, i will see him and gladly serve him.77 the finding of fossils of ‘a man at least 2.3 m tall’ and the bones of animals larger than the modern certainly solicited steno’s philosophical interest for links between observation of nature and scripture. in july 1668, borelli informed the prince that the vessel with its naturalistic cargo had shipwrecked and that he provided a new collection of fossils. similarly to the first shipment, it included ‘stones taken from mountains twenty miles far from the sea’78 and other geological specimens. clearly, there was a keen interest for fossils at the medici court in connection with steno’s activities of 1667. specimens from malta are not all wrapped in their stoney casing, but imagine them to be [originally] contained in the same soft stone in which you see the tongue stones, or teeth; these teeth, vertebrae and eyes are dispersed in black stone, some small some large [see fig. 5] such observations, and better ones, will be made over there by those illustrious philosophers, being myself humbly busy with laying down this book of mine on paper, in the hope to complete it in short time.79 we thus know that, at least since summer 1667 and while working at a larger dissertation on solids naturally enclosed in other solids, steno involved a group of 77 g. a. borelli to prince leopold, 1 december 1667, in ref. 38 (mg), gal. 278, f. 95r-95v. 78 g. a. borelli in ref. 38 (mg), gal. 278, f. 95r-95v. 79 g. a. borelli to prince leopold, 8 july 1668, in ref. 38 (mg), gal. 278, 195r-195v. informed people in a fervent activity directed towards definitely proving that fossil shells and ‘tongue stones’ did not form inside the rocks, and thus verified their utility as a means to ‘philosophise’ on historical events. we can also reasonably speculate that ‘philosophising’ included a discussion of matters distinctly related with biblical events: remains of large terrestrial animals of african affinity provided information on a ‘time of giants’, while marine fossils, whether from malta, sicily or tuscany, would mark the time when waters covered the land, ending the existence of ‘those races of a size larger than ours’ – in borelli’s words. 5. earth’s history unrolled in tuscany in may 1668 steno had informed magalotti about his intention to complete a ‘treatise on the earth and the bodies found in it’, described as ‘a succinct, not to say disordered, account of the chief things that i have resolved to set down in the dissertation itself, not only more distinctly, but also at greater length, with in addition, a description of the places where i have observed each item’. the final text was completed in august 166880 after months of additional fieldwork traveling ‘from the arno to the tiber’ (that is, from florence to rome: he apparently never suceeded in moving farther south). the prodromus addressed some of the basic questions of natural philosophy: what is the nature of matter, what is movement, and what is the method to answer 80 g. scherz, in ref. 1 (k&m), p. 209. figure 4. skull of a large ox dug up in val di chiana (width of horns about 105 cm); a similar specimen is mentioned by borelli in letters to prince leopold. photograph by saulo bambi, specimen reproduced courtesy of the museum of natural history, university of florence. figure 5. malta ‘large tongue stones’ (in the terminology used in 1667) from unspecified ‘old museum collection’ (= ‘antica collez. del museo’, written in the 19th century): similar specimens were sent by borelli in 1667. photograph by saulo bambi, specimen reproduced courtesy of the museum of natural history, university of florence. 70 stefano dominici these questions? more importantly, steno took a clear position regarding earth’s history, choosing the universal flood as the fulcrum of the discourse, the occurrence of which he could now clearly demonstrate. as far as the nature of tuscany allowed, steno’s method presented evidence of the other biblical events mentioned above, one concerning the third day of creation, when the aristotelian element earth started to exist separated from water, another concerning the time when giants populated the earth. to these he added in the prodromus a further biblical event, the repopulation of the planet, occurring after the deluge had swept away “all things which have the breath of life, and whatever was on the dry land” (gen 7, 22). this repopulation, starting from a handful of noachian survivors, soon spread all over the world following god’s command (“increase and multiply, and fill the earth and have dominion over it”: gen 9, 1). evidences of this were represented by the ruins of ancient civilizations, from the etruscan in tuscany, studied by steno’s contemporary antiquarians and briefly presented in the prodromus, to the chinese in the far east, then made popular by martini’s chronicles (see above notes 40-41). the first part of the book is methodological, abstract and complex, but worth the effort of reading – implies its author – because it promises to solve a problem of natural philosophy that troubled contemporary authors: ‘namely the way in which marine objects had been left in places far from the sea’, a problem concerning ‘a kind of universal deluge’ (p. 6).81 in the first part of the book (pp. 6-23), steno presented a new category of phenomena, ‘solids naturally contained in other solids’,82 bringing order to observations of different kinds: if one wishes to reduce solids enclosed naturally within solids to definite classes, by the above method, some of them will be found to have been produced by apposition from an external fluid, this refers either to sediments such as the strata of the earth […] or angular bodies […]. other solids are produced through apposition from an internal fluid.’ […] ’ it will be easy, given the solid and its location, to make a definite statement about the place of its production. (p. 23)83 the prodromus then considered specific classes of solids, including ‘strata of the earth’ (pp. 26-28), explaining the historical meaning of the regularly-stacked bodies of turbidite sandstones that form large part of the apennines. these are sedimentary strata characterised 81 numbers in brackets refer to pages in the original 1669 publication, translated in ref. 1 (k&m), pp. 621-660. 82 n. morello, ref. 39, p. 79-80. 83 n. stensen, prodromus, in ref. 1 (k&m), pp. 632-633. by sharp or erosive bases, tabular geometry (fig. 6), good-sorting of the clastic component and sedimentary structures that indicate settling of particles while the water mass was still moving (fig. 7). to steno they were documents of the third day of creation, immediately before the separation of dry land from sea and when a ‘universal fluid’ was all that there was. differences in layers at the same place can be produced either by the diversity of particles leaving the fluid in succession, as this fluid is gradually dissipated more and more, or by dif ferent f luids being conveyed there at dif ferent times: so it happens that sometimes the same arrangement of layers is repeated in the same place, and often evident signs exist showing the ingress of new material. (p. 26) if all particles in a stony stratum are observed to be of the same nature and of fine size, it cannot reasonably be denied that this stratum was produced at the time of creation from a fluid that then covered all things; descartes, too, accounts for the origin of the earth’s strata in this way. (p. 28)84 the signif icance of these primordial strata is enriched by their association with widely-separated ‘high mountains’ (the apennines). this fact proved that on the dawn of the third day of creation a fluid covered all things, as explained at the end of the book: that there was aqueous fluid, however, at a time when animals and plants had not yet appeared, and that the fluid 84 n. stensen, prodromus, in ref. 1 (k&m), pp. 635. steno refers to rené descartes’ principia philosophiae (1644), containing rather a model of the earth, than an account of its history: see m. j. s. rudwick, ref. 7, pp. 55-59. figure 6. inclined, unfossiliferous strata of ‘macigno’ sandstone at the historical monte ceceri quarries (outcrop about 20 m-thick, locality 1 in fig. 1; similar strata occurred at the gonfolina quarries, locality 2 in fig. 1). strata are bounded by surfaces that once were ‘parallel to the horizon’, to use steno’s words (canis carchariae dissectum caput, written in 1666). photograph by the author. 71a man with a master plan: steno’s observations on earth’s history covered everything, is proved conclusively by the strata of the higher mountains which are free from all heterogeneous material; the outline of these strata testifies to the presence of a fluid; their material bears witness to the absence of heterogeneous bodies; the similarity in materials and outlines of strata from different mountains that are widely separated proves indeed that the fluid was universal. (p. 73)85 by ‘heterogeneous material’ he meant the petrified remains of ancient living beings (see below). all three passages stress sorting of the particles that form the sedimentary bed and their origin by settling from a fluid (fig. 7). an explanation of their actual position on ‘higher mountains’ as the key to infer the universality of the primordial fluid, had been anticipated in canis carchariae (without specifying if in relation to the first flood, when solid matter separated from the universal fluid, or the second universal flood, when all breathing 85 n. stensen, prodromus, in ref. 1 (k&m), p. 654. creatures living on land were wiped out) where earthquakes had been called into action: no weight should be attached to the arguments set out by people when they say that bodies of this kind ought to be found everywhere if they owe their existence to the waters covering all places, or at least, that such bodies when found, should not be found only in high places. […] it would be easy, to show how great are the changes in soil caused frequently by earth movement.86 other classes of solids included ‘mountains’ (pp. 32-34) and ‘angular bodies’, or crystals in modern terms. here he informs us that ‘the majority of the minerals with which human effort is engaged did not exist from the beginning of things’ (p. 44). by exclusion, the third day of creation, when solid earth first formed, is still documented in the natural world by some surviv86 n. stensen, canis carchariae, in ref. 1 (k&m), p. 587-588. figure 7. turbidite sandstone of the macigno fm (detail of one of the strata in fig. 6), showing sedimentary structures (monte ceceri quarries, near fiesole; locality 1 in fig. 1; coin for scale: 22 mm). finer-grained particles have settled above coarse-grained ones as a fluid transports them in ripples, in light colour, finally giving way to mud deposition, in dark colour. stratal surfaces are parallel one to another (fig. 6), but all are inclined with respect to the horizontal, meaning they have been titlted after their deposition. photograph by the author. 72 stefano dominici ing mineral. he was possibly thinking of the minutest clasts that make up turbidite sandstones of the appennines – although no evidence of this thought exists, but of course not including the largest and youngest crystals quarried at that time in tuscany. for their size, these formed the object of steno’s long discussion of geometric properties of regular solids, in pages that have attracted the attention of historians of mineralogy and which formed a long digression in the central part of the book (pp. 37-53). also at the core of the book (pp. 53-61) is the discourse on organic fossils. evidence of their marine origin included a comparison between modern animals and fossils he had seen in tuscany, including borelli’s specimens, with fossils embedded in their matrix. steno’s 1666 interest in demonstrating that glossopetrae were shark teeth is not repeated in the prodromus. their heuristic role as proof of the marine origin of the sediments in which they were found, hence proof of the biblical flood, is completely substituted in the prodromus by the much more ubiquitous shelled molluscs. examples abound, while he recalls shark’s teeth only in passing: there are shells of oysters, of remarkable size, in which are found several oblong, worm-eaten cavities [fig. 2] in all respects similar to those that are inhabited by a certain type of shellfish in the rocks of ancona, naples and sicily. […] in lumps of earth brought here from malta, besides various teeth from various sharks, are found also various shellfish, so that if the number of teeth persuades us to ascribe their production to the earth, the construction of the teeth and their abundance in each animal, the similarity of the earth to the sea bed, and the other marine bodies found in the same place favour the opposite opinion.87 then he turns to remains of terrestrial animals and affirms his trust on the biblical account of the same evidence: for others, difficulty arises from the size of the femurs, crania, teeth, and other bones that are dug from the earth; but there is not much either in this objection that unusual size should suggest a method beyond the powers of nature, since: 1. in our age, men of very large stature have been observed. 2. it is certain that there existed at one time men of gigantic size. 3. often the bones of other animals are mistaken for the bones of human beings. 4. to attribute to nature the production of truly fibrous bones is on a par with saying that nature can produce the hand of a man without the remainder of the man. (p. 62) 87 n. stensen, prodromus, in ref. 1 (k&m), pp. 650-651. the statement ‘it is certain that there existed at one time men of gigantic size’ is a reference to borelli’s gigantic ‘human teeth’ and to the ‘time of giants’ narrated in genesis 6, 1-4 – again, steno obviously had the bible in mind – while his familiarity with fossil bones and teeth of terrestrial animals echoes borelli’s inputs on the lack of modern analogues of the bones of the ‘chiana’ gigantic ox (fig. 4) and other large animals. in analogy with marine remains, terrestrial ones (including plants, pp. 65-67) were associated with fluvial conglomerates. these abound in the upper arno valley and other places between florence and arezzo (for example locality 5 in fig. 1) and prompted yet another vision of solid particles moved by a liquid. the place from which the said bones are dug was built up from various strata that are filled with stones rolled down from the surrounding mountains by the force of torrents. (p. 65)88 the series of proofs of the unrolling of events that match the biblical narrative is completed by the geological description of the hill upon which the town of volterra is built (locality 4 in fig. 1). in this section steno merges observation of nature with antiquarianism and historical accounts, trusting the authority of classic authors, as he had done two years before in canis carchariae. most important, this is also the point he introduces absolute time in the narrative, adopting the language of the chronologists that measure the number of years that have elapsed between some key events, albeit in steno this takes the form of rough estimates. it is worth recalling here the obvious, that the science of chronology was essentially biblical, although not only biblical, as exemplified by the prodromus itself. earth’s history was only a few days longer that human history, but a sufficiently long stretch of time to fit all the events that mattered, according to an average 17th century thinker.89 there are those to whom the length of time seems to destroy the force of the remaining arguments, since there are no recollections in any age to confirm that floods have risen to the places where many marine bodies are found today, if the universal deluge is excepted, from which time it is estimated that 4000 years have elapsed up to the present.90 it is certain that before the foundations of the city of rome were laid, the city of volterra was already powerful; but shellfish of every kind are found in the huge stones that are found in certain places there. […] the whole hill on which the oldest of the etruscan cities is built rises from marine 88 n. stensen, prodromus, in ref. 1 (k&m), p. 652. 89 m. rudwick, ref. 7, pp. 9-23; a. grafton, ref. 41. 90 n. stensen, prodromus, in ref. 1 (k&m), pp. 651-652. 73a man with a master plan: steno’s observations on earth’s history sediments, laid on top of other, parallel to the horizon, in which there are many non-stony strata which abound in true molluscs that have suffered no change in any way, and so it is possible to say with certainty that the unchanged molluscs that are extracted from them today were produced more than 3000 years ago. from the founding of the city to the present day we reckon more than 2420 years have elapsed; and who will not grant that many centuries have elapsed since the first men transferred their homes there until it grew to the size that flourished at the time of the founding of the city? if we add to these centuries the time which elapsed between the laying down of the first sediment of the hill of volterra and the withdrawal of the sea from the same hill, when strangers flocked to it, we shall easily go back to the time of the universal deluge. (p. 63-64)91 the final section of the prodromus (pp. 67-76) strictly concerns the fit betwen events inductively demonstratated for tuscany and those narrated in the bible. they are preceded by a sentence that perhaps justified the opinion that steno was aware of consequences from the church: ‘but lest anyone be afraid of the danger of novelty etc.’ on the other hand, judging from the fact that for steno biblical history was history tout court, these closing passages appear a summary of what he had finally proved, proud to announce the coherency of the marvellous plan of god. their content had been forewarned in the introductory chapter: the fourth part describes various conditions of tuscany not dealt with by historians and writers on things of nature, and proposes a kind of universal deluge that is not rejected by the laws of natural movements. (p. 6)92 accompanied by the now-famous schematic drawing of the six periods during which the present tuscan relief took shape,93 the final part of the prodromus is a counterpoint between the voices of the scripture and nature, the former proposing, the latter answering (whenever possible), sometimes both remaining silent. steno’s discussion of his six periods revealed the final purpose of the dissertation and of all his commitment to the study of fossils, crystals and rocks, and retrospectively the climax of a lifetime search for truth: not to found a new science (‘geology’), but to reconcile philosophy and theology, physics and metaphysics: how the present state of anything discloses the past state of the same thing is made abundantly clear by the exam91 n. stensen, prodromus, in ref. 1 (k&m), pp. 651-652. 92 n. stensen, prodromus, in ref. 1 (k&m), p. 625. 93 s. j. gould, hen’s teeth and horse’s toes: further reflections in natural history. new york, norton 1983, 413 pp. ple of tuscany, above all others. […] with regard to the first aspect of the earth, scripture and nature agree in this respect, that everything was covered with water; but of how and when it began, and how long it lasted as such, nature says nothing, while scripture speaks. […] at the time when the strata of unmixed material, obvious in all mountains, were being formed, the rest of the strata did not yet exist, but everything was covered with a fluid devoid of plants, animals, and other solids. since no one can deny that the strata are of the kind that could have been produced immediately by the first mover, we recognize from this the obvious agreement between scripture and nature. (p. 70) about when and how the second aspect of the earth, which was flat and dry, began, nature is likewise silent, while scripture speaks […] when the third aspect of the earth, which is believed to have been uneven, began, neither scripture nor nature determines; nature shows that the unevenness was of some magnitude; scripture, moreover, mentions mountains at the time of the deluge; as to the rest, neither scripture nor nature determine when those mountains, of which scripture makes mention, were produced […] reason persuades us that, in the first centuries of the world’s existence, cavities were gnawn out by water and by fire, so that slighter collapses of strata followed from this. […] the fourth aspect, when all was ocean, seems to cause more difficulty, although in truth it is not difficult. the production of hills from marine deposits testifies that the sea was higher than it is now, and this not only in tuscany but also in very many places far enough from the sea […] if the activity of a living creature can bring it about that sometimes places flooded with waters are made dry by its decision, and sometimes are flooded with new waters, why should we not willingly concede to the first mover of all things the same freedom and the same powers? with regard to the time of the universal deluge, sacred history, reviewing everything in detail, is not opposed by secular history. the ancient cities of tuscany, some of which are built on hills produced by the sea, were founded more than 3000 years ago; in lydia, however, we come nearer to 4000, so that it is possible to reckon from this fact that the time at which the earth was abandoned by the sea is in accordance with the time of which scripture makes mention. […] nature does not contradict what scripture determines about how high the sea was. (p. 72)94 steno was finally asserting in the latin language directed not just to his italian readers, but to the whole european community of learned men, that a universal principle of geometry, perfectly entrenched in the new philosophy, confirmed biblical facts. this would have helped to silence unorthodox thinkers and re-assert the supremacy of a literal reading of the biblical text. if steno’s sensibility had been shaken by criticism towards standard chronology, alive in certain cultural circles, 94 n. stensen, prodromus, in ref. 1 (k&m), pp. 653-655. 74 stefano dominici biblical references in the prodromus were more than a tribute to religion by a catholic convert. they formed instead the conclusion of a philosophical and theological journey in the search for ‘true religion’ that had commenced before travelling to tuscany. his reasoning gave a final sense to a long study to find the meaning of fossils shells and ‘tongue stones’. 6. after the prodromus in the same year of the publication of the prodromus, steno continued to carry out geological fieldwork in the light of his theory, as testified by a letter written in october 1669 after visiting quarries in hungary (present day slovakia), a new occasion to study the rocks produced during the time of the first ‘universal fluid’. my journey to visit the quarries caused me great happiness not just for the novelty of the observations, which were very few, but for the autopsy of those things, that upon reading metallic authors are understood with much difficulty. i have seen nonetheless something consistent with my opinions on the transformations that the earth underwent, inasmuch that in the same places soils of macigno are inclined with respect to the horizon, so that in that place cannot have been materially made.95 the letter proves that the method exposed in the prodromus, nicely expressed with borrowed words from the anatomist (‘the autopsy of those things’), was once again applied with success, this time to strata observed outside of italy. the science inaugurated by steno relied on the observation of nature and on concordance with scripture. the attempt at reconciling inconstistencies occupied learned men96 and missionaries, particularly among the jesuits including in 1667 athanasius kircher.97 debates such as this continued into the eighteenth century, while a steadiliy increasing number of savants across europe presented new theories of the earth, and skepticism towards biblical chronology reached further.98 earth as sketched in the prodromus looked much 95 n. stensen to m. malpighi, 27 october 1669, in ref. 40 (adelman), p. 429-430. ‘metallic authors’ referred to the work of late renaissance learned men like michele mercati. ‘macigno’ refers to a particular type of sandstone quarried near florence. this is devoid of fossils and thence to steno it is the material evidence of the third day of creation. 96 debates among protestants in the dutch republic were fierce, while chronologists contemporary to steno investigated “the nature of ancient and modern, eastern and western calendars and established the dates of great events”: a. grafton, ref. 41, p. 45. 97 r. rappaport, ref. 5, pp. 77-79. a. ziggelaar in ref. 2 (rosenberg), p. 140. 98 r. h. popkin, a. j. vanderjagt, scepticism and irreligion in the seventeenth and eighteenth centuries, brill, leiden, 1993, 373 p. like the model introduced by descartes in his principiae philosophiae of 1644, with its inner cavities justifying the collapse of originally-concentric sedimentary strata at its surface.99 but descartes despised history,100 while steno searched different sources, both textual and natural, the latter based on geometry. few contemporary natural philosophers were equipped with steno’s experience of the natural world, many distintly favouring the study of annals and biblical scholarship, with a penchant for establishing systems often disconnected from empirical evidence. despite not having steno’s experience in the natural world, most still accepted scripture and classic authors as trustworthy sources. among contemporary authors, the sicilian painter agostino scilla (1639-1700; see above note 72) had studied a very large variety of marine fossils and their sedimentary context, as he demonstrated in his la vana speculazione disingannata dal senso of 1670. himself creator of the wonderful engravings that illustrated his book, rivalling those of eisenhoit used by steno, scilla did not cite the dane. however, he surely knew canis carchariae through borelli and malpighi, academicians with whom he was connected in sicily. similarly to steno, scilla interpreted marine fossils as evidence of the biblical deluge, seeking further evidence for his interpretations in the work of classical authors and antiquarians.101 robert hooke (1735-1703)102 authored a rudimentary theory of the earth in 1668 based on steno’s hypothesis of 1667 that most fossils originated in the sea, but dismissing the flood as the cause, invoking in its place the action of earthquakes. the latter he called into action, together with other natural causes, to also explain other biblical episodes, such as the time of giants, while paying close attention to contemporary biblical scolarship.103 in his 1715 theory of the earth, the astronomer edmond halley (1656–1742), of the same baconian circle as hooke, still relied on chronology in genesis, however more critically interpreted.104 steno’s lesson certainly informed the other great contemporary philosopher and pioneer in the study of the earth, the german polymath gottfried wilhelm 99 m. j. s. rudwick, ref. 7, pp. 55-56. 100 r. rappaport, ref. 5, pp. 64-65; m. j. s. rudwick, ref. 7, p. 55. 101 p. findlen, ref. 73, pp. 119-159. 102 british natural philosopher, active in montpellier at the time of steno’s residence there, and one of the founding members of the royal society in london, hooke deciphered the organic origin of fossils as early as 1663, publishing the idea in his micrographia (1665): t. yamada, in ref. 2 (rosenberg), pp. 107–126. 103 w. poole, ref. 4, pp. 43-49; k. birkett, d. oldroyd, the uses of antiquity (ed. s. gaukroger), springer, dordrecht, 1991, pp. 145 – 170. 104 w. poole, ref. 4, pp. 45-46. 75a man with a master plan: steno’s observations on earth’s history leibniz (1646-1716). leibniz had met steno more than once between 1677-1680 and the history of the world, the main theme of the protogaea that the german would complete in 1693, formed the object of their discussion. leibniz, deeply influenced by the dane,105 left the clearest testimony of the primary significance that the full dissertation on solids was meant to have for contemporary philosophers: i have often incited him [steno] further to carry them out [geological studies] and to draw from them conclusions to find out the origin of the human kind, the general water flood and some other nice truths which would confirm what the holy scripture tells of that.106 all of the above authors, and others, were evidently influenced by steno. with them, evidence that biblical scolarship genuinelly informed the work of early modern men of science is therefore ample. they were still natural philosophers, not geologists, but their science was for the first time driven by the observation of nature, to which they adapted the authority of preceding authors. in this important phase of the history that eventually led to modern geology during the last quarter of the eighteenth century,107 steno was the first to publish a history of the earth based on the study of fossils and sedimentary strata, albeit in the summary form to which he felt pressed by a variety of factors. we can still comment on today the fact that steno accepted an age of the earth inconceivable by modern standards, but this should in no way influence our understanding of his role in the history of science. 7. conclusions nicolaus steno’s contribution on the study of the earth, passed on to us through two published essays of 1667 and 1669, looks to the relationship with contemporary culture and with the transnational society of learned men to which he belonged. steno and his contemporaries shared the belief that the bible was an historical book, and that the book of genesis constituted a means to learn about the early part of earth’s history. steno thought that his work as a natural philosopher could find in nature evidence for the mysteries of creation. it is evident that steno took scripture as a guide to comprehend the structure and composition of the 105 c. cohen, a. wakefield, protogaea, by w.g. leibniz, university of chicago press, chicago & london, 2008, pp. xiii-xlii. 106 g. w. leibniz, quoted in ref. 1 (k&m), p. 226; see also f. sobiech, in ref. 2, p. 181; d. garber, in ref. 13 (a&l). 107 m. j. s. rudwick, ref. 7, pp. 79-127. earth beginning with his student years in copenhagen, amsterdam, and leiden, in his subsequent explorations of the tuscan region, and in his readings of and interactions with fellow natural philosophers at the medici court. in tuscany he perfected a method that allowed him to reconstruct historical events independently, but consistently with scripture. this method was based on the application of simple geometric principles to the study of different types of geological objects, from crystals and fossils, to rocks and strata, and on to mountains and the whole earth. evidence in his writings from 1659-1669 is consistent with an interest to carry out an anatomy of the earth nurtured through the years, partly hidden by the primary interest in the anatomy of animal and human bodies.108 it is also hypothesised that this was one of the reasons for travelling to tuscany where he could carry out the necessary field work within the right cultural milieu. steno was a meditative man whose anatomical studies had significance inasmuch they disclosed the immense wisdom displayed by god in creating the world. the consistency of his study of the earth with the narrative of scripture would have blunted criticism of the skeptics, reinforcing the authority of the bible. acknowledgments i thank reviewers eric jorink and jacob bek-thomsen for providing thoughtful and constructive feedback, which was very helpful in improving the manuscript. i thank gary d. rosenberg who edited the paper many times, helping to focus and correcting the english with much patience, and nuno castel-branco, for discussing aspects of steno’s achievements and sharing his knowledge of stenonian primary and secundary literature. 108 the connection between anatomy and the idea of landscape is explored by rosenberg, g.d., “an artistic perspective on the continuity of space and the origin of modern geologic thought”, earth sciences history, 2001, 20, 127-155; g. d. rosenberg, “the measure of man and landscape in the renaissance and scientific revolution”, in the revolution in geology from the renaissance to the enlightenment (ed.: g. d. rosenberg), geol. soc. am. mem., 2009, 203, 13-40. substantia. an international journal of the history of chemistry 6(1): 49-76, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1376 citation: daly p.f., cohen j.s. (2022) history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer. substantia 6(1): 49-76. doi: 10.36253/substantia-1376 received: aug 08, 2021 revised: nov 20, 2021 just accepted online: nov 22, 2021 published: mar 07, 2022 copyright: © 2022 daly p.f., cohen j.s. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* 1 university of pittsburgh medical center, pittsburgh, pa usa 2 chemistry department, ben gurion university, beer sheva, israel *corresponding author. email: cohenjk@post.bgu.ac.il abstract. in the past 30 years there has been a significant increase in the number of publications on phospholipid (pl) metabolism, both for the medical purposes of detection and diagnosis of cancer and for the monitoring of the treatment of human cancers. most of the work has focused on the pathway that produces phosphatidylcholine, the major component of human cell membranes. the trigger for this research was the advent of applications of nmr spectroscopy in vitro and in vivo in the 1980’s and observations that most cancer cells and tumors had significant increases in the water-soluble pl precursors and breakdown products. increased phosphocholine (pc) has been focused on as a marker for cancer using magnetic resonance spectroscopy (mrs) and positron emission tomography (pet). mrs is now used clinically to aid in the diagnosis and severity of some brain tumors; and choline pet is used for the diagnosis and staging of recurrent prostate cancer, paid for by medical insurance companies. another major area of research starting in the 1990’s was the development of specific choline kinase (ck) inhibitors aimed at the isoenzyme ck-a. this isoenzyme is markedly upregulated in cancer cells and unexpectedly was found to have a role in oncogenic transformation independent of its enzyme function. keywords: phospholipid metabolism, phosphocholine, mrs, pet, choline kinase, cancer diagnosis. 1 * list of abbreviations used: 18fch, 18f-fluorocholine; ala, alanine; bcr, biochemical recurrence; ck, choline kinase; csi, chemical shift imaging; ct, computed tomography; dwi, diffusion weighted imaging; fda, united states food and drug administration; fdg, 18f-fluorodeoxyglucose; ga-68, gallium-68; gpc, glycerophosphocholine; gpe, glycerophosphoethanolamine; hc-3, hemicholinium-3; hgg, high grade glioma; lac, lactate; mpmri, multiparametric mri; mri, magnetic resonance imaging; mrs, magnetic resonance spectroscopy; mrsi, magnetic resonance spectroscopic imaging; naa, n-acetyl-aspartate; nmr, nuclear magnetic resonance; pc, phosphocholine; pcr, phosphocreatine; pde, phosphodiester; pe, phosphoethanolamine; pet, positron emission tomography; pl, phospholipid; pme, phosphomonoester; psa, prostate specific antigen; psma, prostate specific membrane antigen; ptdcho, phosphatidylcholine; ptdeth, phosphatidylethanolamine; tcho, total choline peak; tcr, total creatine peak. http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 50 peter f. daly, jack s. cohen introduction lecithin was one of the first organic substances described, isolated by the french chemist theodore gobley from egg yolk in 1845.1 the chemical structure of phosphatidylcholine, one of its main components, was not established until 1874.2 over the next century much work was done that led to our understanding of the metabolism of the pl components that make up the cell membrane of mammalian cells.3 at first pl metabolism in cells and tissues were studied by invasive techniques, such as cell lysis and extracts4 and freeze-trapping.5 however, it was eventually realized that these techniques gave unreliable results because of the rapid release of kinases that degraded the substances of interest. it was realized that noninvasive techniques were needed to quantitatively assess the levels of pl metabolites in intact cells and tissues.6 foremost among these methods was the use of noninvasive nmr spectroscopy (mrs) to detect phosphate-containing metabolites such as atp using 31p mrs as first observed by mildred cohn in 1960.7 metabolism of intact cells was investigated by 31p mrs using a perfusion technique with cells trapped in a gel8, 9 and tissues were investigated in vivo using specially developed surface detection coils.10 this included direct investigation of phosphate-containing metabolites in tumors grown on nude mice.11, 12 these studies resulted in the observation that the levels of pl metabolites such as pc and phosphoethanolamine (pe) are higher in rapidly dividing cells such as cancer cells that are non-contact inhibited than in normal contact-inhibited cells.13-15 several authors have identified these studies as the trigger initiating interest in use of these findings in cancer diagnosis and detection.16-20 parallel noninvasive studies were carried out using proton (1h) mrs, but these were more difficult due to the presence of the huge h2o solvent peak, requiring water-suppression methods.21 for tissues in vivo, because of the greater sensitivity of the method, spatial localization techniques were developed using gradient methodology.22, 23 although these mrs methods demonstrated the basic observation that increased cell membrane biosynthesis could be used as a monitor of cancer cells, 31p mrs was too insensitive and initially 1h mrs was too cumbersome to be applied in vivo and in the clinic for human applications. a much more sensitive tomographic method was needed and that has become positron emission tomography (pet) that has allowed these research observations to be applied clinically to the detection and diagnosis of cancer.24, 25 eventually 1h magnetic resonance spectroscopic imaging (mrsi) was developed to be more sensitive and less cumbersome and is now used clinically in brain tumors.26 also, as a result of the differences between pl metabolism in cancer and normal cells, it was realized that kinase inhibitors could be effective anti-cancer drugs and this has resulted in the development of potential anti-cancer therapeutics.27, 28 phospholipid (pl) metabolic pathways the two biochemical pathways for the two main components of the pl membrane in humans, ptdcho (phosphatidylcholine) and phosphatidylethanolamine (ptdeth), were worked out by eugene patrick kennedy in 195629 and are commonly referred to as the kennedy pathways (figure 1). research on these two pathways has continued at a steady pace since 1956, but greatly increased starting in the late 1980s due to observations made using nmr spectroscopy which was being used in vitro in cell suspensions and in vivo in animal and human tumors. these studies indicated these pathways were more active in cancer cells. the pl membrane makes up 70% of the dry weight of human cells and ptdcho and ptdeth make up to 70% of the lipid portion of the membrane. the kennedy pathways,31 are relatively simple three step pathways that are completely analogous. furthermore, choline is trimethylethanolamine and the 3 extra figure 1. kennedy pathway (center bold pathway) showing biosynthesis of the main ptdcho component of mammalian cell membranes from pc and the break-down pathway to glycerophosphocholine (gpc). a parallel pathway exists for ptdeth.30 the enzymes involved in the pathways are shown in italics. abbreviations: cdpcho, cytidine diphosphate-choline; cho, choline; ck, choline kinase; ct, cytidylyltransferase; dag, diacylglycerol; ffa, free fatty acid; g3p, glyerol-3-phosphate; gpc, glycerophosphocholine; lpl, lysophospholipase; lyso-pc, lysophosphocholine; pa, phosphatidic acid; pct, phosphocholine transferase; pd, phosphodiesterase; pla, phospholipase a; plc, phospholipase c; pld, phospholipase d. 51history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer ch3 groups in choline (figure 2) allow for it to be more easily observed in 1h nmr spectroscopy in vivo and in vitro since the signal derives from the 9 equivalent h atoms of the trimethylated nitrogen atom. most of the research since 1990 has focused on the choline pathways. for the sake of simplicity, we will only show figures of the choline pathways although the ethanolamine pathways are completely analogous.29 the simple three step kennedy pathway32 for synthesizing phosphatidylcholine is: choline to phosphocholine to cdp-choline to phosphatidylcholine. this is the central synthetic pathway in figure 1 going from left to right. the degradative pathways occur via the phospholipase a (pla), phospholipase c (plc), and phospholipase d (pld) pathways that are shown above and below the central synthetic pathway in figure 1 going from right to left. the metabolites that are seen in 31p mr spectra of in vitro cell suspensions and in vivo are pc in the synthetic phosphatidylcholine pathway; and pe in the analogous synthetic ptdeth pathway (not shown) and gpc (glycerophosphocholine) and gpe (glycerophosphoethanolamine) in the degradative pathway starting with phospholipase a (pla). the degradative pathway via phospholipase c (plc) contributes a small percentage of the pc peak in the nmr spectra. the degradative pathways have also drawn interest not only because they produce gpc and gpe which are observed in the 31p nmr spectra of tumors. but the degradative pathways also produce the metabolites phosphatidic acid (pa) via phospholipase d (pld); and diacylglycerol (dag) via phospholipase c (plc) which are second messengers within the cell involved in multiple functions including growth and the mitogenic activity of growth factors via the ras family of proteins.33-36 the ras proteins have enzymatic activity and exist in an “on” and “off ” state. when turned on they trigger a cascade that ultimately turns on genes involved in cell growth, differentiation, and survival. overactive signaling inside the cell can ultimately lead to cancer.37 ck is the first enzyme in the kennedy pathway and has been found to be overproduced in almost all cancers beyond their need for phosphatidylcholine synthesis and has been under intense study in the past 25 years as a key enzyme in cancer and necessary for oncogenic transformation. ck also interacts with the ras protein family for signal transduction and high concentrations of ck have been noted to turn on ras proteins for signal transduction.17, 38 multiple ck inhibitors have been synthesized as potential chemotherapy agents for cancer.27 as the first step in the synthetic pathway ck phosphorylates choline to pc. the next enzyme in the pathway is cytidylyltransferase (ct) which is rate limiting and pc accumulates and is easily seen in 31p mr spectra in vitro in cancer cells and in vivo in tumors. application of mrs in 1980 jack cohen joined the national cancer institute with the intention of using nmr spectroscopy as a tool to study the metabolism of cancer cells. a varian 400 mhz nmr spectrometer was purchased, and studies began in 1981. the basis of this work were the attempts made to devise a system whereby this noninvasive nmr technique could be used to study cancer cells in vitro. previous attempts using suspensions of cells had proved unsuccessful, since the large number of cells (ca. 109 cells) in 1 ml in a 10 mm 31p mrs tube required to obtain sufficient signal-to-noise, used up all the available nutrients and became ischemic before any useful results could be obtained.39 our first attempt to overcome this problem was to suspend cancer cells in an agarose gel and attempt to perfuse it with a solution containing nutrients and oxygen.40 but this was not really successful. in order to enable the cells to metabolize, the solution had to be in contact with all of the cells as much as possible. we then devised a method to place the cell suspension in a liquid gel and flow it through a fine capillary (0.5 mm id) that was dipped in a container of ice, whereupon the mixture gelled and the cells were trapped and the spaghettilike gel threads were then extruded into an nmr tube and could be perfused with the nutrient-containing and oxygenated solution and remain metabolically active for days8 (figures 3-5). using this technique we were able to see a high level of atp in the cells as well as other metabolite signals (figure 6), and by adding other metabolites or drugs to the solution being pumped through the cells we could monitor changes in the metabolism of the cells.9, 42 figure 2. chemical structures of ethanolamine and choline. 52 peter f. daly, jack s. cohen we carried out a series of studies that resulted in greater understanding of the metabolic response of several cancer cell lines grown in culture under different circumstances. 15,16, 43-46 in earlier studies the phosphomonoester (pme) peaks were erroneously assigned to sugar phosphates (sp), but we confirmed their assignment to pc and pe by the addition of choline and ethanolamine (separately) to the perfusion solution.13 this was the first observation of the enzymes of the pl pathways functioning in real time in intact cells by mrs. on addition of ethanolamine, all four peaks, pc, pe, gpc, and gpe reacted to ethanolamine as expected by wellestablished substrate and inhibition effects. ethanolamine inhibits ck and the phosphodiesterases that break down gpc and gpe to choline and ethanolamine, and it is the substrate for ethanolamine kinase producing pe. all four peaks can be seen reacting to the ethanolamine infusion as expected in figure 7.13 one of our initial observations was that the peak assigned to pc and pe in the spectrum of cancer cells was found to be higher than expected (figure 6) and higher than the same peak in in vivo studies of normal tissue that were used as controls.47, 11 this important observation of elevated pc and pe in cancer cells was figure 3. diagram of the apparatus used to embed cells within agarose gel threads. a mixture of cells in medium is extruded through a fine teflon capillary in chilled ice. the gel thread is then extruded directly into medium in the 10-mm screw-cap nmr tube.41 figure 4. schematic of the perfusion system showing the arrangement of the polyethylene insert.41 figure 5. photomicrograph of gel-threads showing cancer cells embedded in perfusable gel.41 figure 6. representative 31p nmr spectrum at 162 mhz of wildtype mcf-7 human breast cancer cells (~108/ml) perfused with imem media (pi-free) in agarose gel thread (0.5 mm); 200 scans were accumulated with a recycle time of 40 sec and a 90° pulse. the peak assignments are denoted: pe, pc, pi, inorganic phosphate; gpe, gpc, pcr, phosphocreatine; atp, adenosine triphosphate, dpde, diphosphodiesters; nad, nicotine adenine dinucleotide.41 53history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer the basis for many future studies and has had significant influence in subsequent studies of cancer diagnosis and detection. in fact, in several reviews,17-20 this observation has been singled out as the seminal observation that resulted in much greater research activity in this field (figure 8). note that a similar pattern of increase in research activity was found for every topic that was searched in this field. this observation of increased pc in cancer cells was later confirmed by several authors using as controls noncancerous cells grown in culture.38, 48 this subject has been extensively reviewed by glunde and coworkers.49 in which they document increased pc/pe in 6 different cancer types, including breast,50, 51 ovarian,52 prostate,53, 54 cervical,55, 52 brain56, 57 and endometrial58 cancers. of significance was the observation of the pme to phosphodiester (pde) ratio, the more malignant the cell line the more pc and pe were present and the less gpe and gpc were observed. it is this ratio that is more significant, not the absolute concentrations. in the first observation of this type in 1986, comparing the perfused wild-type cell line to the adriamycin-resistant cell line derived from it, adding up the pme and the pde concentrations, the wild-type had a pme/pde ratio of ca. 2, but the resistant more malignant cell line ratio was about 16.47 some biochemists looking at choline metabolites call this the pc/gpc “switch” as the malignancy progresses.38, 30, 19 we later improved the perfusion technique by using basement gel membrane as the gel substance.59 meanwhile others had developed other methods of monitoring the 31p mrs of cells using both suspensions aerated by oxygen60 and bioreactors.61, 62 it should also be mentioned that similar perfusion studies were performed with 13c labelled metabolites observed by 13c mrs63 or by 1h mrs using the 13c-1h spin-spin (j) coupling to gain higher sensitivity.64, 65 direct proton mrs studies of choline levels have also been measured.66 it should be pointed out that the signals of the pls themselves are not observed in these 31p spectra of cells, because they are extensively broadened by spin-spin (t2) relaxation due to their macromolecular structure and restricted motion leading to efficient t2 relaxation. by contrast, the metabolites that are smaller molecules with extensive molecular motion, even though within the viscous milieu of the cell, provide narrower resonances. in effect the cellular metabolites provide a 31p mr spectrum that is in fact superimposed on the top of a very broad pl baseline. development of choline-pet scanning as a diagnostic method for prostate cancer the observations of the 1980s and their confirmation by further cell studies in the 1990s that the majority of cancer cells had unusually high levels of pc and gpc increased interest in using this fact as a way to diagnose and stage cancer; and to monitor and adjust cancer therafigure 7. effect of ethanolamine in the perfusate. shown are quantitative 31p nmr spectra of cells grown in imem medium with 15 mm choline and no ethanolamine, harvested at log phase, and then perfused with buffer a, 11 mm glucose, plus 2 mm ethanolamine at 37oc. each spectrum represents a l-hr accumulation. hours 2 to 16 are shown.13 figure 8. plot of number of hits vs. year for a search of “phosphocholine and cancer” using the scifinder (cas) search engine, with 1,485 hits at maximum.. 54 peter f. daly, jack s. cohen py. since the 1990s the main problem with using mrs for these purposes was the low signal to noise ratio in mrs requiring large “voxels” or cubes of tissue for obtaining a good spectrum. with phosphorus spectra this required voxels that were multiple centimeters in diameter and would sample tissue other than the tumor, including normal tissue and necrotic tissue. 1h spectra using proton mrs was developed and could obtain spectra from 1 cm3. 67, 68, 23 while this was helpful with brain tumors it was still too large a volume for many other common cancers. to overcome the signal to noise problem 11c-choline for human positron emission tomography (pet) scans was synthesized in 1997 by a japanese group led by hara.69 historically, the first synthesis of 11c-choline for pet scans was in 1983 and was used to observe normal brain tissue in a monkey.70 the japanese group however used their own synthesis as there were no details for the synthesis given in the 1983 paper. radiolabeled choline has been used since 1997 in pet in cancer research for imaging brain and other tumors.69, 71, 72 this is based on the first step in pl synthesis, choline being rapidly metabolized to pc by ck (figure 1). in addition most cancers have increased membrane transport of choline compared to normal cells.17 the two forms of choline most commonly used in pet scanning are 11c-choline and 18f-f luoromethylcholine,73 which is commonly called 18f-fluorocholine (18fch). in 11c-choline one of the 12c carbons in the n-trimethyl group of choline (see figure 2) is replaced by an 11c atom. in 18fch, one the of the hydrogens in the n-trimethyl group of choline is replaced by 18f. 18fch was first synthesized by degrado in 2000.74, 75 they found that 11c-choline and 18fch behaved similarly in cell cultures and also in their ability to be metabolized by ck. later studies showed that 18fch was comparable in diagnostic ability to 11c-choline, but is easier to use because of its longer half-life.76-78 11c has a half-life of 20 minutes and 18f of 110 minutes allowing for 18fch pet images to be obtained for a longer time, from 5 min to 60 min after injection. other choline analogs were synthesized,74 but these contained additional carbon atoms and were not transported as well by choline membrane transport proteins or metabolized as well by ck.74 since ck is overexpressed in most cancers and rapidly metabolizes choline to pc; most cancers contain higher concentrations of pc compared to normal cells.79 this generates a visible signal in the pet scanner. from the time 11c-choline and 18fch were synthesized in 1997 and 2000 it was found that multiple tumors could be found by choline-pet, including brain, head and neck, breast, lung, esophageal, liver, kidney colorectal, prostate, bladder, uterine, ovarian cancers, and lymphomas.80 for medical use though, it must be shown that it is better than other imaging methods, cost effective, and also has the ability to obtain an image in a time that is comfortable or tolerable for the patient. when pet is combined with a ct or mri scanner it gives a more accurate location of tumors or metastases.73 since 2000 when the pet/ct was first invented most studies have been done with the pet/ct scanner. the initial studies done from 1997 into the early 2000s showed that 11c-choline or 18fch did produce clearly delineated images of tumors with a good signal to noise ratio. but for most tumors it was not better than 18f-fluorodeoxyglucose (fdg) pet scans for tumors, which was already in widespread use. fdg works well because it is a glucose analog, and most cancers have a high rate of glucose uptake and utilization. and for brain tumors amino acid pet tracers were also superior.73 however prostate cancer is an exception in that it is more slowly growing and does not absorb fdg rapidly. in addition, prostate cancer is one of the most common cancers in men with a high mortality rate. it was shown in 2003 that 18fch pet scans were superior to fdg for restaging prostate cancer after recurrence and this resulted in a marked decrease in the use of fdg for imaging prostate cancer and an increase in cholinepet,73, 81 both for the initial staging and restaging of prostate cancer after relapse. unfortunately, in prostate cancer relapse is high so comparative imaging in initial stage and relapse is of utmost importance. prior to choline-pet tracers, staging was done using ct, mri images, and ultrasound. most of the research on the clinical applications and actual clinical use of choline-pet has occurred in europe, japan, and australia.24 this is due to the difficulty of getting approval from the fda (united states food and drug administration) for new pet tracers and financial barriers such as uncertain reimbursement in the usa.24, 82 11c-choline was approved by the fda in 2012 but 18f-choline has not been approved as of 2021, even though it was developed and tested in the usa at duke university in 2000.74 after initial studies from 1998 to 2003 showing the feasibility of choline-pet and choline-pet/ct there have been thousands of studies since 2003 focusing on the clinical applications of choline pet. the area that it has proven the most useful is in the restaging of relapsed prostate cancer. the use of choline pet/ct has become common since about 2010 in many parts of the world for the initial staging and restaging of prostate cancer.24, 73, 83 a 2021 paper from france started by saying “f-choline pet/ct is considered a cornerstone in the staging and restaging of patients with prostate cancer.”84 another 55history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer study published in 2020 focused on the “real world” use of choline-pet showed that it was commonly used for both initial staging and restaging and resulted in a change of therapy in 58% of the patients.85 in addition, new pet radiotracers have been developed in the past decade that focus on prostate specific membrane antigen (psma) or amino acid tracers such as 18f-facbc (fluciclovine) for imaging prostate cancer; and studies are ongoing comparing the effectiveness of each of these tracers compared to 11c-choline or 18fch.24 also, when using choline-pet in patients with prostate cancer, tumors other than prostate cancer are picked up incidentally in 1 to 2 % of patients.84 staging of prostate cancer with cholinepet compared to mri initial (primary) staging; locating the cancer in the preoperative prostate numerous studies were done from 2003 onward evaluating the use of choline-pet scanning for the initial staging of prostate cancer.73 one study from 2006 focusing on the local detection of prostate cancer nodules by 11c-choline within the prostate preoperatively compared with biopsies done preoperatively86 did show choline-pet could find 83% of prostate nodules that were 5 mm or greater in diameter, but only 4% of nodules smaller than that for an overall sensitivity of 66% compared to the biopsies. 5 mm is generally considered the lower limit in size detection for pet scans in general -not just for choline studies. another study in 201087 looked at the preoperative evaluation of cancer nodules within the prostate as compared to preoperative biopsies, or examination of the prostate by a pathologist after surgical removal. a combination of standard mri images combined with gadolinium enhanced images of the preoperative prostate found 88% of the nodules, 11c-choline-pet found 73% of the nodules, and fdg-pet found only 31%. multiparametric mri (mpmri) studies in 2015 using dwi (diffusion weighted imaging) showed mpmri to be superior for detecting cancer in the preoperative prostate as well as local extensions outside the prostate.88 for modern prostate cancer imaging mpmri uses four sequences: t1-weighted images, t2-weighted images, dwi, and dynamic contrast enhanced (dce) imaging. most commonly t2-weighted images with dwi and dce are use or t2 weighted images with just dwi. in the past mrs of the prostate was also used as a fifth option to be part of the mpmri workup but mrs of the prostate is not commonly used currently. lymph node and bone metastases the two other areas of importance in the initial staging are metastases to nearby lymph nodes and bone. choline-pet/ct was found in many studies to be superior to ct and conventional mri scans at finding metastases to the lymph node. one reason may be that ct and conventional mri rely mostly on the size and appearance of the lymph nodes whereas choline pet/ct that has a functional component was able to detect micrometastases to the lymph nodes.89 the sensitivity of these studies was only about 50% however when compared to the lymph nodes that were removed at the time of surgery and examined by a pathologist.89, 73 for this reason, the european association or urology in 202190 still recommends lymph node removal for proper staging of prostate cancer at the time of initial diagnosis. since pet/ct images the entire body, one important value of choline-pet/ct is that it can detect lymph nodes with prostate cancer outside the area of a standard mri scan or outside the surgical field of a standard lymph node dissection.91-93 for these reasons choline-pet/ct for detecting metastases to lymph nodes has been commonly used in europe since 2010 (figure 9).73 for staging of bone metastases choline pet/ct has consistently shown more accuracy than bone scan in its ability to detect both bone and bone marrow metastases (figure 10).94 it also has higher image resolution.95-97 in patients with intermediate to high-risk prostate cancer it was found that choline-pet/ct was more sensitive and specific at detecting bone marrow metastases than bone scan or ct alone. for bone metastases they reported a 100% sensitivity and a 90% specificity with cholinepet compared to bone scan.95 one study showed an advantage of choline-pet/ct over mri or mri dwi for detecting bone metastases in 47 high risk patients.88 it should be noted that many of the studies were performed on intermediate to high risk patients. in the figure 9. a shows a right external iliac lymph node with a large uptake of 11c-choline. b shows the same area after 4 months of successful treatment.24 56 peter f. daly, jack s. cohen higher risk patients, the sensitivity of choline-pet/ct increases dramatically. restaging after relapse (treatment failure) many men treated for prostate cancer relapse and need to be restaged. in the vast majority of cases the relapse is found by an increase in the prostate specific antigen (psa). this is also called biochemical recurrence (bcr) in prostate cancer. psa is an enzyme found predominantly in the cytosol of prostate cells.24 for most men without prostate cancer the normal serum level is about 0.7 ng/ml and in prostate cancer it can increase dramatically to 100 or 1000 ng/ml but in most cases levels above 6 to 10 are worrisome. most men treated for high-risk prostate cancer have the prostate and pelvic lymph nodes removed at the time of initial diagnosis. in these men the psa level goes below 0.2 ng/ml. an increase of the psa on two measurements taken 3 months apart indicates recurrence. for men treated only with radiation therapy without removal of the prostate an increase of 2 ng/ml from the lowest measurement during treatment indicates recurrence, sometimes called biochemical failure.73 as in the initial staging, mpmri proved to be superior to choline-pet scanning for locating a recurrence in the prostate or in the prostate area of men who had undergone prostatectomy.98, 99 where choline pet/ct stood out was its ability in restaging after treatment failure to detect lymph node and bone metastases.83 choline pet/ct showed an overall sensitivity for recurrence in the lymph nodes, bone, and other sites in 86 to 89% of patients and its use is recommended by the european association of urology.90, 100-102 this far exceeded the detection rate of fdg-pet and mpmri. for detection of all lymph nodes compared to the surgical dissection of the lymph nodes after recurrence, the sensitivity was about 60%.103-107 these sensitivities make it far superior to fdg-pet81, 105 and mpmri99 for restaging of local and more distant lymph node metastases. of note, choline-pet/ct findings at restaging have allowed for site directed radiation therapy to target the area and to calculate the radiation dose. this directed “salvage radiation therapy” by choline-pet/ct has led to improved disease free survival.108-110 one study showed that a combination of salvage lymph node dissection and radiation therapy in patients led to a 70% five year disease free survival in patients staged with choline-pet/ct.111 in addition to its usefulness in detecting relapse into the lymph nodes choline-pet/ct was able to detect prostate cancer in 15% of patients with negative bone scans and is equivalent to mpmri for detecting bone metastases.101, 99 another advantage of choline-pet/ct is its ability to detect the more aggressive osteolytic metastases.112 this allows corrective treatment to be started to prevent fractures of those bones. for these reasons, choline-pet/ct is often the preferred imaging technique in relapsed prostate cancer treatment failures24, 73, 83 and is commonly recommended in treatment guidelines.113, 90 historical guidelines for use of choline-pet for prostate cancer the european association of urology (eau) guidelines on prostate cancer90 first mentions the use of choline-pet/ct in the 2010 guidelines for locating metastases to bone during initial staging, but states that the use in relapse is unclear. by 2015, the guidelines did not recommend choline-pet/ct for initial staging. but for staging in relapse, choline-pet/ct was useful for detecting lymph node and bone metastases if the serum psa level was greater than 1 to 2 ng/ml and was more sensitive than bone scan. by 2018, the eau guidelines gave a strong recommendation for the use of choline-pet/ct or psma-pet/ct following bcr after radiotherapy to stage local lymph node metastases or distant metastases to bone or other tissue. the 2021 guidelines discuss that choline-pet/ct can be used for detecting bone (but not lymph node) metastases at initial staging and will simultaneously detect bone and other more distant metastases, but it is not a strong recommendation. for cases involving relapse after radiotherapy the 2021 eau does give a strong recommendation for choline-pet/ct or figure 10. a to c clearly shows the progression of bone metastases during multiple cycles of treatment. the large bright spot in the lowest part of the figure is the normal liver which concentrates the 11c-choline that is injected. th is thoracic vertebrae, c is cervical vertebrae.94 57history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer psma-pet/ct for patients being considered for curative lymph node salvage treatment and can change management in up to 48% of patients. it is noticeable that the formal recommendations are more conservative than what is reported above as actual common use of choline-pet/ct in initial staging and restaging. however, the recommendations are consistent with publications highlighting that it is more sensitive in cases of relapse than at the initial staging. one reason for this may be that the biochemical studies on cancer cells show that the levels of pc increase as the cells become more malignant. with relapse it is the more malignant and aggressive cells that predominate. psma pet scan for prostate cancer psma is a folate hydrolase glycoprotein24 that, despite its name, is found in more tissue than just prostate. despite the similarity of the name this is a different protein enzyme than prostate specific antigen (psa) which is mostly in the cytosol of prostate cells. in prostate cancer psma is overexpressed by 100 to 1000-fold. a newer psma pet agent gallium-68 psma-11 was recently approved by the fda in dec 2020114, 115 and has been used and studied in europe and australia since 2015.116, 117 many recent papers claim it is more sensitive and specific than choline-pet at lower levels of psa and future head to head comparisons are being planned. there have been other psma-pet tracers developed. since psma is an enzyme, they have in common that they target the substrate recognition site on psma. to date it is gallium-68 psma that has been the most studied. it should be noted that “psma pet tracer” refers to the whole family of psma tracers and not to any one in particular. correlation with prostate surface antigen (psa) level for choline and gallium 68 (ga-68) it has been noticed that there is a strong correlation between the sensitivity of a pet imaging agent to detect prostate cancer in patients, and the serum level of psa. this is because the higher the serum psa the more advanced the cancer. it has become the norm to divide the sensitivity of pet imaging agents into 3 categories. the sensitivities below a psa of 1 ng/ml, those sensitivities for psa levels between 1.0 to 2.0 ng/ml and the sensitivities for a psa level above 2.0 ng/ml.24 a recent review24 in patients with a relapse showed ga-68 psma to be more sensitive at all levels. the authors cautioned that this was pooled data from multiple studies, and they were not standardized. however prospective headto-head studies of choline vs ga-68 pet/ct scanning is underway. multiple studies published in 2020 and 2021116, 118, 117 also show that ga-68-pet/ct is more sensitive than choline pet/ct and is replacing choline pet/ct in many centers. however, the experience gained with choline pet/ct over the past 20 years cleared the way and is influencing and guiding the applications of ga-68 pet/ct. basically, they are the same applications such as staging and guiding of therapy but with a more sensitive agent. it remains to be seen if choline-pet/ct will still have applications that ga-68 cannot be used for in prostate cancer and other cancers. choline kinase as a target of chemotherapy the earliest pl enzyme target for chemotherapy and the one most studied has been ck.119 however other enzymes in the pathway have also been proposed as targets.120 the development of ck inhibitors for possible cancer treatment has been closely connected to the biochemical studies on this enzyme and its importance in two different functions: 1) cancer transformation and 2) the catalyzing of choline and atp to produce pc. by 1998, it had become clear that there were two forms of ck – an alpha and a beta form and their amino acid sequence had been determined.121 subsequent studies showed ck alpha to be the more important isoform in cancer.122 to date the most potent ck alpha inhibitors developed have been mn58b and rsm-932a which is also called tcd-717.27, 119 the first paper published on interfering with the pl pathways by ck inhibition was in 1974.123 the compound used was purinyl-6-histamine and had been observed to be cytotoxic to tumor cells in vitro with little to no effect on normal cells in vitro or to have any effect on dna or proteins. the study made “preliminary observations” about purinyl-6-histamine’s effects as a ck inhibitor and the morphological changes observed in the membrane of cancer cells being more pronounced than those of normal cells, but there were no follow-up publications. there were two more papers published in 1983124 and 1985125 studying the effects of hemicholinium-3 (hc-3) on krebs ii ascites carcinoma cells. they found that hc-3 inhibited both the choline transport mechanism across the cell membrane and also inhibited ck intracellularly. they also found that the synthesis of ptdcho was diminished in krebs ii ascites carcinoma cells by hc-3 but not in normal liver cells. 58 peter f. daly, jack s. cohen in 1987 the 31p nmr spectra of mda-mb-231 cancer cells were monitored while being observed in intact cells being perfused in the nmr spectrometer by a buffer solution without any choline. the introduction of hc-3 into the perfusate caused a reduction of the pc peak by over 50% in 8 hours (figure 11).13 this would indicate that the reduction in the pc peak observed in this experiment was due to inhibition of ck and not only to inhibition of choline transporters. hc-3 would become the template that most future ck inhibitors would be based on.27, 119 as discussed in the section on “applications of mrs,” subsequent studies done in the 1990’s confirmed that most cancer cells studied had high levels of ck and pc. a review article by podo referred to 1983 to 1993 as the “pioneering decade”19. mrs studies on cells grown in vitro led to the hypotheses that the increased pe and pc levels in cancer cells were involved in cell membrane synthesis, and cell growth in cancer cells,13, 126, 127, 15 and that “specific oncogenes resulted in the increased production of choline and ethanolamine kinase.”16 these observations triggered further studies and confirmation of the hy potheses involving the pl pathways and the enzymes and oncogenes involved. most of the studies have focused on ck.17, 120 further studies showed that the ck alpha gene also functions as an oncogene involved in tumor initiation and progression.120, 128, 129 of the alpha and beta forms only ck alpha has been found linked to tumor transformation. increased expression of ck alpha 1 is oncogenic to cells, but overexpression of ck beta is not. increased production of ck alpha 1 mrna is found in breast and lung cancer cell lines, but there is no change in ck beta mrna levels.122 from 1987 to 1995 multiple papers were published showing that the ras oncogene causes an activation of the ck enzyme130, 34, 131-136 causing an increase in pc. data from one of the papers34 indicated that pc may function as a second messenger in cells involved in cell growth. at that time hc-3, which was first reported in 1974137 was the most potent inhibitor of ck and served as the template for the development of numerous ck inhibitors that fall into two categories: 1) bis-pyridiniums and 2) bis-quinoliniums.27, 119 hc-3 itself had a paralyzing respiratory effect at therapeutic levels for treating cancer,138 so ck inhibitors were developed that were both more effective with no or reduced side effects in vivo.27, 119 in 1997, numerous bis-pyridiniums were produced in the lab of juan carlos lacal131 and the compound named mn58b proved to be the most effective. nih3t3 cell lines that had been transformed by ras, src, and mos oncogenes were profoundly inhibited in their growth by the new bis-pyridiniums ck inhibitors by a factor of 600 to 1000 and were effective in the low micromolar range.139 the ras, src, and mos transformed cells had elevated levels of ck activity and the degree of inhibition correlated with reduced production of pc. mn58b was later shown to significantly inhibit the growth of xenograft tumors.140, 139, 141 later studies showed that mn58b was 20 fold more effective at inhibiting the ck alpha enzyme compared to the beta form of the enzyme.27, 122 the next set of new ck inhibitors studied were in the bis-quinolinium class. in 2005 lacal’s laboratory studied forty more compounds and compound 40 was the most potent in the bis-quinolinium class.142 it was subsequently labeled as rsm-932a and is also called tcd-717. tcd-717 completed a phase 1 study in solid tumors in 28 patients between jan 2011 and february 2014.143 tcd-717 was selected for the phase 1 trial as it has no detectable toxicity in mice at levels that cause 77 percent tumor growth inhibition in vivo. in addition, it caused reversible cell cycle arrest in nontumor cells but cell death via apoptosis in cancer cells.144 the study was sponsored by translational cancer drugs pharma which is located in spain, but the studies were conducted at johns hopkins university and the barbara ann karmanos cancer institute in detroit, michigan. to date results of the phase 1 trial have not been published, but in 2021119 lacal referring to the phase 1 trial stated that “the toxicology studies have already been addressed” and indicated that rsm932a/tcd717 has “paved the way for future development”. rsm932a/tcd717 has a unique mechanism of action and was found to not bind to the pockets on ck alpha where choline and phosphate are catalyzed like figure 11. effect of hc-3 in the perfusate. quantitative 31p nmr spectra are depicted of cells grown in imem with 15 mm choline and 10 mm ethanolamine, harvested at log phase, and then perfused with buffer a, 11 mm glucose, plus 100 mm hc-3. each spectrum represents a 1-h accumulation.13 59history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer other ck alpha inhibitors bind, but to bind to the surface of the enzyme.145 this caused both a severe reduction in both pc and in the levels of ck alpha. one hypothesis is that rsm932a/tcd717 causes a drastic reduction of the level of ck alpha protein by causing a conformational change that makes it susceptible to proteases.119 in some tumors inhibition of ck alpha with no reduction in ck alpha levels within the cell is insufficient to cause cell death.146, 147 however, in glioblastoma cells inhibition of ck alpha by pure enzyme function inhibitors such as v11-0711 that has no effect on the level of the enzyme is sufficient to lead to tumor cell death.119 the mechanism of cell death in tumors by ck inhibitors may vary depending on the cell type. a 2021 review article titled “recent advances in the design of small molecule ck alpha inhibitors and the molecular basis of their inhibition” shows that this remains an active area of research.28 in addition to small molecule inhibitors, sirnas (silencing rnas) have also been developed against ck alpha and phospholipase d and are under active study and produce reduced cell proliferation in xenographic tumors but have not yet reached phase 1 patient studies.120 development of clinical applications of mrs/mrsi/mri introduction: magnetic resonance spectroscopy (mrs) of tissue metabolites in a freshly amputated frog leg was first reported in 1974 by d.i hoult et. al. in george radda’s research group at oxford where they observed phosphate metabolites by 31p mrs.148 in that first report they labeled the observed peaks as sugar phosphates, pl, pi, creatine phosphate, and the gamma, alpha, and beta peaks of atp. this was one year after the first paper on the feasibility of magnetic resonance imaging (mri) was published by paul lauterbur.149 since the late 1980s mri and mrs have been closely linked, with localized mrs being recorded after an mri is obtained. in 1980 the earliest in vivo human mrs was reported by j.d. cresshull et. al. in radda’s lab observing the 31p spectra from a human arm and the effects on pcr (phosphocreatine) and pi before, during, and after the removal of a tourniquet.150 the first in vivo spectrum of a human tumor was done by 31p mrs in 1983 by griffiths et al.151 of a rhabdomyosarcoma and showed prominent peaks in the pme region and the pde region not seen in normal muscle. the pme area is now known to be pe and pc but was assumed to be sugar phosphates at that time. in 1985 in vivo 31p mr spectra of neuroblastomas in two children with metastases to liver and muscle showed a high concentration of pmes in the tumor compared to the 31p nmr spectra of the normal liver and muscle tissue in vivo in the same children, which showed much smaller pme peaks. the large pme peak returned to normal size if the neuroblastoma was successfully treated or if it spontaneously regressed (a common feature for neuroblastoma in infancy). this initial observation of 1) a high pme peak that 2) diminishes with resolution of the tumor has been one of the main uses of mrs in cancer ever since. the pme peak in neuroblastoma was assigned to pe at 10 mm concentration, with a smaller contribution from pc and 2,3-dpg (2,3disphosphoglycerate).152 they also reported a small pde peak which in high resolution 31p mrs of biopsy material was identified as gpe and gpc. as was discussed earlier in the section on application of mrs, extracts and cell studies were also done concurrently with the early in vivo 31p mr studies. at that time there were conflicting reports of the origins of the pme peak in cells and in vivo from tumors. many early 31p mr studies assigned the pme peak to sugar phosphates. others assigned the pme peaks to pc and pe using acid extracts of cancer cells,19 but the enzymes creating these peaks were not determined. in 1987 the first 31p mrs studies of cancer cells in real time in vitro studied with enzyme substrates and inhibitors (figure 7) confirmed the pme peaks were predominantly pe and pc; and they were produced by ck and ethanolamine kinase in the kennedy pathways, and the pde peaks were mostly gpc and gpe.13 by 1989 in vivo 1h spectra of human brain and brain tumors were being published which showed multiple metabolites in the 1h spectra, including a large peak that was a combined peak of choline, pc, and gpc called the total choline peak or tcho peak.153, 23 biochemical studies established that the dominant peak in the tcho peak is pc with a contribution from gpc and a smaller contribution from free choline.17 since that time most in vivo spectra of cancer in humans have been 1h spectra since it has greater sensitivity and can be obtained from smaller volumes than 31p spectra.18 because mrs can measure some metabolites localized in vivo it has always held out the promise that it could be useful for diagnosis and monitoring of treatment. it is the unique radiofrequency of the two hydrogen atoms in water that provide the images obtained by clinical mri machines. the hydrogens in fat also contribute somewhat to the images. water is 55.5 molar which means the two hydrogen atoms in water are at 111 molar. due to this high concentration the 1h radi60 peter f. daly, jack s. cohen ofrequency of water observed from the human body produces a very strong peak with an extremely high signal to noise ratio. because water does not make up 100% of the volume of human tissue the signal is correspondingly decreased. by contrast, the concentration of other metabolites seen by 31p or 1h mrs such as pc, pe, gpc, gpe are in the range of 1 to 10 millimolar or .001 molar to .01 molar. this is a concentration difference of approximately 10,000 to 100,000 fold and makes obtaining spectra from patients reliably, quickly, reproducibly, easily, and with a high signal to noise very difficult and has been the major barrier to the widespread use of mrs in medicine, despite major attempts over the past 30 years.154, 155 as of today, common use of single voxel mrs or multivoxel mrsi occurs in major research hospitals, but not in community hospitals where the vast majority of mri machines are located. the two main mr nuclei used in vivo have been 31p and 1h spectra. of the two, 1h has been used more often since 1h has 16 times intrinsically more signal intensity than 31p.148 also pc and gpc have 9 hydrogens in the trimethyl part of choline that give off the identical radiofrequency signal (see figure 2) that also increases the signal to noise ratio. the main disadvantage of 1h spectra is that choline, pc, and gpc have their radiofrequency signal so close together that in vivo it is just one peak called the tcho peak. although in vivo spectra have been used in areas other than cancer, these studies mostly involve peaks in the spectra not related to pl metabolism.156 whereas its use in aiding in the diagnosis of cancer and monitoring of therapy has relied predominantly on the pc and gpc peaks; and to a lesser extent, the pe and gpe peaks when 31p nmr is used. the three areas of cancer where it has been used the most is in brain, breast, and prostate cancer. as of 2021, 354 clinical trials were found under the search “cancer and magnetic resonance spectroscopy” at clinicaltrials.gov. about 80% of nih clinical trials have been in brain, prostate, and breast cancer, in that order.157 magnetic resonance spectroscopy and spectroscopic imaging in brain tumors localized 1h mrs of the human brain was first reported in 1985158 and multiple papers on high resolution 1h mrs of the human brain soon followed.159, 160 as of today multiple resonances can be observed by 1h mrs of the brain and brain tumors which include tcho, naa (n-acetyl aspartate), total creatine (tcr), glutamate/glutamine (often abbreviated glx), lactate (lac), alanine (ala), lipids, myo-inositol, and a broad macromolecule peak.161, 26 usually the tcho peak is just called “the choline peak” and the tcr peak is just referred to as “creatine”. 2-hydroxyglutarate was first seen in 2012.162 by 1989 frahm et. al reported on 8 primary brain tumors and one metastatic breast cancer tumor to the brain.153, 160 they found the spectra were remarkably different from normal brain tissue by having a high tcho peak and a low naa peak. but histologically similar tumors gave similar spectra to each other. similar results were reported on spectra obtained at 4 tesla in 1989.163 the tcho peak has been found to be predominantly pc164, 26 and naa is a marker of normal neuronal tissue.165, 26 these papers looked at gliomas, meningiomas, one neurilemmoma, one arachnoid cyst, and one metastasis due to breast cancer. they concluded 1h mrs may become an important tool for differentiation of tumors as well as for planning and following therapy. they also concluded that the 1h mrs method was better than 31p mrs since spectra could be obtained on smaller voxels which avoided sampling both the tumor and the surrounding normal tissue.163 these early studies were single voxel studies. however, in 1982 truman brown published on nmr chemical shift imaging (csi)166, 167 where spectra are obtained from multiple voxels adjacent to each other in a square grid of n by n voxels; and then a gray or color scaled image of the intensity of a metabolite such as choline can be made from the individual spectra in each voxel. this can be extended to a cube that is n by n by n voxels. if it’s a flat grid it’s 2 dimensional csi and a cube is 3 dimensional csi. csi is now frequently referred to as mrsi (see figure 13 from 2021). because the metabolites are in such low concentration compared to water these images do not give the same high resolution as standard mri but methods for increasing their resolution have improved markedly since the late 1980s.168 in 1990 luy ten et al. produced mrsi of brain tumors on voxel sizes of 1.225 ml (7 by 7 by 25 mm) and produced low resolution images showing elevated tcho and decreased naa in tumors with noticeable heterogeneity within the same tumor.161 by 1992 1h nmr spectra on over 200 brain tumors had been reported. some of these reports used csi but most used single voxel spectra.169 as of 1992 the most common observations on primary brain tumors were an elevated tcho, decreased tcr and decreased naa (see figure 12 from 2003).170 tcho, tcr, and naa are the three most prominent peaks in the 1h spectra of brain and brain tumors. metastatic cancers to the brain and gliomas frequently contained lac whereas meningiomas, neurinomas, and lymphomas did not. meningiomas often contained ala. 61history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer increased pme and decreased pcr were not as commonly observed with 31p mrs of brain tumors due to the large voxel sizes that would also include normal and/ or necrotic tissue and would dilute the tumor signal.169 by the mid to late 1990s most brain mrs was 1h mrs. increased tcho and decreased naa and decreased tcr are still the most reliable change in the spectra from normal to malignant brain tissue seen in 1h mrs or mrsi of brain tumors.26 in 1996 a pilot study using 1h mrs was done to see if it could distinguish between recurrent or residual brain tumor vs delayed cerebral necrosis in children following radiation therapy since this could not be done by standard imaging techniques.171 12 children were studied by 1h mrs and the results were confirmed by biopsy. markedly decreased tcho, tcr, and naa were expected to indicate necrosis and easily visible tcho and tcr was expected to identify residual or recurrent tumor tissue. biopsies were done after the spectra and mrs identified 5 out of 7 patients with tumor and 4 out of 5 patients with necrosis. the conclusion was 1h mrs showed promise for differentiating necrosis from tumor. as of 2021 this is one of the common clinical uses of 1h mrs.26 in 1996 and 1998 preul et al used pattern recognition analysis of the six most common peaks observed in 1h nmr spectra in the 1990s.172, 173 for each profile, the metabolites were plotted by connecting peak heights with a straight line in the order with which the metabolites appear in a 1h-mr spectrum from left to right: tcho, tcr, naa, ala, lac, and lipids. the most common brain tumors are gliomas, so called because they derive from glial cells. glial cells are not neurons but non-nerve cells that support the neurons of the brain. there are 4 types of glial cells: astroctyes, oligodendroctyes, ependymal cells, and microglia. the gliomas are graded i to iv in increasing grade of malignancy. sometimes a tumor will be referred to as a grade ii glioma or sometimes more specifically as a grade ii astrocytoma, or grade ii ependymoma etc; if the glial cell of origin is identified by histology. an anaplastic astroctyoma is a grade iii astroctyoma. glioblastoma multiforme is a grade iv astrocytoma. grade i to ii are low grade. grade iii to iv are high grade. figure 12. spectra of normal brain tissue (parietal white matter) compared to tumors. the increased choline and decreased or absent naa in the tumors is well demonstrated. cr is tcr, mig is myo-inositol, cho is tcho, glx is glutamate plus glutamine, naa is n-acetyl aspartate, l1 and l2 are lipids, lac is lactate, mm is macromolecules, ala is alanine which is characteristic of meningiomas.170 62 peter f. daly, jack s. cohen preul et al. reported they could correctly classify 104 out of 105 spectra which included normal brain tissue and the five most common adult brain tumors that are shown in figure 12. biopsies of the tumors were done after the spectra were obtained. they concluded 1h mrs can “enable accurate, noninvasive diagnosis of the most prevalent types of supratentorial brain tumors”.173 however, this paper did not include the spectra of other brain disorders such as abscesses, necrosis, lymphomas, and tumefactive demyelinating lesions. it was later found that brain tumor spectra can overlap with these pathologies and this overlap reduces the accuracy of 1h mrs of brain tumors to 60 to 80% and has been the primary reason mrs is not used more frequently in the diagnosis of brain tumors.26 by the end of the 1990s into the early 2000s pattern recognition techniques were being used by several groups to diagnose different types of tumors by 1h mrs or mrsi.174-176 in europe a multicenter project called “interpret” was set up to give computer-based decision support to radiologists in diagnosing and grading brain tumors. spectra were collected from 334 patients from 2000 to 2002 and used automated pattern recognition.177, 178 another project called etumour from 2004 to 2009 expanded the interpret approach.177 but these techniques have not been easy to transfer to general radiology clinical practice due to difficulty of obtaining spectra, the overlap in appearance of spectra of different tumors, and heterogeneity within the same tumor.179 current established clinical areas: the studies done from 1989 to 2010 established the areas that are most useful now for 1h mrs/mrsi in brain tumors. further studies from 2010 to 2021 solidified these areas. those areas are: 1) diagnosis, particularly of masses on the mri that can mimic primary brain tumors in appearance, 2) grading of tumors which also relates to prognosis, 3) post treatment evaluation, especially for differentiating growth of the tumor from radiation effects, and 4) treatment planning for biopsy, surgical resection, and radiation therapy.26, 180 the first 3 are used clinically and the fourth area is currently an active area of research.26 the clinically useful areas are covered by some insurers.180, 181 by 2020 it was established that elevated tcho and reduced tcr and naa in primary brain tumors are the most important observations and the most useful ratios are tcho/naa and tcho/tcr. the metabolites most used by 2021 are tcho, naa, tcr, lac, lipids, and myo-inositol.26 1) diagnosis the diagnosis of brain tumors up to 2010 has been previously discussed. from 2010 onwards more studies contributed. in the past the standard approach was first a needle biopsy of the tumor followed by surgical removal. on the mri it may be difficult to tell a brain tumor from metastatic disease, tumefactive demyelination, lymphoma, edema, abscess, or necrosis. and spectra of high-grade gliomas (hgg) can overlap with other primary brain tumors and non-neoplastic disease, so mrs is not used alone but in combination with mri and other imaging techniques this combined imaging can form a “virtual biopsy” on some, but not all, brain tumors before surgery to differentiate primary brain tumors from these other masses and the needle biopsy may not be needed.26, 182 one study on 69 adults from 2008 attempted to differentiate between tumors and their mimics by mrsi combined with perfusion imaging.183 36 of the 69 adults had brain tumors and the other 33 adults had a different diagnosis. the mrsi correctly classified 84% of the 69 lesions by using the ratios of naa/tcho, naa/tcr, and tcho and naa normalized to signals from a normal area of the brain. however, when the mrsi findings were combined with perfusion imaging the specificity increased to 92% for the correct categorization. in another study from 2006 of 32 children the specificity was 78% for correct categorization, 13 of the children had tumors and 19 had a benign lesion.164 both metastases and gliomas have elevated tcho and decreased naa compared with adjacent normal tissue. but lipids and macromolecules can appear in the 1h spectra and tend to be higher in metastases compared to gliomas.184, 185 a study done in 2013 showed an 80% specificity using this method26. this illustrates that the additional peaks in the 1h spectra of brain tumors add to the diagnosis rather than just relying on the increased tcho and decreased naa levels. gliomas often have microscopic extension into the surrounding brain tumor not seen on the mri whereas metastases usually do not. metastases tend to have a sharper border on the mri. studies published from 2004 to 2018 showed that spectra from the edematous area surrounding gliomas tend to have a high tcho/naa and tcho/tcr.184, 186, 187, 188 one study found this could discriminate a primary glioma from a metastasis with 100% sensitivity and 89% specificity.189 primary central nervous system lymphomas tend to have a lower tcho/naa ratio than primary brain tumors and lower myo-inositol.190, 191, 192 tumefac63history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer tive demyelinating lesions (tdl) overlap in appearance with primary brain tumors on mri.193 one report in 2018 found that a tcho/naa ratio of greater than 1.72 was more consistent with hggs than tdl.194 also tdl frequently has a high lac peak usually not found in untreated brain tumors.26 spectra from brain abscesses were found to be fairly distinct. in 1995 and 2004 it was published that they tend to have decreased tcho, tcr, and naa and often have signals from amino acids not seen in tumors.195, 196 similar results were found for abscesses in 2010 and 2014.193, 197 other observations made during 1989 to 2010 were that necrotic areas have low levels of most metabolites but an increased lipid signal.179 2) grading of tumors and prognosis another area of importance is whether it is a high or low grade tumor. low grade is grade i to ii, high grade is iii to iv. where high grade are the more malignant tumors. multiple studies found that the tcho level in astrocytomas correlated with the grade of the tumor. the higher the tcho level the more malignant the tumor.164, 180, 168, 198 however, in 1993 and 2003 some high grade astrocytomas were found to have low levels of tcho perhaps due to the higher grade tumors having necrotic centers179, 199 it was found in 2000 the spectrum could vary greatly depending on which part of the tumor was sampled.200 by 2009 this led to mrsi being preferable since it accounts for the heterogeneity of tumors and necrotic areas and the voxel with the highest tcho signal can be chosen for spectral analysis and biopsy.201 one study in 2007 using perfusion imaging to correlate with the spectra found there was no difference in the spectra of high grade vs low grade gliomas in areas of low blood perfusion. but in the regions with high blood perfusion, the tcho, plus the glutamate plus glutamine peak; and lac plus lipid peak, were higher in high grade vs low grade gliomas.202 low grade gliomas tend to have a modest choline elevation and a modest naa reduction and usually do not have lac peaks or lipid peaks. hggs have more noticeable change from normal brain tissue including markedly increased tcho and decreased tcr, naa, and myo-inositol.203 since decreased tcr is seen the tcho/tcr is usually higher in hggs than in low grade gliomas. the presence of lac and lipid peaks is more typical of grade iv gliomas and not common in grade iii gliomas.185 but there is still overlap in the appearance of the spectra of high vs low grade gliomas, so the use of ratios is helpful. a metaanalysis of 1228 cases in 2016 found that the tcho/tcr, tcho/naa, and naa/tcr ratios were the most helpful and had specificities in the 60 to 70% range.204 numerous papers have been published up to this time on using mrs for prognosis (prediction of survival) independent of histologic grade.205, 206, 207, 208 most papers noted a high tcho/naa ratio, and the presence of lac and lipids were associated with a shorter survival rate in adults. a related finding was also made in pediatric brain tumors. in one paper on 76 children low tcho and low (lac +lipid) levels compared to tcr were found to be a strong predictor of survival.209 2-hg (2-hydroxyglutarate) has been used more frequently since it was first seen in 2012 and it’s detection strongly indicates gliomas with isocitrate dehydrogenase mutations which tend to be low grade.162, 26 3) post treatment evaluation mrs has been found to be useful in differentiating between tumor progression or persistence versus radiation necrosis on the mri following radiation treatment.210, 211 in up to 24% of glioma patients receiving radiation therapy, radiation necrosis can develop.179 multiple publications from 1996 to 2017 showed increased tcho compared to normal brain tissue, or increased tcho/tcr ratios, or tcho/naa ratios suggested recurrent tumor; whereas reduced tcho, naa, and tcr levels implied radiation necrosis.171, 211, 212, 213, 214, 215 in addition, radiation necrosis areas frequently showed increase lipid and lac signals compared to tumors.216, 217, 218 in a meta-analysis of 447 cases published in 2014 mrs has a specificity of differentiating tumor from radiation necrosis of 83% by using the tcho/tcr ratio.219 another metaanalysis of 203 patients published in 2017 showed mrs has performed better than other radiology techniques at differentiating radiation necrosis from tumor with a sensitivity of 91% and a specificity of 95%.220 4) biopsy and treatment planning 1h mrs or mrsi was suggested as early as 2006 and 2008 to be useful in guiding the biopsies of tumors and planning the therapy based on tumor extent and aggressiveness including targeting radiotherapy.221, 222 this is currently an active area of research using whole brain mrsi.26, 168, 223 zhong et al recently used tcho and tcho/naa maps to guide surgical biopsies by targeting areas of high tcho or high tcho to naa.26, 168 (see figure 13). zhong et al also proposed mrsi maps such as these could be used in the future to plan radiation therapy, as have other studies.224, 225 a future strategy would be to treat areas of highest tcho/naa with higher dose radiation therapy. a 64 peter f. daly, jack s. cohen multisite trial was just completed and a phase ii study is being planned.226, 227 current established technical advances in mrs/mrsi a major technical advance from 2010 to 2021 was a 10-fold improvement in spatial resolution. it was recognized in 2010 that one of the major limitations of mrs and mrsi was the large spatial resolution of 1 cm3 for mrsi and 4 to 8 cm3 for single voxel mrs was a limiting factor.179 this greatly improved by 2021. the resolution in mrsi in figure 13 is 0.1 ml but new developments may soon produce 2 mm by 2 mm by 3 mm resolution or 0.018 ml voxels.168 currently it is mostly university research centers and a few clinical centers that are using mrs and mrsi for the clinical purposes discussed.154, 228 the overwhelming need for transferring already existing technology at research centers for mrsi to current non-research clinical mri machines for neuroimaging was addressed in a figure 13. upper left image: flair image of a grade ii astrocytoma with segmented volume of hyperintensity (pink outline) compared to upper right image: t1 image overlaid with an mrsi colormap of tcho/naa ratio. lower right image: outlined volumes show boundary for tcho/naa of 2x (yellow) and 5x (red). the areas of highest tcho/naa were targeted for biopsy. the upper and lower images are the same images, only the outlines are different. the tcho/naa from normal contralateral white matter was set as equal to 1.0. reprinted by permission from springer nature, reference 168, copyright 2021. 65history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer 2021 consensus statement written by multiple experts at leading research centers worldwide.154 the authors pointed out that mrsi methods on clinical mri machines have remained little changed in the past 20 years despite technical improvements over the past two decades that have greatly improved the quality of mrsi at research facilities producing the quality seen in figure 13. these improvements, primarily software updates, should bring brain mrs to the point of being an imaging modality (mrsi) and the review of the actual spectra (mrs) would be secondary. the authors pointed out they were recommending methods and uses that have already been demonstrated for neuroimaging that could be transferred to clinical practice at their current stage of development. mrsi uses smaller voxels and can sample areas of the brain that single voxel spectroscopy cannot. the consensus group also reviewed the use of 7t mri machines for spectroscopy although these machines are currently at research centers only and not at standard clinical radiology departments. the mrsi shown above (figure 13) is from a 3t mri.168 while most clinical mri scanners are 1.5t, commercial 3t scanners are becoming more common at both research and clinical mri centers229. these higher field magnets greatly improve the speed of acquisition and resolution of mrs and mrsi. there are already many 7t mri scanners at research centers and in 2017 clinical 7t mri scanners were cleared for clinical use in both europe and the usa.230 these improvements should lead to further expansion of the reimbursement from more insurers for brain mrs and mrsi than currently exists.180, 181 prostate and breast cancer mrs/mrsi in addition to brain tumors, prostate and breast cancer are the other cancers that have received the most interest. but brain masses have had the most clinical success. this is due both to the nature of brain masses and technical facility. multiple tumors can metastasize to the brain and on mri there are multiple tumor mimics and mrsi combined with mri is often the best method for diagnosis short of biopsy. multiple metabolites can be seen, making mrs more useful; and both the skull and the highly sensitive nature of brain tissue make biopsy and surgery a much higher risk. also, it is technically easier to do mrs/mrsi on the brain as it is a large organ compared to the prostate, the ability to keep the head still in a comfortable position with an mrs head coil and avoid motion artifacts due to breathing is a major advantage; and brain tumors tend to be fairly large at the time they are found. the first 1h spectra of prostate cancer using a transrectal probe was published in 1990 and showed a high citrate peak in normal prostate, and a low citrate peak in prostate cancer.231 the first in vivo 31p mrs of prostate cancer was published in 1991 and showed a high pme peak and pcr peak.232 by 1996 three dimensional mrsi of the prostate with 0.24 to 0.7 ml voxels was done and multiple papers had been published showing a high tcho level and low citrate level in prostate cancer compared to normal prostate tissue.233 the high tcho/citrate ratio in prostate cancer is analogous to the high tcho/ naa ratio in brain tumors where tcho is a marker of malignancy and low citrate is a marker of lack of normal prostate cells. by 2012 the european society of urogenital radiology (esur) was endorsing mrsi of prostate cancer as part of mpmri studies of the prostate for diagnosis after relapse and for judging tumor aggressiveness and monitoring treatment response. however, they also pointed out that dwi did the same thing.234 by 2020 mpmri involving t1, t2, dwi, and dce (dynamic contrast enhanced) imaging was in common use but mrsi was not.235 much of this had to do with technical difficulties including the use of an endorectal coil and the fact that dwi had turned out to be quicker, easier, more reproducible, and could give the same information for diagnosis, judging aggressiveness, and monitoring of therapy due to the highly cellular and unusually dense nature of prostate cancers that severely inhibits diffusion of water.236, 155 however, further technical developments in mrs and mrsi such as avoiding an endorectal coil will likely make mrsi of the prostate useful and are still being studied.234, 155 by 1988 1h and 31p mrs of human breast cancer in vivo were published. the 31p spectra showed high levels of pmes, pdes, atp, and pi compared to normal tissue and these peaks reduced with successful treatment. the 1h spectra showed a high water to fat ratio for the tumors of 2.2 but only 0.3 on average for normal breast tissue.237 and by 1989 more publications appeared describing the use of 31p nmr spectroscopy for monitoring breast cancer treatment in vivo.238, 239 these papers noted both the increased pmes in tumors and their decrease with treatment. by 1991 extracts of surgically removed tumors showed the broad pme region was predominantly pc and pe and the pde region was mostly gpe and gpc as had been found in tumors in nude mice and cell studies.16 although many studies were done in the 1990s of breast tumors by 31p mrs240, 241 by the early 2000s most spectra were 1h mrs, since it could be performed on a tumor one tenth the size and analysis of multiple 1h mrs studies showed a sensitivity of 83% and a specificity of 85% at detecting breast 66 peter f. daly, jack s. cohen cancer based on the tcho peak. the specificity rose to 92% if 1h mrs was combined with mri.242 unlike brain and prostate there is not an additional metabolite in the breast 1h mrs spectra as a marker for normal tissue similar to citrate or naa so the determination is based almost solely on tcho. also, there are technical problems caused by very large fat peaks in breast tissue not found in prostate and brain spectra.156 a 2014 review pointed out that the development of mrs for breast cancer lagged behind the developments of mrs for brain and prostate but still felt it should be useful for diagnosis and monitoring of therapy.243 but by 2019 the conclusion was still that mrs of breast tumors was “promising” and “proven to have a role in clinical care” but further work was needed in improving the technique.244 to date mrs is not reimbursed by insurers for either prostate or breast cancer and is still considered experimental.180 future trends in phospholipid research and cancer one obvious area for future exploration is the role of the ethanolamine kennedy pathway in cancer metabolism. most tumors have large amounts of pe in them, often more than of pc, but this area has not been well studied biochemically or in mrs, and ethanolamine kinase-1 is found to be elevated in breast and prostate cancer cells.245 in addition, the degradative pathways for both ptdcho and ptdeth have not been as well studied although these pathways are involved in some of the production of pc and presumably pe as well as producing second messengers involved in cell growth. and these enzymes may also be a target for therapy in addition to ck or in combination with ck inhibitors.18, 49 and as discussed earlier, work continues on the development of ck inhibitors119 and using mrsi of brain tumors for guiding biopsy and treatment and for prognosis.26 another area that is developing is the use of 1h mrs ex vivo on biopsy tissue or tumor tissue removed at surgery by high resolution magic angle spinning (hrmas). as the name implies hr-mas involves placing tissue in a tube that is then spun at a specific angle calculated from nmr physics that results in improved signal to noise and higher resolution allowing many more metabolites to be seen than in vivo mrs.246, 247 in addition, chemical exchange saturation transfer (cest) and hyperpolarized 13c are being studied.49 certainly, any future as yet undiscovered physical technique for in vivo mrs/mrsi that can greatly increase the signal to noise level will have a profound impact. choline pet is being explored for use in hepatocellular carcinomas248 and in hyperparathyroidism.249 hepatocellular carcinoma is slow growing and, like prostate cancer, does not avidly take up fdg for pet scanning. hyperparathyroidism often involves nodules of parathyroid tissue which can be difficult to localize but show up well on choline pet scanning and the technique has been shown to be useful in a recent meta-analsis.249 while this is not intended to be a definitive list of all the future areas of research involving choline metabolism and choline mrs/mrsi, even a cursory review of the literature shows this to still be a very rich area for research. conclusion the sine qua non of medical research is the ability to go from “bench to clinic,” from basic research in the laboratory to the application to human healthcare. the 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how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 5(2): 97-120, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1312 citation: kenndler e. (2021) tit capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. substantia 5(2): 97-120. doi: 10.36253/substantia-1312 received: may 10, 2021 revised: jun 15, 2021 just accepted online: jun 16, 2021 published: sep 10, 2021 copyright: © 2021 kenndler e. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler institute for analytical chemistry, faculty of chemistry, university of vienna, vienna, austria e-mail: ernst.kenndler@univie.ac.at abstract. this review is the first in a series that deals exclusively with electrophoresis of ions. since in modern terminology “electrophoresis is the movement of dispersed particles relative to a fluid under the influence of a spatially uniform electric field”, electrophoresis is not limited to colloidal particles, it includes ions as well. the history of electrophoresis of ions therefore begins in 1800 at the same time as that of electrolysis, because the two phenomena are so inextricably linked “that one cannot happen without the other” (faraday, 1834). between 1800 and 1805 about half a dozen different theories of electrolytic decomposition and the movement of the particles – for which we coin the term electrophoretic current – were formulated, all contributing to the discourse, but lacking consistency and none fully convincing. they are discussed nonetheless because most of them fell into oblivion, even though they are interesting for historical reasons. however, from 1805/1806 the predominant theory, formulated by theodor von grotthuß and independently by humphry davy assumed that polarized molecules of water or dissolved ions form chains between the two electrodes. only the terminal atoms of these chains were in direct contact with the electrodes and were liberated by galvanic action, but are immediately replaced by neighboring atoms of the same type. this decomposition and recombination of the molecules driven by electric forces which follow the “action at a distance” principle like in coulomb´s law takes place over the entire chains; they represent the electrophoretic current. however, in 1833 michael faraday refuted all previous theories. two of his groundbreaking findings were of particular importance for the electrophoresis of ions: one was that electricity consists of elementary units of charge. the ions thus carry one or integer multiples of these units. the other was the revolutionary theory of the electric lines of force in early 1840s, and of what was later called the electric field. with these findings faraday fundamentally changed the previously prevailing view of the electrophoresis of ions. keywords: ion electrophoresis, history, action at a distance, lines of electric force. http://www.fupress.com/substantia http://www.fupress.com/substantia 98 ernst kenndler 1. introduction while the discovery of three phenomena electrolysis, electrophoresis of colloids and electroosmosis was discussed in part 1 of our historical review about capillary electrophoresis[1] the present part 2 will focus on the ensuing studies of the electrophoresis of ions, along with the inextricably linked electrolysis. historic sources reveal that electrophoresis was discovered by nicolas gautherot in 1801[2] and independently by ferdinand friedrich von reuß in 1807. [3, 4] however, both discoveries have in common that the experimenters observed the motion of colloids and coarse granular particles, dispersed in water, when the electrodes of a voltaic pile were dipped into the dispersion and the electric circuit was closed. the large size of the particles enabled the observation of the particle ś movement by naked eye. yet, this was one of the reasons why electrophoresis has been attributed to particles of this relatively large size over more than a century after its discovery. it is to note that iupac also shares this view and recommends that electrophoresis is “the motion of colloidal particles in an electric field”.[5] but this view fell short and was for good reasons expanded since nearly one century to ions, small charged particles of atomic or molecular size. at this point it is emphasized that colloids do not differ from ions only by their size, but also by their structure.1 notwithstanding this difference, the updated and more generalized definition of electrophoresis currently agreed by the majority of the scientific community reads that “electrophoresis is the movement of dispersed particles relative to a fluid under the influence of a spatially uniform electric field”.2 according to this definition, electrophoresis encompasses a general principle.3 1 electrophoresis of colloids, as well as electroosmosis, belong to the class of electrokinetic phenomena. colloids, to be precise, colloidal particles, are an own phase in a second phase, they form heterogeneous dispersions, in which the two phases form an electric double layer at their interphase. ions, in contrast, form homogeneous solution with the continuous medium in which they are dissolved. 2 in our text, we usually added the adjective “charged” to the term “particle” as it facilitates its reading. however, this is not required and the adjective “charged” can be omitted. the reason is that an uncharged particle can move under the influence of a field by electroosmosis, but in this case it does not move relative to the fluid but just like the fluid. when the motion of an uncharged particle is caused by diffusion or convection, it does move relative to the fluid, but not caused by the electric field. only a charged particle will definitely move in the field relative to the fluid due to the electrical force acting on it; therefore, the addition of the adjective is needless. 3 we think that it is necessary to account for this wider view of electrophoresis, since it is at present mainly considered as a separation method only. in contrast, we endorse the above cited general definition (see. e.g. refs. [6] and [7.). it should be noted that this definition with regard to this broader view at electrophoresis, reference is made to the more detailed discussion in part 1 of this series. does this generalizing definition of electrophoresis lead to a dilemma concerning the date of its discovery? it was already inferred on the occasion of electrolysis in 1800 that dissolved ions migrate in their solutions under the influence of an electric field. this finding clearly corresponds to the criterion of electrophoresis. in contrast to colloids or coarse granular particles the motion of ions could not be directly followed visually due to their small size, but their migration and the direction in which they move had been proven indirectly from their concentrations close to the electrodes and their decomposition products which were formed by the simultaneous electrolysis process. contemporary researchers therefore concluded that ions undoubtedly also move by what we call electrophoresis, at the same time when electrolysis occurs. we therefore consider the commencement of electrophoresis, strictly speaking the electrophoresis of ions, to be the day when william nicholson and sir antony carlisle split water into gaseous hydrogen and oxygen by electrolysis[8, 9] with the newly discovered galvanic electricity.4 for william cruickshank the migration of the parts of the decomposable “body” and their perplexing occurrence at the separate poles was a “mysterious” phenomenon, for humphry davy ”the agency of galvanism is at present involved in obscurity”, and this unintelligible effect provoked an intense research of its causes. the entire first series of our historical retrospect focuses exclusively on ions in solutions. this series about ions consists of this and of following articles and covers the period between 1800 and the end of the long 19th century in 1914,5 or what we termed in part 1 the 1st applies to all dispersed particles, from the smallest inorganic ions up to viruses, bacteria and cells. moreover, in none of the definitions or recommendations electrophoresis is limited to separation methods. note that neither gautherot nor von reuß, the classical discoverers of electrophoresis, carried out separations. so we find no sound reason not to base the view on electrophoresis on the general principle outlined above. in this sense electrophoresis is not a separation method, but can be utilized as such. 4 we briefly mention that a different terminology was used in the original documents compared to the current ones. even the term electrophoresis was unknown until the short 20th century. in the present article we use – ahistorically – the modern terminology, but occasionally also the contemporary one of the original works, for instance when we quote verbatim. “pole”, i.e., was substituted by “electrode” not until 1833. 5 we borrowed the term long 19th century from eric hobsbawm’s trilogy on european history between the french revolution in 1879 and the begin of world war i in 1914. it is the same period of time, in which all the main principles and theories of electrophoresis were already known, but – surprisingly – no attempts were made in this “1st epoch” to use them for a separation method; see part 1.[1] 99capillary electrophoresis and its basic principles in historical retrospect. epoch of electrophoresis. we repeat that the electrophoresis of colloidal particles is not included, since its history cannot be told without that of the ions. a historical retrospect of electrophoresis of colloids, together with that of electroosmosis, will be the topic of a future separate series of articles. the narrative in the present part 2 of this series about ions spans the period from the discovery of electrolysis in year 1800 to the 1840s. in those 1840s, michael faraday overthrew the hitherto established concept of the action at a distance by the introduction of the groundbreaking theory of the lines of electric force or lines of action (later called field lines of the electric field). one would expect this part 2 to continue with electrophoresis only. however, it is inevitable to consider that the theories of electrophoresis would have remained in the dark without the results obtained by electrolysis. indeed, one can argue that the theories about electrophoresis had their roots in the conclusions drawn from the experimental results of electrolysis. before we begin the historical review of the development of electrophoresis, we would like to mention briefly that almost all technical terms, with the exception of galvanic electricity, which have been used so far in this text, were unknown at this point in time. moreover, the term electrophoresis remained unknown even during the long 19th century. still, we find it useful to coin a new term in the present part. our motivation is that in the early literature the complete electrical current flowing during electrolysis was expressed by many different and ambiguous phrases such as “the flow …, the transmittance …, the transfer …, the transmission of electricity, ... the transport of galvanic electricity” and several others. however, this complete current consists in two different forms. the galvanic current is the current of electrons in the metallic conductors of the circuit, and differs principally from the flow of charges which are carried by the dissolved ions. hence, we think we have every reason to merge the various historical and confusing expressions for the flow of the charges by ions in solutions into the single and unambiguous term electrophoretic current .6 this term is not usual, but it is to the point, and is full in line with the definition of electrophoresis. 6 we coin the term electrophoretic current analogue to the term galvanic current. we mention, however, that we are not consistently replacing the various terms used at that time by electrophoretic current. we replace them when it is appropriate in the context. 2. how does electricity flow through water or through solutions of compounds dissolved therein during their decomposition? in the beginning of research in the effect of galvanic electricity on water7 and its electrolyte solutions, researchers in britain dominated this area for the first two years after its discovery. admittedly, their investigations were rather directed on the chemical transformation of the constituents of the liquid at the electrodes by electrolysis than on the f low of the electric current through the liquid. their findings were published mainly in nicholsoń s journal,8 which served them as a kind of “central organ”. this can be said considering the remarkable large number of the appropriate papers in volume iv from 1801, which was the first to publish articles on this subject. the title page of this volume of historic merit is shown in figure 1. it was the volume where william nicholson reported the discovery of the decomposition of water by galvanic electricity.[9] in addition, in the same volume william cruickshank proposed a first theory of electrolysis and – please note – the inextricable linked transport of electrified particles of atomic size in solution between the poles.[11] 2.1 september 1800: the first theories by william cruickshank and by johann wilhelm ritter 2.1.1 w. cruickshank´s theory of the oxygenated and the deoxygenated electric fluid william cruickshank, a friend of nicholson,9 was the first who reported his investigations on the present 7 it is important to realize that through the period under consideration water that was used for the experiments was never pure, but was always contaminated with impurities. even when it was distilled, it certainly contained electrolytes. water with highest purity was first obtained around 1890 by adolf heydweiller, a coworker of friedrich kohlrausch, after fiftyfold distillation under vacuum in a quartz apparatus. we mention this fact because the detailed process of the electrolytic decomposition of water depends on its purity, and on the kind of the contaminants or on the intentionally added compounds such as acids, bases or salts. acidulation, for instance, increases the speed of the generation of the gases. in this context, faraday stated in 1834 that “even water itself, which so easily yields up its elements when the current passes, if rendered quite pure, scarcely suffers change, because it then becomes a very bad conductor”.[10] 8 this periodical journal was founded in 1797 and published by william nicholson entitled journal of natural philosophy, chemistry & the arts. it was commonly called nicholson´s journal, and merged in 1814 with the philosophical magazine to the philosophical magazine and journal, later named the philosophical magazine. please note the combination of natural philosophy, chemistry and arts at the time. 9 there is not a very detailed record of william cruickshank`s life. he was born in north-east scotland in the 1740s or 1750s. known is that in 100 ernst kenndler topic, remarkably as early as july 1800 in nicholson ś journal.[11] cruickshank began his experiments by repeating those of nicholson and carlisle, albeit with another device. briefly, he used a horizontally placed glass tube, completely filled with water, with both openings closed with cork stoppers.10 then he inserted wires made from silver through the corks at each end into the water and connected them with a voltaic pile composed from plates of silver and zinc. after completing the cir1765 he received his master from king’s college in aberdeen and later a diploma from the royal college of surgeons of england. in 1788 he got a position as assistant at the royal military academy, and as lecturer in 1796 until 1804. he died in 1810 or in 1811 in scotland. in addition to his first theory of the decomposition of water, he invented the trough battery.[12] 10 unfortunately, in the original paper in nicholson´s journal the drawings of the devices were not printed, because cruickshank missed the deadline to submit them. their schematic reproductions are found in the comprehensive and detailed study about electricity from 1751 till 1807 by amy alice fisher.[13] cuit, he observed that gases were evolved at the two poles, with hydrogen at the silver wire and oxygen at the zinc wire.11 in addition, he observed corrosion of the zinc wire. upon adding a tincture of litmus or brazil wood, and carrying out the experiment again, he observed that at the zinc wire the water became acidic, at the silver wire alkaline, effects that were noted also by others. he decomposed also “metallic” solutions, that are solutions of salts of metals. with silver dissolved in nitrous acid he got a precipitate of needle-like crystals in the form of arbor dianae.12 in the same paper he tried to find out how far the influence of galvanic electricity is reaching. to this end, he connected two tubes described above for their communication by a silver wire, a 1st class conductor, that was passed through a cork of each tube. after closing the circuit, he observed the usual corrosion or disengagement of gases at the poles, what convinced him that an even greater number of tubes connected in series would give a similar result. in the subsequent article in the issue of september 1800,[14] cruickshank addressed that significant problem which was incomprehensible since its discovery: the occurrence of the individual gases in the water at the two different poles when galvanic current is applied. to attempt to solve this, cruickshank used single tubes as described above, and carried out a series of quantitative measurements of the gases which evolved under various conditions. based on his findings he formulated the first theory of the transport of the particles which were decomposed during electrolysis (ref. [14], pp. 257, 258). for water as liquid, cruickshank hypothesized that the “galvanic influence (whatever it may be) is capable of existing in two states, that is, in an oxygenated and deoxygenated state”. since its affinity for oxygen is weaker than for solid metals, cruickshank assumed that upon 11 one has to differentiate cruickshank´s designation of the metals of the wires inserted into the liquid in which decomposition occurs, on the one hand, and of the plates of the voltaic pile, on the other hand. this terminology was later used by others, but not by everyone. cruickshank, who applied the common configuration of the pile, which was made from plates of silver and of zinc, did not define the poles as positive or negative. he stated instead; “in future, to avoid circumlocution, i shall call the wire attached to the silver plate, the silver wire, and the other the zinc wire.” this terminology did not define the metal of the wire (e.g. gold, silver, platinum, iron, etc.), which was occasionally used as pole immersed into the liquid under study, it refers to the metals of the pile`s plates onto which the wires were attached. we will italicize these wires regardless of their metal. in the present example, it could be confusing because both wires consist of silver. 12 arbor dianae, lat. tree of diana, also philosopher’s tree, lat. arbor philosophica, the silver tree, is formed when silver is precipitated from a silver salt solution by reduction. it has a shape like a tree, and consists of crystals of silver or silver amalgam. these trees were named by alchemists relating to the name for silver, diana. figure 1. title page of the remarkable volume iv of journal of natural philosophy, chemistry and the arts, called nicholson’s journal. in this volume from 1801, in the six issues from july to december 1800 the notable number of 13 papers (out of a total of 58) were published which exclusively dealt with galvanic action. 101capillary electrophoresis and its basic principles in historical retrospect. the deoxygenated “galvanic influence” (probably somewhat like a galvanic electric fluid) from the silver wire enters the water, disrupts it into its components and seizes the free oxygen, whereby hydrogen gas is segregated. then, the electric fluid, together with the oxygen, passes the water to the opposite pole, where the oxygen is transferred to the zinc wire, and is released as a gas. eventually, after transmission of the oxygen, the deoxygenated electric fluid flows back to the pile. note that cruickshank believed that the two evolving elements came from the same water molecule. in case that the interposed liquid is a solution of a salt from a metal, the deoxygenated electric fluid passes from the silver wire, seizes the oxygen of the metal calx, transports it to the zinc wire, where oxygen is released and the deoxygenated electric fluid enters the metallic pole. yet, cruickshank recognized the somewhat inconsistent suppositions of his theory, and finally conceded: “in ref lecting on these experiments it would appear, that (….) the water must be decomposed; but how this can be effected, is by no means so easily explained. for example, it seems extremely mysterious how the oxygen should pass silently from the extremity of the silver wire to that of the zinc wire, and there make its appearance in the form of a gas.” (ref. [14], p. 257; note the attribution “extremely mysterious.”) in the aforementioned vol. iv of nicholsoń s journal also other researchers, e.g. william henry, col. henry haldane and humphry davy reported the electrolysis of water, and all agreed that water is a compounded body, composed from about two parts of hydrogen and one part of oxygen. however, one researcher, johann wilhelm ritter from jena in germany, one of the most passionate followers of the romantische naturphilosophie (romantic nature philosophy),13 was strictly convinced that water was an undecompounded body, a chemical element. 2.1.2 september 1800: j. w. ritter’s theory of the metamorphosis of water by galvanic action johann wilhelm ritter was the opponent of the current hypothesis of the electrolysis of water (please pay heed to footnote 14) he believed that water does not 13 ritter was strongly influenced by friedrich wilhelm joseph schelling, the main philosopher of the romantischen naturphilosophie “the romantic nature philosophy considered the human being as a whole in the system of nature. philosophy provided a system of thought from which the events of nature observation can be read.” transl. from ref. [15], p. 23. 14 johann wilhelm ritter (1776, (samitz (zamienice) near haynau (chojnów), silesia 1810, munich) was a german physicist (initially decompose under galvanic action and therefore formation and migration of ions do not occur. that may sound like a paradox, taking into account that he was the first researcher in germany who experimentally fractionated water into gaseous hydrogen and oxygen using galvanic electricity. we find him noteworthy in the present historical retrospect not only because he pioneered the research in galvanism in germany (together with theodor von grotthuß, see below), but also, due to his outstanding and unusual personality in the scientific community. he was a somewhat strange person of vivid imagination, unusual mental agility and seemingly borderless inventive creativity.15 humphry davy, for example, characterized ritter ś person and activities in his bakerian lecture in 1826 (ref. [21], p. 385) as follows: “ritter’s work contains some very ingenious and original experiments on the formation and powers of single galvanic circles; (….) : and in the obscurity of the language and metaphysics (…..) , it is difficult to say what may not be found. in the ingenious, though wild views, and often inexact experiments of ritter, there are more hints which may be considered as applying to electro-magnetism than to electro-chemistry, … ”. without having a regular income, ritter began his research, notwithstanding the problems of getting access to the current literature sources in jena16 where he conducted his scientific and philosophical studies.[24] he carried out his experiments knowing only how to put a voltaic pile together, but without having knowledge of comparable experiments that were already done. nonetheless, he was able to complete his investigations and to publish his results as early as in september 1800,[25] remarkably just two months after nicholson and carlisle, and at the same date when davy had completed his first experiments on this subject albeit under relevantly better conditions. in his first experiments he subjected water to galvanic action with a simple, self-made device, and measured quantitatively the volumes of the two gashe was an apothecary), philosopher and an extraordinarily multifaceted personality. he can be considered as an outstanding scientist, but till at present time he is quite underestimated. without never getting a position at a university (he only became member of the bavarian academy of science in 1804, see his portrait in figure 2) he contributed as autodidact to galvanism, e.g. by the independent discovery of the electrolysis of water in september 1800. in the course of these experiments, he invented electroplating. he discovered uv-radiation in 1801,[16]. and invented the dry cell battery in 1802. ritter built the battery from 600 zinc-copper plates. it reached a potential of more than 700 volt. in the last years of his live his interest turned, influenced by the german theosophist franz xaver von baader, to siderism and radiesthesia..[17],[18],[19]. he died in poverty at the age of 33 by tuberculosis. 15 the character of the protagonist is borrowed from the real person johann wilhelm ritter in the novel “die unglückseligen” (the unfortunate ones) by the german woman writer thea dorn.[20] 16 see e.g. his letter to horkel.[23] 102 ernst kenndler es which were separately generated at the electrodes by collecting them in two tubes after closing the circuit.17 although ritter identified the two gases as oxygen and hydrogen in roughly the correct proportions of one to two and a half volumes, he asked himself the same question that british researchers did, namely “kann sich aber das nemliche atom wasser in einem und dem nemlichen augenblicke zugleich an diesem und wieder an jenem drathe befinden ? – und doch müßte das der fall seyn , wenn beyde gasarten , beyde stoffe, das oxygen und hydrogen , von einer wirklichen zersetzung des wassers herrührten.” (but can the same atom of water be on this and on that wire at the same moment? – and yet this would have to be the case if both types of gas, both substances, oxygen and hydrogen, resulted from a real decomposition of water.) ritter could ignore this problem because he believed that water was an element and not a molecule. he was 17 a drawing of this device is depicted on p. 372, (fig.3, tab.v) of voigt´s magazin, ref. [25].. the complete name of this little-known journal was magazin für den neuesten zustand der naturkunde mit rücksicht auf diedazu gehörigen hilfswissenschaften, herausgg. von johann heinrich voigt. convinced that the collected hydrogen and oxygen were not decomposition products of water, but they were still water which was transmuted into other forms. as a proof for his conviction he filled a v-shaped glass tube (depicted in figure 3) halfway with concentrated sulphuric acid, and covered the acid meticulously on both side pieces with distilled water, taking care to avoid any mixing of the two liquids.[25] the acid was intended to act as a barrier to prevent the transfer of water or of its components through the acid and thus to the opposite side piece. to this end he selected concentrated and rectified sulfuric acid after testing that it did conduct electricity,18 but did not evolve even a trace of gas under the action of galvanic electricity. ritter dipped one pole through the one, the other pole through the other opening of the tube into the water, completed the electric circuit, and observed the immediate and separate formation of gaseous hydrogen and oxygen at the individual poles (a and b in the original “fig. 15”) without any gas showing anywhere else in the tube between a and b. after he had executed several similar experiments and obtained the same results; he concluded (p. 390) “so ist es also durch versuche nun nicht bloß auf das vollständigste erwiesen: daß die bey der einwirkung des 18 the conscientious experimenter michael faraday found the very reverse and explained “681. on experimenting with sulphuric acid, i found no reason to believe that it was by itself a conductor of, or decomposable by, electricity” and continued “when very strong it is a much worse conductor than if diluted”.[10]. this comment suggests that ritter’s sulphuric acid still contained traces of water. figure 2. portrait of johann wilhelm ritter, wearing the uniform of the bavarian academy of sciences. about 1804. unknown artist. taken from ref. [22]. figure 3. the v-shaped glass tube with side pieces of 2 german inches (i.e. about 3 cm) in length was first filled halfway with pure concentrated sulphuric acid. the acid was then overlaid with distilled water, into which the two poles a and b were dipped. the poles, made from gold, were connected with the voltaic pile. taken from ref. [26], after p. 326, taf. 1, fig. 15. 103capillary electrophoresis and its basic principles in historical retrospect. verstärkten galvanismus auf wasser erzeugten beyden gasarten, das hydrogen wie das oxygen, keinesweges von einer sogenannten zersetzung des wassers herrühren können, sondern überdies noch: daß auch die erzeugung jeder einen gasart ein proceß sey, der ganz und gar nicht mit dem der erzeugung des anderen zusammenhänge, sondern daß, beyde durchaus unabhängig voneienader, und einzeln, statt haben können.” (thus, it is not only proved to the most complete extent by experiments: that the two types of gas, hydrogen and oxygen, produced by the action of the amplified galvanism on water can´t at all result from a so-called decomposition of water, but, moreover, that the generation of each type of gas is also a process which is in no way connected with that of the generation of the other, but that both can take place entirely independently of one another and individually.) these results convinced ritter once and for all to have demonstrated that water on both sides was in fact independently transmuted by a kind of metamorphosis into another modification by electricity, but not decomposed.19 he took this result as evidence that oxygen is water minus electric fluid, and hydrogen is water plus the electric fluid, but they still remain elemental water. a severe disadvantage to follow ritter’s argumentation was his circuitous and protracted style of writing, which was very difficult to understand even for native speakers. this peculiarity was communicated by the anglo-irish physician and mineralogist william babington20 in a letter dated december 1800, entitled “on the state of galvanism and other scientific pursuits in germany” and printed in nicholsoń s journal.[27] nevertheless, von grotthuß acknowledged ritter (ref. [28], p. 113) that he – although he never graduated from university – possessed the ability and acumen to refute all theories proposed prior to 1805 about the flow of electricity during the electrolysis of water (see ref. [29]). 19 ritter carried out all these experiments in jena within days, namely from september 28 to 30, 1800. 20 william babington (1756, portglenone near coleraine, irland 1833) reported, for instance, in his letter to the editor: “…the principal galvanic discoverer here is a young man, called ritter, at jena, in saxony: about two years since he published the result of his almost innumerable experiments, in which he established all its laws, and anticipated almost all the newer experiments. unfortunately the book was written very obscurely, and was still more obscured by the language of the newer philosophy. ….. this suggested to him to interpose some substance between the extremities of the wires, which was at the same time capable of conducing the galvanic influence, and of remaining perfectly unaltered by it. …. thus it is proved, that water under certain circumstances, may be wholly converted into oxygen gas, and under others, into hydrogen-gas; the rationale of this phaenomenon is as yet in obscurity”. the present author illustrates his intricate and circuitous style by one example taken from pages xxi and xxii of his book about siderism: one single sentence, which is composed of many subordinate clauses and nested sentences, consists of the remarkable number of 297 words.[17] ritter published his theory in september 1800, at exactly the same date as cruickshank. so there are two philosophers who could have claimed priority, although their theories could not be more different, but the credit goes to only cruickshank. only his theory deals with the motion of particles, a criterion of electrophoresis. however, in the end, cruickshank ’s theory as well as ritteŕ s theory of the “einfachheit des wassers” (“elementariness of water”)[24, 30] soon failed due the investigations of davy, von grotthuß, and others. 2.2 other theories from 1800 till 1805 in autumn 1800 humphry dav y, too, wondered whether the formation of oxygen or hydrogen gas took place when the water is filled into separate vessels (each connected to the pile with a wire). the water was not in direct contact in davy ś experiments either, but in contrast to one of cruickshank ś devices (in which the two tubes were connected by a silver wire), it communicated through 2nd class conductors.[31] first, davy closed the electric circuit by dipping the fingers of his right and his left hand into the water in the separate vessels, and observed the disengagement of gases at the poles. the gases were also generated when communication was through three persons, or by connecting the two vessels with muscular or living plant fibers, respectively, or with moistened thread, all acting as 2nd class conductors. this result led him to conclude that not only galvanic current in the metallic wires, but also the flow of the current by electrified bodies in the connecting wet organic matter enabled the communication of the water in the separate vessels. davy investigated, in addition to that of water, the electrolysis of aqueous solutions of various acids and bases. he found, among other effects, that pure hydrogen was always generated at the one pole, but at the other pole oxygen was either released as gas or it oxidized the metal of the wire. he published his results between september and december 1800 in three papers in the notable vol. iv of nicholsoń s journal mentioned above.[31-33] nevertheless, af ter having executed numerous experiments davy restrainedly summarized in december 1800 his attempts to clarify these difficult to understand invisible motion through water and other menstrua. he stated (ref. [33], p.400) “many new observations must be collected, probably before we shall be able to ascertain whether water is decomposed in galvanic processes. supposing its decomposition, we must assume, that at least one of its elements is capable of rapidly passing in an invisible form through 104 ernst kenndler metallic substances, or through water and many connected organic bodies; and such an assumption is incommensurable with all known facts.” it is worth noting that at the turn of 1800 to 1801 in germany four researchers independently realized that the order of the metal plates on the voltaic pole built by earlier philosophers was misleading. in the past, the pile was composed of plates of zinc (z) and silver (a) with an interposed wetted layer (w) in the sequence [-szwszw… szwsz+]. but k. w. böckmann,[34] a. von arnim, who entitled his paper “über die benennung der endpole der voltaische säule“ (on the designation of the end poles of the voltaic pile),[35] p. erman[36] and w. gruner[37] discovered that the proper sequence of the pile should be [-zwszws...zws+], which is obtained by omitting the zinc and the silver plate, respectively, at the two extremities of the earlier pile.21 we can especially recommend reading the expounded and informative comments of the highly competent editor of ann. phys., ludwig wilhelm gilbert, on ermań s[38] and on von arnim ś[39] contributions.22 however, at the european continent several other theories of electrolysis and the electrophoretic current were formulated in these years. this happened for the most part in germany, france, italy, and in sweden. in germany, among others, paul ludwig simon (1771 1815, berlin), professor at the building academy in the faculty of architectural physics in berlin,[40, 41] and christian heinrich pfaff, professor of medicine, physics and chemistry in kiel,[42] stepped forward with theories of the action of electricity on water which are not going 21 karl wilhelm böckmann (also boeckmann) (1773 1821, karlsruhe), physicist and chemist, professor for physics. (carl joachim friedrich ludwig) “achim” von arnim (1781, berlin – 1831, wiepersdorf ), göttingen. paul erman (1764 1851, berlin), professor for physics in berlin. johann ludwig) wilhelm gruner (1771, halle on saale – 1849), court apothecary in celle. 22 in von arnim´s paper gilbert (1769, berlin – 1824, leipzig) wrote as a part of a comprehensive comment somewhat caustically: “… wenn also nicholson seine voltaischen säulen auf folgende weise errichtet: s., z., fl., s., z., fl., s....z., fl., s., z., so sind die erste silberund die letzte zinkplatte der säule offenbar überflüssig und nicht als glieder der galvanischen ketten, sondern bloß als ein willkürlich hinzugefügter metallleiter zu betrachten, der, ohne etwas zu ändern, so gut fehlen als da seyn kann. nach ihnen den ersten pol den silberpol, und den letzten den zinkpol zu nennen, wie man es bisher gethan hat, ist daher gewiß unschicklich und verwirrend, ... “ (so if nicholson builds his voltaic pile in the following way: s., z., fl., s., z., fl., s....z., fl., s., z., the first silverand the last zinc plate of the pile is evidently superfluous but to be considered merely as an arbitrarily added metal conductor, which can be lacking as well as be present, without changing anything. terming the first pole the silver pole and the last the zinc pole, as has been done thus far, is therefore certainly improper and confusing. ... ). [fl. stands for the wetted layer; the author]. to be discussed further.23 in france a. f. fourcroy, l.n. vauquelin and l. j. thénard24 published a number of papers in magasin encyclopédique, ou journal des sciences, des lettres et des arts. in 1800 and 1801. in 1801 citoyens fourcroy and vauquelin hypothesized the circulation of the electric fluid from the positive to the negative pole. they assumed that this fluid decomposes water at the positive wire, where oxygen is released as gaseous bubbles. there, the positive fluid combines with hydrogen, and the combined hydrogen is transported unseen by an assumed fluidum deferens, the galvanique, to the negative wire. the galvanique enters this wire, whereupon the hydrogen is evolved as gas bubbles.25 an “electric acid ” (“l´ossielettrica”), an expansive liquid with fineness like heat and light, smelling similar to phosphorus, and tasting pungently was conjectured in 1800 by luigi valentino brugnatelli (1761 1818, pavia), professor of chemistry in pavia, italy, and friend of volta.[44, 45] according to his theory, the electric acid easily enters the metals, and dissolves them – such as water dissolves a salt – as soon as it is set in motion (“quando l ósielletrico é in moto”). it is soluble in water, and in such a dissolution most metals are oxidized at the expense of water, whereupon hydrogen is formed through decomposition. the metal oxides formed by this reaction combine with the electric acid under formation of metal électrates (“osielettrati”). for example, the électrate of copper is green, that of silver is white, both are transparent and insoluble in water. their most pronounced capability is that they can be carried away through the water by the electric acid over comparably long distances. finally, the électrates are precipitated at the metal of the pole as salt-like crusts.26 23 paul ludwig (also paul louis) simon (1771, berlin – 1815, berlin); christoph heinrich pfaff (1773, stuttgart 1852, kiel). 24 antoine françois, comte de fourcroy (1755 1809, paris); louis-nicolas vauquelin (1763 – 1829, saint-andré-d’hébertot, normandy); louis jacques de thénard (1777, la louptière, near nogent-sur-seine (aube) 1857, paris). 25 their hypothesis is published in séance publique de l´ecole de mêdicine de paris, du 24 vendèmiaire an 10, [sept. 24,1801; the author] in-4°., page 67. and reads: “les cc. fourcroy et vauquelin, …, admettent l´existance d´un fluide particulier, qu´ils nomment galvanique, et qui circleroit du côté positif de la pile, vers le côté négatif. selon eux, ce fluide décompose l´eau en sortant du côté positif: il laisse échaper l´oxygène en bulles; mais il se combine avec l´hydrogène pour former un liquid, lequel traverse l´eau, …. , pour aller gagner l´extrémité du fil négatif. là le galvanique abandonne son hydrogène, et le laisse échapper à son tour sous forme de gaz, tandis que lui-même pénètre dans le fil.” (ref. [43], p. 157.) 26 alessandro volta explicitly distanced himself from brugnatelli´s theory and stated in ref. [46]., p. 264, “ich habe keinen antheil an seinen meinungen oder ideen über die electrische säure, die electrisch-sauren metalle, u.d. m.“ [ann. phys. (gilbert ed.) xiv (7), p. 264.] (“i have no share in his opinions or ideas about the electric acid, the electric-acidic metals, etc).” 105capillary electrophoresis and its basic principles in historical retrospect. to his surprise, when he visited paris with volta, brugnatelli found a paper in the issue of august, 1801 (le 11 fructidor an 8) of ann. chim., authored by the belgian étienne-gaspard robert. around 1800 robert executed experiments with galvanism, and read one of his works before l’institut national de france in august 1801, which was published in the aforementioned ann. chim., entitled “expériances nouvelles sur le fluide galvanique”.[47] he proposed a theory which was very similar to brugnatelli ś,27 and in which he termed brugnatelli ś electric acid “l ácide galvanique”. robert was well-known by his stage name stephan kaspar robertson, also robert-son,28 whereby it was peculiar back then as it is today, why ask a professor of physics would choose a stage name.29 due to his interest in many various areas. it was not surprising that the german physician johann friedrich erdmann was fascinated by the recently discovered galvanic electricity, and in its applications to medical issues.30 he decomposed water by electrolysis and obtained hydrogen and oxygen in right proportions as usual. in 1802 erdmann put forward the hypothesis that galvanic electricity flows into the water at the + pole, and leaves it at the pole.[56] by entering water at the + pole, it binds hydrogen, since the latter has a larger affinity to electricity than to oxygen, and thus oxygen is liberated. hydrogen unites to hydrogenated electricity, 27 chapitre x. expériences et observations sur le galvanism, par mm. nicholson, carlisle, robertson, cruickshank, henry and davy; ref. [48]., p. 282 ff., §. ii. expériences et observations de m. robertson, see p. 294. 28 the hyphen in robert-son is not a printing error. 29 robert had a remarkably eventful biography (see his mémoires).[49],50]. born in 1763 as étienne-gaspard robert in liège, belgium, he studied at leuven, and became professor of physics, specialized in optics, at l’école centrale du département de l’ourthe. in 1791 he moved to paris to strive for a career in art as a painter. there, he attended in 1792 and 1793 the scary ghost-raising show phantasmagorie, and easily figured out that the ghosts were created by the use of a laterna magica. he premiered his own show (under the stage name robertson) in paris in 1798 which he later performed with great success around the world. during these trips he became fascinated by ballooning and flew balloon shows in vienna, dresden, leipzig, moscow and other cities. he considered some flights by himself as being scientific, because he connected them with meteorological investigations. he managed to publish three of his flights in ann. phys. in 1804 as communications to the editor ludwig wilhelm gilbert.[51],[52],[53]. it is interesting to read gilbert´s critical comments and references to errors in robertson´s reports, which make up a large part of the papers. robert died in 1837 in paris. 30 erdmann (1778, wittenberg 1846, wiesbaden) published, for instance, in 1803, one year after his doctorate in medicine, a paper entitled “beschreibung zweier von dr. brunner in wien erfundenen voltaisch-elektrischen apparate zur entdeckung des scheintodts und zur wiederbelebung der scheintodten” (description of two by dr. brunner in vienna invented voltaic-electrical apparatus to discover the apparent death and to revive the apparent dead),[54] and in 1804 one about “galvanische versuche, angestellt im wiener irrenhaus“(galvanic experiments, employed in the vienna madhouse).[55] which traverses the liquid towards the pole, where the electric matter intrudes the metal of the pole and hydrogen is released as gas.31 since in the first years after 1800 the subject of most of the works was the decomposition of solutions of arbitrarily chosen salts, acids and bases by galvanic electricity, it was quite difficult to find a coherent structure in the results obtained under these widely varying conditions. this gap motivated the swedes wilhelm hisinger and jöns jacob berzelius “to search for as many as possible general results from the experiments we and others have performed, so that the phenomena” of the electric decomposition and the motion of the ions could be better understood and even foreseen (ref. [57], p. 115 116). they published a systematic study of nearly thirty selected electrolytes in 1803 in german translation[57] from swedish and in 1804 in a condensed version in french. [58] it can be said that this work did not contain really new aspects, but the categorization of the experimental outcomes enabled them to formulate certain valuable rules, which they summarized in seven points. we cite those rules which have a direct context to the motion of decomposed particles. they read32 “versuch, aus den obigen sowohl, als aus anderen bekannten galvanischen versuchen, einige allgemeine folgerungen herzuleiten. 1. wenn sich die electrische säule durch eine flüssigkeit entladet, so sondern sich die bestandtheile dieser flüssigkeit dergestalt von einander ab, daß sich einige von ihnen um den negative pol, andere um den positiven ansammeln. 2. diejenigen stoffe, die sich zum drahte eines und desselben poles hin begeben, stehen unter sich in einer gewissen analogie. zum negativen pol gehen alle brennbaren körper, alkalien und erdarten; zum positiven hingegen sauerstoff, säuren und oxydierte körper. 7. wasser wird in wasserstoff und sauerstoff zerlegt, die aber in unzerlegtem wasser unauflöslich sind, daher ersteres vom negativen, letzteres vom positiven draht, gasförmig entwickelt wird.” (attempt to draw some general conclusions from the above, as well as from other known galvanic experiments. 1. if the electric column is discharged through a liquid, the components of this liquid separate from one another that some of them collect around the negative pole, others around the positive. 2. those substances which move to the wire of one and the same pole stand in a certain analogy among themselves. all combustible bodies, alkalis and earths go to the negative pole; to the positive, on the other hand, oxygen, acids and oxidized bodies 7. water is fragmented 31 this paper was an extract of his doctoral thesis entitled “utrum aqua per electricitatem columnae a cel. volta inventae in elementa sua dissolvatur?“, which he defended on may 2, 1802, at the medical faculty of the famous alma mater wittenbergensis. 32 points 3, 4, 5 and 6 are not directly relevant for the topic at hand, therefore we leave them out. 106 ernst kenndler into hydrogen and oxygen, which, however, are insoluble in undecomposed water, so the former is developed in gaseous form from the negative, the latter from the positive wire.). hisinger and berzelius interpreted their findings as the result of the electrostatic attraction and repulsion of the ions to and from the respective charged poles.[57] they assumed these electric forces to follow the principle of the action at a distance. in the concept of the action at a distance33 the forces are strongest at their poles and diverge then in the inverse ratio of the square of their distance. the two forces cross in the middle between the poles and compensate each other at the point of neutrality or indifference point. decomposition happens not at the poles, but near or at this point. this concept was later a key part of humphry davy ś theory of the electrolysis and the motion of the decomposed particles.[62] hisinger and berzelius were not really convinced of this hypothesis. they doubted the assumption of decomposition at the point of indifference, as this contradicted what was observed in practice (ref. [57], p.148) therefore, skeptical about their still unsatisfactory results, they concluded “wir wagen kein raisonnement über das wie der obigen zerlegungen. doch scheint uns am meisten natürlich, dieselben durch attraction der electricität, die sie auf gewisse stoffe, und repulsion,34 die sie gegen andere äußert, zu erklären, ob uns gleich diese erklärung wenig genügend scheint.” (we do not dare upon making any reasoning about how the above decompositions are made. yet it seems to us most natural to explain them by the attraction of electricity, which it expresses for certain substances, and repulsion, which it expresses against others, although this explanation seems little sufficing to us.) however, none of the theories proposed thus far had been considered as generally valid due to contradictions and inconsistencies, and the confusion about the transport of hydrogen and oxygen. the question of the flow of the electric current through water during its decomposition remained. but in 1805, this patchwork of disorientating theories was resolved by the surprisingly only twenty years old german student theodor von grotthuß. 33 the concept of the action of a distance, expressed also as the inverse square law, applied to newton’s law of universal gravitation,[59],[60] and to coulomb´s laws for the electrostatic repulsion of equally charged and the attraction of oppositely charged points.[61] 34 they relativized on p. 148, footnote 3: “daß unter repulsion richtiger eine geringere verwandschaft als eine wirkliche zurückstoßung zu verstehen sey, wird man leicht einsehen”. (it will be easy to see that by rejection it is more correct to mean a lesser relationship than an actual rejection.) 2.3 1805: c. j. t. von grotthuß´ theory of the electrophoretic current during the electrolysis of water and of the bodies which it holds in solution during his stay as a student of natural sciences in italy from 1804, baron christian johann dietrich theodor von grotthuss (also c. j. théodore de grotthuss)35 formulated a theory that made him highly recognized, in particular that of the flow of electricity during the decomposition of water. his theory was so plausible to his contemporaries that, unlike the ones discussed above, it found general acceptance. it was compelling 35 christian johann dietrich theodor von grotthuß (1785, leipzig, germany 1822, geddutz (at present day gedučiai), lithuania. see his portrait in figure 4), member of a german-baltic noble lineage, began his university studies in leipzig in 1803, and continued six months later at école polytechnique in paris, then from 1804 in italy. he left italy in 1806 and returned via paris, munich and vienna in 1898 to his manor geddutz in courland. since his return to his manor von grotthuß tended to live secluded from the scientific community. there he continued his electrochemical research, and investigated the chemical effect of light.[63]. in 1819 he formulated the photochemical absorption law (named grothuss-draper law, or the principle of photochemical activation; this law was independently formulated in 1842 by the english-born american scientist john william draper). (for details, see e.g. ref. [64]). figure 4. portrait of baron christian johann dietrich theodor von grotthuß (c. j. théodore de grotthuss). photogravure by meisenbach and riffart & co. in leipzig, produced prior to 1894, undated. 107capillary electrophoresis and its basic principles in historical retrospect. because it could provide an answer to the previous question how hydrogen or oxygen can traverse water in the form of a gas from one pole to the other.[65-67] in chapter ii of “mémoire sur la decomposition de l’eau et des corps qu’elle tient en dissolution à l’aide de l’ électricité galvanique” which grotthuß published in 1805 in rome,[65] and in 1806 in ann. chim. in paris,[67] he postulated that in each water molecule – he assumed that it was made of (ho) – the hydrogen and the oxygen atom are positively and negatively polarized, respectively.36 upon application of an electric potential the molecules orient themselves with their polarized atoms in direction of the oppositely electrified poles, forming a chain in the liquid in this way, schematically depicted by ((+)h-o(-))((+)h-o(-)). in §. 20. of his treatise, he formulated his basic idea as follows “il est clair que, dans toute cette opération, les molécules d`eau situeés aux extrêmités des fils conducteurs, seront seules décomposées, tandisque toutes celles placées intermédiairement, échangeront réciproquement et alternativement leurs principes composans , san changer de nature. j`en déduis que, s̀ il était possible d`établir un courant d`électricité galvanique dans de l èau, de façon qù il décrivit dans celle-ci une ligne parfaitement circulaire, toutes les molécules du liquide situées dans ce cercle, seraient decomposées, et a l`instant recomposées: d`où il suit que cette eau , quoique subissant l èffet de l`action galvanique, resterait toujours eau.” (it is clear that, throughout this operation, only the water molecules located at the tip of the conducting wires will be decomposed, whereas all those located at intermediate positions will exchange their composing principles reciprocally and alternatively, without changing their nature. from this i deduce that if it were possible to apply a galvanic current in water such that it follows a perfectly circular line, all the water molecules of the liquid located in this circle would be decomposed and instantly recomposed: whence it follows that this water, although subjected to the effect of galvanic action, will always remain water.)37 in figure 5 the scheme of the mechanism of the flow of the electrophoretic current during the decomposition of water is depicted. the u-shaped tube (“fig.1er”) is filled with water into which two poles connected to a voltaic pile are dipped. the water molecules are pictured as a series of circles with positive and negative charges, which is the stylized way of depicting von grotthuß´ real conception of a chain or row of polarized ((+)h-o(-)) molecules but does 36 in his next paper dated 1807[68]. he depicted the water molecule as composed of one hydrogen and two oxygen, what he repeated in his work from 1811,[69]. and from 1818.[70] 37 the english version is published in ref. [71]. not display a sequence of ions since grotthuß refused the presence of free ions from water. he believed that an ion is always associated with its oppositely charged ion. 38 according to his theory, each of the elements of a molecule is subject to an attractive and a repulsive force, acting in contrary directions. the negative pole attracts the positively polarized hydrogen atom and repels the negatively polarized oxygen of the water molecules, the positive pole accordingly attracts oxygen and repels hydrogen.39 these electric forces are sufficiently energetic to overcome the chemical affinity in the terminal water molecules (that is to say, only in those at the ends of the chain). considering for example hydrogen q at the end of the circular line (positive q of the water molecule qp at the negative pole in figure 5), decomposition of molecule qp occurs, because it gives up its hydrogen q, which is in direct contact with the pole, to the electricity of the negative wire. but at the same time as hydrogen atom q is liberated to hydrogen gas, the chain is instantaneously (“à l`instant”) re-hydrogenated by hydrogen 38 comment of the author: in the fourth circle .after the minus pole of the tube in “fig. 1” a minus should be inserted, not a plus; in the english translation of this paper in phil. mag. from 1806 this error was corrected, see plate ix, fig. 1 in ref. [66]. 39 although grotthuß initially assumed that the forces follow the inverse square law according to the action at a distance, he nevertheless believed that the atoms move with constant velocity, what is a contradiction in itself. figure 5. schematic drawing illustrating grotthuß´ concept of the flow of the electric current during the electrolysis of water. “fig.1re” shows a u-tube filled with water, which forms of a chain of positively polarized hydrogen and negatively polarized oxygen atoms. it is important to realize that the circles with + and – signs are not ions, they are schematic depictions of the polarized atoms of the intact, neutral water molecules (which consist here from one hydrogen and one oxygen). during the complete process, free ions are not present in water.38 for a more detailed explanation see text. taken from ref. [67]. 108 ernst kenndler x of the adjacent molecule, a transfer which occurs in the same moment. oxygen reacts analogue at the positive pole. it is decisive that only those atoms of the water molecules are segregated which are in direct contact with the poles. all other water molecules, which are between the poles, only exchange their atoms reciprocally, but do not change their nature. on these grounds, the flow of the electric current is caused by both kinds of atoms which continuously travel in opposite direction within the aligned chain of water molecules between the terminal atoms, forming an electrophoretic current in this way. the crucial fact of the matter is that ions are never present in their free form, because upon disintegration of the molecules the atoms bind immediately to the partner atoms of the next following molecules. hence, all molecules in the solution are subject to the permanent and instantaneous process of decomposition and recomposition.40 it must be noted that grotthuß initially assumed, but later withdrew, that the force of attraction or repulsion follows the action at a distance as davy and berzelius did. yet, it is of paramount importance that grotthuss’ theory gave an answer to the apparently paradox effect of the evolvement of hydrogen and oxygen at the separate poles, because in his theory the evolved gaseous elements of water do not originate from the same water molecule and therefore do not travers the liquid. grotthuß´ theory was widely accepted41 but to his annoyance was initially attributed to the famous scientists davy and berzelius, and not to the unknown young german student. it took about fifteen years until grotthuß asserted his priority on the theory in volume 1 of his book entitled “physisch-chemische forschungen”,[28] which he published in 1820, and in which he had collected his main scientific papers (volume 2 did not appear anymore). this book can be regarded as his scientific testament, since two years later he committed suicide. in the introductory commentary of his article from 1805 which he translated into german by himself in 40 the german translation and comments were published in 1808 by johann salomo christoph schweigger, professor of philosophy, physics and chemistry, and editor of journal für chemie und physik.[72] 41 the author points out the following inconsistency in grotthuß´ description of his theory: according to this theory, negative oxygen p combines after the release of positive hydrogen q with neighboring positive hydrogen x under formation of the new molecule ((+)p-x(-)). in this configuration, the negative oxygen p is that atom which is closest to the surface of the – pole. to get into the proper position the molecule has to rotate by 180° to ((+)x-p(-)) in order to re-position hydrogen x onto the surface of the – pole. these rotations apply to all molecules in the chain. grotthuß´ did not mention this necessity. faraday pointed to this fact when he explained that ice as ordinary insulating dielectric cannot be electrolyzed, whereas liquid water can (experimental researches in electricity fourteenth series, 1839; 1705.)[73],[74] “physisch-chemische forschungen” grotthuß wrote somewhat embittered (ref. [75], pp. 113-115): “meine (…) theorie ist später von davy (…). und von berzelius (…) ohne meiner zu gedenken, weiter verbreitet und (…) jetzt von allen chemikern (…) angenommen worden; nur muß ich bedauern, daß viele von ihnen, wiewohl fälschlich, nicht mir, sondern den beiden letztgenannten chemikern diese theorie zuschreiben die ich jedoch weit früher aufgestellt (…) habe42, (…) nachfolgender aufsatz wurde von mir 1805 in neapel entworfen, und noch in demselben jahre in rom gedruckt. (…) daß diese grundidee von mir ein ganzes jahr (…) früher als davy (…) aufgestellt worden ist, brauch ich wohl kaum noch hinzuzufügen. diesen 1805 in rom in französischer sprache gedruckten aufsatz43 sandte ich an fourcroy nach paris und dieser ließ ihn einige monate später nämlich im april 1806 in den annales de chimie aufs neue abdrucken,44 davys obenangeführte abhandlung betreffend, über einige chemische wirkungen der electricität wurde erst am 20. november 1806 von ihm in der königl. gesellschaft zu london vorgelesen und erschien erst 1807 in den transact. philos.45 gedruckt.” (my (…) theory was later disseminated by davy (…) and berzelius (…) without further commemorating me, and is now accepted (…) by all chemists; but i must regret that many of them, albeit falsely, attribute this theory not to me, but to the latter two chemists, though i have it established much earlier, (…) the following essay was drafted by me in naples in 1805, and printed in rome the same year (…). i hardly need to add that this basic idea was put forward by me a whole year (…) earlier than davy. i sent this essay, printed in french in 1805 in rome, (…) to fourcroy in paris, and a few months later, in april 1806, he reprinted it anew in the annales de chimie. davy’s above-mentioned essay about some chemical effects of electricity was read only on november 20, 1806 by him at the royal society in london and appeared printed not until 1807 in the transact. philos.). [citations added by the author]. in this complaint grotthuß referred to davy ś celebrated bakerian lecture,46 read on november 20, 1806, entitled “on some chemical agencies of electricity” (ref. [62], p.29). yet in chapter i of grotthuss´ aforementioned paper[67] the subject was the “action of galvanic electricity upon certain bodies dissolved in water”, p. 330-334 in the english version[66]). in this theory, “metallic” solutions47 42 see e.g. ref. [76], p. 691. 43 see ref. [65]. 44 see ref. [67]. 45 ref. [62]. 46 the bakerian medal and lecture is awarded annually by the royal society and was established in 1775 by henry baker. humphry davy was awarded the medal every year between 1806 and 1811, and then in 1826. 47 meant were solutions of metal salts or metal oxides. 109capillary electrophoresis and its basic principles in historical retrospect. form a chain of charged particles in the same way as water, which move electrophoretically towards their respective electrodes. grotthuß wrote (on p. 338 of ref. [66]) “x xiv. the polar arrangement, such as exists in the elementary molecules of water traversed by the galvanic current, ought to be established equally among the elementary molecules of every other liquid body, provided they are solicited by the same forces. in the metallic solutions the electric polarity takes place among the elements of the oxide, the oxygen of which passes to the positive pole, and the metal of it is deposited at the negative pole.” grotthuß observed that with certain salts “the molecules of the metal in solution are revived, assuming a symmetrical arrangement, which extends in the direction of the galvanic current.” this symmetrical arrangement mimicked the shape of leaves of ferns, or of trees with limbs and twigs; its generation was therefore named arborisation.48 the metal trees grew continuously larger at the negative pole, but hydrogen was never formed as gas there during the galvanic action. quite remarkably, grotthuß stated that the arboreal growth from the negative toward the positive pole was always in the direction of the current. he took this fact as evidence of the correctness of his theory regarding water which he described in chapter ii of his paper. 2.4 november 1806: humphry davy´s bakerian lectures, catalysts for resurgence of research in galvanic electricity in britain after a four-years hiatus after a gap of four years since his last publications on galvanic electricity in 1802, humphry davy presented the results of his recent investigations in his celebrated bakerian lectures, read november, 1806,49[62] and november, 1807.[78] davy reported the results of his numerous elaborate experiments with galvanic electricity under various experimental conditions, and with a large number of compounds. with respect to the action of the galvanic electricity on water davy presumed (in the same manner as grotthuß) that the constituents of water, hydrogen and oxygen, are positively and nega48 arborisation of metals without electricity had already been executed by alchemists. by galvanic electricity it was described first in 1800 by cruickshank with silver trees (arbor dianae),[11]. in 1800 by brugnatelli (published in annali di chimica, 1800, t. xviii, p. 136; excerpt in ref. [45]., in 1801 by gruner as dendrites of silver from silver salt solutions (ref. [37], pp. 216-227.) and in 1805 by ritter as tree of lead dendrites.[77] 49 it was the same bakerian lecture that was discussed in the previous section, which dealt with the decomposition of water; now the focus is to that of salts, acids and bases.[62] tively polarized (electropositive and electronegative), and form a conducting chain. davy assumed that upon completing the electric circuit oxygen and hydrogen are attracted by or repelled from the electrified metallic surfaces of the oppositely charged poles, and the electric forces follow the action at a distance. water is split into its elements when its chemical affinity in the molecule is overcome by electrical forces. the energies of the particles which are electrophoretically moving are transferred from one particle to the “immediate neighboring particle of the same kind”, which causes the rows of both elements to move towards their respective poles. at this point, note that each relocated particle is immediately substituted by that behind, and the water remains unchanged within the internal volume. this brings davy to the point to state “in the cases of the separation of the constituents of water, (…..) forming the whole of the chain, there may possibly be a succession of decompositions and recompositions throughout the fluid.” and he continued, referring to a neutral point, which is characteristic for the action at a distance “it is easy to explain, from the general phenomena of decomposition and transfer, the mode in which oxygene and hydrogene are separately evolved from water. the oxygene of a portion of water is attracted by the positive surface, at the same time that the other constituent part, the hydrogene is repelled by it; and the opposite process takes place at the negative surface; and in the middle or neutral point of the circuit, whether there be a series of decompositions and recompositions, or whether the particles from the extreme points only are active, there must be a new combination of the repelled matter.” davy also wondered whether the particles of the salts can pass from the one to the opposite pole through different “menstrua”, even when they possess a stronger attraction to them. an example of an experimental arrangement for this question is shown in figure 6. in one of these experiments davy filled dissolved muriate of barytes50 into tube a with the positive, and distilled water into tube b with the negative pole. first he poured muriatic and nitric acid, respectively, into the middle tube. once the circuit was closed, the barytes, like most other alkaline substances, passed through the acids without any problems, and were transmitted to tube b with the negative wire. vice versa, these acids 50 barytes, a term which dates back to late 18th century, is a mineral which consists of barium sulphate. in the main text muriate of barytes means barium chloride. muriatic acid is hydrochloric acid. 110 ernst kenndler passed trouble-free electrophoretically through aqueous solutions of barytes.51 however, attempts to pass barytes when sulphuric acid was inserted into the middle tube gave a completely different result: after closing the circuit, barytes could not be found in the distilled water in tube b, but sulphate of baryte precipitated in the middle tube. the same effect was observed when a solution of sulphate of potash52 was in tube b with the negative pole of the circuit, a saturated solution of barytes in the middle tube, and distilled water in that with the positive pole. in this case sulphuric acid could not be found in distilled water in tube a after closing the circuit, but again sulphate of baryte precipitated in the intermediate tube. due to its insolubility, in both cases this salt became excluded from the galvanic action, inhibiting the further transmission of baryte to the negative, and of sulphate to the positive pole as consequence. this result was clear evidence that the electrophoretic current is due to the migration of ions through the solution, and is an important finding for the subject at hand. davy summarized his observations in section “vi. some general observations on these phenomena, and on the mode of decomposition and transition” commencing 51 note that barium chloride and nitrate are well soluble in water, in contrast to the sparingly soluble sulphate. 52 potash is a mixture of water soluble potassium compounds and potassium-containing materials; its main component is potassium carbonate. in the present context sulphate of potash stands for potassium sulphate. with the repetition of the known facts (pp. 28, 29) “…that hydrogene, the alkaline substances, the metals, and certain metallic oxides, are attracted by negatively electrified metallic surfaces, and repelled by positively electrified metallic surfaces; and contrariwise, that oxygene and acid substances are attracted by positively electrified metallic surfaces, and repelled by negatively electrified metallic surfaces; and these attractive and repulsive forces are sufficiently energetic to destroy or suspend the usual operation of elective affinity.” in an attempt to generalize the theory that he had put forward about the electrolysis of water and the simultaneous electrophoresis of the ions he continued “it is very natural to suppose, that the repellent and attractive energies are communicated from one particle to another particle of the same kind, so as to establish a conducting chain in the fluid; and that the locomotion takes place in consequence; …” and he expressed (see figure 7 and its legend) that “solutions of neutral salts forming the whole of the chain, there may possibly be a succession of decompositions and recompositions throughout the fluid.” 2.5 theories as of 1807 at the european continent in france the chemist jean rené denis riffault (1752 – 1826) and the physicist and mathematician nicolas maurice chompré (1750 1825) published in 1807, too, a theory about the transition of electricity in solutions of acids or bases. they hypothesized that two simultaneous currents fragment the bodies into their elements throughout the solution and not only at the poles. they assumed that the flow of the negative electricity collects the acids and transports them to the positive pole, and the same happens vice versa with the bases. in their opinion the currents were the stronger the closer they were to their respective poles.[82, 83] jean-baptiste biot, the french physician, mathematician, and astronomer, described his somewhat complex theory in 1824 in chapitre xvii. effets chimiques de l’appareil voltaïque. pp. 628-651 of his book précis élémentaire de physique expérimentale.[84] biot assumed that the decomposable substance possesses opposite electrical states close to the two poles. the fluid is most positive at the positive pole, from where its positive polarity decreases with increasing distance, and reaches neutrality at the indifference point in the middle between the poles. from here on, it approaches the negfigure 6. drawing of davy´s experimental arrangement for the study “on the passage of acids, alkalies, and other substances through various attracting chemical menstrua, by means of electricity”. it shows three glass tubes with platinum wires as poles in the two outer tubes a and b, which communicate with the middle tube by strips of amianthus c (i.e. a fine silky asbestos), wetted with distilled water. the experiments are described in the text. it clearly confirms the migration of ions by electrophoresis. taken from ref. [79]. 111capillary electrophoresis and its basic principles in historical retrospect. ative pole and becomes increasingly negative. when a salt particle is disassembled at the negative pole, its acid part becomes more negative than the undecomposed ones. it is thereby repelled from the pole and increasingly attracted by the positive pole and by the particles of the undecomposed positive fluid around this pole. in contrast to davy, biot assumed that the particle is attached to electricity for the duration of the transition and is therefore drawn to the pole with the opposite charge. thus, decomposition of the particles happens in the portions of the solution close to the poles, but not between them.53 the sw iss chemist aug uste ar t hur de la r ive (1801, geneva 1873, marseille) published in 1825 a theory that dismissed grotthuß´ and dav y’s concepts of electrophoretic motion through decomposition and recombination.[85] de la rive assumed a combination 53 comment of the author: this configuration will most likely not form a stable chain because the particles ⊙ and ○ in the vertical rows are in direct contact with those of like charge. in addition, the molecules would not be arranged parallel in the chain and thus not perpendicular to the current, but would rotate alternately by 90° and form a chain that is arranged as … ⊙○⊙○⊙○ … . the same applies for berzelius´ theory, but not for grotthuß´. of the decomposed bodies with the electricity which is released from respective poles. concerning water, the electricity from the positive pole unites accordingly with the hydrogen, moves to the negative pole where it is decomposed into electricity and hydrogen, which is set free as gas. an analogue process takes place with the electrified oxygen, which travels from the negative pole to the positive one. in contrast to grotthuß´ and dav y ś theories, in that of de la rive the successive decomposition and recompositions in the course of the current does not occur. decomposition of the particles happens only at the poles, but no recomposition follows. for completeness we mention the french mathematician jean nicolas pierre hachette (1769, mézières 1834, paris). in 1832, in the same year michael faraday presented his first series of experimental researches in electricity,[86] hachette assumed the successive decomposition of water by a magneto-electric current.[87, 88]. however, he did not discuss the migration of the decomposed parts. he concluded (ref. [87], p. 73) “il résulte de cette experience, 1° qu’il n’est pas nécessaire, comme on le croyait, que l’action des deux électricités positive et négative, soit simultanée pour la décomposition chimique de l’eau; 2° que l’action, dont la discontinuité n’est qu’instantanée, peut aussi produire cette décomposition.” (it results from this experiment, 1°, that it is not necessary, as it was believed, that the action of the two electricities, positive and negative, be simultaneous for the chemical decomposition of water; 2° that the action, the discontinuity of which is only instantaneous, can also produce this decomposition.) in any case, tak ing the various theories into account, it is remarkable how long grotthuß´ from 1805 lasted. notwithstanding its replacement by rudolf clausiuś much better-founded theory in 1857,[89-91] clausiuś theory – which will be discussed in the subsequent part 3 of this series – was acknowledged, but largely ignored; and that of grotthuß was accepted almost unchanged for eight decades. although grotthuß´ theory is rather a subject of the history of electrochemistry, his name is still connected at present time to the special mechanism of the electrophoretic transport of h+ in aqueous solutions (named proton-jumping or proton-hopping). this grotthußmechanism explains the extraordinarily high ion conductivity and ionic mobility of h+ due to the presence of clusters of water molecules and their involvement in h+ transfer (see e.g. ref. [92]). figure 7. illustration of davy´s theory of the electrophoretic migration of the oppositely charged particles of a neutral salt during electrolysis. p, n: positive and negative poles. ⊙, ○: positiv and negativ particles of the neutral salt ○⊙, which forms a conducting chain in the solution. left and right pictures: arrangement prior and after closing the circuit. see the main text for details and footnote53 for author’s comment. taken from ref. [80]. nearly the same scheme is depicted by berzelius to illustrate his similar theory in ref. [81], p. 278. 112 ernst kenndler 3. as of 1832: michael faraday´s poineering contributions in electricity michael faraday54, having attended only elementary school was given by a fortunate coincidence and on his own initiative the position as sir humphry davy ś laboratory assistant in march 1813. this was the beginning of his outstanding career. at first he assisted davy with chemical experiments, and was allowed to carry out some by himself.55 in 1820 he was fascinated by the discovery of electromagnetism by hans christian ørsted 56,[99] and began research in this new field, concurrently to his chemical work on organic compounds. in autumn of 1821 he discovered the electro-magnetic rotation.[100] during 1824 and 1826 he attempted, to “convert magnetism into electricity“, but without success.[101] after a break until 1831 he returned to investigate electromagnetic phenomena and to electricity. in this year he made the important discovery of the electromagnetic induction.[86] 3.1 faraday´s series of “experimental researches in electricity” from 1832 to 1834 faraday published eight comprehensive papers of the series entitled “experimental researches in electricity”. in this series faraday communicated the results of his pioneering research on electromagnetism, magneto-electric induction, electricity and electrolysis in phil. trans.[10, 86, 102-107] after his investigations of electromagnetism in 1831 and 1832 he focused his research on electrical and electrochemical topics. the “new law of electric conduction” was published in 1833 in the fourth series of experimental researches in electricity,[104, 108] and aroused his interest in electrochemical decomposition. although faraday is better known 54 michael faraday was born in 1791 in newington butts, now part of london, and died in 1867. instead of going into details of faraday´s biography, we refer to a recently published paper by f. bagnoli and r. livi in this journal.[93]. in their publication the scientific focus is not on the migration of ions by electrophoresis. we have avoided duplicating information, although in some cases it was is inevitable, for example in definitions or in verbatim reproductions of faraday’s statements. 55 faraday’s first scientific publication which he was allowed to publish as laboratory assistant by his own name was about “analysis of the native caustic lime” and appeared in 1816 in vol. i of the journal of the science and of the arts, later named the quarterly journal of science, literature, and the arts.[94]. the subsequent experiments dealt especially with compounds from chlorine and carbon, and the isolation of “bi-carburate of hydogen” (i.e. benzene) and other arenes (see e.g. refs. [95],[96],[97],[98]). 56 hans christian ørsted (in german hans christian oersted; 1777, rodkøbing – 1851, copenhagen) was a danish physicist, chemist and nature-philosopher. he was a friend of johann wilhelm ritter. for his work on electrolysis where he derived the laws named after him his theories about the motion of ions, which superseded those put forward so far, cannot be emphasized enough. hence, faraday evaluated and criticized these theories in the fifth series,[105, 109] § 11. on electro-chemical decomposition, read june 20, 1833, 481. 491.)57, and presented his own conclusions. that being said, faraday published numerous important contributions in many scientific fields, but in this review only those will be discussed which had a closer connection to the present topic. it is mentioned that these contributions do not necessarily follow a chronologic order in this text. they are, nevertheless, dealing with the migration of ions in solution in direction of lines of electric force, in accordance with the definition of electrophoresis given above. note that faraday coined two new key terms (in the previous sentence marked in italic): ion and lines of electric force. we take thus the occasion to begin with faraday’s proposal of a new, unified terminology, which replaced the earlier less systematic one, und will end this review with faraday s̀ groundbreaking theory of the lines of electric force, also the electric lines of force, the basis of james clerk maxwell ś field theory. 3.1.1 faraday`s recommendation for a defined terminology in the preliminary of his bakerian lecture in which faraday summarized his results in the seventh series[10] he pointed to the confusing and arbitrary denotations applied thus far in electro-decomposition issues and recommended their replacement by a consistent and well-defined terminology.58 for this purpose, he suggested to use artificial words, constructs of ancient greece words, viz. by replacing the term pole by electrode, and to distinguish between anode and cathode. he also suggested the terms ion, anion, cation, electrolyte, electrode, and electrolyze.59 57 the numbers, here 481. and 491., are those of the sub-sections of the paragraphs which subdivide the entire series. 58 although berzelius opposed against it, meaning: “faraday glaubt, ... daß unsere gewöhnlichen wissenschafts – benennungen … unzureichend werden; daher hat er andere eingeführt, von denen ich aber nicht glaube, weder daß sie in irgend einer hinsicht nothwendig waren, noch daß sie befolgt zu werden verdienen.“ (ref. [110], pp. 37,38) (faraday believes ... that our common scientific designations ... are becoming inadequate; hence he introduced others, but i do not believe that they were necessary in any way or that they deserve to be obeyed.) 59 one might wonder about the reason why faraday did not introduce the term electrophoresis (greek ἤλεκτρον and φόρεσις (phóresis) “the act of bearing”, means thus “the act of bearing electricity”). probably he avoided its use because the simple and common device for the generation of electricity, the “electrophorus” was still widely known since volt´s time (see part 1 of this series).[1]. but the author must confess that he did not search for an according text passage, neither in the six 113capillary electrophoresis and its basic principles in historical retrospect. since the historical background of the creation of this new terms was already briefly discussed in a previous issue of this journal,[93] we will not go further into the details of their origin. yet, it is remarkable that it is still standard nomenclature even today, about two centuries after faraday ś recommendation. 3.1.2 the inextricable connection of electrolysis and the electrophoretic current a central point in faraday ś theories was the cooccurrence of electrolysis and the electrophoretic current. he considered the two phenomena as being so inseparable, “that one cannot happen without the other”. the importance of this connection for faraday becomes clear as he repeated his conviction in various formulations (see § 13 of the seventh series,[10] and the eighth series[107], p. 436), which read, for example “854. on the other hand, the relation between the conduction of the electricity and the decomposition of the water is so close, that one cannot take place without the other. … 855. considering this close and twofold relation, namely, that without decomposition transmission of electricity does not occur...... 858. those bodies which, being interposed between the metals of the voltaic pile, render it active, are all of them electrolytes (476.); and it cannot but press upon the attention of every one engaged in considering this subject, that in those bodies (so essential to the pile) decomposition and the transmission of a current are so intimately connected, that one cannot happen without the other. … 923. … an electrolyte is always a compound body: it can conduct, but only whilst decomposing. its conduction depends upon its decomposition and the transmission of its particles in directions parallel to the current; and so intimate is this connexion, that if their transition be stopped, the current is stopped also; if their course be changed, its course and direction changes with them; …” in these statements the flow of charge carried by ions is phrased as “conduction of electricity, transmission of electricity, transmission of a current, transmission of its particles, transition [of particles]”, all of which express what we name the electrophoretic current. 3.1.3 1833/1834: faraday´s theory of the electrophoretic migration of the ions during electrolysis, and his seminal concept of the lines of force volumes of faraday´s correspondence,[111]. nor in the seven volumes of his diary (the “experimental notes”).[112] the part following the preliminary in the aforesaid seventh series in 1834[10] can be seen as the focus of his point of view at the motion of ions in solution during electrolysis. in this part faraday reported his experiments of the relation between current and electrochemically decomposed matter, what he already did in the fifth series in 1833.[105] one might ask how this relation can contribute to the problem of the migration velocity of an ion; we detail it as follows. with reference to the previous theories, the velocity of migration is determined by the electrical forces that act on the ion by the action at a distance. in this case, the electric forces and therefore the migration velocity are not constant but vary with the distance between ion and electrodes. we recall that electricity was throughout considered as a fluid. over the course of his research, faraday began to doubt these previous theories about the continuous character of electricity and the action at a distance. it was his unparalleled merit, thanks to his studies of electricity and magnetism, to open the window for a new look at the migration velocity of ions. 3.1.4 the absolute quantity of electricity, a consequence of the law of definite electrochemical action in the fifth series faraday argued “505. that for a constant quantity of electricity, whatever the decomposing conductor may be, … the amount of electro-chemical action is also a constant quantity, i.e. would always be equivalent to a standard chemical effect founded upon ordinary chemical affinity”. in the seventh series[10] in 1834 he presented as conclusion which he derived from the quantitative measurements of numerous electrolytically decomposed electrolytes the “ law of definite electrochemical action”, or the “law of the definite chemical action of electricity” (807.) which he expressed in different phrasing, for example as “732. … with respect to water, that when subjected to the influence of the electric current, a quantity of it is decomposed exactly proportionate to the quantity of electricity which has passed, … 783. the law was expressed thus: the chemical power of a current of electricity is in direct proportion to the absolute quantity of electricity which passes. 810. …the results prove that the quantities so decomposed are perfectly definite and proportionate to the quantity of electricity which has passed. 836. electro-chemical equivalents coincide, and are the same, with ordinary chemical equivalents.” note that faraday accentuated the quantity of electricity, not its intensity, what he already did in the third series (ref. [103], 329.). 114 ernst kenndler the forecited extension to quantitative experiments enabled faraday to show that the law of definite electrochemical action is generally valid. the electrochemical equivalent is a property of a particular ionic species (see section vii of the seventh series, “on the definite nature and extent of electrochemical decomposition”).[10] he explained that the anions and the cations of an electrolyte decompose in portions of electrochemical equivalents, that is to say, in quantities which are given by their atomic weigh divided by their charge number. thus, the electrochemical equivalent weight of hydrogen is 1, that of oxygen is 16/2 = 8, etc. (p. 111). because of the law of definite electrochemical action faraday came to his fundamental conclusion that “an absolute quantity of electricity associated with the particles or atoms of matter” exists (§13). he wrote “852. the theory of definite electrolytical or electro-chemical action appears to me to touch immediately upon the absolute quantity of electricity or electric power belonging to different bodies. …, yet there is an immensity of facts which justify us in believing that the atoms of matter are in someway endowed or associated with electrical powers, to which they owe their most striking qualities, and amongst them their mutual chemical affinity.” from this insight faraday derived that electricity consists of fundamental quantities. ions are therefore always charged by one or integer multiples of this charge unit.60 3.1.5 faraday`s rejection of the action at a distance faraday contradicted especially the established concept of the action at a distance, the inverse square law. one might remember that grotthuß formulated in §. 18. of his original paper from 1805[65] this action at a distance concept in regard of the transport of the charged particles in water as follows: “§. 18. l’action de chaque force par rapport à une molécule d’eau située sur la route du courant galvanque, est en raison inverse du quarré de la distance à laquelle elle s’ exerce.”61 60 it may appear questionable to the reader that we are discussing properties that seem to be only relevant in electrolysis. however, since the migration velocity of an ion depends on its charge, the findings just discussed are of outmost importance for electrophoresis. 61 grotthuß` own translation into german in his book from 1820 reads: “§. 18. der einfluß einer jeden kraft hinsichtlich auf ein teilchen wassers, welches in der richtung des galvanischen stromes liegt; wirkt umgekehrt wie das quadrat der entfernung in welcher sie sich äussert“ (ref. [28]., p. 122). in the english version published in phil. mag. it was translated as: “xviii. the action of each force, in respect to a molecule of water situated in the direction of the galvanic current, is in the inverse ratio of the square of the distance to which it exercises its influence.” (ref. [66], p. 335). from his magneto-electric investigations faraday realized that this action at a distance does not apply, and this previous concept was false. fortuitously, this part of grotthuß´ theory was already withdrawn by himself in 1820, about one decade prior to faraday’s criticism. most probably faraday did not have knowledge of grotthuß´ comments in the german translation of his article, which he published in his book “physisch-chemische forschungen” (this book is quoted above)[28]. grotthuß added (in §. 18, p.122) “die annahme daß die polarelectricität (ga lvanismus) umgekehrt wie das quadrat der entfemung wirke, ist grundlos und nicht einmal ganz zuverlässig für die gewöhnliche electricität erwiesen (m, s. simon im 28sten bde. von gilberts annalen62). daher hätte dieser paragraph füglich wegbleiben können.” (the assumption that the polar electricity (galvanism) is inverse of the square of the distance is proved groundless and not even completely reliable for the ordinary electricity (m, see simon in the 28th volume of gilbert’s annals). therefore, this paragraph could have stayed off.) 3.1.6 the migration of ions and the electric lines of force already in the fifth series, § 11, iii., “theory of electrochemical decomposition”,[105] read a few months prior 62 ref. [113], specified by the author. figure 8. drawing which illustrates michael faraday´s concept of the electrophoretic migration of the ions during electrolysis. in the upper scheme anions a and a´ migrate towards the anode, p, cations b and b´ to the cathode, n. they are moving parallel to the lines of forces, which fill the space between the two electrodes. for details, see main text, quoted sub-section 519. in faraday´s fifth series. taken from ref .109. 115capillary electrophoresis and its basic principles in historical retrospect. to the seventh series,[10] faraday described his view at the migration of ions. in his opinion, “the two elementary electric currents, moving in opposite directions, from pole to pole, constitute the ordinary voltaic current.”63 he stated that the influence that is present in the electric current has to be strictly devised as “an axis of power having contrary forces, exactly equal in amount, in contrary directions.” (517.). this theory was in clear contradiction to the earlier established concept of the action at a distance and the point of indifference or neutrality and marked a fundamental change in the principles of ion migration. faraday considered the decomposing bodies as a mass of particles, which contribute to the final effect given that they are in the course of the electric current. the effect of the electrochemical decomposition is based on an internal corpuscular action, which originates from a force, that either adds to the common chemical affinity, or determines its direction. the combining particles pass in opposite directions because the usual chemical affinity is reduced, weakened or partially neutralized by the influence of the electric current in one direction parallel to its course, and reinforced or supplemented in the opposite direction. the author comments that this is in fact the description of the electrophoretic motion. faraday expounded his theory again in section 519. of the fifth series (ref.[105], p. 696¸ german translation ref. [109]) explaining (see figure 8).64 “519. in this view the effect is considered as essentially dependent upon the mutual chemical affinity of the particles of opposite kinds. particles a a, fig. 7, could not be transferred or travel from one pole n towards the other p, unless they found particles of the opposite kind b b, ready to pass in the contrary direction: for it is by virtue of their increased affinity for those particles, combined with their diminished affinity for such as are behind them in their course, that they are urged forward: and when any one particle a, fig. 8, arrives at the pole, it is excluded or set free, because the particle b of the opposite kind, with which it was the moment before in combination, has, under the superinducing influence of the current, a greater attraction for the particle a ,́ which is before it in its course, than for the particle a, towards which its affinity has been weakened.” consequently, all composite particles in the course of the current act conjointly, except those which are in con63 this attribution deviates from ours, because the ordinary voltaic current is the flow of electrons (electrons were unknown at the time). in contrast, “the two elementary electrical currents that move from pole to pole in opposite directions” is the flow of charge carried by ions in solution. it is the current for which we coined the term electrophoretic current. 64 the collection of all 14 series of the experimental researches in electricity, reprinted from the phil. trans. of 1831 – 1838 is published in ref. [73]. tact with the poles. they “consist of elementary particles, which, whilst they are in one direction expelling, are in the other being expelled”. the acting particles (i.e. the ions) which represent the electric current move in direction of the electric lines of action or lines of electric force. like the lines of magnetic force65 the electric lines do not necessarily form a straight line between the electrodes, neither must they be parallel, but they do not cross.66 due to its importance, we repeat the explanation of the line of force which faraday gave about one decade later, viz. in the nineteenth series, read in november 1845.[114] he stated “:—thus, by line of magnetic force, or magnetic line of force, or magnetic curve, i mean that exercise of magnetic force which is exerted in the lines usually called magnetic curves, and which equally exist as passing from or to magnetic poles, or forming concentric circles round an electric current. by line of electric force, i mean the force exerted in the lines joining two bodies, acting on each other according to the principles of static electric induction, which may also be either in curved or straight lines.” 3.1.7 the migration velocity of the ions and its assumed context with the decomposition of equal chemical equivalents of anions and cations faraday’s replacement of the earlier theory of the action at a distance by that of the electric lines of force67 and the conclusion of an elementary charge unit had farreaching consequences for the question of the migration velocity of the ions. in the earlier concept of the action at a distance this electric force acting on an ion varied with the in the inverse ratio of the square of the distance from the electrodes, and consequently its drift velocity varied as well. in faraday ś theory, the velocity in the electric field, in contrast, is constant during the motion of the ion along a field line.68 that is to say, in a homo65 in the first series of experimental researches in electricity, read november 1831, faraday reported the induction of electric currents and the generation of electricity from magnetism. in this paper, faraday defined for the first time the lines of force as ”by magnetic curves, i mean the lines of magnetic forces, however modified by the juxtaposition of poles, which would be depicted by iron filings; or those to which a very small magnetic needle would form a tangent.”(ref. [86],114.; footnote at p. 154). these magnetic field lines can be visualized by iron files poured onto a sheet of paper with a magnet underneath. 66 all these properties apply for all configurations. in a homogeneous electric field, for example in the field between two plate electrodes, nearly all lines are straight and parallel, and, as all others in all configurations, are perpendicular to the surfaces of the plates. 67 ref. [114], 2149., and ref. [115],1662. 68 to emphasize the importance of faraday´s theory of the lines of electric force for electrophoresis, and his conclusion that ions carry elementary charge units, we skip a period in the development of the theory of 116 ernst kenndler geneous field ions migrate with an equal and constant velocity along the field lines that run parallel to one another. faraday brought forward this argument in the eighth series read june 1834,[107] p. 448, that “964. … if any number of them [anions and cations] enter as ions into the constitution of electrolytes, and, forming one circuit, are simultaneously subject to one common current, the anions must move in accordance with each other in one direction, and the cations in the other. nay, more than that, equivalent portions of these bodies must so advance in opposite directions; for the advance of every 32*5 parts of the zinc … must be accompanied by a motion in the opposite direction of 8 parts of oxygen … of 36 parts of chlorine … , of 126 parts of iodine … ; and in the same direction by electro-chemical equivalents of hydrogen, … lead, copper and tin, …” it can be seen that faraday based his conclusion on the opposite movement of equal electrochemical equivalents of cations and anions of an electrolyte to their respective electrodes during electrolysis. in the simplest case the electrolyte consists of two ions with a single charge each. then, an anion cannot be oxidized on the anode unless a cation is reduced at the same time on the cathode. due to the requirement to reach their electrodes at the same time faraday concluded that the migration velocities of cations and anions must also be equal. faraday did not provide any values for this velocity. on the top of that, it will be seen later that his hypothesis was based on a mistake in reasoning. the first systematic attempts to measure the values of the drift velocity were made by wilhelm hittorf in the 1850s. yet, hittorf did not determine the absolute, but the relative velocities of the various ion species to one another, referred to as transference or transport numbers. this topic, and the subsequent studies to determine the actual migration velocity of an ion will be the subject of the following part 3 of this historical retrospect. ion migration. today it is well-known that the electrical force acting on an ion is proportional to its charge, z.e, and the strength of the electric field, e = u/d. here z is the number of charges, e the electron charge, u the potential difference and d the distance between the electrodes. that is, on ions with the same number of charges an equal electrical force is acting, independent of its distance from the electrodes. this is in clear contradiction to the action at a distance. this force accelerates the ion, but the oppositely directed frictional force of the medium increases with increasing speed. the frictional force depends on the size and shape of the ion and is thus different for different ions. when both forces are equal, the ion moves with a constant migration velocity (for the sake of simplicity, we have considered an ion at infinite dilution). 4. summary by following the general definition that “electrophoresis is the motion of dispersed particles relative to a fluid under the influence of a spatially uniform electric field” we have chosen a probably unusual view at electrophoresis in this part 2, since the focus is aimed exclusively at ions. this view is justified because, as defined above, ions of atomic or molecular size are also the subject of electrophoresis, not just colloidal particles as is conventionally considered. due to the inextricable linkage between ion migration and electrolysis the histories of these two phenomena are also intrinsically related. it is for this reason that this review begins with the year 1800 when electrolysis by galvanic electricity which was considered as a fluid at that time was discovered. it extends over the time until the 1830s and early 1840s when michael faraday superseded the previously established concept of action at a distance by that of the electric lines of force, which were later referred to as field lines of the electric field. it is pointed out that during the electrolysis of decomposable compounds by galvanic electricity two kinds of currents can be differentiated in the closed electric circuit. the galvanic or voltaic current is the flow of charges carried by electrons in the metallic parts (electrons were not known at the time). but decomposition can only take place if an electric current flows through the liquid from one pole to the other. although this process is obviously invisible to the naked eye, the several observations provided evidence that electricity was actually being transported through the liquid, e.g. due to the increased speed of electrolysis at higher concentrations of decomposable bodies, the analytic determination of parts of the decomposed molecules close to one pole, e.g. of potassium at the negatively charged electrode after electrolysis of muriate of potash, or by the kind of the decomposition products formed at the poles by electrolysis for this flow of these charged particles, later named ions, between the poles, which is an electric, but not a galvanic current, we coin the term electrophoretic current. while not common, it fully conforms to the definition of electrophoresis quoted above. taking these facts into account, the history of electrophoresis begins in 1800 with w. nicholsoń s and a. carlisle ś experiments of decomposing water by the aid of a voltaic pile. remarkably, just two months after their publication, as early as in september 1800, the first theories of the action of galvanic electricity on water were presented by w. cruickshank in britain and by j. w. ritter in germany. both researchers hypothesized that gaseous hydrogen and oxygen, evolving at the separate poles, 117capillary electrophoresis and its basic principles in historical retrospect. came from the same water molecule. in the following years, not surprising due to the novelty of the phenomena, experiments were carried out mainly for the acquirement of the results of galvanic action on solutions of arbitrarily chosen compounds and different experimental set-ups. in all cases the researchers were convinced that the two ions that assemble the decomposable molecule are tightly bound to each other, and could only be separated by the action of galvanic electricity, when the electric force from the connected voltaic pile overcame their chemical affinity. davy and berzelius assumed that the ions migrated because they were attracted or repelled by the charged poles, whereby the electric forces obeyed the action at a distance. that is, the forces decrease in the inverse ratio of to the square of the distance from the poles and cross at the point of indifference or neutrality. the compounds are decomposed near or at this point, but the decomposed particles appear at the poles, which makes this hypothesis quite difficult to comprehend. the action at a distance brought forth that the ions moved with varying, but not with constant velocity. in 1803 berzelius and w. hisinger were able to create a classification based on the properties of the ions involved in electrolytic decomposition and the direction of their electrophoretic migration towards their respective poles. it was a first step to systematically categorize compounds into electropositive and electronegative classes. back in 1800, beginning with cruickshank and ritter, several other theories about the electrolytic decomposition and the electrophoretic current were developed. works up to 1805 include the theory of the italian l. v. brugnatelli from 1800, who, to his surprise, found that the belgian e.g. robert (also robertson and robert-son) had already published almost the same theory before him; they report the theories of the french a. f. fourcroy, l.-n. vauquelin and l. j. thénard in 1800 and 1801, of the german j. f. erdmann in 1802, of h. davy, who paused after 1802 for four years, and of the swedes w. hisinger and j. j. berzelius in 1803. however, one of the most plausible theories at that time, which surprisingly outlasted almost eight decades, was presented in 1805 by theodor von grotthuß (also c.j.t. de grotthuss). he hypothesized that water or dissolved salts form a chain of polarized molecules, and only the terminal atoms of the chain, which were in direct contact with the surfaces of the oppositely charged electrodes were set free by galvanic electricity. however, important for electrophoresis is grotthuß´ hypothesis how the current flows through water or salt solutions. he assumed that the liberated terminal atoms are instantaneously replaced by the neighboring atoms of the same species, which led to a permanent decomposition and recombination of the molecules in the chain, and to the electric current in this way. it was thus believed that free ions were never present in the fluid. to his disappointment, the priority of his theory was initially assigned to the widely recognized scientist davy, who published a similar theory about one year later. indeed, in december, 1806 davy read a celebrated bakerian lecture with a theory in which he also assumed a chain of molecules, and a similar process of decomposition and recombination as grotthuß. after grotthuß and davy, fewer theories were formulated, e.g. by the french j. r. d. riffault and n. m. chompré in 1807, and after a break of about fifteen years, by the french j.-b. biot in 1824, then by the swiss a. a. de la rive in 1825, and the french j. n. p. hachette in 1832. however, all these theories were dismissed in 1833 by michael faraday, who unambiguously rejected the concept of action at a distance. based on his experience, which he had gained from his previous studies of magnetism and electromagnetism, faraday developed the theory of lines of magnetic and electric force, which served james clerk maxwell for the mathematical formulation of the field theory. this was one of faraday’s groundbreaking contributions to the further development of electricity and electromagnetism and thus to electrophoresis as well and opened a new era in these topics. another major contribution, which he deduced from his law of definite electrochemical action, was his proof that electricity consists of individual elementary charge units. the consequence of faraday’s seminal theories was that ions move at constant velocities parallel to the lines of the electric force that fill the space between the electrodes. thus, after more than three decades the concept of the action at a distance and its consequences were superseded. what remained was the conviction that electrolyte molecules consist of tightly bound ions of opposite charge, which can only be separated by electrical forces, whereupon they are permanently and instantaneously decomposed and recombined forming in this way the electrophoretic 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[115] m. faraday, phil. trans. 1838, 128, 125-168. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 6(2): 55-77, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1769 citation: kenndler e. (2022) capillary electrophoresis and its basic principles in historical retrospect. part 4. svante arrhenius´ electrolyte dissociation. from 56 theses (1884) to theory (1887). substantia 6(2): 55-77. doi: 10.36253/substantia-1769 received: jun 06, 2022 revised: jul 20, 2022 just accepted online: jul 21, 2022 published: september 1, 2022 copyright: © 2022 kenndler e. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. capillary electrophoresis and its basic principles in historical retrospect. part 4. svante arrhenius´ electrolyte dissociation. from 56 theses (1884) to theory (1887) ernst kenndler institute for analytical chemistry, faculty of chemistry, university of vienna, währigerstrasse 38, a 1090, vienna, austria e-mail: ernst.kenndler@univie.ac.at abstract. since the main interest of svante arrhenius, a student at uppsala university, was the electrical conductivity of highly dilute electrolyte solutions, which had not yet been determined at the beginning of the 1880s, he decided to determine experimentally the molecular conductivities of aqueous solutions of about fifty electrolytes and their dependence on the dilution. in his dissertation, which he began in the winter of 1882/1883, he summarized his results and considerations in 56 “theses”. he observed that strong acids had a high molecular conductivity, which increased only slightly with increasing dilution. weak acids, in contrast, had low molecular conductivities, but these increased abruptly above a certain dilution. arrhenius’ innovative hypothesis was that electrolyte molecules are composed from two parts, “an active (electrolytic) and an inactive (non-electrolytic) part,” with the proportion of the active part increasing with increasing dilution at the expense of the inactive part. moreover, the electrically active part, which conducts electricity, was also the chemically active part. arrhenius introduced the activity coefficient, later quoted as the degree of dissociation, which indicated the proportion of active molecules to the sum of active and inactive molecules. he tentatively related activity coefficient to molecular conductivity. he assumed that the higher the activity coefficients of different acids at the same equivalent concentrations, the stronger they are. arrhenius tested his hypothesis taking the heat of neutralization of acids with a strong base measured by thomsen and berthelot. strong acids developed the highest neutralization heats, i.e., the activation heat of water, since they consisted entirely of active h+ and ohions, which combined to inactive h2o. weak acids developed correspondingly less. the established parallelism between the molecular conductivities of acids and their heats of neutralization was the first proof of arrhenius’ hypothesis. he relied on thermochemistry and completed his dissertation. he presented his dissertation in june 1883 and published it in 1884 to obtain his doctorate. at that time, wilhelm ostwald was investigating the affinities of acids to bases, i.e. the intensity of the effects of acids on the rates of reactions they cause. he took the rate constants as a measure of the relative strength of the acids. after receiving arrhenius’ thesis, he measured the acid´s molecular conductivities and found a remarkable proportionality to the reaction rate constants of the hydrolysis of methyl acetate and the inversion of cane sugar caused by them. this was the second proof of arrhenius’ hypothesis, based on the results of chemical kinetics. a memoir presented in 1885 by j. h. van ‘t hoff on the analogy between the osmotic pressure of a highly dilute solution separated from the pure solvent by a http://www.fupress.com/substantia http://www.fupress.com/substantia mailto:ernst.kenndler@univie.ac.at 56 ernst kenndler semipermeable membrane and the pressure of an ideal gas containing the same number of particles as the solution led to probably the most convincing proof of the arrhenius hypothesis. this analogy corresponded to avogadro’s well-known law, which is pv=rt. he found that the pressure for non-conductors such as glucose followed this law, but was higher for electrolytes. this deviation was accounted for by the van ‘t hoff factor i, which indicates into how many particles the solute – at least partially – has dissociated, so that the modified law is pv=irt. the factor i could be deduced from raoult’s freezing point depression, and could also be calculated using arrhenius’ degree of dissociation α. the degree of dissociation, in turn, was determined from the ratio of the conductivity of a dilute electrolyte solution and that under limiting conditions. the agreement found between the factors i determined by the two independent methods was the third proof of the arrhenius hypothesis. there was a fourth proof, namely the additivity of physical properties. with these four nonelectrical and independent proofs, the 56 theses of arrhenius’ dissertation became the groundbreaking theory of dissociation of substances dissolved in water, which he published in 1887. in 1903 the nobel prize in chemistry was awarded to him “in recognition of the extraordinary services he has rendered to the advancement of chemistry by his electrolytic theory of dissociation”. keywords: dissociation theory, arrhenius, electrolyte, solution, activity coefficient. introduction the 1880s, to which this article refers, were remarkable years, for in that decade the prevailing view that the molecules of electrolytes consist in their solutions of oppositely charged ions which are tightly bound together and can be separated only by an electric force acting on them was replaced by a radically different theory. this conventional view dated back nearly eight decades to the time of theodor von grotthuß and humphry davy. this view was challenged but by no means generally replaced by the free-ion hypothesis of rudolf clausius in 1857.[1-3] we have described its history in our earlier articles[4, 5] and do not repeat it here. instead, we will focus on the pioneering theory of svante arrhenius. arrhenius’ scientific interest was in the conductivity of highly dilute electrolyte solutions. this was the subject of his dissertation, which ultimately consisted of a collection of 56 theses or propositions. he presented his dissertation to the royal swedish academy of sciences in june 6, 1883, and published it in 1884.[6, 7] after a break of about three years, he published his theory of electrolyte dissociation in 1887.[8, 9] remarkably, arrhenius managed to form his hypotheses into a solid theory by relying on results obtained by other scientists in the fields of non-electrical phenomena in physics and chemistry. in this article, the chronology of this successive confirmation of his theory is traced. the historical overview, starting from a collection of 56 theses of a dissertation up to the groundbreaking theory “ueber die dissociation der in wasser gelösten stoffe”[8] (on the dissociation of substances dissolved in water) is the subject of the present article. svante arrhenius: biography svante august arrhenius, born in 1859 in vik (also wik or wijk) near uppsala, swedish kingdom, attended the cathedral school in uppsala, matriculated in chemistry and mathematics at uppsala university in 1876, graduating as early as 1878. his photo from that year is shown in figure 1. he then began studies of chemistry with lectures in mathematics and laboratory work in autumn of 1878 at the swedish chemist, mineralogist and oceanographer per teodor cleve, professor of chemistry from 1874 to 1905 at the university of uppsala. arrhenius, however, realized that his interests lay more in the overlapping area between physics and chemistry. since the opportunities to work on such topics were not favorable at uppsala university, he changed to the physical institute of the swedish academy of sciences in stockholm in 1881, figure 1. photo of svante arrhenius from 1878, the year when he began his studies at the university in uppsala. provided by courtesy of the archives at the royal swedish academy of sciences. 57capillary electrophoresis and its basic principles in historical retrospect where erik edlund (1819 – 1888), professor of physics, agreed to supervise him for his dissertation on the condition that he works independently and deals with topics of his own choosing. edlund had a very great diversity of interests from which arrhenius profited considerably. edlund explored, for example, electric sparks,[10, 11] atmospheric electricity and aurora borealis,[12] streaming potentials and dealt with theories of electrical phenomena.[13, 14] after arrhenius had initially tried to find a method for determining the molecular weight of chemical compounds in solution – albeit unsuccessfully and without knowledge of raoult’s paper from 1882[15] – a topic he had begun at uppsala, and which he continued in edlund ś laboratory, he turned his interest to the electric conductivity of dilute electrolyte solutions. arrhenius´ first publication most readers probably do not know that arrhenius’ very first publication was not his dissertation, but his own article published shortly before. in the spring of 1882 he had the opportunity to carry out independently in edlund’s physical laboratory a study of the polarization of electrodes, an undesirable effect of great importance in determining the resistances of electrolyte solutions. he measured the time course of the decrease in polarization current at the electrodes after the direct current had been switched off. from the results he derived some general conclusions which, however, need not be further discussed in the present context. arrhenius paper “undersökning med rheotom övfer den galvaniska polarisationens försvinnande i ett polarisationskärl, hvars plattor äro förbunda genom en metallisk ledning”[16] (examination of the disappearance of galvanic polarization in a polarization vessel with a rheotome, the plates of which are connected by a metallic conductor) was dated october 11, 1882. it is probable that arrhenius did not choose the subject of this study by chance, for knowledge of the operation of the device was of advantage for the measurements of the conductivities of dilute electrolyte solutions in his dissertation, which he began in the winter of 1882/1883, only a few weeks after the publication of this first paper. the dissertation: recherches sur la conductibilité galvanique des électrolytes when in the winter of 1882/1883 arrhenius began with a dissertation studying highly diluted solutions, he was faced with the unpleasant situation that only a few publications had appeared on the subject up to that time, mainly those published by friedrich kohlrausch[17-25] and rudolf lenz.[26-29] although kohlrausch and lenz had published reliable values for conductivities in recent years, they were of little help to arrhenius. kohlrausch reported comprehensive studies of the conductivities of a large number of dilute solutions from 1874 to 1879,[1724, 30, 31] but their electrolyte concentrations were too high for arrhenius’ objective. they were usually greater than about 5% by weight and reached for some solutes nearly 100%. in 1878 lenz did investigate solutions with lower molecular electrolyte concentrations in the range of 10-2 equ.l-1, but his work was limited to the small group of potassium, sodium and ammonium salts and hydrogen acids.[28] moreover, the concentration ranges were still too high for arrhenius’ purposes. arrhenius emphasized on pages 3 and 4 of his dissertation “recherches sur la conductibilité galvanique des électrolytes”[6, 7] – the dissertation was written in french – that kohlrausch had announced several times a work with conductivities in highly dilute solutions. but since this had not yet appeared – kohlrausch ś article “ueber das leitungsvermögen einiger electrolyte in äusserst verdünnter wässeriger lösung” (on the conductivity of some electrolytes in extremely dilute aqueous solution) was not published until 1885[32] – arrhenius decided to begin the investigation he had planned even without knowing kohlrausch’s results. arrhenius carried out the experimental part of his dissertation in edlund’s laboratory in stockholm in the winter of 1882/1883 and spring of 1883. in may 1883 he wrote the second, theoretical part of his dissertation at his parents’ home in uppsala. initially arrhenius wrote his dissertation in one part, but it was rather complicated to read and somewhat confusingly structured. sven otto pettersson, then docent of physics in uppsala, who was asked by arrhenius to read the dissertation in advance, found the work worthy of submission, but advised arrhenius to restructure it; so arrhenius divided it into two parts. he also recommended to avoid the term dissociation, since it was understood to mean the decomposition of a compound into its smaller constituents under the influence of heat. according to petterssoń s advice arrhenius divided the initial version into part 1[6] which consisted from 63 pages, and into part 2[7] with 89 pages. it may be confusing that arrhenius did never use the term dissociation in his dissertation. dissociation for thermal decomposition was introduced in 1857 by the french chemist henri étienne sainte-claire deville (1818 – 1881) in his paper “sur la dissociation ou la décomposition spontanée des corps sous l’ influence de la 58 ernst kenndler chaleur” (on the spontaneous dissociation or decomposition of bodies under the influence of heat).[33] examples are the decomposition of ammonium chloride on heating into hcl and nh3, or of molecular iodine j2 into its atoms, and the reversible recombination of the gaseous particles to the parent molecules on cooling. pettersson foresaw that the term dissociation for the cleavage of electrolyte molecules in solutions would meet with disapproval from the chemistry professors at the university. therefore, arrhenius used in his dissertation the terms electrically active and inactive for the ionic and the nonionic particles. we emphasize that we rely on the two-part dissertation submitted to the royal swedish academy of sciences in june 1883 and published in 1884.[6, 7] première partie. la conductibilité des solutions aqueuses extremement diluées déterminée au moyen du dépolarisateur in part 1, “the conductivity of extremely dilute aqueous solutions determined by means of the depolarizer”,[6] arrhenius first described in detail the apparatus and the devices, the experimental conditions and the chemicals.1 he paid special attention to the control of the correct function of the “depolarisateur” edlund had constructed,[34] and by which he could transform constant into sinusoidal alternating current.2 it is schematically depicted in fig. 3 of arrheniuś dissertation[6], and explained there and in edlund ś paper from 1875.[34] 1 we give here a more detailed description of his experimental conditions, because arrhenius performed his experiments in a very contrarian manner compared to kohlrausch, who measured the conductivities in about the same years. in part 3 of our series, we described how much importance kohlrausch attached to measuring values that were as accurate as possible. he then derived empirical laws from them. arrhenius, on the other hand, as he himself said, was satisfied with less accurate values. he was, however, able to recognize in them an existing tendency from which he deduced his hypotheses. 2 edlund’s depolarizer, incidentally, was severely criticized by e. dorn,[35] [36]. but his criticism was rejected by edlund.[37]. it is, however, remarkable that even in 1886, two years after the completion of arrhenius´ dissertation the problem of measuring accurate conductivities with alternating current was still a matter of question, at least for oliver lodge, to whom we will return below. he added a critical comment in ref. [38], footnote 1 on p. 384 in “translation of a letter received from dr. arrhenius respecting the above criticism” which read: “this opens a large question, viz., how far it is advisable to depend on the use of alternating currents as a device for avoiding polarisation difficulties …. unless the question of electro-chemical capacity be thus considered, and either eliminated by calculation or proved to be negligible by experiment, the presumed advantage of alternating currents in dealing with electrolytic resistance is illusory.” nowadays, depolarizer is the obsolete synonym for an electroactive substance (see iupac, https://doi.org/10.1351/goldbook.d01599, compendium of chemical terminology, 2nd ed. (the “gold book”). the measuring cell which arrhenius used is shown in figure 2. it served for both, the preparation of the different dilute samples and the measurement of their resistances in a rather unconventional, but economical manner. the measurement procedure was as follows. first, a weighed amount of electrolyte was placed in the glass vessel where it was dissolved in 35 cm3 distilled water. the quantity of water and therefore the concentration of the electrolyte were determined by weighing the vessel before and after filling. after measuring the resistance, part of the solution was removed and replaced by distilled water, and the two liquids were mixed directly in the vessel. the dilution was determined again by weighing the vessel after replacing a part of the solution and after refilling with solvent. this procedure was carried out several times in succession, preparing solutions with three to six different concentrations, usually four to five. solutions were diluted till the measured resistance approached that of pure water (in fact, the lowest concentration arrhenius measured was in the range of about 10-4 normal.3) the resistances of the dilute electrolyte solutions were between several hundred and about 120000 ohm. the reproducibility was of the order of 1% or less. however, the chosen procedure had the disadvantage that the concentrations were not determined by quantitative analysis and were therefore of low accuracy, which consequently affected the molecular conductivities, a systematic error that arrhenius readily accepted.4 arrhenius measured the electrical resistances of 47 compounds, i.e. salts, bases, and acids at various dilutions5, and from these their molecular conductivities6. he found that the conductivity in dilute solutions 3 arrhenius often used the term “normal” as a measure of the concentration. it was introduced by karl friedrich mohr in 1855 in his textbook about titrimetric analysis.[39] 4 arrhenius pointed out this low accuracy in § 13. conductibilité moléculaire. p. 38. “from formula (3), the molecular conductivity can be calculated in each special case. the named formula contains the amount of dissolved electrolyte (p). it was not possible to determine this quantity analytically, but only by weighing the electrolytes. as the substances examined are hygroscopic and also somewhat impure, this determination cannot possess great accuracy.” in his reply from 1886 to oliver lodge´s criticism on his low accuracy (ref. [38], p. 386), he wrote: “6. that the last work of kohlrausch contains as you say incomparably better experimental data (especially more accurate) is true enough. but without my data i could not have formed a coherent picture of the whole.” 5 the apparent paradox that the conductivity of an electrolyte solution decreases with increasing dilution, but its molecular conductivity increases, has already been clarified in our previous article[5].in connection with kohlrausch´s law of independent ion migration. 6 the molecular conductivity k/m is the ratio of the specific conductivity, k, and m, the concentration of the solution in g.equiv. per liter. it is the equivalent conductivity, as rudolf lenz emphasized in his study of https://doi.org/10.1351/goldbook.d01599 59capillary electrophoresis and its basic principles in historical retrospect for most electrolytes is proportional to the number of electrolyte molecules. if this is not the case, it must be assumed that chemical reactions take place upon dilution, but he had no conclusive explanation at first. yet it was these effects that attracted his particular interest in his work. arrhenius introduced a quantity he called “dilution exponent” and measured its dependence on the dilution for a given electrolyte. the dilution exponent was the ratio by which the resistance of a salt solution increases when it is diluted by water to twice its volume. in the best case, the exponent is 2.7 haloїd compounds in 1877.[26] 7 to be precise: as arrhenius measured and tabulated resistances, he in § 13. he calculated the molecular conductivities, actually the conductivity at an electrolyte concentration in equivalent per liter of solution, as function of the concentration in the series of dilutions prepared from of one and the same electrolyte solution. he found from his own data, and from those he has taken from publications of kohlrausch[23, 24] und lenz,[28] that the molecular conductivity increases with increasing dilution for all 47 electrolytes he investigated (in the summary of part 1 he mentioned only 45 electrolytes). the electrolytes were salts, and only five bases and acids8 each. their molecular conductivity approached a certain limiting value; the same result found kohlrausch.[23] for most electrolytes, especially for simple ones like the alkali halogenides, molecular conductivity increased slightly and linearly with increasing dilution. however, some solutes, especially ammonia and acetic acid, exhibited deviating properties. their conductivity remained at low values at lower dilution, but abruptly increased when dilution increased. we have discussed these effects already in part 3 of our series;[5] see the lower part of figure 5 there. the complete plot was published by kohlrausch in 1885.[32] to find an explanation for this deviating shape of the curves, arrhenius resorted to hittorf ’s observation of the formation of complex salts of cadmium and iodine.[40] he stated on p. 60 in thesis 11. (the entire dissertation comprised 23 paragraphs and 56 theses, in french “propositions”): “aqueous solutions of all electrolytes contain the dissolved electrolyte at least in the form of molecular complexes”, and attributed the observed irregularities to possible chemical decomposition of complex molecules with increasing dilution. he postulated in thesis 2: “if two or more salts are dissolved in the same non-conducting solvent, the conductivity of the solution is equal to the sum of the conductivities which the solution would possess if only one salt were dissolved at one time and the other salt alone at another time.” in § 16. chemical action, he formulated the following important two theses: thesis 4. if, when diluting any solution, the conductivity does not change in proportion to the amount of electrodefined the dilution exponent as the ratio by which the resistance increases when a given electrolyte solution of the series is diluted. it is obvious that this indicates the corresponding decrease in conductivity. if the solution is diluted exactly to twice its volume, the dilution exponent should be 2, because the number of the initial conducting molecules is exactly bisected. arrhenius found that most electrolytes had values of 1.95 to 2, but some deviated with higher, others with lower values. 8 arrhenius measured the resistances of hydrochloric, nitric, sulphuric, phosphoric and boric acid. figure 2. scheme of the cell arrhenius used for the measurement of the resistance. glass vessel, height, ca. 150 mm; diameter, 25 mm. a, b: platinized platinum electrodes, 2/7 mm thickness. lower electrode a welded to a thick platinum wire, fused into a narrow glass tube k, which passed through the center of the conical cork or rubber plug d, attached to tube r at the top at f. upper electrode b: perforated in center to allow tube r to pass through. two long platinum wires, riveted to plate b, attached to the tube at point c. one of these wires formed with t one of the poles. k, small rubber plate to hermetically seal vessel at the bottom. the test liquid (30 to 40 cm3) filled the vessel to a point slightly above b. reproduced from fig. 4 of arrhenius´ dissertation.[6] 60 ernst kenndler lyte, a chemical change must have occurred in the solution due to the addition of the solvent. thesis 5. if two substances are dissolved in water at the same time and thesis 2. is not applicable, a chemical process must have taken place between the two. in § 17. he discussed the peculiarities of hydrates,9 and in § 20. the nature of the resistance of electrolytes. he attributed the large conductivity of acids to the fact that they have hydrogen as a cation which, because of its small molecular volume, penetrates most easily into the solvent. in the last chapter, § 21: properties of solutions of normal salts, he makes a whole series of conjectures and speculations. the most important hypotheses, however, relate again to the decay of complex molecules, such as those of hittorf quoted above. he argued in theses 11, 12 and 13 that complexes probably decay upon the addition of solvents, so that the complexity approaches asymptotically a lower limit. from this follows the important hypothesis that the more completely complexes decay, the more molecular conductivity increases. important for the further development of his theory is his conviction (p. 60, 61) thesis 11. aqueous solutions of all electrolytes contain the dissolved electrolyte, at least in part, in the form of molecular complexes. thesis 12. the limit, to which the complexity of a normal salt dissolved at extreme dilution tends to approach, is of the same degree for all normal salts. (probably this thesis applies for all electrolytes.) thesis 13. it is likely that this limit is reached only when the salts are divided into simple molecules as represented by the chemical molecular formula. from today’s perspective, this could be seen as a pre-stage to his dissociation theory, as it transfers the idea of the decay of molecular complexes into individual molecules to the decay of molecules into their ions. however, the remaining problem was why the molecular conductivities of most electrolytes regularly increase with increasing dilution, and why some of them increase in deviating manner. 9 by hydrates arrhenius meant acids and bases, using the prevailing term for them. the theory of hydrates of compounds, not necessarily only of electrolytes, will be the motive of a vigorous rejection of arrhenius’ theory of dissociation of electrolytes right after its publication. this earlier hydrate theory should not be confused with the modern theory of solvation or hydration of charged particles. this interesting chapter on this controversy, usually not even mentioned in textbooks and therefore widely unknown, will be covered in a future part of our review series. seconde partie. théorie chimique des électrolytes part 2, “chemical theory of electroly tes”[7] of arrheniuś dissertation began in §1 with his considerations of “ammonia as electrolyte”. it was well known by him that compounds such as liquid, pure and anhydrous ammonia – its boiling point is -33°c -do not transport electricity, but they become conductors when water is added. in volume ii. p. 147, of marcellin berthelot ś10 mécanique chimique, § 2. dissoiution des gaz,[51] he found par exemple, la solution du gaz ammoniac, saturée à basse température se trouve contenir l’eau et le gaz suivant des proportions définies: soit azh3+h2o2, très sensiblement. cet hydrate cristallise d’ailleurs dans un mélange refrigerant. (for example, the solution of ammonia gas, saturated at low temperature, contains water and gas in defined proportions: i.e. azh3 + h2o2, very substantially. this hydrate crystallizes in a refrigerant mixture.) [symbol az stands for french azote, i.e., nitrogen. authoŕ s note]. since, according to the prevailing hydrate theory, hydrates were generally assumed to be dissolved in the same composition in which they crystallize from their solution, arrhenius thus had every reason to believe that ammonia hydrates exist at least partially in solution as azh40h. berthelot further wrote mais tous ces composés sont peu stables, et susceptibles de subsister seulement en présence des produits de leur décomposition; c’est-à-dire que le gaz dissous [h3az], le liquide dissolvant et leur combinaison forment un système en équilibre, équilibre dont les conditions varient avec la température et la pression. (but all these compounds are not very stable, and likely to remain only in the presence of the products of their decomposition; that is to say, the dissolved gas, the dissolving liquid and their combination form a system in equilibrium, an equilibrium whose conditions vary with temperature and pressure.) this means that the equilibrium nh3+h2o = nh4oh is established. from these three components water and ammonia are non-electrolytes, only the weak 10 marcellin pierre eugène berthelot (1827 – 1907) was the most influential and respected chemist in france in his time. he was famous for his innovations in many scientific areas, among others in organic synthesis,[41],[42][43] and in biochemistry and pharmacology. he introduced thermochemistry, where he coined the terms exothermic and endothermic, before thermodynamics took over the dominant role. his standard books about thermochemistry (e.g. refs. [44],[45],[46]) with numerous data were used by arrhenius to support his theory. since midst 1880 berthelot´s interest turned to the history and philosophy of sciences,[47] in particular to alchemy.[48],[49],[50] 61capillary electrophoresis and its basic principles in historical retrospect base nh4oh has the capability to contribute to electric conductivity by splitting off the cation nh4+ and the anion oh-. according to the law of mass action, the equilibrium shifts towards nh4oh when water is added, which is reflected in thesis 14. “the conductivity of an ammonia solution is caused by a small amount of azh4oh, which is contained in it and which increases with the dilution of the solution.” kohlrausch observed the same effect upon dilution of acetic acid we have already mentioned above, and an analogue relation between conductivity and dilution with other acids he had investigated.[21] based on these facts arrhenius came to the main conclusion that the amount of the conducting part of the electrolyte increases with dilution at the expense of the non-conducting part, and formulated one of the most important theses of his dissertation, which turned out to be the nucleus of his later dissociation theory. literally it reads (and stated that thesis 15. also applies to bases). thesis 15. la solution aqueuse d’un hydrate quelconque se compose, hors l’eau, de deux parties, l’une actife (électrolytique), l’autre inactive (non-électrolytique). ces trois parties constituantes, l éau, l’ hydrate actif, et l’ hydrate inactif, forment un équilibre chimique, tel qu´à une dilution la partie active augmente et la partie inactive diminue. (l’actlvité électrolytique se confond avec l’activité chimique). (the aqueous solution of any hydrate is composed, apart from water, of two parts, one active (electrolytic), the other inactive (non-electrolytic). these three constituent parts, water, active hydrate, and inactive hydrate, form a chemical equilibrium, such that on dilution the active part increases and the inactive part decreases.) (the electrolytic activity is equal to the chemical activity). then arrhenius introduced the term “activity coefficient”11 and defined it as le coëf ficient d’activité d’un électrolyte est le nombre exprimant le rapport du nombre d´iones qu’ il y a reéllement dans l’ électrolyte, au nombre d´iones qui y seraient renfermés, si l´électrolyte était totalement transformé en molécules electrolytiques simples. (ces molécules sont nécessairement constituées d’une manière analogue à celle des sels.) (the activity coefficient of an electrolyte is the number that expresses the ratio of the number of ions that are present in the electrolyte to the number of ions that would be present if the electrolyte were totally transformed into simple electrolytic molecules. (these molecules are necessarily constituted in a manner similar to that of salts.) 11 it is equal to the dissociation ratio oliver lodge defined in 1885 on p. 756 of ref. [52] for dissociated molecules in solutions. in § 3. hypothesis of clausius and williamson, arrhenius addressed the question of the number of free dissociated ions in a dilute electrolyte solution, resorting to the free-ion hypothesis of clausius. arrhenius tried to draw conclusions from this hypothesis, which are exemplified in figure 3. although this figure was used for a different conclusion, it is fully suitable for the present one. in this figure, two molecules of the same electrolyte are shown (we negate the curve labeled mm,n). the upper molecule consists of cation a and anion b, the other one of a1 and b1. all ions are charged with the same amount of electricity. cation a1, for example, can split off and combine with anion b of the next molecule. as a result, cation a is released and can unite with anion b1. in solutions, of course, not only these two molecules, but any larger number a2b2, a3b3, ... anbn … are present, so that this process extends over several molecules. however, it will not end until the cation of the last molecule has united with the anion of the first. though arrhenius believed that this process was very fast, there were still free ions existing for short time during this exchange. these have moved in a closed loop, as well as the electricity charged with them. this transport of electricity was called by arrhenius a circular current. it is the natural state of electrolyte ions in a solution – mind you – without an applied electric potential, that is, under the condition that no current flows through the solution. this means that circulating currents occur permanently in an electrolyte solution. because of its connection with the circular flows just discussed, § 6 shall now be treated prior to § 4. however, before continuing with this paragraph, we point out that this concept of the circular current was already introduced by grotthuß as early as 1819 who called it infinite circular molecular exchange, but was hardly taken note of. figure 3. schematic drawing of the flow of the circular current. for explanation, see main text. 62 ernst kenndler although an excerpt of grotthuß´ work appeared in gilbert’s annalen der physik,[53] his entire work was published in the scarcely accessible annalen der curländischen gesellschaft für litteratur und kunst. grotthuß wrote in his article in reference to figure 5, shown below as figure 4 “in den flüssigkeiten, die aus heterogenen elementartheilchen bestehen, ...., muss zwischen diesen elementartheilchen ein beständiger galvanismus, und dadurch ein beständiger wechselseitiger polarischer molekularaustausch unterhalten werden, den man durch das auf taf. iii in fig. 5 dargestellte kreisförmige schema ausdrücken kann. jede wasserzersetzung, die man mit dem namen chemische belegt, ist daher nur eine störunung des fortwährenden molekulargalvanismuis, oder eine ausgleichung des unendlichen kreisförmigen molekularaustausches zu einem endlichen linienförmigen.“ (in liquids consisting of heterogeneous elementary particles …. a constant galvanism must be maintained between these elementary particles, and thus a constant mutual polaric molecular exchange, which can be expressed by the circular scheme shown on plate iii in fig. 5. any water decomposition, which is called chemical, is therefore only a disturbance of the continuous molecular galvanism, or a leveling of the infinite circular molecular exchange to a finite linear one.) after this retrospect to the unexpectedly early concept of the infinite circular molecular exchange by grotthuß, which resembles also williamson’s 1850 hypothesis[54] on the permanent exchange of “radicles” between molecules by double decomposition we continue with § 6. it addressed arrhenius’ conclusion about the consequences of this current when a second electrolyte, cd, is dissolved in the solution instead of a single electrolyte, e.g., ab as described above. § 6. the double decomposition. if ab and cd move through the inactive solvent by the circular current, again without being driven by an applied electric force, consequently the pairs ad and cb also form from ab and cd by double decomposition. thus, all four electrolytes are present in the solution at the same time. their amounts depend on the respective activity coefficients of the electrolytes (the present degree of dissociation). if these are equal, the amounts of all four substances are also equal. if initially one equivalent each of ab and cd are dissolved, half an equivalent of each of the four electrolytes ab, cd, ad and cb will be found at equilibrium. for unequal affinity coefficients, a corresponding equilibrium is reached by double decomposition, and thesis 29. applies: “every salt dissolved in water partially decomposes into acid and base. the amount of these decomposition products is the more substantial the weaker the acid and the base are and the greater the amount of water is.” this thesis leads inevitably to the chief question of the strength of acids and bases. kohlrausch differentiated two groups of acids (the same applied for bases). strong acids show a linear dependence of the molecular conductivity on the number of dissolved molecules, weak acids do not. for both groups some examples of the molecular conductivity, λ, are listed in table 1. it should be recalled that arrhenius had previously equated the molecular conductivity with the activity coefficient. considering the molecular conductivities of the acids and bases from table 1, he formulated thesis 33. “the greater the activity coefficient (molecular conductivity) of an acid, the stronger it is. this thesis also applies to bases”. with this thesis he indirectly formulated his acidbase theory. it stated that acids are compounds that dissociate into h+ ions and negatively charged anions in an aqueous solution. analogously, bases dissociate in water to ohions and to cations. remarkably, he did not define it literally at any point in his dissertation, but it can be clearly understood as such because of the multiple mentions of the active parts of acids and bases. the values of the molecular conductivities in table 1 indicate that the hydrohalic and nitric are strong acids, acetic acid is weak, boric acid is the weakest. in the group of the bases, sodium and potassium hydroxide are strong, ammonium hydroxide is a weak base.12 arrhenius, however, was not satisf ied with the fact that the ranking of the strength was based only on the conductivity, and wanted to evaluate it by an independent method which was not based on electric 12 water is a special case, it has the lowest conductivity of all compounds; it is listed in the group of acids, but it as was generally known that it can also act as a base. figure 4. circular current in a liquid which consists of positively and negatively charged particles. grotthuß did not call them ions in his text, because this term was unknown in his time. note that no electric potential is applied, and therefore no current flows through the liquid. taken from ref. [53]. 63capillary electrophoresis and its basic principles in historical retrospect properties. in his nobel lecture, held december 11, 1903 on “development of the theory of electrolytic dissociation”[55] he admitted that he himself felt that a single line of evidence was not sufficient for a well-founded theory. he said “if this concept had only been applicable to accounting for the phenomenon of electrical conductivity, its value would not have been particularly great.” “an examination of the numerical values adduced by kohlrausch and others for the electrical conductivity of acids and bases as compared with berthelot’s and thomson’s measurements of their relative strengths in terms of their chemical effect showed me that the acids and bases with the greatest conductivity are also the strongest. i was thus led to the assumption that the electrically active molecules are also chemically active, and that conversely the electrically inactive molecules are also chemically inactive, relatively speaking at least. etc.” for the sake of completeness, we think it appropriate to include a chapter, albeit brief, on thermochemistry, which, incidentally, was later replaced by the emerging field of thermodynamics. 1st proof. thermochemistry, heat of neutralization thermochemistry, a branch of physical chemistry, deals with the exchange of heat energy at changes of state of a chemical system, e.g., at phase transformations and chemical reactions. it hypotheses that all chemical changes involve the generation of heat, that the heats of reaction were direct measures of the chemical affinity, and that those processes take place where the most heat is generated. such processes are dissolving, mixing, diluting of substances, the decomposition and recombination of compounds, the decomposition of salts by acids, the determination of the stoichiometry of acids and bases, the reaction of acids with bases, i.e., neutralization reactions, the change of the aggregate state such as melting or evaporation, etc. thermochemical experiments were first described 1838 in a paper from the estate of pierre louis dulong (1785 – 1838),[56] followed by the comprehensive “thermo-chemische untersuchungen” (thermochemical studies) by germain henri hess13 from 1840 to 1842,[57-65] and between 1844 and 1850 by the investigation of abria,[66] by pierre antoine favre (1813 – 1880) and johann theobald silberman (1806 – 1865),[67, 68] and by thomas andrews (1813 – 1885).[69-72] however, the main contributions to the recent theory were published by the danish chemist hans peter jørgen julius thomsen14 as early as 1853 and 1854 in four papers on “die grundzüge eines thermo-chemischen systems” (the principles of a thermo-chemical system) in poggendorff ś annalen der physik und chemie.[73-76] nevertheless, the french chemist marcellin berthelot quoted above, who did not formulate a slightly modified form until 1865 as a lecture (in lessons at the collège de france in 1865 and published it the same year in the revue des cours scientifiques, see also ref. [77]) and also not until 1869 as a journal article in annales de chimie et de physique[77] claimed the priority of thermochemistry, which led to a lifelong fierce controversy between the two scientists. after a hiatus of fifteen years, thomsen continued from 1869 to 1871 with extended studies on “wärmetönung” (“heat toning”), as he called it, that is, the heat released or absorbed by the change of state of a sys13 hess formulated the law named after him,[57] also known the law of constant heat summation. it states that the heat evolved or absorbed in a chemical process is the same whether the process takes place in one or in several steps. 14 hans peter jørgen julius thomsen (1826 – 1909) was professor for chemistry at the university of copenhagen from 1866 till 1891, and from 1883 till 1902 director of the polytekniske læreanstalt, the later danish technical university. table 1. molecular conductivities, λ, of strong (group i) and weak (group ii) acids and bases. concentrations of electrolyte solutions: 1 g equiv. solute per liter solution. the conductivities were taken or calculated from ref. [21], that of distilled water see première partie, § 8.[6] the table is reproduced from arrhenius´ dissertation, seconde partie,[7] p. 14 and 15. 64 ernst kenndler tem. of all the heats of reaction measured by thomsen, arrhenius was most interested in the heat of neutralization of an acid with a strong base in order to classify acids according to their strength on the basis of the amounts of heat they released. between 1869 and 1870 thomsen published a series of six paper on “thermochemische untersuchungen”[78-83] (thermochemical studies) with heats of reaction of numerous acids, including those of neutralization. he collected the results from 1100 calorimetric experiments and 600 chemical reactions in “thermochemische untersuchungen. i. neutralisation und verwandte phänomene” from 1882.[84] it was the first volume of a series of four.15 cutouts from the tables with the values of monobasic hydrochloric, acetic and hydrocyanic acid which he published in 1869[79] and 1870[82] in annalen der physik und chemie are shown in the upper panel of table 2. the main source arrhenius quoted in his work was marcellin berthelot ś 1879 book “essai de mécanique chimique fondée sur la thermochimie.” tabulated values of the heat of neutralization from tome 1. calorimétrie”,[44] livre iii (données numeriques), chapitre vi (chaleurs de formation des sels), p. 383 ff., are shown in the lower panel of table 2. these rounded values were taken by arrhenius in his dissertation in part 2, p.68. in his dissertation arrhenius discussed the reasons for the greater heat of neutralization of the strong acids and the lower heat of the weaker acids. he formulated the principle in § 20, p. 67, of part 2. it read § 20. degagement de chaleur aux reactiones chimiques. “as we know, mr. thomsen claims that all bases, when in the form of dissolved hydrates, release the same amount of heat by neutralizing the same amount of an acid. this simple fact is called “saline thermoneutrality”. in contrast, not all acids release the same amount of heat when they combine with a base. this fact seemed very bizarre to the savants of thermochemistry. however, according to the above, it seems easy to explain it. it is obvious that from the thermochemical point of view, two hydrates can be equal only when they are both in the active state. in the inactive state, the analogous compounds do not play the role of hydrates (acids or bases), 15 thomsen´s motivation to publish this series from 1882 and 1886[84],[85],[86],[87]. was due to reasons of priority. in the introduction of the first volume in 1882 (p. 12, ref. [84].) thomsen wrote “schon im jahre 1853-54 hatte ich in den annalen der physik und chemie, bd. 88, 90, 91 und 92 [73],[74],[75],[76] die fundamentalen dynamischen gesetze der chemischen processe entwickelt. da man aber mir die priorität hierfür hat streitig machen wollen, werde ich im folgenden einige hauptpunkte dieser abhandlungen wieder hervorheben.“ (already in 1853-54 i had developed the fundamental dynamical laws of chemical processes in annalen der physik und chemie, vol. 88, 90, 91, and 92. since, however, one has wanted to dispute my priority for this, i will again emphasize some main points of these treatises in the following.) since they cannot unite with another type of hydrate of opposite sign and form water and salt. so, instead of assuming with thomsen that the hydrates are in “dissolved state”, we assume that they are in “active” state. then we express the following, very plausible hypothesis: le procédé chimique à cause duquel un système d´un équivalent l’acide (actif) et d’un équivalent de base (aussi active) se transforme en un nouveau système, consistant d´un sel (non compliquè) et de l’eau, est accompagné d’un même dégagement de chaleur indépendant de la nature des hydrates. (the chemical process of converting a system consisting of one equivalent of an (active) acid and one equivalent of a (also active) base into a new system consisting of a (non-complex) salt and water is accompanied by the same heat evolution, which is independent of the nature of the hydrates). table 2. heats of neutralization for different acids and bases. upper panel: thomsen´s values from 1869 and 1870 for the monobasic hydrochloric, hydrocyanic and acetic acid. t; temperature in °c. α; number of equivalent base added to 1 equivalent acid. concentrations: varying, typically 1 eq. in 200 or 400 l water. taken from refs. [79, 82]. lower panel: table from berthelot´s 1879 book which was reproduced by arrhenius in his dissertation, part 2, p. 68.1. temperature 15°c. numbers are in kcal. for details, see main text. 1 berthelot´s values in the lower table are rounded; thomsen had given accurate values, for example, 2770 cal for hcn. these differences were insignificant for the ranking of the acids according to their strengths. moreover, the heat of neutralization depends on the temperature.[79] 65capillary electrophoresis and its basic principles in historical retrospect arrhenius then described the sequence in which the neutralization reactions occurs: 1. neutralization through the active parts of the hydrates. 2. new formation of active from inactive parts. 3. neutralization of the newly formed active parts. 4. formation of complex molecules of the resulting salt. 5. possible solidification of the salt. he concluded that the sum of the generation of heat in processes nr. 1 and 3 must be constant at the formation of one equivalent of salt. this is the reason why the heat of neutralization of strong acids with strong bases is about constant, and agrees with the experimental values shown in table 2. process nr. 2, the new formation of active from inactive parts, in contrast, is accompanied by the absorption of heat. he expressed it in theses 52, 53, and 56: thesis 52. la transformation de l´état inactif en l´état actif d´un hydrate ( faible) est accompagnée par une absorption de chaleur. (52. the transformation from the inactive to the active state of a (weak) hydrate is accompanied by heat absorption.) thesis 53. a la neutralisation, un acid faible dégage en général moins de chaleur qú un acide fort. une proposition analogue est valable pour les bases (on neutralization, a weak acid generally releases less heat than a strong acid. an analogous proposition is valid for bases). thesis 56. la chaleur de neutralisation dégagée par la transformation d´une base et d’un acide parfaitement actifs en eau et en sel non-compliqué, n’est que la chaleur d’activité de l’eau. (the heat of neutralization released at the conversion of a perfectly active base and acid into water and a simple salt is nothing but the heat of activation of the water.) the heat of neutralization is therefore a measure for the strength of an acid or a base. for strong acids and bases it is given by the reaction of their active parts, the h+ and the ohions of the completely dissociated electrolytes, under formation of the inactive water molecule. this amount corresponds to the heat of activation of water, which is necessary to completely split water into h+ and oh-. this amount is about 13700 cal mol-1 at 18 °c,16 and corresponds to the experimentally found neutralization heat of a strong acid with a strong base. when a weak acid is neutralized with a strong base such as naoh, the inactive part of the acid must be converted to the active, which requires heat absorption. the total heat balance of the reaction is thus less than 13700 cal, and its magnitude is the measure arrhenius had assumed for the strengths of acids. since the heats 16 the heat of neutralization depends on the temperature. thomsen reported that it decreases by 43 cal °c-1, see footnote 16. of neutralization correlate with the molecular conductivities, arrhenius succeeded in confirming his original hypothesis, that is, the results of thermochemistry were the first proof which he had mentioned as a necessity in his nobel lecture. he concluded his dissertation with the summary of part 2, of which we reproduce the key passage. it read dans la partie présente de cet ouvrage, nous avons d’abord fait voir la vraisemblance·de ce que les électrolytes peuvent se rencontrer sous deux formes différentes, l’une active, l’autre inactive, de sorte que la partie active est toujours, dans les memes circonstances extérieures (température et dilution), une certaine fraction de ln quantité totale de l’ électrolyte. la partie active conduit l’ électricité et est ainsi en réealité électrolytique, mais non pas la partie inactive. in the present part of this work, we have first shown the verisimilitude that electrolytes can occur in two different forms, one active, the other inactive, so that the active part is always, under the same external circumstances (temperature and dilution), a certain fraction of the total quantity of the electrolyte. the active part conducts electricity and is therefore actually electrolytic, but the inactive part is not. [boldface by the author]. this was the first step towards what later became known as the dissociation theory of electrolytes in solutions. he completed his dissertation and submitted it to the swedish academy of sciences. presentation of dissertation, its low grading, and the consequences arrhenius presented his hypotheses in a lecture held at the royal swedish academy of science on june 6, 1883, and submitted them at uppsala university in a slightly modified form as dissertation in 1884.[6, 7] however, robert thalén, the physics professor, and per teodor cleve, the chemistry professor at the university who evaluated the dissertation were not convinced, and arrhenius’ doctoral thesis was given a poor grade. it was awarded a forth class, its defense a third class. this rating was too low to lecture as a docent, and the uppsala faculty offered him only an unpaid position, what he refused. immediately after the disappointing assessment in 1884, arrhenius sent copies of his dissertation to several european physical chemists, most of whom did not respond,17 except wilhelm ostwald, professor at the 17 we would like to comment that although the english physicist sir oliver joseph lodge (1851 – 1940) mentioned above did not contact arrhenius directly, he subjected the two parts of arrhenius’ dissertation separately to an extraordinary detailed critical analysis of almost every 66 ernst kenndler riga polytechnic.18 ostwald described his ambivalent judgment to reply or not in chapter 11 of his “lebenslinien: eine selbstbiographie”[90] (lines of life: a self-biography; also lifelines: an autobiography) after reading arrhenius’s dissertation. he found that “the work contained obvious weaknesses (which were also exaggeratedly emphasized by other critics afterwards); so that i still had to reckon with the possibility that those correct results had only turned out that way by chance”. ostwald had already executed experiments about the specific affinities of acids and bases. he conducted them during the time arrhenius was working on his dissertation, but in contrast to him, using various non-electrochemical methods. his investigations, which led to the second proof of arrheniuś hypotheses, were a good fortune for arrhenius. he said retrospectively in his nobel lecture “development of the theory of electrolytic dissociation” held on december 11, 1903 (we continue with this lecture which we have cited above up to “etc.”) “. ….. etc. the norwegian research scientists guldberg and waage had developed a theory according to which the strength of different acids could be measured …… by their capacity of increasing the speed of certain chemical reactions. in conformity with this we can suppose that the speed of a reaction produced by an acid is proportional to the number of active molecules in it. i had only a few experiments by berthelot to demonstrate this law, but in 1884 ostwald published a large number of observations which proved that this conclusion was correct.” these observations of wilhelm ostwald, to which arrhenius referred, will be the subject of the following chapter. paragraph, thesis and equation in a report of the british assiciation for the advancement of science.[88]. the entire analysis contained no less than 27 closely printed pages (part i, p. 357362, part ii, p. 362-384.) lodge pioneered radiotelegraphy and discovered electromagnetic radiation earlier than heinrich hertz. he held patents for radio and the moving coil loudspeaker. he was familiar with electrophoresis as well. in 1886, he invented the moving boundary method,[89] an electrophoretic method that replaced hittorf´s method for determining transference numbers. we have described the latter method in detail in part 3 of our historical review.[5] the moving boundary method had the great advantage that the transference numbers could be measured in much less time, with much less effort and without chemical analysis of the constituents in the electrode compartments, at lower cost and, above all, with much higher accuracy. in 1881 he became professor of physics and mathematics at university college liverpool. from 1900, lodge was the first rector of the new university of birmingham. in the late 1880s lodge developed a keen interest in spiritualism and telepathy and became a member of the ghost club. founded in london in 1862, the ghost club is a paranormal research organization. the club is concerned with ghosts and hauntings, but has also studied ufos, dowsing and cryptozoology. 18 in the following we will tell more about ostwald, since he played an eminently important role in arrhenius’ life. 2nd proof. ostwald´s “studien zur chemischen dynamik” (studies on chemical dynamics): molecular conductivity and affinity coefficient wilhelm ostwald, born in 1853 in riga, now capital of latvia, studied from 1872 chemistry at the university of dorpat, now tartu, estonia. in 1882, at the age of 29, he became a professor at the riga polytechnic, where he continued the work he had made in dorpat.[91-95] from 1882 to 1884 ostwald, already professor in riga, published the first three parts of the series on “studien zur chemischen dynamik” (studies on chemical dynamics) but without knowing about arrhenius’ dissertation. a photograph of ostwald taken at the time when he began with these studies is shown in figure 5. the goal of ostwald’s “studies in chemical dynamics” was to determine the relative strengths of acids based on the intensity of an acid’s effect on a base. his aim was to express this intensity by a number which he quoted as “affinitätsgröße” (affinity value, affinity, in some papers affinity coefficient) of the acid. he determined this affinity from the reaction rate of the acid with the corresponding reactant. in other words, the greater the affinity of an acid in a reaction under unchanged conditions, e.g., at constant temperature and concentrations, the stronger the acid. he chose acids for his new research because he had already done earlier work with these compounds in dorpat between 1877 and 1881 on other questions and with other methods.[93-97] in his first paper of this series,[98] dated december 1882, ostwald determined the rate of complete conversion of acetamide by different acids, all under the same conditions. for “zweite abhandlung”[99] ostwald hydrolyzed methyl acetate to acetic acid and methyl alcohol. this reaction was analogous to that described by m. berthelot and l. péan de st. gilles in 1862 for the formation of esters from acids and alcohols.[100-103] the subject of “dritte abhandlung: die inversion des rohrzuckers” (third treatise: the inversion of cane sugar)[104] was the influence of acids on the rotation of polarized light of cane sugar. investigations on the course of inversion as a function of reaction time had already been successfully carried out in 1850 by ludwig wilhelmy19 but remained 19 ludwig ferdinand wilhelmy (1812 – 1864) was a german physicist and physical chemist. he is considered the first to publish quantitative studies on chemical kinetics. in 1850, using a polarimeter, he measured the conversion of sucrose into fructose and galactose after the addition of acid (we have quoted it in the main text; it is the reaction ostwald studied in his third treatise). he formulated the kinetics of the reaction in complex differential equations and published in 1851 the book “versuch einer mathematisch-physikalischen wärme-theorie”[105] (attempt of a mathematical-physical theory of heat). 67capillary electrophoresis and its basic principles in historical retrospect largely unnoticed.[106, 107] in 1862 j. löwenthal and e. lenssen[108, 109] also described the influence of acids on the inversion of sugars. ostwald added the corresponding acid solution to a solution of cane sugar and determined the inversion rate from the optical rotation measured with the aid of a thermostated polarization tube. the rate constants were calculated by wilhelmy ś formula.[106, 107] this method was the most accurate and the least labor-intensive and time-consuming of the methods used, since it did not require chemical analysis to keep track of its progress. the affinities of the acids obtained by this third treatise agreed sufficiently well with those from the hydrolysis of methyl acetate. this result definitively confirmed the conclusion drawn from the previous treatises that the order of the affinity corresponds to the order of the strengths of the acids. ostwald thus succeeded in compiling such a list by three independent methods. ostwald had just completed the third treatise – it was dated april 1884 – when he received in june 1884 the dissertation arrhenius has sent to him. he reported in chapter 11 of his autobiography [90] that at this day he had a tooth ulcer, his wife gave birth to their daughter, and, last but not least, he received the dissertation. the tooth ulcer healed, mother and daughter were well, but the dissertation gave him a headache and a restless night. at first he thought the work was nonsense. after closer study, however, he realized that the author had treated and partly solved the great problem of the proportionality of the affinity coefficients of acids and bases and their electric conductivity in a much more comprehensive way than he had. we quote a passage from his autobiography which we regard as typical of the integrity of ostwald’s character. he describes with admirable sincerity the moral dilemma he faced. should he, who was himself working on a new branch of research, prevent a possible competitor, or should he include him? we reproduce in the footnote 20 what ostwald reported on this. immediately thereafter, ostwald began to measure the molecular conductivities of the acids whose affinity coefficients he had determined in his “studien zur chemischen dynamik” described above, and meanwhile informed arrhenius by letter about his plan. to measure the conductivities, he aimed to apply alternating current according to kohlrausch’s method,[25] but did not yet have any equipment available in riga. he therefore borrowed a resistor box from the riga telegraph office for a short time, copied it himself in the polytechnic’s workshop, and performed the measurements on his extensive collection of acids, which he possessed from earlier investigations. the measurements were completed in a few days, and he immediately submitted the results for publication to journal für praktische chemie as “notiz über das elektrische leitungsvermögen der säuren” (note on the electrical conductivity of acids), dated july 1884.[110] in this publication he held that the rate of chemical reactions depends on the velocity and thus on the conductivity of the ions which are involved. he mentioned that in his “studies in chemical dynamics” of 1883 20 ostwald wrote: “one can easily imagine what a confusion of feelings such a realization must arouse in a young researcher [ostwald] who has only to make his future and suddenly finds himself confronted with a highly energetic co-worker in the field which he had chosen so lonely and remote. in addition, the work contained obvious weaknesses ......, so that i still had to reckon with the possibility that those correct results had only turned out this way by chance. for a few days, as in bürger’s ballad, the black and the white companion [gottfried august bürger (1747 – 1794) was a popular german poet; author´s note] fought over my soul. it was certainly not difficult to keep this sudden competitor in the background by silence, since at present only a few professional colleagues cared at all about such questions. then, because of the existing errors, one could condemn the whole thing and, besides, the publication in the writings of the swedish academy of sciences was an obstacle for the dissemination anyway, since these hardly came into the hands of the chemists. so all i had to do was ignore the writing to keep the competitor at bay, if not for good, then for the foreseeable future. ... i did not learn the details of the technique of fighting unwelcome coworkers as well as competitors until later. ... on the other hand, the scientific idealism that i had acquired as a self-evident prerequisite for all work in this highest field of human progress ... was active. ... in addition, the joyful feeling asserted itself to be able to plow a virgin soil shoulder to shoulder with a new fellow worker [arrhenius], ..., especially since i found him equipped with intellectual working means which i had not used before and which, in combination with those familiar to me, ensured an all the more effective progress. … “ figure 5. photo of wilhelm ostwald from 1882, the year he became a professor at the riga polytechnic. unknown author. reprinted with permission. © copyright gerda and klaus tschira foundation, 2022. 68 ernst kenndler and 1884 he showed that the rates of reactions affected by acids are proportional to the affinity of the acids as determined by him.[98, 99, 104] therefore, there is also a proportionality between the reaction rates and the electrical conductivity. he pointed out that svante arrhenius arrived at the same result by a different route, by that which he published in his dissertation in 1884. in contrast to the many controversies about the priority of theories by other researchers, ostwald emphasized with remarkable righteousness on p. 93 ”dem autor dieser abhandlungen, die zu dem bedeutendsten gehört, was auf dem gebiet der verwandtschaftslehre publicirt worden ist, kommt nicht nur die priorität der publikation, sondern auch die der idee zu“ (to the author of these treatises, which belong to the most important what has been published in the field of affinity theory, comes not only the priority of the publication, but also that of the idea.) since arrhenius’ dissertation was submitted to the swedish academy on june 6, 1883, and published in may 1884, he received it directly from him not until june 1884. he emphasized this chronological order by noting: “i give these details in order, in stating the independence of my efforts in this field from arrhenius’ work, not to fall into the appearance of an unmotivated priority reclamation.” ostwald then gave in a table (table 3) the comparative values obtained by three independent methods. column i of this table lists the conductivities of the acids measured by him, column ii the rate constants of the catalysis of methyl acetate and column iii the rate constants for the inversion of cane sugar. comparing these values ostwald concluded eine übereinstimmung, wie sie die drei reihen bieten, habe ich selbst nicht erwartet; diesselbe ist wohl geeignet, jeden zweifel an der bedeutung der affinitätsgrössen zu heben. bedenkt man, dass weder die temperatur, noch die verdünnung bei den drei verglichenen versuchsreihen diesselbe war, so darf man die uebereinstimmung der drei reihen, deren unterschiede im uebrigen ganz gesetzmässig verlaufen wohl befriedigend nennen. in bezug auf die weitgehenden consequenzen, welche aus diesem ergebnis gezogen werden können, muss ich auf die oben citirten arbeiten von s. arrhenius verweisen. riga, juli 1884. (i myself did not expect an agreement such as that offered by the three series; this is probably suitable to remove any doubt about the significance of the affinity coefficients. considering that neither the temperature nor the dilution was the same in the three series of experiments compared, one may quote the agreement of the three series, whose differences are otherwise quite lawful, as satisfactory. with regard to the far-reaching consequences which can be drawn from this result, i must refer to the above cited work of s. arrhenius. riga, july 1884). immediately after the publication of this note, ostwald traveled via stockholm to uppsala where he met arrhenius, and spent three days with lively discussions, and borne of great personal sympathy. they agreed that arrhenius should come to riga as soon as possible for joint work. for this, however, arrhenius first needed his habilitation. through ostwald’s offer of a position in riga, arrhenius was appointed docent in uppsala. moreover, arrhenius received in 1886, with edlund’s support, a three-year traveling scholarship from the royal swedish academy of sciences to meet leading physicists in europe. he first used it for cooperation with ostwald in riga in 1886, visited friedrich kohlrausch in würzburg in 1886 and 1887, ludwig boltzmann in graz in 1887 (see the photo in figure 6), van ’t hoff in amsterdam in 1888,21 and again in 1888 ostwald in leipzig, where ostwald became professor of physical chemistry in 1887. 21 where he published by support of van ´t hoff ”theorie der isohydrischen lösungen“,[112] concluded march 1888. table 3. column i. records the conductivities of the acids measured by ostwald after he received the dissertation arrhenius has sent to him, column ii. the rate constants of the hydrolysis of methyl acetate, column iii. the rate constants for the inversion of cane sugar. the values were related to hcl=100. taken from ref. [110]. 69capillary electrophoresis and its basic principles in historical retrospect 3rd proof. van ´t hoff´s theory of osmosis it was a beneficial coincidence that in the midst 1880s jacobus henricus van ’t hoff22 investigated the osmotic pressure between the dilute solution of a solute and the pure solvent, which were separated by a semipermeable membrane. he was referred by t he dutch botanist hugo de vries to the work of wilhelm pfeffer (1845–1920), then professor of botany in basle. in 1877 pfeffer had measured the osmotic pressure, p, with membranes23 that were permeable only to water, but not to solutes.[115] he found that, at a given concentration, p is proportional to the absolute temperature, t; at a given temperature, p is inversely proportional to the volume, v, or proportional to the concentration. pfeffer describes this dependence by 22 the dutch physical chemist jacobus henricus van ’t hoff (1852 – 1911) was one of the most renowned scientists of his time. he made important contributions in various fields of chemistry. in addition to the subject treated here, namely the theory of the osmotic pressure of dilute solutions, he proposed the tetrahedral structure of the bonds of the carbon atom, explained optical activity, and developed stereochemistry. he contributed significantly to chemical kinetics and thermodynamic issues. he was the first nobel laureate in chemistry in 1901 “for his discovery of the laws of chemical dynamics and osmotic pressure in solutions.” 23 pfeffer produced membranes by placing two different solutions into contact in a cell made of clay. one solution contained copper acetate, the other potassium ferrocyanide. the detailed properties of numerous membranes and the conditions for their formation were described by moritz traube in 1867.[113] those used by van ‘t hoff are found as experiment no. 145 on page 244 in ref. [114]. p=kt/v or pv=kt, where k was a constant of proportionality. applying the laws of boyle, henry, gay-lussac and avogadro, van t́ hoff deduced that the constant k is equal to the gas constant r. the equation for the osmotic pressure read thus pv=rt. it is expressing the analogy between the osmotic pressure of a compound in solution and the pressure of the compound when it is in the gaseous state under the same conditions, i.e., at the same temperature and in the same volume. van ´t hoff presented his theory at l ácadémie royal des sciences de suède on october 14, 1885 as memoir entitled “lois de l`équilibre chimique dans l`état dilué, gazeux ou dissous” and published it in kongliga svenska vetenskaps-akademiens handlingar.[116] on p. 43 he emphasized this analogy by stating la pression exercée par les gaz à une température déterminée si un méme nombre de molécules en occupe un volume donné, est égale à la pression osmotique qu’exerce dans les mémes circonstances la grande majorité des corps, dissous dans les liquides quelconques. (the pressure exerted by the gases at a given temperature determined if the same number of molecules occupy a given volume, is equal to the osmotic pressure exerted by the great majority of bodies, dissolved in any liquids under in the same circumstances).24 transformed to modern terminology: the osmotic pressure, π, is directly proportional to the concentration, c, of the solute, or to the number of dissolved particles per unit volume, respectively. this relation is formally equal to the equation of state of an ideal gas, and reads πv=nrt (n is the number of moles) or π=crt.[118] however, van ‘t hoff found in experiment that the relationship held good for non-electrolytes as solutes, e.g., for glucose, but for electrolytes the osmotic pressures were higher. for such solutions the equation had to be modified to pv=irt (now π=icrt, with i being the van ’t hoff factor. for strong electrolytes these factors, i, were integer numbers, and were equal to the number of ions upon complete dissociation. for electrolytes, e.g., with formula ab, the van ’t hoff factor was 2, it was 3 for a2b, etc. remarkably, non-integer numbers were measured for weak electrolytes, indicating partial dissociation of molecules into ions and uncharged fractions. it was shown that van ‘t hoff factor i and arrhenius’s degree of dis24 van ´t hoff published in 1866 the very similar, but not the same paper ”l`équilibre chimique dans les systèmes gazeux ou dissous à l`état dilué” in archives néerlandaises.[117] figure 6. photograph taken during arrhenius´ visit of ludwig boltzmann in graz in 1887.[111] date: october 1887. source universität graz. author unknown. arrhenius is the fourth from the right, standing behind boltzmann. public domain. the photograph shows, standing from the left: walther nernst,. heinrich streintz, svante arrhenius, richard hiecke. sitting, from the left: eduard aulinger, albert von ettingshausen, ludwig boltzmann, ignaz klemenčič, victor hausmanninger. 70 ernst kenndler sociation α are related to each other.25 for arrhenius, the results of van ‘t hoff ’s osmotic pressure theory were the most convincing confirmation of the theses of his dissertation.26 this was the third proof and the decisive step towards a well-founded dissociation theory. ostwald was highly dissatisfied with the fact that the journals established in the1880s published scientific papers in the field of physical chemistry mostly intermingled with publications covering a wide variety of fields. in his opinion, papers on physical chemistry topics did not receive the attention they deserved. he therefore decided to found a new journal focusing on the field of physical chemistry, and published the first issue of this “zeitschrift für physikalische chemie, stöchiometrie und verwandtschaftslehre,27 in 1887 with van t́ hoff as co-editor and with the collaboration of the most prestigious european scientists. it was, like the following issues, a resounding success. this journal offered arrhenius a platform for the distribution of his theory, including explanatory state25 van ‘t hoff wrote about these deviations of the osmotic pressure for solutions of electrolytes from avogadro’s law, that arrhenius pointed out by letter to him the connection of factor i with the degree of dissociation (ref. [118] , p. 501.) 26 van ´t hoff´s theory of the osmotic pressure offered the theoretical explanation of the observations of the lowering of the freezing point of solutions with different solutes by françois-marie raoult in 1882. [15] raoult measured this lowering with six different solvents and about two hundred compounds as solutes and found empirically (transl. from french) (i) all bodies, on dissolving in a definite liquid compound which can solidify, lower the freezing point. (ii) in all liquids, the molecular lowering of the freeing point due to the different compounds approaches two values, invariable for each liquid, of which one is double the other.) (iii) the normal molecular lowering of the freezing point varies with the nature of the solvent.) (iv) one molecule of any compound dissolved in 100 molecules of any liquid of a different nature lowers the freezing point of this liquid by a nearly constant quantity, close to 0.62 degrees.) if water is the solvent, and molar concentrations are taken, raoult´s law can be expressed as: when one mole of particles is dissolved in one kilogram of water, its freezing point decreases by 1.86°c (if dissolved in 100 g water, the freezing point decreases by 18.6°c). the corresponding temperature difference is called the molar freezing point depression. this effect is independent of the type of the solute. it holds good only for very dilute solutions. note that arrhenius will make use of it in his dissociation theory which he publishes in 1887. we clarify the depression by an example, because the relation between concentration and temperature is sometimes given confusingly. strong electrolytes consisting of two univalent ions give the molecular depression 2x1.85 =3.7, those consisting of one bivalent ion with two univalent ions give 3x1.85 =5.55, those of one tetravalent ion with three univalent ions give 4x1.85=7.4, etc. non-electrolytes give 1.85°c depression (the difference between 1.85 and 1.86 is insignificant in practice). 27 in 1928 the title was shortened to zeitschrift für physikalische chemie and a new numbering was assigned, in 1954 the numbering was changed again, since 1979 the journal is published with the subtitle international journal of research in physical chemistry and chemical physics. ments for the unconvinced readers. ostwald published arrhenius´ paper on electrolyte dissociation[8] in this first volume.28 the theory: “ueber die dissociation der in wasser gelösten stoffe” (on the dissociation of compounds dissolved in water) arrheniuś seminal publication on the dissociation of dilute electrolytes[8] essentially contained the results of his dissertation and the proofs we have already discussed above. so we will only briefly repeat these parts. it is noticeable that he did not present the theory chronologically, that is, not with the theses of his dissertation that electrolyte molecules are divided into an electrically active and an inactive part even when no current passes the solution. the reason for this may have been that many chemists were skeptical of clausius’ hypothesis of free ions, which arrhenius considered one of the precursors of his theory. arrhenius began his publication with van ‘t hoff ’s theory of the osmotic pressure exerted by dilute solutions of any substance on semipermeable membranes[116, 117] which is described above in the 3rd proof. its decisive result was that a factor, the van t́ hoff factor i, has to be introduced. it was an integer or a fractional number, and depended on the number of all dissolved particles in the solution which, as it was believed also by ludwig boltzmann,[121] “bombard” the membrane. arrhenius went on to consider the activity coefficient as defined after thesis 15 in his dissertation, symbolized by α and called degree of dissociation in his dissociation theory. α can be determined from the ratio of the molecular conductivity λd of the diluted solution and the limiting molecular conductivity, λo as α=λd/ λo. he showed, as also proved by kohlrausch, that at the limit of infinite dilution there is complete dissociation. in this case α=1, at lower dilution α<1. arrhenius 28 remarkably, max planck published in the same volume a theory of dissociation independent of arrhenius and based on thermodynamics, entitled “über die molekulare beschaffenheit verdünnter lösungen” (on the molecular nature of dilute solutions), in which he dealt mainly with raoult’s law of freezing point depression.[119]. he introduced a constant i, the decomposition coefficient, of dissolved molecules, which was identical with van ‘t hoff ’s constant i calculated for aqueous solutions of various substances, but had a different physical meaning there. unlike arrhenius, planck did not link his theory to electrical conductivity. it was therefore less general and received little attention. to remain in the context of what are now called colligative properties, it should be mentioned that planck, in the paper “über den osmotischen druck”[120] from 1890, showed that both the existence and the magnitude of osmotic pressure follow directly from the same general thermodynamic principles that underlie the laws of vapor pressure and freezing point of a solution, without reference to molecular conceptions. 71capillary electrophoresis and its basic principles in historical retrospect showed that if α is known, the factor i could be deduced as follows. if m is the number of inactive molecules, n the number of active molecules, and k the number of ions into which each active molecule splits, then i=(m+kn)/(m+n). consequently, since α=n/(m+n), the relation between i and α reads i=1+ α(k-1), and can be calculated from the known value for k and the measure value for α. second, the van ‘t hoff factor i can be determined from raoult’s law of freezing point depression, i.e., from the freezing temperature t, as i=t/18.5. arrhenius thus had two independent methods to obtain the van ‘t hoff factor and to compare their agreement. the values for 24 compounds out of a total of 86 which were calculated by the above methods are shown in table 4. by comparing the values of i for the individual compounds in the 4th and the 5th columns of the table, arrhenius observed indeed a pronounced agreement of most of them (the deviations of copper and cadmium salts were explained by their tendency to form complex molecules). he thus concluded that the following hypotheses to calculate the figures were correct. (1) van ‘t hoff ’s law is valid not only for the majority, but for all compounds, that is to say, also for electrolytes in aqueous solutions. (2) each electrolyte in aqueous solutions consists partly of active molecules and partly of inactive molecules. the inactive molecules are converted into active ones when diluted, with the effect that only active molecules are present in solutions under the limiting condition of infinite dilution. this led to the 3rd proof of his hypothesis. after a discussion of possible objections of chemists, which essentially concerned the effect of molecular complexes, arrhenius gave further evidence of the validity of his theory, which he summarized under the concept of additivity of physical properties, and which we have not explicitly discussed as 4th proof in the previous part of this text. arrhenius considered the properties of dilute salt solutions as additive when the sum of the properties of the parts of the solution, that is the solvent and the parts of the molecules which actually coincide with the ions, is equal to the property of the solution. these additive properties are physical in nature and can be expressed in numerals. arrhenius cited the following additive properties in favor of his theory. 1. the conductivity. its additive property was described in 1879 by kohlrausch in his law of independent ion migration.[23] the conductivity of a salt solution is therefore the sum of the conductivities of the positive and negative ions. that of water as a solvent is usually negligible, except in extremely dilute solutions (see ref. [122] and the discussion about pure water in part 3 of our series[5]). however, this applies only to so-called strong electrolytes, that is, completely dissociated compounds such as the salts of monobasic acids and the strong acids and bases. for weak acids and bases, e.g. for acetic acid, hydrocyanic acid and ammonia, the additivity does not apply, except for extremely dilute solutions for the reasons already mentioned above. 2. the heat of neutralization in dilute solutions. this has already been discussed in the chapter about the 1st proof above. 3. the specific volume and the specific gravity of dilute salt solutions. claude-alphonse valson reported table 4. comparison of the van ´t hoff factors, i, for dilute aqueous solutions of non-conductors, bases, acids and salts, derived from raoult´s freezing point depression, t (column 4) and from its relation to the degree of dissociation, α, as given in the above text (column 5). α was measured from the ratio of the conductivities of the dilute solution and those at limiting conditions. temperature t is in °c. the paper lists a total of 90 solutes. substance formula α i= t/18.5 i= 1+(k-1)α non-conductors methyl alcohol ch3oh 0.00 0.94 1.00 phenol c6h5oh 0.00 0.84 1.00 acetone c3h6o 0.00 0.92 1.00 acetamide c2h3onh2 0.00 0.96 1.00 bases lithium hydroxide lioh 0.83 2.02 1.83 sodium hydroxide naoh 0.88 1.96 1.88 ammonia nh3 0.01 1.03 1.01 methylamine ch3nh2 0.03 1.00 1.03 acids hydrochloric acid hcl 0.90 1.98 1.90 nitric acid hno3 0.92 1.94 1.92 sulphuric acid h2so4 0.60 2.06 2.19 hydrogen sulphide h2s 0.00 1.04 1.00 boric acid b(oh)3 0.00 1.11 1.00 hydrocyanic acid hcn 0.00 1.05 1.00 formic acid hcooh 0.03 1.04 1.03 acetic acid ch3cooh 0.01 1.03 1.01 salts potassium chloride kcl 0.86 1.82 1.86 ammonium chloride nh4cl 0.84 1.88 1.84 potassium cyanide kcn 0.88 1.82 1.82 sodium acetate ch3coona 0.79 1.73 1.79 ammonium sulphate (nh4)2so4 0.59 2.00 2.17 copper sulphate cuso4 0.35 0.97 1.35 mercuric chloride hgcl2 0.03 1.11 1.05 cadmium iodide cdj2 0.28 0.94 1.56 cadmium nitrate cd(no3)2 0.73 2.32 2.46 72 ernst kenndler 1871 that the specific gravity (which is the ratio of the density of an object, and a reference substance), is an additive property.[123] 4. the specific refractive power of solutions. it was shown by john hall gladstone in 1863 that the so-called refractive equivalent is an additive property.[124] this additivity also applies to dilute aqueous solutions of dissociated electrolytes. 5. the capillarity phenomena. they are, according to valson[125] additive properties of solutions of salts. however, since they can be traced back to the specific gravity they required no further justification. 6. the freezing point depression. its additivity by salts in water was discussed in 1885 by raoult.[126] some properties are proportional to the freezing point depression. guldberg[127] and van t́ hoff[116] showed this for the lowering of the vapor pressure, and the osmotic pressure, hugo de vries for the isotonic coefficient.[128] with this additional evidence for his theory, arrhenius completed his seminal paper. ostwald promoted arrheniuś dissociation theory, nonetheless many chemists initially disapproved it. their objections were mainly the same which were already directed against clausius’ theory, and which arrhenius had tried to present as untenable in his dissertation in part 2 on pages 6 and 31. in passing, it should be mentioned that ostwald first actively defended the theory in 1888 in his articles in volume 2 of the same journal,[129, 130] in 1889 with w. nernst in the joint paper “über freie jonen” (on free ions) in volume 3,[131] and in many other papers and at various occasions. we have described in part 3, p. 97-98, of the present series[5] that in this 1889 paper capillary electrophoresis was performed in one of four occasions in the entire 19th century. beside his pioneering theory, arrhenius contributed with numerous publication on this subject. in the years from 1887 to 1889, he published eight papers.[112, 132-139] in addition to the following attacking “electrolytic dissociation versus hydration”[140] from 1889. it was addressed to the proponents of the prevailing hydrate theory, english chemists who vehemently rejected his theory.29 this “early” hydrate theory dates back to the 1810s and is probably not known in detail to today’s chemists. it is not to be confused with the modern hydrate theory, which is now known to every chemist and physical chemist. the followers of the early hydrate theory, most notably henry edward armstrong and spencer umfreville 29 the paper was communicated by himself in english; an exception, since he usually published in german, and preferably in swedish in kongl. svenska vetenskapsakademiens handlingar, bihang tili kongl. vetenakapsakademiens handlingar and in öfversigt öfver kongl. vetenskapsakademiens förhandlingar. pickering, considered arrhenius’ assumption that anhydrous ions exist in aqueous solutions to be incompatible with their theory.30 they suspected that, especially in highly dilute solutions with their extreme excess of water, the dissociation theory was in conflict with the law of mass action. in 1903, about fifteen years after the publication of his theory, arrhenius received the nobel prize in chemistry “ in recognition of the extraordinary services he has rendered to the advancement of chemistry by his electrolytic theory of dissociation.”31 it is therefore somewhat surprising that some advocates of the hydrate theory held to their strict rejection of electrolyte dissociation decades after the nobel prize was awarded. we will not finish thus the story about this rejection without mentioning that, as reported in ref. [141], p. 1559, even in the 1930s prof. louis albrecht kahlenberg32 taught electrochemistry at the university of wisconsin disregarding the existence of ions in solutions. early hydrate theory and transformation of its parts into the modern one arguably deserved its own historical overview because of the decades-long importance of the former and its role in combating dissociation theory, especially since it has fallen into oblivion. summary when in the early 1880s the swedish doctoral student svante arrhenius decided to investigate the electrical conductivity of highly diluted electrolyte solutions as the subject of his dissertation there were hardly any studies on this topic in the literature. most of them were published by his 18 years older contemporary friedrich kohlrausch, who had been measured conductivities at 30 indeed arrhenius stated verbatim on p. 32 of his 1889 pamphlet [author´s note: n is the number of water molecules that form complexes of defined stoichiometry with a salt molecule]: ”but as we have no ground for attributing any particular value to n, and as it is besides probable that many salts (e. g. most of those of potassium) exist only in the anhydrous state, the simplest and likeliest assumption is that the ions of the salts, and consequently the salts themselves, exist in solution without water of hydration.” 31 to wilhelm ostwald the nobel prize in chemistry 1909 was awarded “in recognition of his work on catalysis and for his investigations into the fundamental principles governing chemical equilibria and rates of reaction.” 32 louis albrecht kahlenberg (1870 – 1941), a us american chemist, was professor of physical chemistry at the university of wisconsin, where he taught and carried on research for forty-seven years until his retirement in 1940. beside others, his scientific area was ion conductivity in non-aqueous solutions. politically, he was opponent of america’s entry into world war i, which was unnecessary in his opinion. he was a doctoral student of wilhelm ostwald at the university of leipzig, where he received a phd, but rejected arrhenius’s dissociation theory. 73capillary electrophoresis and its basic principles in historical retrospect higher concentrations, and extended his measurements to highly dilute solutions in these years. at first glance, the completely different ways in which arrhenius and kohlrausch conducted their experiments and interpreted their results are striking. kohlrausch was known for his extremely careful execution of his experiments, for the search and elimination of possible sources of error, and the associated time-consuming and labor-intensive investigation of the solutions with the intention of obtaining the most accurate measurement results possible. these exceptionally accurate data allowed him to derive empirical equations from them (see, e.g., ref. [5]) arrhenius carried out his conductivity measurements in a contrary manner. he did not attach any particular importance to the high accuracy of his measurements, but rather intuitively detected a certain tendency from the data obtained, from which he derived hypotheses rather than empirical laws.33 as part of his dissertation arrhenius measured the electrical resistances of dilute solution from about fifty different electrolytes, and calculated their molecular conductivities as a function of their dilution. he summarized his observations and his conclusions in 56 theses, of which we quote some of the most important. he recognized that the strongest acids – he examined only 5 – were those with the highest molecular conductivity. he observed that the molecular conductivity increased with increasing dilution, and he distinguished two different groups of electrolytes. in the first group, the strong electrolytes, the molecular conductivity increased very little and almost linearly with dilution, approaching the maximum value under limiting conditions. it was assumed that this increase was due to decreasing frictional resistance between the electrolyte molecules as their distances increased with dilution. the second group, the weak electrolytes, behaved completely differently. their molecular conductivity initially remained at a low level with increasing dilution, but increased abruptly at sufficient dilution. arrhenius could not initially explain this deviant behavior because there was no reason to attribute it to the frictional effects mentioned above. 33 this difference was emphasized by the above mentioned english inventor of the moving boundary method[89]. whom we also mentioned in part 3 of our previous historical article. in a critical commentary in ref. [115] lodge began his analysis – not very encouragingly for arrhenius – with “whatever may have been the importance of the first part of this memoir at the date of its appearance (1883), the publication last october in wiedemann’s annalen of a masterly memoir by prof. f. kohlrausch on the same subject throws it into the shade; for there can he no doubt that while the ground covered by both is similar, the kohlrausch memoir is greatly superior, both in the experiments made and in the discussion upon them.”) kohlrausch remained essentially with the investigation of the strong electrolytes. however, the said deviant behavior aroused the special of interest of arrhenius. to explain this effect, he made the bold hypothesis that the number of conducting molecules had to increase by splitting the electrolyte molecules into two parts. one part is electrically active, it conducts electricity, the second, electrically inactive part is non-conducting. he further hypothesized that with increasing dilution, the proportion of active parts increases at the expense of the inactive ones. at infinite dilution, all inactive parts are completely dissociated, a verb arrhenius avoided to use in his dissertation. arrhenius introduced the activity coefficient (later called degree of dissociation), which indicates the proportion of active molecules to the number of all molecules, if these were completely dissociated. the active parts must be capable of double decomposition, since a permanent exchange with those of other molecules takes place, which – in the absence of an electric potential – leads to a circular current of the ions in the solution. arrhenius’ hypothesis explained both, the high molecular conductivity of the strong acids, as they consist of the electrically active molecules, and the behavior of the weak acids with their initially small activity coefficient that increases sharply with increasing dilution. to confirm his hypothesis, arrhenius borrowed results from thermochemistry, especially those of the dutch physicist julius thomsen. thomsen had determined the heats of neutralization of acids in their reaction with a strong base. he found that strong acids evolve the largest heats of neutralization, weak acids develop smaller heats. these results were consistent with the arrhenius hypothesis, since strong acids, like strong bases, already consist of the active h+ and ohions (their counterions do not contribute to the neutralization), which combine directly to form the inactive water and release its activation energy. in the case of weak acids, in contrast, the inactive part must be transferred into the active part for neutralization, a process that absorbs heat and reduces the heat balance accordingly. this was the first proof of the arrhenius hypothesis, which was based on a non-electrical thermochemical phenomenon. arrhenius, however, was of the opinion that the conductivities measured by him and the heats of neutralization were not sufficient for a solid theory. without conducting any further experiments himself, he found three more proofs to confirm his hypothesis. the next, the second proof resulted from wilhelm ostwald’s studies of the affinities of different acids on bases. ostwald’s measurements concerned the kinetics of chemical reactions and the influence of the strength of the acids, 74 ernst kenndler which determines their reaction rate. among others, he investigated the effect of about forty different acids on the reaction rates of hydrolysis of methyl acetate, and on the inversion of cane sugar. after reading arrhenius dissertation which he received in 1884, he concluded that the stronger an acid is, the more pronounced its affinity should be, as indicated by its molecular conductivity. thus, ostwald measured the molecular conductivities of diluted solutions of his acids, and found an astonishing high parallelism with the rate constants. this was the second proof of arrheniuś hypothesis: it was based on chemical kinetics. perhaps the most important piece of evidence was the analogy found by j. h. van ´t hoff between the osmotic pressure exerted on a semipermeable membrane by a dilute solution and the pressure of a gas composed of the same number of particles. this pressure depends only on the number of dissolved particles, but is independent of their electric charge. the deviation of the osmotic pressure from that of avogadro’s law is expressed by van ‘t hoff factor i, which is the number of all solute particles. on the one hand, i can be determined experimentally by raoult’s freezing point depression. on the other hand, it can be calculated with the aid of arrheniuś degree of dissociation, α. if the values of i obtained from both methods agree, the value for α is correct, and arrheniuś dissociation hypothesis is confirmed. the actual agreement found was the third proof. in addition, the additivity of physical properties, such as the specific gravities of solutions confirmed the hypothesis. based on these four proofs, arrhenius had successfully developed the seminal theory “ueber die dissociation der in wasser gelösten stoffe” in 1887 from the collection of the 56 theses of the 1884 dissertation. finally, we would like to address an apparent discrepancy between the subject of our article series – the history of the basic principles of capillary electrophoresis – and that of the present arrhenius dissociation theory. although the most important properties studied by arrhenius were the conductivities of electrolyte solutions, neither his dissertation nor his dissociation theory gives any indication of the associated mobility of ions in free solution under the influence of an electric field. since this ion mobility is a central property in electrophoresis, one could assume at first glance that the dissociation theory has only little significance for electrophoresis. however, the opposite is the case, as it allows to express the conductivity and thus the mobility over the whole range from zero to its maximum value by means of the degree of dissociation, which can take all values between zero and unit. for this reason, the dissociation of weak electrolytes described by arrhenius will certainly be of great relevance in the practice of ion electrophoresis. it will be indispensable for electrophoresis as a future separation method. in this respect, its detailed treatment in this article was justified. references [1] r. clausius, ann. phys. chem. 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[141] k. j. laidler, can. j. chem. 1997, 75, 1552-1565. substantia. an international journal of the history of chemistry 1(1): 77-96, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-14 citation: m. fontani, m.v. orna, m. costa, s. vater (2017) science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity. substantia 1(1): 77-96. doi: 10.13128/substantia-14 copyright: © 2017 m. fontani, m.v. orna, m.a costa, s. vater.this is an open access, peer-reviewed article published by firenze university press ( h t t p : / / w w w. f u p r e s s . c o m / s u b s t a n tia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the authors declare no competing interests. historical article science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 1 dipartimento di chimica “ugo schiff ”, università degli studi di firenze, via della lastruccia 13, sesto fiorentino (fi) italy. e-mail: marco.fontani@unifi.it 2 the college of new rochelle, new york, usa. e-mail: maryvirginiaorna@gmail.com 3 freiberg university of mining and technology, faculty of chemistry and physics, leipziger straße 29, freiberg, germany. e-mail: sabinevater1993@googlemail.com abstract. a not very recent, but widely documented, event whose echo still resounds, the discovery of artificial radioactivity, might still cause some historians to lose a little sleep. the topic of this article recounts a noble attempt by historians of science to make known to the general public a woman who managed in a backward country like românia mare1 to ascend the ranks of the university hierarchy and enter the hallowed halls of academe. we could talk about a romanian madame curie, similar to lise meitner (1878-1968), who embodied the same figure for the german world; but romanian historians add other ideas. stephanie (ştefania) mărăcineanu (1882-1944) the correct spelling of her name is in brackets according to some would be nothing less than the discoverer of artificial radioactivity as well as the chemical transmutation of lead into gold and mercury, and of artificial rain. the discovery of induced or artificial radioactivity is universally attributed to the daughter and the son-in-law of marie (1867-1934) and pierre curie (1859-1906). furthermore, irène joliot-curie (1897-1956) and her husband, frédéric joliot (1900-1958) were awarded the nobel prize in chemistry 1935 for this work. this study is divided into both an historic framing of the real and presumptive discoveries and in an analysis of the original data in light of our current knowledge of physics. an initial historic study, albeit partial, and with the aim of shedding light on the female personalities in the field of radioactivity, has already been done.2 other scholars have examined ştefania mărăcineanu's work focusing on its social, political, cultural and ideological aspects.3 but no matter how much scientists try to be objective, they must always struggle between their beliefs and their human prejudices, including all of their habits of thought more or less imposed, and often inadvertently, by the society and the country in which they are formed.4 it will therefore be our task to take account of the difficulties hitherto reported, and for that it will be absolutely necessary to exercise judicial restraint. keywords. mărăcineanu, artificial radioactivity, history of chemistry, 78 marco fontani, mary virginia orna, mariagrazia costa and sabine vater science whispered about in the hallways at the beginning of the 1920s, when the phenomenon of radioactivity had finally been clarified as spontaneous nuclear fragmentation, a series of controversial publications initially given to the press with the full support of respected professors appeared in minor journals, as well as in prestigious ones such as comptes rendus of the french academy of sciences. one example is the controversial case of marie curie’s not-so-young student, ştefania mărăcineanu, who obtained a ph.d. at the institut du radium at the age of 42, and within five years, she published some articles containing her scientific results. with a nonchalance at the limit of scientific orthodoxy, she announced four different (false or incomplete) findings: artificial radioactivity induced by alpha bombardment, the transmutation of lead into mercury and gold, the discovery of artificial rain, and an alleged link between earthquakes and radioactivity.5 only one of these discoveries, if true, could assure a nobel prize; they were of such magnitude that three of them would have placed her in the pantheon of scientists in all of history. on the contrary, if one, or more, of these presumed breakthroughs, so hastily announced, should prove a huge blunder, it would have severely compromised her career.we will set aside for the epilogue of this story a duplicate turn of events: two of the four announcements were immediately branded as examples of “pathological science,”6 but at the same time ştefania mărăcineanu could be found in her home country with a university professorship and membership in the romanian academy of sciences.7 after her first article on artificial radioactivity, there was no talk of this except as a springboard for her subsequent discovery. critics attacked her on this second far trickier topic: the transmutation of the elements. on the one hand, mărăcineanu did not seem to be aware of the possible scope of her first discovery, and would persist in dwelling on a subject much more intriguing as the transmutation of lead, but this was not acceptable to the scientific community. despite the fact that her work on chemical transmutation induced by solar radiation was immediately refuted, on the contrary, decades after her death, in her native romania, a historiographic approach to her work on artificial radioactivity smacking of a lively, colorful, even aggressive, revisionism had reached a crescendo. unfortunately many of these enthusiastic interpretations are not supported by the same scientific rigor and the data reported counting on a posthumous rehabilitation are either very weak or ontologically unacceptable because the authors seem to rewrite history for their own convenience. furthermore, none of the authors were able to produce any new documentation8 or got themselves lost in a useless speculative extrapolation of phrases taken out of context, passing over the most controversial and fallacious aspects.9 in a post-ideological period such as the first decade of the 21st century, freed from certain cultural constraints, greater objectivity is not only possible but required. this is a new task laid upon the shoulders of those who “do” history of science: to be vigilant and never regard certain discoveries as unassailable, and to uncritically accept a new revisionism that might be vaguely nationalistic.10 regarding scientific knowledge: we do not know whether it can and whether it should be considered a cumulative cognitive process and, above all, axiomatic and immutable, but the events related to this episode have in themselves some aspects so conflicting, embedded in an aura of alchemy and xenophobia as to create doubts that “science” can be advanced as a symbol of progress and civilization. artificial radioactivity ştefania mărăcineanu had begun to work in marie curie’s laboratory in the early 1920s when she was about 40 years old. in 1923, her paris address was rue cassette, 11. it is known that nicolae iorga11 (1871-1940) had founded the „şcoala română din paris”12 in 1920 and probably ştefania mărăcineanu was one of the first scholarship recipients to go to the french capital. at that time, she was busy working on her phd that she received two years later. in this case we can speak of scientific “maturity,” in which a scientist, over the years, has probed and tilled different (scientific) fields and has come to full consciousness of himself/herself and has already given signs of his or her genius. we have to start by saying that we are basically opposed to using the birth certificate as a yardstick, but it is undeniable that in scientific disciplines such as physics or physical chemistry unlike love or literature age is not simply a bourgeois convention, but an objective fact. her phd research was supposed to focus on a more accurate measurement of polonium’s decay constant. this element, highly radioactive but with a relatively short half life,13 was concentrated as much as possible and electrolytically purified. it was the 10th anniversary of the outbreak of world war i: marie curie commissioned the no longer young romanian phd student to determine this element’s decay constant with a level of precision and accuracy unimaginable in 1914, before europe was falling to pieces. 79science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity as is now well known, radioactivity may either be natural or induced (artificial), depending on whether nuclear decay is spontaneous or is caused by means of some other nuclear reaction. in 1924, only natural radioactivity, discovered by henri becquerel (1852-1908) in 1896, was known. marie curie, the greatest expert in the world in the field of radioactivity, had discovered two naturally occurring radioactive elements (calling them radium and polonium). certainly she could not have imagined that within a decade of these discoveries, the courage she had exhibited and the intellectual satisfaction she had derived from her life’s work would bestow on her a gift with a two-edged sword. contaminated by her radioactive substances and prematurely robbed of her health, marie curie would be brought to her grave in july 1934; in january of that same year, although worn out and suffering from a chronic fever, she witnessed the greatest discovery that ever took place at the institut curie through the work of her daughter and son-in-law: artificial radioactivity. as mentioned previously, in 1922, ştefania mărăcineanu was trying to record the average half life of polonium in that same period. polonium (po) has 33 isotopes, all of them radioactive, the number of nucleons ranging between 186 and 227. the isotope 210po is a pure alpha-emitter and has a half life of 138.376 days, the longest of its five naturally occurring isotopes (table 1).14 the subject of mărăcineanu's doctoral research was to accurately and precisely determine the decay constant of element 84. this was, for marie curie, a fundamental topic and at the same time a great worry: in fact, the value of the half life varied from 135 to 143 days depending on the source from which the polonium was extracted: for many radiochemists, such a wide range was uncomfortable, and even unacceptable.15 at the french academy’s session of june 23, 1923, the newly appointed academician, georges urbain (1872-1938), read mărăcineanu's phd thesis to the assembly. the polonium used came from ampules of emanation [i.e., radium] which had been previously used for medical purposes. the electrolytic process for the obtaining of the polonium-free radium-d impurities [e.g., pb; see table 2, below] had been developed in the chemistry laboratory of the institut du radium. a drop of polonium chloride, pocl2, solution was deposited on a metallic or glass plate and left to evaporate. the plate was subsequently rinsed with distilled water to remove traces of acid. an ionization camera, complete with a piezoelectric quartz electrometer (as a current compensator), to detect alpha particles allowed for the determination of the activity of the radioelement in the form of an electric current over the course of time. mărăcineanu was able to derive polonium’s decay constant by measuring the logarithm of the current against time. ştefania mărăcineanu conducted numerous experiments divided into two series: the first series of 38 measurements was carried out between march and may of 1922. she re-covered the polonium with slips of aluminum foil of varying thicknesses between 3/1000 and 7/1000 of a millimeter. in the second set of measurements, which began in may, she offset the aluminum sheet by 1 mm from the plate on which she had deposited the polonium. table 1. the naturally occurring isotopes of polonium. isotope old name z n isotopic mass (u) half life type of decay daughter isotope 210po radium f 84 126 209.9828737(13) 138.376(2) d α 206pb 211po actinium c’ 84 127 210.9866532(14) 0.516(3) s α 207pb 212po thorium c’ 84 128 211.9888680(13) 299(2) ns α 208pb 214po radium c’ 84 130 213.9952014(16) 164.3(20) ms α 210pb 215po actinium a 84 131 214.9994200(27) 1.781(4) ms α (99.99%) 211pb β− (2.3×10−4%) 215at table 2. the products of the decay of radium-226. the products of 226ra decay were initially called radium-a, radium-b, radium-c, etc. later they were understood to be other chemical elements chemical symbol of the isotope emanation of radium (em) 222rn radium a 218po radium b 214pb radium c 214bi radium c1 214po radium c2 210tl radium d 210pb radium e 210bi radium f 210po 80 marco fontani, mary virginia orna, mariagrazia costa and sabine vater ştefania mărăcineanu derived a half life equal to 139-140 days in all cases except when the measurements were recorded on a lead plate. in this case, the value was shorter: 135 days. concerned with this unexplained variation of what was supposed to be a constant, she began to conduct a series of additional experiments to determine the reason for this anomaly. thanks to previous work done by marie curie in 1920, she could exclude the presence of 210pb, radium-d, from the sample. she also examined the aluminum sheets and observed that they were not radioactive. a likely source of error could have been the effect of saturation for measurements conducted over a long period of time (greater than 136 days), but in this case as well, ştefania mărăcineanu had taken drastic precautions. the result left no doubt that no error had been committed, so much so that the director of the institut in person, marie curie, felt compelled to give an interpretation to the phenomenon observed: she said she witnessed a “penetration of polonium into the substance used to support it.” marie curie asked her to conduct a third set of measurements in support of this hypothesis, and this was completed in december, 1923. the diffusion phenomenon increased when the support was heated; the phenomenon was observed over a range of metal supports. if the support were glass, no penetration (diffusion) effect of polonium into the support was observed. however, the problem was not resolved: at first it was assumed that the disintegration of the polonium helped it to penetrate lead’s crystal lattice. this conclusion was rather hard to accept. later she resorted to the hypothesis of microcracks (or faults) in the metal support. this allowed her to shelve the problem for a short time. a practical arrangement made it possible to calculate the decay constant: diluted solutions were used,16 no heat was applied, and glass was substituted for lead as the solid support. induced radioactivity by solar radiation having finished her phd with marie curie, ştefania mărăcineanu continued her research first in romania (for a short time) and later at the institute of optics at the meudon observatory, near paris, under the supervision of henri deslandres (1853-1948). mărăcineanu noticed that the decay constant of polonium, far from remaining immutable, varied depending on which metal was used as a support for the sample. she also noticed that the atoms of the substrate were “transformed” into radioactive isotopes. in all this, her superiors suspected nothing, but not for the reasons that the supporters of ştefania mărăcineanu eventually gave. if what she timidly asserted had really happened, this experiment would have shed light on the phenomenon of artificial radioactivity ten years in advance. it was not so, and, as we shall see, could not have been otherwise. continuing her doctoral work, in an article of november 25, 1925,1 ştefania mărăcineanu suggested that sunlight could have an action on the radioactive decay of uranium and polonium. after extended periods of exposing sheets of nonradioactive lead to direct sunlight, they would later be shown to be radioactive. likewise, uranium oxide, if exposed to sunlight, began to show a change in the decay process, a variation that mărăcineanu called “curious periodic variations.” she tried many other things, but only pb and sb exhibited such behavior. after exposure to the sun these elements were able to: • expose photographic plates • if placed in front of a zinc sulfide screen (detector), many scintillations were observed • lead or a pb/sb alloy exhibited a weak ionization current, detectable with an electroscope. over the years marie curie had also observed a change in the decay constant of uranium, with an order of magnitude of about 3%. ştefania mărăcineanu stated that by the action of sunlight, this change was amplified up to 50%. on august 2 of the following year, ştefania mărăcineanu published a further note in which she pointed out the progress of her discoveries,18 with reference to the observed solar effects on polonium. she placed a drop of a solution of highly purified polonium chloride on a somewhat thin lead sheet (1/10 mm). the polonium-210 she used was a pure alpha emitter. at the atomic level, 0.10 mm of lead is extremely thick and easily stops the alpha particles emitted by polonium, but inexplicably, she discovered an ionization current on the opposite side of the metal plate which was not exposed to the alpha source. she could think of only two reasons for this effect: induced radioactivity or the following hypothesis. polonium is a very strong alpha emitter, but ştefania mărăcineanu dismissed this fact. as a side effect (which, for ştefania mărăcineanu, was the primary effect), she observed that if the lead sheet on which the polonium solution had been deposited were exposed to the sun or kept in the shade, the ionization current varied widely. at the conclusion of her work, mărăcineanu reported: “one might have thought of a penetration of polonium from one side to the other of lead, but if this were the case, one would have had to have a loss of polonium inside the lead, which has not been observed”.19 81science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity this sentence could have been the starting point to see if, indeed, the scientist had observed the phenomenon of artificial radioactivity, but how often does it happen that ideas ahead of their time are overlooked or dismissed? and she herself, first of all, put forward a very different explanation for the observed phenomenon. by further work on polonium decay curves in bismuth, curves obtained from experimental observations after deposition of the polonium and before irradiation, ştefania mărăcineanu speculated that the facts “... seem to show that solar radiation can cause the reintegration of radium-e [bi] from radium-f [po], and thus can cause a reversal in the radiation series”.20 this unorthodox hypothesis, based on an actual observation but certainly misunderstood, should have been immediately rejected, both by marie curie, her former director, as well as by henri deslandres. things did not go well. curie maybe was busy with wedding preparations for her daughter irène, who was to marry the young and promising engineer, frédéric joliot (who would be assured a more flexible career by marrying the daughter of his employer). henri deslandres, on the other hand, was an astro-physicist who had done all of his scientific work before the mere mention of “radioactivity” was whispered by marie curie to her husband, pierre, in the late 19th century. at the time, he was 73 years old, much older than pierre curie, and perhaps too sidelined at this point to contribute to the debate by siding in favor or not of this hypothesis. but this was not the case. as we will see in three notes, which appeared in the comptes rendus, he encouraged and praised the work and discoveries of ştefania mărăcineanu. a further communication from ştefania mărăcineanu appeared in comptes rendus reporting on the session held on may 30, 1927.21 in this case as well, marie curie never said a word.22 perhaps she was occupied both within and outside of the laboratory walls with many other affairs: after her daughter’s wedding on october 9, 1926, her new son-in-law was promoted, to the great chagrin of marie curie’s long-standing collaborators, to the rank of “prince consort”.23 irène, meanwhile, was “in a family way”,24 and marie was “experimenting” with the idea of becoming a grandmother. following the advice of her colleague lebel, ştefania mărăcineanu began to study the radioactivity of the lead sheets used as covering for french public buildings and therefore exposed to the sun’s rays from time immemorial. it happened that the paris observatory’s roof was covered with lead sheets. ştefania mărăcineanu, as she herself confessed a year later, climbed up to the top of the cupola and at high risk began to scrape off some of this roof covering in order to subject it to analysis. since she found that the samples’ radioactivity was so high as to be off the scale, she assumed that the lead radioactive by solar induction had an extremely rapid decay rate. as a matter of fact, mărăcineanu carried out her measurements three times a day, after breakfast, lunch, and dinner. but not only that, said she: “at noon, when the sun hits the instrument, the lead appears to become twice as active...”.25 to compare these results with ordinary lead, she also prepared daily a solution of “white” lead by treating commercial galena (pbs) with acid,26 and observed: “commercial lead, prepared every day with galena, is not, as is known, radioactive…”.27 henri deslandres, her advisor and director of the observatory at meudon, was so favorably impressed with ştefania mărăcineanu's research that he published a brief note28 in the margin of the previous article where, in the euphoria of discovery, sent out an enthusiastic appeal to readers: “the people here have lead (that has lain) for a long time in the sun, and who do not have the necessary apparatus to do research on radioactivity, are asked to send a sample to the observatory of paris”.29 the research was begun in earnest. twenty days after the last communication a new work appeared30 by ştefania mărăcineanu in comptes rendus. following the advice of her director, she extended her research to other metals besides lead and polonium, such as copper and zinc. these last two elements were, like lead, used for the protection of the limestone ledges of the observatory. ştefania mărăcineanu collected specimens of them and observed that the surfaces hidden from the sun’s rays exhibited no radioactivity. she posed the dilemma of whether the radioactivity might be due to atmospheric radioactivity deposited over the years on coatings of copper and zinc, but in a short time disproved this hypothesis because there was no any trace of radioactivity in the blocks of limestone. this article, too, was followed by a laudatory note31 by her superior about as long as the article which preceded it: “mademoiselle mărăcineanu's research on the old roofs of the observatory of paris is of increasing interest. lead is not the only metal that acquires, under the influence of the sun’s rays, a special radioactivity…”.32 dwelling on the more practical aspects of how to continue these experiments, deslandres pointed out that the radioactivity that we can define as induced was not attributable to the diffusion of only radioactive bodies as happened for polonium, but it was an established fact that it was a special action of light on matter and could be said that it clarified the action of ultra-x rays, very penetrating x-rays, whose cosmic origin was demonstrated by werner kolhörster (18871946),33 robert a. millikan (1868-1953) and russell m. otis.34 82 marco fontani, mary virginia orna, mariagrazia costa and sabine vater deslandres expressed a personal interest in the research of his romanian assistant because it allowed him to reminisce over events that had occurred more than thirty years before when, in 1896, he had observed the emission of particles and x-rays from the sun, the other planets, and nebulae. these 19th century works were collected in a monograph35 in precisely the year in which ştefania mărăcineanu began her collaboration with him. ştefania mărăcineanu's third article36 in 1927 appeared on july 11. in this case as well, at the suggestion of henri deslandres, she repeated the experiments of depositing polonium solutions on 0.1 mm thick lead plates. but this time, again at deslandres’ suggestion, she subjected the plates to a potential of 120,000 volts. for the occasion, they had to dismantle a large transformer that operated the observatory and dedicate it to this use. after depositing the polonium solution, the experimental samples were divided into four groups: 1. plates not subjected to any potential 2. plates subjected to high voltage only 3. plates subjected to high voltage and solar radiation simultaneously 4. plates subjected only to solar radiation in these cases, radioactivity was not observed on the surfaces of the lead plates not exposed to polonium; despite the fact that an extremely high voltage was applied, no nuclear rearrangement could be said to have taken place because there was no substantial difference between samples 1 and 2 . this was certainly a negative result. however, increased radioactivity continued to be observed in the samples exposed to the action of sunlight. for the first time ştefania mărăcineanu reported the following phenomenon: “it has been observed that the ionization current exhibited on the opposite side (of the plate) is proportional to the initial amount of polonium deposited”.37 but what is even more surprising is ştefania mărăcineanu's almost prophetic conclusion. apparently, following the reasoning that she reported in the article, it seemed evident that henri deslandres, the teacher with his “forced suggestion” and counterproductive increase in the complexity of the experiments, derailed the entire project. however mărăcineanu remained stubbornly faithful to her earlier ideas; stripping the experiments bare from unnecessary complications derived from sunlight or high voltage, she seemed to really observe the phenomenon that less than ten years later would take the name of artificial radioactivity and so she closed the the article with the words: if we consider the appearance of the curves, the ionization current, which increases daily by itself, passes through a maximum, then decreases according to an exponential law, as happens when a radioactive substance is formed, develops, and then decays. i think that a new radioactive substance is being formed in the body of the lead.38 again henri deslandres wanted to comment with a note on the work of his student.39 outside of congratulating her and highlighting the enormous importance of the subject in the scientific landscape and recognizing its extreme complexity, he added almost nothing new. meanwhile the alleged discovery of radioactivity induced by solar radiation gave ştefania mărăcineanu an unexpected fame on a global level:40 within a short time she became the most famous romanian scientist in the world. the field of radioactivity lent itself to this sort of thing: it was a relatively new field of research; it was a kingdom ruled by a tiny little woman that she, marie curie, had created herself and the “world of little nations” wanted to have at home a “little curie,” to pamper and show off to exalt their own homegrown glories to their citizens. in a late positivist spirit, radium was viewed as an instrument of human progress, the weapon to fight cancer, which, in the years of industrialization, was defined by the late-19th century pharmacopoeia as the most widespread and insidious disease, which nothing could oppose. all this, like a fairy tale, fascinated the public and newspapers competed to bring often with sensationalist reportage the most diverse and contrary reports, both scientific and pseudo-scientific, to the attention of the public. among these they found wide-ranging opportunities in ştefania mărăcineanu. already in 1925, during his official visit to paris, king ferdinand i of romania (1865-1927) and his wife, queen marie of edinburgh (1875-1938), invited ştefania mărăcineanu to demonstrate her scientific achievements to them. the queen, impressed by the work of her compatriot, took her personal prerogative to subsidize her research on chemical transmutation. in 1929, in iasi, ştefania mărăcineanu received the award in memory of the recently-deceased king ferdinand given by the foundation of the same name.41 the announcement of the discovery of chemical transmutation 1928 marked a year of more radical change. in march of that year, in fact, ştefania mărăcineanu published together with her director, deslandres, a further development on the research on this phenomenon.42 from januar y 20 to februar y 17, ştefania mărăcineanu exposed to sunlight not only lead, but also old copper, aluminum, iron and zinc plates. she repeated, in parallel, experiments with other samples of the same 83science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity elements, but obtained from commercial venues. only lead showed radioactivity. with a complex reasoning resulting from a series of measurements, she excluded the idea that the specific activation of lead derived from a radioactive emanation from the atmosphere (external contamination). a careful study of the results led ştefania mărăcineanu to a suddenly change the ideas that she had espoused in the previous summer and she asserted instead: “in my experiments on lead, i have always found (decay) periods of this order of magnitude and at one point i thought of a reintegration of lead into polonium by solar energy”.43 in other words, after an understandable hesitancy, ştefania mărăcineanu, announced that she had observed a chemical transmutation process by the action of sunlight. she reported that this phenomenon could be explained if associated with another inexplicable phenomenon, the presence of alpha particles, and the appearance of extremely penetrating rays (γ rays, perhaps, but these are not specifically named). as a corollary to this controversial hypothesis, ştefania mărăcineanu speculated that the change in the decay constant of polonium was due precisely to this phenomenon. this would explain why, four years before, she had obtained such a variation in her data. a year passed and ştefania mărăcineanu left france for her native romania. we do not know the reason for this more or less voluntary removal from the observatory at meudon. in her native country she gave to the press an article44 having as its subject the effects of solar radiation on radioactive phenomena and transmutation. it was work conducted in france, described in summary in some communications in comptes rendus, but quoted in full in romania. if it had been national pride or an ill-concealed desire to reduce the effects of a likely fiasco that drove ştefania mărăcineanu to explicitly publish the phenomenon of transmutation of the elements in a romanian journal is not known. the fact is that, in this work, values were observed in the spectroscope, i.e., the appearance of spectral lines, attributable to elements that would be formed by the transmutation of lead explicitly appear. in confirmation of this hypothesis, the appearance of helium (alpha particles) and mercury lines were observed. in both publications, that of 1928 in the comptes rendus and that in the bulletin de la section de l’academie scientifique roumaine, the word transmutation is not to be ascribed to an alchemical concept, but to the idea of radioactive decay (or its unlikely opposite: “radiative accretion”). if we must impute any kind of an error to mărăcineanu, it would be to have formulated the concept of chemical reversibility in the process of radioactive decay, and to accept the fact that lead was not the end of the line for the thorium and uranium decay series (that includes radium): pb + α → po pb → hg + α the extensive work of ştefania mărăcineanu consisted of numerous pages and photographs of samples taken from lead roofs that had been exposed for centuries to solar radiation. she took her time about her means of investigation, employing a few tricks to enhance the observed effect and in the end she added a note in italics that could not go unnoticed: “the action of solar radiation could possibly cause a transmutation of 0.001% lead in gold”.45 at the end of the article after the usual sentences relating to the circumstances of the work that scientists always expect, with a little bit discovered and much more to do, you can read in ad hoc italics, like a wagnerian finale, the words: but it is in solar radiation that one must recognize the philosopher’s stone and the source of formidable radioactive energy, which will become needed more and more.46 the year 1929 opened auspiciously for ştefania mărăcineanu. her publications appeared both in romania and in france and her work could be said to be truly cutting edge. many scholars began to repeat her experiments, seeking to confirm her observations, but also to shed more light on an effect of nature that she had discovered and that she too easily had wished to define using such “hot button” words as “transmutation” and “philosopher’s stone.” the olympic calm of the european colleagues comes to an end by return mail, professor nicolae vasilesco karpen (1870-1964), who a few days earlier had presented ştefania mărăcineanu's work to the romanian academy of sciences, was forced to report a preliminary note under the signatures of charles fabry (1867-1945) and e. dubreuil in which the two french physicists expressed their censure of tests carried out by the romanian scientist that they repeated in their paris laboratory: they were the experiments relating to the transmutation of lead into gold, mercury, and helium.47 they pointed out: the experiments in question were conducted with results exactly contrary to those reported by mlle. mărăcineanu.48 84 marco fontani, mary virginia orna, mariagrazia costa and sabine vater that was the first salvo that began to discredit the romanian researcher’s work. shortly thereafter, she was the object of a great deal of criticism for her real or alleged discoveries. first the french, and then many other scientists, began to pour down condemnation on her like so many arrows.49 on february 22 of that same year, it was the director of the institut du radium herself, marie curie, who pressed mlle. eliane montel50 (1898-1992) into service to investigate the embarrassing phenomenon of induced radioactivity discovered in the heart of her own laboratory. montel studied the evidence in great detail with the aid of a rigorous photographic analysis; the methodology followed was that of ştefania mărăcineanu, but she obtained very different results: as mărăcineanu observed, a lead sheet on which was placed a solution of polonium hydrochloride exhibited radioactivity after the polonium had been removed. however, the radioactivity observed was not due to its induction by polonium in the lead as elizabeth róna (1890-1981) and e.-a. w. schmidt demonstrated,51 but to its penetration through microscopic cracks, between the lead crystals, and conveyed by the presence of a weakly acidic environment. this hypothesis was suggested to eliane montel by fernand holweck (1895-1941) and her laboratory subsequently tested it. lead sheets were melted and then cooled so as to obtain crystals whose dimensions were visible to the naked eye. then a solution of polonium hydrochloride was deposited on the sheets and their radioactivity was monitored photographically. what struck eliane montel was that on her photographic emulsions she saw the outlines of lead crystals, i.e., the regions where the polonium had penetrated them. eliane montel asserted without a doubt that polonium passed through the lead only in the zones which she called “faults.” it was a clear proof that damaged the hypothesis advanced by ştefania mărăcineanu on induced radioactivity. a few months later, on may 25, 1929, the dutch professor a. smits and his assistant mlle. caroline henriette macgillavry52 (1904-93) published an extensive piece of research53 on another aspect of mărăcineanu’s work: the radioactivity of lead induced by solar radiation. their work was conducted on sheets of lead from the roofing of the observatory of paris as well. the results were encouraging and gave confirmation of the comments previously made by ştefania mărăcineanu.54 smits and mac gillavry reported the following: ... these results were perhaps of great importance because if the lead really is activated and emits α particles, it is likely that there is a transmutation of lead into mercury.55 this was the first, albeit modest, confirmation ştefania mărăcineanu’s work outside of french and romanian borders, but it was short-lived. on february 9, 1930 she wrote from paris, where she resided at 9 rue ernest cresson, to her friend alexandrina fălcoianu.56 it is an excerpt of a letter that foreshadows possible friction between her and her french colleagues: i will fight, dear lady, for me, for justice, the honor of our country, and for women.57 a few months later she will have come back to romania for good. in fact, a deed of patent on artificial rain, dated june 10, 1930, gives her address as boulevard col. mihai ghica n. 57, bucharest. six days before she drafted the letter to her friend, february 3, 1930, the french physicists charles fabry and e. dubreuil officially opened hostilities against ştefania mărăcineanu and released a statement which seriously criticized her work and her heterodox theories. the two french colleagues also neglected to mention mărăcineanu’s earlier work that had appeared in the very same comptes rendus, as well as the encouraging articles of the famous astronomer, deslandres, which had supported ştefania mărăcineanu. even if they were correct, it was a petty attack on a “foreigner” as well as a chauvinistic attempt to make sure that a french institution was not tarnished. the experimental work was conducted by e. dubreuil at the institut d’optique. he had repeated the romanian researcher’s same experiments but ended up getting totally negative results, even in the case of lead. her reply was swift: seven days later, ştefania mărăcineanu transmitted her reply in the pages of comptes rendus.58 it was, however, weak both in tone and in content. she realized she was a foreigner and could not reply to such aggressive criticism in the same tone with which she had been attacked. she hypothesized that her colleagues, fabry and dubreuil, had scraped lead from the observatory roof in the precise places where she had taken her samples and by so doing, they would have analyzed the underlying layer, which had not been exposed to sunlight for the centuries to which her own samples had been subjected. in addition, ştefania mărăcineanu openly reprimanded dubreuil, saying that when she was at the institute of optics, he had provided the spectra and had offered to interpret them. the romanian researcher acknowledged the negative assessment of her work and tried to scientifically counter the accusations brought against her. if the cause of the radioactivity of the lead could be debated and could even change her hypothesis, she was firmly convinced that her observations were correct so much so that they 85science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity were confirmed by professor smits, the director of the chemistry department of the university of amsterdam. as support, ştefania mărăcineanu reported some excerpts of a personal communication sent to her by smits which confirmed the results that she had arrived at: in the arc spectra of lead, the spectral lines of mercury were readily apparent. this evidence could only lead to one conclusion: the transmutation of lead into mercury by the action of solar radiation. in support of her statement, mărăcineanu emphasized that traces of mercury are always in lead and that scientists have always defined this fact as a “permanent impurity” without specifying any others. now she, ştefania mărăcineanu, could explain this presence as the slow transformation of lead into mercury (with α particle emission) brought about by the prolonged action of solar radiation. ştefania mărăcineanu cited the data of professor smits before their publication: the amount of observed alpha particles was equal to impingement of 1.6 α-particles per second on a surface area of with a diameter of 16 cm2. at the conclusion of her article, mărăcineanu summarized her convictions as a challenging hypothesis: wouldn’t this be the result of a transmutation that has moved beyond lead in the periodic series of elements? and is radioactivity not a general property of matter?59 but the attack had not been able to direct the french colleagues to the pages of a french newspaper that appeared with calculated coolness: i can’t understand how messrs. m. fabry and dureuil haven’t found [traces of gold, helium or mercury].60 ştefania mărăcineanu had also given some samples of lead sheets used for the meudon observatory roof lining to some french colleagues: augustine boutaric61 (18851949) and mlle. madeleine roy62 (1900-40) who conducted in turn their own personal investigation.63 in addition to the samples supplied by the romanian researcher, the two dijon chemists analyzed lead sheets from old and recent roof coverings: the palace of versailles, the tiles donated by the alchemist mme mary dina-shillito64 (1876-1938), owner of the avenières castle (1050 meters above sea level) and even vallot observatory on mont blanc (4362 meters high). in addition to the lead study they analyzed cladding sheets of zinc and copper which, exposed to sunlight, would be expected to become radioactive. the boutaric and roy results refuted the hypothesis advanced by ştefania mărăcineanu, according to which lead would not be the terminus of the atomic disintegration of all radioactive decay processes, but simply the next-to-last stop before its slow transmutation into hg. boutaric and roy put forth three hypotheses: 1. all the metals studied were undergoing a process of spontaneous disintegration (presumably emission of alpha particles, although these were not expressly mentioned in the article) 2. radioactive impurities were present in all their samples 3. radioactive products could accumulate over time in the atmosphere (water vapor, fog, rain, snow and ice) the fact that only the face exposed to the elements exhibited radioactivity automatically excluded both the first and the second hypothesis. to confirm the third hypothesis, the chemists analyzed the stones in the walls of the buildings from which the lead was taken and did not observe any radioactivity, which they ascribed to the slow but continuous disintegration of the lithic material through weathering. although ştefania mărăcineanu’s relationship with smits and macgillavry was most cordial and collaborative, in her latest work she quoted incorrectly and without permission some data extracted from a personal letter sent by them to her superior, the former director of the meudon observatory. smits and macgillavry were forced to issue a note of reprimand in the comptes rendus65 in which they expressed disappointment not only about the violation of communications protocol (citing publicly a work not intended for publication), but also certain doubts about ştefania mărăcineanu’s conclusions. the two dutch authors, although they had confirmed the radioactivity in the lead exposed to the sun, were not able to experimentally determine if that property was indeed of extraterrestrial origin or due to a radioactive deposit by atmospheric agents. deslandres, the man to whom smits had sent the letter containing the confidential data, the former director of the observatory, and ştefania mărăcineanu’s patron, replied by return mail in the pages of comptes rendus.66 far from offering the slightest form of apology, she continued to cite smits’s work as a support for her hypothesis, or rather she kept on saying that although the action of the sun’s rays were not yet regarded as established as the cause of the radioactivity of lead, to her way of thinking, it was indisputably the most likely. at this point, what we are witnessing in these more recent articles, is a fact both objective and sad at the same time: the experimental data had been supplanted by a flood of words and personal opinions. to make the situation more problematic, deslandres improperly cited the work of reboul67 and pokrovsky68 regarding the capacity of solar radiation to modify the radioactivity of uranium. 86 marco fontani, mary virginia orna, mariagrazia costa and sabine vater as befits any article which does not conclude with the certainty of solid experimental results, this intervention ended with a terse: “it is necessary to wait for further study of these facts”.69 ştefania mărăcineanu also provided samples of lead to other french colleagues, lepape adolphe (1886-1977) and marcel geslin (1894-1962) who immediately carried out similar experiments.70 their investigation was extended to other coatings: not only to metals such as lead, copper and zinc, but to stone such as slate, as well as the deposits left from rainwater in gutters. their conclusions were positive; lepape and geslin observed in all materials the emission of penetrating radiation. but the next step threw more light on the phenomenon: the dust in the air could have been the vehicle of radioactivity, with the help of rainwater. ştefania mărăcineanu, as many often do when finding themselves in unpleasant situations, tried to get out of the line of fire by replying jointly to smits, boutaric and lepape, with an article in the bulletin de la section de l’academie scientifique roumaine.71 there were only two reasonable ways out: admit error or place the blame on others, and she chose the second way. she said that from 1895 on, astronomers like sir oliver lodge (1851-1940) in england and henri deslandres in france had the intuition that the sun emitted “radioelectric” waves; but deslandres had gone further and better in that regard: in 1898 he proposed the existence of an unspecified “penetrating corpuscular radiation” emitted by the sun. it was a way to shift many of the shortcomings of her research on her old colleague. but it should also be reasonably said that ştefania mărăcineanu firmly believed in her results and could not accept the simple idea that the roof samples she observed had been contaminated by radioactive atmospheric dust. her article was a meticulously drawn up objection to her colleagues’ data, though not always backed up by thorough research and reliable data. in fact, she cited in her favor the research of some of her colleagues: nodon in bordeaux, fauvot of courmelle, and risler and werner kolhöster, without supplying any bibliographic references. on june 11 of that year, augustine boutaric and mlle. madeleine roy published an article72 in which they confirmed the results of lepape and geslin: radioactivity accumulated on ancient rooftops was due to rainwater. it was a simple and effective work. an analysis of the sand and charcoal used for making rainwater potable was collected in a closed tank of an old building. they observed radioactivity of about the same amount and type found in samples exposed to sunlight. it was the “coup de grace” to the complex theory put forth by mărăcineanu and abundantly supported by old deslandres. for ştefania mărăcineanu it was the beginning of the end. after having departed france for good, she completely abandoned her research on the phenomenon of induced radioactivity for a very long period of time. eleven years later, smack dab in the middle of world war ii, josé baltá elías73 (1893-1973) decided it was time to dust off the phenomenon of radioactivity induced by solar radiation. he began his research in 1935 but the worsening of the spanish political situation, ensuing in civil war, had delayed the publication of his findings for six years, by which time international interest in this subject had waned considerably. the results however, deserve to be reported because they contradict both ştefania mărăcineanu, but also augustine boutaric and mlle. madeleine roy. in his view, and supported by the highest precision instruments, the phenomenon of radioactivity induced by solar radiation was not observed for the simple reason that it did not exist.74 heedless of the criticisms that rained down from all sides, ştefania mărăcineanu published her last work concerning radioactivity and the transmutation of lead. in this work, containing repetitive material and lacking even a minimal bibliography, she sought to take stock of all her previous work on balance: as the joliot-curie team had discovered artificial radioactivity for the light elements, so she had done for heavy elements (lead) and otto hahn (18791968) for uranium, although this finding is reported without any specific notation. she also speculated about how it would take place. to do this, she proposed a new mechanism, “chemical transmutation for integration.” alpha particles (positive) expelled by polonium would be able to overcome lead’s coulomb barrier since, before the impact with the nucleus, it would be subjected to great acceleration due to the attractive force of the outer electron cloud of the atom. and finally, mărăcineanu suggested a second phenomenon independent of the induced radioactivity in the lead, but still a property of the same element: the lead, in itself, would encounter a very slow process of radioactive decay with the formation of mercury. she estimated a very long half life for the lead, of the order of 1027 years. current observations suggest that the age of the universe is about 13,799,000,000 years (1.3799 × 1010 years),75 with an uncertainty of about 21 million years. the figures provided by mărăcineanu are not accompanied by any supporting experimental data. her estimate is totally unreliable and can only serve to put the researcher in an even worse light. since this estimated 87science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity time period was too large to cause the spontaneous transmutation mercury, even the author of the article, ştefania mărăcineanu had to come to the conclusion that lead would be a metastable element and external agents such as sunlight could accelerate the spontaneous process by a factor of 1029. in point of fact, the decay period would change from 1027 years to only 200 days. biography ştefania was born june 17, 1882 in bucharest and her birth was added to the official registry the next day by her 20-year-old father, sebastian mărăcineanu. very few details of her childhood have been found. what we do know is that they were not happy years; ştefania did not like to talk about them. in 1907, she enrolled at the facultatea de ştiinţe a universităţii din bucureşti where, three years later, she received a doctorate in the chemical and physical sciences.76 she followed courses in pedagogy for a short period and, in 1914, she passed the qualifying examination that permitted her to teach in secondary schools. she was present in bucharest, teaching at the “şcoala centrală” during the austro-german invasion of 1916. after the conclusion of world war i, she obtained a scholarship and went to the institut du radium in paris, where she worked on and off until 1925.77 meanwhile, she had enrolled at the sorbonne for a research phd, which she obtained in 1924. returning to romania in 1925, the faculty of science at the university of bucharest gave her a post as assistant instructor. however, in that same year, she returned to paris for four years, working at the astronomical observatory of meudon. in 1929 we find ştefania mărăcineanu back once again in romania. in that year, she had the opportunity to hold a conference on the constitution of matter at the “şcoala centrală de fete” that she subsequently repeated at the “universitară carol i.”78 it was printed79 and it served as the nucleus of a manual on radioactivity that ştefania mărăcineanu would write some years later.80 when in 1929 she returned to romania for good, perhaps in response to criticism leveled at her for her improbable discoveries, ştefania mărăcineanu installed, manned and directed the first laboratory for the study of radioactive substances in romania. meanwhile, on january 15, 1934, irène and frédérick joliot-curie announced the results of their experiments and shocked the world with their discovery: artificial radioactivity. with uncommon haste, the nobel committee awarded them the nobel prize in chemistry the following year. in early june of 1934, irène joliot-curie, after having brought her terminally ill mother to the sanatorium of sancellemoz in the haute savoy, traveled to vienna to hold a conference hosted by the famous physicist stefan meyer (1872-1949). on june 5, 1934 in the neues wiener journal, an article appeared that reported excerpts of that conference, including anecdotes, bits of the animated discussions with colleagues, the opera galas, and interviews with journalists. among the latter, the name of ştefania mărăcineanu was mentioned, and the enlightening contribution to understanding this new physical phenomenon of this relatively unknown researcher was emphasized.81 it was a romanian, miss mărăcineanu, who a few years ago was probably the first one to observe that non-radioactive elements could be made radioactive under certain conditions, meaning they emit radiation similar to the type which, until now, has been only observed for the few radioactive elements. it was the only recognition, albeit marginal, that marie curie’s daughter was willing to give to the romanian researcher. on november 29, 1935, eleven days before irène joliot-curie and her husband received the nobel prize from the hands of the king of sweden, in romania, nicolae vasilescu-karpen82 (1870-1964) gave a lecture at the academy of romanian science entitled: radioactivitatea artificială şi lucrări româneşti în acest domeniu83 with clear allusions to the work of ştefania mărăcineanu’s unique research done years earlier. on june 24, 1936, ştefania mărăcineanu officially asked the academy of sciences of romania to support her officially and to recognize the priority of her work. her request was granted and in 1937 she was elected a corresponding member of the academy of sciences of romania, and two years later sefa de lucrări, i.e., director of research. in a letter preserved at the academy of sciences, mărăcineanu, wrote a strongly critical version of the events that took place in paris in the early twenties, while marie curie was still living: nu contest premiul nobel soţilor curie joliot pentru perfecţionarea ce au adus în această descoperire ca metode de investigaţie, punere în evidenţă a fenomenului şi chiar pentru aporturi noui. cer însă să mi se recunoască rolul ce am avut în această descoperire. am fost prima care am îndrăsnit să anunţ acest fenomen în 1924,când părea o nebunie. aceiaş metodă a întrebuinţat şi d-na joliot curie la începutul cercetărilor d-sale. ... singura deosebire consista în faptul că d-sa aşeza foiţa metalică peste poloniu iar eu depuneam polonium pe foiţa metalică. 88 marco fontani, mary virginia orna, mariagrazia costa and sabine vater d-na pierre curie nu mi-a permis a da această explicaţie în teza de doctorat şi mia spus: vom continua lucrarea şi va figura şi numele d-tale. am făcut totuşi rezerve în teza de doctorat. […] imediat după obţinerea gradului de doctor am publicat pe propria mea răspundere la academia română…84 by 1941 ştefania mărăcineanu was 59 years old and was nearing the end of her life and just in time to be appointed associate professor. it would be her last personal “victory,” as documented in several passages taken from letters addressed to colleagues. she spent much of her time in the laboratory, in a workplace which she had personally built at the cost of great sacrifice: ... laboratorul acesta este viaţa mea,de care nu m’aş putea despărţi de cât când n’aş mai fi.85 from personal sources, it can be clearly seen that the final days of the scientific collaboration between ştefania mărăcineanu and marie curie was not painless: a fost o persecuţie şi o opoziţie care m’a urmărit pas cu pas, de când am rupt cu institutul de radium pe chestia dreptului meu.86 for as long as she lived, the (romanian) academy denied her the highest recognition by not creating a professorship of radiochemistry. this could have been due to the concurrent political situation. the follies and the horrors of the despotic regime of king carol ii (1893-1953) of romania led him to accede to, in 1940, the triple dismemberment of his kingdom.87 when, in june of 1941, general ion antonescu (1882-1946) threw romania into the war against the soviet union, many romanians were happy about it. what attracted them was not only the possibility of regaining the lost province of bessarabia, but the prospect that the uncomfortably neighboring and powerful russian state, a constant threat to national integrity for over twenty years, would be destroyed. that thousands of persons would be sent to their slaughter on the battlefields of odessa, sebastopol, stalingrad, and the caucasus, although appalling, ultimately did not seem to matter very much. for ştefania mărăcineanu the news that arrived on june 20, 1942 was the prelude to the end of her career; the ministry of culture announced its decision to relieve her of her position by reason of age, effective october 1, 1942. her retirement would be neither a long nor happy one. she undertook volunteer work at a hospital, at câmpulug muscel, in the muntenia region, but at the same time she continued to devote herself to various scientific issues that were dear to her heart. on february 5, 1943, ştefania mărăcineanu sent a communication to the academy of sciences of romania, entitled “artifical rain during the drought year of 1942.” it would be her last work; she took care to assure her academic colleagues that her data were officially recorded. however, with the country at war and all that followed from that, the work was never published. simultaneously with the worsening of the war against the soviet union, ştefania mărăcineanu’s health continued to deteriorate. she had been certifiably ill from cancer for quite some time, undoubtedly caused by long and unprotected exposure to nuclear radiation. she died on august 15, 1944 in bucharest, two weeks before the soviets invaded the city which was devastated by u.s. air strikes and direct fire from russian artillery in the front line. as a result, the documents concerning mărăcineanu’s death were destroyed. her last resting place, along with many other romanian personages, is the bellu cemetery in bucharest.88 although some historians record her date of death as march 18, 1947, and the place of burial bellu cemetery, in fact, neither this nor the previous data were confirmed by the “consiliul general municipuli bucuresti.” the only burial documents on file in the monumental cemetery is related to a certain ştefan mărăcineanu, who died march 18, 1944. ironically, the authenticity of ştefania mărăcineanu’s discoveries as well as the circumstances surrounding her end, are still a topic of discussion. conclusion: could the alpha radiation emitted by polonium activate lead? leaving aside any quantum interaction, “tunneling,” or short-range effects, but maintaining a purely deterministic perspective, it may be assumed that: the minimum kinetic energy required for an alpha particle to diminish the distance between itself and the lead nucleus, equal to or less than the sum of their nuclear radii, is obtained as a simple interaction between two charged particles which are acted on only by the coulombic force. cross sections (σ) for inelastic scattering of α particles on lead are not reported in the literature, but the energies of α particles emitted by polonium are known to be about 5 mev.89 in the case of bombardment of a lead target (pb) with alpha particles (he), the barrier (determinable in mev) is given by the approximate formula: 0.9⋅z1 ⋅z2 a13 a23 (1) 89science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity where z1 and z2 are the atomic numbers of the two elements and a1 and a2 are the atomic masses of the interacting nuclei. the value obtained is about 20 mev, or about four times the energy of alpha particles emitted by isotopes of po, and therefore a simple calculation excludes alpha particle activation of lead by that source. in fact, recent work shows that lead activation can occur with alpha particles with energies of about 40 mev,90 or even 30 mev.91 however, relying purely on classical physics, the theoretical results can have different values from those observed in the laboratory by a factor of ten. having recourse to quantum mechanics can help the investigator explain how some phenomena can happen when a deterministic calculation predicts that they are forbidden. in fact, a not so simple quantum calculation permits, for a sufficiently short period of time, that an alpha particle can have a much greater kinetic energy than normal because of the tunneling effect, provided that heisenberg’s uncertainty principle δeδt ≥ ! 2 (2) is not violated. therefore, it would be theoretically possible that an alpha particle with an energy of about 5 mev could overcome the coulomb barrier between itself and a lead nucleus, thus giving rise to the latter’s activation as allegedly observed by ştefania mărăcineanu. however, it should be mentioned that enrico fermi (1901-54), in his work on slow neutron bombardment of a large number of known elements, did not observe the activation phenomenon for lead.92 in the end, in the case of the “official” discovery of artificial radioactivity by irène and frédéric joliot-curie at the beginning of 1934, an aluminum foil was bombarded with alpha particles from a radium source with energies of about 4.6 mev.93 in this case, eq. 1 would give an approximate result as 4.8 mev. in light of our current knowledge of the physics of cosmic rays and on the basis of the work appearing in the literature,94 cosmic rays would have been able to induce radioactivity in the lead nuclei. but since all the substances present in the lead were exposed to the cosmic rays as well, then they all should have become radioactive, which we know is not the case. cosmic rays, or rather cosmic radiation, is a shower of high-energy particles arriving from outer space. it is very different from the alpha and beta radiation emitted by radioactive nuclei. when the primary radiation coming from space interacts with the atoms and molecules of the atmosphere, it produces swarms (a sort of decay) of secondary particles, some of which may reach earth. the primary cosmic rays have much higher energies than those in play in the decay of the radioactive substances, while secondary swarms have much lower energy, but higher than those required for activation of the lead and through which ştefania mărăcineanu may have observed this phenomenon. but it must be said that the flow of secondary particles that reach sea level is very low; only one particle per cm2 per minute. this heterogeneous mix of modern data and those reported in the 1920s and 1930s shows that it is impossible to treat them strictly quantitatively. therefore, it is not possible to give a clear assessment of the reliability of the investigations conducted by mărăcineanu. it is not possible to make clear-cut, definitive judgment, although ştefania mărăcineanu’s hypothesis was possibly derived from erroneous experimental data or certainly by poor interpretation of them. on the other hand, it is possible to point to an objective piece of data, about which romanian historians are very insistent: how ştefania mărăcineanu was removed from marie curie’s entourage and how some members of the institut du radium openly condemned and refuted her work. but not only that. these historians claim that the results were stolen from mărăcineanu, at night, when, for a reason not specified, she was not at home. romanian sources make mention also of a great scandal and a subsequent lawsuit that involved her and the curie family. if we follow these allegations to their appropriate conclusion, the chair at the university of bucharest that would be given to ştefania mărăcineanu would be at the price of her silence. but all these statements, with no supporting documentation, are nothing but speculations, incipient libel. if they actually existed, they would deserve to be studied thoroughly and objectively. to date, the only evidence proving the hostile resentment of the “clan curie” against ştefania mărăcineanu is in a document produced by the latter; in a letter addressed by the romanian researcher to lise meitner on march 12, 1936 and found in the meitner files of churchill college archives (cambridge), she wrote:95 madame, j’ai présenté au mois de février mes travaux sur la radioactivité artificielle à l’appréciation de la science allemande. vous éte une autorité dans la spécialité et votre opinion la dessus comptera beaucoup. j’espère que les travaux vous ont été déjà présentées par qui de droit. madame, je ne demande pas une faveur, mais seulement96 la justice et je fais chaleureusement appel à vôtre97 esprit de “équité” et a vôtre amour pour la science. je ne demande pas à tenir les lauriers de m.me joliot-curie; mais je demande seulement que l’on reconnaisse la part que j’ai joué au début de cette découverte et que l’on contrôle aus90 marco fontani, mary virginia orna, mariagrazia costa and sabine vater si la question de la pluie artificielle. j’ai vu qu’en france on commence à parler aussi de cette question sans mentionner mes expériences dans cette direction. madame, vous avez été connue moi dans l’élève de m.me curie, je ne sais pas de quelle manière m.me regarderez cette question; dans tous les cas, je vous prie beaucoup de ne pas en parler au m.me j. curie. ne pas lui écrire que je me suis adressée aussi à vous. elle ne m’aime pas et elle s’appuye98 sur une group organisation très puissante judéo-massonique.99 elle est communiste.100 m[’]en parle ici, je la croyons,101 car j’ai eu l’occasion de sentir sa puissance. seulement en allemagne on pourrait me rendre raison. je vous prie d’agréer, madame, l’expression de mes salutations très distinguées, dr. stéphanie mărăcineanu102 it was known that at the institut du radium, there was competition among the scientists, not only present, but downright encouraged. it was compounded by the alleged disparities in the treatment of some of its members at the expense of others. not surprisingly, people grumbled about the special treatment that mme. curie had reserved for her daughter.103 ştefania mărăcineanu did not belong to the curie family circle and, moreover, she was a foreigner. the same adjective with which mme. curie had been labeled at the beginning of the century, before marrying a frenchman (and university professor), then, widowed, and then trying to steal a married woman’s husband. yet, the insidious poison of xenophobia with which she was greeted in france by the most reactionary fringe of the country turned into a paternalistic scientific nepotism towards her daughter, who was assured according to some – a too rapid career at the institute which she directed. regarding the more personal, marie became extremely jealous: the most prestigious discoveries in the field of radioactivity could not but be due as if it were by right of blood – to any other than a member of her family. and so it seemed regarding the discovery of artificial radioactivity in 1934: a milestone in the study and understanding of atomic nuclei. when a great discovery reaches its fiftieth or hundredth anniversary, it is usually remembered with great celebration in the country that boasts of being the birthplace of the discoverer and recognizes him/her first as their own child and then as a their teacher. if the country is really great, it organizes a conference where scholars discuss the discovery, and commissions documentaries on the life of this man or woman of science. this is exactly what happened in 1984 for the celebration of the fiftieth anniversary of the discovery of artificial radioactivity.104 when the discovery involves a minor character, maybe embarrassing or in a marginal country, often we limit ourselves to a biographical retrospective, perhaps out of a condescending gallantry, not wanting to point out the inadequacy of the small country or the mediocre scientist compared to such a great discovery: in fact, because of ingrained prejudice, the discovery is assumed to be less influential. in our study, however, elements of judgment are mixed up with the most insidious and agonizing doubts: did ştefania mărăcineanu actually discover induced radioactivity? to this question we can answer with certainty: no. but it might be better to reformulate a more complex question thus: when ştefania mărăcineanu announced her discovery was it reasonable to consider her correct? although it may seem counterintuitive, with what was written a moment ago, the answer is: yes. therefore, we could sense a certain “stink of persecution” in her regard and so feel first hand “the ostracism assigned to her by mme curie.” the same aloofness that marie experienced as a student would then be ascribed to her students when she became a professor, and romanian historians perhaps too often tend to emphasize this. an objective fact, already well documented, is the decline of french science (chemistry105 and physics) between the two world wars. it can be said that most of french science was addressed by leading ideas coming from paris and in paris there were the so-called tetrarchs: marie curie, for radioactivity; paul langevin for theoretical physics; jean perrin (1870-1942) for physical chemistry; georges urbain (1872-1938) for general chemistry and mineralogy. all these famous people, as well as being linked by having maintained relationships with their own subordinates or colleagues,106 had strongly authoritarian, if not downright despotic, personalities.107 let’s not dwell too much on the details of events that could simply be traced to adulterous characters in the public eye, but this point of view is also very important, not merely voyeuristic, because it solidifies with uncommon clarity a bond, sometimes ideological, sometimes loaded with political and social tensions, that allows us to appreciate yet more the strength and power of these “masters of french science.”108 after the death of marie curie, direction of the institut du radium passed to andré debierne (1874-1949), who had, in common with many of his colleagues, the dubious repute of observing physical or chemical phenomena that do not exist, for example, the frigdaréction a supposed nuclear reaction that would take place at temperatures of the order of -200 °c. as another example, georges urbain posited a unifying theory of organic chemistry with mineral or inorganic chemistry109 (homéomérie) on a basis so qualitative and so simplistic as to be already obsolete at the time of its publication, so much so that no one ever considered it. 91science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity his many colleagues and disciples were careful to mention it only at the time of drawing up his numerous obituaries.110 finally jean perrin, a sacred cow of french science: ministre de la troisième république, founder of cnrs (centre national de la recherche scientifique), the father of the atom, nobel laureate in physics in 1926, between the end of world war i and the early 1920s put forth with stolid determination the fallacious radiative theory, according to which every chemical reaction would be caused by luminous radiation and its kinetic energy would be determined by the intensity of said radiation.111 perrin, in addition to being the author of erroneous assumptions, was the mentor of two famous physicists, yvette cauchois (1908-1999) and horia hulubei (18961972) who, in turn, announced the discovery of three nonexistent chemical elements: sequanium, dor, and moldavium.112 when, in the early 1920s, ştefania mărăcineanu arrived in paris, we are no longer in the belle epoque, where the capital was one of the driving forces of an enthusiastic confidence in the future, nurtured by continuous discoveries and inventions, regularly augmented by recurring expositions. we could advance the hypothesis that the environment of the chemists and physcists in france in those years113 could have stimulated students and researchers over a healthy competition in the search for new physical phenomena and that this research has turned into obsession of wanting to discover something new at any cost, thus committing inevitable blunders. if an urbain was driven to do this to refresh his fame in a futile attempt to bring down upon himself the attention of the nobel foundation, for ştefania mărăcineanu, we could talk about self-deception.114 the illusion of finding oneself before a vast unexplored ocean that represented the ultimate structure of matter and to be able to scrape together a few more great experimental discoveries escaped the scrutiny of the great scientists of the previous generation. but ştefania mărăcineanu’s flaw, like many researchers formed at the institut du radium, was that although they belonged to the generation following that of marie curie, continued to remain mentally contemporary, unable to grasp many of those discoveries that would have been the preserve of scientists more cosmopolitan: in the u.s., britain, and germany. because ultimately ştefania mărăcineanu, coming from a peripheral and marginal country in terms of the international scientific scene, had acquired french know-how when it was at its lowest point at the international level. for example, jean perrin, the undisputed head of french physical chemistry between the two world wars, forbade publication of any article on quantum mechanics in the journals he directly or indirectly controlled.115 on the one hand we have the characters (curie and perrin to name only two) so famous that they have become monuments of our cultural history that the very idea of attacking them frightens us. yet we have to pull together the threads of this story. for a long time a misunderstanding has surrounded the figure of ştefania mărăcineanu as if the glow of the flames burning bucharest in her long siege, had clouded her virtues as a scientist and the city collapsing into ruin deleted along with her true and presumed discoveries its anti-semitism and adherence to an authoritarian fascist regime, which it was replacing bloodily with a long communist dictatorship. it is difficult in this climate to move important details out of the shadows, like the fact that in her narrow view of the physical world, ştefania mărăcineanu, saw too many phenomena being derived from or, ultimately, due to radioactivity. certainly to ştefania mărăcineanu it was not an easy life, but it should be added that when, in 1929, she returned to romania, she did not stop to making an “incendiary tour” wherever she went, thundering against her old mentor and, after her death, against her daughter. her improbable discoveries of the 1920s were side by side, a decade later, with others: she wanted to see a correlation between exposure of radioactive substances to air and the formation of storm clouds or earthquakes. it was almost a leap of faith, made with an old nationalistic spirit of science in spite of the continued declining times; world war ii was unveiling its monstruous dimensions and its obscene ideology leading to the extermination of men, women, old people, and children, using in all this the only too willing and zealous men of science. it is a situation in which mărăcineanu took part, against her will, at the end of her life: a military conflict, the political and cultural identity, which has destroyed the conscience of a generation of her scientific peers. at a time when all the characters seem to “shout and no one listens to the other’s voice,” we can only conclude that stories like these are in our opinion – an incomparable antidote to the temptation of writing scientific hagiographies.116 acknowledgments the authors wish to thank mr. adrian tudoroiu, doctors alessandro ciandella, dina scarpi, roberto di camillo and stefano fedeli, professors roberto livi, andrea stefanini and massimo chiari for their help in the preparation of the present work. 92 marco fontani, mary virginia orna, mariagrazia costa and sabine vater a simple thank you cannot express the immeasurable help from the personnel of the biblioteca del polo scientifico di sesto fiorentino in the persons of laura guarnieri, serena terzani, sabina cavicchi, marzia fiorini, sabrina albanese and angela landolfi, as well as the archives assistants julia schmidt and heidi egginton of the churchill college archives centre (cambridge, uk). bibliography 1. greater romania, which assumed the name of romania between 1918 and 1940. in 1918, romania was defeated by the austro-germans but actually won the war. it participated with the winners in the partition of the territories of both its austro-hungarian enemy as well as of its russian ally. the only country that had its territory doubled by the terms of the peace of versailles, romania basically had designs on establishing its hegemony over the entire area of the lower danube. but it made the error of overestimating its own strength, leading to the failure of its more ambitious ideas and to a foreign policy that struggled mightily to forge its own path in a post-world war i europe, skirting both integration and a less-welcome annexation, thus paralyzing its internal politics for twenty years. 2. m. popescu, m.f. rayner-canham, g.w. raynercanham, “stefania mărăcineanu: ignored romanian scientist” in “a devotion to their science: pioneer women in radioactivity” by marelene f. raynercanham, geoffrey w. rayner-canham editors, 1997, chemical heritage foundation, philadelphia & mcgill-queen’s university press, montreal; pp. 87-91. 3. i.n. iacovachi, noesis, no. 10, 1984; m. rogai, evenimentul zilei, 13 septembrie (2009); g. marcu, ziarul financiar ziarul de duminică, 26 noiembrie 2009; professor ing. dănuţ şerban’s website: http://www. stefania-maracineanu.ro/; last access 06/12/2016. 4. m. rogai, formula as, nr. 928, 2010. 5. m. popescu, m.f. rayner-canham, g.w. raynercanham, “stefania mărăcineanu: ignored romanian scientist” in “a devotion to their science: pioneer women in radioactivity” by marelene f. raynercanham, geoffrey w. rayner-canham editors, 1997, chemical heritage foundation, philadelphia & mcgill-queen’s university press, montreal; p. 90. 6. i. langmuir, “colloquium on pathological science”, held at the knolls research laboratory, niskayuna, new york on 18 december 1953. a recording of the actual talk was made, but apparently lost, but a recorded transcript was produced by langmuir a few months later. see also: i. langmuir, physics today, 1989, 42, issue 10, october, pp.36–48. 7. the alleged discoveries relating to artificial rain induced by radioactive substances and the link between radioactivity and earthquakes, as we shall see, were not refuted presumably for two reasons: the announcements were made in minor scientific journals, in the middle of world war ii; in addition, mărăcineanu died shortly after the publication of these works. 8. j.-p. adloff, g. b. kauffman, chem. educator, 2008, 13, 318-325. 9. www.segretidipulcinella.it/sdp24/temp_02.htm, last accessed 18/10/2016: stefania mărăcineanu (18821944), in segreti di pulcinella, rivista di letteratura e cultura varia, numero 24. 10. g. steinhauser, g. loeffler, r. adunka, j. radioanal. nucl. chem., 2013, 296, 157-163; arhivele naţionale ale româniei – direcţia municipiului bucureşti, stefania mărăcineanu; ion n. iacovachi, noesis, 1984, no. 10. 11. romanian historian, politician, and man of letters. president of the council between 1931-32, he was also adviser to king carol ii (1893-1953). for reasons of cultural affinity, he was fascinated by italy, although not an admirer of benito mussolini (18831945) and fascism. he was rather suspicious of soviet and german hegemonic designs on his country and because of his firm opposition to the romanian government’s pro-nazi policy, he was assassinated by elements of the radically fascist “iron guard” in 1940. 12. professor ing. dănuţ şerban’s website: http://www. stefania-maracineanu.ro/; last access 06/12/2016. 13. the half life, t1/2, and the decay constant, λ, are often used interchangeably; they are related by t1/2 = 0.693/λ. 14. m.e. wieser (2006). iupac technical report, pure and applied chemistry, 2005, 78(11), 2051–2066; g. audi, a. h. wapstra, c. thibault, j. blachot, o. bersillon, nuclear physics a., 2004, 729, 3–128; n. e. holden. “table of the isotopes.” in d. r. lide. crc handbook of chemistry and physics (85th ed.), 2004, crc press. p. 11-50. 15. m. curie, c.r., 1906, 142, 273; rutherford, e., phil. mag. 1905, 10, 290; marckwald w., jahr. d. rad., 1905, 136; meyer, von sweidler, wien ber., 1906, 115, 63; regener, ber. der d. physik ges., 1911, 13, 1027. 16. this precaution was considered necessary because of the extreme difficulty in the treatment of polonium. one milligram of the isotope 210po (the only one manageable because the other four isotopes’ half lives were too short), emits the same number of alpha 93science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity particles as five grams of radium. in the process of decay, polonium-210 also releases a large amount of energy. 17. ş. mărăcineanu, c.r., 1925, 774. 18. ş. mărăcineanu, c.r., 1926, 345. 19. “on aurait pu croire à une pénétration du polonium d’une face a l’autre du plomb; mais dans ce cas on aurait dù avoir une forte perte de polonium à l’intérieur du blomb, ce qui n’a pas été constaté…” 20. “…semblent inique que le rayonnement solaire peut provoquer la réintégration du radium-e [bi] a partir du radium-f [po], et donc una reversibilité dans la série radiactive” 21. ş. mărăcineanu, c.r., 1927, 1322. 22. madame curie was a combative woman and so sure of herself that she never gave way in debate, even when fraught with a possible acrimonious aftermath. she savagely attacked both willy marckwald and sir william ramsay when they committed egregious errors in the field of radioactivity. the two colleagues harbored bitter memories of this incredible woman’s stubborn tenacity. it seems very strange that marie curie did not openly take a position on this matter, which was nurtured under her own roof. see m. fontani, m. costa, m. v. orna, “the lost elements: the periodic table’s shadow side”, oxford university press (2015), p. 471-475. 23. the institute of radium, according to bertrand goldschmidt (1912-2002), one of the last students to have known her personally, was ruled despotically and with certain inclinations toward nepotism by marie curie. after her death, andré debierne (1874-1949), the new director, had repeatedly clashed with her daughter, irène joliot-curie (18971956). the following anecdote is worth quoting as an explanatory example: “during one disagreement, when irène objected to the appointment of bertrand goldschmidt to a position she believed belonged to someone else, debierne retorted ‘goldschmidt possesses a quality that all the others do not have he did not work with your mother. now get out of here!’ “ goldschmidt, b. atomic rivals. rutgers university press, new brunswick & london; 1990, page 19. 24. marie curie’s granddaughter, hélène joliot, was born on september 17, 1927 and at 21 years of age, she married michel langevin, the grandson of her grandmother’s lover, paul langevin (1872-1946). 25. “a midi, quand le soleil darde sur l’appareil, le plomb semble devenir deux fois plus active…” 26. it is not clear what lead compounds might have been formed; their identities would certainly depend upon the acid used. it is also not clear if the lead compound thus formed were reduced by experiment to elemental lead prior to testing. 27. “le plomb du commerce, préparé toujours avec la galéne, n’est pas, comme on sait, radioactif…” 28. h. deslandres, c.r., 1927, 1324. 29. “les persone qui ont du plomb longtemps insolé, et qui n’ont pas appareils nécessaires à la recherche de la radioactivité, sont priées d’en envoyer un échantillon à l’observatorie de paris”. 30. ş. mărăcineanu, c.r., 1927, 1547. 31. h. deslandres, c.r., 1927, 1549. 32. “les recherches de mlle mărăcineanu sur le toitures anciennes de l’observatorie de paris offrent un intérêt de plus en plus grand. le plomb n’est pas le seul métal qui acquiere, sous l’influence des rayons solaires, une radioactivité spéciale…”. 33. w. kolhorster, physikalische zeitschrift, 1914, 14, 1153; w. kolhorster, naturwissenschaften, 1926, 14, 290. 34. r.a. millikan, r. m. otis, physical review, 1926, 27, 645. 35. h. deslandres, c.r., 1922, 622. 36. ş. mărăcineanu, c.r., 1927(ii), 122. 37. “on a vu que le courant d’ionisation donné par la côte opposé est proportionel à la valeur initiale du polonium déposé”. 38. “si l’on considère l’allure des cuorbes, ce courant d’ionisation qui augmente chaque jour de lui-même passe par un maximum, descend ensuite d’après une loi explonetielle, ainsi qu’il se passe, quand une substance radioactive prend naissance, se développe et se detruit, je pense qu’il y a formation d’une substance radioactive nouvelle dans la masse du plomb”. 39. h. deslandres, c.r., 1927(ii), 124. 40. the argus, 1927 august 6, saturday, no. 25269, p. 10, australia, melbourne; kalgoorlie miner, 1927 august 15, monday, vol. 33, no. 8680, p. 1, australia, kalgoorlie; the canberra times week-end edition, 1927 august 19, friday, vol. i, no. 67, p. 12, australia, canberra; the border watch, 1927 august 20, saturday, vol. lxv, no. 6661, p. 2, australia, mount gambier; the western argus, 1927 august 23, tuesday, vol. 34, no. 1937, p. 2, australia, kalgoorlie; the daily news, 1927 august 30, tuesday, vol. xlvi, no. 16.329, p. 9, australia, perth; the evening post, 1927 september 10, saturday, vol. civ, no. 62, p. 13, new zealand, wellington; the geraldton guardian, 1927 september 17, saturday, vol. xxi, no. 4743, p. 1, australia, geraldton. professor ing. dănuţ şerban’s website: http://www.stefania-maracineanu.ro/; last access 06/12/2016. 41. professor ing. dănuţ şerban’s website: http://www. 94 marco fontani, mary virginia orna, mariagrazia costa and sabine vater stefania-maracineanu.ro/; last access 06/12/2016. 42. ş. mărăcineanu, c.r., 1928(ii), 746. 43. “si l’on considère l’allure des cuorbes, ce courant d’ionisation qui augmente chaque jour de lui-même passe par un maximum, descend ensuite d’après une loi explonetielle, ainsi qu’il se passe, quand une substance radioactive prend naissance, se développe et se detruit, je pense qu’il y a formation d’une substance radioactive nouvelle dans la masse du plomb”. 44. ş. mărăcineanu, bullettin de la section scientifique de l’academie roumaine, 1929, 12, 5. 45. “l’action du raynonnament solaire porrai peu-être provoquer une transmutation del 0,001% plomb en or”. 46. “mais c’est dans les radioations solaires qu’on doit voire la pierre philosophale et la source de la formidabile énergie radioactive, don’t la necéssité s’impose et s’imposera de plus en plus”. 47. n. vasilesco karpen, bullettin de la section scientifique de l’academie roumaine, 1929, 12, 60. 48. “les expériences en question ont conduit à des résultats exactement contraires à ceux indiqués par m-lle mărăcineanu”. 49. it is not inconceivable that the french physicists were particularly “sensitive” to a similar subject, whose only result could only lead to the accusation pathological science. the unfortunate incident relating to nancy rays or “n” rays was a blow to the pride of french science, whose ghost had to be still very present in their minds. regarding this see: nye, m. j., historical studies in the physical sciences, 1980, 11(1), 125. 50. she was a french chemist and physicist. on the recommendation of the physicist, paul langevin in 1926 she arrived at the curie institut du radium laboratory as an “aide-bénévole” (a volunteer) and then the following year became a “travailleur libre” (independent collaborator). she became paul langevin’s lover twenty years after he had had a turbulent affair with marie curie, and she remained faithful to him, especially in the period of his exile in troyes during the war. from their relationship, paul gilbert langevin (1933-86) was born. 51. e. róna, e.-a.w. schmidt, wien. ber., 1927, 136, 65. 52. she was a dutch chemist and crystallographer. after completing her studies in 1932 she became assistant to the chemist a. smits at the general and inorganic chemistry laboratory of the university of amsterdam. she is mainly known for her work in x-ray crystallography. 53. smits, a., macgillavry, c.h., proceedings of the koninklijke nederlandse akademie van wetenschappen, 1929, 32, 610. 54. ş. mărăcineanu, c.r., 1925, 774. 55. “…ces résultats étaient peut-être de grande importance parce que si vraiment le plomb s’active et émet des particules α, il estvraisemblable qu’il y a une transmutation de plomb en mercure”. 56. dănuţ şerban -  drumurile mele toate ..., ştefania mărăcineanu,  memoriae ingenii, revista muzeului naţional tehnic prof. ing. dimitrie leonida, octombrie 2013, page 6. 57. voi lupta, dragă doamnă, şi pentru mine şi pentru dreptate şi pentru onoarea ţării şi a femeilor. 58. ş. mărăcineanu, c.r., 1930, 190, 373. 59. “ne serait-ce pas là le resultat d’une transmutation poussée au delà du plomb dans la serie periodique des éléments? et la radioactivité ne serait-elle pas une propriété générale de la matiére?” 60. “je ne peux pas comprendre comment m. m. fabry et dureuil n’en ont pas trouvé [trace d’or, d’helium ou de mercure]”. 61. he was a french physicist and chemist. he was appointed associate professor of physical sciences in 1908. he then became professor at the faculty of sciences at dijon, where he spent all of his career. he was also a member of the academy of sciences, arts and letters of dijon. wounded in world war i, he was decorated with the legion of honor in 1929. 62. a. boutaric, bulletin de l’asociation des diplomes de microbiologie de la faculté de pharmacie de nancy, 1941, 19/23, 5. 63. a. boutaric, mlle. madeleine roy, c.r., 1930, 190, 483. 64. mme mary wallace shillito was the widow of a wealthy mauritian businessman, assan farid dina (1871-1928). both were allegedlly occultists and alchemists. she died at the age of 62 of a heart attack brought on by an accident, and is buried in geneva. 65. a. smits, mlle. macgillavry, c.r., 1930, 190, 635. 66. h. deslandres, c.r., 1930, 190, 637. 67. g. reboul, c.r., 1929, 189, 1256; g. reboul, c.r., 1930, 190, 374. 68. pokrovsky, zeitschrift fuer physik, 1930, 59, 127. 69. “il faut attendre que l’étude des faits ait été pousée plus loin”. 70. a. lepape, m. geslin, c.r., 1930, 190, 676. 71. ş. mărăcineanu, bullettin de la section scientifique de l’academie roumaine, 1930, 13, 55. 72. a. boutaric, mlle. m. roy, c.r., 1930, 190, 1410. 73. catalan physicist, whose name is often written as josep baltà i elies. 74. j. baltá elías, anales de física y química, 1941, 180. 75. c.r. lawrence, jpl, for the planck collaboration, 95science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity astrophysics subcommittee, nasa hq (18 march 2015) “planck 2015 results” (see page 29 of pdf ). 76. faculty of science of the university of bucharest. 77. professor ing. dănuţ şerban’s website: http://www. stefania-maracineanu.ro/; last access 06/12/2016. 78. middle school for girls. 79. s. mărăcineanu, radioactivitatea şi constituţia materiei. (efectul razelor solare in fenomenele radioactive), editura casei coalelor, bucuresti, 1929, pp. 37. 80. s. mărăcineanu, radioactivitatea, tipografia c. lazarescu, bucuresti, 1936, pp. 218. 81. i. joliot-curie,“gespraech mit irene curie. die tochter derr radiumentdeckerin in wien” “conversation with irene curie. the daughter of radium’s discoverer at vienna”, neues wiener journal, 5 giugno 1934, pag 6. 82. “romanian engineer and physicist, and also known for some of his achievements in mechanical engineering and electrochemistry. he created a controversial contrivance that goes by the name of the karpen pile: a battery capable of self-perpetuating recharge which provided power for over 60 years. a fraud according to scientists; an example of perpetual motion according to some newspapers”. sandru, ovidiu.  “karpen’s pile: a battery that produces energy continuously since 1950 exists in romanian museum”. retrieved  20 july  2012. http:// www.greenoptimistic.com/karpen-pile/; last access 06/12/2016. 83. “artificial radioactivity, a discovery of romanian [scientists] in this area”. professor ing. dănuţ şerban’s website: http://www.stefania-maracineanu.ro/; last access 06/12/2016. 84. i do not dispute the award of the nobel prize to mme. joliot-curie for the advancements that she made to this discovery, such as investigative methods, highlighting the phenomenon that i consider to have discovered. but i ask you to recognize the role i played in this discovery. i was the first to announce this phenomenon in 1924 when it seemed utter foolishness. mme. joliot-curie used the same method that i used at the beginning of her research. ... the only difference is that she placed a metal sheet over polonium, while i deposited a polonium solution on the metal foil. pierre curie’s widow [in this second stage of the letter, the romanian researcher refers to marie curie in 1923] did not allow me to give this explanation in my thesis and assured me that if i listened to her, the work would be continued and that when my phd was finished, an article in my name would appear. in that case, i held back. […] immediately after obtaining the phd, i published my results on my own at the romanian academy”. english translation from http://www.mnt-leonida.ro/09noutati/090043nouta ti2013.10.17/stmaracineanu2013ar.pdf; last access 06/12/2016. 85. “... this laboratory is my life, from which i could never be separated.” english translation from http:// w w w. m nt l e o n i d a . r o / 0 9 no u t at i / 0 9 0 0 4 3 no u t a ti2013.10.17/stmaracineanu2013ar.pdf; last access 06/12/2016. 86. it was persecution and personal opposition that has followed me step by step, since i broke off with the institut du radium ... english translation from from: http://www.mnt-leonida.ro/09noutati/090043nouta ti2013.10.17/stmaracineanu2013ar.pdf; last access 06/12/2016. 87. france was the only ally and guarantor of romanian borders. her collapse under german tanks in may 1940 threw the romanian government into complete panic. king carol decided to make a last-minute proposal to hitler to curry favor with the axis, but a few days afterward, russia commanded romania to cede the province of bessarabia, while the axis didn’t bat an eyelash. during july and august 1940, the hungarians and bulgarians prepared (with german support) to further amputate romania (the kingdom of transylvania and southern dobruja). the day after signing the diktat of vienna (august 30, 1940) king carol named general antonescu governor, and abdicated in favor of his son, michael (b. 1921) who ten years earlier had been deposed with a coup d’état. 88. information supplied by gheorghe bezviconi (19101966) in his book “necropoli capitale”, published posthumously by the institute of history “nicolae iorga,” 1972. 89. d.g. karraker, a. ghiorso, and d.h. templeton, phys. rev., 1951, 83, july, 390. 90. woolum, s. dorothy, d.s. burnett, l.s. august, nuclear instruments & methods, 1976, 138(4), 655. 91. j.j. howland, d.h. templeton, i. perlman, physical review, 1947, 71, 552; d. h. templeton, j.j. howland, i. perlman, physical review, 1947, 72, 766. 92. e. amaldi, o. d’agostino, e. fermi, b. pontecorvo, f. rasetti, e. segrè, proceedings of the royal society, 1935, 149a, 522; o. d’agostino, e. fermi, b. pontecorvo, f. rasetti, e. segrè, ricerca scientifica, 1934, 1, 380. 93. w.y. chang, phys. rev., 1946, 70 november 1, 632. 94. j. clay, k.h.j. jonker, physica (the hague), 1938, 5, 171. 95. cca, doc. reference mtnr 5/12; letter from ştefania mărăcineanu to lise meitner, 12/03/1936. 96 marco fontani, mary virginia orna, mariagrazia costa and sabine vater 96. word written between the lines. 97. grammatically, it should be “vos”. 98. in the original letter, the “y” is written “i”. 99. it should be: “maçonnique”. 100. words added between the lines. 101. in the original letter, the “y” is written “i”. 102. madam, in february i presented my work on artificial radioactivity to the attention of german science. you are an authority in this field and your opinion on it will be highly esteemed. i hope that the work has already been presented to you by those people who may be concerned. madam, i do not ask for a favor, but only justice and i warmly do appeal to your spirit of “equity” and your love for science. i do not ask for the laurels of madame joliot-curie; but i only ask that the part i played at the beginning of this discovery is recognized as well as my pioneering work on artificial rain. i have seen that in france they are beginning to talk about this subject without mentioning my experiments in that area. madame, you have known me as mme. curie’s pupil, i do not know how she would have looked at this question; in any case, i beg you very much not to speak of me to mme. j. curie. do not write to her that i have also addressed you [by this letter]. she hates me and she belongs to a very powerful judeo-masonic organization. | she is a communist |. i speak of it knowledgeably, believe me, because i have had occasion to feel her power. only in germany can i be vindicated. please accept, madam, the expression of my most distinguished greetings, dr. stéphanie mărăcineanu 103. e. tina crossfield, “irène joliot-curie: following in her mother’s footsteps”, in “a devotion to their science: pioneer women in radioactivity” by marelene f. rayner-canham, geoffrey w. rayner-canham editors, 1997, chemical heritage foundation philadelphia & mcgill-queen’s university press, montreal pp. 97-124. 104. e. amaldi, “la radioactivité artificielle a 50 ans, 1934-1984”, éditions du physique, 1984, pp. 164. 105. j.c. gomes, “georges urbain (1872-1938), chimie e philosophie”, doctoral dissertation, 2003, université de paris x, nanterre, 235-242. 106. m. charpentier-morize, “perrin, savant et homme politique”, 1997, ed. belin, 217-226; b. bensaudevincent, langevin (1872-1946)  science et vigilance, paris, ed. belin, 1987, 271. 107. j.c. gomes, ibid., 40-44. 108. a colleague, fortunée schecroun (1896-1978), known as nine choucroun, officially became the compagne of jean perrin after the death of heniette perrin (1869-1938); eliane montel (1898-1992) had a lengthy relationship with paul langevin after he left his first lover, marie curie, and their bed-sit that they had rented in rue de banquier, not far from the sorbonne. finally, georges urbain (1872-1938), left a widower in 1936, married his “personal nurse,” jacqueline nancy ullern (1910-78), nearly forty years his junior. 109. g. urbain, scientia (milan), 1934, 56, 71; g. urbain, bulletin de la société chimique de france: memoires, 1937, 4, 1612. 110. between 1938 and 1940, about a half-dozen obituaries were published to remember him. also, two biographies came out on the occasion of the centenary of his birth (1972). in one of them, there is an outline of his homéomérie theory. 111. j. perrin, annales de physique, 1919, 11, 5. 112. m. fontani , m. costa, m.v. orna, “the lost elements: the periodic table’s shadow side”, oxford university press, 2015, p. 331-334. 113. d. pestre, physique et physiciens en france 1918-1949, edition des archives contemporaines, 1984; m.j. nye, from chemical philosophy to theoretical chemistry 1800-1950, university of california press, 1993. 114. r. trivers, annals of the new york academy of science, 2000, 907, 114. 115. m. charpentier-morize, “perrin, savant et homme politique”, 1997, ed. belin, 107-109. 116. r. hoffmann, in m. fontani, m. costa, m.v. orna, “the lost elements: the periodic table’s shadow side”, oxford university press, 2015, p. xvi. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments firenze university press www.fupress.com/substantia preface it is a great honour for me to write these few lines of preface to the special issues of substantia dedicated to the 150th anniversary of the periodic table by dmitrij mendeleev. in 2019 there are other important anniversaries besides that of the periodic table. one of these is the centenary of primo levi’s birth. i believe these two anniversaries are strictly related, in fact the periodic table by levi has been considered by the royal institution of great britain as the “best book of science ever written”. it would be sufficient to recall an impressive excerpt from “iron”, a tale of the the periodic table, to acknowledge the uniqueness of this literary work: “we began studying physics together, and sandro was surprised when i tried to explain to him some of the ideas that at that time i was confusedly cultivating. that the nobility of man, acquired in a hundred centuries of trial and error, lay in making himself the conqueror of matter, and that i had enrolled in chemistry because i wanted to remain faithful to this nobility. that conquering matter is to understand it, and understanding matter is necessary to understand the universe and ourselves: and that therefore mendeleev’s periodic table […] was poetry …”. when we designed the project related to these special issues, we had in mind levi’s work and in particular his wonderful tales that belong to the periodic table. i like to recall this homage to a chemist-writer-witness to introduce the six topics that are associated to the special volumes of substantia. as president of the university of florence which is the owner of the publisher firenze university press, i am truly grateful to the editors – marc henry, vincenzo balzani, seth rasmussen, luigi campanella, mary virginia orna with marco fontani, and brigitte van tiggelen with annette lykknes and luis moreno-martinez – for accepting the invitation made by the editor-in-chief pierandrea lo nostro and for the extraordinary work for the preparation of these special issues. of course the choice of the six subjects was not accidental: we tried to identify some features of the chemistry realm, related for several reasons to the periodic table. they are strikingly associated to the great challenges for our future: these are water, sustainability, energy, open chemistry, the history and the educational perspectives of the periodic table. during its long path of progress and civilisation mankind has strongly modified nature to make our planet more comfortable, but at present we must be very careful with some dramatic changes that are occurring in our earth. science and technology, and chemistry primarily, can help mankind 8 scientific board to solve most of the environmental and energy problems that emerge, to build a radically different approach from that that has prevailed in the last two centuries. it is a fantastic challenge, since for the first time we can consider nature not as a system to simply exploit, but a perfect ally for improving life conditions in the whole planet. chemistry has already engaged and won a similar challenge when, understanding the pollution problems generated by a chaotic and rapid development, succeeded in setting up a new branch, green chemistry, that turned upside down several research topics. now is the time to develop sustainable chemistry: the occurring events demand that chemists propose new routes and innovative approaches. in the last two centuries we have transformed immense amounts of matter from nature into waste without thinking that we were using non renewable energy sources. we have been acting as our natural resources were unlimited, but knowing that they are instead limited. now we are realizing that it is not possible to continue along this road. our planet and our atmosphere are made of finite materials and their consumption during the last two centuries has been impressive. some elements that are crucial for current and future industrial countries are known to be present on earth crust in very small amounts and their recycling from waste cannot be a choice anymore, but it is rather an obligation. climate is another big problem associated to the terrific changes occurring in some equilibria, both as a consequence of the violent industrial development and energy consumption. we need, and we will always need more and more, an immense amount of energy. the only solution to secure wellness to future generations is the conversion to renewable energy sources. in this view, food and water, due to the strong increment in the demographic indices, could become the true emergencies for billions of individuals. looking at the picture i tried to draw in this short preface it becomes more clear why we selected those topics for our special issues. i am optimistic, and i have the strong confidence that chemistry, that studies matter and its transformations, will give mankind the picklock to overcome those challenges. we will definitely need insightful minds, creativity, knowledge and wisdom. luigi dei president of the university of florence firenze university press www.fupress.com/substantia substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna firenze university press www.fupress.com/substantia preface it is a great honour for me to write these few lines of preface to the special issues of substantia dedicated to the 150th anniversary of the periodic table by dmitrij mendeleev. in 2019 there are other important anniversaries besides that of the periodic table. one of these is the centenary of primo levi’s birth. i believe these two anniversaries are strictly related, in fact the periodic table by levi has been considered by the royal institution of great britain as the “best book of science ever written”. it would be sufficient to recall an impressive excerpt from “iron”, a tale of the the periodic table, to acknowledge the uniqueness of this literary work: “we began studying physics together, and sandro was surprised when i tried to explain to him some of the ideas that at that time i was confusedly cultivating. that the nobility of man, acquired in a hundred centuries of trial and error, lay in making himself the conqueror of matter, and that i had enrolled in chemistry because i wanted to remain faithful to this nobility. that conquering matter is to understand it, and understanding matter is necessary to understand the universe and ourselves: and that therefore mendeleev’s periodic table […] was poetry …”. when we designed the project related to these special issues, we had in mind levi’s work and in particular his wonderful tales that belong to the periodic table. i like to recall this homage to a chemist-writer-witness to introduce the six topics that are associated to the special volumes of substantia. as president of the university of florence which is the owner of the publisher firenze university press, i am truly grateful to the editors – marc henry, vincenzo balzani, seth rasmussen, luigi campanella, mary virginia orna with marco fontani, and brigitte van tiggelen with annette lykknes and luis moreno-martinez – for accepting the invitation made by the editor-in-chief pierandrea lo nostro and for the extraordinary work for the preparation of these special issues. of course the choice of the six subjects was not accidental: we tried to identify some features of the chemistry realm, related for several reasons to the periodic table. they are strikingly associated to the great challenges for our future: these are water, sustainability, energy, open chemistry, the history and the educational perspectives of the periodic table. during its long path of progress and civilisation mankind has strongly modified nature to make our planet more comfortable, but at present we must be very careful with some dramatic changes that are occurring in our earth. science and technology, and chemistry primarily, can help mankind to solve most of the environmental and energy problems that emerge, to 8 scientific board build a radically different approach from that that has prevailed in the last two centuries. it is a fantastic challenge, since for the first time we can consider nature not as a system to simply exploit, but a perfect ally for improving life conditions in the whole planet. chemistry has already engaged and won a similar challenge when, understanding the pollution problems generated by a chaotic and rapid development, succeeded in setting up a new branch, green chemistry, that turned upside down several research topics. now is the time to develop sustainable chemistry: the occurring events demand that chemists propose new routes and innovative approaches. in the last two centuries we have transformed immense amounts of matter from nature into waste without thinking that we were using non renewable energy sources. we have been acting as our natural resources were unlimited, but knowing that they are instead limited. now we are realizing that it is not possible to continue along this road. our planet and our atmosphere are made of finite materials and their consumption during the last two centuries has been impressive. some elements that are crucial for current and future industrial countries are known to be present on earth crust in very small amounts and their recycling from waste cannot be a choice anymore, but it is rather an obligation. climate is another big problem associated to the terrific changes occurring in some equilibria, both as a consequence of the violent industrial development and energy consumption. we need, and we will always need more and more, an immense amount of energy. the only solution to secure wellness to future generations is the conversion to renewable energy sources. in this view, food and water, due to the strong increment in the demographic indices, could become the true emergencies for billions of individuals. looking at the picture i tried to draw in this short preface it becomes more clear why we selected those topics for our special issues. i am optimistic, and i have the strong confidence that chemistry, that studies matter and its transformations, will give mankind the picklock to overcome those challenges. we will definitely need insightful minds, creativity, knowledge and wisdom. luigi dei president of the university of florence firenze university press www.fupress.com/substantia substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo substantia. an international journal of the history of chemistry 6(2): 5-6, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1741 the cultural revolution: ecological and social vincenzo balzani emeritus professor in chemistry university of bologna, italy member of the accademia dei lincei email: vincenzo.balzani@unibo.it our world is sick because of the bad relationship between human society and the planet and even more because of the discords within human society itself. we are slipping more and more towards ecological and social unsustainability. both scientists and philosophers say it, and pope francis highlights these views in the laudato sì: “ doomsday predictions can no longer be met with irony or disdain. [...] the pace of consumption, waste and environmental change has so stretched the planet’s capacity that our contemporary lifestyle, unsustainable as it is, can only precipitate catastrophes”.1 here then, as the pope writes, “ bold cultural revolution” is needed.2 the myth of a continuous and permanent growth has dominated human society for several years. an absurd myth that leads us to consider our planet only as a container of resources, without limits. the planet is actually a system with limited resources, consisting of chemical elements and their compounds, some relatively abundant, others scarce. in addition, resources are unevenly distributed across the planet, so there is a strong competition between peoples and between nations to get hold of them. investigations by the international agency oxfam show that the gap in inequality between rich and poor, both at the level of people and nations, continues to widen without restraint.3 thus, as pope francis wrote in the laudato sì, “ we are faced not with two separate crises, one environmental and the other social, but rather with one complex crisis which is both social and environmental”.4 in the most recent encyclical fratelli tutti pope francis explains that the cultural revolution that is necessary to achieve ecological and social sustainability cannot be accomplished through some partial changes in the humansplanet relationship or in the international relationships. instead, the basis on which our cultures rest must be radically changed. we must accept and appreciate diversity, acknowledge our limits and recognize that we are all children of god, brothers and sisters who are born, live and die in the same common home, planet earth. in other words, the mandatory cultural revolution requires that humans and nations pass from the situation of inhabitants in the same planet, often engaged in commercial competition or even at war with each other, to that of brothers and sisters that love and esteem each other. the main cause of ecological unsustainability is the use of fossil fuels. it is therefore necessary to resort to alternative energy sources, the renewable energies of the sun (photovoltaic), wind (wind power) and water (hydroelectric) which, without generating pollution and without causing climate change, provide electricity, a form of energy much more valuable than heat produced by fossil fuels. renewable energies are not only the answer to the climate crisis, 1 encyclical letter “laudato sì” of the holy father francis on fraternity and social friendship. 2015. ch. iv, 161. (https://www.vatican.va/content/ francesco/en/encyclicals/documents/papa-francesco_20150524_enciclica-laudato-si.html) 2 encyclical letter “laudato sì” of the holy father francis on fraternity and social friendship. 2015. ch. iii, 114. (https://www.vatican.va/content/ francesco/en/encyclicals/documents/papa-francesco_20150524_enciclica-laudato-si.html) 3 https://www.oxfam.org/en/reducing-inequality-what-your-country-doing-tackle-gap-between-rich-and-poor 4 encyclical letter “laudato sì” of the holy father francis on fraternity and social friendship. 2015. ch. iv, 139. (https://www.vatican.va/content/ francesco/en/encyclicals/documents/papa-francesco_20150524_enciclica-laudato-si.html) 6 vincenzo balzani but also the key to fighting energy poverty. as reported in avvenire by the director of the power shift africa,5 some developed nations, especially italy and germany, instead of supporting africa in the development of renewable energy, push many african countries to pour their limited financial reserves into the development of an industry based on fossil fuel extraction. in nature, the energies supplied by the sun, wind and water are very abundant, but to convert them into electricity we need equipment (photovoltaic panels, wind turbines, dams, etc.) that must be built starting from the material resources that earth provide. however, the amount of these materials is limited, so we must use them with maximum efficiency and recycle them. for this and other reasons it is necessary to abandon the disposable linear economy, powered by fossil fuels, and adopt a circular economy that uses renewable energy and that is based on reuse, repair and recycling of everything we produce. only in this way ecological sustainability can be achieved because the planet will be protected and not degraded, and its resources will be shared in sobriety. a wise policy can also be implemented to reduce inequalities through the development of common services (school, health, transport, etc.) and an economy based 5 https://www.powershiftafrica.org/ on taxes and subsidies aimed at helping the weakest, as every person is worth and must not be forgotten. the awareness that in a globalized world no one is self-sufficient will allow us to undertake fruitful collaborations between nations and to give strength to peace. then there is another problem. the limited material resources needed to convert the energies of the sun, wind and water into electricity are not equally distributed on earth. for example, some fundamental chemical elements, such as lithium for batteries and neodymium for wind turbines, are not found in europe, but mainly in chile, the former, and china, the latter. a country can cope with the scarcity of an important resource in two ways: with war, as often happened in the past for oil, or with collaboration and trade agreements. will nations continue to be so reckless that they wage wars to conquer the resources they do not have, or will they finally understand that every war is a defeat for all? here is another aspect of the mandatory cultural revolution, indicated by pope francis in the encyclical fratelli tutti: promoting a “universal aspiration to fraternity”6 and “social friendship”7 to build a better world starting from the common belonging to the human family and recognizing that “as children of the one god, we are all brothers and sisters”.8 6 encyclical letter “fratelli tutti” of the holy father francis on fraternity and social friendship. 2020. introduction, 8. (https://www.vatican.va/ content/francesco/en/encyclicals/documents/papa-francesco_20201003_ enciclica-fratelli-tutti.html) 7 encyclical letter “fratelli tutti” of the holy father francis on fraternity and social friendship. 2020. ch. iii, 106. (https://www.vatican.va/ content/francesco/en/encyclicals/documents/papa-francesco_20201003_ enciclica-fratelli-tutti.html) 8 encyclical letter “fratelli tutti” of the holy father francis on fraternity and social friendship. 2020. ch. viii, 279. (https://www.vatican.va/ content/francesco/en/encyclicals/documents/papa-francesco_20201003_ enciclica-fratelli-tutti.html) substantia. an international journal of the history of chemistry 2(1): 5-6, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-36 editorial why chemists need philosophy, history, and ethics since many years national and international science organizations have recommended the inclusion of philosophy, history, and ethics courses in science curricula at universities. chemists may rightly ask: what is that good for? don’t primary and secondary school provide enough general education such that universities can focus on chemistry alone? is that only a conservative call back to an antiquated form of higher education? or do they want us to learn some “soft skills” that can at best improve our eloquence at the dinner table but is entirely useless in our chemical work? the answers depend on what you understand by chemistry, philosophy, history, and ethics. let’s begin with chemistry. if the prototypical chemist were somebody who secludes himself in his laboratory, ponders on some selfimposed questions, and once in a while comes up with an idea to impress his colleagues, there would perhaps be little need. however, modern chemical research is a highly connected activity, conducted in teamwork that is typically interdisciplinary. it is project-based, that is, it seeks a solution to a problem that the scientific community or society at large, or both, consider important, and which mostly aims at the improvement of material conditions of life. the results are likely to have an impact on future research and the technological world we live in. similarly, if chemical research consisted in following simple routines, in doing some minor modification here and there to produce easily predictable results, there would be little need either. however, scientific research results are expected to be novel in the proper sense, i.e. they cannot be predicted, derived, automatically produced, or bought with grant money, contrary to the expectations of many science policy makers and managers, and unlike the usual rhetoric of grant proposals. such creative, and even more so groundbreaking, work requires questioning the received wisdom, what is taken for granted in science at the moment. thus, if you want to be a successful chemist, you cannot just apply what you have learned in your chemistry class. on the contrary, you must be able to challenge exactly what has been taught to you to be the edifice of science, and take it only as a provisional state in the course of the ongoing research process of which your work is meant to become a part. next let’s see what kind of philosophy, history, and ethics is needed for chemical research, and what not. if philosophy of science were the marveling at theories from physics, as the popularization of physics has long articulated it, it would be of little use for chemistry. indeed, most chemists have a much better understanding of the benefits and limits of quantum mechanics in their own field. however, philosophy is a way of asking questions about what is taken for granted but badly understood, and it usually aims at a better understanding. such as science (which historically emerged out of philosophy) asks question about nature that don’t bother ordinary people, so does philosophy of science asks question about science that scientists once stopped asking. what are the goals of science? how do scientists develop and establish knowledge? how is their knowledge organized, on which presuppositions does it depend? which fundamental concepts do they use and how can those be defined? and so on. while the professional philosopher has learned to take any intellectual edifice apart within minutes, a little training in philosophy helps scientists to raise the right questions at their research frontiers where the received taking-for-granted view is just deadlocked. moreover, many chemists are inclined to say that everything is chemistry, as do many physicists, biologist, engineers, mathematicians, etc., each for their own discipline, claiming a privileged access to the world. however all such disciplinary chauvinism is not only built on ignorance of the diversity of modern science, it is also poisonous to any interdisciplinary teamwork. only if you take your own chemical (or physical, biological, engineering, etc.) way of asking questions and solving problems no longer for granted but understand its disciplinary peculiarities that might essentially differ from that of other, equally acceptable, disciplines, you will be prepared for interdisciplinary teamwork. abstract as it 6 joachim schummer is, the philosophical understanding of different disciplinary approaches helps break the interdisciplinary barriers of conceptual misunderstandings and lack of mutual appreciation, which is more needed than ever. as a sideeffect, you will understand your own field, chemistry, much better if you are able to look upon it from the outside, such as you understand your own culture much better once you have spent some time abroad. if history consisted in setting up a fact sheet of whodid-first-what-and-when, that would not help either, other than to commemorate the ancestors and give them due credit. however, professional historians of science try to understand the scientists of the past from their own perspective, how they saw the world, what goals, beliefs, and methods they had, and in which social and cultural context they worked. because all that frequently differs considerably from our present perspective, history trains our capacities of thinking science differently, exactly what the creative mind needs as a starter. furthermore, history turns the static textbook view of the scientific edifice into a processual view of scientific evolvement, with all its entwined paths, dead ends, and prematurely given-up alternatives. history thus teaches you to understand science as a complex process, which you need in order to make creative and convincing contributions to it in the presence. moreover, only by looking at chemistry in its social and cultural context and their interactions over time, you understand what chemistry means in a broader sense, what role it plays in society, what societal expectations, hopes, and fears it raises. if ethics were a form of moral indoctrination, of making people comply with fixed rules, we would better do without. however, ethics, one of the oldest philosophical disciplines, is a technique of abstract reasoning about norms and values, of balancing different values, and of building moral arguments that try to justify why this is better than that. chemists who are engaged in research projects that aim to improve the material conditions of life, must be able to understand all ethically relevant aspects of their work and to develop moral justifications for what they do – if they really aim at improvement in the full sense. they must so in three different senses. first, they are morally obliged to do so because they will be held accountable for all possible adverse effects of their research work. second, because all technological innovations transcend traditional life forms, their moral assessment cannot simply follow traditional norms tailored to ordinary life contexts. instead for each possible innovation we have to develop moral deliberations anew, which of course requires being acquainted with the tools of moral reasoning. finally, if the goal of chemical research is material improvement according to general values, chemists can only be successful if they know all these values and are able to connect them in a balanced way to their research projects. chemical success thus depends as much on ethical competence as on chemical knowledge. in sum, education in philosophy, history, and ethics, each rightly understood, helps improve chemistry by making it more creative, more open to teamwork, and more aware of the social and ethical contexts that partly define it. it is therefore no additional luxury but in the self-interest of chemistry as a science to open itself to these fields. that has already been done in many countries, albeit mostly upon the request of accreditation agencies or governments, because society needs a stronger chemistry for the solution of many of its current problems. for the same reason, a journal like substantia that aims to broaden the chemical horizon is particularly important and welcome. joachim schummer editor-in-chief of hyle: international journal for philosophy of chemistry (www.hyle.org), js@hyle.org substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi substantia. an international journal of the history of chemistry 5(2): 5-6, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1383 our short talks pierandrea lo nostro department of chemistry “ugo schiff ”, university of florence, italy e-mail: pierandrea.lonostro@unifi.it we recently organized the first edition of substantia short talks to discuss some hot topics within the community of our journal. it was a recorded online event, that took place online on july 1, 2021, at 4 pm cest. in 2020, during the covid-19 pandemic that forced us to restrain or limit our social and cultural activities, we thought to offer a lively cultural happening to strengthen our interactions and to ponder on some remarkable issues that affect our lives as scientists and citizens in a globalized world. examples that came up to our minds were quite some. just to mention a few: the protection of intellectual property and the worldwide distribution of life-saving drugs (e.g. the anti-covid vaccines) at very low costs; the relationship between science and politics, i.e. black lives matter and the harsh debate between some international scientific journals and publishers; or the denial of freedom and democracy and even the lack of scientific dissemination in some countries, and so forth. not to speak about the side effects of the frenzied race to publish and the slavery to bibliometric indicators. what are the most important forces that drive research and dissemination in science today? and what can we do to improve the state of the communication between the society and scientists? what does the pandemic have to say in this respect? these are only a few among the several questions that spring from our minds. and their echo often reverberate in substantia as key points of some articles. these are the reasons why we decided to organize these “short talks” as a parallel contribution to our efforts to make science more transparent. this time our event features three contributions on peer review, big science and on the most advanced outcomes of current studies carried out by a young researcher in a specific field of chemistry. each contribution lasted 20 minutes, leaving room for questions and answers. we began with seth rasmussen from north dakota state university in fargo, who spoke about “the good and the bad of peer review”. peer review started in 1831 in the uk with willian whewell who proposed to receive the comments of two fellows of the royal society on submissions to the philosophical transactions. peer review truly is the central core of scientific publishing. it is necessary to guarantee the reliability of a paper, in the scientific community but also before the society. this process is the real core for the publication, of a reliable, solid and trustable article. interestingly, not so many people know that there are different kinds of peer review: single blind, double blind, post-publication, open, transparent, and collaborative peer review.1 sometimes the process is rough, for different reasons, and the editorial staff has to handle this crucial and delicate step very carefully. in any case this is by far the most important stage in the publication process. then it was the turn of helge kragh, from the niels bohr institutet in copenhagen. he gave an historical overview on “big science: opportunities and challenges”. this is a key issue with strong political ramifications. in fact big projects are so expensive that only governmental agencies can provide the necessary financial sources. they may also include other non scientific roles, such as managers, technicians, officers, secretaries, public accountants, and so forth. the work is usually carried out in a centralized system of large scale facilities http://www.fupress.com/substantia 6 pierandrea lo nostro where big and sophisticated, very expensive machines are employed, for example particle accelerators (cern in europe) or neutron sources (ornl in the us). the term “big science” was introduced by derek j. de solla price, in a 1963 book that presented an overview of the 1962 brookhaven national laboratory pegram lectures.2 certainly the topics and questions addressed in big projects are of paramount importance for science and for the society, however some significant drawbacks exist. for example the incredibly huge number of co-authors,3,4 sometimes larger than 5,000! this fact has important negative consequences, for example the impossibility to establish each author’s credits (who did what), practical problems (e.g. answering the reviewers), and ethical issues. of course when such a gigantic amount of money is invested, labs and instruments must work full time, with the consequence that methodologies and techniques may take the advantage over topics and science. the third contribution was from andreas lesch, a young electrochemist working at the university of bologna. his presentation “electrochemical detection of viable bacteria and biofilms” addressed some hot topics, particularly in view of the next pandemic that some expect will be due to antibiotics resistance in pathogens,5 and of controlling the growth of biofilms on all kinds of surfaces. electrochemistry concepts and techniques can be very useful in the detection of viable bacteria, particularly when time is a key issue for establishing the correct therapy. the main conclusions of the presentation were the production of flexible and reproducible electrodes through inkjet printing,6 their application to detect viable bacteria,7 and the opportunities given by scanning electrochemical microscopies for investigating biofilms.8 in line with substantia’s vision and scopes this talk on the most recent advances in research in this particular field, was combined with the two previous contributions that do deal with current science activities but in another way. this attitude of the journal springs from our inter and multidisciplinary interests. today science is deeply divided, there are only few chances to exchange high level information between scientists working in different fields. in other words, the unification of knowledge is a fantasy, due to the over-specialization and to the reluctance to make contents and concepts easily available to other scientists. it is not a question of science popularization, it is a question of sharing. and of promoting truly interdisciplinary studies. notes 1. https://authorservices.wiley.com/reviewers/journalreviewers/what-is-peer-review/types-of-peer-review. html 2. de solla price, d.j. little science, big science. 1963. new york: columbia university press. 3. aad, g. et al. combined measurement of the higgs boson mass in pp collisions at = 7 and 8 tev with the atlas and cms experiments. phys. rev. lett. 2015, 114, 191803. 4. cms collaboration., lhcb collaboration. observation of the rare  bs0  →µ+µ−  decay from the combined analysis of cms and lhcb data. nature 2015, 522, 68–72. 5. nadimpalli, m.l.; chan, c.w.; doron, s. antibiotic resistance: a call to action to prevent the next epidemic of inequality. nat. med. 2021, 27, 187–188. 6. zhu, y.; jović, m.; lesch, a.; tissières lovey, l.; prudent, m.; pick, h.; girault, h.h. immuno-affinity amperometric detection of bacterial infections. angew. chem. int. ed. 2018, 57, 14942-14946. 7. nagar, b.; jović, m.; costa bassetto, v.; zhu, y.; pick, h.; gómez-romero, p.; merkoçi, a.; girault, h.h.; lesch, a. highly loaded mildly edge-oxidized graphene nanosheet dispersions for large-scale inkjet printing of electrochemical sensors. chemelectrochem 2020, 7, 460-468. 8. darvishi, s.; pick, h.; oveisi, e.; girault, h.h.; lesch, a. highly loaded mildly edge-oxidized graphene nanosheet dispersions for large-scale inkjet printing of electrochemical sensors. sensors & actuators: b. chemical 2021, 334, 129669. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 3(1): 5-7, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-182 editorial i won a project! juan manuel garcía-ruiz laboratorio de estudios cristalográficos, instituto andaluz de ciencias de la tierra, csic-universidad de granada, spain yes, i know that playing the lottery is one way to pay taxes for those who do not know statistics. but in the future, we may “win in a raffle” to do many things, such as being a member of a board of directors, a councilman, or even a member of parliament because in the future it is very likely that councilmen, deputies and many other public positions will be chosen randomly. there is a controversial but solid theory supporting that randomness is one of the best mechanisms for optimizing selection processes1,2,3,4. scientists have already begun to test this idea, and in fact, they may already get a project if they present it to an interesting program of the volkswagen foundation called experiment!5 the program “experiment! in search of bold research ideas”6 aims to fund radically new scientific ideas, ideas that go against the dominant thinking in a scientific discipline, crazy ideas or ideas of dubious feasibility that would have no or very little chance of being selected in the classic science funding program. projects cannot formally last more than eighteen months and have maximum funding of one hundred and twentythousand euros. the program started in 2013 and is an absolute success. every year, the foundation receives around six hundred applications, prescriptively german. 1 b. henning, the end of politicians: time for a real democracy, 2017. 2 l. carson, p. f. l. carson, b. martin, random selection in politics. greenwood publishing group, 1999. 3 o. dowlen, the political potential of sortition: a study of the random selection of citizens for public office. andrews uk limited, 2017. 4 g. delannoi, o. dowlen, sortition: thoery and practice. andrews uk limited, 2016. 5 the non-profit volkswagen foundation is the largest private foundation for research and academic teaching in germany, spending more than 200 million euros in 2018. despite its name, it is independent and not affiliated with the automaker company. 6 https://www.volkswagenstiftung.de/en/funding/our-funding-portfolioat-a-glance/experiment six hundred and forty applications have been received this year. the internal evaluation team of the volkswagen foundation selects one hundred and fifty of the most scientifically daring proposals, those best suited to the objectives of the program. subsequently, these one hundred and fifty proposals are evaluated by a panel of ten scientists from different countries in the world, except germany. this panel of experts rejects a few of those one hundred and fifty applications that for some important reason should not be funded by this program, mainly because they are not radically new or because they are obviously viable. finally, out of all the others, the panel selects the fifteen that it considers the best, and which will be financed by experiment! it is easy to see that selecting fifteen proposals, out of a hundred and fifty that have been selected from more than six hundred applications, is very complicated for an expert, not to mention agreeing on them with the other nine colleagues on the panel. to avoid endless discussions, each member of the panel has a joker, a wild card – which can only be used once – to approve a specific project, thus putting an end to the discussion about that project. the volkswagen foundation tries to ensure that the selection is as impartial as possible. for example, the system is double-blind: neither the candidates know the panel members nor the panel members know who the candidates are. there are no names of people or institutions on the forms, and the foundation itself takes care of deleting any possible data from the proposal that could be used to identify the candidates’ names, age, genre, or university of origin. but even so, the existence of a problem of equanimity derived from the enormous competitiveness of the program has been detected. when experts evaluate and compare those ca. one 6 juan manuel garcía-ruiz hundred and forty research proposals that they have considered, in principle, eligible for funding by the program, they always find some of them outstanding, which should be clearly funded. let us say there are five of them. however, when it comes to selecting the other ten that can still be funded, they find that there are many more than ten proposals that are so good that it is technically impossible to decide which of them is better than the others. and that’s when problems arise. when the differences between projects are small, when it is difficult for an expert to assess the superiority of one project over another objectively, aspects come into play that are subjective to the evaluator and that cause the rational evaluation system to fail. among these factors is the tribal instinct of scientists, that is, the irresistible tendency to support those projects that are closer to their discipline and their way of thinking, what we could call intellectual nepotism. in addition to introducing injustice in the evaluation, this bias favors the most common disciplines over the rare ones, reducing the thematic diversity of the selected proposals. in order to tackle this problem experiment! has, for the last two years, launched an experiment that may seem too daring to some. but that’s what this program is all about! the experiment consists in selecting not only the fifteen projects by the panel of experts but also an identical number of projects by lottery. not among all the projects submitted, but among all the projects considered eligible for funding by the panel, including the fifteen approved for their technical quality in the opinion of the evaluators. that is to say, fifteen projects are selected by technical evaluation of the experts and fifteen projects by pure chance, by lottery. a total of twenty-five projects have been selected this year because, during the lottery, projects already approved by the panel can be awarded. only a list of the twenty-five projects is made public without revealing which were selected by the panel and which by lottery, and the follow-up and treatment that the foundation will make of all of them will be identical. the comparative study of the benefits of the two selection systems will be carried out by an external evaluation company. we will see what comes out of this trial, the first to be conducted with a significant number of projects. the idea of raffling project funding repels the academic world. accustomed to peer review, i.e., decisions about the quality of a paper (to be published) or a project (to be funded) or a researcher or professor (to fill a position) are made by experts of the same rank as the candidates, the proposal that an entire academic effort be the subject of a lottery draw, abandoned at random, seems unfair, irrational, even obscene. however, precisely one of the stronger points of the lottery system is the cost/benefit ratio for the researcher as well and for the advancement of science. a study has recently been published which concludes that when calls for funding research projects are very competitive, the effort researchers waste in writing their proposals may be comparable to the total scientific value of the research they intend to support7. the authors of the study themselves suggest that it would be more effective to replace peer review with a partial system of lotteries – such as experiment! or to fund on the basis of researchers’ past scientific successes rather than on their research proposals for the future. of course, many considerations can be made about the goodness of a lottery funding system. it depends on the external framework in which the researcher operates, the type of research program, the length and difficulty of the application forms, the number of calls to which a researcher can apply in a given country, the reasons for which it is presented, whether merely scientific or rather promotional, etc. but, in my opinion, the draw system is not unworthy and it should be investigated on which context its effectiveness depends and which modifications would optimize it. it should be explored as what it is, as a complex system, and its behavior analyzed with numerical simulations and the analysis of real cases such as the experiment! program. and, of course, the equations “selection by peer review = fair and rational” and “selection by lottery = unfair and capricious” should be forgotten: the lottery comes into play when the technical evaluation system by peer review ceases to be fair and effective, and not to replace it but to improve it. nowadays, the use of chance in the management of public affairs is reduced to popular juries in some countries. however, the lottery selection mechanism has been used in many moments of history by political systems that have worked well, from classical greece to the prosperous and stable republics of venice or florence8. in the outstanding greece of the 6th century b.c., practically all public positions were chosen by lottery. even army positions, excluding, for reasons of efficiency, those of the highest rank. the lottery system was widely used in the selection of public offices in florence in the fourteenth and fifteenth centuries, and even the doge of venice, as well as many of the public and elective offices of the city of the signoria, were chosen by a complicated 7 k. gross, c. t. bergstrom, contest models highlight inherent inefficiencies of scientific funding competitions. plos biology, 2019, vol. 17, no 1, p. e3000065 8 b. manin, the principles of representative government. cambridge university press, 1997. 7i won a project! system that included largely random selection9. the advantages of the random selection system are many, since, for example, it complicates corruption and bribery, makes factions useless, makes unnatural agreements impossible, disqualifies long-term promises, and reduces electoral expenditure to almost zero. imagine a congress in which deputies were elected at random. imagine a lady from spain, a farmer, a lesbian chosen by pure chance to be member of the european parliament. she could not say “we lesbians think ”, nor “we women farmers believe”, nor “we spanish want”, because she would realize, or they would make her realize, that she is not there representing anyone except herself and that the strength of the system is that each of the raffled seats in the parliament votes and decides in their own conscience, for their own interests. that sum of nonprostituted interests is what gives strength to the lottery election mechanism. but let’s leave the management of public affairs for another time, and let’s return, to finish, to the academy, that is what interests me now. in my opinion, the most worrying thing about the evaluation of experiment! is how to make an objective and relevant comparison between the two groups of projects funded, those selected by the panel of experts and those selected by lottery. as we made clear at the beginning, this program is looking for bold, daring, doubtlessly viable projects based on ideas that move in the diffuse and changing frontier of knowledge. how to evaluate the results of projects that by their very nature should fail in most cases? what criteria should be used to qualify the productivity of a project that is going to explore a niche not yet trodden by science? this problem is totally new in evaluation and its solution is nothing trivial. on the other hand, the result of the comparison will be very dependent on the composition of the panel, on the selection criteria of its components. when we had to design the evaluation system for the explora program – dare to discover, dare to be wrong – a pioneering spanish program in the financing of bold ideas, it became clear that the database of the national evaluation agency should not be used. the reason is that this task requires colleagues who are open-minded, nonegocentric, intellectually generous, with excellent scientific culture, and if possible with a certain sense of smell to detect in a proposal the semi-hidden potential that straddles the genius and the naive. we have to look for evaluators who would have bet on columbus, on marconi, on wegener. that is not easy. only nine years 9 j. s. coggins, c. f. perali. 64% majority rule in ducal venice: voting for the doge. public choice, 1998, 97(4), 709-723. https://doi. org/10.1023/a:1004947715017 ago, during the evaluation of a program for bold ideas, an advanced facial recognition project and another one about crypto currency were rejected, because they were useless (who’s going to be interested in that?). the role of the panel of experts is crucial because the final list of projects selected by these programs where the intellectual risk is assessed is the only, or more precisely, the best message that can be sent to future candidates to convince them that, fortunately, there are programs that don’t care about financing failure if the frontier of knowledge is explored with audacity. acknowledgments the author acknowledges the team of the experiment! program of the volkswagen foundation, and dr. enrique perez (institute of astrophysics of andalucía) for useful discussions of this subject. dr. alfonso garcía-caballero is also acknowledged for help with the english version of the manuscript. substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 4(2) suppl.: 33-37, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-824 citation: t. gettongsong, m. taseidifar, r.m. pashley (2020) new resins for ion exchange applications and a process for their sustainable regeneration. substantia 4(2) suppl.: 33-37. doi: 10.36253/substantia-824 copyright: © 2020 t. gettongsong, m. taseidifar, r.m. pashley. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. new resins for ion exchange applications and a process for their sustainable regeneration tanita gettongsong, mojtaba taseidifar, richard m. pashley* school of science, unsw canberra, northcott drive, canberra, australia *corresponding author: r.pashley@adfa.edu.au abstract. the report is concerned with the design and synthesis of a mixed bead resin for high salt level desalination. the resin allows for the simultaneous exchange of both anions and cations, within the same polymer. this improves the efficiency of desalination at seawater levels. a novel process for sustainable and low energy desalination for brackish water has already been achieved via ion exchange resins as explained below. the advance in resin technology improves a novel membrane process with closed– cycle regeneration of the resin. it is a superior alternative to reverse osmosis. keywords: thermal decomposition, bubble column evaporator, zwitterionic polymer resin, desalination, ion-exchange resin, ammonium bicarbonate, hollow fibre membrane. 1. introduction current desalination techniques like distillation and reverse osmosis (ro) are so energy intensive processes that they are often marginal economically.1 a promising alternative discussed in this volume comprises mixed cation and anion ion-exchange resins, that remove salt. it offers several advantages in desalination, such as low-input pressure, simple setup, high efficiency and also does not require an extensive pre-treatment. success requires removal of the salt and regeneration of the resin by the ammonium bicarbonate technology described 2-4 and further below. ion exchange beads, in typical commercial applications, are mixed and widely used in order to adsorb different ions onto their surfaces. the process has been used over many years in various water treatment processes, and consumes less energy than distillation and reverse osmosis. however, it has limited capacity to remove and adsorb ions in seawatwer and even fairly concentrated brackish water. an ion-exchange resin reaches a ‘spent’ point, at which the majority of the ion-receiver sites on the surface of the beads are depleted and no longer adsorb ions in aqueous solution. this problem can be resolved by maintaining separation of cationic and anionic beads following by regeneration of each with large volumes of strong acid and strong base. this limits the economic viability of the technique for desalination applications.2,5 34 tanita gettongsong, mojtaba taseidifar, richard m. pashley our published results2 have shown that ammonium bicarbonate (ab) can regenerate the spent resin without the need for separation of cationic and anionic resins and also the use of strong acid and strong base regeneration. ammonium bicarbonate (ab) is a thermolytic salt, which is capable of decomposing in aqueous solution at low temperatures, ranging between 35 and 80 °c.6 the decomposition is described by below reaction: nh4hco3 (aq)≜nh3 (g)+co2 (g)+h2o (1) using an ab solution as regenerant resolves the regeneration issue, and apparently for the first time. ammonium bicarbonate is unique in having the necessary properties for regeneration. the decomposition of the product ab solution also provides drinking water, as well as re-forming the resin.5 this work relates to use of mixed bead resin for high salt level desalination and also potential processes for regeneration of the resin. the resin material produced the polyampholytic hydrogel and zwitterionic resins to simultaneously exchange ions and cations in desalination at salt concentrations approaching seawater levels, and the regeneration process is comprised of washing the resin with high concentration of ammonium bicarbonate solutions. the recovery of the latter compound can be performed using either, a closed cycle hollow fibre membrane system or by using a suitable bubble column evaporator (bce). these methods offer the advantage of re-using the ammonium bicarbonate as an in situ regenerator for the mixed bead resin desalination system. 2. material and methods 2.1. materials certified reagent grade chemical (>99% purity) ammonium bicarbonate (nh4hco3) was supplied by sigma-aldrich and was used without further purification. aqueous solutions were prepared using deionized, ultrafiltered water (milli-q). for the decomposition experiment using a bubble column evaporator, a glass sinter column (büchner type, pyrex® borosilicate, vwr) with 120 mm diameter filled with 250 ml solution was used. the inlet air temperature was varied using a tempco air heater (300w) with a thermocouple temperature monitor and an ac variac electrical supply. the gases (air and nitrogen) were produced by cylinder (coregas pty ltd, australia) and a boc gas flow meter. 2.2. synthesis of strong acid and strong base polymer resins the resin is synthesised by synthesis of two different strong acid and strong base resins. the resins comprise a chemical cross-linked polyampholytic resin and a crosslinked zwitterionic polymer, both resins containing strong acid and strong base on the same polymer. 2.2.1. a chemical cross-linked polyampholytic resin materials 2.2.1.1. materials 2-acrylamido-2-methylpropanesulphonic acid sodium salt solution (amps) (anionic monomer), 3-(methacryloylamino) propyl-trimethylammonium chloride solution (mptc) (cationic monomer), ethylene glycol dimethacrylate (egdma) (crosslinking agent), 25% glutaraldehyde (ga) and alpha-glutaric acid (initiator) were used for synthesis. several salts: 98% sodium chloride, 99% sodium sulphate, magnesium chloride (ar grade) and magnesium sulphate (ar grade) were used to study swelling and conductivity and absorption properties. chemical structures of amps and mptc compounds are shown in figure 1. all chemicals were purchased from sigma-aldrich, australia as a reagent grade. 365 nm, 230 volts, 8 watts uv-lamp and 365 nm ultraviolet crosslinker replacement tubes were purchased from john morris scientific pty ltd. 2.2.1.2. methods several different reaction cells were tested for the uv polymerisation process to produce the polymer. the most suitable method was based on using an array of glass tubes of 1 cm diameter and 0.8 cm inner-diameter and of 10 cm length. cross-linked polyampholytic resins were synthesised within the glass tubes using the one-step copolymerisation of an anionic monomer, a cationic monomer and a crosslink agent (egdma). 2-oxoglutaric acid was used as initiator. cross-linked polyampholytic resins were produced with a range of o n h so3 na+ amps o n h n+ cl mptc figure 1. chemical structures of the cationic and anionic monomers used to produce the polyampholytic hydrogel. 35new resins for ion exchange applications and a process for their sustainable regeneration different composition ratio. the ratio of momoners are shown in table 1. 0.5 m nacl was used to fill the reaction cell. the uv reactions used 8 watts at 250 volts, with a 365 nm ultraviolet lamp, for 15 hours. after reaction, the product was immersed in water for 1 week to allow the product to equilibrate and to wash out the residue unreacted chemicals. 2.2.2. a crosslinked zwitterionic polymer 2.2.2.1. materials p-phenylene diamine and glutaraldehyde in dimethyl formamide (dmf) and 1,3-propane sultone in dmf were used as reactants for synthesis of the zwitterionic compounds. all chemicals were purchased from sigmaaldrich, australia as a reagent grade. 2.2.2.2. methods this resin was prepared using 5 mmol of p-phenylene diamine in 20 ml of dmf and 5 mmol of glutaraldehyde in 20ml of dmf were prepared separately in a different beaker. the solution was mixed and refluxed at 80°c for 1 hr. then, 15 mmol of 1,3-propane sultone in 10 ml of dmf was added in the reaction and refluxed at 70°c for 3 hr. the final product was washed several times with hot water to remove residual unreacted chemicals. figure 3 shows the chemical structure of the zwitterionic polymer. 2.3. bubble column evaporator system as an example for the ammonium bicarbonate recovery laboratory grade air and nitrogen separately was heated at 275 °c using a tempco air heater (300 w) with a thermocouple temperature monitor and an ac variac electrical supply to produce high-surface-area gas/water interface into a 120mm diameter open-top glass column (büchner type, pyrex® borosilicate, vwr) filled with 250 ml of the ammonium bicarbonate solution. the bubble column evaporator apparatus used to study improved decomposition with a high-temperature gas (air) flow is shown in our previous work.7 the actual temperature of the dry gas flowing into the solution was measured at the centre of the sinter by a tenmars thermometer (±1.5 °c) without any solution in the column. the gases (air and nitrogen) were produced from cylinders (coregas pty ltd, australia) and a boc gas flow meter was used to measure flow rates. the temperature of the column solution was also continuously monitored using a thermocouple positioned at the centre of the column solution. the air flow at temperatures of 300–600 °c was needed to produce gas temperatures just above the glass sinter up to 275 °c, and this necessitated the use of steel and brass connectors for the downstream output from the heater and the use of fm insulation rock wool as an insulating material. using the measured electrical conductivities of the nh4hco3 solutions at different time intervals, the percent decomposition of nh4hco3 at time (t) in the either membrane or the bubble column evaporator process was calculated using the formula: decomposition%=[1 – ]×100 (2) where [nh4hco3]t is the concentration of nh4hco3 at time (t) during the decomposition operation and table 1. the different molar ratios of reactant chemicals used for the polyampholytic resin syntheses. monomers crosslink agent initiator* amps mptc 1 1 0 1 1 1 0 4 1 1 1 1 1 1 1 4 1 1 2 1 1 1 2 4 *note that the initiator concentrations 14 refers to the ratio of monomer and 0.25% mole of initiator (i.e. for ‘1’, with ‘4’ corresponding to 1%). o s o o 1,3-propane sultone p-phenylene diamine nh2 h2n figure 2. chemical structures of the cationic and anionic monomers used to produce the zwitterionic resins. figure 3. the zwitterionic polymer compound. 36 tanita gettongsong, mojtaba taseidifar, richard m. pashley [nh4hco3]0 is the initial concentration of nh4hco3, just before pouring the solution into the membrane contactor or the bubble column evaporator. electrical conductivity values of all the solutions were measured using a eutech con 700 conductivity bench. 3. results and discussion 3.1. polyampholytic and polyzwitterionic resins ion adsorption equilibria were studied for both resins using monovalent (nacl) and divalent (mgso4) salt solutions. typical results for the polyampholytic resin are shown in figure 4 this graphs the absorption of salts by crosslink hydrogels. similar adsorption isotherms were obtained with the polyzwitterionic resin, with a maximum nacl adsorption of about 28 mmol/g (dry wt). both resins indicate enhanced adsorption capacity compared with typical results obtained using commercial mixedbed strong acid-strong base systems. these give about 5 mmol nacl/g (dry wt). the high adsorption rates show an increased efficiency of using the new resins in desalination compared to commercial resins. in addition, the latter resins are expected to have a shorter operating lifespan due to their regeneration using strong acid strong base this damages their polymeric structures. the results in figure 4 were obtained based on the electrical conductivities for different solutions when they were exposed to different ion exchange resins. these results are given below in table 2-5. 3.2. ab decomposition using the bubble column evaporator some typical decomposition results (using air and nitrogen) obtained under different solution conditions are given in figure 5. these results clearly demonstrate that the improved bubble column evaporator process is much more efficient for nh4hco3 decomposition than the standard method using simple stirred heating (i.e. without bubble column evaporator) at the same solution temperature of around 57 °c. the results in figure 5 obtained for different stirring conditions showed that figure 4. adsorption of cross-linked polyampholytic resins equilibrated in nacl and mgso4. table 2. electrical conductivity results for the hydrogel polymer dry sample (weight 0.05 g) in 50 ml nacl solution. concentration (m) conductivity (ms/cm) before after 0.2 19.14 18.74 0.25 23.2 22.8 0.3 27.3 26.4 0.4 34.9 33.7 0.5 41.3 40.5 table 3. electrical conductivity results for the zwitterionic polymer dry sample (weight 0.05 g) in 50 ml nacl solution. concentration (m) conductivity (ms/cm) before after 0.1 10.43 10.34 0.3 27.5 24.8 0.5 35.4 34.1 table 4. electrical conductivity results for 0.2 m salts solution (conductivity in solution). conductivity (ms/cm) day 0 day 1 day 2 day 3 nacl 18.98 18.66 18.62 18.38 mgso4 15.96 15.92 15.82 15.69 di water 0.0025 0.01329 0.037 0.053 table 5. electrical conductivity results for 0.2 m salts solution (conductivity in gel) conductivity (ms/cm) day 0 day 1 day 2 day 3 nacl 15.64 16.73 16.3 mgso4 13.5 13.75 14.03 di water 0.0363 0.042 0.0573 0 5 10 15 20 25 30 35 40 0 0,05 0,1 0,15 0,2 0,25 0,3 0,35 0,4 0,45 0,5 e qu ib ri um s or pt io n (m m ol /g (d ry )s or be nt ) equilibrium conc. in solution (mol/l) mgso4 nacl 37new resins for ion exchange applications and a process for their sustainable regeneration the decomposition rates for simple heating (without bubble column evaporator) remained the same, which indicates that the continuous mixing by the bubbling process in the bubble column evaporator did not itself contribute to the nh4hco3 decomposition. during the experiments, it was also observed that the presence of nh4hco3 at concentrations above about 0.5 m inhibited bubble coalescence to a similar degree as 0.17 m nacl,8 and that fine (1-3 mm diameter) bubbles were produced in the bubble column evaporator process. the thermal decomposition of ammonium bicarbonate solutions into ammonia and carbon dioxide gases and the resulting reduction in nh4hco3 concentration can clearly be seen by the increase in bubble size. 4. conclusion and future work an ion exchange resin was used for high salt level water desalination, with the resin comprising either a chemically cross-linked ampholytic polymer resin or a cross-linked zwitterionic polymer resin, on the same polymer chain, wherein the ampholytic polymer resin and the zwitterionic polymer resin each contain strong acid and base groups on the same polymer chain. the current laboratory system could be scaled up and optimised either with a commercial mixed-bed resin (strong acid/strong base mixed resin) or a novel mixed bead resin of the type used in this study but using ammonium bicarbonate for the closed-cycle regeneration of the resin, which offers an energy efficient desalination process. the resin regeneration process could also be combined with the bubble column evaporator method in order to recycle ammonium bicarbonate in a simple and efficient way. this can potentially be used as a new method to treat brackish groundwater in remote communities to replace current techniques, such as, reverse osmosis and thermal distillation which both have expensive maintenance requirements and are more difficult to establish. 5. acknowledgment the authors gratefully acknowledge the australian research council for funding this research. 6. references 1. i. c. karagiannis, p. g. soldatos, water desalination cost literature: review and assessment, desalination, 2008, 223, 448-456. 2. n. p. g. n. chandrasekara, r. m. pashley, regeneration of strong acid/strong base mixed-bed resins using ammonium bicarbonate (ab) for a sustainable desalination process, desalination, 2017, 409, 1-6. 3. n. p. g. n. chandrasekara, r. m. pashley, study of a new process for the efficient regeneration of ion exchange resins, desalination, 2015, 357, 131-139. 4. n. tarannum, m. singh, synthesis and characterization of zwitterionic organogels based on schiff base chemistry, j. appl. polym. sci., 2010, 118, 2821-2832. 5. n. p. g. n. chandrasekara, r. m. pashley, enhanced ion exchange capacity of polyampholytic resins, sep. purif. technol., 2016, 158, 16-23. 6. g. w. gokel, dean’s handbook of organic chemistry, mcgraw-hill, new york, 2004. 7. m. shahid, x. xue, c. fan, b. w. ninham, r. m. pashley, study of a novel method for the thermolysis of solutes in aqueous solution using a low temperature bubble column evaporator, j. phys. chem. b, 2015, 119, 8072–8079. 8. v. s. j. craig, b. w. ninham, r. m. pashley, the effect of electrolytes on bubble coalescence in water, j. phys. chem., 1993, 97, 10192-10197. figure 5. percent decomposition of nh4hco3 solutions at different concentrations in the bubble column evaporator (with an inlet gas (air and nitrogen) temperature of 275 °c and column solution temperature of 57 °c) compared with simple heating in a stirred vessel at around 57 °c. substantia. an international journal of the history of chemistry 5(2): 165-167, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1372 citation: gerontas a. k. (2021) review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021. substantia 5(2): 165-167. doi: 10.36253/ substantia-1372 copyright: © 2021 gerontas a. k. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. book review review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas coburg university of applied sciences, germany e-mail: apostolos.gerontas@hs-coburg.de bringing the ethics of chemistry to the classroom and the existence of a domain of knowledge whoever has attempted to bring ethical discussions on chemistry to a student audience of chemistry and related fields knows of the problem: in contrast to the relatively robust bioethical literature, the literature of chemical ethics is poor, disconnected, and scattered all around the place even in rare cases that it exists. this is an interesting fact, especially if one considers the extended moral (and moralist) discussions over chemistry and its products, and that a great part of the bioethical challenges of the last forty years or so have been generated not by biology (or medicine) per se, but from their marriage to chemistry and its practices. the lack of ethics of chemistry literature dictates to the lecturer unprecedented levels of creativity and demands extra workload to be effective –and this, in times where ethics courses, in general, have become a necessity. it is this gap that the editors of this book (schummer and børsen, ethics of chemistry: from poison gas to climate engineering, world scientific, 2021) have detected, and they strove to create a collection of case studies to cover it. in the introduction of the volume, the editors state teaching as the first aim of its existence –and add the establishment of the ethics of chemistry as an autonomous discipline in its own right. while the first aim of the book is quite effectively achieved, the second remains wanting at the end –not by fault of the editors or the contributors, but due to the current external conditions of the selected domain of knowledge. the problem introduced in the introduction as the quest for the ethics of chemistry remains unresolved in the whole volume because it is rather fundamental. due to the chronic underdevelopment of the ethics of chemistry, substantial living space has been taken over by other “ethics” and their discourses. even in cases where the basic underdetermination of new chemical substances is what is causing the moral issue, the reader cannot avoid http://www.fupress.com/substantia http://www.fupress.com/substantia 166 apostolos k. gerontas thinking of these cases in terms of bioethics, ethics of technology, business and corporate ethics, or simply issues of public policy and law. establishing the ethics of chemistry as a domain in its own right demands nowadays more than just offering cases where chemistry is the moral protagonist; calls also for a demonstration that chemistry is the primal and decisive protagonist, both on the level of problem and remedy –that the cases can and should be treated on this level. in the intro of the volume, schummer and børsen do offer a brief introduction to ethics and ethics of chemistry (stressing the contrast with the ethics in chemistry), present their chosen classification of the subjects covered, and suggest how their volume should be used in the classroom. their introduction to philosophical ethics is quite appropriate for the intended audience –undergraduate students of chemistry and related fields and, maybe, beginner teachers –and is well written and informative. similarly, the categories in which the included studies are separated (misuse and misconduct, unforeseen local consequences, global and long-term influences and challenges, challenging human culture, and codes and regulations) seem well thought and wisely chosen. what is however missing, is the crucial sub-chapter that would help the teacher justify the “ethics of chemistry” category of knowledge to the students –as opposed to bioethics, ethics of technology, business ethics, or just politics. the reply to the question “why ethics of chemistry, and not something else” could have been maybe articulated historically and philosophically. a short section of the introduction could explain to the reader that the wish-to-transform characteristic of our civilization, the wish-to-enhance and the means to do these, could be viewed as inheritances of alchemy and early chemistry, establishing thus the primacy of chemistry and its ethics vis-à-vis biology and industry (indeed almost as one of the editors does in later chapters). it ś not articulated in the introduction, however, and it is left somewhat hanging also in most of the 18 (otherwise superb) contributions. the editors opt instead for a short cultural history of chemistry (useful as an alternative organizing sub-chapter and principle for the essays), which does demonstrate why chemistry has a relatively bad name among the public –but not why it should have its own autonomous ethics discipline. the ghost of this problem of living space for ethics of chemistry is haunting the greatest part of the book, more apparent in some cases and less in others. when presented with the emblematic case of thalidomide, for example, students tend to deal with it in terms of clinical trials and regulations, even though the issue had indeed been created by chemical underdetermination. the treatment of the subject by ruthenberg in chapter 6 is historically accurate and ethically solid, but, in the end, the reader is left with the impression that the average student is right to perceive the subject as one of medicinal ethics and public policy –and not primarily as a chemistry story. when presented with the agent orange story in the classroom, students tend to deal with it as a case involving primarily company and government. jacob and walters offer an excellent piece on agent orange in chapter 7, discussing the responsibility of the chemist at the point of invention, and deploying scummeŕ s older argument that, since the first synthesis is the causal step for the existence of a substance, the chemist is somehow responsible for it. and yet, it is clear (and visible to most students) that this attribution of responsibility – even without moral judgment – would be practically ineffective and even have adverse effects in the production of new chemical substances. since a synthetic chemist wouldń t know the adverse effects of a substance at the point of invention, and since these effects can be wholly investigated by a multitude of researchers of different fields (inside the company, or generally after publication, which, yes, means proliferation, but transparency too), the subject becomes once again an issue of company and government (the latter argument is appropriated from a student assignment of the year 2016, to make a point). similarly, while a chemist might as well participate in the steering of a company (indeed historically, chemists were more often also businesspeople than any other scientific group), the decisions of a company are more often treated by business ethics and law than anything else. this is even admitted on the very title of chapter 5, by eckerman and børsen on the lessons from bhopal. are such cases, cases in ethics of chemistry? if yes, it has to be demonstrated how, and why. thankfully, the case for an ethics of chemistry becomes clearer and more persuasive in other chapters of the book. the piece of schummer on “chemists playing god” (chapter 16) and the ambitions to create artificial life is significantly closer to mark in the quest for ethics of chemistry since it establishes the historical background linking current bio-scientific practices (and hopes) to chemical and alchemical views of centuries before, as well as the link of the current reactions to chemical products to religious views of the past. such argumentation would have been of use in the introduction too –establishing chemistry as ethically and historically more fundamental than either biology or industry. schummer ś piece again on the ethics of chemical weapons research (chapter 3) does offer a case where the aforementioned responsibility at the point of the invention makes absolute sense: it is indeed involv167review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen ing a chemical decision and leads not only to the attribution of responsibility but also to heavy moral judgment. contakes and jashinsky follow a similar path in their contribution concerning the case of napalm and their criticism of the “ just” war thinking (chapter 4). that the two pieces are related to chemical warfare has of course something to do with their clarity of argument and effectiveness: weapons research is one of the few domains where the chemist knows beforehand (or, at least has good reasons to suspect, unless of course, he is too naïve) the aims, purposes, and potential uses of the substances that he or she is synthesizing –having thus clear responsibility for their existence and effects. however, the careful reader might become a bit uneasy reading exactly these cases –at least, if the subject of establishing an ethics of chemistry is dear to him or her. do these stories mean that autonomous ethics of chemistry is possible only in a few special cases where the chemical underdetermination is canceled by the explicit a priori stating of the aims of the research? on the level of creating a useful collection of case studies and essays for the classroom, the volume is absolutely and straightforwardly successful. the introduction offers all the basic knowledge that would be necessary to a student for an early engagement with the subject of ethics: basic philosophical terms are clarified, applied ethics is introduced, and the material of the book is logically and usefully organized. while the chapters form units, they can be read fully independently from one another –a characteristic that would make this volume extremely useful to every teacher. furthermore, the cases are arranged in more than one way (a fact well thought to satisfy different categories of teachers or different types of courses): they can be viewed as cases according to topics, cases according to the cultural history of chemistry, and cases according to the fields of chemistry. it is imaginable that thus the volume might be of use also for students far removed from the study of chemistry –even for students of the humanities that might want to learn more about the moral challenges presented by the practice of one of the most transformative crafts of our (post-)modern world. to this latter purpose, the part of the volume concerning the cases where chemistry is challenging human culture might be crucial. admittedly, there could have been more chapters included here –both for interested chemists and non-chemists. after all, it is chemistry that it is about, and it is hardly impossible to think of another discipline that has been more challenging, improving and disrupting, to the human routines the last two centuries (to the point that, in most european languages, the word “chemical” is commonly deployed as the opposite of the word “natural”). as it is, the section contains three contributions: the “playing god” of schummer (chapter 16, mentioned already), vishnubhakat ś “normative molecule” concerning patents and dna (chapter 17), and birkholm ś ethical judgement on chemical psychotropics and nootropics (chapter 15). vishnubhakat does an elaborate job in presenting a case study of the myriad genetics lawsuit (a case that had caused noise concerning who can patent what and to what extent in the biotech and medical genetics world and is often discussed in bioethics courses and, presumably, in intellectual property courses). he demonstrates clearly how and why dna is a special case, and why the application of patent legislation and norms of property might cause significant complications (the extended experience of the author in chemistry, law, and patents makes for an excellent read). at the end of the piece, however, the reader is left with the question of whether the special position of the dna in the chemical ontology, makes it indeed a too special case. birkholm on the other hand presents an interesting case on chemical psychotropics applying his three-step model to raise the question of responsibility for their effect on population and culture. the broad, captivating, and well-informing piece is examining a serious issue with potentially disturbing social repercussions: psychotropics´ use has expanded through the years, leaving the domain of traditional treatments and colonizing everyday life, in dangerous and culture-altering ways. indeed, it could be even claimed that psychotropics and nootropics cannot even be classified as pharmaceutical substances anymore. they are instead means of enhancement, intervention, and standardization (which is almost to be expected in a culture so focused on the “realization of one’s potential” and “self-invention”). the return to aristotle ś epistēmē and phronēsis, with phronēsis being the most valuable of the intellectual virtues, had been an appropriate return to the greek roots of ethics, and most welcome, and the proposed threestep model seemed useful. still, however, the expansion of the pharmaceutical companieś responsibility for the problem examined, to the individual employees of these companies left some argumentation to be desired (especially since it was built up by an analogy to the individual accomplices of the third reich). the sections of the volume that would be of immediately visible value to students of chemistry were of course those involving misuse and misconduct (first thematic section, chapters 2-4) and codes and regulations (last thematic section, chapters 18-19). the first section contains the two pieces on chemical weaponry (discussed earlier) and a piece of stemwedel on scientific misconduct. she 168 apostolos k. gerontas chooses to present a fictional case (“the case of the finicky reactions”, which has however tantalizing similarities to known real cases) to be able to control the setting, the conditions, and the known variables of her case. her strategic choice proves correct (indeed, the narrative of real cases of misconduct can never be complete: the perpetrators have no motive to share their information with ethicists), and offers the reader an ethical chapter that reads as good prose. that at the end of each part of the drama, the reader is confronted with the appropriate ethical questions has an excellent teaching effect. the ethical analysis of the drama is complete and well written, ideal for students of science (and the fact that the protagonist of the story is called anna bijou can be taken to be a bonus to the reader). for teaching purposes, it would be helpful if this particular section of the volume had a bit more weight, and contained a couple of scientific misconduct cases more, similar to the one of stemwedel. similarly, the section of codes and regulations would have benefited from some case studies of relevant controversies and violations and their treatment. concluding this review, it should be stressed that this book constitutes a step forward on both fronts that its editors stated as aims. on the front of creating teaching material for classes on ethics of chemistry, it comes to fill an unquestionable gap, collecting high-quality pieces that would function pedagogically with a broad array of students. it is imaginable that chapters of this book will find their way into classes of ethics of chemistry, corporate ethics, history of science, cultural studies of science, science and society courses, climate science, law, and, of course, philosophy of science; and that is a major strength of this volume. on the other hand, this very strength on one front brings with it a weakness on the other. the very fact that the volume can be useful so broadly, and far away from chemistry and its students, demonstrates a problem of breathing space for the domain of ethics of chemistry. historically, there is always a time lag between the naming of a new disciplinary domain –which constitutes a claim of existence –and the actual recognized existence of it, in academic circles and beyond. in the between, the discipline has to grow, achieve its means of communication and vocabulary of expression, and receive an organizational structure –and the ethics of chemistry is not there yet. it is of vital importance however that ethics of chemistry does indeed get there (even as a latecomer), and this volume is a step in the right direction. meanwhile, and until the ethics of chemistry gets there, i know that í ll be using this ethics of chemistry in my courses. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas op04281_168-168.pdf substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 3(2) suppl. 5: 9-13, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-265 citation: m. v. orna, m. fontani (2019) setting the table: a retrospective and prospective of the periodic table of the elements. substantia 3(2) suppl. 5: 9-13. doi: 10.13128/substantia-265 copyright: © 2019 m. v. orna, m. fontani. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. editorial setting the table: a retrospective and prospective of the periodic table of the elements mary virginia orna1, marco fontani2 1 chemsource, inc., 39 willow drive, new rochelle, ny 10805, usa 2 dipartimento di chimica “ugo schiff ”, università degli studi di firenze, via della lastruccia, 13 sesto fiorentino (fi) italy e-mail: maryvirginiaorna@gmail.com, marco.fontani@unifi.it abstract. the major theme of this special issue volume is “the history of the periodic table, the discovery of the elements, and of the materials that changed the course of history: the development of the periodic system and its consequences.” after a brief chronological retrospective on the development of the periodic table, each paper contributed to this volume will be summarized, with some editorial comments. keywords. ordering elements, periodic table, history, understanding chemistry, mendeleev sesquicentennial. introduction this year we celebrate the 150th anniversary of the periodic system (18692019), indisputably “one of the most significant achievements in science, capturing the essence not only of chemistry, but also of physics and biology;1 ...[the] table it gave birth to hangs in every chemistry classroom in the world and is one of the field’s most recognizable symbols. but the solid squares and familiar patterns of today’s table mask one of its fundamental characteristics: ‘the’ periodic table does not exist”2 and when ‘the’ table really came into being is a matter of debate. some would place its beginnings in 1860 at the karlsruhe congress, where some 140 european scientists from 11 european countries and mexico gathered to debate the chaos surrounding fundamental definitions and measurements in chemistry.3 this was probably the most inconsequential conference ever held in the sense that very little was actually resolved on site. on the last day of the conference, the italian chemist, stanislao cannizzaro (1826-1910) of the university of genoa, described his teaching method regarding the importance of atomic weight. thanks to one of his colleagues, the conferees went home with a reprint of cannizzaro’s paper published two years earlier in the italian chemical journal, il nuovo cimento, in 1858.4 the paper stressed the importance of avogadro’s hypothesis which, taken to its logical conclusion, was critical in determining the atomic weights 10 mary virginia orna, marco fontani of the elements.5 by their own admissions, it was this document that inspired the creation of dmitri mendeleev’s (1834-1907) and julius lothar meyer’s (18301895) periodic tables.6 but realizing that we stand on the shoulders of the giants of the past, we cannot forget that it was antoine laurent lavoisier (1743-1794) who, toward the end of the 18th century, published the first credible list of elements upon which all future chemical endeavor was based.7 from there, it was a matter of intellectual stepping stones that led us to the creation of the periodic table – a perfect illustration of how science makes progress.8 pathway to the periodic table departing from lavoisier, the first such stepping stone was john dalton’s (1766-1844) revival of the greek concept of atom in 1805, taking it a step beyond by quantifying relative atomic weights based on hydrogen with a weight of one. what follows is elucidated in much greater detail in eric scerri’s very helpful paper, “the discovery of the periodic table as a case of simultaneous discovery”.9 in 1829, johann döbereiner (1780-1849) discerned a relationship among “triads” of elements in which the central member’s atomic weight was the average of those of the other two. he also discerned similarities in their chemical and physical properties, but not all of the known elements fit into his groupings.10 a german chemist, leopold gmelin (1788-1853), chemist and son of the prominent chemist johann friedrich gmelin (1748-1804), professor at the university of heidelberg, among other things, worked on the elements’ classification. in 1843 he established the basis for expanding döbereiner’s classification system.11 in addition to those of julius quaglio (1833-1899) and heinrich adolf baumhauer (1848-1926), his table is believed to be one of the earliest precursors to the periodic table.12 according to eric scerri,13 among mendeleev’s competitors “there was a danish chemist and mineralogist gustavus hinrichs who fled to the united states when he was a young man. he set up a very interesting and rather original periodic system which was arranged like spokes of a bicycle”. hinrichs stated his ideas as early as 1855 and published it in his book programme der atommechanik in 1867. in 1862, shortly after the karlsruhe congress, geologist alexandre-émile béguyer de chancourtois (18201886) proposed classifying the elements on a cylindrical three-dimensional form arranged in order of cannizzaro’s atomic weights. his resulting “vis tellurique” clearly showed periodic trends in the elements.14 in 1864, william odling (1829-1921), an attendee of the karlsruhe congress and a strong proponent of cannizzaro’s view, published a table containing 57 elements and noted proportional numbers of the elements as seen in successive rows.15 we can reckon that béguyer de chancourtois’ and odling’s contributions were giant steps along the way to the development of the periodic table and the latter occurred almost simultaneously with john alexander reina newlands’(1837-1898)16,17 promulgation of his “law of octaves” in which he arranged the known elements in order of atomic weight, assigned to each an ordinal number (!), and correctly predicted the existence of the then-unknown element germanium. this was a major advance, especially the almost prescient divination of the number 8 before any hint of the existence of electrons or electronic configuration.18 but we are not there yet. in 1862, julius lothar meyer published a table containing 27 elements. he classified the elements into six chemical families according to their valences – a firsttime conceptual advance in arranging the elements according to their combining power. he published an updated table containing 50 elements two years later, and also predicted the possibility of yet undiscovered elements, but gave no details. meyer’s evolution of thought was brought to a head by his 1870 publication in liebig’s annalen19 in which he plotted the molar volumes of the elements as a function of atomic weight that clearly showed periodicity. however, since dmitri mendeleev had published his table in 1869, a long drawn-out priority dispute arose from which mendeleev eventually arose the victor – some say because of his longevity: he outlived meyer by twelve years. both scientists were honored for their mutual “discovery of the periodic relations of the atomic weights” with the royal society of london’s davy medal in 1882. mendeleev’s discovery so, who really discovered the periodic table? the question seems moot since the iypt was promulgated for 2019, the 150th anniversary of mendeleev’s publication, not meyer’s nor anyone else’s. our own opinion would be to answer “all of the above.” we all stand on each other’s shoulders. our ideas come from somewhere and someone else. mendeleev was indebted to those who went before, most notably cannizzaro, but also those others who stepped into the roiling sea of elemental chaos and attempted to put some order into it. the standard version for mendeleev’s discovery reads something like this: on a single day, february 17, 11setting the table: a retrospective and prospective of the periodic table of the elements 1869 (according to the julian calendar then in use in russia), he produced his first variant, which he called an attempt at a system of elements based on their atomic weights and chemical similarity, written on the back of a letter received from a friend. from there he proceeded to two incomplete rough drafts, arranging the elements horizontally so that those closest in atomic weight would fall under one another in the same column. his methodology was to make a card for each of the 63 then-known elements, including its symbol and chief properties, and then arrange the cards by playing a “game” of “chemical solitaire” that led to the full draft table of the elements.20 igor dmitriev, director of the mendeleev museum and archives at saint petersburg state university, takes issue with this version. he claims that mendeleev discovered the periodic law in the process of writing his textbook, principles, by following a non-linear, complicated, and difficult pathway that occurred in stages involving an enormous amount of work and the reconciliation of often incorrect and contradictory information. in his thinking, mendeleev denied the existence of sharp boundaries, which almost forced him to construct an initial arrangement of elements that contained three major divisions, or structural blocks, arranged from left to right: typical metals intermediate elements “with a less sharp chemical character” typical non-metals working with at least five variants of the above structure, mendeleev was able to confirm in his own mind his two major hypotheses: the causal dependency of the elements’ properties on their atomic weights, and the periodic nature of this dependence. it was on the basis of these two fundamental concepts that he drew up the table we are familiar with today, and that he allowed room for yet-undiscovered elements whose properties he uncannily predicted21 (figure 1). note the question marks for elements that would be expected to have atomic weights of 45, 68, and 70. according to dmitriev, his table did not spring full blown “from the head of zeus” all in one day.22 so, one hundred and fifty years later, we are still struggling with “the” table – or some variant of it, of which there are hundreds. although the typical classroom-style table has become an icon, with its 18-column main body and two rows of f-block elements arranged in order of increasing atomic number, it does not satisfy the demands placed on it by the development of quantum mechanics and atomic physics. now we know that one of mendeleev’s principles, that of the causal relationship of the elements to atomic weight, is not the logic that dictates the arrangement. there is also the challenge of reconciling an order based on chemical properties vs. an order based on electron configuration. a table for everyone as a result of these problems, there is no one standard periodic table. some chemists prefer a table based strictly on adherence to atomic number as the organizing principle, leading naturally to a 32-column arrangement, favored by eric scerri.23 another 32-column table, the so-called left step table, devised by charles janet (1849-1932) in 1928, based strictly on atomic orbital and electron-filling order, is getting more attention these days.24 janet’s table follows the madelung rule, which janet intuited before erwin madelung (1881-1972) ever even published it! some scientists think it may be a solution to the f-block-group 3 dispute.25,26 for futurists, the 172-element table devised by university of helsinki theoretical chemist pekka pyykkö, is based strictly on calculated electron configurations, effectively bypassing the current placement questions.27 carnegie mellon chemist paul karol takes another tack when viewing his crystal ball: he bases his predictions about future synthesis, measurement, and determination of chemical properties of new elements on qualitative, rather than theoretical, considerations.28 consensus has it that there are enough periodic tables to go around for everyone. we can all have our own favorite table. as for us, what works best is best; what is comfortable, like a pair of old slippers, is the favorite. figure 1. mendeleev’s 1869 table as published in the russian journal of chemistry, 1869, 1, 60 and in the zeitschrift für chemie, 1869, 12, 405-406. 12 mary virginia orna, marco fontani this special issue here is a brief glimpse of the delightful and informative essays that make up this special issue. initially, john emsley takes up the theme of the volume in the title of his paper, “the development of the periodic system and its consequences.” of the many hundreds of forms of the periodic table that have been proposed, one has come to the forefront: that approved by the international union of pure and applied chemistry (iupac). in his lead-off paper, the development of the periodic table and its consequences, emsley traces the 250-year old story of how chemists arrived at it in the first place. next, father and son team of jürgen heinrich and alexander maar discuss the periodic table from the standpoint of its universality in many different senses: geographical, historical, pedagogical and philosophical, as well as what we deem “universal” in virtually every field of human endeavor, from poetry to pop culture to science fiction. although the periodic table as we know it had its genesis in the latter half of the 19th century after many tentative “baby steps” along the way toward the concept of the elemental universe as an ordered one, professor ferdinand abbri puts his finger on the driving force for order: the feverish discovery of elements in scandinavia over the course of the 18th century. the figure of jöns jacob berzelius dominates these efforts through his own vision and classification of substances, influencing the course of scientific thinking throughout the first half of the 19th century. orna and fontani in “mendeleev’s family,” point out that dmitri mendeleev himself now occupies a welldeserved place within the periodic system under the title of “mendelevium,” element 101, and that, by this attribution, he belongs to a special “family,” the actinides. how this family was uncovered, grew, and developed is the topic of their essay. to be credited with the discovery of an element is a singular honor awarded to only a chosen few. but “discovery” is not a simple issue in terms of priority recognition, neither in the distant past nor the recent present. professor helge kragh explores some of the controversies arising over priority disputes with respect to their reasons and their scientific implications. carl auer von welsbach (1858-1929) was a worldfamous entrepreneur, discoverer, inventor and experimental chemist. in this issue, his work in the field of the rare earths and related elements is described using source material from the archives of the auer von welsbach museum (founded in 1998) heretofore not accessible to the general public. from 1880 to 1882, auer von welsbach studied with robert bunsen in heidelberg, specializing in the field of spectral analysis. using this method, he discovered praseodymium and neodymium in 1885 and ytterbium and lutetium in 1905. gerd löffler shows how his three great discoveries in addition – the incandescent mantle, the metal filament lamp, and pyrophoric flint – were the basis for his ongoing exploration of the chemical and physical properties of the lanthanides and actinides. since one of the great unifying principles of all science is embodied in the periodic table, an examination of the many extant written documents leading up to its creation and improvement is a rich and rewarding activity. professor gregory girolami reviews and assesses the value of some of these works, spanning a time frame from boyle and lavoisier to just before mendeleev. the chapter by seth rasmussen, “a brief history of early silica glass: impact on science and society,” follows the evolution of silica glass from the wide variety of glass vessels developed in the roman period to improvements in glass quality through new composition formulae and production techniques that reached their culmination in the borosilicate glasses of the 20th century. the virtually perfect glass for use as chemical glassware would not have been possible without the expansion of our knowledge of new elements via the periodic system. in 1907, four years after dmitri mendeleev’s death, st. petersburg state university, where he lived and worked for forty years, set up the mendeleev museum and archives. mendeleev’s own personal effects form the basis of this remarkable museum, which is well worth a visit. “mendeleev at home” describes the contents of the museum, embellished by personal photographs taken during a visit in 2007. this short contribution at the end of this special issue aims to convey the atmosphere in which the most iconic of scientific icons was conceived and developed. conclusion we can conclude in no better fashion than to quote the inimitable peter atkins for his view of the unique character of the periodic table. “the periodic table is arguably the most important concept in chemistry, both in principle and in practice. it is the everyday support for students, it suggests new avenues of research to professionals, and it provides a succinct organization of the whole of chemistry. it is a remarkable demonstration of the fact that the chemical elements are not a random clutter of entities but instead display trends and lie 13setting the table: a retrospective and prospective of the periodic table of the elements together in families. an awareness of the periodic table is essential to anyone who wishes to disentangle the world and see how it is built up from the fundamental building blocks of chemistry, the chemical elements… for it is a part of scientific culture.”29 and no matter how many areas of chemistry the periodic table has influenced, we can never forget that it was a chemist who provided physicists with the key to unlock the structure of the atom, to perceive its essentially orderly arrangement both physically and mathematically, and to literally give birth to the field of atomic physics. given the achievements of the past 150 years, we cannot even conceive of the developments to be made over the next 150 years using the periodic table as a tool and guide. references 1. unesco. international year of the periodic table of chemical elements 2019. https://en.unesco.org/commemorations/iypt2019, last accessed on 27/04/2019. 2. s. lemonick, chem. eng. news 2019, 97(1), 26. 3. c. demilt, j. chem. educ. 1951, 28, 421. 4. s. cannizzaro, il nuovo cimento 1858, 7, 321. 5. science history institute. stanislao cannizzaro. https://www.sciencehistory.org/historical-profile/stanislao-cannizzaro, last accessed on 08/03/2019. 6. a. j. ihde, j. chem. educ. 1961, 38, 83. 7. lavoisier often used various terms to describe material substances, and not always correctly. when he developed his new nomenclature, he fell into the error of listing light and heat as distinct elements. 8. the periodic table is 150 years old this week. the economist, 28 february 2019. 9. e. scerri, phil. trans. r. soc. 2015, a 373, 20140172; http://dx.doi.org/10.1098/rsta.2014.0172, last accessed on 09/03/2019. 10. j. w. döbereiner, poggendorff ’s ann. phys. chem. 1829, 15, 301. 11. royal society of chemistry. news events and features. http://www.rsc.org/news-events/features/2019/ jan/finding-the-periodic-table/, last accessed on 12/03/2019. 12. e. renatus, chem. unserer zeit 1983, 17(3), 96. 13. video featuring eric scerri: other discoverers of the periodic table. the mystery of matter: search for the elements. http://www.mysteryofmatter.net/mendeleev.html , last accessed on 29/04/2019. 14. a.-é. béguyer de chancourtois, c. r. acad. sci. 1862, 54, 757, 840, 967. 15. w. odling, q. j. sci. 1864, 1, 642. 16. j. a. r. newlands, chem. news. 1865, 12, 83, 94. 17. c. giunta, bull. hist. chem. 1999, 24, 24. 18. presently, however, it is recognized that newlands’ work had major limitations: the “law of octaves” is applicable only up to calcium; it failed when applied to elements of higher atomic masses. in fact, newlands placed two elements in the same space in order to fit elements into the table. 19. j. l. meyer, justus liebig’s ann. chem. 1870, supp. 7, 354. 20. b. m. kedrov, den’ odnogo velikogo otkrytia. izd. sotsial’no-ekonomicheskoi literatury, moscow, russia, 1958. 21. d. mendelejeff, zeit. chem. 1869, 12, 405. 22. i. s. dmitriev, scientific discovery in statu nascendi: the case of dmitrii mendeleev’s periodic law. hsps 2004, 34(2), 233-275, university of california press, berkeley, ca, usa. 23. e. scerri, the periodic table: its story and its significance, oxford university press, new york, ny, usa, 2006. 24. c. janet, considérations sur la structure du noyau de l’atome. imprimerie départementale de l’oise, beauvais, france, 1929. 25 t. siegfried, science news 2015, 23 april, https:// www.sciencenews.org/blog/context/old-periodictable-could-resolve-today%e2%80%99s-elementplacement-dispute, last accessed on 10/03/2019. 26. p. j. stewart, found. chem. 2010, 12(1), 5. 27. p. pyykkö, p. phys. chem. chem. phys. 2011, 13, 161, http://dx.doi.org/10.1039/c0cp01575j, last accessed on 29/04/2019. 28 p. j. karol, in elements old and new: discoveries, developments, challenges, and environmental implications, american chemical society symposium series vol. 1263 (eds. m. a. benvenuto, t. williamson), american chemical society, washington, dc, usa, 2017, pp. 41-66. 29. p. w. atkins, the periodic kingdom, basic books, new york, ny, 1995, p. vii. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna firenze university press www.fupress.com/substantia doi: 10.13128/substantia-4 substantia. an international journal of the history of chemistry 1(1): 5, 2017 substantia in latin means substance, matter, material, that is the realm of chemistry. indeed, chemistry has always studied – since its ancestor alchemy – matter around us and its transformations. an international journal with this title opens its own perspective to every theme associated to this fantastic discipline: history of the chemical thought, relationship between chemistry evolution and mankind, position of science and scientists in the society, role of creativity in the progress of the field of science mostly connected to the daily life, and many other intriguing aspects. chemistry has always wanted to challenge what primo levi used to call the mater materia (mother matter), trying to solve the infinite mysteries of such ineffable sphynx, and during this long lasting struggle chemists and matter have been at the same time friends and enemies. this journal aims at investigating some topics of history of chemistry, but has also the ambitious scope of ensuring that scientists continuously ponder and worry about a different way of working with respect to that our society, infected by the terrible profit-syndrome, day by day suggests and dictates. in 1933 maria skłodowska curie, speaking about the decision not to patent the procedure for isolating radium, that sounded outrageous to some people, pointed out: “humanity needs practical men … but humanity also needs dreamers, for whom the disinterested pursuit of an end is so captivating that it becomes impossible for them to think of their own material profit.” another great polish scientist, albert sabin, pursued the same path in the 1960s for the anti-polio vaccine. he decided not to patent his discovery, thus permitting very low production costs, and earning not even a penny out of it. the justification for his stance looks almost naïve in a world that was already irremediably infected by the disease of capitalistic profit at all costs: “lots of people insisted that i should patent the vaccine, but i didn’t want to: it is my present to all the children in the world.” the aim of this journal is to inspire those who are working in the world of chemistry about the harmful effect of the market on research, the importance of disclosing the scientific results, the necessity of recovering the unity of knowledge and culture in the frame of a multi-disciplinary approach. we want to create bridges between disciplines, but also between different perspectives and languages: as an example the appreciation of the “far and diverse”, both in space and time, and the choice of adopting open access. today we terribly need   bridges against walls and it is not by chance that we launch this new journal, with these distinctive features, from florence, the cradle of the renaissance: we take the baton of the cultural florentine renaissance from the camerata dei bardi, progenitor of the modern opera, and from the accademia del cimento, mother of the contemporary scientific societies. acta herpetologica vol. 11, n. 2 december 2016 firenze university press substantia. an international journal of the history of chemistry 3(1): 131-138, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-81 citation: g. ferraris (2019) early contributions of crystallography to the atomic theory of matter. substantia 3(1): 131-138. doi: 10.13128/substantia-81 copyright: © 2019 g. ferraris. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article early contributions of crystallography to the atomic theory of matter giovanni ferraris dipartimento di scienze della terra, università di torino, via valperga caluso 35, 10125 torino, italy e-mail: giovanni.ferraris@unito.it abstract. after briefly presenting early hypotheses on the submicroscopic origin of symmetry and polyhedral morphology in the crystals, the structural model proposed by haüy in 1784, based on the periodic repetition of integrant molecules made up of simple molecules, is discussed. it is then highlighted how – through investigation of crystal hemihedry, isomorphism (mixed crystals) and optical activity – researches aiming at overtaking drawbacks of haüy’s model brought basic ideas to achieve the modern knowledge of the atomic structure of matter. the atomic-scale interpretation of properties of the crystalline state soundly contributed, among others, to properly define molecules and atoms, determine the atomic weights, hypothesize stereoisomerism, build the periodic table of elements and define ionic radii and bond. keywords. isomorphism, stereoisomerism, integrant molecule, crystal morphology, atomic theory. 1. introduction the introduction of the concept of atom as indivisible constituent of the matter dates back to the greek philosopher democritus (~ 460 b.c. ~ 370 b.c.), but only at the end of the nineteenth century the modern science made the atom from a debated philosophical category definitively transit to a physical certainty. towards the end of its long and troubled history, the concepts of atom and molecule intertwined and sometimes even clashed. only the determination of the first crystalline structures – made possible after the discovery of the x-ray diffraction by max von laue (1879-1960) in 1912 – convinced the entire scientific community that atoms and molecules are different entities, both necessary to model the structure of matter at atomic scale. the contribution of crystallography to the atomic theory of matter can certainly not be limited to the irrefutable evidence acquired through the aforementioned structural determinations. in fact, for centuries the geometric regularity (symmetry) of the crystal morphology has played a stimulating role to develop hypotheses on the submicroscopic structure of the matter suitable to explain the macroscopic observations. in this article, only contri132 giovanni ferraris butions of the pre-diffraction era, inspired by morphology-related investigations, are qualified as early ones. following ingenious but quite approximate earlier hypotheses on the internal structure of the crystals – mostly based on close packing of particles – and nicolas steno’s (niels steensen, 1638-1686) statement on the constancy of the angles between corresponding faces in all crystals of the same mineral1 – later assumed by jeanbaptiste romé de l’isle (1736-1790) as a genuine law of nature2 –, in the last quarter of the eighteenth century the french crystallographer réné just haüy (1743-1822) proposed a revolutionary model based on the periodic repetition of a submicroscopic polyhedron named integrant molecule and comparable to the unit cell of the modern structural crystallography. this model preceded the atomistic theory of john dalton (1766-1844) for over thirty years and represented a first modern and general attempt to reasonably represent the atomic structure of the matter. although the integrant molecule was primarily intended as a tool to explain the crystal morphology, we shall see that haüy’s structural model contributed to inspire amedeo avogadro (1776-1856) and andré ampère (1775-1836) to draw fundamental theoretical consequences from the results published by jean louis gay-lussac (1778-1850) on the chemical combination of gases. subsequently, as illustrated in this paper, researches aiming to overcome drawbacks of haüy’s model brought sound contributions in issues such as: distinct roles of atoms and molecules; determination of the atomic weights; stereoisomerism of chemical groups; building of mendeleev table; definition of ionic radii; nature of the chemical bond. 2. early hypotheses before the second half of the eighteenth century various conjectures on the internal structure of the crystalline materials had been proposed aiming to explain features of the crystals, such as their symmetry and polyhedral morphology. among the scientists who investigated the property-structure relationships of crystals we find famous names, usually better known for their important contributions to frontier non-crystallographic problems. the italian polymath gerolamo cardano (15011576), inventor of several mechanical devices, including the cardan shaft with universal joints, in 15503 noted the hexagonal symmetry common to the cells of the honeycombs and to the prismatic habit of quartz crystals and assumed for the latter an internal structure based on hexagonal particles. intriguing is the case of johannes kepler (1571-1630) – best known for his laws of planetary motion – who, in a booklet published in 16114, where he questions on the origin of snow crystals morphology, derives close packings of spheres (figure 1) but, surprisingly, he does apply this finding to the investigated morphology. robert hooke (1635-1703), discoverer of the law of elasticity that bears his name, in 16655 attributed the morphology of the rock alum (kal(so4)2·12h2o) crystals to a compact packing of submicroscopic spheres (figure 2). in 16906 christiaan huygens (1629-1695) proposed an anisotropic model of crystal structure based on a compact packing of ellipsoids (figure 3) to explain – via his well known wave theory of light – the birefringence observed in calcite by rasmus bartholin (1625-1698) in 16697 (figure 4). it might be worth to recall here that birefringence has been the first physical property to be explained via an anisotropic structure of the matter, i.e. an inherent characteristic of the crystalline state.8 finally, in 1749 michail vasil’evič lomonosov (17111765) – mineralogy was among his multifaceted interests – imagined that the morphology of the niter (kno3) crystals was related to a submicroscopic packing of hexagonal particles.1 1 the original manuscript (m.v. lomonosov, dissertatio de generatione et natura nitri, concinnata pro obtinendo praemio, quod illustris scientiarum academia regia liberalitate berolini florens proposuit ad 1-mum aprilis anni 1749) is kept in the archives of the berlin-brandenburgische akademie der wissenschaften (berlin, germany). in 1934 it has been printed for the first time.9 figure 1. close packing of spheres described by j. kepler. (from reference 4, pp. 9-10). 133early contributions of crystallography to the atomic theory of matter 3. haüy and the integrant molecule molecules and atoms were not yet clear and distinct concepts, when in 176610 pierre joseph macquer (17181784) defined the integrant molecule as a submicroscopic particle consisting of simple molecules that, as a matter of fact, correspond to the modern atoms. in 1784 haüy adopted the integrant molecule as polyhedral building block of his general and innovative model of crystal structure aiming to explain symmetry and morphology of the crystals.112 haüy’s model (figure 5)13 hypothesized a periodic arrangement of an integrant molecule, whose polyhe2 actually, in the reference 11 haüy named constituent molecule (molécule constituante) the building block of his model and adopted the term integrant molecule (molécule intégrante) few years later.12 dral shape and chemical nature of the constituent simple molecules are characteristic of each mineral species and, by extension, of any crystalline material. the idea of an integrant polyhedral molecule as basic building block was suggested to haüy by the cleavage polyhedron of crystals – originally observed in calcite – that can be reduced to microscopic dimensions by iterated cleavages. haüy did not conceive empty spaces in the matter; therefore, both integrant and simple molecules had to be space-filling polyhedra. that clearly appears in a drawing (figure 6), published (1822) in his treaty of crystallography14, where, also considering critical comments received in the meantime, he improved his structural model of the 1784 essai by graphically showing packing of simple molecules filling an integrant molecule. the model was widely accepted, thus contributing to the advancement of a theory of matter based on molecules and atoms. in particular, the terminology of haüy was adopted by avogadro in his theoretical interpretation15 of the experimental results obtained by gay-lusfigure 2. morphology of the rock alum crystals related to close packing of spheres by r. hooke. (from reference 5, opposite to page 82). figure 3. anisotropic structure model based on close packing of revolution ellipsoids proposed by c. huygens to explain the birefringence of calcite; a bidimensional section through the revolution axis of an ellipsoid is shown. (from reference 6, pp. 92-93). figure 4. birefringence in calcite observed by r. bartholin. h and g, ec and fd are the double refracted images of b and a, in the order. (from reference 8, p. 12). 134 giovanni ferraris sac16, which led him to hypothesize that, under the same conditions of pressure and temperature, equal volumes of different gases contain the same number of (integrant) molecules. precisely, the keystone to reconcile the ideas of gay-lussac (simple ratio between the volumes of reagent gases) with those of dalton17 (fixed relationship between the reactant masses) was the distinction between the concept of integrant molecule (today molecule) and that of simple molecule (today atom); a step this, not made by dalton who, instead, conceived atoms only. independently, in 1814 andré ampère (1775-1836) proposed18 the same hypothesis of avogadro. whereas, the latter did not quote haüy’s model – whose influence on his work seems, however, hardly deniable19 – ampère made explicit reference to this model with the variant of locating polyhedral atoms not inside, but at the vertices of the polyhedron representing the integrant molecule. for long debated, but never sufficiently clarified reasons (cf., e.g., 20), the distinction between molecules and atoms affirmed by avogadro was practically neglected for half a century. in fact, it was only at the first international congress of chemistry (karlsruhe 1860) that stanislao cannizzaro (1826-1910) (cf., e.g., 21) brought to general attention the paper that avogadro had published since 1811 in a well known international journal (reference 15). consequent to this revival, the majority of chemists and physicists accepted the idea of molecule as aggregation of chemically bound atoms. 4. isomorphism vs. atoms haüy’s model was unable to explain hemihedral symmetries, polymorphism and isomorphism. efforts to overtake these drawbacks, not only led to discover bravais lattices, point and space groups, but also to reach agreement on the definition of molecule and atom. among early post-haüy structure models able to explain hemihedral symmetries it is worth to quote the contribution by william hyde wollaston (1766-1828) who, in 1813, proposed mixed compact packages of spheres and ellipsoids, even of different color (nature), to explain relations between structure, morphology and chemical-physical properties of the crystals.22 hemihedral boracite, mg3b7o13cl (space group mm2, but pseudo-cubic -43m), was one of the minerals debated at that time for its puzzling morphology. it was investigated by wollaston and again, a quarter of century later, by gabriel delafosse (1796-1878) who proposed a structure model based on a network of tetrahedra (figure 7).23 as pioneering models quoted in paragraph 2, at variance with haüy’s space-filling model, wollaston’s and delafosse’s models contain “empty” space between building blocks, thus prefiguring a situation shown by modern diffractometric and microscopic methods. research on the crystallization of compounds from water solutions with variable composition lead to discover mixed crystals (solid solutions), i.e. the co-crystallization of two (or more) compounds whose crystals bear figure 5. haüy’s model of a cubic crystal showing the periodic translation of a basic cubic building block (integrant molecule) and how different crystallographic forms can be obtained subtracting integrant molecules from an original cube. (from reference 13, vol. 5, fig. 13). figure 6. two sections of a cubic integrant molecule filled with simple molecules. (from the atlas of reference 14, pl. 69, figs. 13 and 14). 135early contributions of crystallography to the atomic theory of matter the same morphology and chemical formulas differ only in the chemical nature of one element (isomorphism). in this field, pioneer results were published by nicolas leblanc (1742-1806)24 and françois sulpice beudant (1787-1850)25 without reaching sound conclusions on the nature of the crystals showing mixed composition: either double salts or solid solutions? beudant named crystalline mixtures (mélanges cristallines) these crystals that instead wollaston considered to be solid solutions.26 continuing t he research of beudant, eilhard mitscherlich (1794-1863) studied crystallization from water solutions of mixed salts with analogous chemical compositions. on the basis of chemical analyses and crystallographic measurements on the precipitated crystals, mitscherlich definitively established what the above-mentioned authors had only glimpsed: compounds with similar chemical formula that display the same morphology can co-crystallize two by two and in some cases three by three (for example, ammonium and potassium salts with iron salts).27 in a subsequent article28 mitscherlich, likely influenced by the morphology of the crystals, introduced the term isomorph (= same form) referring to the chemical elements that, substituting each other, give rise to a group of co-crystallizing compounds. he wrote: “the same number of atoms combined in the same way produces the same crystalline form. the latter is independent of the chemical nature of the atoms and is determined only by their number and arrangement”3. the atomistic interpretation of isomorphism was soon successfully tested by mitscherlich and his master jöns jacob berzelius (1779-1848), who determined atomic weights via a procedure suggested by the following reasoning. if the co-crystallizing ar and br compounds differ in their chemical composition for the substitution of a for b atoms only, one can derive the ratio between the atomic weights of a and b from the following equality: (atomic wt of a) (wt of a combined to r) --------------------= -----------------------------. (atomic wt of b) (wt of b combined to r) the resulting first list of correct atomic weights was published by berzelius in 1828.30 as further keystone of the atomistic theory of isomorphism, one can here recall that dmitrij ivanovič mendeleev (1834-1907) fruitfully exploited it to build his periodic table of elements. he was particularly interested in relating macroscopic properties to microscopic proprieties and, in this context, he used suggestions from the crystal morphology to fill various boxes of the table with elements whose yet unknown chemical properties were hypothesized via isomorphism between their compounds and those of already well characterized elements.31 5. optical activity vs. stereochemistry the rotatory polarization (optical activity) discovered in quartz crystals by jean baptiste biot (18741862)32 was one of the properties not explainable by haüy’s structure model because it does not admit acentric crystals. the explanation, still essentially valid today, was given in 1824 by augustin j. fresnel (1788-1827) who, although adopting the term integrant molecule, went well beyond haüy’s model, which includes only periodic translations as repetition operations. here are the words of fresnel: “we conceive that this [optical activity] may result from a particular constitution of the refractive medium or of its integrant molecules, which establishes a difference between right-to-left and left-toright. such would be, for example, a helicoidal arrangement of the molecules of the medium, which offers inverse properties according to whether these helices are either dextrorsum or sinistrorsum”.33 3 a recent analysis of the background of mitscherlich’s work can be found in reference 29. figure 7. model of boracite structure based on a framework of tetrahedra as proposed by g. delafosse. (from reference 23). 136 giovanni ferraris however, it has been necessary to wait for a further quarter of a century before, again by investigating optical activity, louis pasteur (1822-1895) proposed a mechanism able to explain the existence of substances showing rotatory polarization both in the crystalline state and in solution, while others display this property only in the solid state. for his results pasteur is indebted to the theory of isomorphism too, and, as reported in his article34, to observations by mitscherlich on the optical activity of tartrates that biot had published in 1844.35 precisely, pasteur discovered that the racemes of tartrates are not solid solutions (mixed crystals), but fifty-fifty mechanical mixtures of leftand right-handed crystals. having in mind the drawings of tartrate crystals published in 1841 by hervé de la provostaye (1812-1863)364 (figure 8), pasteur identified in racemes the two types of opposite handed crystals via their specular morphologies and, patiently, under the microscope, separated them from one another.5 4 this turns out to be the only article in which de la provostaye describes tartrates, but for some unknown reason the reference made by pasteur to the figures of this article does not match the numbering shown therein. 5 for a recent analysis of pasteur’s work see references 37 and 38. pasteur’s explanation at the atomic scale was that, as fresnel had supposed in 1824, optical activity of a crystalline compound is determined by helical arrangement of groups of atoms / molecules in the structure. considering that biot had published since 1839 his observations on the absence of rotatory polarization in fused quartz and opal (i.e., in amorphous silica)39, pasteur concluded that a crystalline optically active compound preserves this property in solution only if it is due to the spatial arrangement of its atoms (stereoisomerism) in a group (molecule) which survives the structure collapsing. thus, as a matter of fact, a distinction between molecular and non-molecular compounds was proposed; actually, this hypothesis will be fully accepted by the scientific community only after the evidence brought by experimental determination – via x-ray diffraction – of the crystal structure of nacl and diamond in 1913. 6. final remarks the excursus through a selection of results achieved by crystallography between the second half of the eighteenth century and the first half of the following century, clearly highlights how – mainly thanks to the then leading french school6 – the search for relationships between macroscopic (morphology) and submicroscopic features (structure) of crystals has contributed substantially to clarify the atomic structure of matter. in particular, the science, through the analysis of properties such as isomorphism (mixed crystals) and optical activity, moved from unspecified submicroscopic particles to a clear distinction between atoms and molecules. although this article is limited to the pre-diffraction period, it is worth to remember the influence that – via diffraction results – isomorphism had in establishing concepts such as ionic radius and its consequences in terms of definition of chemical bond and of relationships between structure and properties. in fact, the resolution of crystal structures, especially of minerals, followed to the discovery of x-ray diffraction in 1912, made available experimental data to define the radius of the sphere of influence of the elements linked by chemical bonding. among several pioneers on this matter, one has to remember at least william lawrence bragg (1890-1971)44 and victor moritz goldschmidt (1888-1847)45 who in 1920 and 1926, respectively, published detailed tables of ionic radii obtained via analysis of the interatomic distances. the concept of radius connected with the length of predominantly ionic chemical bonds was success6 cf. references 40, 41, 42 and 43; in particular, reference 43 is fully dedicated to the nineteenth century french crystallography figure 8. hemihedral crystal of tartaric acid from the article of h. de la provostaye (reference 36, pl. 1, fig. 2) that inspired the research of l. pasteur on the optical activity (reference 34). 137early contributions of crystallography to the atomic theory of matter ful, such that it was extended to other types of chemical bonds, defining atomic, metallic, covalent and van der waals radii. besides, goldschmidt correlated the size of the cation ionic radii with the geometry of their coordination polyhedra, laying the groundwork for the five rules later established by linus pauling (19011994);46 rules that are still useful tools for the validation and description of non-molecular crystalline structures. finally, in 1921 lars vegard (1880-1963)47 discovered that the cell parameters and the volume of the members of an isomorphous series are normally a linear function of the chemical composition. references 1. n. steensen, de solido intra solidum naturaliter contento dissertationis prodromus, typographia sub signo stellae, florentiae, 1669. 2. j.b. romé de l’isle, essai de cristallographie, ou description des figures géométriques, propres aux différents corps du règnes minéral, connus vulgairement sous le nom de cristaux, didot, paris, 1772. 3. g. cardano, de subtilitate rerum, iohan petreium, norimbergae, 1550. 4. j. kepler, strena, seu de nive sexangula, godefredum tampach, francofurti ad moenum, 1611. 5. r. hooke, micrographia, jo. martyn and ja. allestry, london, 1665. 6. c. huygens, traité de la lumière, pierre vander aa, leide, 1690. 7. r. bartholin, experimenta crystalli islandici disdiaclastici, quibus mira et insolita refractio detegitur, danielis paulli, hafniae, 1669. 8. g. ferraris, dove la luce si fa in due, in la luce fra scienza e cultura. 2015, anno internazionale della luce, accademia delle scienze, torino, 2017, pp. 3-14. 9. m.v. lomonosov, sobranie sochineniy [selected works], vol. vi, pp. 111–152, izd-vo an sssr, leningrad, 1934. 10. p.j. macquer, dictionnaire de chimie, lacombe, paris, 1766. 11. r.j. haüy, essai d’une théorie sur la structure des cristaux, gogué & nèe de la rochelle, paris, 1784. 12. r.j. haüy, annales de chimie 1789, iii, 1. 13. r.j. haüy, traité de minéralogie, 5 vols., louis, paris, 1801. 14. r.j. haüy, traité de cristallographie, bachelier et huzard, paris, 1822. 15. a. avogadro, journal de physique de chimie et d’histoire naturelle 1811, 73, 58. 16. j.l. gay-lussac, mémoires de la société de physique et de chimie de la société d’arcueil 1809, 2, 207 and 252. 17. j. dalton, a new system of chemical philosophy, part 1, s. russel, manchester, 1808 18. a. ampère, annales de chimie 1814, 90, 43. 19. g. ferraris, amedeo avogadro e la cristallografia, in a duecento anni dall’ipotesi di avogadro, accademia delle scienze, torino, 2013, pp. 41-52. 20. m. morselli, amedeo avogadro, d. reidel, dordrecht, 1984. 21. i. guareschi, amedeo avogadro e la sua opera scientifica, in opere scelte di amedeo avogadro, utet, torino, 1911, pp. i-cxl. 22. w.h. wollaston, philosophical transactions of the royal society 1813, 103, 51. 23. g. delafosse, mémoires des savants étrangères 1843, 8, 641. 24. n. leblanc, de la cristallotechnie, ou essai sur les phénomènes de la cristallisation, no printer, paris, 1802. 25. f.s. beudant, annales des mines 1817, 2, 1; annales des mines 1818, 3, 239 and 289. 26. w.h. wollaston, annales de chimie et de physique 1817, 7, 393. 27. e. mitscherlich, abhandlungen der königlichen akademie der wissenschaften berlin 1818–1819, 427; annales de chimie et de physique 1820, xiv, 172. 28. e. mitscherlich, annales de chimie et de physique 1822, xix, 350. 29. s. salvia, ambix 2013, 60 (3), 255. 30. j. berzelius, annales de chimie et de physique 1828, xxxviii, 426. 31. d.i. mendeleev, zeitschrift für chemie 1869, 12, 405. 32. j.b. biot, mémoires de la classe des sciences mathématiques et physiques de l’institut impérial de france 1812, part 1, 1. 33. a. fresnel, bulletin des sciences par la société philomathique de paris 1824, 147. 34. l. pasteur, annales de chimie et de physique 1848, xxiv, 442. 35. j.b. biot, compte rendu 1844, 19, 720. 36. h. de la provostaye, annales de chimie et de physique 1841, 3e série iii, 129. 37. h. flack, acta crystallogr. sect. a, 2009, 65, 371. 38. j. fournier, chimie nouvelle 2014, 116, 42. 39. j.b. biot, comptes rendus 1839, 8, 683. 40. a. authier, early days of x-ray crystallography, oxford university press, oxford, 2013. 41. j.g. burke, origins of the science of crystals, university of california press, berkeley, 1966. 42. j. lima-de-faria (ed.), historical atlas of crystallography, springer, dordrecht, 1990. 138 giovanni ferraris 43. s.h. mauskopf, transactions of the american philosophical society 1976, 66, 1. 44. w.l. bragg, philosophical magazine 1920, 40, 169. 45. v.m. goldschmidt, det kongelige norske videnskabers selskab skrifter 1926, no. 2, 1; det kongelige norske videnskabers selskab skrifte 1926, no. 8, 1. 46. l. pauling, the nature of the chemical bond and the structure of molecules and crystals: an introduction to modern structural chemistry, cornell university press, ithaca, 1939. 47. l. vegard, zeitschrift für physik 1921, 5, 17. substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 6(1): 121-127, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1426 citation: shirakawa h. (2022) path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article. substantia 6(1): 121-127. doi: 10.36253/substantia-1426 received: oct 07, 2021 revised: jan 15, 2022 just accepted online: jan 16, 2022 published: mar 07, 2022 copyright: © 2022 shirakawa h. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa professor emeritus, university of tsukuba, tennodai, tsukuba, ibaraki 305-8577, japan abstract. the 2000 nobel prize in chemistry was awarded jointly to alan j. heeger, alan g. macdiarmid, and hideki shirakawa “for the discovery and development of conductive polymers.” unlike metals, organic polymers or plastics do not conduct electricity. the three laureates found that polyacetylene can be doped on a film, which was initially synthesized by shirakawa following a failed experimental trial by a korean scientist, hyung chick pyun. later, pyun insisted that he was the discoverer of polyacetylene films with silvery sheen. this note sheds light on the true history of the synthesis of polyacetylene films. keywords: polyacetylene film, nobel prize 2000, polymerization, ziegler-natta catalyst, fortuitous error, serendipity. introduction on october 10, 2000, the royal swedish academy of sciences announced that plastic can indeed, under certain circumstances, be made to behave like a metal – a discovery for which professor alan j. heeger, professor alan g. macdiarmid, and i, hideki shirakawa, received the nobel prize in chemistry in 2000. this public announcement was followed by a story about the initial discovery of polyacetylene films: “once – by mistake – a thousand-fold too much catalyst was added.”1 professor bengt nordén, chairman of the nobel committee for chemistry, also used the term “mistake” in the prize announcement.2 commenting on a trigger of our achievements, he stated that the road to the discovery had started in 1967, when shirakawa found that “by mistake” “a student [pyun] had taken a thousand times too much catalyst” when polymerizing acetylene gas to make something called polyacetylene. at the beginning of my nobel lecture entitled “the discovery of polyacetylene film: the dawning of an era of conducting polymers,” given on december 8, 2000 at aula magna, stockholm university, i acknowledged dr. hyung chick pyun (1926–2018), among other important contributors, for sharing a “fortuitous error” that motivated further work toward the discovery of polyacetylene films.6 http://www.fupress.com/substantia http://www.fupress.com/substantia 122 hideki shirakawa in his recent article,3 professor seth c. rasmussen discussed the event leading to the discovery of polyacetylene films by fortuitous error, based mainly on a “working english translation” of pyun’s account written in korean. carefully reading pyun’s two original documents written in 2002 and 2013 (through japanese translation), 4,5 i found numerous factual errors, distortions, and assumptions. in this note, i would like to correct them and present what happened regarding the synthesis of polyacetylene films with metallic luster, based on my memory and my laboratory notebooks. pyun’s experimental trial in his article,3 rasmussen asserts that the core of the discovery of polyacetylene films resulted from the performance of both myself and pyun, a scientist visiting japan from south korea, quoting the “fortuitous error” that i mentioned in the nobel prize lecture6 and is described in the les prix nobel: the nobel prizes 2000 and its reprints.7 this description is acceptable if the core of the discovery is interpreted as an important trigger for the synthesis of the metallic polyacetylene films. i repeat that the occurrence of the “fortuitous error” was a trigger for the subsequent synthesis of metallic polyacetylene films but not the successful synthesis itself. however, rasmussen does not present the discovery in this manner. most descriptions in the article are based on pyun’s accounts5 and third-party records, such as press reports by the nobel foundation and royal swedish academy of sciences at the time of the nobel prize announcement and award. the article lacks any of my own input, except for my printed nobel lecture and scientific papers. as a result, it depicts a biased account that contains serious errors. in his document,5 pyun insists that he was an actual discoverer of polyacetylene films and not shirakawa. he states, “a good result will be anticipated with the stirring speed reducing as much as possible during the polymerization process. one day, when i tried an experiment on acetylene polymerization with this idea, it happened that a stirring motor stopped suddenly, presumably due to setting the rotation speed too slow. i was very panicked at first, but with careful inspection of the reaction flask, i found that a silvery membrane had formed on a surface of the catalyst solution, to my surprise.” he adds, “on this day, for some reason, the then assistant [research associate] shirakawa was not in the laboratory.” these descriptions contain the two following factual errors: 1) “a silvery membrane had formed” and 2) “on this day, for some reason, the then assistant shirakawa was not in the laboratory.” the exact date of “this day” is not clear because the trial run was not recorded on my laboratory notebook as the trial run was not mine. according to my memory, what happened on “this day” is as follows. one of pyun’s two academic supervisors was professor yoneho tabata (1928–2019) of tokyo university, faculty of nuclear engineering. due to tabata’s prolonged trip to the united states, pyun could not perform any primary research during the period, which he described as his free time. the “this day” that pyun refers to likely occurred in august 1967 considering these circumstances. one day, pyun came to my office and asked to try acetylene polymerization as he was interested in acetylene polymerization and polyacetylene. i provided an experimental protocol for performing acetylene polymerization as a trial experiment at my research laboratory (room number 404) at the research laboratory for resources utilization, tokyo institute of technology. as mentioned above, because this trial run was not my own research work, any relevant data, including the date and conditions for the polymerization, were not recorded in my laboratory notebook. i gave pyun normal guidelines for the polymerization process, such as a solvent, species of the catalyst components, and their concentrations. i expected that the product would be in a powdered form as usual. after briefly instructing pyun on the handling of lab wares and equipment, i returned to my office, a preparatory room next to the no. 404 lab. the no. 404 lab, which i used as my own lab, was designed by professor sakuji ikeda (1920–1984) as a tracer experiment for handling radioisotopes. when you enter the room from the passageway, you enter my office, a small preparatory room that students and i used as a study room. the no. 404 lab is accessible from the preparatory room. according to the lab rule, study desks were not placed in the no. 404 lab, so researchers and students spent their time in the preparatory room and only entered the lab to perform experimental work. at that time, the lab was freely open only to graduate and undergraduate students who were under my guidance. therefore, pyun could not carry out experiments for acetylene polymerization in my absence. on that day, after some time, pyun came to my office to say that the polymerization had stopped. as this experiment should have been easy to perform, i was puzzled by what could have gone wrong. i checked the apparatus carefully with him, the occurrence being inconceivable. i then found that the magnetic stirrer had stopped and, after watching for a while, the mercury manometer, which indicates the acetylene’s pressure, did not decrease. 123path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article we confirmed that the acetylene monomer had not polymerized, meaning that the reaction had not taken place. the reaction flask was, therefore, detached from the vacuum line, and we looked carefully inside the flask. if the reaction had proceeded normally, we would have observed a powdery product, but instead, we found that a black flappy or spongy matter had formed on the surface of the catalyst solution. the product, which was extracted using a pair of tweezers, was like a black rag. it was not “the silvery membrane” that pyun described. if the reaction had proceeded normally, the product would have been a powder. the trial was clearly a failure, and pyun was in agreement. i remember the result of the run clearly, even now. successful synthesis of polyacetylene film with metallic luster i still do not fully understand why pyun’s trial run failed. however, because the product was not a powder but a quite different form, i thought that it might be possible to synthesize polyacetylene into a thin film by changing the polymerization conditions. i was also strongly motivated to clarify the cause of the failure. immediately after pyun’s failure, i started a series of polymerization experiments with graduate students under my guidance by changing the concentration of the catalysts and other conditions. pyun was not involved in this series of experiments. within one to two weeks, my students and i could successfully synthesize films of polyacetylene that were self-standing and could be easily handled by increasing the concentration of the catalysts by 1,000 or more times the normal condition. the self-standing film was such that it did not need lining. by improving the polymerization conditions and methods, we also found that a thin film with a silvery metallic sheen could be obtained by polymerizing acetylene on the glass surface of a reaction f lask when a concentrated catalyst solution was applied to the glass surface of the flask. the side stuck to the glass surface of the reaction flask displayed a metallic luster, while the other side facing the acetylene gas took on a black color and a matted texture. the difference in the appearance of the two sides was clarified by observations made through transmission and scanning electron microscopic observations. scanning electron microscopic observations of a surface of the polyacetylene film revealed that the film was composed of entangled fiber-like long microcrystals (fibrils) with a diameter of ca. 200 å. the morphology of an extremely thin film with several micrometers in thickness observed by a transmission electron microscope was also found to have the same microstructure. from these observations, it was clear that the whole film was composed of entangled fibrils. because these films are composed of loosely entangled fibrils and inevitably lead to low bulk density, the incident light on the surface of the fibrils scattered randomly. consequently, both surfaces of these films appear matted black due to random ref lections. the films formed on an interfacial surface of vapor/liquid (catalyst solution) reflect the trend strongly. therefore, both sides of such films are the same matted black and show no metallic silverly luster. however, on the side of the film that touches the glass wall of the reaction flask applied by the catalyst layer, the growing fibrils are forced onto the glass wall during the polymerization reaction. thus, the surface of the film facing the glass wall becomes flat with a higher density than the other surface. when incident light shines on this side of the film, the light reflects in the same direction, and the surface presents a silverly metallic sheen. following this process, cis-polyacetylene synthesized at a very low temperature (as low as -78 degrees centigrade) has a copper-like reflection color. all double bonds in the cis-polyacetylene have a cis form of geometric isomeric double bonds through the conjugated molecular chain. the cis form of polyacetylene results in a reflection spectrum shift to higher energy than that of trans form, because the bandgap of the cis form is larger than the trans form, which has a silvery sheen. the fortuitous error i referred to pyun’s trial run as a “fortuitous error” because, as a result of that failure, a black flappy or spongy matter was formed instead of the powdery product that should have formed under normal conditions. this accident became a trigger for the successful synthesis of films with a metallic sheen. immediately after pyun’s trial run, while continuing experimental trials to clarify the reason for the failure, we found that films formed on the surface of a much more concentrated catalyst solution – a thousand times more – instead of the traditional mmol/liter order of concentration. using these films as a specimen for infrared spectroscopy, raman scattering spectroscopy, x-ray diffraction, and normal vibrational analysis, among other tests, our primary intention to clarify the mechanism of acetylene polymerization reactions with ziegler-natta catalysts was accomplished within an unexpectedly short period (just less than two years). because the unforeseen failure of pyun’s test run had triggered the successful syn124 hideki shirakawa theses of polyacetylene films, and i thought of this fortuitous error as a result of “serendipity,” i introduced this occurrence as a typical example of fortuitous error at domestic academic meetings and workshops, as well as international conferences and institutions. however, our polyacetylene study, published in academic journals internationally or domestically received little attention at the time.8 as context, it may be pointed out that research activities on organic and polymeric semiconductors declined globally after the 1960s, after being very active from the early 1950s to the 1960s. in particular, natta et al. succeeded in synthesizing polyacetylene by the polymerization of acetylene using so-called zieglernatta catalysts in 1958.9 the product was an intractable black powder used for the elucidation of various chemical and physical properties of polyacetylene. several years after our successful synthesis of polyacetylene films, i was invited to conduct collaborative research with macdiarmid, department of chemistry, university of pennsylvania. macdiarmid had been intrigued by the silvery metallic luster of the polyacetylene film (with a silvery sheen) when he visited and gave a seminar at the tokyo institute of technology in 1975. in september 1976, we began joint research on the chemical and physical properties of polyacetylene with heeger, a solid-state physicist of the physics department at the university of pennsylvania. on november 23, 1976, when we tried to add a small amount of bromine to a piece of polyacetylene film, we found, to our surprise, that the electrical conductivity of the polyacetylene film increased a hundred thousand times. this epoch-making result was reported at an international conference held in new york city in may 1977, and we followed up with two consecutive communications.11 the result initiated considerable interest among many researchers around the world. the newborn field was named conductive (conducting) polymers and synthetic metals, and a new journal entitled synthetic metals was born in october 1979. with increasing research activity in this field, the episode of the successful synthesis of the silvery films of polyacetylene was shared widely among researchers. when i delivered talks at academic meetings and lectures at universities and institutions, i referred to the episode as a typical serendipitous event. as pyun’s trial run was unsuccessful, i did not mention his name in view of his honor. to avoid embarrassing him, i referred to him in evasive terms, such as “a foreign researcher,” “a visiting researcher,” and sometimes simply “a researcher,” “a student,” or “a graduate student.” i now regret not mentioning his name. the episode resulted in gossip among researchers about how this “foreign researcher” did not understand japanese and could not follow directions. i am very sorry that pyun had to endure this. pyun’s research subject i do not remember the exact date of pyun’s visit as a foreign researcher to the lab of ikeda, division of macromolecular materials, research laboratories for resources utilization, tokyo institute of technology, as i have no written record of his visit. however, his visit occurred one year after i started my post as a research associate in the division in april 1966. according to pyun’s document,5 he visited japan in may 1967 and returned to korea in march 1968. i am unsure when i first met pyun in person or at laboratory meeting. however, i have a vivid memory of how he first introduced himself as he told me that his family name was “hen 邊” – that is, the side (hen) of a triangle. i knew that he grew up in the era of japanese colonization, and he was forced to be educated in japanese. later, he struggled through the korean war (1950–1953). however, he never communicated about his difficult life in korea. he was always easy to work with and he never expressed any inability to understand japanese. as i had only recently joined the lab, i was not informed about how and why pyun had joined the ikeda lab as a foreign associate. however, i knew vaguely that his research purpose was the clarification of certain polymerization mechanisms using isotopes as one of his supervisors was tabata, department of atomic engineering, university of tokyo. i found out only recently that, as mentioned above, pyun’s research in tabata’s lab was interrupted for some time because tabata’s return from his visit to the united states was delayed. during this period, pyun visited my lab to conduct the trial run on the polymerization of acetylene, feeling that he had free time to work on subjects outside his main focus during tabata’s absence. according to rasmussen’s article and pyun’s documents, pyun’s research subject was the copolymerization of ethylene and tetrafluoroethylene and the analysis of its molecular structure by infrared spectroscopy. there was no discussion at the lab meeting that pyun had joined the research group to study acetylene polymerization. at that time, i was unaware of whether ikeda was unwilling for pyun to deviate from his primary subject of interest, and i did not know that tabata’s return had been delayed. however, i accepted his offer to perform a trial run without hesitation. it was very clear that the 125path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article trial run was an experience test for him, and he did not undertake it as a research collaborator in the ongoing work in ikeda’s lab. it turns out that, as described below, pyun conducted two or more related tests after this initial test. however, i am sure that his additional experiments were performed after our group’s establishment of the synthesis of self-standing polyacetylene films with a silvery luster. i was hired as a research associate in the division of macromolecular materials, research laboratory for resources utilization, tokyo institute of technology, on april 1, 1966, and i continued my research work in the same lab for five years during my graduate student days. at that time, dr. shu kambara (1906-1999) was the professor, and ikeda was the associate professor of the division. soon after, kambara retired on march 31, 1967, and subsequently, ikeda was promoted to the position of professor on august 1, 1967. ikeda had been engaged in research on the vulcanizing mechanism of natural and synthetic rubber using radio isotopes from his associate professor days. after becoming professor of the division, he then continued to work on the mechanism of ethylene and acetylene polymerization with ziegler-natta catalysts using tracer techniques. when i became a research associate, ikeda was very close to his work on ethylene polymerization and had just started research on acetylene polymerization, and i participated in this work. when pyun came to my lab to request permission to perform a trial run on acetylene polymerization, his intention, i later realized, was quite different from what he originally stated. when i was a graduate student, dr. masahiro hatano (1930–, who later moved to the chemical research institute of non-aqueous solutions, tohoku university) was a research associate under kambara and undertook research on the polymerization of compounds with carbon-carbon and carbon-nitrogen triple bonds for the synthesis of polymer semiconductors. the kambara and ikeda lab has a long history of research on acetylene polymerization and polyacetylene, and hatano developed acetylene polymerization for many years and accumulated relevant techniques. pyun was interested in related research work on semiconducting polymers, which he sought to learn more about by joining ikeda’s group. in fact, he wrote in his document5 that “i thought of spending my unexpected free time carrying out acetylene polymerization as i learned from various reports in the lab that this lab [the kambara and ikeda lab] had conducted related studies for nearly ten years, and i was much interested in such work.” regarding his research purpose, he also writes, “i thought that even if acetylene polymers are powder, if the polymerization can be controlled to produce particles larger in size, various properties [of acetylene polymers], such as conductivity, would be closer to true values.” as mentioned above, he writes that it would be better to decrease the stirring speeds as much as possible during the polymerization reaction to increase the size of the particles. i never heard such a clear idea from him at that time and only learned of it after reading his document. it is worth noting that while he writes that it would be better to increase the size of particles, he provides no idea of how to produce polyacetylene in film form. as mentioned above, pyun’s trial run was not recorded in my laboratory notebook. while it would be best to check pyun’s notebook regarding the trial run, i learned from reading his documents that he was unable to bring the notebook home following ikeda’s instructions. his laboratory notebook went missing after that. his document5 include many inconsistent descriptions of his stay in japan. the following is one example: “about two weeks after starting my work at professor’s tabata lab at the university of tokyo, i went to the tokyo institute of technology to take the deuterated stocked ethylene in the ikeda lab. there i encountered professor kambara’s retirement memorial lecture, which had started just then in the auditorium.” he continued with the following observations: “the audience was full in the auditorium, and the title was ‘a history of the development of polymer science and engineering in japan.’ i was staggered on hearing professor kambara’s words in the last part of his lecture in front of such a large audience. he disclosed ‘a long-awaited method of producing polyacetylene in the form of polyacetylene film had been attained in japan, and the inventor is the assistant [research associate] shirakawa of the ikeda lab.’” kambara’s retirement date was march 31, 1967, and by custom, lectures by retiring professors were held just before their retirement. if the date of pyun’s visit to japan was may 1967, as noted in rasmussen’s article, it would be impossible for him to attend kambara’s final lecture as it was before his visit to japan. therefore, this must be a continuity error. pyun further infers that the abovementioned audiences provided information to the mass media in japan and that the media caused a media circus immediately after the announcement of shirakawa’s nobel prize in chemistry. soon after the announcement by the nobel committee on october 10, 2000, three young journalists visited my home and questioned me closely as to why pyun was not a joint prize winner, which left me with an unpleasant memory. the journalists were from one of three big presses in korea; if my memory is correct, the press was the dong-a ilbo. from this, i learned for 126 hideki shirakawa the first time that pyun was known as a leading scientist in the synthesis of polyacetylene in korea, and thus he missed receiving what would have been korea’s first nobel prize in chemistry. i have no memory of any discussion with pyun regarding research, especially on acetylene polymerization and the properties of polyacetylene during his one-year stay at the tokyo institute of technology and the university of tokyo. however, i realized that pyun was highly interested in polyacetylene as an important candidate in semiconducting polymer by reading related articles before visiting japan. in his document, he describes that while in japan “my study of polyacetylene study was stopped after all…,” calling up for me his strong emotion toward polyacetylene study. record of pyun’s work in my laboratory notebooks to refresh my memory to write this note, i checked my 15 laboratory notebooks used during my period at the tokyo institute of technology and more than 20 notebooks related to my research works. these showed me that pyun conducted several experiments on acetylene polymerization. the date of these experiments cannot be specified, but presumably, it was in mid-september 1967, after we established the synthetic method of self-standing polyacetylene films with a silvery sheen. the first assumable description was a series of runs in which pyun carried out three polymerizations of deuterated acetylene by changing the polymerization temperature. the results of the elemental analyses of the deuterated polyacetylenes are recorded in my notebook no. 3, page 442, as pe-1 polymerization temperature 60 degrees centigrade, pe-2 polymerization temperature 20 degrees centigrade, and pe-3 polymerization temperature -78 degrees centigrade, respectively. the code “pe” can be understood as pyun’s initial. he synthesized deuterated acetylene by himself as precursors for the synthesis of deuterated ethylene, such as c2h2d2 and c2d4, as monomers for deuterated polyethylene. it was my assumption that he tried to polymerize the deuterated acetylene prior to his primary purpose. the next record was on the mass-spectroscopy analysis of ethylene-d4, synthesized by pyun. the result is described in my notebook no. 3, page 444, october 13, 1967. the ethylene-d4 was synthesized by an additional reaction of deuteron to acetylene-d2 for the copolymerization of ethylene and tetrafluoroethylene. for his primary purpose, pyun synthesized acetylene-d2 himself as an intermediate for the synthesis of ethylene-d4. presumably, he attempted to polymerize the acetylene-d2 as a monomer. his experimental results, mentioned above, were recorded twice in my notebook because i was familiar with the application procedures for elemental analysis and mass-spectroscopy. thus, his products, acetylene-d2 and ethylene-d4, were passed to each analytical lab via me, and the data were, necessarily, recorded in my notebook. the first appearance of the term “polyacetylene film” is recorded clearly in my notebook no. 3, page 452, on november 8, 1967, as x-ray scattering analysis was carried out in the x-ray analysis room of the department of textile engineering. the measurements were performed at two different temperatures – 21 and 80 degrees centigrade – to measure the estimated thermal expansion coefficient of polyacetylene films. it should be noted that these analyses were carried out for a series of measurements of the various physical properties of polyacetylene films, and there was no relation to pyun’s research. closing remarks the nobel committee announced that our nobel prize in chemistry in 2000 was awarded “for the discovery and development of conductive polymers” based on the doping of polyacetylene attained by the three laureates. it should be noted that it was not for the synthesis of polyacetylene films. however, there is no doubt that the synthesis of polyacetylene films was a key factor in the discovery of conducting polymers. in this account, i have presented the truth to the best of my ability, based upon my memories and my notebooks. i further want to stress that pyun’s contribution was minimal and that his claims that he was the discoverer of the synthesis of polyacetylene were his strong belief, but they were not supported by the truth of what happened. however, his one-year stay in japan was not satisfactory, and as one of the concerned personnel, i regret that his research work was not attained fully due to several unfavorable events during his stay in japan. acknowledgements i wish to thank dr. yasu furukawa for alerting me to the historical article by rasmussen and its supporting information. my special thanks go to doctoral graduate student lee jinyoung, graduate school of interdisciplinary information studies, the university of tokyo, and her supervisor, associate professor dr. ken ito, interfac127path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article ulty initiative in information studies, graduate school of interdisciplinary information studies, the university of tokyo, who translated pyun’s korean documents into japanese. lastly, i would like to thank dr. naresh pandya, kapiolani community college, and associate professor dr. katsuro anazawa, the university of tokyo, for their suggestions on a draft of this paper. references 1. the nobel prize in chemistry 2000, 2021, https:// www.nobelprize.org/prizes/chemistry/2000/ popularinformation / 2. nobel media ab 2021, 2021, https://www.nobelprize. org/prizes/chemistry/2000/prize-announcement/ 3. s. c. rasmussen, new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry. substantia. 2021, 5, 91–97. 4. h. j. pyun, i can’t doubt the facts…, (in korean). kaeri magazine. 2002, 10, 7–8. this is a shorter version of the document in note 5. 5. h. j. pyun, what is a nobel prize? (in korean). 2013. (an unpublished document provided by professor rasmussen). 6. h. shirakawa, the discovery of polyacetylene film: the dawning of an era of conducting polymers. in les prix nobel, the nobel prizes 2000 (ed.: nobel foundation), stockholm, 2000, pp. 217–226. original speech: https://www.nobelprize.org/prizes/chemistry/2000/shirakawa/lecture/ 7. h. shirakawa, nobel lecture: the discovery of polyacetylene film – the dawning of an era of conducting polymers. rev. mod. physics. 2001, 73, 713 – 718; h. shirakawa, the discovery of polyacetylene film – the dawning of an era of conducting polymers. angew. chem. int. ed. 2001, 40, 2575-2580. 8. h. shirakawa, s. ikeda, infrared spectra of poly(acetylene). polym. j. 1971, 2, 231–244; h. shirakawa, t. ito, s. ikeda, raman scattering and electronic spectra of poly(acetylene). polym. j. 1973, 4, 460–462; t. ito, h. shirakawa, s. ikeda, simultaneous polymerization and formation of polyacetylene film on the surface of concentrated soluble ziegler-type catalyst solution. j. polym. sci. polym. chem. ed. 1974, 12, 11–20. 9. g. natta, g. mazzanti, p. corradini, polimerizazione stereospecifica dell’acetilene. atti accad. naz. lincei, rend., cl. sci. fis., mat. nat. 1958, 25, 3-12. 10. m. akhtar, c.k. chiang, m. j. cohen, j. kleppinger, a. j. heeger, e. j. louis, a. g. macdiarmid, j. milliken, m. j. molan, d. l. peebles, h. shirakawa, synthesis and properties of halogen derivatives of (sn)x and (ch)x. ann. n. y. acad. sci. 1978, 313, 726–736. 11. h. shirakawa, e. j. louis, a. g. macdiarmid, c. k. chiang, a. j. heeger, synthesis of electrically conducting organic polymers: halogen derivatives of polyacetylene. (ch)x. jcs chem. commun. 1977,16, 578–580; c. k. chiang, c. r. fincher, jr., y. w. park, a. j. heeger, h. shirakawa, e. j. louis, s. c. gau, a. g. macdiarmid, electrical conductivity in doped polyacetylene. phys. rev. lett. 1977, 39, 1098–1101. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 4(2) suppl.: 69-77, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-832 citation: a. garrido sanchis (2020) thermal inactivation of viruses and bacteria with hot air bubbles in different electrolyte solutions. substantia 4(2) suppl.: 69-77. doi: 10.36253/substantia-832 copyright: © 2020 a. garrido sanchis. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. thermal inactivation of viruses and bacteria with hot air bubbles in different electrolyte solutions adrian garrido sanchis school of sciences, university of new south wales, canberra, australia e-mail: a.garridosanchis@adfa.edu.au abstract. inactivation of viruses has been an insuperable inhibition to the use of recycled water. substantial success in solving the problem has recently been achieved using a hot column evaporator (hbce). here we extend the technique to inactivate e. coli and ms2 viruses in different electrolyte solutions (0.17m nacl and 0.01m cacl2). an increase in the inlet air temperature, from 103 to 250 °c, substantially improved the destruction of both pathogenic groups in either solution. e. coli proved to be more susceptible than viruses to inactivation in the hbce. the phenomenon of inhibition of bubble coalescence above 0.17m for the nacl solutions makes the hbce process for this solution more efficient than for cacl2 solutions. in part, this is because of the higher air/water interfacial area with nacl. keywords: virus, e. coli, inactivation, coalescence inhibition, hot bubble column evaporator (hbce), sterilisation. 1. introduction inactivation of microorganisms, specifically viruses and bacteria is the central problem for the sterilisation of aqueous solutions for almost any application. pathogens have to be inactivated before the water can be used for industry or drinking water. wastewater from human activities usually contains bacteria like e. coli and human enteric viruses like hepatitis and rotavirus. if this water is to be reused, even for example in agriculture, it has to be disinfected. familiar methods for inactivating viruses, bacteria, and other microorganisms in aqueous media include heat, chemicals (e.g. ozone), irradiation (e.g. ultraviolet treatment), high-pressure treatment, and filtration (e.g. membrane filtration). only reverse osmosis (ro) and nano-membrane pore scan block viruses. heat treatments are energy-intensive. better cheaper technologies are urgently needed. such a technology has already been developed.1 it is a surprisingly simple and successful method that kills viruses. it uses carbon dioxide or combustion gases in a bubble column. the process is now being scaled up for major industrial use. however, why and how it kills pathogens 70 adrian garrido sanchis is still obscure. it is to gain insight into the thermal mechanism that inactivates viruses and bacteria at different inlet air temperatures (103, 150, 200, and 250 °c) that is the goal of this work. for a more detailed account of bubble column evaporators see the first paper in this volume. bubble column evaporators (bce) are typically in the form of cylindrical containers. a gas is introduced at the bottom of the column, via a porous frit. a continuous flow of rising bubbles passes through the liquid.2 a gas-liquid bubble column provides a heat transfer rate between gas and liquid 100 times more efficiently than via bulk.3 this heat transfer efficiency in a hot bubble column evaporator (hbce) has been used in this work to inactivate e. coli and the ms2 virus for water reuse, without the need for boiling.4 it does so by transferring heat from the hot air bubbles to the surfaces of pathogens contained in the solution through collisions.5 the hbce process requires less thermal energy than solution boiling because of the lower operating temperature of the solution. (the specific heat capacity per unit of weight, cp, of air is four times lower than that of water). following from a previous work5 two model solutions were chosen. the first one was 0.17 m nacl. this is the concentration at which bubble coalescence is fully inhibited6 and so gives an increased hot air/water interfacial area which should enhance the performance of the hbce. the second solution at 0.01 m cacl2 is at a concentration less than that for bubble coalescence inhibition. so gas pathogen surface area is much reduced compared with the nacl solution. but calcium adsorption by proteins should decreases pathogen surface charge (especially for the viruses) so this might be expected to reduce repulsive electrostatic forces with bubbles and so increase the hbce inactivation efficiency. the phenomenon of bubble-bubble interactions in electrolytes has remained unquantified until 1993.6 gas passing through a frit at the base of a water column produces bubbles. these ascend the column, the bubbles collide, fuse, and become larger. the column stays clear. however, when nacl is added, and above an effective physiological concentration of 0.17 m, suddenly the bubbles no longer fuse. the column becomes dense with the production of a high-density of bubbles (typically 1–3 mm diameter).6 the same phenomenon is responsible for the foaminess of the ocean, and the lack of foam production in freshwater. the phenomenon occurs for a wide variety of electrolytes, always at the same effective concentration 0.17 m or the equivalent debye length for all salts 1:1 2:1 2:2 3:1… and mixtures. for another class of electrolytes, there is no effect of salt on fusion inhibition. 2. material and methods 2.1. experimental solutions. monovalent (1:1) and divalent (2:1) electrolyte solutions of 300 ml were prepared and sterilised by autoclaving in an aesculap 420 at 15 psi, and 121-124 °c for 15 minutes. a nacl concentration of 0.17 m nacl or higher (≥ 99% purity, obtained from sigma-aldrich) in milliq water, prevents bubble coalescence and increases the performance of the hbce process by producing a higher air/water interfacial area. see ref6 for detailed results. 0.01 m cacl2 solutions (≥ 99% purity, obtained from sigma-aldrich) in milli-q water do not reduce bubble coalescence, these solutions were chosen to reduce the virus and bacteria charge, perhaps reducing repulsion between bubbles and pathogens potential of increasing the hbce inactivation efficiency, without affecting ms2 viability in this salt solution.5,7 2.2. media preparation for experiments with e. coli. the plate count method is commonly used for the identification of e. coli in marine water, treated drinking water, and wastewater. the water quality is assessed based on the ability of e. coli colonies to propagate in a layer of agar in the form of colony-forming units (cfu).26,34 for each experiment, 1 liter of medium was prepared from two solutions (a and b). solution a was composed of 6 g of nacl, 13 g of tryptone, 1 g of yeast extract, and 1,000 ml of milli-q water. a ph value o 6.9 was measured with a thermos scientific orion star a214 ph meter. this solution was aseptically dispensed into two vessels, broth media, without agar, and the other one containing 1.41% agar (molecular biology-grade from sigma-aldrich). to dissolve the agar, the solution was heated to boiling and then sterilized by autoclaving in an aesculap 420 at 15 psi, and 121-124 °c, for 15 minutes. solution b was used to enhance e. coli growth. this solution was prepared by adding 0.010 g of thiamine and 1 g of glucose to 50 ml of milli-q water and filtered through a 0.22 µm filter for its sterilization and then was aseptically added to solution a (in a proportion of 1:20), once cooled to 50 °c. the 1.41 % agar solution was poured into 100 × 15 mm petri dishes which were placed within the sterile field area around the bunsen burner created by the updraft of the flame.26 71thermal inactivation of viruses and bacteria with hot air bubbles in different electrolyte solutions 2.3. media preparation for experiments with viruses. a specific optimized double layer plaque assay technique was used to assess the concentration of active ms2 viruses. this plaque assay method is commonly used for the detection of ms2 in treated drinking water, wastewater, and marine water. the water quality is assessed based on the ability of bacteriophages to kill the host bacteria and allow phages (circular zone of infected cells) to propagate in a confluent lawn of bacterial host cells, immobilized in a layer of agar.8,9,10,11 the double layer plaque assay requires an adequate growth medium to achieve better visibility and higher consistency. 10, 11 the medium is not commercially available. therefore, it was prepared for each experiment in the form of two solutions, a and b. solution a contains 15 g of tryptone, 1.5 g of yeast extract, 12 g of nacl, and 1,425 ml of milli-q water. a ph value of 6.9 was measured with a thermos scientific orion star a214 ph meter. this solution was dispensed aseptically into three vessels with different amounts of agar (1% for the bottom agar, 0.5 % for the top agar, and no agar for the broth media). the agar used in these experiments was molecular biology-grade, obtained from sigma-aldrich. these solutions were first heated to boiling to dissolve the agar and then sterilized by autoclaving in an aesculap 420 at 15 psi, and 121-124 °c, for 15 minutes. solution b was used to improve the visibility of the viruses. this solution was prepared by adding 1.5 g of glucose, 0.441 g of cacl2, and 0.015 g of thiamine to 75 ml of milli-q water and filtered through a 0.22 µm filter for its sterilization and then was aseptically added to solutions a (in a proportion of 1:20), once cooled to 50 °c. the bottom agar was poured into 100 mm x 15 mm petri dishes which were dried within the sterile field area around the bunsen burner created by the updraft of the flame, to maintain local environmental sterility, until the agar was not too dry or too moist.9 2.4. bacterial strain escherichia coli c-3000 (atcc 15597) e. coli is a gram-negative bacteria with a straight cylindrical rod shape of 1.0-2.0 µm size.12 it is found in the gastrointestinal tract of animals and humans. e. coli strains can be harmless or pathogenic to the host. as a result of fecal contamination, they can be found in water and soil. therefore, it was selected as a representative model for bacteria in water13,14 for the e. coli inactivation experiments and also for the virus sterilization experiments, as the ms2 virus-host.11 e. coli c-3000 (atcc15597) is a biosafety level 1 organism 15 and can be used as the ms2 virus-host.11 for a successful plaque assay, for virus inactivation experiments, the escherichia coli c-3000 (atcc 15597) must be in an exponential growth phase. this was achieved by growing two separate bacterial cultures: an overnight culture and a log phase culture.10,11,16 the overnight culture was grown in 10 ml of broth media at 37 °c for 18-20 hours in a labtech digital incubator; model lib-030m, while shaking at 110 rpm with a psu-10i orbital shaker. this overnight culture resulted in high numbers of bacteria in the culture and was used as a reference standard. for a successful plate count, the concentration of e. coli from the overnight culture was calculated by serially 10-fold diluting 0.50 ml of e. coli overnight culture into a tube containing 4.50 ml sterile saline solution.10 to start the log phase e. coli culture, 1 ml of the overnight culture was transferred into 25-30 ml of broth media and incubated for 3 h at 37 °c, with gentle shaking at 110 rpm. to prevent loss of f-pill by the cells, they were then quickly cooled in a refrigerator, at 5 °c. a uv-vis spectrometer, uvmini-1240, was then used to measure the optical density (od) of the log phase e. coli culture. od readings at 620 nm of between 0.8 and 1.1 indicated that the culture can be used in the plaque assay for the virus experiments and as a standard for the e. coli experiments. 2.5. viral strains ms2 (atcc 15597-b1) a freeze-dried vial of ms2 bacteriophage was acquired from the american type culture collection (atcc). bacteriophage ms2 (atcc 15597-b1) was replicated using escherichia coli c-3000 (atcc 15597) according to the international standard iso 10705-116 and the ultraviolet disinfection guidance manual of the united states environmental protection agency.17 ms2 is a bacteriophage member of a class called group i. its entire genome has been sequenced. it is a positive-sense, single-stranded rna molecule of 3,569 nucleotides and it has an icosahedral structure. the virus has a hydrodynamic radius of about 13 nm.18 the concentration of the ms2 bacteriophage was calculated by adding 1.0 ml of broth media to the vial and serially 10-fold diluted 10 times by passing 0.50 ml of the bacteriophage into a tube containing 4.50 ml of broth medium.10 0.20 ml of the 4 hours host (log phase e. coli culture) and 10 ml of 0.5% top agar layer were poured over the petri dishes with 1% bottom agar, dried around the bunsen burner, 0.1 ml aliquots of 10-6 to 10-11 dilutions were inoculated on the surface of 14 petri dishes. after overnight incubation, 18-24 hours at 37 °c, individual plaques were countable and the concentration of the ms2 bacteriophage was calculated using the equation: 72 adrian garrido sanchis undiluted spiking suspension in pfu / ml = (pfu1 + pfu2… pfun)/(v1 + v2…. vn) [1] where pfu is the number of plaque-forming units from plates, vn is the volume (in ml) of each undiluted sample added to the plates containing countable plaques and n is the number of useable counts. 2.6. hot bubble column evaporator process (hbce) in the hbce process, 27 l/min of ambient air was pumped through a silica gel desiccator, for dehumidification, and from there the dry air was passed through an electrical heater that maintained a hot air temperature, just above the sinter surface, of 103 °c 150 °c, 200 °c or 250 °c, depending on the experiment. the base of the bubble column evaporator was fitted with a 40-100 µm pore size glass sinter (type 2) of 135 mm diameter. once the solutions with known concentrations of virus and e. coli were prepared, two rounds of experiments (one for viruses and the other one for bacteria) were conducted in the hbce. the temperature of the hot air (103 °c, 150 °c, 200 °c, 250 °c for this study) was measured, before the introduction of the solutions in the column, with a thermocouple above the sinter in the center of the dry column. the hot air passed through the sinter, in the form of bubbles, into the 300 ml solutions (0.17 m nacl and 0.01 m cacl2). this inactivated the pathogens (ms2 viruses and e. coli) and heated the solution to a steady-state temperature (of 34 to 55 °c, depending on the inlet air temperature). 2.7. disinfection experiments a total of 18 viral and bacterial sterilization experiments were conducted in two solutions: 0.17 m nacl and 0.01 m cacl2 at 4 different inlet air temperatures (103 °c, 150 °c, 200 °c, and 250 °c) in the hbce. the evaluation of bacteriophage and e. coli results was performed by the plaque assay and plate count methods (respectively).8,10,19 for each experiment, the target number of pathogens per 0.1 ml aliquot was 290. the following equation [4] was used to determine the spiking volume (that is, the volume that was taken from the virus/bacteria stock): [2] where s is the virus/bacteria stock volume (ml) added to 300 ml of solution, t is the target number of pathogen per sample, b is the total number of samples in 300 ml and c is the concentration (pathogen/ml) in the virus/ bacteria dilution to be used for spiking.17 once the solutions with the known concentration of pathogens were prepared the inactivation experiments at different temperatures were conducted in the hbce. 1 ml samples were collected from 10 to 15 mm above the central area of the sinter. for each sample, 0.1 ml was spotted in triplicate following the double layer or the plaque count technique,17 the same procedure that was used to determine the concentration of the ms2 bacteriophage or e. coli. 2.8. zeta potential measurements zeta potential measurements were performed using a nano zeta sizer (zetasizer nano zs malvern instruments ltd.)20 to study the ms2 virus and e. coli surface charge in various electrolyte solutions containing 108 ms2 viruses/ml or 108 e. coli c-3000/ml. trapped air bubbles in the zeta cells were carefully avoided in the disposable zeta cells used to conduct the zeta measurements. 2.9. data analysis the linear decay model was used to study the time dependence of inactivation of pathogens (ms2 virus or e. coli). plate counts were performed for all 18–21 plates from each of the experiments. the mean and standard deviation of each triplicated sample were obtained using bacterial survival factor, log10 (nt/n0), where n0 is the initial number of pathogens per sample and nt is the number of pathogens after a set exposure time in minutes.21 the decimal reduction time (d-value) was used to measure the temperature impact on both pathogenic groups (virus and bacteria). this can also be defined as the time needed to inactivate 90% (i.e. 1-log) of e. coli or virus (heat resistance). the z-value is the temperature change required to change the d-value by a factor of 10. d-values and z-values were calculated using a linear exponential decay model or thermal death model.22 log (nt) = log (n0) – [3] [4] where, d = the decimal reduction time, -(1/d) = the slope of the curve. the z-value is the increase in temperature needed to reduce the d-value by 1-log. it measures the impact of 73thermal inactivation of viruses and bacteria with hot air bubbles in different electrolyte solutions a change in temperature on e. coli or virus inactivation. thus: [5] where, t1 is the first temperature of the interval, t2 second temperature of the interval, and d1 and d2 are the d-values at t1 and t2. 3. results and discussion 3.1. theoretical model estimate of thickness and temperature of the transient hot water layer around the hot bubbles used in the inactivation of viruses and bacteria the hbce process successfully sterilised water contaminated with e. coli and ms2 viruses using hot air bubbles in two different solutions (0.17 m nacl and 0.01 m cacl2). this inactivation process appears to be triggered by collisions between the bacteria and viruses with the hot air bubbles.5,23,24 in the hbce, a thin layer of heated water must also be formed transiently around the surface of the hot air bubbles, once they are released into the column. the thickness and the temperature of this thin, transient layer can be roughly estimated and it appears that this may be an important parameter to understand inactivation rates of virus and e. coli occurring at the hbce. the collisions between these heated water layers, as well as the hot air in the bubbles themselves, is considered as the fundamental mechanism proposed for pathogen inactivation (e. coli and virus).24,5 during the hbce experiments the inlet air temperature was always between 103 and 250 °c and the estimated average temperature of the heated water layers was in a range of 66 to 70 °c (see table 1). by comparison, the column solution temperatures were always significantly lower (i.e. from 32 to 55 °c) (fig. 1). in the theoretical model, the temperature and the thickness of the hot water layer around the surface of a 1 mm diameter air bubble were estimated roughly for a range of inlet air temperatures using the formula: tavg= [6] where tavg (in °c) is the average (transient) temperature of the hot water layer surrounding the air bubble and tc (°c) is the steady-state temperature of the solution in the hbce, with the assumption that the hot air bubbles had cooled from their initial inlet temperature to 100 °c when they first enter the bubble column. the thickness of the transient has been estimated by balancing the heat supplied by the cooling bubble with the heat required to raise the film to this average temperature (see table 1). thus, since the volume of the film v is given by: v=4πr2z [7] where r is the bubble radius with a constant value of 0.001 m, z the layer thickness around the bubble and r>>z, this thermal energy balance is given by.25 cp∆tv=cwater∆t4πr2ρwz [8] where cp air heat capacities per unit volume, cwater is the air heat capacity per unit weight, is the liquid water mass density, ∆t is the cooling of the air bubble (from inlet temperature to 100 °c) and ∆t is the transient temperature increase in the water layer, relative to the column solution temperature. in practice, likely, at least half of the heat supplied by the cooling bubble will be used in evaporating water into the bubble, and hence the calculated, roughly estimated, film thicknesses should be about halved. figure 1. model used to estimate the thickness and temperature of the hot layer around the air bubble at different inlet air temperatures. table 1. estimated thickness and temperature of the transiently heated water layer around the air bubbles at different inlet air temperatures. inlet gas temperature tin (°c) column solution temperature tc (°c) density of water (g/cm3) hot layer thickness δ (nm) average temperature of hot layer tavg (°c) 103 32 0.99053 2 66 150 45 0.99022 39 72.5 200 51 0.98758 87 75.5 250 55 0.98569 142 77.5 74 adrian garrido sanchis when the inlet gas temperature increases, so does the thickness of the surface hot water layer around the bubble surface (fig. 1). consequently, the volume of the inactivation area is increased and this should make the inactivation rate more effective. typical results from this model are given above (table 1). therefore, the inlet air temperature has a direct relation with pathogen inactivation as will be shown. 3.2. temperature effects on pathogen inactivation in the hbce in two different solutions the impact of temperature for ms2 viruses and e. coli inactivation in the hbce process at 103 °c, 150 °c, 200 °c and 250 °c inlet air temperatures was studied using two solutions: 0.17 m of nacl and 0.01 m cacl2 (table 2). 3.3. solution comparison. a 0.17 m solution of nacl will inhibit bubble coalescence and so will increase the interfacial area of the bubbles within a bubble column 6, whereas the other solutions of 0.01 m cacl2 do not produce bubble coalescence inhibition 4, 26 (table 3). higher bubble interfacial areas were expected to increase will increase the chances of a collision between pathogens and hot air bubbles so improving virus and bacteria inactivation rates. the zeta potential for viruses presented lower values for cacl2 than for nacl solutions. presumably, this can be attributed to the absorption of calcium on the ms2 virus. e. coli did not present this selective absorption so that a similar zeta potential was observed for both electrolyte solutions for this pathogenic group (see table 3). to understand the effect of hot air on different solutions (0.17 m nacl vs 0.01 m cacl2) when thermally inactivating pathogens, such as ms2 virus and e. coli, decimal reduction times (d-values) at four inlet air temperatures, 50 °c intervals, were obtained (table 2). the correlation between the log of the d-values and the corresponding temperature was represented in fig. 2 and 3. a d-value is the time needed to inactivate 90% (i.e. 1-log) of the pathogens. to measure the heat resistance of these pathogens, z-values have been calculated. the z-value gives the temperature required to change the d-value by a factor of 10 and reflects the temperature impact on a pathogen (e. coli and ms2 virus in our study). the smaller the z-value, the greater the sensitivity to heat. figures 2 and 3 show the minimum air bubbling times, at different temperatures, needed to achieve 1-log pathogen (virus and bacteria) inactivation in 0.17 m nacl and 0.01 m cacl2 solutions. above and to the right of the lines the pathogens will be sterilised by 1-log. at low inlet air temperatures, between 100 and 150 °c, both pathogenic groups ms2 viruses and e. coli present higher inactivation rates in cacl2 than in nacl solutions with d-values of 33.00 and 75.19 min for e. coli and virus in cacl2 solutions and 121.95 and 65.36 min for nacl solutions (see table 2 and figures 2 and 3). for an intermediate range of temperatures, 150 to 200 °c nacl solutions show better inactivation rates for e. coli with d-values of 9.31 min. than do cacl2 solutions do for viruses with d-values of 23.75 min. at higher temperatures, 200 to 250 °c, both solutions presented similar inactivation rates for e. coli with d-values in a range of 3.5 to 3.8 min. for viruses, nacl solutions inactivated almost 3 times faster than cacl2 solutions with a d-value of just 6.15 min. (see table 2 and figures 2, and 3). virus (z-value= 145 °c) and e. coli (z-value= 105 °c) inactivation in cacl2 solutions is less temperature dependent than in nacl solutions with z-values of 77 °c for virus and 76 °c for e. coli see table 2. the effect of 0.17 m nacl on the inhibition of bubble coalescence makes the hbce process more temperature-dependent (reduced z-values of 77 °c) than when table 2. d and z values for e. coli and ms2 virus in 2 different solutions (nacl and cacl2). pathogen solutions d-values at different inlet air temperatures (min.) z-values (°c) 102 °c 150 °c 195 °c 205 °c 250 °c virus 0.17m nacl   121.95   29.41 6.15 77 0.01m cacl2   75.19   23.75 15.5 145 e. coli 0.17m nacl 65.36 9.31 3.87     76 0.01m cacl2 33.00 18.73   3.51   105 table 3. zeta potential and bubble coalescence values for virus and bacteria in nacl and cacl2 solutions. pathogen solution % coalescence zeta potential (mv) virus 0.17 m nacl 0 -6.32 0.01 m cacl2 94 -2.55 e. coli 0.17 m nacl 0 -12.50 0.01 m cacl2 94 -12.20 75thermal inactivation of viruses and bacteria with hot air bubbles in different electrolyte solutions using cacl2 solutions. it can reasonably be assumed that this is due to the higher air/water interfacial bubble area produced. consequently, there will be an increase in the volume of the transiently heated layer around the bubbles (see table 1). when this volume increases, the chances of collision between pathogens and hot air bubbles will also increase with the consequent improvement in heat transfer. 3.4. pathogenic group comparison the world health organisation (who) studied the sterilization properties of hot liquids for thermal inactivation of bacteria and viruses in their guidelines for drinking-water quality.27 who concluded that water temperatures above 60 °c effectively inactivate both pathogenic groups and when the temperature range lies between 60 and 65 °c, the inactivation of bacteria occurs faster than inactivation of virus. these studies proved that at 60 °c water temperature e. coli needs 600 seconds to reach a 3 log reduction compared with 1,350 seconds for viruses like echovirus 6, coxsackievirus b4, enterovirus, coxsackievirus b5 to reach the same 3 log reduction. for e. coli and ms2 virus inactivation in the hbce was improved by increasing the inlet air temperatures from 103 to 250 °c. the thermal inactivation effect is more effective when the inlet air temperature increases. this is probably because of a thicker and hotter transient heated water layers created around the rising air bubble surface28 (see table 1). e. coli and viruses will be thermally inactivated by the collisions with this layer. to understand the temperature effect of inlet air for thermal inactivation of pathogens (ms2 virus and e. coli) decimal reduction times (d-values) at four different inlet gas temperatures, at intervals of 50 °c, were obtained and the correlation between log of the d-values and the corresponding temperature was represented in figures 4 and 5. again, d-values and z-values have been calculated to assess the temperature impact on the pathogens. figures 4 and 5 show the minimum hot air bubbling times at different temperatures to achieve 1-log pathogen figure 2. comparison of the impact of temperature on ms2 virus inactivation between 0.17m nacl and 0.01m cacl2 solutions. figure 3. comparison of the impact of temperature on e. coli inactivation between 0.17m nacl and 0.01m cacl2 solutions. figure 4. comparison of the impact of temperature on e. coli and ms2 virus in 0.17m nacl solutions. figure 5. comparison of the impact of temperature on e. coli and ms2 virus in 0.17m cacl2 solutions. 76 adrian garrido sanchis (virus and bacteria) inactivation in 0.17 m nacl and 0.01 m cacl2 solutions. above and to the right of the lines the pathogens will be sterilised by 1-log. for both solutions and for the entire range of temperatures e. coli was inactivated much faster than ms2 virus, therefore, e. coli proved to be more sensitive to hot air bubbles than ms2 virus (fig. 4). at 150 °c inlet air temperatures e. coli presented d-values of 9.31 min. in nacl solutions and 18.73 min. in cacl2 solutions while the d-values for ms2 virus at the same temperature were 121.75 min. in nacl and 75.19 min in cacl2 (figures 4 and 5, table 2). when inlet air temperature raised to 200 °c d-values for e. coli were 3.87 min in nacl and 3.51 min in cacl2 for virus these values were much higher with 29.41 min for nacl solutions and 23.75 in cacl2. we can infer then that in the hbce process, viruses and e. coli are inactivated when they are immersed in the hot water layer around the hot air bubbles or the bubbles themselves. the results agree with who with a faster inactivation for bacteria than for viruses, at similar water temperature 27. but this phenomenon is considerably enhanced by using the hbce for both solutions. thus, the inactivation rates for viruses are much slower than for bacteria even though the gas temperature range for the virus (150 to 250 °c) was higher than for the bacteria (103 to 205 °c). this difference, might in part, due to the large size/momentum effect of e. coli compared with viruses. in a turbulent regime within the hbce , the signif icantly larger momentum of e. coli cells is more likely to enable direct contact with the hot air phase what will increase their inactivation. a more likely contributor is the destruction of phospholipid bilayers of the bacteria with high temperatures. 4. conclusions this work has shown that viral and bacterial inactivation in the hbce process can be substantially improved by raising the inlet air temperature, from 103 °c to 250 °c. according to the hot water layer theoretical model, when the inlet gas temperature increases, so will the thickness and the temperature of the transient heated water layer around the rising air bubble surface, and this appears to facilitate pathogen inactivation. when thermal processes are used for water sterilization faster inactivation is always observed for bacteria than for viruses, at similar water temperatures. this phenomenon is considerably enhanced when using the hbce independently of the solution. the effect of 0.17 m nacl on the inhibition of bubble coalescence makes the hbce process more temperature-dependent than with cacl2 solutions by producing a higher air/water interfacial area and a better heat transfer. 5. acknowledgments the author thanks professors ric pashley and barry ninham for their helpful suggestions and advice and review. 6. references 1. a. garrido sanchis, r. pashley, b. ninham, virus and bacteria inactivation by co2 bubbles in solution, npj clean water, 2019, 2(1), 5. 2. n. kantarci, f. borak, k.o. ulgen, bubble column reactors, process biochem, 2005, 40(7), 2263-2283. 3. w.d. deckwer, on the mechanism of heat transfer in bubble column reactors, chem eng sci, 1980, 35(6), 1341-1346. 4. m. shahid, r.m. pashley, r.a.f.m. mohklesur, use of a high 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(b) entails self-consciousness, in so far as the agent who expresses the judgment must be aware that the two apprehensions are submitted to his/her own scrutiny and that it is his/her task to extract a mutual relation. since (b) lasts around 3 seconds, the semantic value of the pieces under comparison must be decided within that time. this implies a fast search of the memory contents. as a fact, exploring human subjects with sequences of simple words, we find evidence of a limited time window , corresponding to the memory retrieval of a linguistic item in order to match it with the next one in a text flow (be it literary, or musical, or figurative). while apprehension is globally explained as a bayes inference, judgment results from an inverse bayes inference. as a consequence, two hermeneutics emerge (called respectively circle and coil). the first one acts in a pre-assigned space of features. the second one provides the discovery of novel features, thus unveiling previously unknown aspects and hence representing the road to reality. keywords. human language, homoclinic chaos, synchronization of neural spike sequences, bayes inference, inverse bayes inference, circle hermeneutics, coil hermeneutics. 1. perception, judgment and self-consciousness figs 1 and 2 introduce the difference between a-apprehension or perception that rules the motor reactions of any brainy animal, and b-language ,only humans, and that provides judgments. figs 3 and 4 show why the scientific program is a linguistic one and what is the reason of its success. with this in mind, we explore whether and how cognition unveils reality… following the philosophy of cognition of bernard lonergan [lonergan], i discuss two distinct moments of human cognition, namely, apprehension (a) whereby a coherent perception emerges from the recruitment of neuronal groups, and judgment (b) whereby memory recalls previous (a) units coded in a suitable language; these units are compared and from comparison it follows the formulation of a judgment. 42 f. tito arecchi the first moment, (a), has a duration around 1 sec; its associated neuronal correlate consists of the synchronization of the eeg (electro-encephalo-graphic ) signals in the so-called gamma band (frequencies between 40 and 60 hz) coming from distant cortical areas .it can be described as an interpretation of the sensorial stimuli on the basis of available algorithms, through a bayes inference [arecchi,2007; doya et al.]. precisely, calling h(h= hypothesis) the interpretative hypotheses in presence of a sensorial stimulus d (d=datum), the bayes inference selects the most plausible hypothesis h*,that determines the motor reaction, exploiting a memorized algorithm p(d|h), that represents the conditional probability that a datum d be the consequence of an hypothesis h. the p(d|h) have been learned during our past; they represent the equipment whereby a cognitive agent faces the world. by equipping a robot with a convenient set of p(d|h), we expect a sensible behavior. the second moment, (b),entails a comparison between two apprehensions (a) acquired at different times, coded in a given language and recalled by the memory. if, in analogy with (a), we call d the code of the second apprehension and h* the code of the first one, now – at variance with (a) h* is already given; instead, the relation p(d|h) which connects them must be retrieved; it represents the conformity between d and h*, that is, the best interpretation of d in the light of h*. thus, in linguistic operations, we compare two successive pieces of the text and extract the conformity of the second one on the basis of the first one. this is very different from (a), where there is no problem of conformity but of plausibility of h* in view of a motor reaction. let us make two examples: a rabbit perceives a rustle behind a hedge and it runs away, without investigating whether it was a fox or just a blow of wind. on the contrary, to catch the meaning of the 4-th verse of a poem, we must recover the 3-d verse of that same poem, since we do not have a-priori algorithms to provide a satisfactory answer. once the judgment, that is, the p(d|h) binding the codes of the two linguistic pieces in the best way, has been built, it becomes a memorized resource to which to recur whenever that text is presented again. it has acquired the status of the pre-learned algorithms that rule (a). however-at variance with mechanized resources whenever were-read the same poem, we can grasp new meanings that enrich the previous judgment p(d|h). as in any exposure to a text (literary, musical, figurative) a re-reading increases our understanding. (b) requires about 3 seconds and entails self-consciousness, as the agent who expresses the judgment must be aware that the two successive apprehensions are both under his/her scrutiny and it is up to him/her to extract the mutual relation. at variance with (a), (b) does not presuppose an algorithm, but rather it builds a new one through an inverse bayes procedure [arecchi, 2010]. this construction of a new algorithm is a sign of figure 1. plato said that we see the shadows of things, like a prisoner constrained to view the end of a cave and forbidden to turn and see the outside world. this occurs indeed in perceptual tasks, where the sensorial stimuli are interpreted by “algorithms” and generate (within1 sec) a motor reaction. the procedure is common to all brainy animals. figure 2. in linguistic operations, humans code a perception in a linguistic code andretrieve it by short term memory (around 3 sec)comparing it to a successive coded perception. from the comparisonit emerges a connection that increases the details of the observed thing. 43cognition and reality creativity and decisional freedom here the question emerges: can we provide a computing machine with the (b) capacity, so that it can emulate a human cognitive agent, as expected in theturing test? the answer is not, because (b) entails nonalgorithmic jumps, insofar as the inverse bayes procedure generates an ad hoc algorithm, not available previously. the scientific endeavor can not be carried on by an ai (artificial intelligence ) device, since it entails a linguistic step, as shown in fig. 3. fig. 4 explains why galileo’s program provides certainties, rather than probabilistic expectations. 2. the brain operations-role of homoclinic chaos let us introduce “deterministic chaos”.[arecchi,2004 b] since poincaré (1890) we know that a dynamical system is extremely sensitive to the initial conditions. that yields the so called “butterfly effect” whereby a tiny shift in the initial conditions yields a large difference in course of time . precisely, a difference of initial conditions induces a divergence of the dynamical trajectories in course of time. in the case of a meteo dynamical model, accounting for most atmospheric features (wind, pressure, humidity, etc) but neglecting the motion of a butterfly wing could lead to a wrong prediction(from sunny to rainy).loss of the initial information occurs over a time t whose inverse is called k (kolmogorov entropy). in the meteo model such a t may be days, in a dynamical model of the solar system it takes millions of years. we call geometric chaos the above trajectory divergence. another type of chaos,that we call temporal chaos, consists of regular closed orbits that however repeat at irregular times (fig. 5). a single neuron in the brain undergoes temporal chaos and its electrical output consists of a train of spikes (each one high 100mv and lasting 3 ms). the minimal inter-spike separation is 3 ms; the average separation is 25 ms in the so-.called g band of the eeg(electro-encephalo-gram). a neuron communicates with other neurons in two ways [arecchi,2004 a, singer,womelsdorf. & fries]: – either directly , by coupling its spike train to another neuron via an electric line called axon, – or indirectly, by building with nearby neurons a local potential (detectable as an eeg signal) and providing a signal χ to a distant neuron, that consequently re-adjusts its firing rate. fig. 6 shows the direct synchronization of two trains over a time dt. the neurons involved in the coupling are confined in a thin layer of the brain (thickness 2 mm) called the cortex. groups of nearby neurons contribute to a common task forming a specialized area that builds global interactions with other areas (fig. 7). the areas are visualized via the amount of oxygenated blood required by a working region and visualized by f-mri (functional magnetic resonance imaging). fig. 8 visualizes the competition between two neuron groups i and ii fed by the same sensorial (bottomup) stimulus, but perturbed (top-down) by different interpretational stimuli provided by the long term figure 3. the scientific program is a linguistic task. galileo’s approach consists of extracting mathematical features; it implies a linguistic operation, according to fig.2. figure 4. once the object under investigation is reduced to a collection of mathematical features, one applies millennia of mathematical wisdom and predicts the future behavior. 44 f. tito arecchi memory. i wins, as the corresponding top-down stimulus succeeds in synchronizing the neuron pulses of this group better than in group ii. this means that, over a time interval δt, neurons of i sum up coherently their signals, whereas neurons of ii are not co-ordinated, hence yielding a smaller sum. as a consequence a reader gws (= global workspace, name given to the cortical area where signals from different areas converge; it is located in area f of fig.7) reads within δta sum signal overcoming a suitable threshold and hence eliciting a motor response [dehaene]. thus, the winning interpretation driving the motor system is that provided by i. what represented in fig. 8 models the mechanism (a) common to any animal with a brain. 3. perception as a bayes inference neurosciences hypothesize a collective agreement of crowds of cortical neurons through the mutual synchronization of trains of electrical pulses (spikes) emitted individually by each neuron [singer et al., dehaene et al.] .the neuro-scientific approach is summarized in fig. 8. however, a global description of the above process can be carried on in probabilistic terms, without recurfigure 5. homoclinic chaos; the dynamic trajectory is a closed orbit starting from s (saddle point) and returning to it. projecting on a single direction, we observe spikes p repeating in time. the time separation between two spike occurrences depends on the relations between α and g, thus it can be controlled by a voltage applied to s, as the signal χ. figure 6. direct coupling of two neurons by synchronized spike trains; synchronization missed after dt for an extra-spike in the upper train. figure 7. topology of specialized cortical areas ,each one being active as a large collection of synchronized neurons; mutual communication occurs via eeg signals. multisensory interactions will combine into a unified pattern involving frontal cortex, temporoparietal regions as well as unimodal cortices: a = auditory cortex; v = visual cortex; m= higher-order multisensory regions; f = prefrontal cortex figure 8. competition of two cortical areas with different degrees of synchronization. 45cognition and reality ring to the details of the process. in 1763, thomas bayes, looking for a reliable strategy to win games, elaborated the following probabilistic argument[bayes]. let us formulate a manifold of hypotheses h about the initial situation of a system, attributing to each hypothesis a degree of confidence expressed by an a priori probability p(h). any hypothesis, introduced as input into a model of evolution, generates data. let us assume that we know the model and, hence, can evaluate the probability of the data conditioned by a specific hypothesis h; we write it as p(data|h). the model is like an instruction to a computer, thus we call it algorithm; it generates different data for different h. if then we perform a measurement and evaluate the probability p(data) of the data, we must conclude that there is an h more plausible than the other ones, precisely the one that maximizes the probability conditioned by the data p(h|data), that we call the a posteriori probability of hand denote as h*. this procedure is encapsulated in the formula, or theorem, of bayes, that is p(h*)=p(h|data) = p(h) [p(data|h)/p(data)] to summarize, the a posteriori probability of h, conditioned by the observed data, is given by the product of the a priori probability of h, times the probability p(data|h) of the data conditioned by a given h, that we call the model, and divided by the probability p(data), based on a previous class of trials (fig. 9). fig. 10 summarizes the whole perception procedure, that is initiated by an external stimulus and concluded by a motor reaction [arecchi, 2007]. successive applications of the theorem yield an increasing plausibility of h*; it is like climbing a mountain of probabilities along its maximum slope, up to the peak. after each measurement of the data and consequent evaluation of the a posteriori h*, we reformulate a large number of new a priori h relative to the new situation, and so on (fig. 11). notice that darwinian evolution by mutation and successive selection of the best fit mutant is a sequential implementation of bayes theorem. 4. linguistic operations as inverse bayes in fig. 11 the recursive application of bayes using the same algorithmor modelis visualized as climbing a probability mountain. the bit length of the algorithm is the algorithmic complexity of the cognitive task. however, in everyday life we experience jumps toward different algorithms, that means going to climb different mountains (fig. 12). the associated multiplicity of choices corresponds to attributing different meanings figure 9. bayes inference. figure 10. starting with a large number of presumed hypotheses h, the occurrence of the data selects the h* that satisfies the above relation and drives a suitable reaction. 46 f. tito arecchi to the input data; the number of alternative choices will be called semantic complexity [arecchi, 2007]. this swap of the model is a creative jump proper of language operations. it is the root of goedel-1931 incompleteness theorem and turing-1936 halting problem for a computer, as discussed in a previous paper [arecchi, 2012]. altogether different from (a) is the situation for (b), that – implying the comparison between different apprehensions coded in the same language (literary, musical, figurative, etc.) – represents an activity exclusively human. in fact, the second moment (b) entails the comparison of two apprehensions acquired at different times, coded in the same language and recalled by the memory. (b) lasts around 3 sec; it requires self-consciousness, since the agent who performs the comparison must be aware that the two non simultaneous apprehensions are submitted to his/her scrutiny in order to extract a mutual relation. at variance with(a), (b) does not presuppose an algorithm but it rather builds a new one through an inverse bayes procedure introduced by arecchi [arecchi,2010]. this construction of a new algorithm is the source of creativity and decisional freedom. language indeed permits an infinite use of finite resources [humboldt]. it is the missing step in turing’s claim that human intelligence can be simulated by a machine [turing]. the first scientist who explored the cognitive relevance of the 3sec interval has been ernst pöppel [pöppel 2004, 2009]. this new temporal segment has been little explored so far. all the so-called “neural correlates of consciousness” (ncc) are in fact electrical (eeg) or functional magnetic resonance (fmri) tests of a neuronal recruitment stimulating a motor response through a gws (see fig. 8); therefore they refer to (a). in such a case, rather than consciousness, one should call itperceptual awareness,that we have in common with brainy animals. fig. 13 shows how an inverse bayes procedure provides the best comparisons of two successive pieces of a linguistic text, thus generating a judgment. while in perception we compare sensorial stimuli with memories of past experiences, in judgment we compare a piece of a text coded in a specific language (literary, musical, figurative) with the preceding piece, recalled via the short term memory. thus we do not refer to an event of our past life, but we compare two successive pieces of the same text. such an operation requires that: i) the cognitive agent be aware that he/she is the same examiner of the two pieces under scrutiny; ii) the interpretation of the second piece based upon the previous one implies to have selected the most appropriate meanings of the previous piece in order figure 11. recursive application of bayes is equivalent to climbing a probability mountain, guided by the model ,that is, the conditional probability that an hypothesis generates a datum. this strategy is common e.g. to darwin evolution and to sherlock holmes criminal investigation; since the algorithm is unique, it can be automatized in a computer program (expert system). figure 12. comparison of two different complexities, namely, i)the algorithmic c. , corresponding to the bit length of the program that enables the expert system to a recursive bayes; and ii)semantic c., corresponding to the occurrence of different models. bayes m eaning inform ation complexity, semantic----à (multiple models) complexity, algorithmic (single model) creativity= swap of model climbing up a single peak is a non-semiotic procedure on the contrary jumping to other peaks is a creativity act, implying a holistic comprehension of the surrounding world (semiosis) 47cognition and reality to grant the best conformity (from a technical point of view, this conformity is what in the philosophy of cognition of thomas aquinas was defined as truth = adaequatio intellectus et rei (loosely translated as : conformity between the intellectual expectation and the object under scrutiny) in fig. 10 we have generically denoted as top-down the bunch of inner resources ( emotions, attention) that, upon the arrival of a bottom-up stimulus, are responsible for selecting the model p(d|h) that infers the most plausible interpretation h* driving the motor response. the focal attention mechanisms can be explored through the so-called ncc (neural correlates of consciousness) [koch] related to eeg measurements that point the cortical areas where there is intense electrical activity producing spikes, or to f-mri (functional magnetic resonance imaging) that shows the cortical areas with large activity which need the influx of oxygenated blood. here one should avoid a current confusion. the fact that a stimulus elicits some emotion has nothing to do with the judgment that settles a linguistic comparison. as a fact, ncc does not reveal self-consciousness, but just the awareness of an external stimulus to which one must react. such awareness is common to animals, indeed many tests of ncc are done on laboratory animals. it is then erroneous to state that a word isolated from its context has an aesthetical quality because of its musical or evocative power. in the same way, it is erroneous to attribute an autonomous value to a single spot of color in a painting independently from the comparison with the neighboring areas.all those “excitations” observed by fmri refer to emotions related to apprehension and are inadequate to shed light on the judgment process. the different semantic values that a word can take are associated with different emotions stored in the memory with different codes (that is, spike trains). among all the different values, the cognitive operation “judgment” selects that one that provides the maximum synchronization with the successive piece. thus emotions are necessary but not sufficient to establish a judgment. on the other hand, emotions are necessary and sufficient to establish the apprehension as they represent the algorithms of the direct bayes inference. this entails a competition in gws (fig. 8) ,where the winner is the most plausible one; whereas in the judgment-once evoked the panoply of meanings to be attributed to the previous piecethese meanings do not compete in a threshold process, but they must be compared with the code of the next word in order to select the best interpretation. recent new terms starting with neuro-( as e.g. neuro-ethics, neuro-aesthetics, neuro-economics, neurotheology) smuggle as shear emotional reactions decisions that instead are based on judgments. the papers using those terms overlook the deep difference between apprehensions and judgments. the question is discussed in detail in the conclusions. a very successful neurological research line deals with mirror neurons, that is, neurons that activate in subjects (humans or higher animals) observing another subject performing a specific action, and hence stimulate mimetic reactions [rizzolatti]. here too, we are in presence of mechanisms(empathy)limited to the emotional sphere, that is, very useful for formulating an apprehension, but not a judgment. 5. two different hermeneutics, that is, interpretations of cognitive data fig. 14 shows how a cognitive agent a reads an object b. the circle refers to a bayes cognition, whereby an algorithm is taken as necessary and sufficient to generate knowledge of b. whenever a reconsiders b, he/she finds the same b already memorized. on the contrary, expressing the knowledge in a language and comparing successive pieces by inverse bayes, entails an increase of details of b (b1,b2, etc.) that improve the cognition of the agent (a1,a2, etc). as for the circle, in information science, an ontology is a formal definition of the properties, and figure 13. the inverse bayes procedure that occurs in linguistic endeavors, whereby a previous piece ofa text is retrieved by the short term memory and compared with the next one: the appropriate conditional probability is no longer stored permanently but it emerges as a result of the comparison (judgmentand consequent decision). 48 f. tito arecchi mutual relationships of the entities that exist for a particular domain of discourse. an ontology lists the variables needed for some set of computations and establishes the relationships between them. for instance, the booklet of the replacement parts of a brand of car is the ontology of that car. the fields of artificial intelligence create ontologies to limit complexity and to organize information. the ontology can then be applied to problem solving. nothing is left out; we call this cognitive approach “finitistic” as no new insight is provided by repeated trials. on the contrary, in any human linguistic endeavor (be it literary, or musical or figurative) a starts building a provisional interpretation a1 of the text ; whenever a returns to b, he/she has already some interpretational elements to start with, and from there a progresses beyond , grasping new aspects b2, b3…and hence going to a2 and so on (coil). to carry on a coil program, we do not need a large amount of resources; language makes an infinite use of finite resources [humboldt]. the coil hermeneutics describes also the inter-personal dialogue. if the object b of cognition is a human person as a, then the changes b1,b2, etc are not only due to an increased knowledge by a, but also to an intrinsic change of b who re-adjusts his/her relation with a. thus, if b is another human subject, then b undergoes similar hermeneutic updates as a; this is a picture of the dialogical exchange between two human beings. (persons). 6. conclusionstwo aspects of linguistic creativity we conclude by stressing two well known aspects of linguistic creativity. first, if we start a linguistic endeavor, a wealth of possible situations emerge , giving rise to ambiguous behaviors as it occurs in most products of human creativity, that – like the etruscan chimera – display apparently contradictory behaviors, from ulysses to dom quixote (fig. 15). the onset of chimeras is explained in fig. 16 as the lack of an external referent b. altogether different is the what takes place when the language is interpreting scientific observations. in fact, the repeated comparison extracts elements of reality, as hinted in the coil hermeneutics. figure 14. two kinds of interpretation of a text, or hermeneutics, namely, the circle, whereby the interpreter a attributes a finite and fixed set of meanings to the text b, and the coil, whereby a captures some particular aspects of b and-based on that informationa approaches again the text b discovering new meanings. the novel insight provided at each coil is an indication of how language provides new semantic apertures. figure 15. a linguistic action that proceeds from a known piece toward an unknown one is like the etruscan chimera: it can generate mutually conflicting behaviors , as it occurs in most characters ,from ulysses to dom quixote.when instead the linguistic comparison regards two observed items (as it occurs in reading the verses of a poem, but also in scientific observations), then we really increase our personal knowledge with an element of reality. figure 16. how chimeras emerge in linguistic creations. 49cognition and reality applying our hermeneutics to the scientific program, we have two possible approaches. as the size of the observed world increases from a few particles to many, within a universal scientific description associated with a fixed-algorithm (as an ai tool would operate) we witness an exponential increase of the size c of the computational program ( called the algorithmic complexity) as well as a reduction of the time interval t over which predictions are reliable, that is, an increase of the kolmogorov entropy k=1/t (fig. 17). a more efficient scientific program consists of linguistic comparisons of different situations, with the help of inverse bayes inference, applying non-algorithmic jumps as the horizontal lines of fig. 12. we are somewhat manipulating the set of attributions of the item under study, emphasizing novel aspects and overlooking some previous ones. such a change of paradigm [kuhn] leads to novel theories with lower c and k. a very familiar example is the formulation of maxwell’s electromagnetic equations, unifying electric, magnetic and optical phenomena. the novel values we attribute to some features leads to the so called effective science [hartmann, 2001]. an outstanding example is offered by landau theory of phase transitions. in fig. 18 we list the so-called neuro-by products (neuro-ethics, neuro-aesthetics, neuro-economics, etc.) meaning that the decisions in that specific matter result from brain processes signaled by f-mri. one would attribute to emotions the role that is instead proper of a linguistic act, thus requiring an inverse bayes. precisely, the emotions select a particular meaning to be assigned to the piece of text h* in order to optimize its matching with the next one d; they are crucial for maximizing p(h*|d) but they are not all , just a piece of the whole tapestry (see fig. 13). final consideration. does ai operate by inverse bayes in a linguistic elaboration? answer: only in a very limited way. indeed, ai refers to a built-in “ontology”, consisting of a large, yet finite, list of properties of each item. (see e.g. the informational use of the term ontology to list the component parts of a car). thus ai can build p(h*|d) for each h* and d , and it can do it in a much faster way than a human. however the human exploits emotions in selecting the meaning of h*, thus he/she can go beyond the large, yet limited ontology available to ai and attribute to h* novel aspects previously unknown. this is the creativity of human language, already addressed by humboldt , and absent in ai. bibliography arecchi f.t. (2004a). chaotic neuron dynamics, synchronization and feature binding, physica a 338: 218237. arecchi f.t. (2004b). caos e complessità nel vivente (lezioni tenute alla scuola universitaria superiore, pavia), iuss press-pavia, pp. 248 figure 17. normal science vs. paradigm shift  effective science [hartmann, kuhn]. let c be the bit length of the algorithm and k the kolmogorov entropy, i.e., the inverse of the time t beyond which the initial information is lost by dynamical chaos. a computer program that evaluates kepler’s orbits, as bacon, has small c and k. as the physical system gets richer, both c and k increase and a scientific search carried on by an ai system would be affected by higher and higher c and k. however, a linguistic actor as a human scientist can act by a “jump of paradigm”, that is, change code and introduce a new scientific theory (effective description) with low c and k. against the ncc (= neural correlates of consciousness) role (f.crick, c. koch) ncc means : there is a brain area , localized by f-mri , whereby specific human endeavors emerge , classified as ethics aesthetics economics theology mathematics etc. “neuro-” on the contrary, in phenomenology (from husserl to varela) it makes no sense to isolate the brain but one must account for the whole cognitive being in dialogue with the world . the inverse bayes stems from a comparison of meanings and not from a single emotion highlighted by f-mri. figure 18. it is fashionable to speak of neuro-ethics, neuro-aesthetics, neuro-economics, etc., overlooking the essential role of inverse bayes. hence, the neuro-xxxx should be regarded as scientific misunderstandings. 50 f. tito arecchi arecchi f.t. 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(1612). terza lettera a m. welser sulle macchie solari, opere, vol. v (pp. 187-188). firenze: edizione nazionale, barbera 1968. hartmann s. (2001). effective field theories, reduction and scientific explanation, studies in history and philosophy of modern physics 32b, 267-304. humboldt w.(1836). on language: on the diversity of human language construction and its influence on the mental development of the human species. trans. peter heath, cambridge: cup, 1988. koch c. (2004). the quest for consciousness: a neurobiological approach. englewood, us-co: roberts & co. publishers. kuhn t. (1962 1st ed.; 1996, 3rd ed.). the structure of scientific revolutions, university of chicago press. lonergan b.s.j (1970). insight, a study of human understanding, philosophical library, new york. pöppel e. (2004). lost in time: a historical frame, elementary processing units and the 3-second window, acta neurobiologiae experimentalis, 64: 295-301. pöppel e.(2009). pre-semantically defined temporal windows for cognitive processing, philosophical transactions of the royal society b, 364,1887-1896. rizzolatti g. et al. (1996). premotor cortex and the recognition of motor actions, cognitive brain research, 3(2), 131-141. singer w. & gray c.m. (1995). visual feature integration and the temporal correlation hypothesis, annual reviews of neuroscience 18, 555-586. singer w. (2007). binding by synchrony, scholarpedia, 2(12), 1657. tommaso d’aquino (1269). summa theologica, pars prima, quaestio 16. turing a. (1950). computing machinery and intelligence. mind 59, 433-460. womelsdorf t. & fries p. (2007). the role of neuronal synchronization in selective attention, current opinion in neurobiology, 17, 154-160. substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi substantia. an international journal of the history of chemistry 1(2): 123-132, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-32 citation: i. bainbridge (2017) zvi enrico jolles pioneer in applied chemistry. substantia 1(2): 123-132. doi: 10.13128/substantia-32 copyright: © 2017 i. bainbridge. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declared that no competing interests exist. historical article zvi enrico jolles pioneer in applied chemistry irene bainbridge alderford house – sible hedingham, halstead, essex, co9 3hx e-mail: imbainbridge@onetel.com abstract. when i brought to florence the death mask of prof. angelo angeli, earlier this year, i was greeted most warmly but with some puzzlement as to how it came to be in my possession. i discovered that my father, a pupil of angeli and later a rising figure in florentine chemistry between 1924 and 1938, had been completely forgotten there after he was expelled from italy to comply with the fascist racial laws of 1938. this biography aims to fill that gap. it was originally written by his son, joshua jolles, on the occasion of the dedication of a meeting room at the casali institute, jerusalem in 2005, and has been revised in 2017 by his daughter, irene bainbridge, for substantia. it is a story of diligence and adventure, tenacity against many odds, and finally the triumph of optimism over adversity, to be celebrated in florence, his alma mater, with the establishment of the fondo jolles, for the preservation of many documents relating to his life and work. keywords. applied chemistry, organic chemistry, scientific biography, racial laws. 1. acknowledgements of florence chemistry museum hugo schiff (frankfurt-on-main 1834 – florence 1915), discoverer of the schiff bases and schiff reagent, is considered the founder of the florentine school of chemistry, having been for fifty years professor of chemistry in florence. the school created by him in 1864 developed further under his successor angelo angeli and produced chemists of international calibre, whose faces we can to some extent see in the images preserved in the section of chemistry of museum of natural history of the university of florence. in the past few months one of the hitherto unknown faces has finally regained a name: zvi enrico jolles, assistant to angelo angeli and “libero docente” in applied chemistry, exiled from teaching in 1938 by the disgraceful implementation of the racial laws. thanks to the generosity of the jolles family the documents that attest to zvi jolles’ activity in florence have now been brought to florence. they will form part of the fondo jolles, an important endowment for the chemistry section of the museum: first, because the donation refers to a person who played a significant role in international chemistry; second, because it fills a lacuna in the academic history of florence; and finally, because it provides new and completely unedited primary 124 irene bainbridge information about angelo angeli and his school, in the voice of someone who was very close to him. so close as to have been entrusted by angeli with preparing his death mask – a mask zvi actually took with him in his enforced exile. prof. andrea goti, director of “ugo schiff” chemistry department of florence and scientific supervisor of chemical heritage project of florence university, prof. antonio guarna, founder of chemical heritage project of florence university 2. introduction zvi enrico jolles was born on 23rd april 1902 in lvov (lemberg) in the province of galicia in the austrohungarian empire. his life was a remarkable odyssey which reflected much of the history of the 20th century: from austria, to british mandate palestine, to italy, to britain, and then to israel. he saw incredible technical advances, from the excitement when electric lighting first reached his home, to atomic energy and men on the moon. he first went to palestine, travelling on foot or in a donkey-cart, as a young zionist pioneer to help reclaim the land, where he endured many hardships and survived typhus and malaria; then he returned forty years later by el al jumbo jet to find the zionist dream come true a strong and vibrant modern state of israel, making great strides in science and technology. he built up a successful academic career in italy but had to leave hurriedly as a refugee from fascist persecution with nothing except the knowledge in his head. in britain, he was briefly interned on the isle of man1 as an “enemy alien” at the beginning of world war ii. he built up his career again in the chemical industry, originating many novel products and processes. he suffered a terrible blow, losing to the nazi monsters most of his close family who had remained in europe. he survived the “blitz” in london, life-threatening illnesses, heart attacks, all the time retaining his faith and optimism, his love of family, and devoting himself to the study of chemistry, hoping that one day he would find full scope for his treasury of knowledge and ideas. on retiring from his post as head of research of a chemical company in britain, he returned to israel as a scientific advisor to the government and played a leading role in the foundation of the casali institute of applied chemistry. he was appointed to a newly created chair in applied chemistry in the hebrew university and was the first director of the institute. sadly, when he was at last beginning to see his ideas for it coming to fruition, he left this life on 13th june 1971, aged 69 years. 3. leaving poland for the promised land bernard jolles, the father of zvi, had been a modestly prosperous timber merchant producing pit-props for coal-mines and railway-sleepers for the polish government. his father’s father had been at one time an innkeeper and then a printer. on the whole, they were scholarly people; in the male line there were distinguished scholars and rabbis, some of whom combined enlightenment and secular learning with their study of torah and talmud. on the side of his mother (malka leiter) was a numerous extended family throughout the province of galicia who played an active role in community social and charitable activities. they were traditionally observant, as were most jews in those parts. they kept the shabbat so strictly that writing or cutting paper with scissors was forbidden. it was a household of order, discipline and study. at the age of four zvi was sent to the “cheder” where he learned to read and write hebrew and study the torah. by his diligence and concentration he avoided the slapping and ear-pulling which were the regular teaching aids in those classes. later he went to a state school, the gymnasium, where he first encountered anti-semitism. the worst perpetrators were some of the teachers. three to four centuries earlier the jews, who had been expelled from spain and were migrating eastwards across europe, had been accepted by the polish kings as they helped to bring development and prosperity to their host country. the family name of jolles is believed to have originated in spain but from the 16th century onwards appears to have spread to holland, austria, poland, russia and even england. over the course of the 19th century, the historic territories of the polish kings had been carved up between austria, russia and prussia. the glory days of poland had long gone, but there were lingering folk memories of a once great kingdom and noble traditions. from the moment when an idyllic family holiday in a carpathian mountain village was cut short by the outbreak of the first world war in august 1914, the region was plunged into turmoil. first the austrians fought the russians; then, as the austrian empire crumbled and russia was convulsed by the agonies of the revolution, the conflicting imperial armies melted away. polish nationalism revived and by 1917-18 machine-gun fire 125zvi enrico jolles pioneer in applied chemistry raked the streets of lvov as poles fought ukrainians for control. none of this was good for the jewish community, who had enjoyed peace and stability under austrian rule. for three centuries they had prospered but now they were exposed in quick succession to the endemic anti-semitism of russians, cossacks, ukrainians and poles who terrorised this once peaceful old town, often venting their frustrations on its jewish inhabitants. in his early teens zvi jolles had reached the conclusion that poland could no longer be his country and that as long as the jewish people did not have their own land they would wander the world for ever, never quite belonging anywhere. the zionist dream – a homeland for the jewish people in the land of israel gave him hope and inspiration. zionism was an intellectual ferment among young jews. zvi joined the hashomer hatzair (“the young guard”) and listened eagerly to outstanding speakers such as hirsch lauterpacht (much later professor of international law at cambridge university, who memorably expressed the concepts of “human rights” and “crimes against humanity” at the nuremberg trials). many young people in those days idealised socialism but zvi focused his thoughts on returning to the ancestral land of israel. at the age of sixteen he left school and went to train on a farm, to prepare himself for the hard physical labour that lay ahead. in 1917 the balfour declaration2 gave a completely new impetus to zionism and at the age of seventeen zvi jolles set off on foot through the chaos and anarchy of central europe in the aftermath of the great war, to make his way to palestine. it was a hazardous adventure. with the help of friends and supporters of the zionist movement, he crossed the balkans, often hidden in peasants’ hay-carts, sometimes given shelter by jewish families, until he reached turkey. here, he was promptly arrested and imprisoned for having no passport. he was rescued by the british consul, who provided him with an identity card as a palestinian resident under the british mandate. he completed his journey by ship to jaffa and was sent by hashomer hatzair to degania, a kibbutz in the north. at first, he spoke entirely in the language of the bible, but soon became fluent in modern hebrew. from 1919 to 1924 he worked as a halutz (“pioneer”), harvesting oranges and lemons, draining marshes, ploughing stony hillsides, planting trees, building roads by hand. the pioneers lived in tents by the roadside. in the evenings they sang hebrew songs round the camp-fire; then guarded the settlements at night. on the road they were building from haifa to nazareth he met david horowitz, afterwards governor of the bank of israel, who much later was able to give first-hand testimony of their experiences to a un fact-finding mission. unknowingly zvi was one of the very first of the third aliyah (“going up”) that followed ww1 and the balfour declaration: a select group of inspired young people who were prepared to endure all kinds of hardships and privations in pursuit of their pure zionist ideals. some of them were to become leading political and public figures in the development of the jewish state, others distinguished academics in europe and the usa. a reunion of these halutzim in london in the 1950s revealed their later achievements in many walks of life. zvi returned to poland briefly in 1922 to take his matriculation examinations for entry to university. all along this had been his intention while working on the land a textbook always with him in the roadside tent. the occasion to go to university came sooner than he expected or desired, as a result of contracting typhus and malaria that he was fortunate to survive. polish universities operated a numerus clausus for jewish applicants, so he left for italy in 1924. 4. idyllic italian years the duce, benito mussolini, had thrown open italian universities to foreign students, free of fees. it was a grandiose gesture which succeeded in attracting many young intellects to italy. many were jews who were glad to leave the anti-semitism of poland and eastern europe for study and work in a friendly and relatively free country. zvi made his way to florence where he signed up to study engineering but switched to chemistry after a few months because to him it was far more exciting, reaching towards an understanding of the secrets of figure 1. zvi enrico jolles (left) with a colleague in a laboratory of the institutes of chemistry of the university of florence (from the private collection of the jolles-bainbridge family, now in the fondo jolles at florence university museum of natural history). 126 irene bainbridge life. at the same time, he enrolled his younger brother benjamin to read medicine and sent him a telegram to come quickly from lvov. it was for a long time a matter of regret to him that he had not chosen medicine for himself; but he had been motivated by the length of the courses and the necessity to start earning a living as soon as possible. his father was finding it difficult to continue sending his sons an allowance for their keep in italy because the newly formed polish government was unfavourable to jewish businesses, many of which were in serious decline. zvi’s brother, benjamin, had also found difficulty in getting admission to a polish university because of the restrictive quota. after completing his medical studies in florence he went on to become an outstanding pioneer of new methods in radiotherapy and palliative care. he was the only one of the immediate family whom zvi managed to extricate from poland before the havoc of the holocaust destroyed the rest of the family along with the whole jewish community which had flourished in lvov. the streets and houses are still recognisable today, but there is no trace of the lively communities which once existed. indeed the yad vashem memorial in jerusalem is grim testimony to the genocide which decimated the jews of europe. meanwhile, zvi showed such promise that he was greatly favoured by professor angelo angeli (an internationally renowned chemist referred to by his pupils as the ”maestro”), who appointed him as his assistant. when zvi had disembarked in naples he spoke in his best high-school latin. now he rapidly became f luent in italian, later delivering lectures and writing many scientific papers in that language. he was an outstanding chemist and soon made his mark. in collaboration with the maestro, he became expert in the chemistry of nitro-, nitrosoand azoxycompounds,. he took his doctorate “summa cum laude” and was soon guiding and teaching colleagues who had started their studies at the same time. in 1930 he was awarded the prestigious “ugo schiff prize” in chemistry3. though dogged by the lack of italian nationality, zvi threw himself energetically into appointments such as “assistente volontario” and “supplente” in the department of chemistry. during angeli’s last illness he took on the burden of most of the teaching duties of the maestro and supervised many doctoral students’ theses4 and dissertations. indeed, among them are some now illustrious names such as giovanni speroni. angeli wrote letters5 to support zvi’s application for citizenship but he died in 1931 and did not live to see it granted later that year. promotion to “assistente incaricato alla cattedra di chimica organica” and “aiuto in chimica farmaceutica” and further qualifications followed, including diplomas in pharmacy: from parma a professional one and from florence an academic one. finally in 1936 he attained the “libera docenza”. those were fertile years in his work both at the university and in outside appointments and he was the recipient, for two consecutive years, of the university prize for “operosita”6. he was appointed consultant to the explosives firm bombrini parodi delfino, and to the directorate of naval armaments in rome; and in the long hot summer vacations, while we holidayed with our mother in the cool of the dolomites, he would travel to ferrara to act as consultant to the zuccherifici nazionali (national sugar laboratories) for their annual sugar beet campaign. 1n 1937 he created a special course in applied chemistry which was attended by a wide range of people beside the undergraduates and doctoral students: industrial and government chemists, military officers and business executives. this new course soon gained official recognition by the university: professor passerini, then head of the faculty, wrote commending it7 and in 1937 zvi was confirmed associate professor of applied chemistry7. it was in florence that he met his wife, nidda coceani, who was doing a doctorate in italian literature of figure 2. zvi with the “maestro” angelo angeli in pracchia (pistoia, italy); (from the private collection of the jolles-bainbridge family, now in the fondo jolles at florence university museum of natural history). 127zvi enrico jolles pioneer in applied chemistry the “romance period”. she had trained as a schoolteacher in gorizia and was taking advantage of the offer of free university tuition extended to residents of venezia giulia. it was to be seven years before they were able to marry, only when they had achieved financial security: that was how people conducted their lives in those times. they had two children, giosuè (joshua) and irene, and enjoyed a happy family life, often entertaining colleagues and students at their home. during those years, lasting friendships were forged, as is clear from the correspondence with colleagues both inside and outside italy and now preserved in the fondo jolles of the “ugo schiff ” department of chemistry of florence university. 5. escape to england and a new life alas, it was too good to last: mussolini on his illfated visit to nazi germany, signed an accord which created the fascist “axis”; and in 1938 the italian fascist government began to apply its own punitive racial laws8 in italy, a country which had traditionally been tolerant of minorities. on 13th october 1938 zvi received a letter from the rector of the university9 informing him that he was dismissed from his teaching posts and any other official appointments “on account of hebrew race”. he had also had his italian citizenship revoked by the september 1938 legislature. he did not tarry. on 24th october 1938 he arrived in folkestone, england, carrying a precious invitation from his sponsor, professor robert robison (of the “robison ester” in sugar metabolism). they had met briefly at the 10th international congress of pure and applied chemistry in rome in 1936, where zvi jolles had presented a paper. his entry to england on an italian passport was problematic, being on condition that he would be returning to italy within one month. he worked initially at the lister institute for preventive medicine in london, where he applied his knowledge of sugar chemistry to carry out research into the protective coat which surrounds certain bacteria. unfortunately this was temporary, unpaid work and there was an urgent need for a salary to support his wife and family as his meagre savings were rapidly dwindling. when he arrived in england he spoke the english of dickens, having read “david copperfield” in his polish high school. now for a third time, he became fluent in figure 3. zvi (in the centre) with collaborators at pontelagoscuro, just before the departure from italy; (from the private collection of the jolles-bainbridge family, now in the fondo jolles at florence university museum of natural history). figure 4. giosuè and irene in italy (1938); (from the private collection of the jolles-bainbridge family, now in the fondo jolles at florence university museum of natural history). 128 irene bainbridge a new language, writing scientific texts and innumerable letters of application for financial support and permanent work, using his beloved olivetti typewriter, one of the few possessions he brought from italy. amid the mounting tensions of the 1930s, british men and women of goodwill could see that there was no time to lose. a group of mainly oxford, cambridge and london academics, under the leadership of lord beveridge, had earlier established the academic assistance council, which then became the society for the protection of science and learning (spsl). its express purpose was to extricate threatened academics mainly jewish from the nazi and fascist menace in continental europe. the aim was to help them rebuild their careers. a key figure in the work of the spsl was esther simpson10, assistant secretary at the time, who helped scores of refugee academics and their families, whom she came to know personally. the natural empathy she brought to the task was a lifeline through what were very difficult times. for my parents it was a hand-to-mouth existence as the loans from the society were necessarily small. but they kept us going through those dark years. much of the correspondence with my parents from that period is preserved in the archives of the spsl in the bodleian library in oxford11 . it was with immense gratitude that zvi accepted ongoing help and moral support from them. it is recorded that he later repaid every penny he received, but the support went far beyond the material help available. although in britain there was an initial reluctance to adopt the newcomers and give them full scope for their professional talents, it is true to say that the virulent anti-semitic policies in nazi germany and most of eastern europe created a veritable “brain drain”, benefiting britain and indeed the us, who thereby gained a long-lasting lead over the rest of the world in science, technology and medicine. in the summer of 1940 zvi was delighted to be offered a place with the imperial chemical industries in their research department in blackley, manchester, but this was short-lived. only two weeks later, on 10th june 1940, italy entered the war, invading france in support of their nazi allies (to the great reluctance of most italians who saw germany as a traditional enemy of italy and austria a hated occupying power in important areas of northern italy). two policemen came to the ici library to arrest zvi. ironically, on arrival in england, zvi was regarded as an italian citizen and therefore now became an “enemy alien”. following churchill’s famous instruction to “collar the lot”, zvi was swept up with germans and austrians, nazis, fascists and anti-fascists, socialists, refugees from fascism, restaurant owners, waiters and chefs, icecream merchants, businessmen, students, sailors from merchant ships caught in british ports, opera singers and instrumental musicians, roman catholic priests and monks, and a sizeable contingent of jewish academics and students; all interned together on the isle of man1 in what had been, in times of peace, a popular holiday resort. the only common factor to this assorted bunch was their origin from countries now at war. through the thorough, impersonal, even-handed workings of british bureaucracy they were housed by nationality in the hotels and boarding-houses of the island, surrounded by barbed-wire fences and guarded by the army. it was in this incongruous setting that he met an italian jewish businessman and engineer, alberto casali, who had been sent to britain by the stock distillery company of trieste, owned by his family, to study british distilleries. he, too, found himself interned as an “enemy alien”. thus began a life-long friendship which, many years later, had far-reaching consequences. it was not long before there was a veritable university in session! zvi jolles very soon began to teach chemistry to many of the students whose university courses had been interrupted. zvi was fond of relating how quickly everyone fell into their accustomed professional and occupational habits and attitudes. the chefs figure 5. zvi enrico jolles in the passport photo of 1938; (from the private collection of the jolles-bainbridge family, now in the fondo jolles at florence university museum of natural history). 129zvi enrico jolles pioneer in applied chemistry cooked, the businessmen organised rotas, the musicians rehearsed and presented recitals and the academics taught the students and discussed the latest theories. zvi’s internment only lasted six weeks – it was not long before the intervention of ici, in those days a real power in the land, secured his prompt return to their research department. when they heard he was leaving, his fellow-internees, fascists, students, priests, sea captains, saved their meagre rations, from which some of london’s finest chefs cooked up a banquet in his honour, attended by representatives of all the diverse groups. he was lucky not to have been selected for transportation to the colonies. the ill-fated “arandora star”, bound for canada, with twelve hundred on board, was torpedoed by a german submarine in the irish sea. hundreds went down with the ship. there were only five hundred and thirty survivors, many of whom were then loaded onto the “donera” bound for australia! back in the ici research department, zvi jolles immersed himself in searching for novel chemical compounds which could have useful applications in medicine or technology. from his experience in sugar chemistry, he envisaged the many hydroxyl groups of cellulose and other polysaccharides as rows of hooks to which appropriately reactive molecules could be attached, perhaps as carriers or linking agents for other molecules with desirable properties. arising from this work it occurred to him that it should be quite feasible to attach dyestuffs chemically to cotton fibres, giving them exceptional reistance to wash and wear. dyeing of cotton had hitherto depended not very successfully on physical properties such as hydrogen bonding, van der waals forces, molecular configuration, or on precipitation of the dye within the fibre for instance as metal salts. true chemical bonding was a kind of holy grail; it had been investigated but was not seen as a practical proposition for industrial application. zvi jolles brought fresh thinking to it, with his expertise in other areas of chemistry. 6. difficult times new developments the research department in hexagon house lay in a deep valley by a tributary of the river irwell, just outside manchester. the village of blackley had been overwhelmed by the industrial revolution; its rows of terraced houses were occupied by the workers who toiled in its sprawling industries. the main road spiralled down into the valley, which was almost permanently shrouded in a pall of acidic yellowish fog with tints depending on the prevailing production process taking place in ici’s plant. on a cliff high above the valley stood the “woodlands club”, a substantial victorian pile which served as ici’s clubhouse, where the senior staff of the research department held their monthly meeting with their eminent external consultant, professor (later sir) robert robinson (later to become president of the royal society). prof. robinson was sceptical of the notion of dyestuff-fibre combination until zvi brought to the meeting some extremely wash-fast brilliant orange cotton squares where the colour proved to be in true combination with the fibre. the work was not taken further at this time unfortunately, perhaps because zvi jolles now began to suffer serious ill health; but the soundness of the basic idea was vindicated in ici’s later development of a whole range of procion dyes. during this time zvi had received news that his father and two brothers in lvov had been murdered by the germans their hiding-place believed to have been betrayed by a polish janitor, later hanged as a nazi collaborator. externally, zvi bore the dreadful news stoically, but it must have affected him deeply. as a result of a laboratory accident, he suffered a serious burn to his left hand; from then on he was dogged by illness year after year, no doubt aggravated by the grief within him. he spent many months in hospitals. supported by his wife and with tremendous fortitude he emerged from this dark period as resolute as ever and went on to write important contributions to major chemical reference books “quinones” in thorpe’s dictionary of applied chemistry12 and chapters on azo-, azoxyand nitrosoaromatic compounds, diazo-resins, hydroxylamines and others in “the chemistry of carbon compounds”13 (elsevier). in 1954 zvi was intrigued to read an advertisement by a small chemical company in london seeking to recruit a head of research and apparently having links with israel and he was eager to return, this time hoping to contribute to the development of a chemical industry there. in the dark days of 1941 he had already met dr. chaim weizman (himself a chemist and later to become the first president of the state of israel) in london to discuss this possibility, but had never been able to follow it through then because of health problems. within three months in this small company, zvi had developed a novel process for one of their main products. now came a curious twist: f.w.berk & co ltd., established in 1871 by a family of german immigrants, bought out the smaller company. berk manufactured a range of bromine compounds and had active links with israel, specifically with the dead sea works. zvi , now 130 irene bainbridge head of research of the whole company, once again took up the challenge of a new direction. since the 1920’s bromine had occupied a “niche” market, being used in the manufacture of lead “antiknock” additive to motor fuel. about 90% of the world bromine consumption at one time was, in fact, just for this use. but by the 1960’s public awareness of health and environmental issues was beginning to make a serious impact on the use, in all kinds of applications, of chemicals which contaminate the environment with toxic residues. this was bad news for bromine producers such as israel which had, in the dead sea works, one of the world’s richest sources of bromine. though there were major outlets for bromine in agriculture and photography, the outlook was not encouraging. not to be defeated, in 1959, zvi unveiled a comprehensive programme of work on fire-retardants for a variety of materials based on bromine, (particularly for use on passenger aircraft) a significant innovation in this field. with this project, he had found a circuitous route back to israel! he saw that the chemical literature, which had an abundance of information on chlorine and its compounds, was severely lacking it on the analogous bromine compounds as well as on the element itself. he set about compiling a monograph on the neglected halogen. with the assistance of an excellent personal secretary mrs. elsie barrett, wife of a chemist and herself an accomplished landscape painter he planned and collected material for his book. then once again, circumstances turned against him and he was struck down by a heart attack in 1963. with his characteristic faith and optimism, he carried on. the book “bromine and its compounds”14 (ernest benn, 1966) was widely acclaimed and became a standard reference work. 7. the realization of a dream in 1963 berk had asked zvi jolles to go to poland to represent them at the poznan trade fair. it was a bittersweet experience for him, his first visit to poland since he had left in1922 and all the tragic events that followed. he still spoke polish f luently and was well-received. then in 1964 he was asked to visit israel on behalf of the company. how he must have enjoyed that! it had taken him precisely forty years to return to the land he had dreamed about as a boy and worked in as a young man. when in 1966 he retired from his post as head of research at berk he was invited to israel as consultant to the national council for research and development (prime minister’s office) with special reference to the utilisation of israel’s raw materials. it was then that he thought of creating a bromine institute, taking as a model such establishments as the tin research institute in holland. each year in october, zvi and nidda travelled to israel, returning via italy in april or may, spending a few weeks in gorizia, trieste or venice, and reaching home in england in june, a very pleasant itinerary, which was some compensation for all the hard years. in recognition of the impetus that zvi jolles could give to applied chemistry in israel, he had been invited to the hebrew university in jerusalem as a visiting professor. when he travelled in 1966, he took with him copies of the bromine book, fresh off the press. taking a train to trieste, he went to visit his old friend alberto casali at his villa in opicina, in the hills above the town. alberto was now the head of the stock distillery company, with factories in italy, austria, south america and israel. he had been for some years the honorary british consul in trieste and had been decorated by the italian government for services to industry and exports. zvi and alberto talked about israel’s need to develop a lead in technology. the two men found much common ground and alberto casali decided to back the vision of an institute of applied chemistry. there followed a year and a half of negotiations with the weizman institute in rehovoth that ultimately stalled; then one day zvi had lunch with avraham harman, formerly israel’s ambassador to washington and at this time president of the hebrew university. within a week the whole scheme fell into place – the creation of the casali institute of applied chemistry15 on the givat ram campus was agreed. by 1969 the casali foundation had been established and the alberto and kathleen casali fellowship foundation was supporting a number of post-doctoral stufigure 6. zvi (left) with alberto casali; (from the private collection of the jolles-bainbridge family, now in the fondo jolles at florence university museum of natural history). 131zvi enrico jolles pioneer in applied chemistry dents at the hebrew university with grants and scholarships. by 1971 the foundation stone had been laid. the work of the institute was meanwhile taking place in borrowed premises, by kind permission of professor shaul patai. zvi jolles had been appointed professor of applied chemistry in the hebrew university and the first director of the institute, a fitting culmination to his career. while always maintaining the highest scientific standards of pure research, he was eager to find practical ways in which his work could benefit the wider community. unfortunately zvi jolles was now seriously ill, needing an operation, and as he felt he might not be able to see the building of the institute to its completion, he asked professor gabriel stein to take care of it until his return. not long after the operation he left this life on 13th june 1971 and was buried on the mount of repose (har hamenuhot) on the west side, looking towards tel aviv, in the section for professors of the hebrew university. 8. conclusions it has been our privilege to write about our father, zvi jolles. a man of exceptional qualities and culture, he spoke seven languages and understood at least nine. his warm personality and entertaining company, combined with a compassionate and courteous nature, endeared him to all who knew him. now almost half a century later, we can see how his aim to benefit society by research and development is being successfully achieved in his brainchild of applied chemistry in jerusalem, using modern technology in fields as diverse as biodegradable polymers, biomedical composites, security, forensics, environmental science, energy, water conservation, pharmaceutics, and geochemistry. 9. acknowledgements we are extremely grateful that florence university, his old alma mater, from which he was so cruelly exiled, should now see fit to house an archive in his name in the “ugo schiff ” department of chemistry, where the first flowering of his life’s work began. we would like to express our sincere thanks to prof goti, head of the department of organic chemistry, to prof antonio guarna and dr laura colli for their invaluable help and encouragement throughout the project, and to dr. anna teicher for her expert historical advice. i would like to express particular appreciation to dr. laura colli for her dedication and professionalism. she has driven the project forward with determination, gentle firmness and sheer hard work that is now reaping rewards with the establishment and progress of the chemical heritage project at florence university. we are very fortunate that it is in such capable hands for the time being at least. it is to be hoped that the support and recognition her work deserves will be ongoing. i owe her my personal thanks for guiding me through the stages of setting up the fondo jolles in memory of my father, with the vision and sensitivity she has brought to the task. bibliography 1. connery chappell, island of barbed wire, robert hale, london 1984. 2. sir martin gilbert, israel a history, black swan, 1998. 3. fondo jolles of “ugo schiff ” chemistry department of florence university, document: ugo schiff prize. figure 7. zvi in jerusalem, 1970; (from the private collection of the jolles-bainbridge family, now in the fondo jolles at florence university museum of natural history). 132 irene bainbridge 4,5. fondo jolles of “ugo schiff ” chemistry department of florence university, document: letters and lists. 6. archivi attività scientifica dell’ateneo, le monnier 1941. 7. fondo jolles of “ugo schiff ” chemistry department of florence university, document: passerini letters. 8. francesca cavarocchi, alessandra minerbi in razza e fascismo, vol.1 & 2, (enzo collotti), 1999. 9. fondo jolles of “ugo schiff ” chemistry department of florence university, document: dismissal letter. 10. ray cooper, refugee scholars conversations with tess simpson, r.m.cooper, 1992. 11. archives of society for protection of science and learning ref. zvi enrico jolles in bodleian library, oxford. 12. j.f. thorpe, thorpe’s dictionary of applied chemistry, longmans green, vol x, 1950. 13. a.e.h .rodd, chemistry of carbon compounds, elsevier, vols 3a, 3b, 1952, 1956. 14. z.e.jolles, ed. bromine and its compounds, ernest benn, london, 1966. 15. z.e.jolles, a project for an institute of applied chemistry prime minister’s office, jerusalem, 1969. held in fondo jolles and institute of applied chemistry, website http://casali.huji.ac.il. full curriculum vitae of z.e. jolles up to october 1969 is held by fondo jolles of “ugo schiff ” chemistry department florence university. substantia. an international journal of the history of chemistry 4(2) suppl.: 39-48, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-826 citation: t. gettongsong, m. taseidifar, r.m. pashley, b.w. ninham (2020) novel resins for efficient desalination. substantia 4(2) suppl.: 39-48. doi: 10.36253/substantia-826 copyright: © 2020 t. gettongsong, m. taseidifar, r.m. pashley, b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. novel resins for efficient desalination tanita gettongsong1, mojtaba taseidifar1, richard m. pashley1,*, barry w. ninham2 1 school of science, university of new south wales, canberra, northcott dr, campbell australia 2 department of applied mathematics, research school of physical sciences, the australian national university, canberra, australia *corresponding author: r.pashley@adfa.edu.au abstract. this paper reports the synthesis and properties of new polymer resins containing strong acid and base groups for optimising applications in desalination. several polyampholytic gels were synthesised with a ratio of 1:1 of strong acid (sulphonate) and strong base (quaternary ammonium) groups and a zwitterionic resin with a 1:1 strong acid and base ratio. the physico-chemical properties of these highly charged resins were studied in electrolyte solutions over a range of ph values, in particular: effects of chemical cross-linking, water and electrolyte swelling; bulk electrical conductivities and surface charging properties in different ph values. the results from absorption of nacl showed that the resins have considerable potential for more effective desalination than other resin-based techniques. keywords: zwitterionic polymer resin, polyampholytic resins, desalination, ionexchange resin, ammonium bicarbonate. introduction one of several themes of this substantia volume on novel technologies for water processing concerns desalination. it has been shown that mixed cationic and anionic ion exchange resins can be used to great effect in a new desalination process. this is far more efficient in all aspects (in excess of 30%) to the present best reverse osmosis (ro) and other techniques in use. the claim may seem extravagant. but it is the result of extensive evaluation by a major international company that builds ro plants worldwide. our aim here is to seek to improve this new ion exchange based technology even further. if we can build an ion exchange resin in which cationic and anionic exchange sites are on the same polymer, nanometers apart only, that in principle should do the job. few such synthetic polymers are known. hydrogels are composed of three-dimensional networks of polymers made of natural or synthetic materials that possess a high degree of flexibility. they have the ability to swell or de-swell, and to retain a significant fraction of water within their structure. in this study we have developed a new method to synthesise polyampholytic hydrogels containing strong acid and strong base 40 tanita gettongsong, mojtaba taseidifar, richard m. pashley, barry w. ninham ionic groups. the chemical and physical properties of highly charged hydrogels are of interest besides because of their potential as controllable shape materials.1 shape can be controlled in several ways: by moderating the electrostatic interaction between the strong acid and base groups, their degree of hydration and hydrophobicity and also by the extent of chemical cross-linking within the resin. the range of control variables, including chemical composition make these materials of interest for their mechanical and electrical properties, their water absorption/swelling properties and their potential for selective solute separation. especially because of the proximity of the cation and anion groups, the hofmeister effect and other specific ion effects offer wide flexibility beyond electrostatics alone. the combination of chemical bonding as well as hydration/hydrophobic interactions and van der waals forces offers a remarkably diverse range of materials with wide-ranging properties, and hence applications to specific ion separation.2,3 the background to hydrogels by definition a hydrogel is a polymeric material which swells significantly when immersed in aqueous solution. these polymers can be covalently or ionically crosslinked to control this swelling.4 hydrogels typically have water contents over 80% (by wt). non-crosslinked polyampholytic compounds can show gel-like properties due to ionic cross-links that are formed by one molecule with other polymer chains, which induces enhanced plasticity and higher yield stress. these compounds will completely dissolve in aqueous concentrated salt solutions (e.g. 4 m nacl) at high temperatures (> 50 °c), typically within days.1 this has been assumed to be because the electrostatic binding between the numerous oppositely charged groups, holding the matrix together, is weakened by the presence of an excess of oppositely charged ions in an immersing solution and also with increasing the temperature. prima facie this is not so. because even without salt the effective debye length is so small that electrostatic forces will be screened. with 4 m salt they are irrelevant. for many applications it is important to introduce controlled chemical cross-linking and swelling. the current study takes this issue on board for several hydrogels and, for comparison, a typical non-swelling polyzwitterionic resin. polyampholytes have already been used as additives in papermaking to improve strength.5 they are being considered for some biological replacement applications6 and for controlled drug release.7 recently, polyampholytic hydrogels have also been employed for the efficient removal of heavy metal ions from contaminated wastewater.8 these applications are facilitated by the highly accessible open structure of these swollen polymers in water.9 it was shown first by chandrasekar and pashley10 that commercial strong acid and strong base mixed resins might be used to advantage for desalting water; the exhausted resin being regenerated by a process involving ammonium bicarbonate (ab) rather than acid and base washing.10 see also other papers in this volume for detailed application. polyampholy tic latices have small particle sizes that are similar to the polyampholytic resins. typically, they contain weak acid and base carboxylic and tertiary amine groups. they have been recently synthesised and they show high ability to adsorb different divalent metal ions such as ca(ii), cd(ii), cu(ii), mg(ii), ni(ii), pb(ii) and zn(ii).11 another study has shown that these latices can exchange both cations and anions.12 similar ionic exchange properties are found in protein molecules as well as in biomolecules, which have both cationic and anionic sites to adsorb multivalent ions of either sign.13-15 there are a variety of factors that affect ion adsorption properties of polyampholytic ion exchange resins; including ph of the electrolyte solution16,17, temperature18,19, ionic strength of the electrolyte solutions20,21, the ratio of acid to basic groups and the affinities of specific counter ions.22-24 the polyampholytic latices are zwitterionic, and usually show a ph where they have net zero charge (pzc), or an isoelectric point (iep). in order to assign an effective iep of such latices that throws light on the behaviour of adsorption sites present on the particles, surface charge measurements and ionization models can be used.25-27 hydrogel based compounds sy nt hesised w it h 2-acrylamido-2-methylpropane sulfonic acid (amps) have attracted extensive attention due to their strong ionizable sulfonate group. amps dissociates completely over a wide ph range, so the hydrogels derived from it show ph independent swelling properties.28, 29 hydrogels containing amide and sulfonic groups, can form coordinate bonds with metal ions for water purification.30 ayman et al.31 prepared acrylamide (am) and amps based hydrogel. they found that these hydrogels can take up several heavy metal ions, such as cu (ii), cd (ii) and fe (iii) from aqueous solutions. the recovery of hydrogels was also produced by immersion in acidic media. yan et al.32 synthesised a series of homogeneous cross-linked uncharged and sulfonated hydrogel membranes using poly(ethylene glycol diacrylate) (pegda) copolymerized with amps. different concentrations of sodium chloride solutions were used to determine the 41novel resins for efficient desalination uptake of ion content (na+ and cl-) based on charge density measurements on the membranes. a novel development in hydrogels all the studies mentioned above dealt only with the physical properties of the final hydrogels without considering a way to regenerate them. therefore, interest has focused on finding novel sorbents with high adsorption capacities, fast adsorption/desorption rate, and easy separation and regeneration. the present work offers a novel regeneration process for depleted resins, using ammonium bicarbonate, that can regenerate the resins. since it can also be readily decomposed into ammonia and carbon dioxide gases, this offers a reusable compound for the adsorption/desorption regeneration process. that is, without the need to use acid and base regeneration. this property is unique to ammonium carbonate and is the basis of our desalination process. the work is motivated by a novel patented ion-exchange water desalination process with pct application number: pct/ au2019/p110031.33 the main subject of the patent is a cross-linked organic polymer containing mixed beads of both positively and negatively charged ions at the nano scale. by integrating the positively and negatively charged ions on the one polymer, the ions are much closer together, at a nano scale, which substantially improves their absorption capacity. the innovation relates to the application of a new, simple and low-cost method for continuously removing salt from the resin (i.e. resin regeneration process). the use of an environmentally inert ammonium bicarbonate (ab) wash avoids the requirement for the depletion of expensive chemical reagents (i.e. acids and bases) or for heat required for resin regeneration. these are major advances. these two innovations open up the possibility for other high-value applications of the technology, in addition to desalination applications, such as selective solute removal from contaminated water, for example, heavy metal ions and pfas ions. materials & methods 3-(methacryloylamino) propyl-trimethylammonium chloride (mptc) and 2-acrylamido-2-methylpropane sulfonic salt solution (amps) were used as strong acid cationic and strong base anionic monomers, respectively. alpha-ketoglutaric acid was used as the initiator. ethylene glycol dimethacrylate (egdma), and 25% glutaraldehyde (ga) were used during the synthesis as the chemical crosslinking agent. to synthesise the zwitterionic polymer compounds n’n’-methylene bisacrylamide, peg 400 and 1,3-propane sultone were used as monomers. several salts: 98% sodium chloride, 99% sodium sulphate, magnesium chloride (ar grade) and magnesium sulphate (ar grade) were used to study swelling and conductivity properties. all chemicals were used as purchased from sigma-aldrich, australia without further purification. electrical conductivity values of all the solutions were measured using a eutech con 700 conductivity bench. a zetasizer nano instrument (malvern instruments ltd.) was used to study the size distribution of the dry ground resin particles and the zeta-potentials of these particles dispersed in various electrolyte solutions. the chemical structures of the monomers used to produce the polyampholytic hydrogels are show in figure 1. the synthesised resins were characterised by microelemental analysis using vario micro cube elemental analysers (elementar analysensysteme gmbh, germany) and by fourier-transform infrared spectroscopy (ftir) in kbr from 400‒4000 cm-1, using a jasco ft/ ir-6000 ftir spectrometer. polyampholyte hydrogel synthesis method polyampholyte hydrogels were synthesized using a one-step copolymerization process. a mixed aqueous solution (monomers and initiator) was prepared and poured into the several reaction cells. it was found that glass cells with 0.5 cm tube diameter and 9.5 cm long were suitable for the polymerisation reaction. the fraction of chemicals in the reaction have been studied in different ratios, as shown in table 1. they were each irradiated with 365 nm uv light, 8 watts, (john morris scientific pty ltd.) for 15 hr at a distance of 5 cm. after polymerization, the product was immersed in a large amount of water for 1 week to reach equilibrium and to wash away the residual, unreacted chemicals. parameters were varied for the polymerization reaction; for example, the time for irradiation, distance between reaction cell and uv light source, as well as the ratio of chemical reactants and crosslinking agents. in the crosslinking processes, the product was treated by reflux reaction with glutaraldehyde and by uv copolymerization with added egdma. for our study, several reaction cells were designed and developed for the polymerization reaction, as shown in figure 2. firstly, a rectangular metal sheet made from 42 tanita gettongsong, mojtaba taseidifar, richard m. pashley, barry w. ninham tin and an upper plate glass cover was used, as recommended in the literature. however, the results showed that tin metal also reacts with the chemicals. th erefore, an all-glass rectangular reaction cell was developed. nevertheless, atmospheric gases still diff used into the mixture during uv polymerisation and aff ected the reaction. oxygen gas is known to react with radicals and can change the polymerisation reaction. an array of glass tubes with closed-off ends to reduce gas inlet diff usion was therefore used and this was found to be the most suitable reaction cell for the uv polymerisation reaction. zwitterionic resin synthesis method th e “zwitterionic” polymer shown in figure 3 was synthesised using 5 mmol of p-phenylene diamine (0.54 g) in 20 ml of dimethylformamide (dmf) together with amps* mptc** (a) monomers for synthesis of polyampholytic hydrogel *2-acrylamido-2-methyl-1-propanesulfonic acid sodium salt solution **3-(methacryloylamino) propyl-trimethylammonium chloride p-phenylene diamine 1,3-propane sultone (b) reactants for synthesis of zwitterionic resins figure 1. chemical structures of the monomers used to produce: (a) the polyampholytic hydrogel and (b) the zwitterionic resins. table 1. th e ratio of monomers (molar ratio), initiator and crosslinking agent used in various synthesis reactions. in this table the initiator concentrations 1-4 refer to the ratio of monomers and 0.25% mole of initiator (i.e. for ‘1’, and with ‘4’ corresponding to 1%). amps mptc 2-oxoglutaric acid egdma 1 1 1 1 1 4 1 2 1 2 1 1 1 1 1 1 1 1 4 2 1 1 1 2 1 1 4 2 a) rectangular metal sheet b) array of glass tubes figure 2. th is schematic fi gure shows the diff erent types of reaction cells that were designed and developed in the study. (a) rectangular metal and glass sheet with the reactive monomer liquid in the space between (b) an array of glass tubes with closed-off ends, with the reactive monomer liquid enclosed in the tubes. 43novel resins for efficient desalination 5 mmol of glutaraldehyde (0.47 ml) in 20 ml of dmf, prepared separately in a different beaker. the solutions were mixed and refluxed at 80 °c for 1 hr. then, 15 mmol of 1,3-propane sultone (1.32 ml) in 10 ml of dmf was added to the reaction and refluxed at 70 °c for 3 hr. the final product was washed several times with hot water to remove residual chemicals. the product was found to have a black gel-like form. the reason behind the colour is unclear, perhaps due to absorption of all light by the product, because of the aromatic ring of the product which has homo-lumo energy gaps that absorbs light in the visible wavelengths (400‒700 nm), causing the black appearance. from the molecular diagram it is clear that the c3 chain connecting the sulphonate to the imine n cation is not of sufficient length to allow close contact between the oppositely charged groups. this supports the view that this is indeed a zwitterionic polymer. however, it should also be realised that this polymer is not actually a pure zwitterionic polymer in any case because of the presence of a second imine group, which will readily become protonated in aqueous solutions below ph 10. this is due to the pka value of the imine group, which is around 10. in typical aqueous solutions this polymer will therefore actually be a 2+/1ionic polymer and on dissolution will also act to increase the solution ph. powdered resin samples preparation the products of the various polyampholyte hydrogels and the zwitterionic resin compound were allowed to completely dry in a fume cupboard at room temperature. a mortar and pestle dry-grinding system was used to produce finely ground particle samples of each dry resin. the resins were all in the water-washed state, prior to drying, to maintain maximum electrostatic binding of the polymer matrix and hence solid rigidity, to enhance dry-grinding efficiency. ft-ir results the ft-ir spectra was obtained for both resin samples and are given in figure 4. broad absorptions figure 3. the chemical structure of the pseudo zwitterionic polymer studied here, as quoted in34. figure 4. ft-ir spectra for zwitterionic resin (sample 1) and hydrogel resin (sample 2). 44 tanita gettongsong, mojtaba taseidifar, richard m. pashley, barry w. ninham around 3400 cm-1 indicate free o‒h. th e absorptions at 2900–3000 cm-1 are due to the c‒h asymmetric stretch. th e carboxybetaine was characterised by absorptions at 1181 cm-1 (c‒co‒c) stretched band in sample 2 for the hydrogel resin. also 1640 cm-1 indicates c=o stretching in this sample. th e aromatic ring stretching absorptions (c=c and c=n) for the sample 1 (zwitterionic resin) can be seen in the range 1413-1605 cm-1. th e characteristic absorption for sulfonate groups present in both resins, appear at 1034 cm-1, 1035 cm-1 and 1640 cm-1, which are highly intense.34 results and characterisation several polyampholytic hydrogels, produced without chemical crosslinking, were made from a ratio of 1:1 (amps: mptc) with initiator. th ese resins readily produced a clear fi lm on drying but were also easily dispersed in water, losing their structure, as illustrated in the example in figure 5. several polyampholytic hydrogels were formed with chemical crosslinking using egdma and ga. th ese were added to the polymerisation reaction mixture to reduce the aqueous swelling properties of the hydrogels. an example of a suitable ratio of polyampholyte hydrogel with crosslinking agent is 1 : 1 : 2 : 1 (amps : mptc : egdma : initiator ). note that in this scheme ‘1’ for the initiator refers to a level of 0.25 %. th e polymerisation results obtained show that chemically crosslinked hydrogels prevent the release of the constituent polymer chains when immersed in water, while still allowing substantial aqueous uptake or swelling. by comparison, the zwitterionic polymer containing similar charged groups, that is sulphonate and quaternary ammonium groups, produced a black powder which showed little or no swelling in water, as illustrated in figure 6. th e results of a swelling study showed that both zwitterionic polymer products did not show any signifi cant swelling in either pure water or a range of electrolyte solutions. th ese observations are consistent with the extent of chemical cross-linking expected in the fi nal product and the hydrophobicity of these polymers. a qualitative evaluation of the relative hydrophobicity of the powdered resin samples can be achieved using a simple ‘water fl oat test’. small amounts of both the cross-linked hydrogel (dry ground into powder) and the zwitterionic resin (dry ground) powder were carefully sprinkled onto the surface of water. th ese observations indicate that the zwitterionic resin is much more hydrophobic, which is also consistent with its lack of swelling when immersed in water. by comparison, the hydrogel resin both swells substantially in water and is water wet, and so readily enters the aqueous phase. th e fi nely dry-ground resin samples were dispersed by simple stirring in water and 1mm nacl solution at room temperature and the particle size distributions were measured using a malvern zetasizer light scattering instrument (model zs). in addition, the zeta potentials of the dispersed particles of each resin were measured in 1 mm nacl solution, at room temperature. typical results obtained are shown in table 2. th e elemental analysis for two polymer resins show similar results for n, h and s atoms in their chemical structures, except that the zwitterionic resin had a higher level of carbon compared to the hydrogel resin. th is is because the zwitterionic sample comprises a higher level of carbon in its aromatic rings. th ese results are averaged based on two analyses for each sample and the average values are given in table 3. a summary of typical results obtained using the two powdered resin samples dispersed in 1mm nacl in different ph values at room temperature is given in table 2. th e results indicate that the polyampholytic particles are typically clumped together in water. th is cannot be due to electrostatic binding between the positive and negative charged groups on facing polymer particles (a) (b) figure 5. these photographs illustrate that the polyamplolytic hydrogels formed without the use of chemical crosslinking agents formed clear plastic fi lms when dry (a) and then when equilibrated with excess water (b), the polymer chains completely dispersed. figure 6. th e product of the zwitterionic synthesis dry product (on left ) and the aft er 24 hours water-swelling (on right). 45novel resins for efficient desalination alone and must involve some specific hydration effects. it is known from extensive work on microemulsions, force measurements between surfactant bilayers and nmr that the quaternary ammonium group has two tightly bound water molecules of hydration. bromide, chloride, iodide and fluoride all bind strongly, and the ion pair is effectively neutral. these anions displace divalent sulphate ions. on the other hand sodium binds very strongly to the sulphonate group whereas other cations do not. so we expect that addition of nacl to the dispersion will weaken this inter-polymer-polymer binding, due to reduced hydration and polymer bridging forces. polymer swelling could not cause the large particle size differences seen in table 2. addition of salt should increase the swollen size of individual particles, as reported by kudaibergenov and ciferri, 2013.9 but as for above the effect can be expected to be ion specific. osmotic pressure effects caused by the 1 mm nacl solution will only be about 0.05 atm, which is too small to cause any significant dewatering of the resin particles. the standard argument for the overall negative zeta potential of the hydrogel particles in 1 mm nacl solution, shown in table 2, supposes that this is expected for polymers with similar densities of positive and negative charged groups because the na+ ion is more strongly hydrated than the clion and so is less readily adsorbed onto the particle surface. biological cells and the common, natural inorganic particles, such as quartz and clays, are negatively charged for the same reason. however the classical theory is erroneous but usually reasonable at very low salt.3537 we persist with the classical colloid science approach keeping in mind that it can be misleading. the zwitterionic resin particles were found to have a lower (in magnitude) negative zeta potential, see table 2. this is consistent with the additional imine group present on this zwitterionic molecule (see figure 3). it will protonate, depending on ph, and so should reduce the overall negative potential. a comparison of water swelling of the cross-linked (1:1:2:1 sample) polyampholytic hydrogel in pure water and in various 0.2 m electrolyte solutions was studied visually. the solutions were equilibrated for 24 hr at room temperature. the results showed that water content was typically found to be around 90% for chemically cross-linked gels immersed in a range of electrolyte solutions. these swelling results indicate that pure water produced the greatest swelling and that all of the salts reduced the swelling to a similar extent relative to pure water. and that there appeared to be no significant specific ion effects on the degree of swelling, even when the osmotic pressure of the solution was increased, say for mgcl2 and na2so4 solutions. at least the differences between the monovalent sodium and divalent magnesium are not significant. (that need not be so for other cations like nickel, or anions in the hofmeister series that have not yet been tested.) conductivity values bulk electrical conductivities of the swollen gels were measured and compared with bulk solution values for: water, nacl and mgso4 solutions, over a 3-day period. these results, given in tables 4-7, showed that the conductivity was reduced in the swollen gels by around 10 percent for each solution. in other words, there appeared to be no specific ion effects and the gels with a high-water content, gave electrical conductivities, even the two different electrolytes, roughly consistent with their water volume fraction. these results reflect the high-water content of these hydrogels. that these single polymer resins can make useful ion exchange resins is clearly demonstrated by their ability to absorb nacl from solution, as shown by the results given in table 4. the absorption trend shows that the zwitterionic resin offered a significant absorption capacity from 1 to 28 mmol/g for nacl solution from 0.1 m to 0.3 m, respectively. while the hydrogel resin absorption capacity increased from 4 to 9 mmol/g for the two nacl solutions. these results compare favourably with the most efficient commercially available, mixed-bed, strong acid and strong base resin systems, which absorb nacl from aqueous solution at a level typically of about 2.5 mmol/g. table 2. particle size distribution (radius in nm) and zeta potential (mv) of the two polymer resins in different ph solutions. note that all the samples were prepared in 1mm nacl solution and ph adjusted using 0.1 m naoh and 0.1 m hcl solution. ph size (r / nm) zeta potential (mv) hydrogel zwitterionic hydrogel zwitterionic 3 915 3849 -8.79 -5.65 6 1194 14700 -9 -19.2 9 9142 9180 -15.9 -17.5 table 3. total elemental analysis of two synthesised polymer resins. %c %h %n %s zwitterionic 53.44 5.81 8.98 5.40 hydrogel 43.92 8.60 8.69 6.24 46 tanita gettongsong, mojtaba taseidifar, richard m. pashley, barry w. ninham additional comments in the course of this work it was realised that the ‘zwitterionic’ polymeric resin compounds containing amide groups reported by tarannum and singh34 have been erroneously defined as zwitterionic. in fact, they are anionic resins only. this is because the nitrogen atom in the amide group will not be protonated under normal solution conditions. it can actually be protonated only in very strong acid solution. that is, the zwitterionic structure reported in the literature can only be formed in very strong acid solution. for all practical uses the resin acts as an anionic, sulphonated, resin. the pka of the conjugate acid nitrogen in an amide group present in the hydrogel resin, is about -0.5, which means that an acid with 3 m concentration is required to protonate the amide group in this resin to form a zwitterionic compound. adsorption isotherms for the zwitterionic resins showed a maximum nacl adsorption of about 28 mmol/g (dry wt.), while for the same concentration of nacl, hydrogel resins had adsorption levels of about 9 mmol/g (dry wt.). in addition, as also mentioned earlier, the other zwitterionic compound, used in this work, will have a protonated imine group in most aqueous solutions, in addition to the zwitterionic (sulphate/quaternary ammonium) group. hence, this compound is also not a ‘true’ zwitterionic polymer. this work was designed to extend the efficiency of a novel patented ion-exchange water desalination process. 33 in this patent, ammonium bicarbonate (ab) solution has been used to regenerate depleted mixed bed ion exchange resins for subsequent use in desalinating salt solutions. a bubble column evaporator (bce) can then be used to decompose the ab product solution into drinking water, ammonia (nh3) and carbon dioxide (co2) gases; this is the subject of another work published in this special issue of substantia. the gases can then be collected into a cool aqueous solution for reuse in further regenerating the resin. a commercial-in-confidence report on this patent was prepared by the international engineering company arcadis for breakthrough water technology on behalf of a major international gold mining group. the results in this report show that this method is likely to be up to 30% more efficient and less energy consuming than current reverse osmosis (ro) and ion-exchange desalination processes. we will be working on this method to scale up the technique for commercial usage. this project aims to establish in a larger scale pilot unit for further testing, evaluation and development. table 8. the resin absorption capacities (+/0.5 mmol/g) estimated from the measured absorption from aqueous nacl solutions (i.e. 0.1 and 0.3 m). resin mmol/g of absorption 0.1m 0.3m hydrogel 4.3 9.3 zwitterionic 1.0 28.1 table 4. electrical conductivity results for the hydrogel polymer dry sample (weight 0.05 g) in 50 ml nacl solution (with an average experimental error of about ± 0.05 ms/cm). concentration (m) conductivity (ms/cm) before after 0.2 19.1 18.7 0.25 23.2 22.8 0.3 27.3 26.4 0.4 34.9 33.7 0.5 41.3 40.5 table 5. electrical conductivity results for the zwitterionic polymer sample (weight 0.05 g) in 50 ml nacl solution (with experimental error ± 0.05 ms/cm). concentration (m) conductivity (ms/cm) before after 0.1 10.4 10.3 0.3 27.5 24.8 0.5 35.4 34.1 table 6. electrical conductivity results for 0.2 m salt solutions (conductivity in solution) with experimental error ± 0.05 ms/cm. conductivity (ms/cm) day 0 day 1 day 2 day 3 nacl 18.9 18.7 18.6 18.4 mgso4 15.9 15.9 15.8 15.7 di water 0.002 0.013 0.04 0.05 table 7. electrical conductivity results for 0.2 m salt solutions (conductivity in gel) with experimental error ± 0.05 ms/cm. conductivity (ms/cm) day 0 day 1 day 2 day 3 nacl 15.6 16.7 16.3 mgso4 13.5 13.7 14.0 di water 0.04 0.04 0.06 47novel resins for efficient desalination conclusions a new uv method to produce polyampholy tic hydrogels was developed. it was found that it is very difficult to chemically cross-link the gels to reduce swelling in water. interestingly, the gels have a high-water content and their electrical conductivities, even in different electrolytes, are consistent with their water volume fraction. strong acid and strong base polyampholytic gels have some unusual chemical and physical properties. we also found that some zwitterionic resins reported in the literature have been erroneously classified. the results are encouraging. there is clear advantage for desalination applications for a resin with cationic and anionic ion exchange sites angstroms apart on the same polymer. by comparison, with conventional mixed cationic and anionic beads, presently available and evaluated and proposed for desalination, as is outlined in this volume, the oppositely charged groups can be millimeters apart. while we have seen in earlier papers that the mixed cationic and anionic resins are much more efficient than reverse osmosis, the new structures would be more efficient still. some further study to confirm the robustness of the regeneration process is necessary to confirm its expected successful availability as an efficient desalination system. a final comment. because of the very large variation in specific ion binding capacities of both the quaternary ammonium and sulphonate moieties of the gel it might be expected, that combined with the ammonium bicarbonate process, it might well have applications beyond ordinary desalination per se. there are very major problems with natural drinking water contamination with fluoride. and the perennial problem of nitrate and phosphate ions in runoff water in agriculture. we hope to tackle these issues subsequently. acknowledgments the authors would like to thank dr. mokhlesur rahman for his support and suggestions on the synthesising procedures. the authors also would like to thank dr. remi rouquette of macquarie university for the elemental analysis and the ftir analysis. 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gas, bubbles, salt and heat, curr. opin. colloid interface sci., 2017, 27, 25-32. 36. f. cugia, m. monduzzi, b.w. ninham, a. salis, interplay of ion specificity, ph and buffers: insights from electrophoretic mobility and ph measurements of lysozyme solutions, rsc advances, 2013, 3(17), 58825888. 37. a. salis, l. cappai, c. carucci, d.f. parsons, m. monduzzi, specific buffer effects on the intermolecular interactions among protein molecules at physiological ph, j. phy. chem. lett., 2020, 11(16), 68056811. substantia. an international journal of the history of chemistry 3(2) suppl. 3: 65-70, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-371 citation: h.-m. peter, c. sutter, w. schwenk (2019) study of a section of a self-purifying stream in specific relation to its water flow behaviour. substantia 3(2) suppl. 3: 65-70. doi: 10.13128/substantia-371 copyright: © 2019 h.-m. peter, c. sutter, w. schwenk. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. study of a section of a self-purifying stream in specific relation to its water flow behaviour heinz-michael peter, christine sutter*, wolfram schwenk institut für strömungswissenschaften, d-79737 herrischried e-mail: c.sutter@stroemungsinstitut.de abstract. the mettma, a mountain stream in the black forest in germany, had been polluted at a point source by effluent discharge from a brewery, and showed a section of self-purification along 8 km, without further interferences, following the effluent outfall. this section of stream had served as an excellent study model of the self-purification phenomenon, as much in the physico-chemistry and biology as in the hydrodynamic attributes of the water. the biological evolution along the stretch of self-purifying stream showed a succession of species typical of the food chain. to document the hydrodynamics of the stream water the drop picture method, a standardized testing method developed by theodor schwenk, was used, based on optically revealing internal flow structures. the watersamples upstream of the pollution source showed diverse and well shaped flow structures, whereas the samples at the effluent outfall appeared with a drastic reduction and inhibition of flow shape diversity and differentiation. after that point the internal flow structures became increasingly intense and diverse the further downstream. this evolution in movement diversity proceeded in parallel to the development of the biotic community, which showed a similar increase in diversity, differentiated morphology and functional differentiation away from the pollution point to the extent that at a distance of 8 km of the point source downstream a state similar to upstream of the effluent outfall was re-established. keywords. self-purification, water quality, flow structure, hydrodynamics, drop picture method. introduction the evaluation of water quality in lotic systems relies in principle on the analysis of physical, chemical and biological characteristics. our proposition here is to study a new descriptor of water quality, not just based on its constituent elements but taking into account the general and most outstanding characteristics of water as a liquid: its ability to move and flow, an essential function in its role as a life mediator. the hydrodynamics of water can be shown by using the drop picture method, developed by theodor schwenk and published in 1967.1 we looked at this new criterion of hydrodynamic behaviour and applied this methodology along a length of stream polluted at point source by biodegradable organic effluent, and compared the results with customary testing parameters. 66 heinz-michael peter, christine sutter, wolfram schwenk i. study framework and sampling this study included ten measurement campaigns from 1972 to 1977 carried out on the mettma,2 a mountain stream in the black forest, in collaboration with the institute of limnology, university of freiburg (germany).3,4,5 the mettma is a trout-inhabited stream, oligotrophic and with a low flow rate (150 to 1500 l/s) depending on the season. the ten surveys were done in different situations, including all seasons of the year. in this article however, we used the results collected in a testing survey carried out during a period of low water (192 l/s), the 26th of july 1974. at a certain point a brewery discharged organic pollutant into the stream, in a row effluent quantity of 6000 inhabitants equivalent. subsequently, the stream crossed a wooded mountainous zone and had no other interference apart from a dilution factor of 3 due to small tributaries. the study was terminated by the installation of a treatment plant at the brewery in 1977, and was spatially limited by the construction of a weir 9 km downstream of the effluent injection. the study included 11 sampling stations, one upstream and further stations 50, 300, 700, 1450, 1800, 3000, 3900, 5100, 7150 and 8000 m downstream of the effluent injection. different parameters were measured: temperature, ph, surface tension, dissolved oxygen, ammonium, phosphate and nitrate concentration. in addition, the biological situation of the ecosystem at the stations and the hydrodynamical quality of the water were analysed. ii. analysis and sequence of physicalchemical parameters ii.1 temperature the introduction of effluent increased the stream temperature from 10 to 13°c. the temperature was only slightly reduced over the total study section of 8000 m (fig. 1) ii.2 ph the mettma is naturally slightly acidic, with ph values of typically between 6.1 and 7.0. immediately downstream of the effluent injection, ph values oscillated between 6.1 and 10.4 because of the neutralization of the effluent. the ph levels stabilized after 3000 m. ii.3 surface tension the initial surface tension values corresponded to water free of surface-active substances, but decreased drastically at the effluent injection from 73 to 57 dyne/cm. the brewery effluent was chiefly composed of organic matter. 3000 m downstream, surface tension values stabilized at levels somewhat lower than the initial values (fig. 1). ii.4 dissolved oxygen close to total saturation upstream of the outfall, the dissolved oxygen values dropped dramatically to 35% at the injection due to the high oxygen demand of bacterial activity and oxidation of organic matter. oxygen levels progressively returned to their initial values 7150 m downstream (fig. 1). ii.5 ammonium and phosphates organic nitrogen and phosphorus were introduced by the effluent and microbially mineralised to ammonium and phosphates. phosphates reached maximum concentrations 50 m and ammonium 300 m downstream as products of the breakdown of the introduced organic matter. these pollutants were totally metabolised at the downstream checkpoint of 7150 m (fig. 2). ii.6 nitrate a product of the oxidation of ammonium, nitrate was initially only present at low levels. its concentration increased progressively along the length of the study section, levels did not totally stabilize at 8000 m downstream of the effluent injection (fig. 2). figure 1. evolution of temperature, dissolved oxygen and surface tension along the length of study section of the self-purifying stream (peter 1994). 67study of a section of a self-purifying stream in specific relation to its water flow behaviour iii. biological analysis iii.1 evolution of the biotic community initially, the mettma was an oligosaprobic balanced stream ecosystem ty pical to the trout zone. it was inhabited by a wide variety of animal and plant species which constituted its biotic community. 40 different species of benthic fauna were indicative of this diversity (fig. 3). the brewery effluent added an organic load equivalent to the raw effluents of 6000 inhabitants. this profoundly modified the ecological equilibrium of the ecosystem (fig. 4). the system became polysaprobic. life conditions favoured the development of filamentous bacteria (sphaerotilus natans) and ciliates and excluded other species. in this first polysaprobic zone which stretched for approximately 300 m, the number of benthic species plummeted to 2. the filamentous bacteria eventually detached themselves and were transported several hundred meters further, where they were deposited and became important nutrients for colonies of sludge-worms (tubifex tubifex) and chironomid larvae (prodiamesa olivacea). this degradation zone where the breakdown of organic matter dominated, ended with the appearance of blackfly larvae (odagmia ornata) and monocellular algae 2000 m downstream of the injection point. this marked the beginning of the primary production zone, with a succession of plant species from algae and mosses to higher vegetation. species of herbivores, such as freshwater limpets (ancylus fluviatilis) and mayfly larvae (baethis rhodani) as well as carnivores, such as stream amphipods (gammarus fossarum) and figure 2. ammonium (nh4+), nitrate (no3-) and phosphate (po43-) concentration in μg/l, as well as the oxygen saturation in % (peter 1994). figure 3. number of species (taxa) of animals on the stone substrate during the course of the self-purifying section (after schreiber 19756). figure 4. typical representatives of the benthic fauna the length of the self-purifying stream section (according to peter 1994). 68 heinz-michael peter, christine sutter, wolfram schwenk predatory larvae of various insect species, reinhabited the biotope. the trout-zone had fully regenerated after 7000 to 8000 m, the number of fauna species in the benthic zone reattaining its initial value. iii.2 polarities if we take into consideration the evolution, distribution, variety, morphology, mode of nutrition and locomotion of the benthic fauna, the following can be observed: • at the beginning of the self-purifying study section, species diversity was very reduced while population density was high. the organisms generally had a homogenously segmented morphology with radial symmetry. sensorial organs were very primitive. most organisms were sedentary and saprophage. their rhythm of activity depended only on the supply of nutrients, their life activity being orientated towards metabolism. • at the end of the self-purifying study section as before the eff luent outfall there was a greater species diversity while the population numbers remained modest. the morphology of the organisms was more complex with heterogeneous segmentation, axial symmetry and a greater body surface area. sensorial organs were located at the head, organisms were more mobile and were herbivores or carnivores. they followed day-and-night and seasonal rhythms. their activities were orientated towards sensorial functions and locomotion. iv. hydrodynamic analysis iv.1 the drop picture method the drop picture method, developed by theodor schwenk, allows the study of water’s aptitude for movement, its hydrodynamics. the method is carried out by the systematic and controlled agitation of a water sample through the impact of drops of distilled water released at 5 second intervals. each impact on the very shallow water sample creates internal movement and flow forms. the addition of a tiny amount of glycerine to the water samples facilitates the photographic optical visualization of the flow movements via a schlieren optic system. successive drops renew the created flow movements, so that a whole series of 30 drop-generated images was documented for each sample (fig. 5). the drop picture method was examined in the 2000s to optimise and standardize the testing methodology.7,8 the results are usually interpreted qualitatively, but may additionally be analysed based on quantitative analysis of for example the degree of development of vortex forms. the drop picture method indicates the given movement capacity of a water sample based on the level of complexity and differentiation of its internal flow forms. it is a morphological method, complementary to physical-chemical analysis, revealing more information about the hydrodynamic qualities of a water sample than its chemical composition. it is a system to evaluate water quality based on positive, life-giving criteria, rather than on exclusion of negative criteria. figure 5. drop picture method procedure and chlieren optic device. 69study of a section of a self-purifying stream in specific relation to its water flow behaviour iv.2 application to the section of self-purifying stream the testing points were identical to those of the previous studies. the water samples were analysed on the same day as they were collected. 30 images were produced for each water sample. here the 20th is selected to facilitate comparison between samples (fig. 6). we will now discuss the most distinctive phases along the stream self-purifying section.upstream of the eff luent outfall, drop-generated image revealed a garlanded composition of vortices where more extended vortices alternate with more stocky ones. leafy vortices could be observed, as well as radial dendritic structures. the successive 30 images during the analyse were relatively balanced, showing differentiated and varied structures, which were regenerated with each successive drop. downstream of the effluent injection the drop-generated images were significantly different. they were simply and solely composed of a disc-shape structure centred on the central point of impact. the forms were rudimentary, undifferentiated and monotonous. • 1800 m downstream, the disc-shape structure shrunk while in the centre the beginnings of differentiation the buds of heads of vortices could be identified. • about 3000 m downstream, the beginnings of leafy vortices and dendritic structures could be observed again. the closed disc-shape form had disappeared. by the end of the studied stretch of stream, the internal flows of the drop-generated image had returned to be the varied, complex and differentiated and polymorphic as in the sample upstream of the effluent injection. v. comparison of the different descriptors v.1 physical-chemical parameters and hydrodynamic evaluation v.1.1 point of inflexion the evaluation of the hydrodynamics of a given water sample is not based on any one drop-generated image but rather on the evolution of the ensemble of images. at some point each of the samples reaches a state where after a certain number of drops the garlanded structure shrinks, disappears and is replaced by a more rigid disc-shaped structure. this is what we call the “point of inflexion”, which occurs sooner or later in the tests, depending on the hydrodynamic qualities of the sample in question. this is a useful parameter. the drop number at which it occurs can be used to compare water samples taken along the length of study stream in question. w hen a disc-shaped structure appears in the first drop-generated image, the point of inflexion has already taken place before the start of the testing. v.1.2 comparison of results the graphical comparison of the levels of oxygen saturation, the point of inflexion and surface tension demonstrated a relationship between levels of oxygen and the point of inflexion. this relationship was however not causal but demonstrated that there is a correlation between these two factors and water quality. in most of the measurement surveys, the evolution of physical and chemical parameters stabilised well upstream compared to where the point of inflexion had stabilised (fig. 7). this in contrast only returned to its pre-effluent levels at the very end of the length of studied stream, parallel to the reestablishment of the biotic community to its initial figure 6. drop-generated images after the 20th drop the length of self-purification. figure 7. evolution of oxygen saturation, surface tension and point of inflexion (peter 1994). 1800 m upstream 3000 m 50 m 8000 m 700 m 70 heinz-michael peter, christine sutter, wolfram schwenk levels. this point of inflexion thus appeared to be a more sensitive descriptor, indicative of the overall state of the stream ecosystem. v.2 the biotic gradient and stream hydrodynamics it appeared that along the stream in question: • where the drop-generated image, in reference to previous images, had a closed, discand monotonous shape • where the drop-generated image showed a lack of mobility and a predetermined evolution, • there was the least species diversity, with the presence of sedentary, simple-structured organisms, whose activities were confined to their metabolic activity, that is to say after the effluent outfall. in addition: • where the drop-generated images revealed a maximum of polymorphic, diverse flow shapes, with the greatest complexity of movement in the water, where the images had a differentiated structure without being predetermined in their evolution • this is where biotic populations were varied and balanced, individual organisms having a more differentiated anatomy, complex nutrition and locomotion as well as being more sensitive to their environment due to more advanced sensorial organs, that is to say upstream of the effluent outfall and at the end of the stretch of self-purification. conclusions this comparative study of the physical-chemical, biological, and hydrodynamic characteristics of a selfpurifying section of the mettma proved that there are parallels between the degree of diversity in the biotic community and the degree of movement diversity in water samples from the same testing stations. in the degradation zone, where metabolism processes determined the physiology and activity of the animal population, water samples showed monotonous and weakly defined flow shapes. in contrast, in the primary production zone where, thanks to primary production by vegetation, anabolic processes dominated, the water samples showed diverse and differentiated water flow shapes. thus, very different phenomena could carry the same signature of a shared intrinsic quality. physical-chemical parameters are descriptors of a specific moment of the stream. the biological indicators reveal a more integrated long-term picture of the water, whereas the hydrodynamic analysis revealed the momentary but holistic state of the water. references: 1. schwenk, t. (1967). bewegungsformen des wassers. stuttgart. 2. peter, h. m. (1994). das strömungsverhalten des wassers in der biologischen selbstreinigungsstrecke des schwarzwaldbaches mettma. sensibles wasser 4, 1-160, herrischried. 3. franke, u. & schwoerbel, j. (1972). hydrographie, chemie und nährstoffracht eines mit organischen abwässern verunreinigten gebirgsbaches. arch. hydrobiol. suppl. 42, 95-124. 4. reichardt w. & simon, m. (1972). die mettma ein gebirgsbach als brauereivorfluter. mikrobiologische untersuchungen entlang eines abwasser-substratgradienten. arch hydrobiol. suppl. 42, 125-138. 5. schwoerbel, j. (1972). falkauer fließwasser-untersuchungen an der mettma. arch hydrobiol. suppl. 42, 91-94. 6. schreiber, i. (1975). biologische gewässerbeurteilung der mettma anhand des makrozoobenthos: methodenvergleich. arch. hydrobiol. suppl. 47, 432457. 7. wilkens, a., m. jacobi & w. schwenk (2000). die versuchstechnik der tropfbildmethode. dokumentation und anleitung. sensibles wasser 5, herrischried. 8. wilkens, a., m. jacobi & w. schwenk (2005). understanding water. edinburgh.1 1original title: suivi du parcours d’autoépuration d’un ruisseau par la dynamique de ses eaux (2004). société hydrotechnique de france. shf-publications 28èmes journées de l’hydraulique, 31-38. paris substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 1(2): 111-121, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-31 citation: f. naso (2017) mario betti: a giant in the chemistry scenario of the twentieth century. substantia 1(2): 111-121. doi: 10.13128/substantia-31 copyright: © 2017 f. naso. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declared that no competing interests exist. historical article mario betti: a giant in the chemistry scenario of the twentieth century francesco naso synchimia srl, spin off university of bari, italy, dipartimento di chimica, via orabona, 4, 70126, bari e-mail: francesco.naso@uniba.it abstract. the life of the chemist mario betti (1875-1942) is presented by focusing on the activity performed at the university of several italian cities. born in bagni di lucca, a small town in tuscany, in 1897 he graduated in chemistry at the university of pisa, under the supervision of roberto schiff, nephew of the famous ugo. in 1900, he moved to the university of florence, where he published a three component reaction which became known world-wide as the betti reaction and, nowadays, represents a synthetic tool of increasing use. the product deriving from the reaction can be easily obtained optically resolved and used as ligand in catalysts of nucleophilic attack on carbonyl compounds. since then, stereochemistry was the subject in which the most relevant achievements of the italian chemist were made. after working in florence, betti spent a ten years long period at the university of siena, where he covered the role of faculty dean and rector. in 1922 he was hired by the university of bologna as successor of the famous giacomo ciamician. in this article the many merits of this open minded and farsighted man will be presented against a background with chemistry and chemists of the 20th century playing on the scene. the conclusion is reached that the chemical heritage of mario betti, after a long time from his death, appears richer than previously thought. keywords. betti reaction, betti base, mannich reaction, chirality, asymmetric synthesis. 1. introduction chirality (the existence of a couple of compounds that are non-superimposable mirror images, i.e. enantiomers) is a wide topic of paramount importance in chemistry. several features of interest concerning this type of stereoisomers, and, especially, the maniacal preference shown by mother nature towards one of them, are still unclear. the chemist-writer primo levi was attracted by this “beautiful and fertile”1 theme ever since he started to prepare his degree thesis on the stereochemical problems connected with the walden inversion.2 later on, after becoming very famous for his literary masterpieces, he wrote an article where his enthusiasm for the enigmatic subject appears unchanged.1 as for me, stereochemistry, including chirality, was one of the areas in which i enjoyed working since the early stages of my 112 francesco naso scientific career. during this activity, reading literature papers i met the name of mario betti and eagerly studied his work, thus becoming aware of the importance of his ideas and achievements. at the same time, i got convinced that the scientific potential generated by the betti’s chemistry was far from being fully developed. as a consequence, my dedicated co-workers and myself decided to embark on a journey with the aim of expanding the betti’s chemistry and to use it as a tool for developing our interest in stereochemistry.3,4 furthermore, we wrote a review5 in order to increase further the attention towards the work of the italian scientist. the present contribution, that is mainly of biographical nature, aims to go in the same direction, hopefully, with the same success. 2. mario betti: the life6-10 2.1 the betti family and the pharmacy in bagni di lucca: music and drugs6,7 mario betti and his twin brother, adolfo, were born in bagni di lucca on march 21, 1875 from adelson and dalmanzina amadei. bagni di lucca is a small town in tuscany, situated about 60 miles northwest of florence. the town is rather well known for its thermal baths, that attract visitors from italy and foreign countries. it seems also worth noting that the celebrated chemist davy visited frequently the town with the aim of studying some hydrological problems. adelson betti was a chemist who owned an antique pharmacy, that had been established in 1709 and, after being run by generations of descendants of the first owners (the ghiareschi’s), in 1833 was inherited by adriano betti, son of ippolito and maria teresa ghiareschi. along the years, the place reached a high level of professionalism and attractiveness, also due to an uncommon library endowed with rare books. the pharmacy was also known by the inhabitants of bagni di lucca as “the english pharmacy”. the unusual adjective derived from the fact that around 1870 the pharmacy was awarded by the queen victoria the title of “pharmacy of the british embassy”, with the right of using the royal english coat of arms. adelson betti, son of adriano, was the subsequent owner of the pharmacy. being fond of music, he used to play organ in the bagni di lucca church. often, another young musician was playing there and the same man was frequently welcome as a guest at the betti house, located at the upper level of the pharmacy. one may imagine a place enveloped within a cloud of dream melodies, especially upon hearing that the young musician was giacomo puccini (1858-1924). the excellent hospitality of the betti’s was reciprocated by puccini who, gladly accepting an adelson request, composed the hymn vexilla regis for the local church. this musical background greatly inf luenced the two adelson’s twins. one of them, adolfo, after studying in italy and belgium, became a famous violinist, teacher and music editor. in particular, he is known for having led for years (1923-1929), as a first violinist, the flonzaley quartet. the ensemble, that was considered as the earliest topnotch american string quartet, gave approximately 2500 performances in the united states and another 500 in europe. when the quartet disbanded, adolfo betti taught music in new york for several years, receiving in 1933 the coolidge medal for eminent services to chamber music in the united states. later on, he returned to italy, becoming the mayor of bagni di lucca at the end of world war ii. adolfo betti died on december 2, 1950.7,11,12 the twin brother mario was also culturally inclined towards humanities, especially music and painting. however, he was afflicted by deforming arthritis and, on the other side, his presence in the pharmacy was badly needed by his father. at the time a pharmacy located in a small town represented an aggregation centre for the most important cultured men of the place. discussions on politics, social problems and other topics went on with a high frequency. this sort of cenacle was beneficial for the formation of the young mario. needless to say, a pharmaceutical path was planned for him. 2.2 the pisa period9,13 in 1892 mario betti registered as a student at the chemistry school of the university of pisa. the school had a high reputation, thanks also to the presence in previous times of well known chemists, such as raffaele piria (1814-1865), stanislao cannizzaro (1826-1910) and cesare bertagnini (1827-1857). at the beginning, betti chose to follow the course that, eventually, would have allowed him to obtain the “diploma in farmacia”, that he needed to direct a pharmacy and, as a result, a quiet future in bagni di lucca was easily predicted. however, after the first year, the university student realised that his growing interest in chemistry could have been hardly satisfied upon reaching this target. therefore, he changed his plans by asking to the faculty to be transferred to the second year of the course in chemistry and pharmaceutical sciences. the faculty was very reluctant to express the necessary opinion in favour and the transfer procedure stopped at a dead end. the young student, who had plenty of drive, decided to grasp the net113mario betti: a giant in the chemistry scenario of the twentieth century tle by lodging complaints in a letter addressed directly to the minister of education in rome, who happily solved the problem within a short time. most frequently, the research performed at the institute of pharmaceutical chemistry of pisa dealt with synthesis and behaviour of heterocyclic compounds or with relationship between structure and physical properties. at the same institute betti became a pupil of roberto schiff (1854-1940), son of the famous physiologist maurizio (1823-1896) and nephew of the great chemist ugo (1834-1915). the betti’s supervisor was of high intellectual level, but unhappy with his teaching duties (pharmaceutical chemistry), that he never liked. roberto felt much more attracted by the passion of collecting artworks, a field in which he had a rare expertise, luckily associated to a large availability of money deriving from his marriage with matilde giorgini (1860-1940), a rich girl who was a granddaughter of alessandro manzoni (1785-1873), one of the most famous italian writers and poets of all time. in spite of this distraction, roberto was able to establish with his student a fruitful co-operation, in which his fanciful ideas were driven into the real world by the experiments of the younger co-worker.9,13 in 1897, betti obtained his degree with a thesis on the reaction of methylisoxazolones with aldehydes and coauthored with roberto schiff the first two papers of his career.14,15,16 2.3 the florence period in 1898, betti moved to the university of florence as an assistant of ugo schiff, who was founder and director of the institute of chemistry. the famous chemist, well known for his bad tempered character, was not adequately friendly with his colleagues and showed a severe behaviour towards his students. a few anecdotes will suffice to understand the man. when a student started to work towards his thesis in the lab, schiff was used to play always the same scene. he gave to the student a low quality match box warning him with these words: you must keep in mind that you descend from berzelius because berzelius taught chemistry to the old wöhler and the old wöhler taught chemistry to me. a school can be honoured by its pupils, but it may be also stained: think it over.9,13 schiff was a follower of the classic approach to organic chemistry without any enthusiasm towards physical chemistry “interferences”. with his caustic style he liked to express the following opinion: one day some chemists lost their wish of working and for this reason they invented physical chemistry.9 the schiff ’s behaviour towards people of other disciplines was even more drastic. in 1879 the physicists and the chemists of the university of florence had to move to the same building. once they had moved there, schiff got in contrast with the physicist antonio roiti (1843-1921), an expert of electrology, who had to run his experiments during the night, due to the interferences caused by the trams passing in the neighbourhood during the daytime. at night, with the aim of disturbing the experiments of his colleague, schiff enjoyed moving metallic masses in the corridors of his floor located below the level of the physicist labs.13 the chemist augusto piccini (1854-1905), who in 1893 was professor of pharmaceutical chemistry in florence, is considered the author of a witty classification of the schiff family group. such a classification, related with oxidation state of the elements and nomenclature, required the definition of schiffico for maurizio, schiffoso for ugo, and iposchiffoso for roberto. even without inventing an english translation of these terms, the tricky joke is easily understood by taking into account that schifoso in italian means nasty.9,17 these funny tales have been reported here with the intention of emphasising the difficulties that betti expected when he entered the institute of chemistry in florence. he was going to face a supervisor who had a diametrically opposite character. fortunately, a miracle occurred because the two men shared the high sense of figure 1. ugo schiff and mario betti during a lecture in a classroom (courtesy of “ugo schiff ” chemistry department of florence university. chemical heritage project dco155). 114 francesco naso duty and the passion towards research. this was sufficient to establish the character compatibility needed. the driving forces towards a fruitful coexistence were strenghtened by the fact that the behaviour of the younger scientist was paved with a constant serenity, a convincing reasoning, and a kind way of acting. after a short time, due to a simple incident, schiff was obliged to take a long sick leave, during which betti became responsible for all research and teaching activities. on his return, ugo schiff deeply appreciated the work that had been made by his worthily substitute. his hearth became less hard, since he realised that, after all, his co-worker was inspired by the same ideals.9 on the other hand, the chemistry environment was very sparkly and this had a beneficial effect on the scientific productivity. in the florence laboratories, betti developed his interests in stereochemistry with important studies on the relationship between optical rotatory power and the structure of groups connected with the stereocentre.18 on performing these studies, a great advantage was achieved by the synthetic versatility of the reaction, nowadays known as the betti reaction, that in the original version produced 1-(α-aminobenzyl)-2-naphthol 1 (scheme 1), starting with 2-naphthol, benzaldehyde, and ammonia.19a the product begun to be known with the name of the author (i.e. betti base, 1) and the multi-component process was published in organic syntheses,19b a prestigious international book series, where only independently checked synthetic procedures are reported. finally, the base was also easily resolved into his optical isomers by means of tartaric acid. meanwhile, betti had gained high scientific reputation. the italian chemistry community had a clear sign that a new shining star was rising in italy during an important meeting held in parma (i.e. congresso della società per il progresso delle scienze, september 27, 1907). betti gave a speech on his research in a session chaired by emanuele paternò (1847-1935). at the end of the talk, the great chemist giacomo ciamician (18571922) expressed his enthusiasm and appreciation to the speaker in front of the audience.8,9 2.4 the siena period in the same year betti won a public selection for the chair of pharmaceutical chemistry in cagliari, where he worked two years and founded the institute of pharmaceutical chemistry. at the end of his stay in sardinia, another public selection led him to the university of siena. the time spent in this university was ten years long and fruitful and betti kept forever pleasant memories of this period. his professional experience was enriched by highly qualified management roles. indeed, he became first dean of the faculty of sciences and afterwards, at the age of forty, the youngest rector in italy. 2.5 the bologna period two subsequent competitive examinations occurred in the betti life. in 1921 he became professor at the university of genoa. in this city he met a young chemist who appeared to him very eager to explore the exciting world of molecules. giovanni battista bonino (18991985), this was the name of the enthusiastic fellow, impressed professor betti to such an extent that within a couple of weeks the young chemist was called to cover a temporary position as a technician at the university, in view of a more rewarding research oriented job. in january 2, 1922, giacomo ciamician died in bologna. the top level university, to which the famous chemist had contributed his highly qualified chemistry, stimulated the interest of many italian professors, who were eager to move to bologna. the success at the competition appeared soon an up-hill task. the italian term for “public competition” is “concorso”, but people of the community invented a whimsical neologism by making the “absolute superlative” of concorso, i.e. concorsissimo, and, besides this grammatically amusing term, nothing appeared more appropriate to convey to the interested people the idea of “the most difficult public competition of the century”.6 eventually, a prestigious ad hoc committee was formed. the group included authoritative chemistry professors, such as nicola parravano (18831938) and guido pellizzari (1858-1938). the merits of each of the many applicants were scrutinised and mario betti was unanimously selected.6 meanwhile, a new building was ready to host the chemists of the university of bologna. the direction of the new institute was entrusted to betti, who had to face financial problems that appeared exceedingly severe. updated instrumentation as well as furniture for the wide space were badly needed. on the other hand, the money granted was not sufficient even for the basic activity of the structure. the university fund that was scheme 1. structure of 1-(α-aminobenzyl)-2-naphthol. 115mario betti: a giant in the chemistry scenario of the twentieth century allotted each year amounted to 25,000 italian lire, a sum that, converted in today value, should roughly corresponds to 20,000 euro. nevertheless, betti undertook the uphill task and was able to give the start to the institute, that was called “ istituto di chimica giacomo ciamician” to honour the great chemist, who had made well known world-wide the top level chemistry performed at the university. during the early years of his stay in bologna, betti started to show his deep interest in the relation between in vitro chemical reactions and biochemical transformations. he realised that the boundaries between the two areas could be more blurred than commonly thought at the time. he wrote up his ideas on the matter in a book where topics connected to his stereochemical interests (e.g. asimmetry and life, enzymes) were dealt with.21 furthermore, he presented a communication on the same subject at the “congresso della società per l’avanzamento della scienza”, bologna, (from october 30 to november 5, 1926). the talk was scheduled for october 31 at the “archiginnasio”, one of the most important buildings of the city. in the same day, the leader of fascism, benito mussolini, was visiting bologna where the day before he had inaugurated the new stadium of the city (“stadio del littoriale”). mussolini wanted to attend the meeting and to listen some lectures of special interest, including the talk of betti.6,22 the meeting proceeded as expected. mussolini gave a talk in which he urged chemists to do both fundamental and applied research. furthermore, he was proud to mention the cases in which his government had spent a consistent amount of money to support scientific projects. the reader of this article will soon understand that this is the standard type of talk that even today any important politician would give at a scientific meeting. however, a difference does exist. luckily enough, in italy and in many other countries no politician would dare to share the opinion that mussolini expressed by encouraging chemists to work in areas of interest for the needs of war-time. at the end of his participation to the meeting, mussolini left the building in a procession of cars. after a stretch of road, he was shot by a teenager, anteo zamboni (1911-1926). the italian “duce” remained uninjured, whereas the shooter was immediately captured and lynched by a crazy crowd. lieutenant carlo alberto pasolini was the first to identify and to catch zamboni. the lieutenant was the father of pier paolo, (1922-1975), the famous italian writer, poet, movie director and intellectual.23 the comparison between man and mother nature in the matter transformation continued to be a fascinating topic for betti. meanwhile, his ideas were conveyed also to the man at the street. in some case the betti’s thoughts were not fully understood. in one article, the italian newspaper “la nazione” (april, 26-27, 1942) wrote: at other times a man like professor betti could undergo the risk of being sent to the stake.6 a critical point was the fact that betti oriented his interest not to philosophical problems concerning the reasons why things occur in nature but rather he wanted to know how they occur. in particular, due to his expertise, for betti one of the most important questions was how the chirality problem might be brilliantly solved with one enantiomer selection in reactions involving asymmetric natural agents, whereas a chemist working with common reagents is inevitably bound to obtain only mixtures containing equivalent amounts of antipodal isomers. indeed, several literature papers had shown the possibility of obtaining optically active material from a racemic mixture just by using the intervention of an enzyme as a catalyst that, due to its chemical nature, has many resolved stereo-centres. the process went through the preferential “destruction” of the faster reacting of the two isomers leaving unchanged and recoverable the slower reacting one. betti chose to evaluate a revolutionary innovation. the reaction of a normal grignard reagent with aldehydes was performed to produce an alcohol, but instead of a common solvent he used optically active dimethylbornylamine. as a result, the alcohol showed a small but significant optical resolution, thus evidencing the first asymmetric synthesis based on the use of a chiral ligand.24 we shall deal with this process in more details later on. for the moment, it seems more convenient to focus on the milestones of the route followed by betti in his attempt to imitate mother nature. indeed, almost at the same time, he wanted to check the possibility of using circularly polarized light as physical agent to induce asymmetry in the formation of an optical active compound. attempts had been made by using racemic mixtures to effect an asymmetric destruction, reporting cases of success. betti reasoned that chances could be higher by working in the gas phase, where intermolecular forces are weaker. for this reason, he chose to perform the reaction of addition of chlorine to propene. this process had also an additional advantage since it leads to a liquid product that separates from the gaseous reagents, in a way that, if a suitable reactor is used, the effect of the light after the addition reaction is avoided. this would makes unlikely any disturbing post-reaction on the liquid phase, such as an asymmetric destruction of the product. as a result of the actual experi116 francesco naso ment, a weakly optically active 1,2-dichloropropane was obtained. the first asymmetric synthesis under the influence of circularly polarized light had occurred.25,26 however, as we shall see later on, this result was considered controversial. during all his academic activity, betti showed a great interest also on applied problems for which he used his capacity of innovation. perhaps due to sentimental ties with his home town, he became a highly reputed expert of thermal water of many italian regions. in this field he introduced the use of the mobile laboratory with which it was possible to analyse water at the spring. another topic of interest was represented by chemistry and properties of rubber. the anti-gas mask used during world war one was significantly improved by him.6 towards the end of the year 1941, the health problems of betti became rather critical. nevertheless, he continued to do research. a communication on the asymmetric synthesis was presented at a meeting of the academy of sciences of bologna held on april 19, 1942. mario betti died on may 13. he was 67 years old. on may 15, 1942 bologna honoured the teacher and the scientist. the next day bagni di lucca honoured his son. more recently, the citizens placed a slab of marble on the external wall of the betti’s house that still include the antique pharmacy. the names of mario and adolfo betti were engraved in the epigraph together with a few nice words recalling the merits of the two men.27 atoms and notes, reactions and scores, chemistry and music are now close together. the life of betti was spangled by a variety of honours and a full list would be to long. just to mention a few, he was a member of accademia dei lincei and of the società italiana delle scienze detta dei xl. in 1939, he was nominated senator of the kingdom of italy. at that time the chairman of the senate was guglielmo marconi, who had already received the degree of doctor honoris causa in physics from betti, dean of the faculty of sciences at the university of bologna. 3. the chemical heritage of mario betti 3.1 the transition period most of the top papers of the last period of the life of betti had been co-authored by elio lucchi, who also worked at the same university. unfortunately, due to an accident, he died a few months after the departure of the senior scientist. for this reason, the important work that was going on in bologna suffered a stop. the passing of the torch had failed and the light on the betti’s chemistry became attenuated. during the same difficult period another great school of chemistry was rising in bologna, i.e. the school of industrial chemistry. when betti died, his former co-worker bonino was the dean of the faculty of industrial chemistry. in subsequent years he returned to the ciamician institute and the school of industrial chemistry was led by another farsighted great chemist, angelo mangini (1905-1988).28 the building with the labs was located on a hill and the chemistry developed there was called “the chemistry of the hill” whereas the ciamician institute was downtown in the lowland. under the leadership of bonino and mangini many difficulties deriving from the war times had to be overcame by both the “hill” and the “lowland” school. eventually, within a reasonable numbers of years they were both able to reach a high standard and a great reputation. in the years 1961-1968 bertoluzza and marinangeli of the ciamician institute published a series of papers29 dealing with one of the betti favourite themes, i.e. correlation between optical rotatory power and the nature of the group bound to the stereogenic centre. betti had made extensive work and established a correlation between structure and optical parameter. bonino, who figure 2. mario betti (courtesy of dr. massimo betti). 117mario betti: a giant in the chemistry scenario of the twentieth century had co-authored several papers on the topic, considered the betti correlation as “ the most important contribution to organic chemistry of the earliest part of the 20th century”.8 the merit of bertoluzza and marinangeli was represented by the efforts of revisiting the correlation with a new approach that included theoretical calculations, u.v. spectroscopy, and circular dichroism. in my opinion, despite the interest stimulated by his correlation, nowadays the fame of betti is supported by more solid bases and these will be dealt with in the following sections. 3.2. the betti reaction and the betti base thus far the attention of this article was focused on the “man betti” and to the scenario where he played, whereas chemistry was only occasionally mentioned. now, it is time to reverse the approach and to give a deeper insight into the activity of this great chemist, enlightening at least its most highest peaks. as already said, in its original version the betti reaction was represented by a multi-component process in which 2-naphthol, an ethanol solution of ammonia and 2 equivalents of benzaldehyde were involved. the product obtained in high yield could be described as deriving from the equilibrium between an iminoand an oxazino form. treatment of the reaction mixture first with hcl and then with naoh gave 1-(α-benzylamino)2-naphthol. many variations on the amino-reagent were considered, but it took a few decades to read about the possibility of replacing ammonia with a secondary amines. indeed, in a work reported in 1935 by littman and brode,30 dimethylamine and piperidine were successfully used. although commonly the research on this topic is focused on synthetic aspects, it seems reasonable that the reaction proceeds according to the following equations. the mechanism that was suggested as operating depended upon the nitrogen base used. (i) reaction with ammonia. when ammonia is used, as in the case of the prototypal reaction, the first step of the reaction should be the formation of an imine (scheme 2), that would be then attacked by the carbon nucleophile at the 1position of the naphtol (scheme 3): once the betti base 1 is formed, benzaldehyde easily leads to the imino-oxazino equilibrium between 2a and 2b, from which the final compound is regained by acidbase treatment (scheme 4). a similar sequence would be followed when a primary amine is used. (ii) reaction with secondary amines for the reaction with a secondary amine, the production of an aminal 3 as intermediate was suggested by littman and brode (scheme 5).30 the benzylidene diamine would then react with the carbon nucleophile leading to the final product by a substitution reaction. often, the betti reaction is referred to as a mannich or a mannich type reaction.31 indeed, the two reactions are very similar both in a form and with substance. if instead of a naphthol we consider the enol deriving from a carbonyl compound suitable for the mannich reaction we should envisage a behaviour very similar to the one reported above, provided that the oxazino-imino compounds are considered products deriving from the second attack of an aldehyde molecule. a problem arises when priority and name attribution to the two reactions are taken into account. betti published his reaction in 1900,19a whereas the paper of mannich appeared twelve years later.31 therefore, it is inappropriate to qualify the betti reaction as a mannich reaction. it would be tempting to do the reverse, but, after a century, it seems hopeless to modify a well established terminology practice. tilting at windmills should be better scheme 2. formation of the imine. scheme 3. formation of the betti base. scheme 4. post-reaction and regeneration of the betti base. 118 francesco naso replaced with a factual recognition of the merit of the italian scientist. during his activity betti was able to achieve a variety of optical resolutions and, actually, the first case that he studied was represented by his homonymous base, resolved with the classical procedure involving tartaric acid.20 since the possibility of obtaining a compound with high enantiomeric purity in a straightforward manner represents a convenient tool in organic synthesis, in 1998 at the university of bari we undertook work concerning the preparation of the betti base and similar structures, that we called using the plural form, i.e. betti bases. furthermore, we repeated the resolution of the prototypal base bringing minor changes to the original procedure and extending the resolution to other members of the family. the absolute configuration of 1-(α-benzylamino)-2-naphthol was established by x-ray experiments and this gave to us the possibility of assigning the configuration also to other bases. subsequently, prompted by our work, other research groups published important contributions reporting interesting and useful advances.5 a significant progress was achieved by palmieri32 with the reaction between 2-naphtol, arylaldehydes and (r)–phenylethylamine in absence of a solvent (scheme 6). the product 4 resulting from the reaction with benzaldehyde was enriched up to of 99% in one optical isomer with two stereogenic centres. 3.3 asymmetric synthesis the paper of palmieri and co-workers leads us to the theme of stereodifferentiating reactions,32 that becomes of special importance when the scientific activity of betti and his merits are presented. in 1940 betti e lucchi reported that the reaction of benzaldehyde with methylmagnesium iodide in n.ndimethylbornylamine as a solvent gave a 73% yield of 1-phenylethanol showing an optical rotation of +0.30°.24 the same alcohol was obtained with a rotation of +1.33° by reacting phenylmagnesium iodide with acetaldehyde in the same solvent. in their work the two authors reported a scheme that clearly suggests the reason why the reaction could lead to optical active product, showing the interaction between ligand and metal in the nucleophilic attack. such an interaction was fated to be the crucial aspect of a large number of reactions whose synthetic application have mushroomed under a variety of aspects.33 two years after the publication of betti and lucchi, their reactions were repeated by tarbell and paulson,34 who were not able to reproduce the stereochemical results. these authors attributed the optical activity that betti and lucchi had found to the formation of an optical active impurity as by-product of the reaction. it would be tempting to compare carefully the details of the two papers reporting contrasting results and to search for the origin of the differences between the two couples of scientists. a detailed analysis was performed by rosini35 in an engaging paper characterised also by an elegant and enjoyable style. a possible source of the discrepancy could be attributed to a difference in the stereoisomeric composition of the amine used by the two groups, but the inadequate information available does not permit to reach a safe conclusion. nevertheless, as appropriately commented by noyori,33 independently from the contrast existing between the results obtained in the two laboratories, the original concept of betti and lucchi remained valid. an undisputed proof appeared in 1953 when cohen and wright reported the reaction between ethyl benzoylformate and ethylmagnesium chloride in a mixture of benzene and (+)-dimethox ybutane.36 the resulting ethyl 2-hydrox y-2-phenylbutanoate showed an extent of asymmetric synthesis reaching about 5%. since the work of cohen and wright, the enantioselective alkylation of aldehydes was produced by many groups. a variety of ligands were used with enantiomeric excesses reaching very high values. the use of a catalyst having two co-ordinating centres, such as aminoalcohols, gave excellent results. scheme 5. reaction with a secondary amine. scheme 6. reaction between 2-naphtol, arylaldehydes and (r)–phenylethylamine. 119mario betti: a giant in the chemistry scenario of the twentieth century a large part of the merit that led noyori to achieve the nobel prize in chemistry 2001 derived from this type of synthesis. in connection with our work concerning the exploitation of the betti base, we entered the field with success by introducing ligands having the betti base structural theme.4,5 after sixty years, the betti original stereochemical idea was found to work at the best level by using the homonymous base. rosini noted that the story presents some fascinating aspects.35 as one would have expected, the work of our research group in bari elicited (and is still eliciting) many other applications, thus enlarging the arsenal of chiro-methodologies available to the chemist. 3.4. absolute asymmetric synthesis. in the writing of rosini a slight sensation of suspense accompanies the reader when the author deals with another paper by betti and lucchi concerning the synthesis of optically active substances.35 the work was presented at the congress held in italy in 1938, i.e. x° congresso internazionale di chimica, roma, maggio 15-21, 1938. the theme of the important meeting was rather appealing: chemistry at the service of human kind. a detailed report of the work appeared in the second volume of the abstracts.25 as usually, in the introduction betti and lucchi briefly review previous work made by others on the asymmetric synthesis performed in the presence of dextro or levocircularly polarized light. in a few words, a different situation existed between asymmetric destruction of racemic compounds and asymmetric synthesis: experiments on deracemization had led to products showing optical rotation, whereas in the case of asymmetric synthesis no compound with a defined and stable optical activity had been obtained at the time. the experiment set up by the two italian authors was represented by the gas phase addition of chlorine to propene to produce 1,2-dichloropropane. as already mentioned, a suitable apparatus was devised in order to separate the liquid product as soon as formed, thus avoiding an artefact connected with the possible deracemizazion of the produced chloroderivative. eventually, in the experiment performed by betti and lucchi the dihalogeno-compound produced under the effect of dextro or levocircularly polarized light was found to be optical active with rotations in the ranges from +0.040° to +0.050° and from –0.035° to –0.040°, respectively (the polarimeter sensibility was 0.005°). three years after the betti’s death, davis and ackerman reported the absolute asymmetric synthesis of tartaric acid,37 thus lending support to the feasibility of absolute asymmetric synthesis. surprisingly, three decades later boldt and coworkers failed to carry out the asymmetric cyclopropanation reaction between diazoalkanes and trimethylethene under the effect of circularly polarised light.38 the authors were then assailed with doubts concerning the possibility of achieving absolute asymmetric synthesis. their doubts became even more consistent when they decided to repeat the chlorination of propene and the synthesis of tartaric acid. the results previously reported were not reproduced and the sad story was told in a paper in which the scepticism of the authors was made clear even in the title (sinde absolute asymmetrische photosynthesis möglich?).38 however, almost in the same period evidence against this excessive scepticism was obtained by the successful absolute asymmetric synthesis of eptaand octa-elicenes.39 the reason of the difficulty met in the attempts to reproduce the betti results remains unclear. the enigma appears even more surprising if one considers that in the case investigated by the italian chemists it is not possible to invoke the formation of an adventitious by-product since the dichloropropane obtained in the reaction was characterised also by transformation into a different optically active compound, i.e.propylene glycol diacetate.26 so no wonder that the mystery that wraps the process stimulates interest even nowadays.40 considering the discussion presented in both sections 3.3 and 3.4, it seems wise to express the idea that the failure in reproducing results previously obtained by others cannot be taken as a verdict that the results are wrong. when discrepancies arise, extensive experiments should be repeated under strictly identical conditions. this is particularly valid when the expected results are associated to small values. 4. conclusions the end of the 20th century and the beginning of the present century have witnessed a steady increase in the production of work concerning the betti chemistry, whose importance now is appreciated in its real dimensions. the present article has been written with the aim of reporting together with the life of betti the peaks of his scientific and academic career. in spite of controversial aspects that inevitably occur in the activity of any great man, the stature of the chemist remains of a high standard. the trend of the impact of the work of the italian scientist in chemistry reveals that this opinion is even bound to be enforced in the future. the high moral stature of the man revealed by his personal history represents an added value. 120 francesco naso acknowledgments i’m indebted to dr. massimo betti, the grandson of mario, for kindly making available to me the couple of the manuscripts mentioned as ref. 6 and 7. it was a privilege for me to meet the ninth betti generation of chemists and to have “first hand” information on the protagonist of this article. on the chemistry side, i wish to express my gratitude to my former co-workers drs. cosimo cardellicchio and maria annunziata capozzi for sharing with me the enthusiasm to revisit the betti chemistry world. references 1. p. levi, l’asimmetria e la vita. articoli e saggi 19551987, einaudi torino, 2002, p.200. 2. p. levi, l’inversione di walden, tesi di laurea in chimica pura, regia università di torino, 1941. 3. c. cardellicchio, g. ciccarella, f. naso, e. schingaro, f. scordari, tetrahedron: asymmetry, 1998, 9, 3667. 4. c. cardellicchio, g. ciccarella, f. naso, f. perna, p. tortorella tetrahedron, 1999, 55, 14685. 5. c. cardellicchio, m.a.m. capozzi, f. naso, tetrahedron: asymmetry, 2010, 21, 507. 6. m. betti, chi era mario betti, manuscript sent to the author by massimo betti on july 13, 2010. 7. m. betti, l’antica farmacia betti di bagni di lucca, manuscript sent to the author by massimo betti on july 13, 2010; see also htpp://www.farmaciabetti.it/ storia.html., last accessed 30/05/2017. 8. g. b. bonino, discorso commemorativo del prof. mario betti tenuto dal prof. giovanni battista bonino nell’aula magna dell’università, 1943, tipografia compositori, bologna. 9. s. berlingozzi, gazz. chim. ital. 1953, 83, 693. 10. a. coppadoro, chimica e ind., 1942, 24, 187. 11. www.arsc-audio.org/journals/v19/v19n1p25-62.pdf., last accessed 18/03/2017. 12. htpp://pronetoviolins.blogspot.it/2014/06/adolfo-betti.html, last accessed on, 18/03/2017. 13. m. fontani, m.v. orna, m. costa, chimica e chimici a firenze. dall’ultimo dei medici al padre del centro europeo di risonanze magnetiche, firenze university press, firenze, 2015, 38. 14. m. betti, r. schiff, gazz. chim. ital., 1897, 27, ii, 206. 15. m. betti, r. schiff, ber. 1897, 30, 1337. 16. a list of 124 papers by betti and coworkers is reported in ref. 9. 17. for a variation of the scale, see m. fontani, m. costa, chimica e ind., 2011, 93, 106. 18. for reviews of the work on the topic, see m. betti, gazz. chim. ital.,1923, 53, 417; m. betti, g. b. bonino, memorie accad. sci. istituto bologna, 1925-1926, [8], 3, 39; 1929-1930, [8], 7, 81; trans far. soc. 1930, 26, 337. 19. (a) m. betti, gazz. chim. ital., 1900, 30, ii, 310; (b) organic syntheses, 1929, 9, 60. 20. m. betti, gazz. chim. ital.,1906, 36, ii, 392. 21. m. betti, problemi e aspetti della chimica della materia vivente, 1926, zanichelli, bologna. 22. a. charachalios, giovanni battista bonino and the making of quantum chemistry in italy in the 1930, in: chemical sciences in the 20th century. bridging boundaries, c. reinardt ed., chap. 4, p.75, wiley vch, weinheim, 2008. 23. https://storiedimenticate.wordpress.com/2012/10/31/ anteo-zamboni/, last accessed on 31/05/2017. 24. m. betti, e. lucchi, boll. sci. fac. chim. ind. bologna, 1940, i-ii, 2. 25. m. betti, e. lucchi, ricerca sci., 1937, 8, ii, 130; atti x congresso int. chimica, roma, 1938, 2, 112. 26. m. betti, e. lucchi, memorie accad. sci. ist. bologna, 1942, ix, 203. 27. http://www.chieracostui.com/costui/docs/search/ schedaoltre.asp?id=11081 , last accessed on 01/04/2017. 28. f. p. de ceglia (ed.) scienziati di puglia, secoli v a.c.xx1 d.c.: angelo mangini e i misteri della chimica organica dello zolfo, adda editore, bari, 2007, p. 551. 29. a. bertoluzza, a.m. marinangeli, annali chim. 1961, 51, 322; 1961, 51, 981; 1962, 52, 731; 1964, 54,1020; 1968, 58, 205. 30. j. b. littman, w. h. brode, j. am. chem. soc., 1935, 52, 1655. 31. c. mannich, w. krosche, arch. pharm., 1912, 250, 1647. 32. c. cimarelli, a. mozzanti, g. palmieri, e. volpini, j. org. chem. 2001, 66, 4759. 33. r. noyori, m. kitamura, angew. chem. int. ed. engl., 1991, 30, 49. 34. d. s. tarbell, m. c. paulson, j. am. chem. soc., 1942, 64, 2842. 35. g. rosini, rendiconti accademia nazionale delle scienze detta dei xl. memorie di scienze fisiche e naturali, 2003, 27, 1. 36. h. l. cohen, g. f. wright, j. org. chem., 1953, 18, 432. 37. t. l. davies, j. ackerman, jr., j. am. chem. soc., 1945, 67, 486. 38. p. boldt, w. thielecke, h. luthe, chem. ber, 1971, 104, 353. 121mario betti: a giant in the chemistry scenario of the twentieth century 39. w. j. berstein, m. calvin, o. buchardt, j. am. chem. soc. 1972, 94, 414; 1973, 95, 527; tetrahedron letters, 1972, 2195; h. kagan, a. moraddpour, j. f. nicoud, g. balavoin, r. m. balavoine, r.h. martin, j. p. cosyn, ibid., 1971, 2479. see also, a. guijarro, m. yus, the origin of chirality in the molecules of life , rcs publishing, cambridge, 2009, p. 48. 40. https://ilblogdellasci.wordpress.com/2017/05/22/qualcuno-puo-aiutarmi-a-spiegare-un, last accessed on 25/05/2017. substantia. an international journal of the history of chemistry 6(1): 133-143, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1498 citation: ramírez c.a. (2022) lipids, chloroform, and their intertwined histories. substantia 6(1): 133-143. doi: 10.36253/substantia-1498 received: nov 11, 2021 revised: jan 04, 2022 just accepted online: jan 10, 2022 published: mar 07, 2022 copyright: © 2022 ramírez c.a. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article lipids, chloroform, and their intertwined histories carlos a. ramírez department of chemical engineering, university of puerto rico, mayagüez, puerto rico email: carlos.ramirez9@upr.edu abstract. lipids and their fatty acid constituents, in particular, have been the subject of academic and industrial research initiatives since their isolation by michel-eugène chevreul in 1813. fatty acids can be saturated or unsaturated, their physical properties depending on the aliphatic chain length and degree of saturation. they constitute the building blocks of many lipid groups like triglycerides and phospholipids; are key additives in commercial foods, pharmaceuticals, and cosmetics; and can cross cell membranes. chloroform was synthesized in 1831 by samuel guthrie and has had a tortuous history of interactions with mankind: from an anesthetic in obstetrics, dentistry, and surgery, to being labeled as a potential carcinogen in the 1970s. it has also had important nonmedical applications such as in chemical engineering mass transfer systems designed to estimate binary gas diffusion coefficients. although chemically dissimilar, lipids and chloroform intertwined their scientific paths through the work of jordi folch and associates in the 1940s-1950s, in which many lipid-based brain molecules were isolated and characterized. this article outlines the separate histories of lipids and chloroform, and those research initiatives in which they have acted synergistically. the narrative covers the interplay of chemical compounds with different historical backgrounds, but with physical properties which continue to foster their interaction. keywords: lipids, fatty acids, cell membrane structure and function, chloroform synthesis and uses, lipid-based brain tissue components. i. introduction modern-day students and young researchers sometimes fail to identify events in one discipline that can help explain similar phenomena in another. they also have difficulty envisioning how materials with different physicochemical properties can lead to common applications. it is precisely this latter problem that serves as the goal of the present article. lipids and chloroform have long, separate histories. they have also shared scientific pathways for many decades, a fact likely unknown to most readers. as the initial step of an experimental research project involving a specific class of lipids and chloroform, their individual histories were scrutinized. their isolation, characterization, and synthesis were thoroughly studied, in many cases going back to the original published sources in the 19th century. http://www.fupress.com/substantia http://www.fupress.com/substantia 134 carlos a. ramírez it is our goal to summarize the historical scientific highlights of lipids (fatty acids in particular) and chloroform, leading to their combined usage to this day. their individual histories will be addressed separately, while their intertwined pathways will be covered in the last section. the best example of the synergistic use of lipids and chloroform is that their physical and chemical properties served to determine the structure and function of new families of mammalian brain tissue components. ii. lipids and their fatty acid constituents biochemistry is the science dealing with the chemistry of life, as well as the title of a timeless textbook written by professor albert l. lehninger of the johns hopkins university school of medicine, baltimore, md, usa.1 a chapter of this venerable reference is entitled “lipids, lipoproteins, and membranes”, a subject matter relevant to this work. lipids are natural substances present in animal and plant tissues. they are mostly insoluble in water, but soluble in many organic solvents. lipids are actually families of compounds, with similar physical and chemical characteristics, and can be conveniently grouped according to their backbone structure (table 1 and figure 1). for example, acylglycerols (triglycerides) are the most abundant lipids in nature. the reader must have heard of them when, during a routine medical checkup, the doctor pulled his/her ear for having a high blood triglyceride level. solid triglycerides are known as “fats” and their liquid counterparts as “oils”. they all have a glycerol (triol) backbone joined through ester linkages to fatty acids. the latter consist of a hydrocarbon (aliphatic) chain of varying length and degree of saturation, indicating the presence or absence of double bonds, with a carboxylic acid terminus. the following discussion will focus on fatty acids, since they are the building blocks of many lipid groups, as well as being part of our current research interests. in a later section, we will return to the broader lipid family as we explore its historical relationship with chloroform. fatty acids were first isolated in 1813 from animal fats (“corps gras”) by the french scientist micheleugène chevreul (1786-1889), professor of chemistry at the lycée charlemagne, paris.2 they have been the subject of extensive academic and industrial research ever since. within the body, fatty acids are found in their esterified form since they are practically insoluble in water. to illustrate with a numerical example, the saturated 6-carbon hexanoic acid has an approximate solubility of 1 g fatty acid per 100 g water at room temperature. this translates to a very small fatty acid mole fraction of order 10-3, with this quantity being relevant in mass transfer processes such as those found typically in the field of chemical engineering. the water solubility decreases considerably as the number of aliphatic carbons in the chain increases. fatty acids are transported in blood bound to serum albumin, a globular protein with an approximate molecular mass of 68000.1 they can also cross cell membranes, of which they are key constituents, by diffusion (proportional to a concentration gradient) and protein-facilitated mechanisms.3-12 fatty acids are metabolic precursors of many physiologically-relevant molecules as well as a source of energy for the organism. free (unbound) fatty acids are either unsaturated (single or multiple double bonds along the aliphatic chain) or saturated (no double bonds). they are named according to the number of carbon atoms in the chain and the location of the double bonds, if any. for example, the 16:0 saturated fatty acid corresponds to the 16-carbon palmitic acid [ch3(ch2)14cooh] which melts at +63.1°c. on the other hand, the 16:1(d9) monounsaturated fatty acid represents a 16-carbon chain with a double bond between the 9 and 10 carbons (by convention the carboxylic acid is the first carbon). this compound is known as palmitoleic acid table 1. lipid classification according to their backbone structure.1 the saponifiable lipids can be hydrolyzed to their building blocks which include fatty acids, while the nonsaponifiable lipids cannot be hydrolyzed. triglycerides are the most numerous in nature. phospholipids are the main constituents of cell membranes. lipid type molecular backbone complex (saponifiable) acylglycerols or triglycerides glycerol phosphoglycerides or phospholipids glycerol 3-phosphate sphingolipids sphingosine waxes high-molecular-weight nonpolar alcohols simple (nonsaponifiable) terpenes multiples of the 5-carbon hydrocarbon isoprene steroids perhydrocyclopentanophenanthrene prostaglandins obtained by cyclization of 20-carbon unsaturated fatty acids such as arachidonic acid 135lipids, chloroform, and their intertwined histories [ch3(ch 2)5ch= ch(ch 2)7cooh] which melts at -0.5°c. industrial applications of fatty acids include the preparation of soaps, detergents, and lubricants. they are also used as additives in foods, cosmetics, and pharmaceuticals. the book fatty acids and their derivatives by anderson w. ralston, assistant director of research at armour and company, chicago, il, usa, is still the classic starting point for both researchers and enthusiasts of fatty acid biochemistry.13 due to their importance in physiology and food science, fatty acids have been extensively characterized from the standpoint of their physicochemical and dissociation properties. the chronological development of some of these research lines is as follows: a) their very low aqueous dissociation constants were determined as far back as the 1930s, indicating that the vast majority of the fatty acid molecules in solution are nonionic;14-17 b) the mutual solubility of fatty acids and water has been known since the 1940s, demonstrating the effect of aliphatic chain length and temperature on this property;18-25 c) solute partitioning studies of fatty acids in organic solvent/aqueous systems, relevant to industrial separation and purification processes, have been undertaken since the 1950s to determine their relative solubility in immiscible media;26,27 d) chemical reactions at oil/water interfaces involving fatty acid-containing molecules were identified in the 1960s, with applications to the hydrolysis of triglycerides in the intestinal tract and to atmospheric photochemistry;28,29 and e) lyman c. craig and coworkers at the rockefeller institute for figure 1. two-dimensional chemical structures of some of the lipid groups in table 1. the fatty acids are the building blocks of triglycerides and phospholipids, which are saponifiable through alkali hydrolysis. the simple lipids like steroids are nonsaponifiable. source: https://cnx. org/resources/00a0b827644d73bfb8695b81a7c7801a. 136 carlos a. ramírez medical research, new york city, ny, usa, designed in the 1940s-1950s a rotary, multi-stage, liquid-liquid extractor using chemical engineering mass transfer principles to isolate and purify fatty acids from their mixtures, with one benchtop model allowing several thousand quantitative extractions in a few hours of operation!30-34 these landmark historical efforts highlight the importance fatty acids have attained in modern science, particularly their relevance in molecular transport across biological membranes which are discussed below. solute exchange across cell membranes is vital to animals and plants. elegant reviews have addressed the subject of transcellular transport of fatty acids, notwithstanding their limited solubility in aqueous media and the existence of lipid-based membrane resistances.4-6,12 debate in the literature lingers on the actual mass transfer mechanisms involved, but it is known that fatty acids are transported with relative ease through triglycerideand phospholipid-rich cell membranes. to support these findings, the fluid-mosaic model for membrane structure was proposed by singer and nicolson in 197235 and, even though it has been upgraded conceptually in the last fifty years due to refinements in experimental techniques and instrumentation, remains relevant to this day.36-48 the original model is sketched in figure 2 (top) and shows a phospholipid bilayer interspersed with globular (integral) proteins. membrane phospholipids contain fatty acids attached through ester linkages. their hydrophilic heads point outward to the aqueous media, while the hydrophobic ends (fatty acids) point inward. the upgraded model depicted in figure 2 (bottom) indicates that membrane architecture is more complex than originally proposed. current scientific knowledge describes the membrane as consisting of protein and lipid domains. these are constituted by multiple chemical species that interact dynamically with the cytoskeleton and the extracellular matrix. the most important lines of research related to membrane structure and function since the appearance of the fluidmosaic model35 are: a) the isolation and characterization of membrane proteins;38,47 b) elucidation of membrane molecular signaling and trafficking pathways;41,42,45-47 c) proof of the existence of membrane protein and lipid domains;36,37,43-47 d) a description of membrane lateral motion, confinement, and turnover;38-40,42,43,45-47 e) the roles played by membrane-associated cytoskeletal fences and the extracellular matrix in restricting the lateral diffusion of membrane components;44,47 and f ) characterization of the asymmetry of lipid distribution between the leaflets of the plasma-membrane bilayer.38,46-48 it is clear from these research thrusts that lipid biochemistry is a continuously evolving discipline, and that it plays a pivotal role in advancing our understanding of cell membrane structure and function. we postpone further discussion of lipids to the section following the historical development and uses of chloroform. figure 2. top: colorized version published by nicolson (2014)47 of the singer and nicolson (1972)35 fluid-mosaic membrane model. originally, it consisted of a phospholipid bilayer with interspersed proteins that could traverse the membrane. the hydrophilic phospholipid heads point to the external and cytoplasmic aqueous media, while the hydrophobic fatty acid tails point inward. bottom: nicolson (2014)47 also provided an upgraded membrane model containing what modern-day scientists believe to be more realistic structural and functional features. the basic lipid bilayer architecture is preserved, but in this drawing the membrane has been peeled up (at the right) so that the viewer can appreciate several membrane-associated cytoskeletal (bottom left) and extracellular (top left) interactions. integral proteins, glycoproteins, lipids, and oligosaccharides are represented by different colors. protein and lipid domains are evident throughout the membrane. science moves at a rapid pace in its attempt to unravel the functional attributes of these and many other membrane structures. 137lipids, chloroform, and their intertwined histories iii. chloroform synthesis and its uses in medicine and chemical engineering chloroform (trichloromethane; chcl3; cas registry number 67-66-3) was synthesized and purified in 1831 by samuel guthrie (1782-1848), who studied medicine under his father’s tutelage, and may be considered to be a self-made farmer, chemist, and industrial manufacturer from sackets harbor, ny, usa.49 an interesting historical note is that chloroform’s right of discovery was contested for many years, with the french pharmacist eugène soubeiran and the german chemist justus von liebig claiming priority supported by their independent chemical syntheses. in 1888, a committee appointed by the chicago medical society examined the available scientific evidence and concluded that guthrie was the rightful discoverer of chloroform, almost sixty years after the events in sackets harbor had taken place and forty years after his death. guthrie worked in his home/farm laboratory to improve gunpowder preparations (leading to several near-fatal explosions!) as well as carrying out liquor distillations. one of his batch reaction-distillations produced what came to be known as “guthrie’s sweet whiskey”, a solution of chloroform in ethanol quite popular among the local alcohol-consuming clientele. the consecutive liquid-phase reactions thought to have taken place in guthrie’s boiler-distiller in his historical synthesis are as follows:50 a) ethanol reacts with calcium hypochlorite to give acetaldehyde, calcium chloride, and water. 2c2h5oh + ca(ocl)2 → 2ch3cho + cacl2 + 2h2o b) acetaldehyde reacts with calcium hypochlorite to give chloral and calcium hydroxide. 2ch3cho + 3ca(ocl)2 → 2ccl3cho + 3ca(oh)2 c) chloral reacts with calcium hydroxide to give chloroform and calcium formate. 2ccl3cho + ca(oh)2 → 2chcl3 + (h-coo)2ca chloroform has a molecular mass of 119.38 g/mol and is a colorless liquid at room temperature with a sweet, ether-like smell. it has a normal boiling point of 61.2°c, a mass density of 1479 kg/m3, and a viscosity (a quantity proportional to its resistance to flow) of 5.37 x 10-4 pa×s [kg/(m×s)] at 25°c. these are very important physical properties for describing its behavior in momentum, energy, and mass transport systems such as those typically encountered in chemistry and chemical engineering. for comparison, liquid water has a molecular mass of 18.02 g/mol, a normal boiling point of 100°c, a mass density of ~1000 kg/m3, and a viscosity of ~1.0 x 10-3 pa×s [kg/(m×s)] at room temperature. thus, chloroform is denser but less viscous than water at room temperature. its solubility in water is very low since 1 ml dissolves in about 200 ml water at 25°c. however, as we shall see later, chloroform is an excellent solvent for lipids! chloroform was first used as an obstetric anesthetic in 1847 by sir james young simpson (1811-1870) of edinburgh, scotland. a very famous patient who received the wonderful chemical on april 7, 1853, was her majesty queen victoria (1819-1901). after inhaling chloroform for 53 minutes through a folded handkerchief during labor, she delivered her eighth child, prince leopold.50 illustrations of chloroform’s early use as an anesthetic are shown in figure 3 (top and middle). following this headline performance, chloroform quickly gained worldwide popularity in related medical specialties such as dentistry and surgery. it has seen action in the treatment of battlefield wounds since the american civil war [1861-1865; figure 3 (bottom)]. readers may also recall its sinister role in well-known fictional crime novels such as agatha christie’s the plymouth express51 and why didn’t they ask evans?,52 in which the assassins subdue their victims temporarily with a chloroform-soaked textile fabric applied to the nose and mouth pending further plans. due to its potential carcinogenicity, chloroform was banned from human use as an additive in pharmaceuticals and cosmetics by the united states food and drug administration in 1976.53 however, it is still used in carefully-monitored industrial operations as an intermediate in the production of bactericides, fumigants, insecticides, and fluorinated refrigerants. the synthesis/discovery and medical applications of chloroform have been discussed in excellent books49,50 and archival references.54,55 an important nonmedical use of chloroform, perhaps unknown to the scientific community at large, is its role in mass transfer experiments leading to the estimation of diffusion coefficients (diffusivities) of binary gas pairs, with atmospheric air being the traditional second component. diffusion coefficients are key parameters in the design and analysis of mass transfer systems typically found in chemical engineering. examples of the latter include gas absorption, membrane separations, evaporation phenomena, multicomponent distillation, and controlled drug release from diffusion-based systems. the diffusive mass transport rate of a substance in a given medium is directly proportional to its diffusivity; therefore, knowledge of its magnitude is critical to the chemical engineer involved in research or designing an industrial-scale process.56-59 138 carlos a. ramírez the classical method to estimate binary gas diffusivities is the stefan column developed by josef stefan (1835-1893), professor of mathematics and physics at the university of vienna, during the second half of the 19th century.60,61 the original vertical column consisted of a pure liquid phase of volatile species a up to an initial height z10, overlaid by a gas phase containing the evaporated a and a stagnant species b (usually air). all symbols are defined in the nomenclature. through the years, the most common operational version of the column, depicted in figure 4, has been the descending interface modality, which does not require liquid replenishment. in this case, the liquid-gas interface descends to z1(t) after an elapsed time t following the start of the evaporation-diffusion process, while gas a ascends by diffusion and convection (bulk gas motion) to the top of the column at z2. a sweeping stream of pure gas b flows steadily and slowly at the top to remove gas a, maintaining its concentration at essentially zero at that location. this boundary condition is critical when developing mathematical models for the transport of gas a within the column. for the experimental situation depicted in figure 4, the solution of the mass conservation differential equations in the gas and liquid phases is well established in the literature,58 yielding a simple algebraic expression from which the diffusivity of a in b may be calculated: (1) (2) in equation (1), the z-coordinates represent specific vertical locations in the column (m), with z = 0 corresponding to the bottom (refer to figure 4), and t is time (s). in equation (2), c is the molar density of an ideal gas at constant temperature and pressure (mol/m3), cl is the molar density of pure liquid a (mol/m3), dab is the fickian binary gas diffusivity of a in b (m2/s), and ya is the mole fraction of gas a at a specific location within the column. at z1(t), ya is calculated by stipulating that vapor-liquid equilibrium conditions prevail at the interface. at z2, ya is commonly assumed to be zero due to infinite dilution of gas a in the sweeping stream. for a standard evaporation-diffusion experiment using the stefan column, dab can be calculated by regression analysis from equations (1)-(2) and experimental data of interfacial position versus time, z1(t). at this point the alert reader may rightfully ask: how is chloroform related to the stefan column? interfigure 3. top: inducing chloroform anesthesia by inhalation through a cloth. source: https://survivalstronghold.com/wp-content/uploads/2016/11/administering_chloroform_rag.png. middle: chloroform flasks and masks for holding a textile material over the patient’s nose and mouth. source: https://www.riverjunction. com/assets/images/4299/etherset.jpg. bottom: chloroform use for the treatment of a wounded soldier during the american civil war. source: https://www.ourgreatamericanheritage.com/wp-content/ uploads/2015/08/2363273317_f9cc2da0ea_o.jpg. 139lipids, chloroform, and their intertwined histories estingly, chloroform was one of the first substances tested in the column, when georg baumgartner in 1877 determined its diffusion coefficient in air to be about 7.3 x 10-6 m2/s within a temperature range of 17.5-20.3°c.62 although this value may seem small at first sight, leading one to the erroneous conclusion that chloroform is a poor diffusant in air, diffusivities of the order 1 x 10-5 m2/s are quite common in binary gaseous systems, as well as being several orders of magnitude higher than those in liquids! therefore, for a given chemical species such as chloroform, its diffusion in gases is very fast relative to its diffusion in liquids. this information is crucial to a chemical engineer when attempting to design a diffusion-based mass transfer system. for the interested reader, well-known compendia are available containing diffusivities obtained by the stefan column method for many gas pairs, including references to the original publications.63-65 in addition, a detailed compilation of binary diffusion coefficients for inorganic and organic compounds in air relevant to atmospheric chemistry has been presented recently.66,67 in the 1950s researchers first became aware that the stefan column binary diffusivities may be inaccurate due to “end effects” at the top of the column, where the sweeping stream interacts with the gas phase, and at the liquid-gas interface, where curvature due to surface tension can affect the mass transport area and the diffusion path length for gas a from z1(t) to z2. unfortunately, the early studies could not correlate such end effects to the systems’ operational and geometrical settings, limiting their subsequent use. in recent years, we have addressed this gap in scientific knowledge by reporting our efforts to quantify the various stefan column end effects and their impact on the gas diffusivity estimates. these studies clearly show that factors such as column nonisothermality,68 sweeping gas stream reynolds number (dimensionless ratio of fluid inertial to viscous forces) and column aspect ratio (gas phase height to column inside diameter),69 liquid phase composition,70,71 and interfacial shape and cur vature72 must be rigorously accounted for in the diffusivity calculations to minimize estimation errors. our findings to date have hopefully made stefan column researchers aware of some of the common pitfalls the analyst may find when estimating binary gas diffusivities from experimental interfacial descent versus time data. by continuing this line of research, chloroform and other common volatile solvents may help us attain an even better understanding of the stefan column mass transport dynamics, leading to more accurate binary diffusivity estimates. figure 4. classic sketch of the stefan diffusion column showing the liquid and gas compartments.68,69 the operating modality depicted is that of the descending liquid-gas interface without liquid replacement. pure volatile liquid a is charged initially to a height z10. its level falls to z1(t) after an elapsed time t following the start of the evaporation-diffusion process. liquid a evaporates at the interface and its vapor ascends through stagnant gas b (air) until it reaches the top of the column at z2. a steady and slow gas b sweep at the top maintains the concentration of a very close to zero at that location. the binary gas diffusivity of a in b can be calculated from fundamental mass transport principles applied to gas a and experimental interfacial descent versus time data (refer to the text for details). symbol definitions can be found in the nomenclature. 140 carlos a. ramírez iv. merging of the lipid and chloroform histories lipids and chloroform intertwined their scientific paths in the 1940s and 1950s through the work of spanish biochemist/professor jordi folch (1911-1979) and collaborators at the rockefeller institute for medical research, the mclean hospital research laboratories, and at harvard medical school. in 1957, researchers jordi folch, m. lees, and g. h. sloane stanley modified their own published procedure for the isolation and purification of total lipids from animal tissues.73 they developed painstaking analytical methods to extract and purify lipids from animal tissue quantitatively, concentrating on white (axon bundles) and gray (neural cell bodies) brain matter. the team relied on chloroform’s dissolving power for organic lipid-based compounds as the key reagent. the tissue was first homogenized with a 2:1 (volume:volume) chloroform-methanol solution followed by filtration. the filtrate, which contained lipid and nonlipid matter, was washed with a five-fold volume of water with minimal lipid losses in the wash. the resulting liquid mixture separated into two phases, the lower chloroform phase containing the total lipid extract. the article qualified the chloroform-based, lipid extraction-purification procedure as: a) operationally simple; b) applicable to any scale of starting biological material; c) capable of decreasing lipid losses incidental to the water washing process; and d) yielding an extract which could be taken to dryness without foaming or splitting of the proteolipids.73 besides developing this landmark analytical methodology for extracting total lipids, over the same time period other folch groups isolated and identified many lipid components of brain tissue, using chloroform both as a solvent and extraction medium.74-80 some of the compounds isolated, purified, and characterized from animal brain tissue, with chloroform playing a central role in the extraction-by-dissolution procedures, included: a) αand β-phosphatidyl serine, phosphatidyl ethanolamine, and diphosphoinositide derived from cephalin (figure 5); b) strandin consisting of fatty acids and sphingosine; c) proteolipids (lipoproteins) in normal and tumor tissue; and d) extracts of pure lipids. the isolation and characterization of these molecules led the way to elucidating significant aspects of brain tissue biochemistry. in the last few decades, the lipid-chloroform interaction has continued in applications such as the extraction of lipids from a wide spectrum of animal and plant tissues, as well as in environmental protection and workplace risk minimization by seeking “friendly” alternatives to the solvent’s use. examples of these modern research trends involving the synergistic efforts of lipids and chloroform include: a) extraction and purification of unsaturated fish lipids, which require mild treatment to minimize oxidative decomposition and the production of artifacts;81,82 b) determination of serum triglycerides by extracting the lipids with chloroform, methanol, and diethyl ether, followed by removal of the phospholipids, hydrolysis of the triglycerides, and quantification of their glycerol moieties;83,84 c) determination of pure lipid solubilities in common laboratory solvents such as chloroform to optimize extraction procedures of diverse biological samples;85 d) extraction of environmental contaminants such as chlorobiphenyls and other chlorinated pesticides bound and nonbound to fish lipids;86 and e) reducing the toxicity of chloroform-based tissue lipid extraction methods by substitution with alternate solvents.87-91 given their long, intertwined histories in chemistry and biology, it is very likely that lipids and chloroform will continue to find simultaneous use in as yet unforeseen scientific applications. v. conclusions this article brings together the separate histories of lipids and chloroform. within the lipid family, fatty acids are highlighted since they are the most abundant in nature and are key constituents of cell membranes. fatty acids were isolated by chevreul in 18132, and new lipids and lipid-based biomolecules are constantly being identified and characterized due to improved experimental techniques and instrumentation. not only are lipids of interest to academic researchers, but they find figure 5. many lipid derivatives were isolated, purified, and characterized by professor jordi folch and associates from animal brain tissue in the 1940s-1950s using chloroform’s dissolving and extraction properties for organic compounds.73-80 the work of the various folch teams marked the beginning of the lipid-chloroform scientific interaction, leading to a better understanding of brain tissue biochemistry. it also opened the door to many subsequent research initiatives featuring the synergistic use of both compounds. 141lipids, chloroform, and their intertwined histories important industrial use as ingredients in foods, pharmaceuticals, and cosmetics. chloroform has gone through its highs and lows along its history. first synthesized by guthrie in 183154, it quickly found worldwide use as an anesthetic in obstetrics, dentistry, and surgery. military doctors have applied it to injured combatants for wound treatment since the american civil war. unfortunately, it is presently banned from inclusion in pharmaceuticals and cosmetic products due to its potential carcinogenicity.53 notwithstanding this negative label, chloroform is still used in research laboratories as well as in several carefully-monitored industrial processes. lipids and chloroform are chemical species with different physicochemical properties and unique historical backgrounds. the work of professor jordi folch and associates in the 1940s and 1950s intertwined their histories forever.73-80 the folch teams spawned many lines of research with definite lipid-chloroform synergism, and these activities continue at an accelerated pace to this day.81-91 perhaps the biggest lesson from this story should be addressed to today’s young scientists: even though they have dissimilar physical and chemical properties, lipids and chloroform have shared important common ground in the past, and can be used collaboratively and prudently to tackle challenging scientific problems in the future. acknowledgements academic inspiration for this work was provided by university of wisconsin professors r. byron bird, warren e. stewart, and edwin n. lightfoot. their textbook transport phenomena is a timeless contribution to science, and is highly recommended to young and old 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doi: 10.1002/pca.893. 91. e. cequier-sánchez, c. rodríguez, á. g. ravelo, r. zárate, j. agric. food chem. 2008, 56, 4297-4303. doi: 10.1021/jf073471e. nomenclature latin letters a species a b species b c unsubscripted: molar density of an ideal gaseous mixture; subscripted: molar density of a pure liquid, mol/m3 d fickian diffusivity of a species in a binary gaseous mixture (subscripted), m2/s t time elapsed after starting a standard stefan column evaporation-diffusion experiment, s y mole fraction of a given species at a specific gasphase location in the column (subscripted), z vertical coordinate with origin at the bottom of the column (see figure 4; subscripted), m greek letters λ constant defined by equation (2), m2/s subscripts 10 initial location of the liquid-gas interface 1, 2 specific column locations: 1, liquid-gas interface; 2, top ab a-b gas pair az1 species a at z1 az2 species a at z2 l liquid substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 3(2) suppl. 5: 15-27, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-297 citation: j. emsley (2019) the development of the periodic table and its consequences. substantia 3(2) suppl. 5: 15-27. doi: 10.13128/substantia-297 copyright: © 2019 j. emsley. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. the development of the periodic table and its consequences john emsley alameda lodge, 23a alameda road, ampthill, mk45 2la, uk e-mail: johnemsley38@aol.com abstract. chemistry is fortunate among the sciences in having an icon that is instantly recognisable around the world: the periodic table. the united nations has deemed 2019 to be the international year of the periodic table, in commemoration of the 150th anniversary of the first paper in which it appeared. that had been written by a russian chemist, dmitri mendeleev, and was published in may 1869. since then, there have been many versions of the table, but one format has come to be the most widely used and is to be seen everywhere. the route to this preferred form of the table makes an interesting story. keywords. periodic table, mendeleev, newlands, deming, seaborg. introduction there are hundreds of periodic tables but the one that is widely reproduced has the approval of the international union of pure and applied chemistry (iupac) and is shown in fig.1. how chemists arrived at this iconic table makes an intriguing story and it can be traced back more than 250 years. however, it has become invariably linked to a man who lived in st petersburg in the mid-ninteenth century: dimitri mendeleev. early attempts to bring order to the elements the great french chemist, antoine laurent de lavoisier (1743–1794) was interested in the elements and, in 1789, he sought to bring order to them in his book traité elémentaire de chemie (elements of chemistry)1. in this he listed 33 substances which he regarded as elements – see fig. 2. lavoisier separated them into four categories that we could describe as gases, which comprised light, heat, oxygen, nitrogen, and hydrogen; nonmetals, which consisted of sulfur, phosphorus, carbon, chloride, fluoride, and borate; metals, this was the largest group with antimony, arsenic, bismuth, cobalt, copper, gold, iron, lead, manganese, mercury, molybdenum, nickel, platinum, silver, tin, tungsten, and zinc; and earths, which were lime, mag16 john emsley nesia, barytes, alumina, and silica. lavoisier and his colleagues suspected that the ‘earths’ were probably capable of being broken down further and he wrote: ‘we may even pressume that the earths may soon cease to be considered as simple bodies.’ clearly light and heat were wrongly classified as elements, and borate was boron-with-oxygen, as were the earths which were the oxides of calcium, magnesium, barium, aluminium and silicon. technology of the time could not decompose them further. heating a mineral with carbon in a furnace would generally remove all the oxygen as co2, but for some minerals this did not happen, hence lavoisier’s belief that these were fundamental elements. in all, his list included 26 that we now know to be true elements. however, he made no attempt to organise his list into elements with similar properties, so his list cannot be regarded as a fore-runner to the periodic table, although he might have eventually listed the elements in other ways, had he not been guillotined in 1794. meanwhile chemistry was undergoing a major shift with the writing of john dalton who, in 1805, not only proposed that elements must exist as single atoms but he calculated their relative weights. the next attempt to bring order to the elements was a theory put forward in 1815 by 30-year-old william prout (1785–1850). he submitted a paper entitled ‘on the relation between the specific gravities of bodies in their gaseous state and the weights of their atoms’ and he asked that it be published anonymously, although it became known he was the author.2 in this paper he proposed that all elements had relative weights, so-called ‘equivalent weights’, which were multiples of the weight of hydrogen, taken as 1. his theory would explain why so many weights were whole numbers, or nearly so. it was a far-sighted suggestion, and today we know the explanation is that 99.98% of the mass of an atom resides in its nucleus which is made up of protons and neutrons both of unit mass. because the majority of elements have one dominant isotope, this explains why their weights are whole numbers. however, there were several important exceptions, such as chlorine (35.5), copper (63.5), and zinc (65.4) which have a variety of isotopes. charles daubeny (1795-1867) was appointed professor of chemistry at oxford university in 1822. he figure 1. the periodic table. 17the development of the periodic table and its consequences produced a panel listing 20 elements with their relative weights, which still exists, and his listing was reproduced in the third edition of e. turner’s elements of chemistry, published in 1831. however, the list in no way corresponds to a periodic table. another chemist to make a contribution to classifying the elements was johann döbereiner (1780 – 1849). in 1829 he announced his law of triads.3 he called it ‘an attempt to group elementary substances according to their analogies’. he had noticed that of three chemically similar elements, the weight of the middle element was the average of the lighter and heavier members. lithiumsodium-potassium formed such a triad, and others were chlorine-bromine-iodine and sulfur-selenium-tellurium. by 1843, ten such triads had been identified. the first attempt to arrange all known elements in a regular pattern was made in 1862 by a french geologist alexandre-émile béguyer de chancourtois (1820–1886). he wrote a list of them on a piece of tape, in order of weight, and then wound this spiral-like around a cylinder. the cylinder surface was divided into 16 parts, based on the atomic weight of oxygen. chancourtois noted that certain triads came together down the cylinder, such as lithium, sodium and potassium whose atomic weights are 7, 23 (7+16), and 39 (23+16). this coincidence was also true of the tetrad oxygen-sulfurselenium-tellurium. he called his model the vis tellurique (telluric screw) and published it in 18624 – see fig.3. this was the first formulation which revealed the periodicity of the elements. a boost to element discovery came with the development of atomic spectroscopy in 1859 by bunsen and kirchhoff in germany. this revealed that each element had a unique pattern of lines in its visible spectrum. because an element always gave the same pattern, no matter its source, it was realised that here was a technique for uncovering new elements. merely submitting a mineral to atomic spectroscopy, immediately showed whether a new element was present. as a result, rubidium, caesium, and thallium were announced in the years 1860-1863. in 1860, the italian chemist stanislao cannizzaro (1826–1910) presented a paper to the first international figure 2. lavoisier’s classification of the elements. figure 3. chancourtois’ listing of the elements [reproduced by kind permission of the master and fellows of st catherine’s college, cambridge]. 18 john emsley chemical congress, at karlsruhe in which he gave the atomic weights of the known elements.5 a young russian chemist, dimitri mendeleev, who was doing postgraduate research in germany, was in the audience and picked up a copy of the list and took it back to st petersburg when he returned there in 1861. previously, chemists had used so-called equivalent weights determined from their oxides, and which were variable. an attempt to classify the elements was made by an englishman, 27-year old john alexander reina newlands (1837–1898). in 1863 and 1864 he had published papers dealing with relative weights and in 1864 he gave a talk entitled ‘the law of octaves’ at a meeting of the london chemical society. he had arranged 56 elements into groups and noted that there seemed to be a periodic repetition of similar properties at intervals of eight. the title of his talk was chosen by analogy with octaves in music. it was an inappropriate choice, and it is said that one member of his audience sarcastically asked newlands whether he had ever thought of arranging the elements in alphabetical order instead. the society’s journal refused to publish his talk as a paper. however, he wrote accounts in chemical news, in 18646and 1865,7 so we know what he was proposing. eventually, the royal society of london awarded him its prestigious davy medal in 1887 in belated recognition of his achievements, and given ‘for his discovery of the periodic law of the chemical elements’. also, in london at the time was william odling (1829–1921), who was at the royal institution. he also came near to devising the first periodic table. he published a paper in 1864 in the quarterly journal of science entitled: ‘on the proportional numbers of the elements’. he arranged the known elements in the same way as mendeleev was to do, and he too even left gaps where there were missing elements. however, unlike mendeleev, he didn’t have the confidence to predict their existence and physical properties. odling even left gaps that were later to be filled by helium and neon, long before the noble gases had been discovered. periodicity among all the elements had been noticed by the german chemist julius lothar meyer (1830– 1895). he drew a graph of atomic volumes of the 49 elements then known versus their atomic weights which showed a periodic rise and fall: fig. 4. he also devised a periodic table of elements. he wrote a paper and gave it to a colleague, professor adolf remelé, (1839–1915), asking for his comments. unfortunately, these were slow in coming, and before he could submit it for publication, mendeleev’s definitive paper had appeared. meyer’s version was eventually published in 1870,10 only a few months after mendeleev’s paper. dmitri ivanovich mendeleev (1834–1907) дмитрий иванович менделеев in 1867, 35-year-old dmitri ivanovich mendeleev began to write a textbook: the principles of chemistry. (this was published as a two-volume work in 1869 (vol.1) and 1871 (vol.2), and was translated into other languages.) he wondered how best to deal with the many elements with their diverse properties. he became obsessed with bringing some kind of order to the 63 elements then known, and he told his colleague a.a. inostrantcev that he had spent sleepless nights wrestling with the problem. mendeleev’s discovery of the periodic table is said to have occurred on february 17th. this was the date based on the ancient julian calendar still in use in russia. for the rest of europe, using the gregorian calendar, it was march 1st. on that day he had planned to visit a local cheese factory, but decided instead to work in his study. he had written details of every element and its physical properties on pieces of card, including its atomic weight, and the formulae of any hydrides and oxides which it formed, these indicating its valency or oxidation states. he then began to arrange the cards in various ways, until one arrangement seemed to him to be the best and he wrote that down on an envelope which still exists: see fig. 5. its printed version is fig. 6, from a paper he submitted to the russian journal of chemistry, this was a new publication of the russian chemical society which he had helped to set up. it appeared in may of that year.9 what mendeleev had done eventually made him one of the most famous scientists of all time. he also sent copies of his table of elements to other chemists, calling it ‘essai d’une systeme des elements d’après leur poids atomiques et fonctions chemiques’ (assessing a system of elements according to their atomic weights and chemical functions.) he wrote in french because this was the forfigure 4. lothar meyer’s graph showing periodicity. 19the development of the periodic table and its consequences eign language he had been taught at school and he had spent a little time in paris when he was doing a postgraduate course in germany under robert bunsen. what mendeleev had announced was fundamental to chemistry and science. in effect he was saying that the chemical elements conformed to a pre-determined pattern of relationships which we now call the periodic table. what followed was to transform a large part of chemistry from a disorganised jumble of facts into a disciplined science. mendeleev’s periodic arrangement of the elements might easily have gone unnoticed, but his paper was summarised in the leading german journal, zeitschrift für chemie, and so got wide publicity. by 1872 his table had been rearranged so that the groups were vertical rather than horizontal – see fig 7. also, mendeleev’s first table had some elements in the wrong place because he had ranked them in order of atomic weights and these were not always reliable. these faults were soon corrected. mendeleev was so sure that he was right in his concept of a periodic table, that he could see there were elements missing. he predicted that these must exist and for some of them he gave their likely physical properties, such as melting point, density, and basic chemistry. the first of these was discovered in 1875 by paulémile de boisbaudran (1838–1912) and he called it gallium. he measured its properties, including the density, which he said was 4.7 g/cm3. he was then told that his new element was the missing one in group iii of mendeleev’s table and that he had predicted its properties, for which its density would be 5.9 g/cm3. boisbaudran was alerted to this by mendeleev and so checked his measurements and discovered he had made an error; the correct density was 5.956 g/cm3 just as mendeleev has said. in 1879, the swedish chemist, lars nilson (1840– 1899), discovered scandium. it too had the properties mendeleev predicted. it was also in column iii and came below boron, and he had referred to it as eka-boron. its atomic weight was 44 (mendeleev predicted 44) and its density was 3.86 g/cm3 (mendeleev predicted 3.5 g/cm3). finally, in 1886, the german chemist, clemens winkler (1388−1902), discovered germanium, which was almost exactly as mendeleev had predicted for the element below silicon in group iv, right down to the density of its oxide which he said would be around 4.7 g/cm3 and turned out to be 4.703 g/cm3. he said that the boiling point of its chloride would be a few degrees below 100oc. it was 86oc. mendeleev’s table had eight columns with the roman numerals i to viii, corresponding to the chemical valencies (oxidation states) of the elements. this property was revealed by the chemical formula of the highest oxide. yet it brought together elements that were quite dissimilar, such as metals and non-metals. for example, in group v we find vanadium and phosphorus, which have almost no chemistry in common. mendeleev consequently split the columns of his periodic table into two sub-groups labelled a and b. vanadium was in va, phosphorus in vb. the same pattern was repeated in the other columns with the exception of group viii which figure 5. mendeleev’s envelope with the first periodic table. figure 6. the periodic table in mendeleev’s first paper. 20 john emsley contained metals that were very similar and which occurred in sets of three. these were iron-cobalt-nickel, ruthenium-rhodium-palladium and osmium-iridiumplatinum. mendeleev was to become a celebrity chemist. he visited many other countries, and won many awards such as the copley medal of the royal society of london, their highest award which had been founded in 1737. (the list of scientists given this award includes charles darwin, dorothy hodgkin, and albert einstein.) for reasons that are still unclear, mendeleev failed to gain a nobel prize despite being nominated three times, in 1905, 1906 and 1907, the year before he died. had he lived another year or two it is more than likely he would eventually have been rewarded this way, but nobel prizes can only be given to living scientists. early periodic tables and new elements basically, there have been two approaches to devising a periodic table. the first lists all the elements in a continuous line, rather like the numbers on a tape measure, and this is then looped in such a way that like elements come together. the second version chops the tape into segments and stacks these in rows or columns so as to bring together elements with similar chemical properties. the former approach is what chancourtois had used in 1862 for his telluric screw, and what many others have done since. the table versions are direct descendants of mendeleev’s table. an example of an early periodic table – fig.8 – can be found in the book by henry roscoe (1833–1915) and carl schorlemmer (1834-1892) called a treatise on chemistry. this was a comprehensive two volume text of 2400 pages, which first appeared in 1878 and was reprinted many times.12 this did not sub-classify elements into a and b columns, although it placed them in alternative rows as in later editions. although mendeleev did not realise it, there was a group of elements missing from his table. these were the noble gases, and when they were discovered 30 years later, they were to exert an influence on the way the table was perceived. roscoe and schorlemmer’s later editions contained these elements. the lightest noble gas, helium, had in fact been reported the year before mendeleev produced his table. it had been detected by the french astronomer, pierre j. c. janssen (1824–1907), on tuesday 18th august 1868. he had travelled to india to study the total eclipse that would be observed there. thankfully the sky was not overcast with clouds, and he was able to record the corona spectrum, which clearly showed an unknown element was present. later that same week, two british astronomers, norman lockyer (1836–1920) and edward frankland (1825–1899), viewed the sun through a london fog and observed the same spectrum. lockyer expected the new element to be a metal and so he called it helium, deriving the name from helios, the ancient greek sun god. some chemists thought he was being presumptuous in finding a new element on the sun and having the effrontery to name it. however, they were wrong – and so was he. it was a new element, but it was not a metal; it was a gas. helium is also present in the earth’s atmosphere but only in infinitesimally small amounts – 5 p.p.m. – as it is continually being lost to space. it is also present in uranium minerals that emit alpha particles which are the nuclei of helium atoms. in 1888, the us geologist william hillebrand (1853-1925) noted that the mineral uraninite (uo2) gave off bubbles of gas when dissolved in acid, but he could not identify it. per teodor cleve figure 7. the first periodic table with vertical groups. figure 8. textbook version of the periodic table – 1913. 21the development of the periodic table and its consequences (1840–1905) at uppsala, sweden, in 1895, confirmed that the gas was helium. another unreactive gas was discovered in 1894, by lord rayleigh (1842–1919) and william ramsay (1852–1916). they were intrigued by the discrepancy in the density of nitrogen gas that was extracted from air, compared to that which was formed by the decomposition of ammonia. the difference was a mere 0.05% but rayleigh did not believe his density measurements were wrong and deduced that the nitrogen produced from air must be contaminated with another gas. he went on to isolate this and it was essentially argon which constitutes around 1% of the air and it is formed when the potassium isotope 40k undergoes radioactive decay. ramsay now realised that helium was not a unique element, but was head of a group that was missing from the periodic table. he began the search for them and discovered three gases: neon (atomic weight 20), krypton (84) and xenon (131), which he extracted from liquid air. the element at the bottom of the group is radioactive radon, whose longest-lived isotope is 222rn with a half-life of only 3.8 days. this element was discovered by friedrich ernst dorn (1848–1916) in 1900, and he discovered it as the gas which collected in sealed ampules containing radium. although the first inclination of chemists was to place the noble gases at the left-hand side of the periodic table because their valency was 0, they are now on the right-hand side and this is the logical location when we regard the rows of elements as additions to the various electron shells surrounding the nucleus, each being completed with a noble gas. moseley’s system of numbering the elements – see below – revealed that those of atomic number 43, 61, 72, 75, 85, 87 and 91 were as yet unknown. these are all radioactive elements with short half-lives. technetium (43) was first obtained in 1937 when emilio segrè (1905– 1989) and carlo perrier (1886–1948) at the university of palermo in sicily separated it from a sample of molybdenum which had been bombarded with deuterons in the cyclotron at the university of california, berkeley. (segrè was to be dismissed from his academic post in 1938 because he was opposed to mussolini’s fascist regime, so he emigrated to the usa.) promethium (61) was claimed in 1938, by a group at ohio state university but they lacked chemical proof that it was the missing element and, at that time, such proof was deemed as essential to support a claim for a new element. then, in 1945, a group at oak ridge, tennessee, usa, were able to separate isotope-147 of element-61 and so were able to confirm it as required. element 61 was also made using a cyclotron to bombard neodymium with atoms of deuterium. element 78 (francium) was extracted from actinium in 1939 by marguerite perey (1909–1975) at the curie institute, paris, france. element 85 (actinium) had been discovered by andre debierne (1874–1949) in 1899 and he extracted it from the uranium ore pitchblende. it was later made by bombarding bismuth (element 83) with alpha particles in a cyclotron, and this was achieved by a group at berkeley which now included refugee segrè. the isotope produced had a half-life of 8.3 hours which they named astatine from the greek word astatos (unstable). a dilemma of the periodic table in its earliest form was that some elements did not fit the strict sequence of ordering by atomic weight. why did some elements have higher atomic weights than others which came after them in the table? the best example of this was the tellurium/iodine conundrum, with the former having atomic weight 127.6 while the latter’s atomic weight is 126.9. mendeleev was sure that the atomic weight of tellurium had to be wrong; it had to be less than that of iodine, so he used a value of 125, that had been determined by a czech chemist bohuslav brauner. in 1911, the english radiochemist frederick soddy (1877–1956) proved that elements had isotopes, which finally resolved the issue of pair reversal, thereby allowing an element of larger atomic weight legitimately to occupy a position in the table before its neighbour. transuranium element 93 had been wrongly claimed but never confirmed before it was finally produced in 1939 by edwin mcmillan (1907-1991) and philip abelson (1913-2004) at berkeley in 1940. it had a half-life of 2.3 days. the named it neptunium based on the planet which comes beyond uranus after which uranium (element 92) had been named. this element occurs naturally in uranium ores as a result of radioactive decay processes. its longest-lived isotope is np-237, with a half-life 2.14 million years. elements beyond uranium were produced in various ways using nuclear processes in the 1950s, 1960s… and in the current century. eventually a group of russian and american scientists, working at the joint institute for nuclear research in dubna, near moscow, were able in 2002 to produce atoms of the element at the end of the bottom row (7p) of the periodic table which is oganesson. the long form of the periodic table from the time of mendeleev’s first periodic table in 1869, it has undergone several changes, although we can still recognise some of mendeleev’s original groups 22 john emsley such as the halogens (now group 17). despite advances in atomic theory, mendeleev’s 8-column periodic table remained in use for almost a hundred years. eventually, the so-called long-form gradually displaced it as manmade elements were announced and interest focussed on the final row. today the standard version is the long-form: fig.1. this was first advocated by the swiss inorganic chemist alfred werner (1866-1919) in 1905, and had 18 columns, with two rows for the lanthanoids and actinoids. (these were previously referred to as lanthanides and actinides.) so why did the long-form periodic table become the preferred one, compared to the hundreds of others which have been suggested? the answer is that it is logical, easy to understand, and to extract information from. when designing a periodic table of elements, the primary data which determines their arrangement is atomic number. clearly such a linear sequence of elements has to be organised in some way, and the most obvious guideline is the one which mendeleev used, i.e. to place elements with similar properties in table format, with lightest elements at the top and with increasing atomic weight as you descend the group. although mendeleev was not aware of it, he had based his table on the two basic properties of an element: the number of protons in its nucleus and the occupancy of its electron shells. understanding the periodic table came only with the discovery of the electron in 1896 by j.j. thompson (1856-1940), the proton in 1911 by ernest rutherford (1871-1937), and the neutron in 1932 by james chadwick (1891-1974). in 1904 a japanese scientist, hantaro nagaoka (1865-1950), put forward the theory that atoms consisted of a central nucleus around which electrons circulated. in 1909 ernest rutherford proved that the nucleus was tiny and positively charged, which he did by bombarding a piece of very thin gold foil with alpha particles, and observed almost all of these passed through and that very few encountered an atom. it appeared that atoms consisted of a tiny, positively-charged nuclei in which almost all the mass was concentrated. in 1913, the physicist henry g.j. moseley (1887– 1915) formulated the property of atomic number in his paper8 entitled ‘the high-frequency spectra of the elements.’ this we now know to be the number of protons of positive charge in the nucleus. he showed that the sequence of elements in the periodic table was really in the order of their atomic numbers. sadly, he was shot by a sniper in world war i. that same year, niels bohr (1885–1962) linked the form of the periodic table to the atomic structure of atoms. the electronic composition of the elements explains today’s arrangement of the periodic table with its s, d, p, and f blocks. these reflect the occupancy of electron orbitals around the atomic nucleus, these being 2 (s), 6 (p), 10 (d), and 14 (f). the order in which these are filled, results in the extended long-form of the periodic table with rows of 2, 8, 8, 18, 18, 32, and 32 elements. combinations of these numbers give rise to 8 (= 2+6), 18 (= 2+6+10) and 32 (= 2+6+10+14) which are the lengths of the various rows of the table. the orbital nearest the nucleus is just a single orbital and labelled 1s, the next is a pair of orbitals labelled 2s and 2p, the next is a trio of orbitals, 3s, 3p and 3d, and so on. however, these begin to overlap, so that the next one, 4s, is actually occupied before the 3d sub-orbital.. the sub-orbitals can hold increasing numbers of electrons and these are the basis of the various blocks of the periodic table. the s-block consist of two groups (numbered 1, the alkali metals, and 2, the alkaline earths), the p-block elements consist of six groups (numbered 12 to 18), some of which have also got names such as the chalcogens (group 16) and the halogens (group 17). the d-block elements have ten groups (numbered 3 to 11), and the f-block elements consist of two rows 4f and 5f which are not given group numbers. at first approximation, the order of occupancy of orbitals is as follows: 1s / 2s, 2p / 3s, 3p / 4s, 3d, 4p / 5s, 4d, 5p / 6s, 4f, 5d, 6p / 7s, 5f, 6d, 7p. it still remains to be satisfactorily explained by quantum mechanics. if the elements are arranged in rows of increasing atomic number, and in columns having the same electron outer shell, then we arrive at the long form of the periodic table. across a row of the periodic table we are adding electrons to a particular shell until that shell is full when we arrive at one of the noble gases. consequently, these represent a natural break in the table. however, the long-form of the periodic table predates our knowledge about electron configuration, and it first appeared in 1923 when the american chemist horace g. deming (1885–1970) created it for his textbook general chemistry – see fig. 9. he placed the lanthanoids at the bottom of the table. he referred to them as ‘rare earths’ although some are relatively abundant. the value of deming’s table was soon appreciated, and within a few years it was widely used. the pharmaceutical company merck employed it in its advertising. it was also distributed to american schools as a teaching aid. in an internal document of the lawrence berkeley laboratory  of the late 1930s there is a periodic table closely resembling the modern form (figure 10). however, it places thorium below hafnium, protactinium below tantalum, and uranium below tungsten. 23the development of the periodic table and its consequences in 1929, the amateur french chemist charles janet (1849–1932) came up with an extended long form of the table – see fig. 11. mendeleev knew of thorium and uranium, and their chemistry made them suitable to place in his groups iv and vi respectively. and so, things remained, until synthetic elements started to be produced in the 1940s. then, in 1942, the american chemist glenn t. seaborg (1912–1999) drew the table in the form we know today with the f-block elements shown as a separate group below the d-block. seaborg’s colleagues at the university of california advised him not to publish his table as it was mere speculation, but he went ahead anyway and today we have names for all 15 of these elements. eventually the number of artificially produced elements has extended the periodic table to element 118 (organesson); atoms of this lasted all a fraction of a millisecond. (its half-life is 0.89 milliseconds.) whether physicists can extend the table further remains to be seen. seaborg avoided the controversy of which elements should go below scandium and yttrium in group 3 – lanthanum and actinium, or lutetium and lawrencium. he put all of them in the f-block, giving it 15 elements instead of the 14 which theory demands, and this is the table that the international union of pure and applied chemistry (iupac) has on its website – see fig 1. seaborg was eventually to be honoured by having element 106 named after him: seaborgium. numbering of the groups the normal periodic table has 18 columns numbered 1 to 18, but it was not always so. before iupac judged this to be the preferred configuration, there were other conventions, including roman numerals and letters. the change-over from the 8-column periodic table to the modern form was not without its difficulties. when mendeleev’s periodic table of 8 groups was turned into the long form of 18 groups, the europeans numbered the groups on the left-hand side ia to viii, and on the right-hand side they were numbered ib to viib, thus: ia, iia, iiia, iva, va, via, viia, viii, ib, iib, iiib, ivb, vb, vib, viib, viiib however, the american journals favoured a different classification: ia, iia, iiib, ivb, vb, vib, viib, viii, ib, iib, iiia, iva, va, via, viia, viiia which was more in keeping with mendeleev’s notation. both systems numbered the alkali metals groups ia, and the alkaline earth metals iia but after that they diverged. the scandinavians preferred a system based on letters rather than roman numerals: m1, m2, t1, t2, t3, t4, t5, t6, t7, t9, m2’, m3, m4, m5, m6, m7, m8 with m standing for main groups and t for transition metals. when the american chemical society also decided to drop roman numerals, they use a simple numbering system but differentiated the transition metals groups with a ‘d’ thus: 1, 2, 3d, 4d, 5d, 6d, 7d, 8d, 9d, 10d, 11d, 12d, 13, 14, 15, 16, 17, 18. figure 9. the deming periodic table of 1923. figure 10. the lawrence berkeley periodic table of the 1930s. figure 11. charles janet’s table of 1929. 24 john emsley the numbering of groups was tackled in new scientist in january 1984 when readers were asked to comment on the various systems and to suggest alternatives. the response was overwhelming and came from all over the world. hundreds of letters were received and the consensus was that simply numbering the columns 1 to 18 was best. the international union of pure and applied chemists (iupac) preferred the groups simply be numbered this way and, after much heart searching, the american chemical society (acs) agreed. the f block does not fit into the numbering system but this poses no problem since the 4f and 5f periods of elements are best dealt with as separate rows below the table. problematic elements we may think that the arrangement of the periodic table has finally been determined, but there are five elements whose position in the table is still debated. they are hydrogen (element atomic number 1), helium (2), lanthanum (57), lutetium (71), and actinium (89). hydrogen and helium. because hydrogen has a single s-electron, logic says that it should be in group 1 of the s block, but the other elements in that group are the alkali metals and clearly that is not what hydrogen is. helium has two s-electrons and so should be in group 2 but it’s not a metal either. helium is a noble gas and so placed at the top of group 18 while hydrogen sits incongruously at the head of group 1. however, helium is not a p-block element so it is out of place in that part of the periodic table. it has been possible for helium to form stable chemical bonds, so maybe janet was right to put it above beryllium and this is where it is to be found in some tables. there are tables which place hydrogen by itself, or with helium, in the very centre of the table, floating free above the other elements. others place hydrogen above fluorine, although it shares little in common with the halogen gases. some tables give it double billing and place it above both lithium and fluorine. there are other ways of deciding how to place these elements based on their atomic radii or 1st ionisation potentials. lanthanum and lutetium. the lanthanoids, elements of atomic numbers 57-71, posed a problem for the early periodic table since only a few of these had been discovered, and yet all seemed to prefer the oxidation state 3 so should come in group iii of the periodic table. the story of rare-earth discoveries began with yttrium in 1794. this metal was contaminated with traces of other rare-earths. first erbium and terbium we extracted from it in 1843, and then erbium yielded holmium in 1878, thulium in 1879, and so on, until finally lutetium was identified in 1907. this came as a result of painstaking work by the french chemist, georges urbain (18721938) at the sorbonne in paris. he called the element lutecium, later changed it to lutetium. for these elements to be incorporated into the periodic table, they had either to be placed as in the unwieldy extra-long form of the table, or be located in rows beneath the table. the question then arose as to which element should occupy group 3, below scandium and yttrium, with lanthanum (element 57) being the most obvious on as it follows immediately from element 56 (barium), with actinium (element 69) below it. in 1982, william b. jensen (1948–) of the university of wisconsin-madison took issue with this arrangement. he gave chemical reasons why the element in group 3 of the main table should be lutetium,11 and many agreed with his point of view. this being so, then the lanthanoids were lanthanum to ytterbium. some periodic tables fudge the issue and have both lanthanum and lutetium as part of a 15-member list at the bottom of the table, indicating this with la-lu in group 3. however, this jars somewhat as there cannot be 15 f-electrons, but this is the arrangement in the iupac table of fig. 1. in 1902 the czech chemist bohuslav brauner (1855– 1935) had said that there should be an element 61, coming between neodymium and samarium. this was confirmed by moseley in 1914. attempts were made to discover it and, in the 1920s, chemists in italy and in america, claimed to have found it. the difficulty with promethium is that the isotope with the longest half-life is pm-145, and that is only 17.7 years. there was no way that this element could be successfully extracted from terrestrial sources. tiny amounts do occur in uranium ores as a result of fission, but the calculated amount is around a picogram (10-12 g) per tonne of ore. a more realistic claim to have obtained element 61 was made in 1938 by a group at ohio state university. they bombarded praseodymium and neodymium with neutrons, deuterons and α-particles in a cyclotron and detected element 61 in the debris. they proposed the name cyclonium for the new element, but their detection of element 61 was not accepted as a discovery because chemical proof for the missing element was lacking. finally, such proof was forthcoming in 1945 from the work of j.a. marinsky, l.e. glendenin, and charles d. coryell at oak ridge, tennessee, usa. they had the new technique of ion-exchange chromatography at their disposal and with it they were able to separate isotope-147 of the missing element and analyse it. they wanted to call the element clintonium after the clinton 25the development of the periodic table and its consequences laboratories in which the work was done, until coryell’s wife suggested promethium basing it on the prometheus of greek mythology who stole fire from the gods and gave it to humans, and this became its name. element 103: both american and russian physicists claimed to have been the first to make atoms of atomic number 103, and so complete the actinoid series, giving them the right to name it. in 1958 physicists at the lawrence berkeley national laboratory bombarded curium-244 with nitrogen-14, and californium-252 with boron, and said they had identified it. they named it lawrencium. then, in 1965, physicists at the soviet union’s nuclear research centre bombarded americium-243 with oxygen-18 and obtained atoms of it. they also repeated the lawrence berkeley experiment and failed to confirm what the americans had claimed. the russians proposed that element 103 be named rutherfordium. this dispute over names was part of a larger issue regarding the claims and names of various new elements in this part of the periodic table. the disputes were only resolved in 1992 when an international committee called the transfermium working group (twg) met to decide the issue of names. as regards element 103, they decided that the discovery of 103 had been made by both russian and american laboratories and that the name should be lawrencium; rutherfordium was then to be the name of element 104. completing the bottom row of the periodic table became the province of atomic scientists and the strict chemical proof, that had previously to be met to confirm a new element, no longer applied. circular periodic tables soon after mendeleev published his table, other chemists suggested other ways of arranging the elements. among the alternative types of table, a circular arrangement was common and indeed one such table appeared soon after mendeleev’s publication – see fig. 12. this was proposed by a german mineralogist and chemist, heinrich baumhauer (1848–1926), in 1870. he continued to promote this version and produced a cobweb-like table in 1902 – see fig. 13. neither version became popular. in 1957, the latvian chemist edward mazurs compiled a complete list of all 700 known periodic tables and published them in his book: types of graphic representation of the periodic system of chemical elements. today there are more than a thousand, although many are very similar, and logging on to google images reveals many of them. most tables are two-dimensional, but there are several three-dimensional versions and these come in the shapes of cylinders, pyramids, spirals and even trees. these artistic versions can be very attractive and make ideal displays for science exhibitions, but they are not very practical when it comes to teaching chemistry and figure 12. the first circular table. figure 13. the 1902 table. 26 john emsley extracting information about the elements and their relationships. one circular table which was well publicised was that drawn by otto theodor benfey (1925). he was born in berlin but was educated in england, and eventually moved to the usa in 1947. in 1963 he became editor of the acs magazine chemistry, and in 1964 he published his own circular version of the periodic table in that journal. he justified it by saying that he wanted to highlight the continuity of the elements, and he referred to it as the periodic snail – fig. 14. part of his aim was to emphasise the lanthanoids and actinoids and also to include a section for the elements beyond the actinoids. circular versions of the periodic table continue to be proposed, but despite their elegance and the tantalising analogy with electrons in shells around a nucleus they all suffer the drawback of being difficult to read and to abstract the information from. moreover, they tend to crowd together the more important elements at their centre while giving the less important elements more room at the periphery. some circular periodic tables verge on being works of art and one such is that devised by philip j. stewart of oxford university which he published in 2007 and which he describes as a galaxy of elements;12 fig. 15. if you want to examine all known tables consult mark leach of manchester, england, who has a complete collection of periodic tables on his website metasynthesis.com. there is also the website internet  database  of periodic tables (address :  https://w w w.metasy nt hesis.com/webbook /35_pt/pt _database.php?pt_ id=943) where there are hundreds of them of bewildering diversity. a final word it is probably impossible to say definitely that the periodic table which today appears every where, in books and lecture theaters, on t-shirts and ties, on tv programmes and in films, is the ultimate version. it will of course change slightly if new elements are produced. since atoms of these will last for less than a second, then it may appear pointless to extend the table. in which case it is more than likely that the iupac table (fig. 1) will still be the preferred version so long as there is chemistry. and mendeleev’s achievement has been acknowledged by naming an element in his honour: element 101 is mendeleevium (md). this was first made in 1955. it is highly radioactive with a half-life of 52 days. even if someday we communicate with another part of the universe, we can be sure that one thing both cultures will have in common is an ordered system of the elements that will be instantly recognisable. perhaps the most artistic periodic table is that by the glasgow artist, murray robertson, which is entitled ‘visual elements’ and for which he had created a stunning computer graphic for each element. this can be accessed, via the internet, on the royal society of chemistry’s web site. if you wish to access a more dramatic version online, there is the periodic table of videos produced by nottingham university (www.periodicvideos.com) with presenters martyn poliakoff and pete licence. also accessible as an app is the periodic table of theodore gray which is also available in book format. finally, if you want a real hands-on periodic table this is available from rgb research and produced by max whitby and figure 14. the ‘snail’ periodic table. figure 15. the galaxy periodic table. 27the development of the periodic table and its consequences fiona barclay (https://periodictable.com/). it comes complete with a sample of each element that it is legally available. the larger versions of this kind of table of so-called ‘element collections’ can be seen at several institutions, such as the science history institute in philadelphia, pennsylvania, and at company sites such as the dow chemical headquarters in michigan. theo gray is the author/web-master of the remarkable website https://periodictable.com/ and he has written a book: the elements. today there is a permanent tribute to mendeleev’s discovery of the periodic table in the form of an impressive sculpture on the wall of the building where mendeleev worked: fig. 16. references 1. antoine laurent de lavoisier, traité elémentaire de chemie, paris, 1789. 2. anonymous (prout, william),  annals of philosophy. 6, 321, 1815. 3. döbereiner, j. w., annalen der physik und chemie. 15, 301, 1829. 4. emile de chancourtois a., comptes rendus de l’académie de sciences, 54, 757, 840, 1862. 5. cannizzaro, s.l. & de luco s., il nuovo cimento, 7, 321-368, 1858 8, 967, 1862. 6. newlands j.a.r., chemical news, (aug 20th) 10, 94, 1864. 7. newlands j.a.r., chemical news, (aug 18th) 12, 83, 1865. 8. moseley h.g.j. philosophical magazine, 6th series, 26, 1024, 1913. 9. dimitri mendeleev, journal of the russian chemical society, 4, 60, 1869. 10. meyer, l., annalen der chemie und pharmacie, supplementband vii, 354, 1870. 11. jensen w., j. chem. ed., 59, 634, 1982. 12. h.e. roscoe & c. schorlemmer, a treatise on chemistry, macmillan, 1878. 13. stewart, p.j., foundations of chemistry 12, 5, 2010. books about the periodic table hugh aldersey-williams, periodic tales: the curious lives of the elements. harper collins: new york, 2011. marco fontani, mariagrazia costa and mary virginia orna, the lost elements, the periodic table’s shadow side, oxford university press, new york, 2014. michael d. gordin, a well-ordered thing, basic books, new york, 2004. masanori kaji, helge kragh and gabor pallo, early responses to the periodic system, oxford university press, new york, 2015. sam kean, the disappearing spoon: and other true tales of madness, love, and the history of the world from the periodic table of the elements. little brown: new york, 2010. ulf lagerkvist, the periodic table and a missed nobel prize, world scientific, 2012. edward mazurs, types of graphic representation of the periodic system of chemical elements, self-published, 1957. ben mcfarland, a world from dust: how the periodic table shaped life, oxford university press, new york, 2016. eric r. scerri, the periodic table; its story and significance, 2nd edn., oxford university press, new york, 2007. eric r. scerri, the periodic table; a very short introduction, 2nd edn., oxford university press, new york, 2019. j.w. van spronsen, the periodic system of chemical elements; a history of the first hundred years, elsevier, amsterdam, 1969. ben still, the secret life of the periodic table: unlocking the mysteries of all 118 elements. cassell: london, 2016 paul strathern, mendeleev’s dream; the quest of the elements, hamish hamilton, 2000. alberts stwertka, a guide to the elements, revised edn., oxford university press, oxford, 2018. figure 16. periodic table on a wall. saint petersburg, russia. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna substantia. an international journal of the history of chemistry 3(2) suppl. 5: 49-58, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-378 citation: f. abbri (2019) discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances. substantia 3(2) suppl. 5: 49-58. doi: 10.13128/substantia-378 copyright: © 2019 f. abbri. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri dsfuci –università di siena, viale l. cittadini 33, il pionta, arezzo (italy) e-mail: ferdinando.abbri@unisi.it abstract. during the eighteenth century sweden was a propitious context for the discovery of chemical substances and elements. at the beginning of his scientific career jöns jacob berzelius contributed by his experimental research and discoveries to the preservation of the high scientific profile of his native country. electrochemistry and chemical atomic theory marked berzelius’s scientific life and organized his vision of chemistry and his classification of substances. berzelius used his lärbok i kemien to spread his discoveries and to frame his conception of chemistry. focusing on berzelius’s textbook of chemistry the paper tries to enlighten a specific vision of chemical science which was very influential in the first half of the xix century. keywords. swedish science, berzelius, textbooks of chemistry, communicating science. 1. center and periphery in eighteenth century chemistry the traditional reconstructions of eighteenth century chemistry focused on the scientific relationships between paris and the british research centers with some incidental reference to various german political contexts. the recent historiography of science has started to pay attention to peripheries and to their interactions with the main scientific centers, and such a new perspective has allowed to draw some richer and more complex pictures, to locate forgotten paths of knowledge, and to reconstruct some actual networks of personal and institutional relationships. thanks to these current approaches, new light has been cast on theories and experimental pratices of eighteenth century chemistry. in the eighteenth century swedish science played a major role as regards the development of mineralogy, metallurgy, chemistry, and of the natural and experimental sciences. at the beginning of the eighteenth century, losing the great northern war, the kingdom of sweden was no longer a military, imperial power,1 it was a minor power but still played a significant role owing to its metallurgical activities and its production of guns. chemists and mineralogists of the bergkollegium (board of mines), chemists at uppsala 50 ferdinando abbri university and members of the royal swedish academy of sciences were an important reference to the scientific culture of that time.2 johan gottschalk wallerius (1709-1785), torbern olof bergman (1735-1784) and the pharmacist carl wilhelm scheele (1742-1786) were the protagonists of the swedish scientific scene, particularly with respect to the interpretation of the discoveries of airs or gases. in the rich landscape of enlightenment chemistry it is possible to identify french stahlism, british experiments and discoveries of gases but also a true swedish theory which lavoisier himself considered a primary critical reference.3 swedish naturalists were famous for their discoveries of minerals and chemical elements, for some refined theories of gases by scheele, and of the chemical affinities by bergman. the translations into various languages of wallerius’s, scheele’s and bergman’s papers demonstrate their ideas were spread all over europe. in italy it was customary to say that sciences were migrating into cold northern europe. at the end of the eighteenth century sweden had seemingly lost that very high position of prestige enjoyed during the enlightenment; the second edition (1796; the first one had been edited by bergman in 1775) of henrik teofilus scheffer’s chemiske föreläsningar (chemical lectures) contained a traditional, pre-lavoisian chemical theory; the brief inledning till chemien (1798) by the finn johan gadolin (1760-1852), professor at the university of åbo (turku), presented a concise exposition of antiphlogistic chemistry (antiphlogistiska systemet) which was shaped according to the highly popular philosophie chimique (1792) by antoine-françois fourcroy.4 the history of swedish chemistry is unavoidably connected to the name of jöns jacob berzelius (17791848), a dominating authority of european science during the first half of the nineteenth century. berzelius was highly successful; he was the discoverer of many chemical substances and four elements, an impressive experimental scientist, a theorist of stoichiometry and chemical atomism, a prolific writer and editor of several journals. jenny beckman has recently reconstructed berzelius’s publication strategies emphasizing his efforts to spread his discoveries and conceptions, and his plan for preserving the status of european scientific language in the swedish tongue.5 it is generally argued that the development of organic chemistry and the birth of unitary theories made berzelius’s dualistic theory obsolete, but it must be stressed that berzelius’s influence continued during the whole century, as demonstrated by stanislao cannizzaro who suggested to read and read again berzelius’s works and papers. 2. a center for chemical research: scientific pilgrimages to stockholm. in 1815 christian gottlob gmelin (1792-1860), a young german naturalist who was to become the professor of chemistry at the university of tübingen, left his native land moving to stockholm in order to improve his knowledge of chemistry. he remained one year in sweden and paved the way for some other german naturalists. in the background of the chemists of the first half of nineteenth century the specialization in stockholm was a common trend for many german naturalists. in the map of the nineteenth century chemistry stockholm was next to paris (the lavoisian school), london (humphry davy) and manchester (john dalton). gmelin’s path was followed by eilhard mitscherlich (1794-1863), heinrich rose (1795-1864), gustav rose (1798-1873), gustav magnus (1802-1870) and friedrich wöhler (1800-1882), and the latter became the grand and noble father of german chemistry. at the beginning of his career justus liebig planned to go to stockholm, but eventually choosed to go to paris.6 this new scientific pilgrimage to stockholm was caused by berzelius. from 1812 to 1819 thanks to the patronage of wilhelm hisinger, a naturalist and industrialist, berzelius founded a laboratory of chemistry in stockholm; in 1819 he became the permanent secretary to the royal swedish academy of sciences, and founded a new laboratory at this institution which was then located at stora nygatan in the ancient part of the city (gamla stan), and here the young german chemists went to improve their knowledge. since 1829 the laboratory of chemistry was in drottinggatan, next to adolf fredrik kyrkan, where there was the new seat of the academy, and this laboratory continued to be one of the crucial places of the history of european chemistry. if we want to draw an exemplary picture of chemistry in the first half of the nineteenth century we must have recourse to berzelius: the portrait of berzelius as a young, poor student of medicine at uppsala university can be compared with one of the official portraits of the old, noble berzelius, laden with medals, reputation and fame. this comparison can give the image of the surprising career of an orphan boy from a swedish provincial district, but it also proves that between the end of the eighteenth and the beginning of the nineteenth century the science of chemistry could offer the opportunity for prestigious and social redemption. to berzelius we owe a surprising series of experimental discoveries, a new chemical nomenclature, the development of electrochemistry, the establishment of chemical atomism, the discovery and verification of stoi51discovering elements in a scandinavian context chiometric laws, the dualistic theory, the formulation of the concept of isomerism, and the beginnings of a proper organic chemistry. in the light of some crucial experimental discoveries berzelius could renew, invent, and organize the whole domain of chemistry. at the end of the nineteenth century henrik gustaf söderbaum (1862-1933) published in german the first historical reconstruction of berzelius’s chemistry,7 and at the beginning of the twentieth century he started publishing manuscripts, travel diaries, correspondence (bref or brev), and from 1929 to 1931 a three volume levnadstecking, that is a biography of berzelius.8 the publication of the correspondence offered the historian a fundamental resource, and the mammoth correspondence between berzelius and wöhler, edited by otto wallach (1847-1931) and published in 1901, gave a unique opportunity for understanding some main chapters of the history of chemistry in the first half of the nineteenth century.9 the new established international history of science and of scientific thought has favoured a revival of interest in berzelius’s work. in 1981 evan h. melhado published a volume on jacob berzelius. the emergence of his chemical system which contains a detailed reconstruction of the background of eighteenth century chemistry, an explanation of berzelius’s debt to lavoisier’s theory and of the differences between lavoisier’s system and berzelius’s. the second part of this volume, devoted to the berzelian theory of salts, presents a detailed historical analysis of the genesis and structure of the berzelian system of chemistry.10 berzelius contributed to the cultural and philosophical controversies of his time and he severely criticized f.w.j. schelling’s natural philosophy, and the naturphilosophie which was welcomed in sweden by naturalists, physicians, philosophers and theologians. in 1992 melhado and tore frängsmyr edited a volume on enlightenment science in the romantic era. the chemistry of berzelius and its cultural setting, which is the best recent, overall work on the swedish chemist. among the contributions to this volume one must point out the papers by anders lundgren on chemical atom, and by alan j. rocke on berzelius’s animal chemistry. melhado’s novelty and tradition in the chemistry of berzelius (1803-1819) is a wide-ranging detailed reconstruction.11 the af handling om galvanismen (1802) and the föreläsningar i djurkemien (1806-1808) mark the beginning of berzelius’s scientific career which is characterized by the publications of papers in swedish and in german in the acts of the swedish academy of sciences and in german scientific journals. the german texts were the basis for translations into french and english. colin a. russell reconstructed berzelius’s electrochemical theory, lundgren has clarified the question of the berzelian chemical atomism,12 and thanks to the contemporary historiography of chemistry one can schematize the main stages of berzelius’s stochiometric research in the following way: in 1811 berzelius published in the paris “journal de physique” his outstanding essai sur la nomenclature chimique;13 the same year he started publishing in ludwig wilhelm gilbert’s “annalen der physik” the first part of the versuch, die bestimmten und einfachen verlhätnisse aufzufinden, nach welchen die bestandtheile der unorganischen natur mit einander verbunden sind (1811-1812);14 in 1819 in paris berzelius published his essai sur la théorie des proportions chimiques et l’ influence chimique de l’électricité which contains a coup d’oeil on the theory of chemical proportions, the order of chemical substances, the method to calculate the relative number of atoms in chemical combinations, some observations on nomenclature, the classification of substances starting with the oxides, and one hundred and twenty alphabetical tables of the atomic weights of the main substances.15 these publications confirm the impressive quantity of experimental research that berzelius made in his laboratory for establishing the true order of the well-known and newly discovered chemical substances. here, i do not want to resume berzelius’s discoveries and theories, i only hope to show some aspects of his work, in connection with the history of his chemical textbook because my aim is to clarify the berzelian image of science which was so influential during the nineteenth century. through a consideration of his chemical textbook, it can be appreciated the interactions in his thought between didactics of science and strategies of communication. berzelius built a network of personal relationships which became an instrument of information and controversy, and he used the stockholm academy of sciences as an arena for the dissemination of a specific, swedish image of chemistry. 3. a favourite chemical textbook. in 2000 anders lundgren and bernadette bensaude-vincent edited a volume on communicating chemistry, devoted to textbooks and their audiences, 17891939. it is a very important collection of essays aimed at understanding the value and historical meanings of the chemical textbooks. in his introduction to the study of chemical textbooks john hedley brooke clarifies the main problems which are met in the study of scientifc textbooks, and notwithstanding many methodological 52 ferdinando abbri complications this study reveals that textbooks can be more enthralling than their unglamorous image might suggest. 16 a historical analysis of berzelius’s various försök and versuche allows to clarify the genesis of his discoveries, the formulation and modifications of his conclusions, in short the construction of a science. a study of his highly popular textbook of chemistry may be useful for giving a picture of his didactics of science and of the structure of his chemistry, but the origin and the development of this textbook comprise a very complicated history which reveals all the difficulties in defining a stable body of scientific knowledge when the science is making daily progress and is the focus of controversies and diverging approaches. in communicating chemistry there is an important paper by marika blondel-mégris devoted to berzelius’s textbook and to its multiple translations, but the center of her study is the german context and wöhler’s editions.17 the vicissitudes of this textbook appears to be still more complex in germany and when its fate in france, italy, spain and the netherlands is made clear. at the very beginning of the nineteenth century berzelius was dissatisfied with the chemical textbooks of his time. we must keep in mind that he was a selftaught man in chemistry, and he studied this science by reading lavoisier’s traité élémentaire de chimie (1789) and christoph girtanner’s anfangsgründe der antiphlogistischen chemie (1792), two works which marked the shift from the theories of phlogiston to the antiphlogistic approach. in germany lavoisier’s chemistry was not welcome, and many german chemists used it because it was clear but they did not believe that it was also true. in 1808 in stockholm the first volume (förra delen) of berzelius’s lärbok i kemien appeared. it opened with the author’s statement that since sweden has not had a complete textbook of chemistry written in swedish for a long time, and such a textbook was necessary because swedish young people cannot use the utländska lärböker, foreign textbooks. berzelius also states that he has tried to treat chemistry in all its generality (i allmänhet).18 this first volume confirms berzelius’s belonging to enlightement philosophy, because it presents a very simple definition of chemistry, which remained unchanged in all the other editions, and underlines the recent status of chemistry as a recognized science, notwithstanding its very long history. the writing of the lärbok was a very hard task because berzelius used his textbook both to encode knowledge, that is to reorder accepted science, and to present his new experimental discoveries. the second volume could only be published in 1812, the third one in 1818, but in 1817 the second edition of the first volume (första delen) was published, and it was an improved and partially rewritten text (omarbetad och betydlygt tillökt). in the preface of this second edition no reference to swedish young people was made; berzelius only emphasized that chemistry had made great progress in the past ten years, mentioning the decomposition of alkalis, the doctrine of chemical proportions and the importance of electricity as a chemical agent.19 berzelius put aside the swedish destination of his textbook, he remained faithful to the swedish tongue but at that time he was aware of the diffusion of his text in germany. it is important to note that a comparison of the title pages of the 1808 and 1817 editions shows a significant increase in berzelius’s accademic qualifications, and this growth confirms his successful professional and scientific achievement. in the enlightenment cultural setting the french editions of a scientific text were the groundwork for the translations into english or italian, whereas german or russian texts and local academic translations continued to use latin which guaranteed their circulation. in the case of berzelius’s textbook the german versions became the reference texts for the translation into french, and from french into other languages, so a novelty developed: the german texts were used for the dissemination of the swedish science outside sweden. on the 19th of october 1825 from berlin wöhler informed berzelius that the capital of prussia “ist jetzt ein wahrer sammelplatz für scandinaver” (a true place of reunion for scandinavians), because together with the swedish chemist carl palmstedt (1785-1870) there were some other swedes and four norwegians: the scandinavian naturalists carefully considered the german scientific context.20 together with mitscherlich, wöhler was the official voice of berzelius in germany and the main protagonist of the diffusion of his textbook, but before wöhler started translating from swedish, berzelius’s work had already gained some attention. historians do not usually recall that in 1816 johann georg ludolph blumhof (1774-1825), a naturalist of the grand duchy of hesse, published in leipzig the translation of the first volume of the lärbok with the title of elemente der chemie der unorganischen natur. in blumhof ’s vorbericht it is stated that berzelius is famous for his literary productions and for his outstanding observations and discoveries which make the first two volumes of his lärbok a reference text. blumhof underlines that berzelius deals with chemistry “bloss in allgemeinen”, without references to its pratical applications, but he thinks that the teaching of chemistry permits an application of knowledge by those naturalists who are interested in industry and in the 53discovering elements in a scandinavian context practical arts.21 the elemente is a useful text to chemists because it contains all the discoveries of the present age; it is therefore an updated textbook, but it is also written “im ächt philosophischen geiste”, which is missing in the other “chemischen lehrbücher”.22 to blumhof, a precise description of the laboratory experiences, an up-todate presentation of chemistry, a philosophical spirit that shapes the writing and the structure of the topics are the peculiarities which make berzelius’s text a fundamental contribution to science. blumhof ’s translation was limited to the first swedish volume of 1808. in 1820 in dresden, for k.a. blöde’s edition of the first volume of berzelius’s lehrbuch der chemie the translator used the second swedish edition.23 the second volume was translated by palmstedt and the third one by wöhler; the three volumes were reprinted in reutlingen in 1821, 1824 and 1828. in 1825 in dresden the first volume of the lehrbuch der chemie was published in a new translation by wöhler, and on the front page it is stated that berzelius had changed in swedish the blöde-palmstedt translation and that wöhler had translated it and included berzelius’s modifications. in fact, the volume opens with a long vorerinnerung signed by berzelius and dated stockholm, july 16th, 1825, in which are listed all the novelties compared with the original plan of 1807, for instance davy’s discovery that alkalis can be reduced to metals, the properties of the new metals, the newly discovered properties of known metals, the discoveries of new radicals, new earths, and so on.24 in a letter from berlin dated the 25th of july, 1825 mitscherlich informed berzelius that wöhler had checked the translation from swedish into german of the additions, declared that wöhler understood swedish, and the swedish chemical books, better than his other former pupils, and suggested his master and friend a full involvement of wöhler in the german editions of his textbook.25 wöhler’s editions from 1825 to the fourth, grand edition of 1835-1841 in ten volumes contain updates and additions directly furnished by berzelius. in the last years of his life berzelius, unable to carry on laboratory research, prepared a new german edition of his textbook, published in 1843-1848. in 1843 he wrote the dutch chemist mulder that “je poursuis toujours avec assiduité le travail pour refondre mon lehrbuch”.26 a comparative and detailed study of these editions is very difficult owing to the mammoth quantity of printed materials which they contain, but it could surely furnish much information about the knowledge added by berzelius to the various german editions of his textbook. wöhler was the official spokesman for berzelius in germany, and from germany to the remaining parts of continental europe, but the historical relevance and the scientific impact of the berzelian textbook is confirmed by a three volume edition published in stuttgart and edited by heinrich f. eisenbach and carl august hering. the title of lehrbuch, adopted in 1820, is conserved but on the front page it is stated tha that stuttgart edition contains some updates relating to new research and discoveries and this statement explains why chemists were so attentive to the novelties coming from stockholm. the editors declare that berzelius’s volumes could be used for vorlesungen (lectures) and selbstudium (personal learning) by numerous groups of people: physicians, pharmacists, administrators, agronomists, craftsmen, and industrialists.27 this specification shows that chemistry was by then socially relevant as a science, and a science able to favour some productive activities, so a sort of continuity was established between modern chemistry and the seventeenth century project by johann rudolph glauber (1604-1670) for the use of a chimistry which could favour dess teutschlands wohlfahrt (prosperitatis germaniae, 1656-1661).28 the german edition of 1832-1833 confirms berzelius’s deserved reputation and his importance in the history of modern chemistry. in the presentations of the various editions of his textbook which i have been able to study, it is always stated that the swedish chemist is so famous that a translation of his textbook needs no justification or explanation. in their vorrede eisenbach and hering write that the plan of the textbook is what “die natur der sache” requires: a general introduction containing some notions derived from physics, the chemistry of inorganic substances, which follows the order of salts and their bases, and the doctrine of chemical combinations which closes the inorganic chemistry and opens to the organic chemistry.29 in his vorrede to the 1835 german edition berzelius states that it is not an easy enterprise to outline a good plan for a lehrbuch because a textbook has a different aim from a handbuch whose main feature is a strict systematic order. in a lehrbuch this order is to be carefully sought because the exposition of the science is to begin from the most simple concepts that can be easily kept in mind. the writing of a chemical textbook is very demanding and the attention of the reader is to be captured, and when the stated goal is reached, the study of a science does not prove to be hard. berzelius acknowledges that he has not adopted a perfect systematic order because he wants to introduce in science that lightness which is helpful to a beginner.30 many different needs and preoccupations converge around berzelius’s textbook: the pedagogical aim is connected with the project of a book which could 54 ferdinando abbri present an orderly system of chemistry, but this science was in such a dynamic state that updates, corrections and adjustments of the book were continuously required. in order to further illuminate the historical meaning of berzelius’s textbook it is appropriate to recollect some data concerning the other editions. on november 1828 berzelius received a letter from a.-j.-l. jourdan, a french physican, who was charged by the paris printer didot to translate the lehrbuch. jourdan discussed the french title with berzelius, who preferred that of éléments de chimie, asked him to send updates and modifications in comparison with the german edition.31 this request is common to every translator who wanted to include chemical novelties the planned edition, and therefore the various translations are full of berzelius’s experimental and theoretical changes. from berzelius’s correspondence it can be understood that he sent some updates in swedish (tilläg) to wöhler, who translated them into german (zusätze) in order to assure their dissemination in europe. the first volume of the traité de chimie traduit par a.j.l. jourdan was published in paris in 1829,32 and aroused berzelius’s violent protests because of translation errors; these protests are documented in berzelius’s letters to pierre-louis dulong.33 in june 1829 from stockholm berzelius recalled that in berlin he had asked the advice of mitscherlich, heinrich and gustav rose, magnus and wöhler before accepting didot’s and jourdan’s proposal for a french translation of his textbook,34 and this episode confirms that berzelius’s german pupils composed a true, compact berzelian school of chemistry. jourdan was replaced by melchior esslinger and the publication of berzelius’s traité in eight volumes was completed in 1833. the paris edition is not the only french version; in bruxelles in 1839 the first volume of the traité de chimie was published. jean-benôit valerius (1807-1873) was the translator taking his text from the fourth german edition. in the avis des éditeurs there is, besides the customary homage to berzelius and the emphasis on his scientific relevance, the statement that this new traduction was made “pour ainsi dire sous les yeux de l’auteur” because it contained the zusätze of the fourth german edition, and therefore it was different from the paris french translation.35 it is stated that the textbook is addressed to professional chemists and above all to those who are beginners in the science. the bruxelles edition was completed in 1846 in four volumes, and the existence of two french translations gave rise to different destinies of berzelius’s textbook in spain and in the ancient italian states. in 1845 rafael saez y palacios and don carlos ferrari y scardini, first and second chemists at the general hospitals in madrid, published the first volume of the castilian translation of berzelius’s lehrbuch with the title of tratado de química; their translation was based on valerius’s french translation. in their presentation the two traductores underlined that chemistry, after its inclusion among the sciences by lavoisier, has not produced a more important textbook than berzelius’s. they used valerius’s edition because it was the most up-to-date version but made note of the fact that “la química no ha quedado estacionada en estos últimos años”, owing to surprising and continous discoveries.36 the second volume was published in 1845, but this literary undertaking started changing with the third volume because the title was modified to tratado de química mineral, vegetal y animal 37 and the following thirteen volumes – the translation was completed in 1851 – were translated using the second french edition that in 1845 esslinger and ferdinand hoefer started publishing in their unending search for the latest version. in the first half of the nineteenth century many cities of the ancient italian states produced translations of scientific textbooks in a competitive system of book trade. from 1826 to 1828 in milan a translation of berzelius’s textbook was published in four volumes with the title of trattato elementare di chimica teorica e pratica.38 during the eighteenth century venice and naples played a major role in the spread of european science and in these cities two different editions of berzelius’s work were published. in venice, the printer antonelli charged the chemist francesco du pré, who contributed to the debates on antiphlogistic theory, to translate the berzelian textbook from the french jourdan-esslinger version. the venice edition was published in eight volumes between 1830 and 1834 and it was entitled trattato di chimica.39 in naples in 1838 giovanni guarini started publishing a new translation of valerius’s edition40 which was completed in nine volumes in 1845. in the italian states chemistry was not officially established but an italian reader at least had at her/his disposal some updated italian versions of berzelius’s textbook. the dutch version must be considered because it marked the involvement of a physician and chemist of rotterdam and utrecht in the network of berzelius’s scientific relationships. on the 24th of june 1834 gerardus (gerit) johannes (jan) mulder (1802-1880) wrote to berzelius sending him the plan of a dutch translation of his textbook compiled by mulder’s three pupils (a.s. tischauser, b. eickma, a.f. van der vliet), and informed him that he was using the berzelian text for his lectures to forty young students. he also informed berzelius that 55discovering elements in a scandinavian context such an editorial enterprise was very risky because the netherlands were a small country where people could read foreign languages. mulder asked berzelius for some unpublished notes in order to enhance the diffusion of the dutch version.41 berzelius was proud of this translation and promised that he would send mulder some unpublished notes prepared for the fourth german edition. in november mulder thanked berzelius and informed him that the editorial enterprise had started, and highlighted the relevance of the unpublished notes. in a letter dated 1835 mulder informed berzelius about the poor state of chemical research in the netherlands and his choice of the berzelian text in order to favour the growth of the socio-cultural perception of chemistry as an outstanding science.42 the first volume of the leerboek der scheikunde was pubblished in rotterdam in 1834 and on title page it was stressed that the translation was based on the third german edition but improved (en vermeerderde oorspronkellike uitgave) by some unpublished portions, and mulder’s voorberigt underscored their scientific relevance.43 the dutch version was completed in 1841 in six volumes. subsequently, mulder became one of berzelius’s most faithful correspondents, and organic chemistry was their favourite topic. mulder and berzelius were both interested in the chemical composition of proteins, and they had a common aversion to liebig. the work of liebig on the radical of benzoic acid, his study of animal chemistry and the applications of chemistry to agriculture are epoch-making, but liebig had a zealous, upbeat character which was the antithesis of berzelius’s philosophical calm. in march 1838 facing liebig’s criticisms, berzelius confessed that “nous [berzelius and liebig] cherchons tous les deux la vérité, c’est une beauté pour laquelle il faut se battre d’une manière honnête”.44 my review of the translations of berzelius’s lärbok – one must note the lack of a translation into english – contains a sequence of data and may be considered dry and boring,45 but it was necessary for understanding the genesis and spread of that specific image of chemistry which berzelius had constructed. berzelius drove home his chemistry by using different strategies of communication and transmission because he wanted his swedish chemistry to be rooted in the chemical communities of the european continent, in spite of the presence of contrasts and controversies. the surprising fate of the lärbok allows the historian to observe the vicissitudes of swedish science from a particular point of view. but berzelius’s textbook was not the only resource at his disposal to describe scientific progress and to weigh in on his own vision of the state of the chemical sciences. 4. a prestigious arena at the end of november 1818 berzelius, who was then in paris, was elected perpetual secretary to the royal swedish academy of sciences. this institution founded in 1739 had always used swedish for its academic transactions (kongl. svenska vetenskapsacademiens handlingar, then nya handlingar) because scientific knowledge and technical expertise major tools in the development of the economy of the kingdom of sweden. the use of swedish did not deter the dissemination of these transactions in europe because partial translations into various languages were available, and up until 1792, the mathematician abraham gotthelf kästner (1719-1800) translated the whole series into german. after 1792 many difficulties arose due to the decline of the cosmopolitan cultural climate of the enlightenment, and to the napoleonic campaigns, which limited the reception of scientific news from stockholm. so, in december, 1820, reforms were introduced into the statutes of the academy, and berzelius became the prime mover of the reappearance of scientific communication from northern europe. the reforms determined that on the 31st of march of each year, an official and solemn session of the academy would take place, during which the secretary was to present an annual report on the status of science. in march, 1821, berzelius presented his first report which came to 150 printed pages. it is the first volume of berzelius’s årsberättelse om framstegen i physik och kemi, that became a yearly journal, whose first series (18211840) amounts to twenty volumes, while the second series, in seven volumes, finishes in 1847,46 the year before berzelius’s death. firstly berzelius aimed at treating all the sciences, and then he focused on chemistry, physics, geology and mineralogy. composing the reports was a heavy duty and his reports became more and more bulky: the report of march 1845 concerning chemistry and mineralogy consists of 692 printed pages. the preparation of the reports obliged berzelius to systematically read all european scientific activity, therefore enabling him to collect an impressive mass of information. the stated aims of the årsberättelse were two: the first one was pedagogical; the second one was cultural and social. berzelius vigorously supported the improvement of students’ chemical preparation; with regard to his chemical textbook, the reports obviated the need for new editions of a massive textbook because they provided an operative, annual update of scientific progress. in presenting his reports berzelius also wanted to reach a general and wide reading public in order to stimulate a social and institutional interest in science. 56 ferdinando abbri berzelius was not just a historian or a rapporteur because the topics he dealt with were the objects of his own personal research. therefore, the reports contain his critical considerations, and his strong criticisms. the official position of perpetual secretary of the academy did not constrain his polemic spirit when the topics were chemistry and mineralogy. the two series of årsberättelse were not limited to a chapter in swedish science because berzelius’s german former pupils got involved in disseminating the contents of the reports beyond sweden. the first three volumes were translated by gmelin; then the faithful wöhler started translating all the yearly volumes with the title of jahrbericht, and he was even able to excise the censorial expressions berzelius used when he criticized german scientists. thanks to his swiss assistant philippe plantamour, berzelius witnessed his reports published in french in paris, and the first volume (1841) contains the statement “traduit du suédois sous les yeux de l’auteur”.47 årsberättelse was conceived as an instrument of renewal of the academy of sciences but it became an arena, an extraordinary literary place which berzelius occupied in order to accomplish two main goals: the communication of knowledge, and of his research; and the severe criticism of certain philosophical and scientific trends of the culture of his time. 5. a brief conclusion sweden, stockholm, and the academy of sciences are very important places in the history of the development of chemistry from the eighteenth century to the first half of the nineteenth century because they were the context of some extraordinary chapters in the adventurous history of modern chemistry. berzelius is a symbol of swedish science. he was aware that the growth of science was a difficult, but essential task, and he became both a steadfast, experimental researcher and a brilliant controversial figure who had committed himself to elucidate the ongoing progress of science. he adopted various strategies of communication, i.e. the writing of a textbook and of annual academic reports on science, and the creation of a network of personal relationships with students and other followers; these strategies allowed him to keep attention on his ideas and research alive. berzelius contributed to the success of chemistry in the nineteenth century, but his ideas were slowly put aside, and together with his dualistic theory his project of a continuous, public information resource about science disappeared. 6. acknowledgments. i am extremely grateful to the staff of the library of the museo galileo of florence, who helped me to sift through the labyrinth of the many editions of berzelius’s lärbok. references 1. m. roberts, the age of liberty: sweden 1719-1772, cambridge university press, cambridge, 1986. 2. h. olsson, kemiens historia i sverige intill år 1800, almqvist & wiksell, uppsala, 1971. t. frängsmyr (ed.), science in sweden. the royal swedish academy of sciences, 1739-1989, science history publications, canton mass., 1989. f. abbri, un dialogo dimenticato. mondo nordico e cultura toscana nel settecento, franco angeli, milano, 2007. 3. m. beretta, the enlightement of matter: the definition of chemistry from agricola to lavoisier, science history publications, canton mass., 1993. 4. h.t. scheffer, the chemical lectures of h.t. scheffer, edited by t. bergman, and j.a. schufler (translator), kluwer, dordrecht, 1992. j. gadolin, inledning til chemien, tryckt i frenckellska boktryckeriet, åbo, 1798. 5. j. beckman, the publication strategies of jöns jacob berzelius (1779-1848): negotiating national and linguistic boundaries in chemistry, annals of science, 2016, 73, 195-207. 6. f. abbri, la mecca della chimica: stoccolma, berzelius e l’accademia delle scienze, in f. abbri, m. segala (ed.s), il ruolo sociale della scienza (1789-1830), leo s. olschki, firenze, 2000, pp. 101-113. 7. h. g. söderbaum, berzelius’s werden und wachsen: 1779-1821, barth, leipzig, 1889. 8. h. g. söderbaum, jac. berzelius. levnadsteckning, almqvist & wiksells, uppsala, 1929-1931, 3 voll. 9. o. wallach (ed.), briefwechsel zwischen j. berzelius und f. wöhler, h.r. wohlwend, vaduz, 1984, 2 voll. (facs. repr. of the 1901 ed.). 10. e.m. melhado, jacob berzelius. the emergence of his chemical system, almqvist & wiksell international, stockholm, the university of wisconsin press, madison wisconsin, 1981. 11. e.m. melhado, t. frängsmyr (ed.s), enlightenment science in the romantic era. the chemistry of berzelius and its cultural setting, cambridge university press, cambridge, 1992. 12. c.a. russell, from atoms to molecules. studies in the history of chemistry from the 19th century, ashgate, variorum, farnharm, 2010, pp. 67-136. a. lundgren, 57discovering elements in a scandinavian context berzelius och den kemiska atomteorin, institutionen för idé – och lärdomshistoria, uppsala, 1979. 13. j.j. berzelius, essai sur la nomenclature chimique, journal de physique, 1811, 73, 253-286. 14. j. berzelius, versuch, die bestimmten und einfachen verlhätnisse aufzufinden, nach welchen die bestandtheile der unorganischen natur mit einander verbunden sind (1811-1812). herausgegeben von w. ostwald, verlag harri deutsch, thun und frankfurt am main, 1998 (repr. of the leipzig 1892 ed.). 15. j.j. berzelius, essai sur la théorie des proportions chimiques, et sur l’influence chimique de l’électricité, chez méquignon-marvis libraire, paris, 1819. 16. j.h. brooke, introduction: the study of chemical textbooks, in a. lundgren, b. bensaude-vincent (ed.s), communicating chemistry. textbooks and their audiences, 1789-1939, science history publications, canton ma, 2000, pp. 1-18. 17. m. blondel-mégrelis, berzelius’s textbook: in translation and multiple editions as seen through his correspondence, in communicating chemistry. textbooks and their audiences, 1789-1939, science history publications, canton ma, 2000, pp. 233-254. 18. j.j. berzelius, lärbok i kemien, förra delen, tryckt hos henr. a. nordström, stockholm, 1808, n. p. 19. j.j. berzelius, lärbok i kemien, första delen. andra upplagan omarbetad och betydligt tillökt, tryckt hos direct. henr. a. nordström, stockholm, 1817, n. p. 20. o. wallach (ed.), briefwechsel zwischen j. berzelius und f. wöhler, h.r. wohlwend, vaduz, 1984, i, p. 91. 21. j.j. berzelius, elemente der chemie der unorganischen natur. aufs neue durchgesehen vom verfasser. aus dem schwedischen übersetzt, und mit einigen anmerkungen begleitet von j.g.l. blumhof. erster theil, bey johann ambrosius barth, leipzig, 1816. 22. j.j. berzelius, elemente der chemie der unorganischen natur. aufs neue durchgesehen vom verfasser. aus dem schwedischen übersetzt, und mit einigen anmerkungen begleitet von j.g.l. blumhof. erster theil, bey johann ambrosius barth, leipzig, 1816. vorbericht des uebersetzers, pp. iii-iv. 23. j.j. berzelius, lehrbuch der chemie; nach der zweiten schwedischen original-ausgabe und nach den vom verfasser mitgetheilten zahlreichen zusätzen übersetzt und bearbeitet von k.a. blöde. erster band, in der arnoldischen buchhandlung, dresden, 1820. 24. j.j. berzelius, lehrbuch der chemie. nach des verfassers schwedischer bearbeitung der blödepalmstedt’schen auflage übersetzt von f. wöhler. ersten bandes erste abtheilung, in der arnoldischen buchhandlung, dresden, 1825. 25. j. berzelius, brev, utgivna av kungl. svenska vetenskapsakamenien genom h.g. söderbaum, xiii. brevväxling mellan berzelius och eilhard mitscherlich (1819-1847), almqvist & wiksells boktryckeri, uppsala, 1932, pp. 56-57. 26. j. berzelius, bref, utgifna af. kungl. svenska vetenskapsakamenien genom h.g. söderbaum, v. brefväxling mellan berzelius och g.j. mulder (1834-1847), almqvist & wiksells boktryckeri, uppsala, 1916, p. 204. 27. j.j. berzelius, lehrbuch der chemie. zu vollständigem auszuge, mit zusätzen und nachträgen aller neueren entdeckungen und erfindungen, bearbeitet von h. f. eisenbach und c.a. hering, in drei bänden. erster band, druck und verlag der j.v. messler’schen buchhandlung, stuttgart, 1831. 28. j.r. glauber, prosperitatis germaniae pars prima – sexta et ultima pars. et a phylochimico quodam latinitate donata, apud joannem janssonium, amsterdam, 1656-1661. 29. j.j. berzelius, lehrbuch der chemie. zu vollständigem auszuge, mit zusätzen und nachträgen aller neueren entdeckungen und erfindungen, bearbeitet von h. f. eisenbach und c.a. hering, in drei bänden. erster band, druck und verlag der j.v. messler’schen buchhandlung, stuttgart, 1831, vorrede, pp. iii vi. 30. j.j. berzelius, lehrbuch der chemie. aus der schwedischen handschrift des verfassers überzetzt von f. wöhler. vierte verbesserte original – auflage, erster band, in der arnoldischen buchhandlung, dresden und leipzig, 1835, vorrede, pp. iii –iv. 31. j. berzelius, bref utgifna af kungl. svenska vetenskapsakademien genom h.g. söderbaum. vii. strödda bref (1809-1847), almqvist & wiksells boktryckeri, uppsala, 1919, pp. 175-179. 32. j.j. berzelius, traité de chimie. traduit par a.j.l. jourdan, sur des manuscrits inédits de l’auteur, et sur la dernière édition allemande, tome premier, firmin didot frères libraires-éditeurs, paris, 1829. 33. j. berzelius, bref utgifna af kungl. svenska vetenskapsakademien genom h.g. söderbaum. iv. brefväxling mellan berzelius och p.l. dulong (1819-1837), almqvist & wiksells boktryckeri, uppsala, 1915, pp. 77-85. 34. j. berzelius, bref utgifna af kungl. svenska vetenskapsakademien genom h.g. söderbaum. iv. brefväxling mellan berzelius och p.l. dulong (1819-1837), almqvist & wiksells boktryckeri, uppsala, 1915, p. 86. 35. j.j. berzelius, traité de chimie. nouvelle édition entièrement refondue d’après la quatrième édition allemande publiée en 1838, par b. valerius. tome pre58 ferdinando abbri mier, société typographique belge adolph wahlen et cie, bruxelles, 1839, avis des éditeurs. 36. j.j. berzelius, tratado de química, nueva edicion completamente refundida, segun la cuarta edícion alemana publicade en 1838 por b. valerius. traducido del francés en castellano por los doctores rafael saez y palacios, y carlos ferrari y scardini, tomo primero, imprenta y libreria de d. ignacio boix, editor, madrid, 1845, los traductores, p. v. 37. j.j. berzelius, tratado de química mineral, vegetal y animal. segunda edicion francese de la quinta edicion, imprenta de d.j. maria alonso, madrid 1848-1851. 38. j.j. berzelius, trattato elementare di chimica teorica e pratica, tradotto da a.r. con aggiunte di carlo frisiani, dalla tipografia di commercio, milano, 18261828, 4 voll. 39. j.j. berzelius, trattato di chimica, tradotto a parigi par a.j.l. jourdan (vol. 1), m. esslinger (2-3-4) recato in italiano da f. du pré, dal premiato stabilimento tipografico calcografico e librario di g. antonelli, venezia, 1830-1834, 8 voll. f. abbri, l’edizione veneta del lärbok i kemien di j.j. berzelius, in a. bassani (ed.), la chimica e le tecnologie chimiche nel veneto dell’800, istituto veneto di scienze, lettere ed arti, venezia, 2001, pp. 73-86. 40. j.j. berzelius, trattato di chimica. prima edizione napolitana conforme alla quarta edizione tedesca, riveduta ed interamente rifusa dall’autore, e pubblicata in francese con note da b. valerius e dal francese voltata in italiano con note e aggiunte da giovanni guarini. tomo primo, presso puzziello tipografo libraio editore, napoli, 1838. 41. j. berzelius, bref utgifna af kungl. svenska vetenskapsakademien genom h.g. söderbaum. v. brefväxling mellan berzelius och g.j. mulder (1834-1847), almqvist & wiksells boktryckeri, uppsala, 1916, pp. 12-15. 42. j. berzelius, bref utgifna af kungl. svenska vetenskapsakademien genom h.g. söderbaum. v. brefväxling mellan berzelius och g.j. mulder (1834-1847), almqvist & wiksells boktryckeri, uppsala, 1916, pp. 18-21. 43. j.j. berzelius, leerboek der scheikunde, naar de derde omgewerkte en vermeerderde oorspronkellijke uitgave vertaald, eerste deel, bij p.h. van den heuvell, te rotterdam, 1834, voorberigt, pp. v-vii. h.a.m. snelders, wie waren de nederlandse vertalers van berzelius’ «leerboek der scheikunde»?, scientiarum historia, 1968, 10, 191-198. 44. j. berzelius, bref utgifna af kungl. svenska vetenskapsakademien genom h.g. söderbaum. v. brefväxling mellan berzelius och g.j. mulder (1834-1847), almqvist & wiksells boktryckeri, uppsala, 1916, p. 89. 45. on the various editions of berzelius’s textbook: a. holmberg, bibliographie de j.j. berzelius, ie partie. ouvrages imprimés, stockholm-upsal, 1933. j.r. partington, a history of chemistry. iv, 1964, rep. martino publishing, new york, pp. 144-145. 46. j. berzelius, årsberättelse om vetenskapernas framsteg afgivne af kongl. vertenskaps-academiens embetsman, p.j. lindus enka, stockholm, 1821-1825, 5 voll. årsberättelse om framstegen i physik och chemie, p.a. norstedt & söner, stockholm, 1826-1840, 15 voll. årsberättelse om framstegen i kemi i mineralogi, p.a. norstedt & söner, stockholm, 1841-1848, 7 voll. 47. j. berzelius, rapport annuel sur les progrès des sciences physiques et chimiques. traduit du suédois sur les yeux de l’auteur par m. plantamour, fortin, masson et c.ie, paris, 1841. eight volumes were published from 1841 to 1849. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna substantia. an international journal of the history of chemistry 5(1) suppl.: 77-87, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1279 citation: s. menchetti (2021) how do crystals grow? steno’s approach. substantia 5(1) suppl.: 77-87. doi: 10.36253/substantia-1279 copyright: © 2021 s. menchetti. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. how do crystals grow? steno’s approach silvio menchetti dipartimento di scienze della terra, università di firenze, italy e-mail: silvio.menchetti@unifi.it abstract. steno (1638-1686) operated in a historical context rich in discoveries and observations done by previous scientists such as vannoccio biringucci, georg bauer (agricola), johannes von kepler, robert hooke, christiaan huyghens, erasmus bartholin, and others. steno also had to fight against some irreducible dogmatic and “mythological” beliefs, such as the vis formativa and succus lapidescens, supported by e.g. michele mercati and anselmo boetius de boot, respectively. in de solido intra solidum naturaliter contento dissertationis prodromus steno deals with almost all aspects of earth sciences and not just “solid inclusions” as it might seem from the full title of the prodromus. this contribution deals only with aspects related to crystallography and minerals in general. the most famous is highlighted by the sentence “non mutatis angulis” which is a clear reference to the fact that interfacial angles of quartz crystals do not change regardless of the size and the number of the faces. this observation was then generalized as a law for all minerals by jean-baptiste romé de l’isle a century later. less well known but of great importance is steno’s assertion that the crystals grow thanks to the addition of particles that come from an external fluid and are not “fed” from the inside like in vegetables; moreover, the speed of growth is not the same for all faces. for example, the faces of the “pyramid” in quartz can grow more or less rapidly than those of the prism (giving rise to either squat or elongated crystals). it can therefore be argued that steno has greatly contributed to the concept of anisotropy in the solid state, typical of all crystals. stenonite, sr2al(co3)f5, is a new mineral dedicated to his memory about sixty years ago. keywords: steno, crystal growth, quartz, interfacial angles, stenonite. introduction to introduce the topic of crystal growth and to highlight steno’s great contribution, it seems particularly fitting to report most of the first page from the foreword by o. grubessi and f.p. sassi,1 of the book “minerals in stamps” by grubessi and pasero, published by the italian society of mineralogy and petrology in 1998. special stones and gems have written the history of earth sciences, and have accompanied the history of man with variegated roles. 1 o. grubessi, f.p. sassi, in minerals in stamps (eds. o. grubessi, m. pasero), felici editore, pisa, 1998, viii +215 pp. 78 silvio menchetti charm, curiosity, magic, science; mystic therapy, magic therapy, physical therapy; belief in extra natural powers and the belief in the action of the product, are intimately bound with the role that stones, minerals and gems, play in our heritage as well as in the mentality of our ancestors. by his nature, man has always been attracted by what is beautiful, precious and mysterious. therefore, his interest in gems and minerals, which often have all these features, is not surprising. in the course of centuries the intrinsic value attributed to these stones has also been modified as a result of external factors. indeed, their rarity and beauty became supplemented on one side by their process, as an expression of human activity and intelligence, and on the other side, by their links with astrology and medicine, as an answer to transcendental requirements. however, the attraction man has for minerals prevails over all the other features in human feelings, a kind of fascination which has not been the least extinguished by the development of scientific knowledge about their structure, properties, and genesis. the well-shaped morphology, the beauty of minerals in general, the flatness and the shine of the faces (fig. 1a), the color that can vary greatly even for the same species (fig. 1b), were certainly some of the many observations on minerals that triggered human curiosity. while most people have limited themselves to expressing wonder and amazement, some have wondered what could be the source/origin of such peculiarities shown by natural objects. what are the relationships between what we can see with the naked eye and what is inside the crystal and which we cannot see? what are the reasons for the variability of shapes, color, luster, hardness? in conclusion, how do crystals form and grow? when steno lived in tuscany he made many observations on the formation and growth of crystals as it can be understood from his de solido intra solidum naturaliter contento dissertationis prodromus.2 actually steno was not the first one to deal with these problems, as reported in the next section where some of the pioneers of this long history will be mentioned. the birth of crystallography in this brief historical excursus, the text by a. authier3, early days of x-ray crystallography, published in 2013, to celebrate the international year of crystallography (2014), will be of great benefit. by personal and perhaps questionable choice let’s begin from the early 1500s, more precisely with vannoccio biringucci or biringuccio (1480-1537) from siena. biringuccio was a great technician who strongly contributed to the literature related to mineralogy and metallurgy of the xvi century. his work de la pirotechnia (fig. 2), written in italian, was published posthumously in 1540. in the ten books that compose it, biringuccio deals with minerals and mostly with melting, separating and alloying of 2 n. stenone, su un corpo solido contenuto naturalmente entro un altro solido. prodromo a una dissertazione. a cura di annibale mottana, edizioni teknos, roma, 1995, 66 p. 3 a. authier, early days of x-ray crystallography, oxford university press, oxford, 2013, 464 p. fig. 1. morphology and colour of minerals. 1a: hematite fe2o3 (https://www.mindat.org/photo-122270.html). 1b: red and yellow crystals of cetineite [(k,na)6sb3+12(sb3+s3)2o18(oh)0.5.5h2o] (collection v. paoletti, photo by b. fassina, published with permission). 79how do crystals grow? steno’s approach metals. de la pirotechnia, repeatedly printed and translated into french, english, spanish and german, had great success especially for its eminently practical aspect. as far as mineralogy and crystallography are concerned, we report (biringucci4, 1914 p. 187-188) his observation on the morphology of ”margassite” (pyrite): “may be found as veins and in form of certain grains, either big or small, all cubic similar to dices, or alternatively prismatic all exactly squared so that no craftsman, with any instrument he uses, could not draw more perfect nor better their angles”. in modern terms (see the italian textbook carobbi, mineralogia, 15 p. 5) this sentence can be expressed as “pyrite occurs in crystals in the shape of a geometrically regular cube but also in the shape of a straight parallelepiped, with dihedral angles between pairs of faces always equal to 90°”. as an example, fig. 4 v. biringucci, de la pirotechnia, a cura di aldo mieli, società tipografica editrice barese, bari, 1914, 198 p. 5 carobbi, mineralogia 1. i fondamenti di cristallografia e ottica cristallografica by f. mazzi and g.p. bernardini uses, firenze, 1983 262 p. 3a shows geometrically regular pyrite cubes with square faces, while in fig. 3b the faces of the pyrite “cubes” are rectangles. but the interfacial angles are always 90°. as it is known, interfacial angles are important in crystallography but not the extension and regularity of the faces. this is the first qualitative reference to what will become the law of the constancy of interfacial angles expressed as a general law by jean-baptiste romé de l’isle in 1783. as we will see, steno also contributed to this point. georg bauer (1494-1555), a doctor, also read and appreciated biringuccio’s work. he is better known by the latinized name georgius agricola. agricola (fig. 4) obtained the baccalaureus artium at the university of leipzig and later studied medicine. he also studied at the universities of bologna and padua and developed his interest in the mineral world especially during his stay as a doctor in the mining town of joachimstal (jáchymov, bohemia) and later in chemnitz, saxony. he was a person of great culture who left several treatises written in latin including: – bermannus (remarkable knowledge on mining), 1530. – de natura fossilium (systematic mineralogy work), 1546. – rerum metallicarum interpretatio (mineralogical glossary in latin and german), 1546. – de re metallica, 1556 (summa of the knowledge of the time in metallurgy and mining), which obscured the fame of biringuccio’s pirotechnia. agricola is often considered the “father of mineralogy”. interesting information on biringuccio and agricola and on the relationships between their works (de la pirotechnia and de re metallica) can be found in the paper origins of mineralogy: the age of agricola by c. schneer [66]. other contributors practically contemporary to steno’s prodromus are discussed below. johannes kepler (1571-1630), was the first to postulate a correlation between the external morphology and the internal structure of crystals. in his 24-page pamphlet, strena seu de nive sexangula, “a new year gift of hexagonal snow”7 he describes snow crystals as the result of the aggregation of water spheres of equal size which, interacting with each other, reach equilibrium, arranging themselves in regular hexagons. studies 6 c. j. schneer, eur. j. mineral. 1995, 7, 721-734. 7 j. kepler, strena seu de nive sexangula, frankfurt am main, gottfried tampach, 1611. english translation: c. hardie with essays by b.g. mason and l.l. whyte, the six-sided snowflakes, oxford university press, oxford, 1966. fig. 2. title page of de la pirotechnia, published in venice in 1540 (https://bibdig.museogalileo.it/teca/imageprovider?image=./000/00 0/302/302960/302960_00005r.jpg). 80 silvio menchetti of snowflakes led kepler to formulate the idea of close packing of spheres. the so-called kepler conjecture, only recently demonstrated8, tells us that there is no way to arrange equal spheres in space with a density greater than that of the hexagonal close packing or the cubic close packing, with centered faces. according to authier [3] (p. 372), kepler’s intuition is a milestone for the concept of the space lattice. robert hooke (1635-1703), contributed to the emerging science of crystallography by developing pioneering models to deduce the distribution of the atoms’ disposition in the structures from the shape of macroscopic crystals. for example, by variously combining identical spheres (close packing), he had managed to reproduce the external shape of alum octahedra (fig. 5). according to hooke9, by combining the equilateral triangle (a) and the square (l) (fig. 5), one can reconstruct the shape of vitriol, quartz, saltpeter etc. authier [3] (p. 399) highlights that hooke “had already implicitly observed the constancy of interfacial angles, noting the extension of crystal faces depended on the number of spheres added on each plane during the growth of the crystal.” rasmus bartholin (1625-1698 brother of thomas, teacher of steno) discovered a curious optical property 8 t. hales, m. adams, g. bauer and 19 others a formal proof of the kepler conjecture, forum of mathematics, pi, 2017, 5, e2, 29 pp., doi: https://doi.org/10.1017/fmp.2017.1 9 r. hooke, micrographia, jo martin, and ja allestry, printers to the royal, society, london, 1665. fig. 3. crystals of pyrite. 3a: pyrite in geometrically regular cubes (https://en.wikipedia.org/wiki/pyrite). 3b: “cubes” of pyrite with rectangular faces (https://i.etsystatic.com/16351195/r/il/5994c7/1719730471/il_fullxfull.1719730471_rcxj.jpg). fig. 4. portrait of georgius agricola (unknown painter, https:// commons.wikimedia.org/w/index.php?curid=4858286). 81how do crystals grow? steno’s approach shown by transparent calcite crystals of helgustaðir (“icelandic spar”) from eastern iceland. a black dot marked on a sheet is doubled in two points when viewed through the faces of a calcite rhombohedron. the phenomenon was later identified and took the name of double refraction. christiaan huyghens (1629-1696) formulated the theory of the wave nature of light useful to explain reflection and refraction phenomena. the phenomenon of double refraction was also explained with huyghens’ theory. he also assumed that calcite was made up of particles in the form of flattened ellipsoids of rotation, with the rotation axis parallel to the ternary axis of the rhombohedron. in this way he explained the rhombohedral cleavage of calcite. fina l ly, domenico guglielmini (1665-1710), a mathematician, chemist and physician lived shortly after steno. he was one of the first to take an interest in salt crystallization. in particular, in his articles, there are important observations on the morphology of crystals such as saltpetre, vitriol, rock salt and alum synthesized in the laboratory. very interesting is guglielmini’s observation on rock salt cubes: although the shape of the crystals may be faulty “the inclination of the sides is always stable, which does not vary by one point from the right angle, typical of the cubic figure” (quoted in p. aloisi, p. 167). it cannot be denied that the constancy of the angles for rock salt is clearly delineated. guglielmini also contributed in an interesting way to the knowledge of the structure of crystals. in a well documented article entitled “domenico guglielmini e la cristallografia”, the author (p. aloisi10) analyzes guglielmini’s writings in relation to the results of biringuccio, steno, hooke, huygens, romé 10 p. aloisi, periodico di mineralogia, 1937, 8, 163-175. de l’isle and haüy and concludes “... without wanting to diminish the great merits of romé de l’isle and haüy, it can be said, it seems to me, that a century before them, and in more difficult conditions, guglielmini had already laid the fundamentals of crystallography” (p. aloisi [10], p. 175). steno steno arrived in italy in 1666, preceded by his fame as a great expert in anatomy, but during the twoyear stay in tuscany he also turned his interest to geology, mineralogy and crystallography. the grand duke involved steno in various problems such as dissections of fish and human corpses, study and cataloging of fossils and minerals, geological excursions, etc. at the end of the two-year period he hastily wrote the famous prodromus (fig. 6), which was edited by his friend vincenzo viviani and published in 1669. fig. 5. hooke’s reconstruction of alum crystals by close packing of identical spheres. after hooke, 1665 [9] (https://authors.library. caltech.edu/23510/1/bmc_hooke%27s_models.pdf ). fig. 6. title page of steno’s prodromus (florentia: ex typographiae sub signo stellae, 1669). 82 silvio menchetti to conduct his research steno could take advantage of the results previously achieved by e.g. vannoccio biringucci, georgius agricola, johannes von kepler, robert hooke, christiaan huyghens and erasmus bartholin but he also had to fight against a series of mythological beliefs, superstitions and dogmatic bonds. particularly hard to believe, at least nowadays, the “vis formativa” for which fossils and minerals would form directly in the rocks by celestial influence (“principle” supported by e.g. michele mercati, 1541-1593) or the “succus lapidescens”, petrifying juice that caused diamonds to reform in their fields a couple of years after they were removed (“principle” supported by e.g. anselmo boetius de boot, 15501636). michele mercati and anselmo boetius de boot were very influential, because they were the personal physician of the pope and of the emperor, respectively. after a preamble of dedication to the grand duke and an illustration of the prodromus content, steno lists a series of almost dogmatic declarations. only those most relevant to the present topic are reported here. 1. a natural body is made up of imperceptible particles accessible to the actions coming from magnet, fire and sometimes light; you can find free passages both between the particles and inside them (stenone [2], p. 9). it seems very likely that steno thought of particles juxtaposed to form a solid and was far from the intuition of a homogeneous-discontinuous-periodic sequence of atoms. 2. distinction between fluid (moving particles) and solid: the particles never move away from each other “for as long as that solid remains solid and intact” (stenone [2], p. 9). but “when a solid is formed, its particles move from one place to another” (stenone [2], p. 9). steno was very interested in the problem of the movement of particles; in fact, he promised to analyze in detail the various causes of motion in the proposed dissertation but which never was published. however, even in the prodromus the exposition of the problem is very detailed and sometimes a little dispersive. after long discussions, which also acknowledge the existence of a divine force, he concludes that the movement of the particles in what is produced by nature derives from the movement of a fluid that enters it. this fluid can come from the sun or other source. (stenone [2], p. 9-10). evidently steno follows descartes on the cosmic ether spread throughout the universe. as we know, this mysterious entity was thought to exist until the early twentieth century. 3. the sequential order of solid formation is defined (see the full title of the prodromus). for example, fossils are formed before the rocks that contain them; mineralized veins are formed subsequent to the embedding rocks (stenone [2], p. 12). this statement is based on steno’s principle of molding as explained by kardel.11 4. bodies with the same shape and intrinsic characteristics will be equal also as regards the place of formation (a somewhat risky statement, as observed by a. mottana in stenone [2] (p. xi), and the way they grow (stenone [2], p. 13). quartz and saltpeter are both formed by deposition from a fluid that is not necessarily aqueous (molten e.g. for quartz). in this regard it is worth mentioning a paper by f. rodolico12 relating to the “cristalli di quarzo descritti da nicola stenone”. interesting observations by steno are reported on the mixed inclusions present in the quartz crystals. steno says that many inclusions are made up of only air and therefore quartz cannot have formed from a water fluid because otherwise all inclusions would be water and it is known “that the water thus contained cannot evaporate for any series of centuries” (stenone [2], p. 26). 5. a natural body is always produced by a fluid (stenone [2], p. 14); at present we know that this is not always true for some metamorphic minerals. 6. the growth of a solid occurs by juxtaposition of particles precipitated by an external fluid and not by “digestion from within” as in a vegetable (stenone [2], p. 14) (see below). this is a concept of great importance in steno’s scientific thought. crystal (quartz) (stenone [2], p. 25-30) to continue our discussion of steno’s crystallographic approach, we should focus on the mineral quartz. steno prefers the term crystal, used by pliny, to quartz, adopted by agricola. it was believed that the clear and transparent quartz crystals, common in the mountains, were formed by a sort of super cooling of “permanently hardened” water. of course steno is against this hypothesis, as can be seen from the sentence “on the basis of what has been exposed so far, it would be legitimate to demonstrate that extreme cold is not the efficient cause of crystal (quartz)” (stenone [2], p. 30). steno’s use of the words, “efficient cause” is very interesting. as we know, aristotle asks himself the following question: why do things arise, grow and die? he identifies four categories of causes in this regard: material, formal, efficient (or moving cause of a change or movement), and final. it is 11 troels kardel, “prompters of steno’s geological principles: generation of stones in living beings, glossopetrae and molding,” in the revolution in geology from the renaissance to the enlightenment (ed. g. d. rosenberg), geological society of america, memoir 203, 2009 boulder, co., pp. 127134. 12 f. rodolico, rivista storia scienze mediche e naurali, 1955, 1-6. 83how do crystals grow? steno’s approach therefore evident that even in the 17th century, the aristotelian categories were still infl uential. according to steno, crystal (quartz) is composed of two hexagonal pyramids, (we know that instead it is the combination of two rhombohedra, direct and inverse) and an equally hexagonal intermediate column that is the hexagonal prism. it is strange that a keen observer like steno never mentions the little faces of the trapezohedron and of the trigonal bipyramid, which are very useful in distinguishing the right from the left quartz. yet he must surely have seen them in the numerous quartz samples at his disposal. aft er specifying the terms that he uses to describe the crystalline form, he goes on to explain the model of crystal growth that occurs by juxtaposing particles from an external fl uid. a) th e crystal grows from an initial germ (on whose nature steno declares himself incompetent) by juxtaposition of particles precipitated by an external fl uid. steno rejects growth by addition within the crystal as would be the case for growth of living things. (stenone [2], p. 27). th is “vegetative” principle recalls the ancient beliefs on mineral deposits whose arrangement was compared to that of the blood veins in the bodies of animals or to the branches of trees in the woods. since a mineral deposit was thought to have formed inside a mountain, it was compared to a large branching tree with roots at the base of the mountain. b) th e particles are not distributed randomly on all planes (faces of the crystal) but, fi rst on the apexes, then on the “pyramidal” faces, and then on the faces of the column (hexagonal prism). th erefore, the faces of the hexagonal prism (quadrilateral planes, constituted by the bases of the “pyramidal” faces) are sometimes large, sometimes small or completely missing (fig. 7a and 7b). (stenone [2], p. 27). furthermore, the quadrilateral planes are oft en striated for the same reason (fig. 8). c) th e crystalline matter is superimposed on the various “pyramidal” faces at diff erent times and in different quantities: therefore the “pyramid” axis does not always form the same straight line with the column axis (see fig. 12, section 4). th e faces of the “pyramids” are hardly equal to each other, and not always triangular (stenone [2] 1995 p. 27) (fig. 9) while the intermediate planes (faces of the hexagonal prism) are not always equal to each other and are not always quadrilateral. th e solid angle of the vertex can be broken down into numerous solid angles so as to appear as an edge (stenone [2], p. 27) (fig. 9). d) it may happen that the crystalline material does not spread evenly on the faces of the “pyramids” and the fig. 8. quartz crystal with striated faces (https://goldenhourminerals.com/listing/864704147/cristallo-naturale-colombiano-di-quarzo). fig. 7. crystals of quartz. 7a: quartz with typical habit. 7b: quartz with “bipiramidal” habit (https://www.mindat.org/photo-188888. html; https://www.mindat.org/photo-156304.html). fig. 9. smoky quartz viewed perpendicular to the vertical axis (https://www.spiriferminerals.com/mini.php?id=2654&width=300&fi le =gfa30d.jpg). 84 silvio menchetti edges develop more than the faces (stenone [2], 1995, p. 27-28) (stepped crystals, fig 10). e) th e hardening occurs at diff erent times so the faces may not be completely smoothed. a fracture surface is smoother than the crystal faces (stenone [2] 1995 p. 28) (fig. 11). f) why does crystalline matter settle at one point of the growing crystal rather than another? steno writes that this depends on the characteristics of the growing crystal and not on those of the nutrient fl uid (stenone [2], p. 28-29). “corpi angolati”: angular bodies aft er quartz (crystal), steno deals with other angular bodies, that is convex solids with interfacial angles; in particular hematite, diamond and pyrite. with angular bodies of iron, he describes the various habits typical of hematite, namely rosettes (including micaceous hematite), “oligisto” with twelve faces and the crystals with 24 faces. steno also investigates the way hematite is formed and grown in analogy to what was said for quartz. for diamond, in addition to the description of the various habits, he examines the analogies with the formation and growth of quartz and rejects the hypothesis that this mineral can re-form, in a few years, in the place from which it was extracted. the marcasite (pyrite) that steno deals with is always in cubes; it is likely that, as mottana (in stenone [2], p. xv) observes, it was not a pyrite from elba which, at least today, is mainly in pentagonal dodecahedra. steno describes the perfection of cubic crystals (although in general steno defi nes them as rectangular parallelepipeds because rarely faces are all the same), and the “trigliph” striated faces for which he fi nds a very complicated explanation linked to the movement of the fl uid. even the relationships with the rocky matrix are described with complex mechanisms for which he also refers to the “magnus” galileo. th e end result, however, leads him to erroneously conclude that pyrite was formed before the embedding rock. non mutatis angulis in fig. 12, the upper part of the only image included in the prodromus is shown. th e fi rst seven drawings represent vertical sections of a quartz crystal. in particular, section 1 (with four sides: a rhombus) refers to a crystal with a “bipyramidal” habit in which the column, i.e. the hexagonal prism, is completely absent (see fig. 7b). in sections 2 and 3 (with six sides) the faces of the hexagonal prism do appear: in section 2 less developed than in 3 (see fig. 7a). in section 4 irregularities appear in the faces such as the axes of the parts that make up the body of the crystal do not form a straight line. sections 5 and 6 show that in the plane of the axis both the number and the length of the sides can change, while not changing the angles. steno defi nes this characteristic with the three words (non mutatis angulis) which have become very famous. at the same time, several cavities remain in the center of the crystal and various little layers are formed. finally, section 7 shows, always in the plane of the axis, the variation in the number and length of the sides when the new crystalline matter overlaps the faces of the “pyramids”. th e growth takes place layer by layer. drawings 8 to 12 show similar variations, but seen in sections perpendicular to the vertical axis. we pass fig. 11 quartz: fracture surface (https://geology.com/minerals/ quartz.shtml). fig. 10. quartz: stepped crystal (https://sma.unibo.it/en/the-university-museum-network/mineralogical-collection-luigi-bombiccimuseum/gallery/). 85how do crystals grow? steno’s approach from a regular hexagon to figures with sides gradually different in length and then also in number. section 13 indicates how, when new matter is added on the face of the pyramids, sometime they change their length and the number of sides composing the base, but without changing the angles (non mutatis angulis). the comparison between steno’s drawing and the result of modern x-ray investigations is impressive (fig. 13). drawings 14 to 19 refer to the various types of hematite described in the text, and are a bit more complex. it should be noted that, for hematite, the sentence “non mutatis angulis” never appears. as a curiosity we can add that schneer13 notes that some of steno’s drawings, from his only illustration (fig. 12), are similar to those of hooke and he wonders if steno may have been influenced by having perhaps seen hooke’s micrographia during his stay in paris. of course the question is unanswered. conclusions as we have already said, steno could rely for mineralogy, crystallography and in general for the earth 13 c. j. schneer, in steno as geologist (ed. g. scherz), odense, university press copenhagen, acta hist. sci. nat. med, 1971, 23, p. 293-307. sciences on the results published before him by scientists of considerable stature. as claimed by authier [3] (p. 400), steno was very familiar with the works of kepler, descartes, bartholin and almost certainly hooke too. however, these authors are never mentioned, perhaps because the prodromus is a hasty text; perhaps they would have been mentioned in the “dissertazione”, which was never published. for example, the two crystallographic-groundbreaking concepts expressed by steno, non mutatis angulis and crystal growth (in particular quartz), had certainly some precursors in biringucci, kepler and hooke. democritus (stenone [2], 1995, p. 3), seneca (stenone [2], 1995, p. 8), hippocrates (stenone [2], 1995, p. 16), descartes (stenone [2], 1995, p. 20) and galileo (stenone [2] 1995, p. 34) are mainly cited for philosophical reasons except galileo mentioned in the discussion on the formation of pyrite, but with the wrong conclusion (certainly not because of galileo) that pyrite was formed before the embedding rock. it should never be forgotten that, mythological legacies, deep-seated superstitions and dogmatic bonds were still widespread and could also lead enlightened researchers to conclusions with no scientific value. an exemplary character to understand this mentality is michele mercati, a great scholar of rocks, minerals and fossils who was responsible for the “vatican metallotheca”, the most important naturalistic museum of the renaissance. in an interesting and exhaustive article entitled “michele mercati (1541-1593) e la metallotheca”, accordi14 illustrates the theories of mercati, basically a follower of aristotle, who, in support of his theses, does not hesitate to report full passages of the greek philosopher. accordi14 (p. 12) writes: “by treating minerals he, like almost all his predecessors, fully accepts the theory 14 b. accordi, geologica romana, 1980, 19, pp. 1-50. fig. 13. growth steps in a plane of quartz when seen down the c-axis. left: enlargement of steno’s sketch (stenone [2]; see fig. 12). right: x-ray topographic image of quartz exhibiting the typical dislocations and bands due to crystal growth (modified after authier, 2013 [3]). fig. 12. detail of plate published in steno’s prodromus. 86 silvio menchetti of their genesis by condensation with the force of heat, or cold, in the presence or absence of air with or without the help of fire; therefore little progress since the time of albert magno (13th century).”another singular aspect concerns citations of previous works. accordi explains why mercati, who cites the numerous sources he consulted, even though he publishes three drawings of the great conrad gesner (1515-1565), never cites him, as if he had never existed. gesner was officially forbidden to mercati as “heretic”: he was a protestant. it is worth remembering that steno had the opportunity to read mercati’s manuscript (on metallotheca) with the permission of the florentine scholar and scientist carlo dati who had found and purchased it in 166515. steno was usually able to eliminate these prejudices from his experimental way of inferring, but he was not always successful at eliminating them from the thoughts of others. as suggested by abbona16 in his extensive essay “niccolò stenone, un modello di ricercatore”, we can refer to steno’s manuscript entitled chaos (discovered only in 1946) as an important source of news about his personality. steno writes: “in matters of natural sciences it is good not to bind to any theory, but to classify observations in order by trying to arrive at some result on one’s own initiative. in the field of natural sciences we derive our knowledge only from experiments and observations and from all that we can detect with metaphysical and mechanical principles.” and he continues “because nothing is more difficult than putting aside prejudices, even modern works are not free from traces of preconceived ideas, and if i wanted to make an exception, i would deserve censorship for my brazen pride” (quoted in abbona [16], p. 68). it is probable that also for this reason his lively and pragmatic prodromus has fallen into oblivion for a long time, despite an english translation and a second edition in latin (shortly after the first florentine edition) printed in leiden, home of the most ancient university of the netherlands where steno had followed courses in medicine, astronomy and others subjects. however, there is no doubt that the prodromus contains very remarkable observations also with regard to mineralogy and crystallography. “non mutatis angulis”: as we have seen previously, these three words appear in the explicatio figurarum about drawings 5 and 6 (longitudinal sections of quartz crystals). the same happens for drawing 13, the cross sectional drawing of a quartz crystal. steno speaks about 15 e. andretta, michele mercati, dizionario biografico degli italiani, 2009, 73. 16 f. abbona, emmeciquadro 2004, 21, pp. 65-86. the number and length of the sides, but it is clear that, being in section, it is about the number and extent of the faces and the non-changing angles are interfacial angles. therefore for quartz the constancy of the dihedral angles is clearly established. a current formulation (derived from carobbi’s mineralogy [5], p. 5) of the general law expressed by romé de l’isle in 1783 is the following: at the same temperature, crystals of the same crystalline substance, (however and wherever they are formed, if with a morphology similar) exhibit faces, determining in pairs (in all crystals) equal interfacial angles. the three words of steno (non mutatis angulis) have had, especially in the past, a very strong following; but can it be assumed that it is really a true anticipation of the first law of crystallography such as to attribute its authorship to steno? according to aloisi [10] (p. 165), this is not the case. “the observation is confined to the explanation of the table; in the text there is no mention of the thing and for the other minerals (oligisto, pyrite, diamond) both in the text and in the explanation of the figures, absolute silence in this regard”. it is interesting to compare aloisi’s opinion with that of authier [3] (p. 399-400): “this is the only place where steno clearly states the constancy of interfacial angles. he presents it as a fact of observation, without proof, and not as an universal law and he refrains from relating it to any atomistic hypothesis about the inner structure of the crystal.” pedersen17 believes that this is essentially a philosophical problem; steno limits himself to describing the constancy of the interfacial angles in quartz and implicitly in hematite. pedersen continues (p. 123) “but it seems to be undeniable that steno was the first scientist who put this insight to fruitful use even if he did not put it into relief as a fundamental law.” in conclusion, biringucci, libavius, huygens, hooke and others have expressed, for a single mineral, some ideas that, sometimes implicitly, lead to the concept of the constancy of the interfacial angles. guglielmini represents a particular case as he deals with artificial salts; however his observations lead explicitly to the concept of the constancy of the angles at least for sodium chloride. finally steno’s observations for quartz are precise and incontrovertible. however, these are entirely confined to quartz and do not even extend explicitly to the other angular bodies (oligisto, pyrite, diamond) that steno deals with. it therefore seems inappropriate to me to consider it a true anticipation of the universal law formulated by romé de l’isle. 17 o. pedersen, stenoniana nova series copenhagen, 1991, 1, pp. 113-134. 87how do crystals grow? steno’s approach “crystal growth”: his is truly steno’s most important intuition. the crystal grows from an initial germ (on whose nature steno declares himself incompetent) by juxtaposition of particles precipitated by an external fluid. the growth takes place layer by layer; the growth speed is not the same for all faces; and the edges can grow faster than the faces. crystalline matter is deposited in one point of the crystal instead of another due to the characteristics of the growing crystal and not those of the nutrient fluid. as dino aquilano18 writes (2014, p. 3): “it is therefore to this danish genius, naturalist, geologist and anatomist ....., that we owe the concept of anisotropy of the solid state, which distinguishes crystals from any other state of aggregation of matter.” steno was also honoured with a mineral species dedicated after him in 1962. stenonite is a rare aluminofluoride carbonate, sr2al(co3)f5, found and described by pauly19 at the ivigtut cryolite locality greenland. the crystal structure of stenonite has been solved and published by hawthorne20 in 1984. aknowledgements i thank luca bindi for helping with the english, stefano dominici for useful advice and troels kardel for providing bibliographic material difficult to find. the manuscript has benefited greatly from the revisions by a. mottana, r. rinaldi and g. d. rosenberg. references [1] o. grubessi, f.p. sassi, in minerals in stamps (eds. o. grubessi, m. pasero), felici editore, pisa, 1998, viii +215 pp. [2] n. stenone, su un corpo solido contenuto naturalmente entro un altro solido. prodromo a una dissertazione, a cura di annibale mottana, edizioni teknos, roma, 1995, p.66. [3] a. authier, early days of x-ray crystallography, oxford university press, oxford, 2013, 464 p. [4] v. biringucci, de la pirotechnia a cura di a mieli, società tipografica editrice barese, bari, 1914, 198 p. [5] f. mazzi, g. p. bernardini, i fondamenti di cristallografia e ottica cristallografica, in mineralogia (ed. carobbi), uses, firenze, 1983, 262 p. 18 d. aquilano, emmeciquadro, 2014, 52, pp. 1-8. 19 h. pauly, medd. grønland, 1962, 169(9), pp. 1-24 20 f. c. hawthorne, can. mineralogist 1984, 22, 245-251. [6] c. j. schneer, eur. j. mineral., 1995, 7, pp. 721-734. [7] j. kepler, strena seu de nive sexangula, frankfurt am main, gottfried tampach, 1611. english translation: c. hardie with essays by b.g. mason and l.l. whyte, the six-sided snowflakes, oxford university press, oxford, 1966. [8] t. hales, m. adams, g. bauer and 19 others a formal proof of the kepler conjecture, forum of mathematics, pi, 2017, 5, e2, 29 pp., doi:https://doi. org/10.1017/fmp.2017.1. [9] r. hooke, micrographia, jo martin, and ja allestry, printers to the royal, society, london, 1665. [10] p. aloisi, periodico di mineralogia, 1937, 8, pp. 163175. [11] t. kardel,“prompters of steno’s geological principles: generation of stones in living beings, glossopetrae and molding,” in the revolution in geology from the renaissance to the enlightenment (ed. g. d. rosenberg), geological society of america, memoir 203, 2009 boulder, co., pp. 127134. [12] f. rodolico, rivista storia scienze mediche e naturali, 1955, pp. 1-6. [13] c. j. schneer, in steno as geologist (ed. g. scherz), odense, university press copenhagen, acta hist. sci. nat. med, 1971, 23, pp. 293-307. [14] b. accordi, geologica romana, 1980, 19, pp. 1-50. [15] e. andretta, michele mercati, dizionario biografico degli italiani, 2009, 73. [16] f. abbona, emmeciquadro, 2004, 21, pp. 65-86. [17] o. pedersen, stenoniana nova series copenhagen, 1991, 1, pp. 113-134. [18] d. aquilano, emmeciquadro, 2014, 52, pp. 1-8. [19] h. pauly, medd. grønland, 1962, 169 (9), pp. 1-24. [20] f. c. hawthorne, can. mineralogist, 1984, 22, pp. 245-251. 1 a new response to wray and an attempt to widen the conversation eric scerri department of chemistry & biochemistry, ucla, usa email: scerri@chem.ucla.edu received: sept 08, 2022 revised: oct 30, 2022 just accepted online: nov 03, 2022 published: xxx this article has been accepted for publication and undergone full peer review but hasnot been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: scerri e. (2022) a new response to wray and an attempt to widen the conversation. substantia. just accepted. doi: 10.36253/substantia-1806 abstract this article begins by examining a recent claim by brad wray that the discovery of atomic number and isotopy constitutes a scientific revolution in the sense of the later writings of thomas kuhn. i argue that although kuhn’s criteria may apply to the change from the ptolemaic to the copernican model of the universe, they do not apply in the above chemical or atomic case. i also examine the wider issue of kuhn’s turning away from internal scientific issues to a consideration of lexical issues. i conclude, as others have done before me, that this may have been a wrong turn in view of the emphasis being placed on questions of sense rather than reference. mailto:scerri@chem.ucla.edu 2 1. introduction in teaching introductory philosophy of science, one makes a distinction between popper and kuhn and the fact that for popper a decisive refutation such as the discovery of black swans is supposed to lead to the abandonment of the ‘law’, that all swans are white, provided there are no non ad-hoc moves that can rescue the theory. by contrast kuhn’s account is said to be more permissive because it allows for the occurrence of anomalies, although these events do not cause the sudden downfall of the paradigm. one needs to wait for more anomalies, which eventually lead to a crisis, a revolution, and eventually the establishment of a new paradigm. an important aspect of this scenario is that there need to be several anomalies.1 in the case of the periodic table there were just two anomalies in which ordering the elements according to their atomic weights failed to classify a total of four elements in their correct groups, as revealed through their chemical properties. these so-called pair reversals consisted of the more significant case of the elements tellurium and iodine with an atomic weight weight difference of 0.7 atomic weight units and the nickel cobalt anomaly (0.2 units). this situation clearly did not constitute a scientific crisis, on its way to becoming a scientific revolution in the sense of kuhn’s early account.2 the modification made by mendeleev and other discoverers of the periodic table of reversing the positions of tellurium and iodine as well as of cobalt and nickel was not ad-hoc, since it accommodated the known properties of these elements. the paradigm of the periodic table was rescued successfully, in that all the other elements could still be ordered according to increasing values of atomic weight. the anomalies that mendeleev and his contemporaries experienced eventually led others to discover isotopes, rather than refuting or revolutionizing the periodic table. similarly, the discovery of numerous radioisotopes in the early 20th century did not lead to the downfall of chemistry’s central paradigm of the periodic table. 3 in the copernican revolution however, it was not just a matter of one or two planets not orbiting as they should, but a major turning inside-out of the prevailing geocentric paradigm. later on, one or two planets were found to have anomalous orbits. this fact did not lead to an overthrow of the copernican paradigm but indeed to the successful prediction of the planet uranus. so much, for the time being, for the way that kuhn originally envisages scientific revolutions. the philosopher of science brad wray has proposed that the discovery of atomic number and change in the manner that elements were defined represented a scientific revolution (wray, 2018).3 however, as i previously responded, once the focus had been narrowed from protons and neutrons to just protons (from atomic weight to atomic number) everything fell into place and there was no revolution to speak of (scerri, 2021).4 as i see it, science develops via a process of greater focus, greater specialization5 and looking at increasingly more microscopic components. for example, the major changes in modern biology and chemistry have come about due to a focus on dna and the electron, in biology and chemistry respectively. science does not progress by merely changing the manner in which scientific entities like planets and elements are defined. science is more about ontology than about the manner in which human beings classify the world. of course, our concepts can prejudice what we observe, experiments are theory-laden and so on. but one need not go overboard in thinking that scientific discoveries cannot occur until the appropriate terminology is available. i suggest that kuhn may have been wrong to place such a big emphasis on scientific lexicon in his later work.6 such a step may have been motivated by needing to respond to his many critics, but he may have thereby taken a step away from what matters most in scientific practice.7 regardless of whether it may be a revolution in the later kuhnian sense, what is more important, or perhaps more interesting, is the question of whether the change from atomic weight to atomic numbering ordering and the related change in the definition of an element is 4 a revolution in a broad sense that other philosophers of science or even scientists themselves might accept. the answer to this latter question must be a resounding no, in my view. neither the change from the use of atomic weight to using atomic number for ordering the elements, nor the way that the term “element” should be understood, represented a scientific revolution in this broader sense.8 2. are there any revolutions in chemistry? in the field of physics there have clearly been some developments which one might want to identify as being of a revolutionary nature. one need only think of einstein’s special and the later general theory of relativity. in addition, the development of quantum mechanics can rightly be considered to have been a major scientific revolution in many respects. in biology one may speak of the darwinian revolution whereby all living creatures, and indeed also plants, became regarded as having descended from a common origin. has the field of chemistry experienced anything as remotely momentous as these revolutions? i believe not, apart from what is generally called the chemical revolution, which is mainly attributed to the work of lavoisier, although even in this case there are many who doubt whether it may have been a genuine revolution (blumenthal, 2013). indeed, the lack of the existence of a philosophy of chemistry, which persisted until relatively recently, can perhaps be attributed to the lack of any major revolution that could compare with the above-named examples from physics and biology.9 the periodic table, which is undoubtedly one of the paradigms of modern chemistry, has stood for over 150 years since its discovery in the 1860s. there has yet to be, i claim, anything resembling a revolution in post-lavoisier modern chemistry. i believe this general background is important when weighing brad wray’s proposal that the discovery of atomic number, isotopy and the new way of identifying elements, that took place in the 1910s and 1920s should be regarded as any kind of scientific revolution. 5 3. wray’s attempt to draw an analogy between the copernican revolution and the events that took place in chemistry in the 1910s and 1920s. wray begins by explaining that before copernicus, all bodies observed in the night sky were regarded as stars, except those that wandered, which were said to be planets. following the copernican revolution, the earth, sun and moon ceased being identified as planets. of course, they still continued to ‘wander’ but they became deprived of their planetary status. in mendeleev’s time there were about 60 elements which shared the characteristic of each possessing a unique atomic weight. notice that there is no analogous contrast between stars and planets in the chemical case in question. all the observed microscopic entities were classified were classified as belonging to one kind, namely elements. this is the first of what i take to be dis-analogies to the astronomical case that was just discussed. following the discovery of atomic number by moseley, and of isotopes by soddy, some observed chemical entities with particular atomic weights were no longer classed as elements. this episode is taken by wray as being a significant analogy to the change accompanying the ptolemaic and copernican view of planets. however, this attempt fails in the chemical case because one could equally well say that all isotopes were now regarded as having unique atomic weights, while some of these weights also corresponded to the weights of elements. i am referring to the not insignificant number of elements which are mono-isotopic.10 for example, the element iodine only has one isotope. the atomic weight of this isotope thus succeeds in identifying this element and in distinguishing it from all other elements. returning to the astronomical case, some of the observed objects, namely the sun, moon and earth changed their status and ceased being planets. in the chemical case some of the detected microscopic entities characterized through their atomic weights ceased being identified as elements. however, in the astronomical case the status of planethood and nonplanethood are mutually exclusive. in the chemical case, some of the thousans of microscopic entities whose weights have been determined ceased being regarded as distinct elements, but by no means all of them. being an isotope and being a distinct element are not mutually 6 exclusive. the isotopes of monoisotopic elements are both members of the general class of isotopes but also members of the class of isotopes which happen to also count as elements in their own right. this is precisely the kind of overlap that wray does not seem to be aware of when he claims that this chemical case represents a violaion of kuhn’s no-overlap principle. as i have just explained, it is simply not the case that atomic weight per se fails to identify all elements. a single isotope of iodine, to return to the same example, can be identified with the only microscopic particles of the element iodine that exist. yet a third dis-analogy has to do with the fact that the term planet is not a natural kind but more of a conventional label assigned by popular consent. one only needs to consider the notorious ‘pluto affair’ that took place in the year 2016, when the international astronomical union ruled that pluto was no longer a planet because of some of the characteristics of its orbital motion (bokulich, 2014). no similar ambiguity exists regarding what is, or is not, an isotope of any element. if a microscopic atomic entity has a unique mass, it counts as an isotope. similarly, each element has a unique atomic number. if an atom is found to have a particular atomic number this identifies it as one of the currently 118 known elements. conversely, the identification of any given element, such as gold for example, is uniquely associated with having an atomic number of 79. said otherwise, the possession of a particular atomic number is both necessary and sufficient for identifying any particular element. none of this kind of precision applies to the conventionally stipulated term of planet. simply put, elements are natural kinds whereas planets are not.11 4. the original kuhn and the later kuhn the refinement in the meaning of a paradigm that took place in kuhn’s later work is not supposed to dismiss the original view, a feature that wray seems to agree with. the two kuhnian senses of what constitutes a scientific revolution are not radically different. kuhn’s 7 later understanding of a revolution, as brad wray concedes, is only meant to be a refinement of his earlier one. in reconceptualizing the notion of a scientific revolution, kuhn was not intending to change his view fundamentally. rather, he regarded his later reconceptualization as a refinement of the view presented in structure. thus, he thought of the new definition as picking out the same sorts of changes that he identified as “paradigm changes” in structure (wray, 2022). however, the way that wray portrays matters suggests that there is a little by way of intersection between the earlier and later kuhn views, except perhaps for the case of the copernican revolution. and even in this case, on wray’s reading we are invited to believe that the real revolution is not the simple fact that the earth and other planets circle the sun, but rather the far less important point that the earth, sun and moon and no longer classified as planets. as some kuhn scholars have written, the more important difference between the ptolemaic and the copernican paradigms had more to do with comets than with the reassessement of whether any particular celestial body was a planet or not (andersen, barker, chen, 2009). there is presumably no sense in which scientific revolutions according to the early and the later kuhn can be considered as incommensurable or said to be populating different worlds. i take it for granted that kuhn did not wish to claim that his youthful and later selves inhabited radically different worlds. more importantly perhaps, it appears that for the later kuhn, the paradigm no longer concerns the ontological question of what objects moves around which other object, but a terminological question of whether to call the sun, for example, a planet or not. but the question of terminology belongs in the realm of human construction, regardless of whether we are speaking of planets or elements. what matters more is the behavior of these entities. in the 8 case of atomic weight and atomic number what matters is whether one concentrates on the proton (atomic number) or on the whole atom (atomic weight). it is more a matter of reference than of sense, or a matter of extension rather than of intension. 5. specific responses to wray’s recent article in an article published in 2022 brad wray returns to our debate concerning whether the discovery of atomic number and isotopes constitutes a scientific revolution in the sense of thomas kuhn’s later views. in his opening remarks wray writes, …one reason scerri and i have different views about this particular case in the history of chemistry is that we are not attending to the same kuhnian account of scientific revolutions (wray, 2022). i find this statement rather odd, given that i went to great lengths to examine wray’s claim in the light of kuhn’s later, as well as his earlier accounts of scientific revolutions and concluded that he was referring to the later view (scerri, 2021) wray returns to this point a little later and says, i have said that the revolution in twentieth century chemistry is a “classic” kuhnian revolution, and scerri is critical of this claim (see scerri 2021, 7.3). this, i think, is simply a verbal dispute. kuhn’s later account of scientific revolutions (see kuhn 2000), the one i draw on, is somewhat different from the account he presents in his 1962 classic, the structure of scientific revolutions (see kuhn 1962/2012). there, as noted above, kuhn characterized scientific revolutions as paradigm changes. perhaps scerri is correct to insist that the “classic” kuhnian view is the view expressed in the structure of scientific revolutions, not the view kuhn later developed, which is the one i draw on. by “classic” i merely meant typical (wray, 2022) 9 in any case i am glad that wray and i appear to be focusing our debate a little more closely on kuhn’s later view and that wray seems to regret his use of the term “classic” in this context. before moving on i would just like to remark that this new qualification by wray, to mean typical cases, raises some new problems, since i am not aware that kuhn or any other authors have re-examined many of his earlier revolutions such that one may speak of typical cases in the later sense. as far as i am aware kuhn speaks of the copernican revolution and the chemical revolutions but no other specific examples after his lexical turn.12 returning to wray, he also writes, kuhn classified the change from the ptolemaic theory to the copernican theory as a scientific revolution, and most philosophers of science would agree with kuhn’s assessment. here, after assuring us that he only wishes to consider kuhn’s later view, wray appears to be returning to the more general claim concerning revolutions or the earlier kuhnian view. yes, it may indeed be the case that most philosophers of science would agree that this astronomical example constitutes a revolution, but especially not for the reasons that the later kuhn claims it to be so. most philosophers and indeed scientists too, would consider this case to be a revolution because it involved an almost literal ‘turn-around’ or inversion of the previously held view. whereas the ptolemaic universe holds that the earth is the focal point around which everything revolves, the copernican view involves an inversion such that everything revolves around the sun. philosophers and scientists do not regard this case as a revolution because of the lexical changes that may have taken place and because a few astronomical bodies were no longer considered as planets as a result. but wray’s regression to speaking of revolutions in the more general sense is rather inevitable, given that the later kuhnian view is supposed to generalize his earlier one, and not 10 intended to provide an altogether different sense. in the final analysis, it may not be possible to divorce the early from the later kuhnian view of revolutions, since the later view was meant only as a refinement of the earlier one. in his recent response, wray also claims that my use of a venn diagram in which i aimed to show the relationship between atomic weight and atomic number is misleading, scerri’s diagram for the chemical revolution has circles representing the parts of an atom—proton, neutron, and electron. this diagram masks over the revolutionary nature of the change that occurred in chemistry. indeed, this diagram is focusing on the wrong concepts, specifically, atomic weight and atomic number. in order to understand the revolutionary nature of the change, we need to focus on the change in the extension of the term “chemical element.” the extension of the term is significantly different before and after the discovery of atomic number. while i accept that part of the alleged revolution in the sense of the later kuhn is supposed to be concerned with the term element, i must insist that the question of the relationship between atomic weight and atomic number is crucial to the discussion. the way in which certain isotopes ceased to be regarded as elements was precisely due to their having a distinct atomic weight, while sharing the atomic number of an element that was already recorgnized as such. moreover, i am claiming that these two concepts show a great deal of ovelap rather than standing side by side as distinct ontological categories in the manner that wray appears to conceive of them, in his own venn diagram that he proposes in his most recent contribution. wray dismissal of my venn diagram which seeks to clarify the relationship between atomic number and atomic weight is puzzling, given that his initial article on this subjected treated two issues, (1) change from atomic weight ordering to the use of atomic number and (2) the discovery of isotopes of elements on a par. for example, the opening words of his original article were, 11 the aim of this paper is to provide an analysis of the discovery of atomic number and its effects on chemistry. the paper aims to show that this is a classic textbook case of a kuhnian scientific revolution (wray 2018, 209). in the same article he also writes, perhaps most significant in this process was the discovery of atomic number. as well as, contemporaneous with this research on atomic number was another research program examining the various anomalous chemical elements that shared the same chemical properties but differed with respect to atomic weight (wray, 2018). these two discoveries complimented each other. once chemical elements were thought of as essentially defined by their atomic number, the notion of an isotope was no longer a conceptual impossibility. another problem with wray’s account is his constantly referring to the discoveries of atomic number and isotopes as bringing about a change of theory in chemistry. however, these specific anomalies did not contribute to bringing about a radical change of theory in chemistry. as i already pointed out in my earlier response, the discoveries of atomic number and of the phenomenon of isotopy did not bring about any change whatsoever to the prevailing chemical theory. the discovery of a better means of ordering the elements does not constitute a theory by any stretch of the imagination and nor does the realization that atoms of the same element may differ in their weights. theories are generally understood as being explanatory frameworks such as quantum theory or the theory of relativity in physics, and not as specific discoveries that resolve equally particular anomalies in any particular discipline.13 12 6. kuhn and the violation of the no-overlap principle kuhn’s later discussions of scientific revolutions is centered around his principle of the violation of no-overlap. kuhn wrote very little on this principle which he first introduced in an article of 1987 titled, 'what are scientific revolutions? (kuhn, 2000). he revisited this theme in 1990 while giving a presidential address to the philosophy of science association (kuhn, 1990). in the course of these writings kuhn gave very few examples, and of the few that he did provide, only one was a scientific case, namely the turn from the ptolemaic to the copernican universe. i am not aware of whether he ever returned to elaborate fully on this ‘principle’. in the course of his speech to the psa kuhn alludes to a book that he is in the process of writing to finally answer his critics but, as is well known, such a book has never materialized.14 given the rudimentary and underdeveloped nature of this principle, i suggest that it may be a little risky for commentators like wray to connect their claims for new revolutions quite so firmly with it. it should also be noted that kuhn’s use of the double negative in the concept of violation of no overlap is rather confusing. such a double negation could amount to saying that there is in fact overlap. and if this state of affairs does exist between two paradigms, or two competing scientific lexicons, there seems to be no reason whatsoever for claiming any form of incommensurability. if the manner in which the earth, sun and moon was classified did show overlap between the ptolemaic and copernican paradigms, there would be no lack of agreement as to whether they were planets or not. clearly such a reading of the violation of no-overlap is not what kuhn had in mind. what then did kuhn mean to say regarding which heavenly bodies were considered to be planets before and after the copernican revolution in connection with his principle? for a more 13 correct, although i still claim rather convoluted use of his principle, i am grateful to vincenzo politi for providing the following passage. ptolemy’s and copernicus’s cosmologies are taxonomically incommensurable, because there cannot exist a conceptual taxonomy in which the moon is both a planet (as in the ptolemaic classification) and a satellite (as in copernicus’s): such a taxonomy would clearly violate the no-overlap principle (politi, 2022). in other words, if the principle was not violated, there would be overlap between the two paradigms since the moon would be a member of both natural kinds. if that were so there would be no incommensurability. but of course, kuhn wants to claim that such a lack of overlap implies incommensurability and consequently the occurrence of a scientific revolution. or as james marcum writes, another important property of kind terms is conceptual, regarding the relations between kind terms and referents. these relations are governed by a non-overlap principle. kuhn notes that “no two kind terms, no two terms with the same kind label may overlap in their referents unless they are related as species to genus” (ibid.). for example, there are no gold rings that are also silver rings, but there are red things that are also beautiful. if two kind terms do have overlapping referents in a speech community, communication failures are inevitable: people simply do nt know how to name those referents in the overlapping region (marcum, 2018). in the case of atomic particles, the objects in question can be characterized by their masses, with each object having a unique mass. in former times such massive particles were all classified as elements. however, since moseley’s work they can be classified as isotopes of a particular element, but some such particles can be classified as both. an isotope of iodine, to return to my earlier example, is an example of a unique isotope but also a case of an atomic particle of a unique element. 14 such isotopes provide examples of where there is overlap and therefore no violation of kuhn’s no-overlap principle. the paradigm which dealt only with elements and the later paradigm which deals in isotopes as well as elements, are not taxonomically incommensurable in the case of monoisotopic elements. kuhn would therefore have to conclude that there is no scientific revolution involved in the change of taxonomy that was brought about by the discovery of atomic number and of isotopes. there are approximately 15 elements that only have one isotope in the same way that iodine has. isotope and element are not at the same taxonomic level, in the same way that cat and dog, two of kuhn’s favorite examples are. an isotope is a subclass of the concept of element in the majority of cases, namely all the elements that are not monoisotopic. it would appear that wray is not aware of these points, otherwise he would not be suggesting that the astronomical case is analogous to the atomic case. the discovery of isotopes does not represent a revolution in the sense of the later kuhn in the same way that the change from the ptolemaic to the copernican model may do. if one places more attention on the reference of the terms planet ,or isotope, i believe that the alleged incommensurabiity dissolves. the fact that the moon circles the earth leads to the moon being classified as a satellite in the copernican model rather than as a planet. but this change only concerns how this astronomical body is being classified. the referent is still that unique astronomical body which waxes and wanes in the course of each month and that we are all familiar with. of course, the situation is a little more complicated than i have just implied since the manner in which natural kinds are identified appears to have undergone an almost cyclic change in the history of philosophy (mcculloch, 1989). very briefly, according to frege, natural kinds were identified by means of sense or through a description of their attributes. in the 1970’s kripke and putnam famously posited their causal theory of reference in which natural kinds were to be picked out according to their intrinsic properties such as the fact that the element gold was and substance whose atoms have atomic number of 79. it is significant that the causal theory of reference was also used to counter kuhn’s talk of incommensurability and 15 to restore the common-sense view that descriptions may change as science develops but the entities in question do not. more recently the kripke-putnam view has been subjected to a good deal of criticism since it seems to completely exclude any form of interest dependence on the part pf scientists. in response, richard boyd has introduced his homeostatic property cluster theory (hpc). boyd postulates the existence of a homeostatic mechanism capable of explaining why those properties are statistically associated with each other and shared by the members of a given kind (boyd, 1991). but none of these recent developments in the study of natural kinds represent a rejection of the attention that contemporary philosophy of science places upon matters of scientific ontology. 7. the wider question one can only hope that thomas kuhn might have approved of wray’s desire to find further examples of scientific revolutions in the later sense of kuhn. moreover, wray’s defence of kuhn in this way appears to be a form of ‘normal kuhnian philosophy of science’, to coin an analogous term to kuhn’s talk of normal science, within which scientists do not challenge the prevailing paradigm. brad wray, who has carried out much work on the views of kuhn, appears to be working only within the limitations of kuhn’s views, albeit the later and supposedly more refined view. wray does not seem to want to pose the question of whether the discovery of atomic number and of isotopes constitute a revolution in the way that other philosophers of science might view the concept. i propose to now take an alternative view of the situation, and one that i believe many of kuhn’s critics might also share. it is well known that kuhn’s original position received a great deal of criticism from historians as well as philosophers of science especially on the question of incommensurability (shapere, 1964; hacking, 1981; scheffler, 1967; putnam, 1981; davidson, 2001; kitcher, 1978). 16 as a more recent critic writes, he [kuhn] argued that these criticisms depended on the “literally correct but regularly overinterpreted assumption that, if two theories are incommensurable, they must be stated in mutually untranslatable languages.” now, if the two theories could not be stated in a single language, they could not be compared. furthermore, these critics claimed that if kuhn were right, then archaic scientific theories could not be translated into modern language. but in structure and elsewhere, that is exactly what kuhn did: he both compared supposedly incommensurable theories with one another and he translated them into modern language. in both cases, his practice would seem to be inconsistent with his conception of incommensurability. (garber, 2012, 505) and in another article, kuhn’s extended attempt to answer the philosophers has always struck me as one of the great tragedies in the history and philosophy of science. it didn’t have to be this way. there is much that was right in kuhn’s idea of the incommensurability of paradigms at the very beginning, in structure. the history of his later struggles with incommensurability is a sad story of a great thinker who allowed himself to be led down a dead end (garber, 2012, 506) indeed, kuhn spent the remainder of his working life in attempting to explain what he had really meant, as well as in modifying what he had originally stated. here is how kuhn expressed himself of this process, my own encounter with incommensurability was the first step on the road to structure, and the notion still seems to me the central innovation introduced by the book. even before structure appeared, however, i knew that my attempts to describe its central conception were extremely crude. efforts to understand and refine it have been my primary and increasingly obsessive concern for thirty years (kuhn, 2000, 228). 17 one of the main qualifications, if not an outright departure from kuhn’s original position, was his turn to an analysis of scientific lexicon and the nature of language more generally. would it be so preposterous to suggest that kuhn’s program began to degenerate from the moment when he started to alter his original bold and startling claims, which so caught the professional and public attention when they were first published? as several authors have written, the main reason why kuhn was mistaken in devoting so much attention to the language of science was that it diverted attention from ontological aspects to terminological ones. said differently, kuhn appears to be taking sides with those philosophers who place greater importance on sense rather than on reference in the longstanding philosophical debate that dates back to frege and even earlier (mcculloch, 1989). kuhn’s move from a concern from matters of scientific ontology to an emphasis on sense has of course been eloquently criticized by alex bird, whereas the structure of scientific revolutions is naturalistic in approach, drawing upon empirical, scientific discoveries where appropriate, his later work is much more philosophical in style and a priori in method. for example, in the structure of scientific revolutions kuhn’s explanation of the relationship between observation, theory and reality was informed by gestalt psychology and by the results of research carried out by his harvard colleagues, the experimental psychologists bruner and postman. later, by contrast, kuhn supported his view with quasi-wittgensteinian considerations from the philosophy of language, while he characterized that view in terms of kantianism (bird, 2002). bird continues by claiming that kuhn’s earlier views would have benefited from a continued naturalistic development and suggests that his later, philosophical approach was not only a failure, but what bird calls a “wrong turning” which contributes to a lack of significance in contemporary mainstream philosophy and even philosophy of science. some of this wrong turning is also attributed to kuhn’s lack of philosophical training. 18 whereas the early kuhn drew many examples from the history of science, he abandoned his use of empirical science for a more a priori approach that was initially motivated by the writings of quine. while the early kuhn focused on the development of science while drawing from many historical episodes, his later output turned almost exclusively to the nature of the language that is used in science. moreover, kuhn later denied that an evolutionary epistemology need be a form of naturalised epistemology, and even regretted an overemphasis on the empirical aspect of his earlier writings. kuhn’s attempt to cast incommensurability within the philosophy of language had begun in the 1960s, when he drew inspiration from quine’s indeterminacy of translation thesis (quine, 1960). furthermore, kuhn seems to have also drawn from quine the notion that what differs between incommensurable languages is the way they divide the world into kinds of thing, or in other words the notion of natural kinds. but a result of kripke and putnam’s work in the 1970s, philosophers have tended to downplay the fact that natural kind terms are picked out by their sense but have focused on a reference that is fixed by a causal connection between the use of the term and the reference itself. the claim is that water refers to that familiar transparent liquid because it has a causal connection to the substance that was baptized as water in the remote past and not because of any description of the liquid. in this respect the later kuhn is very much out of step with contemporary philosophical thinking. stated otherwise, wheras kuhn’s earlier work was very much focused on actual scientific matters or one might say ontological aspects, his later work is seen by many to consist of a retreat to an analysis of language, a shift from reference to the world itself to an analysis of how one describes and categorizes the world. it is for these further reasons that i too believe that kuhn’s reformulation of scientific revolutions may have been misguided. 19 meanwhile brad wray is attempting to have things both ways, since he does plunge into a considerable amount of scientific detail concerning atomic weight, atomic number and isotopy while using kuhn’s later approach to the analysis of scientific change with its emphasis on the language of science and all that this entails.15 i have to conclude that kuhn might not after all have approved of wray’s attempt to support his later writings. acknowledgement i thank the following people for their help and suggestions during the writing of this article, hanne andersen, xiang chen, dan garber, stefano gattei, mark goodwin, vasso kindi, james marcum, vincenzo politi, robert westfall. i also thank the four reviewers of this article for their helpful comments and suggestions. notes 1 i am referring to the original account by thomas kuhn as stated in his classic book, the structure of scientific revolutions. 2 at later stages in the history of the periodic table two further atomic weight anomalies of this kind also emerged. one of them followed the discovery of the noble gas argon, which has an atomic weight that is lower than the element potassium although their ordering is such that argon is placed before potassium. the fourth atomic weight anomaly concerns thorium and protactinium, the latter of which was only discovered in 1917. although protactinium is a whole atomic unit lighter than that of thorium, its place in the periodic table follows that of thorium. this fourth example represents the largest atomic weight anomaly of the four known cases. neither of these further examples were known to exist at the time of the discovery of the periodic system. 3 one of the reviewers of this article reminds me that wray’s suggested revolution concerning the discovery of atmomic number and isotopes is not especially original, since it had previously been discussed by jensen in 1998. 20 4 this statement is somewhat ahistorical in that neutrons were not identified until the year 1930. 5 kuhn makes precisely this point about increasing specialization as science develops in his later writing (kuhn, 1990). 6 at the same time, i do not wish to neglect the relevance of lexicon and linguistic aspects in general in the development of scientific ideas. i am only suggesting that kuhn may be placing too much emphasis on these factors. 7 others have even suggested that this was kuhn’s biggest mistake (garber, 2016). 8 my view is supported in a recent article by pieter thyssen who emphasizes that paneth emphasized the continuity with the older definition of elements while providing a new definition in terms of atomic number which was adopted by iupac (thyssen, in press). 9 the philosophy of chemistry as an academic discipline came into being in the mid 1990s and has continued to develop since them. for example, the international society for the philosophy of chemistry has held an international meeting during each of the previous 26 years while the official journal for this society, foundations of chemistry, began publication in 1999. 10 perhaps wray is not aware of the existence of many mono-isotopic elements which include, beryllium, fluorine, sodium, aluminum, phosphorus, scandium, manganese, cobalt, arsenic, yttrium, niobium, rhodium, iodine, caesium, praseodymium, terbium, holmium, thulium and gold. 11 indeed, elements are perhaps the epitome of natural kinds and have served as the prime example of such in innumerable philosophical articles on the subject (kendig, 2016; scerri, 2020). 12 indeed, it would be rather useful is somebody were to undertake the task of re-examining kuhns earlier revolutions to see whether they stand up in the light of his new criteria having to do with lexical changes, diversification of disciplines and the no-overlap principle. 13 needless to say, i do not deny the epistemic significance of the discovery of isotopes in the development of our knowledge of the structure of atoms and its relevance to understanding the periodic table in a more profound manner than was previously available. i thank a reviewer for suggesting this qualification. 14 it appears that kuhn gave the text of the book to james conant so that he might complete it, something that has not yet occurred. 14 as a reviewer of the present article also points out, wray is incorrect in claiming that cannizzaro proposed using the atomic weights of the elements as a means of classifying them. 21 the use of cannizzaro’s atomic weights to classify the elements was rather carried out by at least six discoverers of the periodic system, of whom mendeleev is the best known. references h. andersen, p. barker, 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history, cambridge university press, cambridge, pp. 113-24, 1981. w.v.o., quine, word and object (new ed.). mit press, cambridge, ma., 1960. e.r. scerri, the periodic table, its story and its significance, oxford university press, new york, 2019. e.r., scerri, on chemical natural kinds. journal for the general philosophy of science, 51, 427– 445, 2020. e.r. scerri, reassessing the notion of a kuhnian revolution: what happened in 20th c. chemistry, a commentary on wray’s claim of the discovery of atomic number as a revolution in chemistry, in b. wray (ed.), interpreting kuhn, cambridge university press, 2021. d. shapere, the structure of scientifc revolutions, philosophcal review, 73, 383-94, 1964. d. shapere, meaning and scinetific change, in scientific revolutions ed. i. hacking, oxford university press, oxford, 1981. i. sheffler, science and subjectivity, bobbs-merrill, indianapolis, in, 1967. p. thyssen, identical or distinct? the debate between paneth,von hevesy and fajans on the nature of isotopes (in press). b. wray, the atomic number revolution in chemistry: a kuhnian analysis, foundations of chemistry, 20, 209–217, 2018. https://link.springer.com/journal/10698 https://link.springer.com/journal/10698 a new response to wray and an attempt to widen the conversation email: scerri@chem.ucla.edu received: sept 08, 2022 revised: oct 30, 2022 just accepted online: nov 03, 2022 published: xxx this article has been accepted for publication and undergone full peer review but hasnot been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: scerri e. (2022) a new response to wray and an attempt to widen the conversation. substantia. just accepted. doi: 10.36253/substantia-1806 abstract this article begins by examining a recent claim by brad wray that the discovery of atomic number and isotopy constitutes a scientific revolution in the sense of the later writings of thomas kuhn. i argue that although kuhn’s criteria may apply to the... 1. introduction in teaching introductory philosophy of science, one makes a distinction between popper and kuhn and the fact that for popper a decisive refutation such as the discovery of black swans is supposed to lead to the abandonment of the ‘law’, that all swans... by contrast kuhn’s account is said to be more permissive because it allows for the occurrence of anomalies, although these events do not cause the sudden downfall of the paradigm. one needs to wait for more anomalies, which eventually lead to a crisi... in the case of the periodic table there were just two anomalies in which ordering the elements according to their atomic weights failed to classify a total of four elements in their correct groups, as revealed through their chemical properties. these... the modification made by mendeleev and other discoverers of the periodic table of reversing the positions of tellurium and iodine as well as of cobalt and nickel was not ad-hoc, since it accommodated the known properties of these elements. the paradi... the anomalies that mendeleev and his contemporaries experienced eventually led others to discover isotopes, rather than refuting or revolutionizing the periodic table. similarly, the discovery of numerous radioisotopes in the early 20th century did n... in the copernican revolution however, it was not just a matter of one or two planets not orbiting as they should, but a major turning inside-out of the prevailing geocentric paradigm. later on, one or two planets were found to have anomalous orbits. ... the philosopher of science brad wray has proposed that the discovery of atomic number and change in the manner that elements were defined represented a scientific revolution (wray, 2018). however, as i previously responded, once the focus had been ... i suggest that kuhn may have been wrong to place such a big emphasis on scientific lexicon in his later work. such a step may have been motivated by needing to respond to his many critics, but he may have thereby taken a step away from what matters ... regardless of whether it may be a revolution in the later kuhnian sense, what is more important, or perhaps more interesting, is the question of whether the change from atomic weight to atomic numbering ordering and the related change in the definiti... 2. are there any revolutions in chemistry? in the field of physics there have clearly been some developments which one might want to identify as being of a revolutionary nature. one need only think of einstein’s special and the later general theory of relativity. in addition, the development... has the field of chemistry experienced anything as remotely momentous as these revolutions? i believe not, apart from what is generally called the chemical revolution, which is mainly attributed to the work of lavoisier, although even in this case t... indeed, the lack of the existence of a philosophy of chemistry, which persisted until relatively recently, can perhaps be attributed to the lack of any major revolution that could compare with the above-named examples from physics and biology. the ... i believe this general background is important when weighing brad wray’s proposal that the discovery of atomic number, isotopy and the new way of identifying elements, that took place in the 1910s and 1920s should be regarded as any kind of scientifi... 3. wray’s attempt to draw an analogy between the copernican revolution and the events that took place in chemistry in the 1910s and 1920s. wray begins by explaining that before copernicus, all bodies observed in the night sky were regarded as stars, except those that wandered, which were said to be planets. following the copernican revolution, the earth, sun and moon ceased being identi... in mendeleev’s time there were about 60 elements which shared the characteristic of each possessing a unique atomic weight. notice that there is no analogous contrast between stars and planets in the chemical case in question. all the observed micr... following the discovery of atomic number by moseley, and of isotopes by soddy, some observed chemical entities with particular atomic weights were no longer classed as elements. this episode is taken by wray as being a significant analogy to the cha... returning to the astronomical case, some of the observed objects, namely the sun, moon and earth changed their status and ceased being planets. in the chemical case some of the detected microscopic entities characterized through their atomic weights... this is precisely the kind of overlap that wray does not seem to be aware of when he claims that this chemical case represents a violaion of kuhn’s no-overlap principle. as i have just explained, it is simply not the case that atomic weight per se f... yet a third dis-analogy has to do with the fact that the term planet is not a natural kind but more of a conventional label assigned by popular consent. one only needs to consider the notorious ‘pluto affair’ that took place in the year 2016, when t... no similar ambiguity exists regarding what is, or is not, an isotope of any element. if a microscopic atomic entity has a unique mass, it counts as an isotope. similarly, each element has a unique atomic number. if an atom is found to have a partic... 4. the original kuhn and the later kuhn the refinement in the meaning of a paradigm that took place in kuhn’s later work is not supposed to dismiss the original view, a feature that wray seems to agree with. the two kuhnian senses of what constitutes a scientific revolution are not radica... however, the way that wray portrays matters suggests that there is a little by way of intersection between the earlier and later kuhn views, except perhaps for the case of the copernican revolution. and even in this case, on wray’s reading we are inv... as some kuhn scholars have written, the more important difference between the ptolemaic and the copernican paradigms had more to do with comets than with the reassessement of whether any particular celestial body was a planet or not (andersen, barker... there is presumably no sense in which scientific revolutions according to the early and the later kuhn can be considered as incommensurable or said to be populating different worlds. i take it for granted that kuhn did not wish to claim that his yout... more importantly perhaps, it appears that for the later kuhn, the paradigm no longer concerns the ontological question of what objects moves around which other object, but a terminological question of whether to call the sun, for example, a planet or... 5. specific responses to wray’s recent article in an article published in 2022 brad wray returns to our debate concerning whether the discovery of atomic number and isotopes constitutes a scientific revolution in the sense of thomas kuhn’s later views. in his opening remarks wray writes, here, after assuring us that he only wishes to consider kuhn’s later view, wray appears to be returning to the more general claim concerning revolutions or the earlier kuhnian view. yes, it may indeed be the case that most philosophers of science wo... most philosophers and indeed scientists too, would consider this case to be a revolution because it involved an almost literal ‘turn-around’ or inversion of the previously held view. whereas the ptolemaic universe holds that the earth is the focal p... but wray’s regression to speaking of revolutions in the more general sense is rather inevitable, given that the later kuhnian view is supposed to generalize his earlier one, and not intended to provide an altogether different sense. in the final ana... in the course of these writings kuhn gave very few examples, and of the few that he did provide, only one was a scientific case, namely the turn from the ptolemaic to the copernican universe. i am not aware of whether he ever returned to elaborate fu... given the rudimentary and underdeveloped nature of this principle, i suggest that it may be a little risky for commentators like wray to connect their claims for new revolutions quite so firmly with it. it should also be noted that kuhn’s use of the double negative in the concept of violation of no overlap is rather confusing. such a double negation could amount to saying that there is in fact overlap. and if this state of affairs does exist betwe... if the manner in which the earth, sun and moon was classified did show overlap between the ptolemaic and copernican paradigms, there would be no lack of agreement as to whether they were planets or not. clearly such a reading of the violation of no-overlap is not what kuhn had in mind. what then did kuhn mean to say regarding which heavenly bodies were considered to be planets before and after the copernican revolution in connection with his princip... 7. the wider question one can only hope that thomas kuhn might have approved of wray’s desire to find further examples of scientific revolutions in the later sense of kuhn. moreover, wray’s defence of kuhn in this way appears to be a form of ‘normal kuhnian philosophy of ... i propose to now take an alternative view of the situation, and one that i believe many of kuhn’s critics might also share. it is well known that kuhn’s original position received a great deal of criticism from historians as well as philosophers of s... as a more recent critic writes, he [kuhn] argued that these criticisms depended on the “literally correct but regularly overinterpreted assumption that, if two theories are incommensurable, they must be stated in mutually untranslatable languages.” now, if the two theories could not... and in another article, kuhn’s extended attempt to answer the philosophers has always struck me as one of the great tragedies in the history and philosophy of science. it didn’t have to be this way. there is much that was right in kuhn’s idea of the incommensurability of par... indeed, kuhn spent the remainder of his working life in attempting to explain what he had really meant, as well as in modifying what he had originally stated. here is how kuhn expressed himself of this process, my own encounter with incommensurability was the first step on the road to structure, and the notion still seems to me the central innovation introduced by the book. even before structure appeared, however, i knew that my attempts to describe its cent... one of the main qualifications, if not an outright departure from kuhn’s original position, was his turn to an analysis of scientific lexicon and the nature of language more generally. would it be so preposterous to suggest that kuhn’s program began... as several authors have written, the main reason why kuhn was mistaken in devoting so much attention to the language of science was that it diverted attention from ontological aspects to terminological ones. said differently, kuhn appears to be taki... kuhn’s move from a concern from matters of scientific ontology to an emphasis on sense has of course been eloquently criticized by alex bird, 1 professors trost and sheldon’s promotion of catalytic technologies, atom economy, and the e-factor metrics in synthetic organic chemistry and the fine chemical and pharmaceutical industries, to speed the early evolution of “green chemistry” mark a. murphy, ph.d., j.d. uvlaw patents llc 171 china creek rd. blowing rock north carolina 28605 uvlawpatents@gmail.com 770-861-7312 received: may 09, 2023 revised: jul 10, 2023 just accepted online: jul 11, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: m. a. murphy (2023) professors trost and sheldon’s promotion of catalytic technologies, atom economy, and the e-factor metrics in synthetic organic chemistry and the fine chemical and pharmaceutical industries, to speed the early evolution of “green chemistry”. substantia. just accepted. doi: 10.36253/substantia-2140 abstract the academic chemical literature (and much current teaching to university students) still often describes “green chemistry,” as having originated in the late 1990s from the united states epa, the “12 principles of green chemistry”, and/or academia. but all of the “12 principles” had already been in “un-enunciated” industrial practice and had produced many commercialized examples of environmentally favorable chemical products and processes in major segments of industry, long before the 1990s. this article briefly reviews the early 1990s publications of professor barry trost and roger sheldon that spread awareness of the importance of catalysis to mailto:uvlawpatents@gmail.com 2 the evolving “green chemical” concepts of “atom economy”, the “e-factor” metrics, and into academic “green chemistry” research. trost and sheldon’s publications admitted that catalysis and “atom economy” had been in practice in the commodity chemicals industry for decades, but encouraged more use of those techniques and concepts in the fine chemical and pharmaceutical industry segments, and into academic research and the teaching of organic chemistry, years before the words “green chemistry” or the “12 principles” came into literature use. keywords green chemistry green engineering history atom economy e-factor environmental quotient catalysis interdisciplinary research evolution industry 1. introduction for the past 25 years, two questionable “narratives” about the origins of “green chemistry” have widely propagated in the academic and governmental literature, and in the trade and popular press, to the effect that 1) “green chemistry originated in the 1990s from the efforts of the us government, us epa and/or academia,” and 2) “green chemistry” should be “guided” by the ‘12 principles’ published by anastas and warner in 1998.” 1,2,3 over the last several years, this author (who conceived the bhc ibuprofen process that won one the earliest presidential green chemistry awards) has argued to the contrary, and previously documented that “green chemistry” was in fact a narrow subset of, and evolved from and renamed, the much earlier and much broader interdisciplinary “pollution prevention” efforts, mostly from industry, during the 1970s and 1980s.4,5,6 separately, the academic literature has long attributed the “green chemistry principle” of “atom economy”7 to professor barry trost of stanford university. the academic literature has also often attributed the “environmental factor” (typically called the “e-factor”) and/or “environmental quotient” metrics of green chemistry to a series of 1990s publications authored by professor roger sheldon. both 1 see anastas, pt., and warner, j. c., (1998) 2 see cann, m.c. and connelly, m.e. (2000) 3 see anastas, p.t. and beach, e.s., (2009) 4 murphy, m.a., (2020a) 5 murphy, m.a., (2021) 6 murphy, m.a.,(2018) 7 the graphical abstract for this article, graphically illustrating “atom economy”, was copied in june 2023 from a wikipedia article on “atom economy available at https://en.wikipedia.org/wiki/atom_economy , attributed there to a wikipedia author astrid 91, and used herein under a creative commons cc0 license. https://en.wikipedia.org/wiki/atom_economy 3 men emphasized the importance of the use of catalysis as a technical tool to achieve improved environmental performance in the chemical industries. both trost and sheldon certainly inspired many subsequent applications of catalysis, to achieve many new examples of good atom economy and e-factors in the fine chemical and pharmaceutical industry segments. but in little noticed early statements, both trost and sheldon admitted that use of catalysis, which had been in widespread use in the commodity chemicals industry for many prior decades, had produced many examples of already commercialized commodity chemical processes that were already in fact “atom economical,” and had excellent e-factors, decades earlier than the 1990s. this article will focus on and briefly review early 1990s publications by professors trost and sheldon that described the use of catalysis as a tool, to promote the introduction of the “atom economy”, “efactor”, and “environmental quotient” concepts into the academic literature, research, and teaching. trost’s and sheldon’s articles also suggested and/or promoted new applications of catalysis to improve environmental performance in the fine chemical and pharmaceutical industry segments, where the environmental performance had historically been much worse than in the commodity chemical industry. sheldon often praised one of the earliest examples of use of the atom efficiency and e-factor concepts in the fine chemical / pharmaceuticals industries, the bhc ibuprofen process, that was conceived and developed in the mid-1980s and commercialized in 1992. this author, who conceived the bhc ibuprofen process in 1984, will add historical perspective and commentary, to further demonstrate that the origins of “green chemistry” were actually a result of long-term, very broad and complex interdisciplinary and evolutionary processes that had their beginnings in industrial practice decades earlier than the 1990s. academic “green chemistry” recently appears to be evolving back toward a much broader interdisciplinary approach, a “paradigm change” this author supports. 2. professor barry trost’s “atom economy” – “a search for synthetic efficiency” professor barry trost, currently an emeritus professor of chemistry at stanford university8, has been very frequently cited in the academic literature as originating and/or promoting the concept of “atom economy”, which is now considered the second of the “12 principles of green chemistry” (after “pollution prevention”). trost published many papers in the 1970s and 1980s illustrating the uses of transition metal complexes for coupling organic molecules, but the first trost paper explicitly describing the “atom economy” concept was published in science in 19919, and was titled “the atom economy – a search for synthetic efficiency.” the abstract of trost’s paper read as follows: 8 professor trost obtained a phd in chemistry at mit in 1965 and moved directly to the university of wisconsinmadison, where he became a villas professor of chemistry and remained until his move in 1987 to become a tamaki professor of chemistry at stanford university. this author (as a graduate student) took a single semester’s course in synthetic organic chemistry from professor trost at madison in 1978, and attended many organic chemistry seminars where professor trost spoke or was present, an experience he will always remember and value. 9 see trost, b.m., (1991) 4 “efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. the limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.” (bolding added) in his second paragraph, trost stated that: “in the quest for selectivity, a second feature of efficiency is frequently overlooked how much of the reactants end up in the product, a feature we might refer to as atom economy …. an alternative process that is both selective and atom economical remains a challenge. the ideal reaction would incorporate all of the atoms of the reactants. major benefits that derive from such processes include more effective use of limited raw materials and decreased emissions and waste disposal…. the ability of transition metal complexes to activate organic molecules makes them attractive prospects for developing catalytic processes with high atom economy. this concept is already embodied in important industrial processes such as ziegler-natta polymerization (5) and hydroformylation (6). however, little or no attention has been focused on developing such methods for the synthesis of complex molecular architecture or for intramolecular processes.” (bolding added). then, with little additional commentary on the “theory” of atom economy, trost’s 1991 paper described many examples wherein “all of the reactions involve simple summation of the reacting partners to form products, and any additional reagents are used only in catalytic quantities to serve as true catalysts.” in a 1995 follow-up paper in angewante chemie10 (entitled “atom economy – a challenge for organic synthesis: homogeneous catalysis leads the way”), trost stated in his graphical abstract that “if all atoms of the starting materials are found in the product and only catalytic amounts of other reagents are needed, a reaction may be defined as ideal. a promising route to this ideal state is approached by the use of transition metal complexes as catalysts for addition and isomerization reactions.” in the body of his full 1995 paper, trost first re-iterated some of the concepts from the 1991 paper, but also stated that: “…the ideal chemical reaction is also just a simple addition (either inter-or intramolecular) in which any other reactant is required only in catalytic amounts. the producers of commodity chemicals have recognized the importance of these issues…. ‘newer’ processes represented by hydroformylation,[2] ziegler-natta 10 see trost, b.m., (1995) 5 polymerization,[3] and hydrocyanation[4] are spectacular illustrations of how practical and important processes that possess these characteristics are. on the other hand, such issues have not been emphasized for production of smaller volume chemicals. clearly, a high priority goal of any chemical production is an environmentally benign design. with the increasing sophistication of the types of substances that we must produce to meet society’s needs, this task in quite daunting.” (bolding added) in the rest of the 1995 paper, trost went on to describe many examples from his laboratories of the use of transition metal catalyzed cross-coupling reactions in the synthesis of complex organic molecules. in 1998, professor trost was awarded one of the epa / acs’s earliest “presidential green chemistry challenge” awards11, for “the development of the concept of atom economy”. the first paragraph of the award description states: “professor trost developed the concept of atom economy: chemical reactions that do not waste atoms. professor trost’s concept of atom economy includes reducing the use of nonrenewable resources, minimizing the amount of waste, and reducing the number of steps used to synthesize chemicals. atom economy is one of the fundamental cornerstones of green chemistry. this concept is widely used by those who are working to improve the efficiency of chemical reactions.” (bolding added) in the second paragraph, the 1997 presidential green chemistry award document stated: “economics generally dictates the feasibility of processes that are “practical”. a criterion that traditionally has not been explicitly recognized relates to the total quantity of raw materials required for the process compared to the quantity of product produced or, simply put, “how much of what you put into your pot ends up in your product.” in considering the question of what constitutes synthetic efficiency, professor barry m. trost has explicitly enunciated a new set of criteria by which chemical processes should be evaluated.” (bolding added). in the 4th paragraph, in discussing the general acceptance of the need for selectivity in chemical processes, the green chemistry award commented: “how much of the reactants end up in the product (i.e., atom economy) traditionally has been ignored. when professor trost’s first paper on atom economy appeared in the literature, the idea generally was not adopted by either academia or industry. many in industry, however, were practicing this concept without explicitly enunciating it. others in industry did not consider the concept because it did not appear to have any economic consequence. today, all of the chemical industry explicitly acknowledges the importance of atom economy.” (bolding added) 11 see https://www.epa.gov/sites/default/files/2016-10/documents/award_recipients_1996_2016.pdf , page 96. https://www.epa.gov/sites/default/files/2016-10/documents/award_recipients_1996_2016.pdf 6 it is important to recognize that prior to the 1990s, while many chemists (especially in academia) were unaware of or uninterested in the “atom economy” and “waste minimization” concepts, both professor trost and the 1998 presidential green chemistry award acknowledged that the concepts of atom economy and waste minimization had been previously practiced in the commodity chemical industry. a much fuller history of the early industrial evolution of the use of catalysis to produce good atom economy and waste minimization will be the focus of another paper in preparation. professor trost then lead the introduction of those concepts into the synthesis of complex organic molecules. for example, in 2002 professor trost published a review article in accounts of chemical research12, that described many uses of transition metal complexes (especially ruthenium complexes) for conducting atom economical reactions in the context of the synthesis of complex organic molecules. one of trost’s most spectacular subsequent examples published in 2008 in nature13, entitled “total synthesis of bryostatin 16 via atom economical and chemoselective approaches.” bryostatins are complex natural products (see the structure drawing below) with potent anti-cancer activity but have extremely limited availability from natural sources. trost and co-worker’s total synthesis strategy for bryostatin did employ numerous stoichiometric reagents and reactions traditionally used in synthetic organic chemistry, but also used new key steps employing homogeneous palladium, ruthenium, and gold catalysts, and very substantially minimized the number of steps and stoichiometric reagents used in the prior synthetic schemes for bryostatins. trost’s synthetic strategy also provided many opportunities for modifications (for example of the pivalate derivative shown in the drawing below) in order to allow preparation of a much wider variety of bryostatin derivatives / analogs than had been available previously. 3. professor roger sheldon’s “e-factor” and “environmental quotient” metrics for green chemistry professor roger a. sheldon’s contributions to the evolution of “green chemistry” were early, many and varied. sheldon obtained a phd in chemistry in 1967, worked at shell laboratories in amsterdam for 10 years, then spent 10 years as vice president for r&d in fine chemicals at dsm andeno. in 1991 he 12 see trost, b.m., (2002) 13 see trost, b.m., dong, g., (2008), “total synthesis of bryostatin 16 via atom economical and chemoselective approaches” 7 moved to the delft university of technology as a professor of chemistry, until 2015, when he moved again to the university of witwatersrand as a distinguished professor of chemistry. while still working in industry in the 1980s, sheldon published several papers on applications of catalytic oxidations in fine chemical manufacture. for example, in 198714, sheldon commented that “there is an increasing trend towards the use of catalytic methods in fine chemicals manufacture. this is largely a result of two effects: the need for cleaner, more efficient technologies due to increasing environmental constraints, and the forward integration of bulk chemical producers who are familiar with catalytic processes.” sheldon’s comment was entirely consistent with this author’s experiences at celanese during the 1980s, because during the 1980s celanese was actively investigating a variety of new technical approaches to fine chemicals and bulk pharmaceuticals involving catalytic methods6. sheldon’s first major literature contribution to “green chemistry”15 occurred very shortly after his move into academia, in the published proceedings of an interdisciplinary march 1992 symposium at texas a&m, focused on waste minimization in the chemical industry. sheldon’s 1992a paper was entitled “catalysis, the atom utilization concept, and waste minimization.”16 only one other chemist was a speaker at the conference, most of the speakers were engineers. a monograph of papers from that interdisciplinary conference was published in november 1992, and the introduction to the book stated: “the subject of this conference reflects the interest that has developed in academic institutions and industry for technological solutions to environmental contamination by industrial wastes. progress is most likely with strategies that minimize waste production from industrial processes. clearly the key to the protection and preservation of the environment will be through r&d that optimizes chemical processes to minimize or eliminate waste streams.” sheldon’s 1992a texas a&m paper received little attention and few literature citations in the academic literature, but in view of several important contributions by sheldon that first appeared in that paper, this paper will reproduce below some important quotes and figures from sheldon’s 1992a paper. sheldon’s abstract stated: “following the advent of the petrochemicals industry in the 1920s, catalysis was widely applied in the manufacture of bulk chemicals. traditionally environmentally unacceptable processes have largely been replaced by cleaner catalytic technologies. fine chemicals, in contrast, have remained largely the domain the synthetic organic chemist who has generally clung to the use of stoichiometric methods.” but times are rapidly changing. increasingly stringent environmental requirements are making the use of classical stoichiometric methods prohibitive. consequently, there is a 14 sheldon, r.a., (1987), “catalytic oxidation and fine chemicals” 15 the term “green chemistry” was coined at the epa by paul anastas in 1991, and first used publicly at an acs conference in 1993, then that terminology rose steeply in popularity in the academic literature (and replaced the prior “pollution prevention” terminology) after the beginning of grants for academic research by the nsf/acs, and the initiation of the epa / acs presidential green chemistry challenge awards in 1996.4,5 16 see sheldon, r.a. (1992a). sheldon’s text, figures, and tables from that paper reproduced in this paper are used herein with the permission of the current copyright holder, springer nature, see references. 8 general trend towards substitution of such antiquated technologies by cleaner catalytic methods that do not generate large amounts of inorganic salts. a useful concept for evaluating the environmental acceptability of various processes for producing a particular substance is atom utilization. the latter is defined as the ratio of the molecular weight of the desired product to the sum of all the materials (excluding solvents) used.” in his introduction, sheldon further stated: “after an induction period of a few decades, we now appear to be in the age of “environmentality”. this is reflected both in the general trends in society as a whole, and in the chemical industry in particular. (see figure 1)…. indeed, integrated waste management and zero emission plants are the catch-words in the chemical corridors of power these days.” (bolding added) sheldon’s figure 1 is shown below. (from sheldon 1992a) readers inspecting sheldon’s figure 1 should recognize that this was analysis and commentary from a highly informed 20-year industrial veteran, regarding the status and trends in chemical industry in the early 1990s. this author, who was a 7-year veteran of the chemical industry in 1990, agrees with sheldon’s description of the status of industry at that time, especially in view of the already widespread popularity and prevalence of the “pollution prevention” efforts in chemical industry during the 1980s.4,5 readers should also notice that there is very considerable overlap between the “general trends in the chemical industry” described by sheldon’s figure 1 and the “12 principles of green chemistry” that were only published six years later, in 1998.1 sheldon’s figure 1 also supports this author’s previous documentation that each of the individual “12 principles of green chemistry” were already in commercial practice in chemical industry, and also used in combinations, long before 1998.4 9 later in his texas a&m paper, sheldon supported his figure 1 “trends” by noting that “in the bulk chemical industry classically environmentally unacceptable processes have largely (but not completely) been supplanted with cleaner catalytic alternatives. in particular, catalytic oxidation and carbonylation are widely used for the conversion of petrochemical feedstocks to industrial chemicals.” sheldon then provided his table 1 of examples, also reproduced below. additional examples of other such existing large volume chemical processes will soon be described in more detail this author’s manuscript currently in preparation. (from sheldon 1992a) but sheldon also noted that in smaller volume segments of the chemical industry (fine chemicals and pharmaceuticals) the environmental performance was much worse, at least as measured in terms of the estimated ratio of the kg of waste products produced per kg of desired product. see sheldon’s table 2, reproduced below. table 2. byproduct formation in chemicals production industry segment product tonnage kg byproduct / kg product oil refining 106-108 ca. 0.1 bulk chemicals 104-106 <1 5 fine chemicals 102-104 5 >50 pharmaceuticals 10-103 25 >100 10 (from sheldon 1992a) this “sheldon” ratio, “kg of waste to kg of desired product”, was originally intended as a much broader metric for the real-world waste / environmental performance of actual commercialized processes, considered as a commercialized final whole, as compared to trost’s concept of an “atom economy” measure of a theoretical 100% efficiency of a hypothetical chemical equation on paper, while contemplating future chemical reactions.17 initially in this 1992 paper, and more prominently in his later papers, sheldon named this ratio of wastes to desired product (in a real-world functioning process) the “e-factor.” this “e-factor” has subsequently become a widely known and routine chemical metric, adopted and used by many others for evaluating the “greenness” of actual industrial chemical processes. but in 1992 sheldon also publicly pointed out that the nature of and/or the toxicity or dangers from the waste also needed to be evaluated. sheldon accordingly formulated an “equation” to incorporate the efactor” and also an “unfriendliness quotient” as well, to evaluate “environmental acceptability” as shown below. environmental = e x q acceptability “environmental factor” x “unfriendliness quotient” (kg waste / kg product) sheldon then commented that “for example, if innocuous salts such as nacl or na2so4 were arbitrarily given an unfriendliness factor of 1, then chromium salts could be assigned a factor of say 100, and toxic metals e.g. pb, cd a 1000. obviously, these figures are debatable and will vary from one company or production unit to another, being partly dependent on the ability to recycle a particular stream.” this author agrees that assigning numerically precise and non-subjective “q” values is extremely difficult. but this author also agrees that “unfriendliness” should be carefully contemplated by scientists and engineers at the same time they evaluate the “e-factor,” as they imagine future processes and products, as well as later for the final commercial processes, even if “unfriendliness” can’t be rigorously defined mathematically. professor sheldon, after having emphasized the importance of catalysis to already existing industrial processes, then turned toward a historical explanation for the good environmental performance of the oil refining and commodity chemical industries, as compared to much worse environmental performance of the fine chemical and pharmaceutical industry segments. in a discussion of “development of organic synthesis and catalysis.” professor sheldon stated: 17 this author was coached that as much of the starting materials as possible be incorporated into the product by his celanese supervisor, adolfo aguiló, in 1983. aguiló advocated the concept be used when imagining new chemical reactions and products, as well as used to evaluate a final process. i had no impression that aguiló believed these concepts to be either his, or new, but only an established part of practice in the commodity chemicals industry. in another manuscript currently under preparation, an explicit example from the 1970’s literature illustrating the use of the “e-factor” concept will be described. 11 “another reason why catalysis has not been widely applied in the fine chemical industry is the more or less separate development of organic chemistry and catalysis (see figure 8) since the time of berzelius, who coined both terms, in 1807 and 1835, respectively.” see sheldon’s figure 8 is reproduced below. sheldon commented that; “in the late nineteenth and early twentieth century catalysis developed largely as a subdiscipline of physical chemistry. following the advent of the petrochemicals industry, catalysis was widely applied in oil refining and bulk chemicals manufacture. industrial organic chemistry on the other hand, really began with perkin’s serendipitous synthesis of aniline purple (mauveine) in 1856….the present-day fine chemicals and pharmaceuticals industries developed largely as spinoffs of this activity.” (from sheldon 1992a) a few paragraphs later, sheldon added that: “fine chemical manufacture has, to this day, remained primarily the domain of the synthetic organic chemist who, generally speaking, clings to the use of stoichiometric methods….indeed, the fine chemicals industry, with its roots in coal-tar chemistry, is 12 rampant with classical stoichiometric technologies that generate large quantities of inorganic salts. examples include sulfonation, nitration, halogenation, diazotization, friedel crafts acylations, and stoichiometric oxidations and reductions…many of these technologies are ripe for substitution by catalytic low-salt technologies.” in subsequent paragraphs, sheldon highlighted the bhc ibuprofen process (as he also did again in many of his subsequent papers) as an already existing example of the applications of catalysis and atom economy and the e-factor in the fine chemical / pharmaceutical industries. this author was the person who initially conceived the bhc ibuprofen process in 1984. that process was developed by a multidisciplinary team at celanese at corpus christi texas, and then commercialized by bhc in bishop texas in 1992.6 this author will review sheldon’s 1992 description of the bhc ibuprofen process, then add some comments below. sheldon’s 1992 texas a&m paper first discussed “ibuprofen manufacture” in terms of ibuprofen’s relatively high production volumes (for a fine chemical / pharmaceutical), and how sales of the prescription drug converted to “generic” status in many countries after boot’s compound patent18 expired. then sheldon commented regarding his figure 14, reproduced below: (from sheldon 1992a) 18 see u.s. patent #3,385,886 to nicholson and adams, issued may 28, 1968, claiming priority to a british patent application first filed february 2, 1961. nicholson was a chemist and adams was a pharmacist. 13 “two routes for the production of ibuprofen are compared in figure 14. both routes proceed via a common intermediate, p-isobutylacetophenone. the classic route, used by the boots company (the discoverers of ibuprofen) involves a further five steps, relatively low atom utilization, and substantial inorganic salt formation. the elegant alternative, developed by hoechst celanese [*] involves only two (catalytic) steps from the common intermediate, 100% atom utilization, and negligible salt formation.” in 1992a sheldon had broadly mentioned solvent waste and toxicity issues in his figure 1 but did not directly comment on solvent usage / waste issues for any of the steps of the boots process. but sheldon19 and many others have since explicitly recognized that solvents were and still are the major source of waste and/or pollution in many processes for producing pharmaceuticals. sheldon mentioned the similarity of the acylation steps of both synthetic routes shown in figure 14, which both react iso-butylbenzene with acetic anhydride to produce p-isobutyl-acetophenone. the boots acetylation reaction used a traditional batch process, solvents, and at least stoichiometric quantities of alcl3 as a co-reagent for the acetylation reaction, which resulted in the stoichiometric quantities of aluminum wastes, also produced a mole of acetic acid waste, though its solvent waste production was not publicly known. in contrast, the bhc acetylation step20 used hf as a liquid catalyst, in a continuous two-phase countercurrent and organic solvent-free process, which very efficiently carries out the acylation reaction, and also very efficiently recycles the corrosive and toxic hf and minimizes the hf inventory required. because of the relatively high production volumes needed, the sophisticated engineering and high capital cost of the bhc custom continuous process was economically and environmentally justified. but had the volume of desired product been a good deal lower, a batch process might have been selected for economic reasons. finally, the mole of stoichiometric acetic acid waste from the acylation step of the bhc process is recovered, but the acetic acid “waste” is inexpensive, relatively non-toxic, bio-degradable, and could have been reasonably waste treated biologically at plant sites unsuited for reclaiming the acetic acid. because the p-isobutyl-acetophenone is a low-melting liquid, the bhc hydrogenation of the acetophenone was and is a solventless, but otherwise is a conventional, low pressure batch hydrogenation over raney nickel, to produce the racemic liquid 1-phenylethanol required for the 3d carbonylation step. the hydrogenation step is perfectly atom economical in theory, and gives very good real yields, so can be viewed as being highly “environmentally acceptable”. many such hydrogenations of ketones to alcohols had been previously known. however, had either the starting acetophenone or the 1-phenylethanol been substantially higher melting substances, or had it been necessary to produce only one enantiomer of the 1phenylethanol (or ibuprofen), a different and more difficult reduction strategy and/or reaction scheme would very likely have been required, both for the hydrogenation and/or subsequent carbonylation steps, unless a final optical resolution step was added that could have “wasted” 50% of the final product. 19 see sheldon 1996, and sheldon 2020, and several of his other articles. 20 see u.s. patent # 5,068,448 to lindley, curtis, ryan, de la garza, hilton, and kenneson, “process for the production of 4’-isobutylacetophenone”, assigned to hoechst celanese corporation. 14 in his 1992a texas a&m paper, sheldon did not comment directly on the final carbonylation step, i.e. the carbonylation of (4’-isobutyl-)1-phenyl ethanol to give racemic ibuprofen. but sheldon remedied that omission in his subsequent 1992b chemistry & industry paper, which stated: “this example is a striking illustration of the benefits to be gained by catalytic thinking….the fact that the key carbonylation step bears a striking resemblance to the modern technology for acetic acid manufacture is no mere coincidence.” (bolding added). sheldon also commented in 1992b that “catalytic conversions, on the other hand, are generally more direct: the acetic acid and ibuprofen syntheses via catalytic carbonylation are illustrations of such brevity.” sheldon, (unlike many subsequent academic commentators who mostly ignored the carbonylation step in favor of praising the hf acylation step, and failed to cite either the celanese patent or name the authors) actually understood the bhc ibuprofen invention, and that the carbonylation step was both the most patentably novel and strategically key step in the bhc scheme. this author will now add some brief comments about that final strategic “key” carbonylation step. the primary celanese technical disclosures were published in u.s. patent # 4,981,995, issued to elango, murphy, smith, davenport, mott, zey (all chemists) and moss (an engineer), and later assigned to hoechst celanese. u.s. patent # 5,166,418, and a european patent application ep 0 337 803 published in 1989 named hendricks, mott and zey as inventors. this author also described some of the other nontechnical influences and events preceding and during the conception and development of the bhc ibuprofen process in murphy (2018). dr. veraderaj elango carried out the early exploratory laboratory work on all three steps, and discovered the combination of palladium, triphenylphosphine, and aqueous hcl as catalyst for the key carbonylation step (initially in the presence of solvents, at modest pressures of carbon monoxide) that looked very promising and highly “atom economical”21. mott and zey then developed an organic-solventless twophase version of the batch carbonylation reaction, in which the 1st phase is a molten combination of the 1(4’-isobutyl)-phenyl ethanol, palladium, and triphenylphosphine, and the 2nd phase is aqueous hcl, then the two phase are strongly mixed together under carbon monoxide to produce the final racemic ibuprofen with good rates and in very good yield. in ep 0 337 803 mott and zey disclosed a method for efficiently separating active chloro-palladium / triphenylphosphine catalyst complexes from the ibuprofen product, and recycling them in the next carbonylation cycle. joel hendricks (an engineer) and mott (a chemist) also discovered that including some ibuprofen with the starting materials substantially increases the reaction rates and selectivities, see u.s. patent # 5,166,418. in his 2010 paper, sheldon estimated that the carbonylation reaction proceeded to 99% conversion, 96% selectivity to racemic ibuprofen, at a catalyst turnover frequency of 375 per hr. a team of chemists, engineers, technicians, and operators managed by dr. larry o. wheeler piloted the process at corpus christi and built and commercialized the process at bishop texas in 1992. one early publication that described the bhc process was a february 8, 1993 article in chemical & engineering news, titled “custom chemicals”, which stated that “environmental issues are the engines that drive the fortunes of the custom chemical manufacturing industry today.” the article discussed the many technical, economic, and regulatory difficulties the chemical manufacturers were encountering 21 the words “atom economy” had not yet been coined at that time (in the mid-1980s), but the workers at celanese (and likely many other industrial chemists of those times) were very familiar with the concept that as much of the weight of the starting materials as possible should be incorporated into the product. 15 while addressing the environmental issues, and featured a version of sheldon’s figure 14 describing the bhc process as one prominent example of a solution to the problems. the bhc ibuprofen process then won chemical engineering magazine’s bi-annual kirkpatrick award for “pioneering chemical engineering innovation” in december 1993. the opening three sentences of the article stated: “increasing the efficiency of a process is an ongoing directive in chemical process industries (cpi). minimizing its impact on the environment is another. traditional bulk-pharmaceutical manufacturing could use some help on both counts,” then went on to describe the bhc ibuprofen process. another later example of a prominent publication that praised the bhc ibuprofen process was cann & connelly’s 2000 acs-supported book intended for students, “real-world cases in green chemistry”. the book devoted a chapter to the bhc ibuprofen process example, as an example of the importance of catalysis and atom economy. it stated that the overall bhc ibuprofen process had a theoretical “atom economy” of 77% but noted that the lost mass / atoms attributable to the acetic acid produced in the first acylation step “is recycled”, implying that the real-world atom economy and environmental acceptability of the bhc ibuprofen process was very high. in real-world practice the yields and efficiencies of each of the steps are in fact all very high, so that viewed together as a whole, the bhc ibuprofen process was a good deal unexpectedly better than the prior boots process, and much better than just “the sum of the parts”. in the first moments and days of conception, this author clearly understood that there was potential for such good future outcomes, but there were many uncertainties. it took the further contributions and teamwork of the many subsequent celanese chemists, engineers, management, and business-people, as well as a joint venture with boots, to turn that potential into a commercial reality that actually improved the environment. 4. professor sheldon’s concept of “catalytic retrosynthesis” later in his 1992 texas a&m paper sheldon introduced into the academic literature his concept of “catalytic retrosynthesis”. sheldon stated: “the example of ibuprofen perfectly illustrates the benefits to be gained by paying attention to the atom utilization in different routes and for being catalysis-minded. indeed, organic chemists should be urged to integrate these aspects into their retrosynthetic thinking. thus in planning an organic synthesis, a ‘catalytic retrosynthesis’ could be constructed, identifying catalytic pathways to the desired product….such a catalytic retrosynthesis for ibuprofen is shown in figure 16.” sheldon’s figure 16 “catalytic retrosynthetic” analysis of ibuprofen is reproduced below. retrosynthetic analysis was of course a standard part of traditional synthetic organic chemistry strategies, originated by e.j. corey of harvard university in the 1960s, a concept for which corey won the nobel prize in 1990. 16 (from sheldon 1992a) this author did in fact, in may of 1984, consider both sides of the retro-synthetic analysis of racemic ibuprofen illustrated by sheldon’s figure 16, and also intentionally used catalytic reactions, (as previously described in detail in murphy (2018).22 in 1984 i was working in a small celanese team that was making major improvements in commercial rhodium-catalyzed methanol carbonylation technology.23 i attended the 10th annual meeting of the organic reactions catalysis society in williamsburg virginia in may 1984, where professor john stille of colorado state university gave a talk on attempts (with modest results) to hydroformylate styrene asymmetrically.24 stille briefly showed a slide of structures of several known “profen” drugs, including ibuprofen, that could be a target for a “hydroformylation” synthetic strategy. in my conference hotel room that night, i conducted a retrosynthetic analysis of ibuprofen (and several other “profen” drugs whose structures stille had revealed 6) and considered both branches of the retrosynthetic analysis illustrated by sheldon’s figure 16. i did not know that first night which of the “profen” drugs stille had shown would have to be single enantiomers, or which ones would have credible / viable commercial markets. i concluded quickly on that night that the “hydroformylation” strategy shown (for ibuprofen) along the right of sheldon’s figure 16 was too long, uncertain, and incomplete to be especially attractive for celanese, though i did not totally discount it. 22 this author never considered (until years later) the combination of the two well-known techniques of catalysis and retro-synthetic analysis to constitute a new “principle”, a proposition this author still considers debatable. 23 see smith et.al, (1987). 24 see stille, j.k. (1985). 17 because i was actively working on methanol carbonylation, it seemed obvious to consider the “carbonylation” strategy illustrated on the left of sheldon’s figure16. the synthetic scheme would have looked much more difficult had a single enantiomer of the ibuprofen been required. fortunately, it turned out (after i got home to celanese) that only racemic ibuprofen was needed. i shared my ideas for the “carbonylation” synthetic scheme with a separate celanese research group in corpus christi exploring new routes to fine chemicals and pharmaceuticals. veraderaj elango, who worked in that group, later found the pd / pph3 / hcl catalyst combination that very efficiently carried out the key carbonylation step, to yield the racemic ibuprofen, in good rates and yields. looking backwards another step, my intuition that night in williamsburg was that a ketone hydrogenation to produce a racemic benzylic alcohol was reasonably likely to succeed in good yields, as many examples of such ketone hydrogenations were known. looking backward another step, i had reasonable initial confidence that a friedel-crafts acylation of isobutyl-benzene to produce the needed acetophenone could succeed, something the literature (including the boots patents) rapidly confirmed when i got home. but i did not know that night what volume of ibuprofen production would be needed, and whether or not it could justify an anticipated high capital cost to build a custom commercial plant to handle the dangerous and corrosive hf, and thereby avoid the use of alcl3 in the acylation step. that question was only answered a good deal later at the end of development, by the team of celanese engineers who did the economic / market estimates and process design work. overall, the three-step bhc synthetic strategy produced by the “catalytic retro-synthetic analysis” seemed to have uncertain but very interesting potential “quality” 4, 25. but a great deal of inter-disciplinary teamwork was needed to resolve the initial uncertainties. as commercialized in 1992, the bhc ibuprofen process directly illustrated six of the “12 principles of green chemistry” (only published years later); 1) prevention of waste rather than treatment or cleanup, 2) catalysis, 3) atom economy, 4) minimization of solvents, 5) energy efficiency, and 6) avoidance of protecting groups). two more of the “12 principles” had been used by nicholson and adams at boots in the 1960s, during the discovery of ibuprofen (designing safer chemicals and designing for degradation). it violated two of the “12 principles”, (less hazardous chemical synthesis and inherently safer chemistry), primarily because of the use of hf in the acylation step, but use of hf was much later determined to be both environmentally and economically superior to the use of stoichiometric quantities of alcl3 in the original boots acylation step. the last two of the later published “12 principles of green chemistry” (use of renewable feedstocks and “real time analysis to prevent pollution”) were irrelevant to the bhc ibuprofen process. looking back from a different perspective, there were indeed many benefits from a retro-synthetic analysis for ibuprofen, using catalytic reactions. it “automatically” routed the analysis toward shorter, and highly atom efficient routes that avoided waste / pollution production and protecting groups, and toward raw material and energy efficiency. 25 see murphy (2020b) 18 ibuprofen was a relatively simple target molecule for a pharmaceutical, but many uncertainties remained after the retro-synthetic analysis in the earliest moments and days of conception. again, the teamwork of many people from many disciplines was required to address and overcome the uncertainties and turn the initial conception into a commercial reality that actually “prevented pollution”. many pharmaceuticals are more complex molecules than ibuprofen, and therefore require more complex analysis, and real-world compromises and teamwork, from the many subsequent scientists, engineers, and businesspeople required to turn original ideas into commercial realities. in the remainder of his 1992 texas a&m article, and in many of his subsequent articles over the following years (see appended reference list for citations to many of sheldon’s subsequent publications), sheldon described and/or predicted many applications and examples of the uses of catalysis in the fine chemical and pharmaceutical industries, to achieve waste and pollution reduction. in sheldon’s later papers he also repeatedly discussed the importance of considering positive economic outcomes to the real-world development and commercialization of environmentally superior commercial processes. improved economic performance was a very important but far too often unrecognized driver of what was termed “pollution prevention” in industry in the 1980s.4,5 recently, sheldon, bode, and akakios summarized thirty years of the subsequent evolution and application of concepts related to green chemistry metrics (sheldon et. al. (2022)). sheldon noted that “the ideal e-factor is zero conforming to the first principle of green chemistry: ‘it is better to prevent waste than to treat or clean up waste after it is formed.’” sheldon also later noted “an important driver for the widespread introduction of green chemistry in chemicals manufacture was always waste prevention at source [4], not only for its environmental benefits but also for its economic competitiveness through efficient and cost-effective use of raw materials.” sheldon noted the e-factor calculations have subsequently undergone some evolution, broadening, and refinements since his earliest paper 30 years ago, to explicitly include solvent losses and water utilization. sheldon now defines the e-factor as “the actual amount of waste, defined as ‘everything but the desired product’ produced per kg of product,” but somewhat later remarked that: “…current thinking is to calculate e-factors both with and without water [8,9]. this has led to the use of simple efactors (sef), that disregard solvents and water in early route scouting, and complete e-factors (cef) that include solvents and water with no recycling [5]. the true commercial e factor will fall between the sef and cef, and can be calculated when reliable data for recycling and solvent losses are known.” this author agrees with sheldon that “simple” e-factors which do not initially address solvent issues can be useful during the conception and exploratory scouting stages of a real-world commercial project. at the stage of conception and early scouting experiments in the ibuprofen project, we were uncertain if the basic catalytic chemistry would function adequately, so we initially and consciously but temporarily ignored the solvent issues (as being totally unpredictable until the basic chemistry and promising catalysts had been demonstrated). consideration of solvents and/or process water questions was delayed until development began, and then it turned out then that solvents were unnecessary during the synthetic 19 chemistry, but necessary during the separation of the expensive pd catalyst from the ibuprofen product, and final purification of the ibuprofen! sheldon also noted in 2022 that “the pharmaceutical industry accepted the challenge and has spent the last 2-3 decades cleaning up their manufacturing operations [3]. however, in the intervening years apis have become increasingly complicated molecules, compared with 40 years ago, thus requiring longer syntheses for their production.” one of many new sources of information and tools, to address such large challenges, can be found on the website of the acs pharmaceutical roundtable.26 trost’s bryostatin total synthesis provided a wonderful example of such challenges, and the use of homogeneous catalysts to shorten very long and complex total synthesis schemes in order to make them practical, and simultaneously improve the final e-factor and environmental impacts as well. 5. paradigm change, evolution, and the future of “green chemistry” some larger perspectives are needed, about the scope and purposes of “green chemistry”. having a “green chemistry” idea, or following a set of “principles”, or even running a few experiments in the lab is only a beginning, toward a much larger goal and/or purpose. in this author’s opinion and experience, the primary goal and/or purpose of “pollution prevention / green chemistry” is not to try to discover or make a new “science”. in this author’s opinion and experience, the goal and/or purpose of “green chemistry” has always been to use already known “science”, engineering, and technology to try to make new and improved real-world processes and products, for the needs of the real-world and its people, also while preventing the formation of waste and pollutants, so as do less damage to the natural world and its environment and ecology. fortunately, a good deal of new “science” has developed along the way. addressing that broader but primary goal, and transforming that goal into real-world reality, has always required consideration of, and contributions from other “sciences” outside chemistry, including biology, ecology, engineering, economics, business, and even politics and policy. for example, pharmaceutical research has always been interdisciplinary, with chemists making molecules for biological testing for activity, toxicity, etc., all for the use of doctors and patients. with the growing use of the techniques of modern biotechnology, to make antibody drugs and rna vaccines, the pharmaceutical industry trend is now toward the increasing importance of biology, and also the engineering techniques necessary for realworld production of such biotechnology drugs, and interdisciplinarity is now increasingly important. furthermore, the efforts of trost and sheldon as described above were only a limited (and very “chemistry focused”) part of the much earlier, broader, international, and interdisciplinary efforts at “pollution prevention” that developed in industry in the 1970s and 1980s.4,5 those much broader “pollution prevention” efforts were a “paradigm change” that embraced everything from the mining of minerals, oil drilling and refining, to end use issues including toxicity, formulations, packaging, coatings, recycling, disposal, and degradability. many industrial chemists were involved in the “pollution prevention” efforts of the 1970s and 1980s, but few academic chemists became involved in such efforts until the 1990s. 26 see the acs pharmaceutical roundtable website, at https://www.acsgcipr.org/ https://www.acsgcipr.org/ 20 professors barry trost and roger sheldon were among the earliest “chemical” academics to become involved. sheldon brought a wealth of knowledge about and experience in the chemical industry with him when he moved to academia in 1991. sheldon’s tables 1 & 2, and figure 8 recognized some of those prior developments in industry, over the prior decades. sheldon recognized that those developments contrasted with, and in some ways conflicted with, the different goals and techniques that had evolved in traditional synthetic organic chemistry, a “field” largely dominated by academic perspectives, goals, and the peer reviewed scientific literature. but with the growth of research in both organometallic chemistry and homogeneous catalysis in both industry and academia in the 1960s and 1970s, the two previously largely separate fields of synthetic organic chemistry and catalysis began to merge, as sheldon’s figure 8 correctly suggested. both trost and sheldon then made substantial contributions to the early evolution of methods for more cleanly synthesizing and manufacturing fine chemicals and pharmaceuticals in the early 1990s, years before the words “green chemistry” were used in public, or the “12 principles of green chemistry” were published in 1998. their later contributions are also indisputable, as are the later contributions by many other scientists, from many “disciplines”, in both industry and in academia. unfortunately, with the publication of the “12 principles of green chemistry” in 1998, too much of the academic and government “worlds” began to narrow the focus toward chemistry only, while largely ignoring the much earlier and much broader interdisciplinary approaches that had produced many environmentally favorable commercial processes in the 1970s and 1980s. in this unfortunate “paradigm change” many academics began to conduct research and teach students based on an inaccurate “narrative” that “green chemistry” had originated at the epa, and could be “guided” by the wildly incomplete and highly academic perspectives of the “12 principles. this author has a very different perspective on, and has published (see murphy 2020a), a very different interpretation of the history of the origins and emergence of “green chemistry”, namely that: “…real-world industrial “green chemistry” emerged as a holistic final outcome from an extremely varied and complex set of parallel evolutionary “random tinkering” subprocesses that began about the time of world war ii, and that evolutionary process accelerated in the 1970s …. that overall evolutionary process was the product of very complex interactions of very many internal and external events, carried out by many human investigators from multiple disciplines and countries, who were individually driven by many different goals, motivations, influences and input factors, including customer / societal needs and desires, economics, the environment, the legal / statutory / regulatory pressures, as well as the constantly evolving state of the underlying sciences of chemistry, biology, and engineering, over decades. many of the resulting individual inventions were also the direct product of individual human creativity, thought, and logic, as aided by intercommunications between the investigators, as well as the constraints of the laws of nature, local circumstances, and elements of chance.”4 this author believes that such an evolutionary and multi-disciplinary view of the history of “green chemistry” can have many implications for the directions “green chemistry” should go in the future. fortunately, in the last ten years or so, some prominent “green” academic practitioners (including 21 professor anastas) and their approaches seem to be broadening and evolving again, toward interdisciplinarity, “sustainability”, and “circular” technologies and economics.27 this author very much approves of and supports returning toward such broader interdisciplinary contributions and perspectives in the future. moving back toward such interdisciplinary and teamwork-based approaches is quite a “paradigm change”. deep knowledge, experience, and “expertise” in each of the relevant sub-disciplines is still required, but is clearly not enough. the interdisciplinary subject matter is far too vast and/or infinite for any one person to understand completely, and a good deal of unpredictability is built into such vastly complex evolutionary processes. yet interdisciplinary teams can address and solve many very complex real-world problems, by limiting and focusing on the scope of the specific real-world problem they are attempting to address, and using interdisciplinary teamwork and iterative, evolutionary approaches.28 lastly, this author is concerned that over the last 25 years hundreds of thousands of university students have been taught that the “12 principles of green chemistry” were the primary cause of the much of the environmental progress of the last 25 years. those narratives neglect the primary early role that industry played, and have left hundreds of thousands of students with a false belief that the us government and academia were primarily responsible for the “green” progress that has been achieved. they also propagate a very questionable belief that top-down “command and control” legal/political governmental mandates were a primary cause the progress over the last 25 years, and neglect consideration of inherently interdisciplinary evolutionary developments that were actually responsible for much of the progress. while such oversimplified narratives may be difficult to avoid when introducing k-12 and undergraduate students to science, this author believes such narratives are somewhat destructive to the understanding and futures of science and engineering graduate students preparing to go out into a profoundly interdisciplinary and evolutionary real-world. this author believes graduate students interested in inherently interdisciplinary fields such as “green chemistry” and “green engineering” should be exposed to and consider evolutionary and interdisciplinary perspectives about science, and their relationships to the extremely complex external and evolutionary technical, social, and legal phenomena that are ubiquitous in the real-world. this author believes such graduate students should be allowed to participate in interdisciplinary graduate coursework and/or seminars addressing environmental problems and solutions. this author is heartened by the indications that both “green” r&d in general, and science and engineering education, seem to be evolving back toward such interdisciplinary approaches, and that these developments may represent another new “paradigm change” in academic education. mark a. murphy ph.d., j.d. is a retired industrial chemist and patent attorney, writing “pro-bono.” he thanks his many prior colleagues from science, engineering, and law, and the authors of the references cited herein, and his wife mary bertini bickers (a woman of many very unusual talents in her own right) for her many forms of support. the opinions stated in this article are solely those of the author and were not induced or financially supported in any way by any other person, business, or legal entity. 27 see for example mulvihill et.al. (2011), iles and mulvihill (2012), constable (2021), and ncube et.al. (2023). 28 see murphy (2020b) 22 sheldon’s figure 1, table 1, table 2, figure 8, and the several text passages quoted herein from sheldon 1992a are being reproduced in this article with the permission of springer nature, current owner of plenum press’s original copyrights. reference list anastas, pt., and warner, j. c., (1998) “green chemistry theory and practice”, oxford university press, new york. anastas, p.t. and beach, e.s., (2009) “changing the course of chemistry,” chapter 1, in “in green chemistry education,” anastas, p.t., levy, i.j., and parent, k.e., editors, acs symposium series volume 1011, washington dc 2009, available at https://pubs.acs.org/doi/abs/10.1021/bk-2009-1011.ch001 . cann, m.c. and connelly, m.e. (2000) real-world cases in green chemistry, published by the american chemical society, washington dc. a copy is available at https://www.amazon.com/real-world-cases-green-chemistrymichael/dp/0841237336 . constable, d.j.c., 2021, “green and sustainable chemistry – the case for a systems-based, interdisciplinary approach”, iscience, 24, 103489, december 17 2021, see https://www.sciencedirect.com/science/article/pii/s2589004221014607 “custom chemicals”, (1993) article by stephen c. stinson in chemical & engineering news, february 8, 71, 6, 3459, see https://pubs.acs.org/doi/10.1021/cen-v071n006.p034 howard-grenville, j., nelson, a.j., earle, a.g., haack, j.a., and young, d.m., “if chemists don’tdo it, who is going to? peer driven occupational change and the emergence of green chemistry,” administrative science quarterly, 2017, vol 62(3) 524-560. https://journals.sagepub.com/doi/abs/10.1177/0001839217690530 kirkpatrick chemical engineering achievement award, chemical engineering magazine, december 1993, pages 94-95, “the award goes to….”, see https://www.chemengonline.com/kirkpatrick-award/ illes, a., mulvihill, m.j., 2012, “collaboration across disciplines for sustainability: green chemistry as an emerging multistakeholder community”, environ. sci. technol. 46, 11, 5643-5649. see https://pubs.acs.org/doi/10.1021/es300803t mulvihill, m.j., beach, e.s., zimmerman, j.b., and anastas, p.t., 2011, “green chemistry and green engineering: a framework for sustainable technology development”, annu. rev. environ. resour., 36, 271-293, see https://papers.ssrn.com/sol3/papers.cfm?abstract_id=1955060 murphy, m.a., (2020a), “early industrial roots of green chemistry ii : international “pollution prevention” efforts during the 1970’s and 1980’s” substantia, 4(2), 2020; see https://riviste.fupress.net/index.php/subs/article/view/894 murphy, m.a., (2020b), “exploring the vastness of design space for greener solutions using a quality approach,” physical sciences reviews, 20200001, see https://www.degruyter.com/document/doi/10.1515/9783110669985002/html?lang=de murphy, m.a., (2021), “early industrial roots of green chemistry : international “pollution prevention” efforts during the 1970’s and 1980’s”, chemistry international, january – march 2021, pgs 23-25, https://www.degruyter.com/document/doi/10.1515/ci-2021-0105/html https://pubs.acs.org/doi/abs/10.1021/bk-2009-1011.ch001 https://www.amazon.com/real-world-cases-green-chemistry-michael/dp/0841237336 https://www.amazon.com/real-world-cases-green-chemistry-michael/dp/0841237336 https://www.sciencedirect.com/science/article/pii/s2589004221014607 https://pubs.acs.org/doi/10.1021/cen-v071n006.p034 https://journals.sagepub.com/doi/abs/10.1177/0001839217690530 https://www.chemengonline.com/kirkpatrick-award/ https://pubs.acs.org/doi/10.1021/es300803t https://papers.ssrn.com/sol3/papers.cfm?abstract_id=1955060 https://riviste.fupress.net/index.php/subs/article/view/894 https://www.degruyter.com/document/doi/10.1515/9783110669985-002/html?lang=de https://www.degruyter.com/document/doi/10.1515/9783110669985-002/html?lang=de https://www.degruyter.com/document/doi/10.1515/ci-2021-0105/html 23 murphy, m.a., (2018), “early industrial roots of green chemistry and the history of the bhc ibuprofen process invention and its quality connection”, foundations of chemistry, 2018, 20: 121-165m; https://doi.org/10.1007/s10698-017-9300-9 ncube, a., mtetwa, s., bukhari, m., fiorentino, g., and passaro, r.,2023, “circular economy and green chemistry: the need for radical innovative approaches in the design for new products”, energies 2023, 16(4), 1752; see https://www.mdpi.com/1996-1073/16/4/1752 “non-waste technology and production, proceedings of an international seminar organized by the senior advisors to ece governments on environmental problems on the principals and creation of non-waste technology and production, paris, 29november – 4 december 1976”, published in 1978 by permagon press on behalf of the united nations as copyright holder. see https://www.sciencedirect.com/book/9780080220284/non-waste-technology-and-production royston, m.g., “pollution prevention pays”, permagon press, 1979, currently available from elsevier science direct at https://www.sciencedirect.com/book/9780080235974/pollution-preventionpays sheldon, r.a., (1987) “catalytic oxidation and fine chemicals”, catalysis today, 1, 351-355. sheldon, r.a., (1992a), “catalysis, the atom utilization concept, and waste minimization”, chapter 10, pp 99-119, in “industrial environmental chemistry” edited by d.t. sawyer and a.e. martell, plenum press 1992, in proceedings based on a march 1992 symposium sponsored by the texas a&m iuccp (industry-university cooperative chemistry program). currently available at https://link.springer.com/chapter/10.1007/978-1-4899-2320-2_9, used with permission of the current copyright holder, springer nature. sheldon, r.a., (1992b), “organic synthesis – past, present, and future,” chemistry & industry, 7 december 1992, 903-906. sheldon, r.a., (1993), “the role of catalysis in waste minimization”, in precision process technology, weijnen, m.p.c., drinkenburg, a.a.h. (eds) precision process technology. springer, dordrecht. https://link.springer.com/chapter/10.1007/978-94-011-1759-3_10 sheldon, r a. (1994), “consider the environmental quotient”, chemtech, 24:3, pages 38-47. see https://www.osti.gov/biblio/7109196 sheldon, r.a., dakka, j, (1994), “heterogeneous catalytic oxidations in the manufacture of fine chemicals”, catalysis today, 19 (2) (1994) 215-246, see https://www.sciencedirect.com/science/article/abs/pii/092058619480186x sheldon, r.a., (1996), “selective catalytic synthesis of fine chemicals: opportunities and trends”, j. mol. mol. catal. a., 107,may 1996, 75-83, see https://www.sciencedirect.com/science/article/abs/pii/1381116995002294 sheldon, r.a., (1997), “catalysis and pollution prevention”, chemistry & industry, jan 6 1997, 12-15 sheldon, r.a., (1997), “towards environmentally friendly chemical processes”, in: swift, k.a.d. (eds) current topics in flavours and fragrances. springer, dordrecht. https://doi.org/10.1007/978-94-0114022-5_4 https://doi.org/10.1007/s10698-017-9300-9 https://www.mdpi.com/1996-1073/16/4/1752 https://www.sciencedirect.com/book/9780080220284/non-waste-technology-and-production https://www.sciencedirect.com/book/9780080235974/pollution-preventionpays https://link.springer.com/chapter/10.1007/978-1-4899-2320-2_9 https://link.springer.com/chapter/10.1007/978-94-011-1759-3_10 https://www.osti.gov/biblio/7109196 https://www.sciencedirect.com/science/article/abs/pii/092058619480186x https://www.sciencedirect.com/science/article/abs/pii/1381116995002294 https://doi.org/10.1007/978-94-011-4022-5_4 https://doi.org/10.1007/978-94-011-4022-5_4 24 sheldon, r.a., (1997), “catalysis: the key to waste minimization”, j. chem tech. biotechnol. 68, 381388, https://doi.org/10.1002/(sici)1097-4660(199704)68:4%3c381::aid-jctb620%3e3.0.co;2-3 sheldon, r.a., (2000), “atom efficiency and catalysis in organic synthesis”, pure and applied chemistry, vol. 72, no. 7, 2000, pp. 1233-1246. https://doi.org/10.1351/pac200072071233 sheldon, r.a., (2010), “introduction to green chemistry, organic synthesis and pharmaceuticals”, chapter 1 in green chemistry in the pharmaceutical industry, editor(s): dr. peter j. dunn, dr. andrew s. wells, dr. michael t. williams, wiley‐vch verlag gmbh & co. kgaa, see https://onlinelibrary.wiley.com/doi/10.1002/9783527629688.ch1 sheldon, r.a., bode, m.l., and akakios, s.g., (2022), “metrics of green chemistry: waste minimization”, in current opinion in green and sustainable chemistry, volume 33, february 2022, 100569, see https://www.sciencedirect.com/science/article/abs/pii/s2452223621001255 smith, b.m., torrence, g.p,. murphy, m.a., and aguiló, a., (1987), “the rhodium-catalyzed methanol carbonylation to acetic acid at low water concentrations: the effect of iodide and acetate on catalyst activity and stability”, j. mol. cat. 39, 115-136. stille, j.k.: (1985), “asymmetric hydroformylation via polymer supported chiral catalysts”. in: robert, l. (ed.) volume 22 of the ‘‘catalysis of organic reactions’’ series. augustine, marcel dekker inc, new york trost, b.m., (1991), “the atom economya search for synthetic efficiency,” science, 6 dec, vol 254 no. 5037, pp. 1471-1477. trost, b.m., (1995), “the atom economya challenge for organic synthesis: homogeneous catalysis leads the way,” angewante chemie international edition in english, volume 34, issue 3, p. 259-281. https://doi.org/10.1002/anie.199502591 trost, b.m., (2002), “on inventing reactions for atom economy”: acc. chem. res., 35, 9, 695-705. https://pubs.acs.org/doi/10.1021/ar010068z trost, b.m., dong, g., (2008), nature, november 27; 456(7221): 485–488. https://doi.org/10.1038/nature07543 https://doi.org/10.1002/(sici)1097-4660(199704)68:4%3c381::aid-jctb620%3e3.0.co;2-3 https://doi.org/10.1351/pac200072071233 https://onlinelibrary.wiley.com/doi/10.1002/9783527629688.ch1 https://www.sciencedirect.com/science/article/abs/pii/s2452223621001255 https://doi.org/10.1002/anie.199502591 https://pubs.acs.org/doi/10.1021/ar010068z https://doi.org/10.1038/nature07543 abstract 1. introduction substantia. an international journal of the history of chemistry 2(1): 17-28, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-38 citation: h.-j. apell (2018) finding na,k-atpase. i from cell to molecule. substantia 2(1): 17-28. doi: 10.13128/substantia-38 copyright: © 2018 h.-j. apell. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article finding na,k-atpase i from cell to molecule hans-jürgen apell dept. of biology, university of konstanz, universitätsstraße 10, 78464 konstanz, germany email: h-j.apell@uni-konstanz.de; telephone: +49 7531 882253 abstract. the oppositely oriented concentration gradients of na+ and k+ ions across the cell membrane as found in animal cells led to the requirement of an active iontransport mechanism that maintains this steady-state condition. as solution of this problem the na,k-atpase was identified, a member of the p-type atpase family. its stoichiometry has been defined as 3 na+/2 k+/1 atp, and a class of na,k-atpasespecific inhibitors, cardiac steroids, was established, which allow the identification of this ion pump. in an effort lasting for several decades structural details were uncovered down to almost atomic resolution. the quaternary structure of the functional unit, either αβ heterodimer or (αβ)n complexes with n ≥ 2, is still under discussion. keywords. sodium pump, active transport, discovery, physiological role, structure. i. history of the need for a sodium pump in the 1930s it was already well known that inside living cells the composition of the ionic contents was significantly different from that of the extracellular space. at that time the physiological investigations were focused mainly on muscle and red blood cells, and the evident asymmetry of high k+ and low na+ concentrations inside and vice versa outside was well documented. during this period hardly any functional properties of the cell (or ‘cytoplasmic’) membrane were known, not to mention understood. it is not surprising that various concepts were developed to explain the asymmetry and how it was sustained. the initially preferred and widely supported idea was that the cell membrane is an almost perfectly impermeable barrier for ions. some scientists were even willing to sacrifice the validity of the second law of thermodynamics in the field of biology in order to explain the experimental observations. a monograph on the historical development of our understanding of membrane transport, which is comprehensive and worth reading, was published about twenty years ago by joseph d. robinson.1 major breakthroughs were achieved when new experimental techniques became available, such as the use of radioactive isotopes of k+ and na+ that allowed the detection of unidirectional fluxes. probably medical requirements of the second world war also contributed, since physiologists were 18 hans-jürgen apell forced to study every detail on the optimization of blood preservation. when 24na+ was introduced into physiological experiments it was shown that this radioactive isotope readily and rapidly exchanged with the stable isotope on the other side of the cell membrane. the membranes of the muscle cells were evidently permeable for na+.2,3 it was also demonstrated that the cytoplasmic k+ concentration could be very well modulated by the extracellular k+ concentration, a clear indication of a k+ permeability of the cell membrane.4 nevertheless, the asymmetric distribution of both cation species remained preserved despite the fact that both ion species were able to permeate through the membrane. as an inevitable consequence, a counter-movement of na+ and k+ had to be assumed that keeps up the concentration gradients. in 1940 h. burr steinbach mentioned in a contribution to a cold spring harbor symposium for the first time the request for a “pumping out the sodium” from the cytoplasm.5 it became clear that ion translocation driven by their electrochemical potential gradients, the so-called passive ion transport, had to be counteracted by energyconsuming transport processes (or “active transport”) that ensured the indispensable condition of stationary high k+ and low na+ concentrations inside the cells and even the electric membrane potential. figure 1 shows a schematic representation of transport pathways and the transporters that were identified as leading actors during decades of investigations of cell membrane properties. a further fruitful approach to advance the understanding of transport processes across the cell membrane was contributed by investigations of red blood cells. already in the late 1930s the blood banks tried to find optimized preservation conditions of red blood cell batches. it was found that the stored cells lost their internal k+ in the course of time, and the concentration of free k+ in the blood plasma reached toxic levels when blood was preserved in the cold. in addition, it was shown that the cytoplasmic na+ concentration increased and that these changes were not primarily caused by deteriorated blood cells.6 the net outflow of k+ in the cold could be reversed at a temperature of 37 °c and in the presence of glucose. this observation indicated that k+ and na+ ions were transported across the membrane against their concentration gradient. in the end, the physiological asymmetry was restored and this action was dependent on glycolysis.7-9 in addition, inhibition of glycolysis by incubation with fluoride caused a delayed loss of k+ from the red blood cells which was no longer balanced by k+ uptake, even at physiological temperature.9 this observation pointed out that glycolysis may not be immediately responsible for k+ inward transport. at that time the underlying metabolic functions were still subject to speculation. later in the 1940s sufficient experimental evidence had been collected to conclude convincingly that active transport of na+ maintains the na+/k+ asymmetry across the cell membrane and that this condition is a steady state and not an equilibrium.10 another step forward was the realization that the na+ flux out of the cell is coupled to the presence of external k+.11 in the early 1950s a focus was set on the energy sources that fuel the concentration asymmetry for na+ and k+ across the cell membrane of the red blood cell. the fact that glucose was metabolized but was not the direct source of energy had been made evident already ten years earlier.9 it was also discussed that glycolysis figure 1. ion transport pathways in animal cells. common to all cells is the inside negative electric potential and the ion-concentration gradients oppositely oriented for na+ and k+, with high na+ concentrations outside and low in cytoplasm and vice versa in the case of k+. in principle, two different categories of transport mechanisms have to be discriminated, active and passive transport. the active transport is split into primary and secondary active transport. in primary active transport so-called ion pumps utilize atp as energy source to translocate ions “uphill”, i.e. against their electrochemical potential gradient. secondary active transport is performed by antiporters (e.g. the na,ca-exchanger) or cotransporter (e.g. the na,pior na,glucose-cotransporter) which translocate one of their substrates “uphill” while the other substrate, usually na+, provides the necessary free energy by its transport “downhill”. a selection of examples is shown in this figure. passive ion transport occurs either by leak conductance which is minimized by the nature and structure of the cell membrane (but unavoidable) or it is facilitated by channels or carriers. these transporters are regulated by different mechanisms to meet the metabolic needs of the cells. key players for the passive cation transport are na+, k+ and ca2+ channels. 19finding na,k-atpase plays a role as atp-generating process.12 in 1954, first experimental studies demonstrated that the k+ accumulation in red blood cells was an atp-requiring process which was activated by mg2+.13 a few years later, the positive proof was provided that active k+ transport occurred only when atp was present,14 and a corresponding finding was made also in squid giant axons.15 in studies of frog skin significant experimental evidence was collected that active na+ transport was a forced exchange of na+ against k+,16 like in the case of red blood cells.11 constructive findings concerning the sodium pump were made possible by another crucial discovery in the early 1950s which eventually turned out to be of eminent importance for all following investigations of the na,k-atpase. when studying the cation transport in red blood cells, hans j. schatzmann found that cardiac steroids blocked the k+ uptake and the na+ outflux. he named the causative process “na-k-pumpe”.17 he was interested in identifying the mode of the blockers’ action and with detailed experiments he proved in his study that these compounds did not affect glycolysis and oxygen consumption. he also concluded that there was a direct blockade of the transport mechanism.17 this finding was supported and fortified by others.18,19 transport was blocked from the outside of the cell,20 and external k+ had an antagonistic effect on cardiac steroids.19 eventually, it became clear that schatzmann had discovered a class of compounds, of which ouabain was the most well-known, that provides highly selective inhibitors of the na,k-atpase. cardiac steroids have become the “custom-made” tool to discriminate the sodium pump from all other atp-hydrolyzing enzymes in whatever biological tissues.21 since at that time enough experimental evidence was collected that na+ and k+ were coupled to maintain steady-state concentrations for both ion species inside the cells, the question was raised whether there exists a constant coupling ratio. to find the answer to that question was not so simple. it was necessary to discover a reliable experimental approach since the active ion transport balanced passive leak fluxes that in turn were dependent on the prevailing ion concentrations on the outside of the cells. from experiments with squid axons it was concluded that because of the passive ion permeabilities an active “secretory mechanism driven by metabolism” had to be present that moved na+ and k+ against their electrochemical gradients.22 the experiments also supported strongly the idea of a coupled system in which na+ was moved out of the cell “on one limb of the cycle” and k+ taken up on the other.22 in 1956 ian m. glynn was able to present experimental data from red blood cells using radioactive tracers, in which active and passive transport could be separated distinctly and na+ efflux and k+ influx were tightly coupled in the active transport. he suggested a one-to-one exchange of na+ and k+.23 a year later robert l. post was able to measure net fluxes of na+ and k+ with an unprecedented accuracy and determined a ratio of 3 na+ for 2 k+, which was constant over the whole experimental concentration range of the transported ions.24 this coupling ratio withstood all challenges and was found to be generally valid (except for a few extremely unphysiological electrolyte compositions). ii. tracing the protein in the 1950s it was quite a challenge to propose the concept that a single protein molecule comprised both enzymatic function, in this case atpase activity only known so far to soluble proteins, and transport function, i.e. vectorial ion movements across the cell membrane. although during these years evidence was accumulated that there exists a tight coupling between both functions, the final proof, the identification of a protein (or protomer) that unites atpase activity and ion transport was still pending. in 1957, the state of the art – with respect to red blood cells – was presented in a meticulously elaborated review by glynn.25 however, even on the basis of this amassed knowledge, no convincing experimental approach was developed to solve the puzzle of the na,k-pump. the breakthrough was eventually provided by a scientist from a completely different field. jens christian skou studied the effect of local anesthetics on nerve conduction with the view of finding a membrane preparation that could be used in monolayer experiments, in which a well-defined enzymatic activity should be detected as function of applied local anesthetics. he finally attained his goal in 1956 by a membrane-fragment preparation from crab nerves and showed mg2+, na+ and k+ dependent atpase activity.26 the history of this development is elaborately described in a comment on his original paper, published in 198927, in skou’s nobel lecture in 199728 and in his autobiographical book, “lucky choices. the story of my life in science”, published recently.29 since active transport of ions was not his field of interest, initially he was not aware of the contribution he had made. only after post triggered the crucial test when both met at a conference in 1958, namely to confirm inhibition of the enzyme activity by ouabain, it was decided that he had identified the na,k-atpase.30 in retrospect skou described his posi20 hans-jürgen apell tion in those early years: “i felt like an intruder in a field that was not mine.”28 the break-through was possible because he serendipitously worked with a membrane preparation from crab nerves that consisted of open membrane fragments in which both sides of the membranes were accessible simultaneously. in contrast, cell membranes of most other cells formed closed vesicular structures upon homogenization. those preparations needed to be treated with detergents before the desired simultaneous access to both sides access of the membrane was obtained. with this information post was able to identify briefly afterwards the na,k-atpase also in red blood cells.31 in 1965 skou had already published a review with reference to numerous tissues in which the presence of na,k-atpase had been verified too.32 today we know that the na,k-atpase is present in virtually all animal cells. a schematic biochemical characterization of the na,k-atpase is shown in figure 2. because cell membranes contain scores of different proteins, at that time the question still remained open, whether the protein which performs atpase activity was also responsible for ion pumping or whether more than one protein had to be coupled to a functional complex. it became a prominent task to isolate and purify the (minimal) enzyme complex that performed as na,k-atpase and analyze its components. in the early 1960s this project was, however, a major challenge because on one hand no standard methods were available to isolate and purify membrane proteins and keep them concurrently functional. on the other hand in isolated complexes no sidedness was given, and therefore, ion transport could not be proven. to overcome this problem, the solubilized complexes had to be reconstituted back into membranes that formed the interface of two compartments which were separate from each other and provided the required sidedness. tissues from which the na,k-atpase can be isolated in reasonable amounts are found either in mammalian brain and electroplax from fish that both contain excitable cells or in tissues specialized to transport sodium, such as the outer medulla of kidney, rectal glands of shark or salt glands of ducks.33,34 early findings showed that the outer medulla of mammalian kidneys is a fairly easily accessible and convenient source. the basolateral membranes of the cells forming the thick ascending limbs of the loops of henle are specifically abundant in na,k-atpase.35,36 when cells rich in na,k-atpase are broken up by homogenization, a membrane preparation can be separated by centrifugation, the so-called crude microsomal fraction of which atpase activities were measured in the order of 200 – 500 µmol inorganic phosphate (pi) released per mg protein and hour. these membranes form vesicular structures with the cytoplasmic surface facing the outside.37 to obtain a purified preparation from such a vesicle suspension that still contains all proteins of the plasma membrane, peter l. jørgensen elaborated in 1969 a specific treatment using a low concentration of the detergent sodium dodecyl sulfate (sds). this method provides, after separation by differential centrifugation, open membrane fragments containing na,k-atpase in high density, the so-called purified microsomal preparation.38,39 by this treatment most of the other proteins and a considerable fraction of the membrane lipids are removed. this approach became subsequently – with minor improvements – the standard routine to isolate and purify the na,k-atpase.40 the protein density is so high that these fragments become stiff enough that they are no longer able to form vesicles. the hydrophobic membrane interior at the edge of the fragments is apparently covered by a layer of sds molecules which prevent contact of the hydrophobic core to the aqueous phase. the resulting fragments contain ion pumps with densities of up to 104 per µm2 as determined from electron micrographs.41 when jack kyte applied in 1971 the shortly before introduced sds polyacrylamide gel electrophoresis to a purified microsomal preparation, he proved a purity of better than 95% and that the na,k-atpase is a protomer of two distinct polypeptides with proposed molar masses of 84 kda and 57 kda.42 the purified microsomal preparations from pig kidney attained atpase activities of up to 2400 µmol pi per mg figure 2. biochemical characterization of the na,k-atpase. the ion pump is an integral membrane protein of animal cell membranes with its enzymatic machinery located on the cytoplasmic side. it hydrolyzes one mgatp complex into adp and inorganic phosphate, pi, and utilizes the released free energy to expel 3 na+ ions from the cytoplasm and to translocate 2 k+ ions into the cytoplasm. ouabain, a cardiac glycoside, is a specific inhibitor that completely blocks the na,k-atpase from the extracellular side of the membrane. 21finding na,k-atpase protein and hour.43 when incubated in solutions with mg2+ and sodium vanadate, an inhibitor of the na,katpase,44 the proteins spontaneously form in the microsomal membranes large two-dimensional crystal lattices in the membrane fragments.43 iii. defining properties in the 1970s advancing biochemical techniques promoted the study of membrane proteins. these were applied successfully to characterize the na,k-atpase with increasing precision in the following decades. a detailed review of the progress yielded during this period has been compiled in a 1979 review by robinson and flashner.45 at first, the most fundamental open question was probably about the subunit composition of the na,katpase: does the functional ion pump consist of a single polypeptide chain or of a complex of two or more subunits? although purified preparations displayed two different proteins in sds gel electrophoresis,42 it was not clear whether the lighter glycoprotein “is a true component of the nak atpase” or a tenaciously bound or coincidentally co-purified unrelated component.46 from the gel-analysis method, applied to numerous purified protein preparations from different sources, the determined ratios of both subunits varied between 2:1 and 1:2 when the heavier subunit was compared with the lighter.42,47,48 these diverse stoichiometries were obtained from experiments in which na,k-atpase preparations from different tissues were used, different amounts of proteins were applied on the gels, and at that time the behavior of glycoproteins on gels was not well understood. it lasted another few years until common agreement was reached that the stoichiometry is 1:1 and that only both subunits together form the active na,katpase.33,49,50 in 1980 the final notation was introduced, in which the large polypeptide was named α subunit and the smaller glycoprotein β subunit.49 it was established that the α subunit is phosphorylated by atp51 and that cardiac glycosides bind to it.52 the location of the ionbinding sites was assumed to be also in the α subunit, but this problem was still under discussion in 1988.53 the role of the β subunit was largely unknown at that time. although it does not carry out enzymatic functions, it is crucial for the activity of the na,k-atpase.54 reduction of a single disulfide bridge that the β subunit possesses in its extracellular c-terminal part leads to a complete loss of the pump’s activities.55 how far various functions of the na,k-atpase are modulated by this subunit was under scrutiny for a long time. convincing evidence, however, was compiled throughout the years that the β subunit is crucial for structural and functional maturation, trypsin resistance in er preparations, appropriate trafficking in the cells and cell-cell adhesiveness.56,57 only after the na,k-atpase could be expressed from cloned cdna it has been shown directly that the α subunit alone is incapable to perform na,k-atpase specific functions.58 the question whether an αβ complex is sufficient to perform na+ and k+ transport fueled by atp hydrolysis could be answered only after the na,k-atpase has been purified functionally and reconstituted as single protein species in a lipid membrane. this experimental approach was successfully introduced in 1974, when the purified na,k-atpase was incorporated in lipid vesicles and inside-out oriented reconstituted pumps transported 22na ions into the vesicles.59 the transport was inhibited when ouabain was present inside the vesicles. as will be shown later, the application of na,k-atpase containing vesicles (or ‘liposomes’) turned out to become an extremely useful tool to investigate functional properties of the ion pump.60 in 1978 for the first time reliable evidence was presented that na,k-atpase isolated from pig kidneys contained a third subunit, a small polypeptide with a molar mass in the order of 12 kda.61 it took until the 1990s before more systematic investigations of this third subunit started, and during the following years a tissue specific distribution was found. some tissues lacked of a third subunit and in others, where it was present, it was a member of the so-called fxyd protein family.62-64 this family consists of seven members. these proteins possess less than 165 amino acids, have a single membrane-spanning segment, and they share the (eponymous) extracellular motive fxyd (with x as place holder for either t, e, y, f). they interact with the α subunit and their function is a modulation of the ion-transport kinetics that allows short-term adaptation to specific metabolic needs of the cells.64 skou reported already rather early experimental results that the na,k-atpases of rabbit kidney and brain exhibited different sensitivity to g-strophantin (ouabain). it was higher by a factor of 5 in the enzyme from the brain than from the kidney.37 in 1976 experimental results were published from ouabain-binding studies using enzyme isolated from ox brain that are explained by the existence of two (or more) enzyme populations.65 in 1979 kathleen sweadner advanced the field considerably when she proved by sds-gel electrophoresis that two forms of the na,k-atpase existed in the brain that differ by 2 kda in molar mass66 which differed in their sensitivity to strophanthidin by almost a factor of 1000. 22 hans-jürgen apell by 1989 three isoforms of the α subunit were identified and a common nomenclature fixed (α1 – α3).67,68 in 1994 a fourth isoform, α4, was identified that is specific to testis.69,70 α1 is the dominant isoform in kidney and heart, the tissue-specific distribution is catalogued extensively.68 for the β subunit three isoforms (β1 – β3) were found.71,72 more precise access to the molar masses became available when amino-acid sequences were obtained from exploiting the analysis of complementary dna that was introduced in the late 1970s73 and the molar mass of proteins could be calculated precisely. in 1985, accurate numbers were published: 1016 amino acids (aas) were determined for the (mature) α subunit of sheep kidney,74 and 1022 aas for the α subunit of torpedo californica.75 that led to a calculated molar mass of 112,177 da for the sheep subunit. for the β subunit the first sequences were published in 1986: 302 aas (sheep kidney)76 with a calculated molar mass of 34.937 da, and 305 aas (torpedo californica).77 due to the fact that glycosylation varies between animals and tissues, a detectable variation in total molar mass has to be expected.78 with this technique and its success, further sequences of α and β subunits from several other tissues were published in 1986: α,β pig kidney,79 β rat brain,80 β human tumor cells.81 thereafter, numerous additional sequences followed in quick succession.82,83 whole families of na,k-atpase genes were identified and their transcriptional competence confirmed.84,85 in 1987 the cloned cdnas of both subunits from torpedo californica were used to produce mrnas by transcription in vitro. these were transferred by microinjection into xenopus oocytes, expressed and trafficked functionally into the cell membrane.58 it was shown that both subunits were necessary for correct folding and transfer to the cell membrane. with an increasing variety of molecularbiological tools that became available, the vast field of amino-acid mutations and protein expression in “foster cells”, such as oocytes,86 yeast,87 or various cell lines,88,89 became accessible. this leap in development opened a completely new dimension of experimental investigations, and they enabled us to gain a major part of our contemporary understanding of function and structure function relationship (see subsequent part ii). with the knowledge of the gene sequence not only of the na,k-atpase but also of other ion motive atpases a comparison of their sequences revealed that there is a whole family of atpases which were named p-type atpases because of their covalently phosphorylated intermediate.90 throughout the years increasingly complex phylogenetic trees of the p-type (super) family have been compiled91,92, in which the na,k-atpase belongs to the type-ii atpases and its closest family members are the h,k-atpase and the sr ca-atpase. iv. insights into the structure before the amino-acid sequence (or primary structure) became available, information on the structure of the na,k-atpase was mostly restricted to gross spatial features from electron-microscopical images41,93 or from spectroscopic studies that allowed an estimation of the percentage of α helices and β sheets present in the protein at various substrate compositions.94 more detailed concepts on the secondary structure were proposed after the tool of hydropathy analysis of the amino-acid sequence of proteins was introduced by jack kyte in 198295 and applied to the α subunit of the na,k-atpase. between 1985 and 1994 many groups tried to derive from the primary structure a spatial organization of the protein in the membrane and especially the number of transmembrane segments. the count varied between 6 and 10 membrane-embedded α helices.53,74,75,79,82,83,96 the proposal of an odd number of transmembrane segments, 7 or 9,79,97 was quickly ruled out, because experimental evidence was presented that both n and c terminus of the α subunit were located on the cytoplasmic side of the membrane.96,98 eventually, consensus was obtained at a count of 10 helices,99 which was confirmed in the end, when detailed tertiary structures became available by x-ray structure analysis from crystals of the complete na,k-atpase.100,101 as shown in figure 3, two major cytoplasmic loops were identified between the second and third transmembrane segment with about 140 amino acids, and between the fourth and fifth transmembrane segment with about 440 amino acids. in the latter loop the phosphorylation site as well as the fitc and iaf binding sites were located, which play important roles for function and analysis of the enzymatic activity of the pump.102-105 in the case of the β subunit it was accepted from the beginning that this small protein has no more than one transmembrane segment. the larger extracellular part with the c terminus76 carries the essential disulfide bridges and is glycosylated at three asparagines.53,78 for a long time the insight to gain understanding of the tertiary structure was confined to low-resolution data provided by electron microscopy, starting with the identification of knob-like structures with a diameter of about 45 å.107,108 a few years later a ‘stalked knob’ was resolved on the cytoplasmic side of the catalytic subunit of the na,k-atpase.93 the next step was the investigation of vanadate-induced two-dimensional na,k-atpase 23finding na,k-atpase crystals109 and a three-dimensional model reconstructed thereof,110,111 as shown in figure 4. no further real improvement in the revelation of structural details was achieved until almost a decade later, the first structure of the sr ca-atpase was solved with a resolution of 2.6 å.112 the structure of this closely related enzyme was used for homology modeling of the α subunit of the na,k-atpase. the resulting structure proposals gained a lot of popularity and were used quite successfully to identify crucial amino acids as targets for mutation studies. yet, another seven years had to pass until in 2007 the first original crystal structure of the na,k-atpase became available at a resolution of 3.5 å in an e2p-analogous conformation with two k+ ions bound.100 two years later, another structure of the na,katpase in the same conformation became available at a resolution of 2.4 å,113 as well as another four years later a complex with a mg2+ and a ouabain bound.114 since then, structures in the e1 conformation with 3 na+ ions in their binding sites were resolved and published.115,116 as already introduced in the analysis of the first caatpase structure, the cytoplasmic portion of the α subunit is subdivided into three domains named n, p, and a.112 this organization was found similarly for all p-type atpases studied so far. the n domain is the largest of the three domains and contains the nucleotide-binding site to which the mg-atp complex binds in a specific orientation that subsequently enables phosphorylation of the enzyme. the p domain includes the conserved aspartate that is phosphorylated by atp. this domain is formed from two segments of the large cytoplasmic loop (between m4 and m5). the a domain is formed by the loop between transmembrane helices m2 and m3 and part of the sequence before m1. it is assumed to be an actuator that moves the phosphate hydrolysis machinery in and out of the active site by large rotational motions. a comparison of the crystal structures in the e2p and e1 conformation is shown in figure 5. these represenfigure 3. secondary structure of the rat na,k-atpase α1 subunit with ten transmembrane helices. the high-lighted aspartate 371 is the amino acid phosphorylated by atp. the drawing is adapted from vilsen et al.106 with permission. 24 hans-jürgen apell tations of the na,k-atpase confirmed also that the structures derived by homology studies of the α subunit based on the sr ca-atpase structure have been rather well-suited. furthermore, the original structures of the na,k-atpase revealed how the β and the additional regulatory fxyd subunit are connected to the α subunit. in combination with the biochemical and biophysical studies on the kinetics of the sodium pump, these structures with almost atomic resolution (and those in further different conformations that hopefully will come) are extremely useful to advance the comprehension of the molecular mechanism of enzyme and transport activity of the sodium pump. for a long time a passionate discussion was carried out on the composition of the functional na,k-atpase, the protein’s quaternary structure. the main opposing proposals were that under physiological conditions the ion pump consists either of a single αβ heterodimer or of an oligomer (αβ)n with n = 2 or even larger. this controversial issue was triggered by the rather early experimental finding that the na,k-atpase exhibits during the course of its catalytic activities two distinguishable affinities for atp binding which were assigned to a high and low affinity site, accordingly.33 this observation may be explained by three different concepts: first, a single αβ heterodimer has one atp-binding site that changes its properties when the enzyme switches its conformation during the pump cycle.34,117 the second proposal was that a single αβ heterodimer has two spatially different atp-binding sites, one to perform the energizing enzyme phosphorylation while the other acts as a regulatory site, used to modulate the na,k-atpase activity,118 a function found in numerous other atp-controlled figure 4. reconstruction of a three-dimensional model of a na,katpase dimer from a tilt series of electron-microscopical images taken from a two-dimensional crystal of na,k-atpase in membrane fragments. upper panel: top view, lower panel side view. the vertical bar indicates the assumed position of the lipid membrane, the cytoplasmic protrusion of the protein is on the bottom. (figure taken from ref. 109, with permission) figure 5. crystal structure of the na,k-atpase in two conformations. the ion pump consists of the α (green), β (cyan) and an regulatory fxyd subunit (magenta). a: e2 conformational state with 2 k+ bound in a e2p-like state in which phosphate is replaced by mgf42(pdb id 2zxe).101 the analyzed crystal had a resolution of 2.4 å. the enzyme was isolated and purified from shark rectal glands. it contains fxyd10 as regulatory subunit. b: transition state of the na,k-atpase preceding the e1p conformation with 3 na+ ions occluded after binding from the cytoplasmic side (pdb id 3wgu).115 the analyzed crystal had a resolution of 2.8 å. the enzyme was isolated and purified from pig kidney. it contains fxyd2 as regulatory subunit. 25finding na,k-atpase enzymes. the third concept was that of an na,k-atpase oligomer, (αβ)2, in which both heterodimers are (tightly) coupled to provide synergistic effects.119 the experimental evidence collected over many years was multifarious and seemed often to be in favor of one proposal but rarely refuted the other(s).120 on one hand, it has been shown that an isolated, monomeric αβ was able to run the enzymatic reaction cycle and to occlude na and rb ions.121-123 in this condition, however, there was no membrane present, hence no sidedness was given and ion transport through the na,k-atpase could not be proven. on the other hand, in membranes na,k-atpase molecules were frequently clustered, and (αβ)n complexes were found when isolated with mild detergents. it was easily possible to crosslink the subunits of two different pumps,124 and in the presence of vanadate, and when the pumps were in a e2 conformation, the emergence of long rows of dimeric twodimensional crystals was detected.125 such a crystal formation was observed also in purified membrane preparations of na,k-atpase after a treatment with phospholipase a2 by which the lipid content of the membrane fragments was reduced.126 extensive crosslinking studies were performed in the group of amir askari and, modulated by the chosen substrate conditions, they substantiated various links between α-α, α-β, and β-β subunits. their interpretation of the results from their crosslinking studies led to the conclusion that the “minimum association state within the membrane must indeed be (α,β)4”.127 but no direct evidence was presented that furnished proof of a functional cooperation between αβ heterodimers. robinson wrote in his book (p.160): “(αβ)n formulations were popular in the 1970s, but αβ was favored in the 1980s when almost all the observations were revised and reinterpreted and when new data favoring the αβ interpretation was reported”.1 conceptual discussions about the requirements of monomeric or oligomeric structures of the na,katpase are multifaceted. the finding that all reaction steps needed for enzyme and transport functions have been documented in the case of monomers confronts the frequently observed spatial arrangement of the na,katpase as patches of two or more αβ protomers in close neighborhood or even in a tight contact that would allow functional interaction. why should such contacts be stabilized or maintained if they are not advantageous? and indeed, the list of published experimental findings is notably that resorts to functional interaction between two αβ protomers. for example, it was used to describe complex kinetic behavior detected in measured substrate dependencies. a first option would be that tight coupling of two protomers could promote substrate binding to one αβ and then modulate the interaction of the other αβ with a second substrate. since in both αβ protomers the pump cycles can (or will) be out of phase, one substrate may affect the interaction with a different one, even on the other side of the membrane. with such additional degrees of freedom and additional selectable parameters that are provided by modeling functional coupling, a complex kinetic behavior may be represented much easier by mathematical reaction schemes.128 furthermore, instead of a permanent tight coupling between two αβ protomers, it may be proposed that an atp-dependent aggregation and separation of the (αβ)2 oligomer exists which leads to different turnover rates when acting as (αβ)2 or (temporarily) separated αβ under control of the atp concentration in the cell.129 it is tempting to see how more complex reaction schemes result in equation systems that allow almost perfect fits of experimental results by mathematical modeling. however, such a success does not justify the reverse conclusion that the underlying model is the right one. another reason to ask for dimers of na,k-atpases is to consider synergistic effects. when the energetics of the ion transport in the sodium pump was analyzed in terms of basic free energies,130 i.e. the amount of free energy needed or being released at each single (experimentally accessible) reaction step of the pump cycle, no ‘power stroke’ was found.131 this fact implies that at no single reaction step of the pump cycle, a driving thrust of energy was released to the “out-side world”. the steps of the pump cycle consuming most energy were found to be the dislocation steps for both k+ ions from their binding sites to the cytoplasm in the e1 conformation. the absence of a power stroke could have its origin, on the one hand, in the mismatch of the application of our comprehension of macroscopic motors to molecular machines. but on the other hand, it could be also the consequence of an energetic coupling between two ion pumps running around their cycles out of phase in a way that energy production and consumption in coupled protomers compensate each other largely like in coupled chemical reactions. for a comprehensive view of quaternary-structure formation it is, however, necessary to consider also the fact that the ion pumps are embedded in a lipid bilayer which is in a liquid-crystalline phase. this two-dimensional liquid has a life of its own that is under control of entropy. the various species of lipid molecules forming the cell membrane differ in the nature of their polar head groups as well as in the lengths of their hydrophobic fatty-acid chains and their number of double bonds. especially the latter properties affect the degree of membrane fluidity. the presence of large rigid particles 26 hans-jürgen apell such as integral membrane proteins is able to promote separation into liquid-disordered and liquid-ordered phases. studies of the molecular interaction mechanisms between proteins and lipids have shown that the match between the thickness of the hydrophobic domain of the integral protein and the bilayer core leads to an accumulation of specific lipids around the protein molecules.132 this observation led to the conclusion that “the proteins end up in the membrane that provides for the best hydrophobic matching”.132 in addition, na,katpase has been found clustered in stable and rigid lipid rafts ‘floating’ in the membrane. those rafts form spontaneously in membranes of (at least) ternary lipid mixtures.133 based on those findings an alternative line of arguments to explain clustering the na,k-atpase in cell membranes can be based on purely entropic effects that lead to an aggregation of na,k-atpase molecules without any functional coupling. but again, counter-arguments may be provided by the observation that in gastric acid-secreting cells an association between the k+-cl cotransporter-3a and the α1 subunit of the na,k-atpase was formed spontaneously in lipid rafts when cholesterol was present, and upregulated atpase activity could be detected in a strictly cholesterol-dependent manner.134 so far nothing is known about the molecular mechanism of the reported effects and about the role of cholesterol in the interactions between both ion transporters. obviously, we still do not have all the pieces of a puzzle to recognize the complete raison d’être of na,k-atpase aggregation. “the paper is (still) open for discussion.” so far we have followed the trace of the discovery of the na,k-atpase, what it is good for and what it looks like, but the crucial question, how it works remains still open. countless scientists contributed during decades to find answers to this question since this ion pump was identified and since protein preparations became available to work hands-on with physiological, biochemical and biophysical methods. an overview on this research will be presented in a subsequent article, “finding na,katpase – from fluxes to ion movements.” acknowledgements this work was supported by the university of konstanz (aff 4/68). references 1. j. d. robinson, moving questions a history of membrane transport and bioenergetics, oxford university press, new york, 1997, p. 373. 2. l. a. heppel; am. j. physiol., 1940, 128, 449. 3. j. f. manery, w. f. bale; am. j. physiol., 1941, 215. 4. h. b. steinbach; j. biol. chem., 1940, 133, 695. 5. h. b. steinbach; cold 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(2021) dante alighieri science communicator. substantia 5(2): 7-17. doi: 10.36253/substantia-1329 received: jun 06, 2021 revised: jun 23, 2021 just accepted online: jun 24, 2021 published: sep 10, 2021 copyright: © 2021 bischi g. i. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature articles dante alighieri science communicator gian italo bischi university of urbino carlo bo e-mail: gian.bischi@uniurb.it abstract. this paper deals with the issue of communication and dissemination of scientific knowledge outside the circle of specialists. in particular, in the occasion of the 700th anniversary of the death of dante alighieri, we will focus on the program for the popularization of knowledge outlined by dante in the convivio and de vulgari eloquentia, as well as several examples taken from his divine comedy concerning mathematical and natural sciences. some solutions for communicating science proposed by dante, such as the explanations of principles and scientific methods within a narrative framework (now often called the storytelling method), in addition to dialogues between characters, anticipate methods for science communication used by several authors after him. examples are provided to show the depth of dante’s knowledge concerning the basic concepts and methods of mathematics, physics and natural sciences (such as chemistry, meteorology, astronomy etc.). in addition, the examples demonstrate how effectively dante used analogies and metaphors taken from sciences within his poetry. keywords: science popularization, dante alighieri, divine comedy, medieval philosophy 1. introduction in europe, during the 12th century, there was a considerable spread of knowledge due to translations of texts from greek and arabic into latin, especially in toledo (south of spain) and palermo (at the court of frederick ii of sicily), two cities where a mixture of arabian, greek and latin cultures thrived side by side for many years, as well as in several other places. authors whose works were translated into latin included aristotle, ptolemy, euclid, archimedes, alhazen, and al-khwarizmi, together with chinese and indian texts imported in europe through arabic versions. such an abundance of latin texts triggered the creation of a network of universities that used latin as a lingua franca and favored an intensive exchange of international scholars and texts. the universities of oxford, coimbra, paris, montpellier, bologna, and salerno were founded in the 12th century, and those of cambridge, salamanca, toulouse, orleans, naples and padua in the 13th century (see e.g. greco, 2014). in these universities the arts of the trivium (grammar, rhetoric, dialectic) and those of quadrivium (arithmetic, geometry, music, astronomy) became common subjects for all students. http://www.fupress.com/substantia http://www.fupress.com/substantia 8 gian italo bischi at the same time, most particularly in the 13th century, abacus schools, used by the emerging classes of merchants, craftsmen, artists, bankers and their sons, were created in many italian cities. in these schools, popular (vulgar) italian language and writing, as well as basic mathematics, accounting, mechanics and other subjects, were taught mainly through examples for practical purposes. dante probably attended this kind of school when he was a child, as he was the son of a merchant, and as an adult he probably attended some lessons at universities as well, in bologna and padua, perhaps even in paris. therefore, he was probably familiar with both kinds of knowledge – the more theoretical kind taught in latin at universities and the more practical one taught in the vulgar language at abacus schools. moreover, dante became used to italian vulgar poetry, which originated at the court of frederick ii in sicily and was adopted by many poets and scholars who shared this passion with dante. in the 13th century new knowledge and new texts (written in latin) became more generally widespread in europe, from the liber abaci by leonardo pisano (fibonacci) to optics and mathematics by robert grosseteste, treatise on astronomy and astrology by john sacrobosco and summulae logicales by pedro hispano, just to quote a few. all these texts were addressed to an intellectual élite. indeed, many scholars held an elitist idea of knowledge, especially regarding philosophy and science (often known as natural philosophy). this was, for example, the opinion of islamic scholar averroes (cordova 1126 marrakech 1198), a famous philosopher, doctor, judge, and author of commentaries on aristotle, who stated that teaching humble people was a wasted effort, and even dangerous because it could lead to misunderstandings, and could be a source of discouragement and humiliation for those who did not have the tools to understand. by contrast, dante alighieri (firenze 1265 ravenna 1321) held a very different opinion. he firmly expressed a democratic idea of knowledge which should be provided to everybody, although at different levels and through different tools. he discussed these ideas in two unfinished books: convivio (written in the vernacular) and de vulgari eloquentia (in latin). in these two treatises dante outlined a detailed program for the dissemination of knowledge. indeed, convivio means banquet, a table that offers the participants the difficult “food” of knowledge, accompanied by the bread that will facilitate its assimilation. in fact, this work is a kind of encyclopedia in which dante explains the great philosophical themes of his time in a language which is comprehensible even to non-specialists, themes ranging from linguistics to science, cosmology and politics. in the preface dante explains why a book like convivio  is needed and why it is written in the vernacular instead of latin. moreover, he clearly states that “all men naturally desire to know” and “science is the ultimate perfection of our soul”. in de vulgari eloquentia (on vulgar eloquence), written slightly earlier, dante examines the problem of the most suitable language to spread knowledge in a universal, clear and effective way. after a comparison between latin and the vernacular, dante considers the “excellent vernacular speech, common to all italians, which can be learned without other rules by imitating the nurse”; in other words, the native language. it was written in latin as it was addressed primarily to the scholars of the time, in order to show them the beauty and usefulness of italian popular language. its objective was the search for a natural language that could be understood by all italians, obtained through a comparative study of different regional dialects and of the way these evolved, in order to find the words and expressions that could be appreciated by people of any italian region. finally, in this book dante analyzes the more suitable metric structures for the poetic form of canto (or song), which is a literary genre developed in the sicilian school of poetry. this poetic form, thanks to its metre and use of rhyme, allowed dante to produce a poem which was suitable for being read out loud and easily memorized so that it could be learned and repeated even by illiterate people. that is exactly what dante will do in the commedia, called divina by giovanni boccaccio. it is worth noting that dante also identifies another difficulty that was emerging in the 13th century. this concerned the specialization of languages within the various professions – thus anticipating a problem that would become a major obstacle to the spread of knowledge today, as maintained by c.p. snow in his famous essay “the two cultures” of 1959. in order to describe this problem, in de vulgari eloquentia dante proposes his own personal reworking of the well-known biblical legend of the tower of babel, where the external influence of god who confuses languages, is replaced by an endogenous, or evolutionary, explanation of the differentiation of languages. after reporting the classical version: almost the whole of the human race had collaborated in this work of evil. some gave orders, some drew up designs; some built walls, some measured them with plumb-lines, some smeared mortar on them with trowels; some were intent on breaking stones, some on carrying them by sea, some by land; and other groups still were engaged in other activities until they were all struck by a great blow from heaven. previously all of them had spoken one and the same language while carrying out their 9dante alighieri science communicator tasks; but now they were forced to leave off their labours, never to return to the same occupation, because they had been split up into groups speaking different languages. dante provides his own explanation: only among those who were engaged in a particular activity did their language remain unchanged; so, for instance, there was one for all the architects, one for all the carriers of stones, one for all the stone-breakers, and so on for all the different operations. as many as were the types of work involved in the enterprise, so many were the languages by which the human race was fragmented; and the more skill required for the type of work, the more rudimentary and barbaric the language they now spoke. today we would say that doctors speak using their own specific language as do physicists, mathematicians, chemists, philosophers, etc., and as a result they no longer understand each other. hence, someone is needed (the scientific journalist, the populizer, etc.) who is responsible for finding a way to communicate knowledge to everyone by using a common suitable language in the divina commedia, many passages can be noticed in which the author shows that he is perfectly at ease not only with astronomy (which is obvious given the structure of the entire work) but also with arithmetic, geometry, logic, physics, and natural sciences in general, to the extent that he uses the stories and the dialogues included in the comedy to communicate scientific concepts and theories, sometimes even at a rather sophisticated level for his times. in the following we shall examine and comment on some of these passages. 2. physics and mathematics in paradise let us start from paradiso, canto 2 (94-106), where dante clearly illustrates the method of experimental science three hundred years before galileo. he uses the words of beatrice, his beloved guide throughout the trip in paradise, to state how strong his faith in laboratory experiments is. dante and beatrice are ascending towards the first heaven of the moon and the poet asks her what is the origin of the moon spots. beatrice invites him to express his opinion and dante attributes the phenomenon to the greater or lesser density of the celestial body (see e.g. greco, 2009). beatrice then announces an explanation that, based on an experiment, will refute dante’s theory: da questa instanza può deliberarti 94 esperienza, se già mai la provi, ch’esser suol fonte ai rivi di vostr’arti. [from this objection an experiment can free you, if you ever try it, for from experience derives the source of all your arts.] that is to say: an experiment can reveal the fallacy of your explanation, as experiments are the starting points of all your knowledge. the statement is peremptory: all your knowledge (down on earth) comes from experiments. note that in this case experience is used to disprove definitively, and not to prove something – a form of what six centuries later karl popper will propose as the “falsification principle”, a way of defining science from non-science, which is at the basis of the scientific method. however, beatrice does not limit herself to such a statement, as she immediately moves on to the description of a real laboratory experiment: tre specchi prenderai; e i due rimovi 97 da te d’un modo, e l’altro, più rimosso, tr’ambo li primi li occhi tuoi ritrovi rivolto ad essi, fa che dopo il dosso 100 ti stea un lume che i tre specchi accenda e torni a te da tutti ripercosso. ben che nel quanto tanto non si stenda 103 la vista più lontana, lì vedrai come convien ch’igualmente risplenda [take three mirrors, and place two of them at the same distance from you, and let your eyes find the third more distant and between the first two. facing toward them, have a light from behind you shine on the three mirrors and return to you reflected from all three. even though the more distant image is not as extended in size, you will see that it is equally bright there] we will not dwell on the details of the experiment but rather highlight the point that dante, through the words of beatrice, is suggesting that an experiment be carried out on earth in order to understand an astronomical phenomenon, thus affirming that the laws of terrestrial physics coincide with those of celestial physics. galileo will have to work hard on such an argument in order to convince aristotelians in the 17th century. and even the statement about experience as the main source of knowledge sounds quite advanced for his time, as it anticipates what will become commonly accepted only after the scientific revolution of the 17th century. in this regard, it is also important to mention dante’s opinion about alchemists, as he imagines them 10 gian italo bischi to be expelled without any appeal, in the tenth bolgia of hell, where they join the company of falsifiers and swindlers. in fact, in canto 29 of inferno, dante meets some alchemists who are tormented as they are not able to see anything on account of the darkness. two of them, grifolino of arezzo and capocchio of siena, present themselves to dante. «io fui d’arezzo, e alberto da siena», 109 rispuose l’un, «mi fé mettere al foco; ma quel per ch’io morì qui non mi mena. vero è ch’i’ dissi lui, parlando a gioco: 112 “i’ mi saprei levar per l’aere a volo”; e quei, ch’avea vaghezza e senno poco, volle ch’i’ li mostrassi l’arte; e solo 115 perch’io nol feci dedalo, mi fece ardere a tal che l’avea per figliuolo. ma nell ’ultima bolgia de le diece 118 me per l’alchìmia che nel mondo usai dannò minòs, a cui fallar non lece». [«i’m from arezzo, and albert of siena» one of them replied, «had me burned, but i’m not here for what i died for there. it’s true i told him, jokingly, of course: “i know the trick of flying through the air”, ‘ and he, eager to learn and not too bright, asked me to demonstrate my art; and only just because i didn’t make him daedalus, he had me burned by one whose child he was. but here, to the last bolgia of the ten, for the alchemy i practiced in the world i was condemned by minos, who cannot err».] in other words, even if grifolino died because alberto of siena ordered to burn him as a consequence of his false claim about his ability to fly, after his death minos, the judge and guardian of hell, condemned him to the tenth bolgia just because he was an alchemist. it is important to point out that in the time of dante alchemy was considered a method to investigate and imitate nature, as stated by the other alchemist speaking to dante: sì vedrai ch’io son l’ombra di capocchio, 136 che falsai li metalli con l’alchìmia; e te dee ricordar, se ben t’adocchio, com’io fui di natura buona scimia». 139 [then you will see that 1 am the shade of capocchio, who falsified metals with alchemy; and you must remember, if i eye you well, how good an ape i was of nature.”] in other words, capocchio believes that dante should remember him as a good imitator of nature. despite this, the poet places him in hell, among those who took advantage of their knowledge to get rich by deceiving others. now we go back to paradise, but we move onto mathematics, as there are really many references to this discipline in the comedy (for a more complete treatment of this topic, see e.g. d’amore, 2001, or bischi, 2015). we start from paradiso, canto 33, where the poet wonders about the difficulty to understand the mystery of the incarnation, that is, the concept of how christ can be both human and divine at the same time. this is not impossible for god, but difficult to demonstrate by a limited human mind. how could dante find an example to explain such difficulty? he refers to the famous (unsolved) problem of greek geometry known as the problem of squaring the circle, i.e. finding the sides of a rectangle whose area is equal to that of a circle of a given radius: qual è ’l geomètra che tutto s’affige 133 per misurar lo cerchio, e non ritrova, pensando, quel principio ond’ elli indige: tal era io a quella vista nova; 136 veder voleva come si convenne l’imago al cerchio e come vi s’indova. [like the geometer who is all intent to square the circle and cannot find, for all his thought, the principle he needs: such was i at that miraculous sight; i wished to see, as was fitting the image to the circle, and how it enters therein] this mathematical problem reminds dante of the mystery of the incarnation, that is, two things of a different nature, one penetrated by the other. this problem was impossible to be solved in euclid’s geometry because, in ancient greece, geometry problems had to be solved by geometric constructions involving only the use of an ungraduated ruler and a compass. such an approach constitutes a form of mental gymnastics, or a test of skills. indeed, dante knew very well how to calculate the area of a circle, and in fact he uses the approximation 22/7 = 3.1428... (often used instead of π 11dante alighieri science communicator = 3.1415... in the abacus books of the middle ages) to measure a circular bolgia. thus, the poet’s suggestion is really remarkable: the squaring of the circle (as well as the incarnation of god) is not impossible to achieve in principle, but it becomes impossible to understand it if resorts only to the use of limited tools, such as a ruler and compass in geometry or the human mind in theology. of course, this example is not easily understood by any reader of the comedy, as it requires a deep knowledge of greek geometry. similar arguments apply to the following passage, taken from paradiso, canto 28, where a reader is assumed to know the legend behind the invention of the game of chess often reported in abacus books as an example of the exponential growth of compound interests. in this passage dante uses the metaphor of sparks issuing from a fire to describe the number of angels revolving around god. but how many are them? the poet could write “so many as the stars in the sky”, or “so many as the grains of sand in the sea”. by contrast, dante prefers to use an arithmetic argument: l’incendio suo seguiva ogni scintilla; 91 ed eran tante, che ’l numero loro più che ’l doppiar delli scacchi s’inmilla [each spark followed its fire, and they were so many that their number enthousands itself beyond the doubling of the chessboard.] dante refers to the famous legend of sissa nassir, a court magician, and inventor of the game of chess, to whom the persian king promised the reward he desired for his invention. the witty inventor then made an apparently modest request: taking the chessboard, the usual square formed by 8 by 8 squares, he asked for a grain of wheat on the first square; twice as much, that is 2 grains, on the second, twice as much again, that is 4, on the third; and then 8, 16, 32 … up to the last 64th square, where 263 grains are required. but as soon as the king realized that the total quantity of grain required to meet the demand was so huge, being of the order of ten billion of billion of grains, instead of rewarding sissa nassir he had him killed. this legend was reported as an example in many abacus books, as this “game of doubling” (or exponential increase) was used as a template for calculating compound interest, and used by banks in dante’s time, when commerce and entrepreneurial activities started to ask for loans, often at rates that today would undoubtedly be defined as usury. with these two examples, we have seen how dante was familiar with both learned mathematics (such as euclid’s elements) taught in latin at universities, and practical mathematics, the kind taught in the vernacular in abacus schools. keeping to the subject of mathematics (and of kings), let us turn to the story of solomon reported in paradiso, canto 13 (88-103). solomon was king of israel from 970 to 931 bc, and he was famous for his wisdom and knowledge. he became king at a very young age, and the bible says that the lord appeared to him in a dream and told him: “ask me what i must grant you” and solomon replied: “lord my god, you made your servant reign in place of david my father. but i am a boy; i do not know how to rule. give your servant a mild heart, that he may know how to do justice to people, and how to distinguish right from wrong”. it pleased the lord that solomon had asked for wisdom in ruling, and he said to him: “why did you ask for this thing, and did not ask for yourself a long life, nor riches, nor the death of your enemies? behold, i grant you a wise and intelligent heart, but i also grant you what you have not asked for, that is, riches and glory such as no king ever had”. dante reports the essence of this legend, but in doing so he replaces the requests solomon did not make with his own wishes: non ho parlato sì che tu non posse 94 ben veder ch’ el fu re che chiese senno acciò che re sufficiente fosse, non per sapere il numero in che enno 97 li motor di qua sù, o se necesse con contingente mai necesse fenno, non si est dare primum motum esse, 100 o se del mezzo cerchio far si puote trïangol sì ch’un retto non avesse. [i have not spoken in such a way that you cannot see clearly that he was a king asking for the wisdom to be a worthy king, not in order to know the number of the movers up here, or if necesse with contingent ever made necesse , not si est dare primum motum esse, or whether in a semicircle one can make a triangle that lacks a right angle.] in other words, dante would have asked god information about the number of angels (appointed to move planets and stars), or whether in a logical proposition a necessary premise combined with a contingent one will give a necessary consequence (a problem which is not trivial, and had already been tackled and negative12 gian italo bischi ly resolved by aristotle), or whether there can be a first motion, i.e. which is not derived from another motion, or, finally, if a triangle that does not have a right angle can be inscribed in a semicircle. dante proposes these questions as examples of something false, because they contradict modes of logical necessity. if there is a motion, then necessarily there is a cause, i.e. another motion that generated it (inertia principle will be proved later, by galileo). if a triangle is inscribed in a semicircle, then necessarily that triangle is rectangular, a direct consequence that the sum of all three angles is equivalent to a flat angle, which follows from the axiom of parallels (the so called 5th postulate of euclid geometry). now, while the statement of physical nature is linked to the question of the existence of god, who was able to create everything from nothing, therefore also to originate movements from nothing, the last statement concerns a rather unexpected example from geometry. moreover, it expresses a doubt about the validity of a basic axiom of euclidean geometry, in particular the fifth postulate. this may raise the question as to whether alternative geometries can exist, namely the non-euclidean geometries that will be introduced in the 19th century. probably we are going too far with our imaginations and we are also pushing dante’s imagination too far. a similar argument applies to the following passage, found in paradiso, canto 15 (55-57) where dante has just met his ancestor cacciaguida and wants to tell him that he is so wise and forward-thinking that he seems to understand his words before he speaks, as if cacciaguida were able to read his thoughts. the description of this situation, expressed by cacciaguida’s words while talking to dante, may suggest to a modern mathematical reader a method for the construction of the whole set of natural numbers based on the principle of induction: tu credi che a me tuo pensier mei 55 da quel ch’ è primo così come raia da l’ un , se si conosce, il cinque e ’l sei , [you believe that your thought flows to me from him who is first, just as from one, if known, ray forth both five and six,] this is a very famous phrase that cacciaguida addresses to dante: you believe that all your thoughts come to me from god (from him who is first) just as all numbers can be derived from number one (for example six comes from five by adding one). in modern notations we would say “given number 1, then from n we get n+1 by induction. however, this general notation that uses variables instead of numbers, was not yet used in dante’s time. for this we have to wait for françois viète in the 16th century. dante just takes two consecutive numbers at random, such as 5 and 6, to say that this rule applies to all numbers. this mathematical metaphor used by dante is really remarkable as it can be seen as a metaphor of creation as well, because one can generate an infinite number of objects by just starting from unity. 3. meteorology, probability and chemistry in purgatory let us descend now into purgatory, where dante meets bonconte da montefeltro in canto 5 (88-129). bonconte was the military leader of the ghibellines of arezzo against the florentine guelphs in the battle of campaldino in 1289. bonconte suffered defeat, he died during the battle and his body was never found. the whole story is interesting, showing a struggle between the powers of good and evil for his soul, and since he had uttered the name of mary with his dying breath and shed a tiny tear, the heavenly faction prevailed and brought his soul into purgatory. however, a demon took possession of his body and dispersed it into a river flood after a big storm. the description that bonconte gives to dante about the weather situation leading up to the storm is a page of intensive scientific revelation. what is remarkable is the way bonconte introduces himself (purgatorio canto 5, 88) «io fui di montefeltro, io son bonconte» («i was from montefeltro, i am bonconte») – where the usage of both past and present tense means that when alive on earth, he belonged to the noble family of montefeltro whereas now in the life beyond, he is just himself. this shows the way in which dante choses any detail with a precise meaning. let us now turn to bonconte’s description of the separation of his soul from his dead body and of the storm that caused the loss of his body in the river. io dirò vero, e tu ‘l ridì tra ‘ vivi: 103 l’angel di dio mi prese, e quel d’inferno gridava: “o tu del ciel, perché mi privi? tu te ne porti di costui l’etterno 106 per una lagrimetta che ‘l mi toglie; ma io farò de l’altro altro governo!”. ben sai come ne l’aere si raccoglie 109 quell’ umido vapor che in acqua riede, tosto che sale dove ‘l freddo il coglie. giunse quel mal voler che pur mal chiede 112 con lo ‘ntelletto, e mosse il fummo e ‘l vento per la virtù che sua natura diede. 13dante alighieri science communicator indi la valle, come ‘l dì fu spento, 115 da pratomagno al gran giogo coperse di nebbia; e ‘l ciel di sopra fece intento, sì che ‘l pregno aere in acqua si converse; 118 la pioggia cadde, e a’ fossati venne di lei ciò che la terra non sofferse; e come ai rivi grandi si convenne, 121 ver’ lo fiume real tanto veloce si ruinò, che nulla la ritenne. lo corpo mio gelato in su la foce 124 trovò l’archian rubesto; e quel sospinse ne l’arno, e sciolse al mio petto la croce [now hear the truth. tell it to living men: god’s angel took me up, and hell’s fiend cried: “o you from heaven, why steal what is mine? you may be getting his immortal soul won it for a measly tear, at that, but for his body i have other plans! ‘ you know how vapor gathers in the air, then turns to water when it has returned to where the cold condenses it as rain. to that ill will, intent on evilness, he joined intelligence and, by that power within his nature, stirred up mist and wind. then the valley, by the end of day, from pratomagno to the mountain chain, was fogbound; and dense clouds charged the sky: so that the saturated air turned into water; rain poured down, and what the sodden ground rejected filled and overflowed the deepest; gullies, whose spilling waters came to join and form great torrents rushing violently, relentlessly, to reach the royal stream. close to its mouth the raging archiano discovered my cold body-sweeping it into the arno, loosening the cross] quite remarkable is the description (109-111) of the water cycle, due to water evaporation and then condensation into liquid water again when the steam, as it rises, encounters colder air layers. this provides a clear-cut explanation of a meteorological phenomenon that was not so clear to people living in the 13th century (see e.g. cornish, 2004). moreover, the description of the whole process of storm occurrence and water flow towards rivers is very rigorous and worthy of a scientific essay. an often-quoted passage of purgatory, dealing with mathematical ideas given by dante in the comedy, is the description of a game of dice in canto 6 (1-3), where an anticipation of some flavor of the concept of probability can be noticed: quando si parte il gioco della zara, 1 colui che perde si riman dolente, repetendo le volte, e tristo impara [when the zara game starts, the loser remains sorrowful, repeating his throws, and sadly he learns] in the zara game (arabic word ‘zahar’ means ‘dice’), which was very popular in dante’s time, each player bets a certain amount of money before three dice are thrown and each of the players, in the short time between throwing the dice and then stopping them, says a number – whoever guesses the result wins the prize. if no one guesses correctly, the amount of money to be won in subsequent games increases. of course, probability theory has a role in the analysis of this game; however this theory did not exist at dante’s time, as we have to wait for cardano (1501-1576), galilei (1564-1642), fermat (1601-1665) and pascal (1623-1662) for these concepts to be introduced in mathematics. however, the combination of the two words “repetendo …impara” (repeating … learns) may reveal an intuitive, veiled awareness of the existence of probability laws. if a player learns, it means that there is something to be understood, hence dante may be aware that not all outcomes are equally probable, in the sense that some outcomes are more frequent than others. moreover, “repetendo” makes one think of a “frequentist” definition of probability, given by the number of occurrences of the event divided by the number of trials, as the number of trials tends to infinity. naturally this is a rather modern interpretation that cannot be attributed to dante. however, the sentence is surely intriguing, as it was in the question about triangles without right angles in a semicircle in the solomon story. finally, in purgatorio, canto 7 (73-75) we can find evidence of dante’s knowledge of chemical elements. indeed, after the enactment of the orders of justice in 1293, dante joined the order of physicians and apothecaries (ancestors of our pharmacists) in order to participate in political life. in addition to medicines however, apothecaries also produced materials for painters, such as white lead, which is lead carbonate, and dante in his vita nova tells of having painted. he painted on wood and therefore had to know the methods of preparation of the wooden boards before painting them. so, we may 14 gian italo bischi hypothesize that his joining the order of doctors and apothecaries was due to this practice, at least as a novice. a description of these materials is given in the following passage: oro e argento fine, cocco e biacca, 73 indaco, legno lucido e sereno, fresco smeraldo in l’ora che si fiacca, da l’erba e da li fior, dentr’a quel seno 76 posti, ciascun saria di color vinto, come dal suo maggiore è vinto il meno. non avea pur natura ivi dipinto, 79 ma di soavità di mille odori vi facea uno incognito e indistinto. [think of fine silver, gold, cochineal, white lead, indian wood, glowing and deeply clear, fresh emerald the instant it is split, the brilliant colors of the grass and flowers within that dale would outshine all of these, as nature naturally surpasses art. but nature had not only painted there: the sweetness of a thousand odors fused in one unknown, unrecognizable.] in the second terrace of the ante-purgatory, the poet sordello shows dante and virgilio the flowery valley where the negligent princes are located: in their lives they were guilty of neglecting their spiritual and earthly duties. dante sees that nature here is luxuriant and beautiful as the grass and flowers have such vivid colors as to surely win the most precious and refined hues used by painters, such as gold, silver, emerald. and the spectacle is not only visual, as the flowers give off a scent that mixes a thousand sweet smells. this can be seen as proof of dante’s knowledge about chemicals (which give rise to colors and smells). in other words, we believe that dante’s involvement in the world of the apothecaries, where chemistry took its first steps, gave him more knowledge and understanding than the pseudoscientific alchemy practitioners, as mentioned in section 2. 4. logic and gravitation in hell let us now turn to inferno, canto 27 (112-123), where among the fraudulent advisers we find guido da montefeltro, father of bonconte, duke of urbino from 1293. he was also a ghibelline military leader, and won many important battles often against the papal army. then he became a friar and entered the franciscan monastic order in assisi in 1296, where he died in 1298. while he was in the monastery, pope boniface viii asked him for advice in order to win a difficult battle. guido argued that he could give him a suggestion but it would involve a lie, and guido knew that as a friar he could not commit such a sin. but boniface told him, “don’t worry, i can absolve you before you commit it”. hence, the pope absolved him in advance and guido was allowed to give his fraudulent advice. when guido died, francis of assisi personally picked him up to take him directly to heaven (this was a privilege of the franciscan friars). however, something unexpected happened due to a logical reasoning, a typical argument of formal logic which nowadays can be expressed by the symbolism of logical operators or set theory. here is the beginning of the story: francesco venne poi, com’io fu’ morto, 112 per me; ma un d’ i neri cherubini li disse: “non portar: non mi far torto. [francis came later, when i had died, for me; but one of the black cherubins told him: ‘do not take him, do not wrong me.] here guido is telling his story, starting from st. francis who went purposely to take him (“for me”), but a black cherub, that is, an angel of hell, ordered st francis not to take him. it may seem really implausible that an anonymous black cherub gives orders to st. francis, but as dante will reveal to us, he is not just any cherub, because he is a logician as well. notice that here we have a struggle between the powers of good and evil similar to the struggle we have seen for the soul of bonconte da montefeltro, the son of guido. however, here the outcome will be different: venir se de dee giù tra ‘miei meschini 115 perché diede ‘l consiglio frodolente dal quale in qua stato li son a’ crini;   ch’ assolver non si può chi non si pente, 118 né pentere e volere insieme puossi per la contraddizion che nol consente”.   oh me dolente! come mi riscossi 121 quando mi prese dicendomi: “forse tu non pensavi ch’ io loico fossi”! [he must come down among my slaves, because he gave the fraudulent counsel, since when, until now, i have been at his heels; for he cannot be absolved who does not repent, 15dante alighieri science communicator nor can one repent and will together, because of the contradiction, which does not permit it.’ oh wretched me! how i trembled when he seized me, telling me: “perhaps you did not think i was a logician!”] the black cherub asserts that guido must instead go down with him to hell because he gave fraudulent advice, after which the cherub was always at his heels – a powerful image implying that the devil follows the sinner from the moment a sinful action is committed until he manages to take him to hell. but dante’s masterpiece comes with logical proof to demonstrate that putting guido in paradise is a contradiction with respect to the laws (i.e. the axioms) of the church. in fact, one cannot absolve someone who does not repent, nor is it possible to repent of sin and at the same time want to commit it, because this would lead to a contradiction. in short, faced with the evidence of a logical demonstration there is no getting round it. not even st francis, founder of the order, can counteract. a question naturally raises concerning the level of dante’s knowledge about logics. a possible answer comes from the following statement in paradiso, canto 12 (134-135): … e pietro ispano, 134 lo qual giù luce in dodici libelli [… and peter of spain, who shines down there in twelve volumes] where dante says that peter of spain (or petrus hispanus) was famous on earth (“shines down there”) being the author of the twelve chapters that make up the summule logicales, a compendium of formal logic that was the reference manual on aristotelian logic in use in european universities for more than 300 years. dante does not mention the fact that petrus was also a pope under the name of john xxi. in short, according to dante, peter of spain was famous for writing texts on logic, not for being a pope. therefore, we can deduce that dante, having read and appreciated such a text, was able to understand and handle subtle questions of logic such as the one raised by the black cherub. and, of course, he used the commedia to communicate such knowledge to people who did not have access to universities. as a final example (among many others) of science vulgarization through the pages of the divina commedia we propose a passage from the last canto of inferno, canto 34 (100-111), where dante uses a remarkable narrative trick to describe the force of gravity as a centripetal force field directed towards the center of the earth. in order to explain this, dante tries to describe what should happen while passing through the center of the earth, where in the commedia lucifer is located (see figure 1, where the spatial structure of the dante’s universe is illustrated). the last portion of hell, before it is closed by the horrible hairy body of lucifer located at the center of the earth, is formed by the last area of cocito, the giudecca, where the traitors of the benefactors are severely punished by being imprisoned in ice. dante and virgilio move towards lucifer and the latin poet invites the disciple to embrace him around his neck while looking for the right moment to step over the lucifer’s body in order to continue the trip beyond the center of the earth to the other hemisphere. when the monster’s wings are open enough, virgil clings to lucifer’s hairy ribs and descends along the demon’s flanks, then, out of breath, he turns and clings to the hairy legs, beginning to climb upwards. dante, attached to his neck, does not realize what really happened, and he wrongly believes that they are returning back to the giudecca. in fact, before twisting around lucifer, he feels the force of gravity pushing him, while now he feels it opposing his direction of motion. because of this he thought he had inverted the direction of his movements, like when you go downhill and then you retrace your steps when going uphill. this is the reason for the following questions, which reveal how dante remains confused due to the centripetal direction of gravity force: «prima ch’io de l’abisso mi divella, 100 maestro mio», diss’io quando fui dritto, «a trarmi d’erro un poco mi favella: ov’è la ghiaccia? e questi com’è fitto 103 sì sottosopra? e come, in sì poc’ora, da sera a mane ha fatto il sol tragitto?». ed elli a me: «tu imagini ancora 106 d’esser di là dal centro, ov’ io mi presi al pel del vermo reo che ‘l mondo fóra. di là fosti cotanto quant’ io scesi; 109 quand’ io mi volsi, tu passasti ´l punto al qual si traggon d’ogne parte i pesi. [«before i am uprooted from the abyss, my master», said i, when i was erect, «speak to me a little to help me out of error: where is the ice? and he, how is he fixed so upside down? and how, in so little time has the sun made the passage from evening to morning?” and he to me: «you imagine that you are still 16 gian italo bischi on the other side of the center, where i laid hold on the fur of this evil worm that gnaws the world. you were on that side while i descended; when i turned, you passed the point toward which the weights all move from every direction.] the narrative trick of the illusion of moving back instead of passing through the center (so that dante cannot realize why he sees lucifero reversed, why he cannot see the ice of the giudecca again, and why he suddenly sees the light instead of darkness) is really a clever way of explaining centripetal gravity force. it is not easy to understand the first time by a lay reader, but is undoubtedly effective in order to stimulate the imagination. dante also explains quite clearly what happens when moving from the northern to the southern hemispheres with regards to daylight and darkness. in short, dante once again shows an effective use of storytelling in order to make important scientific knowledge popular, while at the same time respecting the metrics and the use of rhyme. conclusions in this article we described and commented on several passages taken from the divina commedia by dante alighieri which deal with medieval science. we started from experimental physics (an experiment of optics) and ended with theoretical physics (description of gravitation), running the gamut of alchemy, geometry, arithmetic, logic, meteorology, chemistry. such concepts and methods are described by dante through a narrative device, or storytelling, as well as dialogs between dante and his tour guides (whether virgilio or beatrice) or the souls he encounters during his imaginary journey to the afterlife. hence, we believe that dante can be seen as one of the first, and most important, science communicators, or, in current language, a testimonial or an influencer, communicating the importance of scientific knowledge (see also gilson, 1999, 2001). science communication has a rich history related to long traditions and cultural factors, which are now embedded into more extreme forms like science outreach and public engagement, that is, the set of activities and events designed for the dissemination of research results and scientific knowledge in general among people. osborne and monk (2000) provide an overview of key motivations for science communication. first, there is the utilitarian argument, which states that people involved will gain technical skills and knowledge that will be useful to them. secondly, the economic argument posits that advanced societies require a technologically skilled workforce and, at the same time, the results of research funded by goverment or other institutions must be explained to financers. thirdly, the cultural argument claims that science represents a “shared heritage” and it should be recognized as a wide part of our culture. finally, the democratic argument asserts that science affects most major decisions in society, therefore it is important that both politicians, managers and citizens are able to interpret basic scientific information. dante was mainly motivated by the democratic argument, however even the economic argument can be considered relevant to his time as the emerging classes involved in economic activities needed to increase their knowledge. of course, even nowadays not only scientists, but also scientific journalists, writers and intellectuals in a broader sense contribute to reaching such goals (see e.g. capozucca, 2017). dante alighieri was very active as a science communicator, as he clearly outlined in the convivio and de vulgari eloquentia. the pioneering methods he used to diffuse knowledge among people were not only aimed at involving non-academics, such as the emerging classes figure 1. schematic picture of dante’s travel described in the divine comedy. 17dante alighieri science communicator of merchants, traders, artisans and bankers, but they also included illiterate people. in order to appreciate the extent to which the methods for science communication used by dante in the divina commedia are modern and forward-looking, we propose two short passages from two contemporary well-known italian writers. the first one was written by umberto eco in the weekly italian magazine “l’espresso” (april 28, 2005): a seasoned belief wants things to be known through their definition [...]. i am among those who believe that even scientific knowledge must take the form of stories. [...] our knowledge (even the scientific one, and not only the mythical one) is woven of stories. the second one is taken from a letter written by the italian writer dino buzzati, addressed to the intellectual, poet and engineer leonardo sinisgalli, founder and director of the magazine civiltà delle macchine (house organ of finmeccanica, the main italian group of firms dealing with advanced mechanics, robotics etc.) where the letter was published in the january issue of 1956, p. 78: in civiltà delle macchine the scientists and technicians speak as technicians and scientists as if they were addressing people of the same level, they don’t smirk, they don’t soften their voices, they never have the air of saying, “things are much more difficult and complex, but for you, stupid and ignorant people ...”. the normal rule of science popularization is that scientists stoop to readers’. here it is the reader who rises. as argued several times in this article, both these modern points of view can be found in dante’s pioneering dissemination work, thus confirming his role as modern science communicator and his enduring legacy 700 years after his death. references dante alighieri, convivio, translated by a. s. kline 2008. https://www.poetryintranslation.com/klineasconvivio. php dante alighieri, de vulgari eloquentia translated by steven botterill, cambridge university press 1996. dante alighieri, the divine comedy, inferno; purgatorio; paradiso, translated by allen mandelbaum, everyman’s library, random house, new york 1995. dante alighieri, the divine comedy, volume 1 inferno, translated by robert m. durling, oxford university press, new york 1996. dante alighieri, the divine comedy, volume 2, purgatory, translated by mark musa, penguin books, new york 1985. dante alighieri, the divine comedy, volume 3 paradiso, translated by robert m. durling, oxford university press, new york 2011. dante alighieri, la vita nuova (the new life) translation by a. s. kline, with illustrations by dante gabriel rossetti, poetry in translation, 2001, www.poetryintranslation.com gian italo bischi, matematica e letteratura. dalla divina commedia al noir, egea, milano 2015. giovanni boccaccio, il comento alla divina commedia e gli altri scritti intorno a dante, a cura di domenico guerri, laterza, bari 1918 andrea capozucca, public engagement, storytelling and complexity in maths communication, ph.d. thesis, university of urbino, 2017. https://ora.uniurb. it/retrieve/handle/11576/2656845/82425/phd_uniurb_269927.pdf alison cornish “the vulgarization of science: dante’s meteorology in context”, in science and literature in italian culture from dante to calvino, pierpaolo antonello and simon a. gilson (editors), european humanities research centre, oxford 2004 bruno d’amore, più che ‘l doppiar de li cacchi s’inmilla. incontri di dante con la matematica, pitagora editrice, bologna 2001 simon gilson, ‘light reflection, mirror metaphors, and optical framing in dante’s  comedy: precedents and transformations’, neophilologus, 83 (1999), 241-52 simon gilson, “medieval science in dante’s  commedia: past approaches and future directions”,  reading medieval studies, 27 (2001), 39-77 pietro greco, l’astro narrante. la luna nella scienza e nella letteratura italiana, springer-verlag italia, milano 2009. pietro greco, la scienza e l’europa. dalle origini al xiii secolo, l’asino d’oro edizioni, roma 2014. jonathan osborne and martin monk, good practice in science teaching: what research has to say. open university press, 2001. charles percy snow, the two cultures and the scientific revolution , cambridge university press, 1959. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 6(2): 15-26, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1736 citation: tatini d., raudino m., sarri f. (2022) light-modulated rheological properties in green innovative formulations. substantia 6(2): 15-26. doi: 10.36253/substantia-1736 received: mar 07, 2022 revised: jul 11, 2022 just accepted online: jul 12, 2022 published: september 1, 2022 copyright: © 2022 tatini d., raudino m., sarri f. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. light-modulated rheological properties in green innovative formulations duccio tatini*, martina raudino, filippo sarri department of chemistry “ugo schiff ” and csgi, university of florence, via della lastruccia 3, 50019 sesto fiorentino (firenze), italy *e-mail: duccio.tatini@unifi.it abstract. the addition of azorubine to a viscoelastic aqueous dispersion of sodium oleate (naol, 0.43 m, 13% w/w) and kcl (up to 4% w/w) leads to a green gel-like system whose rheological behavior can be efficiently and reversibly triggered from remote by using uv light. rheology, differential scanning calorimetry (dsc) measurements and phase behavior studies indicate that the original texture of the naol dispersion is significantly hardened upon uv irradiation for 8 hours in the presence of azorubine, showing a seven hundred-fold increase in viscosity. the uv treatment brings about the trans to cis isomerization of azorubine, which modifies the structure of the naol wormlike micellar system, leading to a more entangled, close-textured network. the cooperative effect of kcl on the fluid viscosity is found to be concentration-dependent. the system slowly reverts to its original rheological behaviour after standing for about 1 day. these results are relevant for the development of stimuli-responsive innovative systems based on biocompatible, non expensive and commercially available materials that can be used in a wide range of applications, such as in drug delivery or enhanced oil recovery, where a quick change in the physico-chemical features of the system is required but difficult to be performed. keywords: green chemistry, sodium oleate, azorubine, viscosity, stimulus-responsive. introduction responsive or “smart” materials are functional materials whose properties can undergo controlled and reversible changes in response to an external stimulus [1–4]. the applied stimulus or external field include thermal, electrical, magnetic, ph, uv-visible light, ionic or metallic interactions or combinations thereof [5,6]. the formulation of gel-based stimuli-responsive systems with specific performances is crucial for a great number of applications, and particularly when it is impossible or very difficult to switch on/off their properties, and a remotely controlled trigger is necessary [5,7]. among these systems, viscoelastic surfactant (ves) solutions have attracted great attention due to their unique features and versatility that can be harnessed in a variety of high-tech and everyday applications [8–15]. the amphiphilic nature of ves molecules leads to the self-assembly in solution into small aggregates, which show a complex phase behavior: the 16 duccio tatini, martina raudino, filippo sarri simplest structure are spherical micelles, but also hexagonal, lamellar, vesicular, cubic, reverse phases can be observed, depending on the surfactant packing parameter and global packing constraints [2,16–19]. under certain conditions (i.e. surfactant concentration, salinity, temperature, presence of different counterions, change in the composition of the solvent, etc.) spherical micelles may undergo uniaxial growth and form elongated and flexible structures, usually referred to as ‘‘wormlike’’ micelles (wlm) [19–21]. above a critical concentration these systems show viscoelastic properties, like polymer solutions or bicontinuous three-component ionic microemulsions, as a result of the formation of a densely entangled network [19,22–26]. in our previous series of works we extensively investigated the main physicochemical properties and the phase behavior of wormlike micellar systems based on sodium oleate (naol), a safe, eco-friendly and cost-effective surfactant [19,26]. in the first part we reported on the structure, thermal properties and rheological behavior of naol aqueous dispersions in the presence of a single salt (kcl) via cryo-tem, rheology and  dsc  experiments [19]. in part 2 we illustrated the specific ion effect induced by the addition of different salts on viscoelastic dispersions of sodium and potassium oleate, and we systematically discussed it in terms of the hofmeister series [26]. in a previous work we imparted a voltage-dependent responsiveness to an naol aqueous dispersion through the addition of carbon black particles [27]. prompted by these studies on green formulations with suitable responsiveness to different physical stimuli, in the present contribution we developed a naol-based viscoelastic dispersions that, in the presence of minimal amounts of azorubine, a biocompatible dye, and a salt (kcl) undergo a remarkable change in their rheological properties upon irradiation at a specific wavelength. naol finds application in a wide number of industrial products and commercial formulations, like healthcare products, cleansers, thickening agents, emulsifiers, lubricants and fluids for enhanced oil recovery [28–32]. thanks to its negative charge, naol is more biodegradable and less harmful for the environment compared to cationic surfactants [33]. naol shows a very interesting phase behavior [34] and forms different nanoand micro-structures in solution upon the addition of electrolytes or as a result of ph variation [19]. for an extensive discussion about the structural features and the rheological behavior of naol dispersions please see references [19,26,35–41] and references therein. in this work we report on a moderately concentrated (0.43 m, 13% w/w) dispersion of naol in water that gives rise to a wormlike micellar network with peculiar structural properties and rheology. the choice of this surfactant concentration is related to the naol/water systems’ phase diagram: at this concentration and 25° c the dispersion converts from a simple fluid micellar l1  to a viscous l1* phase that shows shear-dependent birefringence [19]. azorubine is a synthetic azo dye approved for food decorations and coatings and as drink additive [42]. its chemical structure is shown in figure 1. the presence of the azo moiety enables a trans-cis isomerization upon irradiation with light at an appropriate wavelength, usually in the uv region [43–46]. the process may revert spontaneously upon heating since the trans isomer is thermodynamically more stable, or can be induced through irradiation with a visible light [47]. previous studies reported on the introduction of different chromophores in ves systems in order to obtain light-responsive fluids with tunable rheological properties. these photo-active molecules include synthetically modified azobenzenes, [48–54] p-coumaric acid [55,56] and cinnamic acid derivatives [57–59]. we selected azorubine because of its unique advantages in terms of availability, simple manipulation, low cost and, above all, safety. this work is a proof-of-concept that shows the efficacy of combining completely biocompatible and nontoxic materials to obtain a versatile formulation with a viscosity and rheological behaviour that can be remarkably modified through the irradiation with uv light. moreover, all these features make these systems very attractive for a wide range of applications, including agriculture, food industry, cosmetics, “smart” materials, enhanced oil recovery, shale gas extraction, drug delivery and controlled release. materials and methods materials sodium oleate (acs reagent grade, riedel-de haёn, seelze, germany) and potassium chloride (> 99 %, sigma-aldrich, milan, italy) were used as received without any further purification. azorubine (carmoisine, food figure 1. trans-cis isomerization of azorubine. 17light-modulated rheological properties in green innovative formulations red 3 or e 122, disodium 4-hydroxy-3-((4sulphonatonaphthyl)azo) naphthalenesulfonate), food grade quality) was supplied by f.lli rebecchi s.r.l. (piacenza, italy) and used without any further purification. all solutions and dispersions were prepared with milli-q water (resistivity > 18 mω cm at 25°c). sample preparation sodium oleate viscoelastic formulations were prepared by the addition of a weighted amount of surfactant to kcl aqueous solutions at different concentrations (0, 0.1, 0.5, 1, 2, 3, 3.5, 4 % w/w) under constant stirring at room temperature. the final concentration of naol was 0.43 m (13 % w/w) in all the samples. the dye-loaded samples were prepared following a similar procedure: to a 0.18 % w/w (3.6 10-3 m) azorubine aqueous solution the proper amount of potassium chloride and then of the surfactant were added. the final concentrations of kcl were 0.1, 0.5, 1, 2, 3, 3.5, 4% w/w. for all the samples we used milli-q water, which was boiled for 4 h, filtrated and stocked under argon. as reported in our previous works the samples were freshly prepared and tested within 1 hour for the rheological and dsc experiments [19,26]. all these precautions are necessary in order to avoid the uptake of atmospheric co2 by the samples [60]. uv irradiation about 10 ml of sample were placed in a quartz container and irradiated using a camag uv lamp (wavelength 254 nm, 8 w, muttenz, switzerland) for 8 hours. all the experiments were conducted at 25 °c, and the distance between the sample and light source was fixed at 5 cm. rheology measurements rheology experiments were carried out on a paar physica uds 200 rheometer using a plate-plate geometry with a diameter of 40 mm and a measurement gap of 300 μm. the temperature was fixed at 25.0 ± 0.1 °c using a peltier control system for all the measurements. the samples were equilibrated for 15 min at the set temperature before being tested. frequency sweep measurements were carried out within the linear viscoelastic range at a strain value of 1%, which was previously determined by means of an amplitude sweep test. the storage and loss moduli (g’ and g’’, respectively) were measured over the frequency range of 10−3  and 102 hz. the flow curves were acquired in a torque range between 10−1  and 5·103  mn·m. the experimental viscosity (η) was fitted with the cross model (see the results and discussion) to obtain the zero-shear viscosity  (η0),  the infiniteshear viscosity (η∞),  the shear relaxation exponent (m) and the consistency (c). the experiments were repeated at least three times, and silicon oil was applied to the rim of the measurement geometry to prevent water evaporation from the sample. differential scanning calorimetry differential scanning calorimetry (dsc) was performed by means of a dsc-q2000 by ta instruments (philadelphia, pa). the samples were sealed in aluminum hermetic pans and the measurements were conducted under n2 atmosphere, with a flow rate of 50 ml/ min. the samples were first cooled from 20 °c to − 60 °c at 10 °c/min, then heated up to 50 °c at 5°c/min. the thermograms which show overlapping endothermic peaks were analyzed using a linear combination of exponentially modified gaussian (emg) functions, as reported elsewhere [19,26,61,62]. results and discussion flow curve experiments figure 2 shows the flow curves obtained before (solid lines) and after (dashed lines) uv irradiation from the aqueous dispersions of sodium oleate (naol, 13% w/w) in the presence of kcl at different concentrations (0, 0.5, 2 and 3% w/w). the curves for the other kcl concentrafigure 2. flow curves before (solid lines) and after (dashed lines) uv irradiation for 13% w/w naol (0.43 m, black) and in the presence of kcl at 0.5% (green), 2% (blue) and 3% w/w (red). the flow curves for non-irradiated samples are reprinted from [19] with permission from elsevier. copyright 2021. 18 duccio tatini, martina raudino, filippo sarri tions are reported in figure s1 in the supporting information. the experimental data on non-irradiated samples are reproduced from [19] with permission. all the samples show the typical flow behavior of wormlike micellar networks, i.e., a newtonian plateau followed by a steep decrease in the viscosity at high shear stress, due to the shear-induced alignment of cylindrical aggregates. moreover, a concentrationdependent increase in the viscosity is observed upon the addition of kcl [19,63]. the fitting of the experimental viscosity (η) data was performed using the cross model [64]: 𝜂𝜂 = 𝜂𝜂! + 𝜂𝜂! − 𝜂𝜂" 1 + (𝐶𝐶�̇�𝛾)# (1) here η0 is the zero-shear viscosity, m the shear relaxation exponent, η∞ the infinite-shear viscosity, the shear rate and c the consistency. the extracted fitting parameters are reported in table s1 in the supporting information. the results nicely agree with the literature data and confirm the shear thinning behavior of the dispersions, originating from the micelles’ entanglement and their progressive alignment at high shear rates [19,26,34,65,66]. the uv irradiation does not affect the flow properties of the formulations: the profiles, as well as the values of η0 exhibit minor fluctuations within the experimental uncertainty before and after the uv treatment. the flow curves for the naol samples at different kcl concentration (0, 0.1%, 0.5% and 4%) in the presence of 0.18% w/w (3.6 10-3 m) azorubine are reported in figure 3. the flow curves at the other kcl concentrations are shown in figure s2 (see the supporting information). in the presence of azorubine all the formulations exhibit a shear-thinning behaviour that is similar to that found for the naol-kcl systems. the results obtained from the fitting of the experimental data with the cross model are reported in table s1 in the supporting information. after uv irradiation the viscosity of the samples with 0.1%, 0.5% and 4% kcl increases from 6.94 to 13.6, from 278.8 to 728.3 and from 1.852 to 730.1 pa∙s, respectively. for the other kcl concentrations no significant variations in the formulation viscosity are observed after the uv treatment. these findings lead to two important conclusions: (i) azorubine has a remarkable effect as photo-active molecule in modifying the viscosity of the fluids after uv irradiation. a similar light-modulated viscosity change is reported for binary mixtures of naol and a lightresponsive cationic azobenzene dyes [50,54]. in the work of lu et al. the uv irradiation and the resulting transto-cis isomerization of the azo dye (1-[2-(4-phenylazophenoxy)-ethyl]-3-methylimidazolium bromide) induces a decrease in the viscosity of the system, with a transition from a gel-like structure to a newtonian fluid [50]. in our case the opposite effect on the viscosity and the strengthening of the wormlike three-dimensional network is observed: a similar behavior is reported by liu and coworkers on dilute naol dispersions in the presence of three different imidazolium surfactants upon uv irradiation [54]. (ii) the presence of kcl plays a key role in modulating the effect of azorubine. the experimental data reported in table s1 show that the transto-cis isomerization of azorubine induces an increase in the formulation viscosity when kcl concentration is lower than 1% w/w. between 1% and 3.5% no remarkable changes are observed before and after the uv irradiation, suggesting that the major contribution to the strength of the system is provided by the salt. the behavior of the sample containing azorubine and 4% kcl is peculiar and deserves a deeper analysis. the viscosity increases by two orders of magnitude, but the rheological profile shows some differences after the uv treatment (see figure 2, pink curves). a first newtonian plateau appears in the low stress regime, then the viscosity rapidly decreases at a critical shear stress which is considerably lower than the viscosity breakdown point before the irradiation. after this initial decrease the flow curve shows a second, less pronounced plateau, followed by the typical shear-thinning region at high stress values. a similar behavior was reported by griffiths et al. in 2004 for carbon black particles dispersed in an acrylic polymeric matrix [67]. in this case the presence of an intermediate (secondary) newtonian plateau was ascribed to the interaction between the polymer layer and the polymer matrix, in particular to the viscous drag between the polymer chains adsorbed on the partifigure 3. flow curves before (solid lines) and after (dashed lines) uv irradiation for naol 0.43 m mixture in the presence of 0.18% w/w azorubine (3.6∙10-3 m) at different kcl concentration: 0 (black), 0.1% (orange), 0.5% (green) and 4% w/w (pink). 19light-modulated rheological properties in green innovative formulations cles with the polymer in solution. in a more recent work sochi depicts this intermediate region as a characteristic feature of viscoelastic fluids in porous media flow, that may be attributed to the time-dependent nature of the viscoelastic fluid when the relaxation time of the fluid and the characteristic time of the flow become comparable [68]. polacco and coworkers observed two distinct shear-thinning phenomena in polymer-modified asphalts: the first shear-thinning was ascribed to a rigid rearrangement of the aggregate structure, that involves a temporary detachment of polymer chains. as a result, the polymer is able to move between different domains, inducing a transitory strengthening of the network [69]. in our system the appearance of this secondary newtonian plateau may reflect the formation of ordered structures with a different degree of organization. to the best of our knowledge this is the first time that such behavior is found and reported for wormlike micellar dispersions. as a matter of fact the cited literature sources deal with polymeric blends [67,69] or to a more general viscoelastic behavior in porous media flow [68]. further work is necessary to deepen and clarify this phenomenon. the high salt concentration may be responsible for the formation of complex, more entangled structures after uv exposure. these structures are responsible for the remarkable increase in the viscosity of the formulation and exhibit a low resistance to the applied stress, as confirmed by the low critical stress value. this hypothesis is also confirmed by the fact that during the sample preparation the azorubine solution becomes turbid at this salt concentration, suggesting the formation of aggregated structures. the same salt-induced behavior is observed in pure azorubine solutions, without sodium oleate, and presumably reflects the formation of piled up structures stabilized by π-stacking interactions [70,71]. for all the irradiated samples the system recovers its original rheological behavior after standing for about 1 day, indicating a complete reversibility of the process. figure 4 reports the values of η0 as a function of kcl concentration before (solid lines) and after (dashed lines) the uv treatment. for the two sets of samples the viscosity steeply increases in the dilute regime, then it reaches a maximum and progressively decreases at higher concentrations of salt. this behavior has been widely reported for a large number of wormlike micellar systems [22,39,50,63,72–80]. the initial viscosity increase is ascribed to the formation, growth and entanglement of the cylindrical aggregates. the decrease in the fluid viscosity after the maximum upon salt addition is due to the lateral branching along the rod-like micelles, that provide an extra route for mechanical stress relief [72,81,82]. a detailed discussion about the thermodynamic justification and the driving forces behind branches formation can be found in our previous works [19,26]. the experimental results show that azorubine induces two distinct effects on the salt curves (figure 3). the first effect is the shift of the peak maximum to lower kcl concentrations. azorubine is an amphiphilic molecule that can penetrate across the micellar interface at least partially. this results in a flattening of the micelle/ water interface with a significant lowering in the surface curvature. moreover, the electrostatic repulsion between different tubular micelles is screened and the viscosity increases even at lower concentrations of salt. the second effect is the modification of the salt curve shape after the maximum. in the presence of azorubine the viscosity decreases more rapidly, as a consequence of the increased branching density. rogers et al. reported that for several mixed surfactant/salt viscoelastic systems, the branching effect is more evident with sodium salicylate, a hydrotropic salt that can penetrate more efficiently underneath the water/micellar interface salt respect to a simple inorganic salt like kcl [83]. this effect due to branched structures is quite common and found also in nonionic or zwitterionic systems [41]. oscillatory-shear measurements oscillatory shear experiments were performed to explore the viscoelastic behavior of naol-kcl-azorubine systems upon uv irradiation. the storage (g’) and loss (g’’) moduli before and after uv irradiation for the dispersions of sodium oleate in the presence of kcl at different concentrations are shown in figure 5. the frefigure 4. zero-shear viscosity (η0) for the formulations containing 0.18% w/w azorubine (red) and the reference samples without the dye (black) as a function of the salt concentration (a) before (solid line) and after (dashed line) uv irradiation. the trend for non-irradiated naol-kcl samples (black solid line) are reprinted from [19] with permission from elsevier. copyright 2021. 20 duccio tatini, martina raudino, filippo sarri quency sweep curves for other kcl concentrations are reported in the supporting information. for all the samples two distinct regimes are observed, i.e. a predominant viscous behavior at low frequencies (g’’ > g’) and mainly an elastic behavior at higher frequencies (g’’ < g’). the crossover point of the storage and loss moduli (and the corresponding crossover frequency ωc) marks the transition between the two different regions in the viscoelastic spectrum [84]. the decrease in ωc upon salt addition reflects the formation of a more entangled wlm structure with slower relaxation mechanisms [19]. no remarkable variations in g’ and g’’ are observed before and after the uv irradiation with the exception of naol alone, that exhibits higher values of the storage and loss moduli in the low frequency region after the uv treatment. figure 6 reports the storage and loss moduli obtained in the frequency sweep experiments before and after uv irradiation for the samples containing azorubine in the presence of kcl at different concentrations (0, 0.5 and 2%). the frequency sweep curves for other kcl concentrations are reported in the supporting information. the formulations exhibit a viscoelastic behavior that looks similar to those reported in figure 5, indicating that the two frequency-dependent regimes are present. the crossover frequency decreases when kcl concentration is increased from 0 to 0.5%, then it progressively shifts to higher values upon further increase in the salt concentration. the uv treatment has a very minor effect on the viscoelastic properties of the formulations, with the exception of the sample containing kcl 4% (figure s10 in the supporting information). in this case before the uv irradiation the storage and loss moduli show a crossover in the high-frequency region, followed by a remarkable drop at medium and low frequencies, which indicates a predominantly viscous behavior. after the uv treatment g’ and g’’ overlap for most part of the whole frequency range and after a slight decrease at high frequencies they level off to a relatively high constant value in the medium and low-frequency regime. this result is consistent with the remarkable viscosity increase observed after the irradiation (figure 2) due to the presence of light-induced ordered structures. a cole-cole plot analysis was performed to describe the viscoelastic behavior of the naol dispersions in terms of a maxwell model with a single relaxation time (results not shown). unfortunately, this approach does not provide an accurate prediction for the experimental values due to the presence of additional relaxation modes. for this reason, we calculated the continuous time-weighted relaxation spectrum using the values of the storage and loss moduli (trios software, 5.2 version, ta instruments) [85,86]. the relaxation times τr estimated from the spectra are reported in figure 7. in the relaxation spectra an intense primary peak is observed for all the samples, and it was used to extrapolate the relaxation times. additional secondary peaks are clearly detectable, demonstrating the presence of concurrent relaxation modes (reptation, breaking and recombination, rouse motion, etc.) [19]. the comparison between the relaxation times and the viscosity values (see figure 4) shows a similar effect on both the flow and the viscoelastic properties of the dispersions induced by azorubine: the uv irradiation, thanks to the presence of the dye, increases the structuredness of the tridimensional micellar network, resulting in similar trends of η0 and τr. figure 5. storage (triangles) and loss (circles) moduli before (filled markers) and after (empty markers) uv irradiation for naol 0.43 m in the presence of kcl at 0 (black), 0.5% (green) and 2% (blue). the frequency sweep curves for non-irradiated samples are reprinted from [19] with permission from elsevier. copyright 2021. figure 6. storage (triangles) and loss (circles) moduli before (filled markers) and after (hollow markers) uv irradiation for naol 0.43 m + azorubine 0.18 % mixture in the presence of kcl at 0 (black), 0.5 % (green) and 2 % (blue). 21light-modulated rheological properties in green innovative formulations the only exception is represented by naol + kcl 4% in the presence of azorubine: in this case the relaxation time after the uv treatment is very close to the value of the non-irradiated sample. as we mentioned in the previous section, the remarkable increase in the viscosity observed at this salt concentration is probably due to the presence of aggregated structures. differential scanning calorimetry differential scanning calorimetry (dsc) experiments were performed to investigate the thermal properties of the naol-kcl-azorubine systems. the thermograms of the naol dispersions in the presence of kcl at different concentrations (0, 3.5 and 4%) before and after uv irradiation are reported in figure 8. for the dsc curves of the other investigated kcl concentrations see the supporting information. all the dsc thermograms show a free water melting peak at around 0°c. for kcl concentrations above 0.5 % a secondary endothermic peak occurs between -15 and -11°c, and it is related to the melting of the “interfacial” water molecules that are confined in the solventrich domains between the entangled cylindrical micelles [87–91]. a third endothermic peak appears when kcl concentration reaches 4%, as observed in our previous work [19]. this thermal transition is attributed to the melting of freezable bound water, i.e. the water molecules that closely interact with the micellar surface and show a melting temperature remarkably different from bulk water [61,92–96]. the melting temperature, the relative enthalpy change and amount (%) of free water (∆hmf, tmf and wf), interfacial water (∆hmi, tmi and wi) and freezable bound water (∆hmb, tmb and wb) for all the examined samples, before and after uv irradiation are listed in table s2 in the supporting information. a detailed discussion about the theoretical background and the procedures for the calculation of the thermal parameters can be found in [19,26,61]. for the pristine non-irradiated samples wf rapidly decreases, passing from 96% to 46% as the salt concentration increases. similar values are obtained for the naol-kcl systems after the uv irradiation, demonstrating that the endothermic process (i.e. the melting of the free water) is not affected by the uv treatment, as expected. when kcl concentration increases, the melting peak temperatures tmi shift to lower values; conversely ∆hmi shows a progressive increase. as previously reported, the addition of kcl (and the consequent na+/k+ exchange at the micellar surface) leads to the formation of elongated cylindrical micelles, and above a critical concentration (see figure 4) to the branching of the wlm network [19]. for this reason the number of connections and junctions within the micellar network increase, as well as the number of water molecules confined within the intermicellar domains, as evidenced by the values of wi. by comparing the values of the peak temperatures and of the enthalpy changes related to the melting of the interfacial and bound water we conclude that the uv treatment does not alter the hydration state of the naol/kcl systems. for the samples containing azorubine the values of ∆hmf, tmf, wf, ∆hmi, tmi, wi, ∆hmb, tmb and wb are reported in table s2 in the supporting information. the presence of the dye does not induce any remarkable variation in the amount of free and interfacial water, as well as in the values of peak temperatures and figure 7. relaxation time (τr) for the formulations containing azorubine (red) and the reference samples without the dye (black) as a function of the salt concentration before (solid line) and after (dashed line) the uv irradiation. the trend for non-irradiated naol-kcl samples (black solid line) are reprinted from [19] with permission from elsevier. copyright 2021. figure 8. dsc heating curves before (solid lines) and after (dashed lines) uv irradiation for naol 0.43 m mixture in the presence of kcl at 0 (black), 3.5% (light blue) and 4% (pink). 22 duccio tatini, martina raudino, filippo sarri the relative enthalpy changes. the main difference is represented by the freezable bound water melting peak, that appears starting from kcl 3%. as indicated by the viscosity measurements, the negatively charged sulfonate groups in the azorubine molecule have a cooperative effect with kcl in screening the electrostatic repulsion between the micellar surfaces. this synergistic action reduces the amount of salt that is required for the formation of the micellar entangled network (and eventually the branched structures) and affects the thermal transition of the water molecules that closely interacts with the micellar surface, i.e. the freezable bound water. conclusions in this work we illustrate a simple and inexpensive procedure for the formulation of green photo-responsive viscoelastic fluids starting from non-toxic, biocompatible, commercially available materials. the addition of a food azo dye, azorubine, to a dispersion of sodium oleate in the presence of kcl enables the modification of the formulation rheological properties through an external uv light stimulus. the uv treatment brings about the trans-cis isomerization of azorubine, which is partially intercalated between the surfactant polar heads, resulting in a modification of the wormlike micellar structure of naol. this gives rise to a remarkable increase in the formulation viscosity and a variation of the rheological properties, as evidenced by viscosity and oscillatoryshear measurements. the effect of azorubine is mediated by the presence of the salt, since it occurs only in a specific range of kcl concentration. dsc measurements confirm the formation of wormlike micelles above a critical salt concentration, which is lower in the presence of azorubine. the uv treatment does not affect the thermal transitions of the naol dispersions, since no significant variation is detected before and after the irradiation. all these features, combined with the complete biocompatibility and non-toxicity break new ground in a wide range of applications, from shale gas 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[96] l. zhao, l. pan, a. ji, z. cao, q. wang, recrystallization of freezable bound water in aqueous solutions of medium concentration, chin. phys. b. 25 (2016) 075101. https://doi.org/10.1088/16741056/25/7/075101. substantia. an international journal of the history of chemistry 3(2) suppl. 4: 61-74, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-301 citation: l. moreno-martínez, a. lykknes (2019) the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks. substantia 3(2) suppl. 4: 61-74. doi: 10.13128/substantia-301 copyright: © 2019 l. moreno-martínez, a. lykknes. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 1 “lópez piñero” institute for science studies, university of valència, spain 2 department of teacher education, norwegian university of science and technology, norway e-mail: luis.moreno-martinez@uv.es, annette.lykknes@ntnu.no abstract. this essay analyses 31 science and chemistry textbooks from spain and norway with respect to their presentations of the history of the periodic system and what these presentations can teach students about the nature of science (nos). the analysis is based on the source framework, where each letter in source represents an element from the history of science and corresponding attributes of nos. our comparative analysis reveals large differences in the role of history of chemistry between the spanish and norwegian teaching contexts, and similar differences in their inclusion of historical aspects in curricula and textbooks. we argue that the lack of references to women, to errors or failures in the history of the periodic system represents missed opportunities to discuss chemistry as a tentative, collective and socio-cultural enterprise. keywords. periodic system, history of chemistry, chemical education, textbooks, nature of science. introduction the periodic system is one of the best-known and most-used icons of science. it figures in every lecture hall where chemistry is taught, and it is hard to imagine chemistry teaching and chemistry textbooks without it. for chemistry students (and chemists) it might also be difficult to grasp that the periodic system was developed without knowledge of the structure of the atom, which we take for granted today. the history of the periodic system would certainly enlighten students about the particularities of its development, but also give them insight into the nature of scientific development in general. it has been argued that studying chemistry (or science) in a historical context may contribute to the understanding of chemistry as a dynamic process rather than a static set of theories or laws, as a diverse endeavour that relies on intuition as well as logic and clearly depends on the humans involved in the processes.1,2,3,4 aspects such as these are captured in the concept ‘nature of science’, which we will introduce below. 62 luis moreno-martínez, annette lykknes teaching science should therefore be more than just explaining models, theories and laws, and the history of science can help unveil a fuller picture of the scientific enterprise. for the historian, the end products, theories and facts must be understood as temporary end products of a long process. it is now generally acknowledged that knowledge about the process itself can provide very interesting insights about science. despite greater consciousness about science as a process among science educators from the 1960s onwards, the emphasis in school curricula has not radically shifted away from teaching established “facts” or end products to instead exploring how this knowledge was constructed.5 as mccomas and colleagues put it, when summarizing reports from the 1990s, ‘the ideas put forth in textbooks and school science concerning the nature of science are almost universally incorrect, simplistic, or incomplete’.6 although new aspects have been added to more recent curricula, in our experience the use of historical material is still limited; which clearly contrasts with the increased importance attributed to history in science education research in the past few decades.7 the aim of this essay is to explore to what extent and how the history of the periodic system is presented in recent textbooks, and which aspects of the nature of science are conveyed to students through the historical presentations. we will compare texts published in the last 13 years from two different teaching contexts: those of secondary schools in spain and in norway. before presenting the methodology, our analyses and conclusions, we will introduce the concept of nature of science in science teaching, the theoretical framework based on that concept, and the contrasting curricular traditions in spain and norway when it comes to including the history of science. the aspects of the history of the periodic system that we have selected for our analyses will be introduced in the materials and methods section. using history of science to teach the nature of science (nos) when science is taught, teachers and students create various images of science. this wide range of images is made up of values, features and conceptions about how science works. in the context of science education, learning the nature of science (nos) refers to understanding presuppositions, values, aims, and limitations of science, and how knowledge is created and established.5 analyses of science curricula reveal that even though nos is usually not explicitly mentioned, several objectives, contents, skills and evaluation criteria are deeply connected with nos themes in many ways.8 studies of the history of science content in textbooks have, furthermore, provided insight into how nos is presented in textbooks and teaching.9 although nos is itself a dynamic area with no fixed list of attributes, a pragmatic ‘consensus view’ has been compiled, including the most important agreed-upon elements describing science as a process. this consensus view holds that science or scientific endeavour is tentative (always evolving), empirical (relies on obser vation, experimental evidence, arguments, scepticism), explanatory (attempts to explain natural phenomena), communicative (open and subject to peer review), structured in laws and theories (though they serve different roles in science), both evolutionary and revolutionary, interrelated with technology (a two-way relationship), diverse or multifaceted (there is no one scientific method), to a certain extent subjective (influenced by personal values and prior experiences), creative (involving imagination), and socio-cultural (influenced by cultural and social contexts).5,9,10,11 table 1 compares some of the different ways these nos aspects are communicated in the literature. the selected aspects given in table 1 will be used as a basis for our analyses of spanish and norwegian textbooks. in 1974, in a paper entitled ‘should the history of science be rated x?’ published in science,12 the historian of science stephen g. brush critically stated that ‘the teacher who wants to indoctrinate his students in the traditional role of scientist as a neutral fact finder should not use historical materials of the kind now being prepared by historians of science: they will not serve his purposes’.13 his point was that science teachers wanted to keep their success stories, and that the history of science challenged them. although brush’s irony is evident, table 1. a comparative connection between digiuseppe’s (2014)10 and mccomas-kampourakis’s (2015)9 nos aspects. digiuseppe’s nos aspects mccomas-kampourakis’ nos aspects science (is) tentative a way of knowing addresses questions about the natural and material world open to revision empirical based on data and empirical evidence subjective a human endeavourcreative socio-cultural structured in laws and theories assumes an order and consistency in natural systems models, laws and theories explain natural phenomena diverse uses a variety of methods 63the history of the periodic system in spanish and norwegian secondary school textbooks he touched upon a dilemma, as the histories of scientific development presented through a history of science might, indeed, destroy the many ‘hagiographic’ (heroic) tales that are commonly used in textbooks and classrooms. thirty years later, the philosopher and historian of science (and science educator) douglas allchin published a paper entitled ‘should the sociology of science be rated x?’, echoing brush’s article from 1974.14 while the ‘new’ history that brush discussed took heroes of science down from their pedestals, allchin discussed how a sociology of science threatens the image of the ‘idealized and impersonal scientific method found in textbooks’.15 indeed, (degrees of ) subjectivity and tentativeness are among the attributes of the ‘consensus view’ that do challenge the authority of science – which is why science educators do not always embrace all aspects of nos. allchin stressed that idealized, or romanticized, science is a lie. for this reason, he argued, science educators should distinguish between the normative and the descriptive elements of nos in their teaching. allchin also argued that science educators indeed should include errors or failed attempts from the history of science when teaching about the nature of science. in allchin’s words, ‘teaching science without error is like teaching medicine without disease or law without crime’.16 in order to identify the sorts of historical narratives that introduced a misrepresented nos in the teaching context, in another article allchin used the term ‘pseudohistory’ of science (phs).17 he argued that the historical narratives in science education must present the history of science without idealizing past science. from allchin’s approach, historical narratives become phs when they verge on myth. one such myth in the history of the periodic system might be that dmitri mendeleev (1834–1907) was the sole discoverer of the system and that it was conceived during one ‘eureka’ moment. since every history of science teaches nature of science, science educators need to be wary of mythic narratives (what we have called nos from phs approach in table 2). they need to use historical narratives that portray nos more informatively (what we have called nos from hs approach in table 2).17,18 one of the strategies proposed by allchin is to neutralize mythical historical narratives of science by going from the source of the problem to the source of the solution, as we summarize in table 2.18 this so-called source approach allows teachers to recognize myths and control their effect on students. we will use this approach when analysing spanish and norwegian textbooks. in recent years, science education literature has given some attention to the use of the history of the periodic system in chemistry teaching. in 2015, mccomas and kampourakis used mendeleev’s periodic table as an example of a historical case which shows that laws and theories represent distinct kinds of scientific knowledge (the nos aspect ‘structured in laws and theories’).9 as bensaude-vincent had pointed out almost three decades before, mendeleev developed a periodic law which enabled new data to be discovered and phenomena to be explained, and which atomic theory later explained.19 furthermore, the knowledge of the development of the periodic system was among the topics in a questionnaire used by franco-mariscal, olivia-martínez and amoraima-gil in 2016 to analyse how spanish high school students understood the idea of chemical element and its periodic classification.20 based on a review of analyses of the history of the periodic system in textbooks in the usa and latin america, in 2016 niaz suggested several guiding principles for teaching the periodic system using a history of science approach. among them were how the classifications of the elements could be based on atomic mass, the important role of other co-discoverers of the periodic table, and what role predictions played for acceptance of the periodic law.21 similar aspects have been selected for the present analyses and will be presented under materials and methods. history of chemistry in spanish and norwegian teaching contexts during the past decades, the field of history of chemistry has undergone a significant consolidation and renovation.22 however, the history of chemistry is still conspicuous by its absence in many teaching contexts. spain and norway represent different local contexts when it comes to the institutionalization and teaching of history of chemistry at different levels. two surveys of the prevalence of the teaching of history of chemistry in europe, stemming from 2007 and 2015, respectively, table 2. main features of nos according to the source approach, based on allchin (2003).18 every letter in the word source corresponds to an attribute from pseudo-history of science (phs) as well as to an attribute from history of science (hs). nos from phs approach nos from hs approach science-made science-in-the-making overinflated genius opportunities unqualified universality uncertainties retrospect respect for historical context caricatures contingency, complexity, controversy expected results and excuses error explained 64 luis moreno-martínez, annette lykknes reveal that in fact, the situation with respect to history of chemistry teaching is not at all comparable in the two countries. in 2007, history of chemistry was taught for chemistry students at 14 of the 39 universities offering graduate, postgraduate and doctoral studies in spain, most of them as special history of chemistry courses. in norway, two of the four universities in the country offered teaching in history of chemistry, either as part of the chemistry curriculum or as part of a history of science course for prospective teachers. although representatives from both countries in 2015 expressed worry about the lack of institutionalization of the field, history of chemistry is much more prevalent in spain in terms of the history of chemistry groups, journals and teaching offered than is the case in norway.23 if we assume that the knowledge and use of history of chemistry at secondary school level echoes the situation at university level, we would expect a major prevalence of the history of chemistry in the spanish curriculum. the analyses of the curricula in norway and spain have supported that. the spanish chemistry curriculum contains a few competency objectives on the history of chemistry at secondary school level. five history of chemistry issues can be found: atomic models, classification of the chemical elements, acid-base theories, laws of chemical combinations and the origin of organic chemistry.24,25 among them are the ‘importance of the periodic system for chemistry development’26 and the ‘historical development of the classification of the chemical elements’.27 both are part of the upper secondary chemistry curriculum (16–18 year-old students). the history of the periodic system is not explicitly mentioned in the lower secondary school chemistry curriculum (ages 14–16). a recent study on the history of chemistry in spanish secondary education pointed out that several curricular elements make explicit the tentative (evolving), controversial (diverse and multifaceted), creative (involving imagination), under-construction (evolutionary) and socialcultural (inf luenced by cultural and social contexts) nos for both lower and upper secondary education.28 in norway, history of chemistry has had a less prominent role in the chemistry curriculum, which is not surprising given how little attention is paid to history at university chemistry level. a survey from 2004, before the most recent curriculum reform in norway was launched, reveals that students who opted for chemistry in upper secondary school liked ‘historical chemistry’ least of all chemistry topics listed in the survey.29 as of 2006, the national science and chemistry curricula hardly include any history of chemistry. the only specific competency objective for history of chemistry is related to the historical development of the atomic model and the concept of atoms, which is a topic that falls under the main area of ‘language and models in chemistry’ in upper secondary school.30 another competency objective in the chemistry curriculum that is related to nos aspects and might allow for some historical reflections, revolves around scientific method and explanatory models not compatible with chemical-scientific explanations (as part of the main content area, the meta-subject ‘research’).31 as a topic in chemistry, the periodic system is part of the curriculum for the integrated science course in lower secondary school in one competency objective for grades 8–10 (i.e. ages 13–15).32 the periodic system is not explicitly mentioned in the curriculum for upper secondary school (ages 16–18), but might be taught as part of other topics if considered relevant and needed, though treated as ‘repetition’. a new curriculum, which will be implemented from autumn 2020, follows the current curriculum in placing the periodic system as part of lower secondary science, and with no competency objectives for history of chemistry.33 materials and methods although the curriculum is the formal guide to teaching at different levels in spanish and norwegian schools, in practice textbooks serve as the real guides when teachers prepare their teaching, as park and lavonen have pointed out for the american and finnish cases.34 for this reason, textbooks are well suited to inform us about teaching practices and what content is being taught in chemistry at different levels in school. also, since competency objectives in curricula are few and general, textbook authors must interpret the curriculum and therefore, their texts will go beyond the curricula themselves. an example is the history of the periodic system, which as noted is not an explicit part of the lower secondary school curriculum in spain, yet textbooks include it. this also applies to other historical topics. likewise, the periodic system is mentioned in chemistry textbooks for upper secondary school in norway, although it is not part of the curriculum for that level. in both samples textbooks in science/chemistry at lower and upper secondary school levels are included, for the years in which the periodic system is mentioned. in the spanish case, textbooks for compulsory lower secondary education, cse (educación secundaria obligatoria-eso) and upper secondary education, use (bachillerato) from five recognized publishers have been analysed: anaya (s1); santillana (s2); vicens vives (s3); mcgraw-hill (s4); oxford (s5). the sample is made up of 20 textbooks from four educational levels: five textbooks 65the history of the periodic system in spanish and norwegian secondary school textbooks for the third course of compulsory lower secondary education (14–15 year-old students, cse3), five textbooks for the fourth (and last) course of compulsory lower secondary education (15–16 year-old students, cse4), five textbooks for the first course of upper secondary education (16–17 year-old students, use1) and five textbooks for the second (and final) course of upper secondary education (17–18 year-old students, use2). all of these textbooks were widely used in spanish upper secondary schools between 2007 and 2016. moreover, these textbooks have been published by some of the most prestigious publishing houses for education (s1-s5), according to the spanish ranking of the scholarly publishers indicators in humanities and social sciences project.35 the norwegian textbook sample consists of, first, four sets of science textbooks for compulsory lower secondary school (ages 13–15), grade 8 (cse8) and for most of them, grade 9 (cse9), which are the books that present and discuss the periodic system (seven books in total): tellus (n1), trigger (n2), eureka! (n3), nova (n4), published by four different publishing houses. secondly, the first year of the specialized chemistry course in upper secondary school (year 2, use2) uses three textbooks from three different publishers: kjemi 1 (n5), aqua kjemi 1 (n6), kjemien stemmer 1 (n7). in the first year there is a compulsory integrated science course, and in year 3 the periodic system is not discussed. thirdly, as a reference we have included the textbook kjemi for lærere (chemistry for teachers, n8), used in the study programme for prospective science teachers in primary and lower secondary schools who have no prior knowledge of chemistry.36 this study programme takes place either in a university college or at university (varies from city to city). for simplicity, we call it college education (ce) in this article. framework and research items for textbook analyses the methodological framework for our analyses of the history of the periodic system in textbooks is presented in table 3. here, we use the source approach proposed by allchin (table 2), where each letter in source stands for an aspect of nos, and connects it with nos aspects based on work by digiuseppe, and mccomas and kampourakis (table 1). we will present the historical background for each research item separately. i1: different classifications of the chemical elements before and after mendeleev’s periodic system. far from being a product of a single man’s flash of genius, the periodic table was the result of a collective aim which developed over a long period of time. already in the beginning of the 19th century, after john dalton (1766–1844) had introduced his atomic theory and characterized different atoms by their weight, attempts were made to group elements according to their atomic weights. the german chemist johann wolfgang döbereiner (1780–1849) organized the elements into groups of three elements with related chemical proptable 3. the source approach adapted to the history of the classification of the chemical elements. for an explanation of s, o, u, r, c and e, see table 2. research items (i) textbooks mention… nos aspects hs aspects allchin (source approach) digiuseppe mccomas & kampourakis i1. different classifications of the chemical elements before and after mendeleev’s periodic system science-in-the-making vs. science-made creativity human endeavour collective i2. the work of women behind the periodic system opportunities vs. overinflated genius socio-cultural equal i3. mendeleev predicted atomic weights and properties of several elements which were later corroborated uncertainties vs. unqualified universality tentativeness open to revision non-hagiographical non-teleological i4. mendeleev’s periodic system gradually evolved respect for the historical context vs. retrospect creativity contextualized i5. the differences between mendeleev’s and meyer’s approaches to the classification of the elements contingency, complexity & controversy vs. caricatures diverse variety of methods controversial i6. not all of mendeleev’s predictions were successful error explained vs. expected results and excuses tentativeness open to revision non-hagiographical 66 luis moreno-martínez, annette lykknes erties (like reactivity) called triads, where the atomic weight of the central element of the triad was the mean value of the atomic weights of the first and the last elements of the triad. several chemists identified triads, and the idea of triads has been highlighted as an important point in the history of the periodic system because it hinted at a relationship between numerical criteria (the atomic weight) and the properties of the elements.37 atomic weight determinations continued over the course of the 19th century; however, discrepancies existed. the question of which system one should base the atomic weight determinations on was taken up at the first international chemistry congress held in karlsruhe in september 1860. it is thus not by chance that several classifications of the elements emerged in the early post-karlsruhe context. the british chemist william odling (1829–1921), the german chemist lothar meyer (1830–1895) and mendeleev were all present at the karlsruhe congress, after which they had a basis on which to build a system of the elements.38, 39 twenty years after his first periodic system had been published, mendeleev recognized the importance of the karlsruhe meeting for his work on the elements, as ‘[o]nly such real atomic weights [proposed at karlsruhe] – not conventional ones – could afford a basis for generalization’.40 a total of six independent discoverers of the periodic system have been identified: the french geologist émile béguyer de chancourtois (1820–1886), who in 1862 presented his vis tellurique (a periodic helix), and the british chemist john newlands (1837–1898), known for his ‘law of octaves’, are among them, along with the american chemist gustavus hinrichs (1836– 1923), odling, meyer and mendeleev. the development of periodic systems also continued after mendeleev’s famous 1869 system. in fact, between 1782 (with louis bernard guyton de morveau’s simple table) and 1974, many hundred classifications and representations classifications and representations of the ‘periodic law’ appeared, including tables, zigzags, lemniscates, helixes and spirals.41 all of these clearly show why the history of the periodic system can be considered as a history of shaping and sharing. i2: the work of women behind the periodic system in the 1860s, 63 chemical elements were known. many new elements were identified from the 1870s onwards and in particular in the first decades of the 20th century. while it is well known that many (male) scientists contributed to the discoveries of elements, histories of women discoverers are rarely communicated. recognizing that women from different backgrounds and in various roles have contributed to discoveries of elements and to the development of the periodic system is another way of conveying that science is a collective human enterprise where people from all cultures have taken part. by spotlighting women, such stories can also highlight that science is equal, an endeavour for both women and men. element discoveries demanded high-level analyticalchemical competence, and in some cases expertise on radioactivity. examples of element discoveries by women, either alone or on research teams, are polonium and radium (1898), by marie (1867–1934) and pierre curie (1859–1906), protactinium (1918) by lise meitner (1878– 1968) and otto hahn (1879–1968), rhenium (1925) by ida (1896–1978) and walter noddack (1893–1960), with the help of otto berg, and francium (1939) by marguerite perey (1909–1975). women were also involved in work that led to positioning the elements in the right place (see i4 for the example of julia lermontova) and in revealing nuclear processes leading to a better understanding of the atom.42 i3: mendeleev predicted atomic weights and properties of several elements which were later corroborated, and i6: not all of mendeleev’s predictions were successful even though mendeleev’s classification underwent several modifications, one of the known features of all of mendeleev’s periodic systems was that he left blank spaces for as yet unidentified elements. he also predicted their atomic weights and foresaw some of their properties. although the predictions that were later fulfilled influenced the acceptance of the periodic system, it has been argued that the importance of the predictions must be reconsidered.43 for example, in 1882, mendeleev and meyer were both recognized by the royal society of chemistry with the davy medal because of their contribution to the development of the classification of the elements, but no mention was made of mendeleev’s successful predictions. also, it should be noted that mendeleev had many failed predictions. coronium, ether, ekacerium, eka-molybdenum, eka-niobium, eka-cadmium, eka-iodine and eka-caesium were elements predicted by mendeleev which were never found. eka-boron (scandium), eka-aluminium (gallium) and eka-silicon (germanium) are examples of elements predicted by mendeleev which were later identified and which properties turned out to fit well with what mendeleev had foreseen. i4: mendeleev’s periodic system gradually evolved the different versions of mendeleev’s classifications were more than a succession of changes in shape. chemists continued to refine their analytical methods in order to obtain more accurate atomic weights. in the 1870s, the russian chemist julia lermontova (1846/47–1919) worked on the separation of the platinum metals in minerals so 67the history of the periodic system in spanish and norwegian secondary school textbooks that more accurate atomic weights could be determined. this was necessary since the atomic weights of the platinum metals were close in value, and so were their chemical properties; hence it was difficult to place them in the right order in the periodic system.44 another example is the difficulty in positioning tellurium and iodine in the periodic system. in 1871, mendeleev assumed an atomic weight of 125 for tellurium although weights up to 128 had been determined, since placing tellurium before iodine (127) constituted a better match in terms of chemical properties than vice versa.45 thirty-three years later, in 1904, mendeleev presented both elements with the same atomic weight (127) in his periodic table. in fact, tellurium had been found to have a slightly higher atomic weight than iodine (127.6 vs. 126.85), but there was nevertheless no doubt about which family they belonged to in the system – evidence that atomic weight could not be the primary criteria for ordering the elements.45,46 other changes can also be observed by comparing mendeleev’s different periodic systems: some elements disappeared from the system (like didymium, di) and others appeared (like group zero gases – now known as the noble gases in group 18) in subsequent classifications. the periodic system as a table also continued to develop after mendeleev’s time. in 1905, for example, two years before mendeleev died, the swiss chemist alfred werner (1866–1919) reorganized the periodic table, separating the lanthanides so they occupied a separate place in the table similar to the placement of the transition metals in our current long periodic table. in subsequent decades, the british chemist friedrich adolf paneth (1887–1958) moved the lanthanides beneath the main table. likewise, in 1945 the american chemist glenn theodore seaborg (1912–1999) added a separate group of elements beneath the table, the actinides, thereby moving elements 89–96 from the main table to the new group. the justification of the concept of ‘atomic number’ by the british physicist henry moseley (1887– 1915) in 1913 was also an important milestone in the history of the periodic system after mendeleev’s work. the introduction of the atomic number as a better ordering principle for the elements than atomic weight and the irruption of quantum physics in the study of subatomic structure also had an important influence on the development of the periodic system to the present day. i5. the differences between mendeleev’s and meyer’s approaches to the classification of the elements as noted above, in 1882 lothar meyer and mendeleev were awarded the davy medal jointly. as with the systems of mendeleev and the other co-discoverers, the elements in meyer’s periodic systems were organized by increasing atomic weight. both chemists developed their periodic systems while preparing a textbook.47 however, meyer’s and mendeleev’s approaches were different. mendeleev thought chemical properties should take precedence over physical criteria, except for atomic weight. mendeleev also made elaborate predictions for still unidentified elements (not all successful, as stated above) and suggested revisions to what he presumed were inaccurate atomic weights.48 meyer, too, left blank spaces for as yet undiscovered elements and made interpolations for the atomic weights of unknown elements’ based on the values for neighboring elements, but he did not make extensive predictions for unidentified elements like mendeleev did. instead, meyer explored the concept of periodicity through a graph where atomic volume was plotted as a function of atomic weight, making visible trends in atomic volume as a property of atoms.49 scoring system for our content analyses we have defined a scoring system to indicate the extent to which selected aspects of the history of the periodic system have been addressed in the named textbooks (table 4). the scoring system is inspired by niaz.21 the mention has been considered satisfactory (sm) if the textbook: (sm-i1) presents the classifications of the chemical elements as a collective and creative challenge for several chemists before (as well as after) mendeleev. (sm-i2) is inclusive in the sense that women are mentioned, e.g. as discoverers of elements. (sm-i3) uses mendeleev’s ‘correct’ predictions in order to emphasize chemistry-in-the-making instead chemistry as a static corpus of knowledge, but not as a way to emphasize his role as a ‘hero of chemistry’. (sm-i4) refers to post-1869 developments of the periodic system, such as changes in the positioning of elements, introduction of new elements or disappearance of others, the introduction of the atomic number by moseley or the interpretation of the periodic law based on quantum theory. table 4. recording instrument. i1-i6 refer to historical items presented above. the scoring system includes the following scores: sm, satisfactory mention; ns, non-satisfactory mention; nm, no mention. textbook i1 i2 i3 i4 i5 i6 score sm sm sm sm sm sm nsm nsm nsm nsm nsm nsm nm nm nm nm nm nm 68 luis moreno-martínez, annette lykknes (sm-i5) emphasizes that although mendeleev and meyer had important roles in the emergence of the periodic system, their approaches offer similarities and differences. (sm-i6) notes the failed predictions of mendeleev as an opportunity to show that scientific development is not linear, but includes errors and blind alleys. results and discussion the results of the categorization of the texts based on the aforementioned methodological framework are presented in two tables: the spanish textbooks in table 5, and the norwegian textbooks in table 6, followed by analyses of the results by country. spanish textbooks the history of the classification of the chemical elements in spanish textbooks is usually a part of the atomic structure unit, running up to two of four pages. overall, as can be deducted from table 5, spanish textbooks lack references to women in the history of the periodic system and the discovery of the elements (i2) and to the failed predictions of mendeleev (i6). the texts also tend to neglect the differences between mendeleev’s and meyer’s approaches (i5). meyers system is mostly considered identical to mendeleev’s, but independently made. those textbooks that mention the difference between meyer’s and mendeleev’s approaches point out that ‘meyer used atomic volume as a criterion for his classification of the chemical elements’ (santillana (s2) 1º bachillerato, p. 92; santillana 2º bachillerato, p. 53). other textbooks present meyer as ‘a less audacious chemist’ (oxford (s5) 1º bach, p. 97) or mendeleev as a chemist that ‘garnered meyer’s success’ (oxford 2º bach., p. 59). all of these non-satisfactory mentions neglect the differences in approaches of mendeleev and meyer that have been previously indicated, such as the role of prediction or the inclusion of elements with non-established atomic weights. the historical narratives of the classification of the chemical elements presented in the spanish textbooks include pre-mendeleevian proposals (i1). references to table 5. results from categorization of spanish texts on the history of the periodic system. sm, satisfactory mention; nsm, non-satisfactory mention; nm, no mention. research item level i1 i2 i3 i4 i5 i6 publisher cse3 (3º eso) 14-15 year-old students nm nm nm sm nm nm s1 nsm nm nsm nm nm nm s2 nm nm nsm nm nm nm s3 nm nm nm nm nm nm s4 nm nm nm nm nm nm s5 cse4 (4º eso) 15-16 year-old students nsm nm nsm nm nm nm s1 nm nm nm nm nm nm s2 nm nm nsm nm nm nm s3 nm nm nm nm nm nm s4 nsm nm nsm nm nm nm s5 use1 (1º bachillerato) 16-17 year-old students sm nm nm nsm nm nm s1 sm nm nm nsm nsm nm s2 nm nm nsm nm nm nm s3 nm nm nm sm nm nm s4 sm nm sm sm nsm nm s5 use2 (2º bachillerato) 17-18 year-old students sm nm sm sm nm nm s1 sm nm nsm sm nsm nm s2 nsm nm nsm nm nm nm s3 sm nm nsm sm nm nm s4 nsm nm sm sm nsm nm s5 books which mention research items (out of total) 11/20 0/20 12/20 9/20 4/20 0/20 69the history of the periodic system in spanish and norwegian secondary school textbooks döbereiner’s triads and newland’s octave law are quite common, especially in upper secondary education textbooks (bachillerato/bach.). one textbook (santillana (s2) 2º bach.) mentions chancourtois’ vis tellurique from 1862. the inclusion of a such a helical periodic system may help give nuance to the traditional tale of the periodic system as a table and table only. likewise, the mention of several contributors before mendeleev helps to highlight the periodic system as a collective endeavour. that many scientists were involved in its development is explicitly mentioned in one textbook, which indicates that ‘the history of the periodic table is a reflection of the work of a large number of scientists and the effort of the scientific community’ (santillana (s2) 2º bach., p. 52). the history of the pre-mendeleev classifications in spanish textbooks emphasizes the creative and collective nos. references to mendeleev’s correct predictions (i3) were also found in spanish textbooks. these predictions could be interpreted as an opportunity to show chemistry as a dynamic activity instead of a static corpus of knowledge. however, most of the textbooks introduce hagiographical and teleological images of the history of chemistry, which make some of these texts unsatisfactory. several qualifiers are used to present mendeleev as a prophet of chemical order. lower secondary chemistry textbooks, for example, mention mendeleev’s correct predictions as a way to present mendeleev as a ‘genius’ (santillana (s2) 3ºeso, p. 104) or to emphasize ‘the boldness of his work’ (anaya (s1) 4ºeso, p. 200) and ‘his great intuition’ (vicens vives (s3) 4ºeso, p.162). in upper secondary chemistry textbooks, mendeleev’s predictions are presented as ‘the culmination of his career’ (vicens vives 1º bach., p. 240), ‘a milestone’ (santillana 2º bach., p. 53), ‘a great merit’ (vicens vives 2º bach., p 15.), ‘a brilliant confirmation’ (mcgraw-hill (s4) 2º bach. p. 28) and as an example of ‘his sagacity’ (oxford (s5) 2º bach., p. 58). textbooks often refer to the discoveries of what mendeleev had called eka-boron (sc), eka-silicon (ge) and eka-aluminium (ga), which are easy to locate in our current periodic system. one textbook (santillana 2º bach.) refers to eka-manganese (but using the current name, technetium). mendeleev’s wrong predictions are, however, completely neglected. this adds to the narrative of the periodic system and mendeleev as a success story. a mention of failed predictions could have contributed to a more critical and less idealized approach of the nos in science teaching. approximately half of spanish textbooks analysed describe the evolution of the periodic system after mendeleev’s periodic table (i4). references to the contribution of the english physicist henry moseley, the swiss chemist alfred werner, the austrian-born british chemist friedrich a. paneth and the american physicist glenn t. seaborg have been found in several books. all of these reveal the periodic system as an expanding model shaped by several scientists in different historical contexts. this is a satisfactory nos conception, which emphasizes tentativeness as an important feature of science. finally, it should be noted that no significant differences between publishers have been found. furthermore, more references to the history of the periodic system have been observed in chemistry textbooks for higher levels (use). norwegian textbooks as noted above, the history of the periodic system is not part of the norwegian curriculum at any level in school. it is therefore up to the textbook authors and their publishers to include aspects from the history of chemistry if considered useful, and also to select which aspects are relevant. according to the curriculum, the periodic system is to be taught during lower secondary school as part of the integrated science course, but in which year is not specified. most of the authors responsible for the textbooks at this level have included it in grade 9 (the second year of lower secondary school). a few authors have included a brief introduction of the system in grade 8, and delve more deeply into the topic in grade 9. one textbook presents the periodic system only in grade 8 (n4). likewise, a few textbooks for the optional chemistry course in upper secondary school describe the periodic system briefly, even though it is not part of the curriculum. but even where the periodic system is explained in these textbooks, the history of the system is not necessarily touched upon. for example, kjemien stemmer 1 (n7) includes no history at all, but most of the textbooks mention mendeleev and a brief history of the system. some include the mention only in a figure caption, others as part of the main text – usually between a paragraph and a page long (three and a half pages for kjemi for lærere, n8). overall, the historical descriptions in the norwegian textbooks are scarce. no textbook mentions any women in the history of the periodic system (i2), nor do they mention meyer or any other co-discoverer (i5) or mendeleev’s failed predictions (i6). one textbook from lower secondary school (eureka! 9, n3) and one from upper secondary school (kjemi 1, n5) are the only textbooks hinting that any pre-mendeleevian history might exist (i1). eureka! 9 simply states that ‘many people have contributed to solving this difficult task’ (p. 10), while kjemi 1 explains that mendeleev ‘combined earlier scientists’ 70 luis moreno-martínez, annette lykknes works into an original and genial system’ (figure caption, p. 22). the textbook for teacher trainers (kjemi for lærere, n8) is the only one giving a satisfactory account on the periodic system as a collective effort. in this book döbereiner’s triads are mentioned, as are odling’s groups of elements and the discussion around atomic weight determinations leading up to 1860 (p. 77). but odling is not credited as co-discoverer of the periodic system. that the system did take different forms is, however, exemplified by frederick soddy’s spiral system of 1911 (p. 80), giving insight into the many possible ways of organizing the elements periodically, based on the same principles. the most represented topic among our historical items (in 6 out of 11 books) are mendeleev’s ‘correct’ predictions (i3). however, none present the predictions as a complex process including trial and error, not even the textbook for teacher trainers, which states: mendeelev set aside spaces in the periodic system for new elements which would likely be discovered. he predicted which properties these new elements and their compounds would have, and the predictions later turned out to fit very well (p. 78). nova 8 (n4) is more cautious, informing readers that ‘most’ predictions were successful, not all (p. 102). tellus 9 (n1) adds that the predictions of mendeleev helped scientists in their ‘hunt’ for new elements, since the properties of these elements were known. this is how germanium was discovered, the authors state (p. 14).50 another book (kjemi 1, n5) gives gallium as an example (p. 22). two textbooks also include tables comparing mendeleev’s predictions for ‘eka-silicon’ from 1871 with clemens winkler’s (1838–1904) descriptions after his discovery of germanium in 1886, to show how good mendeleev’s predictions were (kjemi for lærere (n8), p. 79; a simplified version is presented in aqua kjemi 1 (n6), p. 28). this ‘success approach’ of the history of the periodic system is in line with traditional, popular accounts of the periodic system of today, which often emphasize linear (whiggish) history and explain mendeleev’s success on the basis of his predictions. only two textbooks mention that mendeleev’s periodic system continued to be developed after his time (i4). eureka! 9 (n3), the textbook for lower secondary school, simply states that ‘[t]he periodic system has been improved in the course of the last 140 years, but has much in common with the one mendeleev devised’ (p. 10). kjemi for lærere (n8) mentions the problems of accommodating rare earth elements (what we today know as lanthanoids) and how this challenge was solved with the use of the concept of ‘atomic number’, introduced by h. moseley in 1913 (p. 79). discussion even though norway and spain represent different teaching contexts, the history of the periodic system presented in textbooks in these countries share some similarities. both spanish and norwegian textbooks neglect the role of the women in the history of the discovery (i2) of the chemical elements and mendeleev’s failed predictions table 6. results from categorization of norwegian texts on the history of the periodic system. sm, satisfactory mention; nsm, non-satisfactory mention; nm, no mention. research item level i1 i2 i3 i4 i5 i6 book series cse8 (grade 8) 13-14 year-old students nm nm nm nm nm nm n1 nm nm nm nm nm nm n2 nm nm nm nm nm nm n3 nm nm nsm nm nm nm n4 cse9 (grade 9) 14-15 year-old students nm nm nsm nm nm nm n1 nm nm nsm nm nm nm n2 nsm nm nm nsm nm nm n3 use2 (2nd year of upper secondary school) 17-18 year-old students nsm nm nsm nm nm nm n5 nm nm nsm nm nm nm n6 nm nm nm nm nm nm n7 ce (teacher education at college level) sm nm nsm sm nm nm n8 number of books which mention research items (out of total) 3/11 0/11 6/11 2/11 0/11 0/11 71the history of the periodic system in spanish and norwegian secondary school textbooks (i6), not surprisingly perhaps, since these aspects have not been highlighted in international textbooks on history of chemistry at university level either. nevertheless, this neglect can be interpreted as a missed opportunity to foster an equal and non-hagiographical approach to the history of science in school. in spanish textbooks, as well as in norwegian ones, references to the history of the periodic system before mendeleev (i1) and after his time (i4) can be found. however, spanish textbooks offer a wider range of references to historical actors and classifications than do the norwegian textbooks. such mentions may contribute to a view of science as a collective and creative enterprise. mendeleev’s successful predictions (i3) can be found in spanish and norwegian textbooks. however, textbooks tend to address this historical issue unsatisfactorily, if it is mentioned at all. instead of presenting chemistry as a complex and tentative activity that is always subject to revision, textbooks use mendeleev’s successful predictions merely to present a success story, just as brush observed in the 1970s. little or no reference to meyer’s and mendeleev’s different approaches (i5) further adds to the depiction of an individual-centred science and thus neglects to illustrate how several approaches to the same phenomena often coexist in science. the political dimension in the history of the periodic system is also neglected in historical narratives in the chemistry textbooks. cases such as the controversies around the name or symbol of some elements (like wolfram and tungsten for element 74 or rutherfordium and kurchatovium for element 104) could have been one way of including such aspects. even though the periodic system has a natural place in today’s chemistry teaching, our analyses have pointed out that authors of current textbooks in spain and norway do not take the opportunity to teach about the nature of science (table 7). of the 31 textbooks that we have analysed, only eight (7/20 in spain and 1/11 in norway) refer to post-mendeleev developments of the periodic system, such as the introduction of the atomic number by moseley or the reinterpretation of the periodic system based on quantum theory. seven textbooks (6/20 in spain and 1/11 in norway) present the classification of the chemical elements as a collective and creative challenge for several chemists before mendeleev, while all but three texts (3/20 in spain and 0/11 in norway) use mendeleev’s successful predictions as a way to emphasize his role as a ‘hero of chemistry’. using the source approach, we can draw the conclusion that these historical narratives do paint an image of science as a process (s) with uncertainties (u) and developed in a historical context (r), not just as a corpus of knowledge (science as a product). however, the other parts of source (o, c, e) are neglected (table 7). as brush predicted many years ago, textbook authors prefer to present science as a work of bright and successful men. nothing could be further from the stories presented by historians of science and nos scholars in science education. conclusion in this essay, we have explored the extent to which the history of the periodic system is presented in recent textbooks, and which aspects of the nature of science can be taught based on historical narratives of the periodic system. our analyses have pointed out that textbooks in spain and norway (though to various extents) introduce three historical contexts: developments before mendeleev’s periodic system, in mendeleev’s time and after his contributions. these aspects, if sufficiently described, may contribute to a portrayal of science as a creative endeavour based on a collective effort. however, the textbooks in our samples seem to miss the opportunity to give a fuller picture through references to women discoverers of chemical elements and to mendeleev’s failed predictions. we may argue that the way the historical narratives are presented in these textbooks contributes to masking the tentative and socio-cultural aspects of nos as a human endeavour. likewise, textbooks in spain and norway tends to be less concerned with the differences between meyer’s and mendeleev’s approaches, losing an opportunity to show the diversity in nos – that scientists use different methods to achieve the same goal. the history of the periodic system offers a wide range of possibilities for teaching chemistry – if teachers, textbook authors and publishers are willing to use it. the textbooks in our sample explore only a few of table 7. source approach applied to norwegian and spanish textbook analysis. sm, satisfactory mention; nsm, non-satisfactory mention; nm, no mention. research item sm nsm nm nos implication i1 7 7 17 science-in-the-making and science-made combined i2 0 0 31 overinflated genius i3 3 15 13 unqualified universality and uncertainties i4 8 3 20 respect for the historical context i5 0 4 27 caricature and controversies unattended i6 0 0 31 expected results and excuses – error dimension missed 72 luis moreno-martínez, annette lykknes these possibilities. we argue that the uses of the history of the periodic system in textbooks for secondary school could be explored further by introducing women as well as men, and errors as well as successes – as allchin has argued. finally, it should be noted that rather than aspiring to present a complete and exhaustive history of the classification of the chemical elements at any level in school, textbooks should instead adjust the content to specific teaching contexts and curricula, and introduce small changes which could contribute to a more nuanced image of science. hence, the history of the periodic system has the potential to endow science teaching with a collective, creative, diverse, tentative and inclusive portrayal of chemistry. to this end, world-wide initiatives such as the international year of the periodic table can help to bring less well-known aspects and recent scholarship to the fore, for the benefit of young people, their teachers and the general public. references 1. k. de berg in international handbook of research in history, philosophy and science teaching (ed: m. matthews), springer, dordrecht, 2014, pp. 317–341. 2. g. irzik & r. nola in international handbook of research in history, philosophy and science teaching (ed: m. matthews), springer, dordrecht, 2014, pp. 999-1021. 3. m. niaz, chemistry education and contributions from history and philosophy of science, springer, new york, 2016, pp. 204-207. 4. m. matthews, international handbook of research in history, philosophy and science teaching, springer, dordrecht, 2014, pp. 1-15. 5. w. f. mccomas, h. almazroa & m. p. clough, science & education, 1998, 7(6), 511-532. 6. ref. 5, pp. 514-515. 7. d. allchin in ships – resource center for science teachers using sociology, history and philosophy of science, last accessed 6 june 2019: http://shipseducation.net/tool.htm 8. e. e. peters-burton in international handbook of research in history, philosophy and science teaching (ed: m. matthews), springer, dordrecht, 2014, pp. 167-193. 9. w. f. mccomas & k. kampourakis, review of science, mathematics and ict education, 2015, 9(1), 47-76. 10. m. digiuseppe, international journal of science education, 2014, 36(7), 1061-1082. 11. the following paper reviews various frameworks for nos, including the consensus view. the main aim, however, is to offer a broader and more comprehensive framework for nos, the so-called family resemblance approach. z. r. dagher & s. erduran, science & education, 2016, 25, 147-164. 12. s. g. brush, science, 1974, 183, 1164-1172. 13. ref. 12, p. 1170. 14. d. allchin, science education, 2004, 88(6), 934-946. 15. ref. 14, p. 935. 16. ref. 14, p. 944. 17. d. allchin, science & education, 2004, 13, 179-195. 18. d. allchin, science education, 2003, 87(3), 329-351. 19. b. bensaude vincent, british journal for the history of science, 1986, 19, 3–17. 20. a. j. franco-mariscal, j. m. oliva-martínez & m. l. almoraima-gil, international journal of science and mathematics education, 2016, 14, 885-906. 21. ref. 3, pp. 164-172. 22. i. suay-matallana & j. r. bertomeu-sánchez, journal of chemical education, 2017, 94, 133–136. 23. euchems-teaching history of chemistry in europe. surveys (2007, 2015), last accessed 25 may 2019: https://www.euchems.eu/divisions/history-of-chemistry-2/references/ 24. real decreto 1631/2006, de 29 de diciembre, por el que se establecen las enseñanzas mínimas correspondientes a la educación secundaria obligatoria. boletín oficial del estado, 5, 5/1/2007, pp. 677773. 25. real decreto 1467/2007, de 2 de noviembre, por el que se establece la estructura del bachillerato y se fijan sus enseñanzas mínimas. boletín oficial del estado, 266, 6/11/2007, pp. 45381-45477. 26. ref. 25, p.119. 27. ref. 25, p. 126. 28. l. moreno-martínez & m. a. calvo-pascual, revista eureka sobre enseñanza y divulgación de las ciencias, 2019, 16(1), 110110. 29. kun survey (2004), last accessed 6 june 2019: https://www.mn.uio.no/kjemi/forskning/grupper/skole/ kun/resultater.html 30. utdanningsdirektoratet, current chemistry curricula for upper secondary school, last accessed 6 june 2019: https://www.udir.no/kl06/kje1-01 31. ref 30, main areas, last accessed 6 june 2019: https:// www.udir.no/kl06/kje1-01/hele/hovedomraader 32. utdanningsdirektoratet, current science curricula for lower secondary school and first year of upper secondary school, last accessed 6 june 2019: https:// www.udir.no/kl06/nat1-03 33. utdanningsdirektoratet, draft for new curricula, last accessed 6 june 2019: https://www.udir.no/laring-ogtrivsel/lareplanverket/fagfornyelsen/ 73the history of the periodic system in spanish and norwegian secondary school textbooks 34. d. park & l. lavonen in critical analysis of science textbooks: evaluating instructional effectiveness (ed: m. s. khine), springer, dordrecht, 2013, p. 220. 35. scholarly publishers indicators in humanities and social science, last accessed 20 may 2019: http://ilia. cchs.csic.es/spi/rankings.html 36. full references to the textbooks are provided in the appendix. 37. for an analysis on the current role of atomic weight and triads in chemistry, see also zambon in this issue. 38. e. scerri, philosophical transactions royal society a, 2015, 373, 20140172. 39. m. kaji, h. kragh & g. palló, early responses to the periodic system, oxford university press, new york, 2015, pp. 50–51, 79. 40. d. i. mendeleev, 1889, in the question of the atom. from the karlsruhe congress to the first solvay conference 1869–1911: a compilation of primary sources (ed. m. j. nye), thomas, los angeles/san francisco, 1983. 41. e. g. mazurs, graphic representations of the periodic system during one hundred years, alabama university press, usa, 1974. 42. a. lykknes & b. van tiggelen, women in their element: selected women’s contributions to the periodic system, world scientific, singapore, 2019. 43. e. r. scerri, the periodic table. it story and its significance, 2007, oxford, oxford university press, pp. 142-146. 44. g. boeck in women in their element: selected women’s contributions to the periodic system (eds.: a. lykknes & b.van tiggelen), world scientific, singapore, 2019,pp. 112-123. 45. j. w. van spronsen, the periodic system of chemical elements. a history of the first hundred years, elsevier, amsterdam, 1969, pp. 238-240. 46. s. mendeléeff, an attempt towards a chemical conception of the ether, longmans, green & co., newyork/bombay, 1904, p. 26. 47. m. d. gordin in nature engaged. science in practice from the renaissance to the present (ed.: m. biagioli & j. riskin), palgrave macmillar, usa, 2012, p. 59. 48. m. d. gordin, ambix, 2018, 65(1), 30–51. 49. see boeck on meyer in this issue. 50. see h. sletten, naturvitenskap, mer enn bare fakta? ntnu-norwegian university of science and technology, norway, 2017, last accessed 6 june 2019, for a study of the inclusion of nos aspects in the tellus textbooks, grades 8–10: https://ntnuopen.ntnu.no/ ntnu-xmlui/handle/11250/2475745 51. publications such as the forthcoming volume in women and elements (ref. 42) may contribute to make women’s contributions more visible in the future. appendix: textbook samples norwegian textbooks (n1) p. r. ekeland, o-i johansen, s. b. strand, o. rygh & a-b jenssen, tellus: naturfag for ungdomstrinnet, 2007, aschehoug, oslo. (n2) h. s. finstad, e. c. jørgensen & j. kolderup, trigger, 2008, damm, oslo. (n3) m. frøyland, j. haugan & m. munkvik eureka! naturfag for ungdomstrinnet, 2006, gyldendal undervisning, oslo. (n4) e. steineger & a. wahl, nova: naturfag for ungdomstrinnet, 2014, cappelen damm, oslo. (n5) h. brandt & o. t. hushovd, kjemi 1, 2010, aschehoug, oslo. (n6) b.-g. steen, n. fimland & l. a. juel, aqua1: kjemi 1 grunnbok, 2010, gyldendal undervisning, oslo. (n7) t. grønneberg, m. hannisdal, b. pedersen & v. ringnes, kjemien stemmer 1, 2012, cappelen damm, oslo. (n8) m. hannisdal & v. ringnes, kjemi for lærere, 2nd ed., 2013, gyldendal akademisk, oslo. spanish textbooks cse-3 (3º eso) (s1) s. zubiaurre, a. m. morales, j. m. arsuaga & a. pérez, física y química 3. educación secundaria, 2011, anaya, madrid. (s2) m. c. vidal-fernández, f. prada, j. l. garcía & p. sanz martínez, física y química 3. eso: proyecto los caminos del saber, 2011, santillana, madrid. (s3) à. fontanet & m. j. martínez, física y química 3. educación secundaria: proyecto nuevo ergio, 2012, vicens vives, barcelona. (s4) a. peña, a. pozas, j. a. garcía-pérez, a. rodríguez & a. j. vasco, física y química 3. eso, 2007, mcgraw-hill, barcelona. (s5) i. piñar-gallardo, física y química 3. eso: proyecto adarve, 2011, oxford, madrid. cse-4 (4º eso) (s1) s. zubiaurre, a. m. morales, f. gálvez & i. molina, física y química 4. educación secundaria, 2012, anaya, madrid. (s2) m. c. vidal-fernández, f. prada, j. l. garcía & p. sanz-martínez, física y química 4. eso: proyecto los caminos del saber, 2011, santillana, madrid. 74 luis moreno-martínez, annette lykknes (s3) à. fontanet & m. j. martínez, física y química 3. educación secundaria: proyecto nuevo ergio, 2012, vicens vives, barcelona. (s4) a. cardona, j. a. garcía, a. peña, a. pozas & a.j. vasco, física y química 4. eso, 2008, mcgraw-hill, madrid. (s5) i. piñar-gallardo, física y química 4. eso: proyecto adarve, 2012, oxford, madrid. use-1 (1º bachillerato) (s1) s. zubiaurre, j. m. arsuaga, j. moreno & b. garzón, física y química 1. bachillerato, 2014, anaya, madrid. (s2) f. barradas , j. g. lópez, p. valera & m. c. vidal, física y química 1. bachillerato: proyecto la casa del saber, 2008, santillana, madrid. (s3) m. j. martínez & à. fontanet, física y química 1. bachillerato, 2012, vicens vives, barcelona. (s4) a. rodríguez, a. pozas, j. a. garcía, r. martín & á. peña, física y química 1. bachillerato, 2012, mcgraw-hill, madrid. (s5) m. ballestero & j. barrio, física y química 1. bachillerato: proyecto tesela, 2008, oxford, navarra. use-2 (2º bachillerato) (s1) s. zubiaurre, j. m. arsuaga & b. garzón, química 2. bachillerato, 2012, anaya, madrid. (s2) c. guardia, a. i. menéndez-hurtado & p. prada, química 2. bachillerato: proyecto la casa del saber, 2011, santillana, madrid. (s3) à. fontanet, química 2. bachillerato, 2014, vicens vives, barcelona. (s4) a. pozas, r. martín, a. rodríguez & a. ruiz, química 2. bachillerato, 2009, mcgraw-hill, madrid. (s5) j. peña & m. c. vidal, química 2. bachillerato: proyecto tesela, 2009, oxford, vizcaya. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo substantia. an international journal of the history of chemistry 6(1): 13-23, 2022 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1524 citation: dei l. (2022) creativity in the art, literature, music, science, and inventions. substantia 6(1): 13-23. doi: 10.36253/substantia-1524 received: dec 03, 2021 revised: jan 04, 2022 just accepted online: jan 08, 2022 published: mar 07, 2022 copyright: © 2022 dei l. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature articles creativity in the art, literature, music, science, and inventions luigi dei dipartimento di chimica “ugo schiff ”, università degli studi di firenze, via della lastruccia, 13, 50019 sesto fiorentino (fi), italy email: luigi.dei@unifi.it abstract. this essay aims to stimulate reflection on the creativity characterising homo sapiens in the different realms in which it occurs. over recent decades scholarly research into creativity has extended the original concept, restricted to geniuses, to a broader field that encompasses the qualities and abilities of every individual, in line with a democratisation of the creative act. however, the aim of this contribution is to illustrate the creativity of geniuses, referring to examples in various fields, according to poincaré’s definition of connecting pre-existing elements into new combinations that are novel and useful. the objective of this study is to show that pre-existing elements can be found in works of art, literature, poetry, and music, as well as in scientific discoveries or inventions. having demonstrated the existence of concrete and real analogies in the various – and apparently profoundly different – fields of human creativity, a second objective was to construct a convincing proof of a notion of a culture characterised by an essential unity, without any separation between humanities and sciences. i trust that the analysis of the creative acts that generated picasso’s les demoiselles d’avignon, michelangelo’s vaticano pietà, primo levi’s the periodic table, giacomo leopardi’s l’infinito (the infinite) and wisława szymborska’s liczba pi (pi), the beginning of beethoven’s fifth symphony and brahms’ fourth symphony the finale of stravinsky’s sacre du printemps, the discovery of x-rays by wilhelm conrad röntgen and of the therapeutic properties of lithium salts for psychiatric disorders by john frederick joseph cade, the invention of incandescent light bulbs by thomas alva edison and many other inventors and of the electronic television by philo taylor farnsworth, may succeed in achieving the first objective and, by extension, the second also. keywords: creativity, genius, cultural unity, science, art, literature, music, inventions. 1. introduction it is well known that the literature on creativity has significantly evolved from the initial approach focused only on creativity as a peculiarity of geniuses in the various domains of human activity to what it has recognised as a democratisation of the phenomenon.1-6 in particular, in a recent very accurate and in-depth study by corazza, a detailed recognition of the literature about this passage from creativity by only geniuses to a broader meaning including qualities and abilities by every individual has been done.7 in the same paper, http://www.fupress.com/substantia http://www.fupress.com/substantia 14 luigi dei besides discussing this phenomenon of “creativity for all”, some other very interesting topics are considered, as the mental processes associated with this broad vision of creativity and even the socio-cultural aspects.8 indeed, the state of the art of the literature allows individuating another further extension of the domain where creativity takes place, in the sense that creativity not only belongs to every human being, but it is also going to become the most important skill for the hyper-technological societies of the future.9 considering this enlarged vision of creativity, it is possible to extend the classical definition according to which creativity requires both originality and effectiveness, in order to contemplate several other requirements, as novelty, utility, aesthetics and authenticity.10-13 in this context, according to the work by weisberg who focused the attention on the intentional novelty as the unique criterion eliminating the effectiveness and trying to bypass the question of value assessment to individuate the novelty and/or originality, we may recognise three pragmatic definitions of creativity as reported in the literature.7,14 according to this background, which refers to creativity in a static view, many scholars have investigated the topic of a dynamic concept of creativity, where the adjective potential is put before originality and effectiveness, with the aim of taking into account all the inconclusive outcomes and stressing the dynamic nature of creativity, as selecting a focus, generating the outcomes through complex processes where inconclusive outcomes play an important and decisive role, assessing them, and finally transforming the outcomes to knowledge.7 independently on this wide vision of creativity, it is worthwhile to recall that, despite the new achievements on the creativity concept above resumed, it remains valid one of the most interesting and comprehensive definitions of creativity which underline originality and effectiveness, like that described by poincaré according to whom creativity can be summarised as the capacity of connecting pre-existing elements into new combinations that be useful.15 this idea was at the centre of a very interesting talk given by umberto eco in florence, italy for the nobel foundation in 2004 which is titled combinatoria della creatività (combinatory of creativity).16 it is interesting to notice that the “usefulness” to which poincaré refers is more appropriately relative to the beauty rather than to the effectiveness. of course, he thinks of beauty not in a strictly aesthetic sense, but rather in the view of mathematicians, that is something associated with elegance, harmony, the economy of signs, operational correspondence to the aims.17 it is curious and intriguing that this idea of connecting things thought at the beginning of the 20th century by poincaré is repeated almost identically by one of the fathers of the ict industry, steve jobs, who defined creativity in a very concise and incisive way. “creativity is just connecting things. when you ask creative people how they did something, they feel a little guilty because they didn’t really do it, they just saw something. it seemed obvious to them after a while. that’s because they were able to connect experiences they’ve had and synthesize new things. and the reason they were able to do that was that they’ve had more experiences, or they have thought more about their experiences than other people. unfortunately, that’s too rare a commodity. a lot of people in our industry haven’t had very diverse experiences. so, they don’t have enough dots to connect, and they end up with very linear solutions without a broad perspective on the problem. the broader one’s understanding of the human experience, the better design we will have.”18 it is obvious that what is written until now about creativity strongly clashes with the etymology of the terms ‘creativity’ and ‘to create’, according to which the word comes from the latin creare with shares with the word crescere (to grow in english) the root kar.19,20 indeed, the most common meaning of the word creativity is associated with the ‘making from nothing’, which is referred especially to god and that, in a figurative sense, becomes inventing, generating new and original things.1-14 in the sanskrit language kar-tr is ‘the person who makes’ (from nothing), the ‘creator’.19 leaving this divine interpretation to philosophy and theology and reminding the previous introductory remarks on creativity, in particular as defined by poincaré, it is worthwhile to mention that even marcel proust agrees, albeit more lyrically, with poincaré. «the only true voyage of discovery, the only fountain of eternal youth, would be not to visit strange lands but to possess other eyes, to behold the universe through the eyes of another, of a hundred others, to behold the one hundred universes that each of them is; […]».21 this lyric vision according to which the true discover, the fruit of the creative act, does not consist in finding new territories, but rather in seeing them with different eyes, perfectly matches with poincaré’s statement where the new territories are simply the pre-existing elements that the creator succeeds to connect generating originality and effectiveness, due to his ability in seeing them in a new combination thanks to his capacity in seeing them with different eyes. in conclusion, we can imagine creativity as an unlimited domain, because the pre-existing elements are in the number of billions and billions, and the combinatory calculus individuates several combinations truly tending to infinite. therefore, we could define creativity as a bottomless pit; indeed, such pit has two negative aspects not coherent with creativity: it is dark, and one has to dive in a random fashion and therefore it is almost impossible 15creativity in the art, literature, music, science, and inventions to sharpen one’s different eyes, to use proust’s expression. another metaphor for creativity is perhaps more appropriate: a sea that offers always new and unpredictable horizons. the present paper aims to illustrate with some examples taken from the art, music, literature, poetry, science, and the world of inventions how creativity continuously opens these new horizons simply by connecting pre-existing elements in some combinations that generate originality and novelty. by this approach we hope to succeed in extending the poincaré’s definition from the domain of the mathematical invention for which it was coined to all the other fields of the human creativity.15 indeed, we will revisit some fruits of creativity in the various domains of human activity we mentioned above discovering many analogies and to possibly conclude that there is no division, in contrast with snow’s idea, between science and art, science and literature, and that humanistic and scientific cultures are two complementary sides of the same medal hanging from the neck of homo sapiens.22-23 2. creativity in art to investigate the connection between pre-existing elements used to create new original and novel combinations in art, two examples will be illustrated, one from painting and the other from marble sculpture. the painting by pablo picasso les demoiselles d’avignon (https://w w w.moma.org/collection/works/79766) has been the subject of several studies focusing on its novelty and, above all, on the idea that it could represent the starting point of the nascent cubism.24-25 the pre-existing elements can be recognised in the five women who had been already represented in the very famous painting cycle dedicated to les baigneuses by paul cézanne. (see for example https://joyofmuseums.com/museums/ united-kingdom-museums/london-museums/the-national-gallery-london/masterpieces-of-the-national-gallery/ bathers-les-grandes-baigneuses-by-paul-cezanne/). it is still controversial whether this reference was in picasso’s mind or not at the beginning of his project to paint his demoiselles d’avignon.26-27 nevertheless, apart from the shapes of the bodies, clearly inspired by the nascent cubism, it is evocative the idea that the blue of the triangles, trapezoids, other irregular figures and some outlines of the bodies can be traced back to the blue of the water close to the bathers. in this view, the bathing women and the blue of the water are the pre-existing elements, and the new, unexpected, and amazing connection is the geometry of the nascent cubism. among all the possible connections of these pre-existing elements – bathers and water – whether he is referring or not to cézanne, picasso sees with different and new eyes the shape of the bathing bodies and the blue-coloured geometries representing the water. another interesting case of connecting pre-existing elements into new combinations that generate beauty in art is the pietà by michelangiolo housed in saint peter’s basilica, vatican city. (https://www.flickr.com/photos/ jorge-11/48126571846) here the pre-existing elements are the well-known sculptural groups called pietà (compassion) mainly made of wood and typical of northerneurope with the german term vesperbild.28 the tradition until michelangiolo, both in painting and sculpture, was characterised by a rigid and geometric structure of the madonna and christ pair. the seated madonna was the vertical element to whom the dead christ in a horizontal position was opposed with a clear association with the geometry of the cross. all the paintings and sculptures focused on this iconography were characterised by rigidity: a striking example is the oil painting pietà by pietro perugino housed at the galleria degli uffizi in florence (https://www.flickr.com/photos/ nikonpaul/31992383947) and executed a few years before michelangiolo’s pietà in the vatican.29 moreover, another example of the strong rigidity of the sculptures is in a vesperbild by an anonymous german sculptor (ca. 13801400) conserved at liebieghaus skulpturensammlung, frankfurt-am-mein.28 (https://www.foglidarte.it/luoghimostre-eventi/699-vesperbild-alle-origini-delle-pieta-dimichelangelo.html) michelangiolo has in front of him the following pre-existing elements: the dead body of christ which of course must remain in an almost horizontal position, the seated madonna who has to hold her son. his extraordinary creativity is to combine these two figures to compose the group with two amazing novelties: softness replacing the rigidity and the horizontal/ vertical contrast that tends to dissolve. the artist concentrates his action to give softness to the marble – it may seem like a paradox or oxymoron while it is an inspired new combination of pre-existing elements! – working briskly at the madonna’s drapery. another virtuoso combination concerns the two arms of the madonna, obvious pre-existing elements. the left arm is completely autonomous and does not even touch christ and the left hand is directed towards us, as if inviting us to meditate with the typical gesture of an almost open hand exposing the palm.30 in sculpting the right arm michelangiolo succeeded in capturing an amazing combination by achieving both the softness and the realistic effect of supporting the heaviness of a lifeless body. he concentrates on the region of the marble that connects mary’s arm, the christ’s right arm and ribs: these 16 luigi dei three elements had to be connected in an original, never seen before way. the creative genius of michelangiolo is expressed with a combination in that area of the statue which produces a kind of an elongated “sausage” of flesh between the arm and the ribs due to the firm hold of the madonna opposed to the weight of christ’s listless body. 3. creativity in literature and poetry probably the most impressive example of the connection of pre-existing elements ingeniously combined to generate the creation of a literary work is il sistema periodico (the periodic table) by p. levi.31 in this wonderful book the writer, a chemist, succeeds in creating one of the most original connections of pre-existing elements. indeed, he starts from the chemical elementary elements of the mendeleev’s table, the bricks of the whole universe, and he associates to each of the selected elements – twenty-one in total – an autobiographical life experience. two extraordinary combinations are worthwhile mentioning in relation to the aim of the present contribution. the first deals with story that we find in the central pages of the book – the eleventh, entitled cerium – where the pre-existing chemical element, apparently completely removed from the dramatic experience of the lager deportation, becomes the fulcrum around which the theme of the “saved and drowned ” is developed, building in a few pages one of the crudest and most realistic testimonies of the shoah.32 in the second – the book’s last one, entitled carbon – the masterful combination of pre-existing elements is that between carbon, the very atom of life and the author’s act of writing: the continuous panta rei of the matter finds concrete realisation through a “labelled” carbon atom that passes from a compound to another travelling in space and time until it arrives in levi’s brain, driving his pen or typewriter to write the final full stop of both the story and the book. keeping the focus on levi’s work, there is another excellent example of an almost jarring combination between two elements: a make-up item such as lipstick and its main chemical component called alloxan which is also found in chicken droppings, a kind of revival of the old latin motto aurum de stercore! «the fact that alloxan, destined to embellish ladies’ lips, would come from the excrement of chickens or pythons was a thought which didn’t trouble me for a moment. […] i will go further: far from scandalizing me, the idea of obtaining a cosmetic from excrement, that is, aurum de stercore (“gold from dung”), amused me and warmed my heart like a return to the origins, when alchemists extracted phosphorous from urine.» (see ref. 31 english transl. story “nitrogen”, pp. 180-181). some years before the publication of the book by the chemist-writer levi, the italian songwriter-poet fabrizio de andré combined the same elements in his very famous song via del campo: «dai diamanti non nasce niente, dal letame nascono i fiori» (transl. « diamonds bring nothing, manure brings flowers »).33 concerning creativity in poetry, it is particularly interesting to analyse two different examples: the poems l’ infinito (the infinite) by the italian g. leopardi and liczba pi (pi) by the polish w. szymborska.34-35 the theme of the infinite is a subject that drew the interest of philosophers, theologists, mathematicians, physicists and astronomers alike since the beginning of human civilisation. indeed, even writers and poets have been fascinated by this topic, but the amazing ways that leopardi finds to describe the infinite in his poem are truly unparalleled. leopardi, according to poincaré’s definition of creativity, establishes several new combinations (see bold below) by connecting pre-existing elements.15,35 the hedge as the limit of finiteness and the farthest horizon as a symbol of infinity; the visual boundless spaces opposed to the auditory, superhuman silences; the same silence and the voice both combined with the wind that moves the plants; the present time perceived through its sound, that is, the living season as opposed to eternity, dead, silent; the final paradoxical and oxymoronic connection between the drowning of the thought on the one hand and the shipwreck of the thinker at the other. how many combinations of these pre-existing elements could the poet choose? we can very well say, an infinite number! but leopardi selected the ones marked in bold below in the poem quoted in its entirety (box 1). we could venture that the reason why among the various possibilities for such combinations only some – very few – extraordinary ones, the fruit of the ingenious creativity, succeeded in generating eternal cultural products, resides in a kind of evolutionary theory involving natural selection. the literary “species”, the fruit of creativity, that show the best “fitness” to the judgment of the posterity survive and do not become extinct, all the others do not survive the natural selection process and end up in oblivion. something similar has been established by a group of scientists who have recently concluded that mutations and gene variability explain why a lot of music of a single genre with various species is produced in each period. then, the free choices of the listeners determine the pressure of the external environment – fitness – and cause some species to become extinct, making certain others durable and transmissible for centuries.37 another fantastic example of an ingenious and incredible combination of pre-existing elements used to 17creativity in the art, literature, music, science, and inventions build a wonderful, unique, and original poem is liczba pi (pi) by the polish poetess w. szymborska.34 in this poem there are a number of brilliant connections of many pre-existing elements to constitute an extraordinary combination: a transcendental number, the number pi, is the pretext to lyrically suggest reflections on mankind, nature, life, consciousness, eternity. a poetic way to look at an ancient philosophical subject, that of finiteness and infinity, thanks to the very ingenious combinations: “five nine two because it never ends”, “the longest snake on earth calls it quits at about forty feet”, but it “doesn’t stop at the page’s edge” and finally it nudges the “sluggish eternity to continue” (box 2). starting from an ordered, infinite set of integers that seem randomly put one behind the other, and which instead represent a very tangible concept, i.e., the ratio between the length of a circle and its diameter, the poetess combines some elements to evoke feelings and emotions perfectly succeeding in making warm and throbbing what is considered by everybody one of the coldest and driest objects, a number! another perfect demonstration of what poincaré intended for connection of pre-existing elements to generate an ingenious combination. 4. creativity in music trying to apply poincaré’s definition of creativity to music is a truly difficult challenge, since the pre-existing elements are the most abstract and intangible. so far, the pre-existing elements have been well tangible and concrete, like marble or coloured pigments, or intangible like words, but still evoking specific concepts or things. in music the combination is made of sounds whose physical frequency and mathematical duration give melody and rhythm, whereas fourier’s spectral analysis and simultaneous presence of different frequencies give timbers and harmony, respectively.37 it is almost impossible to show how some combinations of sounds originate music that becomes original and encounters the appreciation of the listeners: therefore, the strangest and somehow most absurd combination of pre-existing elements which will be illustrated as capable of originating novelty and originality is that of sounds and silence, that is, the use of breaks in music generating something truly original and ingenious. every musical piece obviously starts from silence, but we cannot conclude that the combination between the silence before the first sounds of the musical piece represents a demonstration of an ingenious combination of pre-existing elements, i.e., silence and sound. nevertheless, there are some cases where the composer intentionally combines a break with the first sounds to start his or her musical piece in a very original way, as if the music gushed out of nowhere. two very famous examples where poincaré’s definition could be applied to creativity in music are the beginning of beethoven’s 5th symphony and that of brahms’s 4th symphony. how did beethoven succeed in starting his symphony so that just based on its beginning it was celebrated as “the destiny knocking on the door”? by a combination of a quaver rest, followed by three identical quaver notes and by a final minim note with a crown. the knocking on the door by the destiny is a rest, that is, a silence! the combination between the rest and the four l’infinito sempre caro mi fu quest’ermo colle, e questa siepe, che da tanta parte dell’ultimo orizzonte il guardo esclude. ma sedendo e mirando, interminati spazi di là da quella, e sovrumani silenzi, e profondissima quiete io nel pensier mi fingo; ove per poco il cor non si spaura. e come il vento odo stormir tra queste piante, io quello infinito silenzio a questa voce vo comparando: e mi sovvien l’eterno, e le morte stagioni, e la presente e viva, e il suon di lei. così tra questa immensità s’annega il pensier mio: e il naufragar m’è dolce in questo mare. the infinite always dear to me was this solitary hill and this hedge, that excludes so great a part of the farthest horizon from my sight. but sitting and gazing, boundless spaces beyond it, and superhuman silences, and deepest quiet, i envision in my mind; where almost awed is the heart. and as the wind i hear sighing through these plants, i that infinite silence to this voice go comparing: and i remember eternity, and the dead seasons, and the present and live one, and its sound. so in this immensity my thought is drowned: and sweet to me is shipwreck in this sea. box 1. 18 luigi dei subsequent notes generated what is considered one of the most powerful beginnings of a musical work.38 the music gushes out of nowhere and it makes it in an abrupt and violent way thanks to the combination of the pre-existing elements above described. but the music can also gush out of nowhere like a silence that softly and gently becomes music, as if silence contained somehow music. brahms succeeds in making this miracle with the beginning of his 4th symphony: beethoven started with the silence – the quaver rest – here brahms starts with a quasi-silence, with all the instruments having a crotchet rest while first and second violins playing an upbeat b crotchet with anacrustic rhythm. the creativity manifests itself with this ingenious combination and the conductor’s ability consists of realising this gushing out of music from nothing: one of the best realisations is by carlos kleiber, who brings music out of thin air with a masterful gesture.39 very appropriately, they have written that “this opening is a prime example of brahms’s natural ability to compose within the strictest and oldest of structures, yet with a fluid, modern sound that belies its rigidity”.40-42 one could conclude that in this case the quasi-nothing represented by those rests and by that short upbeat note he creates something truly original, novel, effective, and useful.10-15 but the rests, the silence, can also be an ingenious invenliczba pi podziwu godna liczba pi trzy koma jeden cztery jeden. wszystkie jej dalsze cyfry też są początkowe pięć dziewięć dwa, ponieważ nigdy się nie kończy. nie pozwala się objąć sześć pięć trzy pięć spojrzeniem, osiem dziewięć obliczeniem, siedem dziewięć wyobraźnią, a nawet trzy dwa trzy osiem żartem, czyli porównaniem cztery sześć do czegokolwiek dwa sześć cztery trzy na świecie. najdłuższy ziemski wąż po kilkunastu metrach się urywa. podobnie, choć trochę później, czynią węże bajeczne. korowód cyfr składających się na liczbę pi nie zatrzymuje się na brzegu kartki, potrafi ciągnąć się po stole, przez powietrze, przez mur, liść, gniazdo ptasie, chmury, prosto w niebo, przez całą nieba wzdętość i bezdenność. o, jak krótki, wprost mysi, jest warkocz komety! jak wątł y promień g wiazdy, że zakrzy wia się w lada przestrzeni! a tu dwa trzy piętnaście trzysta dziewiętnaście mój numer telefonu twój numer koszuli rok tysiąc dziewięćset siedemdziesiąty trzeci szóste piętro ilość mieszkańców sześćdziesiąt pięć groszy obwód w biodrach dwa palce szarada i szyfr, w którym słowiczku mój a leć, a piej oraz uprasza się zachować spokój, a także ziemia i niebo przeminą, ale nie liczba pi, co to to nie, ona wciąż swoje niezłe jeszcze pięć, nie byle jakie osiem, nie ostatnie siedem, przynaglając, ach przynaglając gnuśną wieczność do trwania. pi the admirable number pi: three point one four one. all the following digits are also initial, five nine two because it never ends. it can’t be comprehended six five three five at a glance, eight nine by calculation, seven nine or imagination, not even three two three eight by wit, that is, by comparison four six to anything else two six four three in the world. the longest snake on earth calls it quits at about forty feet. likewise, snakes of myth and legend, though they may hold out a bit longer. the pageant of digits comprising the number pi doesn’t stop at the page’s edge. it goes on across the table, through the air, over a wall, a leaf, a bird’s nest, clouds, straight into the sky, through all the bottomless, bloated heavens. oh how brief — a mouse tail, a pigtail — is the tail of a comet! how feeble the star’s ray, bent by bumping up against space! while here we have two three fifteen three hundred nineteen my phone number your shirt size the year nineteen hundred and seventy-three the sixth floor the number of inhabitants sixty-five cents hip measurement two fingers a charade, a code, in which we find hail to thee, blithe spirit, bird thou never wert alongside ladies and gentlemen, no cause for alarm, as well as heaven and earth shall pass away, but not the number pi, oh no, nothing doing, it keeps right on with its rather remarkable five, its uncommonly fine eight, its far from final seven, nudging, always nudging a sluggish eternity to continue. box 2. 19creativity in the art, literature, music, science, and inventions tion for a sensational final twist: the example that comes to mind is represented by those three rests – dotted quaver, crotchet, dotted quaver – after the rapid ten-note sequence by flutes that precedes the thunderous finale chords of the sacre du printemps by igor’ fëdorovič stravinskij. 5. creativity in science two examples of a combination of pre-existing elements to create new progress in science by means of an important and fundamental discovery will be illustrated. it is interesting to notice that a special role was played also by serendipity, i.e., “the faculty or phenomenon of finding valuable or agreeable things not sought for”.43 therefore, the pre-existing elements can be found with some serendipity, but creativity consists of connecting and combining them so as to lead to a new discovery. in relation to this aspect, it is worth mentioning that in science, unlike in the other branches of the human activity described in this work, the above-mentioned combination/connection is associated with the importance of inductive reasoning in ‘creating’ creativity. we could state that inductive reasoning is some kind of prerequisite for the selection of the pre-existing elements to be combined; in other words, inductive reasoning is the sieve that separates wheat from chaff, but the ‘creative jump’ is linked to the ability of homo sapiens to combine the wheat grains to give an ‘original, novel, and useful bread’! the first example is the discovery of x-rays by wilhelm conrad röntgen in 1895. it is well known that several pre-röntgen experiments had evidenced radiations of some kind, but as well characterised as to differ from cathode rays and fluorescence radiation.44 firstly, there were morgan’s experiments in 1785, followed by many other observations involving such great scientists as h. davy, m. faraday, p. lenard, w. crookes, f. sanford, h. helmholtz, h. hertz, i. puluj, n. tesla.45-47 it is difficult to ascertain the true origin of röntgen’s x-rays discovery, but the received hypothesis, as reported by the most important biographers, is that he succeeded in isolating the effects of fluorescent radiation visible to the naked eye, by wrapping in black cardboard a crookes tube where experiments of electric discharges on very rarefied gases were carried out. apparently, the differentiation with the already known cathode rays occurred by serendipity – as is testified by lenard in 1888 who in his experiments observed the effects of cathode rays (perhaps, unknowingly, even of x-rays!) on photographic plates outside the tube in the region of the cathode and measured their penetration through various materials.47-49 indeed, at 1 m distance from the cathode of the crookes tube there was a fluorescent screen painted with barium platinocyanide that showed a green glow even when nothing was apparently coming out of the tube. röntgen thought to connect and combine the following two pre-existing elements: (i) no visible fluorescence coming out from the tube due to the black cardboard, (ii) a fluorescent screen painted with barium platinocyanide placed at a considerable distance far from the tube compared to lenard’s experiments. from this connection, röntgen drew a novel idea, the fruit of his creativity: some invisible rays coming from the tube were passing through the cardboard and succeeding in crossing 1 m of air to react with the barium platinocyanide making it fluoresce. two months of further experiments went by when he thoroughly investigated these new invisible rays before publishing his first paper. he decided to name the rays “x” same as the mathematical unknown.50 but the combination of pre-existing elements did not stop here: during the experiments, röntgen realised that one of the most impressive characteristics of such mysterious rays was the ability to go through some materials, such as paper, books, wood, but not others such as metals and stone. connecting this experimental evidence, he designed three ground-breaking experiments: he made the invisible rays going through three different objects and placed a few inches beyond each object a photographic plate and then darkened the whole room. the first object was a wooden box that contained the small metal weights of a balance; the second consisted in the various parts of his shotgun’s barrel; and the third was the hand of his wife. the amazing combination of preexisting elements originated in a very short time three extraordinary applications of the newly-discovered x-rays: metal detector, quality control in the metal industry, and radiology and radio-diagnostics in medicine! the second example deals with the discovery of lithium-ion therapy for manic depressive patients by the australian psychiatrist dr john frederick joseph cade who worked at the bundoora repatriation mental hospital in melbourne. here the connection and combination of pre-existing elements are truly unbelievable, also because the means and laboratories available to cade at that time were verging on what has been named “ramshackle pantry”.51 the first element from which cade started his research was a conviction, the classical hypothesis to be validated by experiments: depressive diseases (i.e., manic syndromes and bipolar disorders) could be due to chemical metabolic disorders that should determine a change in the chemical composition of the urine of his patients compared to that 20 luigi dei of healthy people. with the aim of checking the validity of such assumption, he injected urine of both ill and healthy people into the abdominal cavities of guinea pigs and, probably due to some preliminary not statistically reliable results, he found that urine from patients with depressive diseases was more toxic to the guinea pigs than that of healthy people.51-53 this unreliability of the experimental result was the serendipity touch, since it convinced cade about the rightness of his hypothesis and led him to focus on the two main nitrogenous components of urine, for which it was important to ascertain the possible specific lethal constituent that, coherent to the hypothesis and the preliminary unreliable experiments, could be particularly concentrated in the urine of ill patients.55 the treatment with the urea solutions led to the same effect of urine from ill patients, but it was impossible to explain the greater toxicity of the urine of manic patients simply in terms of higher concentrations of urea. indeed, urea is toxic for guinea pigs from a certain threshold of concentration and there was no difference in the effect of the urine from healthy or ill people since it was the unreliability of the experiment described, a true mistake, that was going to generate the discovery! cade had the idea to add the second constituent, uric acid, to test whether it had a synergistic – positive or negative – effect, or not.54,55 in his first article in 1947, cade noted that uric acid had a slightly enhancing effect on the toxicity of urea.56 this result prompted him to continue this research strategy, but unfortunately, it was impossible to increase the concentration of uric acid due to its very scarce solubility in water (0.06 g/l equivalent to 3.57.10-4 m compared to 1,193 g/l equivalent to ca. 20 m of urea). therefore, cade selected lithium salt as it was the most soluble salt of uric acid, to increase the concentration of the possible enhancer of urea toxicity. to cade’s surprise, when he injected the guinea pigs with lithium urate in conjunction with urea, the toxicity was reduced rather than enhanced, suggesting that the lithium could have been protective. cade further explored this lead by injecting the guinea pigs with lithium carbonate in conjunction with urea, and once more observed a reduced toxicity. he concluded that lithium itself provided a protective effect against the action of urea. this belief then prompted him to wonder whether lithium per se would influence his guinea pigs. injecting them with large doses of lithium carbonate, he found them to become lethargic and unresponsive. now we can deduce that the lithium ion itself had a protective function against the convulsant death caused by toxic doses of urea.55,56 a mistake and a touch of serendipity coupled with the combination and connection of some pre-existing elements by the creative mind of dr cade: the toxic effect of urea and uric acid, the low solubility of uric acid, the higher solubility of lithium urate, the even higher solubility of li2co3 (1.75.10-2 m) resulted in a novel, original, useful, and effective discovery that had to wait another twenty years to become a worldwideaccepted therapy. but this is another story. 6. creativity and inventions even the inventors can be considered creative in the sense illustrated in the previous section: two examples will be described to demonstrate once again the creative act always as a combination of pre-existing elements. the first case concerns the invention of the incandescent light bulb; despite the fact that the invention is attributed to thomas alva edison the story is much more complex and involves several more inventors who worked for many years between the end of the 19th and the beginning of the 20th centuries.57 these inventors combined pre-existing elements into an ingenious invention that led the american writer oliver sacks to entitle “light for the masses” one of the chapters of his extraordinary book uncle tungsten: memories of a chemical boyhood and here i will illustrate the preexisting elements and the ingenious combination and connection thereof. the pre-existing elements were the following: (i) joule effect condensed in the formula q = i2.r.t, (ii) black body radiation, (iii) heat transfer by conduction, convection, and radiation, (iv) oxidation reactions, and (v) matter phase transitions. the combination of the first two elements led many inventors to design an ingenious new object consisting of a filament of matter that, when heated by an electric current at high temperature, emitted radiation in the visible region of the spectrum as a black body. the third element combined with the fourth convinced these ingenious men to put such filaments in a vacuum to enhance radiation against conduction and convection and inhibit oxidation processes that caused the light bulbs to have a very short lifetime. the combination with the fifth element was the most ingenious and came later: instead of the vacuum an inert gas like argon was used. this prevented oxidation and simultaneously favoured conduction and convection, losing a little bit of radiation power, but lowering considerably the sublimation of the tungsten filament, because of the decrease in heat produced during this transition phase. as a matter of fact, sublimation reduced the life of the filament and caused a blackening of the glass due to condensation of tungsten vapour: in this way, for the first time in the history, humans succeeded in illuminating the dark not by 21creativity in the art, literature, music, science, and inventions chemical combustion, but by radiation-induced electricity. it was the beginning of a new era.59 the second example is the invention of the electronics-based television. probably this is the best example to illustrate poincaré’s definition of creativity. philo t. farnsworth was an extraordinary inventor and the idea to design a way to capture images in movement and reproduce them on a fluorescent screen came to his mind after observing a farmer ploughing a field.60 the pre-existing elements were the following: (i) certain materials, submitted to an electrical potential when illuminated have the properties to generate an electrical current proportional to the illumination intensity, due to a decreased resistance induced by the light, (ii) the electrical signals so obtained can be transmitted at distance by means of radiofrequency waves, (iii) the cathode rays produced in a crookes tube manage to illuminate the phosphors in the internal side of a fluorescent screen, and (iv) the electrical signals of element (ii), that are a faithful mirror of the image collected, can be used to attenuate the cathode rays according to the inverse proportionality law (i.e., strong electrical signal = high illumination of the photosensitive material = weak attenuation of the cathode ray = high illumination of the television screen). the extraordinary connection of these four elements was invented ingeniously by farnsworth thinking of a fast-moving plough. according to the italian standard, the plough (cathode tube emitting cathode rays) ploughed the field (scanned the fluorescent screen) with 625 furrows (lines) repeated 50 times per second! the lines were constituted of alternated microscopic black (no light) and white (light) spots moving exactly in the same way they were collected by the camera. the viewer does not notice this process of image composition due to the double phenomenon of the high speed of the electronic brush and the persistence of the image on the retina of the human eye (1/16th of a second). 7. conclusions starting from the recent review of the literature on creativity research and recollecting the ever current definition by poincaré for the creativity in the mathematical invention, the present contribution tried to demonstrate that the creativity jumps typical of geniuses in the various domains of the human activity can be aptly described in terms of combination and connection of pre-existing elements to generate novelty, originality, and effectiveness.1-15 in particular, some examples of creativity outcomes in art, literature, poetry, music, science, and the world of the inventions were reviewed focusing on the pre-existing elements and on the ingenious combination and/or connection between them to generate the creative jump. the examples illustrated here, while belonging to apparently separate fields of human creativity, reveal, on the contrary, a common matrix precisely in the creative act by the genius who conceived it. in the end, we discovered the common traits of the creation of michelangiolo’s vaticano pietà, beethoven’s fifth symphony’s beginning, primo levi, leopardi or szymborska’s works, the x-rays’ discovery, or television and light bulbs inventions. besides confirming the shrewd intuition inherent in poincaré’s definition of creativity, it was demonstrated that the analogies found in the genesis of the above-mentioned products of creativity were very strong, enabling us to conclude that there is no division, in contrast with snow’s idea, between science and art, science and literature, and that the humanities and sciences are two complementary sides of the same medal hanging from the neck of the homo sapiens.22-23 8. acknowledgments the author expresses his deep gratitude to dr sonia carla torretta for the accurate and careful revision of the english language, and to dr lucia cappelli, librarian of the british 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2016), salt lake city, 2016. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 3(2) suppl. 1: 13-26, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-403 citation: c. j. giunta (2019) watt’s in a name? units of power and energy. substantia 3(2) suppl. 1: 13-26. doi: 10.13128/substantia-403 copyright: © 2019 c. j. giunta. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. watt’s in a name? units of power and energy carmen j. giunta le moyne college, 1419 salt springs rd. syracuse, ny, usa 13214 email: giunta@lemoyne.edu abstract. the origins and adoption of the units of power and energy, watt and joule, are examined, along with their relationships to the achievements of their namesakes, james watt and james prescott joule. the watt and joule came about as part of a group of practical electrical units named and defined in the second half of the nineteenth century. the development of that system and its relationship to the french revolutionary metric system and the current système international (si) are outlined. william thomson (later lord kelvin) and the siemens brothers had important parts in the story; their roles and the units named after them are also described. keywords. nomenclature, units, watt, electricity. introduction scientists are accustomed to eponyms, terms derived from the names of people.1 often the terms refer to laws, chemical reactions, or other discoveries, named for the putative discoverer of the phenomenon.2 fourteen chemical elements have been named directly for scientists, and another two indirectly (named after minerals which had been named after scientists). all 14 of the elements directly named for scientists are synthetic elements, discovered and named only in the years after the second world war. the scientists so immortalized include some who were themselves important discoverers of elements, such as the curies, glenn seaborg, and most recently yuri oganessian; others, such as copernicus, einstein, and mendeleev, discovered no elements, but are honored for other epochal scientific contributions. constants and units are also often named for scientists. as with elements, so with constants, the connection between the constant and the eponymous scientist is sometimes more direct, sometimes less. the planck constant, for example, is named for max planck, the first scientist to use it in a physical problem.3 planck gave the constant the symbol still used for it (h) and a value smaller by just over 1% than the currently fixed value. the avogadro constant, or its numerical value better known to chemists as avogadro’s number, on the other hand, is a quantity that amedeo avogadro never knew, even approximately. avogadro is best known for proposing that equal volumes of gas contain 14 carmen j. giunta14 carmen j. giunta equal numbers of molecules, but he had no idea of what that number might be. jean perrin named the quantity in avogadro’s honor early in the 20th century.4 names of units are the focus of this paper, in particular units of energy and closely related physical quantities such as power and force. the paper was motivated by curiosity over when and under what circumstances the current units of power and energy in the international system of units (système international, si) came to be proposed and adopted. as the title suggests, the watt and james watt are prominently featured. in the course of researching the watt, i learned that the tendency toward eponymy in physical units is more recent than i had expected, dating from the middle to later nineteenth century; that watt thought more about units than i had realized; that the path from the french revolutionary metric system to the twentieth-century si was far from straight; and that the watt was first defined as an electrical unit. the origins of the watt and the joule are so inextricable from the establishment of electrical units and standards in the nineteenth century that the main narrative in the paper (although not its main concern) is how those units and standards came to be. in service of the main focus on eponymy, though, digressions from that narrative include glimpses at aspects of the scientific careers of watt and joule and of two other eponyms prominent in the establishment of electrical units, namely william thomson (later lord kelvin) and the siemens brothers. and in order to round out the main narrative, the relationship of the electrical units to the metric system of units and to the current si will also be outlined. electrical units circa 1860 well before 1860, important force laws for electricity and magnetism had been discovered, and the fact that the two apparently different kinds of phenomena were in fact related was also known. the relationship between electricity and magnetism has implications for the units chosen to describe electromagnetic phenomena. for the purpose of understanding the origins of various electrical units, we may take coulomb’s electrostatic force law or ampère’s electromagnetic force law as foundational. force is a mechanical property with dimensions of m l t–2, where m represents the dimension mass, l the dimension length, and t the dimension time. the choice of one or the other force law as fundamental is arbitrary; however, the choice of either amounts to defining an absolute set of electrical and magnetic units. the set is absolute in the sense that all of the electrical and magnetic units within it would be related to already existing mechanical units. choosing cou lomb ’s law to be f unda menta l amounts to a choice of electrical units called absolute electrostatic units in which electrical charge has dimensions l3/2 m1/2 t–1; the dimensions of current, then, would be charge per unit time or l3/2 m1/2 t–2. however, if one takes ampère’s law to be fundamental, different dimensions result. absolute electromagnetic units have charges of dimension l1/2 m1/2 and currents l1/2 m1/2 t–1. (for more detail, see the appendix.) within an absolute system of units, further choices are needed before units are defined: one must also select the defining mechanical or dynamical units (that is, of length, mass, and time). the system favored in britain for scientific work at this time and eventually adopted more widely was the cgs system, in which lengths are specified in centimeters, masses in grams, and time in seconds. (later scientists would say simply that the centimeter, gram, and second are the base units of the cgs system; however, the term base unit was not yet coined.5 base unit is a useful term, and i will use it anachronistically in what follows.) the cgs electrostatic unit of charge is therefore 1 cm3/2 g1/2 s–1. the corresponding unit of current, then, is 1 cm3/2 g1/2 s–2. in germany, the preferred set of mechanical base units was the millimeter, milligram, and second;6 call it mms. under this system, the electrostatic unit of charge is 1 mm3/2 mg1/2 s–1 and that of current 1 mm3/2 mg1/2 s–2. obviously, electrostatic units have different magnitudes in the cgs and mms systems, even though they are both based on the same fundamental equation. and these units are different than the absolute units based on the electromagnetic force law. neither cgs nor mms electrostatic or electromagnetic units were of convenient magnitude for the practical electrical or magnetic applications of the time, such as telegraphy. submarine telegraph cables were laid in the 1850s, and the first attempt at a transatlantic cable also took place in that decade.7 not surprisingly, a desire for electrical and magnetic units such that a typical laboratory or commercial measurement was comparable in size to the unit (as opposed to many orders of magnitude greater or smaller) emerged around this time. such units were described as “practical.” as we will see below, practical units could be defined in terms of absolute ones (such as the ohm defined as 1010 mms units of resistance) or they could be based on arbitrary standards (such as werner siemens’s mercury standard for resistance). in the later nineteenth century, “practical” and “absolute” were often but not always used as though mutually exclusive, for the term 15watt’s in a name? 15watt’s in a name? units of power and energy absolute was often applied only to units whose relationship to other units in the system had a numerical factor of 1. thus, a unit defined as 1010 mms units of resistance might be called absolute in the sense that it is defined in terms of specified non-electrical units, although it is not itself “the” absolute unit of resistance in the mms system. whether absolute or practical, international units and standards were required for science, industry, and commerce, and they would be much discussed over subsequent decades. names and units just before the start of the formal and organized efforts to define electrical units and standards outlined below, two engineers on the atlantic submarine telegraph project floated a proposed system of practical electrical units. latimer clark and sir charles bright made a presentation at the 1861 british association for the advancement of science (baas) meeting and published their paper in the electrician shortly thereafter. “the science of electricity and the art of telegraphy have both now arrived at a stage of progress at which it is necessary that universally received standards of electrical quantities and resistances should be adopted,” they begin. they go on to propose four practical units, not connected to absolute mechanical units. and to illustrate the relationships among these arbitrary units, they suggest “for this temporary purpose let us derive terms from the names of some of our most eminent philosophers, neglecting … all etymological rules”.8 quantity name definition tension (i.e., electromotive force) ohma 1 daniell cell quantity (i.e., charge) farad charge induced by 1 ohma across 1 m2 plates separated by 1 mm dry air current galvat 1 farad per second resistance volt passes 1 galvat under 1 ohma tension the paper by clark and bright appears to be the beginning of eponymy in scientific units. later committees charged with describing electrical units followed their example, sometimes explicitly,9 although the names on their list were eventually attached to different quantities than they proposed. clearly, eponymy in other aspects of electrical research was already well established: clark and bright refer to daniell’s cells and to a galvanometer without remarking upon those terms. at the same 1861 conference in manchester where clark and bright made their proposal of electrical units, the baas at the behest of william thomson10 appointed a committee to report on standards of electrical resistance.11 the committee initially included several scientists who would become eponyms: alexander williamson (whose name is attached to a synthesis of ethers) and charles wheatstone (best known for the wheatstone bridge electrical circuit), as well as thomson (the thomson in the joule-thomson effect of cooling a gas by letting it expand through a porous plug, later to become lord kelvin). the committee rather quickly expanded its purview beyond standards of resistance, noting that such a resistance unit ought to be part of a coherent system of electrical units. the unit of resistance, and indeed, the other units of the system, ought to “bear a definite relation to the unit of work, the great connecting link between all physical measurements”.12 they advocated basing those electrical units on the “french metrical system” rather than the units in common use in britain. as might be inferred from their preference for the metric system, the committee was not insular or provincial. indeed, they solicited opinions from scientists throughout europe and as far afield as the united states (in the person of joseph henry, then secretary of the smithsonian institution and now an eponym for a unit of electrical inductance).12 in 1865, the committee specified a practical standard of electrical resistance. by now the committee had expanded to 12 members, including such eponymous luminaries as james clerk maxwell (equations of electricity and magnetism), james prescott joule (unit of energy; see below), and charles william siemans (unit of conductivity; see below).13 the resistance unit was intended to be equal to 1010 mm s–1. (an absolute electromagnetic unit of resistance would have dimensions of l t–1, so mm s–1 would be the electromagnetic unit of resistance preferred by germans such as wilhelm weber, who had done important work in this area.) the committee wanted their new standard to have “a distinctive name, such as the b. a. unit, or, as mr. latimer clark suggests, the ‘ohmad’”.10 this name was later changed to ohm, which became the first of yet another set of electrical and magnetic units, eventually to be known widely as the practical system. the committee had chosen its unit because it wanted a decimal multiple of a unit already in use (i.e., not something completely arbitrary or unrelated to existing systems) and because a physical standard of approximately this magnitude had already been developed and found convenient. members of the committee threw around ideas for names of units as well as for ways of indicating decimal 16 carmen j. giunta16 carmen j. giunta multiples or submultiples of units, for it was clear that at least some of the units of any coherent system would be of inconvenient size for at least some practical uses. c. f. varley, one of the committee members, wrote a letter to thomson in 1865 describing unit names he had discussed with latimer clark and fleeming jenkin. the letter tells thomson that clark had proposed the names galvad for potential, ohmad for resistance, voltad for current, and farad for quantity (or charge as we would say). the names for one million units would be galvon, ohmon, volton, and faron respectively. in effect, the multiple 106 was proposed to be represented by a suffix, -on. jenkin objected that denoting magnitude by an ending would lead to confusion, particularly in the case of unclear (“indiscreet”) writing, to which jenkin said he was prone; varley said that that problem also applied “to me and to you [thomson].” varley would like to see a french name on the list, perhaps ampère for the magnetic pole, but he objected to galvad “because galvani discovered next to nothing14.” we see in varley’s letter the same four scientists that clark and bright had in mind four years earlier, now associated with different quantities, but still not with the quantities that would eventually “stick” to their names. we also see an attempt, albeit not adopted, to conveniently refer to multiples of a unit, recognizing that no system would have magnitudes convenient for all applications. the baas committee on standards of electrical resistance continued to meet and report until 1869, investigating such matters as the relationship between electromagnetic and electrostatic units.15 in 1872 the baas appointed another committee, this one “for reporting on the nomenclature of dynamical and electrical units.” included on the new committee were four members of the earlier committee: thomson, maxwell, siemens, and jenkin.16 the following year, that committee reported a preference for the cgs system for both electrical and dynamical units. it proposed a terminology for expressing decimal multiples by appending the cardinal number of the appropriate power of ten to the name of a unit (for example centimeter-nine = 109 cm) and for expressing submultiples by prefixing the ordinal number of the absolute value of the relevant power of ten to the name of a unit (for example, ninth-second = 10–9 s). this suggestion came from committee member g. johnstone stoney, who was the lone dissenting voice against selecting the centimeter as a base unit of the recommended system. his argument that the base unit ought not to include a multiplicative prefix was apparently less persuasive than thomson’s favoring a system in which the density of water was unity. this report proposed names for the cgs units of force (dynamy, dynam, or dyne), work (ergon or erg), and power (ergs per second).17 looking back from the twenty-first century at the development of eponymy in units, this report appears to be a pause. it mentions the ohm, volt, and farad, practical electrical units previously defined by a baas committee that included several of the same members. but for dynamical units, the committee selects names based on greek roots, a classical language still influential in british higher education. international units although the baas consulted widely, expressed a preference for the “french metrical system,” and proposed an international menu of eponyms, it was a national and not an international body. the 1870s and 1880s would see international bodies and international agreements concerning weights and measures. seventeen nations signed the convention du mètre in 1875, thereby establishing the bureau international des poids et mesures (bipm, international bureau of weights and measures) to be directed by an international committee (cipm, comité international des poids et mesures) which itself is under a general conference (cgpm, conférence générale des poids et mesures) consisting of delegates of the member states. the initial signatories were mainly from countries of europe or eurasia (i.e., the russian and ottoman empires), along with a few from the americas. the principal nation that persists in employing non-metric units in domestic commerce, the united states, was among the original signatories. the united kingdom, was represented at the 1875 conference that led to the treaty, but it declined to sign until 1884. the bipm was initially charged with maintaining prototypes of the meter and kilogram, and thermometry and geodesy were also included within its purview. in 1921, coordination of electrical units and standards was added to its range of responsibilities.18 the birth of the metric system in revolutionary france during the 1790s is a remarkable story, summarized here in only the briefest outline. the revolution’s wholesale overthrow of feudal institutions enabled a widespread centralizing and rationalizing reform of weights and measures to replace a patchwork of regional units. in 1790 talleyrand, then bishop of autun and a member of the national assembly, brought up reform of weights and measures in that assembly. after receiving a favorable report, that body decreed in may 1790 that a new set of uniform weights and measures be drawn up. the decree directed the king to “beg his majesty of britain to request the english parliament to concur with 17watt’s in a name? 17watt’s in a name? units of power and energy the national assembly in the determination of a natural unit of measures and weights.” louis xvi, still king of france at the time, sanctioned the decree in august.19 the british declined to participate in the project. the decision to define the meter as the 1/10,000 of a quadrant of the earth’s circumference and to determine its value by measuring an arc of a meridian from dunkirk to barcelona is described, along with the epic execution of the survey, in the measure of all things by ken alder.20 reform of weights and measures continued as the revolutionary government changed (to the convention), decreed a new calendar, suppressed the académie des sciences, and purged the commission of weights and measures. a law of 18 germinal, year iii, (known elsewhere on the continent as 7 april 1795), defined the new units: the meter, the are (an area of a square with a 10-m edge), the stere (a meter cubed), the liter (the capacity of a cube with side 1/10 m), and the gram (mass of a cube of water with side 1/100 m at the melting point of ice).21 in 1798, another attempt was made to give the new system international standing by inviting european scientists to participate in the final stages of defining its standards. invitations were issued by foreign minister talleyrand to nearby countries neutral in the ongoing european hostilities or allied to france (such as the short-lived batavian, cisalpine, helvetian, ligurian, and roman republics).22 platinum standards were made for the meter and the kilogram in 1799, and a law of that year defined the units in terms of the standards. the new system was widely used by savants and bureaucrats and taught in the centralized schools, but it did not displace older units in the marketplace for more than a generation afterwards.21 at the time of our principal narrative in the 1860s, metric units were widely used in science throughout europe, but the units considered basic were typically neither the meter (but the centimeter or millimeter) nor the kilogram (but the gram or milligram). in 1869, the french government (second empire under napoleon iii) invited representatives from european, eurasian, and american countries to take part in an international commission of the meter with an eye toward propagating the use of the metric system in international commerce and constructing new international prototypes of the 1799 standards. this commission, which met in 1870 (just after the start of the franco-prussian war) and in 1872, led to the convention of the meter in 1875 and the permanent international institutions established therein.23 not long afterward, in 1881, the first international electrical congress was held in paris under the auspices of the french government and in conjunction with an international electrical exposition. it would be the first of many such international electrical meetings in the late nineteenth and early twentieth centuries held at international commercial expositions. members of this congress came predominantly from europe, but japan was also represented as well as several countries from the americas. among the actions taken was the adoption of a set of practical electrical units. the congress’s commission on electrical units passed seven resolutions, including: to base its units on a cgs foundation; to keep the practical units ohm and volt with their current definitions of 109 cgs units of resistance and 108 of electromotive force respectively; to define an ampère as the current produced by one volt through one ohm resistance; to define a coulomb as the quantity (charge) such that an ampère is one coulomb per second; and to define a farad as the capacity such that a coulomb in a farad yields a volt.6 these extensions to the practical system of electrical units came after some drama inside the conference chamber. they were adopted after the congress had been adjourned without conducting any business on the previous day, september 20. on that day, the french minister of posts and telegraphs, presiding, opened the meeting and immediately presented his colleague, the foreign minister. the latter told the assembly that a telegram had just announced the death of us president garfield. “he thought that considering the bereavement that fell upon a friendly nation the assembly would wish to show its deep sympathy by immediately adjourning the meeting”.24 apparently, some drama regarding the units in question took place behind the scenes at the conference as well. éleuthère mascart was secretary of the section of the congress that dealt with electrical units. he described the delegates enjoying the spectacle of thomson and hermann helmholtz (himself an eponym in thermodynamics) debating heatedly in french, each with his own distinctive pronunciation. the section got bogged down on the standard for the ohm. on the next day, an unofficial group consisting of mascart, thomson, william siemens, helmholtz, gustav kirchhoff (kirchhoff ’s laws of circuits), rudolf clausius (clausiusclapeyron equation), gustav wiedemann and werner siemens agreed on the definitions of ohm and volt and on appointing an international commission to define the dimensions of the mercury column that was to be the ohm standard. still later mascart and thomson worked out the definitions of ampère, coulomb and farad over a hot chocolate with lady thomson (born frances “fanny” blandy). when mascart read the definitions to the section on september 21, some members were surprised, 18 carmen j. giunta18 carmen j. giunta but after thomson and helmholtz spoke in their favor, the group adopted them.25 several more international electrical congresses gathered in various european cities in the 1880s and 1890s, frequently in paris. at the paris congress of 1889, practical units of work and of power were adopted. the unit of work was called the joule, defined as 107 cgs units of work, the energy dissipated by one ampere through one ohm of resistance. the unit of power was called the watt, defined as 107 cgs units, equal to one joule per second. it was also decided that the output of industrial machines would be expressed in kilowatts rather than in horsepower.26 here we finally meet our featured units, defined as practical electrical units. watt and joule, the scientists and the units james watt (1736-1819) is well known as an engineer whose improvements to the steam engine powered the industrial revolution in britain. that aspect of watt’s life and work is well documented elsewhere27 and will not be discussed here except to note that watt’s name is a particularly appropriate eponym for a unit of power, even though electrical power was outside his expertise. watt is also known to historians of chemistry for his interest in that discipline, including important work on the composition of water.28 watt’s interest in units, though, is what will occupy our attention here. the unit closely associated with watt during his lifetime, the horsepower, was to be displaced by the kilowatt, at least for electrical generators and other electrical machines if the international electrical congress of 1889 was to have its way. the horsepower survives, though, as a unit for rating engines, especially automobile engines. the horsepower was the first important unit of power. units for power and energy arose before the physical concepts themselves, and they were developed largely in response to industrial and commercial needs. those who sold energy or heat (in the form of coal, for example) needed a rational basis for pricing their wares. thomas savery (1650-1717), who patented a “fire engine” before watt was born, suggested around 1700 that the rate at which a horse does work would make an appropriate measure of power. watt made a quantitative estimate of the unit considerably later. horses were, of course, used as draft animals in agriculture at the time, but they were also used for mechanical power in factories. in that application, they usually walked around a circular track, pulling one end of a lever attached to a shaft, whose gears or other linkage ran a pump or other machine. watt estimated the average force and speed of a horse pulling a 12-ft capstan lever, and arrived at 33,000 ft lb/min or 550 ft lb/s. this is the definition of the horsepower unit.29 perhaps less well known is watt’s interest in international units and in multiples of 10 to simplify their use. in 1783 watt wrote to the irish natural philosopher richard kirwan (1733-1812) after experiencing considerable difficulty in converting the weights and measures used by lavoisier and laplace to the english weights and measures to which he was accustomed. in the letter, he proposed to define a “philosophical” pound consisting of 10 (philosophical) ounces or 10,000 grains, a philosophical ounce consisting of 10 drachms or 1000 grains and a philosophical drachm consisting of 100 grains. he also advocated “the ounce measure of water” for the measure of elastic fluids, avoiding cubic inches of different sizes. “if all philosophers cannot agree on one pound or one grain, let everyone take his own pound or his own grain,” he added, seeing that the simplicity of decimal conversions would at least apply to relative measures, whatever the base unit. but it would be better, he noted, if all agreed on the same pound.30 james prescott joule (1818-1889) is likewise a celebrated figure. he is best known in the history of physics for quantifying the “mechanical equivalent of heat” and for contributing to the emerging concept of energy as a key physical quantity. thus, he is a fitting scientist to honor with the name of a unit of energy. unlike watt, joule did important electrical experiments. in the 1840s, he investigated electrical heating and found that electricity gave rise to heat in proportion to the resistance and the square of the current. indeed, over the course of his career, he explored equivalences among thermal, electrical, chemical, and mechanical effects.31 as we have seen, joule served on the baas committee on standards of electrical resistance. indeed, he carried out experiments on the resistance of the baas unit.32 joule also served on the later baas committee for the selection and nomenclature of dynamical and electrical units. it is worth noting that joule was still alive, albeit only for a few more weeks, when the international congress adopted his name as a unit.33 siemens and thomson/kelvin, the scientists and the units the joule and the watt were adopted internationally in 1889, but they had been proposed earlier in an address by william siemens, president of the baas, at its annual meeting in 1882.34 the matter of units, both mechanical and electrical, takes up several pages of 19watt’s in a name? 19watt’s in a name? units of power and energy siemens’s address. he regrets that the uk “still stands aloof ” from the metric system, and he would like the baas to ask the government to join the “international metrical commission” (bipm, established by the meter convention in 1875). moving from mechanical to electrical units, he notes with some satisfaction the past work of the baas on this matter and acknowledges that their practical system was largely adopted by the previous year’s international electrical congress. he ventures to suggest two additions to the practical electrical system, one of “magnetic quantity or pole” and one of power. for the former, he suggests the name weber35 and for the latter he proposes watt. two further units “may have to be added” before too long, he adds, one for magnetic field and one for “heat in terms of the electro-magnetic system.” for the former, he follows thomson in suggesting the name gauss36 and for the latter he proposes joule, to be defined as an ampère flowing through an ohm. both weber and joule were still alive at this time when siemens proposed their names as units. siemens’s own name is now an electrical unit, although whether the unit is named for him or his older brother werner is not clear. werner von siemens was born ernst werner siemens in prussia in 1816. in the 1840s, he went into the field of telegraphy. he investigated insulation for laying underground telegraph wires, finding that gutta percha served admirably. he and johann georg halske formed a partnership for manufacturing electrical equipment, including, eventually, electrical generators and motors, electric elevators and railways. a successful inventor and entrepreneur, siemens maintained a strong interest in basic science. he devised an instrument for measuring alternating current, for example, and helped to fund the german metrology lab, physikalisch-technische reichsanstalt.37 william siemens was born karl wilhelm siemens, also in prussia, in 1823. wilhelm went to london in 1843 to try to market an electroplating patent of werner’s. he stayed in england, where he invented a water meter that earned him quite a bit of money. working with his younger brother august friedrich (1826-1904), he developed an open hearth method of steel manufacture that used otherwise wasted heat from flue gases to burn off impurities from molten iron and to pre-heat incoming air entering the combustion zone. in 1859, william married anne gordon and became a british citizen the same year.37 before long, as we have seen, he took an active part in the baas, serving on its committees on standards of electrical resistance and on nomenclature of dynamical and electrical units, and eventually serving as president. william became sir william shortly before his death in 1883, and werner siemens became werner von siemens in 1888, a few years before his death in 1892. the siemenses enter our story of electrical units shortly after the baas committee on standards on electrical resistance began its work. in the first report of that committee (1862), we see werner siemens among the foreign scientists consulted and we find his letter to the committee included as an appendix.38 elsewhere in the proceedings of that year’s baas conference, we see william (“c. w.”) siemens among the six british scientists added to the committee.39 werner’s letter calls the committee’s attention to a paper he had published in 1860 in poggendorff’s annalen in which he had proposed using a meter-long column of mercury of one square millimeter cross section at 0°c as a unit of resistance, and goes on to describe the advantages of using mercury for such a standard. “should the adoption of the mercury unit be deemed advisable, i would place at the service of the british association any further information or assistance in my power”.38 preliminary measurements relating “siemens’s unit” to other resistance measurements available suggested that the former was very close to 1010 times the absolute electromagnetic resistance unit (mms system) defined by weber. although the mercury standard was not, in the end, adopted to define the baas ohm, the 1881 international electrical congress chose a mercury standard (length to be determined) as its standard for the ohm.40 when the international electrotechnical commission (iec) acted in 1935 to adopt the mks (meter, kilogram, second) system of units that later became the si, the siemens was included as the unit of conductivity, the reciprocal ohm. which siemens is the eponymous one (if there is only one), was left unspecified.41 the name siemens displaced an unofficial name for the reciprocal ohm, namely the mho,42 which was coined by sir william thomson in 1883.43 thomson has crossed our path so often that we ought to pause to focus on him and his eponymous unit. william thomson (1824-1907) is well known to physicists and chemists, although not necessarily by that name. he is better known as lord kelvin, more formally baron kelvin of largs. he was elevated to the peerage in 1892, the first scientist recognized in that way.44 scientists know him for his work on thermodynamics in the 1850s,45 and if they do not know kelvin the scientist they know kelvin (k), the unit of thermodynamic temperature. much of his work in thermodynamics was highly abstract and mathematical; however, he also engaged in practical applications of the science of his day, particularly in electricity and magnetism46. “there cannot be a greater mistake, than that of looking superciliously upon practical applications of science,” 20 carmen j. giunta20 carmen j. giunta he told an audience at the institution of civil engineers in 1883. much of the progress he saw in electrical and magnetic measurement over the previous 20 to 30 years, he attributed to the demands of commercial applications such as telegraphy and more recently lighting.47 during his lifetime, he was celebrated for his role in the transatlantic telegraph cable, and he was knighted soon after its completion in 1866. one later writer even calls thomson the “ruling spirit behind the work” and deems his work on electrical units and standards “his greatest contribution to science”.48 he invented several instruments for electromagnetic measurements and worked on many committees involving units and electrical standards.49 as thomson’s interest in units, standards, and nomenclature suggests, he was a strong advocate for internationally adopted units. during a lecture in the united states in 1884 on the wave theory of light, he made a digression on the virtues of the metric system and the evils of the english system of units. “you, in this country, are subjected to the british insularity in weights and measures,” he observed; so he employed feet and inches in the lecture, but he apologized for using such inconvenient measures. he lamented the action of an english government official who had rescinded a recently introduced mandate to teach the metric system in english schools. “i look upon our english system [of weights and measures] as a wickedly brain-destroying piece of bondage under which we suffer,” he observed. “the reason why we continue to use it is the imaginary difficulty of making a change and nothing else; but i do not think in america that any such difficulty should stand in the way of adopting so splendidly useful a reform.”50 as a member of the british house of lords, kelvin spoke in favor of a bill on weights and measures in 1904 that would have made metric measures mandatory. after recounting how adoption of metric measures in other countries was achieved without hardship, kelvin appealed to british self-regard. he said that while the uk might be grateful to france for inventing it and pleased to see how well it has worked in other european countries, it was interesting to note that the idea was born at home: “james watt laid down a plan which was in all respects the system adopted by the french philosophers seven years later, which the french government suggested to the king of england as a system that might be adopted by international agreement. james watt’s objects were to secure uniformity and so establish a mode of division which should be convenient as long as decimal arithmetic lasted”.51 in 1892, the year thomson was made baron kelvin, the british board of trade, which had worked with thomson on practical and legal electrical standards, proposed the name kelvin in place of kilowatt-hour for “the energy contained in a current of 1000 amperes flowing under an electromotive force of one volt during one hour.” kelvin demurred, pointing out that meters manufactured by other instrument makers reading in kelvins would be confusing for users since he had also designed electrical instruments (albeit no supply meters). kelvin suggested “supply unit” instead. the proposal was revived shortly after kelvin’s death in december 1907. the revived proposal noted that “board of trade unit” could be confusingly abbreviated as btu, which already stood for british thermal unit.52 as anyone who has seen a household electric bill recently can attest, the kilowatt hour (kwh) is still the standard unit for supply of electrical energy. where the kelvin has taken root as a unit name is as the unit of thermodynamic temperature. this is entirely appropriate, for thomson devised the thermodynamic temperature scale in very nearly its current form in 1848.53 during his lifetime, it was known as thomson’s absolute scale or lord kelvin’s absolute scale. in 1948, the ninth cgpm adopted, in principle, the kelvin scale. it stated that the kelvin scale “is recognized as the basic thermodynamic scale to which any temperature measurement must eventually be able to relate”,54 an acknowledgment that the scale and its name were well established in practice. six years later, the tenth cgpm defined the kelvin scale by fixing the triple point of water at 273.16 degrees kelvin.55 and in 1960, the degree kelvin was listed among the six base units of the newly launched si.56 the alert reader may notice the phrase “degree kelvin,” which is not the current name of the unit; the unit and symbol were changed from “degree kelvin” (°k) to “kelvin” (k) in 1967.57 the definition of the unit was changed recently; it is now defined in terms of the boltzmann constant.58 from international electrical units to the international system of units when we last met the watt and the joule, they had been proposed as units by baas president william siemens and adopted at the international electrical congress of 1889. the international electrical congress of 1893, held in chicago, defined a set of “international” units based on cgs electromagnetic unit but defined in terms of practical standards. for example, the international ohm was “based upon the ohm equal to 109 units of resistance of the c. g. s. system of electromagnetic units” and “represented by the resistance offered to an unvarying electrical current by a column of mer21watt’s in a name? 21watt’s in a name? units of power and energy cury at the temperature of melting ice 14.4521 grammes in mass, of a constant cross-sectional area and of the length of 106.3 centimetres.” similarly, the international ampere was described in terms of cgs electromagnetic units (10–1 such units of current) and given a realization in terms of a rate of deposition of silver from silver nitrate solution. the joule and the watt were approved essentially as in 1889, but relative to the international ampere and international ohm.59 the congress recommended that the nations represented there adopt the international units as legal units, that is, to which regulations would refer. many nations did so, and that made changing the international electrical units more difficult thereafter, as many legal codes would have to be revised in the aftermath of such change.60 at the international electrical congress in st. louis, missouri, in 1904, no units or standards were defined, but a resolution was adopted to appoint an international commission on standardization and nomenclature for electrical apparatus. that resolution led to the founding, in 1906, of the international electrotechnical commission, an organization that continues more than 100 years later. the first president of the iec was lord kelvin.61 although no action on units was taken at st. louis, a proposal that would lead eventually to the si made its international debut there. moise ascoli, head of the italian delegation at the congress, read a paper supporting the proposal of his countryman giovanni giorgi (1871-1950), and giorgi’s proposal was included in the printed proceedings of the congress as an appendix to ascoli’s paper.62 giorgi had noticed that the joule, equal to 107 cgs units of energy, was also equal to 1 mks unit of energy, namely to 1 kg m2 s–2. so it (and the watt) would be natural units in a system whose mechanical foundations were the meter, kilogram, and second. that alone was not enough to bring the other practical electrical units into a coherent system. but if one defined one of the practical electrical units arbitrarily as a fourth base unit, then the other practical electrical units already defined would be part of the new coherent system. the system would be neither electrostatic nor electromagnetic in the sense described earlier in the paper: neither coulomb’s nor ampère’s force law was privileged. in the paper presented at st. louis, giorgi selected the ohm as the fourth base unit of the system. as eventually adopted, the ampere was the fourth base unit.63 giorgi had first presented his proposal in rome in 1901 to the italian association of electrical engineers, and he also presented it to the physical society of london in 1902. his system was little more than an academic exercise for more than 30 years until taken up by the iec in the 1930s. david robertson, professor of electrical engineering at the merchant venturers’ technical college in bristol, england, independently devised a similar system, proposing the name newton as the unit of force in the mks system.64 in 1935, the iec adopted the mks system, leaving temporarily undecided the choice of the fourth base unit.63 in the wake of that decision, l. hartshorn and p. vigoureux of the british national physical laboratory proposed newton as the name of the unit of force in the system: “the name of newton is universally associated with the idea of impressed force, … and as newton’s name cannot but occur again and again throughout the teaching of even the most elementary mechanics, pronunciation should present no difficulty in other countries”.65 giorgi was still very much alive at this time. in fact, he was a delegate from italy in iec meetings in 1935 and 1938.66 (robertson’s name and ideas, though, appear to have been forgotten). in the 1920s and early 1930s, the cgpm seemed to be heading in the opposite direction from the iec. having taken electrical matters into its purview in 1921, the cgpm set up a consultative committee on electricity in 1927. (the cipm operates using consultative committees of various specializations.) in 1933 the cgpm adopted in principle the substitution of absolute electrical units for the so-called international units; in effect, this endorsed cgs units over the practical international units.67 the cgpm did not meet again until 1948. by that time, it had received requests to adopt a practical international system of units. the international physical union recommended development of an mks system augmented by a practical electrical unit (but did not recommend that physicists drop the cgs system). at this meeting, cgpm instructed cipm to begin consulting to make recommendations on a single practical system of units.68 at its next meeting in 1954, the cgpm decided on six base units for its practical system of units, namely the meter, kilogram, second, ampere, degree kelvin, and candela.55 and when the cgpm unveiled the si, newton, joule, and watt were listed among the derived units; they are the si units of force, energy, and power respectively.56 as we have already seen, degree kelvin became kelvin in 1967.57 the other eponym we have followed in this paper, the siemens, joined the si as a derived unit in 1971, the same year, incidentally, that saw the mole added as a base unit.69 conclusions although one of the foci of this paper is power (and its units) in the narrow physical sense, the narrative above 22 carmen j. giunta22 carmen j. giunta is full of encounters of science with commercial and political power. we have seen thomson attribute much of the progress in electrical measurement to demands from commercial applications such as telegraphy and lighting. indeed, commercial technologies appear to be the driving force for practical electrical units from the telegraphic engineers clark and bright to the development of the si. the international gatherings of electrical scientists and technologists coincided with great commercial expositions, such as the paris international exposition of electricity (1881) and universal exposition (1889, which featured the eiffel tower), the columbian exposition in chicago (1893), and the louisiana purchase exposition in st. louis (1904). and even on a side branch of the main narrative above, we have seen that werner siemens both practiced science and supported it using the wealth he earned from new electrical technologies.70 over the course of this narrative, we see signs of the much-vaunted international character of science becoming institutionalized, and sometimes being caught up in hostilities that engulfed the wider world. many international scientific bodies were formed in the early twentieth century, in the aftermath of the first world war. the international union of pure and applied chemistry (iupac) and the international astronomical union (iau) celebrate centennials in 2019.71 the international union of pure and applied physics (iupap) was founded in 1922.72 as we have seen, the iec was formed a few years earlier. the turmoil of the french revolution permitted a wholesale change of weights and measures in france. indeed, that nation saw changes in its calendar, which were rescinded, and a proposed change in time units, which never took hold, as well as the reform of its weights and measures, which endured.21 international repercussions of the french revolution limited the active participation of other europeans in the founding of the metric system mainly to states allied with france or neutral toward them.19 given the british reluctance to adopt the metric system even a century later, it seems doubtful that britain would have accepted the invitation of the king of france to join in devising an international reform of weights and measures even in the absence of international tensions surrounding the french revolution; however, under the circumstances of the revolution, such an invitation was a non-starter. the failure of the uk in the early twentieth century and the us still to adopt metric units exhibits a reluctance to change from a familiar system. the effort required to change is obvious, perhaps even exaggerated, while the benefits are less evident, particularly since the system already in place appears to work well enough. this sort of inertia is not confined to scientific matters, of course, but scientists are not immune from it. cgs units were still used in physics courses on electricity and magnetism and in the textbooks used in such courses when i was a student in the 1980s. finally, i found it interesting to learn that the attachment of names to formal entities such as units did not arise until the second half of the nineteenth century, although names associated with inventions and apparatus were considerably older. using google’s ngram viewer, one can see that eponymous terms like copernican system, voltaic pile, and halley’s comet were in use in the first half of the nineteenth century. terms like boyle’s law, hooke’s law, and even pythagorean theorem, however, only start to appear after 1860 or so.73 i have not been able to conclude, even tentatively, what prompted clark and bright to use eponyms for unit names in 1860. their paper (ref. 8) proposes names based on prominent scientists as if off the cuff, as an expedient for the sake of having names to illustrate relationships. indeed, the more deliberative discussion of terminology in their paper concerns prefixes to denote multiples of units. i do not know what influenced them to use eponyms for their four proposed units. one of this paper’s reviewers wondered whether the sheer quantity of new units that needed names was responsible, and i thank the referee for a plausible suggestion. tapping a reservoir of names of scientists would have the advantage of furnishing multiple names in a short time—names, moreover, that would have at least some familiarity and association in the minds of the scientists and engineers who would use the names. i found no evidence either in favor or opposed to this plausible hypothesis, other than to note that the baas committee on the nomenclature of dynamical and electrical units opted not to use eponyms for a set of three dynamical cgs units.17 still, four names for a pair of authors preparing a conference paper is a large number compared to three names for a committee with time for extensive deliberation. it is clear that clark and bright’s example of eponymy in units inf luenced the committees described above. it is not clear, though, that their example had any influence in the appearance of the eponyms boyle’s law, hooke’s law, and pythagorean theorem that began widespread use in the 1860s. appendix74 well before 1860, important force laws for electricity and magnetism had been discovered, and the fact that the two apparently different kinds of phenomena were in 23watt’s in a name? 23watt’s in a name? units of power and energy fact related was also known. the fact that the two phenomena are related has implications for the units chosen to describe electromagnetic phenomena. for the purpose of understanding the origins of various electrical units, we may take coulomb’s or ampère’s force law as foundational. coulomb’s law states that the electrostatic force, fe, experienced by one point charge, q1, in the presence of another, q2, is proportional to the product of the charges and inversely proportional to the square of the distance, r, that separates them. fe = ke q1q2 r2 (1) if we take the proportionality constant, ke, to be 1, a set of so-called electrostatic units results, based on the choice of making the fundamental law of electrostatics as simple as possible. ampère’s force law is a special case of one of the first observed quantitative phenomena that connect electricity and magnetism. it gives the magnetic force, fm, experienced by two long parallel wires carrying a steady current. in such an arrangement, the force per unit length, l, of wire is directly proportional to the product of the currents, i1 and i2, and inversely proportional to the distance, d, between the wires: fm l =2km i1i2 d (2) if we take the proportionality constant, km, to be 1 (the factor of 2 that appears in the equation comes from this special case of two parallel wires), the result is a set of so-called electromagnetic units. the two constants in these laws are not independent: they are related by the relationship ke km = c2 (3) where c is the speed of light in a vacuum.75 at first blush, there appear to be two choices of units, but in fact, these two choices represent two families of electrical units. to specify a set of units requires a choice of a system of mechanical units, that is of units of length, mass, and time. the system favored in britain for scientific work at this time and eventually adopted more widely was the cgs system. to see how this choice of mechanical units defines electrical units, let us derive some cgs electrostatic units. coulomb’s law, with ke = 1, says that two unit charges separated by unit distance (that is, by 1 cm) experience unit force (1 dyne, or 1 cm g s–2). by rearranging coulomb’s law to solve for two equal charges, one obtains the derived cgs electrostatic unit of charge as 1 cm3/2 g1/2 s–1. the corresponding unit of current, then, would be one unit of charge per unit of time, or 1 cm3/2 g1/2 s–2. to obtain cgs electromagnetic units, rearrange equation 2 to solve for two equal currents with unit values for all other quantities, including the constant km. never mind the numerical value: not even the dimensions are the same for the corresponding quantities in the two systems. the cgs electromagnetic unit of current is cm1/2 g1/2 s–1 (compared to cm3/2 g1/2 s–2 in cgs electrostatic units); similarly the cgs electromagnetic unit of charge is cm1/2 g1/2 (compared to cm3/2 g1/2 s–1 in cgs electrostatic units). in the electromagnetic system, km = 1, so ke must be equal to c2. in the si, current has a base unit, namely the ampere, a, so the proportionality constant in ampère’s law also has units. rearranging that law with unit currents, force, and distances shows that km has units of kg m s–2 a–2. the numerical value of km in these units was taken to be exactly 10–7, just the conversion factor that relates the mks unit of energy to the cgs unit of energy. the constants km and ke are still related, so ke = kmc2 ≈ (10–7 kg m s–2 a–2)(3.0·108 m s–1)2 = 9.0·109 kg m3 s–4 a–2 in the si, the proportionality constants in coulomb’s and ampère’s laws are not expressed in terms of ke and km. their standard form in si units are fe = 1 4πε0 q1q2 r2 and fm l = µ0 4π ⎛ ⎝ ⎜ ⎞ ⎠ ⎟ 2i1i2 d (4) where did the factors of 4π come from? as edward purcell explains it in his textbook, “separating out a factor of 1/4π was an arbitrary move, which will have the effect of removing the 4π that would appear in many of the electrical formulas, at the price of introducing it into some others, as here in coulomb’s law”.76 equations of electricity and magnetism that use this convention with respect to 4π are said to be rationalized. the constants that appear in these equations are called the electrical permittivity (ε0) and magnetic permeability (μ0) of vacuum. their values are77 μ0 = 4π×10–7 kg m s–2 a–2 ≈ 1.257×10–6 kg m s–2 a–2 and ε0 = 1 µ0c 2 ≈ 8.854 ×10 −12 kg−1 m−3 s4 a2 24 carmen j. giunta24 carmen j. giunta acknowledgment i would like to thank one of the anonymous reviewers for insightful suggestions on several aspects of the paper. references and notes all urls accessed september 9, 2019. 1. in fact, most dictionaries i consulted give as the first definition of eponym the person from whom a name or term is derived rather than the name or term itself. 2. putative is an important qualifier, for it has been noted that many scientific phenomena are not named for their original discoverers. see stephen m. stigler, “stigler’s law of eponymy,” in statistics on the table, harvard university press, cambridge, ma, 1999, ch. 14, pp. 277-290. the law “in its simplest form is this: ‘no scientific discovery is named after its original discoverer.’” 3. max planck, “zur theorie des gesetzes der energieverteilung in normalspectrum,” verhandlungen der deutschen physikalischen gesellschaft 1900, 2, 237-245. reprinted in german with english translation in hans kangro, ed., d. ter haar, stephen g. brush, trans., planck’s original papers in quantum physics, taylor & francis, london, 1972; available online. 4. jean perrin, “mouvement brownien et réalité moléculaire,” ann. chim. phys. 1909, 18, 5-114 (at p 15). english translation by frederick soddy as brownian movement and molecular reality, taylor and francis, london, 1910; available online. 5. “base unit, n.” oed online. oxford university press; available online. 6. congrès international des électriciens (paris 1881), comptes rendus des travaux, masson, paris, 1882, p 44; available online. 7. see, for example, john watkins brett, “on the submarine telegraph,” notices of the proceedings at the meetings of the members of the royal institution, 2, 394-403 (meeting of mar. 20, 1857); available online. 8. latimer clark, charles bright, “measurement of electrical quantities and resistance,” electrician 1861, 1, 3-4. 9. baas committee on standards of electrical resistance, “report of the committee appointed by the british association on standards of electrical resistance,” report of the 33nd meeting of the british association for the advancement of science (for 1863), pp 111-176; available online. the committee endorsed a simple nomenclature for each unit, “a short distinctive name in the manner proposed by sir charles bright and mr. latimer clark….” 10. fleeming jenkin, “report on the new unit of electrical resistance proposed and issued by the committee on electrical standards appointed in 1861 by the british association,” proc. roy. soc. (london) 1865, 154-164. 11. “recommendations adopted by the general committee at the manchester meeting in september 1861,” report of the 31st meeting of the british association for the advancement of science (for 1861), xxxix-xliv (at xxxix-xl); available online. 12. baas committee on standards of electrical resistance, “provisional report of the committee appointed by the british association on standards of electrical resistance,” report of the 32nd meeting of the british association for the advancement of science (for 1862), 125-163 (at 126); available online. 13. baas committee on standards of electrical resistance, “report of the committee appointed by the british association on standards of electrical resistance,” report of the 35th meeting of the british association for the advancement of science (for 1865), 308-312; available online. 14. paul tunbridge, lord kelvin, his influence on electrical measurements and units, institution of electrical engineers, london, 1992, p 30. 15. baas committee on standards of electrical resistance, “report of the committee on standards of electrical resistance,” report of the 39th meeting of the british association for the advancement of science (for 1869), 434-438; available online. 16. “recommendations adopted by the general committee at the brighton meeting in august 1872,” report of the 42nd meeting of the british association for the advancement of science (for 1872), liii-lviii; available online. 17. joseph d. everett (reporter), “first report of the committee for the selection and nomenclature of dynamical and electrical units,” report of the 43rd meeting of the british association for the advancement of science (for 1873), 222-225; available online. 18. bipm, convention du mètre et règlement annexe, available online. 19. léon bassot, f. e. harpham, trans. “historical sketch of the foundation of the metric system,” columbia school of mines quarterly 1901/02, 23, 1-24. the translator is identified as miss f. e. harpham, chief computer in the astronomical department of columbia university. https://archive.org/details/plancksoriginalpapersinquantumphysics/ https://babel.hathitrust.org/cgi/pt?id=mdp.39015010952508 https://www.oed.com/view/entry/251054 https://babel.hathitrust.org/cgi/pt?id=mdp.39015023185609&view=1up&seq=5 https://babel.hathitrust.org/cgi/pt?id=chi.14773596&view=1up&seq=428 https://books.google.com/books?id=b7xzaaaacaaj&pg=pa111 https://babel.hathitrust.org/cgi/pt?id=njp.32101076796398&view=1up&seq=45 https://babel.hathitrust.org/cgi/pt?id=njp.32101076796380;view=1up;seq=191 https://babel.hathitrust.org/cgi/pt?id=njp.32101076796356&view=1up&seq=402 https://babel.hathitrust.org/cgi/pt?id=mdp.39015050605099&view=1up&seq=556 https://babel.hathitrust.org/cgi/pt?id=mdp.39015010796483&view=1up&seq=55 https://babel.hathitrust.org/cgi/pt?id=mdp.39015010796509&view=1up&seq=318 https://www.bipm.org/utils/common/documents/official/metre-convention.pdf 25watt’s in a name? 25watt’s in a name? units of power and energy 20. ken alder, the measure of all things, free press, new york, 2002. 21. herbert arthur klein, the science of measurement: a historical survey, dover, mineola, ny, 1988, pp 107-125; originally published by simon & schuster, new york, 1974. 22. maurice crosland, “the congress on definitive metric standards, 1798-1799: the first international scientific conference?” isis 1969, 60, 226-231. 23. bipm, the international metre commission (18701872), available online. 24. ref. 6, p 39. the vicissitudes of president garfield from the time when he was shot on july 2, 1881, until his death on september 19 of that year, were followed closely in newspapers the world over. “we have just seen the civilized world gathered as one family around a common sick bed,” according to a short piece titled “the moral influence of the telegraph” (sci. am. 1881, 240). 25. ref. 14, pp 34-39. 26. congrès international des électriciens (paris 1889), comptes rendus des travaux, gauthier-villars, paris, 1890, pp 108-109; available online. 27. see, for example, eric robinson, “james watt, engineer and man of science,” notes and records of the royal society of london 1970, 24(2), 221-232. ben russell, james watt: making the world anew, reaktion books, london, 2014. 28. see, for example, jennifer s. pugh, john hudson, “the chemical work of james watt, f.r.s.,” notes and records of the royal society of london 1985 40(1), 41-52. david philip miller, james watt, chemist, pickering & chatto, london, 2009. 29. ref. 21, pp 237-238. 30. james patrick muirhead, the life of james watt, with selections from his correspondence, john murray, london, 1858, pp 389-390; available online. 31. see, for example, donald s. l. cardwell, james joule: a biography, manchester university press, manchester, uk, 1989. william h. cropper, great physicists, oxford university press, oxford, uk and new york, 2001, ch 5, pp 59-70. 32. baas committee on standards of electrical resistance, “report of the committee on standards of electrical resistance,” report of the 37th meeting of the british association for the advancement of science (for 1867), 474-522; available online. 33. the congress adopted the unit on august 31, 1889; joule died near manchester on october 11. 34. c. william siemens, “[presidential] address,” report of the 52nd meeting of the british association for the advancement of science (for 1882), 1-33; available online. 35. for wilhelm weber (1804-1890). weber’s name had already been in informal use as a unit of current, according to siemens, and his name had not already been attached to a formally adopted unit for fear of confusing it with the informal weber. in the current si, the weber (wb) is the derived unit of magnetic flux. it is just as well that the name was not assigned as a unit of magnetic quantity, the magnetic analog of electrical charge, for isolated magnetic poles have never been observed. 36. for karl friedrich gauss (1777-1855). gauss was a polymath, making important contributions to mathematics and to the physics of electricity and magnetism, among other areas. gauss and the much younger weber worked together for some time at the university of göttingen, and they developed the absolute approach to electromagnetic measurement, that of expressing all such quantities in terms of mechanical units. gauss gave his name to a system of electromagnetic units and to the unit of magnetic field within that gaussian cgs system. see ref. 21, pp 490-495. 37. sanford p. bordeau, volts to hertz … the rise of electricity, burgess, minneapolis, mn, 1982, pp 208-219. 38. ref. 12, pp 133, 152-155. 39. “recommendations adopted by the general committee at the cambridge meeting in october 1862,” report of the 32nd meeting of the british association for the advancement of science (for 1862), xxxix-xliii (at xxxix); available online. 40. ref. 6, p 42. 41. ref. 37, p 219. 42. the nist guide for the use of the international system of units (si) lists the mho along with such formerly acceptable units as the torr, standard atmosphere, and calorie as “unacceptable” for use with the si “including, of course, all of the u.s. customary (that is, inch-pound) units.” (ambler thompson, barry n. taylor, nist special publication 811 (2008); available online. 43. william thomson, “electrical units of measurement,” in institution of civil engineers, the practical applications of electricity, institution of civil engineers, london, 1884, pp 149-174 at p 171 (lecture given 3 may 1883); available online. 44. “kelvin, n. and adj.” oed online. oxford university press; available online. 45. crosbie smith, m. norton wise, energy and empire: a biographical study of lord kelvin, cambridge university press, cambridge, uk, 1989, ch. 9-10, pp. 282-347. ref. 31 (cropper), ch 7, pp 78-92. https://www.bipm.org/en/measurement-units/history-si/metre-commission/ https://babel.hathitrust.org/cgi/pt?id=mdp.39015068160715&view=1up&seq=120 https://babel.hathitrust.org/cgi/pt?id=uc1.b5043513&view=1up&seq=431 https://babel.hathitrust.org/cgi/pt?id=mdp.39015066715650&view=1up&seq=562. joule’s experiments are described in an appendix at pp 512-522 https://babel.hathitrust.org/cgi/pt?id=njp.32101076796513;view=1up;seq=87 https://babel.hathitrust.org/cgi/pt?id=njp.32101076796513;view=1up;seq=87 https://babel.hathitrust.org/cgi/pt?id=njp.32101076796380&view=1up&seq=41 https://nvlpubs.nist.gov/nistpubs/legacy/sp/nistspecialpublication811e2008.pdf https://books.google.com/books?id=kh0faaaaqaaj&pg=pa149 https://www.oed.com/view/entry/102860 26 carmen j. giunta26 carmen j. giunta 46. ref. 45 (smith & wise), ch. 19-20, pp. 649-722. chapters 21 and 22 of the same book describe his work on navigational technologies (pp. 723-798). 47. ref. 43, pp 149-150. this same lecture contains kelvin’s often quoted assertion that “when you can measure what you are speaking about, and express it in numbers, you know something about it.” 48. ref. 14, pp 2-3. 49. we have seen him already as the instigator of the baas committee on standards of electrical resistance (1862-1870) and on its committee on the nomenclature of dynamical and electrical units. he also served on its committee for improving the construction of practical standards for electrical measurements from 1881 until his death in 1907. see reports of the electrical standards committee of the british association, cambridge university press, cambridge, uk, 1913, pp xvii-xxiv; available online. 50. william thomson, “the wave theory of light,” j. franklin inst. 1884, 118 (or 3rd ser. 88), 321-341 (at 323); available online. 51. 130 parl. deb. (4th ser.) (1904) 690-693; available online. the watt letter (ref. 30) was brought to kelvin’s attention just a few days before in a letter from prof. archibald barr, director of the james watt engineering laboratory at the university of glasgow (ref. 14, p 86). 52. ref. 14, pp 60-61. 53. william thomson, “on an absolute thermometric scale founded on carnot’s theory of the motive power of heat, and calculated from regnault’s observations,” philos. mag. 1848, 33, 313-317. 54. bipm, comptes rendus des séances de la neuvième conférence général des poids et mesures (paris 1948), p 89, available online. 55. bipm, comptes rendus des séances de la dixième conférence général des poids et mesures (paris 1954), available online. 56. bipm, resolution 12 of the 11th cgpm (1960), available online. 57. bipm, resolution 3 of the 13th cgpm (1967), available online. 58. bipm, le système international d’unités (si brochure), 9e edition 2019, available online. 59. proceedings of the international electrical congress held in the city of chicago (1893), american institute of electrical engineers, new york, 1894, pp 20-21; available online. 60. ref. 14, p 44. 61. mark frary, in the beginning… the founding of the iec, available online. 62. giovanni giorgi, “proposals concerning electrical and physical units,” transactions of the international electrical congress, st. louis, 1904, vol. 1 (1905), pp 136-141; available online. 63. ref. 37, pp 289-297. 64. david robertson, “the completion of the practical system of units,” electrician 1904, 53, 24-25; available online. in a later note on various systems of electric and magnetic units, robertson acknowledges giorgi’s prior publication and states that he came to similar conclusions independently. (“electrotechnical systems of units,” electrician 1904, 51, 670-672.) 65. l. hartshorn, p. vigoureux, “unit of force in the m.k.s. system,” nature 1935, 136, 397. 66. iec, historical figures, giovanni giorgi, available online. 67. bipm, comptes rendus des séances de la huitième conférence général des poids et mesures (paris 1933), pp 51-54, available online. 68. bipm, resolution 6 of the 9th cgpm (1948), available online. 69. bipm, comptes rendus des séances de la quatorzième conférence général des poids et mesures (paris 1971), p 78, available online. 70. the competing claims of science and technology in the service of state aims in the physikalisch-technische reichsanstalt is the subject of david cahan, an institute for an empire, cambridge university press, cambridge, uk, 1989. 71. iupac, our history. international astronomical union 1919-2019, available online. 72. iupap, about us. 73. google books ngram viewer, available online. 74. see, for example, john david jackson, classical electrodynamics, 2nd ed., wiley, new york, 1975, pp 811821. 75. the value of the ratio was, in fact, a subject of experiments carried out by thomson and by maxwell reported by the baas committee on standards of electrical resistance (ref. 15). 76. edward m. purcell, electricity and magnetism, mcgraw-hill, new york, 1963, pp 449-452. 77. in the redefinition of si base units that went into effect in 2019, km is no longer defined as exactly 10–7 but is an experimentally determined number very close to 10–7. see michael stock, richard davis, estefanía de mirandés and martin j t milton, “the revision of the si—the result of three decades of progress in metrology,” metrologia 2019, 56, available online. https://babel.hathitrust.org/cgi/pt?id=mdp.39015064383691&view=1up&seq=21 https://babel.hathitrust.org/cgi/pt?id=njp.32101072909722&view=1up&seq=345 https://books.google.com/books?id=yxwpaqaaiaaj&pg=pr452 https://www.bipm.org/utils/common/pdf/cgpm/cgpm9.pdf https://www.bipm.org/utils/common/pdf/cgpm/cgpm10.pdf https://www.bipm.org/en/cgpm/db/11/12/ https://www.bipm.org/en/cgpm/db/13/3/ https://www.bipm.org/en/cgpm/db/13/3/ www.bipm.org/utils/common/pdf/si-brochure/si-brochure-9.pdf https://babel.hathitrust.org/cgi/pt?id=mdp.39015068160707&view=1up&seq=54 https://www.iec.ch/about/history/beginning/founding_iec.htm https://babel.hathitrust.org/cgi/pt?id=hvd.hxhjvd&view=1up&seq=160 https://babel.hathitrust.org/cgi/pt?id=njp.32101050973377&view=1up&seq=46 https://babel.hathitrust.org/cgi/pt?id=njp.32101050973377&view=1up&seq=46 https://www.iec.ch/about/history/figures/giovanni_giorgi.htm https://www.iec.ch/about/history/figures/giovanni_giorgi.htm https://www.bipm.org/utils/common/pdf/cgpm/cgpm8.pdf https://www.bipm.org/en/cgpm/db/9/6/ https://www.bipm.org/en/cgpm/db/9/6/ https://www.bipm.org/utils/common/pdf/cgpm/cgpm14.pdf https://iupac.org/who-we-are/our-history/ https://www.iau-100.org https://iupap.org/about-us/ https://books.google.com/ngrams https://doi.org/10.1088/1681-7575/ab0013 https://doi.org/10.1088/1681-7575/ab0013 substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 5(1) suppl.: 29-42, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1276 citation: n. castel-branco (2021) dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64. substantia 5(1) suppl.: 29-42. doi: 10.36253/substantia-1276 copyright: © 2021 n. castel-branco. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64 nuno castel-branco1 department of history of science and technology, johns hopkins university, 3400 n. charles street, gilman hall 301, baltimore, md 21218 abstract. at the height of his scientific career, the anatomist nicolaus steno published the elementorum myologiæ specimen (florence, 1667), a book unlike any other anatomy book until then. rather than an anatomy book, it seemed more like a book of mathematics, with propositions, lemmas and corollaries. steno is thought to have developed his mathematical interests in florence with the school of galileo. however, this article challenges this interpretation and argues that steno’s turn towards mathematics was a gradual process that began earlier in copenhagen and leiden. by surveying steno’s early anatomical writings, mathematical methods such as quantification measurements, mechanical analogies, and geometrical models come to light. more importantly, these methods are read in their own context, by considering what mathematics really meant in the early modern period and how anatomists used it. as such, this article provides a more complete picture of steno’s interest in mathematics and it sheds new light on the rise of mathematics in the early modern life sciences. keywords: nicolaus steno, early modern science, history of anatomy, mathematization, mechanical philosophy, mixed mathematics, quantification, dissection culture. introduction1 when the anatomist nicolaus steno arrived in florence and published the elementorum myologiae specimen (1667), he claimed that the study of the muscles had to become “part of mathematics” and that the cause of “many errors … in the description of the human body” was that “until now anatomy has disdained the laws of mathematics.”2 the book seemed more like a 1 i would like to thank the editors stefano dominici and gary rosenberg, as well as the reviewers peter dear, jeremy gray and françois duchesneau for very helpful comments and suggestions. i also benefitted much from discussions with troels kardel and john heng at the workshop “galilean foundations for a solid earth” in october 2019, in florence. finally, a special thanks to evan ragland and maría portuondo who kindly read and commented on an earlier version of this article. 2 nicolaus steno, elementorum myologiae specimen (florence, 1667), p. iii-iv: “non posse in musculo distincte partes eius nominari, nec motum eiusdem considerari feliciter, nisi matheseos pars 30 nuno castel-branco mathematics than an anatomy book, due to its propositions, lemmas and corollaries, and strong epistemological claims about the role of mathematics in the study of nature (fig. 1).3 this mathematical approach was seen likewise in steno’s most famous work, also published in florence, the de solido intra solidum naturaliter contento (1669), where he laid down the principles of superposition of the earth’s strata and in which he described the formation of crystals and of the tuscan mountains by means of geometry.4 since steno’s earlier works did not myologia fieret,” and “innumerabilium errorum, quibus humani corporis historia fœdè inquinatur, quàm quod matheseos leges anatome hactenus indignata fuerit.” for a full english translation see troels kardel and paul maquet, nicolaus steno: biography and original papers of a 17th century scientist, 2nd ed. (berlin: springer, 2018) (hereafter bop), p. 651. all translations are from bop unless the latin is provided in the footnote, in which case they are mine. 3 for in-depth studies of the elementorum myologiæ specimen see troels kardel, steno on muscles: introduction, texts, translations, (philadelphia: the american philosophical society, 1994); raphaële andrault, “mathématiser l’anatomie: la myologie de stensen (1667),” early science and medicine, 15 (2010), pp. 505-536; domenico bertoloni meli, “the collaboration between anatomists and mathematicians in the mid-seventeenth century with a study of images as experiments and galileo’s role in steno’s myology,” early science and medicine, 13:6 (2008), pp. 665-709. 4 nicolaus steno, de solido intra solidum naturaliter contento dissertationis prodromus (florence, 1669), 78-80; bop, pp. 822-825. see also alan cutler, the seashell on the mountaintop: a story of science, sainthood, and the humble genius who discovered a new history of the earth (new york: dutton, 2003), pp. 105-118. display such an explicit use of mathematics, it may seem that he completely changed his research methods when he arrived in florence. however, as this article argues, that was not the case. rather than a sudden shift, steno’s turn towards mathematics was a gradual process. early in his anatomical career, steno used methods directly associated with the early modern pure and mixed mathematics. the mixed mathematic disciplines, such as astronomy, mechanics or optics, used the methods of pure mathematics – arithmetic and geometry – to explain natural phenomena. such methods included quantification measurements, geometrical models, and even the axiomatic structure of mathematical treatises.5 simple uses of quantification like counting did not necessarily entail an interest in mathematical methods, unless they were used to make stronger epistemological claims. scholars who worked on mixed mathematics aimed to achieve higher levels of certainty in their description of the natural world.6 for that reason, seventeenth-century mixed mathematics, later known as physico-mathematics, used not only mathematical methods but also new experimentation techniques and mechanical analogies to explain natural phenomena.7 for example, historian peter dear explains that the book ars magnesia (würzburg, 1631) by the jesuit athanasius kircher (16021680) was “a physico-mathematical disquisition” on magnetism where experimental accounts were presented in the form of theorems.8 steno carefully studied the second edition of this book as a university student in copenhagen, including the chapters where kircher illustrated magnetic attraction by means of hydrostatic devices.9 besides outlining steno’s early uses of mathematics and mechanical analogies, this article shows that such uses derived in large part from his interest in mixed mathematics and not so much from the mechanical philosophies of his time.10 although steno may be 5 kirsti andersen and henk bos, “pure mathematics,” in katharine park and lorraine daston (eds.), cambridge history of science, vol. 3: early modern science, pp. 696-723, esp. 702. 6 peter dear, discipline and experience: the mathematical way in the scientific revolution (chicago: chicago press, 1995), pp. 32-44; rivka feldhay, “the use and abuse of mathematical entities: galileo and the jesuits revisited,” in peter machamer (ed.), the cambridge companion to galileo (cambridge: cambridge univ. press, 1998), pp. 80-145, esp. 83-100. 7 dear, discipline and experience, pp. 32-62, 151-79. 8 peter dear, “mixed mathematics,” in p. harrison, r. numbers and m. shank (eds.), wrestling with nature: from omens to science (chicago: chicago press, 2011), p. 156; dear, discipline and experience, 172-9. 9 august ziggelaar (ed.), chaos: niels stensen’s chaos-manuscript with introduction, notes and commentary (copenhagen: danish library of science and medicine, 1997), p. 122; athanasius kircher, magnes sive de arte magnetica (cologne, 1643), pp. 527-9. 10 this was also the case for the anatomist fabricius d’acquapendente (1533-1619), see peter distelzweig, “fabricius’s galeno-aristotelian figure 1. “lemma iv: the height of a contracted muscle is equal to the height of the non-contracted muscle.” steno, elementorum myologiæ specimen, p. 21; bop, p. 667. 31dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64 described as a mechanical philosopher, this does not mean that he followed strictly the mechanical philosophies of rené descartes (1596-1650) and pierre gassendi (1592-1655).11 many non-mechanical, early-modern scholars also used quantification methods and mechanical analogies in medicine and anatomy, as seen in the case of the vitalist johannes baptista van helmont (15801644) and the aristotelian william harvey (1578-1657).12 steno’s early interests in mathematics have two important historical implications. first, they provide a more complete picture of steno’s personal interest in mathematics. steno never wrote about what made him turn towards a geometrical explanation of the muscles or when he decided to do it. but historians tend to associate this mathematical turn with the mathematical school of galileo, whose followers steno met in italy in 1666.13 giovanni alfonso borelli (1608-1679), a mathematician trained in the school of galileo, also published, more than ten years after steno, the de motu animalium (rome, 1680-1), a two-volume book on the motion of animals similar to steno’s elementorum myologiæ specimen in many ways.14 a few months after arriving in florence, steno asked borelli to “teach him some things of geometry,” as borelli reported in a letter to marcello malpighi (1628-1694).15 moreover, it was in collaboration with the mathematician vincenzo viviani (1622-1703), teleomechanics of muscle,” in justin smith (ed.), the life sciences in early modern philosophy (oxford: oxford univ. press, 2014); see also alan gabbey, “what was ‘mechanical’ about ‘the mechanical philosophy’?,” in c. palmerino and j. thijssen (eds.), the reception of the galilean science of motion in seventeenth-century europe (dordrecht: springer, 2004), pp. 11-24, esp. 21-23. 11 for a recent account of the complexity of early modern mechanical philosophies see d. bertoloni meli, mechanism: a visual, lexical and conceptual history (pittsburgh: university of pittsburgh press, 2019), pp. 3-24. 12 for quantification in van helmont, see william newman and lawrence principe, alchemy tried in the fire: starkey, boyle, and the fate of helmontian chymistry (chicago, univ. of chicago press, 2002), pp. 56-91; for harvey as a non-mechanical philosopher despite his use of mechanical analogies see p. distelzweig, “‘mechanics’ and mechanism in william harvey’s anatomy: varieties and limits,” in p. distelzweig, b. goldberg and e. ragland, early modern medicine and natural philosophy (dordrecht: springer, 2016), pp. 117-40. 13 see gustav scherz’s biography in bop, pp. 185-193; roberto angeli, niels stensen (turin: edizioni san paolo, 1996; 1st ed., 1968), pp. 120-127. 14 see, for example, richard westfall, the construction of modern science: mechanisms and mechanics (cambridge: cambridge univ. press, 1977), pp. 94-96; and thomas settle, “borelli, giovanni alfonso,” in complete dictionary of scientific biography, vol. 2. (detroit, mi: charles scribner’s sons, 2008), pp. 306-314. for borelli’s mathematical training see bertoloni meli, “the collaboration between anatomists and mathematicians,” p. 678. most of borelli’s books up to then were all on mathematics. 15 borelli to malpighi, 17 july 1666, in howard adelmann, the correspondence of marcello malpighi, 5 vols. (london: cornell university press, 1975), vol. 1, p. 318: “lo stenone è qui, … e mi ha detto … che vuol che io gl’insegni qualche cosa di geometria.” galileo’s last disciple, that steno published the elementorum myologiæ specimen, as historian domenico bertoloni meli explains.16 thus, it would seem reasonable to assume that steno travelled to tuscany to learn mathematics in the italian school of “the great galileo,” as steno later referred to him.17 however, a letter recently acquired by the royal danish library suggests that steno’s interests in mathematics were more developed than previously thought before his arrival in italy. in the same year of steno’s arrival, prince leopoldo de’ medici (1617-75) mentioned to a friend the arrival of “mr. steno, a danish anatomist of young age but remarkable in his work… and a great geometer.”18 this means that steno displayed his mathematical skills to the medici prince before having any prolonged contact with borelli and viviani. while this does not diminish the influence of a galilean school after steno’s arrival in italy, it implies that steno’s mathematical interests and training predated his italian years. this is evident, for example, in steno’s de musculis et glandulis observationum specimen (copenhagen, 1664), where steno had already developed an early geometrical theory of the muscles.19 but besides the muscles, there has been little historical work done on steno’s early interests in mathematics until now.20 the second historical implication of steno’s early interest in mathematics has to do with the development and spread of mixed mathematics into the discipline of anatomy in the second half of the seventeenth centur y. steno’s interests in mathematics developed gradually with his anatomical works, especially those on the glands. these works are representative of the new anatomical research of the 1660s, based not only on new dissection methods such as the regular prac16 bertoloni meli, “the collaboration between anatomists and mathematicians,” pp. 696-706. 17 steno, de solido (florence, 1669), p. 50; bop, p. 802. 18 leopoldo de’ medici to alessandro segni, 27 november 1666, in copenhagen, royal danish library, acc. 2019/54: “il s. stenone danese anatomico gioviane d’età ma insigne nel suo mestiere corredato poi d’ogni sorte di laudazione, e geometra bravo il che molto li giova al suo mestiere et il vero tipo della modestia.” although some dated the letter april 1666, leopoldo’s handwriting says “nov. 1666.” 19 troels kardel, steno: life, science, philosophy (copenhagen: the danish national library of science and medicine, 1994), pp. 25-32; kardel, steno on muscles, pp. 11-16; bertoloni meli, “the collaboration between anatomists and mathematicians,” pp. 697-699. 20 the few works that mentioned steno’s research on the glands barely addressed any mathematics, see harald moe, “when steno brought new esteem to glands,” in j. poulsen and e. snorrason (eds.), nicolaus steno 1638-16868: a re-consideration by danish scientists (gentofte, denmark: nordisk insulinlaboratorium, 1986), pp. 51-96. for a brief mention of the mechanical aspect of steno’s study on glands see d. bertoloni meli, mechanism, experiment and disease: marcello malpighi and seventeenth-century anatomy (baltimore: johns hopkins university press, 2011), pp. 16, 103-6. 32 nuno castel-branco tice of dissections and vivisections, but also on new areas of anatomical interest such as the glands, the lymphatic system, and the circulation of the blood.21 it was in this anatomical context that steno used quantitative measurements, mechanical analogies, and the concepts of flow and speed in his anatomical argumentation. some of these methods had already been used by other anatomists such as william har vey, santorio santorio (1561-1636) and even galen.22 for instance, galen used the quantities of fluid drank (and later expelled) by a man to argue that urine was drawn directly from the blood.23 yet, the epistemologica l role of mathematics was rapidly changing in the seventeenth century and, more importantly, it was still a matter of debate in natural philosophy and medicine. therefore, a look at steno’s early uses of mathematics helps to see exactly how an early modern anatomist adopted such methods. this article’s structure follows the chronological line of steno’s anatomical publications before the elementorum myologiæ specimen, from 1661 to 1664. for reasons of space, i focus mostly on the intellectual aspects of steno’s interest in mathematics, setting aside other considerations. weights and proportions of glands, 1661 nicolaus steno arrived in the netherlands for the first time sometime before april 1660.24 he had already studied for three years at the university of copenhagen under thomas bartholin (1616-1680), one of the 21 frequent dissections and vivissections only became common in the second half of the 17th century, see anita guerrini, the courtiers’ anatomists: animals and humans in louis xiv’s paris (chicago: university of chicago press, 2015), pp. 6, 24; d. bertoloni meli, “early modern experimentation in live animals” in journal of the history of biology, 46 (2013), pp. 199-226. these areas of interest expanded upon the two major discoveries of the late 1620s: the circulation of the blood by william harvey and the lacteal vessels (the lymphatics) by gaspare aselli (1581-1625), whose works were often published together, see domenico bertoloni meli, mechanism, experiment and disease: marcello malpighi and seventeenth-century anatomy (baltimore: johns hopkins university press, 2011), pp. 1-4, 31-7. 22 for quantification and the use of concepts of flow by both galen and harvey see michael shank, “from galen’s ureters to harvey’s veins,” journal of the history of biology, 18 (1985), pp. 331-55. for galen’s mechanical analogies see bertoloni meli, mechanism, pp. 11-16. on santorio and harvey see fabrizio bigotti, “the weight of the air: santorio’s thermometers and the early history of medical quantification reconsidered,” journal of early modern studies 7 (2018), pp. 73-103; and jerome bylebyl, “nutrition, quantification and circulation,” bulletin of the history of medicine, 51 (1977), pp. 369-385. 23 owsei temkin, “a galenic model for quantitative physiological reasoning?” bulletin of the history of medicine. 35 (1961), pp. 470-475, esp. 471-472. 24 scherz’s biography in bop, p. 68. leading physicians of europe and a strong promoter of a new anatomy based in regular dissections.25 in those years, steno became familiarized with the most recent anatomical findings, including the discovery of the circulation of the blood by william harvey and the lymphatic vessels by bartholin himself.26 in his third year, university classes were canceled due to a swedish military siege imposed on copenhagen, and so steno used his time to read beyond the normal university curriculum, engaging with recent scientific literature associated with the new sciences, including some books related to mathematics.27 according to the notebook that he wrote in that year, steno read in full jean pecquet’s (1622-1674) experimenta nova anatomica (paris, 1654), a book which pecquet wrote in collaboration with the french mathematicians gilles personne de roberval (1602-1675) and adrien auzout (1622-1691), and he also read the original and long description of pierre gassendi’s (1595-1655) mechanical and atomistic philosophy.28 when steno left denmark, although his intellectual commitment was to anatomy, he was aware of the new scientific trends flourishing throughout europe. steno’s years in the low countries confirm his commitment to anatomy. in those years, while still in his early twenties, steno earned a solid reputation for his dissection skills among those who witnessed his dissections either in person or through his writings.29 steno lived in amsterdam from march to july 1660, where he took classes of anatomy with gerard blasius (1625-1682) and where he also observed for the first time the parotid salivary duct, later named as ductus stenonianus.30 steno then moved to the university of leiden, where his mentor thomas bartholin had also been twenty years before.31 there, steno met the physicians franciscus sylvius (1614-1672) and johannes van horne (1621-1670), old friends of bartholin who were now prestigious pro25 for more on bartholi in english, see c. d. o’malley, “bartholin, thomas,” complete dictionary of scientific biography, vol. 1, pp. 482-3. 26 scherz’s biography in bop, pp. 47-50. 27 for an overview of what steno read, see ziggelaar, “commentary,” in ziggelaar (ed.), chaos, pp. 459-481. 28 ziggelaar, “commentary,” pp. 473-474. on pecquet and mathematicians see bertoloni meli, “the collaboration between anatomists and mathematicians,” pp. 670-7. 29 scherz’s biography in bop, pp. 72-83, 151, 367; guerrini, the courtiers’ anatomists, pp. 85-87. 30 first named as such by johannes van horne in van horne, mikrokosmos seu brevis manuductio ad historiam corporis humani (leiden, 1662), p. 23. see also henry gray, anatomy of the human body, 20th ed. (philadelphia, lea & febiger, 1918), p. 1134. 31 steno enrolled in the university of leiden in 27 july 1660, see leiden university library, asf 10, fol. 585; as quoted in album studiosorum academiæ ludguno batavæ (the hague, 1875), p. 482. for bartholin in leiden see o’malley, “bartholin, thomas,” p. 482. 33dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64 fessors of medicine and anatomy at the university.32 under their guidance, steno continued his explorations of the salivary duct and salivary glands. upon the suggestion of sylvius and bartholin, steno published his first anatomy book, the anatomica disputatio de glandulis oris (leiden, 1661), the outcome of a university dissertation defense at leiden, presided by van horne.33 the book was published with the elsevier printers, the same house that published galileo’s two new sciences (leiden, 1638) a few decades earlier. in this short book, steno put forward a full description of the salivary glands, the most complete up to then, in a time in which studies on the glands were emerging as a new area of anatomical research.34 half a year later, steno re-edited his text as the first part of a four-part book in 1662, the observationes anatomicae (leiden, 1662). this new book, which was distributed more widely, included steno’s research not just on the salivary, but also on the lachrymal and nasal glands. although a single book, the four parts of the observationes anatomicae show steno’s intellectual progress and how he gradually used more methods and ideas from the physico-mathematics, which he increasingly acknowledged. this research program on the glands started when steno observed for the first time the parotid salivary duct, first in a sheep’s head and then in a dog.35 this duct proceeded directly from the parotid gland, located behind the ear, to the mouth. but the most recent book on glands, the adenographia sive glandularum totius corporis descriptio (london, 1656), written by the english physician thomas wharton (1614-1673), had no mention of this duct.36 the adenographia was the first anatomical publication entirely dedicated to glands, so studies of glands still had much to develop, as the works of steno and sylvius show.37 wharton described the parotid 32 bartholin participated in sylvius’ dissections around the year 1640, see johannes walaeus letter to thomas bartholin, 10 october 1640 in t. bartholin, institutiones anatomicae (1641), p. 408. van horne wrote the letter “de aneurysmate epistola” published in thomas bartholin, anatomica aneurysmatis dissecti historia (palermo, 1644). 33 nicolaus steno, observationes anatomicae quibus varia oris, oculorum, et narium vasa describuntur (leiden, 1662), p. 5 (bop, p. 430). 34 bertoloni meli, mechanism, experiment and disease, pp. 103-106. 35 steno to bartholin, 22 april 1661, in bartholin, epistolarum medicinalium centuria iii (copenhagen, 1667), pp. 88-89: “quod 7 april mihi emptum in museolo solus secabam ovillo capite ductum, à nemine, quod sciam, descriptum invenirem. … et paucis inde diebus in canino capite licet obscurius successit.” (bop, pp. 420-421). for this research of the parotid duct steno also dissected a lamb, a cow, many more dogs, rabbits and he mentioned sylvius’ dissections of human cadavers at the hospital, see steno, observationes anatomicae, §16, §18, §47-48, §50, §19, pp. 15, 17, 46-47, 49, 18-19 (bop, pp. 436, 438, 457-458, 460, 439). 36 for an english translation see stephen freer (transl.), thomas wharton’s adenographia (oxford: oxford university press, 1996). 37 andrew cunningham, “the historical context of wharton’s work on gland in detail, but he did not relate it to the production of saliva because, as steno explained, he saw no salivary duct.38 for wharton, saliva was produced only in the maxillary glands, where he observed a pathway between them and the mouth, now called ductus whartonianus.39 but there were other things that wharton missed. according to steno, the parotid gland described by wharton was actually formed by two distinct glands, the conglobate parotid gland, connected to the lymphatic system, and the conglomerate parotid gland, connected to the mouth  via the salivary duct (fig. 2).40 here, steno was following the twofold division between conglobate and conglomerate glands, developed by his professor franciscus sylvius.41 the conglobate glands were round organs directly connected to the lymphatic vessels, and the conglomerate were larger organs that released fluids into the body, such as salivary or the pancreatic fluids. although sylvius explained this distinction in his writings, steno said he learned it directly from his professor’s dissections at the hospital in leiden, where “medical practice” was taught “daily.”42 the glands,” in thomas wharton’s adenographia (oxford, 1996), pp. xxvii-xxxi. 38 steno, observationes anatomicae, p. 15: “sed non mirum haec à clarissimo viro proposita, quandoquidem praeter vasa cæteris partibus communis nihil in illa observavit.” (bop, p. 437); thomas wharton, adenographia (london, 1656), pp. 124-7. 39 see steno, de musculis et glandulis (copenhagen, 1664), p. 40; gray, anatomy of the human body, p. 1135. 40 steno, observationes, §10, p. 10: “ut itaque distinctè considerentur, poterit hæc de qua nobis sermo est, parotis conglomerata appellari, nomine conglobatarum parotidum reliquis relicto.” (bop, p. 433). 41 steno, observationes anatomicæ, §9, p. 7 (bop, p. 432); bertoloni meli, mechanism, experiment and disease, p. 103. 42 steno, observationes anatomicæ, §10, p. 9: “superiori enim anno iam præcipite, cùm in nosocomio praxin faciendo quotidie doceret clariss. figure 2. parotid glands in the head of a calf. a) the largest is the conglomerate gland with c) the salivary duct, and b) the beanshaped conglobate gland. from steno, observationes anatomicae (leiden, 1662), p. 21. courtesy of wellcome collection. 34 nuno castel-branco to show better wharton’s mistake, instead of arguing on the basis of dissections alone, steno put forward another argument using quantitative measurements. for some glands, including the maxillary and the parotid glands, wharton registered their weights in different animals (table 1). the proportions between the weights of the two glands measured by wharton in a man and in a fetus of a cow were somewhat similar, averaging approximately 0.6. this proportion showed that the parotid had almost twice the weight of the maxillary glands. however, steno argued that the parotid glands were not as heavy as wharton thought, mainly because they were two separate glands, the conglobate and the conglomerate. steno said that in wharton’s case the proportion between the parotid and maxillary glands has not been exactly observed … [unless] besides bigger and more numerous nerves reported through the upper gland, the smaller [conglobate] gland enclosed in the larger [conglomerate gland] increased the weight of the latter, insofar as it was [thought to be] not distinct from the other.43 to show better his point, steno measured the weights of the glands in a calf he dissected. this time, however, the parotid gland was “free from vessels and from the conglobate gland lying beside it.”44 in the end, steno’s proportion of the weights of the maxillary and the parotid conglomerate glands was 0.89, much closer to 1, thus meaning that their weights did not differ much. neither steno nor wharton wrote the precise proportion in a structured format like table 1, but they both referred to it.45 more importantly, with this measurement steno used a quantitative argument to confirm his point on the separation of the conglobate and conglomerate parotid glands, which wharton missed. since by definition conglomerate glands secreted a fluid and steno had found a salivary duct coming out of it, this quantitative point also had an implication on the function of the glands and thus contributed to steno’s argument that the parotid conglomerate gland produced salivary fluid. for a modern scientist, it could be tempting to judge steno and wharton for drawing conclusions on these proportions without enough comparative data, i.e. for lacking what modern science now understands franciscus sylvius exhibuit tum discipulis…” (bop, p. 433). 43 steno, observationes, §12, p. 11: “ne tamen huius ad illam proportionem exacte observatam esse credam, suadet, præter nervos majores copiosioresque per superiorem delatos, minor majori inclusa glandula, quam, utpote a reliqua non distinctam, pondus illius auxisse puto.” (bop, p. 434). 44 steno, observationes, §12, p. 11: “à vasis et sibi apposita conglobata liberatam” (bop, p. 434). 45 steno, observationes, §12, p. 11: “proportione exactè observatam.” as observational error.46 however, in the middle of the seventeenth centur y, when the epistemological value of experiments was still being debated, there was nothing akin to a statistical theory of error.47 in fact, notions of how to perform experiments, and how to report them, were even evolving between steno and wharton themselves. both authors decided to measure and compare the weights of the glands, but there were significant differences in their approaches. first, steno pointed out that wharton’s quantitative data was not precise enough, since wharton did not say what exactly he had weighed: was it the glands and the attached vessels, or did he remove blood vessels and nerves from the glands beforehand? in steno’s words, wharton “seems to have described an abundance of matter from these glands in an undetermined quantity [extensione non determinata].”48 this remark also conveys steno’s understanding of a need to describe the experimental conditions  better. steno tried to improve upon wharton, by saying he detached each gland that he 46 stephen stigler, the history of statistics: the measurement of uncertainty before 1900 (cambridge, ma: harvard univ. press, 1986), esp. 90-1; lorraine daston, classical probability in the enlightenment (princeton, nj: princeton university press, 1988), esp. 271-2; ian hacking, the emergence of probability: a philosophical study of early ideas about probability induction and statistical inference, 2nd ed. (cambridge: cambridge university press, 1975, 2006), p. 130. 47 for seventeenth-century debates on experiments see steve shapin and simon schaffer, leviathan and the air pump: hobbes, boyle, and the experimental life (princeton: princeton university press, 1985), esp. 225-282; dear, discipline and experience, pp. 63-85. for the historical value of approaches that would today be considered wrong see jed buchwald and allan franklin (eds.), wrong for the right reasons (dordrecht: springer, 2005). 48 steno, observationes anatomicæ, §12, pp. 10-11: “quibus clariss[imus] vir copiam materiæ expressisse videretur, extensione non determinata, nisi jam ante constare putasset, materiam in utraque eodem modo esse dispositam, quod & innuit, dum substantiam utrique similem adscribit.” (bop, p. 434). table 1. data from wharton, adenographia, pp. 119-120, 125 and steno, observationes, pp. 10-11. the conversion of units from 17th-century ounces to grams is from wilhelm maar (ed.), nicolai stenonis opera philosophica, 2 vols. (copenhagen: vilhelm tryde, 1910), vol. 1, pp. 227-228. dissected corpses maxillary gland parotid gland proportion 28-year-old man (wharton) 9.8 g 17.6 g 0.56 fetus of a cow (wharton) 7.8 g 11.7 g 0.67 proportion average for wharton’s values 0.62 calf (steno) 125 g 141 g 0.89 35dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64 weighed “from vessels and from the conglobate gland lying beside it.”49 finally, whereas wharton presented the weights only as a secondary detail of his anatomical description, steno used them to argue for the existence of two glands – the conglobate and conglomerate glands. ultimately, in steno’s text, the careful description of how he carried out the measurements and the details he included lent them a greater epistemological value than they had for wharton. steno did not use more quantitative measurements in the observationes, but he resorted to other mathematical approaches.50 after establishing the distinction between the conglobate and conglomerate parotid glands, steno explained that the function of the latter was to produce the salivary fluid, alongside the maxillary glands, already discovered by wharton.51 in fact, steno discovered other glands that produced saliva and he listed five types in total: parotid glands, maxillary glands, sublingual glands, palatine glands and glands of the cheek.52 although steno did not comment on the fluid production rates each gland, he said that “several small vessels in the mouth” transmitted “fluid equally to all parts [ad humorem omnibus æqaliter communicandum].”53 he concluded that the fluid reached all parts equally “in order that the upper parts moisten as well as the lower ones, [and] the internal as well as the external ones.”54 later, when discussing the constitution of the saliva, which steno said required “chymical anatomy,” he used the same kind of discourse, in which he spoke of a quantifiable entity without actually measuring it.55 first, he said that “tasting and smelling” saliva was similar to water because it was “deprived of quality,” however “seeing and feeling [it] judge it less simple than water.”56 again, steno was following the methods of his 49 steno, observationes, §12, p. 11: “à vasis et sibi apposita conglobata liberatam” (bop, p. 434). 50 wharton, on the other hand, did include more measurements, as when he said that the maxillary duct in a cow was thirteen inches long, see wharton, adenographia, p. 131: “ductu tredecim pollices longo provehitur” 51 steno, observationes, §17, p. 17: “verus parotidum conglomeratarum usus, illam, quæ per ductum salivarem exteriorem in exteriorem oris cavitatem excernitur, salivam præparare…” (bop, p. 438) 52 see steno, observationes anatomicæ, §9, p. 8 (bop, p. 432). for a description of the cheek, sublingual and palatine glands, see idem, §18, §20, §21, pp. 17-23 (bop, pp. 438-440). 53 steno, observationes anatomicæ, §22, p. 22: “plura data sunt vascula ad humorem omnibus æqualiter communicandum” (bop, p. 440). 54 steno, observationes, §22, p. 22: “ut autem in ore cum inferioribus superiora, interiora cum exterioribus madefierent” (bop, p. 440) 55 steno, observationes, §25, p. 24: “consideratio chymicam anatomen requirat” (bop, p. 441). 56 steno, observationes, §28, p. 26: “quam itaque sapor, et odor άποιον iudicant, eam visus, et tactus aqua minus simplicem decernunt” (bop, p. 444). professor franciscus sylvius who relied strongly on the senses as a source of information about the constitution of chymical substances.57 indeed, steno concluded that saliva was not “a simple liquid, but a mixed one, and this in a proportion [singulari proportione].”58 but this proportion was discussed only in qualitative terms, even by “the famous sylvius … [who] thinks that in saliva there is much water, a little volatile spirit and very little lixivial salt mixed with, and moderated by a trace of oil and spirit of acid.”59 the mechanical action of bodily fluids, 1661-1662 steno finished the 1661 version of his treatise on the salivary glands with a set of corollaries on the role of the mind on blood circulation, on the glands of the nose and on the filtering of blood in the body, which he expanded in the other treatises of the obsevationes anatomicae.60 corollaries were a structure most common in mathematical treatises, usually associated with euclid’s elements, but also typical of academic dissertations.61 steno did not use a corollary structure in the observationes, as he would later do in his final book on the muscles. but in its third treatise, on the lachrymal glands, steno became much more open when speaking about mechanics and using mathematical concepts. first, he dedicated the third treatise to six intellectuals from the low countries and denmark, two of them mathematicians.62 one was jorgen eilersen (georgius hilarius) (1616-1686), a danish theologian who graduated from the university of copenhagen and the headmaster of the latin school of copenhagen, which ste57 evan ragland, “chymistry and taste in the seventeenth century: franciscus dele boë sylvius as a chymical physician between galenism and cartesianism,” ambix 59 (2012), pp. 1-21. on the use of the word “chymistry” see lawrence principe, the secrets of alchemy (chicago: university of chicago press, 2013), p. 85. 58 steno, observationes anatomicæ, §28, p. 27: “esse iitaque non simplicem liquorem, sed mixtum, idque singulari proportione, ex ante dictis patet.” (bop, p. 445). 59 steno, observationes anatomicæ, pp. 27-28: “clarissimi sylvius … existimat esse in saliva multum aquæ, parum spiritus volatilis, et minimum salis lixiviosi, cum olei spiritusque acidi tantillo misti, temperatique.” (bop, p. 445). f. sylvius, opera medica, hoc est, disputationum medicarum decas (geneva, 1681), p. 11. 60 steno, disputatio de glandulis oris (leiden, 1661) (bop, pp. 462-463). 61 for the use of corollaries in dutch seventeenth-century dissertations, see dirk van miert, humanism in an age of science: the amsterdam athenæum in the golden age, 1632-1704 (leiden: brill, 2009), p. 153-6. for an extensive study of dissertations in the early modern period, see kevin chang, “from oral disputation to written text: the transformation of the dissertation in early modern europe,” history of universities 19 (2004), pp. 129-187. 62 steno, observationes anatomicæ, pp. 80-81 (bop, p. 483). 36 nuno castel-branco no attended before the university.63 although eilersen was academically trained in theology, he wrote several books on mathematics in copenhagen, where he also edited astronomical calendars and almanacs.64 in fact, steno addressed him as a “mathematician and man of letters.”65 eilersen was later appointed as professor of mathematics at the university of copenhagen.66 th e other mathematician was jacob golius (1596-1667), professor of mathematics at the university of leiden since 1629.67 steno was friends with golius, since they discussed topics besides anatomy or mathematics, as when golius informed steno about the emergence of fevers in amsterdam in september 1661.68 golius also “did not disdain either to watch when i [steno] prepared the salivary and lacrimal ducts in a calf,” showing that he sometimes attended steno’s dissections.69 in this third treatise of the observationes, steno explained the production of tears in the eye glands and how they move from the glands to the eyes. but before starting his main narrative description of the lachrymal glands, steno wrote an introduction where he points out the importance of lubrication in mechanical motion. he explains that those who work on mechanics know that, “to facilitate movement, the things to be moved should be smeared by some oily humor.”70 he compares the oil to a third agent that facilitates the mover, like pushing a boat over a surface with the help of rollers laid underneath (fi g. 3) or “smearing with an unctuous fl uid the axle about which the wheel rotates.”71 like these mech63 gustav scherz’s biography in bop, pp. 29-31. on eilersen see s. m. gjellerup, “eilersen, jorgen” in carl frederik bricka (ed.), dansk biografi sk lexikon (copenhagen, 1887-1905), vol. 4, pp. 464-465; and maar, nicolai stenonis opera philosophica, vol. 1, p. 241. 64 j. eilersen, trigonometria plana (copenhagen, 1644); eilersen, progymnasmatum mathematicorum enchiridion (copenhagen, 1656). 65 steno, observationes anatomicæ, p. 80: “d. georgio hilario, mathematico et literatori” (bop, p. 483). 66 for eilersen’s university appointment see gjellerup, “eilersen, jorgen.” 67 w. juynboll, “golius, jacob,” in p. c. molhuysen and p. j. blok (eds.), nieuw nederlandsch biografi sch woordenboek, 10 vols. (leiden, 19111937), vol. 10 (1937), pp. 287-289; and “golius, jacobus” in a. j. van der aa (ed.), biographisch woordenboek der nederlanden, 21 vols. (haarlem, 1852-1878), vol. 7, pp. 270-3. 68 steno to th omas bartholin, 12 september 1661, in th omas bartholin, epistolarum medicinalium centuria iii (copenhagen, 1667), p. 230: “et retulit mihi ante paucos dies clariss. golius sibi à medicó quos dam amstelodamensi per litteras relatuum…” (bop, p. 468). 69 steno, observationes anatomicæ, p. 59: “sed nec clariss. golius mathematum et orient. ling. profess. præceptor colendus cum salivæ et lachrimarum vasa in bubulo adornarem, spectatorem agere dedignatus est.” (bop, pp. 470-1). 70 steno, observationes anatomicae, p. 85: “ut ad motum faciliorem reddendum res movendas humore unctuoso oblinerent” (bop, p. 484). 71 steno, observationes anatomicae, p. 85: “viderunt illi, si movendum inter et fi xum, super quod motus fi eri debet, tertium motu facilius intercedat, opus longe commodius procedere, hinc, ut suppositis cylindris in æquora navem propellunt, sic et, super quem rota volvitur, anisms, steno continues, the bodies of animals also rely on fl uids to make the parts move better. but, unlike machines, the living body “proceeds more skillfully or, i should say, more divinely,” because “both the fl uid that is supplied and the quantity in which it is supplied show a skill far greater.”72 according to him, this was seen in the mouth with salivary fl uid’s enhancement of the movements of the mouth, but most especially in the eyes.73 th e analogy between artifi cial mechanisms and the human body in the works of steno and other scholars is oft en attributed to the widespread infl uence of cartesian thought, especially in the netherlands.74 howpolum liquore pinguiori inungentes gyrationem facilius expediunt.” (bop, p. 485). 72 steno, observationes anatomicae, p. 86: “in automatico autem animalium corpore artifi ciosius, imo divinius hæc omnia geruntur; ibi enim et humor, qui subministratur, et, quo subministratur, modus longe maius artifi cium commonstrant.” 73 steno, observationes anatomicae, p. 86: “sic partium in ore motus accedente saliva promoventur… sed præ cæteris in oculis elegantissimè hæc conspiciuntur.” (bop, p. 486). 74 eric jorink says that the netherlands was “the hotbed” of cartesian philosophy, in “modus politicus vivendi: nicolaus steno and the dutch (swammerdam, spinoza and other friends), 1660–1664,” in raphael andrault and mogens lærke, steno and the philosophers (leiden: brill, 2018) pp. 12-44, esp. 16; see also wiep van bunge, “th e early dutch reception of cartesianism” in steven nadler, tad m. schmaltz, delphine antoine-mahut, th e oxford handbook of descartes and cartesianism (oxford: oxford university press, 2019); g. a. lindeboom, “th e impact of descartes on seventeenth century medical thought in the netherlands,” janus, 58 (1971), pp. 201-206. for the supposed infl uenced of cartesianism on steno, see sebastian olden-jørgensen, “nicholas steno and rené descartes: a cartesian perspective on steno’s scifigure 3. pulling a boat over a fl at surface with the help of rollers laid underneath from simon stevin, les œuvres mathématiques (leiden, 1634), p. 481. courtesy of special collections, th e sheridan libraries, johns hopkins university. 37dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64 ever, there was already a tradition of using mechanical analogies in anatomy since galen and erasistratus.75 thomas wharton, no cartesian himself, also relied on mechanical analogies, as when he compared a muscle in the mouth to a pulley.76 there were, however, conceptual differences in the way anatomists adopted these analogies. for instance, like steno, galen also commented on the body as superior to machines, but he did it mostly to show that mechanical analogies fell short of the full anatomical reality.77 steno explained that the body differed from a machine not in the mechanism itself but in “the humour which is supplied,” which reveals “a skill far greater.”78 but there is more to be said about these mechanical analogies beyond the typical cartesian comparison of bodies to machines. mechanics was considered part of physico-mathematics. thus, in steno’s mind, those who studied and practiced mechanics, the “mechanici” as he called them, relied on mathematics as their main tool to describe the natural world.79 steno in particular had in mind the work of “the most talented [simon] stevin,” one of the leading names of dutch mathematics, and whom steno mentioned in the preface.80 in the sevenentific development,” gary rosenberg (ed.), the revolution in geology from the renaissance to the enlightenment (the geological society of america, 2009), pp. 149-57; and stefano miniati, nicholas steno’s challenge for truth (milan: franco angeli, 2009), p. 95. 75 evan ragland, “mechanism, the senses, and reason: franciscus sylvius and leiden debates over anatomical knowledge after harvey and descartes,” in peter distelzweig, benjamin goldberg and evan ragland (eds.), early modern medicine and natural philosophy (new york: springer, 2016), pp. 173-206, esp. 183-4. 76 wharton, adenographia, p. 131: “fertur sub musculo maxillari tereti biventri, …, qui eidem ramo quasi trochlea vicem præstat.” on wharton as non-cartesian see cunningham, “the historical context of wharton’s work on the glands,” p. xli; wharton, adenographia, p. 154: “hanc opinionem primus proposuit cartesius, lib. de affect. art. 31,32 eamque variis rationibus bartholinus expugnavit, nempe: …”; and wharton letter to mrs. church, 15 may 1673, in wharton, thomas wharton’s adenographia, p. 311. 77 sylvia berryman, “galen and the mechanical philosophy,” apeiron 35 (2011), pp. 235-53, esp. 242-7. 78 steno, observationes, p. 86: “in automatico autem animalium corpore artificiosiùs, imò divinius hæc omnia geruntur; ibi enim et humor, qui subministratur, et, quo subministratur, modus longè maius artificium commonstrant.” (bop, p. 486). interestingly, even descartes nuanced his body-machine comparisons, see gideon manning, “descartes’ healthy machines and the human exception,” in daniel garber and sophie roux (eds.), the mechanization of natural philosophy (dordrecht: springer, 2013), pp. 237-62. 79 steno, observationes, p. 85: “quod mechanicos usus docuit…” 80 steno, observationes, p. 82: “existimat ingeniosissiimus stevinus” (bop, p. 484). for more on stevin see e. j. dijksterhuis, “the life and works of simon stevin,” in e. j. dijksterhuis (ed.), the principal works of simon stevin, vol. 1: general introduction, mechanics (amsterdam, 1955), pp. 3-14; dirk struik, the land of stevin and huygens: a sketch of science and technology in the dutch republic during the golden century (london: d. reidel publishing company, 1981), esp. 52-60. teenth century, one of the main arguments for the study of mechanics was the command it gave its practitioners over phenomena whose operations were marvelous and unseen, like the use of a lever to lift weights that were impossible to lift otherwise. this description fits well with steno’s understanding of the human body, which he described as even more marvelous than inert mechanisms, as we saw. by adopting mechanical analogies, like descartes and others had done, steno was looking for an approach to make the invisible operations of the human body visible. jesuit scholars such as athanasius kircher and gaspar schott (1608-1666), whom steno read in his final year in copenhagen, also used physico-mathematics to unmask the hidden phenomena of nature.81 steno returned to this idea of using mathematics to illustrate hidden phenomena in his preface to the elementorum myologiæ specimen, where he insisted that, by neglecting mathematics, “anatomy has brought the matter to such a point that nothing remains more unknown to man than man himself.”82 speed and flow of blood, tears, and saliva, 1662 steno gestured towards mathematical concepts one more time in his explanation of how the eye glands produced lachrymal fluid. as typical in an anatomical treatise, steno begins by describing the structure of the glands, agreeing with wharton’s description of the two conglomerate glands of the eye, which they both called the lachrymal and innominate glands.83 but when addressing the function of the glands, steno explains, wharton and others “did not believe that such an abundance of tears can possibly come forth from such small glands.”84 in fact, the large quantity of tears that often come to the eye led wharton to agree with hippocrates 81 steno has many notes related to kircher, but for reference to kircher and schott in the same place see ziggelaar, chaos, pp. 253-4. for kircher and schott’s approach to hidden phenomena, see mark waddell, jesuit science and the end of nature’s secrets (burlington, vt: ashgate publishing company, 2015), esp. 5-15, 161-186. 82 steno, elementorum myologiæ specimen, p. iv: “namque dum legitimi principis [mathematicarum] imperium non agnoscens, suo, … eò rem [anatome] tandem deduxit, ut homine nihi homini manserit ignotius.” (bop, p. 651). 83 steno, observationes anatomicae, pp. 86-87: “glandulæ autem interiorem palpebrarum superficiem humectantes binæ sunt: lacrymis altera clariss. whartono innominata dicta …” 84 steno, observationes anatomicæ, p. 92: “non enim [magni viri] crediderunt, posse ex tam parvis glandulis tantum lacrymarum copiam prodire” (bop, p. 490). wharton, adenographia, p. 178: “enim verò hæ glandulæ perexiguæ sunt, et multum humiditatis in se coacervare nequeunt, nè vicesima quidem lachrymarum partem quæ tantillo temporis spacio a nonnullis profunduntur.” 38 nuno castel-branco that tears were produced in the brain.85 not only was the brain the largest organ closer to the eye, but, in humans, tears were also related to emotions and pain, felt mainly by the brain and the nervous system.86 steno, however, describes both eye glands as conglomerate glands, and so, according to his theory of glands, they produce a fluid, which serves to lubricate the eye or, when produced “profusely… it comes under the name of tears.”87 to address the problem of quantity, steno uses a simple mathematical explanation, by saying that if the magnitude of the [tear]drops is compared to the time during which they are formed, no problem will appear here. for the time is not so short that as much humor could not flow in through several vessels as is required to form a drop.88 steno uses the concepts of time and flow to say that the formation speed of tears is slow enough to produce each tear drop. later in the same treatise, steno uses these concepts to put forward a mechanical theory of glandular secretion by blood filtration. steno had already suggested that the salivary glands produced saliva directly from the blood, and not, as wharton claimed, from the nerves.89 in the first treatise, steno said that “arteries supply to the glands, besides heat, also nutriment and together with it the matter of saliva.”90 wharton thought that was unlikely, because there were not sufficient arteries and veins passing through the maxillary glands for “the quantity 85 wharton, adenographia, pp. 181: “ego existimo esse nervos, præcipuè illos, qui decurrentes per plexum retiformem, in eum, ut dixi, copiosas cerebri humiditates effundunt, ex eóque penu sufficientem oculis materiam miniftrant.” elizabeth craik, “the reception of the hippocratic treatise on glands” in m. horstmanshoff, h. king and c. zittel (eds.), blood, sweat and tears – the changing concepts of physiology from antiquity into early modern europe (leiden: brill, 2012), pp. 65-82, esp. 66. 86 on emotional tears as specific to humans see steno, observationes anatomicae, p. 92: “et sequeretur, etiam brutis attribuendas lacrymas, quod multis absurdum videtur.” (bop, p. 490). on the brain as the center of the nervous system, an idea held by most ancient writers, see vivian nutton, ancient medicine, 2nd ed. (new york: routledge, 2004, 2013), pp. 118, 134, 238-240. 87 steno, observationes anatomicae, p. 90: “modò impetuosius profluens lacrymarum nomine venit” (bop, pp. 488). 88 steno, observationes anatomicae, p. 92: “si guttarum magnitudo cum tempore, quo colliguntur, conferatur, nulla hic videbitur difficultas. nec enim tempus adeo breve, quin per plura vasa tantum humoris affluere possit, quantum ad guttam constituendam requiritur;” (bop, p. 490). 89 wharton, adenographia, p. 134: “proximo loco inquirendum, est è quibusnam partibus et perquas vias hic humor in glandulas salivales derivetur. credibile est, è nervoso genere profundi.” 90 steno, observationes anatomicae, §38, p. 35: “ex prædictis itaque facilè liquet, arterias glandulis, præter calorem, etiam nutrimentum, et simul salivæ materiam suppeditare.” (bop, p. 449). of salivary matter that is excreted.”91 in order to solve this problem, steno said that “since saliva does not flow into the mouth with the same speed [celeritate] at which blood arrives, the delay of the saliva in its flowing could compensate the paucity of blood arriving more quickly.”92 he explored this idea further in his study of the eye glands. according to him, the glands of the eye do not have to be as large because “all the humor which emanates from the eyes was [not] collected previously in the glands.”93 for steno, the secretion of lachrymal humor is in fact directly associated with each pulsating passage of arterial blood. as blood flowed normally through the eyes, the glands produce the quantity of lachrymal fluid necessary to keep the eyes normally lubricated.94 but for a larger production of tears, steno argues that disturbances in the blood flow – such as the ones caused by strong emotions – were the main cause, since some components of the blood would feel pressured to follow other paths like “the simple and porous tunics of the capillaries present inside the glands.”95 the particles [partes] of this humor that leave the blood into the glands, which he calls “serum,” “enter with greater speed, as they naturally tend to, so that the speed compensates for the transit through the narrow vessels.”96 therefore, steno concludes that the increasing speed of blood filtration alone produces “great abundance of tears.”97 the speed and flow of blood had also been critical in william harvey’s discovery of the circulation of blood. harvey decided to calculate the amount of blood ejected at each forceful systole of the heart.98 his results made him realize that “in a comparatively short space of time the whole of the blood contained in the body must pass 91 wharton, adenographia, p. 136: “denique, maior est quantitas materiæ salivalis per has glandulas excretæ, quam facile credas ab exiguis illis arteriis et venis quæ ad has partes distribuuntur.” 92 steno, observationes anatomicae, §37, p. 34: “cum enim eadem celeritate, qua sanguis accedit, in os non influat saliva, poterit mora, quam hæc in fluxu suo trahit, illius celerius affluentis paucitatem compensare.” (bop, p. 449). 93 steno, observationes anatomicae, p. 92: “nec, qui ex oculis emanat, humor, totus in glandulis antea fuit coacervatus.” (bop, p. 490). 94 steno, observationes anatomicae, p. 91: “existimo itaque, manifestum satis esse, illum saltem humorem, qui motui palpebrarum inseruit, ex arterioso sanguine in glandulis secretum per descripta modo vasa adferri.” bop, p. 489). 95 steno, observationes anatomicae, p. 94: “eo copiosius per simplices et porosas capillarium intra glandulas existentium tunicas exprimetur serum;” (bop, p. 491). 96 steno, observationes anatomicae, p. 94: “quicquid per alias vias egredi aptum est, ingreditur illas maiori, ac naturaliter solet, celeritate, ut ita viarum angustiam transitus celeritas compenset;” “hi meatus non dilatentur.” (bop, p. 491). 97 steno, observationes anatomicae, p. 94: “celeritas majori lacrymarum copiæ producendæ sufficit.” (bop, p. 491). 98 william harvey, exercitatio anatomica de motu cordis (frankfurt, 1628), chapter 9. 39dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64 through the heart,” and so the blood had to be in circulation.99 however, according to historian roger french, this quantitative method was very rough, and “far less precise than those of sanctorius and van helmont.”100 yet, the point is that neither harvey nor steno were looking for precision in these cases, but only to show the role of quantities in blood circulation.101 in steno’s case it was the changing speed of the circulation that mattered for the production of tears. steno went on to explain where exactly in the blood system these changes occurred and how the mind affected it, saying that it involved the muscles around the heart.102 it was from this early research using quantification and applying notions from mechanics to anatomy that steno began to study muscle physiology, a topic which would remain central in his future anatomical research. mechanism and geometry in the muscles, 1662-4 steno was able to direct his research from the discovery of the salivary duct in the parotid gland to the most relevant topics of anatomy at the time, first to the lymphatic vessels, with the conglobate glands, and then to the circulation of blood – the hot topic of anatomy, still debated at the time.103 starting in 1662, steno began to look at muscle physiology more closely and, in a leap of anatomical mastery, he connected it again to the heart, by arguing that the heart itself was a muscle.104 as steno delved more deeply into this new research, his mathematical yearnings continued to grow. indeed, for steno, mathematical arguments and concepts represented something deeper than they did for other anatomists. later that year, in august 1662, steno wrote a letter to thomas bartholin saying that, after he published the observationes, he “had decided to lay down the anatomical knife until more convenient times and to take up again the nearly-cast-away geometer’s rod.”105 such 99 roger french, william harvey’s natural philosophy (cambridge: cambridge university press, 1994), p. 90. 100 french, william harvey’s natural philosophy, p. 92. 101 bylebyl, “nutrition, quantification and circulation,” p. 383. 102 steno, observationes, pp. 92-97 (bop, pp. 490-4). 103 in 1666, the physician michele lipari in messina still argued that the pulse did not depend on the circulation of the blood but on vital spirits, see bertoloni meli, mechanism, experiment and disease, pp. 58, 66. in 1670s france, physicians still gave long lectures against the circulation of the blood, see guerrini, the courtiers’ anatomists, pp. 207-9. see also bartholin, epistolarum medicinalium centuria iii (copenhagen, 1667), pp. 308-311: “de sanguinis circulatione dissensus” 104 steno, de musculis et glandulis observationum specimen, p. 22: “cor vere musculum esse.” (bop, p. 562). 105 steno to bartholin, 26 august 1662, in bartholin, epistolarum medica decision, however, did not move forward. in his own words, hardly were my fingers, rid of blood, slightly besprinkled with this very pleasant powder [of geometry] that partly the fairly acid faces of famous gentlemen, partly their unfriendly writings that presented my opinion in a sense different from mine, denied me the happiness desired for a long time so that they imposed on me the necessity to answer and also to return to this bloody task.106 these strong words, although unrelated to the rest of the letter, were enough to show where steno’s heart was with respect to mathematics after his successful research on the glands. more importantly, it revealed a previous commitment of steno’s to mathematics for which, he said, “i spent many hours in the past and which i would have treated not as my primary, but as my unique work, if straitened circumstances at home had not so much convinced as forced me to prefer the useful to the pleasant.”107 it is not yet clear what exactly steno did in the many hours that he worked as a geometer in the past, but his studies in copenhagen with jorgen eleirsen, the headmaster of his latin school to whom steno dedicated the treatise on the eye glands, might be the answer. in may 1663, while travelling through belgium with ole borch (1626-1690) and other friends, steno met the mathematician grégoire de saint-vincent (15841667) when visiting the jesuit college of ghent.108 de saint-vincent was an 80-year old jesuit who became famous for his works on the quadrature of the circle and on mechanics, which might have attracted steno’s interests.109 by then, steno was already working on his new inalium centuria iv (copenhagen, 1667), p. 103: “cum pauculas meas luci publicæ exponerem observationes, decreveram, repositio in commodiora tempora cultro anatomico, geometricum radium tantum non abjectum resumere.” (bop, p. 511). 106 steno to bartholin, 26 august 1662, in bartholin, epistolarum iv, p. 103: “sed vix purgati sangvine digiti jucundissimo illo pulvere leviter erant perspersi, cum virorum clarissimorum partim minæ satis acerbæ, partis scripta parum amica meamque sententiam sensu non meo proponentia desideratam diu felicitatem mihi inviderent, et ut respondendi, sic quoque ad sanguinarium illud excercitium revertendi imponerent necessitatem.” (bop, p. 511). 107 steno to bartholin, 26 august 1662, in bartholin, epistolarum iv, p. 103: “non paucas olim impendi horas, quodque non ut primarium, sed ut unicum tractassem, nisi angusta domi res utilia jucundis præferenda non tam suasisset, quam imperasset.” 108 see h.d. schepelern (ed.), olai borrichii itinerarium 1660-1665 : the journal of the danish polyhistor ole borch, 4 vols. (copenhagen: danish society of language and literature, 1983), vol. 2, 26 may 1663: “colloquium institutum in collegio patris societatis jesus, cum patre à s. vincentio jam octogenario, sed vivid adhuc, et novum scriptum intra biennium promittente.” 109 geert vanpaemel, “jesuit science in the spanish netherlands” in moderchai feingold (ed.), jesuit science and the republic of letters (cambridge, ma, 2003), 389-432, esp. 391-397, 405-406, 418-420. 40 nuno castel-branco book, de musculis et glandulis observationum specimen (1664).110 the book, published in 1664 in copenhagen and amsterdam, was his first printed work on muscle anatomy.111 in de musculis et glandulis, steno relied again on mechanical analogies. for instance, when explaining how the muscles contract, steno said that “it is not the tendon which contracts but the flesh comprised between the tendinous expansions.”112 to explain it better and, “since an explanation through similar things greatly pleases many people,” steno mentioned a complex pulley that brings structural posts to the ground by men holding ropes.113 in this example, the men control the machine by each one holding a single cable and pulling it together. in the muscles, the ropes represent the tendons, the weight hooked to the ropes represent the mobile part and the men themselves represent the fleshy fibers. by pulling their ropes together, said steno, “the men indeed move the weight. similarly, the contracting fleshy fibers, while they pull the fibers of the tendon move the mobile part.” 114 however, steno did not push this analogy too far, and stated that it was “only a comparison.”115 steno used a similar mechanical analogy when explaining the motion of the diaphragm, as he compared the abdomen to a pulley.116 if the use of mechanical analogies was similar to steno’s previous description of blood filtration on the glands, his geometrical descriptions, however, were much more explicit and served a more intentional purpose in this treatise than in previous ones. in the first part of the treatise, steno said that most anatomists did not agree on the description of intercostal muscles, because such muscles are difficult to distinguish, although performing the same function together. how110 steno’s first results on the muscles were reported in a letter to thomas bartholin from april 30, 1663. his first dissections on the muscles are mentioned in a letter to bartholin from 26 august 1662. see bertoloni meli, “the collaboration between anatomists and mathematicians,” pp. 696-697. 111 the book was only printed in or after june, since it includes one letter sent on the 12 june 1664, in nicolaus steno, de musculis et glandulis (copenhagen, 1664), p. 84. 112 steno, de musculis et glandulis, p. 19: “qui contrahitur, non tendo est, sed tendinosas inter expansiones comprehensa caro” (bop, p. 561). 113 steno, de musculis et glandulis, p. 19: “cum per similia explicatio multis magnopere arrideat” (bop, p. 561). 114 steno, de musculis et glandulis, p. 20: “ut enim homines breviores redditi, suas dum simul trahunt chordas, pondus movent; sic carneæ contractæ fibræ, dum tendinis trahunt fibras, mobilem movent partem.” (bop, p. 561). 115 steno, de musculis et glandulis, p. 20: “sed cum simile hoc tantum sit, non diutius ipsi immorandum.” (bop, p. 561). 116 steno, de musculis et glandulis, p. 9: “nec enim, cum vel maxime tenditur, in rectam extensum est, nec, circa qvam moveatur, trochleam habet (nisi abdominis hic volueris nominanda contenta)” (bop, p. 555). ever, steno proposed to distinguish them according to “the different angles [they make] with the ribs.”117 steno suggested that this categorization of the muscles carried an epistemological certainty almost as strong as mathematical certainty, for “the one who will not refuse to examine carefully the angles formed by the back, the ribs, the sternum and the muscles must find a demonstration of these muscles, perhaps not less certain than by mathematics.”118 further on, after saying that every muscle was composed of fibers and tendons, steno concluded that the fibers have a very specific disposition, as they “form an oblique parallelogram or the figure of a rhomboid” (fig. 4).119 after explaining how exactly the fibers and tendons were disposed in this geometrical figure, steno felt the need to say that “even when dealing with physics, i give mathematical names to physical and not mathematical lines.”120 steno was alluding to the old epistemological problem of mixed mathematics of whether natural things can be described by means of mathematical entities that do not exist perfectly in nature. steno, however, felt it was better to “leave these details to mathematicians,” and reinforced that both fibers and tendons are composed of fleshy fibers in a different concentration.121 thus, steno’s commitment to mathematics was useful to him only in so far as it served the purpose of argumentation in anatomy. another example comes from a “letter on the anatomy of a ray” to william piso (1611-1678), included in de musculis et glandulis.122 piso was an amsterdam physician famous for his collaboration with the mathematician georg macgravius (1610-1644), with whom he wrote a widely-read natural history of brazil.123 in this letter, steno records not only the weights of the parts of the ray, but also comments on the animal’s geometric shape, just like he had done with the muscles he was studying.124 117 steno, de musculis et glandulis, p. 6: “angulos cum costis constituunt diversos” (bop, p. 553). 118 steno, de musculis et glandulis, pp. 9-10: “sed his missis quorundam musculorum describam in respiratione usum, quorum demonstrationem mathematica forte non minus certam non poterit non invenire, qui, quos dorsum, costæ, sternum, musculi inter se conficiunt, angulos attente examinare non recusaverit.” (bop, p. 555). 119 steno, de musculis et glandulis, p. 15: “ejusdem ordinis fibræ in eodem plano sunt, et parallelogrammum obliquangulum, seu rhomboideam exhibent figuram.” (bop, p. 559). 120 steno, de musculis et glandulis, pp. 15-16: “rem physicam proponenti venia detur, si mathematicis nominibus physicas, non mathematicas, designem lineas.” (bop, p. 559). 121 steno, de musculis et glandulis, p. 16: “sed illam mathematicis relinqvamus ἀκρίβειαν.” (bop, p. 559). 122 steno, de musculis et glandulis, p. 48: “de anatome rajæ epistola.” 123 in leiden, borch met macgravius’ brother, who mentioned a new book by georg on “his mathematical speculations,” apparently also edited by piso. see olai borrichii itinerarium, vol. 1, 27 april 1661, p. 115. 124 steno, de musculis, p. 15, 42 (bop, p. 559, 580). 41dissecting with numbers: mathematics in nicolaus steno’s early anatomical writings, 1661-64 but steno did not add a reason as to why he made these mathematical interventions. it was as if these approaches had already become regular and normal for him. mathematics and nicolaus steno’s arrival in italy considering that steno had already explored mathematical methods for some time, it is fair to ask what he might have been looking for when he went to italy for the first time, in the spring of 1666. before his arrival in italy, steno did not publish any other book. his famous dissection of the brain in 1665 in paris only appeared in print four years later. and there are not many other writings from steno’s sojourn in france, although several scholars like jan swammerdam (1637-1680) and andré graindorge (1616-1676), wrote about their joint activities in paris.125 however, the possibility that steno interacted with french mathematicians like gilles personne de roberval and adrien auzout, both of whom had collaborated with the anatomist jean pecquet, should not be disregarded. steno’s friendship with melchisedec thévenot (1620-1692), whose circles brought together some of the founding members of the académie des sciences de france, suggests that steno might have shared his geometrical interests with them in the critical years before the publication of his seminal elementorum myologiæ specimen.126 steno expanded his mathematical 125 scherz’s biography, in bop, pp. 131-161 126 the académie was founded within a year of steno’s sojourn. see guerrini, the courtiers’ anatomists, pp. 85-88; nicholas dew, orientalism in louis xiv’s france (oxford: oxford university press, 2009), pp. 89-92. approach in that book, a full treatise on the mathematical elements of myology, where he explained better the rhomboid structure of muscles. the book also “call[ed] upon the testimony of vincenzo viviani, mathematician of the most serene grand duke, who was present as a keen observer of these facts and of others contained in the present book.”127 it could be that steno went to italy in search of the mathematical and experimental legacy of galileo, viviani and borelli. but steno never mentioned them in his anatomical works, even when writing on mathematics. and steno’s mention of galileo in his student notebook from 1659 in copenhagen is very short, compared to his notes on the writings of athanasius kircher, jean pecquet and pierre gassendi.128 this is not to say that steno was not influenced by the school of galileo later on in florence. troels kardel rightly points out the striking differences between the de musculis et glandulis (copenhagen, 1664) and the elementorum myologiæ specimen (florence, 1667), especially the role of images. and domenico bertoloni meli argues that the latter’s life-size images carried demonstrative power for steno in the same way as accounts of experiments carried for galileo.129 bertoloni meli also points out that steno’s use of the terms inaequaliter aequaliter to describe the disposition of fibers between tendons, resembles the famous galileo description of the uniformly accelerated motion.130 thus, whereas the school of galileo played an important role in shaping steno’s later writings, it does not seem to have been at the heart of the matter earlier on. in fact, to understand the factors that led steno and other anatomists to mathematics, it is perhaps useful to look away from the shadow of galileo, descartes and other great names of seventeenth-century science.131 finally, even though steno did not mention it, he was likely aware of the italian school of mathematics. the intellectual circles he frequented in the netherlands and france were well informed of the scientific developments of italy, often due to a competitive spirit. an example to be explored further is the race for the lost manuscripts of apollonius’ conics, led by steno’s professor of mathematics jacob golius in leiden and by borelli in florence 127 steno, elementorum myologiæ specimen, p. 119: “amicissimum mihi vincentium viviani, serenissimi magni ducis mathematicum, testem appello” (bop, 739). 128 ziggelaar, chaos, pp. 301-2. 129 bertoloni meli, “the collaboration between anatomists and mathematicians,” pp. 705-706. 130 bertoloni meli, “the collaboration between anatomists and mathematicians,” p. 706. 131 steno’s mentors were generally critics of cartesian anatomy. for bartholin on descartes see jesper andersen, thomas bartholin: lægen & anatomen (copenhagen: fadl’s forlag, 2017), pp. 52-62; for sylvius and van horne see ragland, “mechanism, the senses, and reason.” figure 4. geometrical representation of the muscles in the cover of steno, de musculis et glandulis (copenhagen, 1664). courtesy of wellcome collection. 42 nuno castel-branco around 1660.132 when steno visited borelli in his first months in florence, the latter was already working on his de motu animalium, published posthumously.133 yet, the absence of all these references in steno’s writings only makes him a more interesting character, and speaks to the larger role of mathematics and its broader influences in steno’s career before arriving in italy. conclusion if anything, this article shows that steno’s interest in mathematics had been in his mind at least since his interaction with jorgen eilersen as a young student in denmark. in leiden, steno’s first publications on the glands made use of mathematical ideas, not just with mechanical analogies, but also with the measuring of weights of the parotid glands and the uses of the concepts of lubrication, speed flow to explain the production of salivary and lachrymal fluids. later on, in de musculis et glandulis, steno continued to rely on mechanical analogies while at the same time moving to a deeper use of geometry, by describing the muscles with the geometrical figure of a rhomboid. steno’s attraction to mathematics in his early anatomical research thus becomes an important case of how an anatomist transferred arguments and methods from geometry and mechanics into anatomy and the life sciences, and sheds light on the growing influence of the mixed mathematics and physics in the history of science up to modern times. 132 luigi guerrini, “matematica ed erudizione. giovani alfonso borelli e l’edizione fiorentina dei libri v, vi e vii delle coniche di apollonio di perga” nuncius 14 (1999), pp. 505-568. 133 in a letter to marcello malpighi from 1667, giovanni battista capucci mentions borelli’s work and its similarity to steno’s elementorum myologiæ specimen, see capucci to malpighi, 25 july 1667, in adelmann, the correspondence of marcello malpighi, vol. 1, p. 352: “[borelli] ha promesso a’ nostri amici di colà in breve tempo il suo libro de motu animalium, del qual argomento, dio voglia, ch’il sr. stenone non se n’abbia tolto il meglio, così come ha prevenuto in publicarlo, mentre questo come vostra signoria eccellentissima dice anche procede con principij geometrici. non bisogna publicar l’idee di belle cose, e tirarne a lungo la composizione, e la stampa, sé non vogliono esser involate.” substantia. an international journal of the history of chemistry 5(1) suppl.: 99-114, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1281 citation: d.e. moser (2021) crystalline stenonian time features from earth and beyond. substantia 5(1) suppl.: 99-114. doi: 10.36253/substantia-1281 copyright: © 2021 d.e. moser. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. crystalline stenonian time features from earth and beyond desmond e. moser department of earth sciences, university of western ontario, london, ontario, canada; n6a 5b7 e-mail: desmond.moser@uwo.ca abstract. the writings of niels stensen (steno) on mineral growth and modification in his prodromus, together with his work on time and process in other solids, are here synthesized as five classes of time features defined by changes in the visible continuity of either or both chemistry and orientation. this organization highlights steno’s implicit recognition of the fractal, scale-invariant nature of natural time features with regard to space, time, and material. the effectiveness of this stenonian geochronology framework is demonstrated down to atom scale with modern case studies of the u-pb geochronology of mineral zircon in samples originating from the earth, moon, and mars spanning most of solar system history. recently discovered nano-scale features, here termed chronostructures, were intimated by steno in his corpuscular view of mineral behaviour. the remarkable advances in the prodromus are seen here as resulting from the intersections of steno’s highly attuned approach to visual perception, his adoption of stoic (senecan) ethics early in his career to guide his natural philosophy, and the influence of the galilean scientific environment of florence. it is argued that the scale-invariant, intensive quality of stenonian geochronology makes it an invaluable check on the accuracy of absolute, extensive measurements of geologic time by chemical or isotopic means. in this way steno’s scientific legacy continues to propel human understanding of how we see our place in time. keywords: steno, crystal, zircon, geochronology, fractal, stoic. 1. introduction: the geological writings of the famed anatomist niels stensen, mostly expressed in his “the prodromus to a dissertation on a solid naturally contained within a solid” (hereon referred to as the prodromus),1 have been seen as foundational to the current fields of stratigraphy, palaeontology and crystallography through his elucidation of the principles of sedimentary superposition, the organic origin of fossils, and the law of angular con1 n. stensen, de solido intra solidum naturaliter contento dissertationis prodromus, florence, stella, 1669 (prodromus in following notes). english translation in t. kardel, p. maquet, nicolaus steno, biography and original papers of a 17th century scientist, 1st edition, heidelberg, springer, 2013 (k&m in notes below), pp. 621-660, 100 desmond e. moser stancy in crystals, respectively. steno’s ‘founder’ status, however, is seen by some historians of science as anachronistic,2 given that his authorship of these ideas was ignored for more than a century before acknowledgement in later retrospectives of geography and geology.3,4 more recent historians of science have commented that steno’s prodromus was principally an advance in the cognition of geologic time.5,6 steno’s novel and detailed descriptions of mineral growth have received renewed attention7, and in this paper i propose that his influence on the field of geochronology likewise merits greater recognition, particularly in light of the continuing application of stenonian methods. with steno’s mineralogy as a starting point, i have used his observations of time information in all solids to derive a classification scheme for steno’s vision-based geochronology. the modern relevance of this scheme is illustrated with microscopy case studies, down to atom scale, of the weakly radioactive geochronology of mineral zircon in samples from earth and other planetary bodies spanning most of solar system history. this is followed by a consideration of steno’s method of observational science in the context of his european education and association with the galilean accademia del cimento to explore reasons why steno was able to perceive geologic time hidden from most others. finally, the continuing importance of steno’s approach to the accuracy of both relative and absolute geochronology is discussed. it is hoped that, as it did for me, this treatment links earth scientists and geochronologists more clearly to our observational and philosophic roots as well as to an awareness of the 17th century brilliance of steno working in the galilean tradition. relative and absolute geochronology then and now geochronology is taken here to be the science of measuring time information from natural materials and 2 m. j. s. rudwick, the meaning of fossils. episodes in the history of palaeontology. london, macdonald, london, & new york, american elsevier inc., 1972, 287 pp. 3 n. desmarest, géographie physique. 4 vols. paris, 1794 [encyclopédie méthodique]. 4 c. lyell, principles of geology: being an attempt to explain the former changes of the earth’s surface, by reference to causes now in operation. london, john murray, 1, 1830. 5 k., von bülow (1971) stenos aktualistisch-geologische arbeitsweise, scherz, dissertations on steno as geologist. acta historica naturalium et medicinalium, 1971, 149–162; as cited in ref. 1 (k&m). 6 s. j. gould, the titular bishop of titiopolis. natural history, 1981, 90, pp. 20–24; reprinted in hen’s teeth and horse’s toes, new york, norton’s paperback, 1983, pp. 69–78. 7 a. authier, early days of x-ray crystallography. international union of crystallography/oxford university press, 2013, pp. 299-305. to be of two types; relative, establishing the numerical order of events, and absolute, the age of an event or interval referenced to units of years. in the age of steno, and particularly in the prodromus, the relative and absolute times for events in earth history were based on natural philosophy and biblical scripture, respectively, and were not seen to intersect or conflict as they were derivatives of independent logic systems2,8 with which steno presented faith and natural history as separate domains of knowledge.9 steno’s natural philosophy was likely influenced by that of aristotle, in view of his adaptation of aristotelian form and argument in his early work on hot springs, de thermis10. sambursky provides a concise summary of aristotelian philosophy regarding relative and absolute time: aristotle’s definition “time is number of motion in respect of ‘before’ and ‘after’”—expresses both the association of time with change and the possibility of enumerating this change. it is also evident from his analysis that he realized that the prerequisite for time measurement is a clock, i.e., a periodic mechanism, and that the revolution of the celestial sphere, being a regular circular motion, is the best measure of time “because the number of it is the best known”.11 as noted by many authors, steno declined assigning absolute ages directly to natural solids as on this topic “nature says nothing”,12 but he nevertheless played a pioneering role in ordering sedimentary strata in respect to the directional arrow of time.13 the 19th century saw the ascendence of absolute geochronology after the discovery of the laws of radioactivity and techniques for measuring ratios of elements and their isotopes in rocks and minerals.14 the first measurement of the absolute ages of sedimentary strata is widely attributed to holmes15 who compared 8 a. h., cutler, nicolaus steno and the problem of deep time, in the revolution in geology from the renaissance to the enlightenment (ed. g. d. rosenberg), geological society of america memoir, 2009, 203, p. 143–148. 9 j. bek-thomsen, steno’s historia. methods and practices at the court of ferdinando ii, in steno and the philosophers (eds.: r. andrault, m. lærke), brill, leiden, 2018, p. 233-258. 10 r. rappaport, when geologists were historians, ithaca and london, cornell university press, 1997, 320 pp. 11 s. sambursky, physics of the stoics. princeton, nj, princeton university press, 1987, 166 pp. 12 n. stensen, prodromus, in ref. 1 (k&m), p. 654. 13 g. kravitz, the geohistorical time arrow: from steno’s stratigraphic principles to boltzmann’s past hypothesis, journal of geoscience education, 2014, 62, p. 691-700. 14 e. rutherford, e., & f. soddy, j. chem. soc., 1902, 81, p. 837; reprinted in phil. mag., 1902, 4, p. 370; 1903, 5, p. 576. 15 a. holmes, the association of lead with uranium in rock-minerals, and its application to the measurement of geological time. proceedings of the royal society of london a, 1911, 85, p. 248-256. 101crystalline stenonian time features from earth and beyond the relative (stenonian) geochronology of a section of early paleozoic sediments in norway to absolute ages calculated from the u and pb abundances in minerals (including zircon (zrsio4)) from inter-layered and cross-cutting igneous (once molten) rock bodies. critically, holmes established the premise of the “closed system” for absolute methods; stipulating that an age measurement is only accurate if the sampled volume has remained closed to chemical alteration since its production aside from change due to radionuclide decay. in this light, and in the terminology of thermodynamics, every absolute geologic age is an extensive property of a solid. the extent of the systems in holmes’ pioneering work were mineral grains containing u and its radiogenic pb. as we will see, it is due to this extensive property that the accuracy of absolute methods relies, ultimately, on steno’s relative approach. minerals are defined by the international mineralogical association as the inorganic building blocks of rocks, each characterized by a particular chemical composition and a defined crystal structure. these commonly occur as polyhedral bodies such as the cm-scale specimens described in the prodromus. steno classed minerals as “angular solids”, and focused on samples of “crystal” (quartz) and “iron” (hematite, pyrite) which he collected from the tuscany region, elba, and other localities in central europe16. absolute geochronology using the u-th-pb decay chains has become the benchmark for calibrating the time scale for the earth17 and solar system,18 and the u-bearing mineral zircon plays a major role.19 zircon occurs widely in the crusts of rocky planets, mostly as microscopic grains forming accessory components in rocks over a depth range on the order of 100 kilometres. the primary features of each grain can withstand erosion, mountain building events, transport in magmas, plate tectonic cycles, and meteorite impacts; all the while accumulating either or both external and internal features that bear witness to these events.20 zircon crystals commonly have the width of a human hair, an order of magnitude smaller than steno’s cm-scale samples (fig. 1), yet zircon grains have the distinction of being the old16 n. stensen, in ref. 1 (k&m), p. 208. 17 y., amelin, et al., lead isotopic ages of chondrules and calcium-aluminum-rich inclusions. science, 2011, 297, pp. 1678-1683. 18 j. m. connelly et al., chronology of the solar system’s oldest solids. the astrophysical journal, 2008, 675, p. l121–l124. 19 b. schoene, u–th–pb geochronology, in treatise on geochemistry, k. turekian, h. holland (eds.), 2014, 4, elsevier oxford, p. 341-378. 20 f. corfu, j. m. hanchar, p. w. o. hoskin, p. kinny, atlas of zircon textures. reviews in mineralogy and geochemistry, 2003, 53, p. 469-500. est known pieces of the earth,21 moon22 and mars.23 zircon also has a different crystal structure in comparison to steno’s quartz (tetragonal vs. hexagonal) however it exhibits a similar, long-prismatic habit such that it is weakly to strongly columnar, sharing “intermediate” (prismatic) and “terminal” (pyramidal) faceting reported by steno.24 zircon exhibits internal zoning when a cross-sectional surface is imaged with a scanning electron microscopy and a cathodoluminescence detector (sem-cl).25 these zones are analogous to the colour changes noted by steno in his quartz cross sections of “the plane in which the axis of the crystal lies”26 (fig 1). steno’s cross-sectional depictions were novel in his time, marking a transition from ‘organic’ to ‘mechanical’ mineralogy’,27 whereas such cross-sectional crystal imaging is now a routine component of petrology and absolute zircon geochronology. previous work on stenonian geochronology the framework which steno describes in the prodromus for interpreting the earth resolved not only the immediate question of the nature of fossils, and discriminating their found location from their place of production, but presented a logic structure for identifying geologic time sequences from features discernible in solids.28 steno’s authorship of this structure was largely ignored among later theories of the earth although his concepts and ideas carried on in the work of others such as leibniz29 or were tested and transmitted by later italian geologists.30 receiving most attention was his princi21 j. w. valley, a. j. cavosie, t. ushikubo, d. a. reinhard, d. f. lawrence, d. j. larson, p. h. clifton, t. f. kelly, s. a. wilde, d. e. moser hadean age for a postmagma-ocean zircon confirmed by atom-probe tomography. nature geosci., 2014, 7, p. 219–223. 22 a. nemchin, n. timms, r. pidgeon, et al. timing of crystallization of the lunar magma ocean constrained by the oldest zircon. nature geosci., 2009, 2, p. 133–136. 23 l. c. bouvier et al., evidence for extremely rapid magma ocean crystallization and crust formation on mars. nature, 2018, 558, p. 586–589. 24 n. stensen, in ref. 1 (k&m), p. 639. 25 j. m. hanchar, c. f. miller, zircon zonation patterns as revealed by cathodoluminescence and backscattered electron images: implications for interpretation of complex crustal histories. chemical geology, 1993, 110, p. 1-13. 26 n. stensen, in ref. 1 (k&m), p. 659. 27 w. r. albury, d. r. oldroyd, from renaissance mineral studies to historical geology, in the light of michel foucault’s “the order of things”. the british journal for the history of science, 1977, 10, pp. 187215. 28 m. j. s. rudwick, the meaning of fossils. episodes in the history of palaeontology. london, macdonald, london, & new york, american elsevier inc., 1972, 287 p. 29 d. garber, steno, leibniz, and the history of the world, in ref. 8, p. 201-232. 30 s. dominici, steno, targioni and the two forerunners. journal of mediterranean earth sciences, 2009, 1, p. 101-110. 102 desmond e. moser ple of ‘moulding’31 which had been denoted in the 18th century by desmarest as steno’s “premier principé ”. 32 among the most detailed modern assessments of steno’s work regarding relative geochronology is that of hansen33 who recognized in steno’s writings the “cognition criteria” of chronology, recognition (i.e. resemblance), and preservation. chronology was subdivided into the principles of moulding and intersection. moreover, two underlying axioms related to the quality of orientation were proposed in terms of “conformity,” and “disconformity.” steno’s interpretation of what had been viewed previously as “signs” in natural materials34 were termed “structural”, underpinning a further five principles of geological interpretation leading to “back-stripping” to reconstruct crustal dynamics over time. these organizations of steno’s work on solids were interpreted predominantly from his macroscopic observations of sediments, and, while valid and self-consistent, did not incorporate many of steno’s observations of minerals and mineralized bodies such as agate (“incrustations”). when these too are considered, and paired with steno’s atomistic (corpuscular) view of crystals,35 additional stenonian insights become apparent. 2. method and materials the prodromus has been called “a complex and odd little book ”,36 and in his introductory text steno does apologize to his patron for any seeming disorganization due to the constraints of time and travel. my analysis initially relied on the english translation of the prodromus by winter37, but then mainly fell to translations of the much broader compilation of steno’s works translated by kardel and maquet,1 all of which were approached in several ways. first, all indications, whether in the text or diagrams, of time, motion, and process observed or deduced from natural solids, were noted with particular 31 s. j. gould, s.j. in ref. 6. 32 n. desmarest in ref. 3. 33 j. m. hansen, on the origin of natural history: steno’s modern, but forgotten philosophy of science, in ref. 8 (rosenberg), p. 159-178. 34 t. yamada, kircher and steno on the “geocosm”, with reassessment of the role of gassendi’s works, in the origins of geology in italy (eds. g. b. vai, w. g. e. caldwell), geological society of america special papers, 2006, 411, p. 65–80. 35 w. c. parcell, signs and symbols in kircher’s mundus subterraneus, in ref. 7 (rosenberg), p. 63-74; c. j. schneer, steno on crystals and the corpuscular hypothesis, dissertations on steno as geologist. acta historica naturalium et medicinalium, 1971, 34, p. 293–307. 36 r. rappaport, in ref. 10, p. 202. 37 j. g. winter, the prodromus of nicolaus steno’s dissertation concerning a solid body enclosed by process of nature within a solid. university of michigan studies: humanistic series, macmillan, 1916, 115 pp. attention to steno’s descriptions of minerals and incrustations in the prodromus. the visual-cognition term ‘feature’ (see definition below) was then used to subdivide steno’s descriptions of temporal phenomena into classes according to chronology, process, and underlying material properties causing continuity, or disruption, of either or both chemistry and geometric orientation (table 1). the sources of translated steno quotes in table 1 regarding minerals and strata occur in the main body of text, whereas the remainder are as follows for fossils38 and incrustations.39 note that the s5 class descriptor is based on a translation from hansen (2009) in ref. 8. detailed class descriptions with relevant translations of steno are presented alongside modern microscopy results for the u-pb geochronology of the mineral zircon. all microscopy was performed by the author’s research group and collaborators using previously described electron beam techniques40 at the university of western ontario or using previously described atomic imaging techniques41,42 at the canadian centre for electron microscopy, mcmaster university. terminology for stenonian time features the term feature has been used here to generalize the different signs or visual patterns which steno ascribed to the effects of time’s passage during the production or alteration of solid materials. steno’s raw visual observations are mostly expressed as geometric surfaces, with the word ‘surface’ here used according to the mathematical definition; a generalization of all planes which may or may not have some amount of curvature. steno’s geometric descriptions of surfaces in the prodromus followed either euclidean geometry or projective geometric representations of the platonic solids in the tradition of pierro, kepler and dürer,43 and his single plate of diagrams44 combines these approaches. notably, 38 n. stensen, in ref. 1 (k&m), p. 647-648. 39 n. stensen, in ref. 1 (k&m), p. 630. 40 d. e. moser, c. l. cupelli, i. r. barker, r. m. flowers, j. r. bowman, j. wooden, j. r. hart, new zircon shock phenomena and their use for dating and reconstruction of large impact structures revealed by electron nanobeam (ebsd, cl, eds) and isotopic u-pb and (u-th)/he analysis of the vredefort dome. can. j. earth sci., 2011, 48, p. 117-139. 41 j. r. darling et al., variable microstructural response of baddeleyite to shock metamorphism in young basaltic shergottite nwa 5298 and improved u-pb dating of solar system events. earth planet. sci. lett., 2016, 444, p. 1-12. 42 g. a. arcuri, d. e. moser, d. a. reinhard, d. larson, b. langelier, impact‐triggered nanoscale pb clustering and pb loss domains in archean zircon. contributions to mineralogy and petrology, 2020, 175, p. 59, 1-13. 43 c. j. schneer, in ref. 35. 44 n. stensen, in ref. 1 (k&m), p. 658. 103crystalline stenonian time features from earth and beyond and, perhaps unique for his time, are his two-dimensional projections and juxtaposition of three-dimensional geologic entities, such as sedimentary strata and growth layers within crystals, into a euclidean plane which contains either the downward vector of earth’s gravity or the principal (central) axis of crystal growth. steno does not refer to most of these features in formal geometric terms but as nouns with embedded actions. he does not, for instance, refer in latin to a sedimentary deposit as a planum (plane), but as a stratumthe past participle of sternere “to spread out”. action, motion, and thus time, thereby become embedded meanings in his descriptor of a planar, natural feature. some have referred to parts of steno’s drawings as “structures”, particularly the ruptured strata in his cross-sections of tuscany;45 however, this term derives from structus, the past participle of struere “to pile,… assemble”, whereas, at mineral grain or crystal lattice scales, these features are more accurately described by voids or a breakdown of order. as discussed below, steno’s methods are primarily visual, and consequently the visual term ‘feature’ is adapted here to encompass true structures and other types of recognizable material changes in solids. a ‘ feature’, when used in regard to material objects, is defined in english as “some part which arrests the attention by its conspicuousness”.46 time is implicit in this definition not in regard to the passage of time during production of the object but of time elapsing during the act of its observation during which the mind’s attention is arrested. this process of observation will be discussed later in the context of steno’s methodology. 4. results upon consideration of steno’s observations of all natural solids, five classes of stenonian time features signifying production or modification can be described, along with a brief mention of a sixth ‘origin’ class (table 1). the first two classes of stenonian time features can be considered as one or more euclidean planes in that they, at length scales of observation typical in geology, are surfaces with zero curvature at any point. for steno’s “crystals” the planes in his diagrams are twodimensional projections of symmetrically-related set of crystal facets analogous to sedimentary strata (fig. 1). together they are the primary features of production and establish the reference features for discriminating 45 j. m. hansen in ref. 33. 46 “feature, n.” oed online, oxford university press, december 2020, www.oed.com/view/entry/68848. later, modifying processes and events. the other three feature classes represent, at some scale, disruptions in continuity; what steno described in the case of tilted strata as “obvious inequalities” 47 of angle with respect to the horizon and the gravitational field. at the atomic level in minerals, such discontinuities fall into two broad groups: discontinuity in chemistry, while maintaining crystalline order, and discontinuity due to a breaking or re-orienting of atomic bonds without necessarily changing the chemical composition. each class is denoted with “s” for steno and a subscript identifying the class number, and is described along with comparable features in zircon crystals. a) s0, s1 features representing growth, hiatus, environmental change with regard to the beginning of the formation of a solid, steno acknowledges that such a place must exist but would not speculate further. for minerals he stated that: “there may still be doubt about the place in which the first crystal begins, whether it be between fluid and fluid or between fluid and solid or in fact in a fluid by itself ”,48 and strata are described only as being preceded by a global fluid. nevertheless steno acknowledges the existence of a beginning point and it is represented in this scheme as s0, the first point of production which, for minerals, is taken as the geometric centre of zoning (fig. 1). from there he recognized, in different places in his writings on solids, subclasses of s1 features to which he attributed vectors, pauses, and environmental changes during production. vectors and nature of growth processes steno’s view of mineral growth shared some similarities with sedimentary strata but with important differences in the kinetics of growth. in both solids he saw that; “the growth of all solids is from fluids” and that a body “grows by addition of new particles”.49 hearkening to his choice of the term stratum for sedimentary layers, steno indicates that “new crystalline material, added to the crystal, is spread out over a plane”50 with the important difference that “buoyancy or gravity are not involved”,51 and crystal growth is instead driven by “the subtle fluid permeating all matter”52. thus gravity controls sedimentation in a single, vertical field, whereas particle addition in another field causes crystals to grow 47 n. stensen, in ref. 1 (k&m), p. 653. 48 n. stensen, in ref. 1 (k&m), p. 639. 49 n. stensen, in ref. 1 (k&m), p. 630. 50 n. stensen, in ref. 1 (k&m), p. 642. 51 n. stensen, in ref. 1 (k&m), p. 634. 52 n. stensen, in ref. 1 (k&m), p. 631. 104 desmond e. moser along several, mathematically related directions. steno analogized crystal growth with particles aligning like iron filings in a magnetic field such that “both the number and length of the sides are changed in various ways without the angles being changed.”53. flow in the mineral’s parent liquid did not alter the direction of the field driving crystallization in that “the movement of crystal53 n. stensen, in ref. 1 (k&m), p. 642, also ref. 41. line material […] depends on the movement of the tenuous fluid that flows from the already formed crystal”. 54 successional growth among the most important spatiotemporal deductions by steno was that of the successional growth of lay54 n. stensen, in ref. 1 (k&m), p. 642. table 1. a classification scheme for stenonian time features in solids (top row) based on representative steno descriptions symbolized as; “quotations from steno (transl.)”, ‘author’s condensation of translated text’, and [modern terminology]. arrows represent cases where features in strata are now known to have analogous mineral features. *far left column identifies the quality of the continuity change across each feature relative to its surroundings as; chemical (c) , geometric orientation (o) or a combination of either or both (c||o). see methods for sources of translated steno quotations. “angular solids” [minerals] “strata” [fossil] “incrustations” [concretions] * stenonian time feature class c s5; intra-solid diffusion smallest particles in “inner revolt” [metamorphism] o s4; deformation (brittle, rapid) <— “shattering” causing “obvious inequalities” in angles o s4; deformation (plastic, slow) <— “subsidence”, “twisting into curves” c||o s3; mechanical erosion “fractured sides” [erosional unconformity] c||o s3; chemical erosion dissolution “cavity” leaving “lamellae” [chemical unconformity] ‘shell partly destroyed, eaten away’ c||o s2; end of production surface of “angular solid”, form related to ‘constancy of angles’ “upper surface is parallel to the horizon” final form related to gravity “outer edge of the animal” ‘outer surface of concretion’ controlled by roughness of place c s1; hiatus in production “if…crystal contained by crystal” then ”contained bodies already hard” ‘fluid recession, sediment hardening, and fluid return’ c s1; growth and environmental change during growth “crystal grows while new crystalline material is added to the already formed crystal” colour zoning due to “ingress of new material” strata differences due to “different kinds of fluid from different places through that spot at different times” ‘imprint on each margin of the testulae’ c s1; growth domain crystal layer created by “addition of new particles in succession” “stratum” “testulae” mollusc shells “fluid directs material to the solid on all sides” s0; start of production “doubt about the place in which first hardening of the crystal begins” [nucleation] “creation from a fluid that covered all things” point of nucleation ‘seed’ 105crystalline stenonian time features from earth and beyond ers in solids. for minerals he noted that “crystal growth was not vegetative”55 as in herbaceous plants. his argument against the vegetative mineral growth hypothesis can be traced to his discussion of the growth layers within the class of solids he termed “incrustations” (i.e., agates, geodes). he describes the “diff erences in layers” in these solids with the important time descriptor of relative age; “succession”.56 he recognized the curviplanar geometry and extension of the concentric layers in these “stones composed of layers the two surfaces of which are indeed parallel but are not extended in the same plane”. he then compared these to the concentric, curviplanar growth layers in non-herbaceous woody plants “where they show the round veins of a tree cut transversely”.57 steno contrasts these processes for mineralized bodies with those giving rise to strata, stating that: 55 n. stensen, in ref. 1 (k&m), p. 640. 56 n. stensen, in ref. 1 (k&m), p. 634. 57 n. stensen, in ref. 1 (k&m), p. 633. additions [of particles] made directly to a solid from an external fl uid sometimes fall to the bottom because of their own weight, as in the case of sediments; sometimes the additions are made from a penetrating fl uid that directs material to the solid on all sides, as in the case of incrustations.58 th e outward growth of minerals is now universally recognized and utilized in the fi elds of petrology and mineralogy in which rocks and minerals are examined in polished, transparent sections, and likewise in zircon geochronology where sem-cl microscopy is used to reveal s1, concentric growth banding. th ese represent changes in trace element chemistry inherited from the magma and are expressed as variations in luminescent intensity and/or colour (fig 1). th e orientation of the crystal lattice across the chemical zoning does not change such that banding marks discontinuities in chemistry within a zone of continuous crystal orientation. time gap (hiatus) in growth “stony strata are found between earthy strata” due to a “fl uid, having receded from the sediment that had been deposited, returned again when the upper crust had become hardened by the heat from the sun”.59 beyond outward growth, steno recognized that both the conditions and rate of grow th can vary during the production of natural solids. drawing on his writings on strata, he clearly envisions a scenario wherein either or both a time gap and changes in the formative environment results in variations in visual properties across a set of layers. in his second proposition he states, “if at any time a crystal is partly enclosed by a crystal, a marcasite by a marcasite, then at a time when these contained bodies were already hard, part of the containing body was still fl uid”.60 a corresponding recognition of hiatus in sedimentation was also noted as possible (above). we now know that concentric, apparently continuous, zoning sequences within zircon grains released from a single volcanic eruption lasting days can, in some cases, represent age diff erences of hundreds of thousands of years; their s1 features a product of halting outward growth over this period. th e crystal shown in fig.1 is representative of those from a cretaceous ash layer, now exposed in the canadian rocky mountains. absolute dating of such grains indicates that the zoning represents up to sev58 n. stensen, in ref. 1 (k&m), p. 630. 59 n. stensen, in ref. 1 (k&m), p. 635. 60 n. stensen, in ref. 1 (k&m), p. 629. figure 1. stenonian time features of production (s0, s1, s2; see text) from plate 1 of the prodromus1 showing a) undeformed strata (kmscale), b) growth zones in sectioned quartz (cm-scale) and c) semcl image of a polished section through a zircon microcrystal (note scale bar 5 micrometre scale bar). 1 n. stensen, in ref. 1 (k&m), p. 658. 106 desmond e. moser eral hundred thousands of years of crystallization prior to eruption61. environmental change during growth difference in layers at the same place can be produced either by the diversity of particles leaving the fluid in succession, as this f luid is gradually dissipated more and more, or by different fluids being conveyed there at different times: so it happens that sometimes the arrangement of layers is repeated in the same place, and often evident signs exist showing the ingress of new material. 62 steno was careful to distinguish “place” (i.e., the place or environment where a solid was produced) from the “location”, or site of discovery of that solid, recognizing that “location does not explain production”.63 in the case of strata, steno also recognized that changes in the sedimentary section could reflect changes in sedimentary conditions and sources through time, and that stratal changes vertically result from “different kinds of fluid from different places through that spot at different times”. similarly for minerals, steno understood that the place of production imbues solids with signatures of their native environments, such that “rocks of different types, emitting different fluids, produce crystals of different colours”64. moreover, steno realized that even in the place of production, an environment of crystallization can change during the growth such that “sometimes in the same crystal the parts first hardened are sometimes darker than those hardened last”.65 we now know that igneous minerals commonly show internal compositional layering due to very local effects of growth-limiting elements among other factors such as surface energy, magma viscosity, and temperature, as is known for both quartz66 and zircon.67 b) s2 final form at end of production a second class of stenonian time feature is defined as the exterior or upper surface of a solid at the completion of its growth in the place of production. for miner61 i. r. barker, d. e. moser, s. kamo, g. plint, high-precision u–pb zircon id–tims dating of two regionally extensive bentonites: cenomanian stage, western canada foreland basin. can. j. earth sci., 2011, 48, p. 543–556. 62 n. stensen, in ref. 1 (k&m), p. 634. 63 n. stensen, in ref. 1 (k&m), p. 628. 64 n. stensen, in ref. 1 (k&m), p. 641. 65 n. stensen, in ref. 1 (k&m), p. 641. 66 d. a. wark, b. e. watson, titaniq: a titanium-in-quartz geothermometer. contributions to mineralogy and petrology, 2006, 152, p. 743-754. 67 p. w. o. hoskin, patterns of chaos: fractal statistics and the oscillatory chemistry of zircon. geochimica et cosmochimica acta, 2000, 64, p. 1905-1923 als crystallizing from a liquid, s2 is a polyhedral surface composed of euclidean planes (crystal growth facets) the orientations of which follow steno’s law of angular constancy. figure 2 illustrates steno’s method of projecting this three dimensional surface such that “all the 12 planes laid out in one plane” 68 and neighbouring crystal facets connected by a shared vertex. he recognized it as a time marker implicitly in his use of it to infer order of crystal growth (above). it should be noted that steno did not consider metamorphic minerals, i.e. crystals that grew while most of its surroundings were solid. the s2 surface of such grains reflects some combination of growth processes and surface energies among surrounding mineral phases69. in either case, the final, outer surface represents a discrete point along time’s arrow. this is at once the simplest and perhaps most important time feature for steno’s interpretation of fossils as it occurs at the meeting place of an object with its surroundings (rock, air, etc.) at its present location (table 1). the s2 feature class includes the uppermost surface of a stratum, the final form of an organism, or the outermost atomic layers of a crystal. this was the key time feature used to discriminate between an allocthonous (transported from elsewhere) vs. autochthonous (formed in situ) origin for steno’s fossils relative to their found location (i.e. desmarest’s premier principé). this feature is of central importance in the prodromus and remains a key tool in the modern geochronologic interpretations of minerals such as zircon as to whether or not they are endogenic or exotic to their current setting. c) s3 modifications of original form the s3 class of features, along with the other two remaining classes, share the characteristic of being surfaces marking discontinuities in one or both of chemical composition and crystallographic (atomic) orientation, with the change occurring over a length-scale much less than that of the relevant surfaces. s3 due to chemical erosion (dissolution) just as a crystal has formed from a fluid, so that same crystal can be dissolved in a fluid, provided one knows how to imitate nature’s true solvent.70 following on his basic statement that all solids grow from fluids, steno concludes that the process can operate in reverse (above). it is plausible that steno shows 68 n. stensen, in ref. 1 (k&m), p. 659. 69 r. kretz, on the spatial distribution of crystals in rocks. lithos, 1969, 2, p .39-69. 70 n. stensen, in ref. 1 (k&m), p. 643. 107crystalline stenonian time features from earth and beyond the eff ects of dissolution in his diagram 6 where he describes “that various cavities are left in the very middle of the crystal and various lamellae are formed.”71 (fig. 3). th is diagram could be interpreted to show a partly dissolved quartz crystal with lamellae of relict growth layers (s1) from the originally continuous solid body. alternatively, the lamellae could represent a face of relatively slow crystal growth frustrated due to surface kinetic eff ects. regardless, it is clear that steno anticipated dissolution during natural processes. resorption surfaces similar to the forms in steno’s drawing were produced in zircon by prof. th omas krogh in laboratory etching experiments 72 and rounding of originally equant zircons due to metamorphic fl uids in the crust is now widely documented.73 oft en this stage of resorp71 n. stensen, in ref. 1 (k&m), p. 646. 72 d. w. davis, i. williams, t.e. krogh, historical development of zircon geochronology. reviews in mineralogy and geochemistry, 2003, 53, p. 145-181 73 m. j. kohn, n. m. kelly, petrology and geochronology of metamorphic zircon, in microstructural geochronology: planetary records down to atom scale (eds. d. e. moser, f. corfu, j. r. darling, s. m. reddy, k. t. tion is followed by renewed zircon growth continuous in lattice orientation (i.e. epitaxial growth), but diff erent in chemical composition (fig 3). th is creates a feature visually akin to an angular unconformity in strata, as shown in a 4.02 billion year old zircon from earth’s oldest known rock (fig. 3).74 s3 due to mechanical erosion “nor have i ever seen a crystal whose still unbroken surfaces have the smoothness that the fractured sides of the same crystal show aft er it has been broken apart.”75 steno was clear that a solid body could form in one place and move to another unrelated to its genesis: “since the earth bestows location at least in part to all tait), hoboken, nj, wiley, 2017, p. 35–61. 74 j. r. reimink, t. chacko, r. a. stern, l. m. heaman, earth’s earliest evolved crust generated in an iceland-like setting. nature geoscience, 2017, 7 , p. 529-533. 75 n. stensen, in ref. 1 (k&m), p. 642. figure 2. two views of steno’s fi nal surface of production (s2) in minerals; a) steno’s two dimensional representation of the external, euclidean planes of an ‘iron” crystal (marcasite) b) an sem image of a euhedral, igneous zircon crystal, same sample as in figure 1c (grain length = 250 micrometres). note the mould of a smaller grain (white arrow), likely the mineral apatite, encountered during the last increment of growth before eruption. figure 3. features of modifi cation: a) steno’s quartz crystal and a surface of s3 chemical dissolution. zircon sem-cl images showing b) 4.02 billion year s1 growth features truncated by a s3 dissolution (metamorphic) surface, c) a zircon from beach sand with external s3 surface of mechanical erosion. d) southward view from canada of the niagara river gorge and the type locality for the silurian whirlpool sandstone; inset, sem-cl image of rounded zircon sand grain among quartz grains (red), whirlpool sandstone. all zircon grain lengths ~ 300 micrometres. 108 desmond e. moser the things of the earth, the location by itself does not explain the production of a body”.76 he recognized that “mountains can be destroyed”,77 that cavities can be filled with “earthy material eroded from higher places by the continuous rainfall”,78 and that the particles in sediments sink under their own weight even if “conveyed there from elsewhere”.79 in his series of strata cross-sections he notes “hills and valleys produced there by the destruction of the upper sandy strata”.80these clues to motion and erosion on the outer surface of the earth were also noted for crystals,81 and the incrustations: incrustations are observed to be rough like ordinary stones on the outer surface, since the outer surface of the outer layer depicts the roughness of the place; in torrents, however, incrustations of this kind are often found away from the place of production because the material of the place has been scattered by the bursting of the strata.82 steno recognized the difference between growth faces and those modified by breakage (above) and this is a second type of intersection relationship with the original outer form or surface (s2); one that is due not to dissolution of particles in a surrounding fluid but to mechanical abrasion or breakage during transport which modifies the original form causing an interruption in the continuity of the internal features when viewed in section (fig. 3). zircon grains are extremely resistant to chemical and mechanical breakdown, and the oldest known pieces of the earth are fine, sand-sized grains of zircon in much younger, though still ancient, sediments.83 e) s4 features due to episodes of deformation the earth’s strata can alter position in two ways. the first way is the violent upheaval of strata, whether this be due mainly to a sudden flare of subterranean gases or to a violent explosion of air caused by other great subsidence nearby. this upward thrust of strata is followed by a dispersal of earthy material as dust and the shattering of rock material into pebbles and rough fragments. the second way is the spontaneous slipping or subsidence of the upper strata after they have begun to crack because of the withdrawal of the underlying substance or foundation; […] while some remain parallel to the horizontal, others become vertical; many make oblique angles with the horizon and not a 76 n. stensen, in ref. 1 (k&m), p. 628. 77 n. stensen, in ref. 1 (k&m), p. 637. 78 n. stensen, in ref. 1 (k&m), p. 656. 79 n. stensen, in ref. 1 (k&m), p. 634. 80 n. stensen, in ref. 1 (k&m), p. 660. 81 n. stensen, in ref. 1 (k&m), p. 640. 82 n. stensen, in ref. 1 (k&m), p. 633. 83 j. w. valley et al., in ref. 21. few are twisted into curves because of the tenacity of their material. 84 whereas steno described deformation of the exterior of minerals, he did not remark on internal effects; so, for this class of time feature, we look to his insights gained from sedimentary strata and compare these to modern studies of zircon. as seen in the above quote steno made some highly astute observations, recognizing two styles of deformation of strata and their respective geometric and material consequences. steno was accurately describing the range of mechanical responses to different rates of deformation. he did not depict the first style in the prodromus; that of violent, or very rapid, deformation but it is likely he was referring to the consequences of volcanic activity. the most extreme strain rate events now known to affect planetary crusts occur at the deepest levels of tectonic collision zones, and, at the most extreme end of the spectrum, within large meteorite impact craters as illustrated here with terrestrial and lunar zircon (fig. 4). s4 due to rapid deformation zircon is one of the minerals most resistant to destruction by impact-related shock metamorphism, yet grains develop long-lasting and unique deformation features.85 fracturing and crystal distortions occur in microseconds and often under extreme, short-lived temperatures of up to a few thousand degrees celsius. disordered mineral glasses, instead of secondary minerals, can fill crystallographic fractures, a material difference alluded to by steno: “the main cause of variation by which crystal differs from glass not only in refraction but also in other properties, since, in glass, no parts of the dissolving fluid are present, as they have driven forth by the violence of fire”.86 this deformation style of s4 features has been recognized at the vredefort crater in south africa, offsetting s1 growth zoning and s2 surface of production (fig. 4). we see a similar sequence in the features of >4 billion year old lunar zircons, including those recovered by the u.s. apollo 17 mission near steno crater87 (fig. 4). in both cases, the zircon lattice 84 n. stensen, in ref. 1 (k&m), p. 636. 85 d. e. moser, c. l. cupelli, i. r. barker, r. m. flowers, j. r. bowman, j. wooden, j. r. hart. new zircon shock phenomena and their use for dating and reconstruction of large impact structures revealed by electron nanobeam (ebsd, cl, eds) and isotopic u-pb and (u-th)/he analysis of the vredefort dome. can. j. earth sci., 2011, 48, p. 117-139. 86 n. stensen, in ref. 1 (k&m), p. 643. 87 b. zhang et al., imbrium age for zircons in apollo 17 south massif impact melt breccia 73155. jgr planets, 2019, 124, p. 3205-3218 109crystalline stenonian time features from earth and beyond between fracture sets has been bent by several degrees during shock deformation, a mechanical response in line with steno’s observation for strata which sometimes respond plastically to be “twisted into curves” because of their “tenacity” (above). s4 tectonic fracturing and mineral-fi lled veins steno also recognized a style of deformation features such that some strata crack in a brittle fashion to allow fl uid pathways for new mineral precipitates. an example of this sequence of s4 features superimposed on generations of growth features (s1a , s1b) is illustrated here in one of the oldest known fragments of the earth; a zircon grain from the archean jack hills quartzite from the yilgarn craton of western australia (fig. 5a). th e age, chemistry and microstructure of this grain has been described in detail elsewhere.88 th e central domain (core) has a u-pb age of 4.38 billion years — a time when the mass of the moon had already been separated 88 j. w. valley et al., in ref. 21. from the proto-earth and the fi rst water appeared,89 the latter reminiscent of steno’s fi rst fl uids. th e fi rst set of growth features (s1a) formed during precipitation from a silica-rich magma in earth’s early continental crust. at modern, average rates of tectonic drift , it is plausible that over the last 4 billion years this core domain has circumnavigated the earth several times as microscopic continental cargo on a number of early crustal domains. roughly 3.4 billion years ago, the grain experienced chemical resorption and/or mechanical abrasion which removed s2 and produced a discontinuity surface, s3, over which grew a new, metamorphic domain with chemical layering (s1b) discordant to the older core. a tectonic deformation produced s4 fractures, which reoriented the lattice and its s1a, s1b and s3 features, prior to their being fi lled with a combination of new zircon, quartz, and grains of the rare earth phosphate xenotime, the latter as young as 0.8 billion years ago90(fig. 5). th e mineralogy of the micro-veins, and their younger, intersectional age relationship, are directly in line with steno’s observations of the deformation, veining and growth of secondary minerals.91 th e sequence of production (growth), erosion, deformation, and resumption of growth experienced by this early earth zircon resulted in a geometric arrangement of features that is very similar to that which steno described for the crustal strata of tuscany, illustrating the scale-invariance of stenonian geochronology (fig. 5). s4 deformation and renewed production sequence at atomic scales stenonian cycles of production and modifi cation can also be seen at the atomic level with electron microscopy at the length scale of steno’s then “imperceptible particles”,92 as illustrated here in a 200 million year old igneous mars rock that came to earth as a meteorite (nwa 5298) ~11 million years ago93 (fig. 6). th e cycle of rapid shock-wave deformation and heating, which such shergottite meteorites generally experience as they are ejected to space following an impact event, leaves a record of mm-scale pockets of melting and glass for89 sa wilde, jw valley, wh peck, cm graham, evidence from detrital zircons for the existence of continental crust and oceans on the earth 4.4 gyr ago. nature, 2001, 409, p. 175-178. 90 rasmussen b. et al., metamorphic replacement of mineral inclusions in detrital zircon from jack hills, australia: implications for the hadean earth. geology, 2011, 39, p. 1143-1146. 91 n. stensen, in ref. 1 (k&m), pp. 629. 92 n. stensen, in ref. 1 (k&m), pp. 626. 93 moser, d. e. et al., solving the martian meteorite age conundrum using micro-baddeleyite and launch-generated zircon. nature, 2013, 499, p. 454-457. figure 4. examples of violent deformation features (s4 ) on earth and the moon: a) a boulder of archean (~3 billion year old) crust near the center of the ~250 km wide, 2.020 billion year old vredefort impact structure of south africa. b): sem-cl image of a zircon crystal from this region c) boulder at the edge of steno crater ( apollo 17), d) sem-cl image of a >4 billion year old zircon from near site shown in c). 110 desmond e. moser mation as well as a suite of microscopic s4 deformation features within the regular atomic layering of igneous crystals. th e heating also triggers short-lived chemical reactions and local growth of minerals, including zircon, during cooling en route to space.94 th e resulting continuous and discontinuous patterns among the atomic lattice layers, revealed with electron microscopy, are analogous to the those in strata in steno’s sketches of tuscan geology (fig. 6). we can see in figure 6 that primary atomic layering (s1a) in the mars mineral baddeleyite (zro2), has been re-oriented and disordered across s4 surfaces of deformation. a boundary of chemical reaction (s3) separates the deformed baddeleyite features from younger, atomic layers of undeformed zircon (s1b) at the start of its journey to earth (fig 6). th is atomscale stenonian geochronology, when paired with absolute geochronology methods, allows for back-stripping 94 ibid. and dating of a microscopic deformation and chemical erosion sequence developed on a path between planets.95 f ) s5 chemical dif fusion, chronostructures, and steno’s known unknown process th us i do not determine whether particles of a natural substance can or cannot undergo change, as its shape can, whether there are or are not minute empty spaces whether in those particles, in addition to the ability to occupy space and the property of hardness, there may not be something else unknown to us; for these statements are not widely accepted, and it is a feeble argument to deny that there is anything else in a certain thing because i do not observe anything else in it. 96 95 ibid. 96 n. stensen, in ref. 1 (k&m), p. 626. figure 5. cyclic growth and deformation; a) steno’s depiction of tuscan strata (see text for description of annotations), b) sem -cl image of one of earth’s oldest known mineral grains, zircon with a 4.38 billion year old core. th e 3.6 billion year sequence of growth, erosion, deformation and renewed growth features can be seen in higher magnifi cation view of white dotted box, enlarged in c). 111crystalline stenonian time features from earth and beyond th e fi ft h class of time features are surfaces of chemical discontinuity created by atomic movements and are distinct from the other four classes in terms of both the strength of connection to steno and the source of their geometric form. unlike the other feature classes, steno did not specifi cally predict structures at the atomic scale in nature as this was out of observational range. yet, as can be seen above, he allowed for their existence. th ey are included here as stenonian features because steno’s writings in both the prodromus and his later prooemium on the topic of particle (atomic) motion and heat have been previously interpreted as descriptions of diffusion.97 th is feature class diff ers also in regard to form in that s5 is not a single, discrete surface but a pair of subparallel surfaces bounding a gradient of chemical 97 j. m. hansen in ref. 33. change caused by a migration of atoms aft er solid formation. steno held the cartesian view that “a natural body is an aggregate of imperceptible particles”,98 and with recent advances in microscopy, geochronologists can now image and measure the three dimensional distribution of these particles, as either or both elements and isotopes, within minerals.99 of particular interest in zircon are the isotopes 206pb and 207pb which are the stable decay products of 238u and 235u, respectively. it has recently been found that exposure of zircon to extreme heat in the earth or in impact craters can cause pb isotopes to migrate (diff use) and pile up within the zircon lattice, thereby forming structures sensu stricto (fig. 7). i here introduce the term ‘chronostructure’ for 98 n. stensen, in ref. 1 (k&m), p. 626. 99 j. w. valley et al., in ref. 21. figure 6. stenonian time features at atomic scale in a meteorite from mars; a) a view of mars strata, opportunity rover; b) a stem image of the shock-deformed atomic layers in baddeleyite (s1a) reacting to undeformed zircon (s1b) in mars meteorite nwa 5298; higher magnifi cation stem images of the disturbed baddeleyite lattice (c), and undeformed zircon lattice (d). e) steno’s diagram 22. 112 desmond e. moser this type of s5 feature as it is a concentration of atoms assembled during an event; an outcome of the universal process of elemental diffusion within or between minerals assisted by either or both deformation and temperature.100 zircon presents a special case in that its lattice contains no pb at the time of zircon crystallization due to energetic exclusion. thus, each pb atom seen today is radiogenic and itself an expression of geologic time. zircon pb chronostructures reported so far have a variety of shapes but seem to be mostly spheroidal. examples have been documented from several regions on earth and the moon.101 one example can be seen in a zircon from near the centre of the vredefort structure in south africa where, one billion years after its formation, the largest recognized terrestrial impact event caused its s1 growth zoning to be cross-cut by s4 shock deformation features (fig. 7). these contain nanodomains of pb enriched ~1000x above background levels due to impact-related heating and diffusion. such chronostructures represent a new type of feature in absolute geochronology. 100 e. b. watson, e. f. baxter, diffusion in solid-earth systems. earth and planetary science letters, 2007, 253, p. 307-327. 101 see list of citations in g. a. arcuri et al., in ref. 40. 4. discussion this reconsideration of steno’s time features in minerals in comparison to those for other solids brings to light several themes that illuminate steno’s past and continuing contributions to mineralogy and geochronology. one is his perhaps revolutionary perception of scale invariance among the processes of solid formation in nature; an advance that is implicit in the prodromus but not always recognized. a second theme relates to the source of his observational acuity and the provenance of his scientific philosophy which, together, enabled him to recognize geologic history. finally, the consistent agreement between stenonian geochronology with modern microscopy and zircon geochronology opens the door to considering steno’s large, and largely unrecognized, importance in the practice of absolute geochronology. steno’s fractal features what i demonstrate about tuscany by induction from many places examined by me, so i confirm for the whole earth from the descriptions of many places set down by various writers.102 it is apparent from steno’s geochronology observations (table 1) that he saw his results as transcending geography and spatial scale. steno clearly believed that his findings would have global application, perhaps following the globalist thinking of descartes which had so impressed him103. his view of local processes as a subset of universal operations of the earth can also be seen as in line with the long philosophic history of macrocosms and microcosms which saw the human body as a facsimile of the workings of an animate earth.104 certainly our examples from zircon geochronology show that stenonian features are applicable to samples from the earth and beyond, representing stages in most of the solar system’s history. steno’s implicit awareness of the fractal and scale-invariant properties of the visual records in solids, in regard to both space and time, has not been amplified in previous studies of his work, in general, and in mineralogy, in particular. his freedom of mind in respect to physical scale is illustrated in his plate of diagrams105 wherein he juxtaposes cross sections of cmscale crystals with two dimensional profiles through a mountainous landscape. although cross-sectional views 102 n. stensen, in ref. 1 (k&m), p. 654. 103 d. garber, in ref. 29. 104 g. p. conger, theories of macrocosms and microcosms in the history of philosophy. new york, columbia university press, 1922, 142 pp. 105 n. stensen, in ref. 1 (k&m), p. 658. figure 7. example of a feature resulting from atomic diffusion (a ‘chronostructure’), related to steno’s allusion to such phenomena: left) a sem-cl image of a shock -metamorphosed zircon from the vredefort impact crater zircon, right) perspective view of a three dimensional atom map of pb (concentrated above 2%, green surface) and u isotopes imaged in a microscopic needle sampled from this grain (arrow). 113crystalline stenonian time features from earth and beyond of the earth were not uncommon in the 17th century,106 steno’s clear, connection of mineral and land evolution appears to have been without precedent in european natural philosophy. a metaphor for steno’s awareness of fractal scale invariance appears in his earlier writings when praising the scope of the human mind enabled by the creator: “finally he will penetrate the inside of the earth and discover the hidden mysteries of the minerals. all these representations respond to a sign as if the macrocosmos laid hidden in the microcosmos”.107 this accurate, fractal vision points to steno’s special abilities and method for natural philosophy. steno’s methodologic innovation it is proposed that steno’s achievements in the prodromus were made possible by his innovative pairing of an innate, finely-tuned awareness of the process of visual observation and cognition with a set of stoic ethical precepts gained earlier in his career, all coming to fruition on the galilean soils of florence. unless the mind is tranquil, it will by no means be free to apply itself to a close examination of facts which can and ought to be closely examined, and unless every least detail is noted in so far as the minuteness of the object or its intricate diversity allows, the pathway to error is downhill and very easy.108 the quality underpinning the classes of scale-invariant time features (table 1) is that of the cognition of continuity of visual elements in regard to either chemistry or geometric orientation; but, how do we sense continuity? neuroscience has recently shown that our visual sensory system operates with an inherent “continuity field” such that we have a short-term perceptual bias toward continuity of orientation in geometric forms.109 the timespan of the continuity field’s influence on human perception was measured at ~15 seconds; operating only near the observer’s point of focus. it follows that accurate visual cognition of patterns in nature requires time to overcome this natural bias. there is evidence that steno was very aware from his anatomical training and research that focused, prolonged visual inspection was requisite for accurate science (above). moreover, he recognized the reward of careful observation in teaching and advancing science in his own time: 106 t. yamada, in ref. 33. 107 n. stensen, in ref. 1 (k&m), p. 74. 108 n. stensen, in ref. 1 (k&m), p. 112. 109 j. fischer, d. whitney, serial dependence in visual perception. nature neuroscience, 2014, 17, p. 38-743. “sometimes it takes years to discover that which can then be demonstrated to others in less than an hour”.110 philosophers who presaged the work of linnaeus in the next century concentrated on “the external (and particularly the visible) structures of natural objects” 111 and, as mentioned above, steno’s examination of the internal zones of crystals was, in this regard, an innovation. moreover, upon his arrival in florence, steno immediately engaged with the members of the accademia del cimento which followed in the ‘anti-scholastic’ galilean scientific tradition of experimentation and observation, and responded by taking the middle way between scholastics and experimentalists.112 his primary instrument was human vision with which he interpreted, or abducted,113 in the language of geo-semiotics,114 meaning from the landscape. it is proposed that steno’s awareness of the need for self-discipline and time spent in observation was also guided by an awareness of the qualities of observation required if his deductions were to be deemed accurate and recognizable to others. i decided to press with all my might in physics for what seneca often urges strongly regarding moral precepts; he states that the best moral precepts are those which are in common use, widely accepted, and which are jointly proclaimed by all from every school.115 perhaps one of steno’s strongest innovations in methodolog y was to integrate the galilean experimentalist tradition of florence with elements of stoic philosophy as expressed by seneca (above). stoic philosophy was respected by the humanists for its systematic approach, and it is perhaps unsurprising to see it appear in steno’s work given his time as a student in leiden, which is considered to have been the heart of neo-stoicism in 16th and 17th century europe,116 and where steno sought out the rich diversity of intellectual thought of the dutch golden century.117 steno applies the stoic (senecan) tradition in ethics of considering only those sensations all can agree on, and falling within the area of intersection of all scholars’ perceptions. steno’s adoption of this aspect of stoicism to his treat110 n. stensen, in ref. 1 (k&m), pp. 128. 111 w. r. albury, d. r. oldroyd, in ref. 27. 112 j. bek-thomsen, in ref. 8. 113 j. e. h. smith, thinking from traces. nicolas steno’s palaeontology and the method of science, in ref. 8, p. 177-200. 114 v. r. baker, geosemiosis. gsa bulletin, 1999, 111, p. 633–645. 115 n. stensen, in ref. 1 (k&m), p. 626. 116 j. lagrée, justus lipsius and neostoicism, in the routledge handbook of the stoic tradition (ed. j. sellars), taylor & francis group. 117 e. jorink, modus politicus vivendi. nicolaus steno and the dutch (swammerdam, spinoza and other friends), 1660–1664, in ref. 8, p. 13-44. 114 desmond e. moser ment of the results of his visual, galilean experiments in the field allowed him to distill and communicate his uniquely systematic interpretation of natural history. steno and modern geochronology to recognize the temporal in the spatial – nobody had done that before stensen –, from the whole rock to read a dynamic course of time, has since then become and remained the main object of scientific geology.118 it can be argued that galilean science, and the prodromus, are similarly rooted in the sensation and measurement of time. in 1654, viviani reported that a youthful galileo used the period of his heartbeat to recognize the isochronous swings of a lantern through the space beneath the duomo of pisa,119 leading, ultimately, to his famous pendulum studies of the strength and orientations of gravity. one might sense echoes of this approach in the prodromus in which steno recognized the geometric tracings of time in solids using his highly attuned perception of discontinuity and its, embedded component of time. steno extended his extraordinary pattern recognition, likely refined through his years of anatomical research, to further place an order on sets of visible features, as in his reconstruction of tuscan geology; “obvious inequalities in the present surface contain within themselves clear indications of various changes, which i shall review in inverse order, working back from the most recent to the first”.120 in both strata and minerals (e.g. fig. 1), steno was thus the first to so methodically order past geologic events based on field experiments, setting the relative geochronology framework which would be employed by holmes in his proof-of-concept of absolute geochronology more than two centuries later. stenonian method continues to be vital in geochronology as technical advances enable sampling of eversmaller volumes and atom-scale observation of elements, isotopes and chronostructures becomes more widely applied; for it is axiomatic that absolute geochronology is dependent on the length-scale of sampling owing to holmes’ principle of the closed chemical system. conversely, steno’s spatial system of relative geochronology is scale-invariant in respect of both space and time. steno’s classes of visible features of production and modification therefore continue to serve as an independent, intensive, time measurement system for interpreting and checking the accuracy of absolute, extensive, geochro118 k. von bülow, in ref. 5. 119 s. gattei, on the life of galileo: viviani’s historical account and other early biographies. princeton university press, 2019, p. 440. 120 n. stensen, in ref. 1 (k&m), pp. 653. nology age measurements to allow us to achieve a more accurate geochronology. 5. conclusion steno’s prodromus has been recognized by many scholars as a brilliant, though loosely organized, advance in human observation and perception of records of geologic time in solids. a reconsideration and classification of steno’s writings on processes deduced from solids, and especially atomistic processes in mineral bodies, in terms of visual time features brings to light additional stenonian advances. successful comparison of steno’s time features with electron microscopy down to atom scale help demonstrate steno’s implicit appreciation of the fractal, scale-invariant nature of time features. steno’s methodologic advances are also discussed; with the proposal that it was steno’s combination of his awareness of the precision and accuracy of the human visual system with stoic, and particularly senecan, precepts in ethics which propelled his remarkable achievements in the rich, galilean scientific environment of florence. finally, it is argued that the intensive quality of stenonian geochronology causes it to be an invaluable check on the accuracy of extensive, absolute geochronologic age values, thus asserting the modernity of steno in the geochronology of solids from earth and beyond. acknowledgement i gratefully acknowledge helpful reviews of earlier versions of this manuscript by yuri amelin and jens morten hansen. many thanks to eric jorink for his review and helpful directions to stoic literature. nuno castel-branco is thanked for assistance accessing steno literature early in the pandemic. gabriel arcuri is thanked for assistance with figure 7. the author gratefully acknowledges his many collaborators associated with the microscopy presented here. helpful editorial comments by g. d. rosenberg are very gratefully acknowledged. stefano dominici is especially thanked for patient and supportive reviews and guidance, important steno references, and direction in navigating historical science literature and conventions. nasa apollo 17 astronauts and mission scientists are sincerely thanked for lunar photograph in fig 5. nasa/jpl/cornell are acknowledged for the burns cliff, endurance crater, opportunity rover image in fig. 6. participants in the oct. 2019 symposium at the university of florence are thanked for many conversations and generous sharing of their wealth of steno knowledge. substantia. an international journal of the history of chemistry 2(1): 77-91, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-42 citation: j. wolfe (2018) from idea to acoustics and back again: the creation and analysis of information in music. substantia 2(1): 77-91. doi: 10.13128/ substantia-42 copyright: © 2018 j. wolfe. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe university of new south wales, sydney, 2052, australia e-mail: j.wolfe@unsw.edu.au abstract. the information in musical signals – including recordings, written music, mechanical or electronic storage files and the signal in the auditory nerve – are compared as we trace the information chain that links the minds of composer, performer and listener. the (uncompressed) information content of music increases during stages such as theme, development, orchestration and performance. the analysis of performed music by the ear and brain of a listener may reverse the process: several stages of processing simplify or analyse the content in steps that resemble, in reverse, those used to produce the music. musical signals have a low algorithmic entropy, and are thus readily compressed. for instance, pitch implies periodicity, which implies redundancy. physiological analyses of these signals use these and other structures to produce relatively compact codings. at another level, the algorithms whereby themes are developed, harmonised and orchestrated by composers resemble, in reverse, the means whereby complete scores may be coded more compactly and thus understood and remembered. features used to convey information in music (transients, spectra, pitch and timing) are also used to convey information in speech, which is unsurprising, given the shared hardand soft-ware used in production and analysis. the coding, however, is different, which may give insight into the way music is understood and appreciated. keywords. information, music, composition, cognition, coding. introduction1 many digital recordings encode microphone signals as 16 bit numbers, which gives a dynamic range (maximum signal range/digitisation step) of 216 = 96  db. the signal is sampled at 44.1  khz. this gives a data transmission rate of 706,000 bits per second or 706  kbaud per channel, not counting error correction bits. a traditional compact disc (cd) can store about a thousand megabytes of data: enough to store several hundred novels, or about eighty minutes of uncompressed recorded music. this raises the questions: where do all these data come from? how much is provided by the composer, by the players and the instruments? 1 this paper was originally presented and published as a plenary lecture at the eighth western pacific acoustics conference, melbourne, 2003. (c. don, ed.) aust. acoust. soc., castlemaine, australia. 78 joe wolfe what happens to that torrent of data when it reaches the listener? the rate delivered by a stereo cd – about one and a half million bits per second – appears to be equivalent to a novel every several seconds. can our ears and brains cope with such a rate? and finally: why do we like it? as a composer and physicist, i try here to address these questions from both sides. i suggest some answers, and indicate where research is currently looking for others. data compression data files can usually be simplified or compressed because they contain much redundancy. for instance, a cd could contain 75 minutes of 1  khz test tone. this is redundancy on a scale of 1  ms: to a suitably sophisticated receiver, the signal could be sent as the text instruction “p  =  (1  mpa)  sin  (2pi*t/ms), 0  <  t  < 4500  s”, which requires only 352 bits in ascii. for an example of redundancy on a longer scale, consider “house music” in which short sound segments are sampled and repeated many times. kolmogorov [1] and chaitin [2] independently introduced algorithmic entropy to quantify the difference between unpredictable and redundant signals. to paraphrase chaitin, consider two binary numbers: 1011110010001101010110111011000001101010 and 0101010101010101010101010101010101010101. the first “looks” random: it was obtained by tossing a coin forty times. the simplest way of transmitting that number is sending the number itself. the second does not “look ” random: it can be reconstructed from the instruction “print ‘01’ twenty times”. that instruction contains more than forty bits of information, but for a very long predictable number, the reproduction instruction may be rather smaller than the number (e.g. the 208 bit instruction “print ‘01’ a million times” produces a 2 million bit output). the algorithmic entropy is proportional to the number of bits of information in the minimum message needed to reconstruct a signal. (it is thus proportional to the log of the number of permutations and consistent with gibbs’ definition.) the more simple or predictable a signal, the lower its algorithmic entropy and the more it may be compressed. conversely, the richer in information, the higher the entropy, and the more it resembles a random signal – at least to a receiver that cannot decode it. when sound signals are stored to be heard by humans, they are often compressed using the mpeg (mp3) algorithms. these take advantage of masking in human hearing: one frequency band may mask others, so the masked sounds are omitted. a reconstructed mpeg waveform produces an auditory illusion: its waveform has little resemblance to the original, but it sounds very similar. recorded music has relatively small algorithmic entropy. indeed, its underlying order, at several different levels, is one of its attractions. at the lowest level, there is high redundancy in the waveform. a note with a definite pitch is quasi-periodic: one cycle with the pitch period is followed by many others very like it. of course, in real, interesting instruments, the periodicity is only approximate: transients and vibrato lead to varying waveforms, as do non-harmonic components in percussion and plucked strings. systems of music notation take advantage of this redundancy. in standard (western) notation, vertical positions of notes on the staff plus accidentals specify pitches and thus, approximately, frequencies. a discrete set of note symbols, plus a few other data (tempo and articulation), specify durations. some information about the type of waveform, and much else, is contained in a word at the beginning of the music: the name of the instrument that is to play it. from this relatively small data set, performers and instruments construct complete waveforms. the information content of written music is relatively easy to quantify because written music is digital in pitch and in time: relatively small sets of discrete pitches and durations are used. in contrast, performed music is only approximately digital: musicians make fine adjustments to the durations and timing and, except for keyboard players, adjust the pitch slightly according to context. these adjustments contribute to musical interpretation, to which topic we shall return. fig. 2 shows a short example: the first two phrases of the theme of the slow movement in mozart’s clarinet concerto. one way of coding it is to sample the pitch regularly in time. the lowest suitable sampling frequency is the metronome marking times the lowest common multiple of its subdivisions. most simple themes could be adequately sampled at a rate of order 10 hz. five octaves (61 notes) covers the range of most orchestral instruments and can be coded with 6 bits (i.e. 61  <  26), so the notes and rests could be coded at about 60 bits-1 (60 baud). most notes are longer than the sampling time, however, so this signal can be compressed by coding for the durations of the notes as well as their pitch. traditional notation does just this, inter alia (fig. 2b). the bar lines appear to be redundant, but to musicians they also give contextual information relevant to musical expression [3]. they also provide a correction mechanism for accumulated errors in duration decoding. 79from idea to acoustics and back again: the creation and analysis of information in music figure 2c shows how a simplified binary parallel coding can represent those aspects of traditional notation used here. this example has a data content of 266 bits and, over a duration of about 13  s, a transmission rate of only 20 baud. no correlation between the quantity of information and its value is implied, of course: many people consider this 266 bit theme more valuable than, say, a gbyte of white noise! the encoding used by music sequencers is close to that of music notation. these, the electronic progeny of the musical automata in fig 1, are computer programs that output signals to synthesisers via a standard music industry digital interface (midi). the midi standard transmits data at 31.25 kbaud in serial form. this permits parallel voices and a range of instructions, and its design allowed bandwidth for further developments. alternative coding protocols have been proposed [4]. more sophisticated representations include expression – variations in loudness, amount of vibrato, fine adjustments to pitch and to timing [5,6]. another crude but pragmatic way of computing data content is to look at the data files of note procesfigure 1. four digital storage media. (a) the cylinder and comb from a music box play 16 bars from lara’s theme (m. jarre). the 18 tines of the comb have different masses and thus play different notes when struck by spikes on the cylinder. it has 18 parallel channels – circles round the cylinder. the loudness is binary (spike or no spike, note or no note). the timing is in principle analog, but is here quantised in multiples of 1/12 of a bar. the uncompressed data content of this cylinder is therefore 18 x 12 x 16 = 3456 bits. (b) the pianola roll in the background also has parallel binary channels, but the length of the hole determines the time the strings sound before the damper is replaced. in that sense, both duration and timing could be analogue, but again they are quantised in this example. the uncompressed data content is 35,000 bits per metre. (c) standard western music notation is (largely) parallel binary digital coding: each line and space (parallel channels) represents a pitch, though that pitch can be varied by sharps and flats. the time coding is encoded digitally in symbols (see fig 2). this example (the rite of spring, i. stravinsky) has about 30,000 bits on this page, which lasts a few seconds, using a coding somewhat like that in fig 2c. (d) the cd also carries a binary digital signal (“pit” or “no-pit” in the track) but it is different in all other aspects. the signal is carried in serial rather than in parallel, and it encodes numbers that are proportional to the pressure of a sound wave. this cd records about 5  x  109 bits, not counting error correction bits. the storage efficiencies are approximately: a)  5  x  105  bit.kg1, b)  106  bit.kg-1, c)  107  bit.kg-1, d) 3 x 1011 bit.kg-1. the apparatus required for re-creation varies greatly in size: that for (a) is shown (~ 0.01 kg), that for (c) is ~ 104 kg. 80 joe wolfe sors. these are to music what word processors are to text, and are widely used by composers and editors to write and to print music (sibelius and finale are commercial examples). they store written music in digital files that are similar to, but more elaborate than that in fig 2c. on my hard disc is a 160  kbyte note processor file for a symphonic work. it takes 23 minutes to play, and so its printed score delivers data to the conductor at an average rate of 900  baud, or 900 bits per second. to achieve the same transmission rate reading this article (not counting figures), one would need to read it at 1100 words per minute. it should be noted that conductors do not absorb all the information in a score in real time. while comparing written music and written text, it is worthwhile contrasting them as well. one difference is cultural: more people can read text than can read music. even to those literate in both, however, the aural re-creation is more important in music. most musicians prefer hearing performances to reading scores, whereas i expect that most text-literate people prefer reading novfigure 2. three ways of coding the first four bars of the theme of the slow movement of mozart’s clarinet concerto. (a) is a semi-log plot of the pitch frequency as a function of time. on the time axis, the larger tics are bars (measures) and the smaller are beats. on the frequency axis, the larger tics are octaves. notes an octave apart have the same letter name e.g. c5 and c6. the reference frequency is the note called c0, which is currently about 16.3  hz. the smaller tics are one twelfth of an octave i.e frequency ratio of 21/12 ≅ 1.059). these are called equal-tempered semitones: they correspond to the notes on an electronic keyboard. (b) is essentially traditional notation. the vertical and horizontal axes have been adjusted to make it an exactly semi-log plot by varying the spacing between lines, which may represent 3 or 4 semitones. the shapes of notes are a digitised code for duration that has several advantages over the analog time scale used in (a). (c) is a parsimonious parallel binary coding, which is more akin to traditional notation than to (a). the pitches of notes are shown by their octave (top 3 bits) and the note names (next 3 bits) with the most significant bit at the top. the next 2 bits allow for accidentals (sharps, flats and naturals) that are not needed in this example unless the key signature is omitted. the next bit indicates slurs: whether the note is continuous with the preceding one (the curved lines or slurs in (b)). the next bit indicates a rest (silence) of the appropriate length. the next 3 bits show the negative log durations with respect to a whole note. semibreves, minims, crotchets, quavers and semiquavers (whole, half, quarter, eighth and sixteenth notes) are represented by 000 to 100. 101 is used for a bar line. the final bit allows an increase of 50% in duration (indicated by a dot in (b)). the duration code 111 is reserved as a signal to toggle the coding to text, so that occasional data such as tempo, key signature, expression marks can be added more efficiently. (the unequal spacing of channels is a guide for the eye only). 81from idea to acoustics and back again: the creation and analysis of information in music els (at a rate of several hundred baud) to hearing them read aloud, at slower rates. in both cases, the auditory transmission contains a great deal more information than does the written version. the origin of information in music melodic and harmonic structures are good examples of redundancy. in a high information/ high entropy signal, all pitches would occur in approximately equal numbers and it would be impossible to predict the next note: a high information signal sounds or looks random. music is ordered2, and this order makes music files compressible. the generation of information is easy to follow in (western) concert music because it is usually written down at several different stages, which may be (i) motifs; (ii) their extension to melody, their transformation and development; (iii) the addition of other voices (usually in harmony or polyphony); and iv) orchestration or arranging. in formal music, this results in an orchestral score. in less formal music, analogous processes may lead to a score that is stored in one or more person’s memory. in improvised music, the entire “score” may never be stored. a motif is a characteristic phrase of several notes. the opening four notes of beethoven’s fifth symphony is an example, of which more anon. a motif is usually the origin of a musical composition. several different pitches over a modest pitch range, and allowing for several different note durations, implies a possible information content of a few hundred bits. although the production of this information is difficult to study in detail, textbooks on composition give advice on producing motifs from simpler patterns. schönberg [7], for example, gives numerous examples of how musically interesting phrases can be constructed from the three notes of a major chord by adding passing notes, repetitions, upbeats, appoggiaturas and alterations of notes. many composers use comparable techniques to produce melodies. the processes used by human composers are rarely written down, and are difficult to study explicitly [3]. it may seem prosaic to speculate that they are algorithms (as yet unknown) operating on aspects of the composer’s background and stimuli, but to do otherwise seems to 2 predictability necessarily implies redundancy. hearing an unknown piece of tonal music from which some notes had been replaced with obvious blanks, many listeners would be able to guess the missing notes with better than chance scores, just as yo_ cou_d gues_ the _issing lette_s in this sentence. lead to cartesian dualism. a range of explicit automata have been devised to create melodies. a famous example is the dice music attributed to mozart, in which casting a die decides among several possible subunits. in electronic versions, a random number generator replaces the die. further, while mozart’s subunits are musical phrases, some composition algorithms start with a scale of notes, some random input and a set of rules. various automatic composers have thus been devised [8] since harry olsen created one in 1951 using rules generalised from the songs of stephen foster [9]. michael smetanin is an example of a contemporary composer who has used simple rules or algorithms to create musical compositions. it is difficult for an outsider to judge the success of such algorithms per se, however, because there is usually some discretionary intervention by a human at the input or output stage. in ‘strange attractions’, smetanin [10] chose a particular algorithm because it gave melodies that he found attractive. an extreme example of choosing an algorithm and then letting nature take its course is ‘white knight and beaver’ by martin wesley-smith [11], in which the composer assigns a note to each of the four bases of the dna code, and then notates musically a section of the genome of the bacterium e. coli3. when other examples are given of tunes created by various algorithms, however, it is usually the case that only the ‘best’ results are presented – so human decision-making has intervened at the output stage. use of a set of “rules” or fashions to generate combinations of notes and then a decision about which ones to keep is a simple model for the way some human composers work. the “rules” need not be laws (such as “the leading note always rises”4) decreed by some authority and observed by composers [12]. rather they may be habits or tendencies in styles of music. for instance, virtually all composers recognise the octave as the most important and harmonious interval. even the ‘democratisation’ of intervals by serialist composers leaves the octave as a very special case [13]. in this case there is a physical explanation: the harmonics of a particular note are a subset of those of the note one octave below, so adding an octave does not, or need not, add any new frequency components. in other cases, the “rules” have more complicated origins: for instance, most compos3 does it sound like something that came out of a human colon, one might ask. well, there are only four notes and they are not discordant. it sounds pleasant and musical, but this listener cannot readily extract a musical meaning. 4 this rule shows a good example of redundancy: if the leading note were always followed by the note above, then an encoding could omit the pitch of the latter, just as one could omit the “u” following “q” in coding english. 82 joe wolfe ers confine themselves to scales with twelve semitones to the octave. this has a little to do with the physical basis of harmony [14], but it also has to do with what conventional instruments and players can play, what we are used to hearing, and a series of compromises among consonance and keeping the number of notes small. the “rules” for composition in most styles would be difficult to list specifically, but the musical heritage and education of the composer must incline him/her towards some patterns and combinations. composers have a variety of processes (algorithms) for transforming an old motif into a new one, such as inverting it, changing the rhythm, reversing it, changing one or more intervals [15]. perhaps the most important stage in producing a good motif is deciding which of many candidates is good. this process, while difficult to analyse, is at least almost universally comprehensible because many music lovers claim an ability to discern a good theme from a bad. thus, in one common method of composition, input data and a series of different, often unconscious algorithms generate a short phrase or idea with perhaps some tens or hundreds of bits. this may be developed into a longer melody. in written music, the data content increases in proportion with the length of the melody, but many of the extra data thus produced are redundant, in the scientific sense. the “same” motif may be repeated, transposed, inverted and otherwise transformed to create a much larger work. for one example, note the similarity in the two phrases in fig. 2. for another, consider the famous opening phrase of beethoven’s fifth symphony: . much is made of this simple phrase: the motif of three quavers followed by a descent of a third is used dozens of times in the beginning. simple modifications of it occur in almost every bar of the movement: it is transposed to different positions in the scale, the final interval is changed to a second and sometimes a fourth, the last of the quavers sometimes falls, or the whole phrase is inverted in pitch. further variants appear in the other movements – a remarkable example of much created from little. the redundancy or structure that is created by repetition with variation is very common in melodies. in the sixteen bar ‘freude’ air of beethoven’s ninth, for example, the phrase of the first four bars is repeated with slight variations in bars five to eight and thirteen to sixteen. this pattern (a,a,b,a) is extremely common, especially in songs. on a larger time-scale, redundancy through explicit repetition is so common that a variety of musical notations exist, including various repeat signs and musical ‘goto’ statements. in formal music, there is often a development section in which the original idea is variously transformed: it may appear in different keys, different rhy thms, inverted or melodically varied or decorated. the transformed phrase is often sufficiently different that a simple coding cannot easily reduce the length of the simplest representation. the data contained in such sections are thus created by treating the input data (the initial phrase). the existence of important structures with a variety of time scales5 have made it difficult to formalise or to automate this operation, however. further, selection among different algorithms and outputs is again an important process. (see the discussions in [3,16].) adding harmonies and counter melodies to a principal melodic line adds more data, but in some instances the extra data have relatively great redundancy. a canon is an extreme case, in which the original melody accompanies itself with a time lag, so the only extra information required is the period of the delay. in a fugue, the same or a similar melody enters with a delay, and often a symmetry operation, i.e. transposed or inverted in pitch, with doubled or halved tempo. in these cases, and in polyphony, several parallel channels of melody are of approximately equal importance. in much music however, there is one melody (or foreground) of pre-eminent importance and a harmony or accompaniment (middleground and background). in many musical styles, the harmony is subject to rules of varying strictness, which to some extent limit the freedom of other voices and thus introduce further redundancy. students of traditional western harmony will agree: it often seems that the combination of strict harmony rules and voice ranges, when applied to the melody set in a harmony exercise, allow only a small number of possible ‘solutions’. in many styles of music, the second most important line is the bass. if strict harmony rules are applied to a given melody and bass line, the possibilities for further parts is severely limited. altos and tenors in choirs, or the players of second violin or viola sometimes feel that theirs are the ‘left over’ notes and that the result is a part that both more difficult and less satisfying than the top or bottom lines. strict rules are extreme examples [12], but it is rare that harmony or polyphony is without rules, whether formal or informal, rigorous or fuzzy. thus the generation of the harmony or accompaniment is often aided by the operation of algorithms on the information in the melody [18,19]. sometimes the harmony is coded in a com5 for example, the use of time-series analysis to predict the next note from the previous several notes may work well for short time scales, but is prone to wander rapidly among keys. reviewed by dubnov and assayag [17]. 83from idea to acoustics and back again: the creation and analysis of information in music pact but inexplicit way, such as chord symbols or figured bass. some of its information (e.g. the chord symbol) is sufficiently important that the composer chooses to specify it, but the octave in which the notes occur, or their timing, is left to the performer. information other than notes, including articulation, ornamentation and expression marks, may be written above or below the musical staff, to convey information about pitch and duration (e.g. trill, staccato etc.) in ways that are more compact and legible than the explicit notation. others carry information about loudness, articulation and tempo (pp, sfz, accel. etc). others, particularly in contemporary music, contain instructions about timbre or tone colour [20]. schönberg proposed the development of klangfarbenmelodie (tone colour melody) in which changing patterns and structures of timbre would attain a status similar to that of changing pitch in traditional melody. achievement of this aim might require extra data at a rate of tens or hundreds of bits per second. some contemporary concert music contains highly specific instructions for performance, sometimes even several instructions per note. where pitch intervals less than a semitone (microtones) are explicitly required, this is indicated by further qualification (half flat etc.). the requirement for slight pitch adjustments is usually implicit: many musicians do not play exactly tempered scales but, according to musical context, make fine adjustments. one of the most important instructions about timbre is the name of the instrument that plays each part. orchestration, the process of distributing the parts among the instruments of the orchestra, adds further information. however, there is sometimes a high redundancy when the same notes are played by different instruments. how many data are stored in an orchestral score? stravinsky’s “the rite of spring” [21] provides an example of high content: it is written for a large orchestra and often the parts are relatively independent. in some sections, there are more than 40 distinct musical lines, although of course at any instant there is doubling of notes (fig 1c). coding just the notes of this score by sampling in time (cf fig 2a) would require high transmission rates – over 100  kbaud – because of the complicated rhythms. traditional coding (fig 2b) is more economical, and requires only several thousand baud6. so a transfer rate of up to several kbaud (equivalent to a few hundred words per second) is available to 6 the example cited is from rehearsal mark 11 in [21]. demisemiquavers with triplets, quintuplets and septuplets at crotchet = 66 require sampling at 924  hz. with 6 bits for pitch, the 31 parts require 172  kbaud. using a code like fig 2b, but with several more bits of articulation and expression marking, 200-300 notes per bar require several kbaud. the conductor of such a work, from the score alone. not all of this is discernible: if one player in a tutti failed to accent a note, or if the bass clarinet and second bassoon exchanged parts, this would probably pass unnoticed. when one is not conducting nor listening to a performance, there is no need to read a score in real time, and one may spend minutes reading carefully a single page of score, which is played in several seconds. the performer: information input and output orchestral players usually read only one line, so they receive and process their written parts at rates of up to a few hundred bits per second. other visual inputs come from the movements by other musicians, especially the conductor’s baton, the leader’s bow and the ‘body language’ of section leaders. musicians hear the sound around them, and read the gestures and ‘body language’ of the conductor. this affects their processing of the written information. the interpretation of a dynamic instruction such as forte depends on the ensemble loudness at the time. fine pitch adjustments depend on the prevailing pitch and harmonic context. players also receive feedback from the interaction with the instrument of their hands, arms and mouths – but this is getting ahead of the logical order, in which the obvious next question is: how much information does the musician put out? some instruments have a binary digital component. in keyboard instruments, and in some percussion, the individual pitches are effectively a finite number of parallel pitch channels. in harpsichords and organs, the keys are strictly digital: a key is either depressed or not, and the player’s control of the loudness of that note is binary. bach reportedly said, disingenuously, of his organ playing: “there is nothing remarkable about it. all you have to do is hit the right notes at the right time, and the instrument plays itself ” [22]. bach, who played the viola too, would of course have known that playing a single, beautiful note on such an instrument requires much more than simply starting and stopping at the right time. the exact timing of the depressing and release of keys are analogue parameters of great importance in musical expression. in the piano, another analogue parameter is the momentum with which the hammer strikes the string. in percussion instruments, there are the complications of the position, speed and angle of the strike. most woodwind and brass instruments have keys and valves used almost always in a binary way: either depressed or not. this does not however restrict the pitch to discrete values because pitch is also controlled by the player’s lips and air pressure. in orches84 joe wolfe tral string instruments, the pitch is controlled by a continuous parameter (position of the finger stopping the string) plus choice of string. phrasing and expression are largely supplied by performers. consciously or unconsciously, musicians decide how to ‘shape’ the phrase. this includes varying the loudness and amount of vibrato of individual notes, and making slight adjustments to indicated durations. a note judged to be important might be given emphasis by increasing the loudness and vibrato, and by increasing its duration slightly beyond the indicated value. this is one notable – and valuable! – difference between a performance by a musician and one by a primitive music sequencer. to some extent these elements of interpretation are similar among musicians [23] and so they may, to that extent, be codified. acousticians friberg, sundberg and colleagues, in consultation with prominent musicians, have induced and formalised performance rules that add such elements of interpretation to a sequence representing written music [5,24,25]. their software produces a ‘performance’ that is much more idiomatic and “musical” than that produced by an ordinary sequencer. these ideas have inf luenced modern commercial music sequencers7. the instrument: input and output written music is an incomplete instruction set. to oversimplify, the individual musician reads at typically 100 baud or less, and outputs time-varying control signals, which may have several times this rate. the instrument outputs an analogue signal. for most monophonic instruments the output spectrum is dominated by approximately harmonic components whose fundamental frequency (which equals the harmonic spacing) determines the pitch. the pitch varies in time (with vibrato and with successive notes) and the amplitudes of the spectral components vary in time. the information required to encode this output depends on the fidelity and dynamic range required. it is at this stage that there is a great increase in the data required for encoding. if the performance is recorded uncompressed on a cd, then it results in the same enormous data transfer rate whether it be the intricate orchestration of ‘the rite of spring’ or one of the much simpler examples given above. on many instruments, players control several interdependent analogue parameters connected with phrasing, such as vibrato, loudness, and variations in timing and intonation. performers may also control several parameters that contribute to the timbre. in string instruments these include bow position, speed and force. in wind instruments, they include blowing pressure, several aspects of embouchure (e.g. lip tension, jaw position, position of lips on reed) and the shape of the vocal tract. these parameters may be adjusted several times per second, and each may have several bits of precision. together they may contribute up to a few hundred baud. the instrument, then, is where the data rate increases dramatically. but surely the instrument is not creating information? rather, we could say that the instrument increases the redundancy – creates redundant data – by a large factor: one period of the note is very similar to the preceding one. this oversimplifies a little: two similar hypothetically identical performances by a player – or even by a music sequencer and synthesiser – will not 7 these typically have a range of settings for ‘expressive’ performance, from meccanico to molto espressivo and molto rubato, with varying interpretations including straight, swing, viennese waltz and funk. figure 3. one information chain, from composer’s original ideas to performed music. the approximate data content is given in bits and kilobytes (1  kbyte ≅ 8000 bits) and the rate of data transfer is given in baud (1 baud = 1 bit per second) and kilobaud. 85from idea to acoustics and back again: the creation and analysis of information in music produce the same waveform, but the differences are not information to be transmitted from composer and player to listener. transmission and radiation in performance, instruments radiate sound into the air. these signals, plus background noise, are convoluted by the delays and multiple reflections of the performance venue. this extra information is recognised by listeners who can discern some details about the venue from listening to a recording – the difference between a cathedral and open air is an extreme example. this information contributes feedback to the conductor and players, who in general adapt their performance to the acoustic environment. for instance, they might play more quietly in a room with a low background noise and more slowly and more marcato in a room with a long reverberation time. a performance creates a sound pressure field: the sound pressure p varies with position vector (r) and time (t). it would take a prodigious number of data to record such a field with a resolution in space and time corresponding to the half-wavelength and half-period of the highest audible frequencies (say 30  µs and 1  cm). of course, the whole field is not sampled by a single listener, who receives just the sound pressure at each ear (p(r1,t) and p(r2,t)), although the positions of the ears may vary in time as the listener moves his/her head. so each ear receives an analogue signal which, if the level of background noise is sufficiently low, may have the same dynamic and frequency range as the sum of the signals from the instruments. our imaginary composer, orchestrator, musicians, conductor and performance venue have now delivered to the ear the great data rate mentioned in the introduction. because of the high signal redundancy, the information rate or algorithmic entropy rate is considerably lower, but still perhaps impressive. the information has been generated by mental processes of the composer and performers, which we may consider as algorithms – subtle and in many cases not understood – processing inputs from memory, education and culture. the instrument has turned this information into the radiated signal, which has been filtered and convolved by the acoustic environment. it’s now time to follow the signal into the listener’s head. the analysis of information the outer and middle ear are, for our purposes, primarily acoustic and mechanical impedance transformers that overcome the mismatch between the air of the radiation field and the cochlear fluid in the inner ear. (they are also filters, transmitting some frequencies more effectively than others.) the qualitative change occurs in the cochlea of the inner ear in which the input signal – single channel analog – is actively filtered, compressed and converted to parallel digital electrical signals in the auditory nerve. because of the position-dependent mechanical properties of the basilar membrane, pitch is in part coded by channel: only low frequency waves reach the apical end of the membrane, so nerve fibres from this region carry information about low frequencies. it is also partly coded in rate of firing, at low frequencies at least, because the hair cells are stimulated at the frequency of the motion8. signal amplitude is also partly coded by channel (some fibres only respond to large signals) and partly by (analog) signal firing rate: overall, larger stimuli produce higher firing rates. the minimum firing rate is not however zero: most neurones have a ‘background firing rate’ – a rate at which they fire in the absence of any signal. this makes a neuron capable of carrying a “negative” signal: if the cell is inhibited by a neighbour, its firing rate falls below the background rate. lateral inhibition among neighbouring cells is useful in amplifying small simultaneous differences. nerves also become less sensitive with continued stimulation, so a changing signal usually has a greater effect than a steady one. for more detail, the reader is referred to reviews of perception and neurobiology [27,28,29,30,31,32]. coding in the auditory nerve the pulses in the nerve fibres, called action potentials9, are binary – either the stimulus is strong enough produce an action potential, which travels along the nerve fibre, or else nothing happens. as in electronics, the advantage of digital signals is their immunity to noise and distortion. nerve fibres are very lossy coaxial cables, so an unamplified signal is substantially lost after transmission of a few millimetres. many stages of amplification and pulse shaping are conducted by the nerve membrane where it is exposed at the nodes of ranvier. what is the data transfer rate at this stage? there are about 30,000 nerve fibres or channels, each capable of 8 experiments with implanted electrodes show that, at low stimulation rates, perceived pitch depends approximately logarithmically on the stimulation rate but also linearly on the electrode position [26]. 9 the voltage inside biological cells is usually tens of mv negative. when nerve cells are stimulated (by briefly making their membrane “insulation” leaky), the internal voltage rises ~100 mv before returning to the resting value. 86 joe wolfe transmitting a few hundred action potentials per second. if the coding were strictly digital, the data transfer rate would surpass that of a cd. the practical rate is much less, because of redundancy: in part because nearby fibres carry highly correlated signals. what happens to this signal in the brain is difficult to follow directly. the experimental observations of psychophysics include integration, sampling and signal treatment at higher levels. effects including the active filtering in the basilar membrane give rise to the masking of weak signals by strong signals in nearby frequency bands. there are only roughly 30 critical bands so, instead of 30,000 parallel frequency channels, perception effectively involves only of the order of 30. for an unmasked tone, the just noticeable difference (jnd) in sound level is roughly 1  db. over a short term dynamic range of 60 db, this gives about 60 perceptible loudness levels (requiring 6 bits). the jnd for frequency may be as small as tenths of a percent for sustained signals, but in our calculation the maximum frequency resolution is limited over most of the range by the temporal sampling rate. the greatest perceptual resolution in time is a few tens of milliseconds. at this rate, the number of different frequency percepts is about 1000 (10 bits). so there are about 16 bits, sampled at up to 30 times per second, in 30 channels. the product gives data transmission rate of 16 kbaud: a considerable overestimate because the jnds increase towards the ends of the frequency range and as sampling rate and number of simultaneous stimuli increases10. whatever the actual maximum rate, to achieve it would require a signal that, at the perceptual level, had no redundancy or order: a signal that sounded random. not music. processing – sorting into notes it is easier to perceive notes (which usually include several or many separate frequency components) than to perceive the individual frequency components of its spectrum. with practice and careful listening, one can distinguish some spectral components in notes in some circumstances11. that naïve listeners rarely do so suggests that we have either a very well-learned or an inbuilt mechanism for combining the various frequency components of a note together and perceiving it as a whole. this capacity is partly explained in terms of two 10 there are further complications such as feedback loops and other control signals which come “downwards” from the brain to the ear, and these affect the “upwards” signals to the brain [33]. 11 or, conversely, a small number of harmonics may be made sufficiently louder than the rest that they can be identified as separate notes, as in harmonic singing. general properties attributed to the nervous system: that change is more noticeable than lack of change, and that things that change in the same way are often grouped together. consider a note comprising several harmonics: if the pitch of the note changes (either melodically or due to vibrato), then the pitches of all its components change in exact proportion; if the loudness changes, then the loudness of the harmonics also changes. evidently we possess signal processors that group these separate, but similarly changing elements together and identify them as a single note. instrumental and operatic soloists make use of vibrato to make their notes identifiable against the sound of the orchestra12. the system works especially well for notes whose spectral components are approximately harmonic, which we identify as having a definite pitch. this capacity may have been important in the evolution of human audition. many human vocal sounds (the vowels in speech, but also inarticulate cries and screams, whether sung or spoken) have at any instant a definite pitch and spectral components which fall in the harmonic series. it is likely that we have evolved hardand soft-ware capable of identifying vocalised sounds among other sounds that do not have harmonic structure, such as wind noise. the system works so well that we hear missing fundamentals and tartini tones. analysis in time the shortest time scale of interest in music is the period of the vibration. this ranges from about 50  μs to 50  ms. for low pitches, the auditory nerve carries some information about pressure variation on this time scale, but while we are aware of pitch, we are rarely aware of the variation in pressure that gives rise to that pitch13. the next time scale is that of transients. when an instrument begins to play a note, there is a short time (tens of milliseconds) over which the amplitudes of the various components vary considerably before ‘settling down’ to establish a relatively unvarying spectrum. these transients are so important to the timbre of a note that different wind instruments are readily confused if the initial and final transients are removed [34]. transients in musical notes are analogous to plosive conso12 this effect is especially useful if some of the harmonics of the soloist occur in a frequency range where the accompanying sounds have relatively low level – if we can hear one component clearly, it seems that we can track other components which have the same vibrato and phrasing. 13 a contrabassoon can play bb0 at 29  hz. when this note is played loudly, we can just detect a periodic variation as the reed opens and closes 29  times per second. most of the sound we hear, however, is in the higher harmonics rather than the fundamental. 87from idea to acoustics and back again: the creation and analysis of information in music nants (d, t, g, k, b, p) in speech or singing. in both cases we are capable of concentrating and hearing them with some clarity, but under most circumstances these details are analysed subconsciously. the third time scale (several tens of milliseconds and longer) is that of notes [35,36]. it is at this level that we sense pitch and timing: the basic elements of melody. with little concentration, we can readily be conscious of the rhythm and the pitch, and also of the timbre of the instrument playing it. it is, however, difficult to introspect much beyond this: although our ears and their associated low-level processing have coded the various component frequencies and how they vary on the scale of tens of milliseconds, we are usually aware of the signal at a higher level: that of pitches, rhythms and timbres. a changing signal is less redundant than a constant one, and our senses reflect this. after a while we no longer notice the sound of the wind, the weight of our clothes, the strange colour of artificial lighting; but we do notice sudden changes in them – changes over time. similarly, we notice sharp boundaries in a visual image rather than a gradual change between two colours or shades – changes in space or channel. changes in time are enhanced by the property of nerves to fire more rapidly when first excited than they do during a steady stimulus. differences in space or channel number are enhanced by neural circuits that effectively subtract the signals from adjacent nerves using lateral inhibition [37]. pitch sensitivity provides a good example. a single note without vibrato is a steady signal, which is probably carried at all times by the same nerve fibres. a note with vibrato is a varying signal, which is probably carried at different times by different nerve fibres. vibrato makes notes more noticeable, and also makes it easier to identify a single instrument in an ensemble. timing sensitivity provides another example. we are usually less conscious of the duration and end of the note than the beginning: a variation in the timing of the end of each note is noticed as a change in articulation – some notes more staccato than others; a variation in the timing of the beginning is noticed as a variation in the rhythm, and is more noticeable. symmetries: the ear and the instrument in this sense, our ears and their associated low-level processing perform a role that is the reverse of that of the instrument: the player controls the note’s pitch, duration and often the timbre; the instrument converts the player’s partly digital, partly analogue parallel signal into a complicated vibration, or equivalently a set of simple (usually harmonic) vibrations in a mechanical oscillator (string or air column). these vibrations, often via an impedance transformer (bridge and body of string instruments, bells of brass instruments) cause a pressure wave that is a single analogue signal: p(t). the ear receives a wave p’(t) and, via impedance transformers (the outer and middle ear) this causes a complicated vibration, or equivalently a set of simple, often harmonic, vibrations in a mechanical oscillator (the basilar membrane). these vibrations are sensed and processed, and we perceive the note’s timing, pitch, duration and timbre. the perception of notes is subject to categorisation (i.e. digitisation): when fine differences in pitch are presented, listeners, especially those with musical training, tend to sort them into the discrete notes in a scale [38]. thus the perception of pitch is partly digital and partly analogue – we perceive a note, but may remark that it was a little sharp or flat. more symmetries: the listener and the composer on time-scales larger than those discussed above, listeners are capable of perceiving structures and features in music: we may identify (whether consciously or otherwise) themes, harmonies, orchestration etc. this article gives no more than some pointers to research in this area. sloboda [3] compares the analysis of linguistic structure by chomsky with the analysis of musical structure by schenker, which uses hierarchies of note groupings and their functions. some seem general, while others are specific to certain cultures. one way of studying this level of structure is by proposing plausible models and comparing their performance with that of human subjects [39-41]. these processes complete the communication symmetry. to the extent that the listener hears melodic patterns, repeats and transformations of thematic material, s/he reverses the process of composition and may leave the concert hall humming the themes or ideas that began the whole process. the information transmitted between the minds of composer and listener may differ in detail, but the coding is physiologically similar in the two minds, in that it involves many parallel digital signals in neurones. between the two, however, the information passes through a coding totally foreign to the operation of the brain – a data-rich, serial, analogue signal. the interpreters for this foreign signal are the musical instrument in one direction and the ear in the other, whose symmetry is discussed above. the performing musicians direct and supervise translation at one end. the listener has an 88 joe wolfe interpretive role that may be the reverse of those of player and composer, depending on training and attitude. a discussion of this is beyond our current aim. musical communication to a communications engineer, music might seem inef f icient and unreliable. dif ferent listeners may extract different messages from the same signal. listeners may differ with the composer over the question “what is it about?” this does not mean, of course, that it is without meaning or value: the signal is rich in information often input by different people (composer, performers, conductor) so it is not surprising that different people extract different subsets of that information, or interpret it differently. to quote aaron copland: “‘is there a meaning to music?’ my answer to that would be, ‘yes’. and ‘can you state in so many words what the meaning is?’ my answer to that would be, ‘no’.” [42]. researchers are however quantifying aspects of the meaning. schubert [43], for instance, measures emotional responses to music in a two-parameter space and finds reasonably consistent responses, with a resolution of a few bits in each direction and a time resolution of seconds. this gives a baud rate not far below that of text being read. in the context of musical enjoyment, the processes of encoding and decoding may be at least as important as any part of the communication. but why do we so enjoy this encoding and decoding? why have we evolved the capacity for this sophisticated, complicated but imprecise method of communication of abstract ideas? does musical ability confer survival advantages on individuals possessing it? why can such abstract communication have powerful emotional effects? these questions are invitations for speculation, but it is interesting to look at them with regard to information coding. music and speech: similarities and complementarities the physiological hardware used for listening to music and speech is the same, and some of the software may be shared too. most speech sounds involve vibration of the vocal folds. the time scale of these vibrations is shorter than that of nerve or muscle response, so any given vibration is very similar to its predecessor, so the sound produced is usually quasi-periodic. these periodic speech sounds (as well as screams, cries, and moans) have harmonic spectra. the ability to discern a set of harmonic frequency components as an entity, and to track simultaneous changes in that set, is an ability to discern one voice or cry from background sound. it is also much of the ability to follow a melody. on the other hand, the signal codings of speech and music are different. oversimplifying for the sake of the argument, we could say that they are almost complementary, especially with regard to digitisation. speech coding is digital in that it uses a discrete set of speech sounds (phonemes). in alphabetic languages, (a subset of) these are all that is recorded, as letters, in the text or transcribed form. further, they are digitised in perception (i.e. they are perceived categorically [44]). phonemes are encoded by features of the sound spectrum (formants and formant trajectories) and by transients. but in music, transients (especially the way notes start) and features of the spectrum are together what we call timbre. most of the ‘text’ of music is notes: digital representation of pitch and timing. these are also perceived digitally (categorically) in music [38]. in speech, however, these features are prosody and (except in tonal languages such as mandarin and thai) they are analog variables, which are not notated. so the texts of music and speech use the acoustical features and digitisation in almost complementary ways, as the table shows. i discuss this in greater detail elsewhere [45]. why music? the capacity to communicate using sound, whether by speech or more primitive articulations, may have been sufficiently important to select for a suitable capacity for sound analysis. this explains (at the evolutionary level) why we have the mechanisms that we use for analysing music. but why do we so use those mechanisms? why do parents sing to infants? why do we like and make music? perhaps signal processing can provide part of the answer. those who write or use automatic speech recognition software know that it is non-trivial to extract the spectral features, envelope and pitch that carry information in both speech and music, especially in the presence of background noise. in some cases, however, it may be easier in music. consider an unaccompanied melody, sung or played by a single instrument, which might be an example of music from our early pre-history. this signal has frequencies that are usually stable during a note, compared with the rapid, continuous (i.e. analogue) pitch changes in speech. rhythms in music are also more regular in music than in speech. in instrumental music and in vocalise (singing without words),  the spectral features change less, and in a more regular way, than they do speech. when we sing to babies [46], is it possible that we are using the reduction89from idea to acoustics and back again: the creation and analysis of information in music ist method to teach them how to listen, developing the skills necessary to understand speech? could music be a game for the ear? games are often described as models of social behaviour, that develop useful mental and physical skills. games develop reflexes, co-ordination and muscular strength that may confer evolutionary advantages. intellectual and socialising games develop skills that could also confer survival or mating advantages. if speech and signal processing skills enhanced our ancestors’ chances of survival or mating, the game of music may have been selected, whether it were transferred between generations by genetics or culture. the basic skills of sound analysis are subtle and beyond introspection, but that is true of many games: we are no more conscious of how we analyse sounds than we are of the muscular control we used to catch a ball. what we do with these skills is sometimes elaborate, but that is also true of games such as cricket and chess. in games and in music, our enjoyment of neurological exercise and challenges seems to require successively more complicated games as our capacities develop. speech carries the meaning of the words spoken, but it also carries information in the way in which the words are spoken. the rhythms and tempi, subtle pauses and variations in articulation and loudness, the overall register and the changing pitch – all carry information. information of this latter type gives subtle shades to the meaning conveyed by the words, and it often tells of the speaker’s emotional state. the ability to convey this information distinguishes a good actor from someone who just reads the words. music also carries expressive information in subtle variations in rhythm and phrasing [24,47], coded in a comparable way [48]. however, an important vehicle for affective information in speech is prosody. these features, completely omitted in the text of speech, are the dominant features of music, whereas the features used to encode the explicit information in speech are used, in music, for timbre and are often varied little. i end by inviting the reader to wonder, as i do, whether this may one of the reasons for the attraction and emotional power of music, this peculiarly coded, abstract method of communication. acknowledgment i thank sten ternström and emery schubert for helpful comments. references 1. kolmogorov, a.n. “three approaches to the definition of the concept “amount of information”.” (1965) problemy peredachi informatsii, 1, 3-11 (russian, cited by chaitin, ibid.) table 1. acoustical features of music and speech signals show complementary coding. (reproduced from [45]). acoustical feature music without words speech fundamental frequency (when quasi periodic) pitch component of melody pitch component of prosody categorised not categorised notated not notated precision possible variability common temporal regularities and quantisation on a longer time scale rhythmic component of melody rhythmic component of prosody categorised not categorised notated not notated precision possible variability common short silences articulation parts of plosive phonemes sometimes notated implicitly notated steady formants components of instrumental timbre components of sustained phonemes not notated notated not categorised per se categorised varying formants not widely used components of plosive phonemes — categorised notated transient spectral details components of timbre components of consonants not categorised categorised sometimes notated notated 90 joe wolfe 2. chaitin, g.j. “information, randomness and incompleteness”. 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(norton, new york, 1980). 21. stravinsky, i. “the rite of spring” (1921). the example cited is from rehearsal mark 11. boosey & hawkes, london (1967). 22. köhler, j.f. “historia scholarum lipsiensium” (1776), quoted by david, h.t. and mendel, a. “the bach reader”, (norton, ny, 1972) 23. repp, b.h. “a constraint on the expressive timing of a melodic gesture: evidence from performance and aesthetic judgment”, music perception, 10, 22-242 (1992). 24. sundberg, j. fribert, a. and fryden, l. “threshold and preference quantities of rules for music performance”, music perception, 9, 71-92 (1991). 25. juslin, p.n; friberg, a., bresin, r. “toward a computational model of expression in music performance: the germ model.” musicae scientiae. spec issue, 2001-2002, 63-122 (2002). 26. fearn, r., carter, p. and wolfe, j. “the perception of pitch by users of cochlear implants: possible significance for rate and place theories of pitch” acoustics australia, 27, 41-43 (1999). 27. barlow, h.b. in “physics and mathematics of the nervous system” (conrad, m, güttinger, w. and dal cin, m., eds) (springer-verlag, berlin, 1974). 28. møller, a.r. “auditory physiology”. (academic, ny, 1983). 29. fletcher, n.h. “the physical bases of perception”, interdisciplinary sci. rev., 9, 6-13 (1984) 30. kandel, e.r. and schwartz, j.h. principles of neural science, (elsevier, 1985). 31. altschuler, r.a., bobbin, r.p., clopton, b.m. and hoffman, d.w. “neurobiology of hearing: the central auditory system”. (raven, ny, 1991). 32. yates, g.k. “the ear as an acoustical transducer”, acoustics australia, 21, 77-81 (1993). 33. spangler, k.m. and warr, w.b. “the descending auditory system” in “neurobiology of hearing” r.a. altschuler et al, eds, pp 27-45, (raven, ny, 1991). 34. berger, k.w. some factors in the recognition of timbre, j. acoust. soc. am. 36, 1888 (1963). 35. warren, r.m., gardner, d.a., brubaker, b.s. and bashford, j.a. “melodic and nonmelodic sequences of tones: effects of duration on perception”, music perception, 8, 277-290 (1991). 36. warren, r.m. “la perception des séquences acoustiques: intégration globale ou résolution tempo91from idea to acoustics and back again: the creation and analysis of information in music relle?” in “penser les sons. psychologie cognitive de l’audition” mcadams, s. and bigand e., eds., presses universitaires de france (1994). 37. shepard, g.m. “neurobiology”, (oxford uni. press, 1988). 38. locke, s. and kellar, l. “categorical perception in a non-linguistic mode” cortex, 9, 355-369 (1973). 39. lischka, c. “understanding music cognition: a connectionist view” in “representations of musical signals”, de poli, piccialii and roads, eds., (mit, cambridge mass, 1991). 40. longuet-higgins, h.c. “artificial intelligence and musical cognition”, phil. trans. r. soc. lond. a 349, 103-113 (1994). 41. longuet-higgins, h.c. and lisle, e.r. “modelling musical cognition”, contemporary music review, 3, 15-27 (1989). 42. copland, a., “what to listen for in music”. (new american library, ny, 1967). 43. schubert, e. “continuous measurement of self-report emotional response to music” in “music and emotion: theory and research. series in affective science.” juslin, p.n. (ed); sloboda, j.a. (ed), eds. pp 393-414. (oxford university press, london, 2000). 44. clark, j. and yallop, c. “an introduction to phonetics and phonology” (blackwell, oxford, 1990). 45. wolfe, j. “speech and music, acoustics and coding, and what music might be ‘for’”. international conference on music perception and cognition, sydney, 2002, k stevens, d. burnham, g. mcpherson, e. schubert, j. renwick, eds. pp 10-13 (2002). www. phys.unsw.edu.au/~jw/icmpc.pdf 46. gérard, c and auxiette, c. “the processing of musical prosody by musical and nonmusical children” music perception, 10, 93-126 (1992). 47. mersenne, m. “harmonie universelle, contenant la théorie et la pratique de la musique” (1636). (facsimile edition, cnrs, paris, 1975). 48. banse, r. and scherer, k.r. “acoustic profiles in vocal emotion and expression” j. personality and social psychology, 70, 614-636 (1996). substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi substantia. an international journal of the history of chemistry 2(1): 103-119, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-44 citation: f.m. rubino (2018) the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry?. substantia 2(1): 103-119. doi: 10.13128/ substantia-44 copyright: © 2018 f.m. rubino. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino università degli studi di milano, department of health sciences, ospedale san paolo, v. a. di rudinì 8, i-20142 milano (italy). e-mail: federico.rubino@unimi.it abstract. accomplishments of hellenistic science and technology in some fields, such as mathematics, physical cosmology and engineering, has recently been re-evaluated and can be considered as of the same level that the scientific revolution in western europe reached at the beginning of the xvii century ce. information on the level of chemical science is scanty; however, independent ancient sources such as the jewish talmud can yield significant clues. the still existing dietary laws include a practice to assess the acceptability of food mixtures with two complementary assessment techniques. one enforces a specific minimum mixing ratio (1:60) of unacceptable-toacceptable ingredients, the other uses a sensory assessment to exclude the presence of a tasty unacceptable ingredient. this practice is likely the first historical example of quantitative analytical chemistry. this article collects clues that this approach is rooted in the implicit acceptance by hellenistic chemical science of an atomic paradigm and on the awareness that interaction of different matter yields product that are different from the starting ones. quantitative assessment of the presence of unacceptable ingredients by sensorial assessment or by mixing ratio likely points to a forgotten practice of hellenistic experimental pharmacology and physiology to test the efficacy of drugs and poisons, that was performed in animals, with the use of a control group, and on human subjects. keywords. dilution, food contamination, halacha, hellenism, jews, kasherut, mixture, talmud. 1. much earlier analytical chemistry than anticipated? humankind practiced empirical chemistry since the farthest of times to produce food, materials and market goods,1 and documental sources report a good deal of recipes since ancient near eastern civilizations.2 studies of paleo-chemistry and ancient chemistry however suffer from several sources of difficulty. one is the fragmentation and obscurity of documental sources, and the inherent limitation in reconstructing technological achievements of 104 federico maria rubino different cultures over time. however, when the contemporary researcher re-considers and follows in detail ancient recipes, such as those reported in early modern “alchemical” documents, the obtained results closely approach the descriptions given by the original authors, as has been recently documented.3-7 paleo-chemistry (and contemporary chemistry) was more often concerned with manufacturing goods, such as metals and alloys, dyes, medicinal drugs and poisons,1 rather than with the intellectual effort to understand the properties of matter. miners often performed assays for metals in ores and alloys, and the composition of ancient pharmaceutical preparations manufactured from mixtures of individual ingredients (each of which needed to be authenticated, especially when it came from remote locations) is often reported in quantitative terms [8]. however, very little is known on the assays, if any, that were employed to identify raw materials and to check their adequacy to specific purposes, such as the integrity of metals, the composition of alloys, of food, drugs, dyes and perfume, an activity that tantamount to analytical chemistry. among the few reported “analytical” methods is the assay of metal ores by cupellation. this technique allows to concentrate precious metals, such as gold and silver, from ores by a solid-liquid extraction into low-melting lead, followed by recovering the precious metal(s) from the latter, more easily oxidized metal, by ashing the metal button in air.9 the described “analytical” method thus essentially corresponds to a small-scale preparation, and weighting in a scale is the final method of measurement.10 seldom are a very small number of material documents, such as the residues of old-time equipment, vessels, raw materials and preparations found in archeological studies and only very recently some could be compositionally characterized.11-13 the only clue that in the antiquity an assay was used to detect a specific component in a mixture is the detection of iron in biological fluids with the use of the extract of oak gall.14,15 the lack of information on other chemical analyses is not surprising, since also the contemporary discipline of analytical chemistry achieved a distinctive status within chemical sciences much later than the traditional branches of mineral (inorganic) and organic chemistry, and of materia medica, the forerunner of pharmacology, toxicology and medicinal chemistry. methods for chemical analysis of minerals, i.e., to distinguish the different simple constituents and to identify new chemical elements were published as early as the early xvii century, even in the lack of a consistent theory on the composition of matter and of an operative definition of what a “simple” chemical body, i.e., a chemical element is. it is only in 1861 that the renowned independent analyst carl remigius fresenius founded the first scientific journal specifically dedicated to analytical chemistry as an independent discipline.16 only in the 1940s the most authoritative of contemporary scholarly journals of analytical chemistry, the analytical chemistry of the american chemical society, gained an independent status, formerly being since 1929 a supplementary issue of the society’s magazine of industrial chemistry.17 2. a reappraisal of hellenism: the boom and the doom. hellenism is the period of mediterranean history that stands between alexander the great’s death in 323 bce and the battle of actium in 31 bce that ended the ptolomean rule of egypt. historians have long considered this as a ripe age with little real intellectual achievement, when compared, on arbitrary terms, with the previous classical period of greek history that established as paradigm of western european culture. among prejudices on this period is that according which abundance of human slave workforce caused a limited interest in mechanization of work, and the consequent lack of a developed production economy. the old mediterranean and greek-romans thus failed to understand and exploit the natural world. the missed opportunity to develop the budding knowledge into a “modern” framework also led to the withdrawal of some intellectual achievements of early hellenism that actually foreran those of the early modern age. in particular, this is exemplified by the fact that ptolemaic model of geocentric universe overcame the aristarchus’ heliocentric one, galenic medicine mostly cancelled herasistratus’ physiology, and archimedean mechanics only found limited exploitation in devices, such as those later described by heron.18 on the contrary, a very recent re-interpretation of the surviving hellenistic and later texts and of material artefacts indicates that the intellectual development, scientific and technological advancement at the peak of that period was at the same level that modern western europe only reached in late renaissance and early modern age. one main scholar to initiate this innovative interpretation, lucio russo, reconstructed some parts of the “lost knowledge”, mainly in the fields of geographical physics, cosmology and astronomic navigation.18-20 a real intellectual boom occurred between the iii and ii centuries bce with the establishment in the recently founded alexandria of the museum and library by tolomy ii eupator.21 other hellenistic kingdoms followed, such as the attalids in pergamon (to tackle an 105talmud and “fossil” analytical chemistry ante-litteram embargo to the export of papyrus as the substrate for writing, the use of parchment was locally boosted), the seleucids in syria and babylon, and elsewhere in the koiné, for which information is much more limited. the abrupt geo-political doom of the hellenistic civilization occurred in the mid-ii century bce, with the almost contemporary destruction of corinth and of cartago in 146 bce. just a few years later, the anti-greek alexandria pogrom sponsored by ptolemy iii euergetes in 137 bce caused the migration of the luckiest scholars to safer remote places. the wholesome destruction of the main intellectual centers of the time determined a break in the transmission of knowledge, surviving scholars relocating to safer areas in the eastern mediterranean, in syria and further eastwards to bactria and maurya india. scholars in the quieter i century ce and later strove to revive the mostly interrupted intellectual activity, but were no more able to recover the loss, and most scientific advancements in applied mathematics, astronomy, geography and navigation, in natural sciences and medicine faded into oblivion, due to the inability to reconstruct the underlying methodological and theoretical framework.22 ancient knowledge in “empirical sciences”, such as in medicine and chemistry, cannot be as easily reconstructed, due to the loss of most original sources, and to the corruption of residual information that could not be understood any more in post-doom times.22 in the field of chemistry, greek and hellenistic scholars had conceived a rationally based precursor of the current atomicmolecular model of the composition of matter as early as the v century bce, building on the first intuitions of democritus, and progressively developed by aristotle, the epicurean school, crisippus and the stoic school.22 after the doom, the tenets on which the budding theory of matter composition had been developed were abandoned, purportedly for their sheer materialistic content. as in other disciplines, such as the drift of hellenistic physical astronomy into astrology, the remnants of that knowledge merged with other philosophical and religious traditions, and evolved into alchemy.23,24 likely, the practical contents that dealt with manufacturing hightech materials, such as imitation gems and gold-looking alloys, dyes, pigments, perfumes, pharmaceutical drugs and poisons, faded into the practical recipes which artisans transmitted through oral tradition, in a social environment that now was well detached from the shrinking population of educated scholars. however, it is conceivable that some “fossil” knowledge of the hellenistic boom, and especially its quantitative applications, was already embedded as common discourse in sources that have been so far untapped, and that their exploration can yield new insight on their knowledge in the other fields. 3. “fossil” information from an old mediterranean people. one possible, and so far little examined, source of information is the talmud, a written compilation of discussions in the application of hebrew religious law (halacha) to everyday affairs that was elaborated in roman palestine (talmud jerushalmi) and in parthian babylonia (talmud bavli)25 from the iii to the vi century ce. halacha developed from the normative books of the “written torah” (torah she-bi-khtav, the pentateuch of the old testament) and on the “oral torah” (torah sheba’al peh), the sources of which were rooted at least four centuries earlier.26,27 the exploration of talmud unveils earlier knowledge science and technology, encompassing – in contemporary terms – animal and human anatomy and physiology, chemical technologies,28,29,30 statistics31,32 (including the earliest-known description of random sampling: chullin 4a), risk prevention and management. one peculiar aspect of halacha is the enforcement of several alimentary taboos, some of which – such as abstinence from pig – are so well known as to become symbolic and even a synecdoche of the jewish identity to the other peoples. the main primary sources of information for the jewish dietary rules are the torah (in particular, deut. 14:1-26 contains the well-known compilation of allowed and forbidden animals for food), the talmud and a much later compilation, the xvi century ce shulchan aruch.33 that summarized halachic rules as enforced by sephardi jewry in the mediterranean area. several treatises of the talmud report the very complicated rules on inacceptable (issur) and acceptable (heter) food and on mixtures, such as in chullin (most loci that are especially pertinent to this essay are between 82a and 98b; v. infra), and related information occurs in treatises that discuss other sources of material impurity. the topic is of a great importance to practicing jews down to present times.34 among the lesser-known food regulations are discarding the sciatic nerve (gid hanasheh) from the thigh of ritually slaughtered animals, completely removing fat from the slaughtered carcass, and completely draining meat from blood, the ban to mixing meat and milk in food (basar be chalav). in particular, the torah states thrice the basar be chalav prohibition (es. xxiii, 19 and xxxiv, 26; deut. xiv, 21), that was unknown before 106 federico maria rubino moses’ covenant was established (in the book of exodus), since abraham offers to the three visitors meat cooked in sour milk (gen. xviii, 7-8). es. xxiii, 19. “bring the best of the firstfruits of your soil to the house of the lord your god. “do not cook a young goat in its mother’s milk. es. xxxiv, 26. “bring the best of the firstfruits of your soil to the house of the lord your god. “do not cook a young goat in its mother’s milk.” deut. xiv, 21. 21 do not eat anything you find already dead. […] do not cook a young goat in its mother’s milk. gen. xviii, 7-8. 7 then he ran to the herd and selected a choice, tender calf and gave it to a servant, who hurried to prepare it. 8 he then brought some curds and milk and the calf that had been prepared, and set these before them. the gid hanasheh prohibition comes earlier in the torah, since it links to jacob-israel’s fight with the angel, who left him lame for life (gen. xxxii, 22-31). gen. xxxii, 22-31. . […] 25 when the man saw that he could not overpower him, he touched the socket of jacob’s hip so that his hip was wrenched as he wrestled with the man. […] and he was limping because of his hip. […] the basar be chalav prohibition had no apparent explanation since the most ancient times of jewish culture, and therefore the religious authorities expanded its application in order not to infringe the ban.35 in general, to avoid cross-contamination of mutually incompatible food ingredients, separate sets of pots are used, and ritual cleaning with water or on fire is performed.34 these food-mixing bans, however, admit an exception to thrashing the forbidden food mixture, in the case mixing of forbidden ingredients occurred by accident. in this case, to test whether the mixture is still admissible as food, two complementary routes are available. one states that if the contaminating ingredient is present in a proportion that is less than one-sixtieth of the main one (bitul b’shishim: one part in sixty), the food is still kosher (ritually acceptable). another possibility is that if the contaminant does not impart to the mixture its distinctive properties of taste (ta’am k’ ikar: the taste is equivalent to the substance), the food is still acceptable.34 both approaches are so familiar to a present-day regulatory chemist or toxicologist, as to remind other similarly “modern” hellenistic accomplishments that are considered as “anticipating” contemporary views in mathematics, in astronomy, in mechanics, in natural sciences. the bitul b’shishim “one part in sixty” approach closely resembles the contemporary practice of toxicological risk assessment, whereby the presence of a contaminant is compared to an enforced lower limit, and decision upon acceptability is taken consequently. the ta’am k’ ikar “the taste is equivalent to the substance” approach corresponds to the use of a sensorial assay, and is similar in principle and setup to what is nowadays performed for similar applications. in particular, it is requested that an unaware, extraneous assessor (the akum, a gentile) taste the mixture for absence/ presence of the undesired ingredient (in modern terms, a blind test). the use of a biological response as endpoint foreruns the now abandoned approach to limit setting for airborne industrial solvents that was in use in the former soviet union, based on the measurement of evoked electrophysiological potentials triggered by body exposure to exogenous substances.36 the criterion whereby acceptability comes when the unacceptable component is no longer perceived is again a forerunner of the alara (as low as reasonably achievable) principle that is adopted in radio-protection and in the management of environmental and occupational risk from carcinogenic chemicals.37 nihil sub sole novi (qohelet, 1,9). the jewish normative texts (several loci in chullin, e.g. especially between 89b and 120a; shulchan aruch’s yoreh de’ah, several loci; see appendix) describe in much detail the transmission of the off-flavor of unacceptable substances from a contained liquid or solid-inliquid to the container, or from an unexpected and not allowed contaminant to the bulk of food. both ancient texts correctly identify as the determinants of the process: temperature, contact time, the nature of the liquid, that of the material and the surface-to-bulk ratio of the immersed solid and the material of the container, and enforce consequently the halachic rules. those reported below are just a few examples that describe both assessment strategies. ch. 89b chap. vii: […] if a thigh was cooked together with the sciatic nerve it is forbidden if it imparts a taste [into the thigh]! (note 11: i.e., if the thigh that was cooked was not sixty times greater than the forbidden nerve; for the rabbis have estimated that if there were more than sixty parts of permitted matter as against one part prohibited, the latter cannot impart a flavor unto the former.) […] ch. 96b chap. vii: mishnah. if a thigh was cooked together with the sciatic nerve and there was so much [of the nerve] as to impart a flavour [to the thigh], it is forbidden. how does one measure this? as if it were meat [cooked] with turnips (note 7: it is estimated by the rabbis that meat cannot impart its taste to any substance that is cooked with it if the latter is sixty times as large in bulk as the meat.). 107talmud and “fossil” analytical chemistry ch. 97a,b: […] the rabbis ruled that one may rely upon a [gentile] cook, and yet [in other cases] the rabbis ruled that the test is sixty [to one]. therefore we say, where substances of different kinds, each kind being permitted by itself, were mixed together, the test is whether or not one imparts a flavor to the other; 1 and if one of the substances was forbidden 2 then we rely upon the opinion of a gentile cook. […] ch. 97b: […] r. nahman said: the [sciatic] nerve [is neutralized] in sixty-fold, but the nerve itself is not to be included to make up this number. (note 14: i.e., there must be sixty times the volume of the forbidden nerve.) the udder is neutralized in sixtyfold, but the udder itself is to be included. (note 15: if an udder which was not emptied of its milk was cooked together with meat, the entire contents of the pot would be forbidden unless there was in the pot sixty times as much as the milk of the udder. (the quantity of milk in the udder is regarded as equal to the volume of the udder). now the udder can also be included to make up this sixty-fold since it is not the udder that is forbidden but only the milk contained in it. in other words, there must be in the pot fifty-nine times the quantity of the udder; v. infra 109a.) an egg (note 16: of an unclean bird which was boiled with eggs of clean birds.) is neutralized in sixty-fold, but the egg itself is not to be included. ………….. it is apparent from the reported excerpts that both assessment practices: bitul b’shishim (one part in sixty), and ta’am k’ikar (the taste is equivalent to the substance) correspond to the likely earliest example of a quantitative analytical chemical assay. it is worth considering that no information on a corresponding quantitative approach is anywhere found in survived texts of greek, hellenistic and greco-roman technology. the particular dilution factor most commonly considered as upper limit for halachic acceptance, 1/60 (approx. 1.6%, or 98.4% pure), matches that which is also nowadays a useful threshold for the presence in a “technical grade” product of undesired contaminants or offproducts, which are devoid of particular concern such as toxicological or microbiological health risk. this level is also close to the minimum detectable amount of some tests designed for the detection of adulterants in food, such as the late xix-century villavecchia-fabris test that discriminates edible from industrial vegetable oils purposely adulterated with 5% sesame oil.38 it may thus be of an interest to understand whether this approach to quantitative chemical analysis might come into the talmud deriving from hellenistic chemical conceptions, to fulfill a specific halachic task. in a complementary way, this notion, which is contained in an early-ce text and the roots of which may well extend several centuries before, may be a clue to reverse-understand the nature and level of hellenistic concepts on the composition of matter and on the relationship with other fields of natural science. as such, this interpretation suffers from lack of sufficient internal evidence, and may generate a circular argument. however, even if the practice of “alternative history” may quickly lead to fictionalized accounts, nevertheless by adopting some rules to control the construction of scenarios the voids in documentation can be credibly filled to re-create plausible descriptions of past events.39 4. alexandria, antiochia and pergamon: mediterranean bridges between hellenism and judaism? a significant cultural interaction of greeks and jews developed starting in the iv century bce, encompassed the early and late hellenism, the roman suzerainty and final conquer of palestine, the diaspora and continued after the fall of the roman eastern and byzantine empire to the parthians and the sassanids.40,41 briefly, and to the aim of this reconstruction, it is conceivable that some elements of hellenistic knowledge in natural science and medicine outpoured into hebrew halakhic discourse that developed in the “oral phase”, even before the discussions started to be registered in writing as the mishnah and gemara, at the beginning of the iii century ce. the talmud and its earlier judaic sources in fact contain several items that have long been recognized as of a likely hellenistic origin.42 some talmudic knowledge may thus represent one of the few remnants of lost hellenistic science and technology that developed and was commonplace before the doom in ptolemaic egypt, in seleucid and hasmonean palestine, and in the hellenistic kingdoms of anatolia, mainly those of pergamon and of bythinia, and did not survive in the transmitted body of text of the greco-roman world. as for the plausibility of this scenario, it is widely accepted now that, in several fields, jews who were in contact with the greek and hellenistic environment reinterpreted greek and hellenistic knowledge, or just the cultural suggestions that their neighbors spread.43 there were one thousand young men in my father’s house, five hundred of whom studied the law, while the other five hundred studied greek wisdom. to further appreciate the possible degree of interaction of palestinian jews who had a role in setting the halacha with the contemporary hellenistic culture, we may recall a famed talmud episode (shabbat, 31a). as known, the rigorous talmud master shammai […] repulsed him (the curious gentile who sought for instant 108 federico maria rubino information on the intricacies of the jewish faith) with the builder’s cubit, which was in his hand […]. shammai was a wealthy architect in i century ce palestine, the cubit was in fact a measuring ruler, a rather sophisticated professional device akin to those in use by technicians and calculators as far as the 1980s, and his professional training very likely included elements of knowledge that was of hellenistic derivation. a clue that greek and hellenistic philosophy was at least known to educated, if observant jews of the early talmudic era is the use of the term “apikoros” to grossly indicate a secular thinker who negates most or all the tenets of judaism, or of any revealed religion for the good. this word first occurs in rabbinic literature in the mishnah (sanh. 10:1),44 and derives from the iv century bce greek philosopher epicurus, who advocated a materialistic explanation of the world and the pursuit of a quiet happiness through vegetarianism and abstention from greed and violence.45 q. horatius flaccus, epist., i, 4, 10. […] me pinguem et nitidum bene curata cute vises, / cum ridere voles, epicuri de grege porcum. (if you ask of myself, you will find me, whenever you want something to laugh at, in good case, fat and sleek, a true hog of epicurus’ herd) d. alighieri, commedia, inf. x 13-15. suo cimitero da questa parte hanno / con epicuro tutti suoi seguaci, / che l’anima col corpo morta fanno. (in this place epicurus and all his followers are entombed, who say the soul dies with the body.) epicurus is the only greek philosopher who is explicitly mentioned in the talmud, while there is no mention of the competing stoic school. sanh. 10:1. […] but the following have no portion in the world to come: he who says that resurrection is not a torah doctrine, the torah is not from heaven, and an apikoros [who denigrates torah and torah scholars] . rabbi akiva adds: one who reads from heretical book […] http://www.emishnah.com/pdfs/sanhedrin%2010.pdf during t he hellenistic period, t here was an increased opportunity for jews to spread, especially in anatolia, where attalus iii and mithridates vi favored the transferred of a large body of jewish settlers.46 it is conceivable that some immigrants belonged to socially educated strata47 and may transmit knowledge and suggestions to the still vital jerusalem center, possibly in the occasion of pilgrimages to the temple.40 given the advancement of agricultural, pharmacological and toxicological studies of natural substances in the anatolian hellenistic kingdoms, in seleucid babylon and in ptolemaic egypt,48,49,50,51,52,53 it is conceivable that such information may reach palestine through multiple routes. 5. at the core of the issue: from drug titration to issur estimation … and backwards. that the late egyptian pharaoh’s court was likely interested in experimentation at large is witnessed by the greek historian herodotus (?485-425 bce). as reported (historiai, part 1, book 2, paragraph 2) psammetichus i (664-610 bce) had a baby raised without hearing any spoken language, in the earliest recorded psychological experiment, to determine whether human beings have an innate capacity for speech, and if so, which particular language is innate. medical studies flourished in hellenistic alexandria and in other cities, and eventually developed into “research-oriented” anatomical and physiological studies.54 reportedly, herasistratus was the first able to differentiate motor from sensor nerves by experiments that would not be possible to perform in animals or in dead human bodies, but only in living humans.55,56 the argument of their cruelty was used by early christian polemists, such as tertullian, against paganism;57 however, the querelle over whether herasistratus really performed such experiments continues.58 a little exploited information to support the likeliness of the information comes from the talmud treatise on womanly issues (niddah, 30b), which reports that cleopatra vii of egypt performed systematic experiments on human fertilization, likely including the use of contraceptive drugs, forced timed intercourse mating and surgical abortion. niddah 30b. […] a story is told of cleopatra the queen of alexandria that when her handmaids were sentenced to death by royal decree they were subjected to a test (note 23: fertilization and subsequent operation) and it was found that both [a male and a female embryo] were fully fashioned on the forty-first day. […] they were made to drink (note 31: before they were experimented on), a scattering drug (note 32: i.e., destroying the semen in the womb) […]. a story is told of cleopatra the grecian queen, that when her handmaids were sentenced to death under a government order they were subjected to a test and it was found that a male embryo was fully fashioned on the forty-first day and a female embryo on the eightyfirst day. as for the availability of the needed experimental tools, detailed knowledge of human fertility is well documented in pharaohs’ egypt. the berlin papyrus of 1.350 bce witnesses the knowledge and application of tests to assess pregnancy, based on the stimulating effect of pregnancy hormones excreted in urine on the germination of corn and barley seeds,59,60 and a later 109talmud and “fossil” analytical chemistry one (papyrus kahun61,62) uses swamp canes to the same purpose. there is clue that those ancient claims are even supported by empirical evidence.63,64 due to the use of deliberate poisoning as a weapon in political struggle in the hellenistic period (and later), efficacy studies on drugs and poisons were much developed, especially in the kingdoms of bithynia (by mithridates iv) and pergamon (by attalus iii).48-54 the high level of knowledge on toxic poisons and their antidotes calls for the use of systematic experiments, reportedly performed even on humans, such as slaves and convicted criminals, as witnessed by several nearly contemporary testimonies, especially regarding the former character.39 it is conceivable that an assessment of the desired level of activity of concoctions (deadly toxic, or sub-toxic, “mithridatic”) should be performed, if the preparations were to be reliably used to their intended purpose. the ii century ce pseudo-galen text theriaca ad pisonem contains an important testimony to this practice, whereby the efficacy of a preparation against venomous animals is tested on animals, with use of a control group, but there is no clear indication that specific doses of the pharmakon were administered. 10r […] we being unable to test it on men do the same on certain other living beings and try to arrive at a true verdict on the drug. so we take cocks – not those that live with us under the same roof, but rather wild ones, and with a rather dry constitution, and we put poisonous beasts among them, and those who have not drunk theriac die immediately, but those who have drunk it are strong and stay alive after being bitten. […] (theriaca ad pisonem, ch. 1;10)8 it is here that the knowledge embedded in the talmud’s bitul b’shishin likely comes forward as a neutral witness. it is conceivable that activity titration of pharmaka was possibly performed by testing the effects of progressive (“scalar”) dilutions according to definite proportions,65,66 an approach that would eventually re-surface in the xiii-xiv century ce, when the montpellier medical school re-discovered the same principle from the alkindi treatise quia primos.67 the measurement systems in the ancient world are difficult to reconstruct, since there were differences among regions and over time. as witnessed also in the talmud, several different scales were simultaneously in use, in particular the sexagesimal, decimal and binary ones. the binary, harmonic or pythagorean scale (1/2n, i.e. denominators in the sequence 1:2:4:8:16:32:64, and so on; figure 1) is used still today for the same purpose. dilutions with this scale are very easy to prepare and ensure a tight control over the concentration of the proband substance, since variation occurs by halving the preceding dilution. moreover, such relative scale allows comparing the strength of different preparations, even when the actual quantity of the active material in a complex mixture is unknown and consistent units of measure may not be available. in fact, this is the case of natural extracts, and until the very recent advent of physico-chemical techniques for separation, identification and quantification of complex mixtures, this was the way to titrate biological drugs such as insulin.68 the actual correspondence to contemporary standards of the talmudic units of measure and their mutual conversion is a matter of current controversy, since it occurs not only the realm of antiquary sciences and archeology, but also has a value for the enforcement of halacha. not only the names and size of units changed over time and varied between different places, but also the scales used to build multiples were heterogeneous and often ill defined. the talmud reports different and partially overlapping measures of volume for liquids and for dry (grain).69 the kav (around 1,22 l; used for both dry and liquid) is the basic unit from which others are derived. the log (around 0.306 l; lev. 14:10) figure 1. scalar dilution of a concentrate (red) active substance in a solvent (white). seven progressive dilutions are shown, starting from the mother liquor and ending with the sixth (1/64). the panel above shows the exponential decrease of the concentration form the arbitrary level of “one unit” to that corresponding to the sixth dilution. the fading of color of a solution subject to the progressive 1:2 dilution is exemplified in the panel below. 110 federico maria rubino corresponds to the babylonian mina and the talmud mentions half-logs and quarter-logs, as well as eighths, sixteenths, and sixty-fourths of a log (a kortov). liquid measures include a hin (around 3.67 l), ½ hin, 1 ∕3 hin, ¼ hin.70 as for the dilution factor of one to sixty that is reported in the talmud (only a slight difference, in real terms, from 1/64), it may be recalled that the number 60 is the base of the babylonian sexagesimal system, the one that is still tenaciously in use to divide time and to measure angles. the babylonian maris has multiples by the factors of 12, 24, 60, 72 (60 + 12), 120, 720, and a sub-multiple, the shekel, as 1/60 of a mina. the number 60 has prime factors 22 * 3 *5 and 12 integer divisors; it is also the product of the numbers of the fundamental pythagorean triplet (i.e., 3 * 4 * 5 = 60, and 32 + 42 = 52). a 3:4:5 pythagorean triangle has a perimeter of (3+4+5=12) units, and the sides differ from one another by one unit (5-4 = 4-3 = 1). early babylonian calculators knew the arithmetic properties that make this device among the most useful for field measurement. it is held that pythagoras only reported and possibly demonstrated as a theorem what amounted to a long known empirical practice that had found wide application in land allotment and building (figure 2).71 given the possibility of hellenistic technology to build finely machined devices, such as the antikythera astronomical clock,72 it is as well conceivable that a pythagorean triplet might be used as reference to manufacture or carve a matching pair of containers, the larger of which exactly contains 60 times as much as the smaller one, as illustrated in figure 3. what may be conceived from the specific value of “sixty” for the denominator in the talmudic criteria of bitul b’shishim is that, in the early ptolemaic times, some alexandrian experimental physicians performed pharmacological activity tests of medicinal preparations through scalar dilution in the geometrical proportion.65 some of herophilus’ disciples and followers, such as mantias and apollonius mys, were reportedly pharmacologists,54 and galen recognized the former as being the father of the “compound drug” tradition, while the latter is the main source of galen’s on the composition of drugs according to places (xii kuhn). dioskorides phakas, allegedly a relative of cleopatra vii philopator, is credited as the first to use a color test to detect iron in biological fluids.15 at some time, poskim (jewish assessors) who were acquainted with this method started to apply it to the assessment of food according to halacha. they came to determine that an eight-fold scalar dilution (1/26 = 1/64, or » 1,6%) was sufficient to lose the taste of some tasty, yet unacceptable ingredient, such as chalav (milk) in basar (meat) and vice-versa, and gid hanasheh (sciatic nerve in halachically slaughtered calves; see above). figure 2. a chessboard that shows the empyrical derivation of the so-called pytagora’s theorem on right triangles and the existence of the pytagoric triplet 3,4,5. figure 3. relationship of two solids (containers), the larger exactly 60 times as much as the smaller, built as a unit-side cube (the smaller, acting as the unit-volume) and as a rectangular prism with sides in the 3:4:5 ratio of the fundamental pythagorean triplet (the larger). 111talmud and “fossil” analytical chemistry the detailed intellectual basis of this method might go lost at the time of the hellenistic doom, or even later, due to the loss of the trans-generational continuity of knowledge transmission in science and technology. what possibly resisted within the halachic tradition was the recollection of the use of a sensorial assessment to test for unacceptable food mixtures (taam k’ ikur), and an approximate appreciation of a generic acceptance threshold value (bitul b’shishim). the one-to-sixty ratio was the closest when the 1:2 geometrical scalar dilution and the babylonian system of multiples of the mina were compared, and so this specific value was consolidated some time during the formation of the talmud. such consolidation might occur in palestine or in babilonia, due to the exchange of scholars since the most ancient hillel and shammai time [73], but only in the bavli there is a chullin treatise concerning food. the jewish community of alexandria did not develop an autonomous halachic tradition and referred to palestine (niddah 69b) until its dissolution following the 115-117 ce revolt under trajan. however, they shared with the palestinian masters several intellectual skills in the field of textual interpretation74 [e.g. p.66] and in mechanical technology74 [e.g. p.66]. niddah 69b: our rabbis taught: twelve questions did the alexandrians address to r. joshua b. hananiah. (note 33) three were of a scientific nature, (note 34: lit., ‘the way of the earth’, worldly affairs) three were matters of aggada, three were mere nonsense and three were matters of conduct. this explanation can be strengthened by considering that the talmud masters did not always accept as such any of the two possibilities to enforce kasherut on mixtures, and in particular highlighted the difference between mild-tasting prohibited ingredients (the basar b’chalav) and strongly tasting ones, such as spices (tavlin), some of which may be halachically prohibited34 [passim]. 6. sensorial assessment and sensorial theory: an implicit acceptance of atomism? the criteria of bitul b’shishim (one part in sixty) and of taam k’ ikar (the taste imparts identity to the substance) represent two coordinate and complementary strategies for halachic food assessment that closely resemble contemporary approaches to regulatory food toxicology. as highlighted above, the first option is more akin to “assessment by modelling” in that estimation and calculation is employed to decide the heter vs. issur issue. the second option necessarily resorts to “assessment by measurement” and employs a biological sensor as the measuring device of a physico-chemical phenomenon: such is, in fact, the action of tasting. that chemical analysis owes to sensorial assays its beginnings is apparent from the etymology itself of the terms employed to describe its operations. test, saggio (in italian), assay, all derive from the sensorial assessment performed through the mouth: to taste, assaggiare; the wise (il saggio) is the man who knows by personal appreciation, who has learnt to distinguish the taste of salt, il sapore di sale, from that of other substances. the very possibility to use taste as an assessment technique, as in the case of food halacha by taam k’ikar is not only rooted in human common sense, but is implicitly founded on a sensorial theory, and in turn on an underlying theory of matter. it is here that halacha shows its likely derivation from previous (i.e., old mediterranean) methods of assessment of the strength of preparations with sensorial or biological activity, such as of tasty spices or pharmacologically active preparations. information in the talmud may thus shed light on the prevailing theory of matter in hellenistic time, and possibly on its evolution or transformation over time, down to the late middle age. it is generally accepted that non-atomistic theories developed by aristotle and his successor theophrastus, were largely prevalent, while democritean atomism did not develop beyond the imaginative level depicted in the epicurus-lucretius tradition. the aristotelian fourelement, four-quality theory was fully exploited in several branches of knowledge, in particular as the foundation of the four-humor physiological model that was the mainstay of the galenic medical thought for the best of the following fifteen centuries.75,76 in turn, its application to materia medica classified remedies, such as spices and herbal medicines, according to their purported qualities (hot-cold, humid-dry) and attempted to assign to each herb the nature of the qualities and a semi-quantitative appreciation of the respective strength, as “grades” in a cardinal scale.4 the overall aristotle-theophrastus sensorial theory (de sensu; de sensibus)77,78,79 classifies the five senses into three groups. the first group of senses includes sight and hearing, and, in both cases, no physical contact occurs between the sensing organ and the object from which the stimulus originates. the second group includes touch, for which the interaction of the receptor with the stimulus is of direct physical contact. the third group includes smell and taste, the nature of which is somewhat ambiguous, and the interpretation of which by aristotle and theophrastus is uncertain, but like112 federico maria rubino ly foreruns the contemporary, physiologically correct receptor-agonist theory and identifies the transporters of the stimuli of taste and smell as material entities that diffuse from the object to the organs of sense [80,81,82]. although aristotle and theophrastus did not adhere to atomism, nevertheless, the sensorial theory of smell and taste as such is only justified as long as the transporters of the stimulus are of a material constitution (and so are the matching receptors).83,84 furthermore, a law according to which the strength of the stimulus is directly proportional to the quantity of the transporters of the stimulus holds, and by consequence the weaker the stimulus, the weaker is the presence of the substance. it is thus conceivable that the logical bases for halachic rules such as bitul bitushin stem by a more or less direct intellectual route from familiarity with, and the acceptance of greek or hellenistic knowledge by the masters of the talmud, in a field that we may now consider at the merge of physical chemistry and physiology. several loci of the talmud where medical knowledge is instrumental to solving halachic issues show that greekhellenistic medical theory was pragmatically accepted and re-elaborated according to need.85,86,87 another strong clue that the theory of matter implicitly accepted by the masters of the talmud is corpuscular and atomistic is the strong attention that the talmud gives to the regulation of the halachic status of (food) mixtures. this includes the transport of the status of substances to vessels and through vessels to other (food) substances, caused by absorption-desorption phenomena (ta’am balua, absorbed taste). in particular, the transmission of taste is fastidiously related to parameters of time (one day, ben yomo, or more than one day, eino ben yomo), temperature (sparking hot, libbun gamur), physical condition and comminution of the interacting substances (chaticot, pieces or lach, liquid mixture) and the material of the containers (essentially pottery, metal or glass). to get rid of the prohibited ta’am, decontamination with either hot water (hagala) or with fire (libbun) is prescribed, according to the nature of the issur and of the container.34 [passim] the xvi century ce shulkan aruch treatise summarized most food-related halacha in the yoreh de’ah section (see supplementary), with reference to the original talmudic source and to the later elaboration of the main middle age commentators (according to the hebrew time scan, the geonic and rishonic period). the closest earliest similar observation to that reported in the xvi century yoreh de’ah occurs in vannoccio biringuccio’s treatise on metals (de la pirotechnia, 1540), with just the plain observation that bulk metal takes more time to dissolve than comminuted one. more strikingly, the phenomenological basis and fundamental laws of masstransfer and chemical kinetics only became apparent in the late xix century (ce!), when investigation on catalysis in organic chemistry started and the laws of absorption-desorption, enzyme kinetics and dose-response were rationalized. there is an even more sophisticated issue in the talmud that may hide a fossil notion of a hellenistic theory of matter transformation (i.e., of modern chemistry). cooking entails the (irreversible) transformation of some components of food into others with different characteristics, such as taste, smell or texture, and halachic status, as well. in particular, a regulation considers that two different (food) substances, each with its own halachic status, can combine to produce another, with an individual, specific halachic status, usually from allowed to forbidden (chaticha na’aset neveila) [34, passim]. the avodah zarah of the mishnah (2:6) and of the talmud (37b) contain a regulation, bishul yisrael, according to which jews can only eat food that is prepared by jews (or under supervision of a jew). avodah zarah 37b. […] a comparison is to be drawn with water — as only water which has undergone no change [is permitted to jews] so also must the food have undergone no change [at the hand of heathens]. […] ears of corn should also be prohibited when roasted by them […] wheat should be prohibited when milled by them […] however this law applies only to those foods that, according to the talmud, are “fit for a king’s table” (oleh al shulchan melachim) and/or are not usually consumed raw (az 38a). avodah zarah 38a. […] whatever is eaten raw does not come within [the law of what is prohibited] on account of having been cooked by heathens. […] whatever is not brought upon the table of kings to serve as a relish with bread does not come within [the law of what is prohibited] on account of having been cooked by heathens. […] it is thus conceivable that its formulation by the masters of the talmud reflects their knowledge of, and the agreement on, a theory of matter according to which forms of matter irreversibly become (transform) into a different one (davar hadash) by natural or voluntary human means.88 the same is likely to apply to the talmud commentators and halacha regulators who lived in the west european middle and early modern age, since no substantial theoretical change in the theory of matter occurred until truly atomistic theories developed in the late xvii century ce.89. thus, if this chain of reasoning could be retrieved from the ancient jewish sources, it would strengthen 113talmud and “fossil” analytical chemistry the possibility that the hellenistic theory of matter already distinguished physical mixtures (myxis) from the product(s) of chemical reactions (krasis) that occur between mixture components.20 [pp. 157-167] such processes were already common in the antiquity and led to new materials that do not exist in nature (such as soft glass), to dying products (the reversible air-induced reduction-oxidation reaction of indigo and of purple mussel extracts that originates the two famous colors), and to other artificial goods. as a recent example, the halachic status of mono and di-glyceride emulsifiers that derive from natural fats, has been assessed by considering their relationship to the starting products. some contemporary jewish religious authorities in the usa decided that the meaning of “fit for a king’s table” is that the product should stay edible throughout the process that transforms a raw, inedible (or halachically forbidden) food into the finite product. since one of the preparation steps of glyceride emulsifiers entails the formation of an inedible, even caustic, mixture of fat with strong acid, this event breaks the edibility chain, since now the concoction is no more oleh al shulchan melachim (or for anyone’s mouth, really).90 7. conclusions, and a roadmap for further study. the several, however far from exhaustive, nuggets of talmudic information reported here suggest that the elaboration and incorporation of greek, hellenistic and later knowledge into the hebrew talmud occurred very early, and continued through the centuries. such cultural event was likely occasioned by the proximity of jewish scholars, who also were the earliest talmud masters, to gentiles who practiced hellenistic science and technology, especially in large cosmopolitan cities. the cultural melting pot of alexandria is one likely candidate, yet in several other areas of the hellenistic and roman world, and in parthian babylonia, occasions of interaction between learned individuals may have played a similar role. such interaction, direct or mediated as it might develop, would induce hellenistic advances in science and technology into the halachic discussion of the time, and this embedded knowledge survived the hellenistic doom and was preserved as a component of talmudic knowledge even when its hellenistic roots had been severed. this cultural phenomenon may not be unique in the history of western judaism. as ptolemaic alexandria might be the cradle of the hellenistic-judaic interaction in the iii to ii century bce, as well islamo-judaic al-andalus-sepharad visited by christian post-docs in the x-xii centuries ce was where quantitative studies of the pharmacology of simple and mixed remedia65,67 could be re-appraised through the inherently quantitative approach of halacha. the intellectual pathway towards quantitative pharmacology traced by the al-kindi – gerard of cremona – arnald villanova – jordan de turre connection of the montpellier medical school66 in fact developed at the same time of the flourishing catalan-provençal geonim. even the converted jew who took part in the gospel vs. talmud polemic debates at least until the paris talmud fires of 1240 ce might play a yet unconsidered role in highlighting to the christian scholarly world some unsuspected sides of talmudic thought.91,92 later, throughout the humanism, renaissance and until the counter-reformation, there was a surge of interest among educated gentiles on studying hebrew to meddle into their texts, such as the hebrew source of the septuaginta and the kabbala,93 as a source of prisca sapientia. in addition, “court jews” were among the first to get involved in chemical manufacturing of high-tech commodities, such as dyes, drugs, gunpowder.94 due to the perceived complexity of the operations, chemical manufacturing was long known as “practical alchemy” or “white witchcraft”, and a then current (and still lasting) prejudice23,40,93,95 considered jews in general as particularly suited, for the good and for the evil, in the “esoteric” science of transformation of matters. in all cases, geopolitical events beyond the pale of individuals would close the short “windows of opportunity”, and in general, the jewish intellectual world contributed much less than deserved to the development of western culture at large. the recently started preparation of a version of the talmud in italian69 is expected to facilitate data mining of this huge text by means of information technology, independent from halachic studies and from knowledge of the specific hebrew language. furthermore, availability of an increasing volume of related information through computer-aided translation will prompt investigations on the possible (and even likely) transmission of ancient mediterranean knowledge in the hebrew talmud, and through this text, its comments and other hebrew sources into that of the reawakening western europe: if not now, when? references 1. s. c. rasmussen (ed), chemical technology in antiquity. acs symposium series vol. 1211 2015, american chemical society. 114 federico maria rubino 2. m. levey, osiris 1956, 12: 376-389. 3. l. m. principe, ambix 1987, 34: 21-30. 4. l. m. principe, the secrets of alchemy. university of chicago press, 2013. 5. h. 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(5702-1942) new york, the jewish theological seminary of 115talmud and “fossil” analytical chemistry america. 44. j. r. labendz, hebrew union college annual, 2003 74: 175-21 45. a. keimpe (ed.), the cambridge history of hellenistic philosophy 2008 cambridge histories online. cambridge university press. 46. m. rostovtsev, the american historical review 1921 26(2): 203-224; p.221. 47. r. buitenwerf, book iii of the sibylline oracles and its social setting. with an introduction, translation, and commentary. 2003 brill, leiden 304-320 (https: // books.google.it/books?isbn=9004128611). 48. j. scarborough, studies on ancient medicine 2008 138-156. 49. l. m. v. totelin, early science and medicine 2004 9: 1-19. 50. s. norton, molecular interventions 2006 6: 60-66. 51. l. totelin, phoenix 2012 66(1-2) 122-144. 52. p. schneider, phoenix 2012 66(3-4) 272-297. 53. a. j. marshall, phoenix 29(2): 139-154 (1975) 54. h. von staden, herophilus: the art of medicine in early alexandria 1989 cambridge. 55. h. von staden, in: alexandria and alexandrianism. kenneth hamma (ed.) the j. paul getty museum 85-106 (1996) 56. l. russo, la rivoluzione dimenticata. 2° ed. 2013 feltrinelli, milano; chap. 5. 57. quintus septimius florens tertullianus, (155-230 ce) http: //www.tertullian.org/anf/anf03/anf03-22. htm (access: 2017) 58. j. ganz, istoriâ mediciny 2014 4(4): 5-12. 59. h. p. bayon, proc r soc med. 1939 32(11): 15271538. 60. p. ghalioungui, s. khalil, a. r. ammar, med hist 1963 7: 241-46. 61. j. m. stevens, med j aust. 1975 2(25-26): 949-52. 62. l. smith, j fam plann reprod health care 2011 37(1): 54-5. 63. r. haimov-kochman , y. sciaky-tamir, a. hurwitz, eur j obstet gynecol reprod biol. 2005 123(1): 3-8. 64. http: //gifh.wordpress.com/2012/02/19/la-travagliatastoria-del-test-digravidanza/; ; http: //www.laprovinciadicomo.it/stories/cultura-e-spettacoli/292109_test_ di_gravidanza_egizio_funziona_dopo_4_mila_anni/ (last access 2017) 65. m. r. mcvaugh, bull hist medicine 2017 91(2): 183209. 66. j. ricordel, revue d’histoire de la pharmacie, 2001 89ᵉ année, n°330, 135-148. 67. arnaldus de villanova. aphorismi de gradibus. edidit et praefatione et commentariis anglicis instruxit michael r. mcvaugh. 1975 granada; barcelona. 68. c. sinding, bull hist med. 2002 76(2): 231-70. 69. r.s. di segni (ed.) talmud babilonese trattato rosh hashanà. 2016 giuntina, milano. 70. encyclopedia judaica. units of measure. at: http: // www.torahcalc.com/info/biblical-units/; https: //www. sil.org/system/files/reapdata/.../silewp2014_003.pd; http: //www.ajdler.com/jjajdler/talmudic3.pdf; also: http: //www.jewishencyclopedia.com/articles/14821weights-and-measures; www.dafyomi.co.il/general/ info/units-of-measurement.pdf; dafyomi.shemayisrael.co.il/general/.../units-of-measurement.pdf (last access 2017) 71. l. russo. la rivoluzione dimenticata. 2° ed. 2013 feltrinelli, milano, ch. 2, 52-53. 72. antikythera mechanism research project at: https: // www.antikythera-mechanism.gr/ (access 2017) 73. y. z. eliav, in: the archaeology and material culture of the babylonian talmud. 2015 (markham j geller, ed.), brill, leiden 186-224. 74. s. lieberman. hellenism in jewish palestine. (57221962) new york, the jewish theological seminary of america; passim; p.66; p.94. 75. e. nicholas. the alphabet of galen: pharmacy from antiquity to the middle ages: a critical edition of the latin text. 2012 univ. of toronto press. 76. p. holmes, j amer herbalist guild 2002 spring/summer: 7-18. 77. aristotle. de sensu et sensibilibus. tr. it. a. l. carbone in: l’anima e il corpo, parva naturalia. ii ed. 2015 bompiani (milano). 78. aristotle. de anima. tr. it. g. movia in: l’anima. vii ed. 2015 bompiani (milano). 79. theophrastus of erebus. de sensibus. tr. it. l. torraca in: i dossografi greci. 1961 cedam (padova). 80. r. sorabji, the philosophical review 1971 80(1): 55-79. 81. t. k. johansen, phronesis 1996 xli/1, 1-19. 82. j. ellis, phronesis 1990 xxxv/3, 290-302. 83. j. mansfeld, phronesis 1996 xli/2, 158-188. 84. b. stansfield eastwood, rheinisches museum für philologie, neue folge, 124. bd., h. 3/4 268-290 (1981) 85. s. t. newmyer, aufstieg und niedergang der römischen welt ii 1996 17(3): 2895-2911. 86. s. s. kottek, aufstieg und niedergang der römischen welt ii 1996 17(3): 2912-2932. 87. f. rosner, aufstieg und niedergang der römischen welt ii 1996 37(3): 2866-2887. 88. k. abelson, m. rabinowitz (rabbis), proceedings of the committee on jewish law and standards i 19801985 187-190. rabbinical assembly, 1988 http: // www.rabbinicalassembly.org/yoreh-deah (last access 2017) 116 federico maria rubino 89. b. t. moran, distilling knowledge: alchemy, chemistry, and the scientific revolution. 2005 harvard university press. 90. k. abelson (rabbi), proceedings of the committee on jewish law and standards i 1980-1985 181-185. rabbinical assembly, 1988 http: //www.rabbinicalassembly.org/yoreh-deah (last access 2017) 91. a. fidora, j. of transcultural medieval studies 2014 1(2): 337-342. 92. a. fidora, j. of transcultural medieval studies 2014 2(1): 63-78. 93. g. scholem. kabbala e alchimia [tr.it.] 2015 se. 94. d. jutte, isis 2012 103: 668-686. 95. g. ferrario, in: chymia: science and nature in medieval and early modern europa. 2010 m. lopez perez, d. kahn, m. rey bueno (eds.) cambridge scholars publishing, 19-29. 117talmud and “fossil” analytical chemistry supplementary materials shulchan aruch part ii: yoreh de’ah (http://www.torah.org/advanced/shulchan-aruch/archives.html) loci yoreh de’ah chapter 7a absorption if forbidden food (or an object that has absorbed forbidden food within the past 24 hours) is in contact even momentarily with hot liquid in a utensil that has been on a fire, or with salty liquid for 18 minutes, or with any liquid for 24 hours, permissible food that was in contact with the liquid for that period of time becomes forbidden unless the forbidden components are less than 1/60 of the total. (69:1,9,11,15,18;70:6;98:4; 104:1-2;105:1-3) in estimating 1/60 only food below the surface of the liquid is considered (see 94:1; 98:4; 99:1,4; 105:1). if the utensil has not been on a fire, but a hot component comes from such a utensil (see 68:10-11, 13,15), the surface of the permitted food must be peeled off where it comes in contact with the liquid (105:3). even if the components are hot, if they do not come from utensils that have been on a fire and the liquid is not salty (see 69:9 and 91:7) and the permitted food remains in it for less than 24 hours, the food need only be washed off and the liquid is permitted (91:1-4;105:2-3). these and the following rules also apply to contact between milk and meat products (87:10;91:4-6; see 92:1,4-6). on absorption from a forbidden egg that is still in its shell see 86:5-6. if the components are near a fire and hot but not in contact with liquid, and an object that has absorbed forbidden food touches permitted food, it becomes forbidden unless the forbidden components are less than 1/60 of the total; and the same is true if forbidden food of a type that sometimes contains fat touches permitted food, even if the forbidden food is absorbed in other food; but if the forbidden food is of a type that never contains fat, the places where it touched the permitted food need only be removed to a depth of a fingerbreadth, and this must be done in any case if the places where it touched are known (see 68:4,9;105:4-5,7-8). if the components are not near a fire and a hot component that has been on a fire is added, the places where the permitted food touches a forbidden component need only be peeled (68:10-11,15;92:7;94:8;105:6). if no component has been on a fire only washing is needed, and nothing need be done if the components are dry (91:1-4). if the components are not near a fire, but a forbidden food component is heavily salted (see 69:8;70:6) and not entirely dry (see 91:5;95:7), the places where a permitted component touches it even momentarily must be peeled; (see 69:8,18;70:6;105:1) and if the forbidden food is of a type that sometimes contains fat, the permitted food that touches it becomes forbidden unless the forbidden components are less than 1/60 of the total, and it must also be peeled if the places where it touched are known (64:16,20; 65:1; 69:9,16,18,20;70:1-4; 72:2;105:9-11). salt causes absorption even in an object (see 69:16-17), but it does not draw out forbidden food that has been absorbed in an object (69:16;70:2;105:12-13). if the forbidden food is meat from which the salt is drawing blood, and the salt is also drawing juices out of the permitted food, or the permitted food is on top, it does not absorb the blood and need only be washed (70:1-4); or if the permitted food is meat that still contains blood, any blood that it absorbs in this way can be extracted together with its own blood, though other blood that it absorbs cannot (69:2;70:2,6;72:2). similarly, the blood that a fire draws from meat is not absorbed in other meat that is near the fire, but other blood is (69:4,20;76:1-2;77:1). yoreh de’ah chapter 7b absorption cont’d some substances absorb more easily or less easily than others; for examples see 64:18-19;96:5;121:1. pressure (as in cutting with a knife or grinding in a mortar) increases the depth of absorption; see 94:7 and 96:1-3 as well as 10:1-3;64:16;89:4. even in cases where the forbidden component is less than 1/60 of the total, if it can be recognized or separated it must be removed; and if it is attached to or first entered a permitted component, that component is forbidden and must be removed if it can be recognized (69:11;72:2-3; 73:6;90:1;92:24;94:3;98:4; 106:1-2). when a permitted food component becomes forbidden because of thorough mixing (see ch.8a) or absorption it is regarded as entirely forbidden even if it absorbed an amount smaller than its volume (92:4;98:5;99:3,5;106:1;107:2), but if it absorbs meat or milk it is not regarded as being entirely meat or milk (94:6). if an object absorbs an unknown amount of forbidden food it is regarded as entirely forbidden (see 94:2) unless the absorption was of a type that requires only peeling (98:4). 118 federico maria rubino loci if it absorbs a known amount of forbidden food it is not regarded as entirely forbidden unless it is made of pottery or it has also absorbed an unknown amount of permitted food (98:5; see 92:5-7 and 94:6). permitted and forbidden foods should not be heated together in an enclosed space (such as an oven) unless one of them is covered or both of them are in containers and the oven is not completely enclosed, but if this was done the food remains permitted if the oven is not completely enclosed unless one of the foods has a sharp taste or unless a mixture containing even a tiny quantity of the forbidden food would be forbidden (90:2;97:3;108:1-2; see ch.8a). some foods absorb odors even if the source is covered; see 108:4. similar laws apply to heating them one after the other if the first one causes steam to form in the oven (108:1; see also 92:7-8;93:1; 105:3). tasting forbidden foods even without swallowing them is forbidden (108:5), but smelling them is not forbidden unless it is forbidden to derive benefit from them (108:7). an object that was in contact only with cold, unsalted forbidden food can be cleaned by thorough washing (121:1), but if it has absorbed forbidden food it should not be used even with cold, unsalted permitted food even after it has been washed unless it is earthenware (see 69:16; 94:7;121:5). if an object made of metal, wood or stone absorbed forbidden food in the presence of hot liquid, the absorbed food can be removed from it by immersing it in boiling water at least 24 hours after the food was absorbed in it (91:5;108:3;121:2). if the absorption was in the presence of heavy salt or of hot liquid that is no longer in a utensil that has been on the fire, it is necessary only to scrape off the object’s surface where the food or liquid touched it; see 92:9 . if it absorbed forbidden food by heating in the absence of liquid (this includes frying) the absorbed food can be burnt out of it by heating it to a high temperature (97:2;121:4-6). if it is a knife it may be used with cold food after thoroughly cleaning or grinding it down; to use it with hot food it must be heated to a high temperature or ground down and immersed in boiling water (see 10:1-3; 64:17;69:20; 89:4;94:7;121:7). these laws are also treated in orach chayim 55:1-2; see 121:3. on the procedures for cleaning utensils that were used with forbidden wine see ch.10b. orach chayim 55:1-2; see 121:3 yoreh de’ah chapter 8a mixtures of food cont’d if forbidden and permitted foods are mixed together thoroughly the mixture is permitted if no one forbidden component is more than 1/60 of the total (98:1,6,9; see 99:1-2,4). in defining a component, things that have the same name are regarded as the same whether or not they taste the same; see 98:2. for some types of forbidden foods amounts different from 1/60 are required; for other types any amount makes a mixture forbidden (see 98:7-8). if an intrinsically forbidden component can be detected by its taste or by its effect on the mixture (e.g., 87:11; 102:1), or if a forbidden component can be recognized but cannot be removed (104:1,3), the mixture is forbidden even if the component is less than 1/60 (98:8; 105:14). it is forbidden to mix forbidden food with permitted food to produce a permitted mixture; if this was done, the person who did it or for whom it was done is forbidden to derive benefit from the result (94:5-6;101:6). it is forbidden to use a utensil that has absorbed forbidden food if the utensil is sometimes used for less than 60 times as much permitted food (99:7;122:5). if a mixture contains less than 1/60 of a forbidden component, and more of that component is added so that the total reaches 1/60, the mixture becomes forbidden; but if a mixture contains less than 1/60 of meat (or milk) it does not become forbidden even if milk (or meat) is added to it afterwards (99:6). if an entire (dead) creature or (named) body part that has always been forbidden is mixed with any amount of permitted food the mixture is forbidden, but if the forbidden component can be recognized and removed the remaining mixture is permitted if the forbidden component was less than 1/60 of it (100:1-3). similarly, if a portion of food that is intrinsically forbidden and is large enough to serve to guests in its present condition is mixed with any amount of permitted food, the mixture is forbidden as long as the portion may have remained intact (69:14;81:2; 92:3; 101:1-7; 105:9;106:1). if food that is only temporarily forbidden or that can be made permitted without much effort is mixed with any amount of permitted food of the same type, the mixture is forbidden until the forbidden component becomes permitted; but if it is mixed with permitted food of a different type, or is not intrinsically forbidden, or became forbidden only after it was mixed, or can be recognized and removed, the mixture is permitted if the forbidden component is less than 1/60 of the total (102:1-4). 119talmud and “fossil” analytical chemistry loci yoreh de’ah chapter 8b mixtures of food cont’d if forbidden food is tasteless or gives a mixture a permanent bad taste (or if it is a creature: itself has a bad taste) it does not make the mixture forbidden unless it is the majority ingredient, but it should still be removed from the mixture if possible; see 81:8;95:4;100:2;103:1-4; 104:1-3;107:2;122:1;123:25. food absorbed in an object loses its taste after 24 hours and no prohibition results if it is reabsorbed in other food afterwards (93:1;94:4;95:2;103:5,7;122:4,67), but food adhering to the surface of an object does not lose its taste, and in any case if an object has absorbed forbidden food it should not be used with permitted food even after 24 hours until the absorbed food is removed from it (122:2-3; see ch.7b). milk or meat absorbed in an object and reabsorbed in meat or milk within 24 hours results in a prohibition, but if it is first reabsorbed in something else it becomes a “second-order” taste and can no longer result in a prohibition (94:5,9;95:1-3). in strong-tasting food, even absorbed tastes that are 24 hours old or second-order are not permitted (95:2;96:1-5;103:6;122:3). precautions should be taken to avoid the possibility of forbidden and permitted things becoming mixed up; see 101:8-9;110:10;123:23. if a piece of forbidden food that is not large enough to serve to guests becomes mixed up with two or more pieces of permitted food of the same type the pieces are all regarded as permitted, but one person should not eat all of them (109:1, and see ch.9). if they were cooked together the result is forbidden unless the forbidden food is less than 1/60 of the total of the food that is in doubt (109:2, and see 111:7; a person is allowed to add permitted food to the mixture before cooking it to ensure that the forbidden portion is less than 1/60). if a piece of forbidden food becomes mixed up with pieces of permitted food of a different type and cannot be distinguished, it is not regarded as permitted unless it is less than 1/60 of the mixture (109:1); but if it is more than 1/60 the mixture is not regarded as entirely forbidden, and if more permitted food is added to it until the forbidden portion becomes less than 1/60 the mixture becomes permitted (92:4). if an object that has absorbed forbidden food becomes mixed up with other objects they are all permitted (102:3; 122:8). if an “important” forbidden thing (for example, a living creature or anything that is counted rather than measured) becomes mixed up with any number of permitted things of the same kind the mixture is forbidden (e.g. 86:3), but if the things lose their importance (for example, the living creatures are slaughtered and are not large enough to serve to guests) and this was not done deliberately the mixture becomes permitted (110:1-2), and if one of the things is accidentally destroyed the others become permitted because we assume that the forbidden one was destroyed (this also applies to creatures, large portions, and things that are only temporarily forbidden), but they should be eaten two at a time by more than one person and they should not all be eaten at once (110:7). see ch.11 on the case where the things are forbidden because of idolatry. substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi 1 the italian neo-idealists and federigo enriques the dispute between benedetto croce and federigo enriques: a defeat for enriques? luca nicotra * *editor in charge of «artescienza», of the «bulletin of philosophy of human sciences» and of the «periodic of mathematics». engineer and science journalist; luca.nicotra1949@gmail.com. received: jun 01, 2023 revised: jun 26, 2023 just accepted online: jul 03, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: l. nicotra (2023) the italian neo-idealists and federigo enriques. the dispute between benedetto croce and federigo enriques: a defeat for enriques? substantia. just accepted. doi: 10.36253/substantia-2177 abstract: the controversy that between 1908 and 1912 saw benedetto croce and giovanni gentile opposed on one side and federigo enriques on the other did not actually have a conclusive episode, but its end was perceived, for its results on culture, on society and teaching in italy, as a "defeat" of enriques. a more careful examination of the events and of the historical context in which it took place seems, however, to clearly demonstrate that we can speak not of a personal defeat of the great mathematician from livorno, but rather of a defeat of the commendable attempts at cultural and social modernization of italy in an international perspective, of which enriques was not the only actor but certainly the most exposed. such intentions were crushed by the myopic provincial conservatism of italian neo-idealism, favored by the fascist regime, concerned only with affirming in the world an alleged autarkic national cultural superiority, based on the traditional literary-humanistic culture, ignoring the progress of the new technical-scientific thought, due to its nature instead placed in an international context. 1 – federigo enriques: an intellectual in all areas federigo enriques was one of the leading figures in the cultural panorama, not only in italy but also in europe, in the first half of the 20th century. mathematician, philosopher and historian of science, he wrote works in each of these fields which – as guido castelnuovo1 said – «would alone be enough to fill and illustrate the entire life of a scientist». although it is not possible to separate the three directions mentioned by castelnuovo in the intellectual activity of enriques, it is possible to distinguish them into three periods in each of which one or the other of the three directions prevailed: 18931906 (mathematics), 1906-1922 (philosophy) and 1922-1946 (history of science). in 1 castelnuovo (1947). 2 reality federigo enriques was not only a mathematician, philosopher and historian of science, as recalled by his brother-in-law guido castelnuovo, in his commemoration held at the accademia nazionale dei lincei on 11 january 1947. due to the extraordinary variety of his cultural interests of which will be explained later enriques was an allround intellectual, and in particular one of the most notable references for overcoming the barriers between the "two cultures". abramo giulio umberto federigo enriques this is his full name was born on the 5th of january 1871 in livorno from giacomo enriques, of jewish origins with portuguese descent, and matilde coriat, born in tunisia and bilingual (italian and french). in 1882 he and his family moved from livorno to pisa, where federigo attended secondary school. in 1887 he finished high school and enrolled at the university of pisa, also attending the highly prestigious scuola normale superiore, where he was taught by enrico betti (1823-1892), ulisse dini (1845-1918), luigi bianchi (1856-1928), vito volterra (1860-1940) and riccardo de paolis (1854-1892, the leading italian mathematicians of the time. even before graduating, in 1890 he published his first academic scientific memoir: alcune proprietà dei fasci di omografie negli spazi lineari ad n dimensioni (some properties of homograph bundles in linear spaces with n dimensions). 2 but federigo enriques' first (non-academic) publication dates back to 1885, when he was just 14 years old: table of perfect integer squares and cubes contained in 100000 (pisa: nistri, 1885), a 10 page file in 16-ths. in the summer of 1891, at the age of twenty, he graduated in mathematics with de paolis, defending a thesis entitled alcune proprietà metriche dei complessi di rette ed in particolare di quelli simmetrici rispetto ad assi (some metric properties of complexes of lines and in particular of those symmetric with respect to axes), published four years later.3 in november 1892, after a few months spent in pisa, he arrived in rome to continue the specialization course in algebraic geometry held by luigi cremona who, with his “birational transformations”,4 he had effectively introduced in italy that new line of research, already promoted by corrado segre. on this occasion, in rome he got acquainted with guido castelnuovo, who, together with corrado segre and luigi cremona, was the leading representative of the italian school of algebraic geometry, of which enriques himself would later join as the main protagonist. subsequently he spent a few months of 1893 in turin completing his specialization course with segre. during the period of the specialization course in rome, enriques published various academic works5 which earned him in 1894 the position of teaching projective geometry at the university of bologna. the first important results of his studies in algebraic geometry were the article ricerche di geometria sulle superficie algebriche (geometry research on 2 enriques (1890). 3 enriques (1895). 4 cremonian transformations generalize homographies, as, for example, in the plane straight lines no longer change into straight lines but into curves of a higher order. they are called "birational transformations" because to any point of the initial space they associate another point of the transformed space whose coordinates are rational functions of those of the starting point. 5 in 1892: le omografie cicliche negli spazi ad n dimensioni; le omografie armoniche negli spazi lineari ad n dimensioni. nel 1893: sui gruppi continui di trasformazioni cremoniane nel piano; sopra un gruppo continuo di trasformazioni di jonquières nel piano; una questione sulla linearità dei sistemi di curve appartenenti ad una superficie algebrica; sui sistemi lineari di superficie algebriche le cui intersezioni variabili sono curve iperellittiche; sugli spazi pluritangenti delle varietàcubiche generali appartenenti allo spazio a quattro dimensioni; ricerche di geometria sulle superficie algebriche; le superficie con infinite trasformazioni proiettive in se stesse. 3 algebraic surfaces)6 of 1893 and his university textbooks lezioni di geometria descrittiva (lesson of descriptive geometry)7 and lezioni di geometria proiettiva (projective geometry lessons)8 published the following year. in 1896, at the age of 25, he was appointed full professor of projective and descriptive geometry at the university of bologna. in 1903 the first edition of a highly successful series of mathematics textbooks for upper secondary schools, which were adopted throughout italy until the 1970s, was published with the title ementi di geometria (elements of geometry), written with ugo amaldi. in 1906 he published the volume problemi della scienza (problems of science),9 which due to its contents can be considered twinned with the famous books by henry poincaré: la science et l'hypothèse (1902), la valeur de la science (1905) and science et methode (1908). the book, written with material taken from previous articles by enriques, contains his scientific philosophy, his psychological approach to the principles of geometry and anticipates albert einstein's views on the concepts of time, space, motion, force. in the same year he founded the “società italiana di filosofia” (italian philosophical society sfi) in bologna and chaired it until 1913. the following year, in 1907, he founded the «rivista di scienza» (science magazine), which would then take on the name «scientia» in 1910. in 1908 he participated in the iii international congress of philosophy in heidelberg and there he received the task of organizing and presiding over the iv congress to be held in bologna in 1911. in 1912 he published scienza e razionalismo (science and rationalism),10 the book that contains more than any other the philosophical thought of enriques, in which current philosophical views are compared with ancient ones. in the years from 1912 to 1914, the second edition in two volumes of the questioni riguardanti le matematiche elementari (questions concerning elementary mathematics)11 was published, written together with other distinguished italian mathematicians, which constitutes his major work dedicated to the teaching of mathematics. as president of the national association of university professors, in the years 1913-1915 he formulated a reform project for the italian university, which however was not approved. in 1919 he was elected president of the "mathesis society" (founded in 1895), a position he held until 1932. in 1921 he assumed and maintained the direction of the «periodico di matematiche» (mathematical periodical) until 1938, being removed due to the racial laws. he will take over the direction from the fall of fascism until the year of his death, 1946. the following year, in 1922, he moved from bologna to rome where he became full professor first of higher mathematics and then of higher geometry at the university "la sapienza". in the same year his book per la storia della logica (for the history of logic)12 was published and the following year he founded the "national institute for the history of physical and mathematical sciences" in rome, within which the "school of the history of sciences" was created. in 1923 the first volume of gli elementi d’euclide e la critica antica e moderna (euclid's elements and ancient and modern criticism)13 was published, the first italian critical edition of euclid's work, written with other collaborators. it will be completed in 1935 with the fourth volume. in 1925 he was appointed director of the mathematical section of the 6 enriques (1893). 7 enriques (1894a). 8 enriques (1894b). 9 enriques (1906). 10 enriques (1912). 11 enriques (1912, 1914). in 1927 the third edition in 4 volumes was published. the first edition had come out in 1900 with the title questioni rigardanti la geometria elementare (questions concerning elementary geometry). 12 enriques (1922). 13 the second, third and fourth volumes were published in 1930, 1932 and 1935. 4 "enciclopedia italiana" by giovanni gentile, a position he would hold until 1937. in 1932 the first volume of the storia del pensiero scientifico (history of scientific thought),14 written with giorgio de santillana, dedicated to antiquity, was published. the work remained unfinished, but in 1937 the compendio di storia del pensiero scientifico (compendium of the history of scientific thought)15 was published (with giorgio de santillana), which contained the periods not included in the previous work. in 1934, in paris, his book signification de l'histoire de la pensée scientifique16 was published, in which enriques reaffirmed the theoretical value of science. following the introduction of the racial laws also in italy, in 1938 he was removed from university teaching and relieved of all public offices. however, he continued to have relations with france, where in 1941, in paris, his book causalité et déterminisme dans la philosophie et l'histoire des sciences was published, which contains a critical examination of the problem of determinism. with the fall of fascism, in 1944, he finally returned to teaching at the university of rome, until his death following a heart attack on 14 june 1946 in rome. 2 a controversy with multiple interpretations the controversy between federigo enriques and the major representatives of italian neo-idealism, benedetto croce and giovanni gentile, began in 1908, reached its climax in 1911 and ended up being exhausted without a well-defined solution in 1912. there was, therefore, no document or an event that can be considered as the final "battle" that with its outcome has somehow decreed the winner and the loser. «however, croce's authority had the practical effect of making a large part of the philosophical and cultural circles line up on positions that were hostile to enriques, so that the end of the controversy was commonly perceived as a ''defeat'' of the enriques».17 there are many questions that, after more than a century, it is legitimate to ask today about the meaning and outcome of that "clash". it was really only an unfortunate "academic controversy" or rather a real "conspiracy" concocted by croce and gentile to eliminate their most formidable opponent from the italian cultural scene and, with him, everything that was linked to his efforts of renewal and cultural and social modernization of italy at the beginning of the 20th century? how much "personal" and how much "academic" was the controversy which, in any case, took on an official public dimension? if we want to give the sense of a "personal" defeat to that story, was federigo enriques really the only defeated? weren't there other scientists and philosophers who shared his same aspirations for cultural renewal in italy and the idea of a scientific philosophy that would bring science and philosophy closer together? and if, on the other hand, we want to see it in impersonal terms, it was only the scientific world that capitulated under the conceit and arrogance of a so-called superior culture or, rather, it was not the defeat of the aspiration to modernity, into which italy could enter on the threshold of the new century like other more advanced european nations? to try to give an answer to these questions, as objective as possible, in the sense of coherent with the facts that can be established, it is necessary to analyze the multiple meanings that that clash assumed: between provincial conservatism and international modernism; between a secular traditional literary-humanistic culture (which erroneously included philosophy too) and a scientific culture with its new scientific 14 enriques (1932). 15 enriques (1937). 16 enriques (1934). 17 israel (1993). 5 philosophy; between neo-idealism and positivism/neo-kantism; between different ways of conceiving society; between the personal aspirations of the contending parties for the philosophical and cultural hegemony in italy. all these facets of the controversy saw enriques as protagonists in the forefront, on the one hand and gentile and croce on the other, these however with often overlooked but in reality, substantial differences, above all in their personal different consideration of science. furthermore, it should be noted that enriques was not the only protagonist of that controversy, which in reality, in a more latent and discrete form, had already begun much earlier, through the work of a large group of other prominent personalities of science and in particular of italian mathematics of the second half of the nineteenth century. enriques, however, was undoubtedly the major champion of that clash, assuming the most exposed position to the attacks of neo-idealist philosophers. if, therefore, we want to speak of personal defeat, the only defeated was not enriques but, with him, also all the italian mathematicians, physicists, chemists, naturalists and philosophers who, albeit in different ways, shared his aspirations of cultural and social renewal of post-risorgimento italy and the beginning of the 20th century. from the brief outlines that follow, two characteristics emerge, essential for better understanding both the meaning of the clash between enriques and croce-gentile and the consequences, normally attributed to its outcome, on the difficulties of a solid affirmation of scientific culture in italy: the connotation of italian science at the end of the 19th century and at the beginning of the 20th century, on the one hand, and the strong presence of italian scientists in leading government positions until the rise of fascism, on the other, a phenomenon which would disappear in the following years until nowadays. 3 science in italy between the 19th century and the early 20th century to understand the cultural background of federigo enriques, and the same controversy that saw him engaged against the italian neo-idealists, it is useful to look at the italian scientific context over the period from the mid-nineteenth century to the early twentieth century. from the following pages emerges a picture of italian science which, in the years between the 19th and 20th centuries, places it in the first places internationally, with some interesting characteristic features. this primacy of italian science at an international level, which also extends to national political life, strengthens in federigo enriques the conviction of being able to assign to science, also in italy, a leading place alongside literary-humanistic culture. a first characteristic of our scientific community of the time was the desire to enter an international context, which at the time was essentially identified with the european one.18 this aspiration is part of the modernization process that had already affected the most industrialized and technologically advanced countries of europe. the modernization of society also involves scientific research, which requires being informed of the most advanced research conducted in other countries,19 so 18 the united states of america at that time had not yet conquered the international cultural leadership that has characterized them from the end of the second world war to the present day. 19 in particular «in the years of enriques the culture of a philosophical-scientific-historical orientation was more significant in france and germany than in england. enriques was very attached to france and germany» (lombardo radice, 1982). 6 modernization and internationalism are two inseparable faces of the science of the time. international competition led italian science, at that time, to reach top positions, engaging it in frontier research which gave fundamental results in mathematics, physics and chemistry. 3.1 the first italian scientific community the conscience of a national scientific community, in italy, can be traced back to the creation of the "union of italian scientists", wanted by the zoologist carlo luciano bonaparte, (son of luciano, younger brother of napoleon i) and by vincenzo antinori, giovanni battista amici, gaetano giorgini, paolo savi and maurizio bufalini. however, its main promoter was prince carlo luciano bonaparte, who, animated by nationalist fervor, convinced the grand duke of tuscany leopold ii to promote the first meeting of italian scientists in pisa from 1 to 15 october 1839, hosting scholarly memoirs in six sections: physics, chemistry and mathematical sciences; geology, mineralogy and geography; plant botany and physiology; comparative zoology and anatomy; medicine; agronomy; technology. the choice of pisa seems the most suitable, both due to the fact that it is located in tuscany, where leopold ii is known for his scientific interests, and due to the fact that it was the birthplace of galileo galilei, universally recognized as the father of modern science. the meetings were first held on an annual basis until 1847, each meeting being made up of several meetings held on different days over a period of 15 days. subsequently they resumed in unified italy in 1861 in florence with an extraordinary edition in 1862 in siena (x meeting) and in 1873 in rome (xi meeting). they conclude with the last one of 1875 in palermo (xii meeting), on the occasion of which the regulation of the “italian society for the progress of sciences (sips) is approved, which therefore is to be considered the continuation of the "union of italian scientists”. already in these meetings it is possible to glimpse the spirit of international openness that will increasingly characterize the activities of our national scientific community. indeed, some famous foreign scientists were also invited to the meetings, among which the names of william herschel and charles babbage stand out, and the proceedings of the meetings were sent to the most important foreign scientific institutions. 3.2 mathematics in the first half of the 19th century, mathematics, both in teaching and in research, had suffered a long period of decline in italy compared to the rest of europe. but after the proclamation of the kingdom of italy, thanks to the work of many risorgimento and post-risorgimento mathematicians, the situation changed radically, starting a golden age of italian mathematics. the most prominent mathematicians of this period are enrico betti (1823-1892), francesco brioschi (1824-1897), giuseppe battaglini (18261894), felice casorati (1835-1892), luigi cremona (1830-1903) and eugenio beltrami (1836-1900). these mathematicians also actively participate in the events of our risorgimento.20 however, despite being "patriots", they did not choose blind nationalism, but worked to give the mathematical research of a unified italy an international connotation, establishing ties with the rest of europe. battaglini's students were several illustrious specialists in algebraic geometry: enrico d'ovidio, riccardo de 20 bottazzini, nastasi, (2013). 7 paolis, ettore caporali, domenico montesano, as well as the algebraists alfredo capelli and giovanni frattini. in 1858 betti, brioschi and casorati visited the universities of göttingen, berlin and paris. on november 291863 brioschi, with his student engineer giuseppe colombo, founded the royal higher technical institute in milan (which will later take on the name polytechnic), taking analogous german institutions as a model. bernhard riemann, invited to teach at the “scuola superiore normale” in pisa, rejected the proposal for health reasons, but remained in italy from 1863 to 1866, the year in which he died in selasca, on lake maggiore, on 20 july. those years were therefore an unrepeatable occasion for fruitful exchanges of ideas between the great german mathematician and our pisan mathematicians. the work of betti, brioschi, casorati, cremona and beltrami gives extraordinary results , not only for their research but also for the formation of new generations of brilliant mathematicians, who bring italian mathematics to the highest international peaks in the period from 1880 to first world war with: ulisse dini (1845-1918), cesare arzelà (1847-1912), salvatore pincherle (1853-1936), gregorio ricci curbastro (1853-1925), giuseppe veronese (1854-1917), luigi bianchi (1856-1928), giuseppe peano (1858-1932), ernesto cesàro (1859-1906), vito volterra (1860-1940), corrado segre (1863-1924), guido castelnuovo (18651952), federigo enriques (1871 -1946), tullio levi-civita (1873-1941), guido fubini (1879-1943), francesco severi (1879-1961), leonida tonelli (1885-1946), guido ascoli (1887-1957). the fame of these mathematicians is international, so much so that felix klein, for his great enzyklopädie der mathematischen wissenschaften (encyclopaedia of mathematical sciences), entrusts the drafting of many entries to italian mathematicians, including salvatore pincherle, luigi berzolari, orazio tedone and federigo enriques. in 1907 klein asked the latter to draft the article prinzipien der geometrie, dedicated to the principles of geometry, which would turn out to be a real monograph on the subject. algebraic geometry, due to the preponderant contribution of italian mathematicians (and enriques will be one of its fathers together with corrado segre, luigi cremona, guido castelnuovo and francesco severi) will be known in germany as l'italienische geometrie, the italian geometry. there are also international awards. in 1907 federigo enriques and francesco severi received the bordin prize from the academie des sciences in paris. in 1909, the same prize was awarded to giuseppe bagnera (18651927) and michele de franchis (1875-1946) for their work on the classification of elliptical surfaces. the philosopher and logical-mathematician bertrand russell defines peano as «the great master in the art of formal reasoning» (russell, 1970, p. 74) and henry poincaré, in the french newspaper «le temps», refers to the “palermo mathematical circle” as to the largest mathematical organization in the world. and he has every reason to affirm it: out of 924 members, 618 are foreigners, that is almost 70%! on the proposal of vito volterra, the iv international congress of mathematics was held in rome from 6 to 11 april 1908. there were 700 participants in the congress. italy is present with the highest number (213), followed by germany (174), france (92) and austria-hungary (74). volterra, in his inaugural speech, confirms the international character of science, which also informs the italian one. 3.3 physics pietro blaserna, antonio pacinotti, damiano macaluso, galileo ferraris, augusto righi, orso mario corbino, domenico pacini, antonino lo surdo and guglielmo marconi are the leading figures in italian physics from the mid-19th century to the beginning of 8 the 20th century.21 physics, until about 1870, was essentially conceived as galileo intended it: an experimental science, in which mathematics was reserved an auxiliary and instrumental function, a means of expressing quantitatively relationships between the physical quantities object of the experiment. language and heuristic tool, then. but in the last thirty years of the nineteenth century, experimental physics was joined by the mathematical physics of betti, volterra and other physicist-mathematicians and engineers, such as luigi federico menabrea and alberto castigliano, whose research converged into the rising building science. only in 1926 orso mario corbino explained very clearly the need to introduce theoretical physics, in addition to mathematical physics, to re-establish the lost contact between mathematical physicists and experimental physicists: he will introduce the first chair of theoretical physics in italy, held by enrico fermi. the first-degree thesis in theoretical physics is that of the homonymous son of the philosopher giovanni gentile, giovanni gentile jr (1906-1942), achieved in pisa in 1927. the differences of methodological approach in the research of mathematical physics and theoretical physics22 also explain the different professional connotations of the authors: mathematicians the authors of mathematical physics research and physicists the authors of theoretical physics research. but in the period considered here, prior to the famous dispute between enriques and the neo-idealist philosophers, which began in 1908, theoretical physics does not exist as a separate discipline, being identified with mathematical physics. this explains why many mathematicians of the time were also physicists. in 1844 carlo matteucci and raffaele piria founded the journal «il cimento, giornale di fisica, chimica e storia naturale» (the cimento, journal of physics, chemistry and natural history) in pisa, which in 1855 became «il nuovo cimento, giornale di fisica, chimica e storia naturale» (the new cimento, journal of physics, chemistry and natural history), often abbreviated to «il nuovo cimento,». forty-two years later, in 1897, it became the official press organ of the "italian physics society" and one of the most authoritative and famous physics journals. the first great reformer of italian physics is pietro blaserna (1836-1918), who graduated in physics with honors at the age of 21 from the university of vienna and then assistant to henri-victor regnault at the university of paris, where he dealt with theory gas kinetics. in 1862 at the age of just 26 he was called to fill the chair of experimental physics first at the institute of higher studies in florence and then, the following year, at the university of palermo. in 1872 he went to rome to hold the chair of experimental physics. blaserna radically reformed the teaching of physics by introducing the institution of the "practical school", i.e., the physics laboratory. furthermore, in 1881, on the model of the most advanced european university centres, blaserna established a 21 giuliani (1996, 2013). 22 the works in mathematical physics and theoretical physics are characterized by a strong presence of mathematics, but with a different use of it. mathematical physics works place the main interest in solving the mathematical problem faced and the comparison between mathematics and experience is not generally foreseen. the physical aspects of the problems addressed influence only the choice of the starting postulates, limiting their generality. their goal is not so much the acquisition of new physical results but that of obtaining a rigorous formalization of already existing physical theories, following a hypothetical-deductive approach. on the contrary, in theoretical physics works, the role of mathematics is auxiliary and instrumental, being used as a language and tool to quantitatively express relationships between physical quantities and to formalize the physical theory which remains, however, the true object of the research. theoretical physics works involve the comparison with the experiment and are often themselves generated by seeking an interpretation to previous experimental results. furthermore, theoretical physics research does not always follow a rigorous hypothetical-deductive method. 9 more modern physics institute in via panisperna in rome. in this same institute, a few decades later, enrico fermi's famous roman physics school was born. blaserna's research spans various fields of physics: properties of real gases, study of the ionization of air, thermodynamics, optics, geophysics, electrotechnics, acoustics, musical physics. antonio pacinotti (1841-1912) has remained known in the history of science for the conception of the famous ring that bears his name, which is none other than the first rudimentary realization of the direct current dynamo, the first dynamic machine generating electricity .23 as he himself recounts, he had the idea one evening during the second italian war of independence in 1859 in which he participated as a volunteer sergeant, and it was published for the first time in the june 1864 issue of «il nuovo cimento», in a paper entitled descrizione di una macchinetta elettromagnetica (description of an electromagnetic machine). unfortunately, as with other discoveries made by italians, even that of the direct current dynamo was plagiarized by foreigners. the paternity of the invention of the dynamo was publicly acknowledged to pacinotti by galileo ferraris but never in france. the official priority of the invention of the direct current dynamo was recognized to him long after his death, at the chicago universal exposition of 1933 and in 1934 at the congress of electrotechnical scientists, on the occasion of the 75th anniversary of his conception. in 1900, there were just 71 physicists in italian universities, making up a scientific community that was too small and poorly equipped to deal with the new experimental discoveries and new ideas of the decade 1895-1905. however, original research was also recorded in this period, such as, for example, those on magneto-optical effects. in 1885, the engineer galileo ferraris (1847–1897) discovered the principle of the rotating magnetic field, which is the foundation of the alternating current electric motor. in 1898 damiano macaluso (1845-1932) and orso mario corbino (1876-1937), experimenting on vapors of alkali metals, discovered that the faraday effect takes on particular characteristics when the wavelength of light approaches that of the absorption lines of the atoms constituting the vapour: the macaluso-corbino effect is still today the object of experimental and theoretical study. corbino also studies the hall effect in bismuth discs, in which a circular symmetry is maintained: the original radial current, produced by a potential difference applied between the center and the periphery of the disc, is partially transformed into circular current by the magnetic field applied perpendicular to the disk. this line of research intertwines with that of mathematical physics of which vito volterra is the greatest representative, thus constituting a real italian tradition of research.24 a leading position in italian physics of this period is held by antonio garbasso (18711933). his research concerns primarily, since the time of his degree in physics at the university of turin, electromagnetism and its relationship with optics and in a more advanced age also spectroscopy. after graduation, he follows master classes with heinrich rudolf hertz at the university of bonn and with hermann von helmholtz and emil aschkinass at the university of berlin. he carries out studies and research on xrays, just discovered by wilhelm conrad röntgen in 1895. winner of two competitions for the chair of mathematical physics and experimental physics, he chose the latter, teaching experimental physics at the famous "istituto di studi superiori, pratici e di perfezionamento" in florence,25 succeeding the illustrious mathematician and physicist 23 previously, the only way to generate electricity was the electro-chemical static one of the electric cells or batteries. 24 nicotra (2021a). 25 which will later become the university of florence. 10 antonio roiti (18431921).26 in arcetri garbasso creates the italian school of cosmic ray physics (arcetri school), which conquers leading international positions in this line of research thanks to enrico persico (1900-1969), giorgio abetti (1882-1982) and the students of garbasso (antonino lo surdo, rita brunetti, giuseppe occhialini, bruno rossi, franco rasetti, francesco rodolico, vasco ronchi, gilberto bernardini, daria bocciarelli, lorenzo emo capodilista). garbasso also actively devoted himself to politics as a senator of the kingdom of italy from 1924 to 1933 and mayor of florence from 1920 to 1928 with some brief interruptions. he adheres to the fascist regime but disagrees with the gentile reform which penalizes scientific teaching. in 1908 blaserna called to rome the sicilian physicist orso mario corbino, professor of experimental physics at the university of palermo, to hold the chair of complementary physics. it will be corbino who will continue blaserna's work of reforming italian scientific research, leading it to deal with frontier research of the time. ten years later, in 1918, corbino will hold the chair of experimental physics at the royal physical institute left vacant by the death of pietro blaserna and will also replace him in the direction of the institute. corbino, in sicily, had dedicated himself to cutting-edge research in the field of "modern physics" and wants to transform the physics institute in via panisperna into a center of excellence at the european level, which it will later become with the "ragazzi di fermi” (fermi’s boys). corbino is a scientist in the modern sense of the term. his activity is not limited to pure research, but also involves applied research, the industrial world, and politics. in 1909 the nobel prize for physics was jointly awarded to guglielmo marconi (18741937) and karl f. raun (1850-1918) in recognition of their contribution to the development of wireless telegraphy. it is the first nobel awarded to an italian scientist.27 the researches of the italian physicists antonino lo surdo (1880-1949) and domenico pacini (1878-1934) are the basis for the researches that will yield the nobel prize for physics respectively to johannes stark (1874-1957) in 1919 and to victor f. hess (1883-1964) in 1936. vito volterra28 he is undoubtedly the undisputed leader of the italian scientific community in the second half of the 19th century and the first decades of the following 20th, until his isolation by fascism after 1926. his contributions to mathematics and physics are so numerous and known at international level to be called by the us newspapers "mister italian science". the public and academic offices of volterra are numerous and at an international level. his specialty is mathematical physics, but his interests range well beyond scientific ones, generously embracing humanistic and historical culture in particular, thus giving a shining demonstration of how false the separation between the so-called two cultures is, the humanities and science. he is also a tireless scientific organizer. volterra is co-founder and first president of the “italian physical society” in 1897 and does not miss an opportunity to relate italy with the most qualified international scientific circles, through the exchange of researchers between the scientific communities of different countries, showing an incredible modernity of views on science policy. in 1900 volterra was called by blaserna to teach mathematical physics at the royal institute of physics of the "la sapienza" university of rome, in via panisperna. we owe him and orso mario corbino the creation of the famous physics 26. the precarious economic conditions of the young vito volterra would have forced him to abandon his studies, if he hadn't been helped by roiti, who offered him a position as preparatory assistant at the "institute of advanced, practical and improvement studies" in florence in 1877 (nicotra, 2021a). 27 for the background of this nobel, see bischi (2017). 28 nicotra (2021a). 11 school in via panisperna, which will be led by enrico fermi, of whom volterra follows the first steps of the scientific career by giving him a scholarship from the rockefeller foundation in 1924 at the institute directed by paul ehrenfest in leiden. in 1917 he created the "inventions and research office". in february 1919 the "international research council" was established, of which volterra was appointed a member. in the same year volterra wanted to replicate the international scientific initiatives on a national level, proposing the establishment of the “national research council” (cnr), which should have incorporated various already existing research bodies: the “inventions and research office”, the “committee for the chemical industries and the aeronautical institute”. the project was approved by the orlando government, but due to bureaucratic difficulties the activity of the cnr began five years later, in 1924, with volterra as its first president. certainly, his example must have had a strong influence on the education of enriques, who was his pupil in pisa. many characteristics of volterra can be found in enriques: versatility, the unified conception of culture, the passionate commitment to organizing events and scientific institutes of great prestige. 3.4 chemistry it is the chemistry of the late nineteenth century that demonstrates, even before the physics of the early twentieth century, that the world at a microscopic level is not characterized by continuity but by discontinuity. in 1912, max planck himself, who twelve years earlier had discovered the "elementary quantum of action" and therefore discontinuity in physics, wrote: physical forces, gravity, electric and magnetic attractions or repulsions, cohesion, act continuously; the chemical forces, on the contrary, according to quanta. this law should be connected with that which permits masses in physics to act on one another in any quantity, whereas in chemistry they can act only in sharply defined, discontinuously variable proportions. italian chemistry is represented in this period by two illustrious names, stanislao cannizzaro and giacomo ciamician, and by another equally illustrious who preceded them: amedeo avogadro. all three have made fundamental contributions to this science. in 1811 avogadro (1776-1856) proposed the famous law that today bears his name: equal volumes of gaseous substances, at equal temperature and pressure, contain an equal number of molecules. avogadro gives the molecule the role, followed today, of the fundamental unit of chemistry. for avogadro, reactions are exchanges between molecules. he gives a simple explanation of the relationship between the microscopic and macroscopic world, or between molecules and volumes, providing, among other things, a very simple way to determine the molecular weight. his ideas, however, are too ahead of their time. they clash with those of the powerful swedish chemist jöns jacob berzelius, who disputes avogadro's idea according to which the organic-biological world and the inorganic world are made of the same matter and obey the same physical laws. furthermore, berzelius and others contest avogadro for some anomalies in the application of his law. we had to wait at least half a century, 1860, before avogadro's brilliant ideas were accepted by the scientific community, thanks to another great italian: stanislao cannizzaro (1826-1910) from palermo, a student of the great calabrian chemist raffaele piria (1814-1865), professor at the university of pisa, considered the founder of modern 12 chemistry in italy. cannizzaro accepts august kekulé's invitation to participate in the congress of chemists from all over europe in karlsruhe, germany, between 3 and 5 september 1860, during which he once again proposes avogadro's clear distinction between atom and molecule. on the last day of the congress, a note of his on atomic weights, written in 1858 and published in the sunto di un corso di filosofia chimica (summary of a course in chemical philosophy), was distributed, a synthesis work of his lessons as professor of chemistry in genoa. in this note, cannizzaro explicitly refers to avogadro's law of 1811. cannizzaro's report receives the full support of another congressman, the chemist dmitrij ivanovich mendeleev, and thanks to his clarity of exposition, congress officially accepts avogadro's hypotheses. cannizzaro demonstrates very clearly the falsity of the objections posed by berzelius and others against avogadro's law: the anomalies they detect in its application are only apparent, because they are due to dissociations of a thermal type. cannizzaro demonstrates that in every compound every different chemical element is present with at least one atom and finally demonstrates that molecules, despite being compound entities, have their own specific chemical identity and therefore are the constituent units of matter from a chemical point of view. it is a great international affirmation of italian chemistry. harold hartley will write: the karlsruhe conference, thanks to the presence of cannizzaro, was destined to have a decisive influence on the progress of chemical theory and to be a milestone in its history. thanks to the new approach of avogadro and cannizzaro, chemistry, just like physics, can apply mathematics and chemists can now write the formulas of molecules with great precision and ease. cannizzaro himself, thanks to these new instruments, is able to measure the exact atomic weight of 21 different chemical elements. emanuele paternò (1847 – 1935),29 a pupil of stanislao cannizzaro, became a professor of chemistry at the university of turin at the age of just 24 and in 1872 he succeeded cannizzaro in the same chair at the university of palermo, later also becoming its rector from 1886 to 1890. in 1871 he founded the «gazzetta chimica italiana» (italian chemical journal). his main research concerns photochemistry, in particular the action of light on organic molecules. in 1909, together with george büchi, he discovered the paternò-büchi reaction. freemason, he held important political offices for many years: mayor of palermo from 1890 to 1892, senator of the kingdom of italy from 1890 to 1935 and vice president of the senate from 1904 to 1919, as well as numerous high parliamentary offices. raffaello nasini (1854 1931),30 after graduating, trained as a chemist in the roman laboratory of stanislao cannizzaro and in the laboratory of hans heinrich landolt in berlin. professor of general chemistry first at the university of padua and then of pisa, he devoted himself to research on gases, on the theory of solutions, on electrolytic dissociation and then on electrochemistry, of which he launched the first university course in padua in 1900, probably the first in all of italy. after the discovery of argon by lord rayleigh and william ramsay in 1894, he develops a particular interest in terrestrial gaseous emanations which will also lead him to be interested in radioactivity. nasini's research activity spans various and different fields of chemistry with interdisciplinary results: organic, general, inorganic chemistry, physical chemistry and 29 de condé paternò di sessa m., paternò di sessa o. (2018). 30 macchioni (2019). 13 also industrial chemistry. in the latter field, his studies on the boraciferous fumaroles of larderello are noteworthy, giacomo ciamician (1857-1922), graduated from the justus liebig-universität of gießen in germany, trained as a chemist at the school of stanislao cannizzaro in rome. on 11 september 1912, invited by his american colleagues to the viii international congress of applied chemistry, he proposed photochemistry as a future research direction for chemistry. on 27 september of the same year, in «science», he published his report: la fotochimica dell’avvenire (the photochemistry of the future). the proposal of the trieste chemist was revolutionary for those times: fossil solar energy (alluding to fossil coal) was not the only energy source of solar origin useful for the development of civilization. we can learn from plant photosynthesis, using light to carry out a lowtemperature chain reaction, thus creating a low-cost industrial photochemistry: an artificial photochemistry, of which ciamician is considered the founder. a research program that already in 1903, he had begun to implement with a chemical device capable of capturing solar energy and transforming it efficiently and he had spoken about it in a speech given at the university of bologna on november 7, 1903. mario betti (1875 1942),31 who succeeded giacomo ciamician in 1923 at the university of bologna, made contributions in organic, naturalistic and hydrological chemistry. in particular, he carries out original studies on organic bases, on the optical antipode doubling of many compounds and on spontaneous oxidation reactions. the general synthesis reaction of heterocyclic derivatives devised by him is known as the "betti reaction". he has carried out studies on the relationship between the chemical structure and the rotary power of the elements and on the qualities of mineral and thermal waters. from 1939 until his death (1942) he was senator of the kingdom of italy. original contributions on the study of ternary and quaternary metal alloys and on heterogeneous catalysis are owed to nicola parravano (1883 1938),32 a pupil of stanislao cannizzaro and emanuele paternò. 3. 5 engineering many italian engineers of this period are responsible for the birth of the building science, a set of different disciplines of a physical, mathematical and experimental nature: analytical mechanics, theory of elasticity, continuum mechanics, science of materials. the casati law of 13 november 1859 on public education unifies, in the rising kingdom of italy, the training of engineers and architects with the establishment of the engineering application schools, separating their studies from those of mathematics, following the model french from the ecole polytechnique. thus, were born the school of applications for engineers of turin in 1860 and the royal higher technical institute of milan in 1863. other pre-existing institutions would follow their example, such as the school of applications of bridges and roads existing in naples since 1811, the school of pontifical engineers in rome since 1817. furthermore, new engineering application schools were born in palermo in 1866 and in genoa in 1870 and still others in bologna, padua, pisa, turin. luigi federico menabrea (1809-1896), considered one of the greatest italian scientists of the 19th century, teaches at the school of application engineering in turin, having left significant contributions in the field of continuum mechanics and building science. he is also the author of the first scientific work on computer science: 31 naso (2017). 32 fontani, salvi (2015). 14 notions sur la machine analytique de charles babbage published in french in 1842. menabrea was the first to give a formulation of structural analysis based on the principle of virtual jobs, becoming a forerunner in the introduction of energetic principles in continuum mechanics. his theorem of minimum of the elastic potential energy of a deformable body, enunciated in 1858, is well known in the building science. at the same school of engineering application in turin, giovanni curioni (1831-1887) would teach from 1865, author of the mighty 6-volume treatise, l'arte di fabbricare, which also contains a course on topography. numerous memoirs on the science of construction assured him international fame. to the engineer eugenio barsanti33(1821-1864) we owe the conception and construction of the first internal combustion engine to an idea of his matured in 1841: illustrating to his students at the collegio san michele in volterra, where he taught mathematics and physics, an experiment on the explosion of a incendiary mixture of air and hydrogen, he had the idea of using the rapid expansion of the mixture to raise a piston. in 1851 barsanti met the engineer felice matteucci (18081887) with whom he would collaborate for the rest of his life building various models of internal combustion engines. the two engineers presented the invention of the internal combustion engine on 5 june 1853 at the accademia dei georgofili in florence and, in 1854, obtain the patent in england with the title obtaining motive power by the explosion of gases. eng. quintino sella (1827-1884) is, together with luigi menabrea and giuseppe colombo one of the scientist figures who most have a strong presence in postrisorgimento italian politics. repeatedly minister of finance in 1862, in 1864-1865 and in 1869-1873, he contributed to the work of transformation and enhancement of rome not only as the capital of italy but also as a european scientific centre. his expertise as an engineer in the mining field earned him various public positions in the sector and his studies in mineralogy various international awards as a scientist. in 1855 he designed and built a machine, the "electromagnetic sorter", based on the principle of electromagnets, to separate magnetite from cupriferous pyrite, obtaining the patent, which was awarded a gold medal at the universal exhibition in london in 1862. eng. giuseppe colombo (1836-1921) was one of the first professors at the royal technical institute of milan, becoming in 1865 holder of the chair of mechanics and industrial engineering, that he would hold until 1911. in 1897, after brioschi, he became the second rector of the milan polytechnic. he was also a passionate scientific communicator, much appreciated by an audience of all social classes, collaborator and then director of the technical magazine «l'industriale», published from 1871 to 1877. elected a member of parliament in 1886, he was appointed minister of finance in 1891, treasury minister in 1896, first vice president and then president of the chamber of deputies from 1899 to 1900, finally senator of the kingdom of italy in 1900. giuseppe colombo also possesses a brilliant and courageous entrepreneurial spirit: he understands the application potential of edison's dynamos to produce electric lighting and electricity in distributable form, as were gas and water. he asks for and obtains from edison the exclusive right for italy to use his method. with john william lieb, a technician of the edison company, under his guidance, on june 28, 1883, in milan, next to the duomo, in a building built on the site of a former theater in via santa radegonda, he inaugurated the first power plant of the 'continental europe. his most famous writings certainly remain his numerous technical manuals, in particular the manuale dell’ingegnere civile ed industriale (manual of the civil and 33 his real name was nicolò. eugene is the name he took as a priest in the scolopi order. 15 industrial engineer) (more familiarly known as " il colombo") whose first edition, from the publisher friend ulrico hoepli of milan, dates back to 1877. it will remain for decades, with numerous reissues and updates, the practical guide of generations of engineers, still on the market today. a place of honor in the construction of the theory of elasticity, to which many mathematical engineers-physicists of the time made fundamental contributions, is undoubtedly occupied by carlo alberto castigliano (1847-1884), a pupil of curioni. born into a family of humble origins, during his studies he had to face economic difficulties due to the loss of his father and then also of his stepfather, who had married his mother who was widowed for the second time. in 1871 castigliano obtained a degree in pure mathematics and in 1873 a degree in civil engineering, discussing the thesis intorno ai sistemi elastici. dissertazione (on elastic systems. dissertation), published in turin in the same year. it contains the proof of the principle of elasticity or theorem of minimum work stated, but not proved, by menabrea in 1858: let us consider an elastic system made up of parts subject to torsion, bending or transversal sliding, and of rods jointed to those parts and to each other: i say that if this system is subjected to the action of external forces so that it deforms, the tensions of the rods after deformation are those which minimize the expression of the molecular work of the system, taking into account the equations that exist between these tensions, and assuming constant the directions of the rods and of the external forces. this theorem proved menabrea's principle in more general terms and will be known later as primo teorema di menabrea (or “menabrea's first theorem”). this was the object of dispute between menabrea and castigliano, who accused menabrea of plagiarism having not explicitly acknowledged his work. indeed, in 1875, menabrea, in another attempt to prove his principle of minimum energy, made use of castigliano's demonstration, which he simply quoted in a footnote. another result that made castigliano famous all over the world is another theorem at the foundation of the theory of elasticity, the theorem of derivatives of work, known as castigliano's theorem,34 used for calculating the displacements of a structure and therefore its stiffness with a test load. once the elastic deformation energy has been calculated with the beam theory, it is sufficient to calculate its partial derivatives with respect to the applied forces to obtain the displacement. finally, stiffness is the ratio between the applied force and the displacement it causes. castigliano was appointed a member of the accademia nazionale dei lincei and of the academy of sciences of turin and in 1861 received the title of count. his results on the theory of elasticity, published in various works, were published in french in turin by the publisher negro in 1880, in the work théorie de l'équilibre des systèmes élastiques et ses applications. this work, more than any other, made him known throughout the world. 34 the author formulated it as follows: «... the displacement (or rotation) of an elastic solid element is defined by the partial derivative of the deformation work, expressed as a function of the external forces (or moments), performed with respect to one of these forces that is applied to the element considered at the point and in the direction of the desired displacement". in more modern terms: «for a body whose behavior is part of th e 1st order theory, with fixed constraints, not subject to temperature variations, the generalized displacement, relative to a generalized force pi due to all the forces acting on the body, is given by the partial derivative of the elastic potential energy with respect to the same force pi » (cartapati, gallo curcio, piccarreta, 1972, chap. ix). 16 castigliano owes many works of application of the theory of elasticity to engineering, and also the invention of an instrument, the multiplier micrometer, to measure the deformations produced by loads in metal constructions, which was very widespread in railway operations. camillo guidi (1853-1941), who succeeded curioni in 1882, was responsible for the text lezioni di scienza delle costruzioni (lessons on the building science) with an axiomatic-deductive approach, which was taken up and perfected by eng. gustavo colonnetti (1886-1968) who took over from him the chair of building science in 1928. his book principi di statica dei solidi elastici (principles of statics of elastic solids) dated 1916 was later republished under the title scienza delle costruzioni (building science) by einaudi in 1941, remaining a classic for the teaching of that discipline until the seventies of the twentieth century. 3.6 politics another characteristic aspect of italian science of the period between the 19th and 20th centuries is the political and, in italy of the risorgimento, also military commitment by numerous italian scientists, a phenomenon almost completely absent in the political reality of of our country today.35 the italian scientific community of mathematicians, physicists, chemists and naturalists of the last decades of the nineteenth century and the first decades of the following, on the wave of nineteenth-century positivism, is firmly convinced that science can play a leading role in cultural social and economic development of italy. the presence of many great italian scientists in active politics with key governmental positions, bears witness to this. the following became prime ministers: the doctor luigi carlo farini and the engineer luigi federico menabrea (three times). the engineer giuseppe colombo is president of the chamber of deputies. the chemist emanuele paternò was vice president of the senate from 1904 to 1919. the following become ministers: the engineers luigi federico menabrea, quintino sella and giuseppe colombo, the mathematician luigi cremona, the physiologist carlo matteucci and the physicist orso mario corbino. the mathematicians francesco brioschi and enrico betti are undersecretaries. the following deputies or senators are elected: the mathematicians ottaviano fabrizio mossotti, francesco brioschi, enrico betti, luigi cremona; the physicists orso mario corbino, giovanni cantoni, augusto righi, antonio pacinotti, galileo ferraris, antonio garbasso; the chemists emanuele paternò (senator from 1890 to 1935), mario betti, raffaele piria, stanislao cannizzaro; the physiologists carlo matteucci, jacob moleschott, giulio bizzozero, camillo golgi. 4 the battle of neoidealism against 19th century positivism on the philosophical level, the main reason for the dispute opened by the italian neoidealists against enriques was the erroneous (or wanted?) identification of enriques' philosophy with nineteenth-century positivism, opposed by neo-idealism. enriques, from a young age, strongly and clearly appealed to positivism, but later his criticisms of positivism made him deviate from it clearly, as he himself declared. however, his criticisms were not fully understood by the italian neo-idealists and his philosophy was superficially branded as positivist. it is therefore appropriate, to understand how much 35 bottazzini and nastasi (2013); nicotra (2021b). 17 that dispute was animated by other real reasons, to recall the fundamental points of positivist thought and enriques' reasons for dissent from it. 4.1 characteristics of positivism positivism was a philosophical movement that was essentially the result of the industrial revolution of the first half of the 19th century and of the rising capitalism of the most industrialized european countries: england, france and germany. it was founded on the exaltation of scientific and technological progress. its name derives from the latin positum, the past participle of the verb ponere: "that which is placed", that which is founded, that which has its basis in the reality of concrete facts. the founding thought of positivism was expressed by the french philosopher augusto comte (17981857) in the famous discours sur l'esprit positif (1844) in five points, summarized as follows (comte, 1985, pp. 47-48): the opposition of real to chimerical; the opposition of the useful to the useless; the opposition of certainty to indecision; the opposition of the precise to the vague; the opposition of the word "positive" to the word "negative", to highlight the opposition of organizing to destroying the new modern philosophy. 4.2 the value of science for positivism and for enriques like positivism, enriques gave science a primary place in the theory of knowledge. on the other hand, the points of divergence between the positivist thought and the philosophical thought of enriques on the value of science are various and substantial. the first major point of divergence is the purely utilitarian value of science for positivism,36 while for enriques it is above all fully theoretical and only subordinately utilitarian. for positivism, science has absolute value, since its conquests are definitive and fully true; for enriques, on the other hand, science has only a relative value because it is always approximate, never concluded, being in a continuous evolution and improvement: ... science is a process of successive approximations which indefinitely prolongs its roots in the unconscious inductions of common life, and pushes its branches ever higher, touching on an ever wider, more certain and more precise knowledge. 37 and because his purchases imply other previous ones: science as well as approximate is also relative. this implies that the meaning of a scientific fact must be subordinated at all times to all the knowledge acquired. precisely because everything is relative, it is not permissible to take any fact or principle as an isolated one, nor to establish an absolute hierarchy of knowledge which places a primitive knowledge independent of the development of knowledge considered as a whole.38 a consequence of the relative nature of science is enriques' criticism of the absolute classification of the sciences enunciated by the positivists auguste comte and antoine augustin cournot, founded instead on the conviction of the absolute value of scientific knowledge. 36 as for neo-idealism. 37 enriques (1912, pp. 20,21). 38 there. 18 furthermore, enriques contested positivism for limiting itself to explaining the "how" without seeking the "why" of a phenomenon: ... hypotheses and imaginative representations lead beyond positive science. in this respect the causal explanation implies something more than the simple answer to the question of "how a certain phenomenon occurs". science goes beyond this explanation when it tries to explain the "why."39 positivism identifies the "brute fact" with the "scientific fact", attributing a scientific value to experimental or observational data. comte stated that science must be made up only of ideas, hypotheses and theories that do not go beyond the reality of directly available data, thus affirming the absolute objectivity of the brute fact. for enriques, on the other hand, "brute facts" (experimental or observational data) have no meaning in themselves but receive it from the ideas according to which they are interpreted, ordered and correlated, thus becoming "scientific facts". but this doctrine [positivism], taken literally, would remove all value from science, reducing it to a simple collection of recipes. because even what we rightly call "facts" receive their meaning precisely from the ideas according to which they are interpreted. [....] a fact is never the brute encounter of certain sensible data, but the connection of several data of a certain order, dominated by an idea: its affirmation always implies recognizing objective and subjective data, separable up to a certain point, but never in an absolute sense.40 it is in this passage from the "brute fact" to the "scientific fact" that the construction of scientific knowledge consists of: whoever intends to understand the differences between the brute fact in the vulgar sense of the word, and the scientific fact, first of all sees in the latter a much clearer conditional character. [...] so a scientific fact grows, so to speak, from a multitude of brute facts contained in it; it gains in generality as it sums up new, more extensive relationships in itself.41 enriques' distinction between brute facts and scientific facts is in perfect agreement with poincaré's thought: we cannot be satisfied with pure and simple experience. no, this is impossible; it would be tantamount to completely disregarding the true character of science. the scientist must order; science is made with facts, as a house is made with stones; but a heap of facts is as little a science as a pile of stones is a house.42 from his own words the collocation of the philosophical-scientific thought of enriques in the field of that experimental rationalism expressly mentioned by him is clear: but on the other hand, we can see how every observation and every experience has scientific value only insofar as it is based on a reasoning; otherwise he is reduced to 39 enriques (1945, p.107). 40 enriques (1936 b). 41 enriques (1906, pp.101, 102). 42 poincaré (1950, pp. 137-138). 19 waiting for nature to be kind enough to instruct us, answering by chance questions that we don't know how to ask or interpret.43 it is that physical-mathematical method of investigation which galileo and newton assumed as a paradigm for the birth of modern science, founded on the symbiosis between experiment and mathematics, which had it must be pointed out a brilliant precursor in leonardo da vinci: i believe that instead of defining what the soul is, which is something that cannot be seen, it is much better to study those things that can be known through experience, since only experience does not fail. and where one of the mathematical sciences cannot be applied, one cannot be certain.44 enriques' highly interdisciplinary mentality and the particular place he has always assigned to psychology widen the domain of ideas according to which raw facts must be interpreted, ordered and correlated so that they become new acquisitions of science: the study of science, conceived as a "fact", must be aided by the teachings of history and the results of psychology.45 even more explicitly, he himself mentions the role of psychology in the genesis of scientific theories: now in this second aspect, scientific theory appears to us as a psychological development, which proceeds in a properly inductive sense, that is, it draws new hypotheses from new associations, and from the verification of these it rises to more extensive and more precise associations and hypotheses. 46 for positivism, reality is the experimental or observational datum itself, while for enriques, reality is not identified with the experimental datum, but with what remains invariant in its mathematical representation: …the knowledge of a real always implies the coordination of conveniently associated data. in other words, reality is not a pure datum but something constructed thanks to the coordinating rational activity.47 this identification of reality with the invariance of its mathematical representation will be found several years later in paul dirac, for whom the renaissance motto «pulchritudo splendor veritatis» was valid, i.e., the identification of the beauty of a mathematical formula with its truth. but why does beauty for dirac lead to truth? the answer is simple: an equation, for dirac, is beautiful if it contains invariants and invariance guarantees truth: therefore, beauty leads to truth. 5 the scientific philosophy of federigo enriques 43 enriques (1906, p. 126). 44 leonardo da vinci (codice atlantico a 119 v). 45 enriques (1906, p. 79). 46 enriques (1906, p. 150). 47 enriques (1912). 20 we have seen previously what results of primary importance and what international connotation reached italian science in the second half of the nineteenth century and in the first years of the new century. enriques had fallen into that international climate of cultural and social modernization which had science and scientists as its driving force and among these, first and foremost, volterra. enriques was perhaps the italian mathematician closest to the multifaceted scientific and cultural personality of the latter, of whom he had been a pupil. unlike volterra, however, he never exposed himself politically and instead, unlike his master, he cultivated strong philosophical interests. like volterra, he had exceptional qualities as an indefatigable cultural organizer and firmly held the idea of interdisciplinarity, as a corrective to the cultural isolation produced by the excesses of specializations. furthermore, like volterra, he rejected a clear distinction between pure and applied mathematics and demonstrated a remarkable ability to weave broad and intense cultural relationships with scientists and philosophers from all over europe: france, germany, united kingdom, belgium, russia, sweden. he had a privileged relationship with france,48 due both to the fact that french was his second mother tongue (being federigo's mother of french-speaking origins) and to the particular consonance of his philosophical and scientific thought with that of many french scientists and philosophers. the foreigners with whom he had cultural exchanges form a long list of prominent figures in the scientific and philosophical fields.49 evidence of these contacts can be found in the copious correspondence that enriques maintained with his brother-in-law and collaborator guido castelnuovo, between 1894 and 1905.50 many of his works were written directly in french and published in france before being translated and published in italy. from 1895 to 1946 (the year of his death) as many as 56 works by enriques were published in french, and he was also awarded various important positions in france, such as that of corresponding member of the "académie des sciences morale et politiques" and that of director of the series "philosophie et histoire de la pensée scientifique" in the series "actualités scientifiques et industrielles" of the publisher herman of paris.51 federigo enriques did not recognize the status of an autonomous discipline to philosophy, as he considered it a synthesis of critical observations on the sciences, referring to the thought of the pre-socratic philosophers. he criticized the use of the term philosophy as «… a noun rather than an adjective (philosophical activity or spirit)».52 for this reason it makes no sense to speak of a philosophical system of enriques, but rather of his cultural program based on philosophy understood as a critical synthesis of the various sciences, a positive gnoseology, a philosophy of knowledge understood as the construction of a system of disciplines in which science (particularly mathematics), 48 nastasi t. (2012). 49 henri poincaré, emile picard, pierre humbert, emile borel, paul emile appell, jacques hadamard, paul painlevé, xavier léon, emile meyerson, héléne metzger, henri berr, andré laland, henri bergson, léon brunschvicg, louis couturat, edouard le roy, lucien lévy-bruhl, alexandre koyré, georges sarton, charles singer, wilhelm ostwald, max noether, felix klein, ernst mach, albert einstein, otto neurath, franz brentano, gösta mittag-leffler, oscar zarisky. 50 bottazzini, conte, gario (1996). 51 enriques published in this series a series of six volumes, which came out between 1936 and 1939, some of which (such as, for example, les ioniens…) in collaboration with giorgio de santillana. in 1936: les ioniens et la nature des choses; le problèmes de la matière: pythagoriciens et eléates; les derniers “physiologues” de la grèce. in 1937: le problème de la connaissance; empirisme et rationalisme grecs; platon and aristote; in 1939: mathématiques et astronomie de la période hellénique. 52 enriques (1912, pp. 235-236). 21 philosophy, history, didactics and educational sciences interact organically in the formation of knowledge. a more concise definition of scientific philosophy can be: unification of knowledge on a scientific basis, with the history of science and the philosophy of science in a central position. although not constituted in a philosophical system, it is possible to speak of a philosophical thought of enriques, characterized by the composition of different antitheses in new syntheses: 1. reason-experience in experimental rationalism; 2. rationalism-historicism in historical rationalism; 3. intuition-logic united in a single active process; 4. induction-deduction united in the single inductive-deductive process. enriques' scientific philosophy was conceived as a philosophical approach of the scientists themselves to science, and consequently brought together philosophy and science in the same scientist, as at the dawn of philosophical thought. the idea of a scientific philosophy conceived instead as a collaboration between scientists and philosophers must have been widespread enough perhaps even before the publication of the philosophical writings of enriques, if already in 1906 the unione tipografico editrice di torino (utet) published a large volume of 868 pages, titled saggio di filosofia scientifica (pandynamismo) libri tre (physis-psyche-ethos) signed by roberto gaetani d'aragona. in the "introduction" the author clearly indicates the meaning he intends to give to scientific philosophy: the function of philosophy, as we have just said, is to coordinate, select, synthesize the products of the individual sciences for a high rational, economic, biological purpose, whereas that of the individual sciences consists in coordinating, selecting, synthesizing in short and comprehensive formulas the results of sensuous experience in order to know the causal link between a group of observed facts. but philosophy has not always been understood in this way, the individual sciences have not always been distinguished from it. [...] it is also true that [man] has confused the proper function of philosophy with that of the individual sciences. indeed, not even today does everyone agree on the goal that philosophy must set itself, on its limits, on its method; just as there is no agreement on the proper function of each special science.53 d'aragona dwells extensively on the interdisciplinarity that at the time involved scientists of various disciplines (physicists, chemists, physiologists, mathematicians, etc.) and formulates a clear definition of scientific philosophy, as it was understood at the time: … the philosophers will bring together the results obtained by all the technical scientists, and, working on this collected, elaborated, selected, coordinated material, they will create a new synthesis, they will build the scientific philosophy, which will be the true, the healthy, and not the fantastic, convoluted, empty philosophy, based on nothing. [...] philosophy will be the heart of the scientific organism, the technical sciences, the single organs.54 53 d’aragona (1906, pp.3,4). 54 d’aragona (1906, p. 5) 22 the idea of enriques' scientific philosophy can also be found in the famous wiener kreis (vienna circle),55 founded in vienna in 1922 by the german physicist and philosopher moritz schlick. the wiener kreis was a philosophical and cultural club which brought together many prominent philosophers and scientists of the time.56 in this circle schlick founded a new philosophical direction, known by the names of logical positivism or neo-positivism or physicalism, which spread throughout the rest of europe and in the anglo-saxon countries. for his studies in the history of science, for his adherence to the project of a unitary encyclopaedia of science and for his conception of the new "scientific philosophy", enriques figures, in the manifesto of the club, a reference thinker alongside henri poincaré, hermann ludwig ferdinand von helmholtz, bernhard riemann, ernst mach, pierre-maurice duhem, ludwig boltzmann and albert einstein. in fact, the philosophical-scientific approach of the vienna circle, expressed in its manifesto57 written by hans hahn, rudolf carnap and otto neurath, contains all the salient features of enrique's thought: the unitary conception of science, scientific research as a collective work, the denial of an autonomous existence of philosophy as a discipline in itself, the intelligibility of scientific knowledge, the project of a scientific philosophy.58 6 the clash for the philosophical and cultural hegemony in italy enriques' philosophical thought could not be appreciated by gentile and croce, not because of his presumed adherence to nineteenth-century positivism, as they contested and in reality, denied by enriques himself, but because it profoundly undermined the cultural leadership of their philosophy. federigo enriques was not only a great mathematician, a philosopher and a historian of science but also a great teacher, a passionate cultural organizer, an innovative reformer of culture: in short, an all-round intellectual of great stature. it is essential to underline this versatility of his figure as an intellectual, because it is closely connected with his cultural ideal of synthesis of the different sciences and more generally of the 55 initially named “verein ernst mach” (ernst mach company) by hans hahn in honor of ernst mach. 56 ernst mach, rudolf carnap, otto neurath, philipp frank, friedrich waismann, hans hahn, gustav bergmann, carl menger, herbert feigl, viktor kraft, ludwig von bertalanffy, hans reichenbach, kurt gödel, carl hempel, alfred tarski, willard van orman quine, alfred julius ayer, arne naess. ludwig wittgenstein and karl popper did not physically attend the circle but maintained cultural relations with it. 57 h.hahn, l.carnap, o.neurath, wissenschaftliche weltauffassung. der wiener kreis (the scientific conception of the world. the vienna circle) dedicated to moritz schlick was published in the first international conference of the circle held in prague in 1929. in italian: h.hahn, l.carnap, o.neurath, la concezione scientifica del mondo (1979), edited by a. pasquinelli bari: laterza. 58 «the scientific conception of the world is characterized not only by peculiar theses but, rather, by the basic orientation, by the perspective, by the direction of research. it has as its goal the unification of science. its intention is to connect and coordinate the acquisitions of individual researchers in the various scientific fields. from this program, derives the emphasis on collective work, on intersubjectivity, as well as the search for a global system of concepts. accuracy and clarity are pursued, dark distances and impenetrable depths rejected. in science there is no "depth"; everywhere is the surface: all experience constitutes an intricate network, sometimes inscrutable and often only partially intelligible. everything is accessible to man and man is the measure of all things. in this there is an affinity with the sophists, not with the platonists; with the epicureans, not with the pythagoreans; with all advocates of the mundane or the earthly. the scientific conception of the world knows no insoluble riddles. clarification of traditional philosophical questions leads, in part, to unmasking them as pseudo-problems; in part, to convert them into empirical questions, subject, therefore, to the judgment of experimental science. precisely this clarification of questions and statements constitutes the task of philosophical activity, which, however, does not tend to establish specific "philosophical" statements. the method of this clarification is that of logical analysis» (hahn, carnap, neurath, 1979, pp.74,75). 23 different "knowledge", in the spirit of the unity of culture which he contrasts with the centrifugal tendencies of the various “particularisms”, as he called specializations. a cultural ideal opposite to that of croce and gentile, for whom it was "vain hope" to believe that the analytic and synthetic tendencies could coexist in a single philosophical perspective. the international connotation of the scientists' work was not very welcome to fascism, to which gentile adhered. as pietro blaserna said in his introduction to the collective volume cinquanta anni di storia italiana (fifty years of italian history), published on the occasion of the first fiftieth anniversary of the unification of italy, it «flies like an eagle and knows neither limitations nor frontiers, nor customs tariffs and differentials». this absence of «frontiers» certainly could not have pleased fascism, which in fact always exerted a control action on the activities of our scientists, contributing to the dismemberment of fermi's group of physicists.59 the emigration of almost all the "boys of via panisperna" was influenced not only by the racial laws of 1938 but also by the usual reasons for the lack of funds destined for research, which became very strong with the death of corbino and marconi, their "patrons". , both passed away in 1937. in contrast to this international connotation of our scientific community, also aimed at pursuing a modernization and progress of italian society, we find instead the culture of the neo-idealism of croce and gentile characterized by a provincial attachment to the cultural traditions of our country, strongly biased towards the literary-humanistic disciplines. 60 furthermore, his affirmed and acclaimed versatility placed enriques, in the eyes of the two greatest italian philosophers of the time, as a formidable opponent in the conquest of cultural hegemony in our country, unlike other men of science of great fame and prestige, such as giuseppe peano , giovanni vailati and vito volterra, but much more "confined" in their respective scientific programs and, therefore, considered harmless by croce and gentile,61 since culture in italy is traditionally only humanistic: croce and gentile are not worried by those "two or three modest and withdrawn logicians who cultivated an english garden next to their house”.62 the «two or three modest and withdrawn logicians» are peano, vailati and volterra in the allusive words of giovanni papini, quoted above. enriques, then, combined with his cultural versatility an extraordinary ability to organize events and cultural institutes 59 franco rasetti (1901-2001) emigrated to canada in 1939, where he taught at the laval university of québec; emilio segrè (1905-1989) in 1938 was at the university of california, "berkeley". in that same year, the enactment of the fascist racial laws forced him to stay there for the rest of his life; since 1936, the year in which he went to paris to carry out studies with irène curie and frédéric joliot, on the collisions of neutrons with protons and on the electromagnetic transitions between isomers, bruno pontecorvo never returned to italy, living and working in various foreign countries (usa , united kingdom, finland and finally ussr); enrico fermi (1901-1954) after receiving the nobel prize, at the end of 1938, moved directly to the usa with his wife of jewish origins, and remained there until his death. 60 lombardo radice (1982). 61 vailati, who could have been a potential opponent in the conquest of philosophical hegemony in italy, died in 1909. peano was now on the threshold of retirement and his philosophical interests were limited to formal logic understood as an integral part of mathematics. while volterra firmly shared together with others such as enrico betti, ulisse dini, luigi bianchi, giuseppe peano and enriques the aversion and concern for the separation between humanistic studies and mathematics, however, he devoted a large part of his activity to the applications of science aimed at socio-economic progress of italy. 62 guerraggio, nastasi (1993, p. 58). 24 of the highest order, which reflected the absence of boundaries of specialization in his fervor for unitary culture. enriques' main opponents in the battle for philosophical and cultural hegemony in italy were certainly giovanni gentile and benedetto croce, but the style, intensity and results of the controversies that characterized that battle were very different for the two greatest italian philosophers of the era. therefore, it is convenient to treat enriques' relations with gentile and with croce separately. furthermore, the controversy that saw them as protagonists for the philosophical and cultural hegemony in italy included different aspects: on the surface they only seem to be ideological differences, but behind the scenes clear personal jealousies emerge on the part of the two idealist philosophers, who took the form of a real "conspiracy" against the livorno mathematician. 6.1 – enriques and gentile a useful source for forming an idea of the evolution of the personal relationships between enriques and gentile are the 24 letters sent by the livorno mathematician to the sicilian philosopher in the period from 14 june 1907 to april 1942.63 gentile's criticisms of enriques always remained within the orthodox limits of ideological differences, expressed in articles, without ever bordering on indecorous denigration, as instead happened with croce. there was always a relationship of mutual esteem between the two, despite the "difference of views", which strengthened after 1923 to the point of assuming the connotation of a true friendship, which can be explained by gentile's undisputed intellectual honesty which allowed him to recognize other people's commendable goals, beyond differences of views, both in the cultural and political fields.64 the heading of the letters mentioned reflects and confirms this evolution of the interpersonal relationships between enriques and gentile, passing from the « distinguished colleague», of the letters from 14 june 1907 to 12 june 1910, to the «dear minister», of 23 december 1922 and 15 april 1923, to dear gentile», of the letters between 20 december 1924 and 8 december 1940, ending with a «dearest friend» in the letter of april 1942, written by enriques to share with gentile his «affectionate participation» in the «immense pain» for the loss of his son, the theoretical physicist giovanni gentile junior, known as giovannino. gentile's attitude towards science changed radically after the first world war, probably due to the influence of both his pupil ugo spirito and his sons gaetano (doctor) and giovannino (theoretical physicist). science had fully entered the gentile family, as transpired, in 1935, from giovanni gentile's own words: which [italian scientists] have therefore opened the doors of their congresses to philosophy. and it is to be hoped that the philosophers will abandon their tradition of their special congresses.65 the controversy between enriques and the italian neoidealisis began in 1908 with giovanni gentile, following his severe criticism of enriques' volume problems of science (1906), which appeared in «la critica» (1908, vi, pp. 130-146). , in which the sicilian 63 guerraggio, nastasi (1993). 64 during the republic of salò, when, on 21 november 1943, he was nominated by mussolini as president of the italian academy transferred from rome to florence, gentile proposed to the duce the appointment of academics, including non-fascists. 65 guerraggio, nastasi (1993, p.68). 25 philosopher denied enriques' "scientific philosophy" the value of a true philosophy, "oscillating between philosophy, never achieved, and the particular science hardly philosophized, with i don't know what advantage of the scientific spirit". gentile rejects enriques' conception of a science that is never complete and always perfectible, which he attributes to the incorrect identification between the history of knowledge and knowledge: «the progressive correction of knowledge is the history of knowledge», while knowledge is a «vision of the eternal» since the «formal theory of knowing» is out of time. furthermore, gentile disputes the unitary recomposition capacity of individual scientific acquisitions, which is the heart of the spirit of the scientific philosophy advocated by enriques thanks to the «substitution [...] of social work for individual efforts». he considers it a contradiction and a «vain hope»: what is this all of the enthusiasts of the new scientific philosophy? [...] the contradiction [...] between the analytic tendency and the synthetic tendency, which today fatally oppose each other in the mind of every scientist, is a true contradiction, and more profound than enriques thought because it is basically the fundamental contradiction of thought.66 the denial that the analytic and synthetic tendencies of science can coexist in a single philosophical perspective, in the new scientific philosophy, leads gentile to harshly criticize also the validity of the «science magazine» founded by enriques the year before, in 1907, with the engineer-philosopher eugenio rignano, the chemist giuseppe bruni and the doctors antonio dionisi and andrea giardina: a magazine which discusses, in the same issue, the electromagnetism of the universe, mediumship, the relationship between chemistry and biology, the need for light that plants have, consciousness, the austrian economic school, the main laws of sociology , of the origins of religious celibacy, of the reform of the teaching of elementary mathematics, etc., in my opinion, can only encourage scientific amateurism, of which i don't know how much science can benefit. 67 an accusation, that of "scientific amateurism", which clashes with the plethora of excellent names of the collaborators of the journal. among the italians: vito volterra, giuseppe peano, guido castelnuovo, giovanni vailati, orso mario corbino, enrico fermi, edoardo amaldi, camillo golgi, gino loria, ludovico geymonat. among the foreigners: bertrand russell, ernest rutherford, sigmund freud, henri poincaré, emile picard, albert einstein, arthur eddington, werner heisenberg, rudolph carnap, otto neurath, ernst mach, hans driesch, pierre janet, jules tannery. gentile, however as enriques challenged him in 1909 in the preface to the second edition of the problems of science dwells only on chapter iii ("the problems of logic") of the book, criticizing enriques' empirical reduction of logic to psychology. gentile ignores the remaining chapters iv, v, and vi dedicated to geometry and mechanics, not having the preparation to be able to understand their content, as he himself confessed in a letter to croce: 66 «la critica», a. vi 1908, pp. 130-146; also in paolo casini, federigo enriques e i filosofi neoidealisti. 67 «la critica», a. vi 1908, p. 130-146; also in guerraggio, nastasi (1993, p. 59). 26 tomorrow, i hope to write the review of enriques, which is a book that i don't know which way to take, not to say too badly with the fear of not having understood, through my fault, what good there may be.68 enriques replies to gentile's criticism, without however quoting it, in the "preface to the second edition" of problems of science (1909), claiming the originality of his research in the gnoseological theme: but most of the more superficial critics, among the philosophers who have examined my work, have believed they could limit themselves to the first two chapters, and have not seen at all the new solution to the problems of kantian criticism developed in the subsequent ones. the following year, in 1910, enriques polemically tackled the hegelian dialectic in the article hegel's metaphysics considered from a scientific point of view,69 published in the «rivista di filosofia»70 in which he qualified hegel «as a great fantasy and a pauvre intellect» while recognizing in him «an extraordinary imagination, poetic genius, coherence of sentimental inspiration». hegel's style, continues enriques, «... already reveals to us a fundamental aspect of the hegelian psyche which is adverse to scientific thought». enriques defined the hegelian dialectic as an «interesting psychological document, or a tissue of empty verbal associations of formalism», making fun of some obvious “horrors” of the hegelian dialectic: the absurd a priori deduction of the law of gravitation; the definition of light as a pure ideality, which is particularized in the star and recovers its universality in the sun; the dialectical figure who assimilates the obligatory trajectory of the moon to the "rigidity" of the concept and the free trajectory of comets to the "dissolution" of the same logical entity; the magnet seen as a syllogism, where the poles are joined in the middle term. croce reads enriques' article on hegel and urges gentile to reply: you will have seen enriques's nonsense on hegel's metaphysics, published in the place of honor in the "revue de métaphysique". it is also full of insolences against the hegelians. if you want to dedicate a review or a small variety (but short: 3 or 4 pages at the most) go ahead and send it to me soon.71 but he adds in the subsequent letter to gentile dated february 3, 1910: do not accentuate too much the polemic against his person and against his society.72 gentile follows croce's "advice" by writing the article scherzi innocenti intorno alla metafisica hegeliana in «la critica», reacting harshly to those that: they seem insolent and they are not. they are the only way in which professor enriques is capable of expressing his quite dispassionate historical judgment about 68 letter dated palermo, july 26, 1908, in giannantoni (1974, p. 253). 69 enriques (1910). 70 immediately afterwards translated into french: la métaphysique de hegel considérée d'un point de vue scientifique in the review «revue de métaphysique et de morale», 1910, viii, pp. 1-24). 71 croce a. (1981). 72 croce a.(1981, pp. 368-370). 27 the value of hegelianism considered from his point of view: they are the forthright, naively accepted, written and published expression of of what professor enriques feels. enriques reading the hegelian encyclopedia.73 this is the only occasion in which gentile crosses the ideological terrain of contrast, indulging in hostile personal appreciations: let's say it frankly: prof. enriques demonstrates in a thousand ways the most commendable practical zeal for the increase of philosophical studies in italy, and has even come to create the name, if not yet the reality, of an italian philosophical society. but shouldn't he also do something to his own advantage, endeavoring to educate himself mentally and form a clear concept of the present state of philosophy, conscientiously studying its history? 74 6.2 – enriques and croce even benedetto croce with regard to the «rivista di scienza» expresses, in «la critica», a negative judgment on its multidisciplinarity: there is and cannot be anything in common except the material unit of the periodical, a unit which is not that advantage (when it is an advantage) that one can believe: because it can also be a damage, and a serious one. the controversy became more bitter with the subsequent intervention by benedetto croce in his interview given to guido de ruggiero in "il giornale d'italia" on april 16, 1911, immediately after the iv international congress of philosophy in bologna: willing professor enriques, who with zeal but little preparation dabbles in philosophy" [...] "and takes on the burdens of the philosophers' congresses, as meritorious as mine would be meritorious and disinterested, if i organized mathematics congresses. his resentment at the intrusion of the mathematician enriques into his field of study, philosophy, which he believes should be cultivated only by professional philosophers, is evident in croce's words. croce, unlike gentile, denies any cognitive value to science, considered a set of "pseudo-concepts" (abstractions derived from empirical data) as opposed to the "pure concepts" of philosophy (specific cognitive forms of reality as a continuum of infinite individuations), recognizing them only as a practical utility. position, therefore, in stark contrast to that of enriques. the controversy soon degenerates into personal attacks by croce against science: scientific knowledge is not true knowledge, but devices of a practical order. the related concepts are pseudo-concepts, suited to tiny minds not to the universal minds of idealist philosophers. 73 gentile (1910). 74 gentile (1910, p.145). 28 men of science [...] are the embodiment of mental barbarism, deriving from the substitution of schemes for concepts, of piles of information for the philosophicalhistorical organism.75 on the contemporary discoveries and conceptual arrangements of frege, peano and russell, croce expresses himself as follows: the new devices [of mathematical logic] are to be recommended, if anything, to traveling salesmen [so that] they persuade customers and merchants of the usefulness of the new commodity and buy it [...] their philosophical nullity remains [...] fully proven.76 and against enriques: with the procedures of prof. enriques one can, at most, when one is lucky [...], drag along a crowd of the ignorant [...] nothing more treacherous than the crowds of the ignorant [...] like nothing more faithful and persistent than the little chosen ones who, feeling joined by truths, they know they have the present and the future for themselves.77 as giorgio israel states, the polemic «continued with decreasing intensity until 1912 without definite conclusions. however, croce's authority had the practical effect of making a large part of the philosophical and cultural circles line up on positions hostile to the e., for which the end of the controversy was commonly perceived as a “defeat" of the e. ».78 croce does not even spare francesco severi, who had criticized the intolerance of idealism, admonishing him in a poisonous way: to the prof. severi who is a man of study i would like to address a prayer; and it is not to risk discussing concepts that belong to a field foreign to him, and to enter in which i don't know if he has the inclination (everyone has their own inclinations ), but he certainly doesn't have the preparation.79 7 the conspiracy of croce and gentile it has been said previously that the presence, in the " controversy" between croce, gentile and enriques, of a strong personal component raises the suspicion of a real "conspiracy" concocted by the two philosophers, to eliminate from the italian cultural scene their most fearsome opponent. the correspondence between croce and gentile seems to corroborate this further reading of the clash. gentile's scientific lack of preparation confessed to croce, in preparing to write «la critica» the review, warmly supported by croce, of the problems of science, suggests that more than the intellectual need for an "honest" critique of the book by enriques has guided the pen of gentile the will of a personal attack instigated by croce. a clash probably matured from certain jealousies shared with his friend croce, which arose from the alternation, within the space of only two years of important events which constituted 75 croce b. (1908). 76 croce b. (1909). 77 therein. 78 israel, (1993). 79 croce b. (1914). 29 many dangerous signs of encroachment by enriques in the field where croce and gentile felt undisputed protagonists. in 1906 the "mathematician" enriques had created the "italian philosophical society" and made his debut in the philosophical field with the problems of science. the following year, in 1907, he had founded «rivista di scienza» and organized the 2nd congress of the “italian philosophical society” in parma, in which enriques, with his inaugural speech il rinascimento filosofico nelle scienza contemporanea e il valore della scienza (the philosophical renaissance in contemporary science and the value of science)80 underlines the importance of the debate that logicians, physicists and mathematicians have opened or intend to start with philosophers. finally, in 1908, at the iii international congress of philosophy, enriques was invited to participate as president of the italian philosophical society, receiving the task of organizing the 1911 iv international congress in bologna. enriques always made himself very available for a serious and constructive dialogue with gentile and croce, despite the declared strong ideological differences, showing on several occasions his willingness to involve them in all his initiatives of a philosophical nature. but he always receives, in response, attitudes of total closure and hostility. in a letter dated june 14, 1907, enriques explicitly invites his "colleague" gentile to participate in the 2nd congress of the italian philosophical society (sfi), to be held in september in parma, in conjunction with the congress of the italian society for the progress of sciences: distinguished colleague, ... now it would be desirable for our meeting to be attended largely by the most valiant philosophers. [...] the purpose of this letter is precisely to ask you to come to the congress and to bring you some communication, eg. on the new hegelian movement in italy or on any other theme you prefer. i will add that i would also gladly invite croce; but i am held back by the doubt that my question does not please him, since he is a stranger to our society.81 but gentile refused enriques' invitation, as can be seen from the subsequent letter dated 15 july written to gentile from riccione, where enriques was on holiday. in the same letter, enriques' willingness to establish a wider collaboration with gentile also clearly appears, which concerned both the management of the sfi itself and the participation in the iii international congress of philosophy scheduled for the following year, in 1908, in heidelberg: dear colleague, ... i am very sorry that you cannot intervene also because i was counting on consulting with you on many issues that concern our social action [that of the sfi], and on what we can do to prepare for the next congress in heidelberg.82 furthermore, enriques tries to involve gentile in the project of a series of philosophical texts to be produced with the sandron publishing house: with sandron we are in principle in agreement for a collection of works under the title: library of the italian philosophical society. now we need to think about putting this into action by presenting respectable names to the public. please think 80 enriques (1908). 81 guerraggio, nastasi (1993, p. 143). 82 guerraggio, nastasi (1993, p. 144). 30 about it too. we are very grateful to you for the report on german philosophical societies which we await with keen interest. have me, dear colleague, cordially with the highest esteem yours f. enriques.83 in a letter dated february 1910, gentile expresses to croce all his disagreement with enriques' role as "protagonist" in the organization of the iv international congress of philosophy to be held in bologna the following year: dearest benedetto, i have rethought the matter of the philosophical congress of bologna; and i am convinced that we must absolutely resign from the organizing committee, if prof. enriquez does not recognize the advisability of leaving the main position which he has taken on himself, and he does not defer to the whole committee, or at least to the first nucleus of it, as designated by the heidelberg congress, and of which, if i am not mistaken , you too take part in the deliberation on the ways and methods of organizing the congress, reserving for yourself only the part that the committee itself will assign to you, naturally considering your special condition of being in bologna.84 in the same letter, gentile's jealousy and resentment for the notoriety evidently enjoyed by enriques as an all-round intellectual, therefore not only as a mathematician, but also as a philosopher and, not negligibly important, as a cultural organizer are clearly expressed: if the newspapers must continue to talk and gossip about the congress as a personal work of prof. enriquez; 85[...] if the prof. enriquez must present himself to the congress as the most competent representative of the italian studies of logic and general philosophy, and then speak at the inauguration as the president of the italian philosophical society; i do not agree. [...] and, in any case, i believe that this role, which it seems to me that they are arrogating, of head boy does not benefit him or the italian studies.86 8 the legacy of the "defeat" of enriques when speaking of the consequences of croce's philosophy on events in italy, i think we must distinguish three aspects: croce's anti-scientism, the failure of enriques' cultural program, the difficulties of affirming scientific culture in italy with the consequent delay of its industrial development compared to other countries. croce's anti-scientism opinions on croce's anti-scientism are very different: those who, like giulio giorello, affirm it without any doubts and those who, like corrado ocone and giuseppe giordano instead consider it a false reading of croce's thought.87 on croce's anti-scientism, i confess that i know nothing about science, his expressions of contempt for mathematics, science and scientists themselves are unequivocal and numerous. it is only a sleight of hand, of which certain philosophers are 83 there. 84 guerraggio, nastasi (1993, pp. 60-61). 85 this is the (incorrect) spelling of the original. 86 guerraggio, nastasi (1993, pp. 60-61). 87 giorello, ocone (2012); giordano (2016). 31 masters, wanting to overturn them and disguise them with the usual empty whirlwinds of meaningless words. giulio giorello, in his dialogue with corrado ocone on 19 november 2012 è vero che croce odiava la scienza? (it is true that croce hated science) published by reset,88 quotes a passage from croce's work la storia come pensiero e come azione (history as thought and as action), where the philosopher from pescasseroli says that science performs its "useful office" certainly not when it «makes abstractions, builds classes, establishes relationships between classes which he calls laws, mathematical formula and the like. all of these are works of approach aimed at saving acquired knowledge and procuring new ones, but they are not the act of knowing». and what else is the act of knowing? i agree perfectly with giorello when he observes: i would like to know what this act of knowing is for the scholar from pescasseroli! in 1938 we are now far from newton; in 1900 planck introduced the first quantum hypothesis, in 1905 einstein revived quantum theory, reshaped statistical mechanics and laid the foundations of relativity; in 1915-16 general relativity was born; quantum physics went on with bohr and his model of the atom to the formulations of what will be called quantum mechanics in the strict sense. the science is this: calculus, general topology, algebraic topology, functional analysis, differential geometry, etc. where is the act of knowing if not in mathematics? it is significant that at the very beginning of the 1930s paul dirac insisted that mathematics surpasses the empirical information of the world and defines the new objects which will then be explored and controlled in the laboratory. 89 an attempt to redeem croce's anti-scientism was made by giuseppe giordano,90 who drew attention to a 1940 work by croce, il carattere della filosofia moderna (the character of modern philosophy), republished in 1991, in which the philosopher recognized science as a human product , having its own history and therefore its own author: not unlike poetry, a scientific theory is born from a dark background, almost a glimmer that gradually grows in strength and creates clarity, or like a very lively lightning that cuts through the darkness and then seems to get lost and requires long tension and patience waiting for it to return and for the clear light to remain still. sometimes this process lasts chronologically for a long time, and of the great works of science as of those of art we can say equally what has been said sometimes of one or the other, which are youthful thoughts implemented in manhood. 91 in the same work croce, very clearly, recognizes the same genius in the scientist that instead kant considered the exclusive gift of the artist: but one is not a newton without a gift of genius equally generous from nature as the one it bestowed on the poet.92 the thought that croce expresses in his 1940 volume, il carattere della filosofia moderna (the character of modern philosophy), is unfortunately too late to correct the 88 giorello, ocone (2012). 89 therein. 90 giordano (2016). 91 matrogregori (1991). 92 therein. 32 widespread idea of his anti-scientism. however, it is very interesting, because it overshadows the same historicism that belonged to enriques, with which he instead argued at the beginning of the twentieth century. the failure of enriques' cultural program many words have been spent on the question of the outcome of the controversy between enriques and croce-gentile, hypothesizing very different scenarios. however, one fact seems certain, from what we have been able to reconstruct of those events: enriques was left substantially alone in that battle. yet, in 1908, there were still leading scientific personalities who, with their authority, could have teamed up with enriques. among the mathematicians, the aforementioned ulisse dini, cesare arzelà, salvatore pincherle, gregorio ricci curbastro, giuseppe veronese, luigi bianchi, giuseppe peano, corrado segre, guido fubini, leonida tonelli, guido ascoli and guido castelnuovo himself, enriques' brother-in-law. only severi and volterra had the audacity to enter into conflict with croce, denouncing the intolerance of his philosophy towards science. among the physicists, damiano macaluso and the distinguished orso mario corbino, pietro blaserna, antonio pacinotti, guglielmo marconi, domenico pacini, antonino lo surdo were still alive. in short, there was an italian scientific community of the highest order, internationally established, which could have intervened in favor of enriques. why didn't this happen? there was probably an incapacity of our scientific community to know how to face croce's dialectic on a philosophical and cultural level with equal vis-à-vis. only enriques could oppose it, but while croce had a multitude of supporters on his side, enriques was essentially alone. a first cause of the failure of enriques' cultural project, centered on the collaboration between philosophers and scientists, or rather on the application of the scientific method to philosophy, with the birth of scientific philosophy, is certainly the bitter dispute between enriques and the italian neo-idealists, whose it was said. but ludovico geymonat adds two more to it. one is enriques' misunderstanding of the importance that modern mathematical logic and mathematical formalism were increasingly assuming, which according to geymonat transpires from the same work per la storia della logica (for the history of logic, 1922) and which manifested itself openly in the contrasts with giuseppe peano:93 unfortunately, there were many mathematicians in those years, in italy and not only in italy, who viewed research in logic with strong suspicion; but it was certainly particularly serious that this attitude was also shared by a scholar like enriques who did not want to be and was not a pure technician of science. it ended up by throwing a considerable discredit, among "pure mathematicians", towards mathematicians who also dealt with other problems (logical, historical or philosophical). [...] the aforementioned closure with regard to logic has notably weakened the position taken in favor of rationalism, the claim to defend, in our century, the rights of reason without basing this defense on full recognition of the merits acquired in this field by the most refined logical-formal research. however, it is certain that the serious gap did not contribute to making the criticisms raised by the two authors in question effective (or at least immediately effective) [alluding to enriques and the french epistemologist gaston bachelard] against the intrusive idealistic, spiritualistic, irrationalists.94 93 who also saw vito volterra on enriques' side. 94 geymonat (1976, vol. vii, pp .690-691). 33 the other reason for the failure of enriques' program is, according to geymonat, its psychological orientation (common to bachelard) clearly expressed in his work il significato della storia del pensiero scientifico (the meaning of the history of scientific thought, 1936) where: we read that the task incumbent upon it is to enucleate the genesis of scientific ideas, of the great changes they underwent, of the "natural errors" and of the "nonsenses" which even the greatest scientists incurred. it is a study that demonstrates to us the coexistence of both the rational and the empirical factor in cognitive processes, and therefore the irreducibility of science to only one of them.95 geymonat's hypotheses are certainly plausible and apparently very restrictive. indeed, however, the lack of a united front on the part of the scientists and philosophers who were on their side must have constituted an element of weakness against the much more solid and united opposing front of the neo-idealists. i believe another hypothesis on the failure of enriques' cultural program could be, more generally, the incomprehension of enriques' philosophical thought by the entire italian cultural establishment of the first half of the twentieth century. a clear manifestation of that hiatus between humanistic culture and scientific culture which, a few decades later, would be stigmatized by the english physicist-writer sir charles peirce snow in his famous lecture the two cultures, held at the university of cambridge on 7 may 1959 and then republished , with some additions, in the small volume of the same title in 1963. there was probably a lack of preparation on the broader cultural level, on the part of the basic italian scientific community (the secondary school science teachers), unlike those who instead gravitate in the humanistic field. for a long time, the third pages of newspapers were always dedicated to topics of a literary, philosophical (but not philosophy of science) and artistic nature, rarely to scientific topics and when this happened it was only with reference to sensational practical applications of scientific discoveries. i think richard feynman has nailed this problem right by writing: and i believe that science has remained a marginal phenomenon because we scientists are waiting for someone to ask us questions or invite us to explain einstein's theory to people who don't even understand newtonian mechanics, while nobody ever invites us to attack miraculous healings nor does he ask us what the science of astrology thinks today. i think we should mostly write in newspapers.96 furthermore, the lesser ability, compared to the risorgimento and postrisorgimento past, to "combine scientific research and civil commitment" should not be underestimated. but, after the war, it was the philosophers, first with croce and then with gentile, who settled in the palazzo della minerva where mathematicians had been at home for decades as well as in parliamentary halls. with the isolated exception of volterra [...] the mathematical community no longer has a voice in the political institutions of a country that had seen them among the protagonists for so many decades.97 95 geymonat (1976, vol. vii, p. 691). 96 feynman (2002, pp. 121-122). 97 bottazzini, nastasi (2013, p. 416). 34 even the influence of the catholic church, traditionally not prodigal towards science, has certainly held back the spread of a scientific mentality and culture in our country, where its presence is greatest. it should be kept in mind that in post-risorgimento italy secularism and anti-clericalism were much stronger than at the beginning of the twentieth century. in a more realistic vision that takes into account the real complexity of human events, probably all the scenarios mentioned above should be taken into consideration, without excluding anyone. the influence of croce on the scientific and industrial development of italy as for the difficulties of affirming scientific culture in italy, i believe that they are not to be attributed only to crocianism and the infamous gentile reform, although they had a considerable weight. giorello says: italy would be scientifically backward due to the fault of benedetto croce: this is a historiographical myth that even an anti-crociano like geymonat has repeatedly contested and which was the subject of the issue 4/2012 of il mulino by an intervention by alessandra tarquini. italy's backwardness in the scientific field is the result of bad choices by politicians on the one hand and of cultural resistance and the inability of the scientists themselves to communicate on the other and which are therefore independent of croce's idealism. at the cultural level, if anything, there are other forces that could be attributed to the scientific delay, see for example the nefarious influence of the church on some aspects of bioethical research.98 opinions on this issue are also very varied and conflicting. particularly curious is the opinion of the physicist carlo bernardini, who attributes the difficulties of development of scientific culture in italy to none other than our own language, penalized compared to english, in the ability to communicate science.99 and to think that modern science was born in italy with the beautiful vernacular of galilei! returning, however, to the topic already treated by bottazzini and nastasi (2013) of an insufficient presence of men of science in political and social life compared to the risorgimento era, i like to close these pages with the thought of gaspare polizzi, which i fully share: but even in our republican italy the presence of mathematicians, and more generally of scientists, in the public and political scene will no longer be as consistent as in the nineteenth century, and above all science will no longer be seen as a decisive orientation for cultural and productive development of the country. and this is perhaps one of the underlying problems that do not allow italy to return to being a great nation of culture and science.100 acknowledgment 98 giorello, ocone (2012). 99 bernardini, de mauro (2003). 100 polizzi (2014). 35 the author expresses his gratitude to dr. federico enriques, nephew of federigo, for reviewing the text and dr. 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(2022) capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility. substantia 6(1): 77-105. doi: 10.36253/substantia-1423 received: oct 01, 2021 revised: dec 15, 2021 just accepted online: dec 16, 2021 published: mar 07, 2022 copyright: © 2022 kenndler e. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler institute for analytical chemistry, faculty of chemistry, university of vienna, währingerstrasse 38, a 1090, vienna, austria e-mail: ernst.kenndler@univie.ac.at abstract. since electrophoresis is a physical phenomenon – it is the movement of dispersed charged particles relative to a liquid under the influence of a spatially uniform electric field – its history is not limited to its use as a separation method. the history of capillary electrophoresis in particular, i.e. electrophoresis in capillary-sized open tubes, therefore does not begin in the 1960s, as is commonly assumed, but already a century earlier, if one refers to its principles. capillary electrophoresis of ions was first performed by the french physicist edmond becquerel in 1861, about the same year as that of colloidal particles. becquerel owns therefore the priority. it was subsequently performed on three other occasions in the long nineteenth century, by wilhelm beetz in 1865, by wilhelm ostwald and walther nernst in 1889, and by friedrich kohlrausch and adolf heydweiller in 1895. all of these experiments were carried out in the context of research on conductivity and ion migration. based on the theories of grotthuß, davy, and faraday, it was believed until the 1840s that both the anions and the cations of a dissolved strong electrolyte – to which this review refers – migrate at the same velocity or speed in an electric field, but experimental observations in the mid-1840s cast doubt on this view. wilhelm hittorf was the first to show that these ions could migrate at different speeds, still consistent with faraday´s laws. he was able to prove his hypothesis with experimental data and determined the migration velocities of the two types of ions in an electrolyte relative to the sum of their velocities, which he termed “überführungszahlen” (transference or transport numbers). however, they did not initially yield the absolute velocities of the ions. this was achieved later by f. kohlrausch, who devoted four decades of his research life, namely from the end of 1860 to about 1910, to the study of the conductivity of electrolyte solutions and the migration of ions. he discovered in 1879 that ions move independently from each other in solution (1st kohlrausch law). it is remarkable that until the late 1880s it was generally believed that free ions do not exist in solutions in the absence of an external electrical force, but that ions were always tightly bound to their counterions. this belief dated back to grotthuß in 1805. although rudolf clausius hypothesized in 1857 that free ions are actually present in solutions as result of their thermal motion, this did not find further resonance. it is also remarkable that during this whole period under consideration no attempt was ever made to separate ions with the same charge, although their different migration properties were already known. continuing his research, http://www.fupress.com/substantia http://www.fupress.com/substantia 78 ernst kenndler kohlrausch found empirically in 1900 that at extremely low concentrations the molar conductivity of ions, i.e. the conductivity related to their concentration, is a function of the square root of their concentration and approaches a certain limit at infinite dilution (2nd kohlrausch law). as a precursor to this law, he derived in 1885 for larger concentration ranges the little-known relationship of molar conductivity as a function of the cubic root of concentration. he calculated the migration velocities of ions from their conductivities and characterized the migration behavior by their mobility, which is a central property in electrophoresis. kohlrausch was certainly a formative investigator of the electrophoretic properties of ions, but his work focused mainly on strong electrolytes. this review covers the research results in the field of mainly this class of electrolytes in the period from 1840 to about 1910; but it also reports on the personal background of some researchers who, despite important contributions, have been unjustly forgotten, as well as on researchers who were active outside the scientific community. mention is made, for example, of gustav theodor fechner, who was the first to prove the fact, indispensable for electrophoresis, that ohm´s law also applies to electrolyte solutions. however, in contrast to the generally applied results of his investigations, he himself was rather ignored by later researchers. the conductivities and electrophoretic properties of weak electrolytes, which were known to kohlrausch and his contemporaries but hardly explicable to them, at least until 1884, are not discussed in detail in this review. in that year, svante arrhenius published his groundbreaking theory of electrolyte dissociation as his dissertation. this theory and the resulting consequences for the whole subject of electrolyte solutions require, however, a separate historical retrospect. keywords: first capillary electrophoresis, ions, strong electrolytes, hittorf, clausius, kohlrausch. introduction although the motion of dissolved charged particles by electrophoresis1 during electrolysis was the topic of part 2 of this series[4] the magnitude of their migration velocities was not subject of discussion.2 that part covered the period from the first observations of electrolysis and the inextricably linked electrophoresis in 1800, and the assumption that electrical forces from the electrodes exert on the ions by action at a distance. this concept was superseded in the mid-1830s by michael faraday’s pioneering theory that ions move at electric lines of force, which led to james clerk maxwell’s field theory. [5] at the time when the action at a distance was widely accepted, the migration velocity of the ions was believed to vary with their distance from the electrodes, while as consequence of the field theory the assumption of a constant velocity prevailed. in no case, however, was the magnitude of the velocity of ion migration addressed. this will be the subject of this part 3. in short, and just for the sake of historical completeness, we mention the first attempt to measure the migra1 to avoid misunderstandings, we indicate how we define electrophoresis. it is not just the migration of particles in an electric field, which, like colloids, have an electric double layer. nor is it just the powerful separation method in use today, whose overwhelming importance, for example, for genomics, proteomics, metabolomics, and numerous other important areas we highlighted in part 1.[1] it is in principle, as hanns lyklema most generally defined it, “the movement of dispersed particles relative to a fluid under the influence of a spatially uniform electric field”. [2][3] we therefore have every reason to call such migrations electrophoretic (see also part 2 of this series).[4] 2 it should be noted in advance that the present part of our historical review deals mainly with single pure strong electrolytes in free solutions. tion velocity by peter mark roget,3 which he already undertook in 1807. roget tried to determine the migration speeds of oxygen and hydrogen generated by the electrolysis of water,4 but without success, as described in refs. [6, 7], chapter galvanism, p. 30. michael faraday then took up the subject only in 1833 in the fifth series of experimental researches (refs. [8, 9]; 524. – 535.). in the eighth series[10] from 1834 he explicitly argued that both the anions and the cations of an electrolyte travel at the same speed in opposite directions at the electric lines of force, and based this assumption on the law of the definite electrochemical action. he argued that equal chemical equivalents of oppositely charged ions are required at their respective electrodes at the same time, otherwise electrolysis cannot happen. we discussed this point already in part 2.[4] faraday briefly returned to the subject of migration velocities of particles in solution in 1838 in the thirteenth series.[11] at the end of this article he reviewed earlier attempts to measure the speed of electricity in metallic conductors, which had been unsuccessfully carried out by william watson in london in 1747 and 1748. [12, 13] that of light was carried out (with some success) by charles wheatstone in 1834.[14] faraday himself speculated on an approximate velocity of the ions in solu3 the british physician peter mark roget (1779, london – 1869, west malvern, worcestershire) was fullerian professor of physiology an der royal institution from 1834 till 1837. 4 roget tried to measure the time interval between the closing of the electric circuit and the appearance of the gases on the separate electrodes, which were 46 inches (i.e., ca. 117 cm) apart. after the completion of the circuit, however, no measurable interval could be determined; a result which was predicable taking into account the already known theories of grotthuß and davy. 79capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 tion, (ref. [11], pp. 164, 165) but only vaguely.5 in none of his contributions, however, faraday reported on values of the migration velocities. the assumption of equal ion velocities was challenged by frederic daniell and william allen miller by contradictory results of the electrolysis of copper and of zinc sulfate solutions in a double membrane cell, i.e., a cell divided by two diaphragm. after electrolysis, they found the same amount of copper in the cathode compartment as was initially put in. the amount of reduced copper plus the quantity that remained dissolved was exactly that as before electrolysis. from this, they concluded that the copper ions do not migrate and only sulphate traverses the entire distance between the electrodes. they hypothesized that the flow of the electrophoretic current6 was mainly by the anions, while the cations contributed little.[15, 16] claude servais pouillet observed a similar effect in 1845 when he electrolyzed a solution of gold chloride.7 he used a u-shaped tube with one of the electrodes in each arm. after passing the current, he found almost 5 the english apothecary, physician and natural philosopher sir william watson (london, 1715 – 1787) charged wires with electric machines in london in 1747 and 1748.[12][13] however, differences in the time of appearance of the discharges at the two extreme ties of a wire of 4 miles in length could not be determined visually. charles wheatstone attributed this miscarriage to the laggardness of the observing eye. he therefore constructed a device with rapidly rotating mirrors with which time intervals for the occurrence of electrically generated sparks could be measured beyond a millionth of a second. the measured velocity of light was either 576000 or 288000 miles per second, depending on the experimental circumstances assumed.[14] if we take the english mile, standardized in 1592 by the english parliament as 1609 m, the latter velocity is about 460000 km.s-1. faraday himself attempted to derive an approximate value for the velocity of ions in solution, not of the action of electricity (nrs. 1651. and 1652. in the thirteenth series). it just ended with a hypothetical comparison of the quantity of electric power equal to the effect appearing instantly at the distance of 576000 miles from its source, on the one hand, with the effect which is obtained by the movement of hydrogen and oxygen after electrolysis of water through a certain distance of one tenth of an inch within an hour and a half, on the other hand. 6 our justification for coining the term electrophoretic current for the flow of charges carried by ions is given in detail in part 2.[4] we emphasize that by electrophoresis we mean the movement of charged particles under direct current conditions, but not under alternating current conditions. under both conditions the electrical conductivity nevertheless has the same values. 7 claude servais mathias pouillet (1790, cusance, doubs – 1868, paris) was a french physicist, and politician until the february revolution from 1848. his research comprised optics, photometry, thermodynamics and electricity. his main publications were, among others, the book “élémens de physique expérimentale et de météorologie”, published in 1827,[17] and “mémoire sur la chaleur solaire, sur les pouvoirs rayonnants et absorbants de l’air atmosphérique et sur la température de l’espace“(memoir on the solar heat, on the radiating and absorbing powers of atmospheric air and on the temperature of the space) in 1838.[18] claude pouillet must not be confused with his brother marcellin pouillet, who was chemist at conservatoire des arts et métiers. no gold in the arm with the negative electrode, but gold in its initial content in the one with the positive electrode. pouillet concluded from this result that the negative electrode took up the gold, while the chloride was transported to the positive electrode through a series of decompositions and recombinations and was set free there. like daniell and miller, pouillet concluded that the migration velocities of the anions and the cations are not the same, contrary to previous belief.[19, 20] alfred smee8 had a different point of view. he assumed that the primary process is the decomposition of water when a metallic solution (i.e., a solution of a salt of a metal) is subjected to galvanic action. the following reduction is a secondary process caused by the hydrogen produced first by the metal from its salt solutions.[21, 22] in summary, all experiments reported so far have led to different and contradictory assumptions about the electrophoretic migration velocities of ions but none has contributed to the central question of their magnitude. however, before continuing the discussion of further approaches to determining the ion speeds, initiated by wilhelm hittorf and his concept of the transference number, the author will not fail to show that theories long believed to have been overcome still had ardent supporters in the middle of the long nineteenth century, albeit rarely. at that time, it came as a surprise that established theories, e.g., those of m. faraday, were still rejected by staunch proponents of the phlogiston doctrine. one of these advocates was william ford stevenson (1811 – 1852), after all fellow of the royal society, who in 1846 published a book whose title already fully reveals its content. it reads “most important errors in chemistry, electricity, and magnetism, pointed out and refuted: and the phenomena of electricity, and the polarity of the magnetic needle accounted for and explained by a fellow of the royal society”.[23] moreover, stevenson was so violently provoked by the award of the gold medal of the royal society to the noted physico-chemist william robert grove9 in 1847 that he wrote a second conspicuously polemical book in 1849 entitled “the composition of hydrogen and the non-decomposition of water incon8 alfred smee (1818, camberwell – 1877, finsbury circus) was an english electro-scientist, metallurgist, chemist and surgeon. 9 sir william richard grove (1811, swansea, wales – 1896, london) was a welsh advocate. he did not practice this job; instead he became interested in electrical phenomena, and published his first paper on this topic in 1838.[24] grove improved the voltaic battery and invented a fuel cell battery what he reported in 1839,[25][26] and which is named after him. a basically similar cell[27][28] was invented by the german-swiss physicist and chemist christian friedrich schönbein (1799, metzingen – 1868, baden-baden). 80 ernst kenndler trovertibly established, in answer to the award of a medal by the royal society whereby the contrary doctrines are absolutely affirmed, also the absurdity of the existing systems of electricity and magnetism demonstrated and the true one given.”[29] in this book, which, like his earlier one, was published by the author himself because all journals had refused to accept it, he again vehemently rejected all previous theories about the effect of electricity on liquids because they did not agree with the phlogiston doctrine. he was going so far as to accuse the committee of the royal society, which awarded grove the golden medal, of complete incompetence. we briefly quote verbatim one of his numerous attacks on the committee, for example that on pp. 22-23. every body must know that the appreciation of a paper upon a special subject, such as chemistry, must finally depend upon the opinions and report of those gentlemen who are presumed to be specially acquainted with the subject. my observation must therefore be understood to apply exclusively to the committee of chemistry, and to no other portion of the royal society. of the names of the gentlemen composing this committee i am at this moment ignorant, and i have no motive whatever to induce me to make the inquiry. i must, however, remark, that a total absence of information (a fact which will be elicited from a perusal of these pages) in a conclave of scientific men upon a subject on which they were voluntarily about to pronounce, and actually did pronounce, a most important opinion (an erroneous one, as may be supposed) pregnant with vast consequences is, i believe and trust without a parallel in the annals of science.10 to remind the readers of the state of science at that time, we mention that already more than four decades ago, viz. in 1804, the last prominent supporter of the phlogiston theory died, john priestley, who defended this doctrine as late as 1803 with the book “the doctrine of phlogiston established and that of the composition of water refuted”.[30] we refer, on the other hand, to some contemporary works, e.g., those of michael faraday in 1846,[31] of james clerk maxwell ś first paper also in 1846,[32] of rudolf clausius and of james prescott joule in 1850,[33, 34] to name only the best known, and come to the works of wilhelm hittorf, who raised the knowledge of ion migration to a next level. 10 the capital letters and italics correspond to the original text. w. hittorf: relative migration velocities and transference numbers of ions of an electrolyte from 1853 to 185911 wilhelm hittorf developed a promising attempt to measure the migration velocities of ions.12 he described his basic idea in 1853 in a first paper out of four, entitled “ueber die wanderung der ionen während der elektrolyse. erste mittheilung.”[36] (on the migration of ions during electrolysis. first notice.)13 this concept was still based on the traditional view that a cation, c, and an anion, a, are tightly bound in solution in the absence of an electric field, forming a single macroscopically uncharged unit or molecule ca. consequently, free ions were believed not to exist. note that in hittorf ś conception the distance between the molecules was much larger than the moleculeś size. this differed significantly from the theories of grotthuß, davy and berzelius, in which the molecules in the chains to which they arrange were in direct contact (see part 2 of our series). this greater distance between the molecules is a precondition for hittorf ś theory. hittorf based his concept on the relationship between the velocity of ions to their respective electrodes and the change in their concentrations there before and after electrolysis. hittorf believed, in contrast to the established assumption of equal velocities, that ions migrate at different speeds, and postulated that this hypothesis can be confirmed by determining the change of their concentrations in their solutions at the electrodes by chemical analysis. he assumed that more of fastermoving cations must be found at the cathode and fewer of slower-moving anions at the anode, and vice versa. in hittorf ś concept the molecules ca with cations c and anion a are initially aligned under the influence of the electric potential, so that the ions are directed towards their respective electrodes, as shown in fig. 1, row a (anions are depicted as black semicircles, cations 11 on november 24th of the same year 1859 charles darwin published his seminal book “on the origin of species by means of natural selection, or the preservation of favoured races in the struggle for life”.[35] 12 johann wilhelm hittorf (1824, bonn – 1914) studied mathematics und natural sciences in bonn. after receiving his doctorate in 1848, he was given the position of a university lecturer in the following year. in 1856 he became professor of physics and chemistry at the university of münster (westphalia) and director of laboratories from 1879 to 1889. in the 1850s hittorf contributed significantly to electrochemistry with the introduction of the transference numbers of ions, and constructed the instrumentations for their determination. hittorf directed his research further to the passage of the electric current through gases and to the emitted spectra, and discovered the electron rays, later called cathode rays. 13 the engl. translation was published in harper’s scientific memoirs from 1899, ref. [37], pp. 49-80. 81capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 as open semicircles; single-charged ions are considered). next, the assembled ions of molecule ca separate from each other and move to the nearest oppositely charged ion,14 with which they combine to form a new molecules ac (row b). note that the ion travels as a free ion during the movement over this distance. prior to the next step, this newly formed molecules ac had to rotate by 180° from ac to ca in order to get their proper position, that is to say, to be aligned with the respective electrodes (row c). then, this process of decomposition and recombination continues as long as the electric potential is applied and the ions are finally decomposed electrolytically. the number of cations and anions decomposed by electrolysis is the same, independent of their velocities and in accordance with faraday ś law of definite electrochemical action (see chapter 3.1.4. in part 2). in order to prove the validity of his concept experimentally, a vessel of a measuring device was first filled with a solution with a given initial concentration of the electrolyte. in contrast to daniell ś instrument, the vessel was not separated by a membrane, a diaphragm or another porous boundary. in figure 1 the ions of the molecules are depicted as full and empty semicircles. if we suppose that the velocities of both ion species are equal, the ions reassemble into new molecules in the 14 we called it counterion in previous part 2, and will use this term in our publications. it is customary in modern phraseology. middle of their distance, and both travel along the same distance in a given time. therefore, the change of their concentrations in their respective electrode compartments would be the same. in the general case, when the two types of ions have different velocities, they travel different distances within a certain time before reuniting to form the next molecule. then, eventually, more ions of the faster species reach the solution near the respective electrode, and fewer ions of the slower species reach the oppositely charged electrode. thus, the number of ions of the two species in their electrode compartments is unequal. we emphasize again that this argument is valid even if, according to faraday’s above-mentioned law, the same number of both ions is electrolytically decomposed in their compartments. the question arises as to how hittorf solved the problem of separating the vessel into an anode and cathode compartment without inserting a porous boundary. hittorf ’s solution, which circumvented this problem is shown schematically in figure 2.15 there, the electrolyte solution is separated not by a real boundary but by an imaginary one, indicated by the vertical line, which can be placed anywhere. the cathode is on the left side, 15 in this figure, the representation of the molecules in the vertical direction and in direct contact to each other is as in berzelius’ paper, ref. [38], p. 278, is in discrepancy with hittorf´s own assumption on p. 180, ref. [36] “der zeichnung liegt die annahme zu grunde, daß die entfernung zwischen den benachbarten atomen des elektrolyten größer als diejenige ist, in welcher die chemisch verbundenen ionen jedes atoms von einanander abstehen“ (the drawing is based on the assumption that the distance between the neighboring atoms of the electrolyte is greater than the distance between the chemically bonded ions of each atom.) this requirement is satisfied in figure 1. however, the deviation in figure 2 has no consequence for hittorf´s conclusions. [the author]. figure 1. hittorf´s concept and determination of the relative velocities and the transference numbers for the case that anions and cations have equal migration velocities. anions: black semicircles; cations: open semicircles. in solution, the ions are present in pairs as macroscopically uncharged molecules, since all ions unite with their oppositely charged ions by electrostatic attraction. there are no free ions present. row a: when an electric potential is applied, the molecules are aligned in the direction of their respective electrodes. row b: the molecules are split into their ions, which migrate towards their corresponding electrodes, but reassemble with the oppositely charged ions in their immediate vicinity to form new molecules. row c: the molecules rotate 180° to take the proper position in the field. details can be found in the text. the figure is reproduced from hittorf´s publication from 1853 (ref. [36], plate ii, after p. 352). figure 2. hittorf´s concept and determination of the relative velocities and transference numbers for the case that anions and cations have different migration velocities. anions: black full circles; cations open circles. cations migrate in direction of the arrows to the left, anions to the right. details are described in the text. (from ref. [36]). 82 ernst kenndler the anode on the right side. the cations are depicted as open circles, the anions as black circles. the transfer mechanism involving the 180° rotation is the same as described above. in the present example, the initial number of each ion type or equivalent is 18 (top row), the fictitious cathode compartment (left) contains 8 molecules, the anode compartment 10. after completing the circuit, the ions migrate with velocities, v. in the case depicted in figure 2 the cations cross the fictitious boundary faster than the anions. we assume, for example, that the anions travers ⅓, the cations ⅔ of their distance after their dispartment and the following recombination. but how can these different distances be determined? hittorf turned this problem from the molecular to the molar scale, and developed the following method, for which we select at random the conditions in the anode compartment. he considered the change of the numbers (or equivalents) of anions and cations there. he recognized that from the begin of the electrolysis, shown in the top row, to its end (in the bottom row) the number of cations is reduced from 10 to 6, that is, 4 cations traversed the boundary and migrated towards the cathode. the number of anions in the anode compartment changed from 10 to 12, that is, it increased by 2. in the solution, 6 from the 12 anions remained and 6 were electrolytically decomposed; this decomposition applies to the cations as well. thus, 2 anions crossed the boundary and moved into the anode compartment. to conclude, in the anode compartment a reduction of cations from 10 to 6 happened, equals 4, and the change of the number of anions is from 10 to 12, equals two. it follows that the change in equivalents in the anion compartment for the anions and for cations is ⅓ and ⅔. this result which would be obtained by experiment is identical to our input assumption. generally speaking, if the one ion traverses 1/n of the distance, the other (n-1)/n, after electrolysis the compartment of the former ion contains 1/n equivalent more of the one, and (n-1)/n equivalents less of the other ion. hittorf termed these numbers “überführungszahlen” (transference or transport numbers) which we symbolize by τ. their sum (τ++τ–) equals one. as mentioned above, they can be derived by quantitative chemical analysis of their concentrations. the transference numbers express the migration velocity of the one ion relative to the counterion in a given electrolyte. the smaller the transference number of the ion, the slower is its migration velocity relative to its counterion. in the above example τ– was ⅓, τ+ was ⅔, which is consistent with our initial assumptions about the different distance the two ions travel before forming a new molecule, or that the cation migrates at twice the speed of the anion. in general, the ratio of the transference numbers is equal to the inverse ratio of the velocities by τ+/τ–=v–/v+. it should be noted that one does not obtain the absolute migration velocity of an ion, but only that relative to the counterion of the same electrolyte. it is also mentioned that the transference number expresses the fraction of current, i, transported by one type of ion in relation to the total current, i.e., the sum of the currents of both types of ions. it reads, for example, for the cation τ+=i+/(i++ii). to get the currents hittorf used a poggendorff silver electrometer to simultaneously measure the total amount of current flowing during electrolysis and obtained (i++ii). then, he recalculated i+ from the number of equivalents of the cation which he determined by chemical analysis in the anode compartment, and received the fraction of the current which was transported by the cation, and which is equal to its transference number τ+. since (τ++τ–)=1, the transference number, τ–, of the anion can be calculated without measuring it. it is therefore sufficient to measure the concentration, and thus the value of τ, of only one ion in one compartment, and neither both in the same compartment, nor all four in the two compartments. for the experimental determination of the concentrations of the ions after electrolysis, hittorf modified the cell of daniell and miller by omitting the membranes. readers interested in details are referred to the comprehensive description in hittorf ś first notice of 1853[36] which after all covers the three pages 187-189. the schematic drawing of the device is given in fig. 4 in plate ii, after p. 352. in this first notice hittorf examined different copper and silver salts. he found that their transference numbers were independent of the (low) current. their changes, within the investigated temperature range between 4°c and 21°c proved to be unreliable.16 relevant for future research, especially for that of friedrich kohlrausch, was his observation that the transference numbers can depend significantly on the concentration of the electrolyte. 16 note that we are discussing transference numbers, not conductivities. the german physicist gustav heinrich wiedemann (1826, berlin – 1899) observed that the electric conductance (or resistance) of electrolyte solutions depends on their viscosity. he varied the viscosity of the solution by varying the temperature and/or the salt concentration, and supposed a relation between the electric behavior and the mechanistic properties of the solutions. however, wiedemann found that these conclusions were based on imperfect and preliminary experiments (see ref. [39], pp. 169, 170). wiedemann´s conclusions nonetheless preceded walden´s rule or walden´s product (named after paul walden, a russian-latvian-german chemist), which he formulated in 1906,[40] sixty years after wiedemann´s assumptions. walden´s rule states that the product of the conductivity of an electrolyte solution at limiting conditions and the viscosity of the solvent is constant and independent of the solvent. 83capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 hittorf also speculated on possible sources of error, primarily with respect to the role of water, since he assumed, contrary to popular belief, that instead of the cation of the salt, h+ from the water could be reduced directly. however, he found that this primary, direct reduction of h+ to gaseous hydrogen could be neglected. to support his opinion, he used solvents that were not decomposed electrolytically and measured the transference numbers in absolute ethanol and, in later notes, in amyl alcohol. his results made it clear that water did not contribute to the current; it acted only as an electrochemically inactive solvent of the salts. for the second notice from 1856 hittorf constructed an improved device, again without membrane, and investigated whether or not electroosmotic flow affected the transference numbers.[41] he compared the results measured in devices with and without a membrane, and obtained the same transference numbers. history showed that it is not uncommon for a front of critics and opponents to form when a new theory or method is introduced.17 this also happened with hittorf, and so he began his third notice in 1859[42] with a reply to wiedemanń s critique.[39] then a comprehensive reply to the derogatory reproaches [43, 44] of gustav magnus18 followed, whom he called ”hauptgegner meiner arbeiten“ (main opponent of my works). in ref. [42], p.342, hittorf wrote magnus hatte in seiner ersten abhandlung, §9, meiner elektrischen arbeiten erwähnt und angegeben, daß dieselben mit der zersetzung, welche die elektrolyte durch den strom erfahren, nichts zu thun hätten und über die daniell śche theorie … nichts lehren. (magnus had mentioned my electrical work in his first paper, §9, noting that it had nothing to do with the decomposition of electrolytes by the current and that it taught nothing about daniell’s theory.) the rigor with which hittorf rejected this criticism is evident in the fact that it extended over twenty printed pages. the remaining part of this third notice dealt with the transference of compounds that hittorf had not examined in the second notice. a paragraph in the fourth and last notice[45] worth noting comprised, beyond the determination of transfer17 svante arrhenius, for example, was even lampooned when he presented his dissociation theory. ironically, 25 years later he was awarded the nobel prize. we will tell this episode in the next part 4 of our historical review series. 18 heinrich gustav magnus (1802, berlin – 1870) was an influencing german chemist and physicist. in 1845 he became professor of physics, chemistry and technology at the university in berlin. his students or coworkers were, among others, a. von baeyer, e. du bois-reymond, r. clausius, p. von groth, h. von helmholtz, g. kirchhoff, a. kundt, e. sarasin, j. tyndall and e. warburg. ence numbers, hittorf ś critique of clausiuś theory.[46] we will return to this theory below. contrary to established opinion, clausius postulated that free ions do exist in solution even in the absence of an electric potential due to their motion caused by their thermal energy. hittorf strictly rejected this theory and commented on p. 584 der schluß, zu den hr. clausius aus seinen prämissen gelangt, steht meinen erfahrungen nach mit der wirklichkeit im widerspruch, … es sind bloß die letztgenannten zersetzungen, welche die theorie der elektrolyse von hrn. clausius brauchen kann. bis jetzt ist kein chemiker so kühn gewesen, sie anzunehmen, … (the conclusion mr. clausius draws from his premises is, in my experience, at odds with reality, … only the latter decompositions can use mr. clausius’ theory of electrolysis. until now, no chemist has been so bold as to accept it.) we see that hittorf was not only the target of criticism, but was himself a critic. the last part of this paper dealt with the determination and discussion of the transference of complex ions, and what he called “double salts”.19 salts of cadmium and iodine, for example, which contain complex anions will play an important role in arrheniuś dissociation theory. at the time of hittorf publications transference numbers by his method were also determined by g. wiedemann[47] and by a. weiske.[48] these and hittorf ś data were later used by friedrich kohlrausch in his studies of conductivities. we already pointed out that a given ion has different transference numbers in electrolytes of different composition, depending on the counterion. for example, hittorf determined τ+ of 0.63 for ag+ as acetate and of 0.47 as nitrate (ref. [36], p. 206).20 from these data it follows that the silver ion velocity is 1.7 times higher than that of acetate, and about 10% lower than the nitrate velocity. regrettably, the method provided only the relative ion velocities, but not the absolute values of the individual ion species. the decisive advance towards the solution of this problem was initiated by kohlrausch’s work on the conductivities of electrolyte solutions, in particular by his law of independent ion migration. we will discuss it below. 19 it can be assumed that the majority of readers have little interest in details. we have therefore included them in this footnote. these double salts consisted, for example, of k, ag, and cn, or na, pt, and cl. their number was rather limited, since most were not stable when dissolved in water. hittorf measured and discussed the transfer, for example, of the complex salts consisting of cadmium and iodine, which he was able to dissolve undecomposed in absolute ethanol and in amyl alcohol. 20 these values are in good agreement with current transference numbers, at 25°c, e.g., of 0.624 for ag+ (0.01 mol.l-1) as acetate and of 0.4648 as nitrate.[49] 84 ernst kenndler the reader may wonder that this historical review does not even mention a certain empirical law which – as generally assumed – friedrich kohlrausch had confirmed by careful measurements in 1869.[50] it had, however, already been applied earlier, namely in the 1830s by michael faraday and in the 1850s by wilhelm hittorf in their investigations of the electrophoretic current in solutions of ions. it was also an indispensable law in further research on this subject and is still daily practice. what is meant is the law about the connection between electrical potential difference, resistance and current strength, which georg simon ohm had found empirically in the middle of the 1820s, albeit for metallic wires, i.e., for 1st class conductors.[51-56] that it also applied to 2nd class conductors, that is to say, to solutions of ions, was by no means a foregone conclusion because of the fundamental difference in the nature of conduction. so how did it come about that ohm’s law proved to be valid also for solutions of ions? a leap in time, back to 1831: g. th. fechner´s proof that ohm´s law applies to solutions of electrolytes before we get to kohlrausch ś above-mentioned conductivity measurements, we have to realize that he did, in principle, measure the resistance or the specific resistance of the electrolyte solution, a property that we have yet not even addressed in this historical retrospect. to do this, we have to go back to the 1820s, to the time when faraday made experiments in organic chemistry in davy ś laboratory. at that time georg simon ohm pioneered the research in electric resistance of 1st class conductors. ohm was not affiliated with the scientific community at the time of his research. he was a school teacher at the jesuit gymnasium in cologne when he derived his law in mid-1820s. he performed his experiments in the laboratory of this college with wires made of different metals and various lengths and diameters. he published his preliminary results initially in two treatises in 1825.[51, 52] as he was not satisfied with his work,21 he developed a new theoretical approach, which led to the law named after him. this well-known law says that the current strength is directly proportional to the electric potential difference 21 in the last two sentences at the end of his second paper from 1925,[51] ohm complained about the lack of support for his research: “meine arbeit·fängt allmählig an, sich zu einem ganzen zu runden. nur bedaure ich, daß ich häufig aus mangel an mitteln, untersuchungen abbrechen muß, die ich so gern weiter verfolgt hätte“ (my work gradually begins to round off into a whole. my only regret is that i often have to abandon investigations that i would have liked to pursue further, due to lack of funds.) and indirectly proportional to the resistance of the conductor. ohm published his new theory in 1826.[53-55] in his opus magnum “die galvanische kette, mathematisch bearbeitet” (the galvanic chain, mathematically processed) [56] he summarized in 1827 the results together with a comprehensive mathematical treatment. ohm ś work did not attract much attention, but the interest changed when french physicists claimed priority of the law for claude servais mathias pouillet,22 who rediscovered ohm ś law years later and published his results in 1837[57] (german version in ref. [58]; the editor, johann christian poggendorff, added a critical comment to this version, cited in footnote 23). pouillet derived the according relations rather from experimental results which was considered as being superior to ohm ś merely theoretical approach. his assertion of priority provoked a heated debate, led primarily by jean claude eugène péclet, who published a harsh rebuff of pouillet’s claim in an essay entitled “lettre touchant un passage de la dernière édition du traité de physique de m. pouillet” (letter concerning a passage in the last edition of the traité de physique by m. pouillet)[61] stating c’est seulement en 1837 que m. pouillet a publié son mémoire dont toutes les formules se déduisent de celles de m. ohm par de simples transformations, comme m. henrici l’a démontré (annales de poggendorff tomes liii[62] et liv[63] ), … (it was not until 1837 that m. pouillet published his memoir, all the formulas of which can be deduced from those of m. ohm by simple transformations, as m. henrici has shown (pogg. annal. liii and liv),…)24 finally and at last ohm’s priority was recognized internationally, and in 1841 he received the prestigious copley medal from the royal society in london. nevertheless, in germany it lasted until 1852 that he became professor for experimental physics at the university in munich, at the age of 63, two years before his death. 22 we quoted pouillet already in the introduction of this review. 23 poggendorf commented: „wiewohl die resultate dieser abhandlung zum theil nur bestätigungen der von ohm („die gaivanisehe kette” und schweigg. journ. bd. xxxxvi s. 137),[59] entdeckten, auch von fechner (maaßbestimmung über die galvanische kette) und früher von pouillet selbst (annal. bd. xv s. 91)[60] beobachteten gesetze sind, so schien doch die unverkürzte mittheilung derselben,schon weil sie so wenig berücksichtigt wurde sind, nicht überflüssig. p.” (although the results of this treatise are partly only confirmations of the laws discovered by ohm (“die gaivanisehe kette” and schweigg. journ. bd. xxxxvi p. 137),[59] also by fechner (maaßbestimmung über die galvanische kette) and earlier by pouillet himself (annal. bd. xv p. 91)[60] so the unabridged communication of them seemed not superfluous, already because they were so little considered. p.) [citations added by the author]. 24 complete literature sources added by the author. 85capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 initially regarded of minor importance, his law was later recognized as highly significant for the technology of ever-widening electrical telegraphy, especially after the mid-1850s with the introduction of the single-wire system by samuel morse. we have mentioned above that after his publication in 1827 ohm ś work was widely ignored, and only few scientists recognized its importance, with gustav theodor fechner25 as ohm ś main supporter (his portrait is shown in figure 3). 25 gustav theodor fechner (1801, groß-särchen, now żarki wielkie, near muskau in lower lusitia – 1887, leipzig) attended the academy of arts in dresden from 1814, and studied medicine there from 1817 and in leipzig from 1818, where he graduated in 1823. however, he left the field of medicine and completed his habilitation in 1823 at the philosophical faculty. he was appointed professor of physics in 1834; his research focused on galvanism and optics. due to a severe eye complaint from 1840 to 1843, he retired. in 1860 he expanded weber´s law to weber-fechner law. this law expresses the non-linear relationship between psychological sensation, s, and the physical intensity, i, as s = k ln i. fechner’s scientific merits should not be underestimated, although they were, because he extended ohm’s theory of the 1st to 2nd class conductors. his work is therefore indispensable for electrophoresis. he is also worth noting because, in addition to his scientific interests, he had a penchant for writing satirical pseudo-scientific works. in 1821 he published his first paper ever; it was entitled “beweis, daß der mond aus jodine bestehe” (proof that the moon consists of iodine),[65] published under his pseudonym dr. mises. it is a humorous pamphlet against materialistic medicine. of similar kind was his scientific satire from 1825 “vergleichende anatomie der engel” (comparative anatomy of angels).[66] in these early 1820s, fechner prepared the translation of jean-baptiste biot ś textbook “précis élémentaire de physique expérimentale”[67, 68] into german, which appeared in 1824 and 1825, but he found the description of electricity and of the theory of galvanism in this book highly out of date. in order to raise these themes to the contemporary level, he decided to upgrade it by ohm ś theory. at this occasion, he found keen interest in this topic, and expanded his research from the hitherto investigated metallic conductors to liquids, pioneering in this way the quantitative context of electric potential difference, current and resistance in ion solutions.26 after two years of extensive experimental work, fechner presented his results and conclusions in the book “massbestimmungen über die galvanische kette” published in 1831.[69] fechner demonstrated that ohm ś law not only applies to metallic conductors, but also to electrolyte solutions. he gave a résumé of these findings (amongst others) by stating on pp. 235-236 of his book … (i) der leitungswiderstand der flüssigkeiten ist dem abstande der erregerplatten darin direct proportional… (ii) der widerstand der flüssigkeit steht im umgekehrten verhältnisse des querschnittes der flüssigkeit… .(iii) der widerstand der flüssigkeit ist unabhängig von beschaffenheit der plattenpaare… (iv) der widerstand der flüssigkeit nimmt ab mit der quantität saurer oder salziger bestandtheile, die man in dieselbe hinzufügt. (v) durch fortgehends gleiche zumischungen gleicher antheile säure wird der widerstand des brunnenwassers auch fortgehend um gleiche quantitäten verringert…“ ((i) the electric resistance of the liquids is directly proportional to the distance of the excitation plates therein. (ii) the resistance of the liquid is in inverse proportion to the cross section of the liquid … (iii) the resistance of the liquid is independent of the nature of the plate pairs … (iv) the resist26 the water fechner used in his experiments can be considered rather as a dilute electrolyte solution. water with the highest purity which was available for him was well water, which certainly contained a relatively high amount of ions. all the more his results are to be appreciated. figure 3. portrait of gustav theodor fechner (1801 – 1887). date and author unknown. source, ref. [64], public domain. 86 ernst kenndler ance of the liquid decreases with the quantity of acidic or salty components are added to it. (v) by continuously adding equal amounts of acid, the resistance of the well water is also continuously reduced by equal quantities…) if we convert these formulations into a modern notation, we get for a given solution that (i) r=prop l; (ii) r=prop(1-a); (iii) r≠f(u); (iv) and (v) r=prop(-s.c). symbol r stands for the electrical resistance of the liquid, l is the distance between the electrodes, a is the cross sectional area of the electrodes, u is the electrical potential difference, and c is the concentration of acidic or salty additives to water; s is a factor of proportionality. it is seen that these findings actually represent the first evidence that ohm ś law also applies to liquid conductors.27 it is worth noting that the combination of (i) and (ii) leads to equation r=prop(l/a), in accordance with modern notation as r=ρl/a, in which ρ is termed electrical resistivity or specific electrical resistance. after his retirement, fechner focused mainly on philosophy and topics of psychophysics and psychological aesthetics. during this time he published works mainly based on natur philosophie and religious-mystical ideas.28 r. clausius’ theory: free ions are present in electrolyte solutions even without an applied electric field coming back now from fechner ś time to 1852, when rudolf clausius29 turned his interest on 2nd class conductors after publishing his paper about the work done on 1st class conductors and the heat generated thereby30,[84-86] in “ueber die elektricitätsleitung 27 it is clear that points (iv) and (v) do not have counterparts in pure metals, but the observations were nevertheless correct and preceded at least within a small concentration range the measurements of the conductivities by f. kohlrausch. 28 fechner published, for example, poems,[70] a book about the soul life of plants,[71] 3 vol. about things of heaven and the hereafter,[72][73][74] about psychophysics,[75][76][77][78] a book with the mysterious title “the day view versus the night view”,[79] but also a paper in pogg. ann. phys. chem. “ueber die bestimmung des wahrscheinlichen fehlers eines beobachtungsmittels durch die summe der einfachen abweichungen” (on the determination of the probable error of an observation mean by the sum of the simple deviations.)[80] 29 rudolf (julius emanuel) clausius (1822, köslin, province of pomerania in prussia, now koszalin, poland) -1888, bonn] is one of the first theoretical physicist of the nineteenth century and a central founder of thermodynamics (2nd law of thermodynamics), and the kinetic gas theory. he created the concept of entropy and contributed significantly to fundamental concepts of statistical mechanics. less known is his work on free ions in solutions, which he carried out mainly during his research activities as professor at the eth in zürich in the 1850s. 30 in this paper clausius derived the theoretical basis of the empirical in elektrolyten” from 1857[46] (engl. vers., on the work performed and the heat generated in a conductor by a stationary electric current,[87] french vers., mémoire sur la chaleur dégagée par les courants électriques.[88]), clausius expressed his rejection of the established view of the transport of electric charges through electrolyte solutions, a theory that was going back to theodor von grotthuß. even in clausiuś time (and later), it was generally assumed that the electrolyte molecules, called the complete molecules by him, were composed of atoms or groups of several atoms, which he called partial molecules.31 each molecule consists, as was believed, of two tightly bound partial molecules of opposite charge (i.e., ion and counterion). we recall that in the theories of grotthuß and davy the molecules form a continuous chain that extends without gaps from one electrode to the other. only the terminal molecules of this chain are in direct contact with the electrodes and are the first to be decomposed during electrolysis. then, an instantaneous recombination of the ions with the counterions of the neighboring molecules, and the decomposition of the newly formed molecules happens along the entire chain. we will not repeat this mechanism of the flow of electricity as we discussed it in detail in the previous part 2 of our series.[4] important to emphasize is that the established theories of grotthuß and davy exclude the presence of free ions in solution in the absence of an electric potential, because an electric force would be mandatory to separate the tightly bound ions of a molecule. in his said paper from 1857 clausius radically broke with this conventional view[46, 87, 88] he first considered a liquid that contains “electrolytic molecules”, i.e., electrolytes. clausius’ basic condition for all further considerations was that electric neutrality had to be in every volume element of the liquid. if there was no external electric force, the molecules were dispersed in an arbitrary order and possibly vibrated around a certain equilibrium position. he further assumed that in the same molecule the attraction between ion and counterion, which are close to each other, is greater than the attraction of one ion to the counterion of another molecule. clausius assumed, in analogy to his paper “ueber die art der bewegung, welche wir wärme nennen”[90] (the nature of the motion which we call heat)[91] from results of j. p. joule,[81] m. e. lenz, the father of robert lenz[82] and edmond becquerel.[83] 31 clausius did not use the terms ion, anion and cation in this paper, although they have been known since 1834, when michael faraday introduced them.[89] clausius differentiated the neutral “gesamtmolecüle” (complete molecules), which were combinations of the oppositely charged ions, which he called “theilmolecüle” (partial molecules). for the sake of simplicity, we name clausius´ “complete molecule” as molecule, and, “partial molecules” as ions, and cations and anions if appropriate. 87capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 the same year that – in absence of an electric field – the electrolyte molecules do not remain permanently in the liquid in an equilibrium position around which they oscillate. on the contrary, they are moving and their motion is irregular. moreover, an ion can be disconnected from its molecule due to its thermal energy and then moves randomly between the other molecules in the solution. it can happen that this ion attracts the counterion of another molecule more strongly than the ion and counterion of this molecule attract themselves. in this case, this ion and the counterion of the molecule form a new molecule and the parent ion is set free. it then moves in the solution between the other molecules and reacts with one of them in the manner just described; then the whole process continues. a second possibility for the formation of free ions assumed by clausius was that two different molecules interact with each other. in this case, it can happen that the ion of one molecule takes a preferred position over the counterion of the other molecule and these two ions combine to form a new molecule. this process releases two ions, which either combine to form a new molecule or disperse between the other molecules in the solution and act there as described above. we emphasize again that we have described the situation in the absence of an external electric force. it was considered by clausius as the natural state of electrolytes in solution. when an external electrical force acts, the first reaction of the molecules would be to rotate into the proper position towards their respective electrodes (what davy and berzelius did not take into account, but hittorf did). then the force would separate ion and counterion of a molecule and drive them in opposite directions. in this case the ion of one molecule may combine with the counterion of the other. however, this can only happen if the attractive force between the ion and the counterion of the one molecule is overcome. clausius argued that the influence of the external electric force not only starts from a certain strength, but that even the slightest force acts in the manner described above. the magnitude of the effect increases with the strength of the force. that is, the effect fully complies with ohm’s law. he wrote (we reproduce verbatim the engl. version, ref. [87], p. 99-100) but in order to separate the already combined partial molecules, the attraction which they exert upon each other must be overcome, for which a force of a certain intensity is necessary; hence we are led to the conclusion, that so long as the force acting within the conductor does not possess this requisite intensity, no decomposition whatever can take place; but that, on the other hand, as soon as the force has attained this intensity, a great many molecules must be simultaneously decomposed, inasmuch as all are exposed to the influence of the same force, and have almost the same relative positions to each other. and continued so long as the moving force acting within the conductor is below a certain limit, it causes no current whatever; so soon as it attains this limit, however, a very strong current is suddenly produced. this conclusion, however, is in direct contradiction to experiment. the smallest possible force gives rise to a current accompanied by alternate decompositions and recombinations, and the intensity of this current increases in proportion to the force, according to ohm’s law. however, in the original paper written in german, this passage has another meaning; it reads (ref. [46], p. 346-347) so lange die im leiter wirksame treibende kraft unter einer gewissen gränze ist, bewirkt sie gar keinen srom, wenn sie aber diese gränze erreicht hat, so entsteht plötzlich ein sehr starker strom. dieser schluß widerspricht aber der erfahrung vollkommen. schon die geringste kraft bewirkt einen durch abwechselnde zersetzungen und wiederverbindungen geleiteten strom, und die intensität dieses stromes wächst nach dem ohm’schen gesetze der kraft proportional. [the reader’s attention is drawn to footnote 32]. if an external electric force acts, the cations and the anions in the solution do not move randomly, but are driven in opposite directions. in addition, the force facilitates the decomposition of the molecules, and the detachment of an ion from its molecule occurs more frequently than without such electric force. clausius assumed that the number of positive and negative ions which move in opposite direction is not necessarily equal, it depends on their activity of molecular motion, which can be different for different ions. the counterdirected movement of both types of ions represents the galvanic current33 in the liquid. its strength is given by the sum of the flows of both ions. 32 the author would like to add a note here. he refers to the misleading or even wrong translation of clausius’ original work in the english version, which he has marked in italics in the main text. clausius wrote verbatim: “dieser schluß widerspricht aber der erfahrung vollkommen.” the english version reads: “this conclusion, however, is in direct contradiction to experiment.” the term erfahrung is translated here by experiment, but the correct translation is experience – in fact a crucial difference. in the french version the sentence is correctly translated as “… en d´autres termes, aussi longtemps que la force est au-dessous d´une certaine limite, il n´y a pas de courant, et dès que cette limite est dépassée, il nait subitement un courant intense. cette conclusion est évidement contraire à l´expèrience.”, ref. [88], p. 254.) 33 we call it, as defined in the previous parts of our review, the electrophoretic current. it is not the flow of charges carried by electrons. the 88 ernst kenndler this theory also offers the explanation why the conductivity of a 2nd class conductor increases with increasing temperature: it is because the greater the activity of motion of the particles due to their thermal energy in the solution, the more the decomposition of the molecules is facilitated. although clausius’ innovative theory of the permanent presence of free ions offered new explanations for the properties of electrolyte solutions and became widely known, it is noteworthy that the majority of the scientific community (but not its elite) did not replace the theory published by grotthuß half a century ago in 1805. this lack of scientific acceptance was criticized, to quote an arbitrarily chosen example, in an 1879 publication, another two decades after clausius’ work. franz exner,34 professor of physics at the university of vienna and teacher of two nobel laureates, pointed out in his publication “ueber die electrolyse des wassers” (on the electrolysis of water), ref. [92], p. 350) … dass die clausius’sche hypothese über die constitution der flüssigkeiten der theorie der electrolyse… mit den bekannten thatsachen nicht nur nicht im widerspruche steht, sondern durch dieselben auf das entschiedenste bestätigt wird. unter allen umstânden aber ist es an der zeit, die jetzt noch fast ausschliesslich citirte grotthuss’sche theorie der electrolyse endgültig fallen zu lassen; denn seit wir … einen klarern einblick in das wesen dieser vorgänge erlangt haben, erscheinen die von der grotthuss’schen theorie geforderten, von molecül zu molecül fortschreitenden zersetzungen und wiedervereinigungen als eine absurde vorstellung. (… that clausius’ hypothesis of the constitution of liquids does not contradict the theory of electrolysis … not only with the known facts, but is most decidedly confirmed by them. under all circumstances, however, it is high time to finally abandon grotthuß´ theory of electrolysis, which is almost exclusively cited; for since we … have gained a clearer insight into the nature of these processes, the decompositions and reunifications which progresses from molecule to molecule, as required by grotthuß´ theory, appear to be an absurd notion.) it took nevertheless another decade before the existence of free, non-associated ions, as formulated in svante arrheniuś seminal theory, was accepted, albeit reluctantly and against fierce opposition. charges are carried – notabene – by ions, which is the unique feature of electrophoresis. 34 franz serafin exner (1849, vienna – 1926) was an austrian physicist. in 1891 he became professor of physics at the university of vienna and succeeded j. j. loschmidt. his best-known students were the polish physicist marian smoluchowski, and the austrian physicists erwin schrödinger (nobel laureate for physics 1933), and victor franz hess (nobel laureate for physics 1936). f. kohlrausch’s fundamental contributions to ion conductivity, velocity and mobility friedrich kohlrausch,35 who coined the subject of ion conductivity and ion migration (of strong elecrolytes) in the next decades, concluded his habilitation in 1863, not in electrochemistry, but “ueber die elastische nachwirkung bei der torsion“[93, 94] (elastic aftereffects during torsion) at the university of göttingen, where he became private docent in 1866 and in 1867 associate professor. during the four years in göttingen from 1866 to 1870 he was mainly, though not exclusively, engaged in research on geomagnetic and electrical measurements, and in investigations of the resistance and conductivity of electrolyte solutions.36 kohlrausch’s entry into electrochemical research in 1868 together with his coworker and former doctoral student wilhelm august nippoldt37 kohlrausch published his first contributions to electrochemistry in 1868 and 1869 in various versions.[50, 105-107] the overarching subject of these papers was ”ueber die gültigkeit der ohmschen gesetze für elektrolyte und eine numerische bestimmung des leitungswiderstandes der verdünnten schwefelsäure durch alternierende ströme“ (on the validity of ohm’s laws for electrolytes and a numerical determination of the electric resistance of dilute sulfuric acid by alternating currents).[106, 107] in this paper, kohlrausch and nippoldt posed three questions: (1) how can the influence of the polarization of electrodes be exclud35 friedrich kohlrausch (1840, rinteln-on-weser – 1910) was a german physisist. he studied physics in erlangen and göttingen, where he received his doctoral degree in 1863. in 1867 he was appointed to a professorship in göttingen. famous for his exact experimental work, his accurate measurements and his outstanding level in research, kohlrausch became professor at eth zurich in 1870, at technical university darmstadt in 1871, at the university of würzburg 1875, and at the university of strasbourg as from 1888. he was successor of h. von helmholtz at the physikalisch-technischen reichsanstalt in berlin, where he was director between 1895 and 1905. the reichsanstalt was founded in 1887 and was the first government-financed research institution worldwide, where their staff members – in contrast to the universities – were not committed to teach. prominent members were walther (hermann) nernst (1864 – 1941), emil (gabriel) warburg (1846 – 1931), walther (wilhelm georg) bothe (1891 – 1957), albert einstein (1879 – 1955) and max (karl ernst ludwig) planck (1858 – 1947). 36 beside these main topics he also dealt, e.g., with the construction of an apparatus which serves for room cooling,[95]. the speed of propagation of the stimulus in the human nerves,[96] elastic effects after torsion,[97][98] geomagnetic observations in göttingen,[99][100][101][102] the amount of electricity generated by an influence machine,[103] and others. 37 the title of nippoldt´s dissertation was “untersuchungen über den galvanischen widerstand der schwefelsäure bei verschiedenen konzentrationsgraden” (studies on the galvanic resistance of sulfuric acid at various degrees of concentration.)[104] 89capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 ed when determining the electrical resistance of liquids? (2) does ohm’s law also apply to decomposable conductors?38 and connected with this: how can clausius’ postulate be proven that ohm’s law still holds for the smallest possible electromotive forces? (3) how does the electrical resistance of decomposable conductors depend on their concentration?39 clausius explicitly pointed out in his paper about free ions from 1858, discussed above, that “the smallest possible force gives rise to a current accompanied by alternate decompositions and recombinations, and the intensity of this current increases in proportion to the force, according to ohm’s law.” since clausius gave no experimental results for this “smallest possible force”, and did not cite any sources in which this force was given,40 we find this central argument vague and indefinite and a weak point in clausius’ chain of reasoning (see also footnote 32). however, kohlrausch and nippoldt took up this challenge and attempted to measure a critical value of this force. unable to achieve a sufficiently low alternating current, they applied thermoelectric current instead, generated by a pair of cu-fe wires. and indeed, kohlrausch and nippoldt were able to spectacularly determine the lowest electromotive force at which the electrolytic decomposition of the zinc vitriol solution still occurred, i.e., they measured whether or not current and emf were in direct proportion.41 their results led them to conclude that ”… die gültigkeit des ohmschen gesetzes … bis zu einer elektromotorischen kraft von 0,00000233 38 kohlrausch and nippoldt called here electrolyte solutions, i.e., 2nd class conductors, as opposed to metals, “decomposable conductors”. 39 kohlrausch, of course, was not the first to research the conductivity or resistance of electrolyte solutions. such earlier investigations had been discussed and compared in g. wiedemann`s “galvanismus”(ref. [108], pp. 191-208). wiedemann reported on a. de la rive (1830); g. t. fechner (1831), see the chapter “leap in time” above; c. s. m. pouillet (1837); m. e. lenz (1838); f. c. henrici (1845) w. g. hankel (1846); e. becquerel (1846); e. n. horsford (1847); e. becker (1850, 1851); g. wiedemann (1856); a. saweljew (1856); w. schmidt (1859). none of these researchers, however, has systematically studied this topic for about four decades and none of them has contributed with such fundamental findings. in this respect, the justification that kohlrausch has coined the topic seems appropriate. 40 in a letter to the chairman of the deutschen bunsengesellschaft, w. nernst, from may 24, 1908, kohlrausch himself wrote about clausius’ argumentation and his and nippolt´s measurement: “nach den von clausius entwickelten vorstellungen dürfte dies wohl als wahrscheinlich gelten, war jedoch niemals an der erfahrung gepriüft worden. diese lücke wurde ausgefüllt.“ (according to the ideas developed by clausius, this is very likely, but had never been tested on experience. this gap was filled.).[109], p. 385. note that kohlrausch insisted on a test. 41 the solution of zinc vitriol (i.e., zinc sulphate) electrolyzed by amalgamated zinc electrodes to exclude polarization contained 16.6 g of the salt in 100 g solution. this solution was filled into a tube with 2400 mm2 cross-sectional area and had a length of 83 mm. the current was measured with nobili’s astatic galvanometer. oder 1/429000 grove hierdurch als bewiesen ansehen kann“ (… the validity of ohm’s law … down to an electromotive force of 0.00000233 or 1/429000 grove can thus be regarded as proven). this emf in grove is equivalent to 4,2.10-6 v. referring to the work of h. buff from 1855,[110] kohlrausch and nippoldt deduced that this weak electrical force which decomposed their electrolyte was greater than the force of its chemical affinity. thus they agreed with clausius’ theory, but their conclusion was based on factual data (p. 379). they ended the paper with the nonetheless qualifying remark die prüfung des ohmschen gesetzes für elektrolyte auf noch kleinere kräfte als die obigen auszudehnen, darf weder als überf lüssig noch als unmöglich bezeichnet werden. (to extend the test of ohm’s law for electrolytes to even smaller forces than the above may be said to be neither superfluous nor impossible.) the first and third questions posed above related to one of the main sources of errors in measuring the electrical resistance and conductivity of liquids, namely the polarization of the electrodes. two options were known to minimize polarization. to use alternating instead of direct current; and to measure with amalgamated zinc electrodes, that were not polarized. kohlrausch and nippoldt opted for alternating current, which they generated in their laboratory using a rather elaborate device they built themselves.42 they mounted, in addition, large-area platinum electrodes to reduce the current density there. sulfuric acid as the test substance was diluted in water at different percentages[106, 107] and the resistances were determined.43 their reciprocals, the “relative conductivities”, are plotted in figure 4. they were in accordance with earlier contributions by other authors, but were more accurate. the curve of the relative conductivity of the solution vs. the specific weight of the sulfuric acid diluted in steps of ten (percentage of acid) increased at low concentrations, but then reached a maximum at 1.233 specific weight which equals 31.5 weight % of sulphuric acid hydrate (the “hydrate theory” is addressed in the following part 4 of our historical reviews). 42 in their first electrochemical experiments, kohlrausch and nippoldt used a rather complicated apparatus to generate alternating current, which was later replaced by one that was much easier to handle. they produced equal but oppositely directed currents of short duration and rapid succession by induction with a rotating magnet using large-area platinum electrodes (later, a small induction coil was used). the number of revolutions of the magnet was determined by means of a siren fixed in the axis of the magnet and its pitch was compared with a set of organ pipes. the induction currents were observed with a sensitive weber bifilar dynamometer, which was later replaced by a wheatstone bridge. 43 the resistance was related to that of mercury. 90 ernst kenndler kohlrausch ś finding that the conductivity depends on the concentration of the dissolved electrolyte initiated one of his major research activities. he carried out analogue measurements, also with alternating current,44 and published the results in 1875 with otto grotrian,[111, 112] and in 1876 in a paper with a similar content, but with an improved experimental set-up.[113] in the same year he published the preliminary version of the law of independent ion migration,[114] the subject of the following chapter. the law of independent ion migration: 1st kohlrausch law around the 1850s several authors, to name wilhelm hankel,[115] gustav wiedemann[39, 47] and wilhelm beetz[116] investigated the relationship between the electrical resistance of electrolyte solutions and their viscosity.45 in 1856 wiedemann came to the preliminary conclusion that under the conditions of his experiments (ref. [47], p.229) “ … würde … der leitungswiderstand der zähigkeit der flüssigkeiten direct … proportional seyn. (…would … the resistivity be directly proportional to the viscosity of the liquids.)46 44 the salt content in the solutions was between ca. 3% and 30% (w/w). it seems perhaps superfluous to nearly always indicate the concentrations of the electrolytes in the respective measurements. however, this is not the case, since they play a central role in the migration properties of the ions. 45 the device to measure the viscosity was based on the findings of the german hydraulics construction engineer gotthilf ludwig hagen[117] and the french physiologist and physicist jean léonard marie poiseuille.[118][119][120] the device resembled the nowadays used standard u-tube viscometer. 46 see also refs. [39], pp. 169, 170; [108], pp. 421-426; [121], pp. 632-634, and [122] the german physicist georg quincke47 modeled in 1871 the resistance to the motion of “theilmolecüle” (partial molecules), the ionic constituents of a “gesammtmolecül” (complete molecule) in a thin thread of a liquid solution and brought into play not only the viscosity of the liquid but also the mutual attraction and repulsion of the ions.[123] he argued that this electrical interaction is compensated by the corresponding effect of the neighboring counterion and is therefore irrelevant, and concluded that die specifisches leitungsfähigkeit der gesamten flüssigkeit ist gleich der summe der partiellen specifischen leitungsfähigkeiten der einzelnen bestandtheile. (the specific conductivity of the entire liquid is equal to the sum of the partial specific conductivities of the individual components.) this reads in eq. (26) on p. 16 that λ= λ1+λ2+…λr. here, λ is the specific conductivity of the solution, and λi are those of the individual ionic constituents, the partial molecules, with i ranging from 1 to r.48 in the second half of the 1870s otto grotrian found a striking connection between electric resistance and mechanic frictional resistance.[124, 125] rudolf von lenz, in the same years, investigated a relationship between the resistance of haloïd salt solutions and their density (not of their viscosity).[126, 127] all researches agreed that the liquid of the solution decelerates the motion of the ions and thus increases the resistance of the current. by the way, this is a prerequisite for a constant migration velocity of an ion driven by a constant force in the theory of electric lines of action of michael faraday (see part 2, chapter 3.1.6.). this point of view was shared by kohlrausch, who supposed that the source of the frictional resistance and thus the influence on the migration velocity of the ions in dilute aqueous solutions can only come from the water molecules due to their large excess over all other constituents. taking into account this connection between electrical force and mechanical resistance in ion transport, kohlrausch came up with the key idea that 47 georg hermann quincke (1834, frankfurt/oder – 1924, heidelberg) studied physics, chemistry and mathematics, and presented his doctoral thesis on “kapillarerscheinungen bei quecksilber“ (capillary phenomena with mercury) at the humboldt-university in berlin in1858. in 1875 he became successor of gustav kirchhoff at the university of heidelberg, where he retired in 1907. interesting for the present subject are his scientific activities in capillarity, in the electric properties of colloidal particles and in electroosmosis (we will come back to these important contributions in a later review). 48 note that quincke used clausius´ phraseology, and that this equation has some similarity with kohlrausch´s law of independent ion migration. figure 4. “relative leitfähigkeit” (relative conductivity) vs. specific weight (also density) of dilute sulphuric acid. the resistance was measured with alternating current as described in the main text. abscissa: specific weights of the acid solution at 18.5°c from 1.0504 to 1.5025, corresponding to a content of the acid from 8.3 to 60.3%. the curve depicts the “leitungsvermögen” at 22°c. from ref. [107], p. 386. 91capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 the extent of this mutual influence is most likely different for different ions, which would lead to their unequal migration velocities. he communicated his hypothesis in 1876 – the preliminary version of the law of independent ion migration – and confidently stated (ref. [114], p. 215)49 ist nun die lösung sehr verdünnt, so wird diese reibung vorwiegend an den wassertheilchen stattfinden. demnach wird man weiter zu schließen versucht sein – und dies ist ein schluß, der meines wissens noch nicht gezogen worden ist – daß jedem elektrochemischen elemente (z. b. dem wasserstoff, chlor oder auch einem radicale wie no3) als solchem ein bestimmter widerstand in verdünnter wässeriger lösung zukommt, gleichgültig, aus welcher verbindung es elektrolysirt wird. (if the solution is very dilute, this friction will mainly take place on the water particles. accordingly, one will be tempted to conclude further – and this is a conclusion which, to my knowledge, has not yet been drawn – that every electrochemical element (e.g., hydrogen, chlorine or even a radical like no3) as such has a certain resistance in dilute aqueous solution, regardless of the compound from which it is electrolyzed.) he argued, on the one hand, that the current is related to the sum of the velocities (v–+v+) of the two oppositely charged ions.50 the current is, according to ohm’s law, also in inverse proportion to the resistance, that is to say, it is proportional to conductivity λ. hence the conductivity is proportional to (v–+v+).51 he pointed 49 in this early paper he took values for electrolyte concentrations in the low weight percent range. 50 in the following discussion electrolytes with two single-charged ions are considered for the sake of simplicity (for other electrolytes the corresponding equations have to be extended by the numbers of ions, v, and the charge numbers, z. since electrolytes with v–=v+ and z+=|z–|=1 are regarded, the molar and the equivalent concentrations and the respective conductivities are the same. 51 we point out that at the time of kohlrausch there was no standardized terminology, nor were the symbols of the physical and chemical quantities unified. kohlrausch, for example, used the terms “leitungsvermögen” or “leitfähigkeit” of the solution, which is “conductibility” or “conductivity” in english, and ascribed it in some papers by symbol k, in others by λ. more misleading is kohlrausch´s usage of the term “beweglichkeit”, with symbols l+ and l-, in other papers u and v, which is translated into english as “mobility” (a point that has been mentioned in the english translation of kohlrausch´s paper from 1876[114] in harper’s scientific memoirs from 1899 (ref. [128], footnote at p. 89). in kohlrausch’s paper from 1876 “beweglichkeit” is a dimensionless number, which is the velocity of migration of an ion related to that of hydrogen. the latter has the arbitrarily chosen value of 1. kohlrausch initially formulated in his hypothesis of independent ion migration that the conductivity is the sum of the “beweglichkeiten” of the ions, which he expressed by λ=(l++l–) or by k=(u+v) (comp. with the different notations given in the main text). in later papers, kohlrausch used the term “wanderung” (engl. migration) instead. somewhat problematic for the reader of kohlrausch’s original works may be that he often changed terms during the four decades of his scientific activity. this is understandable, because, as we mentioned above, there was no standardized nomenclature. however, since this review is not intended to be a textout that, on the other hand, hittorf ś transference number expresses the ratio of the velocity of an ion to the sum of the velocities of both ions, e.g., for the anion by τ–=v–/(v–+v+). for two electrochemically equal electrolytes, (1) and (2), with a common anion and with cation velocities of v+(1) and v+(2), respectively, he set λ(1)/λ(2)=(v–+v+)(v–(1)+v+(2)), expanded the equation by v–, and obtained the relationship λ(1)/λ(2)=τ–(2)/τ–(1). the corroboration of his hypothesis required that the ratio of the conductivities of the solutions of two electrolytes with a common ion had to be equal to the inverse ratio of the transference numbers of the common ion (it was already noted above that the transference number of an ion in an electrolyte depends on its counterion). kohlrausch scrutinized his hypothesis on the basis of transference numbers of about a dozen electrolytes from monobasic acids52 (salts of alkalis and earth alkalis as chlorides, bromides, iodides, nitrates, perchlorates and acetates), and actually found a good agreement with his theoretical prediction. thus he concluded on p. 219 die annahme von der unabhängigen beweglichkeit der ionen läßt sich zweitens durch die überführungszahlen allein prüfen und hierdurch auch an körpern, deren leitungsvermögen noch nicht bekannt ist, bestätigen oder widerlegen. (secondly, the assumption of the independent migration of the ions can be proved by the transfer numbers alone and thus confirmed or disproved on bodies whose conductivity is not yet known.) to this end, kohlrausch took four compounds, which were composed of two pairs of ions, and related their resulting eight transference numbers to one another. in fact, he was able to calculate “beweglichkeiten” (verbatim “mobilities”), the velocities relative to that of hydrogen. this hypothesis must not be confused with the final law of independent ion migration kohlrausch published three years later.[130] at the end of his 1876 paper (on p. 222) he came nevertheless to the conclusion that further experimental investigations were necessary to decide whether this aforementioned statement applies also in general or not. he began to examine systematically and with exceptional accuracy numerous aspects of the influence of various book of physical chemistry, we usually adopt the terms as kohlrausch used it in the respective paper, unless they are completely misleading. in the cases where it could lead to confusion, we will use the modern terminology and symbols. 52 it is hardly known that acids with 1, 2 and 3 h+ ions and bases with corresponding ohions were called mono-, diand triatomic until 1853, when faustin-j. (also faustino) malaguti (1802 – 1878) proposed in his “leçons élémentaires de chimie” (ref. [129], p. 331) to call them mono-, diand tribasic acids and mono-, diand triacidic bases, respectively. it is still modern nomenclature. 92 ernst kenndler experimental variables on the conductivity of electrolyte solutions till around 1910 (that is, please note, still in the long nineteenth century). during this time period, he published almost 145 papers on this subject. but first he continued work on his above-mentioned hypothesis for the next three years and published his results in 1879 on 120 pages of an ample paper that consisted of three parts.[130, 131] in theoretical part iii[130] he derived in detail the law of independent ion migration, which is also named 1st kohlrausch law. in § 15 of this part iii he defined the quantity m, which he called the molecular content, as the number of electrochemical molecules per unit volume.53 he defined the “moleculares leitungsvermögen” (the molecular, later also molar conductivity), k/m, of the electrolyte in aqueous solution as conductivity, k, related to the molecular content, m. this quantity will be used by him in his future papers. then, in § 18, he reported the remarkable finding of the similar difference in the molecular conductivities of two single-charged salts with a common ion. to give some examples: the difference for the pair k and li is 274 for the chlorides, and 272 for the iodides; it is 160 for k and na as chlorides, and 185 for their iodides; for the chlorides of k and nh4 it is 21, and 14 for their iodides (all in the measure he used). these results encouraged him to formulate the final version of the law of independent ion migration in § 21, p. 168.[130] this derivation, expressed in modern notation, begins with the fact that the molar conductivity λ of an electrolyte solution is the sum of 53 we have already mentioned that, tedious for the current reader, kohlrausch often changed the nomenclature and the phraseology during the long time of his researches. in this § 15 on p. 146 of ref. [130] he defined m as “die anzahl der …. electrochemischen molecüle, welche in der volumeneinheit enthalten sind, werde ich kurz die molecülzahl oder den moleculargehalt der lösung nennen und durch m bezeichnen.“ (the number of …. electrochemical molecules contained in the unit volume, i will briefly call the molecule number or the molecular content of the solution and denote it by m) it is a relative quantity, which is calculated “aus dem procentgehalt und dem specifischen gewicht bei 18° berechnet man die in 1 ccm lösung enthaltene milligrammzahl des electrolytes und theilt letztere zahl durch das electrochemische moleculargewicht der substanz.“ (from the content in percent and the specific weight at 18°, one calculates the milligrams of the electrolyte contained in 1 ccm of solution and divides the latter number by the electrochemical molecular weight of the substance). it clarifies the matter by kohlrausch´s statement on pp. 172-173 in ref. [132] “die untersuchten flüssigkeiten sind bezeichnet nach ihrem gehalte an ,,electrochemischen molecülen” (aequivalenten) in der volumeneinheit. der ,,moleculargehalt” m bedeutet …. die in 1 l der lösung enthaltene menge in grammen, getheilt durch das aequivalentgewicht a des körpers. m = 1 bedeutet also die bei der titriranalyse sogenannte ,,normallösung.“ (the liquids examined are designated according to their content of “electrochemical molecules” (equivalents) in the unit of volume. the “molecular content” m means … the quantity in grams contained in 1 l of the solution, divided by the equivalent weight a of the compound. m = 1 therefore means the “normal solution” as it is known in titration analysis.) later kohlrausch called m the equivalent concentration (what faraday named electrochemical equivalent concentration). the molar ion conductivities, λ+ and λ–, of the two ions, i.e., λ=(λ++λ–).54 to obtain the conductivity of the individual ions, kohlrausch combined λ, as indicated above, with the transference number, τ, what led to the quested ion conductivity, e.g., for the anion as λ–=τ–λ, in which both, λ and τ–, are experimentally determinable measurands. analogously, the cation conductivity is λ+=(1-τ–) or τ+λ, because (τ++τ–)=1. on p. 168, ref. [130] kohlrausch formulated this law of independent ion migration (reproduced verbatim; note the almost identical wording of his 1876 hypothesis, that we quoted above, but which was, in contrast, formulated in subjunctive) as hiernach muß also jedem elektrochemischen elemente – z.b. dem h, k, ag, …, cl, j, no3,… – in verdünnter wäßriger lösung ein ganz bestimmter widerstand zukommen, gleichgültig aus welchem elektroly te der bestandteil abgeschieden wird. aus diesen widerständen, welche für jedes element ein für allemal bestimmbar sein müssen, wird sich das leitungsvermögen jeder (verdünnten) lösung berechnen lassen. (according to this, every electrochemical element – for example h, k, ag, …,. cl, j, no3,… – must feature a very definite resistance in dilute aqueous solution, regardless of which electrolyte the component is deposited from. from these resistances, which must be determinable for every element once and for all, the conductivity of each (dilute) solution will be calculable.) he tested the validity of this theory by calculating the equivalent conductivity of the salts55 by summarizing the tabulated conductivities of their ions (he completed his data with those from robert von lenz.)[126, 136],56 even after taking into account electrolytes with double54 we shall discuss in the following section that, taking into account the results of his research on the concentration dependence of conductivities, the modern notion of this equation reads λ0=(λ+0+λ–0); superscript 0 indicates limiting conditions, that is, when the concentrations approach zero; see also, e.g., refs. [133][134][135] 55 the concentrations of the salts were between around 5 weight % and their solubility limit, which reached for some salts about 80 weight %. 56 the little-known baltic-russian physicist robert von lenz (1833, st. petersburg -1903), son of the german-baltic physicist heinrich friedrich emil lenz (1804, dorpat, now tartu, estonia – 1865, rome) known for lenz’s law in electrodynamics, was professor of physical geography at the university of st. petersburg from 1865 to 1899. he published a paper in 1877, read in 1876, about conductivities of haloïd salts. lenz´s conclusions there resembled kohlrausch´s law of independent ion migration.[126][127] in 1879 he published conductivities of aqueous alkali salt solutions in the concentration ranges from about 10-1 to 10-3 equ.l-1.[136] notably, lenz was the first who systematically determined transference numbers, conductivities and diffusion coefficients of ions in mixed aqueous-ethanolic solutions up to ethanol concentrations of about 94% (v/v). he confirmed the proportionality of conductivity and diffusion rate,[137] which was later expressed quantitatively (for limiting conditions) by the nernst-einstein equation. 93capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 charged ions, kohlrausch found that the calculated values were in satisfactory agreement with the measured ones, considering the limited reliability of the transference numbers.57 eventually, kohlrausch concluded in diesen beispielen sehen wir unsere vermuthung, dass die beweglichkeit eines jons in verschiedenen verbindungen die gleiche ist, mit grosser annäherung bestätigt. (in these examples we see our conjecture confirmed with great approximation that the mobility of an ion is the same in different compounds.) kohlrausch ś finding that ions migrate in the electric potential independent of the counterions was a milestone for the further development of the theories of ion migration. the concentration dependence of the conductivity, and the conductivity at limiting conditions in the above chapter we have described kohlrausch’s first experiments in 1869 and 1870 on the conductivity of electrolyte solutions. this subject fascinated him so much that he introduced his next paper of july 1874 (the precursor of refs. [111, 112]) with the prophetic sentence: “diese in gemeinschaft mit hrn. grotrian ausgeführte arbeit soll den anfang einer geordneten experimentaluntersuchung über die strom-arbeit im inneren der elektrolyte bilden “ (this work, carried out in collaboration with mr. grotrian, is to form the beginning of an orderly experimental investigation of the work of the current inside electrolytes). this undertaking then actually extended over four decades. following this stated intention, in 1875 and 1876 he investigated the resistance or conductivity of a large number of solutions of salts, bases, organic and inorganic acids and their dependence on the electrolyte content.[111-113, 144] their electrolyte concentrations ranged from full saturation down to a few percent by weight. kohlrausch found a steady increase in conductivity with increasing concentration, with some electrolytes having a maximum at a particular concentration. for the discussion 57 transference numbers with higher accuracy and with much less experimental effort than those by hittorf´s method were later determined by the moving boundary method. this method will be discussed in a future paper together with electrophoretic separation methods in free solution. it was introduced in 1886 by oliver lodge,[138] and was further developed by w. c. d. whetham,[139]. by o. masson,[140] by a. noyes,[141] by b. d. steele and r. b. denison,[142] and by others. it was theoretically clarified, in addition to other methods, in 1897 by friedrich kohlrausch with his “beharrliche funktion” (the “persistent function”, better known as “regulating function”).[143] we will, however, not go into the details here. and comparison of the conductivities of the various electrolytes, he considered the indication of the concentration in percent by weight to be inappropriate. the conductivities of sulfuric acid and acetic acid, for example, could be determined at 100 %, while oxalic acid reached only 7 %, both (w/w). note that also in 1876 he published the preliminary version of the law of independent ion migration (ref. [114], see previous section). these measurements were also carried out with solutions with electrolyte concentrations not lower than a few weight percent.58 the “cubic-root” relation, the precursor of the “squareroot law” in his paper from 1885 “ueber das leitungsvermögen einiger electrolyte in äusserst verdünnter wässeriger lösung” (on the conductivity of some electrolytes in extremely dilute aqueous solution)[132] kohlrausch presented his measured conductivities in the low electrolyte concentration range between 10-5 and 1.0 mol.l-1. he completed the actual data with those for molecular concentrations larger than 1 mol.l-1 by his earlier ones and by those published by long,[147] and obtained equivalent conductivities for concentrations up to nearly 10 mol.l-1. since it was not meaningful to plot the molar or equivalent concentration, m, in a linear scale over a range of about 6 orders of magnitude, he chose the cubic root of m as the abscissa.59 the resulting k/m vs m1/3 curves are shown in figure 5. two shapes of these curves were clearly discriminable for kohlrausch. he distinguished therefore two classes of electrolytes. alkali salts of the type a+bwere typical representatives of the 1st class. for these electrolytes, the k/m values decreased only slightly by a few ten percent with increasing concentration in the low concentration range (figure 5, upper scale). in contrast, 2nd class electrolytes like acetic acid and nh3 exhibited a very low molar conductivity at high concentrations (pure acetic acid behaved as non-conductor). they remained at a low level when diluted over a wide concentration range, but rose steeply to values in the same range as those of the strong electrolytes when the solution became highly 58 in 1868/69 also a. paalzow measured the resistance of diluted salts and acids down to the low % range.[145][146] rudolf lenz reported conductivities of haloïd salts in 1877.[126][127] later, experimental results and theoretical discussions about ion conductivities and their concentration dependence were published in 1880 by j. h. long,[147] in 1884 by e. bouty,[148][149][150] by svante arrhenius in his doctoral thesis,[151][152] which kohlrausch provided with some pointed remarks, and by w. ostwald.[153] 59 kohlrausch followed the suggestion of r. lenz in 1878 to relate conductivity to the amount of electrolyte molecules in the solution.[136] 94 ernst kenndler diluted (see the two lowest and concave curves in the bottom scale of figure 5.) kohlrausch recognized from the curves that the molar (or equivalent) conductivities of both classes of electrolytes nevertheless reached a certain limit at concentrations approaching zero.[132] he expressed k/m as a function of m for dilute solutions of strong electrolytes by the equation k/m=a-bm1/3. this relationship stated that the equivalent conductivity is proportional to the cubic root of the concentration, and under limiting conditions it is equal to constant value a. for salts from single-charged ions, if only for these, the curves were approximately linear up to the concentration range of 1 mol.l-1 (see, for example, that for kclo3 in the figure). kohlrausch interpreted this dependence by the assumption that m1/3 corresponds to the reciprocal mean distance between the electrolyte molecules. for the 2nd class electrolytes he had no coherent explanation. this cubic root equation, which applied to a relatively large range of concentration, preceded kohlrausch ś “squareroot” equation for extremely dilute solutions which will be discussed in the following. after the investigations in 1885 kohlrausch was aware of the insufficient accuracy of the data measured so far, as he assessed their quality as too low for the formulation of a sound and general theory, especially with regard of the values at very low concentrations. he therefore tried to identify and reduce the possible sources of errors. this was the goal of his comprehensive and elaborate studies over the next years. in figure 6 a photograph of friedrich kohlrausch ś group at the university in würzburg in 1887 is shown. it was taken when kohlrausch was visited by svante arrhenius, who published in this year his seminal dissociation theory “ueber die dissociation der in wasser gelösten stoffe” (on the dissociation of substances dissolved in water). [155],60 although arrhenius’ theory provided the explanation for the deviating dependence of the 2nd class electrolytes such as acetic acid, kohlrausch was skeptical of it. he continued to focus on strong electrolytes at limiting conditions, preferably on those with single-charged ions. in strict chronological order we had now to proceed with arrhenius’ dissociation theory from 1884.[151, 152]. however, we prefer to continue systematically with kohlrausch’s electrochemical work after 1887,61 and will 60 arrhenius completed his doctoral thesis in 1884. it was published in two parts of “recherches sur la conductibilité galvanique des électrolytes.”[151][152] in 1887, his dissociation theory was published in the first volume of zeitschrift für physikalische chemie, stöchiometrie und verwandtschaftslehre,[155] founded by wilhelm ostwald and jacobus henricus van `t hoff. in 1928 its title was changed to zeitschrift für physikalische chemie. arrhenius’ theory fundamentally changed the previous conception of the behavior of electrolytes in solutions, and was a decisive step in the development of modern physical chemistry. in 1903 he became the first swedish nobel laureate. 61 it should be noted that in 1889 and 1890, due to adverse circumstances, kohlrausch did not publish a single paper. figure 5. equivalent conductivity (“specific molecular conductivity”) as function of the cubic root, m1/3 , of the equivalent concentration, m. the figure shows the left sectors of the total plot, that between zero and 1 equ.l-1 concentrations. the curves were drawn exactly through the measured values. upper scale, strong electrolytes, e.g. kcl, kclo3, etc. lower scale, concave two lowest curves: weak electrolytes acetic acid, nh3. modified; from ref. [132], plate ii, after p. 648. figure 6. photograph of friedrich kohlrausch´s research group at the physical institute of the university in würzburg in winter semester 1886/87, taken in february 1887. standing from left, adolf heydweiller, ewald rasch, svante arrhenius (research visit in würzburg in 1886/1887), walther nernst. sitting from left, wilhelm kohlrausch, friedrich kohlrausch, samuel sheldon (postgraduate; 18871888). source of photograph: ernst h. riesenfeld. svante arrhenius. akademische verlagsgesellschaft, leipzig, 1931. public domain.[154] 95capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 return to arrhenius’ theory and its pioneering consequences in the following, separate part 4 of our series. the “square-root” law: 2nd kohlrausch law in order to achieve the proverbial high accuracy of his experimental results, for which kohlrausch was famous, he examined step by step the effects of possible causes of errors. he tried to reduce the total systematic error at conductivity of solution with molecular concentration of 0.0001 which required errors in conductivity one magnitude lower in each individual step at molecular concentrations of 0.00001. we list a part of the subjects of these studies in condensed form in footnote 62, along with the articles in which they were published. it turned out that two sources of errors were most problematic. one was the well-known polarization of the electrodes, a problem kohlrausch solved, as he had done earlier, by using alternating rather than direct current. he used, in addition, an improved apparatus, the wheatstone bridge, for the measurement of the resistance.63 the second problem was that the water used as a solvent had to be of very high purity. kohlrausch’s coworker adolf heydweiller countered this problem in 1894 with cumbersome and time-consuming purification processes.[158, 172] in their paper from 1900, kohlrausch and his coworker e. m maltby published very accurate conductivities of alkali halides and nitrates in highly dilute solutions in a comprehensive report which covered eighty 62 (▪) influence of solubility of glass ware in contact with the solutions on the conductivity; ascertaining threshold level of conductivity of pure water used as solvent.[156][157][158] (▪) corrections taking into account temperature coefficients of water and of solutions, comparison with previous measurements.[132][159] (▪) estimation of deviations of electrolyte concentrations upon contraction by mixing of solutions and by evaporation of solvent.[160] (▪) measurement of resistance of electrolyte solutions with direct and alternating current.[161][162]163]164] (▪) density measurements of dilute electrolyte solutions.[160][165] (▪) determining and improving the properties of rheostat, capacitor and wheatstone bridge. [166]. (▪) specification and improvement of quality of resistor cells and electric wiring.[167] (▪) investing effect of polarization of platinized electrodes in measuring cell.[168][169] (▪) calibration of thermometer to 0.01° instead of common 0.1° (§ 15) and of the volumina of graduated measuring glassware (§ 16, volumetric flasks; § 18, pipets) in ref. [133] 63 the principle of the device called wheatstone bridge was initially described by the british mathematician and physicist samuel hunter christie (1784, london – 1865, twickenham, london) and reported in 1833 in his bakerian lecture “experimental determination of the laws of magneto-electric induction in different masses of the same metal, and of its intensity in different metals.“[170] it was not noted until charles wheatstone presented it ten years later, mind you, as christie’s invention, in his bakerian lecture “an account of several new instruments and processes for determining the constants of a voltaic circuit.”[171] printed pages and summarized the results of their elaborate investigations.[133] taking the data at lowest m between 1.10-5 and 4.10-5 equ.l-1 (out of a set over a range of up to 1 equ.l-1) kohlrausch expressed the dependence of the equivalent conductivity, here symbolized by λ, on m by the equation λ0-λ=pm1/2; λ0 and p are electrolyte-specific constants.[133],64. he called this equation “quadratwurzel gesetz” (literally “square root law”, better known in english literature as 2nd kohlrausch law).65 the equation signifies the linear dependence of the equivalent conductivity of the electrolyte on the square root of its equivalent concentration, and again applied especially for strong electrolytes with single-charged ions. the intercept λ0 represents the limiting equivalent conductivity of the electrolyte at concentrations m→0. constant p, the slope of the line, depends mainly on the stoichiometry of the respective electrolyte. note that the concentration to the power of ⅓ in the equation in his paper from 1885[132] is substituted here by the power of ½, because the former applied for a much larger concentration range. the decisive factor for the better agreement of the m1/2 – relationship was not the lower measurable concentration of the electrolytes, it was the higher accuracy of the conductivity data at these extremely low concentrations. we illustrate this excellent relationship in figure 7,[135] when kohlrausch had available a larger number of more accurate data.66 the following paper of 1907 is a kind of résumé of kohlrausch ś electrochemical contributions; in it he reconfirmed his earlier works. he subjected his theories of independent ion migration and those of conductance and mobility at limiting conditions to his own criticism. moreover, he reaffirmed the validity of his square root law from 1900[133] not without emphasizing that this law applies only to salts of single-charged ions, and to concentrations not higher than a few 10-5 mol.l-1. for higher concentrations this dependence is represented – as described in the above chapter – by the cubic root equation.[133] kohlrausch also mentioned the alternative equations by max rudolphi[173] and j. h. van t́ hoff,[174] which read in his version (λ0-λ)/λp=cη1/2. exponent p was taken as 2 by the former, and 3/2 by the latter author; η is here the equivalent concentration. kohlrausch pointed out that these equations, however, apply only to individual cases. in 1908 he published three 64 in this concentration range the conductivity of water (purified by up to 40 to 50 distillations under vacuum from a quartz apparatus)[158] was about one order of magnitude lower than those of the highest diluted electrolyte solutions. 65 remember that the 1st kohlrausch law is the law of independent ion migration. 66 the data were taken from sources kohlrausch cited in footnote 3, p. 336, ref. [135] 96 ernst kenndler more papers on electrochemistry, mainly on temperature effects of electrolyte solutions, and on january 4, 1910 he submitted a paper on “practical rules for number corrections, namely for the transition to other atomic weights”.[175] he died on january 17, 1910. migration velocity and mobility of ions the question about the absolute migration velocities of the ions, not only about their relative values, has been systematically treated by kohlrausch in several papers. [114, 130, 159, 176] in 1893 he had available improved values of the conductivity in dilute solutions, a valuable addition of hittorf ś transference numbers, more reliable values for the electrochemical equivalents and the absolute resistance of mercury. therefore, he was able to calculate more accurate data “ueber die geschwindigkeit elektrolytischer ionen” (on the velocity of electrolytic ions).[159] he limited the following calculation to strong electrolytes, from which he could be convinced that the molecules completely decompose to ions (we recall that arrhenius dissociation theory was published as journal article in 1887). we place his derivation into footnote 67 and add only the result after transformation into modern system of units and terminology. kohlrausch derived an equation for the migration velocities at unit field strength, that is to say, at 1 v.cm-1, which he called “beweglichkeiten” (mobilities), and which are, after multiplied by the according factor, the migration velocities in cm.s-1. by transformation this mobility reads μi=λi/f, at limiting conditions μi0=λi0/f, and is today also called mobility of ion, i. here λi is the molar ion conductivity, and f the faraday constant. the velocity v in cm.s-1 at field strength e is accordingly vi= μi.e.68 ion mobilities μi are of decisive importance in all variants of capillary electrophoresis in free solution. they are ion specific parameters that are independent of the potential. they depend on temperature, on electrolyte concentration (more precisely, on ion strength, what was unknown at that time) and on the solvent.69 since the migration velocity can be derived from the known ion conductivity and the chosen field strength, the question posed in this part 3 about its magnitude can be regarded as answered. however, the reason for its dependence on experimental variables, especially on their concentration, was still unknown at that time. the reader will probably note that we have not yet addressed the main question of whether or not electrophoresis experiments in free solution were performed in devices of capillary format in the years under consideration. for this reason, we conclude the present essay by describing the first use of capillaries in electrophoresis and additionally mention that all experiments cited below were performed with direct current. 67 kohlrausch derived the velocities for single-charged 1:1 electrolytes, that is, the molar and equivalent concentrations are the same. he considered a solution with molar concentration m of the electrolyte, which has the conductivity, k, and the “molecular conductivity” k/m, which is the sum of the molar conductivities of anions and cations. he derived the migration velocities of the ions at a potential difference of 1 v.cm-1. he first changed conductivity k from its relationship to mercury to ohm. he calculated the current in amp. at 1 v.cm-1 in 1 cm3 of electrolyte solution with m mol.l-1 concentration, and derived the number of moles electrolyzed by this current. this quantity is released at the electrodes at a distance of 1 cm. from this he derived the sum of the mean velocities of cations and anions and obtained those of the two ion species using hittorf´s transference numbers. the resulting equation expressed the ion migration velocity in cm.s-1, mind you, at a potential difference of 1 v.cm-1, as a function of the molar ion conductivity. readers who are interested in the specific numerical data in this derivation are referred to pp. 402-403 in ref. [159] 68 in modern notation the migration velocity v is in cm.s-1, the mobility μ in cm2.v-1.s-1 or s.cm2.a-1.s-1, and the molar ion conductivity in s.cm2. mol-1. 69 other researchers determined migration velocities of ions in the time period under consideration as well by the moving boundary method. we mentioned them in footnote57. figure 7. dependence of the equivalent conductivity on the square root of the equivalent concentration according to the 2nd kohlrausch law, the square-root law (termed “quadratwurzel gesetz” by kohlrausch) for 1st class electrolytes. the straight lines of electrolytes with the same stoichiometry run parallel, most pronouncedly for salts with 1:1 single-charged ions. they are highlighted in blue. since the letters in the illustrations of that time were mostly very small and hardly legible, we give the formulas of these salts in the order from top to bottom as follows: cscl; kbr; kcl; kno3; kscn; kclo3; agno3; nacl; naf; licl; kjo3; najo3; lijo3; lino3. ordinate, equ. conc.; abscissa, equ. conductivity. modified, from [135]. 97capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 the first capillary electrophoreses of ions at the outset of this particular chapter in the history of electrophoresis, it should be made clear again that electrophoresis is not limited to the separation process as which it is generally regarded today, as already stated in footnote 1 in the introduction to this article. the history of capillary electrophoresis must therefore be considered from this point of view. to maintain continuity with the preceding narrative, we follow up the previous section with kohlrausch’s research around 1900 and address the topic in reverse chronological order. 1895. f. kohlrausch and a. heydweiller in the course of their investigations on pure water in 1894[158] kohlrausch and his coworker adolf heydweiller observed that after applying direct current the electrical resistance of water decreased rapidly. changes in resistance were also observed in normally distilled and in highly distilled water and in some dilute aqueous salt solutions. switching the current off and on resulted in some cases first in a decrease, after some time in an increase of the conductivity; in other cases, the reverse sequence was observed. one can follow their explanations of the reasons for these effects70 in their paper “ueber widerstandsänderung von lösungen durch constante electrische ströme” (on the change of resistance of solutions at constant electric currents)[163] published in 1895. but this is of minor interest here. much more relevant to the issue at hand, they conducted their experiments in narrow open tubes of capillary dimensions because the zone boundaries described in footnote 70 were much sharper there than in tubes of larger diameters. they therefore used u-shaped capillaries with lengths of a few cm and inner cross-sectional areas of 1 mm2 and 0.6 mm2, that is, with radii of 560 and 440 µm. kohlrausch and heydweiller thus performed capillary electrophoresis – mind you – of ions. but they were far from being the first to introduce this method. 70 they related it, for example, to the reaction of the solutions at the electrodes and the migration of boundaries of h+ or ohformed by electrolysis from the one to the other electrode. such effects were called by g. wiedemann “ausbreitung der freien säure vom positiven pol aus” (propagation of the free acid from the positive pole), ref. [39], p. 167, and by h. buff “ausbreitung der säure gegen den negative pol ” (propagation of the acid towards the negative pole), ref. [177], p. 171. when both boundaries meet one another, neutralization takes place, water is formed, and the conductivity of the solution decreases. kohlrausch and heydweiller could visualize the motion of the boundaries by adding acid/base indicators. 1889. w. ostwald and w. nernst we recall that clausius’ theory of free ions from 1858 was proved by kohlrausch’s 1869 experiment using thermoelectricity[107] as described in the chapter above. in 1888, wilhelm ostwald had theorized that free ions must be present in an electrolyte solution, otherwise the principles of electricity would be violated.[178] in 1889, together with walter nernst, he caught up with the experimental confirmation of his theoretical paper and described it in “ueber freie ionen” (on free ions).[179] ostwald and nernst used an apparatus similar to lippmann’s capillary electrometer.71 they modified the simplest version of this instrument, which is depicted in fig. 3 on p. 503 of ref. [180]. in short, they took a tube of several tens of centimeters in length and reduced its lumen at one end to a capillary of 3,7.10-3 cm inner radius. they fixed the tube vertically, poured mercury into it, and immersed the tip of the capillary in dilute sulfuric acid. then they sucked the mercury together with the acid into the middle of the capillary length. a platinum wire served for connection with the mercury. next, they took a glass flask, covered with tin foil and filled with dilute sulfuric acid. this solution was connected to the acidic solution in the capillary via a wet thread. the mercury was grounded, and the positive pole of a small electrifying machine was connected to the outer tin foil of the flask. as soon as the machine was set in motion, the mercury meniscus promptly raised, indicating a potential difference between the two electrodes. remarkably, gas bubbles were formed, dividing the mercury in the capillary at several points. the authors explained this effect as follows. when the tin foil of the flask becomes positively charged, the negative sulfate ions are attracted, while the positive hydrogen ions are repelled. the latter travel through the wetted threat to the solution in the capillary and then through the platinum wire from the mercury to ground. the hydrogen transfers its electricity to the mercury in the capillary and appears as hydrogen gas. 71 lippmann’s capillary electrometer enabled the measurement of very small numbers of electrical charges, and of potential differences down to a few tens of µv. its main part consisted of a capillary half filled with liquid mercury in direct contact with a dilute solution of sulfuric acid. both are connected with wires that serve as electrodes. its principle is based on the relationship between the surface tension, the surface charge density of the mercury and the potential difference of the electrode points. expressed by the lippmann-helmholtz equation, the surface tension of mercury is directly related to its surface charge density. a change in the potential difference leads to a change in the surface charge density, which in turn changes the surface tension. this causes the mercury meniscus in the capillary to rise or fall, which can be accurately measured using a microscope and, after calibration, gives the potential difference between the two electrode points. 98 ernst kenndler ostwald and nernst argued that the motion is caused by influence, also known as electrostatic induction, and the formation of hydrogen on the mercury is clear evidence that decomposition has occurred. since electrolysis does not occur without electrophoretic ion migration, the authors claimed that it was free ions that were moving. they also argued that only their explanation was consistent with the laws of thermodynamics (p.125 ff.). taking this explanation as fact, ostwald and nernst performed capillary electrophoresis – again, mind you – of ions, six years before kohlrausch and heydweiller. 1865. w. beetz the german physicist wilhelm beetz72 had already done research in this field in 1862, albeit with wider tubes, namely one with 13.4 mm i.d. and 297 mm length, the other with 6.2 mm i.d. and 207 mm length;[116] numbers rounded by us. his attention was drawn to the 1861 work of edmond becquerel on the conductivity of electrolyte solutions in capillaries,[181] which we will discuss in the next section. beetz recognized that the conclusions in his work differed in part from becquerel’s. doubting becquerel’s results, he decided to extend his measurements in 1865 from wide tubes to capillaries.[182] thus, for comparison, he measured the resistances and calculated their reciprocal, the “leitungsfähigkeiten” of electrolyte solutions in these capillaries. for this purpose, beetz constructed a device equipped with two grove elements and determined the conductivities of zinc sulfate solutions with non-polarizing amalgamated zinc electrodes, and in six capillaries. the capillaries were between 77.7 and 161.2 mm long and had cross-sectional areas between 28.10-3 and 89.10-2 mm2 (derived from the weights of the mercury-filled tubes), corresponding to inner diameters between 190 and 690 µm; all numbers rounded by us. beetz found that the resistances are directly proportional to the lengths of the capillaries, and are inversely proportional to the cross-sectional area of the capillaries. 1861. the priority: edmond becquerel in 1846 and 1847, the french physicist edmond becquerel73 published the result of his investigations of the 72 wilhelm von beetz (1822, berlin – 1886, munich) studied physics and chemistry in berlin from 1840. from 1850 he was professor of physics at the cadet corps and at the artillery and engineering school in berlin, from 1855 professor in bern, from 1858 in erlangen and from 1868 professor at the technical university in munich. his main field of research was electricity, especially topics of electrical conductivity of liquids. 73 edmond becquerel, together with his father antoine-césar becquerconductivity of electrolyte solutions that were filled in tubes with centimeter dimensions of inner diameter and length. in these works[184-186] he tested whether the relations of lengths and cross sections, as he had found in metal wires, also applies in electrolyte solutions.74 in the april 1861 issue of annales du conservatoire des arts et des métiers, he published an essay with the designative title “études sur la conductibilité des liquides dans les tubes capillaires rhéostat destiné à la comparaison des grandes résistances” (studies on the conductivity of liquids in capillary tubes; rheostat for the comparison of large resistances”.[181] in this paper he reported conductivities of liquids, but measured in capillaries of different inner diameters for comparison with resistances of metallic wires. the device edmond becquerel constructed and used for his measurements in capillaries is presented in figure 8. we describe in the following only the right one of the two glass tubes shown, because the other, similar measuring system had the same characteristics and was installed only for control and comparison. and it is described in more detail because – to the best of the author’s knowledge – it was the first instrument ever used to perform capillary electrophoresis of ions in free solution. the device consisted of a glass tube (ab) closed at the bottom and open at the top, with a diameter of 2 to 3 cm and a height of 50 to 60 cm. it was placed vertically in a larger glass vessel (mn) with 20 cm diameter and a height approximately equal to that of the tube. water was filled into the large vessel to maintain the test solution, an aqueous solution of an electrolyte, at constant temperature. the tube was filled with the solution whose conductivity was to be determined. a capillary (gh) with a constant inner diameter and open on both ends, scaled in half-mm increments, was inserted in the axis of the tube and fixed there. the test liquid was filled into the tube and penetrated into the capillary, forming a narrow column of the electrolyte solution inside. then a metal wire, (cd), made from copper, zinc, silver, or platinum, the type of which depended on the test solution, el, discovered in 1839 a variant of the photoelectric effect, later called the becquerel effect. his main areas of research were phosphorescence of light and its chemical effects. he also investigated topics in optics and electricity. he is the father of nobel laureate (antoine) henri becquerel. for a detailed biography of alexandre-edmond becquerel (1820, paris – 1891) see c. blondel, ref. [183]. 74 it is remarkable that all authors discussed so far completely ignored gustav theodor fechner´s comprehensive contribution about the validity of ohm´s law for electrolyte solution, which he reported in his book “massbestimmungen über die galvanische kette”.[69] he published the same findings already in 1831, see his conclusions formulated in points (i) and (ii) in chapter “leap in time” above. fechner, however, did not carry out his measurements in capillaries. 99capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 were inserted into the tube (ab). the end of the wire in the tube was placed near the bottom of the capillary (gh). the diameter of the other wire, (ab), which was inserted into the capillary from its upper opening, was very close to the inner diameter of the capillary, and acted like a piston. by pressing this wire, the length of the liquid column of the test solution in the capillary could be varied and its position could be measured on the calibrated scale with a magnifying glass. the metal wires, (cde) and (ab), were connected to a bunsen battery consisting of one to ten elements.75 with 75 a bunsen element was invented by robert bunsen in 1841.[188][189] it is an electrochemical zinc-carbon cell with zinc as anode in dilute sulfuric acid, which is separated from a carbon cathode in nitric or chromic this arrangement, the current was forced to flow through the test solution inside the capillary, the length of which could be varied by hand by the wire. the current was measured with an astatic galvanometer. by using capillaries with different cross sections the resistance and the conductivity of the electrolyte solution in dependence on the liquid length and its diameter could be determined. five different capillaries were used with lumen radii of 929, 478, 238, 229 and 183 µm. polarization was minimized by using wires of the same metal as the cations of the test solutions. becquerel found that the resistance of such a liquid thread in a capillary is in direct proportion to its length, which is consistent with theory. however, he found that the product of resistance and the square of the inner diameter varied with decreasing diameter (of capillaries with the same length), and differed from that calculated for the given diameter (see plate on p. 741). on the one hand, beetz agreed with becquerel ś first conclusion. in contrast to becquerel, however, beetz found the resistances to be inversely proportional to the cross-sectional area of the capillaries, that is, the product of resistance and cross-sectional area is constant for capillaries of a given length. beetź s results were in agreement with the present theory, and also with fechneŕ s early findings (see chapter “leap in time”). beetz’s conclusions were plausible, and he had good reasons to explain the deviations from becquerel’s results, which he attributed to improper experimental conditions. we note that edmond becquerel measured the conductivities, no matter whether right or not, and thus the migration properties of dissolved ions in an electric field, i.e., he actually performed electrophoresis. even more, he was (as far as we know) the first to apply electrophoresis in capillaries – again, mind you – of ions. it is noteworthy that the first capillary electrophoresis of colloidal or coarse-grained particles was performed around the same years, 1860 and then 1861, a fact we highlighted in the introduction to part 1 of our series.[1] we will report in detail on this first capillary electrophoresis of colloidal particles in a later article. however, perhaps surprisingly, this will not be the work of either nicolas gautherot or ferdinand friedrich von reuß, as they did not use capillaries in their discoveries. summary around 1840, it was generally believed that the ions of strong electrolytes, like those of salts, migrate in soluacid by a porous pot. a single element delivers an electric potential of about 1.9 v. figure 8. the rheostat constructed by edmond becquerel in 1861 for the first capillary electrophoresis of ions.[187] explanations are included in the main text. reproduced from cnum – conservatoire numérique des arts et métiers – http://cnum.cnam.fr with permission. 100 ernst kenndler tions at the same electrophoretic velocity toward their respective electrodes, a view shaped by the theories of th. von grotthuß, h. davy, and m. faraday. however, this view was challenged by the results of recent experiments, which had shown that the solutions of some strong electrolytes after electrolysis had different concentrations near the two electrodes, in the so-called electrode compartments. these findings were incompatible with the established theory. wilhelm hittorf drew his conclusions from these observations and argued that the earlier view was based on a fallacy. instead, he derived a hypothesis according to which anions and cations actually move electrophoretically at different speeds. in his opinion, concentrations can only differ if one type of ion migrates faster than the other. he related the change in concentration in the electrode compartments to the current that an ion type transports relative to the total current which flows during electrolysis. he termed this fraction of the current, which is equal to the ratio of the velocity of a particular ion to the sum of the velocities of both ion species ”überführungszahl”, i.e., transference or transport number of an ion in a given electrolyte. regrettably, the transference number expressed only the velocity of an ion relative to its counterion, but did not give the magnitude of the absolute velocity. at the end of the 1860s, friedrich kohlrausch began researching the conductivity of electrolytes, a topic that would subsequently occupy him throughout his life. he found that conductivity decreased with decreasing concentration of the electrolyte, but more relevant to him were the conductivities normalized to their concentrations. he observed that the ratio k/m of conductivity, k, and the equivalent or molar concentration, m, of the electrolyte increased with increasing dilution. he quoted k/m as the equivalent and molar conductivity, in modern notation, λ,76 the quantity which turned out to be central for his further research. kohlrausch found that two types of electrolytes can be distinguished. with strong electrolytes, such as neutral salts, the value k/m decreased only slightly with increasing concentration. with weak electrolytes such as acetic acid and ammonia, on the other hand, there was no such dependence, since k/m remained at low values at low dilutions but rose steeply within a certain narrow range of decreasing concentration. he subsequently focused his research on strong electrolytes in very dilute solutions, preferably but not exclusively on those consisting of single-charged ions. 76 for the sake of better readability, we replace the written terms by symbols and restrict ourselves to strong 1:1 electrolytes with single-charged ions. the molar conductivity of the electrolyte solution is λ, that of the ion species λ. the molar concentration is symbolized by m. he was able to show that ion and counterion of an electrolyte migrate independently of each other and that an ion, regardless of which electrolyte it comes from, always has the same “molecular” – now molar – ion conductivity. this was the law of independent ion migration, also quoted as the 1st kohlrausch law, which he derived in 1879. in determining λ at different concentrations, kohlrausch formulated an empirical law which stated that λ decreases linearly with m1/2 for very dilute solutions. it is known as the 2nd kohlrausch law and was called by him the “quadratwurzel gesetz (square root law). the extrapolation of the ion concentration to limiting conditions, i.e., to concentrations approaching zero, led to an ion-specific and concentration-independent variable, the limiting ion conductivity. it is little known that the 2nd kohlrausch law was preceded by the relationship between λ and the cubic root, m1/3, which applied to a larger concentration range. the ion velocities and their mobilities, that is, their drift speed at a unit field strength, could be calculated by kohlrausch by combining hittorf ś transfer numbers with conductivity data and the law of independent ion migration. however, their knowledge did not contribute to a deeper understanding of the form in which ions exist in solutions. it also did not indicate how they drift in the electric field trough the solution, although a connection with the viscosity of the solution and with the frictional resistance has already been assumed. it must be remembered that the generally accepted concept before the late 1880s was not very different from the one introduced by von grotthuß about eight decades ago. it was still based on the conjecture that an ion only exists in solution in an electrically neutral assembly with a counterion, which needs an electric field to divide. rudolf clausius, on the other hand, argued in 1857 that ions in solutions exist in free form as a result of their thermal energy even in the absence of an external electric force, although, as he assumed, only to a small extent.77 we do not wish to diminish the significant contributions of many other scientists to ion migration, but it would not be appropriate to quote names selectively. certainly we must cite the early contributions of g. fechner, but also refer to the later measurements of ion migration velocities by those mentioned in footnote 57 who mainly used the moving boundary method for their determinations. 77 this latter aspect of clausius´ theory, the low fraction of free ions, was retrospectively disproved in 1889 by wilhelm ostwald and walter nernst in their paper entitled “über freie ionen” (on free ions) by the conflictive consequences to the law of thermodynamics and by subtle experiments.[179] 101capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 however, we consider kohlrausch a key figure in the field, having done pioneering work for more than four decades, longer than others, although his greatest achievements in the field of electrophoretic properties were ultimately in the area of strong electrolytes. at the end of kohlrausch’s research, which lasted until about 1910, two questions remained unanswered for him. the first question was why the values of strong electrolytes increase with increasing dilution to a limit at concentrations close to zero. kohlrausch hypothesized that under the limiting, but only under these conditions, possible ion-counterion interactions tend to cease completely. but the second open question, namely why compounds of the 2nd class, weak electrolytes like acetic acid, deviate so much from the usual behavior of the strong electrolytes, could by no means be answered conclusively with this assumption. the answer to the first question was given at the begin of the short 20th century78 by lars onsager,[190, 191] based on the theories of peter debye and erich hückel. [192, 193] but kohlrausch could have seen the solution to the second problem as early as the 1890s, if he had not been so skeptical of the theory of electrolyte dissociation svante arrhenius published in 1887. in fact, this dissociation theory not only provided the plausible answer to this second question but moreover, represented the next, major step toward the modern physical chemistry of electrolyte solutions. this pioneering theory and its consequences in the last decades of the long nineteenth century, or, as we term it, the “1st period of electrophoresis,” which ended in 1914 with the first utilization of electrophoresis as a method for separating compounds in mixtures will be the subject of the following part 4. we attach great importance to close this chapter of scientific research not without pointing out that electrophoresis of ions in free solutions in capillaries was performed for the first time in its history in the second half of the long nineteenth century, in four times between 1861 and 1895. the last time this happened was in 1895, when f. kohlrausch and a. heydweiller applied direct current instead of alternating current to liquids filled in glass capillaries and observed the movement of the boundaries of ion zones caused by unexpected resistance changes. one could speculate whether this phenomenon led him to derive his important “beharrliche funktion” in 1897, the “regulating function”. in 1889, w. ostwald and w. nernst investigated whether free ions are present in solutions according to clausius’ theory. they used the 78 the “short twenties century,” popularized by the noted british historian eric hobsbawm (1917 – 2012) in his book the age of extremes, covers the period between the beginning of world war i in 1914, i.e., at the end of the long nineteenth century, until the beginning of the collapse of the ussr in 1989. for details, see part 1 of our review series. capillary of a lippmann electrometer for their experiments. in 1865, w. beetz investigated ion migration in capillaries because he doubted the results of edmond becquerel, who wanted to compare the conductivities of liquids in capillaries with those of metal wires. in any case, it is recognized that the priority is owned by edmond becquerel, since he first performed capillary electrophoresis of ions as early as 1861. acknowledgement the author would like to thank peter frühauf for his valuable support in the realization of this paper. references 1. e. kenndler, m. minárik, substantia 2021, 5 (1), 119-133. 2. j. lyklema, fundamentals of interface and colloid science. solid-liquid interfaces, vol. 2, academic press, london, san diego, 1995. 3. j. h. lyklema, substantia 2017, 1 (2), 75-93. 4. e. kenndler, substantia 2021, 5 (2), 95-118. 5. j. c. maxwell, phil. trans. 1865, 155, 459–512. 6. p. m. roget, electricity, galvanism, magnetism, and electro-magnetism, robert baldwin, london, 1831. 7. p. m. roget, treatises on electricity, galvanism, magnetism, and electro-magnetism, baldwin and cradock, london, 1832. 8. m. faraday, phil. trans. 1833, 123, 675-710. 9. m. faraday, ann. phys. chem. 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(pogg.) 1865, 125, 126132. 183. c. blondel, in les professeurs du conservatoire national des arts et métiers. dictionnaire 105capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3 biographique 1794-1955, vol. 1 (a – k), institut national de recherche pédagogique, paris, 1994, pp. 168-182. 184. e. becquerel, ann. chim. phys. 1846, 17 (3. sér.), 242-290. 185. e. becquerel, ann. phys. chem. (pogg.) 1847, 70, 238-254. 186. e. becquerel, ann. chim. phys. 1847, 20 (3. sér.), 53-84. 187. annales du conservatoire impériál des arts et des métiers, vol. 1, e. lacroix, paris, 1861. 188. r. bunsen, ann. chem. pharm. (wöh., lieb.) 1841, 38, 311–313. 189. r. bunsen, ann. phys. chem. (pogg.) 1841, 54, 417– 430. 190. l. onsager, physik. z. 1926, 27, 388-392. 191. l. onsager, physik. z. 1927, 28, 277-298. 192. p. debye, e. hückel, physik. z. 1923, 24, 305-325. 193. p. debye, e. hückel, physik. z. 1923, 24, 185-206. substantia an international journal of the history of chemistry vol. 6, n. 1 2022 firenze university press to print or not to print? preprints and publication: how the covid-19 pandemic affected the quality of scientific production pierandrea lo nostro faraday’s dogma stephen t. hyde creativity in the art, literature, music, science, and inventions singlet dioxygen 1o2, its generation, physico-chemical properties and its possible hormetic behavior in cancer therapy marc henry1, miro radman2, luc benichou3, khalid o. alfarouk4, laurent schwartz5,* is the second law of thermodynamics able to classify drugs? laurent schwartz1,*, luc benichou2, jules schwartz1, maxime pontié3, marc henry4 history of research on phospholipid metabolism and applications to the detection, diagnosis, and treatment of cancer peter f. daly1, jack s. cohen2,* capillary electrophoresis (ce) and its basic principles in historical retrospect. part 3. 1840s –1900ca. the first ce of ions in 1861. transference numbers, migration velocity, conductivity, mobility ernst kenndler the early history of polyaniline ii: elucidation of structure and redox states† seth c. rasmussen path to the synthesis of polyacetylene films with metallic luster: in response to rasmussen’s article hideki shirakawa comments on shirakawa’s response seth c. rasmussen lipids, chloroform, and their intertwined histories carlos a. ramírez professor alexander kessenikh (1932-2021) andrey v. andreev1, vadim a. atsarkin2, konstantin v. ivanov1, gennady e. kurtik1, pierandrea lo nostro3, vasily v. ptushenko4,5, konstantin a. tomilin1, natalia v. vdovichenko1, vladimir p. vizgin1 substantia. an international journal of the history of chemistry 1(1): 97-98, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-5 manifesto of the journal preamble in the current historical period, marked by tragic conflicts and dramatic tensions in various areas, it is absolutely appropriate to ponder and recoup the fundamental aspects of culture, e.g. the relationship with the past, people’s common history, and the universal values on which our coexistence and civilization are based upon. in such a context it seems important to deepen the relationship with the past history, and not only the ancient history or that of a few centuries ago, but also the more recent history, of the short century that has just gone. for us, researchers and university teachers of disciplines related to chemistry, it seems crucial to deepen the bonds with those forerunners who preceded us in research and in education, in order to mature a more convinced and deep awareness of the world and of the civilization from which we come and to pass the baton to the future generations, in total liberty, as stated by the art. 33 of the constitution of the italian republic, that reads “the republic guarantees the freedom of the arts and sciences, which may be freely taught.”1 presentation substantia is an international electronic peerreviewed journal. it is published in english by the university of florence, at the initiative of the department of chemistry “ugo schiff ”. the journal aims at offering an original cultural contribution in europe to the history of chemistry and a scientific tool of communication, debate and close examination of all topics related to chemical sciences and similar disciplines. substantia is born in florence, one of the cradles for science, and particularly for chemistry. as a matter of fact it was during the florentine renaissance that the studies and the practices pertaining to chemistry received a new impetus: the camerata de’ bardi was born in the 16th century and promoted a new way to look at sciences, arts and literature (the first records date back to 1573 ad). during the following decades the accademia dei lincei (1603), the accademia del cimento (1657), the royal society in london (1662), the académie royale des sciences in paris (1666), the kurfürstlich akademie der wissenschaften in berlin (1700), the russian academy of sciences in st. petersburg (российская академия наук, rossíiskaya akadémiya naúk, 1724), the kungliga vetenskapsakademien in stockholm (1739), and the american academy of arts and sciences of the massachusetts (1780) were progressively born. these academies became the places of aggregation, dispute and divulgation of the rising chemistry. substantia is addressed to teachers, researchers and university students, and to all those interested in deepening the scientific themes related to chemistry. the journal publishes original articles that comply with the criteria of scientific rigour, originality and depth and it is freely distributed over the internet with no restriction in open access, in compliance with the principles of the “berlin declaration on open access”: open access to knowledge, largest dissemination and visibility on the web for scientific research, and public distribution of the results of the studies. the journal may host monographic issues focusing onto specific themes of interest. the aims of substantia, in the attempt to conjugate scientific rigour and an interdisciplinary outlook, include: 1) the promotion of research activities in history of chemistry through the publication of papers devoted to classical or contemporary chemistry issues, and in particular of studies that leap over the fences of the rigid academic organization and promote the combination and intersection of knowledges, techniques, methodologies and diversified languages 2) the recovery and republication of unpublished or unlikely available works, that represent milestones in the development of chemistry and related disciplines, and whose validity and scientific relevance remain untouched also after decades 3) the recovery or the revival of past literature sources, in the attempt to limit the “loss of knowledge” that 98 manifesto of the journal relentlessly strikes the human culture, and that is inadvertently favored by the extreme fragmentation and specialization of science 4) the promotion of a critical outlook towards current and past theoretical models, in order to encourage and develop the job of young researchers. a space also for similar disciplines substantia will always welcome scientific contributions focusing on topics related to all chemical sciences, physics, mathematics, life and earth sciences, history and philosophy of the sciences, engineering, medicine, economics, social sciences and arts. 1. “l’arte e la scienza sono libere e libero ne è l’insegnamento.” https://www.senato.it/documenti/ repository/istituzione/costituzione_inglese.pdf, last accessed on jan 02, 2017. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments substantia. an international journal of the history of chemistry 2(2): 5-6, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-55 editorial goodnight and goodluck1: the end of a building at the australian national university 2 may 31 marked the end of the old applied maths building at anu. we moved into it in 1971, 47 years ago. for about twenty years before that it had already been home to the famous department of geophysics and geochemistry. before the war, when both lake burley griffin and anu were dreams, there were nurses quarters close by and the old hospital. this building has been a center of research for 70 years: there from the very beginning of anu. with a magnificent view over the lake and the brindabella mountains, the building occupied a prime site on campus, where the freeway crosses the creek. before that the ngunawal peoples who owned this country forever caught fish where the molonglo river turned and passed by black mountain. there was no asbestos. the building worked very effectively for collaboration between scientists. it had been declared a major heritage site twice. no building will replace it for the foreseeable future. academics will just have to double and triple up. its demolition is a significant, symbolic act of barbarism. as henry lawson suggested: “something ought to be said. we should have a party or something”. there are some lines from hamlet that are apt. “my words fly up, my thoughts remain below; words without thoughts never to heaven go”. thoughts, not words. that’s the thing . apart from lamenting the good old days, as one does, why on earth could it matter for the future of universities? first of all remember that in those early times the anu was an institute of advanced studies, a place of cutting edge research, a place in which undergraduate teaching was a diversion from the main game, and not allowed. and research was done in this building of a quality no one imagined. it was first the anu dept. of geophysics and geochemistry founded by the eminent applied mathematician, john jaeger. later it became the research school of earth sciences, one of the leading schools in its disciplines in the world. for nearly twenty years they did their work here. ted ringwood’s high pressure laboratory was the tower block in the center. from that work ted invented synroc, a new way of disposing of nuclear waste. then there was bill compston who developed mass spectrometry that began in western australia and measured the age of the earth. then merv patterson was there. and ross taylor, known for his analysis of rocks that came back from the moon, and for work on the origin of planets. paleomagnetism research was so important for carey’s theory of continental drift. it was still heretical even in the early 1960s. ted’s idea was to put the nuclear waste back into synthetic rocks which resembled those that the uranium originally came from. the competitive technology was to put it inside solid glass and bury it in the ocean. ted missed out because the competition was owned by rockwell international which is an organization that makes hydrogen bombs and whose ceo was a friend of president reagan. reagan and the head of rockwell had adjoining ranches in california. rockwell pushed glass disposal. glass won but to no good purpose because the sea water cracked the glass. if ted had won, the world would have been a better place. after earth sciences moved, our department of applied mathematics came in. it made a lot of remarkable contributions in the natural sciences over the years. and a lot of applied experimental and development work was done over and above only mathematics. we were scientists and engineers who worked in the enabling disciplines, physical, colloid and surface chemistry that underlie all of biology and chemical engineering. for example the department’s laboratories did the first measurements on molecular forces, something isaac newton tried to do in the 1600s and failed. it did 6 barry w. ninham outstanding pioneering work in fibre optics, on porous media which got the equivalent of the nobel prize in chemical engineering. these things were commercialised too. it brought strange new non euclidean geometries into science. they turn out to be common geometries of nature; from inorganic chemistry to biology. it made major contributions to membrane biology and changed the face of physical chemistry. mark oliphant, one of the five eminent founding fathers of anu, was our first research visitor for two years after being moved on from his position for being too old, at age 65! the applied maths building was optimal for personal engagement and collaboration. everybody including myriad overseas visitors, loved it. it had all the right stuff, call it the wisteria, open corridors or a psycho ceramic environment, as well as the old staff centre. this was a pub without peer, famous world wide, great for collaboration. whatever, it worked. it attracted visitors from many countries around the world. it produced over 100 full professors so far in all kinds of fields, in this country and overseas. there were many phds. the department gained all kinds of awards and distinctions. four of its members or colleagues mentored were chairs of the nobel prize committee in chemistry. it is all forgotten now, but what we all did will stand. and it will be remembered elsewhere. at the end of every speech that the elder cato gave to the roman senate, he always finished with: carthago delenda est. carthage must be utterly destroyed. something like that is happening here. we are bemused. why erase the past? why bulldose a perfect working building when funds are being cut? there are plans for a new building in three or five years time. but if you believe that you believe in fairies. meantime academics will have to double and triple up in cramped quarters. not so bad really? there is no reason advanced here for the abolition of a twice declared heritage site with so many triumphs. and memories. imagine if some administrator decided to abolish a college at cambridge, including say newton’s old rooms. it could not happen. and it ought not to have happened here. from the old applied maths building a wide range of immeasurably new technologies came forth based on fundamental research. the life of the building spanned a gentler time for scholarship and learning in universities. with thanks to jan morris of farewell the trumpets, a poem of e.w. horning after the great war catches a whiff of it, and the ghosts of those who were here. ‘who are the ones that we cannot see, though we feel them as near as near? in chapel one felt them bend the knee, at the match one felt them cheer. in the deep still shade of the colonnade, in the ringing quad’s full light, they are laughing here, they are chaffing there, yet never in sound or sight’ the lights are going out in universities across australia, with the triumph of a grim political correctness and the death of history. the old australian larrikin dipped his “lid” to no man. he is gone. the enlightenment has gone and with it science itself. so remember ozymandias, and what we used to think universities stood for, as john molony has so elequently expressed further in a following piece. ozymandias by percy bysshe shelley i met a traveller from an antique land, who said – ‘two vast and trunkless legs of stone stand in the desert. . . near them, on the sand, half sunk a shattered visage lies, whose frown, and wrinkled lip, and sneer of cold command, tell that its sculptor well those passions read which yet survive, stamped on these lifeless things, the hand that mocked them, and the heart that fed; and on the pedestal, these words appear: my name is ozymandias, king of kings; look on my works, ye mighty, and despair! nothing beside remains. round the decay of that colossal wreck, boundless and bare the lone and level sands stretch far away.’ vale applied maths building canberra, 2 july 2018 barry w. ninham substantia. an international journal of the history of chemistry 1(2): 95-98, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-29 citation: h. bouas-laurent, j.-p. desvergne (2017) the master and the slave. a glance at the social life of molecules. substantia 1(2): 95-98. doi: 10.13128/substantia-29 copyright: © 2017 h. bouas-laurent, j.-p. desvergne. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the authors declared that no competing interests exist. feature article the master and the slave. a glance at the social life of molecules henri bouas-laurent, jean-pierre desvergne institut des sciences moléculaires, université de bordeaux, 351 cours de la libération, bât a12, 33405 talence cedex e-mail: h.bouaslaurent@cegetel.net, desvergnejp@gmail.com abstract. low energy interactions induce the formation of molecular assemblies that can display a large variety of sizes and shapes such as dimers, oligomers, colloids, gels, helices, cylinders, etc. these grouping modes mimic human relationships, as people generally flock together according to their affinities. moreover, chemical reactions, undergone under strong energy interactions, that result in bond breaking and formation of new compounds, can also be compared to human behaviour. the fables usually involve animals but rarely molecules to play the role of human beings. in this article, we report a molecular tale where two different 9-substituted anthracene derivatives compete in a photochemical reaction, simulating the behaviour of a master and a slave, respectively. keywords. molecular sociology, photochemistry, aromatic endoperoxides, singlet oxygen, graduate education. introduction oil and water are known to repel each other. despite shaking a mixture of the two in a bottle, they quickly form two distinct layers. the substances soluble in oil are called lipophilic (vitamines a, d, e...) whereas those soluble in water are said to be hydrophilic (sugars, amino-acids...). fats cannot be eliminated with pure water, but require the use of surfactants to bring them into solution. these substances have affinity both to oil and water and contribute to form a single macroscopic phase.1 such behaviour results from low-energy intermolecular interactions as compared to much stronger ones governing molecular bonds. non-covalent intermolecular associations are wide-spread in abiotic as well as in biological systems and are fundamental for the formation of molecular assemblies. these can be very diverse: dimers, oligomers, cylinders, helices, colloids, liquid crystals, cellular membranes, to cite but a few. they form the basis of “supramolecular chemistry”.2 the affinities between molecules mimic human relationships. an interesting example was reported by green et al. in the form of sergeants and soldiers.3 alkylisocyanates copolymers are known to adopt a rigid helical con96 henri bouas-laurent, jean-pierre desvergne formation in solution. the authors observed that, in solutions of copolymers formed from chiral and achiral monomers, even a small proportion (ca 1%) of chiral monomers induced a high enantiomeric excess; thus, a small number of chiral motifs (playing the role of sergeants) can trigger the movements of a large number of achiral motifs (the soldiers). apart from the above soft interactions, chemical reactions transform starting materials into products, through bonds breaking and bond formation. this activity may also be compared to human behaviour. for example, in his third novel “the elective affinities”,4 goethe compared acid-base reactions to love affairs between human couples. amongst other reactions, one of them inspired cohen et al.5 who compared molecules to wolfs and lambs, like in story tales. here, two molecules, reacting fiercely with one another in solution and leading to a mixture of products, become mutually inactive when tightly linked to two different polymers (merrifield resins); a third reactant, in solution, reacts successively with one of them (the wolf ) then with the second (the lamb), to generate a single product with high yield. in this article, we describe a particularly relevant reaction where two different molecules (m and e) compete in an addition reaction to a special reactant produced in situ through light irradiation. the reaction, which is reminiscent of human behaviour, is brief ly described below. materials and methods formation of endoperoxides 9,10-endoperoxides “ao2” (figure 1 ) are formed by a hetero diels-alder addition of singlet oxygen (1o2) to anthracenes “a”.6,7,8 singlet oxygen can be generated by several processes. one of them, photosensitization,9,10,11,12 involves energy transfer from an organic compound in its excited triplet state (t1). anthracene derivatives can be good singlet oxygen producers when they have high yields of triplet formation.8 the energy transfer from the triplet state and dioxygen leads to singlet oxygen 1o2 which can participate in the addition reaction as shown in figure 1. the two anthracene derivatives considered here are 9-isopropyl (e) and 9-tertiobutyl (m) anthracene. although e was found to readily generate 1o2, m was shown to be unable to do so.8 the primarily reached photochemical state is deactivated much too fast and no triplet state can be formed; therefore m cannot act as a sensitizer.13,14 thus, irradiation of e in solution in the presence of dioxygen generates the endoperoxide “eo2” in high yield. under the same experimental conditions, m is not transformed into “mo2” and remains unchanged. competition reaction the irradiation through pyrex of an equimolecular mixture of e and m in solution in dioxygen-saturated ether, at room temperature initially leads to the exclusive formation of the endoperoxide of m (mo2), figure 2. then, after the complete transformation of m, the reaction of e with singlet oxygen begins, leading entirely to the formation of eo2.8 the sequence is illustrated in the following sketches: (1), (2) and (3) of figure 3. one observes that m, the most crowded molecule, is considerably more reactive with 1o2 than e. this is called a steric acceleration, due to a relief of strain in the activated complex that is product-like. the same phenomenon was also noted for other anthracene derivatives.15 the thermal and photochemical stability of the two adducts during the reaction attests to its irreversibility. 8,16 conclusions master and slave the above molecular behaviour is suggestive of human attitudes. singlet oxygen might be compared to food, produced only by e, the slave. as soon as the food is available, o2 a r o o r 9 10 ao2 endoperoxide figure 1. addition of singlet oxygen to 9-alkylanthracenes (hetero diels-alder reaction). o o ch3 ch3 ch3 ch3 ch3 ch3 + 1o2 figure 2. developed formulae of m and mo2 respectively, suggesting the steric overcrowding due to the tertiobutyl substituent. 97the master and the slave. a glance at the social life of molecules m (the master) rushes at it in a gluttonous manner until he has eaten his fill. when he has gorged himself, then the poor slave is allowed to eat. the story stops there because after the meal, both master and slave are in a peaceful longstanding state. the nasty master is not punished, in contrast to what generally happens in fairy tales. one could imagine other scenarios: 1) instead of an equal number of e and m, an excess of m would lead to an accumulation of mo2; thus a single slave would work for many masters. this would delay the meal time of e. 2) if the irradiation is stopped after m’s hunger is satisfied, then in the dark, e would no longer produce the food and be doomed to be starving for ever. today, slavery has been abolished on earth. however, it seems that some inactive people are prompt to eat what others have strained to produce. this observation might be extended to relationships between countries. it could be argued that human beings have common ancestors in the mendeleev table, especially carbon, hydrogen, oxygen, etc., and that their reptilian brain keeps traces of their molecular constitution; this might partly explain their shocking deeds. however, the extreme complexity of human behaviours cannot be traced back to simple chemical reactions. let this short tale contribute to inspire to everybody with a humble attitude. acknowledgements the authors are grateful to dr esther oliveros for her precious information about singlet oxygen and prof. dr herbert dreeskamp for perceptive comments. we warmly thank dr dario bassani for valuable linguistic assistance. references 1. a. lattes, i. rico, la sociologie moléculaire et les tensioactifs, pour la science, mars 1992, n° 173. 2. j.-m. lehn, supramolecular chemistry; concepts and perspectives, vch, weinheim, 1995. version française: la chimie supramoléculaire. concepts et perspectives, de boeck université, 1997. 3. m.m. green, m.p. reidy, r.j. johnson, g. darling, d.j. o’leary, g. wilson, j. amer. chem. soc. 1989, 111, 452. 4. johann wolfgang goethe, “die wahlverwandtschaften” (the elective affinities), 1809. we thank professors henning hopf (braunschweig) and herbert dreeskamp (bonn) for pointing out this information. 5. b.j. cohen, m.a. kraus, a. patchornik, j. amer. chem. soc. 1981, 103, 7620. 6. j. rigaudy, pure appl. chem. 1968, 16, 169. 7. d.o. cowan, r.l. drisko, elements of organic photochemistry, plenum press, new york, 1976, chap. 2, pp. 69-71. 8. r. lapouyade, j.-p. desvergne, h. bouas-laurent, bull. soc. chim. fr., 1975, 2137. under our photooxidation experimental conditions no photodimer was observed. 9. a. braun, m.t. maurette, e. oliveros, technologie photochimique, presses polytechniques romandes, lausanne, 1986 and photochemical technology, j. wiley, chichester, 1991, chap.11, pp. 445-499. 10. f. wilkinson, h. p. helman, a.b. ross, j. phys. chem. ref data 1955, 24, 663. 11. m.c. derosa, r. j. crutchley, coord. chem. rev., 2002, 233-234, 351. 12. e.l. clennan, a. pace, tetrahedron 2005, 61, 6665. 13. h. güsten, m. mintas, l. klasinc, j. amer. chem. soc., 1980, 102, 7936. 14. b. jahn, h. dreeskamp, ber. bunsenges. phys. chem. 1984, 88, 42. 15. n. lahrahar, p. marsau, j. rigaudy, h. bouas-laurent, j.-p. desvergne, austr. j. chem. 1999, 52, 213. figure 3. (1) a solution of m and e in equal amounts is irradiated under dioxygen bubbling; e produces singlet oxygen (the food) in contrast to m, which is unable to do so. (2) m swallows and consumes all the food available. (3) m being entirely transformed into mo2, e can in turn eat the food and generate eo2. 98 henri bouas-laurent, jean-pierre desvergne 16. h.d. brauer, r. schmidt, photochromism, molecules and systems (eds: h. dürr and h. bouas-laurent) elsevier, amsterdam, 2003, chap. 15, pp. 631-653. this chapter describes the formation and decomposition of endoperoxides. some of them, such as heterocoerdianthrone (lifetime 900 years at 20°c) are particularly thermally stable. substantia. an international journal of the history of chemistry 3(1) suppl.: 7-10, 2019 firenze university press www.fupress.com/substantia citation: i. ciabatti, m. fontani, c. martini (2019) the arezzo seminar on precious metals. substantia 3(1) suppl.: 7-10. doi: 10.13128/substantia-599 copyright: © 2019 i. ciabatti, m. fontani, c. martini. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-599 the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 1 r&d manager, tca|precious metals refining. e-mail: i.ciabatti@tcaspa.com 2 department of chemistry “u. schiff ”, university of florence. e-mail: marco.fontani@ unifi.it 3 department of industrial engineering (din), university of bologna. e-mail: carla.martini@unibo.it a golden story gold is a valuable bright yellow metal with a resplendent lustre and high density (more than 19 times the weight of an equal volume of water). due to its inalterability, brilliant appearance and occurrence in the native condition, or elementary state, gold was certainly one of the first metals to attract the attention of men. it was known, highly valued and widely employed by earliest civilization. in our peninsula, etruscan made gold ornaments with great variety of workmanship. some of them survived over the centuries and appear today as perfect as they were over two thousand years ago. under a certain point of view, gold has to be considered the driving force that led to modern chemistry. in fact, the making of gold from other metals, by means of the philosopher’s stone, and the discovery of the elixir of eternal life were the chief aims of the alchemists in the middle ages. it is reasonably correct to say that advances in early chemistry were a direct outcome of such experiments. gold, whose symbol is au (from latin, aurum) has atomic number 79 and atomic weight 196,9665 g/mol. physically, gold is of chief interest for its remarkable ductility, malleability and resistance to chemicals. gold can be drawn into extremely fine wire or beaten into the filmiest gold-leaf. with exception of boiling aqua regia, alkali cyanides or free chlorine, gold will not readily combine with other chemicals (neither compounds nor elements). in every culture, gold was taken as model of wealth. throughout history, human beings have fought and toiled for this precious and durable metal. it is estimated that the greater amount of all gold mined from the earth in the last ten millennia could still be accounted for in the bank and government vaults, and in the widely distributed wealth of ornaments, jewellery, technological or clinical artefacts through the world. no other possession in all time has been so zealously and effectively protected. silver, gold and their alloy (or artificial mixture) called electrum were used for manufacturing ornaments, vessels, weapons, minted for coin8 iacopo ciabatti, marco fontani, carla martini age, as well as for inlaying and plating baser transition metals. the occurrence of gold in nature is quite particular among the other elements. being thermodynamically stable at ambient conditions and the least chemical active of all metals, gold is generally found in the native or uncombined state. gold has not only attracted the interest of alchemists: in recent time also, physicists and industrial chemists looked with interest at this peculiar element. many articles have been written about the presence of gold in sea water. in the last century more than 50 patens have been issued on processes for recovery of gold from sea. we may mention only two of the most significative episodes: the first one occurred at the turn of the xix century, when analysts and chemists realised that seawater was filled with gold. element 79 was just floating out there for being taken. “the trouble was figuring out how to extract this precious metal. for over a century, dreamers, artists, lunatics and well-intentioned inventors have been trying to find a way to pull the trigger on an oceanic gold rush. so far, the search for all those riches proved fruitless. in the early 1920s, the german nobel prize winner and sadly renowned chemical-weapons developer, fritz haber (1868-1934) sought to refill germany’s post-world war i coffers by developing a process to extract gold from the sea. haber and his colleagues spent years trying to perfect a profitable extraction method, involving centrifugal force and electrochemical laws, before realizing they had overestimated the total amount of gold in seawater already in their initial calculations. the project was consequently abandoned. gold was around us but haber discovered its major flaw: it costs more to extract it rather than to take it already minted” [1]. according to the sentence “if you cannot beat them, then join them”, chemists resorted to their skills: create gold! or in better words, they tried to synthesise it artificially. in the second case, as early as 1922, a wealthy man asked georges urbain (1872-1938), member of the french academy of science, a feasibility study before launching the enterprise to synthesise gold via radioactive transmutation. only in recent years – i.e. in the atomic age – the transmutation of bare metals into isotopes of gold was made possible. even though these experiments were experimentally accurate, they also proved that great improvements are still needed to make this “synthesis” economically viable [2]. presently, gold covers a wide range of applications, some of which are related to cutting-edge innovation in science and technology. a few examples: it is well known that gold wires are the backbone of computers. gold coatings protect astronauts as well as aerospace equipment from radiation and heat, thanks to gold reflective properties. gold is a proven material for catalytic converters, but it also plays a key role in innovative tools for medical diagnostics (from wellestablished rapid diagnostic tests to improved hiv/ aids diagnosis technologies, based on the use of gold nanoparticles for sensing the presence of a target molecule at ultra-low concentration). gold-based drugs have been developed and used to treat rheumatoid arthritis and research into the role of gold in cancer treatment is in progress. gold is also involved in the development of implantable electronics, allowing monitoring of patients’ vital signs and warning of potential health problem. from an environmental point of view, gold nanoparticles are involved in the development of more effective solar cells (including stretchable solar panels that can be integrated into our clothing) and fuel cell catalysts, as well as in solving problems related to groundwater contamination, since gold helps break down contaminants. in broader terms, gold will play an increasingly important role in technologies for the transition to a low carbon and a more sustainable economy, as well in protecting our health and well-being [3]. history of the gold-and-silversmith district in arezzo the tuscan gold industrial district is located almost exclusively in the province of arezzo. as it has been well documented by luciana lazzeretti [4]. arezzo, along with vicenza and valenza po, represents one of the highly specialized centres of the italian goldsmith sector. the local gold smithery developed between the fourteenth and fifteenth centuries thanks to the growth of power of the rich bourgeoisie and of the confraternities. initially it was barely able to satisfy the inner market. during the following centuries, the history of gold smithery is closely linked to the development of religious art. by convention it is established that modern goldsmith industry was born soon after 1900. the province of arezzo experienced, after world war ii, a first significant process of industrialization. it was transformed from a purely agricultural economy to an industrial structure. these changes were facilitated by some exogenous factors that modified the productive network of this territory: in particular the crisis of sharecropping and the birth of numerous small and medium industries. citing the study of luciana lazzeretti, … the development of small industry led arezzo towards 9the arezzo seminar on precious metals its great economic and social transformation. the city became, in the late sixties, one of the most advanced poles of economic development, not only in tuscany but also in wider area: central italy. the arezzo economy grew in size and turnover. it experienced a dizzying growth and a continuous increase in production, which was oriented not only to the local market, but also to foreign markets. this was made possible by the continuous progress of technology. the development of the goldsmith sector proceeded at a very intense pace in the decade 1961-1971, also favored by the italian economic boom. the industrial development suffered a sudden setback in the late seventies, when the price of gold and silver surged, due to problems of a monetary nature, international conjunctures combined with the fierce competitiveness of the other italian goldsmiths. in the 1980s, the arezzo industrial economic system lost its initial connotations, i.e. of being an economic center-based on a core of great industries (e.g. lebole, unoaerre) to attain the characteristics of local system of small and medium firms. in the 1990s, the use of a new technology, i.e. electroforming, took place: it was thus possible to create products with higher added value. jewels of great value, incredible lightness and difficult shapes were created. with the development of this and other new technologies, the local arezzo system was able to broaden its products range. it has been able to focus on new markets and satisfy an increasing number of customers. history of tca tca spa was born in tuscany, in the pulsating heart of the italian gold-and-silversmith district [5]. founded in 1977 in arezzo, where the headquarters are located, the tca has two other offices in vicenza and valenza po, for a total of over 100 employees and three industrial installations. the tca has a consolidated experience and a deep knowledge of the gold industry. this tuscan company must be considered a leading company in the global jewellery world. from the initial specialization in the treatment of ashes containing gold and silver, tca grows up to expand its skills to the recovery of platinum, palladium and rhodium. with the motto – “the resources are not infinite, recovering them and recycling them makes them endless” – tca has entered the world of modern jewellery. increasing the recovery percentage of precious metals means reducing extraction costs and environmental impact: the recovery of metal costs less than its extraction, both in economic terms and in terms of co2 emissions. precious metals are present in many sectors of industry and consequently in many waste materials. europe produces 8.7 million tons of electronic waste per year and recycles just over 2 million; in the united states less than 20 percent of electronic waste and only 10 percent of personal computers are recovered. if we consider that a ton of hardware waste contains about 16 grams of precious metals, it is clear that the percentages of recovery of gold and silver could be much higher than the current ones. even the quantity of palladium could be increased up to 90 percent, while today only 5-10 percent is recycled. low recovery rate is also found in jewellery, medical and chemical sectors. every day tca faces its own challenge to increase its skills and put them at the service of the environment and the arezzo area. aim of the present seminar the organization of the seminary “precious metals in the history of science and technology” in arezzo [6] (in may 2018, within the program of events associated with the gold fair) belongs to the history of the economic network of this city and its province. the tca’s sponsorship is a welcome gift to citizens of arezzo. it is at the same time a message to the public of how dynamic and sensitive the present industry is towards its territory. the continuous technological progress and the continuous challenges of the variable financial markets, as well as everything that revolves around this world which we could call “golden world”, is of interest not only for insiders (industrialists and technicians of high specialization), but also for economists, historians, chemists, philosophers, physicists and last but not least, for customers, who will certainly be the first to appreciate the history of what they are going to buy, to either to adorn their homes or their bodies. this transition metal, symbol of both sun and life, has no equal among all the elements of the mendeleev periodic table. for it wars have been fought, prophecies have been launched and countless theories have been debated. gold is certainly the most symbiotic element with man and his inclinations (artistic, technical, speculative or scientific). this seminar aims to bridge the gap between academy and industry; a bridge that connects two opposite banks, the study and the practice of a single river called “knowledge”. and for this we hope that this event may be the first of a series of many other meetings between industrial and academic society. 10 iacopo ciabatti, marco fontani, carla martini the readers of this volume will meet with technical terms as well as with erudite historical and philosophical terms. in fact, the peculiar aim of this publication is to unite different aspects of current, recent or ancient knowledge around this noble element. the past, the present and even the near future are addressed, particularly in the paper where the use and intrinsic value of gold in the monetary and economic field are discussed. in the paper dedicated to the role and the evolution of gold in alchemy, terms such as chymistry, chemistry, alchemy, chemeia, and al-kīmyā merge, from the dawn of time, into a “crucible” of words embracing either the philosophical aspect (linked to the mutability of matter) or the physical experience of the manipulator, or protoscientist. in other, more strictly technical papers we can observe how man loses his centrality in chemistry to the advantage of the objectivity of the experiment. and perhaps, in recent times, we can observe how gold, once again, changes over time acquiring a haphazard halo of mysticism. we are no more talking about alchemy, proto-chemistry or chemistry, but we can take a glance at macroeconomics and most recent monetary theories. as a final remark, we would like to thank for their cooperation all the authors of the papers presented at this seminar. we gratefully acknowledge also the valuable contributions of prof. cristina femoni, stefano zacchini and valerio zanotti, department of industrial chemistry “toso montanari” (university of bologna) in reviewing some of the manuscripts before publication. bibliography [1] https://www.atlasobscura.com/articles/gold-oceansea-hoax-science-water-boom-rush-treasure; last access: november 2018. [2] letter of georges urbain, 14 january 1922, lettres & manuscrits autographes lot n. 323; ader normand: http://www.ader-paris.fr/; last access: november 2018. [3] https://www.gold.org/about-gold/gold-demand/sectors-of-demand/uses-of-gold; last access: november 2018. [4] luciana lazzeretti, birth and evolution of the goldsmith district of arezzo (1947-2001). isbn 88-8453128-4 (online); last access: august 2018. [5] http://www.tcaspa.com/ [6] https://eventotcametallipreziosi.it/ substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe 1 a role for bose-einstein condensation in astrophysics b. w. ninham1,*, i. brevik2,*, o. i. malyi3,*, and m. boström3,* 1department of materials physics, research school of physics, australian national university, canberra, australia, 0200. 2department of energy and process engineering, norwegian university of science and technology, no-7491 trondheim, norway 3centre of excellence ensemble3 sp. z o. o., wolczynska str. 133, 01-919, warsaw, poland. * e-mail addresses: barry.ninham@anu.edu.au; iver.h.brevik@gmail.com; oleksandr.malyi@ensemble3.eu; mathias.bostrom@ensemble3.eu received: mar 21, 2023 revised: may 23, 2023 just accepted online: jun 06, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: b. w. ninham, i. brevik, o. i. malyi, and m. boström, (2023) a role for bose-einstein condensation in astrophysics. substantia. just accepted. doi: 10.36253/substantia-2091 abstract we revive a 60-year-old idea that might explain a remarkable new observation of a periodic low-frequency radio emission from a source at galactic distances (gleam-x j162759.5mailto:barry.ninham@anu.edu.au mailto:iver.h.brevik@gmail.com mailto:oleksandr.malyi@ensemble3.eu 2 523504.3). it derives from the observation that a high-density high-temperature charged boson plasma is a superconducting superfluid with a meissner effect. keywords: bose-einstein condensate, charged bose gas, astrophysical chemistry introduction sporadic forays over the years have explored the possibility that the physics of boseeinstein condensation ought to play some role in astrophysics, e.g. [1,2]. many of the particles involved in stellar evolution are bosons, i.e. have zero or integer spin. bose-einstein condensation is a fundamental macroscopic manifestation of quantum physics. it would seem remiss of the creator not to have employed the phenomenon somewhere in building the universe. especially is this so since fermi-dirac and classical statistical mechanics do figure largely. a suggestion of a role for bose-einstein condensation was made 60 years ago when quasars were first observed [1], and forgotten. later attempts failed because they considered superconductivity and bose condensation as classical low-temperature phenomena like that which occurs for electrons in metals. but the phenomena are not limited and exist for very high-temperature high-density charged particles [1]. we here revive that 60-year-old idea and suggest it might explain a recent extraordinary observation. the phenomenon hurley-walker et al. [3] recently reported an unusually slow periodic low-frequency radio emission from a source at galactic distances (gleam-x j162759.5-523504.3) with a pulse 3 period of 18.18 minutes. one clue to its origin is that high linear polarization has been shown to be characteristic of a source with strongly ordered magnetic fields [4-6]. the observations are unlike emissions characteristic of stars, white dwarfs, white binaries, or exoplanets. furthermore, the 0.5-light-second upper limit on the object’s size and estimated brightness temperature of 1016 k led hurley-walker et al. [3] to propose that a radiation source is a compact object with a rotational origin. the idea with that in mind, we give reasons to consider if bose-einstein condensation [1] might have something to do the phenomenon: (i) stable nuclei in stellar interiors have zero or integer spin. nuclei of higher and higher atomic numbers built up during the evolution of stars. they are charged bosons. (ii) a dense charged high-temperature boson plasma becomes nearly perfect as density increases (i.e., the coulomb collective interactions become so weak that they can be ignored, and we can work with the perfect gas approximation). (iii) it can undergo bose-einstein condensation to a superfluid state. (iv) a conducting superfluid is a superconductor. a rotating superconducting superfluid has a meissner effect. that is, it expels the magnetic field generated by rotation. (v) such a magnetic field would be trapped in the lower-density surface region. this process continues as the star collapses and its rotation speeds up. 4 (vi) massive synchrotron radiation follows that dissipates this increasing build-up of energy. the assumptions i-vi were originally made 60 years ago to explain the newly discovered quasars. schafroth [8], blatt [9], and butler [10] had shown earlier that an ideal charged bose gas below the critical point for superfluidity is a superconductor (see also refs. [7,8-17]). these theories [7-17] call on electron pairing to generate charged bosons that then lead to bose condensation and superconductivity at very low temperatures. our situation is quite different. the stellar objects involve real boson nuclei of even spin. the high-density, high-temperature plasmas are close to ideal. we recall the process of nucleosynthesis in stellar interiors [18-21]. the theory explains how nuclear reactions convert lighter elements into heavier ones through the fusion of atomic nuclei. as the star evolves, the fuel elements involve successive steps, with h, he, c, o, ne, si, fe, and u providing increasingly heavier energy sources that drive the stellar evolution to completion [18]. we need to estimate the critical temperatures and core densities for bose condensation for stars with different fuel elements to check that they can have a boson core region. calculations consider an assembly of ions of even spin, mass m and charge ze, in a background electron gas. under extreme high-density and high-temperature conditions, the system is expected to behave like a mixture of ideal gases. that can be achieved by ensuring that the average energy of coulomb interactions between two ions is small compared to their kinetic energy. at densities approaching the critical value for bose-einstein condensation of ions, i.e., when their 5 chemical potential approaches zero, the mean energy, per particle of the ideal bose gas is approximately equal to kt. the average distance between the particles is then [1] r ≈ 2 √3m/[4πρ] 3 ≈  λ = ℎ/(𝑀𝑣) = ℎ/√2  m kt, (1) where 𝜆 is the de broglie wave length of an ion of mass m and kinetic energy ~𝑘𝑇 (taken in eq (1) equal to mv2/2). the condition that the actual gas be nearly ideal is [1] 2𝑍2𝑒2 𝑟 ≪ 𝑘𝑇. (2) hence, taking the requirement eq. (2) with eq. (1), the critical expressions for temperatures, density, and particle separation can be estimated to be of the order 𝑇𝐶~ 8𝑀𝑍4𝑒4 ℎ2𝑘 (3) ρ𝐶~ 384 𝜋 𝑀4𝑍6𝑒6 ℎ6 ~ 6 8𝜋 𝑀𝑘3 𝑍6𝑒6 𝑇𝐶 3, (4) r𝐶~ ℎ2 4𝑀𝑍2𝑒2 ~ 2𝑍2𝑒2 𝑘𝑇𝐶 . (5) the numerical values are summarized in table 1. we expect that highly charged nuclei will be “dressed” by an inhomogeneous adsorbed relativistic electron cloud (mesons in another guise): just as for charged micelles or highly charged ions in electrolyte solutions. in that case, “bound” counterions are typically 80-90% of the bare charge. the effective charge is 10-20% of the actual charge. without recognising such screening, estimated critical parameters for the separation of heavy ions become unphysical and ridiculous. in table 1, we take two 6 extreme estimates to bound these uncertainties: the unscreened z and z=1. to illustrate our point, we present also the critical temperatures with 10% and 20% effective charges in table 2. for uranium, from table 2, the estimated critical temperatures are 1014 k<tc<10 15 k. these bounds are similar in magnitude to the observed brightness temperature of 1016 k discussed by hurley-walker et al. [3]. fuel element [a,z] 𝑻𝑪 (z=1) [k] 𝝆𝑪 (z=1) [g/cm3] 𝑻𝑪 (z) [k] 𝛒𝑪 (z) [g/cm3] he [4,2] 4.7 × 108 3.5 × 1010 8 × 109 2 × 1012 c [12,6] 1.4 × 109 2.9 × 1012 2 × 1012 1 × 1017 o [16,8] 1.8 × 109 9.0 × 1012 8 × 1012 2 × 1018 ne [20,10] 2.3 × 109 2.2 × 1013 2 × 1013 2 × 1019 si [28,14] 3.2 × 109 8.5 × 1013 1 × 1014 6 × 1020 fe [56,26] 6.6 × 109 1.3 × 1015 3 × 1015 4 × 1023 u [238,92] 2.8 × 1010 4.4 × 1017 2 × 1018 3 × 1029 table 1. the critical temperatures and mass densities for different fuel elements in the core of a boson star are derived from equations (3)-(5). since we did not include screening we present two different estimates (a) based on setting z=1 (columns 2 and 3) and (b) using z 7 from column 1 (columns 4 and 5). here ℎ = 6.626 × 10−27erg s, 𝑘 = 1.381 × 10−16erg/k, 𝑒 = 4.803 × 10−10esu, and we estimate the mass as 𝑀 = 𝐴 × 1.66 × 10−24g (atomic number x proton mass). fuel element [a,z] 𝑻𝑪 (𝒁 → 𝒁 ×0.1) [k] 𝑻𝑪 (𝒁 → 𝒁 × 𝟎.𝟐) [k] he [4,2] 8 × 105 1 × 107 c [12,6] 2 × 108 3 × 109 o [16,8] 8 × 108 1 × 1010 ne [20,10] 2 × 109 4 × 1010 si [28,14] 1 × 1010 2 × 1011 fe [56,26] 3 × 1011 5 × 1012 u [238,92] 2 × 1014 3 × 1015 table 2. the critical temperatures for different fuel elements in the core of a boson star are derived from equations (3)-(5). estimates (a) based on setting 𝑍 → 𝑍 ×0.1 (column 2) and 𝑍 → 𝑍 ×0.2 (column 3). constants used are same as in table 1. 8 with even the lowest densities n(he), the accompanying electron gas is highly relativistic and degenerate. we intend to go beyond these simple estimates using a screened intervening plasma including both magnetic and dielectric susceptibilities. notably, the core temperatures for the seven ages of a 20mo star discussed by trimble are t=1.9 × 10 8k for a star with helium as fuel element and t=3.7 × 109k for a star with silicon as fuel element [18]. these numbers are in surprisingly good agreement with our estimates based on using z=1 in table 1. figure 1. number density (𝑁) of stable nuclei vs. temperature phase diagram for the charged bose gas. the condensation line shown use eq. (4) and the data from table 1. adapted from figure 1 in ref. [1]. the data points from the unscreened model (z from table 1) are shown as red symbols while the results corresponding to z=1 model are shown as blue symbols. we indicate schematically a region relevant for white dwarfs (large black circle) (from figure 1 in ref. [1]). in region i, near the condensation line, 𝜌~ 6 8𝜋 𝑀𝑘3 𝑍6𝑒6 𝑇3, the system is nearly an ideal bose gas. above the condensation line in region ii (high density, high temperature), a rotating gas should become superconducting, region iii corresponds to the classical debye-hückel (high temperature, low density) region, and in region iv conditions are favourable for the formation 9 of a lattice (low temperature, low densities). region v (low temperature, high density), exhibits an energy gap (c.f. eq. (7)), where the quasi-particle elementary excitation energy has the form [1,12,13] ε(𝑝) = √( 𝑝2 2𝑚 ) 2 + (ℏω𝑝) 2 , (7) where 𝜔𝑝 is the classical plasma frequency. a diversion. with bose einstein condensation in stellar systems, further unanticipated complications may occur. as they contract under the influence of gravitational forces, their core densities and temperatures will increase, leading to charged boson core regions with increasingly heavy fuel elements. available nuclear mass models show that not all numbers of proton-neutron combinations would be stable. for each state there is a minimum and a maximum number of neutrons and protons that are stable: a phenomenon known as the neutron and proton drip line [22]. the nuclear mass models demonstrated that certain ensembles of protons and neutrons are inherently unstable. that is, the ground-state configurations of such species are energetically unstable to the emission of a constituent nucleon [22]. the matter is still open. even the established sign of nucleon-nucleon interactions which can be used for plausible models of bose condensation with neutron pairing [2] has been questioned. the data dating back to seaborg’s work from which that conclusion was reached has never been questioned. see references in [23,24]. be that as it may, the possibility that bose condensation and consequent magnetic events of even quarks and other exotic objects in the cores of neutron 10 stars has seriously been broached [25]. returning to our main theme, hurley-walker et al. [3] speculated that their observations might be due to a compact rotating magnetar. however magnetars are made of neutrons, that is fermions. our considerations apply to bosons. our propositions might then be appropriate rather to the early stages of the collapse of one of a pair of rotating massive binary stars. this would be consistent with the very low frequency of the pulses. conclusions quantum coherent bose-einstein condensation is a general property of matter with particles of even spin. therefore, it might reasonably be expected to play a role in astrophysics one way or another, just as fermi-dirac statistics does in the theory of white dwarf and neutron stars. attempts to invoke bose condensation and superconductivity are few [1-2]. the present proposal is unlike the original low temperature theories of superconductivity [10-11, 14-17]. it is concerned with a phenomenon that occurs with charge bosons at high temperature and high density [1]. the charged ideal bose gas is superfluid below its critical point [1,12]. and a rotating superfluid has a meissner effect [8-10] with consequent, expulsion and buildup of large magnetic effects. the observed linearly polarized ultra-long period low-frequency radio emission is known to be related to magnetic fields [5-7]. the bose-einstein condensation could be the origin of the magnetic fields and the phenomenon, not previously observed, might be of wider occurrence, as anticipated in [25] a. mann, “the strange hearts of neutron stars”, nature 579, 20-22 (2020). acknowledgments: the authors thank the "ensemble3 centre of excellence for nanophotonics, advanced materials and novel crystal growth-based technologies" project (ga 11 no. mab/2020/14) carried out within the international research agendas programme of the foundation for polish science co-financed by the european union under the european regional development fund and the european union's horizon 2020 research and innovation programme teaming for excellence (ga. no. 857543) for support of this work. the authors are grateful to professor nikolai bunkin for drawing our attention to the work of hurleywalker and colleagues. references [1] b. w. ninham, “charged bose gas in astrophysics”, phys. lett. 4, 278 (1963). 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[20] f. hoyle and w. a. fowler, “nucleosynthesis in supernovae”, astrophys. j. 132, 565-590 (1960). https://www.e-periodica.ch/digbib/view?pid=hpa-001%3a1957%3a30%3a%3a95&referrer=search https://www.e-periodica.ch/digbib/view?pid=hpa-001%3a1957%3a30%3a%3a95&referrer=search 13 [21] k. m. burbridge, g. r. burbridge, w. a. fowler, and f. hoyle, “synthesis of the elements in stars”, rev. mod. phys. 29, 547-650 (1957). [22] p. j. woods and c. n. davids, “nuclei beyond the proton drip-line”, annual rev. of nuclear and particle science 47, 541-590 (1997). [23] o. k. manuel, b. w. ninham and s. e. friberg, “superfluidity in the solar interior: implications for solar eruptions and climate”, journal of fusion energy, (2003), 21 (3/4), 193 198. [24] o.k. manuel ,c. bolon and p. jangam, “nuclear systematics: ii. the cradle of the nuclides”, journal of radioanalytical and nuclear chemistry 251, 417–422 (2002). [25] a. mann, ”the strange hearts of neutron stars”, nature 579, 20-22 (2020). sporadic forays over the years have explored the possibility that the physics of bose-einstein condensation ought to play some role in astrophysics, e.g. [1,2]. many of the particles involved in stellar evolution are bosons, i.e. have zero or integer ... we here revive that 60-year-old idea and suggest it might explain a recent extraordinary observation. [10] m.r. schafroth, s.t. butler, and j.m. blatt, “quasichemical equilibrium approach to superconductivity”, helv. phys. acta 30, 93 (1957) . [16] j. bardeen, l.n. cooper, and j.r. schrieffer, “theory of superconductivity”, phys. rev. 108, 1175 (1957). substantia. an international journal of the history of chemistry 3(1): 95-99, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-210 citation: c. safina (2019) chuckles and wacky ideas. substantia 3(1): 95-99. doi: 10.13128/substantia-210 copyright: © 2019 c. safina. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article chuckles and wacky ideas carl safina stony brook university, 100 nicolls rd, stony brook, ny 11794, us the safina center, 80 north country road, setauket, ny 11733, us e-mail: csafina@safinacenter.org another big group of dolphins had just surfaced alongside our moving vessel —leaping and splashing and calling mysteriously back and forth in their squeally, whistly way, with many babies swift alongside their mothers. and this time, confined to just the surface of such deep and lovely lives, i was becoming unsatisfied. i wanted to know what they were experiencing, and why to us they feel so compelling and so—close. this time i allowed myself to ask them the question that for a scientist is forbidden fruit: who are you? scientists usually steer firmly from questions about the inner lives of animals. surely they have inner lives of some sort. but like a child who is admonished that what they really want to ask is impolite, a young scientist is taught that the animal mind—if there is such—is unknowable. permissible questions are “it” questions: about where it lives, what it eats, what it does when danger threatens, how it breeds. but always forbidden—always forbidden—is the one question that might open the door to the interior: who? there are good reasons to avoid so fraught an inquiry and the cans of worms such a door could open. but the barrier between humans and animals is artificial, because humans are animals. and now, watching these dolphins, i was tired of being so artificially polite; i wanted more intimacy. i felt time slipping for both of us, and i did not want to risk having to say good-bye and realizing that i’d never really said hello. during the cruise i’d been reading about elephants, and elephant minds were on my own mind as i wondered about the dolphins and watched them pacing fluidly and freely in their ocean realm. when a poacher kills an elephant, he doesn’t just kill the elephant who dies. the family may lose the crucial memory of their elder matriarch, who knew where to travel during the very toughest years of drought to reach the food and water that would allow them to continue living. thus one bullet may, years later, bring more deaths. watching dolphins while thinking of elephants, what i realized is: when others recognize and depend on certain individuals, when a death makes the difference for individuals who survive, when relationships define us, we have traveled across a certain blurry boundary in the history of life on earth—“it” has become “who.” “who” animals know who they are; they know who their family and friends are. they know their enemies. they make strategic alliances and cope with chronic rivalries. they aspire to higher rank and wait for their chance to challenge the existing order. their status affects their offspring’s prospects. their life follows the arc of a career. personal relationships define them. sound familiar? of course. “they” includes us. but a vivid, familiar life is not the domain of humans alone. we look at the world through our own eyes, naturally. but by looking from the inside out, we see an inside-out world. this book takes the perspective of the world outside us—a world in which humans are not the measure of all things, a human race among other races. to understand anything, really, one must go deep, to the roots. in our estrangement from nature we have severed our sense of the community of life and lost touch with the experience of other animals. so while i went in search of particular “who” animals, 96 carl safina i delved into new findings about thought, emotion, and consciousness that apply to many animals. and because everything about life occurs along a sliding scale, understanding the human animal becomes easier in context, seeing our human thread woven into the living web among the strands of so many others. this project differs from other “animal thinking” books in one fundamental way. i’d intended to take a bit of a break from my usual writing about conservation issues, to circle back to my first love: simply seeing what animals do, and asking why they do it. i traveled to observe some of the most protected creatures in the world—elephants of amboseli in kenya, wolves of yellowstone in the united states, and killer whales in the waters of the pacific northwest—yet in each place i found the animals feeling human pressures that directly affect what they do, where they go, how long they live, and how their families fare. so in this book we encounter the minds of other animals and we listen—to what they need us to hear. the story that tells itself is not just what’s at stake but who is at stake. the greatest realization is that all life is one. i was seven years old when my father and i fixed up a small shed in our brooklyn yard and got some homing pigeons. watching how they built nests in their cubbyholes, seeing them courting, arguing, caring for their babies, flying off and faithfully returning, how they needed food, water, a home, and one another, i realized that they lived in their apartments just as we lived in ours. just like us, but in a different way. over my lifetime, living with, studying, and working with many other animals in their world and ours has only broadened and deepened —and reaffirmed—my impression of our shared life. that’s the impression i’ll endeavor to share with you in the pages that follow. keywords. ethology, theory of mind, behaviorism, progress of science. this chapter is an excerpt from a book of the author (c. safina, beyond words: what animals think and feel, henry holt and company, new york, 2015). the same book is available in italian as: “al di là delle parole” by adelphi press (2015). for more contents please visit the website: carlsafina.org. i’d never deny that formal scientific research in controlled conditions has been exceptionally helpful. i’ll also never lose sight of the fact that the real lives of animals are too expansive for laboratories to adequately reflect. yet many behaviorists work only in labs (or, far worse, philosophy departments). now we’ll see how, by slicing reality salami-thin and marinating it in jargon, researchers who confuse sometimes amuse. the search for intelligent life on earth produces a few chuckles along the way. one dog-loving researcher videotaped dogs in a neighborhood park during two years before arriving at the following conclusions: if a dog wanted to play with another dog it was facing, it would usually perform the “play invitation” (that familiar bow: front end crouched low, rear end high). but if the dog the play seeker wanted to romp with was facing away, the play seeker would first get the other dog’s attention – with a paw, for instance, or by barking. in one of those science-marches-on moments, the researcher tells us, “they seem to be reacting to distinct cognitive states.” in everyday terms: from two years of video analysis she discovered that a dog can distinguish another dog’s face from its butt. may i please say this: a dog’s behind is not a “distinct cognitive state.” why not just say that dogs get other dogs’ attention before inviting play? too obvious to seem like science? just minutes after i started searching the formal academic literature for “theory of mind,” a typical recent study popped up. titled “on the lack of evidence that non-human anima ls possess any thing remotely resembling a ‘theory of mind,’” it was published in the philosophical transactions of the royal society. the authors begin, “theory of mind entails the capacity to make lawful inferences about the behaviour of other agents on the basis of abstract, theory-like representations of the causal relation between unobservable mental states and observable states of affairs.” (translation: by watching another’s behavior, we can guess at what they may be thinking.) they continue:“we are entirely agnostic (for our present purposes anyway) about whether an organism’s states are modal or amodal, discrete or distributed, symbolic or connectionist or even about how they come to have their representational or informational qualities to begin with… of course, there are innumerable other factors that also contribute to shaping a biological organism’s behavior.” i can probably understand that study—i just don’t want to. two guys from rutgers university (where i got my own phd, so i am favorably inclined) have published a review called “reading one’s own mind: a cognitive theory of self-awareness.” here we go: “we’ll start by examining what is probably the most widely held account of self-awareness, the ‘theory theory’ (tt). the basic idea of the tt of self-awareness is that one’s access to one’s own mind depends on the same cognitive mechanism that plays a central role in attributing mental states to others… theory theorists argue that the tt is supported by evidence about psychological development and psychopathologies… after making our case against 97chuckles and wacky ideas the tt and in favor of our theory, we will consider two other theories of self-awareness to be found in the recent literature.” no, thanks! theorizing about theorizing seems a very poor substitute for actually watching living beings do their thing. “theory of mind” is probably the most oversold concept in human psychology, as well as the most underappreciated, oft-denied aspect of non-human minds. we’ve all been in relationships where we thought, “i don’t know where i stand with her” or “i don’t know what to expect of him.” as john locke said in the 1600s, “one man’s mind could not pass into another man’s body.” the painter paul gauguin wrote of his thirteen-year-old tahitian wife, “i strive to see and think through this child.” joni mitchell sang, “there’s no comprehending, / just how close to the bone and the skin and the eyes / and the lips you can get / and still feel so alone.” the roman poet lucretius—in what w. b. yeats called “the finest description of sexual intercourse ever written” (not to mention a good translation)—observed bleakly, they gripe, they squeeze, their humid tongues they dart, as each would force their way to t’others heart: in vain: they only cruise about the coast, for bodies cannot pierce, nor be in bodies lost.… all ways they try, successless all they prove, to cure the secret sore of ling’ring love. “the tragedy of sexual intercourse,” yeats howled, “is the perpetual virginity of the soul.” paul valéry, another poet, noted that “the interchange of human things between men requires that brains be impenetrable.” praise the poets for being good scientists. the scientist nicholas humphrey, says, “there are no doors between one consciousness and another. everyone knows directly only of his or her own consciousness and not anyone else’s!” if i want to sneak up on you, or fantasize while flirting, or steal from you, it is crucial that my mind remain unreadable. the more we could open into each other’s minds, the more our brains would need a way to get up and lock the door. so yes, we observe, we resonate, but ultimately we guess. that’s the most we can do. we can choose to reveal ourselves or hide our cards. but the choice is ours. chimps have mainly a theory of chimp mind, if we might put it that way; dolphins, mainly of dolphin mind. humans often experience difficulty understanding even human needs and predicting other people’s actions. and humans who assume that other animals are not even conscious—or who ignore their capacity for conscious experience—show how faulty our theory-of-mind talents are. people in japan and the faeroe islands kill dolphins and pilot whales by running steel rods into their spinal columns while they squeal in pain and terror and thrash in agony. (in japan, it’s illegal to kill cows and pigs as painfully and inhumanely as they kill dolphins.) the lack of compassion for dolphins and whales indicates that humans’ “theory of mind” is incomplete. we have an empathy shortfall, a compassion deficit. and humanon-human violence, abuse, and ethnic and religious genocide are all too pervasive in our world. no elephant will ever pilot a jetliner. and no elephant will ever pilot a jetliner into the world trade center. we have the capacity for wider compassion, but we don’t fully live up to ourselves. why do human egos seem so threatened by the thought that other animals think and feel? is it because acknowledging the mind of another makes it harder to abuse them? we seem so unfinished and so defensive. maybe incompleteness is one of the things that “makes us human.” while some people seem unable to sense the minds of non-human animals, other people see human-like minds in everything. our minds automatically discern human-like faces in things like clouds, the moon, even in food. many believe that rocks, trees, streams, volcanoes, fire, and other things have thoughts, that everything has a mind and is inhabited by spirits that might act for or against us. that’s called panpsychism. the religion that follows from this primal human assumption is pantheism. it is common among tribal huntergatherer peoples, and it’s also alive and well in modern life. on the summit of mount kilauea, in hawaii, i’ve seen offerings of money and liquor, put there by people who think that volcanoes have a god within who watches, tallies favors, and sometimes acts vindictively. don’t get the volcano mad by ignoring it. a little more booze and a few more bills, some flowers and some food and a roast pig occasionally, and the volcano’s fiery goddess, pele, will perhaps be mollified. and this is in the united states, where anyone can just stroll into the visitors’ center and learn some volcano geology. (park rangers have asked visitors to stop leaving offerings of food, money, flowers,incense, and liquor on kilauea because in sum the offerings are more clearly appreciated by rats, flies, and roaches than by the goddess.) it appears that deep belief in the supernatural comes naturally to us. “nonhuman animals may arrive at beliefs based on evidence,” writes philosopher christine m. korsgaard, 98 carl safina “but it is a further step to be the sort of animal that can ask oneself whether the evidence really justifies the belief, and can adjust one’s conclusions accordingly. “yet it is many humans who are demonstrably incapable of asking whether evidence justifies their beliefs, then adjusting their conclusions. other animals are great and consummate realists. only humans cling unshakably to dogmas and ideologies that enjoy complete freedom from evidence, despite all evidence to the contrary. the great divide between rationality and faith depends on some people choosing faith over rationality, and viceversa. other animals’ actions and beliefs are evidencebased; they don’t believe anything unless the evidence justifies it. other animals attribute awareness only to things that are actually aware. while a dog might bark to rouse someone sleeping on the living room couch, they never seek assistance from the sofa itself. or from volcanoes. they easily discriminate living things from inanimate objects and even from impostors. true, skilled duck hunters’ decoys and calls fool passing ducks enough to get them to swerve into gun range, but the ruse must be elaborate or it won’t work. fish can be hard to fool even with artificial lures painstakingly designed to look and act like the real thing. years ago, while doing research that involved tagging migrating falcons, i lured the falcons to my net with tethered live starlings. the frightened starlings did not enjoy this; nor did i. so i put a stuffed starling on a string, wings in flight position, behind the net. of course, in nature absolutely everything that looks like a bird and is covered with feathers and has a gleaming eye and moves up and down is a bird. yet the stuffed bird never fooled one single falcon. they all sized it up, at a glance, as somehow “not real,” and ignored it. that is impressive. other animals are exceptionally good at identifying and reacting to predators, rivals, and friends. they never act as if they believe that rivers or trees are inhabited by spirits who are watching. in all these ways other animals continually demonstrate their working knowledge that they live in a world brimming with other minds, as well as their knowledge of those minds’ boundaries. their understanding seems more acute, pragmatic, and, frankly, better than ours at distinguishing real from fake. so i wonder: do humans really have a better-developed theory of mind than other animals? people watching a cartoon of nothing more than a circle and a triangle moving around and interacting almost always infer a story, involving motives and personalities and genders. children talk to dolls for years, half-believing – or firmly believing – that the doll hears and feels and is a worthwhile confidant. many adults pray to statues, fervently believing that they’re listening. when i was a teenager, our next-door neighbors (americans who’d been born and raised in new york) kept religious statues in every room except their bedroom, lest the virgin witness human lust. all of this indicates a common human inability to distinguish conscious minds from inanimate objects and evidence from nonsense. children often talk to a fully imaginary friend whom they believe listens and has thoughts. monotheism might be the adult version. we populate our world with imaginary conscious forces and beings – good and evil. most present-day people believe they’re helped or hindered by deceased relatives, angels, saints, spirit guides, demons, and gods. in the world’s most technologically advanced, most informed societies, a majority of people take it for granted that disembodied spirits are watching, judging, and acting on them. most leaders of modern nations trust that a sky god can be asked to protect their nation during disasters and conflicts with other nations. all of this is “theory of mind” gone wild, like an unguided fire hose, spraying the whole universe with presumed consciousness. humans’ “superior” theory of mind is in part pathology. the oft-repeated line “humans are rational beings” is probably our most halftrue assertion about ourselves. there is in nature an overriding sanity and often, in humankind, an undermining insanity. we, among all animals, are also frequently irrational, distortional, delusional, worried. yet i also wonder: is our pathological ability to generate false beliefs, to elaborate upon what does not exist, also the very root of human creativity? is our tendency to imagine and even cling to what is false the foundation of all our inventive genius? perhaps believing false things comes bundled with our peculiar, oddly brilliant ability to envision what is not yet, and to imagine a better world. no one has explained where creativity arises, but some human minds lurch along sparking new ideas like a train with a stuck wheel. it’s not rationality that’s uniquely human; it’s irrationality. it’s the crucial ability to envision what is not, and to pursue unreasonable ideas. perhaps other animals don’t need to manipulate logic because their actions are logical. they don’t need tools because they are self-sufficient in their special abilities. perhaps humans need logic and tools because without them we cannot survive, in a sense unable to succeed just as we are. perhaps this is intuited in the story of the fall, the trade-off in going from self-contained creatures like all the others to creatures needing a new way to access new knowledge so that, with much craft and 99chuckles and wacky ideas effort, our distinctly human abilities might compensate for our distinctly human frailties. insight, shared to various degrees by other apes, wolves and dogs, dolphins, ravens, and a few other creatures, relies on an ability to see what is not there. as does turning homeward, or waiting for the mate who happens to be gone at the moment. perhaps the depth of human insight comes with genes that give us a capacity not just to imagine what isn’t there but to insist on it, to fervently hold and pursue unmoored beliefs. what is more irrational than a nonexistent melody, or the dream of human flight, or holding fixed the light of an image, or capturing a musical performance so that it may be heard again and again, or diving deep into the sea and breathing underwater? who could have imagined such things? who else. along for the ride on that singular ability to imagine comes sheer brilliance and utter madness. and maybe more than anything, what “makes us human” is our ability to generate wacky ideas. substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 2(2): 19-25, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-57 citation: j.m. garcia-ruiz (2018) 2001: the crystal monolith. substantia 2(2): 19-25. doi: 10.13128/substantia 57 copyright: © 2018 j.m. garcia-ruiz. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article 2001: the crystal monolith juan manuel garcia-ruiz laboratorio de estudios cristalográficos. instituto andaluz de ciencias de la tierra. csic-universidad de granada. spain e-mail: juanmanuel.garcia@csic.es abstract. in the famous movie “2001: a space odyssey”, stanley kubrick and arthur clarke claim that an extraterrestrial civilization catalyzed the evolution of hominids on our planet. to represent such a powerful civilization, they use a crystal. to date, it seems that we have not been contacted by advanced civilizations and that we are alone to manage our own future. yet kubrick and clarke perhaps intuitively touched a truth about the power of crystals. an argument is developed here that genuine crystals, mainly quartz single crystals, were the earliest catalysts of the abstract thinking, symbolism, and consciousness. keywords. crystals, crystallography, abstract thinking, paleoneurobiology, kubrick, “2001: a space odissey”. the monolith of “2001: a space odyssey” art, in its very different forms, has contributed and contributes almost as much as science and philosophy to create our conception of the outside world. for instance, most citizens believe nowadays that we are not alone in the universe, in spite of the fact that we have no evidence of the existence of extraterrestrial life even in the closest planets and their moons. the science-fiction movie “2001: a space odyssey”1 and the novel based on its script is one of the masterpieces of film that has contributed in large measure to our vision about the great question of the habitability of the universe. the movie, released in 1968, was directed by stanley kubrick based on the script he wrote with the science-fiction writer arthur clarke. the screenplay was based, in turn, on clarke’s 1951 story, “sentinel of eternity”.2 the plot in both cases tells of the tangible existence of alien civilizations much more advanced than our own. how, in a novel or a film, could such a mighty civilization, capable of modifying humankind’s evolution, be visually represented? what would an alien big brother look like? it had to be something that would evoke ultrahuman power, something enigmatic, disturbing and even fearsome, a secular image of god. clarke and kubrick described their vision of the star character of the movie, the monolith, with the following words: it was a rectangular slab, three times his height but narrow enough to span with his arms, and it was made of some completely transparent material; indeed, it 20 juan manuel garcia-ruiz was not easy to see except when the rising sun glinted on its edges. as moon-watcher had never encountered ice, or even crystal clear water, there were no natural objects to which he could compare this apparition. it was certainly rather attractive, … (figure 1).3 they chose a parallelepiped, a transparent slab, perfectly smooth with sharp edges and dihedral ninetydegree angles. in a word, they chose a crystal. as a completely transparent monolith was ill-suited to the art of film, kubrick was compelled to darken the transparent slab, but both authors agreed that the icon had to be a crystal. in fact, in the early versions of the 2001 screenplay,4 the monolith was specified as “a cube about fifteen feet on a side, and it is made of some completely transparent material”.5 they wrote: “the hominids watch, wideeyed, mesmerized captives of the crystal cube.6 moreover, the sequence entitled “killing the lion” ended with the following phrase: “and then one night the crystal cube was gone, and not even moonwatcher ever thought of it again. he was still wholly unaware of all that it had done”. the final version of the screenplay also explicitly talks of a “crystalline monolith”;7 and the hypnotizing sound that attracts moon-watcher “pulsed out from the crystal”.8 clarke also had chosen a crystal for “sentinel of the eternity”: the machine left purposefully on our moon by the alien civilization was a crystal pyramid. he wrote: “perhaps you understand now why that crystal pyramid was set upon the moon instead of on the earth”.9 the sentinel that will alert that humans have the technology to cross the space was a “crystal pyramid” with hard, scratch-proof “crystal walls”, most probably a diamond. the choice of a crystal to represent a supernatural intelligence, or of any machine built by it, was inevitable. in everyday language, the word crystal evokes concepts such as order, purity, transparency, harmony, perfection, reason, intelligence… and power. these are all justified because they allude to the physical and chemical properties that have characterized crystals throughout history, and to how these properties have been transmuted to our cultural heritage through the arts and philosophy. humans have held a fascination for crystals since primitive times, and even today it is thought that crystals hold some enigmatic power. since the very formation of our consciousness, but mainly since the discovery of their three-dimensional order in the nineteenth century, crystals have represented the exact opposite of the atavistic, the biological, and the human. thus, the image of a device placed on purpose by an advanced alien civilization or from that civilization had to be a crystal. the selected shape, a pyramid, or cube or slab, was changing through the different stages of the script – but it was always thought to be a crystalline polyhedron. clarke and kubrick belong to a group of intellectuals who believed in the existence of advanced alien civilizations capable of traveling across the universe that could have purposefully altered the evolution of life on our planet,10 a theory that can be seen as a secular version of christian visitation. more than fifty years after the film’s premiere, we are yet to have any contact with an extra-terrestrial civilization. we have already visited saturn and jupiter, we have found in their moons jets of water11 and clouds of organic compounds12, but no sign of life yet. our rockets and probes have traveled beyond our solar system. it is worth remembering that we have been emitting radio waves into outer space for some 130 years. at the speed they travel, we have already reached celestial bodies that are 130 light-years away, a distance far enough to reach other solar systems such as alphacentauri,13 or the trappist-1 and its seven planets where nasa optimistically pushes astrobiological groups to search for life.14 this means that within a distance of 65 light years from earth either there is no life, or the life that there is either has not noticed (it is not capable of hearing us) or does not know how to respond. or they are a bunch of intelligent but rude aliens that do not want to know anything about us (which, given the state of the management of our planet, would be a sign of intelligence). all in all, we need to sort out our intraplanetary disputes and environmental challenges, because it does not seem that anybody out there is going to come and lend us a hand crystals having taken the position that the vision of kubrick and clarke may remain science fiction for the foreseefigure 1. a frame of the movie “2001: a space odyssey” directed by stanley kubrick. the black monolith was a crystal clear cube in the original script but after considering the technical problems kubrick decided to use a black cube and then a black slab. 212001: the crystal monolith able future, i do not dispute the possibility that the two geniuses responsible for the masterpiece 2001 were not so misguided on the role that crystals have played in evolution. we now know that the first objects that hominids collected without any applied purpose were quartz crystals. a set of varied, irrefutable proofs have been gathered and in part contributed by paleoart experts such as robert bednarik15 and james harrod.16 for example, pei wenzhong, who discovered peking man, published in 1931 the discovery of twenty quartz crystals in the famous zhoukoudian cave along with the remains of homo erectus that date from 700,000 years ago.17 one of them was a perfectly faceted, smoky quartz crystal, a hexagonal prism, biterminated in pyramids of some six centimeters in length. in 1989, at the famous archaeological site of singi talav in india, six practically complete quartz prisms from the lower acheulean strata (300,000 – 150,000) were found (figure 2). these prisms are natural, have not been modified and measure between 7 and 25 mm in length.18 smaller quartz crystals were excavated at the acheulean site of gesher benot ya’aqov, in israel (240-750 years ago).19 bednarik discovered a fragment from a sizeable transparent rock crystal also in the acheulean, this time at gudenushöhle, in austria,20 and quartz crystals at various levels ca. 276-500 kiloyears ago in wonderwerk cave (south africa).21 in summary, almost a million years ago (perhaps even earlier if other discoveries are confirmed), the homo erectus brain was so drawn to the shapes of quartz crystals that they decided to collect and travel with them.22 crystals collected by hominids have been found alongside hominid fossils far from their place of origin. in several cases, the crystals found in these sites (for instance in singi talav) came from different outcrops. despite being collected in different sites, they were identified as objects of the same type, a formidable exercise of pattern recognition. these crystals were not tools since they are too small to be used for any practical purpose. they have not been worked on or modified, nor do they have perforations or signs of use as trinkets or jewels. no, they were objects considered valuable in of themselves. they were esteemed in the acheulean, they continued to be so in the pre-historical and historical eras. and there is no evidence that the human fascination for crystals is waning even today. the question is unavoidable: why were those hominids, still without a developed consciousness, drawn to those quartz crystals? why did they value them and carry them as precious treasures? (figure 3). when homo erectus raised his head and looked at the african savannah or the asian forests, everything he saw was curved or branched. the trees, the bushes, the furrows carved by water, the streams, the clouds, the mountains, the animals, and their fellows: there was not one straight line,23 no object formed by flat surfaces, no polyhedral shapes. today, thanks to the pioneering and quixotic lewis fry richardson24 and the sagacious benoit mandelbrot,25 we know that the geometry of nature is fractal geometry. everything that nature has created on the face of the earth is the product of continuous branching and curvature. everything except crystals. when homo erectus tried to understand the world with their preconscious brains, the first thing they had to do was to find visual patterns, to separate what is the same from what is different. when they found quartz or pyrite crystals, they would have understood that these shiny, polyhedral objects formed by straight lines, flat faces and deterministic angles, free of curves, were utterly unique. we must remember that, with the exception of crystals, the straight line, the grid, polyhedra and, of course, euclidean geometry, were all invented by humans. this exceptional euclidean nature is the reason figure 2. collection of quartz crystals from the acheulian site of singi talav. from reference 18. (d’errico). © an idea of juan manuel garcia-ruiz. photography javier trueba. figure 3. a recreation of the collection of crystals by homo erectus. ©javier trueba/juan manuel garcía-ruiz. with permission. 22 juan manuel garcia-ruiz why rock (quartz) crystals were among the first objects collected by hominids, before the creation of our consciousness. however, there was something even more enigmatic about these objects. everything that homo erectus saw around them had an origin, a history, a beginning and an end. plants sprouted and grew, streams rose up from the rains, as did the forms etched by erosion; animals were born, and they themselves saw their children born: all things, even the rudimentary tools that they had managed to produce, had an origin, had a beginning and an end. however, those mysterious crystals did not. who was the creator of something so singular? that question had to have an answer sooner or later. inevitably, the crystals were seen as “machines”, devices that for the first time “communicated” with the beyond, whatever or whoever the beyond was – any of the versions of the great beyond that the monolith from 2001 encompasses.26 the role of crystals as icons of power grew during human evolution and prehistory. a dramatic example is the case of the dolmen of alberite (cádiz, spain), a funerary installation ca. 6000 years old (figure 4).27 a smoky crystal of quartz of about 45 cm in length was found within a well preserved dolmen. the crystal has a blocky habit, and consists of a well developed {100} hexagonal prism terminated with {101} pyramids faces. its origin is undoubtedly pegmatitic. the crystal is well faceted but it is not transparent, and it has some deformations. this suggests a sophisticated ability to identify single crystals from other rocks and mineral aggregates. the collection and location of this crystal was purposeful because it is the only singular object found in the dolmen. the use and meaning of this object are unknown but indeed was not a tool because there is no sign of hitting or percussion, no pieces have been removed from it, and it is too large to be used as a utensil. most probably the crystal was considered an icon, a means of enormous value, of power. the reason is that this type of pegmatitic quartz crystal does not exist near the area of the location of the dolmen. the closest areas from which this type of crystals are known are the gredos range near madrid, or the galicia massif northwest of spain.28,29 therefore, these early mineral collectors had to transport that crystal from at least 500 kilometers or perhaps 900 kilometers to place it in the dolmen of alberite. only an icon of great relevance would have been the subject of that effort. almost coetaneous with alberite, quartz crystals were labored in many other sites in europe and elsewhere. they worked the crystals of quartz with admirable skill and expertise, capable of converting, for example, a dagger into a work of art rather than a weapon (see figure 5).30 the irresistibly combination of uniqueness, mystery, and harmony is the source of fascination for crystals that has been maintained throughout human history. those little “monoliths” not only sparked the imagination of our ancestors but have also shaped our culture and our thought. they become idols in which to trust, figure 4. the dolmen of alberite. a) the red star shows the location of alberite in south spain. the red circles show the possible provenance of the crystal. b) the quartz crystal found in the dolmen. photograph courtesy of salvador dominguez-bella. c) picture of the dolmen by pedro cantalejo; d) scheme of the dolmen, from the gabinete de bellas artes of the museo of cádiz, junta de andalucía. figure 5. a 25 cm long dagger blade of rock crystal from the copper age found in tomb 10.042-10.049 of the archaeological zone of valencina de la concepción-castilleja de guzmán (seville). photography: miguel ángel blanco de la rubia. courtesy of the atlas research group (university of seville). 232001: the crystal monolith the objects that triggered the belief in the existence of extraterrestrial powers, a power able to communicate by sending storms, stones (meteorites) or energy to make stones (lightning stones or fulgurites): the baethylus or sacred stones that were worshipped for millenniums).31 the use of crystals as objects with magic power was a characteristic shared by many primitive civilizations, including maoris, apache, canadian indian, polynesian and the malagasy of madagascar.32 later on, crystals and minerals were considered arcane curative as described in babylonian tablets33 and the lapidarium of the early and late middle ages and the renaissance;34 later, the harmony of the universe was explained by kepler on the basis on the platonic polyhedra, shapes all of crystalline solids.35 from the mid-nineteenth century, crystals underlay the teaching that converted order and abstraction into the tools to understand the world, not only for science but also for art and philosophy.36,37,38 they are not extra-terrestrial. no alien civilization put them there. their origin is as natural as any other object of nature. but their rarity and their allure probably sparked the imagination of a mind already prepared to grasp the meaning of that singularity. nowadays, our brains are prepared to identify order; in fact, to see order even when order is not there, the origin of some optical illusions. our brains have evolved to seek geometrical patterns to understand the external world.39 but are our brains designed to prefer order? in other words, do crystals attract us because the crystals were among the first elements that our ancestors, starting with homo erectus, collected? or did we gather crystals almost a million years ago because our brain was already designed to prefer order (which benefited the comprehension of nature and therefore could be evolutionarily advantageous)?40 did crystals impact our cultural history because they are firmly linked to the birth of art, symbolism, and consciousness?41 the hypothesis that i propose in this paper is difficult to prove. only circumstantial evidence can be offered so far, but the current evidence is strong enough to be worth of more thoroughly investigations. i foresee two main lines of research to explore further the role of crystal geometry in the ability of hominids and humans to develop an abstract vision of the external world. first, we must increase archeological field studies, particularly in the paleolithic, to find further material to be studied with modern analytical methods. new discoveries of collected crystals and other manuports will help to reconstruct the story of the use of fluorite, pyrite and especially quartz crystals. this will allow revealing with the highest precision when hominids started to collect crystals and how its significance and “uses” evolve with time. among the putative evidence for symbolic behavior, it has been proposed that oldowan hominids were already shaping rocks with geometric shapes, ca. 1.7 ma.42 was the oldowan (mode i) culture already prepared to collect crystals? could the “crystal centered” view i propose help to understand the technological jump from the oldowan to the acheulean?43 oakley were among the first to propose that some of the finer acheulian handaxes look like masterpieces of artistic craftsmanship rather than tools, i.e., they were made with symmetrical perfection beyond technical necessity.44 a mind that searched for perfect mirror symmetry is the first step to produce harmony and beauty with patterns. is this search for symmetry linked to the symmetry of crystals? is there any correlation between the collection of crystals and the evolution of the mirror symmetry of the handaxes during the acheulean? the second line of research must focus on neurological studies. it has been proposed that superior pattern processing is the fundamental basis of most, if not all, unique features of the human brain, and the belief in imaginary entities such as ghosts and gods. the process of pattern recognition involves the electrochemical, neuronal network-based, encoding, integration, and transfer to other individuals of perceived or mentally-fabricated patterns.41 it will also be very important to understand the current perception of crystal symmetry, and fractal order (either mathematical or random fractals) by humans and closely related primates. this will be precious information for establishing whether homo erectus perceived at the neurological level the finding of the “monoliths” one million years ago, and how they impact cognitive milestones in human evolution. finally, the investigation opens a great question. our understanding of the world is based on a limited abstracted vision of a complex physical world. the current level of understanding has been shaped by the euclidean reduction that we began to use almost one million years ago. what would have happened if there had not been any crystals? would an understanding of the world that had not drawn on abstraction have been evolutionarily successful? is there a way to understand the world as it is, and not as we have invented it for ourselves? acknowledgments the research leading to these results has received funding from the european research council under the european union’s seventh framework programme (fp7/2007-2013)/erc grant agreement nº 340863 “prometheus”. the author also acknowledges a grant of the 24 juan manuel garcia-ruiz program salvador de madariaga (ministry of economy and competitiveness of spain). references 1. s. kubrick. 2001: a space odyssey. metro-goldwyn-mayer. 1968. 2. a.c. clarke, the sentinel, avon periodical inc, 1951. 3. a.c. clarke. 2001: a space odyssey. a novel based in the screeplay by a.c. clarke and s. kubrick, arrow books, 1968. page 18. 4. s. kubrick and a.c. clarke, 2001, a space oddisey. typerwritter version of the script written october, 13, 1965. 5. s. kubrick and a.c. clarke, 2001, a space oddisey. typerwritter version of the script written october, 13, 1965, page a14. 6. s. kubrick and a.c. clarke, 2001, a space oddisey. typerwritter version of the script written october, 13, 1965, page a17. 7. a.c. clarke. 2001: a space odyssey. a novel based in the screenplay by a.c. clarke and s. kubrick, arrow books, 1968. page 19 8. a.c. clarke. 2001: a space odyssey. a novel based in the screenplay by a.c. clarke and s. kubrick, arrow books, 1968. page 20. 9. a.c. clarke, the sentinel, avon periodical innc, 1951, page xxx 10. g.d. philips, stanley kubrick: interviews, university press of mississippi, 2013. 11. w.b. sparks, et al. the astrophysical journal, 2016, 829, 1. 12. m.y. palmer et al. science advances 2018, 3, e1700022. 13. e. hand, nature 2012, 490, 323. 14. j. de witt, nature astronomy, 2018, 2,  214. 15. r. g. bednarik. rock art research 2003, 20, 89. 16. j. harrod, arts 2014, 3, 135. 17. p. wenzhong, acta geologica sinica (english edition) 1931, 11, 109. 18. f. d’errico, c. gaillard, m.n. misra. hominidae. proceedings of the 2nd international congress of human paleontology. 1989 pp. 237–39. editoriale jaca book, milan. 19. n. goren-inbar et al., rock art research 1991, 8, 133 20. r.g. bednarik, cambridge archaeological journal 1992, 2, 27. 21. r.g. bednarik, the artefact 1993, 16, 61. 22. r.g. bednarik, developments in primatology: progress and prospects, the human condition. chapter 3: the hard evidence, springer science, 2011. 23. there are some natural straight lines but they are irrelevant for the discussion. for instance, the horizon may appear like a curve line almost straight only in some places of the shoreline. hanging vines are also straight, but they grow in the rain forest, an dangerous ecosystem for the evolution of hominids. 24. l.f. richardson, o. m. ashford, p. g. drazin, the collected papers of lewis fry richardson, cambridge university press, 2009 25. b. mandelbroth, the fractal geometry of nature, w.h. freeman, 1983. 26. aunque kubrick and clarke were atheists they decided to leave the interpreation of the monolith opens. see s. schwam. the making of 2001: a space odyssey. modern library. 1998 27. j. ramos muñoz, and f. giles pacheco (eds.) el dolmen de alberite (villamartín). aportaciones a las formas económicas y sociales de las comunidades neolíticas en el noroeste de cádiz, universidad de cádiz, cádiz. 1996 28. s. dominguez-bella and d. morata. zephyrus 1995 48, 129. 29. s. domínguez-bella, j. ramos muñoz, m. pérez-rodríguez.): “productos arqueológicos exóticos en los contextos de los yacimientos prehistóricos de la banda atlántica de cádiz. inferencias de su documentación”, la ocupación prehistórica de la campiña litoral y banda atlántica de cádiz. aproximación al estudio de las sociedades cazadoras-recolectoras, tribales-comunitarias y clasistas iniciales, (ramos muñoz, j., editor), junta de andalucía, sevilla, 2008, 213. 30. a. morgado, j.a. lozano, l. garcía sanjuan, m. luciañez treviño, c. p. odriozola, d. lamarca irrisarri, a. fernandez flores. quaternary international, 2016, 424, 232. 31. plinio the elder, natural history, volume 36. 32. v. barnouw, adam, an introduction to anthropolog: ethnology. vol. 2 (homewood, illinois,: the dorsey press, 1971). 228. 33. k. reiter,  die metalle im alten orient: unter besonderer berücksichtigung altbabylonischer quellen. mu ̈nster: ugarit-verlag. 1997. 34. j.l. amorós. la gran aventura del cristal. editorial complutense. madrid. second edition, 2017. 35. j. kepler, the harmonies of the world. tr. dr juliet field. pub., by american philosophical society. 1997. 36. b. kahr. crystal growth and design 2004, 4, 3. 37. n. brosterman. inventing kindergarten. new york: harry n. abrams. 1997 38. j.s. rubin, intimate triangle: architecture of crystals, frank lloyd wright and the froebel kindergarten. 252001: the crystal monolith huntsville, alabama: polycrystal book service. 2002 39. d. ackerman i sing the body’s pattern recognition machine. new york, ny: time magazine. june 15, 2004. 40. b.d. beltman, psychiatric annals, 2005, 39, 5. 41. m.p. mattson. frontiers in neurosciences, 2014, 8. 265. 42. j. harrod, arts 2014, 3, 135, page 140. 43. i. de la torre, l. mchenry, j. njau and m. pante, archaeology international 2011-2012, 15, 89. 44. k. oakley. in s. l. washburnand p. dolhinow (eds), perspectives on human evolution, 1972 pp. 14−50. holt, rinehart, and winston. new york. substantia. an international journal of the history of chemistry 3(1) suppl.: 39-44, 2019 firenze university press www.fupress.com/substantia citation: f. abbri (2019) gold and silver: perfection of metals in medieval and early modern alchemy. substantia 3(1) suppl.: 39-44. doi: 10.13128/substantia-603 copyright: © 2019 f. abbri. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-603 gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri dsfuci –università di siena, viale l. cittadini 33, il pionta, arezzo, italy e-mail: ferdinando.abbri@unisi.it abstract. for a long time alchemy has been considered a sort of intellectual and historiographical enigma, a locus classicus of the debates and controversies on the origin of modern chemistry. the present historiography of science has produced new approaches to the history of alchemy, and the alchemists’ roles have been clarified as regards the vicissitudes of western and eastern cultures. the paper aims at presenting a synthetic profile of the western alchemy. the focus is on the question of the transmutation of metals, and the relationships among alchemists, chymists and artisans (goldsmiths, silversmiths) are stressed. one wants to emphasise the specificity of the history of alchemy, without any priority concern about the origins of chemistry. keywords. history of alchemy, precious metals, transmutation of metals. introduction for a long time alchemy has represented a sort of intellectual enigma, a critical difficulty for the philosophical and scientific historiography because of the relationships between alchemy and modern chemistry, which have strongly influenced the reconstructions of the origin of chemistry as a specific and institutionalised discipline. the positivistic tradition constructed and conceptualized alchemy as a form of proto-chemistry, and emphasised the difference between the empirical contents of the alchemical writings which were to be preserved, and the mystic, hermetic, metaphysical dimension which was to be dropped out owing to its unscientific features. this approach deserves to be praised because it called the attention to the historical relevance of the alchemical writings, to the necessity of their analysis, study and edition. in 1887-1888 marcelin berthelot and charles-émile ruelle published the three volume collection des anciens alchimistes grecs, that has been a crucial source for almost a century.1 today berthelot’s approach appears to be unsound because it is obsolete: a suitable historical perspective is to be based on the study of alchemy as a specific, centuries-old form of knowledge, and one must forget or put aside the question of the presumed transmutation of alchemy into chemistry. without denying the existence of some interactions among alchemy, chymis40 ferdinando abbri try and chemistry, one must emphasise that the adventurous events of alchemy, the historical facts concerning the various alchemical traditions are largely different from those of the history of early modern chemistry. ancient and medieval alchemy the entry on “alchemy” of the new dictionary of the history of ideas (2005) is divided into two sections devoted respectively to china and to europe and the middle east in order to enlighten the historical and conceptual relevance of chinese and western alchemy. 2 thanks to joseph needham and his school the history of the chinese science represents a substantial chapter of the present history of science, and the volume 5 (two parts, 1974-1976) of their multivolume science and civilisation in china contains a very detailed reconstruction of chinese alchemy.3 alchemical conceptions and practices were truly present in the chinese empire, and chinese alchemy developed during twenty centuries of documented history, and can be divided into two branches: external alchemy, that is the preparation of elixir through the manipulation of substances, and internal alchemy (inner elixir) aimed at the spiritual perfection of the alchemist. in 2005 fabrizio pregadio has published a volume entitled great clarity. daoism and alchemy in early medieval china in which he states that the crucible was the main tool of the chinese alchemist from a symbolic, ritual and technical point of view,4 and such a statement confirms the multifarious dimensions of the alchemical quest for knowledge. in the western and mediterranean contexts alchemy had practical origins in hellenistic egypt, during the ruling of the last ptolemaic pharaohs and the beginnings of the roman domination, and was codified between the first and the fourth century a.d. in alexandria of egypt. the chemeia was originally constituted of practices of artisans and of recipes aimed at the preparation and imitation of natural substances. in alexandria the first alchemists were devoted to the working of metals, with a particular attention to gold and silver, and to the preparation of artificial, precious stones (pearls and emeralds), and to the colouring cloth using cheaper imitations of the expensive, imperial natural purple. their activities consisted in the imitation of natural, precious substances and of purple cloths, in colouring silver to look like gold, or copper to look like silver, therefore they were a kind of bijoutiers. in alexandria a middle class probably existed which aspired to a way of life similar to that of the greek and roman nobility, and needed some imitations of gems, of precious stones, and of purple because this class could not afford the original and natural ones. these activities of imitation explain why the first alchemical texts, written in greek on papyrus, contain about 250 workshop recipes. the leiden and stockholm papyri date from the third century a.d. and present recipes relating to gold, to silver, to precious stones and to textile dyes. in 1981 robert halleux edited a new version of the original texts of the leiden and stockholm papyri in a new collection dedicated to les alchimistes grecs.5 pseudo-democritus’s alchemical writings have been recently published by matteo martelli in two critical editions, both in italian and in english, and these editions confirm the four main sections of the greek-egyptian chemeia: production of gold, of silver, of artificial gems, which included making and working glass, and colouring wool with artificial purple.6 to martelli we owe some outstanding contributions to the knowledge of the ancient greek alchemy.7 in the context of the greek-byzantine alchemy the chemeia was specified as chrysopoeia (the art of making gold) and as argyropoeia (the art of making silver). alchemy was born as a set of practices but became more and more sophisticated from a philosophical point of view. alchemy acquired a complex whole of philosophical ideas and conceptions as regards matter and cosmos; eastern and greek philosophies became the theoretical base which guided the operations and the experiments, and shaped alchemical language that turned into a difficult and allegorical jargon. thanks to various philosophical and religious concepts, alchemy was transformed into a true philosophy of nature which was destined to play an important role in western culture until the eighteenth century. some particular versions of platonism, of stoicism, of hermetic gnosticism and a few aspects of aristotle’s theory of the elements are traceable in the alchemical thought which presented itself as something new, specific, well defined in the various historical and cultural contexts. the corpus of the greek alchemical writings is composed by anonymous tracts or by pseudonymous tracts ascribed to mythical or famous authors. zosimos of panopolis in egypt (about 300 a.d.) was the first alchemist to sign some systematic treatises of alchemy in which the platonic aspects are coloured by a strong hermetic dimension. however, in zosimos’s writings an outstanding role is attributed to instruments, and his hypomnemata open with some statements perì organon kai kaminon. in her new edition of zosimos’s mémoires authentiques (2002) michèle mertens considers the manuscripts, the preceding editions – berthelot’s and ruelle’s one is qualified as “très mediocre” – the studies on zosimo. in her detailed introduction mertens 41gold and silver: perfection of metals in medieval and early modern alchemy presents a technical introduction devoted to the appareillage de zosimo, to his alchemical instruments and apparatuses.8 the byzantine manuscripts contain many drawings of apparatuses, and berthelot had tried to reconstruct their structure and their presumed working. the progressive increase of the philosophical and mystical dimension in the alchemical literature did not involve an undervaluation of the experimental and practical aspects. in the byzantine collections of greek alchemical manuscripts, the book on the production of gold, ascribed to democritus, has a short introduction devoted to the imitation of purple, and is entitled physikà kaì mystikà, that is natural and secret things, according to lawrence principe’s suitable translation.9 in the middle age greek alchemy was preserved by byzantine culture and from the vii to the xi century the alchemical canon was constructed by byzantine scholars through selections and collections of texts. emperors, monks, theologians and scholars were interested in alchemy, and focused their attention on the making of gold and of precious metals, therefore the byzantine intelligentsia selected a specific type of alchemical tracts which were included in greek-byzantine collections, and such collections were translated into syriac and arabic. starting with the viii century some arabic alchemical texts were produced in the context of an extraordinary flourishing of the arabic culture. from the syriac kīmīyā arabs coined the term al-kīmyā which was very successful and was steadfastly used during the whole middle age and the modern age. owing to the expansion of the arabic empire and the spreading of the arabic as a new common language, in the islamic world it took place an assimilation of knowledge from the greek, persian and iranian sources. in islam, alchemical writings show the inf luences from egyptian, syriac, sabean cultures, too. alchemy strongly rooted in the context of the arabic scientific research, and a latin manuscript, called the morienus, was translated from arabic in 1182 as de compositione alchemiae, and can be considered as the starting moment of the penetration of the arabic alchemy into the latin world: writings ascribed to jābir ibn hayyān, alias geber were the most famous texts of the medieval alchemy. the islamic alchemy is characterized by various aspects, but the alchemical research was focused on the making of gold, using mercury and sulphur, and on the production of an elixir (al-̀ iksīr) which, when combined with some vile metals, could transform them into gold or silver, and even it could be used as a true elixir, able to guarantee a long life or immortality.10 during the xii century the translations from arabic into latin composed a very important corpus of alchemical writings, and alchemy attracted the attention of famous scholars and philosophers: albertus magnus and roger bacon contributed to the development of alchemy in europe. the art of distillation became a central subject of research: the utilization of minerals, concentrated acids, alcohol, and some new techniques of distillation, which allowed to obtain many distillates and the celebrated quintessence, modified in a substantial and dramatic measure the practices of the alchemists. thanks to the research of chiara crisciani and michela pereira, we can now consider the xiv century as the apogee of the latin alchemy: arnaldo of villanova’s, pseudo-ramon lull’s, john of rupescissa’s alchemical works testify to the impressing philosophical level reached by alchemy. alchemy was a true philosophy of nature, based on some outstanding experimental practices, which was focused on the production of the elixir, on the transmutation of metals into silver and gold1, and on the use of mercury in various experiments and chymical processes.11 it is worth noting that during its long history alchemy evolved but maintained a strong core of knowledge: in medieval and modern texts it is possible find recipes and experimental practices which are identical to those contained in the greek papyri of egyptian origins. renaissance and early modern alchemy during the renaissance and the early modern era alchemy had a strong influence on various fields, from cosmology to natural philosophy, from religion to the vision of human history, from pharmacy to mineralogy, from metallurgy to medicine. alchemical texts started being printed with some series of imagines that are still today a resource in order to understand the universe of symbols which nourishes the human psyche. the sun and the moon represented gold and silver, and these noble metals were also portrayed as the king and the queen in order to emphasise their primary role in the processes of transformation. the alchemical and astrological symbols of the sun and of the moon were also used during the xviii century in the tables of affinities to paint gold and silver. metals were considered mixed substances, and like living creatures they were born and grew in the subterranean world: nature had a specific operating time for the maturation of metals in her wombs, and metals composed a sort of ascending ladder to the top of which there were silver and gold. late medieval alchemist aimed at modifying the times of nature, cooperating with nature, but also surpassing her 1 this transmutation was also a process of spiritual progress of the alchemist. 42 ferdinando abbri in the production of the noble metals. transmutations were not dreams or fantastic enterprises but were a true project of acceleration of the natural times, based on man’s ability to perform, because in its origins alchemy was also the art of making. in johannes de monte-snyder’s metamorphosis planetarum, published in german in 1663, it is possible to read about the metamorphosis of plants and of bodies which are guided by the sun and the moon. this text also considers the transformations of metals because mercury and sulphur bind man to the philosophical gold, that is, to the highest principle. during the renaissance many collections of alchemical books were published: in 1572 the printer petrus perna published in basle a collection focused on the turba philosophorum entitled auriferae artis, quam chemiam vocant which was reprinted in 1593 in an enlarged edition of two volumes.12 the turba philosophorum is a islamic treatise in which the alchemical doctrines are exposed in a sort of congress of the pre-socratic philosophers that is presided by pythagoras. in 1546 janus lacinius therapus had published in venice a collection of theoretical, alchemical works, the first part of which contains the pretiosa margarita novella of petrus bonus of ferrara, one of the most important alchemical treatise of the xiv century. 13 in her important book on alchimia. i testi della tradizionale occidentale michela pereira reconstructs the histories of alchemy from the greek world to the modern age, and the chapters of this huge book devoted to early modern philosophical and religious contexts clarify the substantial impact of alchemy, in its various forms and declinations, on modern culture.14 in the age of the scientific revolution alchemical texts were firmly rooted in the european cultural landscape. this presence has caused many historiographical controversies concerning alchemy, the paracelsian tradition, chymistry and chemistry, and so on. here, i cannot resume these debates but i only want to emphasise that a description of the genesis of modern science cannot ignore the question of alchemy. andreas libavius defended alchemy as an art against the paracelsians,15 and in 1602 gaston duclo published his apologia chrysopoeiae et argyropoeiae adversus thomam erastum, that contains a defence of the arts of making gold and silver against thomas erastus, a professor of medicine in heidelberg.16 the controversies about alchemy remained alive and vivid from the renaissance to the age of enlightenment. the exhibitions devoted to alchemy in its relationships with the figurative arts are frequent in the institutional contexts of europe and north america. for example, the exhibition of 2004 on kunst und alchemy at düsseldorf, was focused on the mystery of the verwandlung, namely transformation.17 the catalogue of this exhibition contains chapters on the history of alchemy and thematic chapters aimed at illustrating the ties between alchemy and arts. in many seventeenth century pictures it is usual to find representation of alchemical laboratories and some very diversified images of the alchemist. in his mammoth history of the macrocosm and of the microcosm (1617-1624),18 which is rich of amazing plates, the english physician and philosopher robert fludd (1574-1637) presented a mirror of the whole nature and the image of art together with a description of the human arts. these arts were alchemy as regards the mineral world, agriculture as regards the vegetable one, and medicine as to the animal one. every part of the cosmos is tied to the other parts and these connections produce a complex and linked cosmological whole. among the various connections one can isolate those between saturn and lead, sun and man, moon and woman, but in the underworld sun and moon are connected with gold and silver. in malachias geiger’s microcosmus (1651) the symbol of the potable gold “chimice praeparati” presents a true image of the macrocosm and of the microcosm in which the human figures of the sun and of the moon are entering in the alchemist’s laboratory, and this image confirms that alchemy was both a philosophical cosmology and a series of laboratory practices. the search for the philosophical stone to be used in the transmutation of metals in gold was still a topical argument in late seventeenth century because robert boyle (1627-1691), the supposed father of modern chemistry, was highly interested in the research of this stone and of the secret of the alchemical transmutations.19 during his life isaac newton (1642-1727) devoted much more time to alchemy, theology and sacred history than to mathematics and physics.20 i do not want to emphasise too much the symbolic features of the metallurgical alchemy in the early modern age, and in the final part of my presentation i want to call the attention to the ties between artisans and alchemists, to the relationships among some able goldsmiths, silversmiths, alchemists and chymists in xvii century europe. in 2007 vladimír karpenko published a paper on alchemical coins and medals,21 but we owe to lawrence m. principe’s research some outstanding clarifications about the different social contexts of interest in precious metals. principe has cast light upon the relationships between artisans and natural philosophers, between jewellers and scholars, and has defined the various places and contexts in which the alchemical practices were present in modern age.22 the types of chymical discourses were numberless, but one needs to emphasise 43gold and silver: perfection of metals in medieval and early modern alchemy the ties between high culture and the craftsmanship of the artisans. johann rudolph glauber (1604-1670) was a german chymist, alchemist and pharmacist who was active in amsterdam. he was very attentive to the practical matter, technological and analytical dimensions of the chymical research which he combined with the interest in alchemy. in 1646-47 he published a two-volumes treatise in german, on the art of distillation, and in 16561661 a textbook on the prosperity of germany. in the latter book, he argued that a systematic application of chymical knowledge to manufacturing of goods would lead to higher prosperity in his native country. in 16581659 glauber published a treatise on the salts, but he had already published (1646) a treatise on the true potable gold, and between 1663 and 1664 he published two treatises on the hermetic medicine and on the explanation of the true alchemical secrets.23 in amsterdam glauber became acquainted with the three grill brothers, german jewellers and silversmiths, who were active in the low countries. anthoni grill, an aurifaber, criticized some chymical processes used by glauber and affirmed that the famous chymist did not use a correct process to separate gold from silver. as a jeweller, grill dedicated his attention to the essaying of the precious metals, and had invented a less expensive technique than those used by chymists and alchemists. principe has discovered some sources which point that grill had created a method of producing gold and silver in laboratory, and was able to exhibit some samples of artificially produced gold and silver.24 during his long tour across europe t he danish physician and naturalist ole borch (olaus borrichius, 1626-1690) met grill at amsterdam in 1662. there grill showed him that the combination for some months of lead with a particular spirit of salt had produced a fine piece of good silver.25 in the hague andries grill, anthoni’s brother, had a laboratory and a jeweller shop which were visited by european travellers wishing to observe his practices of obtaining gold and silver. in 1659, k nowing to his financial debts, anthoni grill was obliged to leave amsterdam, and fled to sweden where he became a successful public officer in the field of metallurgy, a crucial activity of the scandinavian country. in amsterdam anthoni grill had acquired a big house and there he built some large chymical laboratories that after his departure were used by glauber for a short time. grill was at the centre of cultural exchanges with travellers, german university professors, visitors of his laboratories and of his shop. they spread all over europe grill’s practical research. the case of the german jewellers of the low countries, reconstructed by principe, demonstrates that the traditional dark, witchlike image of the alchemical and of the chymical laboratories does not fit the historical facts. in the dutch context of the gouden eeuw some fruitful exchanges between artisans and naturalists took place, and were historically significant. a short conclusion in modern age alchemical texts and practices were very popular and alchemists played a crucial role in the history of science because, quoting tara nummedal, “in joining the hands on manipulation of matter with more theoretical speculations about its composition and transformation, alchemists (like physicians) modelled the extraordinary potential of the union of head and hand long before it became a hallmark of modern science”.26 however, alchemy was not able to become a branch of that institutionalised research which produced modern science. in the map of the new knowledge created by the scientific revolution that established the academic topics to be investigated one cannot find alchemy. the modern scientific discourse was often engaged to denounce the “dreams” of alchemy. references 1. m. berthelot, c.-e. ruelle, collection des anciens alchimistes grecs, george steinheil editeur paris, 1887-1888, 3 voll. 2. alchemy, in m. cline horowitz (ed.), new dictionary of the history of ideas, charles scribner’s sons thomson gale farmington hills mi, 2005, i, pp. 38-44. 3. j. needham, lu gwei-djen, science and civilisation in china. volume 5 chemistry and chemical technology, at the university press cambridge, 1974, pp. 1-187. j. needham, ho ping-yü, lu gwei-djen, science and civilisation in china. volume 5 spagyrical discovery and invention: historical survey from cinnabar elixirs to synthetic insulin, at the university press cambridge, 1976, pp. 1 – 208. 4. f. pregadio, great clarity. daoism and alchemy in early medieval china, stanford university press stanford, 2005, p. 9. 5. les alchimistes grecs. tome i. papyrus de leyde. papyrus de stockholm. fragments de recettes. texte établi et traduit par robert halleux, les belles lettres paris, 1981. 6. pseudo-democrito, scritti alchemici. con il commentario di sinesio. edizione critica del testo greco, 44 ferdinando abbri traduzione e commento di matteo martelli, s.é.h.a. paris, arche’ milano, 2011. m. martelli, the four books of pseudo-democritus, maney publishing leeds, 2013. 7. m. martelli, greek alchemists at work: ‘alchemical laboratory’ in the greco-roman egypt, nuncius, 2011, 26, 271-311. m. martelli, the alchemical art of dyeing: the fourfold division of alchemy and the enochian tradition, in s. dupré (ed.), laboratories of art. alchemy and art technology from antiquity to the 18th century, springer heidelberg, 2014, pp. 1-22. 8. les alchimistes grecs. tome iv 1e partie. zosime de panopolis. mémoires authentiques. texte établi et traduit par michèle mertens, les belles lettres paris, 2002, pp. cxiii clxix. 9. l.m. principe, the secrets of alchemy, the university of chicago press chicago and london, 2013, p. 12. 10. l.m. principe, the secrets of alchemy, pp. 27-50. 11. c. crisciani, il papa e l’alchimia. felice v, guglielmo fabri e l’elixir, viella roma, 2002. c. crisciani, m. pereira, l’arte del sole e della luna: alchimia e filosofia nel medioevo, centro di studi italiano sull’alto medioevo spoleto, 1996. m. pereira, l’oro dei filosofi: saggio sulle idee di un alchimista del trecento, centro di studi italiano sull’alto medioevo spoleto, 1992. m. pereira, arcana sapienza: l’alchimia dalle origini a jung, carocci roma, 2001. m. pereira, alchimia. i testi della tradizione occidentale, mondadori milano, 2006. 12. auriferae artis, quam chemiam vocant, antiquissimi authores sive turba philosophorum, apud petrum pernam basileae, 1572. artis auriferae, typis conradi waldkirchii basilae, 1593, 2 voll. see also: u. benzenhöfer, johannes’ de rupescissa liber de consideration quintae essentiae omnium rerum deutsch, franz steiner verlag stuttgart, 1989. j. telle (ed.), rosarium philosophorum. ein alchemisches florilegium des spätmittelalters, vch weinheim, 1992, 2 voll. 13. pretiosa margarita novella de thesauro, ac pretiosissimo philosophorum lapide, apud aldi filios. venetiis. 1546. c. crisciani, pietro bono da ferrara. preziosa margarita novella. edizione del volgarizzamento, la nuova italia firenze, 1976. 14. m. pereira, alchimia. i testi della tradizione occidentale, mondadori milano, 2006. 15. b.t. moran, andreas libavius and the transformation of alchemy. separating chemical cultures with polemical fire, science history publications/usa sagamore beach, 2007. 16. g. duclo, apologia chrysopoeiae et argyropoeiae adversus thomam erastum, excudebat cornelius sutorius ursellis, 1602. 17. kunst und alchemie. das geheimnis der verwandlung, museum kunstpalast düsseldorf, 2014. 18. r. fludd, utriusque cosmi maioris scilicet et minoris metaphysica, physica atque technica historia. in duo volumina secundum cosmi differentiam divisa, johann theodor de bry oppenheim, 1617-1624, 5 voll. 19. l.m. principe, the aspiring adept. robert boyle and his alchemical quest, princeton university press princeton new jersey, 1998. 20. b.j. teeter dobbs, the foundations of newton’s alchemy: or the hunting of the greene lyon, cambridge university press cambridge, 1984. b.j. teeter dobbs, the janus faces of genius: the role of alchemy in newton’s thought, cambridge university press cambridge, 1991. 21. v. karpenko, witnesses of a dream: alchemical coins and medals, in s.j. linden (ed.), mystical metal of gold. essays on alchemy and renaissance culture, ams press new york, 2007, pp. 117-160. 22. l.m. principe, goldsmyths and chymists: the activity of artisans within alchemical circles, in s. dupré (ed.), laboratories of art. alchemy and art technology from antiquity to the 18th century, springer heidelberg, 2014, pp. 157-179. 23. f. abbri, gli arcana naturae: filosofia, alchimia e chimica nel seicento, in w. di palma (ed.), cristina di svezia: scienza e alchimia nella roma barocca, dedalo bari, 1990, pp. 49-68. 24. l.m. principe, goldsmyths and chymists: the activity of artisans within alchemical circles. 25. h.d. schepelern (ed.), olai borrichii itinerarium 1660-1665. the journal of the danish polyhistor ole borch, c.a. reitzels forlag copenhagen, 1983, ii, pp. 58-59. 26. t. nummedal, the alchemist, in b. lightman (ed.), a companion to the history of science, john wiley & sons, hoboken new jersey 2016, p. 66. t. nummedal, alchemy and authority in the holy roman empire, the university of chicago press chicago and london, 2007. w.r. newman, atoms and alchemy. chemistry and the experimental origins of the scientific revolution, the university of chicago press, chicago and london, 2006. l.m. principe (ed.), chymists and chymistry. studies in the history of alchemy and early modern chemistry, science history publications/usa sagamore beach, 2007. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe substantia. an international journal of the history of chemistry 3(2) suppl. 4: 75-82, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-572 citation: g. mebrahtu tesfamariam, m. ayene ejigu (2019) are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? substantia 3(2) suppl. 4: 75-82. doi: 10.13128/ substantia-572 copyright: © 2019 g. mebrahtu tesfamariam, m. ayene ejigu. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. are history aspects related to the periodic table considered in ethiopian secondary school chemistry textbooks? gebrekidan mebrahtu tesfamariam1,*, mengesha ayene ejigu2 1 mekelle university, college of natural and computational sciences, department of chemistry, ethiopia 2 wollo university, college of natural and computational sciences, department of chemistry, ethiopia *e-mail: gebrekidan.mebrahtu@mu.edu.et abstract. the aim of this study was to evaluate ethiopian secondary school chemistry textbooks with respect to presentation of history and philosophy of science (hps) related aspects of the periodic table. we focused on how the textbooks approached the periodic table as a conceptual tool for organizing the chemical elements, and understanding their properties. for this purpose, three grade 9 chemistry textbooks (introduced in the last two decades by the ministry of education of ethiopia) were selected. we conducted the evaluation qualitatively using an adopted version of a four-point criterion developed based on hps framework. our evaluation revealed that that only one of the three textbooks addressed just only one of the four hps aspects of the periodic table satisfactorily, while in the other two textbooks all of the four aspects are generally ignored. it is concluded that most hps related aspects of the periodic table are missed from ethiopian secondary school chemistry textbooks, and the few aspects which are addressed are not properly presented. we believe that this could have negative consequences on the students’ attitude and interest towards science as well as on their understanding of science concepts and performance in the subject. keywords. history and philosophy of science (hps), chemistry textbooks, ethiopian secondary school, periodic table, evaluation. 1. introduction the current structure of the ethiopian education system can be described as 8‐2‐2‐3+ i.e. eight years primary (grade 1–8; age 7–14), two years secondary first cycle (grade 9–10), two years secondary second cycle (grade 11–12), and 3 to 6 years university education. in ethiopia, formal teaching and learning of science begins at the primary level; and chemistry, biology and physics begin to be taught as separate subjects, compulsory for all students, at grade 7. this continues up to grade 10. starting from grade 11, as a preparation for higher education, students have to choose between two options: natural science and social studies. students majoring in science study 76 gebrekidan mebrahtu tesfamariam, mengesha ayene ejigu chemistry, biology, and physics as principal subjects. each subject has its own syllabus, teacher’s guide and textbook (prepared by the ministry of education) which is uniformly used across the country. despite the policy recommendations for a concise and student-centered curricula (where a variety of teaching methods shall be used)1, studies have indicated that the ethiopian science curricula were too theoretical and overloaded; and the method of teaching used by teachers as teacher-centered (commonly called “chalk and talk”) emphasizing recall of large amounts of factual information to pass examinations.2,3,4,5 textbooks are usually considered to be the primary reference materials to carry out classroom instruction in many countries. this is particularly true in schools of developing countries where both teachers and students heavily rely on textbooks for their lessons. for instance, according to yager, nearly 100% of nigerian science teachers rely on textbooks to select appropriate content to teach their students.6 in our experience as science educators and researchers in the country, due to various reasons, ethiopian science/chemistry teachers too rely solely on textbooks. however, these textbooks have not yet reached the standards of developed communities as they are prepared by individuals (usually school teachers or university lecturers) who have little/no experience in textbook preparation, or even worst by foreign (commonly indian) writers who are unacquainted with the ethiopian classroom context. as such, these textbooks can be a source of students’ learning and teachers’ teaching difficulties. this is in agreement with the findings of other international studies which reported that textbook presentation of science content are often incompatible with the suggestions of science education research, and may entail problems if used uncritically.7,8 in addition, in the ethiopian context, studies revealed that school chemistry teachers have a variety of misconceptions about various chemical concepts.9,10,11 as indicated in the country’s national learning assessment report and in a survey study conducted by usaid/iqpep ethiopia, the presence of such compounded problems might be among the possible causes of the alarmingly declining students’ science performance in regional and national examinations.12 as a remedy to the above mentioned problems as well as other teaching-learning deficiencies, many researchers and teachers have suggested the inclusion of history and philosophy of science (hps) in the science curriculum, textbooks, and classroom.13,14,15 teaching and learning of science using hps approach has been reported to have several merits: e.g. for teaching and learning about science as a process, for promoting conceptual change and a deeper understanding of scientific ideas, for fostering public understanding of science, and for positively impacting students’ attitudes and interests toward science.14,15,16 however, it has been argued that science textbooks rarely address in a meaningful way the historical development of science and the nature of science, instead presenting science in a distorted and ahistorical way.17,18 in the ethiopian context, there is no explicit standard which promotes the inclusion of the hps approach of teaching and learning of science. in addition, despite the policy recommendation for application of a variety of teaching approaches, the curricular materials (syllabus, student textbooks and teacher’s guide) which are issued by the ministry of education do not allow for flexibility as teachers are expected to strictly follow these documents. this practically means that there is little/ no room for teachers to flexibly implement hps based teaching (i.e. to use historical cases) in their lessons. this is similar to what has been reported by van bertel et al.19, who on the basis of content analysis of school chemistry textbooks (published in uk and netherlands) identified school chemistry as a form of “normal science education” which is considered to be “dangerous” in that it isolates the learner from the hps and, as such, is narrow and rigid and tends to instill a dogmatic attitude towards science. the periodic table is considered to be an important topic of secondary school and undergraduate chemistry textbooks worldwide. it serves as a source of information for students to learn the fundamental building blocks of chemistry, the chemical elements, and the relationship between them. however, previous studies have reported problems in presenting the periodic table in the textbooks which led to difficulties in teaching and learning the concepts behind it.20,21,22 according to niaz and luiggi, most students consider the periodic table to be a difficult topic.23 studies on chemistry textbooks dealing with the periodic table can be found in many developed countries. this is not, however, the case in developing countries. in ethiopia, specific well-documented studies of chemistry textbooks presentations of the periodic table are lacking. the purpose of this study was therefore to contribute to the understanding of how the periodic system is taught in ethiopia. this way, based on textbook presentations, we will help provide perspectives from an african school practice, and by so doing, contribute to giving a fuller picture of how the periodic table is taught in schools all over the world. 77are history aspects related to the periodic table considered in ethiopian secondary school chemistry textbooks? 2. aspects of history of the periodic table worthy of consideration in chemistry textbooks the periodic table has been considered a conceptual tool because it has contributed much more than mere classification; it has predicted new elements, predicted unrecognized relationships, served as a corrective device, and fulfilled a unique role as a memory and organization device24 which in turn has led to a better understanding of chemistry. in this section, some selected hps related aspects of the periodic table (based on brito et. al.25 and niaz and luiggi23) which we believe are worthy of including in secondary school chemistry textbooks are briefly discussed. in view of this, it should be noted that there were early ideas about atomic theory and accumulation of data with respect to the atomic weights of the elements and their properties; and that there were several attempts to classify elements between 1817 and 1860. for example, by 1829, the german chemist johann döbereiner (1780-1849) presented the law of triads as he noted a similarity among the physical and chemical properties of several groups of three elements and the relation of their atomic weights.24 a major hindrance to the widespread acceptance of such classifications was that no consensus on atomic weight values existed. a significant progress was made only after the karlsruhe conference of 1860 at which the italian chemist stanislao cannizzaro (1826-1910) presented one specific system for atomic weights and wrote a pamphlet which convinced many chemists, after which the stage was set for the discovery of the periodic system. it is generally acknowledged that the periodic system was independently discovered during the 1860s by six individuals, namely: french geologist and mineralogist alexander beguyer de chancourtois (1820-1886), english chemist william odling (1829-1921), american chemist lothar meyer (1830-1895), english chemist john newlands (1837-1898), german chemist gustavus hinrichs (1836-1923), and russian chemist dmitri mendeleev (1834-1907).28,27 by 1869, a total of 63 elements had been discovered and in the same year, mendeleev completed his first form of the periodic system in which he arranged all of these elements based on their atomic weights.23,28 in the 1920s, based on the work of the english physicist henry moseley (1887-1915) and others some years earlier,25 the periodic table was organized according to atomic number instead of atomic weight. this, and the discoveries of the sub-atomic particles, in turn helped chemists to have a deeper understanding of the organization of the periodic table and the properties of the individual elements. inclusion of the above hps related aspects of the periodic table in textbooks may help present the development of the periodic table as a progressive, collective and at the same time sequential and simultaneous endeavor based on different contributions; and thus, it stimulates and encourages students to understand how science progresses and the tentative nature of scientific findings. other hps related aspects of the periodic table that arguably deserve attention in chemistry textbooks are the importance of accommodation (i.e. agreement of observed properties of the elements such as atomic weight/number and other properties with the theory) and prediction (of new elements). the latter can be highlighted by providing as an example at least one of the three elements gallium, scandium, or germanium, and a comparison of the predicted and experimental properties without forgetting to mention that not all predictions were successful. it should also be explained to readers that there has been some controversy among historians and philosophers of science with respect to the relative importance of accommodation and prediction25. however, for classroom teaching, it is sufficient to explain that the success of the periodic table could be partly attributed to accommodations, predictions, or both. this might facilitate the understanding that the same experimental data can be explained by alternative interpretations. overall, inclusion of the hps aspects of the periodic table in chemistry textbooks might help students understand how science evolves through the interactions of theories, experiments, and the work of actual scientists.18 3. research method overall, the study involved four stages. in the first stage, we reviewed literatures that are relevant to the historical and philosophical development of the periodic table and their educational implications. in the second stage, based on the reviewed literature, and particularly inspired by brito et al.,25 we designed a four point evaluation criteria for evaluating ethiopian secondary school chemistry textbooks with respect to how they addressed the periodic table. the third stage involved selection of textbooks for the evaluation in which we selected three 9th grade chemistry textbooks (written by sharma et al.,29 abera and abusie,30 and mamo and tassew31) that the ministry of education of ethiopia has introduced in the last two decades. we selected 9th grade textbooks for the reason that in the ethiopian secondary school chemistry curricula, the topic of periodic table is included in grades 9 and 11 only; and from our survey of these textbooks, we learned that no historical cases of the period78 gebrekidan mebrahtu tesfamariam, mengesha ayene ejigu ic table are presented in the grade 11 textbooks (as the discussion started from the topic of ‘the modern periodic table’). the grade 9 chemistry textbooks, however, had addressed some of the historical aspects. the fourth stage of the study involved evaluation of the selected textbooks based on the developed criteria in which each criterion was scored qualitatively as satisfactory (s), mention (m), or no mention (n). detailed description of the evaluation criteria is given below: evaluation criteria criteria 1: development of the periodic table as a case of progressive sequential/simultaneous discovery. • satisfactory (s): if the textbook emphasizes the development of the periodic table as progressive, collective and at the same time sequential and simultaneous endeavor based on the following contributions: (a) early ideas about atomic theory and accumulation of data with respect to the atomic weights of the elements and their properties; (b) the first attempt to classify the elements by döbereiner, and later by de chancourtois, odling, meyer, newlands, hinrichs, and other attempts before mendeleev; (c) mendeleev’s first periodic table in 1869 based on atomic weights and subsequent contributions; and (d) the contribution of moseley (1913), and the shift from atomic weight to atomic numbers (modern periodic table). • mention (m): if the textbook mentions some of the major contributors without establishing a sequential, collective and progressive development explicitly. • no mention (n): if the textbook included mendeleev and moseley only or if the textbook simply starts from the modern periodic table. criteria 2: the importance of accommodation in the development of the periodic table: • satisfactor y (s): if the textbook explains and emphasizes that an important aspect of the periodic table is accommodation of the different elements with respect to atomic weight/number and other properties such as density, atomic volume, atomic/ ionic radii, ionization energy, electronegativity, electron affinity, etc. • mention (m): if the textbook simply mentions that accommodation of the different elements was important. • no mention (n): if the textbook did not at all mention the role played by accommodation. criteria 3: the importance of prediction as evidence to support the periodic law. • satisfactory (s): if the textbook emphasizes the importance of prediction in the development of the periodic table by providing as an example at least one of the three elements gallium, scandium, or germanium, and a comparison of the predicted and experimental properties; as well as reminding the reader that not all predictions were successful. • mention (m): a simple mention that mendeleev made predictions of new elements, and provides an example (without comparing predicted and experimental properties). • no mention (n): if the textbook states that mendeleev made predictions, and does not provide an example. criteria 4: relative importance of accommodation and prediction in the development of the periodic table. • satisfactory (s): if the textbook explicitly explains the presence of debates among historians and philosophers of science with respect to the relative importance of accommodation and prediction, and presents the merits and demerits of each, and indicates to the students that the success of the periodic table could be partly attributed to accommodations, predictions, or both. • mention (m): a simple mention and comparison of alternate ways of explaining the success of the periodic table with no mention of rivalry and controversy. • no mention (n): if the textbook mentions the role played by accommodation and prediction with no attempt to compare the two. 4. ethiopian secondary school chemistry textbooks accounts: results and discussion as outlined above, three secondary school chemistry textbooks were analyzed to see how the textbooks presented the historical and philosophical aspects of the periodic table; and how accurate, coherent and complete these presentations are. criterion 1: development of the periodic table as a case of progressive simultaneous/ sequential discovery the key idea behind this criterion is to assess the chemistry textbooks to see whether or not they presented the development of the periodic table as a case of progressive and simultaneous/sequential discovery based on different contributions in such a way that it stimulates and encourages students to think that there is more to scientific progress than simple accumulation of data and linear progress through individual discoveries.25 we found that none of the textbooks presented this aspect of the periodic table satisfactorily (s). all the three textbooks simply mentioned (m) three to four of the contributors without establishing a sequential, collective and 79are history aspects related to the periodic table considered in ethiopian secondary school chemistry textbooks? progressive development explicitly. the following quotes (see table 1) are provided as examples: as can be understood from the quotes, the writers of the textbooks have tried to endorse the tentative nature of scientific theories/models. however, the information presented is not articulated, it’s just a string of events with no details; it confuses the teachers and the students even more, as it does not provide them with a way to relate these earlier developments to the final outcome. the scientific process looks even messier. so this is unsatisfactory and unproductive. criterion 2: importance of accommodation in development of the periodic table from the analysis, we found that there are no substantial differences in the way the three textbooks emphasized the importance of accommodation (of the different elements with respect to their physicochemical properties) in the development of the periodic table. none of the three textbooks presented a satisfactory (s) description; three of them just give a simple mention (m). for example sharma et al.29 mentioned the following: “dmitri mendeleev developed the periodic table and formulated the periodic law. because his classification revealed recurring patterns (periods) in the elements…” (p. 39). criterion 3: the importance of prediction as evidence to support the periodic law sharma et al.29 is the only textbook to emphasize the importance of prediction satisfactorily (s) as evidence to support the periodic law. furthermore this textbook compared the properties of at least one of the predicted table 1. some quotations from the evaluated textbooks. textbook quote sharmaet al.29 early attempts to classify elements were based on atomic mass [weight]. the first attempt was made in 1817 by j.dobereiner [who presented the law of triads]. in 1864, john newlands reported the law of octaves. in 1869 mendeleev and lothar mayer independently published periodic arrangements. in 1913 henry mosley determined the atomic number by analyzing x-ray spectra. abera andabusie30 the periodic table has been developed over many years. in 1817 j.w. dobereiner observed that the atomic mass [weight] of bromine was very nearly equal to the average masses [atomic weights] of chlorine and iodine. in 1864, john newlands reported the law of octaves. the periodic law was proposed independently by mendeleev and lothar mayer. [clemens]winkler, in 1876 [1886], discovered germanium. henry moseley, between the years 1911 and 1914, discovered a new fundamental property of elements. mamo and tassew31 in 1817 j.w. döbereiner observed groups of three elements with similar properties. in 1864, john newlands reported the law of octaves. the periodic law was proposed independently by mendeleev and lothar mayer. figure 1. sharma et al.29 textbook representation of importance of prediction as evidence to support the periodic law. 80 gebrekidan mebrahtu tesfamariam, mengesha ayene ejigu elements (ga, sc, and ge) with the observed values. the following are specific examples taken from sharma et al.29: “mendeleev left blank spaces for these two elements in the table, just under aluminum and silicon. he called these unknown elements ‘eka-aluminum’ and ‘eka-silicon’. what he meant by ‘eka-aluminum’ is a currently known element (gallium) following aluminum. later on, in 1874, the element gallium (eka-aluminum’ in mendeleev’s system) was discovered. the observed properties of these elements were remarkably very close to those in mendeleev’s prediction.” (p. 39) this textbook also compared the properties of at least one of the predicted elements (eka-silicon) with the observed properties of germanium. in the textbook, the comparison is clearly presented in the form of a table (see figure 1). the other two textbooks made no mention (n) and hence ignored the issue. in the same way, abera andabusie30 stated the following: “the periodic law provided a working basis for the predication of new elements or unfamiliar elements. it also provided an important stimulus for further chemical investigations.” (p. 75) criterion 4: relative importance of accommodation and prediction in the development of the periodic table none of the textbooks explained the relative importance of accommodation and prediction in the development of the periodic table satisfactorily, and only a textbook by sharma et al.29 made a simple mention (m) and comparison of alternate ways of explaining the success of the periodic table with no mention of rivalry and controversy as exemplified in the quote below: early attempts to classify elements were based merely on atomic mass [weight]… scientists begun to seek relationships between atomic mass and other properties of the elements (p. 37). mendeleev observed that when elements are arranged according to increasing atomic mass, the chemical and physical properties of the elements recur at regular intervals (p. 40). mendeleev left blank spaces for the undiscovered elements and also predicted masses [atomic weights] and other properties of these unknown elements almost correctly (p. 40). from the above quote, one can conclude that the textbook by sharma et al.29 does recognize the importance of accommodations and predictions separately but not the relative importance of the two. in agreement with brito et al25., we argue that textbooks should inform learners that the success of the periodic table could be attributed to accommodations, predictions, or both. this will help students to take the view that the same experimental data can be explained by alternative interpretations. 5. conclusion and implications for chemistry education the purpose of this study was to evaluate ethiopian secondary school chemistry textbooks with respect to the presentation of the historical development of the periodic table of chemical elements which is considered to be a conceptual tool24 that helps to organize a great deal of information, leading to a better understanding of chemistry. as mentioned earlier, three grade 9 chemistry textbooks were selected for the evaluation. we conducted the analysis qualitatively by reading the relevant pages of the textbooks based on a four point evaluation criteria adopted from previous researchers25. as can be seen from table 2, of the four historical aspects of the periodic table, a satisfactory description of only one of them (namely, the importance of predictions as evidence to support the periodic law) is presented by one textbook (by sharma et al.29) only. the same textbook has attempted to present the first aspect i.e. the development of the periodic table as a sequence of discoveries but not in such a way that it informs the student that such development of the periodic table went through a continual controversy in which scientists presented various tentative theoretical ideas. in addition, the information presented is not articulated; it is just a string of events with no details; it may confuse the teachers and the students even more; and as such the scientific process looks even messier. in the other two textbooks (abera and abusie30and mamo and tassew31), all the four historical aspects of the periodic table including the importance of accommodation in development of the periodic table, and the relative importance of accommodation and prediction are generally ignored (i.e. simple mention or no mention). we may conclude that the hps aspects of the predict table are not satisfactorily addressed in ethiopian secondary school chemistry textbooks. that means, the textbooks’ presentation of the said aspects does not table 2. results of analysis of ethiopian secondary school chemistry textbooks accounts of the periodic table based on the history and philosophy of science framework. textbook criteria 1 2 3 4 5 sharma et al.29 m m s m n abera and abusie30 m m n n n mamo and tassew31 m m n n n 81are history aspects related to the periodic table considered in ethiopian secondary school chemistry textbooks? facilitate the students’ understanding of how science evolves as well as its tentative nature which in turn may have negative implications on the students’ chemistry/ science interest as well as on their understanding of and performance in the subject. this is similar to what is concluded by van berkel, de vos, verdonk, pilot19, who based on their study identified school chemistry as a form of “normal science education” which is considered to be “dangerous” in that it isolates the learner from the hps and, as such, is narrow and rigid and tends to instill a dogmatic attitude towards science. as the scope of the current study is limited in several ways, to get a fuller understanding of how hps related aspects of science are taught in ethiopian/african schools, it is recommended for more comprehensive studies to be conducted in the future. acknowledgement the authors would like to thank the editors of the special issue of the substantia journal for their advice and careful editorial work on the article. references 1. federal democratic republic of ethiopia (fdre), education and training policy, addis ababa: st. george printing press, 1994. 2. s. bekalo, g. welford, res paper educ, 2000, 15(2), p. 185-212. 3. e. asfaw, d. otore, t. ayele, z. gebremariam, an option paper presented at the technical workshop on science and mathematics secondary education in africa (seia) follow-up program. january 29 – february 06, 2009, tunis. 4. m. woldeamanuel, h. atagana, t. engida, ajce, 2013, 3(2), p. 28-38. 5. t. semela, camb j educ, 2014, 44(1), 113-145. 6. r. b. yager, the american biology teacher, 1982, 44(6), p. 328-334. 7. c. j. king, int j sci educ, 2010, 32 (5), p. 565-601. 8. e. gudyanga, t. madambi, the dyke, 2014, 8, p. 24-40. 9. y. sileshi, ajce, 2011, 1(1), p 10-28. 10. e. temechegn,a biannual news letter of the chemical society of ethiopia, 2002, 10(1), p. 11-14. 11. a. lemma, ajce, 2013, 3(1), p. 39-59. 12. usaid/iqpep ethiopia, chemistry teachers’ handbook and experimental manual for grade 7 and 8, addis ababa, st. george printing press, 2011. 13. d. hodson, teaching and learning about science: language, theories, methods, history, traditions and values. rotterdam, the netherlands: sense publishers, 2009. 14. m. r. matthews, science teaching: the contribution of history and philosophy of science, new york: routledge, 2014. 15. m. niaz, int j sci educ, 2011, new york: routledge. 16. d. hottecke, c. silva, science and education, 2011,20(3-4), p.293-316. 17. f. abd-el-khalick, m. waters, a. le, j res sci teach, 2008, 45 (7), p. 835–855. 18. s. irez, sci educ, 2009, 93, p. 422-447. 19. b. van berkel, w. de vos, a. h. verdonk, a. pilot, sci educ, 2000, 9 (1-2), p. 123-159. 20. j. l. marshall, j chem educ, 2000, 77, p. 979-983. 21. g. rayner-canham, j chem duc, 2000, 77, p. 10531056. 22. j. robinson, j coll sci teach, 2000, 29, p. 177-182. 23. m. niaz, m. luiggi, in facilitating conceptual change in students’ understanding of the periodic table, pp. 1-49. springer, heidelberg, 2014. 24. a. j. ihde, the periodic system of chemical elements:a history of the first hundred years (eds. j. w. van spronsen), amsterdam: elsevier, 1969, p. 1142. 25. a. brito, m. rodríguez, m. niaz, j res sci teach: the official journal of the national association for research in science teaching, 2005, 42(1), p. 84-111. 26. e. r. scerri, j. sci. educ, 2011, 12, 4-7. 27. e. r. scerri, in tools and modes of representation in the laboratory sciences, p. 163-177. springer, dordrecht, 2001. 28. m. d. gordin, ambix, 2018, 65(1), p. 30-51 29. j. l. sharma, n. angelo, s. johnson, s.tekleyohannes, m. tessema,chemistry student textbook grade 9, new delhi: star publishers, 2010. 30. b. abera, s. abusie, chemistry student textbook grade 9, revised edition, addis ababa: mega publishers, 2005. 31. h. mamo, a. tassew, chemistrystudent textbook grade 9, revised edition, addis ababa: mega publishers, 1999. 82 gebrekidan mebrahtu tesfamariam, mengesha ayene ejigu appendix. ethiopian grade 9 chemistry textbooks considered for the study published in 2010 published in 2005 published in 1999 substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo substantia. an international journal of the history of chemistry 4(1): 63-70, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-586 citation: k. kostecka (2020) astatine – the elusive one. substantia 4(1): 63-70. doi: 10.13128/substantia-586 received: aug 05, 2019 revised: jan 09, 2020 just accepted online: jan 10, 2020 published: mar 11, 2020 copyright: © 2020 k. kostecka. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles astatine – the elusive one keith kostecka science and mathematics department, columbia college chicago, 600 s. michigan avenue, chicago, illinois, 60605-1996, usa e-mail: kkostecka@colum.edu abstract. astatine has proven, since its isolation by corson, mackenzie and segre in 1940 to be an element with a fascinating history with respect to its discovery, confirmation and naming. it has also proven to have an interesting set of physical and chemical properties as well as isotopes of significant note. this element also has several applications of note as well as a captivating chemistry and the question whether it is or is not diatomic. keywords. astatine, discovery/naming, properties of the element, applications of the element, chemistry of the element. introduction since 1922, a search for element 85 [eka-iodine as per dmitri mendeleev’s terminology] was underway involving the efforts of many scientists world-wide (1). claims to the discovery [and confirmation] of the element were made by many individuals until the isolation of the element by dale corson, kenneth mackenzie and emilio segrè.1 significant discussion about the element’s name also occurs in this paper. in addition, this paper also notes selected physical and chemical properties of astatine as well as its many known isotopes. an introduction to the applications of astatine follows and the chemistry of the element is then explored with a final examination made of whether or not astatine is diatomic. discovery and naming early efforts reports of the search for element 85, termed eka-iodine by mendeleev, go back to the year 1922.1 in that year, frederick loring, working with numerical analysis, was led to believe that the element either did not exist or existed in very minute quantities.2,3 a few years later, in x-ray experiments looking for element 87, he and his co-worker john gerald frederick druce 1 a picture announcing the discovery of astatine is seen in figure 1. this image is from www. diarystore.com. http://www.diarystore.com http://www.diarystore.com 64 keith kostecka reported promising results suggesting the presence of both element 87 and element 85.4 many other individuals worked trying to isolate and characterize eka-iodine without noteworthy success during the 1920’s and 1930’s in the uk, germany, british india, denmark, france and switzerland. as the 1930’s drew to a close, horia hulubei and yvette cauchois reported x-ray wavelengths for three spectral lines of eka-iodine in the emission spectra of radon that were closely related to henry moseley’s predicted positions.1,5 this was followed up by manuel valadares, who in the middle of world war ii in italy, repeated hulubei’s work with a large sample of rn and saw new characteristic lines of element 85.6 in the time period 1942-1944, berta karlik and traude bernert noted the detection of α particles and element 85 with a mass of 218. karlik and bernert were also involved in the discovery of naturally occuring astatine in 1942.6-13 even though these [and other] aforementioned scientists did stellar work, they were publishing their research in journals that were not well known. a good number of them also did not have available journal articles from the united states due to, in large part, world war ii. element 85 discovery in 1939 with construction nearing completion on the radiation laboratory at the university of california at berkeley, segrè postulated that adding an α particle at 32 mev to bi-209 would produce an element with atomic number 85.14 this work was done by robert cornog and corson who, with the assistance of mackenzie, saw a number of forms of radiation, including the emission of α, γ, and x-rays and also low energy electrons all having a half-life of about 7.5 hours.15-19 this group was also able to perform chemical analyses on the “material” and track its radioactivity. as a result, corson, mackenzie and segrè, in large part, are regarded as the actual discoverers of element 85. a great deal more is written about the search to find this element in an excellent article written by brett thornton and shawn burdette.1 confirmation of discovery even with the announcement of the discovery of astatine in 1940, confirmation was still needed. this was done by joseph hamilton and mayo soley who put a minimum amount of the new element [with a halflife of approximately 7.5 hours prepared according to the method of corson, mackenzie and segrè] into the food of a guinea pig. given that eka-iodine lay directly beneath iodine in the periodic table, it was logical to assume that this newly found element would have similar properties to those of iodine. after several hours of digestion, the iodine-craving thyroid gland of the guinea pig had filtered and concentrated this new element. therefore, confirmation of the discovery of this new element was, in part, forever ascribed to the digestive system and thyroid gland of a guinea pig.20,21 naming the element from the initial tentative claim of the discovery of eka-iodine in 1925 by loring to the actual discovery of the element in 1940 by corson, mackenzie and segrè, a variety of names were proposed for this new element. in 1931, fred allison used a later discredited magneto-optic method to attempt to discover eka-iodine at the alabama polytechnic institute [now known as auburn university]. using this method, he tested sea water, hydrohalic acids, apatite and brazilian monazite sand; a material that was a source of rare earth minerals.22 in work reported in 1932, he suggested the name alabamine (ab later changing to am) to honor the state where the work was done.22 allison also described, in his paper, chemical tests that unfortunately depended on the magneto-optic method. this method, and allison’s claim to have discovered alabamine, were shown by herbert macpherson to be due to imperfections in allison’s equipment.23 though alabamine was no more, its name and symbol stayed in textbooks and reference figure 1. an announcement of the discovery of the element astatine. 65astatine – the elusive one works until 1947; in addition the name alabamine, surprisingly and allison, as its discoverer, were still listed in the 1991 concise columbia encylopedia.5 in 1937, an indian chemist named de read about allison’s efforts and proceeded to study travancore monazite sand which he believed to contain a significant amount of eka-iodine.1 after performing a series of chemical tests on the monazite, de noted the presence of a black, sublimable substance that he identified as ekaiodine; he named it dakin likely in honor of dacca [now known as dhaka, the capital of bangladesh].24,25 hulubei and cauchois, in 1939, were examining the radioactivity of radon in the hope of seeing eka-iodine. in 1936 they had observed a line that corresponded with where the ka1 line for eka-iodine was expected. in 1939, they reported two further x-ray lines that were consistent with predictions from moseley’s law and the presence of eka-iodine and hulubei announced the discovery of the element. this new data came about from experiments that used higher resolutions than their 1936 work and thus led to enhanced confidence that they had discovered eka-iodine.14 in 1944 hulubei wrote up his work and that of others who had been looking for this new element. this summary included a description of six x-ray lines that were thought to be due to natural radioactive decay. he suggested, as a name, “dor” which was taken from romanian word for “longing” and given that the world was at war and “longing for peace”. unfortunately, t here were many reasons why hulubei and cauchois did not receive due credit for their independent discovery of element 85. reasons for this omision were: the statement of karlik and others that hulubei and cauchois’s sample size was too small and that there were interferences from other elements in the spectra of hulubei and cauchois; other work on element 85 had been refuted even though hulubei and cauchois’s work had not been refuted; wartime scientific communications were generally poor, hulubei had mistakenly claimed discovery of element 87 and that their work was rejected by paneth in 1947 who noted that the work of hulubei and cauchois did not have sufficient means to characterize discovery of element 85.1 in addition, hulubei’s discovery only received experimental confirmation from the work of valadares in italy; the one and only country outside of france that did so confirm hulubei’s work. an additional significant claim of discovery of element 85 came from the work of the swiss physicist walter minder.26 in 1940 he said he saw an extremely weak β decay of radium. in this work, a couple of ionization chambers were attached to an electrometer. chemical tests confimed, in minder’s opinion, a new element which he named helvetium with the symbol hv. in 1942 minder repeated his work and announced the “discovery” [with his british colleague alice leigh-smith] of anglohelvetium. however, this work was not reproducible and discussion of it faded rapidly into obscurity. as a result, credit for discovering eka-iodine went to the team of corson, mackenzie and segrè and not to hulubei and cauchois. now with the definitive discovery of element 85, a name had to be chosen. given that this element is so rare, only having been discovered as naturally occurring by karlik and bernert in 1942,9,13 and elusive as far as its discovery was so concerned, the greek word astatos meaning unstable seemed appropriate.27 element 85 now had a name astatine! in closing this section, it is significant to note the total amount of naturally occurring astatine on planet earth might be as little as a few hundred milligrams to, at a maximum, perhaps 30 grams.27 this amount of astatine is soley due to the decay of thorium and uranium present in the earth’s crust.28 thus, astatine is the rarest naturally occuring element in the periodic table.20 discovery/confirmation of astatine and scientist nationality with any new scientific discovery, there is of course great joy, satisfaction and a sense of accomplishment. though these feelings were likely true for corson, mackenzie and segrè, the same was not true for others involved in the search for element 85. this story showed that nationalistic [and even regional as seen with the work of allison] prejudices strongly influenced who was given credit for the discovery/confirmation of this member of the periodic table. properties with the discovery, confirmation and naming done for the element astatine, characterization was next. some of this work is reported in the nubase evaluation of nuclear and decay properties as compiled from archived information by audi et al.29 work was reported on mass excess, half-life, probability of alpha decay and electron capture of the element. in addition, reports on astatine in nature came from the efforts of karlik and bernert who studied the α-activity from the thorium decay series9,13 and also found a small number of previously unreported 8.4 mev α-particles related to a short-lived 66 keith kostecka at-215 isotope.11 one other significant work on naturally occurring astatine showed that at-219 was present in u-235 ores in minute amounts.30,31 astatine is quite difficult to work with – if one were to have a visible piece of the element, the element would immediately be vaporized due to heat generated by radioactive decay. it has not yet been determined if this issue in exploring the element can be overcome by appropriate cooling.32 as a result, most physical properties of astatine are not known with any degree of certainty. it is also interesting that astatine may only be found in uranium 235 ores, nuclear facilities and/or research laboratories. otherwise, the element is undetectable. physical properties some of the physical properties of astatine are seen in table 1.33,34 based on the colors of the halogen group elements it is likely that a hypothetical solid astatine may be very dark in color, perhaps even black.32 of all the natural halogens, astatine is the least chemically reactive and may even exhibit metallic properties – perhaps even being a superconductor.35,36 a good number of these tabulated properties are theoretical. table 1. selected physical properties of astatine. atomic number 85 atomic mass ~210 grams/mole state at 20°c solid (predicted) density (estimated) 6.35 – 6.50g/cm3 boiling point 230-233°c (estimation) heat of fusion ~ 6 kj/mol (estimation) electron configuration [xe] 4f 145d106s26p5 covalent radius 150 pm van der waals radius 202 pm crystal structure fcc (predicted) chemical properties astatine has many possible oxidation states [-1, 1, 3, 5 and 7] with -1 and 1 being most common.33 only francium is less stable than astatine out of the first 101 elements in the periodic table. when astatine undergoes radioactive decay, the element decays into bi, po, rn or other isotopes of astatine. astatine has an electronegativity of 2.2 [on the revised pauling scale] and a first ionization energy of 899 kj/mol. the chemistry of astatine, difficult due to its short half-life, is “clouded by the extremely low concentrations at which astatine experiments have been conducted, and the possibility of reactions with impurities, walls and filters, or radioactivity by-products, and other unwanted nano-scale interactions”.35 of interest also is the fact that astatine is the least reactive of the halogens. in order to ensure a reaction, dilute solutions of astatine are mixed together with larger amounts of iodine. iodine, acting as a carrier, ensures that there is sufficient material for such techniques as filtration and precipitation to be properly conducted.37-39 isotopes currently, astatine has 39 known isotopes with atomic masses ranging from 191 to 229. according to theoretical modeling, another 37 isotopes might exist.30,40 out of all these possible isotopes, not one is likely to be stable or even long-lived. the most stable isotope, known to date, is at-210 and it has a half-life of 8.1 hours. this isotope has as its primary decay mode β+ which gives the α emitter po-210. of all the possible isotopes, only five have half-lives greater than one hour and they are: at-207 (1.80 hr), at-208 (1.63 hr), at-209 (5.41 hr), at-210 (8.1 hr) and at-211 (7.21 hr). the shortest lived isotope found to date is at-213 has a half-life of 125 nanoseconds (29); this isotope undergoes α decay to the extremely long-lived bi-209 (half-life of 1.9 x 1019 yr). introduction to applications of astatine with the discovery and initial characterization efforts on astatine somewhat complete, significant interest turned to potential applications of the element. given astatine’s similar behavior to iodine in concentrating in the thyroid gland as found by hamilton and soley,21 medical applications of the element and its isotopes became interesting. later work showed that fairly small amounts of astatine could lead to significant changes of structure in the parathyroid gland and other peritrachial tissues.41 further investigation of this take-up of astatine by bodily tissues was then made in guinea pigs, rats and monkeys; in fact the treatment of hyperthyroidism in human beings by astatine was proposed. this was substantiated by the results of tracer experiments where it was found that human beings accumulated astatine in their thyroid glands. benefits of this “tendency” were noted to have to be weighed against hazards from exposure to the radiation of astatine. 67astatine – the elusive one actual applicatons of astatine with the half-life of even the longest-lived astatine isotope only about 8 hours, finding any real world applications have been quite difficult, to say the least. at-210 decays quite readily into po-210 which is notorious; it was used to kill alexander litvinenko in november 2006.42 fortunately though, at-211 is an isotope that has seen some use in nuclear medicine and may also be helpful in the future. much like i-131, at-211 does not emit high-energy β-particles, but instead emits α particles and it is known as one of the few α-emitting radionuclides considered for medical use;43 most other α-emitters cause severe damage to internal organs. a typical α-particle released by at-211 may travel only 70 mm through bodily tissues; an average β-particle emitted by i-131 can travel more than 25 times farther in bodily tissues.44 given this short path length of α-particles in the human body and their high energy (6.0 to 7.5 mev), such particles are very effective at killing cells bound by carrier-targeting agents.45 this short range effectiveness of at-211 can possibly reduce risk of exposure to other bodily tissues and perhaps then be used throughout the human body in treating cancer. this short half-life of at-211 and lesser penetrating ability is a definite advantage in situations where the “tumor burden is low and/or malignant cell populations are located in close proximity to essential normal tissues”.46 significant morbidity in cell culture models of cancers in humans have been achieved with from one to ten at-211 atoms bound per cell.47 there is though a problem with the low stability of astatine to aromatic carbon bonds in vivo.48 developing labelling reagents with more stable aromatic astatineboron bonds has helped in lessening this difficulty and it is possible that further study with other elements may lead to additional scientific advances. astatine-based radiopharmaceuticals have seen a variety of obstacles during the 20th and 21st centuries. world war ii brought such research to a halt for at least a decade. experiments noted that a cancer-selective carrier would need to be developed and it was not until the 1970’s that monoclonal antibodies became available for this purpose. given that astatine tends to become detached from its compounds, is toxic and is also retained in the body [preferentially accumulating in the thyroid gland, lungs and spleen].47,48 at needs to stay attached to its host molecule. mitigating the effects of astatine induced radiolysis of labelling chemistry and carrier molecules is another area needing additional work. chemistry of the element the chemistry of astatine is typically done using masses of 10-13 to 10-8 grams of the element49 or at extremely low concentrations. unfortunately, this lowlevel method allows reactions with impurities, walls, filters and even radioactive byproducts.35 a good number of astatine’s properties have been observed in very dilute solutions typically at concentrations of less than 1 x 10-10 mol/l. even though “astatine … [is] miserable to make and hell to work with,” as noted by patricia wallace durbin,50 it does undergo a variety of chemical reactions. the element has the ability to form compounds with metals; combine with hydrogen; interact with boron and carbon; react with oxygen and other chalcogens and also form compounds with chlorine, bromine and iodine. though there are only a few compounds of astatine with metals, astatides incorporating sodium, magnesium, palladium, silver, thallium and lead have been formed.51,52 given the extraordinarily limited amount of available astatine, estimations, by extrapolation, of the characteristics of agat and naat have been made based on other metal halides.53 astatine also exhibits chemistry with boron and carbon. a variety of boron cage compounds have been made with at-b bonds stronger than at-c bonds.51,54 the compounds carbon tetraastatide (cat4) and astatobenzene (c6h5at) have been prepared.51 astatobenzene (c6h5at) can also be oxidized to c6h5atcl2 by exposure to cl2. this chlorinated compound can then be treated with a basic hypochlorite solution to give c6h5ato2.55 a perchlorate of astatine has also been prepared, [at (c5h5n)2 ][clo4] where the astatine is bonded to each nitrogen atom in the two rings of pyridine.56 reactions of astatine also occur with oxygen and other chalcogens. with oxygen, there is evidence to support the existence of ato-, ato2and ato+ in aqueous solution.57,58 an ato3ion can be obtained by the oxidation of astatine with kocl in a solution of koh.59,60 further chemistry of this ato3species has seen the formation of la(ato3)3 through the oxidation of astatine in a hot na2s2o8 (sodium peroxodisulfate) solution.44 the ato4ion also exists; further oxidation of ato3in a hot, basic solution of xef2 so gives this anion.61 substituting periodate (in either neutral or basic media) will also yield the ato4ion – which is only stable in neutral or basic media.62,63 astatine can also form, with sulfur, the s7at+ ion and the thiocyanate ion species at(csn)2-.64 in addition, cationic astatine compounds with thiourea, thiourea derivatives and some n-acyl thioureas in aqueous solu68 keith kostecka tion have been reported.64 astatine also has the ability to form a selenourea coordination compound with selenium and a colloidal tellurium compond.64 reactions of astatine in the vapor state with chlorine, bromine and iodine have produced the diatomic compounds atcl, atbr and ati.65 atbr is also formed by interacting astatine with an iodine/iodine monobromide/bromide solution whereas ati is prepared by reacting astatine with iodine/iodide solution in an aqueous media.66 excess of iodide or bromide could lead to the formation of atbr2and/or ati2ions or if in a chloride solution, species such as atbrclor atcl2can come about via equilibrium reactions with the chlorides.67 oxidation of at with cr2o7 2(while in a hno3 solution) showed that when adding chloride a compound of either atcl or atocl was produced; similarly, the ions atocl2or atcl2may also be produced.65 polyhalides like pdati2, csati2, tlati2 are directly known or have been presumed to be precipitated in chemical reactions.68-70 the existence of pbati is also likely.71 the possibility of the iatbrion, as determined by quantum mechanical calculations, was found by galland to exist and even predominate in aqueous solutions.72 astatine diatomic or not? all serious students of chemistry know the seven diatomic elements. whether astatine is also diatomic is a matter of debate to this date. as an analog of iodine, it may have an orthorhombic crystalline structure composed of diatomic astatine molecules and also be a semiconductor.73 unfortunately, the structure of solid astatine is not known though some expect it to be a black solid with a metallic appearance.34,74 takahashi, in work reported in 1986, described interactions of astatine with benzene, toluene and monochlorobenzene. in this study, the chemical bond between at2 is quoted to cleave in a two-step mechanism that worked for benzene and toluene but not for monochlorobenzene.75 additional work by takahashi reported in 1991 looked deeper at the chemical behavior of astatine.76 on the other hand, condensed astatine is calculated to behave like a metal at 1 atmosphere of pressure and might possibly be a superconductor but would be monoatomic.77 simply enough, in the gas phase, astatine might be weakly diatomic but when it is solid it is the spin orbit coupling contribution of relativistic effects that weakens the covalent character of a bond in at2 and thus makes solid astatine monatomic.77,78 this also extends to the ability of at to be a halogen bond donor.79 conclusion the discovery [and confirmation of the existence] of the element astatine involved the efforts of many scientists and many years of work in europe, india and the united states. these investigations gave the world the properties of astatine and its chemistry as well as some isolated but medically important applications of the element. the question of whether at2 exists was explored. all in all, element 85 has shown that even though it has an unstable nature, it is still a fascinating and vital member of the periodic table. acknowledgements i would like to thank my department chair, dr. azar khosravani, for her leadership and support in my desire to excel in teaching, scholarship and service. i also would like to thank dr. carmen giunta, professor of chemistry at le monye college in syracuse, ny, for his assistance in the proofreading of this manuscript. references and notes 1. brett f. thornton and shawn c burdette, bull. hist. chem. 2010, 35 (2), 86-96. 2. frederick h. loring, chem. news j. ind. sci., 1922, 125, 309-311. 3. frederick h. loring, chem. news j. ind. sci., 1922, 125, 386-388. 4. frederick h. loring and john gerald frederick druce, chem. news j. ind. sci., 1925, 131, 305. 5. horia hulubei and yvette cauchois, c.r. seances acad. sci. ser. c, 1939, 209, 39-42. 6. marco fontani, mariagrazia costa and mary virginia orna. the lost elements – the periodic table’s shadow side. 2015. oxford university press. p. 331. 7. berta karlik and traude bernert, sitzber. akad. wiss. wien, math.-naturw. klasse, 1942, 151, 255-265. 8. berta karlik and traude bernert, naturwissenschaften, 1942, 30, 685-686. 9. berta karlik and t. bernert, naturwissenschaften, 1943, 31, 298-299. 10. berta karlik and traude bernert, naturwissenschaften, 1943, 31, 492. 11. berta karlik and traude bernert, sitzber. akad. wiss. wien, math.-naturw. klasse, 1943, 152, 103-110. 12. berta karlik and traude bernert, naturwissenschaften, 1944, 32, 44. 13. berta karlik and traude bernert, z. phys., 1944, 123, 51-72. 69astatine – the elusive one 14. dale r. corson, chem. eng. news, 2003, 81, 158. 15. eric scerri, [excerpt]. http://www.scientificamerican. com/article/a-tale-of-7-elements-astatine-excerpt/ (accessed january 2020). 16. dale r. corson and kenneth r. mackenzie, phys. rev., 1940, 57, 250. 17. dale r. corson, kenneth r. mackenzie and emilio g. segrè, phys. rev., 1940, 57, 459. 18. dale r. corson, kennneth r. mackenzie and emilio g. segrè, phys. rev., 1940, 57, 1087. 19. dale r. corson, kenneth r. mackenzie and emilio g. segrè, phys. rev., 1940, 58, 672-678. 20. sam kean, chem. herit., 2014, 32, 5. 21. joseph g. hamilton and mayo h. soley, proc. natl. acad. sci. 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40. earl k. hyde, j. chem. ed., 1959, 36 (1), 15-21. 41. joseph g. hamilton, et al., the accumulation, metabolism, and biological effects of astatine in rats and monkeys, u. of calif. press, berkeley, 1953. 42. poisoning of alexander litvinenko. https:// en.wikipedia.org/wiki/poisoning_of_alexander_litvinenko (accessed january 2020). 43. d. scott wilbur, curr. radiopharm., 2011, 4, 214-247. 44. avgusta k. lavrukhina and alexsandr a. pozdnyakov, analytical chemistry of technetium, promethium, astatine, and francium (translated by r. kondor), ann arbor-humphrey science publishers, 1970, 233. 45. eric j. hall and amato j. giaccia, radiobiology for the radiologist, lippincott, williams & wilkins, philadelphia, 2006, 6, 106-116. 46. michael r. zalutsky and marek pruszynski, curr. radiopharm., 2011, 4, 177-185. 47. d. scott wilbur, curr. radiopharm., 2008, 1, 144-176. 48. francois guèrard, jean-francois gestin and martin w. brechbiel, canc. bio. and radio., 2013, 28, 1-20. 49. anne pichon, http://blogs.nature.com/thescepticalchymist/2013/03/enigmatic-astatine.html (accessed january 2020). 50. darrell fisher, human radiation studies: remembering the early years oral history of dr. patricia wallace durbin, ph.d., 1995, united states department of energy, office of human radiation experiments. 51. john emsley, nature’s building blocks: an a-z guide to the elements (new edition), oxford university press 2011, pp. 57-58. 52. hans k. kugler and cornelius keller (eds), astatine 10-14, gmelin handbook of inorganic chemistry series, 1985, pp. 213-214. 53. hans k. kugler and cornelius keller, 1985. pp. 214-218. 54. matthew g. davidson, contemporary boron chemistry, 2000, royal society of chemistry, p.146. 55. jorgen elgqvist, ragnar hultborn, sture lindegren and stig palm, targeted radionuclide therapy, lippincott, williams & wilkins. 2011, 383, pp. 380-396. 56. jerold j. zuckerman and arnulf p. hagen, inorganic reactions and methods the formation of bonds to halogens (part 1), 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et al., inorg. chem., 1966, 5 (5), 766-769. 74. alfred b. garrett; john s. richardson and arthur s. kiefer, chemistry: a first course in modern chemistry, 1961, ginn. p. 313. 75. naruto takahashi, and kiyoteru otozai, j. of radioanal. and nucl. chem. 1986, 103 (1), 1-9. 76. naruto takahashi, et al., proceedings of the international conference on evolution in beam applications, takasaki, japan, november 5-8, 1991. 1992, pp. 536539. 77. andreas hermann; roald hoffmann and neil w. ashcroft, phys. rev., 2013, 111, 116404-1 to 1164045. 78. nicolas galland, et al., j. chem. theory comput. 2014, (10), 4830-4841. 79. nicolas galland, et al., phys. chem. chem. phys. 2018, (20), 29616-2962. substantia an international journal of the history of chemistry vol. 4, n. 1 2020 firenze university press peer review – critical feedback or necessary evil? seth c. rasmussen particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 consciousness, information, electromagnetism and water marc henry leonardo and the florence canal. sheets 126-127 of the codex atlanticus filippo camerota the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí astatine – the elusive one keith kostecka vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of xx century aleksander sztejnberg substantia. an international journal of the history of chemistry 1(2): 63-73, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-27 citation: l. colli, a. salvini, e. pecchioni, s. cencetti (2017) conservation of paleontological finds: the restoration materials of the “problematica verrucana”. substantia 1(2): 63-73. doi: 10.13128/substantia-27 copyright: © 2017 l. colli, a. salvini, e. pecchioni, s. cencetti. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the authors declared that no competing interests exist. research article conservation of paleontological finds: the restoration materials of the “problematica verrucana” laura colli1, antonella salvini1,*, elena pecchioni2, sandra cencetti3 1 dipartimento di chimica “ugo schiff ”, università degli studi di firenze, via della lastruccia 3-13, 50019 sesto fiorentino (fi), italy. *corresponding author e-mail: antonella.salvini@unifi.it 2 dipartimento di scienze della terra, università degli studi di firenze, via la pira 4, 50121 firenze, italy 3 laboratorio di microanalisi, dipartimento di scienze delle produzioni agroalimentari e dell’ambiente, università degli studi di firenze, via della lastruccia 13, 50019 sesto fiorentino (fi), italy abstract. the materials used in the historical restoration of a fossil collection named “problematica verrucana”, have been studied in order to contribute to the creation of a catalogue of restoration materials used in the past. due to the complexity of the mixtures used with different purposes to restore fossil finds, an extractive technique has been employed in order to separate the compounds soluble in solvents with different polarities. using this procedure several components, even when found in small amounts, have been identified. the chemical composition of the organic and inorganic compounds used in the restoration material has been determined using extractive procedure, ft-ir and 1h-nmr spectroscopies. a preliminary macroscopic characterisation and mineralogical and petrographical analyses have also been performed on the inorganic filling materials found in several samples. the different compositions of various materials used in the restoration of this fossil collection might be related to the particular conservative and esthetic functions of the product applied on the find. keywords. fossil collection, restoration materials, petrographical analyses, spectroscopic analyses, paleontological museum. 1. introduction paleontological museums usually preserve recently acquired finds beside ancient and historical collections, where some fossils could have suffered from serious alteration processes due to prolonged storage in depositories and warehouses, while other fossils could have been “restored” during the centuries.1,7 furthermore, in order to be conserved into a museum, natu64 laura colli, antonella salvini, elena pecchioni, sandra cencetti ralistic finds need to undergo a specific process, called preparation. in the past, the preparation and restoration of damaged pieces were generally made by the paleontologists themselves, often in an empirical and artisanal way3,8 with materials and procedures which have rarely been documented. the natural history museum of florence hosts a fossil collection named fucini collection or “problematica verrucana”. this collection is composed of fossil tracks and fossil seaweeds found by alberto fucini, geologist and paleontologist of the university of florence, on the monti pisani during the first decades of ’9009. the peculiar feature of this collection consists in the fact that the majority of finds show signs of historical restoration, probably performed by fucini himself, perhaps with the aim of facilitating the study of the finds. unfortunately, no documentation about the products applied during these interventions is conserved at the natural history museum. the aim of this research was to identify the materials used for the historical restoration of this collection. with this purpose, several samples recovered from restoration materials were studied by means of chemical and mineralogical analyses. 2. materials 2.1 the finds the fucini collection, or “problematica verrucana”, is made up of more than one thousand pieces; the samples for this study were taken from 17 finds, as described in table 1, with the aim of identifying different kinds of materials. this collection is composed for the most part of fossil imprints or marks that animals have left in their habitat in the past. the comparison between the problematica verrucana tracks and those of several tetrapods has not been completed yet10-13. actually the majority of finds have been identified as either impress or reverse marks (the relief of the impress in the specular portion of the sediment) of small dinosaurs. besides, marks of vegetal rests are also conserved in the fucini collection, principally seaweeds like sewardiella e gothaniella (figure 1). the term “problematica” refers to the difficult interpretation of the type of traces left behind, while the adjective “verrucana” derives from the term monte verruca (in the monti pisani between pisa and lucca italy), as does the term verrucano, a geologic period contable 1. finds and samples. find name igfa type of find sampling zone sample gothaniella sphenophylloides fucinii, forma piumosa 10351 fossil seaweed junction sample 1 chondrites fucillatus 10368 print of a prehistoric reptile junction and back sample 2 thecodontiehnus verrucae 5152 hand-print of a small carnivorous reptile lateral part sample 3 sewardiella verrucana 10323 fossil seaweed lateral, right, part sample 4 sewardiella verrucana fucinii, forma multiradiata 10298 fossil seaweed superior part sample 5 sewardiella verrucana fucinii 10301 fossil seaweed front and lower part sample 7 undefined find 516t undefined track back sample 8 undefined find 748t undefined track back sample 9 sewardiella verrucana fucinii 10302 mold of fossil seaweed back sample 10 sewardiella verrucana fucinii, forma fasciculosa 10315 mold of fossil seaweed lateral, left, part sample 11 undefined find 692t undefined track back sample 12 sewardiella verrucana fucinii, forma rotata 10299 mold of fossil seaweed lateral, left, part sample 13 thecodontiehnus fucinii v. huene 5149 hand-print and foot-print of a reptile similar to varan back, lower part sample 17 undefined find not catalogued back sample 18 rhinocecephalichnus 5195 hand-print and foot-print of a reptile lower part sample19 sewardiella verrucana fucinii, forma lateradiata 10292 fossil seaweed lower part sample 20 undefined find 348t undefined track back sample 21 aigf catalog number of natural history museum 65conservation of paleontological finds: the restoration materials of the “problematica verrucana” sidered as a synonym of permiano, which characterises the relevant area. 2.2 description and function of restoration products according to their macroscopic aspect and main functionality, the restoration materials used in the fucini collection can be divided in four classes, each one containing different kinds of products. products belonging to the same class may vary in colour or aspect of the aggregate. sometimes several pieces of the same materials were sampled, for example when a product was apparently used for different functions (table 2) (figure 2). class a: light-yellow substances with or without aggregate used as adhesive to reconnect separated parts of finds. materials belonging to this class can be divided in three different categories, all containing an adhesive material, either used alone (product a), mixed with aggregates having smaller grains (product b) or larger grains (product c). product a is a yellow-orange amber, transparent and hard material. products b and c are similar to product a. product b is used to attach broken parts of medium-dimension finds; it is applied alone or with paper or fabric. product c is used for pieces of medium and big dimensions. it is rarely used with paper or fabric. class b: hard materials used for junctions and for moulds, which appear of two colours (green or gray). the difference between these two products, classified as product h and product g, is macroscopically limited to the colour. the two products appear like hard and porous mixtures, of light green or gray colour, and of crumbly aspect. the presence of some drops suggests that the product has been applied in a liquid state. the same product has been sampled in finds in which it worked as adhesive, and in moulds. the gray material has been defined “sulphor” by fucini 9. these materials have been used to lend adhesion to broken pieces and to make moulds. class c: gummy pastes used for support purposes. these materials appear as rubbery adhesive pastes probably used for integrations (especially product e) or to create a layer in the back of the finds. product e appears as a partially hardened rubber. the colour is brown. it was probably used for integrations. product f appears like a completely hardened rubber. it appears in the form of small, quite flat, cushions. the shape suggests that the product was applied with the pressure of the fingers. it is found only in the back of the finds: it looks as if it was used to create a support base for photographic sessions. class d: filling materials of various colours. they are five materials which appear as inorganic products used to assemble broken pieces or to reconstruct lacking parts. product k is of dark grey colour and it is hard to the touch. product l and product m have similar aspects, they are hard and compact, but they have different pigmentations (the first one has a grey colour, the second is brownish-red). product n is dusty and friable and of brownish-orange colour; it seems hard, but it is not compact, it appears fragile and dusty. product o figure 1. examples of animal and vegetal finds of fucini collection: find igf 5152, a) hand-print of a small carnivorous reptile: the codontiehnus verrucae; b) igf 1036, a fossil seaweed: gothaniella sphenophylloides fucini. 66 laura colli, antonella salvini, elena pecchioni, sandra cencetti appears, also at a macroscopic level, considerably different than the others: the binder appears of grey-whitish coloration, the aggregate is poorly sorted (dimensions from the micron to the centimetre). 3. experimental section cdcl3 (aldrich, purity 99,9% in d), d2o (aldrich, purity 99.9% in d) and dmso-d6 (aldrich, purity 99.8% in d) were reagent grade and were used without further purification. 1h nmr spectra of solutions were recorded at 399.92 mhz on a varian mercury 400 or at 199.985 mhz on a varian vxr 200. all spectra were reported in ppm using solvent residual peak as reference. ir spectra were recorded on a ft-ir perkin-elmer spectrum bx model, using the spectrum v. 3.02.02 program. the ft-ir spectra of all solid materials were recorded using a mixture of sample (3 mg) and kbr (100 mg). the solutions were analysed using kbr or caf2 plates after deposition and solvent evaporation. in the extraction tests, 12 mg of each sample were introduced into a round bottom flask, equipped with a magnetic stirrer, with 0.7 ml of deuterated solvent (cdcl3 or d2o) and maintained at room temperature under magnetic stirring for 24 hours; then the solid and the solution were separated by filtration. at the end, an extraction with d2o was also performed at 85°c for 6 hours. the solutions were analysed by 1h-nmr spectroscopy and then by ft-ir spectroscopy as reported above. the solid residues were washed with the corresponding non deuterated solvent used in the extractive procedure, dried under vacuum and analysed with ft-ir spectroscopy as reported above. the macroscopic analyses were carried out with a stereomicroscope (zeiss kl 1500 electronic). the mineralogical compositions were determined through powder x-ray diffraction (xrd) using a philips pw 1050/37 diffractometer, with a philips x’pert data acquiring system, operattable 2. description of the samples: class, product and number of finds. sample class product description sample 1 class a product a light-yellow, hard and poorly compact product, present in 76 finds sample 2 sample 3 product b light-yellow, hard and quite compact product, present in 169 finds sample 4 sample 5 product c light-yellow, hard and very compact product, used only for big pieces, present in 8 finds sample 9 class b product g hard and glassy mixture of grey color, present in 11 finds sample 10 sample 11 sample 12 product h hard and glassy mixture of green color, present in 20 finds sample 13 sample 7 class c product e gummy product of brown color, present in 7 finds sample 8 product f gummy product of black color, present in 10 finds sample 17 class d product k dark-grey filling, present in 2 finds sample 18 product l grey filling, present in 22 finds sample 19 product m brownish-red filling, present in 23 finds sample 20 product n brownish-orange filling, present in 3 finds sample 21 product o whitish-grey filling, present in 1 finds figure 2. a) example of class a materials (product c); b) class b (product h); c) class c (product f); d) class d (product m). 67conservation of paleontological finds: the restoration materials of the “problematica verrucana” ing at 40 kv-20 ma, with a cu anode, a graphite monochromator and with 2°/min goniometry speed, in interval 2θ between 2o-62°. the petrographic description was performed using a polarised light microscope zeiss d7082 oberkochen (om) on thin section (30 μm thickness); the microscope photos were taken with a nikon coolpix 4500 with a magnification of 10× and 2,5×. 4. results and discussion the chemical composition of the products used in the historical restoration of the problematica verrucana was studied by means of ft-ir and 1h-nmr spectroscopies. in order to identify all products, also when found in small amounts, some extractions with solvents of various polarity were carried out on the fragments of samples, as reported in the experimental. a preliminary macroscopic characterisation and mineralogical and petrographical analyses were also performed on the inorganic filling materials found in the products of class d. 4.1 characterisation of class a products the chemical composition of the different samples identified as class a (products a, b or c) was analysed by ft-ir spectroscopy on the kbr mixture. the same organic compound, probably used as adhesive, was present in all products of class a as main component (product a, samples 1 and 2) or as ligand for inorganic fillers (product b, samples 3 and 4; product c, sample 5). the ft-ir data [3428 (broad, vs), 2924 (m), 1631 (m), 1423 (m), 1030 (vs) cm-1] suggested the presence of a polysaccharide compound and in particular the fingerprint region of the ft-ir spectrum was similar to the arabic gum spectrum (figure 3). bands attributable to inorganic fillers could not be found in the spectra of product a (samples 1 and 2), whereas different inorganic fillers were detected in the ft-ir spectra of the other class a products. in fact, bands attributable to calcium carbonate [2512 (w), 1799 (m), 1423 (vs), 874 (m), 712 (w) cm-1] and silica [1083 (vs), 794 (m), 778 (m), 694 (w), 517 (w), 467 (s) cm-1] were present in the product b spectrum (samples 3). finally, the presence of some bands of silica [794 (m), 778 (m)] and mica [3628 (m), 1028 (vs), 755 (sp) cm-1] was observed in the product c spectrum (sample 5), while other bands were not detectable due to their overlap with those of low amounts of polysaccharide. 4.2 characterisation of class b products a complete absorption of infrared radiations, in the 4000-1000 cm-1 range, was observed for product g (samples 9, 10 and 11) and for product h (samples 12 and 13), also with a lower concentration of this sample in the kbr mixture. the presence of specific functional groups could not be detected and only a single band at 464 cm-1 was noticed. after extraction with cdcl3, no organic compounds soluble in this solvent were found. in fact, no signals were present in the 1h-nmr and ft-ir spectra recorded on this fraction. nevertheless, a yellow solid was recovered in the nmr tube, which suggested the probable presence of sulphur. no changes were observed in the ft-ir spectrum of the solid insoluble in cdcl3. the behaviour of these samples suggested the presence, as main component, of a grey product, not transfigura 3. product a, sample 2. – a) ft-ir spectrum; b) ft-ir spectrum of arabic gum. 68 laura colli, antonella salvini, elena pecchioni, sandra cencetti parent to the infrared radiation as graphite. because of the presence of this compound, it was not possible to observe other characteristic absorption bands. in order to confirm the hypothesis identifying graphite as the grey part of the solid and sulphur as the yellow part, a mixture containing graphite and sulphur was prepared and analysed by ft-ir spectroscopy. the ft-ir spectrum recorded on this mixture was identical to that recorded on sample 12 (figure 4). moreover, the colour appeared analogous with the sample material one. 4.3 characterisation of class c products the ft-ir spectrum of product e (sample 7) showed several bands attributable to the presence of a mixture of different organic products [2919 (vs), 2849 (s), 1734 (vw), 1710 (w), 1538 (vs), 1458 (m), 1398 (m), 1032 (w) cm-1], probably waxes (1734 cm-1), terpenoids (1734, 1710 and 1398 cm-1) and salts of saturated and monounsaturated fatty acids (1538 cm-1). furthermore, gypsum (caso4·2h2o) [3529 (w), 3404 (w), 1116 (w) cm-1] was identified in lower amounts as inorganic material. the 1h-nmr and ft-ir spectra of the cdcl3 solution (figure 5), obtained by extraction from the solid material at room temperature, suggested the presence as main components of salts of saturated and monounsaturated fatty acids [band at 1538 (vs) cm-1 in the ft-ir and signals at 0.89 (m, ch3), 1.27 (m, ch3-ch2), 1.65 (m, ch2 ch2ch2-coo), 2.00 (m, ch2ch=ch -), 2.38 (m, ch2-coo), 5.41 (m, -ch=ch-) in the 1h-nmr]. low amounts of free fatty acids or terpenoid acids and esters can also be found (band at 1731 (w), 1710 (m) cm-1), whilst glycerol, linoleic and linolenic acids, free or esterified in triglycerides, were not detected in the 1h-nmr spectrum. the solid residue contains gypsum [3535 (m), 3405 (m), 1623 (w), 1116 (vs) e 670 (w), cm-1] together with mica [3613 (w), 1030 (vs), 750 (w) cm-1], while the contemporary presence of silica can be identified for the weak bands at 797 (w), 777 (w), 531 e 472 cm-1. the bands at 2925 (w) and 2851 (w) cm-1 were attributable to the presence of an organic compound insoluble in cdcl3. several bands were found in the ft-ir spectrum of product f (sample 8), attributable to a mixture of several organic and inorganic compounds [3445 (m), 2917 (vs), 2849 (vs), 1736 (s), 1709 (m), 1496 (m), 1465 (s), 1244 (w), 1173 (w), 873 (w), 854 (w), 718 (w), cm-1]. the presence of waxes [1736 cm-1 in the ft-ir and signals at 0.89 (m, ch3), 1.27 (m, ch3-ch2), 1.65 (m, ch2ch2ch2coo), 2.38 (m, ch2-coo), 4.06 (m, o-ch2-) in the 1h-nmr] as main component, probably along with terpenoids (1736 and 1706 cm-1), was identified in the fraction soluble in cdcl3. in the spectrum of the solid resifigure 4. ft-ir spectrum of a graphite/sulphur mixture (a) compared with that of sample12 product h (b). figure 5. product e, sample 7 a) ft-ir spectrum; b) soluble fraction in cdcl3, 1h-nmr (cdcl3) spectrum. 69conservation of paleontological finds: the restoration materials of the “problematica verrucana” due, insoluble in chloroform, bands [3434 (m), 2918 (s), 2849 (m) cm-1, 1496 (vs), 873 (w), 712 (w) cm-1] attributable to a mixture of an organic compound and calcium carbonate were found. in particular, the organic compounds could be diterpenes (sandarac, rosin) polymerised due to ageing, according to their low solubility in chlorinated solvents. 4.4 characterisation of class d products the inorganic filling present in the products of class d was characterised using mineralogical and petrographical analyses. under stereomicroscope observation, product k (sample 17) appears shiny on the surface. it is possible to observe that it is constituted by a binder and the aggregate. the binder is of grey colour and compact. in the aggregate three different typologies of grains are distinguished: the first one presents crystals of fine dimension, white colour, scaly fracture, and greasy surface. the second is constituted by a black and fine particulate of rounded shape. finally, it is possible to observe traces of red particles of fine dimensions. the presence of hemihydrate gypsum as main component with low amounts of bi-hydrate gypsum was detected by ft-ir spectrum [3608 (m), 3564 (m), 3400 (m), 1623 (m), 1152 (vs), 659 (s), 601 (s) cm-1]. low amounts of a protein (1650 and 1549 cm-1) used as binding material were also identified. no compounds soluble in cdcl3 or d2o at room temperature were detected. it is possible to hypothesise that product k has a binder which is probably constituted by gypsum and protein, while the aggregate might be constituted by dolomite. in fact, the mineralogical analyses (xrd) of sample 17 reveal the presence of bassanite (caso4·1/2h2o) and dolomite (camg(co3)2). however, petrographical analyses were not carried out due to the small dimension of the sample and it was not possible to carry out a complete characterisation. product l (sample 18) was sampled from a piece of large dimensions (not catalogued). it was removed from the back of the find. under stereomicroscope observation, it is possible to distinguish a binder and the aggregate. the binder is of white-yellowish colour and it appears compact. the aggregate is constituted by two different typologies of grains: crystals of white colour with a scaly fracture and greasy surface and a fine particulate of black colour and rounded shape. hemihydrate gypsum as main component and lower amounts of gypsum were identified in the ft-ir spectrum [3611 (s), 3549 (s), 3404 (m), 1622 (m), 1150 (vs), 659 (s), 601 (s) cm-1], together with a protein in small amounts (1650 and 1549 cm-1). the mineralogical analysis (xrd) of sample 18 reveals the presence of bassanite (caso4·1/2h2o), gypsum (caso4·2h2o), and traces of quartz (sio2). the observation under the polarised light microscope in thin section shows a binder of grey colour, which is mainly composed of gypsum. the porosity is medium and of irregular shape. the aggregate shows crystals of sub-euhedral shape and fine dimensions (prevalence of 50 μm and rare of 100 μm); the composition is mainly constituted by little needles of gypsum and traces of quartz and calcite. iron oxides with opaque and globular appearance, probably magnetite (fe3o4), are present. the binder/aggregate ratio is 1/2 (figure 6). therefore, product l is constituted by gypsum and protein substances as binder, along with an aggregate mainfigura 6. product l, sample 18 – a) cross nicols image: general view of the plaster with gypsum in the binder and in the aggregate; b) cross nicols image: particular of the binder of dark colour, constituted by gypsum; it is visible aggregate, with prevalence of gypsum and trace of quartz and calcite (in colour brown in the top of image). 70 laura colli, antonella salvini, elena pecchioni, sandra cencetti ly composed of gypsum, iron oxides (probably responsible for the darker pigmentation) and subordinate quartz and calcite. under stereomicroscope observation, product m (sample 19) appears shiny on the surface. it is possible to recognise a binder and the aggregate. the binder is of brick-red colour and compact. the aggregate is constituted by three different typologies of grains: the first one presents crystals of fine dimensions, white colour, scaly fracture and greasy surface. the second is constituted by a black and fine particulate of rounded shape. furthermore, it is possible to observe traces of particles of fine dimensions and of red colour. bands attributable to the presence of hemihydrate gypsum as main component with lower amounts of gypsum were present in the ft-ir spectrum [3610 (m), 3546 (m), 3404 (w), 1622 (m), 658 (s), 601 (s) cm-1]. a protein as organic binder was present in small amounts (1546 cm-1) and the presence of an iron oxide (hematite, 537 cm-1) was also observed. the mineralogical analysis (xrd) reveals the presence of bassanite (caso4·1/2h2o), gypsum (caso4·2h2o), and traces of quartz (sio2). the observation under polarised light microscope in thin section, shows a binder of brownish-red colour, with anisotropic appearance and mainly constituted by gypsum. the porosity is medium, with irregular shape. the aggregate presents dimensions between 50-100 μm in prevalence and rarely 200 μm, of sub-angular shape. it is constituted by gypsum, quartz and traces of calcite and mica. iron oxides are present. the binder/aggregate ratio is 1/3 (figure 7). therefore, product m is constituted by gypsum and protein substances as binder, along with an aggregate composed mainly of gypsum, iron oxides (probably responsible for the brownish-red pigmentation) and subordinate quartz, calcite and mica. the stereomicroscope observation of product n (sample 20) shows a binder and the aggregate. the binder is of yellow colour and compact. the aggregate is constituted by three different typologies of grains: the first one shows crystals of fine dimensions, white colour, scaly fracture and greasy surface. the second is constituted by a black and fine particulate of rounded shape. moreover, it is possible to observe traces of particles of fine dimensions and of red colour. gypsum hemihydrate as main component and lower amounts of gypsum were identified in the ft-ir spectrum [3610 (m), 3549 (m), 3400 (w), 1622 (m), 1151 (vs), 659 (s), 601 (s) cm-1]. the presence of calcium carbonate and traces of a protein were also observed. the mineralogical analysis (xrd) of sample 20 reveals the presence of bassanite (caso4·1/2h2o), g ypsum (caso4·2h2o) and calcite (caco3). the presence of quartz (sio2) is also probable. the observation under polarised light microscope in thin section shows a binder of brownishorange colour, with anisotropic appearance and constituted mainly by calcite and minor amounts of gypsum. the porosity is low and of irregular shape. the aggregate, of variable grain size from 50-300 μm, is constituted by gypsum, calcite and iron oxides. the binder/ aggregate ratio is 1/3 (figure 8). therefore, product n is constituted predominantly by calcite, low amounts of gypsum and protein substances as binder, with an aggregate composed mainly of g y psum, iron oxides (responsible for the brownish-orange pigmentation) and subordinate calcite. figura 7. product m, sample 19 cross nicols image: particular of the gypsum binder with brownish red colour for the presence of iron oxides. gypsum and quartz, constituting the aggregate, are visible. figura 8. product n, sample 20 cross nicols image: particular of the binder of brown colour constituted by lime and gypsum; gypsum, calcite and iron oxides are visible in the aggregate of bigger dimensions. 71conservation of paleontological finds: the restoration materials of the “problematica verrucana” product o is only applied on the catalogued piece igf 348t (indefinite trace). it was removed (sample 21) from the back of the find. under stereomicroscope observation sample 21 shows a binder and the aggregate. the binder is of whitish-grey colour and compact. the aggregate is composed by grains of extremely variegated shape, typology and dimension. the ft-ir spectrum suggested the presence of calcium carbonate [2514 (w), 1432 (vs), 875 (s) and 712 (m) cm-1] and of polysaccharide [3441 (m), 1028 (m), 469 (w) cm-1] as binder. no organic products soluble in cdcl3 were detected. the mineralogical analysis (xrd) of sample 21 shows the presence of calcite (caco3), quartz (sio2), plagioclasealbite (nasi3alo8) and traces of fillosilicates. the presence of larnite (ca2sio4) is probable. the petrographical analyses were not carried out due to the small dimension of the sample. therefore, one can hypothesise that product o has a binder which is probably constituted by a hydraulic lime (for the presence of larnite) and polysaccharide; the aggregate might be constituted by quartz, plagioclase and fillosilicates, but it is not possible to carry out a correct characterisation without a petrographical analysis. 4.5 conservation properties of products class a products are composed of a polysaccharide either used alone as adhesive (product a) or thickened with different inorganic materials as aggregate (calcium carbonate and silica for product b and silica and mica for product c). each different composition of the three products of class a corresponds to a different use of the materials. in fact, rubber is used alone when it is applied as an adhesive, whereas it is mixed with an inorganic aggregate when the product is used to fill internal or external gaps and to reconnect big and irregular pieces (plaster). the presence of calcium carbonate in product b may also be attributable to carbonation of lime; in fact, lime could have been added to polysaccharides to improve mechanical properties. this formulation was probably chosen with the purpose of giving a mimetic effect and finishing touch in spite of a mechanical support and was used for finds of small and medium dimensions. on the contrary, product c which contains an aggregate with larger grains and has a composition with quartz and without calcium carbonate, is preferred to product b, as the dimensions of the find increase. class b materials (products g and h) are compounds used for the fabrication of moulds and junctions. as confirmed by the analysis of a standard mixture, their composition reveals the presence of sulphur and an amorphous carbon product as graphite. these products are also used as plasters; in this case the adhesive properties are conferred to the composite by the presence of graphite. class c materials (product e and f) are mixtures of organic and inorganic compounds. product e is composed of terpenes, waxes, salts of fatty acids, and gypsum. product f is composed of terpenes, waxes, and calcium carbonate. gypsum and calcium carbonate could have also been used as aggregate, especially in product f, where no further aggregate is present to fulfill this function. in product f the presence of carbonate could also be ascribable to lime carbonation. lime could have been added to the mixture to enforce the grip or the hardness of the product 14, 15. from the comparison of chemical, mineralogical and petrographical results for class d materials, one can infer that product k, product l and product m have gypsum and protein substances as binding materials with gypsum, iron oxides (product l and product m) and quartz, calcite and mica (mica only for product m) as aggregates. for product k, a correct identification of the aggregate cannot be performed due to the absence of petrographical analyses; it is only possible to hypothesise (by xrd analyses) a dolomitic composition. the composition of products k, l and m is in agreement with a standard glue-gypsum plaster. in particular, in product k the presence of protein is more copious than expected and it is in agreement with a major hardness of the material. product n differs from the former products of class d; in fact, it can be defined as a plaster with a binder constituted by lime and gypsum; the aggregate (gypsum, calcite and iron oxides) has higher granulometry. probably the presence of lime along with gypsum, the abundance of aggregate and the higher granulometry allowed the development of a tougher structure (in fact the plaster has been used to repair a long fracture in the find) 16-21. product o is probably an hydraulic mortar (for the presence of larnite), perhaps cementitious22 and with a polysaccharide as additional binder. furthermore its function is different: product o was applied to create a firm base to maintain the finds in vertical position during the photographic sessions of fucini, therefore the use of a mortar with higher resistance is to be deemed correct for this purpose. therefore, the products of class d (except for product o with only a particular function of support) were realised by fucini as plasters with a prevalent presence of aggregates with a variable granulometry and the addition of glue to improve the hardness of the material. furthermore, fucini took into account other factors than 72 laura colli, antonella salvini, elena pecchioni, sandra cencetti the compositional characteristics, mainly the colour of the filling, giving importance to the similarity of the pigmentation between restoration products and the finds. products a, k, l, m, n can be compared with similar ancient recipes mentioned in literature. product a is mainly a polysaccharide material, according to the recipe of cecchini23, which contains acacia gum (the cecchini recipe specifies “acacia gum, sugar and honey”). product k is a standard glue and gypsum plaster as, for example, the recipe mentioned in arcolao14. products l and m are glue and gypsum plasters with iron oxide for the pigmentation and sand for the aggregate, in agreement with the traditional recipe of cecchini 23. product n is a plaster realised with lime, gypsum and glue, sand for the aggregate and iron oxides for the pigmentation, and similar products are described in the literature (“lime, glue, gypsum, sand, pigments, alum”) 25. 5. conclusions important pieces of information were obtained analysing the products used for the fossil restoration of the fucini collection. the results show an example of application of traditional recipes in a yet unexplored field. moreover, even among the wide variety of organic and inorganic materials, this study adds new information regarding some combinations of products; for example in the case of plaster of polysaccharide rubber with inorganic aggregate24,25. the possibility to identify materials used in old restorations represents a starting point for the study of conservation of paleontological finds of ancient collections. further insights on these products and especially the extension of this research towards other classes of compounds will allow to obtain a more complete picture on the restoration techniques used on fossils in the past. moreover, some products (especially class d materials and product a) seem to fulfill exceptionally well, even one hundred years later, their conservative and esthetic functions. a dedicated study would also permit to evaluate their applicability to current restorations of paleontological finds. knowing products and techniques, evaluated according to the present status of conservation, will allow to develop operative protocols for the conservation of paleontological material. acknowledgements the authors thank the museum of natural history of the university of florence for the supply of samples. references 1. f. howie, museum climatology and the conservation of paleontological material, the paleontological association, london, 1979. 2. b. kummel, d.m. raup, handbook of paleontological techniques, w.h. freeman and company, san francisco and london, 1978. 3. p. leiggi, p. may, vertebrate paleontological techniques, volume 1, cambridge university press, cambridge, 1994. 4. l. azzaroli, a. berzi, p. brandinelli, s. ciruzzi, i musei scientifici a firenze. problemi di restauro e ricomposizione museale. parte prima. uniedit, biblioteca di architettura, 1984. 5. g. merla, il giornale dell’università, 1951, anno i, n. 12, 345. 6. u. schiff, archeion, 1928, vol.ix, 1. 7. h. howard, handbook of paleo-preparation techniques (revised by russell mccarty), florida paleontological society, gainesville florida, 1994. 8. c. cipriani, appunti di museologia naturalistica, firenze university press, firenze, 2006. 9. a. fucini, problematica verrucana. tavole iconografiche delle vestigia vegetali, animali, fisiche e meccaniche del wealdiano dei monti pisani, vol. i, ii, iii, industrie grafiche v. lischi & figli, pisa, 1936. 10. f. von huene, eglogae geol. helv, 1940, 32 (2), 184. 11. f. von huene, zentralblatt f. min. geol. u. pal., 1940, abt. b., 11, 3492. 12. f. von huene, n. jahrb. f. min. geol. u. pal., 1941, abt. b., 86. 13. m. mazzini, guida del museo di geologia e paleontologia università di firenze, landi, s. giovanni valdarno, 1982. 14. c. arcolao, le ricette del restauro, marsilio, venezia, 1998. 15. e. schiele, berens, l. w. la calce. ed. tecniche et, 1976. 16. a. cagnana, in a. d. costruzione.(edizioni s.a.p. srl), 2000. 17. doc.uni-normal11176. beni culturali. descrizione petrografica di una malta, 2006. 18. doc.uni-normal10924. beni culturali. malte più elementi costruttivi e decorativi. classificazione e terminologia, 2001. 19. doc.uni-normal11189. malte storiche da restauro. metodi di prova per la caratterizzazione chimica di una malta, 2006. 20. l. fieni in le ricette del restauro, (edizioni all’insegna del giglio), 2002. 21. t. turco, il gesso. lavorazione, trasformaione, impieghi, hoepli, milano, 1985. 73conservation of paleontological finds: the restoration materials of the “problematica verrucana” 22. e. pecchioni, f. fratini, e. cantisani le malte antiche e moderne: tra tradizione ed innovazione. pàtron ed. bologna, 2008. 23. g. cecchini, g. giordano, milani, materiali tradizionali per il restauro dei dipinti. preparazione e applicazione secondo il manuale di giovanni secco suardo, associazione giovanni secco suardo, lurano (bg), 1995. 24. m. matteini, a. moles, la chimica nel restauro: i materiali dell’arte pittorica, nardini, firenze, 1989. 25. a. bralia, f. cancelli, c. manganelli del fa, e. pecchioni, museologia scientifica, 1990, 175. substantia. an international journal of the history of chemistry 3(1) suppl.: 11-15, 2019 firenze university press www.fupress.com/substantia citation: a. pacini (2019) apprentices and masters the transmission of ancient goldsmith techniques. substantia 3(1) suppl.: 11-15. doi: 10.13128/ substantia-600 copyright: © 2019 a. pacini. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-600 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini goldsmith in montepulciano via di totona 35, i-53045 montepulciano, siena e-mail: ale.pacini@gmail.com abstract. a historical overview from sumerians to the present day on the goldsmith’s craft following two lines: the apprenticeship in the guilds and the ethical and religious value of gold working. keywords. apprentice, master, ancient techniques, goldsmith. introduction what is the value of knowing the ancient goldsmith techniques today? is it possible, once rediscovered, to put them into practice again? with which advantages and for whom? the answer to these questions depends on the vision one has of the work: whether it is perceived as a shared activity and integrated into the ethical and political sphere of the community, or whether the consideration of the work is an individualistic one. the shared vision implies the preservation and transmission of experiences since a value as such is recognized to technical abilities. in this case the profit is subordinated to a historical identity kept alive over time. the individualistic vision, on the other hand, has as its objective the maximum economic profit in the face of minor expenditure: it is not linked to the context in which it operates, to history, to tradition, it does not imply aesthetic or ethical evaluations. if an individualistic, exclusively economic vision prevails, knowing the ancient goldsmith techniques is of little use: it can be only useful for marketing purposes, regardless the quality of products. but for those who want to give artisan work an ethical, aesthetic and social value, it is necessary to research, study, learn, practice and protect ancient technologies. this contribution, with some brief archaeological and historical examples, wants to remember the importance of a philosophical approach to craft activities, which otherwise are destined to disappear if forced to adapt to the disruptive technological innovations of our day. few human activities can continue to use the same working methods over time without them becoming obsolete. the craftsmanship of the workshop is among these: it has changed little over the centuries and today it is undergoing a period of serious crisis, at least in italy. the validity of the 12 alessandro pacini working methods over time depends on the family-type organization of the artisan laboratory and on the limited and mainly manual production of the artifacts. this gave the crafts a rituality, a respect that sometimes brought them closer to the world of religion or magic. looking back to the most remote past of the goldsmith’s art, we can see that in all ancient civilizations skills and craftsmanship were considered of divine origin. not all human beings achieved the knowledge of the mysteries which lie in the transformation of matter: among the chosen persons, secrets were shared and transmitted within associations of experts (often constituted in trade associations or corporations). thus we are witnessing two parallel stories, that of the divine origin of the arts and that of the professional corporations. mircea eliade writes: “the smelter, the smith and the alchemist claim a common magical-religious experience […] the secret of this experience […] is transmitted through the initiation rites to crafts” (eliade 1987, p. 8). and then: “the celestial smith completes the creation, organizes the world, establishes culture and guides human beings towards the knowledge of the mysteries” (p.153). there are numerous documentary testimonies of the divine origin of the arts and often in particular of the goldsmith’s art, gold having always played a magical role thanks to its beauty and incorruptibility. a list of sumerian kings (written between 2100 and 1900 bc) states that each sovereign was assigned a semidivine mentor, an apkallu, to teach all the arts, including that of the government (pettinato 2004, xxii). in ancient egypt there were various deities connected more or less directly to the artisan crafts: ptah (the god of pottery) who dictated the rules of artistic creation, khnum (who created men by modeling clay on the lathe), neith (the inventor goddess of the shuttling for weaving), thot (the god of magic, writing, geometry and mathematics), maat (the divinity of harmony and equilibrium). in egypt the houses of life were already present in the old kingdom during the third millennium bc and have continued to exist for many centuries maintaining a multidisciplinary pedagogical vision. they were cultural centers where various arts were taught, including writing, embalming, and magic. connected to the royal palace or the temple, there were schools of mathematics and geometry for the calculation of proportions, where the artists learned techniques of ornament and sculpture, and the goldsmith arts. the houses of life probably were also attended by zosimos from panopolis, an alchemist and gnostic mystic who was one of the first authors of alchemy and who lived between the 3rd and 4th century ad in egypt which by that time had become a roman province: “only with a methodical discipline and treasuring the teachings of the ancients can man heal from poverty, that is the loss of the sense of unity between microcosm and natural and spiritual macrocosm” (tonelli 2004, p 101). even the minoan civilization had deities that supervised the crafts activities, such as khousor, kothar and talo. some ceramic tablets found in pilo (a mycenaean city in messinia) attest the existence of professional guilds in crete. in the royal palace g of ebla, in ancient syria (2400-2250 bc), 17000 ceramic tablets were found with cuneiform inscriptions: some indicate the specialization of the craftsmen of precious objects in detail. jacopo pasquali has identified specialized figures in the processing of natural carnelian of light orange color (si-si), and of the heat-treated dark red carnelian (gug-gul). he identified the: puzur-ra-ma-lik lú si (i.e. master cutter of carnelian), the: da-zi-ma-ad (i.e. helper cutter of carnelian), the: ib-du-ma-lik lú si (i.e. expert figure 1. 22 kt gold classic greek style earrings, diameter 2.5 cm. technique: filigree. author: alessandro pacini. figure 2. fibula in gilded silver, garnets and bone. length 3 cm. technique: cuttlefish bone fusion, pure gold leaf gilding. author: alessandro pacini. 13apprentices and masters the transmission of ancient goldsmith techniques craftsman in a processing phase of carnelian natural), the: iš-a-ma-lik lú gul-si (i.e. expert craftsman in a processing phase of the carnelian tractors), the: dumu-nita lú si-si (i.e. apprentice cutter), the: dumu-nita-gùn (i.e. apprentice dyer of carnelians) (pasquali 2005, p.10). given such a specialized level of processing of each single gem, it is possible that corporative work organizations already existed, although they were controlled by the royal palace. in the bible we find the action of the holy spirit at the origin of technical abilities: “moses said to the israelites: «see, the lord has called by name bezaleel, son of uri, son of cur, of the tribe of judah. he has filled him with the spirit of god, so that he will have wisdom, intelligence and science in every kind of work, to conceive projects and make them in gold, silver, copper, to carve the stones to be set, to carve wood and make all sorts of genius work. he also put in his heart the gift of teaching and so he did with ooliab, son of achisamach, of the tribe of dan»”. these are the verses 30-35 of the book of exodus, written between the sixth and fifth century bc, but referring to facts from the mid-thirteenth century bc. in the classical world, artisans played a fundamental economic role and trade corporations were well structured. plutarch in the life of pericles lists various crafts and then writes: “because each art gathered with itself, like a general with his army, the masses of workers and craftsmen […] the various work needs distributed and spread welfare throughout the population” (12, 5-6). pliny in the xxxiv book of natural history recalls some famous greek sculptors including: “silanion, about whom the admirable fact is that he became famous without any teacher” and further on: “silanion was the most scrupulous in terms of technique and a ruthless judge of himself. he often destroyed the finished statues because he was not satisfied with the result, he was nicknamed the madman”. being self-taught at the time was remarkable, out of the ordinary. a trade was normally learned in a workshop, under the guidance of a teacher, from a young age. plutarch and pliny lived in the first century of the christian era when the tutelary deities of the craftsmen still existed: sethlans for the etruscans, efaistós for the greeks, vulcanus for the romans. it was under the romans that the professional guilds (collegia) saw their maximum expansion and the highest levels of organization. in the 8th law of the 12 tables (about 450 bc) it is written: “sodales legem quam volent, dum ne quid ex publica corrumpant, sibi ferunto”, that is: “corporations may give themselves the legislative system they prefer, provided they are not in contrast with public law”. each collegium, which could count hundreds of members led by the magistri, had its status and its seat (schola). naturally it was the colleges that managed the apprenticeship of young artisans. such was the importance of craft corporations in roman times that scholars have identified thirty latin terms that indicated this type of association. at the end of the roman empire, under the roman barbarian kingdoms, the court laboratories produced precious artifacts for the nobility which had a political value, as gifts of exchange when searching for allies. with the beginning of the middle ages the corporations lose power and often disappear, but the apprenticeship continues in the workshop of a master goldsmith who could also be a soldier or an officer or even practice other trades. some medieval jewelers became famous holding prestigious posifigure 3. chalice in gothic style, silver, gilded silver, jaspers, travertine. technique: lost wax casting, embossing, turning, enamels, niello. author: alessandro pacini. 14 alessandro pacini tions, such as saint eligius (588 660) a senior official of the court of the merovingian kings and then bishop of tournai and noyon. the guilds continued to exist: byzantine scholae, lombard consortes (the word appears in the edict of rothari, in 643), ministeria in pavia between the x and xi century. but it was above all the monasteries which preserved and handed down the arts in addition to the classical culture. between the ninth and twelfth century they ideologically dominated europe, their great laboratories produced high-end goldsmiths. moreover, no place was better than the monasteries for associating the profession with spirituality and rituals. theophilus, probably identified with the benedictine monk roger from helmarshausen, wrote what may be considered the first manual of artistic techniques in europe. the communal age between the twelfth and fourteenth century saw the birth and triumph of the arts, that is, the trade guilds that for the first time even had the political control of the cities. magistri, discipuli and laborantes worked within them in a production context organized in a similar way to a family. the apprenticeship lasted for some years, after which a judging commission composed of the consoli dell’arte admitted the matricole on the basis of the quality of the masterpiece, a final essay of the technical and artistic skills possessed. at this point the matriculated to the art could have his mark of production. cennino cennini (1370-1427) wrote: “and as soon as you can, begin to put yourself under the guidance of the teacher to learn, and as late as you can, from the teacher you leave”. and a century later, in full renaissance, lorenzo ghiberti completes the concept saying: “it is convenient that the artist is expert of writing and trained in geometry and diligently has heard philosophy […] and has heard astrology and is taught in perspective and still is most skilled at drawing […] who has also seen the works of the ancients […] rightly i think that there cannot be professed artists except those who from very young age are trained by similar degrees of discipline and fully familiar with the science of letters” (i commentari, i, 2). in the sixteenth century ad, the mercantile ideology contributes significantly to the decadence of the corporations. by then the great merchant companies have more power than the old arts and a clear separation between artist and craftsman comes about. the apprenticeship is less regulated and can be carried out freely by the teacher who considers himself better or more famous. it is no longer necessary to be registered members of a corporation to practice the trade. benvenuto cellini for example never registered with the goldsmith’s guild: he preferred, still a young boy, to wander around italy looking for a good teacher. in pisa, near the ponte di mezzo, attracted by a goldsmith’s shop, he was invited to enter and “immediately [the goldsmith] gave me to work […] silver gold and joys and the first day provided, in the evening he brought me to his house […] with great love he came to see me at my room that he had given me, seeing that i spent all my hours virtuously, he gave me his love like a father” (la vita, x). cellini stayed there for one year (he was 15). the eighteenth century sees the end of the guilds: in tuscany they were abolished in 1770 by the grand duke pietro leopoldo and replaced by an office of manufactures. machines and workers replace shops and craftsmen, there are still small workshops as family units, but the apprenticeship is no longer the exclusive prerogative of craftsmen. in fact, the nineteenth century sees the spread of royal and stately schools, shops of goldsmiths collectors (as the castellani in rome), of artisans (entrepreneurs for themselves) and technical schools (established by cultural associations, rural and craft banks, worker’s leagues). the quality of the teaching however was however high and the same techniques of previous centuries were preserved, with the drawing always at the basis of the work. a couple of centuries later, under fascism, on february 5, 1934, a law on corporations was promulgated: “the corporate principle consisted in the subordination of special interests to the national interest, conceived as the superior interest of production” (chapter viii). pope pius xi re-proposes the corporations in the encyclical quadragesimo anno of may 15, 1931: “it happens by natural impulse that […] those who devote themselves to an art form colleges or social bodies; so that these corporations, with their own right, by many are said to be, if not essential to civil society, at least natural” (84). “it is possible to apply to the professional corporations what leo xiii taught about the form of the political regime, i.e. the choice of the most suitable form is free, provided that justice as well as the common welfare is respected” (87). in those days one could still enter a workshop in the young age and traditional craftsmanship allowed to live in dignity. over the centuries the sacred prerogatives and the magical potentials went lost, but the craftsmanship still remains an activity protected by our constitution in the articles 35: “the state takes care of the training and the professional development of the workers” and 45, paragraph 2: “the law provides the protection and development of the crafts”. this protection exists only on paper, because in reality the new global economic and cultural forms in italy have literally disintegrated it. the main causes were new regulations that prevented apprenticeship directly in the workshop, whilst other serious obstacles are due to the incorporation of artisan laboratories in the industry, with an unbearable legislation for the artisans in terms 15apprentices and masters the transmission of ancient goldsmith techniques of safety at work and taxation. various attempts to recover the teaching of artisanal crafts to young people through courses managed by various bureaucratic agencies and financed as projects proved to be a failure. conclusions the splitting of the transmission of art crafts, which has affected some generations of italians and europeans in the second half of the twentieth century, has led to the irreversible loss of most of the ancient craft techniques, including those of the goldsmiths. in recent years, the coup de grace has been given by technologies based on computerized systems, combined with new products of chemical synthesis, of which the artisans can neither control the origin nor modify the physicochemical characteristics, if not in a very limited way. the use of these techniques and these materials can only disrupt the very nature of the craft. these new technologies are no longer linked to the culture of the community or to the history of the territory, nor to any liturgical or ritual form of manual labor, therefore they are compatible with an individualistic vision of work, much less with a shared vision. although it seems that there is no link between scientific research and traditional craft, we must consider the fact that the discovery of synthetic materials and the invention of technologies for serial production inevitably resulted in the destruction of a working method. this method had existed for centuries, above all the crafts, but now it may end up being relegated to private hobbies or to the amusement of a few enthusiasts, completely emptied of any socio-cultural value, included the fundamental pedagogical one. the freedom of research and experimentation of the scientist, the chemist, should be limited by the awareness that some operations can be harmful to the environment and to society. this limit must be placed by the inventor and not by those holding political and economic power. bibliography m. eliade, arti del metallo e alchimia, bollati, torino, 1987. g. pettinato, la saga di gilgameš, mondadori, milano, 2004. f. cimmino, vita quotidiana degli egizi, rcs, milano, 2001. j. pasquali, il lessico dell’artigianato nei testi di ebla, 2005, quaderni di semitistica 23, università di firenze. la sacra bibbia vecchio testamento, (ed. e. galbiati, a. penna, p. rossano), selezione reader’s digest, milano, 1968. plutarco, vita di pericle, (ed. rcs) milano, 2004. plinio, naturalis historia, (ed. giardini) pisa, 1984. s. maggio, le associazioni professionali nell’alto medioevo, cuecm, catania, 1996. f. diosono, le associazioni professionali nel mondo romano, quasar, roma, 2007. l. ghiberti, i commentari, (ed. ricciardi) napoli, 1947. a. santoni rugiu, nostalgia del maestro artigiano, manzuoli, firenze, 1988. b. cellini, la vita, (ed. colombo) roma, 1964. c. cennini, il libro dell’arte, (ed. le monnier) firenze, 1999. a. tonelli, zosimo di panopoli visioni e risvegli, milano, rcs, 2004. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe substantia. an international journal of the history of chemistry 2(1): 7-16, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-37 citation: s.e. friberg (2018) emulsion thermodynamics – in from the cold. substantia 2(1): 7-16. doi: 10.13128/ substantia-37 copyright: © 2018 s.e. friberg. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article emulsion thermodynamics – in from the cold stig e. friberg ugelstad laboratory, ntnu, trondheim, norway email: stic30kan@gmail.com abstract. thermodynamics has played virtually no role in traditional emulsion research, because emulsions are inherently thermodynamically unstable. the problem with commercial emulsions needing to exist with none or only small changes during use and the industrial stability problem was resolved by formulating colloidally stable emulsions, i.e. the rate of destabilization was reduced. this approach was successful for single-oil emulsions, but encountered problems for double emulsions, for which the simultaneous stabilization of several interfaces within one drop encountered difficulties. naturally, even for such an emulsion, colloid stability is the only option to stabilize the outer surface towards the continuous phase. in fact, the destabilization by flocculation/coalescence proceeds similarly to a single-oil emulsion. but experiments have demonstrated that complex emulsions with a thermodynamically stabilized inner interface retain the individual drop topology during the process. this result opens an avenue to significantly facilitate the formulation of a group of commercially important emulsions, because the cumbersome multiple emulsion stabilization is reduced to the more trivial single-oil emulsion case. keywords. emulsion stability, colloidal stability, interfacial thermodynamics, janus emulsions, emulsion coalescence. introduction the first meal humans and many animals enjoy is an oral emulsion that replaces the nutrients through the umbilical cord. the emulsion in question is a convenient and efficient means to provide the needed mixture of fats, sugars and proteins, which otherwise would be solid and not useful to a toothless newborn. since these emulsions are truly essential, baby milk emulsions have been commercially available for 150 years for the cases, where the mother does not have milk, or does not want to breast feed. the initial modest introduction by henry nestlé has grown to a company with almost $100 billion in yearly sales, reflecting the commercial expansion to other food emulsions, such as cream, butter and ice cream, to mention the most obvious (among the miniscule, but common, applications of milk is to remove the bitter taste from coffee and in some societies from tea an insult to the refined oriental cuisine culture). in addition, emulsions also have a long history in personal care and cosmetics with cleopatra taking baths in donkey milk about 2000 years ago. 8 stig e. friberg this pioneering use of emulsions has developed into a schueller/bettencourt company, l’oreal (actually partly owned by nestlé), which has grown from a modest start in 1909 to an internationally large company with sales at the level of tens of billions of dollars. these are examples of large applications of emulsions for humans, like emulsions in the paint and coatings industry, which add another huge sum. all these tremendous volumes of products, which are daily handled all over the world, are, in fact, thermodynamically unstable compositions, doomed to final separation of the components. nonetheless, the compositions are required to remain virtually unchanged for specific times, varying from seconds to years, depending on the actual purpose. hence, an extensive volume of research1-3 is found on their properties and especially their “stability”. this “stability”, is defined as an unchanged appearance reflecting the commercial needs. a more quantitative measure of emulsion stability would be its half-life, e.g. the time for the number of drops to be reduced to one half by coalescence, figure 1. as a contrast, the so called microemulsions are not emulsions; they are equilibrium colloidal solutions4,5 and have been investigated for different aspects of their interfacial properties.6-8 because they are thermodynamically stable, their preparation is completely different from that of emulsions. these latter are prepared, in most cases, by mechanically dividing a liquid into drops and dispersing these in a continuous liquid, while mircroemulsions are spontaneously formed,5 requiring only the most minute mixing for large volumes. the microemulsions are of considerable commercial interest, (reflected in about half a million google hits) but are not the subject of the present contribution, which is focused on emulsions. their comprehensive and advanced treatments1-3, in turn, examine emulsion stabilization from the viewpoint of colloidal stability, applying the concepts from the dlvo theory,9-11 in which a repulsive force is introduced between drops to reduce the rate of flocculation and coalescence. this action naturally does not make the emulsions thermodynamically stable, but tender serviceable information to retain the properties of traditional emulsions for commercial purposes. this colloidal stability approach was also employed for double emulsions,12 whose more complex topology caused challenging stability problems.13,14 in summary, except for in the area of microemulsions, there was no significant need, nor even a role, for thermodynamics in emulsion research; a mindset that has recently experienced an initial conversion, when janus emulsions were introduced.15,16 these emulsions consist of combined drops of two mutually insoluble oils, figure 2, in which total free interfacial energy of the single drop is significantly less than that of the oils in separate drops. hence, their “inner” topology, figure 2, is thermodynamically stabilized,17-19 and actually has been shown to survive most of the flocculation/coalescence process.20 a brief comment at this stage is necessary to avoid misinterpretation. janus emulsions are not thermodynamically stable, like microemulsions. the janus emulsions, as a contrast, undergo a flocculation/coalescence process and, if left for sufficiently long time, will separate into three, or four liquid layers, depending on the relative density, because of gravitational forces. nevertheless, the feature mentioned in the last part of the former paragraph is significant, because it brings to light a new approach to formulating emulsions with two-oil drops. traditionally, commercial double emulsions are prepared either by first forming an oil/oil emulsion followed figure 1. two emulsion drops of one oil, a, are colloidally stabilized and, when they aggregate (flocculation, a to b), they form an aggregated drop of transitory stability, b. the transient interface dividing them (white line, b) is destabilized and coalescence (b to c) occurs to a single drop, c. figure 2. a. the geometry and interfacial tensions in a janus drop. b. black, o1 volume limited by the contact line, white, o2 volume limited by the contact line, grey, o1 volume penetrating the o2 space from the contact line. 9emulsion thermodynamics – in from the cold by its emulsification in an aqueous phase (o1/o2)/w or by emulsifying one oil in water, followed by emulsification of this emulsion into the second oil plus a final emulsification into an aqueous phase (o1/w/o2/w). all the preparations necessitate independently stabilizing the different interfaces by colloid stabilization; a methodology, beset with a main problem. the transfer of surfactant stabilizers between the liquid phases, which would markedly reduce their stabilizing action, was successfully overcome for individual emulsions after a substantial amount of outstanding research.13,14 conversely, in the alternative methodology using thermodynamic stabilization, the stabilizer is allowed freely to equilibrate between phases, as long as the level of surface tensions are in the order defined in later sections. with this approach, colloidal stabilization is limited to the outer interface towards the aqueous phase, a simpler problem, which has been extensively treated.1-3 in summary, the focus of the attention is shifted from colloidal stabilization, a kinetic phenomenon, to interfacial tensions, a quantifiable equilibrium entity. the transition from one preparation method to the other requires a change in the mind set and the present contribution is an attempt partially to outline the relevant thermodynamic framework. thermodynamic stabilization and interfacial tensions the basis for the thermodynamic framework is the equilibrium of three tensions in one plane, figure 3. these tensions act at the contact line, figure 2, and, combined with the relative volume of the two oil lobes, determine the equilibrium topology of the combination drops. as a result, they are central to this contribution and a summary of their ramifications is useful for the continued analysis with appropriate limitation. the features of figure 3 are relevant only for a case in which γo1/w < γo2/w + γo2/o1 and γo1/w > γo2/w and γo1/w > γo2/o1. an analysis of the consequences from inequalities, outside the ones mentioned, is of algebraic interest, but offer no contribution of value to the problem at hand. instead, the main theme of this examination is to survey the thermodynamic effect on the topology of janus and double emulsion drops and it is convenient to divide the range of tensions into two parts. the first part of the range covers γo1/w > γo2/w + γo2/o1 (relevant for double emulsion drops), followed by γo1/w < γo2/w + γo2/ o1, defining the equilibrium in a janus drop, figure 2. in addition, the intermediate case of γo1/w = γo2/w + γo2/o1 has some features of interest, which will be briefly mentioned. the stipulation γo1/w > γo2/w + γo2/o1 portends a non-equilibrium spreading of o2 or o1 on w, while γo1/w < γo2/w + go2/o1 means a stable equilibrium with defined angles β and δ, figure 2 and 3. for these, one has, with the ratios γo2/w/γo1/w = a and γo2/o1/γo1/w = b, equations [1] and [2]. β = acos((1 + a2 – b2)/2a) [1] δ = acos((1 a2 + b2)/2b) [2] it should be observed that these equations are applicable only to the equilibria in figure 3, and may be used to calculate the interfacial free energy as such for a selected drop topology, but the calculations fail to identify the thermodynamically preferred topology. this topology is obtained first, when the free energy quantity is contrasted with that of a counterpart. the free energy number per se actually implies a counterpart with no interfacial free energy and the approach would show any selected topology to be thermodynamically disfavored and is of no use to judge thermodynamic stability. in addition, the free energy of two-oil emulsion drops also depends on the volume ratios of the two oils and an equitable, but injudicious, choice of a reference topology will result in erroneous conclusions. this fact will later be brought to light. equations [1] and [2] relate the angles β and δ to tensions at equilibrium, but not in an explicitly illustrative manner and a few numbers from a model system are informative as a graphic. figure 4 shows the limitations of the angles β and δ versus the γo2/o1/γo1/w (b) with γo2/w/γo1/w (a) as parameter. the range of the two variables in the figure is limited in order to reflect the conditions in figure 3. so, are numbers for b > 1 excluded, because they would represent a reorganization of the angles in the figure. the δ limit for a =1 varies as δ = 60 + 30(1 b) (degrees) for the same reason. the numbers for the d angle shows the development of the equilibrium/spreading border, figure 4 c, figure 3. angles β and δ for three equilibrium tensions in one plane. 10 stig e. friberg with varied γo2/w/γo1/w (a). the artificial δ value for a = 0 (the oils are mutually completely soluble) is a single point with δ = 0, because, since γo2/w = 0 and γo2/ o1 = γo1/w, the number for angle b becomes irrelevant. in fact, the entire area (except b = 1) denotes spreading. increasing the γo2/w/γo1/w (a) values from zero, results in an expansion of the equilibrium part of the area, reaching the entire area for a = 1. any number for a < 1, however close, e.g. 1 ε (epsilon small) means a 2ε wide area of spreading along the b = 0 axis and ε broad along the axis for maximum δ. after this brief review of the ramifications for the conditions in figure 3, the following sections analyze the interfacial free energy of a single drop, omitting the emulsion inter-drop dynamics. the analysis of the double emulsion drop is built on the inequality γo1/w > γo2/w + γo2/o1, and the spreading means that the o2/w interface does not exist. the drop instead consists of a larger drop o1/w with an o2/o1 drop inside, in accordance with the thermodynamic condition. conversely, the o/w interface is thermodynamically unstable for virtually all positive γo1/w and an assembly of such drops will coalesce like the simpler single-oil emulsions. hence, the potential thermodynamic stabilization is limited to the inner interface of the drop, while the initial coalescence is exclusively concerned with its colloidally stabilized outer surface, as has been shown for janus emulsions.20 hence, at a first glance, the thermodynamic stabilization of the inner interface may be considered only of minor importance, but the extensive research on double emulsions12-14 indicates otherwise. in fact, with the “inner” interface of janus or double emulsion drops thermodynamically stabilized, the only stabilization needed for a commercial double emulsion would be for the interface towards the continuous phase; i.e. a problem, that has been solved using the colloidal stability approach.1-3 the only requirement for the o1/w stabilizers is that the interfacial tensions obey the stated inequality; a non-specific condition. hence, considering the future potential for a new line of formulations and the fact that virtually no information exists, a review of the thermodynamics of both a double emulsion and a janus drop has merits. the examination is initiated at a double emulsion drop, because of the extensive technical and commercial relevance for such emulsions.12-14 double emulsion drop double emulsions have wide use within a number of industries and technologies, as described in a recent and comprehensive review.12 the extensive and highquality research within the area13,14 has applied the colloidal stability approach, illustrating the enhanced difficulties, compared to those of simple emulsions. the problem arises, because of the fact that two interfaces have to be independently stabilized.13,14 a surfactant, acting effectively on the o/w interface, has to be prevented from diffusing towards the o/o interface and vice versa, reducing its stabilizing action. however, the results of recent studies of the destabilization of janus emulsions20 have demonstrated a substantial effect of interfacial thermodynamic factors to modify the coalescence process of these emulsions. in fact, the janus topology was retained during coalescence until the very last stages.20 no such experimental results have been reported for double emulsions, but the potential for such an outcome is estimated sufficiently positive to justify a section on their interfacial thermodynamics in the present publication. hence, the interfacial thermodynamics of a double emulsion drop is examined to outline its prospective stabilizing effect, with a view towards the effect found for janus emulsions. the interfacial free energy basis for a double emulsion drop is the inequality γo1/w > γo2/w + γo2/o1, which, as mentioned, shows non-equilibrium spreading with an appealing application of this condition to estimate the thermodynamic stability of a double emulsion drop. however, this kind of interpretation has to be made with caution, because the term thermodynamic stability is defined only against a specific counterpart. a seemingly figure 4. angles β (a) and δ (b) and areas of equilibrium and spreading (c) versus the ratio γo2/o1/γo1/w (b). the ratio γo2/w/ γo1/w (a) is the parameter with the following numbers. , 0.99; , 0.90; , 0.75; , 0.5. the minimum b number for each a is marked with an arrow; , 0.90, dotted; , 0.75, dashed; , 0.5, full line. for , go1/w implicitly equals unity. 11emulsion thermodynamics – in from the cold attractive such system is two separate drops of the single oils, but leads to thermodynamic contradictions, showing this stabilization outside the mentioned inequality. nonetheless, such a choice per se has distinct algebraic interest, combining a well delineated interfacial free energy and an easily comprehended connection to the destabilization of physical emulsions. the following evaluation focuses on the overall free energy difference between a double emulsion drop and two single-oil drops. the volume fraction of oil 2 in the drop is vo2 and the interfacial free energy of the drops are offered in table 1. table 1. interfacial free energy of double emulsion drops. configuration, drops ife, o1 ife, o2 double drop 4π(0.75/π)(2/3)γo1/w 4π(0.75vo2/π)(2/3)γo2/o1 separate drops 4π(0.75(1 –vo2)/π)(2/3)γo1/w 4π(0.75vo2/π)(2/3)γo2/w regrettably, there is no direct algebraic expression for the relationship between free energy and volumes for the calculation.18,21 instead a realistic example was selected to illustrate the variation in free energy during a coalescence process. the particular emulsion consists of 1.09.109 internally thermodynamically stabilized double emulsion drops, each with a volume of 4.188.10-15 m3. the two oils o1 and o2, with interfacial tensions 0.004n/m (γo1/w), 0.00262 n/m (γo2/w) and 0.00116 (γo1/o2) each occupy one half. the drops are coalesced, two and two, 30 times, leaving only one final drop with a volume of 4.05.10-6 m3 and retained topology. the coalescence covers the free energy change due to interface size increase of both the outer sphere and the inner one, of which the former contributes a majority of the free energy reduction. as is obvious and expected, the emulsion interfacial free energy is exponentially reduced, figure 5, during coalescence; a reflection of the thermodynamic overall instability of emulsions; even when the drops contain more than one interface. the overall reduction in interfacial free energy is certainly expected, but a more essential issue is a comparison of the free energy change, when two double emulsion drops coalesce into one double emulsion drop or to two single oil drops, o1 and o2, during the coalescence. figure 6 depicts this difference between interfacial free energy change from two janus drops, when a double emulsion drop, , or two separate drops, , form. the results in figures 5 and 6 are unequivocal; the coalescence to a single double emulsion drop implies an expected reduction of free energy, while the alternative means an increase. these results are remarkable and conclusions would unquestionably be tempting; both about the general validity of the result and vis-à-vis the technical and commercial effects. nevertheless, such inferences would be premature at this stage, because a more complex geometry after coalescence will, in some cases, lead to a modified result. even so, the results encourage future experimental and numerical evaluations. leaving that aspect temporarily aside, even the more fundamental aspects offer some unexpected results, illustrated by the ratio, rc/d between the interfacial free energy of the combination drop and that of the two separate drops, equations [3] and [4]. vo2 is fraction of o2 volume. rc/d = ifecomb dr/ifesep dr [3] -1,00e-04 1,00e-04 3,00e-04 5,00e-04 7,00e-04 9,00e-04 0 10 20 30 coalescence step figure 5. the difference in interfacial free energy (see text). figure 6. the free energy changes, when two double emulsion drops (example in text) coalesce to form one double emulsion drop, , or two single oil drops, , of o1 and o2, respectively. 12 stig e. friberg rc/d = [(1 – vo2)2/3γo1/o2 +γo2/w] / [(1 – vo2)2/3γo1/w + vo22/3γo2/w] [4] according to these conditions, there are examples, figure 7, which indicate ranges outside the condition γo1/w > γo2/w + γo2/o1, at which the combined drop is thermodynamically favorable to two separate drops. the interfacial free energy of the double emulsion drop is unquestionably less than that of the two separate drops for all volume ratios, when γo1/w > γo2/w + γo2/o1. then again, for γo1/w/(γo2/w + γo2/o1) = 0.85 (curve  in figure 7) the ratio in question is still less than one; an obvious thermodynamic contradiction. if there is no spreading, it is difficult to accept that two separate drops should spontaneously unite to a double emulsion drop. nonetheless, neglecting the fundamentals, focusing on the algebra per se, the trend as such of the curves in figure 7 is anticipated from equations [3] and [4]. the initial increase of the first term of the equation denominator is less than that of the numerator of the equation, giving a downward slope, while the final change is the opposite, giving the minimum of the curve. as a result of the shape of the curves, the rc/d < 1 within a limited range of relative volumes, even for γo1/w < γo2/w + γo2/o1, a purely algebraic result. however, the indisputable conclusion is that the use of two separate spheres is not the correct counterpart to gauge the thermodynamic stability of a double emulsion drop. in fact, the choice of a correct counterpart to evaluate the thermodynamic stability of the double emulsion drop needs a more comprehensive evaluation of the entire tension range. another small detail in figure 7 might be mentioned, for which the inequality γo1/w > γo2/w + γo2/o1 actually is directly applicable to a physical emulsion. the final outcome of the coalescence of a double emulsion, whose interfacial tensions obey the inequality in question, is in the form of three layers of the liquids. at that point, gravity decides the order of the layers in the container. if the liquid densities vary as ρw > ρo2/w > ρo1/w, the order of the three layers will be o1, o2 and w from the top and three layers are found. conversely, if the densities are ranged ρw > ρo1/w > ρo2/w, four layers are found, since the o1 layer is not in direct contact with the water layer, but separated from it by an (infinitely thin) o2 layer, because o2 spreads on w. needless to say, these results are based on single-oil drops as the alternative to the double emulsion drop. in reality, a double emulsion drop will not change to two individual drops, if interfacial tension ratio is moved outside the condition γo1/w > γo2/w + γo2/o1. this will become evident in the analysis of the entire range of interfacial tensions, which shows that, for γo1/w < γo2/w + γo2/o1, the preferred topology becomes that of a janus drop. janus drop the introductory publication on janus emulsions15 was based on microfluidics16 emulsification. this preparation guarantees emulsions at virtual internal equilibrium and led to a number of investigations into the different aspects of janus drops,17-22 the results of which confirmed the agreement between equilibrium predictions and experimental results. these studies formed the basis for an extensive foray into several important aspects of emulsions in biology and medicine, led by weitz.23 the method, as such, enabled the preparation of emulsions, to all intents and purposes, of any complex topology, but was inherently limited to diminutive volumes, preventing applications into commodities. this condition was changed in 2011, when hasinovic et al prepared janus emulsions by traditional vibrational emulsification,24 opening an avenue to large scale production. this pioneering contribution showed microscopy photos of welldefined janus emulsions, figure 8. the image shows well defined drops of an o/w janus emulsion of a vegetable oil, weight fraction 0.18 figure 7. the ife ratios between the interfacial free energy of a double emulsion drop and two separate single-oil drops with γo1/w = 1. symbol γo2/w γo2/o1  0.5 0.25  0.58 0.29  2/3 1/3  0.78 0.39  0.88 0.44  0.98 0.49 13emulsion thermodynamics – in from the cold and a light silicone oil, weight fraction 0.72, while the continuous aqueous phase comprises only 0.1. it is noteworthy that an o/w emulsion with such limited volume of continuous phase is formed in a standard vibrational emulsification; an early indication of the unexpected effect of interfacial thermodynamics on vibrational emulsification process. furthermore, but equally important, the regular janus topology was first achieved by shear after the initial emulsification. both processes were necessary in most cases and deserve separate comments. the emulsification as such is a process, in which a large number of transitory small drops of irregular shape are formed and the freshly prepared emulsion is a result of these drops rapidly coalescing to larger entities.25 this process will favor irregular janus drops for kinetic reasons, because there is virtually no colloidal stability effect involved. assume an equal number, n, of equally sized drops of two mutually insoluble oils, which are allowed to coalesce at a rate, which is independent of specific drop topology. subsequent coalescence of these drops leads to an overwhelming fraction of irregular shape janus drops, in addition to their larger sizes. during the ensuing shear the small attached o2 drops coalesce to a regular janus lobe. the effect of shear was cursory illustrated 26,27 by optical microscopic images, before and after a cover glass was applied on the microscope slide, figure 9. the minute shear from the cover glass resulted in fewer drops, as expected, but also in an extensive topology change to better defined janus drops. in addition, the results of shear also – albeit indirectly – serve to confirm the internal thermodynamic stability of the janus drops. contrary to the case for single-oil emulsions, for which the effect of shear at low rates is to form larger spherical drops, low rate shear of the initial janus drops, left micro-photo figure 9, leads to coalescence of the attached drops and a more regular janus drop. as such, the information in figure 9 also complements and supports later experimental proofs of the thermodynamic stability of the structure.20 these results are concerned with the kinetic factors of the process, leaving the thermodynamics unexamined. the equilibrium angles and tensions of the janus drop are given in figure 2a and the algebra for equilibrium has been reported16-19,27,28 with the following summary. balancing the forces in figure 2a along and perpendicularly to the γo1/ w direction gives the angles β and δ, figure 2a, which, in turn, define the angles μ and ε. μ = η + β [5] ε = η δ [6] furthermore, assuming ro1/w = 1, the radii ro2/w and ro2/o1 are ro2/w = sinη/sinμ [7] ro2/o1 = sinη/sinε [8] these equations control the equilibrium at the contact line, while the entire drop configuration, figure 2b, also depends on the relative volumes of the two dispersed liquids. unfortunately, the latter feature is not easily calculated from given volume fractions. the expressions become prohibitively complex and guzowski et al18 opted to use a computer program to correlate volumes and topology. as an alternative, the volumes are calculated in the present contribution from the geometrical features in figure 2 and the correlations between figure 8. an optical microscopy image of a janus emulsion, prepared by vibrational emulsification. figure 9. a simple experiment illustrating the effect by shearing on a janus emulsion, prepared by vibrational emulsification27. (from reference 27 with permission). 14 stig e. friberg volume ratios and topology are evaluated ex post facto.26,28 the volumes of o1 and o2 are calculated (equations [12] and [13]) via pre-volumes, φo1, black, figure 2b, and φo2 white + grey, figure 2b, separated by the plane through the visible contact line. φo1 = π(1 + cosη)2(2 + cosη)/3 [9] φo2 = π(ro2/w cosμ)2(3 ro2/w + cosμ)/3 [10] the volumes vo1 and vo2 are attained from φo1, φo2 and φo1/o2 (grey, figure 2b), φo2/o1 =πro2/o13(1 – cosε)2(2 + cosε)/3 [11] vo1 = φo1 + φo2/o1 [12] and vo2 = φo1 φo2/o1 [13] in the comparison of interfacial free energies, the single-oil drops as counterparts are now replaced by a direct comparison between the free energies of double emulsion and janus drops. as will be demonstrated, this new comparison is more relevant, removing the “anomalous” results in figure 7. this figure showed the double emulsion drop to have lower interfacial free energy than two separate single-oil drops in a limited range of volume fractions, even for γo1/w < γo2/w + γo2/o1. the reason for this result is that the free interfacial free energy of the janus drop was neglected, as has commonly been the case. figure 10 shows the ratio of the free interfacial energies of a janus drop to those of a double emulsion drop of identical volume. the ratio was limited to the tensions γo1/w < γo2/w + γo2/o1; since the drop equilibrium free energies for janus drops with γo1/w > γo2/w + γo2/o1 is outside the equilibrium conditions and cannot be exactly calculated. the figure demonstrates the janus drop to have a lower free energy than the double emulsion drop in the inequality range γo1/w < γo2/w + γo2/o1. the faulty conclusion from using two single-oil drops as counterpart is now corrected. in addition, there are two details that are of interest. the topology change, when the inequalities change from γo1/w < γo2/w + γo2/o1 to γo1/w > γo2/w + γo2/o1 is of special interest, because it is highly prominent. a complete analysis involves a large number of variables and in the present contribution a simplified example is used to graphically illustrate the phenomenon. the basis for the example is the specific and well defined case γo1/w = γo2/w + γo2/o1. in the calculation the expression is divided by γo1/w, giving γo2/w = a and γo2/o1 = 1 a. the change of inequalities mentioned is represented by γo1/w altered from 1 ε to 1 + ε, in which ε is a small positive quantity. the angles b and d are calculated with the γo2/w and γo2/o1 equal as are the o2 and o1 volumes. the specific selection of these is not essential for the central theme, and the angles β and δ are calculated versus ε. cosβ = cosδ = 1 – (2 ε)ε [14] the radical topology change, caused by the minute alteration of γo1/w from 0.995 to 1.005 is illustrated in figure 11. the minute increase (1%) of the interfacial tension γo1/w causes a drastic topology change with o1 spreading on the large sphere of o2. the activity is the same for smaller ε, but the graphics becomes less instructive, because the visible contact line is transferred to greater η angles with reduced ε. another, perhaps even more drastic consequence, is found of the interfacial tension variation for model sysfigure 10. the ratio of interfacial free energy of a janus drop and a double emulsion drop of identical oil volumes. figure 11. with e = 0.005, γo1/w < γo2/w + go2/o1, a janus drop is thermodynamically preferred. when ε changes to -0.005, o1 spreads on o2 and a double emulsion drop is favored. 15emulsion thermodynamics – in from the cold tems with realistic interfacial tensions.28 as an example, the variation of ro2/w and ro2/o1 (ro1/w =1) with η is truly remarkable, figure 12, for β = 27.8°, δ = 35.4°, γo1/w= 1 and ro1/w = 1. each curve has a discontinuity, at which an infinite radius switches to the opposite sign with changing η. the ro2/o1 versus η switches from -∞ to +∞ at η = δ = 35.4°, while ro2 versus η discloses a discontinuity at η = π β, approximately η = 152.4°, figure 12. the discontinuity of ro2/o1 2 at η = 35.4°, has only a small effect on the volumes of the two lobes, figure 2. instead, the influence is felt on the laplace pressure correlation. σ2δpxx/rxx = 0 [15] the radius ro2/o1 is negative for η < 35.4°, figure 2. in this η range the terms γo2/w/ro1/w < 1 and hence necessitates a negative ro2/o1 to satisfy the laplace requirements, equation [15]. for η = 35.4°, the γo2/w and ro2/w both are 0.65 and, again the laplace pressure condition complies with those in equation [15]. for η > 35.4°, the sign of the radius is opposite to that at η < 35.4°. nonetheless, as mentioned, the effect is not decisive for the size of the volumes, since φo2/o1 is usually small compared to volumes φo1 and φo2, equations [9] and [10]. conversely, the change in ro2 is accompanied by an extreme change in the o2 volume. as shown by friberg28 as well as by ge et al26 in different examples, at η ≈ 154.2° for the janus drop in question, the change represents a partial inversion of the janus drop from (o1 + o2)/w, η = 140°, figure 13, to (o1 + w)/o2 η = 164°. at η = 140°, the ro2/w has reached a value of 3.0 with ro1/w = 1 and ro2/o1 = 0.66. the o1 drop is formed by two lobes, one reaching 0.23 (fraction of ro1/w) into w, o1/w, and a second lobe entering 0.83 fraction into o2, o2/o1. there is, needless to say, no interface between the lobes. together they form a non-spherical drop, o1, with an abrupt sign change of the radius as well as its dimension at the contact line. as expected, the added laplace pressure over the interfaces o2/o1 and o2/w equals the pressure over the o1/w interface. when η is increased to 152.4°, the o1 drop is located at the interface between two infinite phases w and o2. nor in this case is the o1 drop symmetrical, since the γo1/w is different from γo2/o1 and the laplace pressure is equal across the two interfaces of o1. increasing γ to 164°, figure 13, shows an (o1 + w)/o2 janus emulsion and a further reduction of the o1 drop size. these results and those in the preceding paragraphs are correct illustrations of the drop topology, as directed by the thermodynamic requirements. however, the applications to a physical emulsion are fraught with uncertainties and a few comments on the prerequisites for the model system are useful. the γo1/w = 1 is not a cause of concern; it only implies that instead of numerical values for γo2/w and γo2/o1, their ratios γo2/w/γo1/w and γo2/12/γo1/w are used to simplify the algebra. conversely, the second condition ro1/w = 1 causes artificial restrictions on the physical image. it indicates that for each η change, a slice of o1 between the η:s in question is removed and a modified section of o2 is added at the contact line with exactly correct b angle. as is obvious, the conditions, in spite of being thermodynamically correct, are difficult to reconcile with any physical system, especially to the close packing of drops. the second alternative, retaining the o1 volume constant, gives a result similar to the one for constant ro1/w, while the more artificial choice of keeping the entire drop volfigure 12. radii of lobes for the janus drop, dashed line in figure 2, with ro1 equal to unity. squares ro2/w, triangles ro2/o1 figure 13. schematic representation of the inversion of the janus drop in the range η = 140° 164°, black areas are o2, grey areas o1 and white w. expanded o1 areas with correct radii ratios are shown on top with the extension of the contact line as dotted/ dashed. 16 stig e. friberg ume constant leads to some modification. nevertheless, from a physical point of view, the second alternative is the most realistic with o2 added to an already formed o1/w emulsion. for this case, adding o2 brings about a greater and greater o2 lobe of the drop, but causes no emulsion inversion, until the volume of o2 is greater than that of the initial continuous phase o1. as a summary, adding the oils to an initial aqueous liquid gives an o1/w emulsion. adding o2 to this emulsion results in a janus emulsion, (o1+ o2)/w, an emulsion with increasingly larger o2 lobes. when the o2 volume exceeds that of the w, an inversion takes place to an (o1 + w)/o2 emulsion. continued addition of o2 gives rise to a diminution of the relative size of the (o1 + w) drop. conclusions the conclusions to include janus emulsions as a counterpart, when considering the thermodynamic factors for double emulsion drops have been proven correct for selected examples. the extension of these conclusions to janus and double emulsion drops in general would be premature, but, so far, the indications are that the inference has more general validity. acknowledgment the author is deeply grateful to his wife, susan for her unfailing loyalty and support during the research and to the ugelstad laboratory, trondheim, norway for support. references 1. b. p. binks, (ed), modern aspects of emulsion science, the royal society of chemistry, cambridge, 1998 2. j. sjöblom, (ed), emulsions and emulsion stability. 2 ed. taylor and francis; 2006 3. y. liu, in th. f. tadros (ed), phase inversion, encyclopedia of surface and colloid science, 2nd ed., springer, amsterdam, 2013 4. d. j. mitchell, b. w. ninham, j. chem. soc. faraday trans. 1981, 77, 601. 5. s.i. ahmad, s.e. friberg, k. shinoda, j. colloid interface sci. 1974, 47, 32. 6. g. horvath-szabo, j. h. masliyah, j. a. w. elliott, h. w. yarranton, j. czarnecki, j. colloid interface sci. 2005, 283, 174. 7. f. eslami, j. w. a. elliott, j. phys. chem. b 2014, 118, 14675. 8. j. korozs, g. kaptay, colloids surf. a 2017, 533, 296. 9. b. derjaguin, l. landau, acta physico chemica urss 1941, 14, 633. 10. e. j. w.verwey, j. th. g. overbeek, theory of the stability of lyophobic colloids, elsevier, amsterdam, 1948 11. m.boström , v.  deniz, g.v.  franks, b.w.  ninham. adv. colloid interface sci. 2006, 123–126, 5. 12. a. aserin, multiple emulsions: technology and applications, john wiley & sons, new 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interface sci. 2011, 354, 424. 25 h. hasinovic, s. e. friberg, langmuir 2011, 27, 6584. 26 l. ge, s. shao, g. lu, g. rong, soft matter 2016, 10, 4498. 27 h. hasinovic, c. boggs, s. e. friberg, i. kovach, j. koetz, j. dispersion sci. technol. 2014, 33, 613. 28 s. e. friberg, j. colloid interface sci. 2014, 416, 167. substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi substantia. an international journal of the history of chemistry 3(1) suppl.: 17-27, 2019 firenze university press www.fupress.com/substantia citation: d. ferro (2019) the authenticity of the false. substantia 3(1) suppl.: 17-27. doi: 10.13128/substantia-601 copyright: © 2019 d. ferro. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-601 the authenticity of the false daniela ferro institute for the conservation and restoration of cultural heritage cnr-(icvbc) member of planet green chemistry and yococu association e-mail: daniela.ferro@cnr.it abstract. since its first appearance, the jewel is not a mere expression of vanity and seduction, but it is associated with the decorative function with a multitude of meanings that transform it to all effects into a complex and fascinating communication code [1]. the jewel is a perfect combination of nature, technique and individual creativity that interprets the collective sensibility in the various eras. if we then join up it to its being made of precious metals, it becomes the most advantageous and profitable object of forgery [2]. the fakes and counterfeiters began at much the same time and flourished ever since. most of the early productions are not very convincing, either stylistically or technically, this was due to a general lack of detailed stylistic information and an almost total ignorance of ancient technology. until the middle of the last century there was no real science applied to the study of cultural heritage and the falsification or counterfeiting could be unmasked only by stylistic errors or anachronistic details detectable by visual observation although with the help of optical microscopes. with the establishment of archaeometry, each diagnostic application became a real scientific research [3]. in the present work, the chemical and physical studies on ancient goldsmith’s art in the last forty years, highlight the peculiarity of the manufacturing technique and the scientific knowledge of the artisan, which allows not only to discover modern copies, falsifications or counterfeits, but also to unveil the modern experimental approaches implemented for a faithful reproduction of an ancient jewel. keywords. ancient jewellery, archeometry, fakes, castellani family, prenestina fibula. only micro/nanodiagnostic allows to understand and distinguish jewels made as a copy-replica, jewels inspired by ancient artworks or made as a counterfeit. in fact, all the handicraft and the technical procedures included in the jewel manufacturing sequence pertain to the goldsmith’s personality … which cannot be easily reproduced by the forger. introduction in every civilization luxury products represent, in addition to the desire to embellish the appearance, a sign of social distinction, witnessing the wealth and often the power of those who own them. the cultures of the ancient ages, including those that were developed in the italic area, are no exception: in the classification that pliny the elder, 18 daniela ferro who lived in rome in the first century ad, reports in his work, a list of the most coveted goods from his contemporaries, in order of preference in this list all the materials used in the goldsmith’s art appear on time – the processing of precious metals, i.e. gold, silver and their alloy, the electrum – and the glyptic. with this word, deriving from the greek term γλύφω (“engrave”), we mean either the set of materials of inorganic nature (precious stones and hard stones) and organic materials (amber, ivory, coral, shell) that could be carved and engraved, either the art itself. as concerns the real products, however, the highest value, among those of the sea, is attributed to the pearls; among those of the earth’s surface, to the crystals; among those of the subsoil, to the diamond, to the emeralds, to the gems…. among the products derived from animals with respiratory system, for terrestrial animals the highest value is the elephant’s tusks, for the marine ones the shell of turtles … between the terrestrial and marine products, the shells and the purple … we must not omit to say that gold, for which all mortals do follies, occupies only the tenth place in the scale of values, and the silver, with which gold is alloyed, yes and no the twentieth … (pliny the elder, naturalis historia, cap. xxxvii, 204) around the eighth century bc, the acceleration of economic-social differentiation processes and the concentration of huge wealth in the hands of the indigenous aristocracies of etruria, campania and lazio induce, in central tirrenic italy, the establishment of huge accumulations of precious metals that stimulate the luxuriant development of goldsmith craftsmanship. subsequently, with the emergence of rome power and the extension of its influence due to the territorial conquests and the annexation of new provinces, as early as the first century ad new luxury goods such as hard and precious stones, pearls, ivory, silk, begin to flow along the trade routes that connect rome with asia and africa. in italy it is possible to bring back the origins of italian archaeological jewelry to the excavations of herculaneum and pompeii that provided the first jewels, sources of inspiration. thus the reproductions and the diffusion are more precocious in naples than in the rest of italy. augusto castellani in the “discorso sull’ oreficeria antica” [4], argues that the first attempts to copy exactly the ancient creations were made in naples at the beginning of the nineteenth century, in the goldsmith mariano sarno’s bottega. later on, this activity would be undertaken by his father fortunato pio, in roma. the goldsmith bottega of sarno, on the advice and encouragement of learned neapolitan archaeologists and customers, begins to restore excavation jewels, to imitate them in style and to push their creations to falsification. the goldsmith production, under the guidance of sarno, had, for a few years, a great success, and then gradually closed its activity [5]. in addition to the well-known neapolitan archaeological discoveries, in italy there were many other intense explorations often crowned with unexpected as well as important discoveries like that of the regolinigalassi tomb in 1836, in cerveteri (caere) or the bernardini tomb discovered in palestrina at the end of february 1876 during the excavations financed by the bernardini brothers [6]. in this last tomb, a dragon-like gold fibula dating back to the mid-7th century b.c was found. a text that constitutes the oldest written testimony in latin, is engraved on its elongated part, however it has been the subject of doubtful falsification / authenticity issues that raised a twenty years-long discussion. in the context of the nineteenth century, characterized by the rediscovery of the classical world and the strong diffusion of collecting and the antiquarian market, originals, copies, falsifications and pastiche often live with no particular hardships and difficulties both for the craftsman and for the client. [7]. it was common practice, among the artisans of the age, to touch up, reintegrate and reconstruct damaged or mutilated artefacts to satisfy the needs of an antiquarian market, particularly attentive to the integrity of the object rather than to its authenticity. these practices sometimes went as far as the meticulous copies of ancient jewels, which however, in the popular imagination of the average purchaser of the time, had the same value as the original ones [8]. a report of monthly magazine about the london exhibition of 1862, asserts that “every piece on display is an original copy of a true authentic exemplary of an ancient work; that not only the ornamental style, but the procedures used in ancient times have been followed” these arguments are enshrined in our constitution with article 21 which, in the most rigorous respect for the fundamental principle of freedom of expression, protects the right of every citizen to be able to realize and express their thoughts through the creation and dissemination of their production, without any substantial control over the content of the operations performed. it is possible also to cite article 33, which is the principle of freedom of art and science, article 35 according to which, the republic protects the work in all its forms and article 2575 of the civil code, which fixes the original character of creativity that identifies 19the authenticity of the false the personality of the author and reveals its ability to express an idea, or a feeling. [9] in 1977 bloch [10], to describe the phenomenon of ancient reworkings, distinguishes these different types of artifacts: – copies-replicas from a prototype, according to a practice already widespread in the ancient world – copies-counterfeits: products that are exclusively subject to a market law, not by preventing creativity, an essential element of the artist – pastiches, the realization of a work of art, by assembling authentic, i.e. ancient, materials with others of modern production. the difference between the first two classes of artifacts lies in intentionality, which satisfies a precise practical function, that of placing a responding object in the art market, by means of a malicious operation and under the appearance of truth, to a question that would otherwise be unsatisfied [11]. ruled by an economic law, the falsification follows the fluctuations of taste and it is no coincidence that the most famous fakes coincide, over time, with the great archaeological discoveries, of which they imitate the findings. the first etruscan fakes appear in the eighteenth century, the great era of collecting and of the etruscan style. but we must wait for the second half of the nineteenth century, for the production of the finest examples of fakes [12]. the discovery of the regolini galassi tomb in the year 1835, sets a very important date as kick off to the development of a goldsmith’s art that proposes the study of the ancient technologies, undertaken by the castellani workshop. fortunato pio, in fact, was called by the papal authority, as a consultant for the restoration and study of etruscan jewelry and from this moment, a castellani production of archaeological-style jewelry starts. alessandro castellani [8] commented this important discovery in the conference held in london at the archaeological institute in 1861[13]: since there are no scientific studies on ancient goldsmiths’ techniques, even if he is a goldsmith with a long experience, he is faced with problems never found in the creation of any jewelry complex. the jewel decorative components are, in fact, made with techniques that are not always handed down in full, because in addition to being the creations of the single craftsman, the precious alloys and other non-metallic materials undergo transformation with kinetics of more than 2000 years. the gold metal does not show many alterations or corrosions, but it is prone to micro-structural evolutions such as recrystallization and discontinuous precipitation, hence it is rather fragile and may present mechanical damage, especially if it consists of thin sheets, connected to each other by welds, which may have been crushed or torn. clearly, the castellani family was aware of the proliferation of fakes and did not want to be associated with them. augusto castellani, in the “discourse on ancient goldsmiths”[13], talking about the activities conducted in the workshop by the goldsmith sarno, who had a good reputation in the production of faithful reproductions of ancient jewelry, defines the falsification a reprehensible activity and takes the distances: the artists who had been part of the sarno bottega then set about restoring ancient works of art, and also applied their talent to their falsification. in this last reprehensible activity, they were so wonderfully skilled that naples became famous for imitations, so astutely made with colored earths, acids and salts, so much to make it difficult and almost impossible to know if an object was ancient or not. unless they were people who had a long experience in the field of art, and were very experienced in archeology. their archaeological creations and the techniques involved, required a considerable amount of apprenticeship for their artisans, who were asked to apply maximum precision and quality in the execution of the models. this activity led to a revolutionary revival of local craftsmanship, which had its fulcrum in the castellani bottega, where many roman goldsmiths at the time carried out their apprenticeship: fortunato pio had created a sort of “roman school” of goldsmiths. a possible classification of the different types of nineteenth-century “falsification” can be expressed as follows: 1. antique with modern reworking 2. antique with modern additions 3. pastiches of antique pieces 4. pastiches of ancient and modern pieces 5. modern with the addition of antique parts 6. duplicates: pastiches as pendant of ancient pieces 7. duplicates: modern copies as a pendant of antique pieces 8. modern artifacts from ancient types 9. pastiches or modern pieces sold together with antique pieces 10. pastiches or modern pieces sold together ancient items (false documents) 11. neoclassical or historicist pieces 20 daniela ferro among these categories, the numbers 1, 2, 3 and 6 can be considered “good faith” restoration. part of the artifacts, which fall into category 8 and those of n. 11 can be classified as imitations. categories 4, 5 and part of 8 have counterfeiting intentions. the works that belong to the categories 7, 9 and 10 are false in the strict and legal sense of the term. according to hilmeyer [14], the most difficult categories to be distinguished are 4 and 5, which require careful study of all the individual parts of the jewel, which also refers to the techniques of realization of the same. considering all this, in the study of archaeological goldsmith’s art, there is a need to circumscribe the category of “authentic” from that of “reworking”. if it is true that the “fakes”, made in the nineteenth century, must be recognized and appreciated as a phenomenon of a specific historical period, it is also true that recognizing the falsifications is an act of honesty towards of visitors and scholars. at the same time, giving back the right identity to authentic works is a moral necessity rather than an historical requisite [15, 16]. from the above described, it is possible to understand how the identification of nineteenth-century reworking has to be considered as a complex study, especially in the specific case of the castellani’s family. in fact, by virtue of their authoritativeness, they could perform “copies”, “complete” or “rework” precious objects starting from the direct observation of the authentic pieces, that they had the possibility to handle as long as they needed to study their characteristics and compare them directly with the jewels they reproduced. if an initial critical observation can direct and help in the identification of originals /fakes, sometimes the stylistic and formal examination is uncertain and not always sufficient to grasp the differences between two objects, even if it is a question of discriminating in the same artifact, antique and modern decorative elements. these latter being formally identical copies of those already present on the original [16]. a useful tool, in this sense, can be provided by the scientific investigation, which, through chemical and physical analyses, allows the technological assessment of the jewel, identifying the details of the construction technique. if the overall system and the construction scheme of a jewel can be reproduced exactly and with relative ease, it will be more difficult to reproduce the original ancient techniques of decoration elements such as granulation and filigree with a resolution of the order of millimeters [17]. in fact, the ancient technologies used have peculiarities, such as the type of alloy, the execution procedure, the assembly, the welding, the traces left by specific instruments, to be used as diagnostic markers in the study of a modern example from an ancient one. starting from previous studies [18-22] the aim of the present work is to outline how the scientific investigative method, based on the recognition and the temporal and geographical attribution of a goldsmith working process, can be decisive in the attribution of authenticity of an ancient jewel. materials and methods dealing with jewels, it is right to start from the main metal, gold, that is considered noble par excellence, incorruptible, perpetually shining and therefore a symbol linked to the sphere of royalty and the sacred, a sign of power and unalterable wealth over the time. the precious objects found in the archaeological excavations astonish for their unaltered appearance, even if, on a structural level, we must not neglect that gold, like all metals over time, tends to return to its more stable form, which, in the case of gold, is the metallic face centered cubic crystal structure. its mechanical properties can be altered by micro and nano-structure modification. the state of the structure on micro/nano scale becomes complex when alloyed gold is used instead of pure gold: e.g. alloys with silver, copper, often with traces of other metals coming from a possible re-use of metals, such as iron, lead, tin, zinc to cite the most frequent in ancient times. besides, each of the alloyed metals may contain traces of minerals from which they were extracted by metallurgical processes. furthermore, in addition to natural ageing, interaction with the environment, often hypogeal, should be considered in view of the function of jewelry in the funeral contexts. what is described is the basis of archaeological research that aims to trace any clue that bring back to the authenticity of the artifact. in the choice of the analytical method it is indispensable, in addition to the obvious application of nondestructive techniques, to take into account that it is required to go beyond the visible scale and therefore the dimension of the particular to be investigated is the key parameter for the selection of suitable methods. the techniques most frequently used in the study of jewels, are based on x-ray radiography, scanning electron microscopy (sem) coupled with energy dispersive x-ray micro-analysis (eds) and x fluorescence (xrf), using instrumentations suitable to avoid any micro sampling on the object or surface pretreatment. with the application of one or more of these techniques on a considerable number of ancient finds, in the 21the authenticity of the false last years it has been possible to broaden the knowledge on the activity of goldsmith artisans but also indirectly on their scientific knowledge applied to metal processing [23-25]. from these studies it is possible to obtain a big amount of information that allows to compare technologies belonging to different cultures and to identify the processes linked to the creation of the object, establishing its own characteristics that consent us to trace the genuineness of a finding. specifically, each study includes the morphological analysis of the surfaces, by means of images acquired in the various sem modalities, the elemental analysis of the composition of the pre-existing alloy, by eds and /or xrf analysis. the critical discussion of the results made it possible to identify the technique of creating jewelry decoration elements such as: granulation, wire form, welding techniques up to the type of tools used and any non-metallic materials included in the artistic composition [26]. the thin border line among the various forms of jewelry remaking, more or less conforming to legal rules, can be highlighted considering the studies carried out on three types of reproduction of objects, from an evident falsification case, to an attribution of authenticity, the fibula prenestina, passing through nineteenthcentury remakes linked, above all, to models derived from studies on the etruscan jewelry by castellani’s family. results and discussion a case of falsification, appeared recently on an auction catalog, is represented by the pair of gold earrings (fig. 1), consisting of an oval-shaped setting with a frame decorated with short radially engraved strokes, containing a blue-colored dark gem. in the back, on the lower side of the setting, a trapezium-shaped plate is welded to the edge, to which three fixed suspension eyelets are connected. attached to them are three knurled wires, with the end folded to set three small blue-green beads. so many elements to be verified analytically, when stylistically perfectly consistent with the roman imperial jewelry, in particular the type refers to earrings diffused in many variants and defined by the classical sources with the name of “crotalia”, a musical instrument that emits the sound from the tinkling of beads. the observation at sem-eds (fig. 2a), highlights the short parallel lines engraved on the frame: they are irregular and imprecise, giving a scarce decorative effect. the central gem presents many imperfections and especially “bubbles” caused by a higher temperature than the glass transition. the glass components have been characterized by eds analysis (fig. 2b), showing a composition that can be associated with a modern glass, with a high content of lead and cobalt, the latter to impart the blue color to simulate lapis lazuli. besides, the sem observations of the surface at microscale, revealed the presence of abrasive material with silicon and aluminum particles to antiquate the surface. the trick to treat the surface for an antique appearance, is very common in counterfeiting. in another case fig. 3, the filigree-decorated surface showed, at the sem observation, a dense covering with a substance which displayed, by eds analysis, a composition with anachronisms such as nickel and zinc dispersed in an organic matrix. as written above, the knowledge of ancient jewelry technology through micro and nano diagnostic studies [27], is becoming fundamental for the recognition of counterfeits, but in the case of the 800’s jeweler fortunato pio castellani, this type of investigation becomes a discovery of a research method on the etruscan jewelry that has left its mark on the jewel history. the study of the castellani goldsmiths, which include etruscan jewelry restorations, copies for experimental archeology, to use a modern term, and etruscan-inspired jewelry for sale, offers the possibility of discovering their secrets. the integrated study of a pair of “bauletto” earrings, belonging to the collection of “ancient golds” and another of the same type belonging to “modern gold” has figure 1. earrings attributable to the roman imperial period. 22 daniela ferro been the subject of an experimental thesis and chemicalphysical research [28]. this study gave the opportunity to compare the technologies of execution and realization of the overall plane, and the decoration details of the castellani work with those of the ancient etruscan goldsmiths. first of all, the study of the modern earring has been undoubtedly an opportunity to fine-tune the observations and analyses on the technological details used by the castellani. in the analytical determinations, all the processing technologies related to all the decorative elements of the earring, such as granulation (grain shapes, three-dimensionality, welding), watermark (realization of the threads) and tools traces have been considered. each particular of the modern production, is to be considered as anachronistic elements in the subsequent study of the so called “etruscan collection”. the impossibility of subjecting jewels to invasive instrumental investigations, taking into account the exceptional value of jewels, has led to the selection of appropriate diagnostic techniques. a new type of analytical approach, aimed at highlighting structural differentiations on micro / macro scale between the “hand” of the castellani and etruscan goldsmiths has been employed by using modern data processing systems. in fact, the modest variations in composition and the imperfect localization of the castellani’s interventions on a micrometric scale, led to the elaboration of the numerous data obtained from the eds micro-analysis through the statistical method of the classification analysis, allowing to identify correlation areas between elements. the evaluations of the percentage of the elements constituting the au-ag-cu gold alloy trough eds is extremely difficult, as the elements are not homogeneously bound, and therefore minimal variations are not immediately observable in order to characterize, for example, one of the various welding processes. the figure 2. a) backscattered electrons sem image, of the part of the bezel with gem b) structure of the glass gemstone with indicated areas analyzed in eds. figure 3. a) part of a modern jewel made of watermark; b) sem image in secondary electrons of a part of the decoration; c) eds analysis of the substance distributed on the surface. 23the authenticity of the false variables selected to discriminate the various soldering techniques have been: brazing agents, cu salts, silver or other paillons, and the presence of the elements: cu, ag, cd, au. to avoid undermining the final result, before each classification analysis, their degree of bivariate correlation has been calculated using the pearson correlation coefficient, which measures the degree of linear association between two variables. the values of the coefficient vary between -1 and +1. the sign of the coefficient indicates the direction of the relationship between the two variables: directly proportional in the positive case, inversely proportional in the negative case. the results made it possible to define the use of auag alloy for the welding, as traditionally used in the 800s, but there are traces of cadmium that cannot be ignored. on the use of cadmium in castellani’s work, much has been written [29] and having found it on the pair earrings of castellani manufacture, it certifies its use. the skills acquired on etruscan jewelry and on castellani’s production allow us to recognize the parts subjected to modern intervention with the aim to give the jewel back its original aspect. this is the case of the “bauletto” earrings fig. 4, decorated with numerous and dense filigree and granulation motifs. at first glance they appear identical, but a more expert observation reveals several elements of differences. that’s why the first studies concluded that they are original etruscan, but one (n. inv. 53582) presents many subsequent works, while the other (n. inv. 53580) has only a few alterations. if we observe the two earrings at micro/nano scale, many contradictory elements with the etruscan jewelry are evident. this pair of earrings then falls into the category of antique piece with modern rework. as an example of the analysis carried out in each part of the jewel, we report the representative elements of the etruscan jewelry, granulation, watermark and knurled thread, are, as highlighted in fig. 5. as regards the identification of the gold material composition, the sem investigation has been undertaken by selecting an appropriate focused electron probe and by observing the surface in the backscattered electrons mode. based on these results, it has been possible to select micro-areas which were homogeneous for morphology and atomic contrast, for the eds microanalysis. the obtained data are shown in the table of fig. 5, following the criterion of imposing on the system the evaluation of all the chemical element mentioned in the “probable” castellani’s recipes. eds data immediately highlighted the presence of cadmium that, considering only the elements of the gold alloy, ranges from 0.2 to 1.3 wt%. figure 4. pair of earrings, museum of villa giulia n.inv. 53580 and 53582. figure 5. earring n.inv. 53582 sem image in backscattered electrons with indicated the areas investigated by eds method. the table shows the values of the chemical elements in percentage by weight (+0.2%). 24 daniela ferro the sem observation, in secondary electrons, of some areas of the jewel, highlighted the welds, whose realization caused an excessive filling of the spaces between the wires and between the granulation spheres. focusing on the use of metal wires for the filigree decoration, thanks to sem (fig. 6), it is possible to make morphological comparisons that highlight heavy differences between the ancient and the modern parts, certainly not known at the time of the castellani. it is possible to observe that the numerous threads do not all have the same technical execution. some of them show the typical helical grooves, characteristic of the etruscan construction technique that makes use of a twisted foil strip. others, instead have the characteristic parallel streaking, signs that have been produced through the use of a modern wire drawing die. the excessive heat applied has melted part of the original substance in the upper part and in the external side, making it difficult to locate the welding. in fact, the heating allowed diffusion and or local fusion of the metallic elements. therefore, the pair of earrings belonging to the collection of “ancient gold”, given the complexity of the work, have been analyzed by considering each decorative element, in order to obtain more specific information and allow a comparison between them. the application of person’s analysis for each earring allowed the creation of correlation matrices (fig. 7). the most significant evidence derived from the analysis of elemental composition and correlation of the variables is that the au concentration decreases in jewel n. inv. 53580 depends, in equal weight, on the presence of both cu and cd. this indicates the presence of welding with cu salts and addition of modern processing with use of cd, while, in n. inv. 53582, it depends primarily on ag (ag welding) and then on cu (copper salts welding). moreover, a direct proportionality link between ag and cu cannot be found in inv. no. 53580: this means that in the analyzed areas, the two elements are not correlated and therefore a use of an ag-cu alloy is to be excluded. cadmium is present independently of the cu in equal measure in the two objects analyzed. compared to ag, on the other hand, the cd has a null bond for inv. no. 53580, while it becomes important in the case of inv. no. 53580, a sign that probably cd has been used in addition to the welds by ag. the studies here reported demonstrate how the margin of separation between an attribution of authenticity or falsification is inconsistent, if one does not consider the complexity of chemical-physical information drawn from the study of ancient technological processes. what has been described, even if it can not necessarily be exhaustive, indicates however an obligatory route for the attribution or for “re-assigning” the authenticity grade to an ancient finding. a demonstration of this may be the case of the recent restitution of authenticity to a precious object, considered false and deprived of its important historical significance for a long period, the fibula prenestina fig. 8 [30]. the fibula is datable around 670-650 bc and containing the signature of the “manius” artisan, as well as that of the client. the formula employed is that of the figure 6. original wires and threads added during the castellani restoration. figure 7. correlation matrices for each of the pair’s earrings in fig. 4. 25the authenticity of the false “speaking object” by reporting the sentence “manios fecit for numasio”. these indications have represented the fundamental element used by the legendary etruscologist and archaeologist raymond bloch, to fix the birth of the latin alphabet to the vii century bc. the writing proceeds from right to left and uses the letters of the latin archaic alphabet; its wording is influenced by etruscan, sabellian and faliscan languages [31]. so the fibula is considered the oldest document of the latin language but its authenticity, disputed for years, has been proved not only by linguistic data but also by recent chemical and physical analysis. it was officially presented for the first time by the german archaeologist wolfang helbig, in 1887. the scholar claimed to have purchased it from a friend in 1876, and indicated the place where it was found as the bernardini tomb. a princely tomb, discovered in 1851 and excavated from 1871, near the ancient city of prenestae, the current palestrina. after years of academic and judicial disputes over its authenticity in 2009, the application of the integrated epigraphic and archaeometric study has demonstrated its authenticity. the application of the analytical method, to prove the consistency of the techniques used in the construction of the fibula with the ancient working methods, has revealed inconsistencies due to a modern process. however, the real importance of the finding focuses on the verification that the writing has not been performed postrecovery. this has induced studies on the microstructure of the metal, in order to derive useful information for understanding the transformations undergone [32]. as known in its fundamental state, the gold metal has a face-centered cubic crystalline structure (fcc). the specific properties of course are modified when au is alloyed with other metals such as cu or ag. however, while silver is completely soluble in gold at any temperature, copper is soluble in gold only above 410 c, below this temperature au-cu intermetallic compounds are formed. it is therefore clear that in the ternary alloys, the parameters and the mechanism of the recrystallizations after the various treatments that the metal undergoes for the realization of the object, are complex [33]. however, the overall process can be reduced to the following general scheme: a) nucleation of crystalline grains, b) growth of crystals, c) irregular grains form more or less regular structures that grow together d) increase of crystalline grains dimensions observable by optical microscope. recrystallized structures are clearly identifiable in the sem image of one of the traces left by the tip used for the inscription (fig. 9). three situations are related to the alloy modification over time and consequently to the observed alteration of the inscription: 1. in the furrow, the marks left by the roughness of the tracer tool are partially interrupted by recrystallization marks (indicating that recrystallization took place after the inscription was traced). 2. if the inscription had been made recently, i.e. after recrystallization of the alloy, the engraving lines would have appeared jagged, following the intergranular lines of lower mechanical resistance: such a feature was not observed. 3. internal areas of the inscription paths were investigated, using backscattered electron observation with appropriate modifications of the detector operation mode, in order to simulate the effects of grazing light. in this mode, the differences in height between the grooves impressed by the incisor tool and the natural alterations of the metal are highfigure 8. fibula prenestina 670-650 bc. pigorini museum rome. figure 9. modification of the metal microstructure (due to recrystallization) inside the incision groove. 26 daniela ferro lighted. therefore, sem observation of the surface in the furrow area confirmed that recrystallization (i.e. natural evolution of the precious alloy over a very long time) took place after tracing the inscription. this aspect, together with the other scientific information collected with an analytical procedure tailored for the fibula prenestina [32], demonstrated that the ancient find contains so many historical, artistic and technological information that we can never say we know everything about it. this affirmation is particularly true in this case, for which the new investigations, carried out after twenty years of analytical studies on ancient jewelry in general and the etruscan one in particular, have been able to restore its historical credibility. conclusions the jewel is the only one among the ancient finds, that contains all the practical and scientific knowledge of the craftsman who has to create a unique work each time. relying on procedures more or less attested in the period and in the geographic area where it operates, the antique jeweler brings stylistic and technological innovations that gradually become established, and their recognition together with historical artistic elements, allows their chronological collocation. the other important aspect is that the metal, whatever it is, keeps both the information of the operations that have allowed its transformation into a work of art, both of the action of time. the recognition of such transformations provides useful elements for defining its antiquity. the story of ancient gold working is not only related to metallurgical studies, because in the past each object contained meanings and symbolisms, but, at the same time, from another point of view, it is also full of technical and scientific knowledge. translations, interpretations, hypotheses, assumptions: how many times before an old jewel we met the difficulty to understand it, as well to know its history, the technology used in its realization, the scientific knowledge that led to the manipulation of its constituent material, its origin and so on. however, there is only one universal language, that always existed and always will exist and that is translatable in any language: chemistry. the identification of products and chemical processes that led to the physical realization of wondrous works of art, provides important data to complete the history of the work of art itself, allowing to define also the cultural grade of the contexts in which the object was manufactured. someone wrote: the work of art is born from the idea of form and search for technical means to realize the minimal details. in this sense the artist is at the same time, scientist and technologist. from this point of view, research turns its attention to the problems of the past with the knowledge of today, trying to identify the chemistry and physics concepts and applications, which, obviously on empirical basis, the ancients had and which we can interpret through scientific laws, now. the treated argument covers the research carried out in recent years on archaeological items in precious metals. the investigation on micro/ nano scale is essential for the identification of diagnostic markers that yield the knowledge of particular processes applied to precious metals workings. the collected data on the smallest details of the production procedure of jewels, provide completely objective comparison of the specific techniques adopted in the creation of the artistic object. in fact, as well known, the precious items were always object of treasuring, trades, spoils of war, reaching places far from the original provenance. in this view each jewel contains information on particular geographical areas and/or different socio-cultural situations. different examples of the described cases studies help to understand the mismatch between scientific investigation and historical knowledge. but the more immediate goal is the transfer of enthusiasm for a 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1361-1379, 1997. 19. d. ferro, a. bedini, i.a. rapinesi, il recupero di elementi in oro per acconciature e capi di abbigliamento dalle necropoli di età imperiale del suburbio di roma, bollettino della unione storia ed arte n1.terza serie gennaio/dicembre 2005-2006. 20. d. ferro, le impronte dei falsari: indagini strumentali per riconoscerle, in de re metallica : dalla produzione antica alla copia moderna, l’erma di bretschneider, roma 2006. 21. d. ferro, e. formigli, a. pacini, d. tossini, la saldatura nell’oreficeria antica, libro edizioni kappa, roma, 2008. 22. d. ferro, perizia tecnica e sapere scientifico nel gioiello antico, in ornamenta 3 ante quem soc. coop. isbn 978-88-7849-056-7 alma mater studiorum università di bologna, 2011, 353-368. 23. d. bagault , t. borel , m.f. guerra m. f., les bracelets articulés de la collection campana, in trésors antiques, bijoux de la collection campana, f. gaultier e c. metzger eds., musée du louvre, 2006. 24. r. baines , technical antecedents of early hellenistic disc and pendant ear ornaments, in the art of the greek goldsmith, eds d. williams, london, trusttes of the british museum 1998. 25. m.f. guerra, fingerprinting ancient gold with proton beams of different energies, nuclear instruments and methods in physics research b 226, 2004, 185-198. 26. d. ferro d., e. formigli, a. pacini, d. tossini, experimental archaeology approach to the study of “copper salt” weldings, in archaeometallurgy in europe, milano 2002. 27. j. ogden, classical gold wire: some aspects of its manufacture and use, in classical gold jewellery and the classical tradition, j. ogden and d. wakeling eds., society of jewellery historians 5, 1991. 28. d. ferro, v. virgili, a. carraro, e. formigli, l. costantini, a multi-analytical approach for the identification of technological processes in ancient jewellery. archeosciences, revue d’archeometrie 33, 2009, 351-357. 29. j. ogden, la riscoperta dell’arte perduta alessandro castellani e la ricerca della precision classica, in i castellani e l’oreficeria archeologica italiana, l’erma di bretschneider, roma, 2005, 159-176, isbn 88-8265354-4 30. la fibula prenestina, bullettino di paletnologia italiana, istituto poligrafico e zecca dello stato vol. 99, 2011. 31. r. bloch, à propos des inscriptions latines les plus anciennes, in acta of the fifth international congress of greek and latin epigraphy, cambridge 1967, cambridge, 1971, 175-181. 32. d.ferro, e.formigli, risultati delle recenti indagini archeometriche sulla fibula di manios, in la fibula prenestina, bullettino di paletnologia italiana, istituto poligrafico e zecca dello stato vol. 99, 2011, 43-72. 33. w.s. rapson, structure and mechanical properties of carat gold jewellery alloys, in gold bulletin 20 (4), 1987, 90. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe substantia. an international journal of the history of chemistry 3(2) suppl. 6: 13-24, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-511 citation: a. di vincenzo, m. a. floriano (2019) visualizing solubilization by a realistic particle model in chemistry education. substantia 3(2) suppl. 6: 13-24. doi: 10.13128/substantia-511 copyright: © 2019 a. di vincenzo, m. a. floriano. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. visualizing solubilization by a realistic particle model in chemistry education antonella di vincenzo, michele a. floriano* università degli studi di palermo, dipartimento di scienze e tecnologie biologiche, chimiche e farmaceutiche, viale delle scienze, ed. 17, 90128 palermo, italy. *e-mail: michele.floriano@unipa.it abstract. an application for the visualization of the mixing process of two different types of structureless interacting particles is presented. the application allows to demonstrate on a qualitative basis, as well as by quantitatively monitoring the time evolution of the fractions of aggregates of different sizes, that the formation of a homogeneous mixture is the result of favorable solute-solvent interactions as well as by temperature. it is suggested that, along with the use of suitable macroscopic examples, visualizations by the present application are useful in elucidating concepts related to miscibility/solubility. the application is based on a two-dimensional realistic dynamic model where atoms move because of their thermal and interaction potential energies and their trajectories are determined by solving numerically newton’s laws according to a molecular dynamics (md) scheme. for this purpose, a web-based md engine was adapted as needed. it is suggested that, when possible, using a realistic simulation rather than simple animations offers several advantages in the visualization of processes of interest in chemistry education. first of all, in a simulation the outcome of the process under study is not set a priori but it is the result of the dynamic evolution of the system; furthermore, specific parameters can be systematically varied and the effects of these changes can be investigated. the application can be used at different levels of detail and in different instruction levels. qualitative visual observations of the obtained mixtures are suitable at all levels of instruction. systematic investigations on the effect of changes in temperature and interaction parameters, suitable for senior high school and college courses, are also reported. keywords. chemistry education, intermolecular interaction, mixtures, molecular dynamics, particle model, solubility. introduction the particle model of matter has been extensively used in the past to interpret and visualize different kinds of chemistry processes and phenomena for education purposes also pointing out its shortcomings as a potential source of misconceptions.1-15 an effective way of introducing the particle model of matter, in our opinion, is to quote a quite famous sentence16 by richard feynman (19181988), nobel laureate in physics in 1965: 14 antonella di vincenzo, michele a. floriano if, in some cataclysm, all of scientific knowledge were to be destroyed, and only one sentence passed on to the next generations of creatures, what statement would contain the most information in the fewest words? i believe it is the  atomic hypothesis  (or the atomic  fact, or whatever you wish to call it) that  all things are made of atoms—little particles that move around in perpetual motion, attracting each other when they are a little distance apart, but repelling upon being squeezed into one another. in that one sentence, you will see, there is an  enormous  amount of information about the world, if just a little imagination and thinking are applied. the above sentence suggests that the main ingredients to be stressed and clarified are: existence of discrete particles, motion and interactions. these concepts are equally important and they must be all present in any exhaustive implementation of the particle model for education purposes but they should be introduced gradually in a process of progressive development of the model inspired by the comparison between its predictions and experimental evidences. in particular, when only still pictures are used, the dynamic properties of matter are inevitably lost in spite of the fact that they are as important as structural considerations in determining the system overall behavior. this is important for physical properties, where no changes in chemical identity of the particles are involved, as well as for chemical transformations. due to the continuing progress in computing power and in modelling software, in addition to advanced tools for the visualization of molecular structures, many different dynamic visualization tools have become readily available, either on the web or stand-alone, even for popular devices such as tablets and smartphones.17-23 however, in most animations,22, 24-29 particle motion is defined in a more or less arbitrary way. realistic dynamic models are seldom used for education purposes.30-35 a computer application for the visualization of the aggregation and growth process of nanoparticles by a molecular dynamics (md) realistic model has been recently presented.36 in the same study, the advantages of adopting, when possible, a molecular simulation perspective rather than using simple animations have been discussed. in this work, we preset an application, based on the same realistic model, designed to introduce a progressive development of the particle model for visualization and education objectives. the application was specifically implemented for elucidating solubility, i.e. the phase behavior of a two-components mixture of different particles. after a brief summary of the molecular dynamics (md) method, the application is discussed by following a step-by-step sequence leading to its final objective. the molecular dynamics method in the md simulation method, a fixed number of atoms/molecules move in a given volume and behave as classical objects. their motion is the consequence of both thermal and interaction potential energies. the particle motion is ruled by newton’s classical laws: mir̈i = – ∇i(r1, r2, ……, rn) (1) where ri is the position vector of the i-th atom and mi is its mass. hence, in order to calculate the trajectory of each atom, one needs to solve numerically 3 second order differential equations for each time step dt. as a consequence, for the design of an md simulation, substantial computing and programming abilities are required. however, as already pointed out36 and as done in the present work, an efficient and easy to use webbased resource37 can be used. the interested reader can find full details about md elsewhere.31, 38-40 in what follows, we will limit the discussion to the dynamic description of a set of n interacting structureless atoms. in the case under consideration, an appropriate form of the interaction energy is given by the so-called lennard-jones (lj) potential: (2) ¹ é ùæ ö æ ö ê ú= -ç ÷ ç ÷ç ÷ ç ÷ê úè ø è øë û !i j i j ij ij σ σ u ε r r 12 6 , , 4 (2) (3) ¹ = å! i j i j i j u u , , , 1 2 (3) where rij is the distance between the i-th and j-th atom, ε is a parameter related to the attractive strength and σ is the atomic diameter corresponding to the contact distance. as a consequence, the total potential energy is calculated as the sum of all pairwise contributions defined by equation 2. in this equation, the first term, sharply increasing with decreasing interparticle distance, is attributable to repulsions at contact distances whereas the negative term represents long-range attractions. in order to start an md simulation, one has to define initial positions and velocities of each particle. a common choice is to place the n particles in random positions of the simulation cell with a velocity distribution close to that given by the maxwell-boltzmann particle distribution41: f v m k t v exp m v k t i b i i i b � � � � � � � � � � � � � � � �4 2 2 3 2 2 2 � � / (4) where f (v) is the probability distribution of speed, mi and vi are the mass and the component of the velocity 15visualizing solubilization by a realistic particle model in chemistry education of the i-th atom, t is the temperature, kb is boltzmann’s constant. the md procedure consists in solving equation 1 for each atom at a given time step and iterating for successive discrete time steps, thereby producing a time sequence of configurations. particle model implementation in this work, we present a computer application42 which uses molecular workbench (mw), an open-access web-based general purpose md engine developed by the concord consortium.37 this java based platform provides 2d and 3d classical molecular dynamics engines. in addition to ready-made examples, the user can design and customize new models or activities. full details about the computation environment are given elsewhere.35 in the use of the application, the first step is to illustrate the opening sentence in feynman’s statement mentioned in the introduction: things are made of atoms— little particles that move around in perpetual motion. when the application is first started, at the top of the page, the user is presented with an empty container: a 100 x 100 x 100 å3 cell. an arbitrary number n (0 ≤ n ≤ 500) of identical monoatomic structureless particles with diameter σ = 2.0 å and mass m = 20 gmol-1, can be placed in random positions of the simulation cell by clicking on the appropriate control after selecting the desired number of particles. it is important to specify that these particles behave as tiny hard spheres and, as a consequence, their shape and size cannot change. after selecting the desired value of the temperature (100 ≤ t ≤ 1000), by clicking on the “run the model” button, the simulation will start and the particles will move by following newton’s laws of motion and undergoing virtually elastic collisions among them. in this case, no longrange attractive interactions were set, i.e. the ɛ value in equation 2 was set to a very small value (ɛ = 0.01 ev). as a consequence, it can be easily observed that, between collisions, particle motion is unaffected by the presence of the other particles. students should be encouraged to observe and describe the behavior of the system and, if desired, the instructor may ask appropriate questions in order to assess students’ understanding. for example, in lower secondary school classes, students might be asked to suggest the nature of the medium in which the particles are moving or whether there might be a tangible consequence of the particle collisions on the container walls. at this stage, other possible qualitative observations that the instructor might consider to initiate, deal with the effect of changing the temperature on particles velocities and/or that of changing the number of particles in the given (fixed) volume on the empty space available to the particles. this latter concept is connected to those of compressibility and density of gases. the instructor will decide the level of the discussion based on the students’ background. it is important to stress that, in this preliminary phase, students should be mainly asked to observe the phenomena on their own and address possible problematic situations appropriately proposed by the instructor. from now on, all further demonstrations by the current application will be implemented in a 2d environment. this choice is justified by the fact that the application should be run interactively and students should be put in the position to observe significant results in a reasonable time. in an md simulation, the most time-consuming step is the double loop (see equation 3) in which the interactions between each particle and its neighbors are calculated. the number of terms to be calculated scales roughly as n2. as a consequence, computing time increases quadratically with n. for this reason, it is important to keep the number of atoms n as small as possible. by adopting a 2d environment, it is possible to reduce drastically the number of particles to be included in the simulation without any significant loss in physical realism, at least for the phenomena and concepts here considered. in the application, the second demonstration, at the bottom of the page, is designed to study in more detail a few of the concepts already introduced. in particular, in addition to their number, the size and mass of the atoms can be changed within specified ranges. different particle colors are used when their mass is changed, in order to indicate that the type of particles has changed. at this point, a definition of substance at the submicroscopic level can be introduced as a portion of matter constituted by identical particles. particles of a given substance, then, are identical but they are different from those of a different substance. thus, a mixture of different substances contains particles of different types. it might be objected that a mass change without a corresponding change in atomic size is unlikely. however, at this stage, it was chosen not to stress the correspondence between atomic properties and their chemical identity. in our opinion, this correspondence will come into play later when elements and periodicity will be introduced. once aga i n, i n i nt roduc tor y science/chem istry instruction (upper primary and lower secondary school classes), effects due to changes in atomic properties (size and mass) and temperature can be investigated on a qualitative basis. in upper high school and introductory university courses, a more quantitative 16 antonella di vincenzo, michele a. floriano approach can be adopted. in this part of the application, it is possible, for example, to calculate the maxwell-boltzmann (see equation 4) speed and velocity distributions. it might be recalled that the difference between the two functions is that, in the former case, one considers a scalar quantity, i.e. the module of the velocity vector. in figures 1 and 2, results obtained with the specified parameters demonstrate that the most probable atomic speed increases with increasing temperature and decreasing atomic mass. this evidence illustrates the connection between temperature and the average kinetic energy of the atoms. the instructor will be able to tune the level of this description to the students’ background even recalling basic concepts about the laws of motion as needed. the corresponding velocity distribution function that can be calculated by activating the appropriate button in the application, will exhibit a maximum at v ≈0 indicating that, since atoms are moving in all directions, there is no net resulting component of the velocity vector. at this point of the teaching sequence, interactions among particles can be introduced. going back to feynman’s quote: …attracting each other when they are a little distance apart, but repelling upon being squeezed into one another. therefore, the interaction energy is negative (attractive) when atoms are at intermediate distances and it becomes positive (repulsive) when they get close to each other. when interatomic average distances are large, the interaction potential approaches zero. for the case under consideration here, a convenient form of the interaction potential is that given by equation 2. the introduction of interactions and the balance with atomic average kinetic energy leads to discussions related to physical states of matter, in particular the existence of condensed (solid and liquid) phases and phase transformations. this topic is not part of the present work and it will not be discussed further. however, many different dynamic applications can be found in the literature. in particular, an explicit connection between interactions, particle motion and phase behavior is available in a recent study36 as well as ready-made examples in the mw website.43, 44 mixtures and solubility the concept of solubility is one of the most common themes in chemistry and, at the same time one of the most difficult to grasp by students on a conceptual basis. anyone is familiar with the macroscopic difference between a solution, such as the result of the addition of a not too large amount of sodium chloride to water, and the result obtained by mixing olive oil and water. however, things get complicated when rigorous definitions are sought. these definitions, on the macroscopic level, essentially involve the concept of phase and, thus, a homogeneous mixture (a solution), consists of a single phase whereas, in a heterogeneous mixture, at least to different phases can be detected. on the submicroscopic scale, in spite of its potential conceptual hurdles, the particle model offers, in our opinion, a more logical figure 2. maxwell-boltzmann probability distribution of atomic velocities (see eq. 4) at t = 300 k for a set of 200 atoms with mass m specified in the legend. the md time step was 1 fs. figure 1. maxwell-boltzmann probability distribution of atomic velocities (see eq. 4) at the temperatures specified in the legend for a set of 200 atoms of mass m = 20 g/mol. the md time step was 1 fs. 17visualizing solubilization by a realistic particle model in chemistry education representation, particularly when the dynamics are also taken into account. in this perspective, in a mixture of particles of type a and type b, a phase is recognizable as a cluster of b particles dispersed within a particles. incidentally, a system containing different phases of the same substance, such as ice floating in liquid water, can be described as clusters of particles of a given type in a given structure within particles of the same type in a different structure. the factors affecting the stability of a mixture of two different substances and determining solubility/miscibility can be rationalized by analyzing the thermodynamics of the mixing process.45,46 this topic has been also the object of many studies for education purposes.47-52 in short, entropy always favors mixing whereas reciprocal particle interactions between like and unlike species can influence the process in both directions. in addition, temperature plays a role in that, in most cases, the mixing of simple systems is favored by an increase in the temperature. all the above ideas have been gathered in the second page of the present application. this page also contains a link to a brief section on general background concepts. when the application is first started, the user is presented with an empty container: a 60 x 60 å2 cell. a barrier divides the cell into two compartments where a specified number of equally sized (σ = 1.4 å) a (blue) and b (green) particles of the same mass (m = 40 gmol-1) can be placed. the user selects the total number of atoms n (50 ≤ n ≤ 200) and the fraction (0-0.5) of b atoms. when this is done, the specified number of b atoms is placed, in random positions, on the left hand side of the barrier; the number of a atoms, resulting from the specified b fraction, is placed, in random positions, on the right hand side of the barrier. in figure 3, a typical configuration of a sample simulation with the specified parameters is shown. furthermore, the strength, ɛ (ev) of the attractive part of the lj potential (see equation 2) between all particles will have to be set. the user can set independently the strength of the potential between a particles (ɛ a-a), between b particles (ɛ b-b) and between a and b particles (ɛ a-b). finally, a specific control allows to set the temperature t of the simulation. when all parameters have been selected, the simulation will start by clicking on the “run the model” button. by clicking on the “mix” button, the gate between the two compartments opens and the two groups of particles mix. during the simulation, the plot on the right will display the time evolution of the fractions, with respect to the total number of b particles present as b monomers, b pairs and b atoms present in larger aggregates. in this plot, the red line, initially set at a value of 1, drops to 0 when the gate is opened. in figure 4, results of a sample simulation performed with the specified parameters are shown. it can be seen that, when all interaction parameters are very small (ɛ ≈ 0 ev), the driving force to mixing is entropy and a homogeneous distribution of b particles in the a solvent is quickly obtained. by running the simulation at different thermal conditions, it is easy to prove that temperature influences the rate of the mixing progress but not its outcome. in figure 5, results from a simulation performed with parameters favoring b-b interactions are shown. it can be seen that, after the barrier is removed, the substances mix but, because of preferential b-b interactions, the solute is present as aggregates of different sizes within the a matrix. by prolonging the simulation, it can be observed that b clusters tend to merge with each other forming larger aggregates, thereby maximizing b-b contacts and minimizing energy. in this case, a heterogeneous mixture of b in a is obtained. the same qualitative conclusions are obtainable from the plot on the right of the same figure: a progressive decrease in the fraction of b monomers corresponds to an increase of the fraction of b aggregates. figure 3. initial configuration of a mixture of a (blue) and b (green) structureless equally sized (σ = 1.4 å) particles in a 60x60 å2 simulation cell. the total number n of particles was 200 and the fraction of b particles was 0.2. at the beginning of the simulation, a and b particles are contained in two compartments separated by the impermeable barrier also shown. 18 antonella di vincenzo, michele a. floriano on the contrary, as shown in figure 6, by adopting conditions favoring a-b interactions a homogeneous dispersion of b in a is quickly obtained. the plot on the right demonstrates that the vast majority of b atoms is present as monomers; a few pairs and slightly larger aggregates are also present. the effect of temperature is demonstrated in figure 7. in this case, the heterogeneous mixture obtained under the conditions of figure 6, was heated to two different temperatures. heating favors the formation of a homogeneous system as shown by the progressive “melting” of the b aggregates. this conclusion is supported by the plot on the right showing a progressive increase in the fraction of b monomers at the expense of large b aggregates. as an additional evidence in support of the previous conclusion, in figure 8 results obtained at t = 500 k from a simulation started from an initial configuration similar to that of figure 3 are shown. at this temperature, contrary to what observed at t = 300 k (see figure 5), a homogeneous b in a mixture is obtained. in the plot on the right, it is demonstrated on a quantitative basis that, throughout the simulation, the vast majority of b atoms is present as monomers. discussion the present application has been designed to introduce the basic concepts of the particle model of matter and, in particular, its dynamic properties. it has been pointed out elsewhere36 that using a realistic model for describing the motion of atoms and molecules, rather than using animations based on more or less arbitrary successions of still pictures, carries important advantages from an education viewpoint. the most relevant advantage is that the phenomenon under study is not a preconceived idea but, rather, it is the result of the physical laws ruling the behavior of the system. with this in mind, as explained above, the application was designed as a realistic md simulation in which simple structureless monoatomic particles move according to newtown’s laws of motion. after a preliminary step, aimed at familiarizing the students with the behavior of a system of non-interacting particles, a realistic interaction potential (see equation 2) was introduced and attention was mainly focused on the properties of mixtures. concepts related to solubility and the processes determining the formation of homogeneous or heterogeneous mixtures are very important in chemistry and, at the same time, they are among the most diffigure 4. left: snapshot of the configuration obtained after 200 ps of a simulation for the mixture described in figure 3 at t = 300 k and no interactions between the particles. right: time evolution of the fraction of b monomers, pairs of b atoms and total aggregated b atoms present in clusters of more than 2 b atoms for the same simulation. the time at which the red line sharply drops to zero indicates when the gate shown in figure 3 was opened and the particles were allowed to mix. the md time step was 1 fs. 19visualizing solubilization by a realistic particle model in chemistry education ficult to grasp by the students. a simplified representation, as that adopted in the present work, might be useful because it attributes to different interactions between solute and solvent particles the origin of the dissolution process. since the adopted model is based on explicit physical laws, it is possible to change specific parameters and observe the effects of these changes on the phenomenon under investigation. in the case under consideration, i.e. the mixing process of particles of different types, in addition to parameters defining the identity of the particles (size and mass), the relevant variables are temperature and attractive straight parameters. as a consequence, the application was designed to focus on the latter. results reported in figure 4 demonstrate on a qualitative basis, that, when no interactions are present, two different substances will mix at any temperature because there is no reason for particles of one type to favor regions reach of particles of the same type. this idea is a qualitative way of describing the spontaneous process which, from a state consisting of two separate a and b substances, leads to a homogeneous a-b mixture, with a corresponding entropy increase; the instructor will be figure 5. left: snapshots of the configurations obtained after 200 ps (top) and after 400 ps (bottom) of a simulation for the mixture described in figure 3 at t = 300 k. the interaction parameters (ev) were: ɛa-a = 0.01, ɛb-b = 0.1 and ɛa-b = 0.05. right: time evolution of the fraction of b monomers, pairs of b atoms and total aggregated b atoms present in clusters of more than 2 b atoms for the same simulation. the time at which the red line sharply drops to zero indicates when the gate shown in figure 3 was opened and the particles were allowed to mix. the md time step was 1 fs. 20 antonella di vincenzo, michele a. floriano able to calibrate the discussion also based on the school level. for high school students, the previous simple explanation will be sufficient, whereas in general chemistry university courses, more detailed references to thermodynamics laws can be made. the results reported in figures 5 and 6 demonstrate the effect of introducing preferential interaction energies between all particle pairs on the resulting mixture. when attractions between solute particles are stronger than those between solute and solvent particles, a heterogeneous mixture will originate in which aggregates of solute particles (a separate phase) are present in a matrix of solvent particles. on the contrary (see figure 6), when attractions between solute and solvent particles are stronger than those between solute particles, a homogeneous system, i.e. a uniform distribution of solute particles in the matrix of solvent particles, is produced. it is important to underline that, in the two cases just described, the temperature is the same. in other words, the balance between kinetic and potential energies is unchanged. in secondary school chemistry instruction, where very limited thermodynamics concepts are present, the above discussion can be based on considerations similar to those used for explaining transformations of the physical state of a pure substance. particles (different or alike) attract each other and, as a consequence, they tend to “stick”. at the same time, thermal motion, which is related to the temperature, pushes them apart. therefore, temperature plays against aggregation and the net result of the competition between these two energy contributions, for a given substance and at a fixed temperature, determines the stable state of the system. low temperatures favor aggregation and so do large interparticle attractions. the above discussion is further supported by the results reported in figure 7, where the temperature was raised and the consequent dissolution of the aggregates, formed at a lower temperature, was obtained. raising the temperature had the effect of shifting the balance between kinetic and potential energies in favor of the former. the same conclusion can be reached by inspection of the results reported in figure 8. in this case, the energy balance was in favor of the kinetic term from the beginning of the simulation and, as a consequence, no b-b aggregation was observed. in summary, in our opinion, the application here presented offers the opportunity of letting the students observe, in an interactive fashion, the basic submicroscopic details underlying a mixing process. it is possible to use the application at different school levels: from the simple qualitative observation of the dynamic configurations, suitable for secondary school classes, to gradually figure 6. left: snapshot of the configuration obtained after 200 ps of a simulation for the mixture described in figure 3 at t = 300 k. the interaction parameters (ev) were: ɛa-a = 0.01, ɛb-b = 0.05 and ɛa-b = 0.1. right: time evolution of the fraction of b monomers, pairs of b atoms and total aggregated b atoms present in clusters of more than 2 b atoms for the same simulation. the time at which the red line sharply drops to zero indicates when the gate shown in figure 3 was opened and the particles were allowed to mix. the md time step was 1 fs. 21visualizing solubilization by a realistic particle model in chemistry education more detailed semi-quantitative analysis, also making use of the time evolution of the fractions of the different aggregated species present in the mixture, more appropriate for college general chemistry courses. in any case, students should be made aware that the observed dynamics are the result of a physically sound model. actually, in most cases, dynamic illustrations of the sub-macroscopic world generated by animations might be indistinguishable from those produced by a realistic simulation. however, students should be made aware of the difference. furthermore, the java based md engine37 here adopted makes it possible to modify and adapt the existing code to special situations and, as a consequence, it is possible to let students’ design computer experiments in introductory computational chemistry courses. needless to say, the physical description, despite its realistic nature, is very simplified. we propose that adopting a 2d representation does not introduce serious limitations as far as the physical reliability of the model is concerned. however, the very simplified nature of the interaction potential and, for example, the absence figure 7. left: snapshots of the configurations obtained after 200 ps (top) and after 400 ps (bottom) of a simulation started from the configuration obtained after 400 ps at the conditions of figure 5. the mixture was heated at t = 400 k (top) and t = 500 k (bottom). the interaction parameters (ev) were: ɛa-a = 0.01, ɛb-b = 0.1 and ɛa-b = 0.05. right: time evolution of the fraction of b monomers, pairs of b atoms and total aggregated b atoms present in clusters of more than 2 b atoms for the same simulation. the two arrows indicate the times when the temperature of the simulation was set to the specified values. the md time step was 1 fs. 22 antonella di vincenzo, michele a. floriano of specific interactions among solvent particles, is not suitable for representing special circumstances, such as aqueous solutions, where changes in solvent structure due to the presence of the solute are crucial. it might be recalled, for example, that these structural rearrangements might also lead to a temperature effect on solubility opposite to that predicted by the present model. nevertheless, such complications might be considered as second order effects with respect to the basic ideas here developed. conclusion the particle model of matter is a powerful tool for describing the structure and the dynamic properties of matter at the submicroscopic level. with the present application, in our opinion, it is possible to demonstrate in a quite effective way that the study of the dynamic behavior is very often crucial in the understanding of fundamental concepts in chemistry. the adoption of a realistic model, based on classical newtown’s laws of motion, rather than using arbitrary animations, offers the added advantage of producing a physically meaningful picture as the outcome of the application of these laws rather than as a known a priori result. as a consequence, system parameters can be freely varied and the effects of these changes on the outcome of the simulation can be systematically investigated. depending on the students’ background and degree of interest, the instructor will be able to calibrate observations and the subsequent discussion as needed. even if students are not fully familiar with classical newton’s laws of motion, appropriate qualitative analogies based on common life situations, such as the motion of macroscopic bodies, could be used to clarify these concepts. in more advanced instruction levels, such as introductory general chemistry university courses, students are certainly acquainted with the physics concepts and basic math tools needed for making full use of the application. finally, it is worth mentioning that the present model and application is particularly suitable for the study of physical transformation of matter. the structureless nature of the particles rules out the possibility of changes in their chemical identity. chemical transformations require more refined models. figure 8. left: snapshot of the configuration obtained after 200 ps of a simulation started from the configuration shown in figure 3 at t = 500 k. the interaction parameters (ev) were: ɛa-a = 0.01, ɛb-b = 0.1 and ɛa-b = 0.05. right: time evolution of the fraction of b monomers, pairs of b atoms and total aggregated b atoms present in clusters of more than 2 b atoms for the same simulation. the time at which the red line sharply drops to zero indicates when the gate shown in figure 3 was opened and the particles were allowed to mix. the md time step was 1 fs. 23visualizing solubilization by a realistic particle model in chemistry education references 1. d. l. gabel, k. v. samuel, d. hunn, journal of chemical education 1987, 64, 695 10.1021/ed064p695 2. d. l. gabel, journal of chemical education 1993, 70, 193 10.1021/ed070p193 3. p. riani, la chimica nella scuola 1995, xvii, 79-85 (italian). 4. e. roletto, p. g. albertazzi, a. regis, «la chimica nella scuola» 1996, 2, 37-47 (italian). 5. m. j. sanger, journal of chemical education 2000, 77, 762 10.1021/ed077p762 6. g. harrison allan, treagust david, in chemical education: towards research-based practice, (eds.: j.k. gilbert, o. de jong, r. justi, d.f. treagust, j. h. v. driel), springer, dordrecht, science & technology education library, 2002, vol. 17, pp. 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(italian) 14. a. h. johnstone, journal of computer assisted learning 1991, 7, 75-83 10.1111/j.1365-2729.1991.tb00230.x 15. a. c. bliss, color research & application 1993, 18, 141-142 10.1002/col.5080180214 16. r. p. feynman, r. b. leighton, m. sands, in the feynman lectures on physics), addison–wesley, 1963, vol. 1, chap. 1, pp. 1 17. n. charistos, m. p. sigalas, l. antonoglou, in leading edge educational technology, (eds.: thomas b. scott, j. i. livingston), nova science publishers, 2008, chap. 4, pp. 105-131 18. m. j. sanger, e. campbell, j. felker, c. spencer, journal of chemical education 2007, 84, 875 10.1021/ ed084p875 19. j. p. suits, m. j. sanger pedagogic roles of animations and simulations in chemistry courses. american chemical society; oxford university press, 2013, vol. 1142 20. l. huang, in chemistry education. best practices, opportunities and trends, (eds.: javier garcía‐martínez, e. serrano‐torregrosa), john wiley & sons, 2015, chap. 25, pp. 621 21. l. l. jones, r. m. kelly, in sputnik to smartphones: a half-century of chemistry education, (eds.: m. v. orna), 2015, vol. 1208, chap. 8, pp. 121-140 22. r. m. kelly, s. akaygun, s. j. r. hansen, a. villaltacerdas, chemistry education research and practice 2017, 18, 582-600 10.1039/c6rp00240d 23. r. tasker, journal of chemical education 2016, 93, 1152-1153 10.1021/acs.jchemed.5b00824 24. k. a. burke, t. j. greenbowe, m. a. windschitl, journal of chemical education 1998, 75, 1658 10.1021/ ed075p1658 25. r. tasker, r. dalton, chemistry education research and practice 2006, 7, 141-159 10.1039/b5rp90020d 26. r. m. kelly, l. l. jones, journal of chemical education 2008, 85, 303 10.1021/ed085p303 27. j. l. plass, b. d. homer, e. o. hayward, journal of computing in higher education 2009, 21, 31-61 10.1007/s12528-009-9011-x 28. s. akaygun, l. l. jones, chemistry education research and practice 2013, 14, 324-344 10.1039/c3rp00002h 29. k. lancaster, e. b. moore, r. parson, k. k. perkins, in pedagogic roles of animations and simulations in chemistry courses, (eds.: m. j. s. jerry p. suits), american chemical society, oxford university press, 2013, vol. 1142, chap. 5, pp. 97-126 30. m. j. ramos, p. a. fernandes, a. melo, journal of chemical education 2004, 81, 72 10.1021/ed081p72 31. o. f. speer, b. c. wengerter, r. s. taylor, journal of chemical education 2004, 81, 1330 10.1021/ ed081p1330 32. q. xie, r. tinker, journal of chemical education 2006, 83, 77 10.1021/ed083p77 33. k. bolton, e. saalman, m. christie, å. ingerman, c. linder, chemistry education research and practice 2008, 9, 277-284 10.1039/b812417p 34. p. r. burkholder, g. h. purser, r. s. cole, journal of chemical education 2008, 85, 1071 10.1021/ ed085p1071 35. c. xie, a. pallant, in models and modeling. models and modeling in science education, (eds.: m. s. khine, i. m. saleh), springer, dordrecht, 2011, vol. 6, pp. 121-139 36. a. di vincenzo, m. a. floriano, journal of chemical education 2019, 10.1021/acs.jchemed.9b00330 24 antonella di vincenzo, michele a. floriano 37. c. xie visual, interactive simulations for teaching & learning science. http://mw.concord.org/modeler/ (accessed febrary 2019) 38. m. p. allen, d. j. tildesley computer simulations of liquids. o. s. p. n. york, clarendon press new york, ny, usa ©1987, 1987 39. l. h. eckler, m. j. nee, journal of chemical education 2016, 93, 927-931 10.1021/acs.jchemed.5b00587 40. c. sweet, o. akinfenwa, j. j. foley, journal of chemical education 2018, 95, 384-392 10.1021/acs. jchemed.7b00747 41. h. j. w. müller-kirsten basics of statistical physics. 42. a. di vincenzo, m. a. floriano particle model introduction. http://mw2.concord.org/tmp. jnlp?address=http://www1.unipa.it/flor/mw/mixtures_1.cml (accessed july 2019) 43. investigating interactions and energy. http://mw2. concord.org/public/student/motionandforce/interaction.cml (accessed july 2019) 44. a phase lab. http://mw2.concord.org/public/student/ stateofmatter/explorephase.cml (accessed july 2019) 45. c. h. p. lupis chemical thermodynamics of materials north holland, new york, 1983. 46. liu is., m. i., in rational thermodynamics), springer, new york, ny, new york, ny, 1984, chap. 5b, pp. 264-285. 47. e. adadan, chemistry education research and practice 2014, 15, 219-238 10.1039/c4rp00002a 48. g. ashkenazi, g. c. weaver, chemistry education research and practice 2007, 8, 186-196 10.1039/ b6rp90029a 49. r. p. bonomo, g. tabbì, l. i. vagliasindi, journal of chemical education 2012, 89, 545-547 10.1021/ ed2003143 50. a. derman, i. eilks, chemistry education research and practice 2016, 17, 902-913 10.1039/c6rp00084c 51. c. tosun, y. taskesenligil, chemistry education research and practice 2013, 14, 36-50 10.1039/ c2rp20060k 52. h.-d. barke, a. hazari, s. yitbarek, in misconceptions in chemistry addressing perceptions in chemical education), 2009, pp. 37-66. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 6 2019 firenze university press where does chemistry go? from mendeelev table of elements to the big data era luigi campanella1, laura teodori2,* visualizing solubilization by a realistic particle model in chemistry education antonella di vincenzo, michele a. floriano* chemistry as building block for a new knowledge and participation stefano cinti tissue engineering between click chemistry and green chemistry alessandra costaa#, bogdan walkowiakb, luigi campanellac, bhuvanesh guptad, maria cristina albertinie* and laura teodori a, f* chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity. sara tortorella,1,2,* alberto zanelli,2,3 valentina domenici2,4 substantia. an international journal of the history of chemistry 3(2) suppl. 4: 13-25, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-503 citation: g. boeck (2019) julius lothar (von) meyer (1830-1895) and the periodic system. substantia 3(2) suppl. 4: 13-25. doi: 10.13128/substantia-503 copyright: © 2019 g. boeck. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck institute of chemistry at the university of rostock, d-18051 rostock e-mail: gisela.boeck@uni-rostock.de abstract. the logo of the “international year of the periodic table of chemical elements” (iypt) shows only dmitri i. mendeleev (1834-1907) and none of the other scholars who were closely related with the discovery of the classification of elements. as early as 1864 the german physical chemist lothar meyer used a table to explain the “peculiar regularities” that were found among the atomic weights; by the end of that decade he had considered more elements and improved the system. among other discoverers of the periodicity, meyer and his colleague karl seubert (1851-1942) determined and recalculated atomic weights. this essay depicts the biography of lothar meyer and evaluates his contributions to the development of a classification system for chemical elements in several steps, to the periodic arrangement of elements. finally, meyer’s opinion of the use of the periodic tables in teaching and organizing the material in courses on inorganic chemistry is presented. keywords. julius lothar (von) meyer, systems of elements, periodic table, use in teaching process introduction it was 150 years ago – on 17 february 1869 (julian calendar) or 1 march 1869 (gregorian calendar) – that dmitri ivanovič mendeleev (1834-1907) arranged a two-dimensional grid of the elements. for this reason, the united nations general assembly and unesco proclaimed 2019 as the “international year of the periodic table of chemical elements” (iypt). the iypt logo shows mendeleev’s portrait. but in the 1860s there were also other scholars who were thinking about a classification of elements. among these meyer stands out as the most known contender to mendeleev. his endeavor was actually also in connection with writing a textbook like mendeleev. this paper is dedicated to the contributions of meyer to the periodic system. it presents his biography as well as his work in connection with the classification of elements, before providing a brief analysis of meyer’s train of thought on periodicity and the role the periodic system can play in chemistry teaching. through this example, we aim to illustrate that while it does not diminish mendeleev’s accomplishments, it does frame these accomplishments in a wider historical context where many similar pursuits were undertaken by the fellow chemists of his time.1 14 gisela boeck lothar meyer – his biography julius lothar meyer (fig. 1) was born in varel, germany on 19 august 1830, in the current district of friesland in lower saxony.2 the gymnasium in varel bears his name today. lothar’s father, heinrich friedrich august jacob meyer (1783-1850), was a physician. he and his wife, anna sophie wilhelmine biermann (1800-1853), had at least eight children, most of whom died young. only three of lothar’s siblings reached adulthood, oskar august emil meyer (1834-1909), who became a professor of physics in breslau and was wellknown for his work on viscosity, eugen theodor meyer (1836-1890), who became a farmer, and selma corinna helmine meyer (1839-1928). initially, lothar was tutored at home. from 1841 until his confirmation he attended a citizens school (höhere bürgerschule), but his school education was interrupted due to poor health, particularly strong headaches. lothar meyer worked in a gardening nursery, regained his health, and from 1847 he was able to continue his education at the old gymnasium in oldenburg. in 1851 he passed his school leaving examination, the abitur. he decided to study medicine and to become a physician like his father, who had died in the meantime. on 8 may 1851, lothar meyer enrolled at the university of zurich, where he attended lectures in medical subjects, but also in chemistry, physics, mineralogy, geology, botany and zoology, until the end of the winter term 1852/53. he was especially interested in carl ludwig’s (1816-1895) instruction in physiology – perhaps this led to his interest in gas exchange of the blood? around easter 1853 meyer traveled to würzburg, and in february 1854 he completed his doctor of medicine with a thesis paper on the pigment cells of frogs. a year later he moved to heidelberg to work with the famous robert bunsen (1811-1899). although he was enrolled for medicine, he was more interested in chemistry. he investigated the behavior of gases in the blood, trying to determine how much oxygen, nitrogen, and carbon dioxide are in arterial blood and to establish regularities for the gas exchange. these results were summarized in the paper the gases of the blood in 1857, which he submitted to the faculty of medicine as a second doctoral thesis.3 it is unclear as to why he felt the need to complete a second dissertation, following his medical degree. even though his first paper on the frog offered poor results, there is no evidence that the faculty granted his degree coupled with an obligation for a second paper. it is also not possible to examine the archived documents in würzburg, as most were destroyed during world war ii.4 it is possible that meyer felt obliged to do this because he was aware of the poor reception of his first paper. later, in heidelberg, lothar meyer met other scientists, including friedrich beilstein (1838-1906), henry roscoe (1833-1915), hans landolt (1831-1910) and august kekulé (1829-1896). meyer remembered that kekulé presented the type-theory of charles gerhardt (1816-1856) and alexander williamson (1824-1904) to the other young chemists, even though bunsen was not interested in these new ideas.5 lothar meyer went to königsberg (today kaliningrad in russia) with his brother, oskar august emil, and landolt in the winter term 1856/57 to expand his knowledge of physics. this exposed him to the lectures of franz ernst neumann (1798-1895) about electromagnetism and the wave theory of light. he also continued his physiological research in the laboratory of gustav werther (1815-1869), he was interested in the effect of carbon monoxide on blood. these results were published in a paper which was submitted to the faculty of phifigure 1. lothar meyer. scan from k. seubert, ber. dtsch. chem. ges. 1896, 28, 1109–1146, here p. 1110. 15julius lothar (von) meyer (1830-1895) and the periodic system losophy in breslau to earn the degree dr. phil. meyer showed that carbon monoxide is attracted to blood by chemical forces. this means that the blood cannot transport oxygen. he was not able to discover which substance attracts the carbon monoxide. this phase of his education exposed meyer to analytical and physiological problems; he was educated in mathematical physics and learned about new theories in chemistry. the time in königsberg was critical for meyer’s turn to physical approaches to chemistry. franz ernst neumann is regarded as the founder of theoretical physics as a university discipline in germany. he connected the use of precise measuring devices with mathematical approaches and the use of error calculation.6 these principles were adopted by meyer. for his habilitation degree, the qualification as privatdozent, meyer worked on the development of chemical theories ranging from claude-louis berthollet (17481822) to jöns jacob berzelius (1779-1848). from easter 1859 onwards, lothar meyer supervised the chemical laboratory of the institute of physiology at the university of breslau (today wrocław in poland). he gave lectures about plant and animal chemistry, photo chemistry, gas and volumetric analysis, and he offered refresher courses on organic and inorganic chemistry.7 in september 1860 the first international conference of chemistry took place in karlsruhe. it was organized by kekulé together with karl weltzien (1813-1870) and charles adolphe wurtz (1817-1884). the goal was the clarification of the atomistic system: what is an atom, what is a molecule, but also to decide the basis for determining atomic weights. in a sparkling speech stanislao cannizzaro (1826-1910) demanded recognition and a consequent application of the theory of amadeo avogadro (1776-1856). cannizzaro also distributed prints of his sunto di un corso di filosofia chimica (short course of theoretical chemistry).8 meyer and mendeleev, who also attended the conference, were struck by this proposal that opened new perspectives. and meyer – trained both in organic and physical chemistry – started to work on molecular theory. he wrote a paper on chemical statics which he first wanted to publish in poggendorff ś annalen der physik.9 he mentioned his intention to publish it in letters to kekulé und hermann kolbe (1818-1884),10 but it seems that he later used this material for his textbook, die modernen theorien der chemie und ihre bedeutung für die chemische statik (modern theories of chemistry and its importance for the chemical statics). in the foreword to the second edition, written in august 1872, lothar meyer says that he had started with the manuscript ten years earlier.11 a letter addressed to his brother corroborates this timing.12 the book was finally published in july 1864; the second edition was issued in 1872, the following editions in 1876, 1883, and 1884. the book became more and more comprehensive, the fifth edition reaching 626 pages. there was no chance for meyer to pursue an academic career in breslau, so he took a position at the forest academy in neustadt-eberswalde, where he had many teaching tasks in the fields of mineralogy, chemistry, physics, and sometimes even botany. this left him little time for scientific work. at first he had to establish a “considerably cute laboratory from miserable cottage”.13 and he complained that he could not find research students, the students of the forest academy were only interested in finishing the chemistry classes.14 so this position posed not only issues of time – he did not have his own students to work with. in 1867 he was appointed to be professor of inorganic science at the forest academy, but in 1868 he left the academy and became a professor of chemistry and the director of the chemical laboratory at the polytechnikum in karlsruhe. there he found better working conditions, teaching only chemistry, and he had his own students for scientific work. from 1868 to 1875 meyer worked in karlsruhe; he turned a professorship in königsberg down. but his health problems had surfaced again. during the winter term 1874/75 he was released from his teaching duties, which were then assigned to august michaelis (18471916). 1876, lothar meyer received a full professorship in tübingen as the successor of rudolph fittig (1835-1910). his financial situation improved, but the most important benefit was that he had finally become a full university professor, as the polytechnic institutions had no rights to award doctorates. meyer was offered a considerably well-equipped laboratory in tübingen’s wilhelmstraße 9 (part of which is still there). meyer and his family lived on the upper floor and he refurbished some of the laboratory rooms for his research interests, improving the technical equipment.15 in tübingen meyer worked together with his colleague karl seubert on the redetermination of atomic weights. the results were published in a book in 1883. later seubert was the first biographer to write about meyer and was responsible for publishing or republishing his most important papers.16 meyer’s good working and research conditions in tübingen, his integration in the social life of this town and his state of health were reasons for turning down professorships in leipzig (1887) and breslau (1889). he received several awards, including the davy medal given to him and mendeleev on 2 november 1882, recognizing their research on the classification of elements. in 16 gisela boeck 1883 lothar meyer became an honorary member of the chemical society london; in 1887 he joined the physikalischer verein (physical society) in frankfurt/main; in 1889 the manchester literary and philosophical society. a year prior to this, in 1888, meyer had been appointed corresponding member of the mathematics and physics section of the prussian academy of science and in 1891 of the academy of science st. petersburg. in 1892 lothar meyer was knighted with the decoration of the honorable cross of the royal house of württemberg. at the start of the 1894/95 academic year, lothar von meyer was elected rector of the university tübingen: shortly after the term, on 11 april 1895, he died. his grave is in the stadtfriedhof cemetery in tübingen. lothar meyer and the classification of elements lothar meyer left his mark on multiple fields of chemistry, but this paper discusses only his activities in connection with the classification of chemical elements. the question of classification systems in chemistry came about as a consequence of the large amount of new knowledge about chemical compounds and elements at the turn from the 18th to the 19th century – especially in connection with the revival of atomic theory and the possibility to determine relative atomic weights, but also with the discovery of many new elements. the atomic weights opened the path to a classification based not only on qualitative properties but also on quantitative data.17 this was connected with attempts for a deeper understanding of the nature of elements and atoms and it was one of the scientific interests of meyer after his turn from physiological to problems of theoretical chemistry. meyer also wanted to show the interrelation between hypothesis and theories based on them.18 lothar meyer’s considerations about the nature of the elements were connected inter alia with ideas of william prout (1785-1850) and johann wolfgang döbereiner (1780-1849). early in the century, the physician prout had observed that atomic weights are whole multiples of the atomic weight of hydrogen, and later proposed that hydrogen should be the primeval matter (greek: prote hyle). the experimental possibilities for determining atomic weights had since then been improved, in consequence, it could be demonstrated already before 1850 that most atomic weights are not integers. but despite the issues with prout’s hypothesis, many scholars continued to debate these ideas throughout the 19th century and beyond. for instance, it has been suggested that ernest rutherford (1871-1937) introduced the term proton in 1920 not only for etymological reasons (greek proton = the first), but also in commemoration of william prout.19 as meyer mentions in the first paragraph of moderne theorien20, he thought that matter consists of discrete particles, the atoms. he posited that it is unclear if these are really indivisible. later meyer followed the idea that atoms consist of smaller aggregates. meyer was also influenced by the theory of triads, as first described in 181621 by johann wolfgang döbereiner, professor of chemistry in jena and well-known for his pneumatic gas lighter, the döbereiner feuerzeug. he also tried to classify around 30 elements based on their chemical analogy, such as ca, ba, sr, or cl, br, i, or li, na, k in the alkali group. he compared their atomic weights and found that the atomic weights of the middle elements of each of the series of three elements were roughly the mean value of the other two. these groups of three elements were later called triads.22 in his 4th edition of 1883, meyer established that döbereiner’s work was propagated by leopold gmelin in his handbuch der chemie.23 meyer was curious about these numerical relations and in his book moderne theorien he discusses “the peculiar regularities”24 that were found between atomic weights by döbereiner and later by many other scholars. meyer used the notion of there being an arithmetic relationship between atomic weights. he suspected that these relationships were responsible for the idea that atoms are an aggregate of smaller units. this explanation was adopted from the homologous series in organic chemistry, which are characterized by the repeated addition of constant fragments. in the first edition of moderne theorien meyer arranged fifty elements into three tables with the aim to underline the mathematical relations between the atomic weights. the first included twenty-eight elements, which were grouped consequently with respect to their increasing atomic weights and valency. he described the relations as “six well-characterized groups of elements”25 (fig. 2). meyer combined elements with the same valency and similar chemical properties. the atomic weight of the elements increases in each row from left to the right. a regular change of valency can be established – but meyer did not use the word periodicity in his text. the table also includes the differences of atomic weights of elements which were paired in the column. meyer underlined the regularity for the differences in the atomic weights. in the first rows one finds as difference nearly 16, later nearly 46 and then 87-90 which is more or less the double value of 46.26 the integration of these numerical values demonstrates again meyer’s interest in finding a similarity to the homologous series. and it is 17julius lothar (von) meyer (1830-1895) and the periodic system noteworthy that meyer uses values with one or two decimal points. it should be mentioned that the increase of atomic weight from row to row has two exceptions. although one can clearly see that tellurium has a higher atomic weight than iodine, meyer arranged te prior to i, which corresponds with the valency. the second exception in the order of increasing atomic weights is thallium which meyer placed after bi in the group of the alkaline metals with valency one. he mentioned that the difference of the atomic weights between ca and tl differs extremely from 2x46 and assumed a wrong determination in the case of tl. question marks in the table indicate meyer’s doubts concerning the correctness of some of these atomic weights. this table also contains gaps, marked with dashes. one example of such a gap concerns the precautionary prediction of the atomic weight. the element following silicon in the group of elements with valency four should have an atomic weight 44.55 higher than silicon (28.5), namely 73,05. but meyer did not discuss this prediction like later mendeleev. the difference 46 of atomic weights and the valency were also the basis for the two other tables of elements published by meyer in 1864 (fig. 3 and 4). meyer did not give an explanation why he did not place the following 22 elements in one table. we can only see that the first (fig. 3) belongs to elements with valency four and six, the second (fig. 4) to valency two, four and mixed. later meyer explained that he contemplated combining all tables in one but he was concerned with the uncertainties and potential mistakes in atomic weights.27 in fig. 4 meyer placed mn and fe on the same spot because of the similarity of the atomic weights. in the consequence he formulated two differences – the difference in the atomic weights ru-mn, and ru-fe. today, the elements of the table in fig. 2 are known as the main group of elements, those of the tables in fig. 3 and 4 are the transition elements. meyer finished his explanations by asserting that there is no doubt about a certain law (bestimmte gesetzmäßigkeit) in the numerical values of the atomic weights. he reasoned that discrepancies are linked with incorrectness of atomic weights. he wrote: we can assume that some of the discrepancies result to some extent from the incorrect determination of atomic weights. but this is not valid for all. it is not fair – as is done often – to correct or to change the empirically estimated atomic weights until the experiment has delivered more exactly determined values.28 by 1866 at the latest, meyer had started to examine the atomic weights with the claim of more correctness. when he arrived in karlsruhe to take his teaching duties, he had no time for this task; it was only in tübingen where he could continue this research program, together with seubert. during his time in eberswalde, meyer was already working on the second edition of moderne theorien. it valency 4 valency 3 valency 2 valency 1 valency 1 valency 2 li = 7,03 (be = 9,3?) difference = 16,02 (14,7) c = 12,0 n = 14,04 o = 16,00 fl = 19,0 na = 23,05 mg = 24,0 difference = 16,5 16,96 16,07 16,46 16,08 16,0 si = 28,5 p = 31,0 s = 32,07 cl = 35,46 k = 39,13 ca = 40,0 difference = 89,1/2 = 44,55 44,0 46,7 44,51 46,3 47,6 as = 75,0 se = 78,8 br = 79,97 rb = 85,4 sr = 87,6 difference = 89,1/2 = 44,55 45,6 49,5 46,8 47,6 49,5 sn = 117,6 sb = 120,6 te = 128,3 j = 126,8 cs = 133,0 ba = 137,1 difference = 89,4 = 2 · 44,7 87,4 = 2 · 43,7 (71 = 2 · 35,5) pb = 207,0 bi = 208,0 (tl = 204 ?) figure 2. meyer’s table of “well-characterized groups of elements”. adapted from l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1864, p. 137. valency 4 valency 6 ti = 48 mo = 92 difference = 42 45 zr = 90 vd = 137 difference = 47,6 47 ta = 137,6 w = 184 figure 3. groups of six elements with the difference of nearly 46 of atomic weights and the valency four and six. adapted from l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1864, p. 138. 18 gisela boeck may be assumed that it is to this aim that he drafted a new, more extensive table with 52 elements in 1868. but this system was not published in a timely manner. it was not until 1895 that seubert published it on two pages along with several important papers about the historical development of the periodic system.29 we assume it was seubert who used not one, but two pages to print the table in a better, readable format (see fig. 5). he explained that it is necessary to combine the two pages in such a manner that c and n, p and si, sb and sn, bi and pb became neighbors.30 only under this condition meyer‘s table would be faithfully reproduced. otherwise the table was just too long to be printed in a book page. in this version meyer also included aluminum and chromium, which had not been presented in 1864. he allotted chromium its own column, but aluminum presented him with problems. seubert noted that meyer first placed al in the fourth column, then moved it to the third column, and finally decided to go with his first decision.31 it is more astonishing that aluminum does not fit in the order of increasing atomic weights. it would fit better in the third row, prior to si. but most elements are placed in rows with regularly increasing atomic weight – from left to right and top down. however, if one checks the table carefully one can find some more irregularities concerning the increasing atomic weight. if molybdenum were placed next to zirconium and vanadium next to tantalum there would be less irregularity. it is unclear whether seubert transferred the data correctly. the original version of the table could not be found. but if one assumes that the new table is a combination of the first three (fig. 2, 3 and 4), one can see table 2 (fig. 3) has been moved to columns 14 and 15.32 in this table mo followed ti, vd followed zr, and w followed ta. thus it is unlikely that seubert made a mistake. the new table has 16 columns, the last of which is empty. hydrogen is not considered. the reason was meyer‘s belief in a special role of hydrogen comparable to prout‘s theory. the already accepted elements of boron, indium, niobium, thorium, uranium, and some rare earths metals are also excluded. if we compare these multiple columns with modern representations of the periodic system, we can find some matches concerning the main group of elements (columns 8 to 13 or the first table from 1864). the table in fig. 5 also displays an empty space for the element following silicon (see in column 8), as it was the case in the first 1864 table (fig. 2). these constant differences were viewed by meyer as proof of the complexity of the atoms, as being constituted as aggregates of smaller units, and he used this constancy in the difference to suggest an element after silicon. while mendeleev went further boldly, also successfully predicting chemical properties for what he called “eka-silicon” (germanium), meyer stopped short and did not elaborate on his prediction. meyer didn’t keep that draft as he gave the original document to his successor in eberswalde. this was the mineralogist and geologist adolf remelé (1839-1915), who reported indeed that meyer had left the hand-written draft to him: when i came in july 1868 as his successor for chemistry, physics and mineralogy i got the inventory which belonged to the teaching post. but he also gave me the self-written arrangement of elements by increasing atomic weights which was a more comprehensive and completed scheme of that from 1864 and established that he will publish it soon.33 it is unclear why remelé did not return this draft to meyer in the years of the priority dispute, or why meyer did not ask for it. remelé showed it to meyer only in 1893; a copy was most likely sent to seubert in 1895.34 long before seubert’s publication of meyer’s draft in 1895, meyer finished a paper about the nature of chemical elements as a function of their atomic weights in 1869 and published it in march 1870.35 it contains a table with 55 elements (fig. 6). hydrogen is again not valency 4 valency 4 valency 4 valency 2 mn = 55,1 ni = 58,7 co = 58,7 zn = 65,0 cu = 63,5 fe = 56,0 difference = 49,2 48,3 45,6 47,3 46,9 44,4 ru = 104,3 rh = 104,3 pd = 106,0 cd = 111,9 ag = 107,94 difference = 92,8 = 2·46,4 92,8 = 2·46,4 93,0 = 2·46,5 88,3 = 2·44,2 88,8 = 2·44,4 pt = 197,1 i (ir) = 197,1 os = 199,0 hg = 200,2 au = 196,7 figure 4. groups of six elements with the difference of nearly 46 of atomic weights and the valency two, four and mixed. adapted from l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1864, p. 138. 19julius lothar (von) meyer (1830-1895) and the periodic system considered with respect to its “exceptional position”36. other elements with uncertainties of their atomic weights were excluded by meyer. it seems that for meyer it was very important to use reliable data. in mendeleev‘s 1869 paper 63 elements were regarded, uncertainties in the atomic weight were simply marked. in contrast to mendeleev who published atomic weights as integers or one decimal point at most, meyer systematically used weights with one or two decimals in his publications. the table in fig. 6 portrays how meyer ordered the elements strictly according to increasing atomic weights, following the first column top down, then repeating this in the second column, etc. he highlighted some uncertainties such as te and os with question marks. what is new is that the column does not combine elements with similar properties – these are found in one row. in total there are nine columns and 16 rows (the second row has three dashes). perhaps meyer was influenced by mendeleev‘s first table and changed the rows and columns? meyer also mentioned the constant differences of the atomic weights: from column i to column ii, and from ii to iii, etc. later meyer changed rows and columns again. figure 5. meyer‘s unpublished draft of an elements‘ system. scan from k. seubert, das natürliche system der chemischen elemente, 2nd edition, engelmann, leipzig, 1913, pp. 6-7. 20 gisela boeck as noted above, this table contains dashes. it seems that these are place holders for those elements with uncertain atomic weights or for elements yet unknown. he wrote: these elements [with uncertain atomic weights g.b.] will later at least partly occupy these gaps which are still in the table. other gaps will be filled by elements which will be discovered in future; prospective discoveries will possibly move one or the other element from its place and substitute it by another one, which fits better.37 in this 1870 publication, meyer also used the newly determined atomic weights and for the first time mentioned a periodic function of the atomic weight: the same or similar properties recur when the atomic weight increased for a certain size, at first 16, later 46 and finally 88 to 92 units.38 from 1864 on, meyer had arranged the elements with respect to chemical properties, such as valency, and thus expressed periodicity but this was implicit. to explain the concept of periodicity more clearly, he used the relation between the atomic volume and the atomic weight. meyer calculated the atomic volume as the quotient of the atomic weight and the density of the elements in the solid state, except for chlorine for which he used the liquid state. the graphic presentation shows the periodicity clearly – it is actually more striking than the tables (fig. 7). like mendeleev, meyer predicted the discovery of new elements but he did not describe any properties. meyer was impressed by periodicity but explicitly mentioned that it was still not clear what the reasons for the periodic change might be: these and similar regularities cannot be a simple coincidence but we must recognize that the empiric way to the establishment is not the key to the recognition of its internal primary link. but it seems that a starting point is found for the study of the constitution of the hitherto undecomposable atoms, it is a guideline for future examinations of elements.39 in the meantime mendeleev had published his natural system of elements, copies of which were sent to other chemists in russia and several other countries. by the end of 1869 the correspondent of the berichte der deutschen chemischen gesellschaft (reports from the german chemical society) viktor von richter (18411891) had reported on the interesting relationship in the system of elements that mendeleev had developed.40 a short review of mendeleev‘s system was also published in the zeitschrift für chemie (journal of chemistry) in germany.41 meyer was acquainted with mendeleev‘s paper and wrote in his own 1870 paper that “the hereinafter published table is in the main identical with that of mendelejeff ”.42 subsequently many readers and also mendeleev understood this phrase as an admission that meyer did figure 6. meyer‘s classification of elements from 1870. scan from k. seubert, das natürliche system der chemischen elemente. 2nd edition, engelmann, leipzig, 1913, p.11. 21julius lothar (von) meyer (1830-1895) and the periodic system not publish his own ideas, but elaborated on mendeleev’s. mendeleev answered with two publications in 1871.43 but subsequently both meyer and mendeleev focused mainly on other scientific problems. meyer did however publish several papers after 1878 on the determination of atomic weights. the priority dispute began again in 1879, but we shall not discuss it further here.44 the periodic system and the course of inorganic chemistry we will now turn to the question of how lothar meyer valued the periodic system as a didactic tool. he was interested in questions like the organization of school and university instruction45, but also in the issue of how to integrate the periodic system into the study of inorganic chemistry. meyer reported on this topic in berlin two years before his death; this lecture was published later.46 in this paper he used the table type presented in fig. 8. it shows that meyer returned to his first ordering: he combined elements with similar chemical properties in one column and not in one row. one can also establish that he separated most of the transition elements from the rest. meyer introduced this distinction already in the second edition of the moderne theorien.47 in that edition one finds also for the first time tables starting with the alkali metals. meyer explained the reason: those elements display the maximum atomic volume for each row.48 sometimes meyer used in his papers presentations of the system which reminds of the spiraled form used by alexandre-emile béguyer de chancourtois (18191886).49 such a representation type was also used for a printed chart (fig. 9).50 it can be assumed that this format is similar to the one he used in the lecture hall in tübingen. meyer noted that he understood his contribution to the periodic system as a modification of the döbereiner system and not as a new qualitative step. he called his system neither a new theory nor a new law. he emphasized that the system would be well-suited to giving students an overview. meyer also pointed out that during the last twenty years this system had only received minimal attention in textbooks, where it received a brief mention or cursory explanation. only a small number of textbooks used it as a fundamental part of the arrangement for the teachfigure 7. presentation of the graph which shows the periodic relation between atomic volume and atom weight. scan from l. meyer, annalen der chemie und pharmacie. vii. supplementband 1871, 354-364. figure 8. one of the last presentations of meyer‘s arrangement of elements in 1893. scan from l. meyer, ber. dtsch. chem. ges. 1893, 26, 1230–1250, here 1232. 22 gisela boeck ing content.51 he established that the course of organic chemistry, with its type-theory and the homologous series, is better systematized than inorganic chemistry. for example, several ways can be used for an overview of the metals. the use of the periodic system must be prepared. if someone is unacquainted with the system he will need explicit instruction, as the system was not selfexplanatory. meyer noted that he had modified his own course several times and emphasized that in any case it is necessary to start with simple substances. in teaching, meyer started with a short introduction about the relation between chemistry and physics he regretted that the type theory in organic chemistry had not found yet an equivalent in inorganic chemistry. then he turned to some aspects of history of chemistry like alchemy or the phlogiston theory. he mentioned johan baptista van helmont (1580-1640), antoine laurent de lavoisier (1743-1794) and bunsen and combined his historical approach with the introduction of elements and compounds which are connected with those savants. later he introduced the atomic weights and discussed the compounds. then he was able to explain the periodic system. meyer mentions using a large chart to illustrate the system in the lecture hall, as well as a model using a rotating cylinder. he started with hydrogen as the foundation for the atomic weights, then he dealt with group vii (compare figure 8). he delayed working with group i, as it seemed too complicated for the students. meyer finished his paper by expressing his wish that readers would try this course and perhaps find a better way of arranging the material on the basis of the periodic system. conclusion today the periodic system has its atom-theoretical explanation. its representation as a table can be found in nearly every chemical cabinet. the subject matter in courses of inorganic chemistry is organized on the basis of the groups of the periodic system. however, lothar meyer’s contribution to this system is often forgotten and mainly mendeleev’s is appreciated. after meyer’s death mendeleev often emphasized the importance of his predictions and their confirmation. for most people this was easy to understand. meyer’s accurateness in determining atomic weights and his reflections on the nature of atoms were not so easily understandable. this paper presented lothar meyer’s biography and key achievements in the field of classification of the elefigure 9. meyer‘s system of elements as chart. combination of four individually printed unbounded parts. scan from l. meyer, k. seubert, das natürliche system der elemente. nach den zuverlässigsten atomgewichtswerthen zusammengestellt. 2nd edition, breitkopf&härtel, leipzig, 1896. 23julius lothar (von) meyer (1830-1895) and the periodic system ments. it demonstrates that meyer tried to find an explanation to döbereiner ś triads and that he started to determine and to recalculate the atomic weights of elements as a result of irregularities in his classifications. meyer was very cautious concerning predictions of new elements, as his main interest was the understanding the nature of atoms. he also was interested in using the periodic table for instruction in inorganic chemistry. by analyzing the successive reworkings of his classification, and the discovery of periodicity as much as the absence of archives allows, it is possible to follow the train of meyer’s thoughts in this endeavor. this demonstrates that the karlsruhe conference was key, as was the case for mendeleev, but also underlines differences between the two pursuits. a convinced atomist, meyer also paid much attention to valency and other atomic properties such as the atomic radii. in his recollections, it is also clear that meyer saw his work as a continuation of prior developments such as döbereiner. he did not predicted new elements explicitly, but he was more successful in placing most elements in the right order. mendeleev ordered all known elements, but with more mistakes than meyer. on the other side he predicted not only the elements but described their properties. mendeleev always insisted on his proposal as being a breakthrough. as this paper illustrates, the finding and development of the periodic system was more than one man’s feat. references 1. m. gordin, in nature engaged: science in practice from the renaissance to the present, (eds. m. biagoli, j. riskin),palgrave macmillan, new york, 2012, pp. 59-82; m. gordin, scientific babel – the language of science from the fall of latin to the rise of english, profile books, london 2017, 51-77; e. r. scerri, the periodic table – its story and its significance, oxford university press, new york et al. 2007, pp. 92-100; k. pulkkinen, curating the chemical elements: julius lothar meyer’s periodic systems, whipple library, cambridge, november 2018-may 2019 (last accessed 21 june 2019). 2. for the biographical summary the following literature was used: k. seubert, ber. dtsch. chem. ges. 1896, 28, 1109-1146; k. danzer, dmitri i. mendelejew und lothar meyer: die schöpfer des periodensystems der chemischen elemente, teubner, leipzig, 1974; g. schwanicke, vareler heimathefte 1995, 8; b. stutte, bausteine zur tübinger universitätsgeschichte 1997, 8, 79–88; h. kluge, i. kästner, ein wegbereiter der physikalischen chemie im 19. jahrhundert – julius lothar meyer (1830-1895), shaker, aachen, 2014. i thank claus meyer-cording for the handwritten family tree including julius lothar meyer. the books written by danzer and schwanicke gave interesting information. but many of them are given without an exact reference. some of the mentioned letters and documents in schwanicke’s paper are not found yet. 3. l. meyer, die gase des blutes, dieterich, göttingen, 1857. 4. information of the archive at the university in würzburg (december 1, and december 10, 2014). 5. l. meyer, ber. dtsch. chem. ges. 1887, 20, 997-1015, here 1000. i thank alan rocke for this reference and especially for an unpublished draft of a paper about meyer’s way to periodicity. 6. j. hennig, in lexikon der bedeutenden naturwissenschaftler, vol. 3, (eds. d. hoffmann, h. laitko, st. müller-wille), spektrum, münchen 2004, p. 69. 7. k. seubert, ber. dtsch. chem. ges. 1896, 28, 11091146, here 1113. 8. s. cannizzaro, il nuevo cimento, 1858, vii, 321-366, l. cerruti (ed.), stanislao cannizzaro, sunto di un corso di filosofia chimica, sellerio, palermo, 1991 or l. meyer (ed.), abriss eines lehrgangs der theoretischen chemie, engelmann, leipzig, 1891. 9. poggendorff ’s annals of physics. 10. archive of deutsches museums münchen, letters of lothar meyer to hermann kolbe (tübingen, 30. januar 1881), hs-nr. 03535 and letters of lothar meyer to august kekulé (breslau, 11. oktober 1862), nl kekulé, nl 228 / 0509. 11. l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1872, foreword. 12. g. schwanicke, vareler heimathefte 1995, 8, 24. 13. archive of deutsches museum münchen, letter from l. meyer to kekulé (neustadt-eberswalde 15.12.1866), nl kekulé, nl 228/0509. 14. ibid. 15. c. nawa, mitteilungen, gesellschaft deutscher chemiker / fachgruppe geschichte der chemie 2017, 25, 125-163. 16. a. windmüller, beiträge zur württembergischen apothekengeschichte 1973, 10, 17-26. 17. compare for example: a. diekmann, klassifikation – system – „scala naturae“: das ordnen der objekte in naturwissenschaft und pharmazie zwischen 1700 und 1850, wissenschaftliche verlagsgesellschaft mbh, 1992; j. w. van spronsen, the periodic system of chemical elements, elsevier, amsterdam et al., 1969; b. bensaude-vincent, in elemente einer geschichte der wissenschaften (ed. serres), suhrkamp, frankfurt/ 24 gisela boeck main, 2nd edition, 2002, pp. 791-827; e. r. scerri, the periodic table – its story and its significance, oxford, new york et al., 2007, pp. 29-62. 18. l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1872, pp. vii-ix. 19. w. h. brock, from protyle to proton: william prout and the nature of matter, 1785-1985. accord, bristol, 1985, p. 217. 20. l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1864, p. 16. 21. h. döbling, die chemie in jena zur goethezeit, fischer, jena, 1928, pp. 200-201. 22. j. w. döbereiner, poggendorfs annalen der physik und chemie 1829, 15, 301. reprint in die anfänge des natürlichen systems der elemente. (ed. meyer), engelmann, leipzig, 1895. 23. l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik. maruschke & berendt, breslau, 1884, p. 136. 24. l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik. maruschke & berendt, breslau, 1864, p. 135. 25. ibid, p.136. 26. ibid, p. 138. 27. l. meyer, ber. dtsch. chem. ges. 1896, 13, 259-265, here p. 259. 28. zum theil allerdings können diese abweichungen mit fug und recht angesehen werden als hervorgebracht durch unrichtig bestimmte werthe der atomgewichte. bei allen dürfte indess dies kaum der fall sein; und ganz sicherlich ist man nicht berechtigt, wie das nur zu oft geschehen ist, um eine vermeintlichen gesetzmäßigkeit willen die empirisch gefundenen atomgewichte willkürlich zu corrigieren und zu verändern, ehe das experiment genauer bestimmte werthe an ihre stelle gesetzt hat. source 24, p. 139 (all translations by the author). 29. k. seubert, das natürliche system der chemischen elemente, 2nd edition, engelmann, leipzig 1913. 30. ibid, p. 7. 31. ibid, p. 126. 32. f. rex, mitteilungen, gesellschaft deutscher chemiker / fachgruppe geschichte der chemie 1989, 2, 3–13, here 10-11. 33. als ich im juli 1868 als sein nachfolger im lehramt der chemie, physik und mineralogie die ihm unterstellten inventarien übernahm, übergab er mir mit dem bemerken, er denke die sache doch bald zu veröffentlichen, eine eigenhändig geschriebene anordnung der elemente nach den atomgrößen, welche eine wesentliche ergänzung und vervollkommnung seines vorerwähnten schemas von 1864 darstellt. a. remelé, zeitschrift für forstund jagdwesen 1895, 27, 721-724. 34. the archive has only a letter with the announcement but not the copy itself. archiv der berlin-brandenburgischen akademie, autographensammlung, chemikerbriefe, briefwechsel seubert-remelé, nr. 94. 35. l. meyer, annalen der chemie und pharmacie, vii. supplementband 1870, 354-364. 36. source 29, p. 12. 37. diese elemente werden voraussichtlich später, z. th. wenigstens, die lücken ausfüllen, welche sich in der tabelle jetzt noch finden. andere lücken werden möglicherweise durch später zu entdeckende elemente ausgefüllt werden; vielleicht auch wird durch künftige entdeckungen das eine oder andere element aus seiner stelle verdrängt und durch ein besser hinein passendes ersetzt werden. ibid, p. 12. 38. dieselben oder ähnliche eigenschaften kehren wieder, wenn das atomgewicht um eine gewisse grösse, die zunächst 16, dann etwa 46 und schließlich 88 bis 92 einheiten beträgt, gewachsen ist. ibid, p. 13. 39. wenn diese und ähnliche regelmässigkeiten unmöglich reines spiel des zufalls sein können, so müssen wir uns andererseits gestehen, dass wir mit der empirischen ermittlung derselben noch keineswegs den schlüssel zur erkenntnis ihres inneren ursächlichen zusammenhangs gefunden haben. aber es scheint wenigstens ein ausgangspunkt gewonnen zu sein für die erforschung der constitution der bis jetzt unzerlegten atome, eine richtschnur für fernere vergleichende untersuchung der elemente. ibid, p.16. 40. v. von richter, ber. dtsch. chem. ges. 1869, 2, 552554. 41. d. i. mendelejeff, zeitschrift für chemie 1869, 12, 405-406. the question of the mistake in the translation is well discussed for example in: m. gordin, scientific babel, profile books, london, 2017, pp. 51-77 or v. a. krotikov, voprosy istorii estestvoznanija i techniki 1969, 29, 129-131. 42. die nachstehende tabelle ist im wesentlichen identisch mit der von mendelejeff gegebenen. source 29, p. 10. 43. d. i. mendelejeff, annalen der chemie und pharmacie, viii. supplementband, 1871, 133-229; d. i. mendelejeff, ber. dtsch. chem. ges., 1871,4, 348-352. 44. compare for example: l. meyer, ber. dtsch. chem. ges. 1880, 13, 259-265; d. i. mendelejeff, ber. dtsch. chem. ges. 1880,13, 1796-1804; l. meyer, ber. dtsch. chem. ges. 1880, 13, 2043-2044. 45. l. meyer, schriften des deutschen einheitsschulvereins 1890, 6, 7-28 and l. meyer, akademie oder universi25julius lothar (von) meyer (1830-1895) and the periodic system tät? den deutschen forstund landwirthen gewidmet. maruschke & berendt, breslau, 1874. 46. l. meyer, ber. dtsch. chem. ges. 1893, 26, 12301250. 47. l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1872, p. 347. 48. ibid, p. 305. 49. a. e. béguyer de chancourtois, comptes rendus hebdomadaires des séances de l´académie des sciences 1862, 54, 757-761, 840-843, 967-971. 50. l. meyer, k. seubert, das natürliche system der elemente: nach d. zuverlässigsten atomgewichtswerthen, breitkopf&härtel, leipzig, 1889 (1st edition) and 1896 (2nd edition). 51. compare for example: m. kaji, h. kragh, g. pallo, early responses to the periodic system, oxford university press, new york, 2015. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo substantia. an international journal of the history of chemistry 2(1): 93-101, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-43 citation: j. ragai (2018) snapshots of chemical practices in ancient egypt. substantia 2(1): 93-101. doi: 10.13128/ substantia-43 copyright: © 2018 j. ragai. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article snapshots of chemical practices in ancient egypt jehane ragai emeritus professor of chemistry, the american university in cairo, 37, sedley taylor road, cb28pn, cambridge, uk e-mail: jragain@aucegypt.edu abstract. this article gives a historical overview of a number of chemical practices carried out by the ancient egyptians and shows that beyond being purely empirical, in more than one instance their methods suggest an understanding of the rudiments of modern day chemistry. a close analysis of some of their preparations indicates that ancient egyptians were familiar with the principles of oxidation and reduction, could control the ph of a solution and were successful in preparing novel compounds through a controlled technology of chemical synthesis. in the latter endeavor it is shown that these ancient people embraced the scientific method, preceding aristotle’s rejection in ancient greece of a purely deductive approach to scientific enquiry. egyptian blue, the only pigment synthesized by the ancient egyptians is also discussed, and attention is drawn to its potential future contributions to modern high-tech applications. keywords. ancient egyptians, chemical synthesis, egyptian blue, kohl, scientific method. “..it appears that egyptians have developed a technology of chemical synthesis in solution that allowed preparations of original compounds..” phillip walter 1 introduction the embryonic stage of modern chemistry “alchemy” can be traced back to ancient egypt, where hermes trismegistus2 said to be a contemporary of moses, founded the art of alchemy often dubbed the hermetic arta. to many the words alchemy and chemistry are linked to “khema” or “chemi”3 which referred to the ancient name for egypt meaning the black land. on the other hand plutarch attributes the name “alchemy” to the ancient egyptian activities, referring to their skills in the extraction of metals, the preparation of alloys, and the working of gold4-6 all of which contributed to the practical part of alchemy. today an observer reflecting on the achievements of the ancient egyptians, would certainly recognize a flurry of activities that could be referred 94 jehane ragai to as ‘chemical’, which not only served their religious beliefs but also had utilitarian, aesthetic, and symbolic connotations. it is generally believed that such accomplishments resulted from purely empirical observations. however the question remains: did the ancient egyptians at any point grasp the chemical significance of some of these practices? in what follows snapshots are provided of some of the most impressive ‘chemical’ achievements of the ancient egyptians, the origins of which can in many cases be traced back to their religious convictions. religious beliefs as catalysts for chemical activities in ancient egypt an almost obsessive horror of death and extinction was reconciled with an absolute faith in immortality. to ensure eternal life, it was essential that the body be preserved in a good condition and that the tomb of the deceased be equipped with implements, stuffed animals, donations, jewelry (in case of the rich and powerful)… that would serve the deceased in the afterlife. corpses as early as the third millennium bc were preserved by a special technique of embalming (referred to as mummification) where the chemical process of osmosis played a crucial role. the main purpose of mummification was the dehydration of the body so as to prevent anaerobic bacteria from living on its tissues, causing their putrefaction and decay. it is very probable that the ancient egyptians did not understand the chemistry behind the phenomenon of osmosis but must have been aware, on a purely empirical basis, of the special role of natron (a mixture of sodium carbonate, bicarbonate with very small amounts of sodium sulfate and sodium chloride) in this dehydration process. it is of significance that herodotus and diodorus used the same word for preserved fish as that for mummy, considering that even in pre-mummification times, salt was used to dry fish.7 with bodies placed on a slanting board and covered with dry natron for forty days, fluids flowed readily by osmosis from inside the body through the skin and to the outer high concentration of natron, resulting in total dessication. bodies were preserved by such a chemical process and satisfied the ancient egyptians dreams of immortality as well as their strong belief in the great beyond8. the precise methods of mummification varied from period to period, and also within the same period depending on the social status of the dead person. the tomb: a promise of eternal life with the onset of the dynastic period (~3300bc) egyptians built elaborate tombs which housed, protected, and equipped their dead for the afterlife. initially built as a flat-roofed, rectangular structure: the ‘mastaba’, which included a shaft that led to an underground burial chamber, would soon give way to the pyramidal structure of the giza pyramids (erected around ~2600 2500 bc). a special mortar was used as a binder to stabilize the heavy limestone blocks that formed the core and outer layers of these massive constructions. alfred lucas7 in his pioneering work on ancient egyptian mortar, asserted that before graeco-roman times, the mortar employed for stone in ancient egypt was mainly ‘gypsum’. some writers on ancient egypt have described ancient egyptian mortar as burnt lime, however, chemical examination by lucas7 has shown that ancient egyptians never used lime until the roman periodb. such results were later corroborated by coppola and co-workers 9 who analysed mortars belonging to the ramesside era and found that they all had a gypsum based binder. when heated at temperatures as low as 110°c-160°c gypsum loses water to produce the powder, plaster of paris (caso4·½h2o) according to the reaction: 2caso4·2h2o —→ 2caso4·½h2o + 3h2o and when water is added to the powder of plaster of paris it rehydrates (absorbs water) and hardens rapidly. 2caso4·½h2o +3h2o → 2caso4·2h2o according to coppola, ancient egyptian workers seemed to be conscious of the fact that the quality of the raw materials and methods of firing influenced the nature of the final product9. there is no doubt that the ancient egyptians recognised on a purely experimental basis the deceptively simple chemical reactions involved in the preparation of gypsum. they also most likely understood that lime mortar entailed the formation of calcium oxide (cao or quicklime) with the subsequent formation of ca(oh)2 (slaked lime) to give mortar. caco3 + heat → cao + co2 and cao + h2o → ca(oh)2 even though lime mortar could have been used in their constructions, they probably realized that the prepheat 95snapshots of chemical practices in ancient egypt aration of cao, requiring a heating temperature close to 900 °c, was not an ideal choice. according to lucas the scarcity of fuel in ancient egypt and the low temperature processing of gypsum undoubtably must have been the reason why ancient egyptians preferred gypsum over lime. it is very probable that the process of preparing a suitable mortar had to be learnt by multiple trials, the results being gauged by the nature of the final product. members of the ruling class and nobles were particularly meticulous in preparing their tombs and strived to ensure that all their needs for the afterlife were addressed. metallic implements, small copper and bronze statuettes representing a variety of deities, colored faience, glass amulets and shawabtis (small statuettes generally 365, that would serve the deceased every day of the year), intricate jewelry… all had to be scrupulously prepared and securely buried with the deceased. the skill for the production of burial implements and accessories, was generally attained through experimental observations, but may have necessitated a certain degree of primitive chemical knowledge. copper and bronze: the beginning of a strong tradition of metal working it is only through heating the copper ore in the presence of carbon (charcoal) as reducing agent that, as early as the old kingdom (~2600 bc), a successful extraction of copper could be achieved in ancient egypt. the ore basically in the form of malachite (basic copper carbonate) was crushed into small pieces and heated, in the presence of charcoal, to temperatures beyond 10000c (reached at by means of blow pipes or foot bellows) changing at first to copper oxide and then to molten copper. cuco3.cu(oh)2 → 2 cuo + co2 + h2o c + cuo → cu + co it would take a thousand years after that discovery for bronze (an alloy of copper and tin) to enter into extensive use in ancient egypt. a wide spectrum of statues, implements, weapons made out of this alloy were all buried in the tombs. as there are no tin ores in egypt, it has been suggested that the tin was probably imported from persia and possibly brought in by phoenician traders10. the egyptians would soon realize in their preparation of bronze, that the melting point of copper could be lowered by alloying it with tin, an observation which would prove handy in many instances. both the extraction of copper and the preparation of bronze seem to have been achieved through trial and figure 1. the kephren pyramid in which gypsum mortar was used. figure 2. interior of a tomb. figure 3. extraction of copper (malachite mixed with charcoal heated with blowpipes and then pouring of the molten copper as shown on the left). 96 jehane ragai error with the results embodied in empirical observations which were methodically recorded and strictly followed. gold: from religious statuary to legendary jewelry identified with the sun god ra and with the dazzling solar light, gold occupied a very special place amongst ancient egyptian metals. its shine and glitter also made it quite attractive for use in ornaments and jewelry. the successful preparation of bronze would pave the way for the progress egyptians would attain in working gold, namely in relation to the successful soldering of intricate pieces of gold jewelry. as judiciously pointed out by cyril aldred: there seems little doubt that ancients soldered their goldwork by the process known as colloidal hard soldering. in colloidal hard soldering, ground copper carbonate, probably in ancient egypt in the form of powdered malachite so commonly used as an eye-cosmetic, is mixed with gum or glue and this adhesive is employed to stick the grains or wire into place, or to coat the adjacent edges of the parts to be joined…11 after heating and gradually increasing the temperature from 100°c to 880 °c, … at about 880°c … the gold in contact with the copper melts to form a welded joint, whereas both gold and copper melt at nearly the same temperature well above this point, viz. 1083°c and 1063°c respectively. 11 this lowering of the melting point of both copper and gold was, as mentioned earlier, certainly inspired by bronze making. there is no recorded evidence, however, that the egyptians had grasped the underlying chemical principle that governs such a phenomenon (lowering of the chemical potential etc…..) as we understand it today. egyptian blue: a reminder of sublime justice and perfection. tomb walls were generally adorned with colored representations, mostly associated with deities, and symbolizing the sacred over the profane. many of these depictions were painted in blue as to the ancient egyptians the blue color had a special significance. worn on the breast plates of egyptian priests, it was regarded as the color of divine truth. the blue colored war crown became very popular during the new kingdom (~1500 bc) and was believed to confer upon its wearers, special protection from mysterious hostile forces.7 lapis lazuli (most important component is lazulite of formula na,ca)8(alsio4)6(s,so4,cl)1-2.) and the naturally occurring blue pigment azurite (cu3(co3)2(oh)2 a basic copper carbonate) were both known to the ancient egyptians. however, the rare occurrence of lapis lazuli and the pale blue color of the azurite pigment, encouraged the egyptians to produce their first synthetic pigment, the well known ‘egyptian blue’b the earliest recorded use of egyptian blue is in the old kingdom (~ 2600-2100 bc) and its preparation continued into the greco-roman period (330bc-400ad)10 c figure 4. bronze statue of the goddess bastet. figure 5. gold pectoral (parts soldered by colloidal hard soldering). 97snapshots of chemical practices in ancient egypt the secret of its manufacture was lost in the fourth century ad, and rediscovered only in the nineteenth. the nature of this pigment has been extensively investigated12-15 and was found to be a calcium-copper tetrasilicate with the formula cacusi4o10 or (cao. cuo.4sio2) with a definite composition and crystal structure. building on previous work and through their own attempts at preparing egyptian blue, wiedemann and bayer13 concluded that the raw materials had to be close to the stoichiometric composition 1 cao, 1 cuo, 4sio2 and that small amounts of fluxes (borax, salt) were needed to catalyse the reaction and to yield a better crystalline structure. it was also observed that in order to achieve a bright blue color the synthesis had to be carried out in an oxidizing atmosphere and at a temperature lower than 10000c. even though it may never have been explicitly indicated, these results suggest that the egyptians must have also been familiar with the rudiments of oxidation and reduction. today egyptian blue is another important and fascinating legacy spawn by this ancient egyptian civilization with the recent observation that when irradiated with visible light, it fluoresces with exceptional strength in the near infrared region of the electromagnetic spectrum 16-17. such a property appears to have an important future in modern high-tech applications, ranging from special fibre optical systems for telecommunications18 , state-of-the-art high resolution biomedical imaging 19-22 luminescent fingerprinting dusting powder 23and security ink technology24. colored amulets: bestowing protection, health and good luck to match their magico-religeous beliefs the ancient egyptians fashioned small and beautifully colored objects (notably scarabs, amulets, ushabtis) made of a ware far better adapted that the rough clay, the so-called egyptian faience. such a ware composed of a body(core) coated with an alkali-based glaze, gave the ancient egyptians the opportunity to produce a wide spectrum of colors. until the xviiith dynasty (1550 – 1295 bc), blue faience was produced from the thermal decomposition of malachite or azurite during the manufacture of the glaze (the color was mainly due to copper cu in the figure 7. hippo goddess (taweret, goddess of childbirth) in blue faience. figure 6. preparation of bronze (heating by means of foot bellows). 98 jehane ragai form of copper oxide cuo ). ancient egyptians would soon become aware that a prolonged exposure to high temperature would favor the green color over the blue.25 caution therefore had to be exercised in the heating of the glaze and it was only during the middle kingdom (2055–1650 bc) that blue became common in faience. during the xviiith dynasty(c. 1550-c. 1292 bc), cobalt in the form of cobalt oxide (coo) was the principal colorant for blue faience and was generally accompanied by a significant amount of copper. an intense blue color was obtained with concentrations of coo as low as 0.05 per cent which turned to violet or indigo when concentration was increased to 0.2 percent. in the coloring of the glaze, the egyptians realised, again probably on a purely empirical basis, that the colors exhibited by metal oxides in minerals could not always be transferred to the vitreous state. in view of the ligand field and crystal field effects, rarely does a transition metal in glass have the same chemical environment as in a mineral. amulets in the form of the ankh sign (the key of life), the eye of horus, or the scarab, were often depicted in blue and were worn by the egyptians and also buried with their mummies providing protection and prosperity. here to the symbolism of color (blue) was added the symbolism of form (amulet). eye makeup: a vehicle to good health and immortality makeup occupied a primary position at all levels of ancient egyptian society and played an important role in funerary rites for the purification of the body26. beauty symbolised holiness – a key to the attainment of eternal life – and eye makeup in particular had an important standing in the ancient egyptians’ collection of cosmetic elements. a close connection was perceived between the madeup eye, the lunar cyclical renewal and the clash between the gods horus and set26. according to one myth, set gouged out horus’s eye in a battle, an event perceived by the egyptians as an interruption of the usual lunar cycle and a threat to the return of the new moon27. for the reestablishment of the cosmic order the eye had to be reconstituted and cured – a task successfully achieved by thot the god of writing. philip walter referring to the rehabilitation of horus’s eye points out that.. …the eye of the god should… be completed, reconstituted with makeup and unguents to ensure by the beneficial power of cosmetics the integrity and the health of the divine eyes, and the victory of the light. 28 the eye of horus adorned with makeup came to symbolise the moon with all its powerful and protective connotations. ancient egyptian religious texts attest to its primary symbolic role and importance: take two eyes of horus, the black and the white, take them to your forehead that they may illuminate your face…29 such beliefs led the egyptians to regularly use eye makeup during their lifetime. they also ensured that upon their death and as a vehicle to good health and immortality, containers holding cosmetic powders would be included in their burial surroundings . kohl and the practice of wet chemistry the 1798 napoleonic expedition to egypt brought back a large number of these powders preserved in alabaster, ceramic, wood or reed jars dating from 2000 b.c., the latter have been kept in the storage rooms of louvre’s laboratories.26,30 amongst these were two forms of eye makeup used since predynastic times: the green eye paint prepared from the mineral malachite which was usually applied to the lower eyelids and the black makeup, known as kohl, generally used for the upper lids. in 1995, a group of french scientists led by chemist philip walter started researching these ancient egyptian cosmetics through a collaborative partnership between the cnrs (national center for scientific research), the louvre department of egyptian antiquities and the scientific laboratories of l’oreal. the colfigure 8. the eye of horus. 99snapshots of chemical practices in ancient egypt laboration lasted close to seventeen years and part of the work entailed the analysis of black kohl26. using scanning electron microscopy in conjunction with x-ray diffraction for structural characterisation and phase identification, walter and co-workers identified two ores of lead namely galena and cerussite (pbs and pbco3), but to their great surprise the analyses also revealed the presence of copious amounts of laurionite (pb(oh)cl) and phosgenite (pb2cl2co3)31. in view of their very rare presence in nature and their copious amounts in the cosmetic vials, it was concluded that these minerals must have been artificially produced. the excellent state of preservation of the containers ruled out any possibility of weathering or alteration effects. for comparative purposes walter and co-workers prepared these lead compounds by stirring lead oxide (pbo litharge) with rock salt (nacl) in carbonated free water to give laurionite (pb(oh)cl) and by adding to the mixture natron (mainly na2co3 and nahco3) to obtain phosgenite (pb2cl2co3). in both cases the prepared minerals were very close in composition and texture to the archaeological compounds32. to avoid the undesirable formation of hydroxides the reactions taking place (equations 1 and 2), seemingly quite simple, had to be closely monitored as a neutral ph needed to be maintained. pbo + h2o + nacl → pb(oh)cl + naoh [1] pbo + h2o + nacl + 1/2na2co3 → 1/2 pb2cl2co3 + 2 naoh [2] such a preparation therefore entailed the repeated addition of fresh water and sodium chloride and the continuous removal of the supernatant liquid. the process required several weeks to reach completion31. as pointed out by patricia pineau, director of research communication for the cosmetics giant l’oreal: without knowing much chemistry, how did they have the foresight to know that a chemical reaction started on one day would produce such and such a result after several weeks?30 this discovery led to the astonishing revelation that the ancient egyptians were in fact quite versed in the rudiments of wet chemistry, a practice which enabled them to synthesise original compounds in solution. the question remained: why did the ancient egyptian add these preparations to their eye makeup? old manuscripts indicated that eye cosmetics ”… were essential remedies for treating eye illness and skin ailments…”32 and the ancient egyptian ebers medical papyrus mentioned kohl for the treatment of a plethora of eye diseases33. intrigued by this situation, the french scientists amatore, walter and co-workers embarked on a project to find out if lead compounds had indeed any therapeutic effects. using ultramicroelectrodes they showed that submicromolar concentrations of pb+2 generated by the partial solubility of laurionite (pb(oh)cl) and added to human skin cells led to the production of no, a molecule which played a role in the body’s immune response.32 commenting on such findings martin oliver from mcgill university suggested that the released nitric oxide could either stimulate the immune cells present in the eye or alternatively kill the disease-forming bacteria close to the eye34 . it is therefore possible that the ancient egyptians realised on a purely empirical basis, that whenever a white paste (identified today as laurionite or phosgenite) was present in the eye makeup preparation, it would have a therapeutic effect on its bearers and would give them greater immunity. this observation may have been the driving force behind this specific synthesis32 . according to bernstein such an activity “….remains the first known example of a large scale chemical process’’ in ancient egypt35 ! some reflective comments having dwelt at length upon some of the fascinating ‘chemical’ accomplishments of the ancient egyptians, it is now perhaps prudent to examine more closely the role of empirical probing as opposed to rational thinking and quantitative speculation in the chemical endeavors of these remarkable people. almost a century ago, l.e. warren referring to the ancient egyptians chemical practices expressed the following opinion: it should be understood that the egyptians in general did not possess an inquiring mind and that ordinarily they would not conduct experiments merely for the purpose of satisfying curiosity or gaining knowledge… 36 more recently wledemann and berke14, with regard to egyptian blue and other ancient egyptian chemical activities, suggested that: …man-made blue pigments required sophisticated chemical and technological developments… ancient chemical achievements could not be based on atomic or molecular grounds. therefore any progress was established by long and tedious processes of empirical probing14 100 jehane ragai there is no doubt that many of the egyptians accomplishments, some of which are described in this text, must have come as a result of long and laborious experimental scrutiny and elaborate processes of empirical trials. however when one considers egyptian blue, the rigorous stoichiometric requirements and the specific conditions for its preparation (oxidizing atmosphere, addition of a small amount of catalytic flux, temperature control)13, must have no doubt involved some degree of quantitative speculation and rational thinking. furthermore, the idea in itself of preparing one of the first known synthesized pigments, suggests the ancient egyptians’ ability to innovate and think creatively. the same is true with regard to the synthesis of the new compounds laurionite and phosgenite using “wet chemistry” in which the acidity had to be controlled over several weeks, and the alkaline supernatant liquid continuously removed with the attendant addition of salted water. this certainly entailed quite an elaborate empirical process but also reflects an activity which is implicitly intermingled with sound knowledge and which is not totally devoid of any rational speculation. with regard to the synthesis of phosgenite, philip walter suggested : we might presume that the observation of natural phenomena may have enabled them to develop and invent such a science. due to the regular flooding of the nile and the presence of the desert, egypt is a country that offers opportunities to observe a large number of mineral formations of exceptional character, especially around the salt lakes of the wadi natrun which supplied the natron so necessary to mummification. these carbonates of sodium are produced by chemical reactions between the salt water of the lake and the limestone substrate of the lake bottom, following very similar mechanisms to those involved in the making of the synthetic constituents of cosmetics…28 it can be therefore be surmised that the ancient egyptians in their synthesis of phosgenite applied a version of our modern day scientific method. assuming that they observed as suggested by walter the natural formation of this compound, this would then have led them to hypothesise, as an informed guess, the needed conditions for a successful preparation, followed by testing through carefully controlled and replicable experiments (control of the acidity through continuous washing…) and ultimately verifying the validity of their hypothesis and checking whether or not it needed modification (obtaining a white compound with immunological effects..). this should not come as a surprise to us since according to the edwin smith papyrus there are indeed indications that the ancient egyptians had a rational approach to medicine in which they applied the present day scientific method37,38. the chemical practices of the egyptians stand in partial contrast to plato’s deductive mode of thinking where pure reasoning was the only route to knowledge at the total exclusion of experimental verification. there is no doubt that the egyptians’ manufacture of these artificial lead–based compounds reflects an inductive approach very much in keeping with our modern scientific mode of inquiry! notes a) “hermeticism, also called hermetism is a religious, philosophical, and esoteric tradition based primarily upon writings attributed to hermes trismegistus39. according to the ‘hermetic view’ man can share in divinity and is therefore at least potentially in constant communication with god. the notion of a mystical ascent to the good acts as a unifying theme in ‘hermetism’. b) other pigments used in ancient egypt were mostly natural minerals. when working in 1980 as a chemical consultant to’ the sphinx project’ at the american research center in egypt (arce), i analysed by x-ray diffraction some blue pigments which were extracted from a cache in the front paws of the sphinx. these were identified as egyptian blue (jehane ragai: special report to arce, 1982). c) my own analysis of a series of ancient egyptian mortars extracted from the great giza pyramid, the second giza pyramid and the sphinx revealed the predominant presence of a gypsum based binder. references 1. p. h. walter, cosmetic and therapeutic chemicals 2003, 1. 2. herodotus, euterpe, vol. 1, lxxxii. 381,earle, philadelphia, p. 1814. 3. the alchemy reader: from hermes trismegistus to isaac newton, (ed.: s. j. linden), cambridge, 2014, p. 5. 4. l. e. warren, j. chem. educ., doi 10.1021/ ed011p146. 5. a history of metallurgy, (ed.: f. habashi), quebec, 1994, pp. 11-42. 6. j. ogden in ancient egyptian materials and technologies, (eds.: p. t. nicholson, i. shaw), cambridge, 2000, pp. 148-173. 101snapshots of chemical practices in ancient egypt 7. a. lucas, j. harris, ancient egyptian materials and industries, dover publications, 1999, p. 283. 8. j. ragai, g. de young in encyclopedia of the history of science, technology and medicine in non-western cultures, (ed.: h. seline), springer publications, 2008, pp. 749-750. 9. m. coppola, m. g. taccia, c. tedeschi, proceedings of conference built heritage 2013, monitoring conservation and management 2013, 1382. 10. h. a. ead, 2011, http://www.touregypt.net/science. htm 11. c. aldred, jewels of the pharaohs: egyptian jewelry of the dynastic period, thames and hudson ltd, 1971, p. 99. 12. w. t. chase, science and archaeology, cambridge, mass, 1971, pp. 80-90. 13. h. g. wiedemann, g. bayer, anal. chem. 1982, 54(4), 619. 14. h. g. wiedemann, h. berke, proceedings of the conference : the polychromy of antique sculpture and the terracota army of the first chinese emperor: studies on materials and techniques conservation 2001, 158. 15. m. s. tite, m. bimson, m. r. cowell in archaeological chemistry iii, (ed.: j. b. lambert), washington, dc, 1984, pp. 215-242. 16. g. accorsi, g. verri, m. bolognesi, n. armaroli, c. clementi, c. miliani, a. romani, chem. commun. 2009, 23, 3392-4. 17. r. brazil, chemistry world 2017, 14(6), 19. 18. d. johnson-mcdaniel, c. a. barrett, a. sharafi, t. t. salguero, j. am. chem. soc., doi 10.1021/ja310587c. 19. g. pozza, d. ajò, g. chiari, f. de zuane, m. favaro, j. cult. heritage 2000, 1(4): 393. 20. g. m. davies, r. j. aarons, g. r. motson, j. c. jeffery, h. adams, s. faulkner, m. d. ward, dalton trans., doi 10.1039/b400992d. 21. n. m. shavaleev, l. p. moorcraft, s. j. a. pope, z. r. bell, s. faulkner, m. d. ward, chem. eur. j. 2003, 9, 5283. 22. m. h. v. werts, r. h. woudenberg, p. g. emmerink, r. van gassel, j. w. hofstraatand, j. w. verhoeven, angew. chem. 2000, 39, 4542. 23. b. errington, g. lawson, s. w. lewis, g. d. smith, dyes and pigments 2016, 132, 310. 24. c. q. choi, scientific american 2013. 25. a. kaczmarczy, r. e. m. hedges, ancient egyptian faience, aris and phillips ltd., london, 1983. 26. p. h.walter, f. cardinali, l’art-chimie: enquête dans le laboratoire des artistes, michel de maule, 2013. 27. g. pinch, egyptian mythology: a guide to the gods, goddesses, and traditions of ancient egypt, oxford university press, 2004, pp. 131-132. 28. p. h. walter, molecular and structural archaeology: cosmetic and therapeutic chemicals 2003, 1. 29. r. o. faulkner, the ancient egyptian pyramid texts, clarendon press, oxford, 1969. 30. b. thorson, the independent, 1999, http://www.independent.co.uk/arts-entertainment/science-the-art-ofancient-egypt-1110924.html 31. p. walter, p. martinetto, g. tsoucaris, r. brniaux, m. a. lefebvre, g. richard, j. talabot, e. dooryhée, nature 1999, 397(6719), 483. 32. i. tapsoba, s. arbault, p. walter, c. amatore, anal. chem., doi 10.1021/ac902348g. 33. r. kreston, discover magazine, 2012, http://blogs. discovermagazine.com/bodyhorrors/2012/04/20/ophthalmology-of-the-pharaohs/#.wbqo_8zx3iu 34. w. r. corliss, science frontiers online, 1999, http:// www.science-frontiers.com/sf123/sf123p01.htm. 35. m. bernstein, m. woods, acs, 2010, https://www. acs.org/content/acs/en/pressroom/newsreleases/2010/ january/ancient-egyptian-cosmetics.html. 36. l. e. warren, j. chem. educ., 1934, 11(3), 146. 37. d. k. mak, a. t. mak, a. b. mak, solving everyday problems with the scientific method: thinking like a scientist, world scientific, 2016. 38. m. stiefel, a. shaner, s. d. schaefer, the laryngoscope, 2006, 116(2), 182. 39. r. audi, the cambridge dictionary of philosophy (2nd ed.), cambridge university press, 1999. picture credits all pictures are from the public domain except for figures 2, 3 and 4 were drawn by fadia badrawi. substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi substantia. an international journal of the history of chemistry 1(2): 99-109, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-30 citation: s.c. rasmussen (2017) the early history of polyaniline: discovery and origins. substantia 1(2): 99-109. doi: 10.13128/substantia-30 copyright: © 2017 s.c. rasmussen. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declared that no competing interests exist. historical article the early history of polyaniline: discovery and origins seth c. rasmussen department of chemistry and biochemistry, north dakota state university, ndsu dept. 2735, p.o. box 6050, fargo, nd 58108-6050, usa e-mail: seth.rasmussen@ndsu.edu abstract. prior to the discovery of its conductive properties in the 1960s, polyaniline was studied and applied as a variety of colored materials and dyes. the history of the discovery and origins of polyaniline are presented beginning with the initial oxidation of aniline by f. ferdinand runge in 1834 and concluding with the first electrochemical oxidation of aniline by henry letheby in 1862. in the process, the reports of aniline oxidation products between 1834 and 1862 are evaluated and discussed in light of modern knowledge, highlighting the various historical contributions to the current field of conjugated polymers. finally, an initial argument for polyaniline as the first synthetic organic polymer is presented. keywords. polyaniline, aniline black, emeraldine, conjugated polymers, oxidative polymerization. introduction modern society is largely a plastic-based culture in which organic plastics have become more ubiquitous than other common materials such as metals, glass, or ceramics. as a result, some have postulated that there is sufficient justification to refer to the period beginning with the 20th century as the age of plastics.1 the bulk of commercial plastics are made up of various saturated organic polymers that are primarily electronic insulators. in contrast, conjugated polymers (figure 1) are a less common class of organic plastic materials that are native semiconducting materials. in addition, these materials are capable of enhanced electronic conductivity (in some cases quasimetallic) in either their oxidized (p-doped) or reduced (n-doped) state.2,3 conjugated polymers are thus organic materials that combine the conductivity of traditional inorganic materials with many of the desirable properties of organic plastics, including mechanical flexibility and low production costs.2,3 this unique combination of properties has led to considerable fundamental and technological interest in these materials over the last few decades, resulting in the current field of organic electronics. in the process, a variety of modern technological applications have been developed, including sensors, electrochromic devices, organic photovoltaics (solar cells), field effect transistors, and organic light-emitting diodes (oleds).2,3 100 seth c. rasmussen discussion of the history of these materials typically begin in the mid-to-late 1970s with the collaborative work on conducting polyacetylene by hideki shirakawa, alan g. macdiarmid, and alan j. heeger,4-7 for which they were awarded the 2000 nobel prize in chemistry. the common view that their work marks the historical origins of these materials is further supported by the language of the award which states that it is “ for the discovery and development of electrically conductive polymers”.8 more recently, however, a number of reports have begun to reveal a more accurate and complete account of the history of these materials, highlighting in particular the documented efforts that predate the commonly cited polyactylene work of the 1970s.9-16 the first report of the conductive nature of these materials was by don weiss in 1963,17-19 but the general study of these polymeric materials far predates even this pioneering work. of the core parent polymers given in figure 1, the oldest of these materials is generally considered to be polyaniline, although exactly when this material was first studied is often a point of debate. various authors have credited different figures with the origin and discovery of this material, originally known as aniline black.20-22 these figures have included f. ferdinand runge20-23 (1794-1867), carl fritzsche9,20 (1808-1871), john lightfoot24,25 (1831-1872), and henry letheby11,26 (1816-1876). the current report will attempt to evaluate the work of these figures in light of current knowledge and thus present the first detailed account of the discovery, origins, and development of polyaniline up through the 1860s. current knowledge of polyaniline production and characteristics in order to be able to evaluate the work of the researchers above, it is first necessary to briefly review our modern understanding of the chemistry and characteristics of polyaniline. polyaniline is readily produced by oxidative polymerization, via either chemical or electrochemical oxidation of aniline.21,22,26,27 most often, such oxidations are carried out in acidic aqueous environments with a ph below 3-4, which is most favorable for the production of the polymeric product.21,22 a significant excess of oxidant is required due to the fact that polymer product undergoes oxidation at a lower potential than the initial aniline, thus consuming oxidant that cannot contribute to polymerization. as a consequence, the polymer product is also always isolated in its oxidized (p-doped) form. neutral, non-doped samples are possible, but must be obtained via reduction following the oxidative polymerization process. polyaniline can thus occur in a number of well-defined oxidation states, of which isolated polymer samples are viewed to exist as averages of these forms.22,27 these states and their corresponding names were initially proposed by arthur g. green (1864-1941) and arthur e. woodhead in 1910,28-31 and range from the fully reduced leucoemeraldine through the partially oxidized protoemeraldine, emeraldine and nigraniline, to the fully oxidized pernigraniline. the three primary forms are given in figure 2. it should be pointed out that the terms emeraldine and nigraniline predate the figure 1. common parent conjugated organic polymers. figure 2. primary oxidation states of polyaniline. 101the early history of polyaniline: discovery and origins work of green and woodhead, with nigraniline originally referring to true aniline black and emeraldine representing a green, reduced form of the material.23,32 unlike the other parent conjugated polymers shown in figure 1, the electrical conductivity of polyaniline is affected by both traditional doping via oxidation, as well as the extent of polymer protonation.21,22 this protonation effect is often referred to as protonic acid doping21,22,27 and the acid doping level can be tuned simply by controlling the ph of the dopant acid solution. as such, each of the forms given in figure 2 can exist as either its base or protonated salt. the most common forms of polyaniline, however, are either the emeraldine base or emeraldine salt (figure 3). as detailed in figures 2 and 3, the color of the polymeric material is dependent on both its state of oxidation and protonation. thus, the most common emeraldine salt is green to green-black, while the emeraldine base is violet-blue to blue-black. in both cases, the observed color is dependent on concentration. the state of the polymer also affects its relative solubility. thus, while the emeraldine base is soluble in organic solvents such as n-methylpyrrolidone, polyaniline protonated by common mineral acids is only soluble in aqueous acids.22,27 runge, kyanol, and its oxidation the oldest of the figures to which the polymerization of aniline is first attributed is friedlieb ferdinand runge (figure 4), who was born in billwärder, germany (near hamburg) on february 8, 1794.33-36 the son of a pastor,33-35 ferdinand (he went by his middle name) was the third of seven children.35 his mother died in 1806 and his father later remarried, with an additional child from the second marriage.35 his family was quite poor and could not afford to send the children for further education beyond the local primary school.34,35 thus, he was apprenticed at age 15 to his uncle, studying pharmacy at the ratsapotheke in lübeck.34-36 he then moved to berlin in 1816 in order to study medicine, but transferred to göttingen after two years, where he attended chemistry lectures by friedrich stromeyer (1776-1835).34,35 after only one semester, however, he transferred again to jena. at jena, runge studied analytical chemistry under johann wolfgang döbereiner (1780-1849)34,35 and finished his dr. med. with a dissertation on belladonna in 1819.33-36 wanting to become a professor, runge then returned to berlin that same year to habilitate as privatdozent.33-35 this required him to first acquire a dr. phil. degree, which he completed in 1822 with a dissertation on indigo.33-35 he remained in berlin where he lectured on phytochemistry and technical chemistry until october of figure 3. protonic equilibria of polyaniline’s emeraldine form. figure 4. friedlieb ferdinand runge (1794-1867). [edgar fahs smith memorial collection. kislak center for special collections, rare books and manuscripts. university of pennsylvania]. 102 seth c. rasmussen 1823, after which he traveled europe with the primary goal of visiting paris.34,35 upon his return, he joined the university of breslau as privatdozent in 1826. he was promoted to extraordinary professor of technical chemistry in 1828,34,35 but this was not a permeant position and he found his conditions unfavorable for development of his practical ideas. he finally ended his academic career in 1831.34,35 he moved to berlin where he was offered a position in the chemical works of the königliche seehandlungs societät (royal sea trade society) at oranienburg (small town near berlin) in 183233-35 or 1833.36 it was here that he began the most fruitful period of his career. among his accomplishments, he discovered a number of species from coal-tar, including pyrrole, quinoline, phenol, and aniline. he then became the technical director of the chemical plant in 1840.33 runge constantly clashed with his superiors, however, and he was ultimately dismissed in 1851,36 with his last day of employment december 31, 1852.34,35 he was granted a small pension, however, providing that he resided locally where his advice could be sought if needed.35,36 he thus remained in oranienburg where he died on march 25, 1867 at age 74.33-36 shortly after the start of his new position at oranienburg, runge began the investigation of distillates of coal-tar, which he separated into acidic and basic fractions.37 from the basic fraction, he isolated a volatile oil with a scarcely noticeable, but peculiar, odor. when treated with acid, the oil formed colorless salts, and both the oil and its salts became aquamarine when treated with chlorine of lime. because of this color response, he named this oil kyanol, from a combination of the greek kuanós (“blue”) and the latin oleum (“oil”).37 this oil was later shown to be identical to the product krystallin isolated from the dry distillation of indigo, which had been previously reported by otto unverdorben (18061873) in 1826. these materials are now both known as aniline.33 runge then found that treatment of aniline with other oxidizing agents resulted in the formation of various dark insoluble dyes. these efforts began with the application of a hydrochloric acid solution of gold oxide to a porcelain plate, followed by a drop of aqueous aniline. heating the combination to 100 °c then resulted in purple-colored spot, which became blue-gray when dried.38 he then went on to show that if one first coated a hot porcelain plate with a solution of copper oxide in hydrochloric acid, and allowed it to dry, an added drop of aniline nitrate solution heated to 100 °c then resulted in a dark green-black spot.38 using copper oxide in nitric acid and aniline hydrochloride gave the same result. in order to confirm that it was the metal oxidant that was causing the color change, he then showed that heating just aniline nitrate or aniline hydrochloride gave no decomposition or reaction. however, the addition of any copper salt then caused the formation of the black material.38 lastly, he showed that the addition of aniline hydrochloride to a hot porcelain plate coated with potassium bichromate also produced a dark black spot. in the process, runge noted that if sufficient amounts of the aniline nitrate or aniline hydrochloride salts could be produced, the colored products resulting from their treatment with metal species could provide a practical use.38 to illustrate this, he first treated cotton with lead chromate, after which he printed the fabric with aniline hydrochloride to give green patterns within twelve hours. if more concentrated solutions of the aniline hydrochloride were used, black patterns developed rather than green. both developed patterns remained unchanged by rinsing in water.20,38 runge had a strong interest in dyeing and the coloring of fabrics, as illustrated by his publication of a three-volume series entitled farbenchemie. the first of these was published in 1834,39 the same year as his initial aniline publications, and these volumes summarized the technical methods and state of the coloring field at the time.33 due to this interest and the results of his studies from various coal tar species such as aniline, runge approached his superiors in 1836 to propose that the chemical works at oranienburg could produce such synthetic dyes from coal tar, but such efforts were never approved.33,36 runge moved his focus onto other studies and it was only much later that the merits of his discoveries with synthetic dyes were recognized. following runge’s initial reports, further related studies on aniline did not appear until 1840 with the efforts of carl fritzsche. fritzsche and aniline from indigo carl julius fritzsche was born on october 29, 1808 in neustadt, germany (then within the kingdom of saxony).40,41 his father was a physician and the town where fritzsche grew up had no grammar school, so he was educated through private lessons until he was 14. he then moved to dresden, where he was employed in the pharmacy of his uncle for five years.40 after that, he moved to berlin where he became an assistant to eilhard mitscherlich (1794-1863) in 1830.40,41 as fritzsche took a doctorate in botany at the university of berlin in 1833, mitscherlich is credited with all of fritzsche’s chemical training.40-42 his initial papers focused on botanical subjects, but with chemical character, and his 103the early history of polyaniline: discovery and origins following papers began to take on greater chemical content.40 he then emigrated to russia in 1834,40-42 where he became the manager of struve’s mineral-water works in st. petersburg.41 he became an adjunct member of the st. petersburg academy of sciences in 1838, becoming an associate member in 1844, and a full member in 1852.40,42 his chemical work, most of which appeared initially in publications of the st. petersburg academy of sciences,40 touched on uric acid derivatives, various oxides of nitrogen, and most critical of the discussion here, indigo and its derivatives. all of the efforts discussed below were carried out in a small laboratory next to his house, but he later shared the new, spacious chemical laboratory of the st. petersburg academy with nikolay zinin (1812-1880) beginning in 1866.40,42 fritzsche enjoyed good health until he suffered a stroke in 1869.40-42 although he recovered from it, he suffered from paralysis on one side, and his speech and memory suffered.40,42 nevertheless, he continued working until his death on june 20, 1871.40,41 in 1840, fritzsche published a paper detailing the isolation of a new species from the decomposition of indigo.43 treating indigo with a hot, highly concentrated solution of base gave a salt mass of reddish-brown color, from which was then distilled a brown oil. further purification isolated a colorless oil, which he called anilin after the spanish name of indigo, añil.41 this material was a base which formed light and highly crystalline salts and was isolated as 18-20% of the original indigo.43 during the publication of this paper, the editor of the journal für praktische chemie, otto erdmann (1804-1869), recognized the similarity of anilin with unverdorben’s krystallin, and highlighted this in a note following fritzsche’s paper.44 two years later, nikolay zinin reduced nitrobenzene to give a species that he called benzidam.45 in a short note directly following zinin’s paper, fritzsche identified benzidam as his own anilin, stating that there can be no doubt about its identity.46 the following year, august hoffmann (1818-1892) then presented evidence that unverdorben’s krystallin, runge’s kyanol, fritzsche’s anilin, and zinin’s benzidam were all the same compound,47 which ultimately became known as phenylamine or aniline. fritzsche found that aniline reacted with exposure to air, taking on first a yellow color and then turning into a brown mass. continuing his 1840 study of the oil, he found that under ‘certain circumstances’ treatment with hno3 caused the production of a blue or green material, which he thought might be indigo, but he was only able to generate it in small quantities.43 he then found that dissolving aniline salts in chromic acid (h2cro4, typically as a h2so4 solution) produced a dark green precipitate, which ultimately became black-blue in color.43 combustion analysis of the precipitate revealed a significant amount of chromium. lastly, he treated aniline salts with potassium permanganate, which resulted in a brown precipitate containing manganese oxide. fritzsche admitted that he had not been able to study these color-forming reactions in much detail and planned to return to these in later publications.43 thus, while he did not follow up on the direct results reported in 1840, he did return to the treatment of aniline with oxidants in 1843, this time applying potassium chlorate.48 mixing an alcohol solution of aniline salt with potassium chlorate in hcl resulted in a blue precipitate, which turned green upon washing with alcohol, and became dark green upon drying. analysis of the composition of the solid revealed an empirical formula c24h20n4cl2o, which is in near perfect agreement with the structure of the emeraldine salt given in figure 3 (x = cl-).48 although this seems to be fritzsche’s last report on the oxidation of aniline, the green aniline materials introduced by runge and fritzsche were later applied to commercial dyes by frederick crace-calvert (1819-1873), samuel clift, and charles lowe. calvert, clift, lowe and emeraldine frederick crace-calvert was born near london on november, 14, 1819.49 in 1835, he moved to france where he studied chemistry at the university of rouen under gerardin. after two years, he then moved to paris to continue his studies at the sorbonne and the college de france. he then became the manager of the chemical works of robiquet and pelletici at the age of 21, but soon left to become an assistant to michel eugène chevreul (1786-1889) in 1841.49,50 he returned to england in late 1846, where he was appointed as a honorary professor of chemistry at the royal institution, and later as lecturer on chemistry at the school of medicine in manchester. he became interested with the properties of carbolic acid and built works for its manufacture in 1865. due to his various contributions, he became a fellow of the royal society and of the chemical society, as well as other societies both at home and abroad. he was seized with a fatal illness in 1873, and died in manchester on october 24, 1873.49 sometime prior to the summer of 1860, cracecalvert, samuel clift, and their assistant charles lowe developed green and blue dyes from the oxidation of aniline for the coloring of cotton, for which they filed a joint patent on june 11, 1860.24,51,52 these methods involved the application of an aniline salt (either the hyrdochloride or 104 seth c. rasmussen tartate) and potassium chlorate to give a green color after 12 hours. this green color was given the name emeraldine,24,50-55 which ultimately became the name adopted for the most common form of polyaniline (figure 3). if the initially produced green dyed fabric was boiled in an alkaline or soap solution, the green color could be converted to a blue color, which was given the name azurine.24,51-54 both the blue color and the method of its production from emeraldine is consistent with the formation of the emeraldine base as outlined in figure 3. cracecalvert presented these results as part of an address before the society of arts, which was then published in the february 7th issue of the journal of the society of arts in 1862.52 later that same year samples printed by these techniques were exhibited in the chemical section at the london international exhibition of 1862.55 the following year crace-calvert also included this in his book lectures on coal-tar colours, and on recent improvements and progress in dyeing and calico printing.53 crace-calvert, clift, and lowe induced the printers wood and wright to apply their methods to generate green and blue colors in the end of 1860.53 wood and wright considered the resulting colors good enough to be commercialized and introduced improvements resulting in a dark shade that could be considered black.25,53 the improvements were achieved by either adding iron salts or other oxidizing agents to the potassium chlorate, followed by treating the color produced on the fabric with either a weak solution of potassium bichromate or bleaching powder. it was also found that copper nitrate could be mixed with aniline hydrochlorate, without the addition of potassium chlorate, and the mixture could be printed on the fabric to gradually give a dark green or black. these two methods gave either a green or blue color, but one that was so dark that it could be viewed as black.53 about the same time, black dyes produced from the oxidation of aniline were introduced by john lightfoot and heinrich caro (1834-1910). lightfoot, caro, and aniline black john lightfoot, jr. was the son of thomas lightfoot (1811-1866), but was named after his grandfather john lightfoot, sr. (1774-1820).25,50 his grandfather, father, and uncle were all colorists and connected with the broad oak print works of accrington, about 20 miles north of manchester.24,25,50 as part of his practical education, lightfoot traveled to france and alsace in 1854.50 he then continued the family tradition by joining broad oak in ca. 1855.25 at broad oak, lightfoot played a leading role in the use of madder, archil (or orchil), and indigo colors. he also began experimenting with the semisynthetic colorant known as murexide, the behavior of aniline colors, methods of fixing new dyes to wool and cotton, and imitations of madder and aniline colors.25 according to lightfoot, it was november 1859 when he first observed that aniline hydrochloride in the presence of potassium chlorate imparted a fast and brilliant black to cotton during printing.25,51 initial efforts in the application of this aniline hydrochloride and potassium chlorate mixture produced little to no color after 24 hours, but he found that when the same formulation was printed with copper rollers, a green color was produced within 12 hours. believing that the copper was a critical factor, he then added a copper salt to the mix to ultimately give an intense black.24,51 the conclusion that the copper was a necessary factor is not consistent with the previous reports of either runge38 or fritzsche,48 both of which produced either green and black materials by treating aniline hydrochloride with chlorate salts alone. in reviewing the formulation given by lightfoot,51 however, it is clear that he used too little potassium chlorate to sufficiently oxidize the aniline salt and thus an additional oxidant such as copper was required for him to generate the color in sufficient intensity. of course, prior to the addition of the copper salts, lightfoot’s process of printing cotton with the green or black aniline dyes was nearly identical to that originally reported by runge.38 in fact, from a chemical standpoint, the methods only differed in the chlorate salt utilized. although lightfoot recognized that the high price of aniline in 1859 was a disadvantage, he continued with experiments in july 1860 and had produced a few samples by 1861.24,25 in 1862, he reported his discovery as a letter to the editor in the december 6th issue of chemical news and journal of industrial science, along with some sample swatches.56 at the end of lightfoot’s letter, the editor added a note that the color was not a pure black, and as with the previous cases of either runge38 or wood and wright,53 was most likely so dark a blue or green as to appear black. however, lightfoot’s black was considered superior to that of wood and wright.25 patents for this process were filed in early 1863,51 with the us patent granted in may of the same year.57 in this patent, lightfoot describes the dyeing of fabric with mixtures of aniline hydrochloride and potassium chlorate, followed by the addition of copper chloride.24,55,57 the patent, however, also covered the use of other copper salts or even salts of other metals.57 the rights were then sold to jakob j. muller-pack of basle.25 a significant limitation in lightfoot’s printing process was that it caused severe corrosion to the rollers of the printing machines, which also led to streaking on 105the early history of polyaniline: discovery and origins the cloth.24,25,55 this limitation was solved by charles lauth, who registered a patent in 1964 that specified the use of insoluble copper sulfide. the insoluble salt was inactive at the time of printing and later converted to soluble copper sulfate by action of the chlorate salt during development of the aniline black, which dramatically reduced the damage to the rollers of the printing machines.24,55 lauth’s process was sold to muller-pack, who combined it with lightfoot’s process in an effort to dominate the european and us markets.25 during this same time period, a second black aniline dye was produced by heinrich caro (figure 5) in 1860.24,25 born on february 13, 1834 in posen, caro attended the realm gymnasium in köln from 18421852.58 from 1852-1855 he attended the königliche gewerbeinstitut (royal trade institute), which trained students for industry, while also attending lectures at berlin’s friedrich-wilhelms-universität (now the humboldt university of berlin).58,59 in april 1855, caro took a modest appointment in the troost factory in mülheim, where he mainly performed analytical work outside the printing shop.58 in march 1857, caro was then sent on a study trip to england in march of 1857, where he visited a large number of printing and dyeing factories, in particular that of john dale and roberts. upon his return to germany, he then carried out his military service in 1857-1858.58 in november, 1859, caro moved to england to try his luck there. although his initial efforts were in vain, he was finally able to obtain a job with john dale, co-owner of the cornbrook chemical works of roberts, dale & co. in manchester.58-60 he later returned to germany in 1866, and on november 1, 1868 he became the coordinating technical director for the badische aniline and soda fabrik (basf).24,58-60 there he oversaw development of new colors including artificial alizarin, eosin, methylene blue, and azo dyes, as well as the initial stages of the indigo synthesis, and contributed towards the structural elucidation of the triphenylmethane dyes.59 he was appointed to the company’s board of directors in 1884 and continued to serve on the board until 1890.60 caro died after a short illness on september 11, 1910 in dresden.58 in 1960, while working for roberts, dale & co., caro developed a process for making aniline purple by the oxidation of aniline with copper salts. after alcoholic extraction of the desired purple dye, a black residue remained which provided an excellent fast black dye for printing on cotton. roberts, dale & co. then commercialized this dye for sale to printers in 1862.24,54,59 as with lightfoot’s original formulation, this residue played havoc with the printing machinery, but it could be successfully printed with wooden hand blocks.24 the efforts of roberts, dale & co. established the advantages of aniline black over other black colorants of the time and it has been proposed to have been the motivating factor for lightfoot to patent his process in 1863.24 as discussed above, the color found more widespread application in british printworks following the introduction of insoluble copper sulfide by charles lauth in 1864.59 by 1871, these black dyes from aniline became known as aniline black.51 aniline black later became the first real general term for polyaniline. following the introduction of aniline black dyes, the next major innovation came from the physician and chemist henry letheby. letheby and the electrolysis of aniline sulfate henry letheby (figure 6) was born in plymouth, england in 1817,61-63 and received his early education figure 5. heinrich caro (1834-1910). [edgar fahs smith memorial collection. kislak center for special collections, rare books and manuscripts. university of pennsylvania]. 106 seth c. rasmussen there.61 he continued his chemical studies in the laboratory of the royal cornwall polytechnic society in falmouth,61,62 where he eventually became assistant and did some lecturing.61 he then moved to london in 1837 to attend the aldersgate medical school, where he became assistant to jonathan pereira (1804-1853), professor of chemistry at the london hospital.61,62 letheby became a licentiate of the society of apothecaries in 1837, and then received his m.b. (bachelor of medicine) from london university in 1842,62,63 after which he succeeded pereira as the chair of chemistry and toxicology at the london hospital in 1846.61,62 he was elected as london’s medical officer of health in 1855,61-64 while also serving as the city’s public analyst.62-64 in addition, he served as the city’s chief gas examiner 62-64 and as a consulting chemist to the great central gas company61,64 in 1858, he received a m.a. and ph.d. from an unknown german university.62 he was a fellow of both the linnean society of london and the chemical society of london.62,63 because of failing health, letheby resigned his city posts in february 1874.62 after a brief illness, he died at the age of 60 on march 28, 1876, at his home in london,61-64 and was buried in highgate cemetery on march 30th.62 after the investigation of two cases of fatal poisonings by nitrobenzenes, letheby began investigations into chemical tests for the presence of aniline, as he had found that nitrobenzene was reduced to aniline after ingestion. thus, he reported the study of acidic solutions of aniline with various oxidizing agents to produce blueto-purple colors in 1862.65 continuing his investigations, letheby then oxidized sulfuric acid solutions of aniline via a pt electrode at the positive pole of a small grove’s cell (an early high current battery) to generate a deep blue to bluish-green pigment that adhered to the electrode as a fine powder.65 as with many of the previous reports of chemical oxidation, the exact color observed depended on the concentration of the aniline solution used. he then prepared the material on a larger scale, using greater quantities of aniline and two larger grove’s cells connected together for intensity.65 using this setup, a thick layer of dirty bluish-green pigment quickly covered the large platinum sheet (4 × 6 in) acting as the positive electrode. the pigment was then removed from the electrode, washed with water and dried to give a bluish-black powder. the powder was insoluble in water, alcohol, ether, or ammonia, and was only soluble in sulfuric acid. immersion in ammonia did cause the powder to acquire a brilliant blue color, but the resulting blue pigment still did not dissolve. when dissolved in concentrated sulfuric acid, the solution formed was either blue, green, or violet depending on the degree of concentration. diluting the resulting acid solution with water then resulted in the precipitation of a dirty emerald green powder, which could be made blue with treatment of concentrated ammonia or blue to purple with the addition of concentrated sulfuric acid. the blue pigment generated by any of the means above could also be partly decolorized by various reducing agents, and in this condition, it became soluble.65 analysis and discussion although the various studies presented above included little to no structural or compositional data, all of the reaction conditions and resulting properfigure 6. henry letheby (1816-1876) [by w. & d. downey albumen carte-de-visite, 1860s © national portrait gallery, london]. 107the early history of polyaniline: discovery and origins ties reported are completely consistent with the modern knowledge of the oxidative polymerization of aniline, as well as the chemistry and characteristics of the resulting conjugated polymer, polyaniline. in addition, it is clear that all four of the historical figures that have been previously credited with the origin and discovery of polyaniline did indeed play critical roles in the early history of this material. however, if we are to assign priority to any of these figures, the credit must be properly given to runge. not only was he the second to discover aniline itself after unverdorben, but he was the first to report its oxidative polymerization and the first to document the successful application of these products as both green and black dyes for printing on cotton.38 although runge’s contributions were not usually recognized during the time periods discussed above, heinrich caro paid tribute to runge during the celebration of his own 70th birthday in 1904, crediting runge with various discoveries including the first formation of emeraldine by copper salts.33 while caro does not go so far as to credit runge with the discovery of aniline black, author emilio noelting (1851-1922) begins his 1889 book scientific and industrial history of aniline black with the statement that the history of aniline black can be traced to the “very old researches of runge”.20 the proper recognition of runge should not diminish the contributions of the remaining three gentlemen, however, all of which left their mark on the history of polyaniline. although fritzsche did little to advance the oxidative polymerization of aniline beyond what was previously reported by runge, he was the third to discover aniline and more importantly gave it the name by which we recognize it today.43 needless to say, there would not be the current term polyaniline without the contributions of fritzsche! also of significant importance is the fact that fritzsche was the first to analyze the elemental composition of the polymerized product to reveal an empirical formula in near perfect agreement with the structure of the modern emeraldine salt of polyaniline.48 of course, the work of both runge and fritzsche may have been lost as academic curiosities if it had not been for the efforts of crace-calvert, lightfoot, and caro to develop these materials into commercial products. in addition, it is their application of this material as a black dye that resulted in the longstanding name aniline black, the primary common designation for this material until the ultimate use of the modern polyaniline. it is hard to quantify how much impact their work had on maintaining interest in polyaniline until its more critical electronic properties were ultimately discovered in the 1960s.9,10,16 lastly, one cannot overlook the contributions of letheby. although he most certainly was not the first to report the oxidation of aniline to polyaniline, as is often claimed, he was the first to demonstrate its electrochemical oxidation and the very first to report on this method for the production of conjugated materials.65 the electrochemical generation of conjugated polymers was the most common route to conductive films of these materials prior to the 1990s, and this still is the most common method utilized for the production of polyaniline. in closing, i would like to postulate a final question for further consideration. if the work discussed above places the first report of the polymerization of aniline to polyaniline with the work of runge in 1834, is polyaniline then the earliest known synthetic organic polymer? i am not the first to propose this possibility,26 but i still feel that this is worth bringing to light once more and to provide at least initial support for such a claim. although the term polymer was first coined by berzelius in 1832, it did not have the same meaning as its modern usage and did not originally refer specifically to macromolecules.66,67 in addition, none of the studies above ever used the term to refer to the oxidation products of aniline and the modern concept of macromolecules was not accepted until the 1920s, after which it was decades before staudinger, carothers, flor y, and others could convince the scientific community that these unusual molecules were real.9 the earliest man-made polymer is generally considered to be polystyrene, whose polymerization was first obser ved in 183968 in which freshly distilled stora x resin produced an oil (styrene, but then called styrol) that converted into a rubberlike substance in the presence of air, light, and heat.66,69 of course, from the discussion above, runge’s conversion of aniline to greenblack materials predates the obser ved formation of polystyrene by five years. in addition, unlike the spontaneous polymerization of styrene, aniline was polymerized via the purposeful addition of an oxidizing agent and its polymerization was carried out under a number of different conditions. a complicating factor in this argument is that what made polystyrene interesting was its obvious changes in physical properties, while the obvious changes in the polymerization of aniline was the resulting color produced, rather than any particular physical change. as such, in that time period of the early 19th century there were no related properties to connect the two materials and polyaniline was not recognized as what we would call an oligomer or polymer until 1910.28-31 still it is clear that polyaniline represents not only an important beginning in the path to conducting organic materials, but to organic polymers in general. 108 seth c. rasmussen acknowledgements i would like to thank tony travis for sharing some of his publications on lightfoot, caro, and anline black, as well as for a number of helpful discussions. thanks also to dave lewis for the helpful discussion on the relationship between fritzsche and zinin. i would also like to thank the department of chemistry and biochemistry of north dakota state university (ndsu) for continued support of my historical research, as well as the ndsu interlibrary loan department, who went out of their way to track down many elusive and somewhat obscure sources. references 1. 100+ years of plastics. leo baekeland and beyond (eds.: e. t. strom, s. c. rasmussen), acs symposium series 1080, american chemical society, washington, d.c., 2011, pp. 1-3. 2. handbook of conducting polymers, 3rd ed. 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albertini, l. teodori (2019) tissue engineering between click chemistry and green chemistry. substantia 3(2) suppl. 6: 29-38. doi: 10.13128/substantia-591 copyright: © 2019 a. costa, b. walkowiak, l. campanella, b. gupta, m. c. albertini, l. teodori. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. tissue engineering between click chemistry and green chemistry alessandra costa1,#, bogdan walkowiak2, luigi campanella3, bhuvanesh gupta4, maria cristina albertini5,*, laura teodori1,$,* 1 diagnostics and metrology laboratory fsn-tecfis-dim, enea cr frascati, via enrico fermi 44, 00044, rome, italy. e-mail: laura.teodori@enea.it 2 department of biophysics, institute of materials science and engineering, lodz university of technology, poland, and bionanopark laboratories, bionanopark ltd, lodz, poland. e-mail: bogdan.walkowiak@p.lodz.pl 3 department of chemistry, sapienza university, piazzale aldo moro 5, 00185 rome, italy. e-mail: luigi.campanella@uniroma1.it 4 department of textile technology, indian institute of technology, new delhi 110016, india. e-mail: bgupta@textile.iitd.ernet.in 5 university of urbino carlo bo, department of biomolecular sciences, via saffi 2, 61029 (pu), urbino, italy. e-mail: maria.albertini@uniurb.it #guest researcher. e-mail: alessandracosta1986@gmail.com *equally contributed $corresponding author: laura teodori abstract. tissue engineering  is a strategy to improve or replace  biological  tissues and organs approached by an engineering point of view, thus combining the principal elements of tissues/organs (i.e. cells, scaffolds and bioactive molecules),  as rebuilding a machine starting from its components. the concept of tissues and organ generation/ regeneration has always impassioned mankind, starting from ancient religious and myth accounts, encompassing the vedic culture, the bible books and the greek myths. nowadays, thanks to advances in biochemical, technical, and medical knowledge many progresses have been achieved in this field. indeed, the recent successful efforts to create biomaterial scaffolds have attracted a great deal of interest. however, despite of the significant progress, the realization of clinical and commercial products is experiencing frustration and slowdowns and sustainable tissue engineering may not be fulfilled with present approaches. the recent philosophy of “click” chemistry, to generate or functionalize synthetic scaffolds to obtain more biocompatible materials, and the introduction of “green” chemistry, focused on minimizing the use of hazardous substances, will give a new twist to tissue engineering and will open new fascinating and promising utilization. in this review we highlight the contribution that both click and green chemistry may represent for the development of new technologies in tissue engineering. the concern for a more sustainable and inclusive technology is also addressed. keywords. tissue engineering, click chemistry, green chemistry, biomaterial. 30 alessandra costa et al. list of abbreviations bmp: bone morphogenetic protein cuaac: copper-catalyzed alkyne-azyde cycloaddition da: diels-alder (reaction) gfs: growth factors go: graphene oxide ha: hyaluronic acid hap: hydroxyapatite mirna: micro-rna mscs: mesenchymal stem cells nps: nanoparticles peg: polyethylene glycol pda: polydopamine ptt: photo-thermal therapy pufas: poly-unsatured fatty acids sp-aac: strain-promoted azide-alkyne cycloaddition te: tissue engineering tnf: tumour necrosis factor 1. introduction mankind has always been fascinated by the idea of tissue/organ generation and regeneration. in the biblical book of genesis, god created man from the dust of the ground and the first woman from adam’s rib. in the greek myth of the titan prometheus, he moulded men out of water and earth and defied the gods by stealing fire and giving it to humanity as civilization. he was then chained by zeus, as punishment, up to the caucasus rocks, where every day an eagle devoured his liver, which would regenerate overnight. the holy rig veda (among the oldest religious texts in the world, composed approximately 2000-1000 bce but also based on earlier oral traditions) contains the first mention of prosthetic and te (tissue engineering): queen vishpala, who was amputated in a battle, was fitted with an iron leg enabling her to return to the battlefield. in sumerian mythology the gods enki and ninmah created humans from the clay of the abzy, the fresh water flowing underground. human attempts to substitute injured tissue/organs or at least to restore their function, led to the creation of first biomaterials through history; defining a biomaterial as any material in contact with a human tissue intended to substitute or restore a lost function, we can find some examples in sutures or foot prosthesis applied in ancient egypt; dental replacement by seashells in mayan population (ca. 600 bce); hand prosthesis during the middle age to endosteal dental implants within the middles of the last century.1,2 kam w. leong, editor in chief of biomaterials, offers a valid current definition of biomaterial as “a substance that has been engineered to take a form which, alone or as part of a complex system, is used to direct, by control of interactions with components of living systems, the course of any therapeutic or diagnostic procedure”.3 thus, the current use and creation of a biomaterial is far from the first inert materials interfacing human body. as in the definition, a biomaterial is something that has been engineered, meaning that the final product has been modified by the addiction/subtraction/substitution of small functional moduli, as the gears of a clock. biomaterials can be synthetic (i.e. polypropylene, polytetrafluoroethylene, polyethylene glycol, pyrolytic carbon, etc.) or biologic (alginate, collagen, extracellular matrix etc.). both types of biomaterials show pros and contras, which discussion is not in the scope of this review. however, chemistry played and is still playing a fundamental role in the creation and technological development of any type of engineered biomaterial. currently, many traditional biomaterials, with well proven mechanical properties and long history of clinical use, are subjects of surface engineering to enhance biocompatibility and ability of use in customized process. this surface engineering uses several different approaches from simple physico-mechanical treatment and surface chemistry up to nano-structurization. biomaterials are one of the key elements in the triad underling te approach being the other two stem/progenitor cells and bioactive molecules (i.e. gfs, chemokines and cytokines, fatty acids, mirnas and any molecule able to activate, modulate and control a cellular response). for this reason, chemistry has also a pivotal role in te. despite the significant progress in vitro and in vivo on animal models, the achievement of the desired clinical and commercial deliverables has been frustrating, especially in diseases that cannot take advantage but from te therapies.4 in addition, the costs of such biotechnology may represent a further barrier for the future clinical diffusion. indeed, sustainable te may not be achievable with current approaches. thus, it is our opinion that a strategy and methodology rethinking are needed, for promoting more inclusive and economical sustainable development together with a low environmental impact. sustainable development of te requires redesigning many chemical processes, which often rely upon technology developed in the 20th century and creating new reactions and protocols under less environmentally harmful conditions, using safer materials and studying more economically affordable translational technology to face diseases not treatable with current available medicine. in this review we want to highlight the contribution that both “click”, and “green” chemistry may repre31tissue engineering between click chemistry and green chemistry sent for the development of new technologies in the te field. click chemistry is an approach described by barry sharpless in 2001 (nobel prize in 2001 for developing chirally catalysed oxidation reactions) based upon the following criteria: “the reaction must be modular, wide in scope, give very high yields, generate only inoffensive by-products that can be removed by non-chromatographic methods, and be stereospecific. the required process characteristics include simple reaction conditions (ideally, the process should be insensitive to oxygen and water), readily available starting materials and reagents, use of no solvent or a solvent that is benign (such as water) or easily removed, and simple product isolation.”5 thus, click chemistry meets the concept of green chemistry. green chemistry is a philosophy based on 12 principles oriented to reduce waste and product toxicity, use renewable source materials and save energy.6 in this review we would also like to give a warning about the possible wealth “divide” and generation of inequality caused by the technological advanced techniques such te and how improvement in scientific fields of research should be oriented to challenge the gap with developing countries. 2. click chemistry contribution to sustainable tissue engineering most of strategies developed in the click chemistry  can serve as an essential approach of green  chemistry. the focus of click chemistry is on reducing the environmental impact of working with potentially toxic materials. this approach is based on chemical reactions which can take place in mild conditions but with a high efficiency, allowing the reaction between several chemical groups to realize a stable product not subject to oxygen reactivity.5 such reactions are also defined orthogonal, intended to avoid other side reactions, since bioactive molecules can present complex structures.7 indeed, bio-orthogonal chemistry  refers to chemical reaction  that can occur inside living systems without interfering with native biochemical processes. the recent development of copper-free  click chemistry  allows forming te materials without the use of toxic catalysts or immunogenic enzymes that are commonly required. 2.1 biomaterials and 3d printing tools one of the major issues in te is the choice of scaffold biomaterial guiding the regeneration process. among biomaterials, synthetic polymeric ones have had a wide success in te because their characteristics are well defined, largely reproducible and possess strong mechanical resistance, even if they showed very low or no consistent bioactivity.8 however, synthetic polymers may not represent a suitable biological microenvironment for i) host stem cells recruitment, ii) providing appropriate cues to promote asynchronous stem cells division and differentiate some of them, iii) promotion of angiogenesis and innervation. synthetic polymeric biomaterials can be made biologically active through the functionalization with biomolecules (i.e. cytokines, drugs, fatty acids, gfs and mirnas and many others). previously described click chemistry approach has been applied to for the creation of biomolecule-polymer hybrids.5 the most famous click reaction has been the cuaac that, however, suffers from the uncontrollable accumulation of cu ions within the biomaterial.9 thus, click chemistry rapidly evolved towards copper-free reactions. diels-alder (da) reactions (nobel prize in 1950) involve diene and alkene as reactant in water and give high efficiency and selectivity. importantly these reactions will not produce toxic products.10 one of the most common applications of da reaction is hydrogels generation for te. hydrogels can be easily injected because the gelation usually occurs at body temperature, can be loaded with hydrophilic molecules and are particularly suitable as environment for highly hydrated tissues, such as cartilage. a hydrogel for cartilage te was developed through da reactions between hyaluronic acid (ha) and furan adipic dihydrazide and between ha and furan aldehyde, followed by peg addition.11 this hydrogel showed the same compressive modulus during the healing process, it was adhesive to cartilage because of the aldehyde-amine schiff-base reaction and it also behaved as smart biomaterial, since it was able to change the structure in response to ph variations.11 hydrogel biomaterial application is not limited to hydrated tissue but can also serve as 3d environment to guide the differentiation of stem cells toward a desired tissue. a peg-based hydrogel releasing dexamethasone, obtained by da reactions, has been studied as 3d environment to induce mscs to form bone tissue. mscs cultivated within this hydrogel showed a high alkaline phosphatase activity and mineralization,12 which could represent a first evidence of bone differentiation. also in vivo a hydrogel created through da reactions was studied for bone regeneration in rat cranial defects, showing bone formation after 12 weeks. this hydrogel was built up by the crosslinking of modified sodium alginate, bioglass and chondroitin sulphate.13 hydrogel biomaterials created by da reaction found a plethora of applications, not limited to skeletal tissues. for example, cardiomyocytes were loaded in a hybrid hydrogel created by the application of da reactions involving modified 32 alessandra costa et al. peg and fully interpenetrating thermosensitive hydrogel based on chitosan. the hydrogel/cardiomyocyte graft was implanted subcutaneously in nude mice and allowed for cell retention and survival for 2 weeks. this hybrid material kept the robust mechanical properties obtained by da reactions and accelerated gelation in situ thanks to the thermosensitive counterpart.14 sp-aac (strain-promoted azide-alkyne cycloaddition) is another copper-free click reaction, in which the ring strain accelerates the reaction between cyclooctyne and azyde.15 several hydrogels of modified peg, ha and dextran for biomedical purposes (bone, cartilage and neural regeneration) have been created with this approach. major advantages of these hydrogels are the possibility to customize biomaterial properties directly in situ, the functionalization with bioactive molecules and photo-patterning in the presence of live cells.16,17,18,19,20,21 sometimes hydrogel biomaterials do not offer the required mechanical strength because of their own nature. cross-linking is a strategy adopted to enhance mechanical strength of biomaterials. the series of reactions involving thiyl and carbon-based radicals in a basic solution leading to the formation of covalent carbon-carbon bonds are known as thiol-ene click reactions and has been used in the development of cross-linked hydrogels.22 applying this strategy, a hydrogel has been created, that can be degraded in a tubular structure when exposed to glucose. such a hydrogel is suitable in neural system regeneration and has been studied as a scaffold material for endothelial and neural stem cells for the creation of a neural like tissue.23 recently, the possibility to link a hydrogel with live cells (c2c12 myoblasts) has been demonstrated.24 in this study both alginate, as backbone of the hydrogel, and myoblasts have been modified with chemical groups able to give rise to a thiol-ene reaction. the main limitation of these reactions is the need of an activator of the catalysis, like uv radiations or photo-polymerization, which poses biological concerns. similar reactions, called thiol-michael reactions, do not need such activators and are permissive towards several chemical groups.25 less frequently te has taken advantage of click chemistry for the creation of biomaterials other than hydrogels. for example, poolman et al. generated a film of polyacrylic acid which thickness and morphology can be tuned controlling the density of the reagents through a layer by layer method.26 microspheres represent another scaffold conformation particularly suitable as a carrier for bioactive macromolecules. microspheres based on cross-linked poly(divinyl benzene) have been functionalized by da reactions to bind poly (ε-caprolactone) and fluorescent rhodamine-b.27 biomaterials should support functional tissue regeneration also guiding cell proliferation and differentiation in the suitable 3d environment. the 3d structure assumes a critical importance during the regeneration of highly hierarchically structured tissues/organs, such as skeletal muscle, heart, lungs or kidney, where the 3d architecture is essential for organ own function. threedimensional bioprinting is trying to meet this challenge. what is used as bioink to print the final tissue structure should meet several parameters: to be biocompatible, not cytotoxic, and rapidly form the final product (e.g. by gelation). bertlein et al. created a bioink, called gelage, obtained by the polymerization of allylated gelatin through thiol-ene click reactions that can be activated both by uv-light and visible-light.28 same type of click reactions has been applied for creation of linear poly(glycidol) based bioink that polymerized under uvlight. the final product was a 20-layer structure enriched with hyaluronic acid with a height of 3.90 mm. click chemistry has been fundamental in te not only for the improvement of biomaterial performance but also for the creation of other tools such as bioink in 3d printing technology, drug delivery and tracking of drugs during release. chemical reactions and molecules involved in click chemistry are extensively described in a review by zou et al.7 2.2 living cells engineering click chemistry can also be a useful tool for engineering living cells to allow the modification of cells with chemical tags. using tagged biomolecules, we can introduce chemical tags into proteins, glycans and lipids in living cells that metabolize such biomolecules releasing the tag. tagged biocomponents can then be exploited for several purposes as cell tracking, cell drug delivery, cell complex, tissue targeting, and tumour labelling.29 click chemistry in living cell engineering is an important application in cell transplantation or cellbased therapy. this latter approach represents a powerful therapeutic method for the treatment of many diseases. however, the therapeutic outcome has not been always successful, due to low engraftment rates or short cell survival after transplantation. in addition, the biodistribution and fate of transplanted cells are not easy to follow due to the inadequacy of in vivo cell tracking methods. thus, to improve these biases, cells functionalization and tracking techniques, through cell engineering, by click chemistry for example, have been introduced. the first application of click chemistry in cell transplantation for taking the transplanted cells was carried out in 2014 by kang.30 this approach was based on sp-aac 33tissue engineering between click chemistry and green chemistry reaction aimed at engineering cell surface with n-azidoacetyl-mannosamine (ac4mannaz) that offers the link with the probe. this approach was then improved in order to stabilize the tracking for longer time (4 weeks), to avoid the impairment with cellular functions, and to make the tag detectable through different technologies, i.e., fluorescence, computed tomography and magnetic resonance.31,32 click chemistry-engineered cells have found an important application also in other fields as the cell-based drug delivery.30 mscs are known to be attracted by tumours, thus mscs have been investigated as an anti-cancer drug carriers.33 cell surface modification using metabolic glycol-engineering and copper-free click chemistry has been used for the functionalization of mscs with nps.31 the authors demonstrated that the combination of metabolic glycol-engineering and the spaac reaction allowed for the modification of mscs with cnps (chitosan nps) in a short reaction time, and that cnp-modified mscs could be tracked over long-term.31 if click chemistry for glycoengineering can be selectively applied to tumour cells it could be possible to functionalize tumour cells with receptors for a specific anti-cancer drug34 or to express immune-stimulant molecules.35 ac3mannaz has been synthetized linked to a substrate that can be cleaved by enzymes highly expressed in different tumours36,37,38 allowing for tumour labelling. 3. green chemistry contribution to sustainable tissue engineering another issue related to te is the sustainability in terms of environment and economic sustainability (discussed in paragraph 4). increasing interest about sustainability in each aspect of individual and society life is now rightfully paid by several countries all over the world, especially in the european union (transforming our world: the 2030 agenda for sustainable development39). the extremely rapid climate change, the consequent environmental mutation and species extinction40 urge the need for a green approach not only in consumables, transports and energy production, but also in biomedical research. green chemistry is defined in 12 principles by anastas and warner (1998).6 here we report the principles as described by linthorst:41 1. it is better to prevent waste than to treat or clean up waste after it is formed; 2. synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product; 3. wherever practicable, synthetic methodologies should be designed to use and generate substances that possess little or no toxicity to human health and the environment; 4. chemical products should be designed to preserve efficacy of function while reducing toxicity 5. the use of auxiliary substances (e.g. solvents, separation agents) should be made unnecessary wherever possible and innocuous when used; 6. energy requirements should be recognized for their environmental and economic impacts and should be minimized. synthetic methods should be conducted at ambient temperature and pressure; 7. a raw material of feedstock should be renewable rather than depleting wherever technically and economically practicable; 8. unnecessary derivatization (blocking group, protection/deprotection, and temporary modification of physical/chemical processes) should be avoided whenever possible; 9. catalytic reagents (as selective as possible) are superior to stoichiometric reagents; 10. chemical products should be designed so that at the end of their function they do not persist in the environment and break down into innocuous degradation products; 11. analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances; 12. substances and the form of a substance used in a chemical process should be chosen so as to minimize the potential for chemical accidents, including releases, explosions, and fires. in te, attention is arising to the use of chemical products that are safe and green, to their substitution with green strategies, and to the obtainment of final products which by-products and disposal are not hazardous for the environment and human health.42 indeed, the creation of several biomaterials requires steps involving cytotoxic solvents, such as the electrospinning of collagen fibres. electrospinning is a very popular technology to form microand nanofibers starting from polymeric mats melted or in solution. polymeric mat is loaded in a syringe whose needle is directed toward a metallic rotating support; both the support and the needle are subject to high voltage field that generate an electrostatic force; when the electrostatic force overcomes the surface tension of the polymeric mat, the fibre starts to form.43 most of the solvents used in electrospinning are organic, cytotoxic and harmful for human health, hence the study of green solvent to be used in biomaterials generated via electrospinning.44 zhou et al. developed collagen-i fibres 34 alessandra costa et al. dissolved in phosphate buffered saline/ethanol solution, thus avoiding the application of cytotoxic organic solvents. such collagen fibres also brought hap microspheres for bone regeneration.45 hap for bone regeneration is also produced in nanoparticle size, because nps resemble the native crystalline structure of bone ecm. a green synthesis of nano-hap has been obtained starting from eggshell waste as source material for calcium, while phosphate was obtained from ammonium dihydrogen orthophosphate.46 another green strategy to obtain nano-hap is based on a backbone of fatty acids (linoleic, lauric and oleic acids) for hap formation.47 pufas, namely linolenic acid, present in flaxseed, has been demonstrated to counteract the negative effects of tnf upon myoblasts in vitro and the degeneration of myofibers in muscular dystrophy in vivo.48 this study suggested that pufas could represent green bioactive molecules to be loaded upon biomaterials for skeletal muscle regeneration. thus, pufas can be green candidate molecules to be used with different purposes in te. the natural protein silk fibroin is probably one of the most known natural biomaterials ever studied. silk fibroin results particularly suitable as biomaterial in tissue regeneration because of its high biocompatibility and good mechanical properties, indeed it has been customized in several forms for different applications in te.49,50,51,52,53 a hybrid biomaterial composed by silk fibroin and graphene oxide (go) has been created using a green method involving silk crystallization through glycerol during lyophilization, thus avoiding organic solvents. aiming at bone regeneration, this hybrid biomaterial was loaded with simvastatin that enhanced the production of bmp-2.54 another green and natural source for the fabrication of biomaterials is represented by polysaccharides, abundant in nature. recently, a composed nanofibrous biomaterial for skin regeneration has been developed via electrospinning of polysaccharides extracted from beta vulgaris together with nylon66. the presence of the polysaccharides contributed to make the biomaterials more hydrophilic. this biomaterial was able to maintain the functionality of the seeded keratinocytes.55 a careful observation of the natural world often inspires scientists for the creation of new biomaterials with innovative, green and affordable characteristics. it is the case of biomaterials incorporating pda, a polymeric oxidation product of dopamine, inspired to the dopamine produced by mussels, able to adhere to several materials. pda has been incorporated in a hydrogel of chitosan and graphene studied as conductive material for cardiomyocytes cultivation. this biomaterial enhanced cardiomyocyte proliferation and spontaneous beating rate.56 natural molecules have been studied as 3d culture environment mimicking the ecm. a collagen/heparin hydrogel able to immobilize growth factors has been evaluated as 3d culture environment for neural stem cells. in this environment neural stem cells formed synaptic connections and showed electrical activity. furthermore, the cells within the 200 μm thick hydrogel could easily detected at a phase-contrast microscope.57 nanomedicine is another field where green chemistry is capturing an increasing attention. the development of nps is extremely important for efficient and targeted drug delivery, in particular but not limited to cancer treatment. however, the production and also the use of nps can produce hazardous molecules and have negative effects for human health both at a molecular and cellular level.58,59 cellular and subcellular mechanisms of interaction with nps have been studied only recently.60 the use of nps has been associated with cell detachment consequent to disruption of tight61 and adherent62 junctions or reduced amount of vinculin at focal adhesion.63,64 nps have also been demonstrated to perturb cytoskeletal integrity and function, inducing the formation of aberrant actin forms.65,66,67 nps cell treatment has also been associated with a decrease in cell motility that can be an adverse effect in healthy cells, but is advantageous in the treatment of cancer cells reducing the possibility of metastasis.68,69 nano-materials customized in 2d films has been developed as photo-thermal convertor for the minimally invasive near-infrared (nir) laserinduced tumour ptt. li et al. produced a bi-dimensional nano-sheet of mos2 incorporating soybean phospholipid that confers colloidal stability to the nano-biomaterial. soybean phospholipid extraction can be done on a large scale and at a low cost since it is present in several plants. soybean phospholipid incorporation follows an easy processing, unfortunately involving chloroform; moreover, the excess can be dispersed simply by water washing. mos2 nano-sheets have been covered by a soybean phospholipid layer to generate a platform for breast cancer photothermal therapy.70 thus, the soybean phospholipids represent a green source for biomaterial creation. nps were also obtained via a green process by mixing chitosan and go in aqueous solution and acetic acid, then rectorite was added to enhance drug encapsulation of doxorubicin hydrochloride for cancer treatment.71 a nano-hydrogel has been created with a simple heating step, without any additional chemical reaction, to denature lysozyme mixed with sodium carboxymethyl cellulose. the nano-hydrogel has been tested for the release of 5-fluorouracil, which release was decreased in stomach and accelerated in intestine, thus protecting the drug through the gastro-intestinal apparatus until the release within the intestine.72 35tissue engineering between click chemistry and green chemistry soluble go is usually obtained by the reaction with hydrazine and hydrazine hydrate which are toxic. a cost-effective and green method has been developed to produce soluble graphene oxide using bacillus marisflavi as a reducing and stabilizing agent at 37 °c in aqueous solution and mild conditions.73 go can be reduced in order to eliminate oxygen groups and obtain a planar conformation,74 thus allowing for incredibly high drug loading efficiency. a green method to obtain reducedgo used riboflavin-5’-phosphate sodium salt dehydrate. the obtained nps were tested as ph-responsive carriers of doxorubicin hydrochloride and showed high bonding efficiency, high stability and effective drug release at ph variation.75 similarly reduced-go has been obtained in eco-friendly, one-step methods using biomolecules such as alanine,76 l-cysteine77 and l-tryptophan together with ascorbic acid and naoh.78 nps of silver nitrate and gold chloride can be prepared through safe, cost-effective and eco-friendly natural materials. nano-spheres of agno3 have been obtained in aqueous solution by mean of egg white,79 while nps of trivalent aurum can be prepared in concentrated broths of seaweeds extracts, both investigated in cancer treatment.80 silver nps for drug delivery has also been obtained by in situ reduction using azadirachta indica and then loaded onto a hydrogel prepared through the environment friendly process involving cross-linked poly(acrylamide) and a rapid redox polymerization with n, n’methylenebisacrylamide in the presence of carboxymethylcellulose.81 silver nps both spherical and cubic has been prepared using another fast and green approach, based on the use of light (λ = 420 nm) to catalyse the reaction, that requires 10 minutes. such ag-nanoparticles showed a good antimicrobial activity and a dose-dependent cytotoxicity.82 interestingly, nps incorporating an anti-tumour drug have been obtained by the self-assembly of ginsenoside, extracted from panaxginseng. ginsenoside nps showed a higher efficacy of delivery, if compared to the free drug, and a prolonged half-life in circulating blood.83 protein extract from plants has also been investigated as wound dressing biomaterial. fibrous biomaterials from soy and corn zein have been fabricated via electrospinning. soy derived biomaterial supported the growth of human dermal fibroblasts and in both biomaterials ecm protein deposition was observed.84 genipin, obtained from geniposide, present in the fruit of gardenia jasminoides has been cross-linked with gelatine and loaded with silver nanoparticles by heat treatment and uv-light, avoiding the use of solvents or reducing agents, with the aim to create a biomaterial showing antimicrobial activity. this green biomaterial resulted successful against staphylococcus aureus and escherichia coli but not against candida albicans.85 green chemistry is not only contributing to the technological development of tools for te purposes, but also guiding society toward a more sustainable research in term of less toxic reagents/products, more cost-effective materials, sustainable sources and energy use. 4. challenging the gap with developing countries and avoiding divide by biotechnology in polarized societies it is of paramount importance to understand and predict the impact of the cost of products and technologies related to te and regenerative medicine (including a variety of products, e.g. biomaterials, stem cells, bioactive compounds), in a society where a wealth polarization is increasingly emerging. indeed, the expensiveness and high technology involved in this area of research, as well as other biotech clinical application, represent a big concern and create a tremendous response among scientists. this issue poses also an ethical problem due to the responsibility to address the increasing rate of diseases in the developing countries and their limited funding for facing them with biotech medical treatments/devices. thus, all the efforts must be devoted to assessing programs of cooperation that will lead to a more inclusive society with equitable access to benefits and reduce inequalities driven by the technology divide in this area of research. otherwise the advancement of such science can be perceived as excluding and ultimately as a new divide. despite the european commission has paid attention to the development of an inclusive society, promoting this initiative within the horizon 2020 program, involving also the scientific area, e.g. through the actions support to open science, open access and open data (see the work program 2018-2019 europe in a changing world – inclusive, innovative and reflective societies), the advances done in the direction of a sustainable and inclusive science are not sufficient. another major concern is related to the lack of regulatory standards among the countries in a globalized world. it may also occur that no standard for safety, quality and efficacy of te and regenerative medicine products is present and this creates a safety gap among countries leading to adverse effect on human and environment health. 5. conclusion over the last years tissue engineering and regenerative related approaches have accelerated through the introduction of more advanced tools, resources 36 alessandra costa et al. and methodologies. the ability to combine chemistry and biology toward a more sustainable development is attracting research, industry and society. during the last decades the application of click chemistry to the development of te related tools allowed extraordinary technological advancements. green chemistry, that is also included in some click reaction methods, represents a challenge for te and regenerative medicine, claiming more attention for a sustainable development of methods and 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floriano* chemistry as building block for a new knowledge and participation stefano cinti tissue engineering between click chemistry and green chemistry alessandra costaa#, bogdan walkowiakb, luigi campanellac, bhuvanesh guptad, maria cristina albertinie* and laura teodori a, f* chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity. sara tortorella,1,2,* alberto zanelli,2,3 valentina domenici2,4 substantia. an international journal of the history of chemistry 1(2): 133-142, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-33 citation: j. lekner (2017) nurturing genius: the childhood and youth of kelvin and maxwell. substantia 1(2): 133-142. doi: 10.13128/substantia-33 copyright: © 2017 j. lekner. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declared that no competing interests exist. historical article nurturing genius: the childhood and youth of kelvin and maxwell john lekner the macdiarmid institute for advanced materials and nanotechnology, and school of chemical and physical sciences, p o box 600, wellington, new zealand e-mail: john.lekner@vuw.ac.nz abstract. william thomson and james clerk maxwell, nineteenth century natural philosophers, were friends and colleagues (thomson was maxwell’s senior by seven years). this historical note gives a description of their early lives, with emphasis on the influence of their fathers and of cambridge on their development. keywords. william thomson (lord kelvin), james clerk maxwell, genius, childhood, youth, history of physics. recent research on electrostatics got me into working contact with the early contributions of james clerk maxwell and william thomson (later baron kelvin of largs, and usually referred to as kelvin). i read their biographies, and was struck by the remarkable similarities in their childhood and youth. both were scots, both lost their mothers at an early age, both had fathers who nurtured them intellectually and were ambitious for their career. this note is mainly about william’s and james’ childhood and youth, and comes to a natural stop at their respective completions of the cambridge tripos examination. only a brief catalogue of their later careers is given. some of their electrostatic researches are discussed in my author’s note at the end. william thomson, lord kelvin (1824-1907) james thomson, william’s father, taught mathematics and geography at the royal belfast academical institution. william was born in belfast. his mother margaret (nee gardner) died in 1830 when william was six. his father became professor of mathematics at glasgow in 1832, and the family of four boys and two girls moved there. an elder brother james (1822-1892, frs) trained as an engineer, and became professor of engineering at glasgow. james thomson senior was a man of wide interests, ‘capable on emergency of teaching the university classes in classics’. his books cover an amazing range: a treatise on arithmetic in theory and practice went to seventy-two editions; other titles include introduction to modern geography, the romance 134 john lekner of the heavens, elements of plane and spherical geometry, euclid’s elements of geometry, algebra, and introduction to the differential and integral calculus (ref. 1, pp 6, 7). and this from a farmer’s son! after margaret died the father taught james and william ‘the use of the globes’ and latin (ref. 1, p 6). james and william were allowed to attend informally their father’s lectures at the university. one of those present at the junior mathematics class later recalled to kelvin ‘as a mere child you startled the whole class, not one of whom could answer a certain question, by calling out: ‘do, papa, let me answer.’ (ref. 4, p 5) james and william matriculated at the university of glasgow at ages 12 and 10, respectively, in october 1834. william ‘...carried off two prizes in the humanity class; this before he was eleven.’ in the next session young william got prizes in natural history and in greek (ref. 1, pp 8, 9). and so on. kelvin recalled (in 1907) ‘a boy should have learned by the age of twelve to write his own language with accuracy and some elegance; he should have a reading knowledge of french, should be able to translate latin and easy greek authors, and should have some acquaintance with german. having learned thus the meaning of words, a boy should study logic’. in natural philosophy, under professor meikleham, william read mécanique analytique of lagrange and mécanique céleste of laplace (ref. 1, pp 11, 12). in 1839 he attended the senior natural philosophy class taught by the professor of astronomy, j. p. nichol, who introduced william to fourier’s théorie analytique de la chaleur. ‘i asked nichol if he thought i could read fourier. he replied ‘perhaps’. ... on the 1st may (1840) ... i took fourier out of the university library; and in a fortnight i had mastered it – gone right through it.’ (ref. 1, p 14). william was fluent in french: in the summer of 1839 the family went to london, and then on to paris, where the boys were left (in the charge of a trusted servant) for about two months to learn french. the father wished them to learn german also; for two months the whole family took lessons in german, and on 21 may 1840 professor thomson and his six children (william was 16, the youngest boy robert was 11) left glasgow for liverpool, london and then by steamer to rotterdam. william’s diary has the entry ‘reached the bar at the mouth of the maas, near brill, at about 4½ o’clock in the morning, where we had to lie till 10. the vessel rolled greatly from side to side, but the rolling was intermittent, as every two or three minutes it calmed down and then rose again with perfect regularity. this probably arose from two sets of waves of slightly different lengths coming in in the same direction from two different sources’. the family visited the hague (the diary notes a visit to the museum to see a stuffed mermaid!), delft, düsseldorf, bonn, cologne, frankfurt am main (where they stayed till 2 august), then onto baden, from where the brothers james and william went on a walking tour of several days through the black forest. the family returned to glasgow in early september. certainly an educational trip, much to the credit of professor thomson. but young william did not spend all his time practising german: he had taken his fourier with him, and surreptitiously read it in the cellar. ‘when my father discovered it he was not very severe upon me’ (ref. 1, pp 16-18). a text by kelland, theory of heat, 1837, stated that the fourier expansions were ‘nearly all erroneous’. william found, while at frankfurt, the cause of the misunderstanding. this resulted in his first publication on fourier’s expansions of functions in trigonometrical series (ref. 8, vol. 1, pp 1-9). in april 1841 william entered peterhouse in cambridge. (he had purposely avoided taking a degree at glasgow, so as to be able to enter cambridge as an undergraduate). the choice of peterhouse had much to do with the presence there of dr. william hopkins, a geophysicist and famous as a mathematics tripos tutor. the maths tripos was an examination conducted (in thomson’s day) over six days, each with 5½ hours of hard writing, covering mathematics and the mathematical aspects of physics. to be placed high on the list, especially to be senior wrangler or second wrangler, was the making of a career. hence the three years of intense preparation and tutoring. young william, 17 when he entered cambridge, was mature enough to realize the importance of the tripos, and organize his life accordingly. he soon saw that there was a separation at peterhouse into the classes of ‘rowing men’ and ‘reading men’. ‘all my friends are among the latter class, and i am gradually dropping acquaintance with the former ... even to know them is a very troublesome thing if you want to read, as they are always going about troubling people in their rooms’ (letter to his father, 12 december 1841, see ref. 1, pp 32-33). however, together with another undergraduate, william bought a single sculling boat for £7. his father was surprized at not having been consulted, and urged william to ‘use all economy consistent with respectability. be most circumspect about your conduct and about what acquaintance you form. you are young: take care you be not led to what is wrong. a false step now, or the acquiring of an improper habit or propensity, might ruin your life.’ (ref. 1, p 37). william made good use of the boat, and rowed on the river cam with another ‘reading’ man, g. w. hemming of st. johns, senior wrangler in 1844. his sister elizabeth wrote on 27 february 1842 that ‘papa’ was reconciled to the purchase of the boat, much to the relief of william, who wrote to his father on 14 april 1842 that ‘the sculling is 135nurturing genius: the childhood and youth of kelvin and maxwell going on with great vigour, and is keeping me in excellent preservation. ... i find that i can read with much greater vigour than i could when i had no exercise but walking in the inexpressibly dull country round cambridge’ (william was used to a more varied topography than the flat land surrounding cambridge). during the summer vacation of 1842 the family were at knock castle (three miles from largs, on the firth of clyde). there william wrote a paper on the linear motion of heat (ref. 8, pp10-15) in which he discusses solutions of the one-dimensional equation for the flow of heat, namely t tt x 2∂ =∂ where t(x,t) is the temperature, in the form t x t d e f x t t x f x( , ) 1 2 , ( , 0) ( ) 2 ∫ π α α( )= + =α− −∞ ∞ in another paper on the uniform motion of heat in homogeneous solid bodies, and its connection with the mathematical theory of electricity (ref. 9, pp 1-14) was written that summer. not bad for an undergraduate of 18. back at cambridge in october 1842, william began his training under the tutor hopkins, with the aim focused on the tripos examinations in the senate house in january 1845. he won a mathematics prize of £5, which he proposed to spend on an illustrated shakespeare, but his father preferred him to buy liouville’s journal de mathématiques. james thomson’s paternal care was ever focused on his son’s long-term prospects: dr meikleham, the professor of natural philosophy at glasgow, was ill. if only he could last till william had completed the tripos (and got the laurels of a wrangler), william might succeed him. a natural wish for the father, to have his son join him as a professor at his university. on 9 april 1843 professor thomson writes to william that dr. meikleham is better; he adds ‘...you must take care not only to do what is right, but to take equal care always to appear to do so. a certain [professor of moral philosophy] here has of late been talking a good deal about the vice of the english universities, and would no doubt be ready to make a handle of any report or gossip he might pick up.’ (ref. 1, p 53). the next letter detailed the requirements of the chair of natural philosophy, which included skill in experiments. this he urges william to attain. william, ever cooperative, replies that in his spare time he is reading cours de physique by lamé, ‘which is an entirely experimental work’. james thomson (4 may 1843) writes of the probable votes in an election of dr. meikleham’s successor, and adds ‘take care to give a certain gentleman here (who, as to private affairs, is more nearly omniscient than anyone i have known) no handle against you. avoid boating parties of in any degree of a disorderly character ... as scarcely anything of the kind could take place, even at cambridge, without him hearing of it.’ (ref. 1, pp 57, 58). and william did avoid boating parties and any scandal, but he did row in the eights for peterhouse, and won the single sculls (ref. 1, pp 58-62). he also played the cornet, and was one of the founding members of the cambridge musical society. the saga of the chair of natural philosophy continued, with dr. meikleham becoming ill and recovering. on 20 april 1844 professor thomson urged william to ‘keep the matter in mind, therefore, and think on every way in which you might be able to get efficient testimonials ... do not relax your preparation for your degree. i am always afraid some unknown or little heard of opponent may arise. recollect, too, that you might be thrown back by illness, and that you ought therefore be in advance with your preparation. above all, however, take care of your health.’ william replied on the 22nd: ‘i am very sorry to hear about dr. meikleham’s precarious state ... it is certainly very much to be wished that he should live till after the commencement of next session.’ preparation for the tripos was to continue during the long vacation, when hopkins would go with a party of reading men to cromer, norfolk. william wished to go too, entailing extra expense for his supportive father, who agrees to the request. but soon william writes from cromer (13 june 1844): ‘ my dear father – i have again to write to you on the same pleasant business that i had to write to you about so lately, which is to say that my money is again all gone.’ (details of his expenses follow.) (ref. 1, p 80). later (12 october 1844) ‘papa’ sent his son the halves of bank notes for £100, noting that the three years’ expenditure was now £774/6/7, and asked ‘how is this to be accounted for? have you lost money or been defrauded of it ...? ... you must exercise the strictest economy that shall be consistent with decency and comfort.’ lest the readers think ‘papa’ a cheapskate, let me remind them of inflation: the value of the pound has diminished by a factor of about 72 between 1844 and 2001,10 so in present currency dr. thomson’s £774 is approximately £60,000. the work of the ‘reading party’ entailed dr hopkins setting examination papers and discussing the students’ answers with them. it went on for two months. after the reading party ended, thomson and a fellow scottish student ‘took a boat and rowed out to sea, and intercepted the g. n. s. steamer trident’, which took them to edinburgh! (ref. 1, p 82) railways were only just being established (the edinburgh to glasgow line opened in 1845), and travel was a major undertaking. 136 john lekner let us fast-forward now to the ordeal of the senate house examinations, set to begin on 1 january 1845. the ‘wrangler’ contestants had trained like olympic athletes for this six-day event. nor was this the end, because the smith’s prize (another week of examinations) followed soon after. and the results were: parkinson of st. john’s, senior wrangler, thomson of peterhouse, second wrangler. the disappointment of william’s family and friends was mitigated by the fact that thomson was judged clearly better in the two smith’s prizes awards, parkinson second. dr thomson continued to advance his son’s education (and the prospects of the chair in natural philosophy at glasgow) by funding a trip to paris in early 1845. william went with introductions to arago, biot, babinet, cauchy and liouville. he presented himself to liouville, with whom he met often and became friends. he also met sturm and foucault, that is almost all of the living french scientists (laplace, legendre, poisson and fresnel were no longer). biot introduced him to regnault, the professor of natural philosophy at the collège de france, and researcher into the physics of heat engines. william worked with regnault in his laboratory, met liouville and cauchy often, and in his spare time (ref. 1, p 128) ‘i have been reading jacobi’s nova fundamenta and abel’s 1st memoir on elliptic functions, but have been rather idle on the whole’. indeed! after four and a half months in paris william returned to cambridge. at the british association meeting he met faraday. soon after he was elected foundation fellow of peterhouse, this being worth about £200 per annum, with rooms in college. this post he held till his marriage in september 1852. in may 1846 the chair of natural philosophy at glasgow became vacant by the death of professor meikleham. the timing was perfect. william and his father quickly gathered testimonials and information about other possible candidates. there were five other applicants. among the testimonials supporting william thomson were those from arthur cayley, george boole, j. j. sylvester, g. g. stokes, m. regnault and m. liouville. to the printed pamphlet of 28 pages containing the testimonials, given to the electors, thomson added an appendix listing his published papers, twenty-six of them. william was 22 at the time of his appointment in october 1846, and kept the chair till his retirement in 1899. our description of young william thomson’s nurture and development stops here. he was not just a mathematically gifted child – he had the great advantage of a highly intelligent and energetic father, dedicated to his son’s advancement. in cambridge he had the support of the best tutor, working in possibly the best environment for mathematics and the natural sciences in britain. in paris he met and worked with the foremost mathematicians and scientists of france. and he was sensible enough to make full advantage of these opportunities, through continuous and vigorous use of his exceptional brain. james clerk maxwell (1831-1879) james’ father was born john clerk, adding the name maxwell upon inheriting the estate of middlebie. he practised law in edinburgh and seemed set on a quiet batchelorhood until he met and married frances cay. a child (elizabeth) died in infancy, and james was born when his mother was nearly forty, at 14 india street, edinburgh (ref. 11, pp 2-3). frances was of a ‘sanguine active temperament’, and energised john to develop the estate of middlebie and enlarge glenlair, their home. professor william thomson, 1846. 137nurturing genius: the childhood and youth of kelvin and maxwell john had a ‘persistent practical interest in all useful processes’; he made a special last for shoes (square-toed) for himself and later for james, and planned the outbuildings of glenlair, down to the working plans for the masons (ref. 11, pp 7-9). even before he was three, little james likewise showed a practical interest in the world. a letter from frances to her sister jane cay gives the picture: ‘he is a very happy man ... has great work with doors, locks, keys, etc., and “show me how it doos” is never out of his mouth. he also investigates the hidden course of streams and bell-wires ... he drags papa all over to show him the holes where the wires go through.’ (ref. 11, p 27). throughout his childhood the constant question was “what’s the go o’ that? what does it do?” if not satisfied with an answer he would ask “but what’s the particular go of it” (ref.11, p 28). his great love was the outdoors, of streams and ponds and the frogs that inhabited them (ref. 11, pp 33-34). with his first cousin jemima wedderburn, who was eight years older, he produced an animation of a tadpole wriggling from its egg and changing into a swimming frog (ref. 11, p 37). james was educated by his mother until she died of abdominal cancer when he was eight. after his mother’s painful death in december 1839, mr. maxwell hired a local lad to tutor james at home. ‘the boy was reported slow at learning, and miss cay after a while discovered that the tutor was rough’ (ref. 11, p 41). just as well she did: his friend and biographer lewis campbell describes the ‘roughness’ (being hit on the head by a ruler, and having ears pulled till they bled), and the lifelong effect this had on james (ref. 11, p 43). and so mr clerk maxwell sent the boy of 10 to the edinburgh academy. he lived with his father’s sister, mrs wedderburn, with occasional stays with his mother’s sister, miss cay. his first day at school was tough: in his gray tweed jacket and square-toed shoes, he was a target for ridicule and worse. he returned home ‘with his tunic in rags ... his neat frill [collar] rumpled and torn ...’ (ref. 11, pp 49-50). his aunts made sure his dress conformed more to the norms, but his nickname ‘dafty’ stuck with him. places in class were allotted according to performance, and james was initially among the rowdy boys, who naturally made things worse for him. for the first two years or so, school was something to endure. fortunately he had the warm refuge of his aunt’s home at 31 heriot row, and its good library, plus the occasional visits of his father, when they would explore edinburgh together. the love between father and son is clear in the letters reproduced in lewis campbell’s biography. in a letter of 19 june 1844, addressed to ‘my dear father’, and signed ‘your most obt. servt. jas. alex. mcmerkwell’ (an anagram, decoded by numbers underneath), he remarks after news of swimming and other outings ‘i have made a tetra hedron, a dodeca hedron and 2 more hedrons that i don’t know the wright names for.’ (ref. 11, p 60). campbell notes that they had not yet begun geometry. at school he excelled in scripture, biography and english, and discovered that latin and greek were worth learning. at about this time lewis campbell joined the school, and began a lifelong friendship. lewis lived at 27 heriot row, and the two boys were continually together for about three years. ‘we always walked home together, and the talk was incessant, chiefly on maxwell’s side. some new train of ideas would generally begin just when we reached my mother’s door. he would stand there holding the door handle, half in, half out ... till voices from within complained of the cold draught, and warned us that we must part.’ (ref. 11, p 68). by july 1845 young james was coming into his own, with prizes for english and english verse, and the mathematical medal. his father now ‘became more assiduous than ever in his attendance at meetings of the edinburgh society of arts and royal society, and took james with him repeatedly to both.’ (ref. 11, p 73). a member of the society of arts, d. r. hay, had written a book on first principles of symmetrical beauty; one of the problems in it was how to draw a perfect oval. james generalized the equation of an ellipse, r1 + r2 = 2a (r1 and r2 are distances from the two focal points to a point on the ellipse, 2a is the length of the major axis), to curves which satisfy mr1 + nr2 = constant. with mr maxwell’s skilled promotion of this work, the result was james’ first paper on the description of oval curves (ref. 12, pp 1-3), which was communicated to the royal society of edinburgh by professor j. d. forbes in 1846. professor forbes took maxwell under his wing, and they became lifelong friends. as it happened, the curves were not new, having been described by descartes, and their optical properties considered by newton and huygens, but maxwell’s practical construction by means of pins and string was new. and what illustrious company for a schoolboy of fifteen! this paper and his other manuscripts on ovals can be found in the scientific letters and papers, (ref. 14, pp 35-67). maxwell was now launched into mathematical and scientific inquiry. his second published paper (1849) was on the theory of rolling curves (ref. 12, pp 4-29), in which he already shows a mastery of plane differential geometry. next, in 1850, came on the equilibrium of elastic solids (ref. 12, pp 30-73), ‘an astonishing achievement for a 19 year-old working almost entirely on his own. the mathematics went hand-in-glove with his experiments on polarized light ... he set out for the first time the general mathematical theory of photoelasticity...’ (ref. 15, p 32). by this time james was at edinburgh uni138 john lekner versity, which he had entered at seventeen. p. g. tait, who was a school friend of maxwell’s and later a collaborator with kelvin on their treatise on natural philosophy, was one of james’ chief associates at edinburgh university, but stayed for only one session, going on to peterhouse, cambridge in 1848. maxwell went to cambridge also, but not till 1850. campbell remarks (ref. 11, p 114) ‘... it is perhaps to be regretted that he did not go to cambridge at least one year earlier. his truly sociable spirit would have been less isolated, he would have gained more command over his own genius ...’. eventually his father was persuaded, and james went to peterhouse, but transferred to trinity college to improve his chances of a fellowship. maxwell’s tutor in preparation for the tripos was the same william hopkins whom we had met earlier as william thomson’s tutor. here is hopkins’ view of maxwell, as recorded by a cambridge contemporary: ‘... he is unquestionably the most extraordinary man [hopkins] has met with in the whole range of his experience; ... it appears impossible for maxwell to think incorrectly on physical subjects; that in his analysis, however, he is far more deficient; ... a great genius, with all its eccentricities ... one day he will shine as a light in physical science ...’ (ref. 11, p 133). unfortunately the letters james wrote as an undergraduate to his father from cambridge are lost. his father’s letters naturally seek his son’s advancement: ‘have you called on profs. sedgwick at trin., and stokes at pembroke? if not, you should do both. ... provide yourself with cards.’ (ref. 11, p 150) james got a scholarship from trinity college in april 1852. at the scholars’ table he was in his element, with free debate on almost any topic. he was elected to the select essay club, a discussion group of twelve students who were known as the apostles. maxwell’s essays delivered to the apostles (chapter viii of ref. 11) have titles such as what is the nature of evidence of design, which begins ‘design! the very word ... disturbs our quiet discussions about how things happen with restless questionings about the why of them all.’ another essay idiotic imps is about pseudo-science (then called dark science), which maxwell exposes and analyses. yet another has the intriguing title has everything beautiful in art its original in nature? a serious late essay, from february 1856, is on analogies: are there real analogies in nature? we need both data and theory to make sense of the world: ‘the dimmed outlines of phenomenal things all merge ... unless we put on the focussing glass of theory and screw it up sometimes to one pitch of definition, and sometimes to another, so as to see down into different depths ...’ in the same essay, maxwell remarks on space and time: ‘... space has triple extension, but is the same in all directions, without behind or before, whereas time extends only back and forward, and always goes forward.’ the arrow of time, which maxwell’s statistical physics was later to clarify! in the midst of preparations for the tripos exams, james took a few days of the 1854 easter vacation, to stay at birmingham with a friend. his father wrote (ref. 11, pp 7, 168) ‘view, if you can armourers, gunmaking and gunproving – swordmaking and proving – papier-mâchée and japanning – silverplating by cementation and rolling – ditto, electrotype – elkington’s works – brazier’s works, by founding and by striking out dies – turning – spinning teapot bodies in white metal, etc – making buttons of sorts, steel pens, needles, pins and any sorts of small articles which are curiously done by subdivision of labour and by ingenious tools ... foundry works, enginemaking ... if you have had enough of the town lots of birmingham, you could vary the recreation by viewing kenilworth, warwick, leamington, stratford-on-avon, or such like.’ james began with the glassworks. maxwell now faced the trial of the senate house examinations, in his year five days of 5½ hours each. ever solicitous and practical, his father wrote ‘you will need to get muffettees for the senate-room. take your plaid or rug to wrap round your feet and legs.’ james was secmaxwell with his colour wheel, circa 1855. 139nurturing genius: the childhood and youth of kelvin and maxwell ond wrangler, e. j. routh of peterhouse senior wrangler. they were declared equal as smith’s prizemen. in october 1855 james clerk maxwell was elected fellow of trinity college. he had supported himself by taking private pupils, but this could now stop. apart from teaching third-year hydrostatics and optics, he was free to do research. he was now 24. he left cambridge in 1856 to take up the chair of natural philosophy at aberdeen, then was professor at king’s college, london from 1860 to 1865, when he resigned to live and work at glenlair. after kelvin and helmholtz declined the offer, maxwell became the first cavendish professor of physics at cambridge in 1871. he had but eight years to live. he died in 1879 of abdominal cancer, aged 48, at nearly the same age that his mother had died of the same type of cancer. we are fortunate in having a warm and affectionate biography by his friend lewis campbell. especially moving are his depictions of james’ childhood and adolescence, and of his early death. we admire his works, and with this biography we can also love him. epilogue william thomson and james clerk maxwell both achieved greatness; it was certainly not thrust upon them. however, both were fortunate in their fathers, in more than their genetics. and their fathers were fortunate in them: in a letter anticipating james’ 21st, mr maxwell says ‘i trust you will be as discreet when major as you have been while minor’, quoting proverbs x.1 [a wise son maketh a glad father.] both sons showed remarkable good will and cooperated fully with their fathers’ guidance and instruction. this in contrast to much modern behaviour, and also to that of the musical genius wolfgang amadeus mozart, who eventually rebelled against his father leopold. thomson and maxwell senior never had to face leopold’s tragedy of having a cherished child spurn them. in the addition to the wonderful love, instruction and support from their fathers, they each had the support of family, in maxwell’s case particularly the comfort of the aunts. in the wider sphere, we should also note that scotland had been important in the european enlightenment and that the rates of literacy were exceptionally high.  william and james grew up in a culture with a strong work ethic and widespread respect for knowledge, a powerful combination. finally, they both had the great advantage of their cambridge experience. this environment suited both, matured them, and gave them lifelong connections with some of the brightest minds then living. author’s note victoria university physicists pablo etchegoin and eric le ru have refined surface-enhanced raman scattering to such an extent that they are able to detect single molecules.16 this remarkable feat is accomplished by using the enhancement of an external electric field (provided by an intense laser beam) in the gap between two close conducting particles. the simplest applicable model is that of two conducting spheres in a steady (dc) external field, which had been solved by maxwell and others.17-19 the solution is exact, and in the form of infinite series which converge rapidly when the sphere separation s is comparable to or larger than the radii of the spheres. however, the field enhancement is large when the sphere separation is small compared to the sphere radii, and there the series converge more and more slowly as s decreases. this is precisely the physically interesting limit, that utilized by pablo and eric to such good effect. so we have the unhappy situation where an exact theory fails to deliver just where it is needed. i got interested, and spent considerable time investigating the exact series, their integral equivalents and especially the logarithmic terms which appear at small s. what started as an exploration of field-enhancement in the limit of close approach of the two spheres20a,d grew to encompass the capacitance of two spheres (at the same potential, or with equal and opposite charges),20b and the polarizabilities (longitudinal and transverse) of a twosphere system.20c in all cases terms logarithmic in the sphere separation s appear in the formulae. maxwell had approached the problem from the other end: he obtained, for quantities related to the capacitance coefficients caa, cab and cbb of two spheres of radii a and b and separation of centres c (with c and s related by c = a + b + s expansions in reciprocal powers of c. there is the remarkable section 146 of his treatise on electricity and magnetism,17 in which he matches spherical harmonic expansions about the two sphere centres to obtain ℓ, m and n coefficients (defined below) as series in reciprocal powers of c. section 146 is seven pages of formulae, in which the calculation is carried to the twenty-second reciprocal power of c! as is well-known, series expansions of this type get more complex the higher the order. maxwell had no computing aids, not even a mechanical calculating machine. i checked all the coefficients in his formulae (using computer algebra, of course) and found all were correct. this attests to maxwell’s amazing ability to carry through very long and intricate calculations, but also raises the question: why did maxwell do this enormous amount of work? his coefficients ℓ, m and n give the total electrostatic energy of the two spheres, carrying 140 john lekner charges qa and qb, as w q mq q nqa a b b12 2 1 2 2= + + (1) the coefficients ℓ, m and n are related to the capacitance coefficients caa, cab and cbb  c c c c m c c c c n c c c c , ,bb aa bb ab ab aa bb ab aa aa bb ab 2 2 2= − = − − = − (2) the total energy expanded in reciprocal powers of the distance between sphere centres c begins21 w q a q b q q c q b q a c q b q a c2 2 2 2 a b a b a b a b 2 2 2 3 2 3 4 2 5 2 5 6= + + − + − + + (3) the first two terms are the self-energies of the two charged spheres, the third is the coulomb energy, the fourth and fifth are due to mutual polarization of the two spheres. maxwell had the information to give the energy up to terms of order c-22, but he did not do that. why not? and, why do all that work and give the results in his treatise? my guess is that (i) maxwell was looking for a pattern in the series, and hoped to sum them completely if he found the pattern; and (ii) he wanted to compare experimental results on the force between two charged spheres with theory, and needed all these terms to do so. there is no hint in section 146 as to his reasons. perhaps neither of (i) or (ii) came to fruition, but he wanted the results of his labours to be available to others. preceding maxwell’s work were the kelvin papers of 1845 and 1853.9 william thomson was 21 when the earlier of these was published. it deals with the force between an earthed sphere and a charged sphere, and uses the method of images that he invented. he obtained an infinite series for the force f(c), in which successive numerators and denominators of terms in the series are related by recurrence relations. it is now easy to write down the complete expression for the energy:21 if sphere a carries charge qa, and sphere b is earthed, the electrostatic energy, and the force between the spheres, are given by w c q c c f c w c( ) 2 ( ) , ( ) ( )a aa c 2 = =−∂ (4) so, if we know the capacitance coefficient caa, a simple differentiation will give us the force. incidentally, the inverses of the relations (2) are     c n n m c m n m c n m , ,aa ab bb2 2 2= − = − − = − (5) so the maxwell coefficients ℓ, m and n could be used directly to give the force as f c q m n( ) ( / )a c12 2 2=− ∂ − (6) the force is always attractive, as is to be expected since the charge induced on the earthed sphere b has opposite sign to qa. the force increases as the separation s between the spheres decreases, and in fact diverges as s tends to zero. a more interesting but more difficult problem is that of the force between two charged spheres (kelvin 1853).9 the maxwell expansion in reciprocal powers of c fails at close approach, and in particular at contact, when the spheres are at a common potential. they share the charge; the force is clearly repulsive, whatever the sign of this charge. again kelvin used his method of images, and again obtained an infinite series for the force. for spheres of equal radii, in contact, his expression for the force is proportional to a double series,      1 2 1.2 3 1.3 4 1.4 5 1.5 6 2.1 3 2.2 4 2.3 5 2.4 6 3.1 4 3.2 5 3.3 6 4.1 5 4.2 6 5.1 6 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 − + − + − − + − + − − + − + − − (7) kelvin notes that adding by vertical columns gives diverging series, while adding by horizontal rows gives a convergent series, which he sums to n( 2 )16 14− . the evaluation of the double sum demonstrates young william’s mathematical skill. he expresses the sums of the first, second and third rows respectively as    d n d n d n 1 (1 ) , 2 1 (1 ) , 3 1 (1 )0 1 2 0 1 2 2 0 1 3 2∫ ∫ ∫θ θ θ θ θ θ θ θ θ θ θ θ+ − + + (8) [for those interested in the mathematics: set θ = e-x to convert  d n 1 (1 )0 1 2∫ θ θ θ θ+ to the more familiar dx x e( 1)x 20 ∫ + ∞ then expand in powers of e-x to obtain the sum of the first row.] noting that (1 ) 1 2 32 2θ θ θ+ = − + −− william writes the sum of the row sums as the integral 141nurturing genius: the childhood and youth of kelvin and maxwell  d n 1 (1 )0 1 4∫ θ θ θ θ+ (9) which he evaluates without further comment as 1 6 ℓn 1 θ (1+θ)3 (3θ2 +θ3)+ℓn(1+θ)− θ (1+θ)2 ⎡ ⎣ ⎢ ⎢ ⎢ ⎤ ⎦ ⎥ ⎥ ⎥ 0 1 = 1 6 ℓn2− 1 4 ⎛ ⎝ ⎜ ⎞ ⎠ ⎟ (10) a reader who verifies each of these steps will appreciate what is involved, but perhaps not the difficulty of its formulation, and certainly not the complexity of the infinite sets of electrical image charges that it is based on. without further discussion william takes the convergent result as correct! when i first saw this i wondered how it was that the (mathematically extremely able) young thomson could be ignorant of riemann’s theorem about conditionally convergent series, namely that they can be summed to any desired result by suitable rearrangement of terms. the answer lay in chronology of course: riemann (1826-1866) was a student at göttingen under gauss (with a spell at berlin) from 1846 to 1849, and did not teach till 1854. his paper on the re-arrangement of series was completed in 1853, but not published until after his death in 1866. in fact the kelvin result is correct. i have obtained it directly from the properties of the capacitance coefficients, and have generalized the result to spheres of arbitrary radii, at arbitrary separation.21 but young thomson’s choice of one result from the infinity of possible sums of that double series is the boldest move i have seen in theoretical physics. p. s. from 1854 there was much correspondence between maxwell and thomson, who became friends. the maxwell letters relevant to electromagnetism are reprinted in ref. 22. annotated bibliography 1. s.p. thompson, the life of william thomson, baron kelvin of largs, macmillan, london, 1910. (this two volume biography was “begun in june 1906 with the kind co-operation of lord kelvin, who himself furnished a number of personal recollections and data”. it was my main source on kelvin; others include refs. 2-5.) 2. a. gray, lord kelvin, an account of his scientific life and work, chelsea, new york, 1908 (reprint, 1973). (written by a former pupil and assistant of kelvin; has first-hand accounts of kelvin’s teaching. andrew gray was kelvin’s successor at glasgow.) 3. j.g. crowther, british scientists of the nineteenth century, kegan paul, london, 1935. (james gerald crowther, 1899-1983, was a full-time scientific writer, and first scientific correspondent of the manchester guardian. he was a socialist (or possibly a communist) and his biography of davy, faraday, joule, thomson and maxwell has the flavour of marxism.) 4. a.p. young, lord kelvin, physicist, mathematician, engineer, longmans, london, 1948. (a brief 41 page biography by an engineer.) 5. d.k.c. macdonald, faraday, maxwell and kelvin, anchor books, new york, 1964. (a lively little book, written by a physicist and author of near zero, the physics of low temperature.) 6. b. wilson, kelvin and stokes, adam hilger, bristol, 1987. (this ‘comparative study in victorian physics’ gives kelvin’s and stokes’ teaching programmes in glasgow and cambridge, as well as detail about their lives and friendship.) 7. c. smith, m.n. wise, energy and empire: a biographical study of lord kelvin, cambridge university press, cambridge, 1989. (with 866 pages of fine print and much detail, this is the definitive modern biography of kelvin. we find for example (a fact entirely missing from ref. 1) that young william proposed marriage three times to sabina smith, and was three times refused. written by historians knowledgeable in science.) 8. sir w. thomson, mathematical and physical papers, 6 vols. university press, cambridge, 1882. 9. sir w. thomson, reprint of papers on electrostatics and magnetism, macmillan, london, 1872. 10. house of commons library, research paper 01/44, 2002. inflation: the value of the pound 1750-2001. (available on-line.) 11. l. campbell, w. garnett, the life of james clerk maxwell, macmillan, london, 1882. (lewis campbell was, since their school days together, a life-long friend of maxwell. william garnett was maxwell’s demonstrator at the cavendish laboratory, which maxwell designed and inaugurated as first cavendish professor. in the main, campbell wrote part i (biographical outline) and garnett wrote part ii (contributions to science). part iii (poems) are maxwell’s verses. apart from maxwell’s letters and papers (refs. 12 and 14) this was my main source. campbell’s part i is perhaps too discreet in some respects, and has a clerical viewpoint: the storm clouds of evolu142 john lekner tion occasionally darken the page, but darwin is not referred to by name.) 12. w.d. niven (ed), the scientific papers of james clerk maxwell, cambridge university press, cambridge, 1980. 13. i. tolstoy, james clerk maxwell: a biography. university of chicago press, chicago, 1981. 14. p.m. harman (ed), the scientific letters and papers of james clerk maxwell, cambridge university press, cambridge, 1990-2002. (vol. i 1846-1862, vol. ii part i 1862-1868, vol. ii part ii 1869-1873, vol. iii 1874-1879; a complete collection of extant scientific letters and manuscript papers, not duplicating the published papers in ref. 12.) 15. b. mahon, the man who changed everything, wiley, new york, 2003. (a lively modern biography of maxwell, written by an engineer and civil servant.) 16. p.g. etchegoin, e.c. le ru, phys. chem. chem. phys. 2008, 10, 6079. 17. j.c. maxwell, a treatise on electricity and magnetism, 3rd ed., clarendon press, oxford, 1891. 18. a. russell, proc. roy. soc. lond. a 1909, 82, 524. 19. g.b. jeffery, proc. roy. soc. lond. a 1912, 87, 109. 20. j. lekner, j. 2010-2011. j. electrostatics (a) 2010, 68, 299; (b) 2011, 69, 11; (c) 2011, 69, 435; (d) 2011, 69, 559. 21. j. lekner, proc. roy. soc. a 2012, 468, 2829. 22. j. larmor (ed), origins of clerk maxwell’s electric ideas, as described in familiar letters to william thomson, cambridge university press, cambridge, 1937. demulsifier selection guideline for destabilizing water-in-oil emulsion for both non-eor and eor application nor hadhirah halim1, ismail m saaid2, sai ravindra panuganti1 1 petronas research sdn bhd, jln ayer hitam, kawasan institusi bangi, 43000 bandar baru bangi, selangor 2 department of petroleum engineering, universiti teknologi petronas, 32610, seri iskandar, perak, malaysia email: norhadhirah@petronas.com received: may 08, 2023 revised: jun 13, 2023 just accepted online: jun 19, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: n. h. halim, i. m. saaid, s. r. panuganti (2023) demulsifier selection guideline for destabilizing water-in-oil emulsion for both non-eor and eor application. substantia. just accepted. doi: 10.36253/substantia-2135 keywords: emulsion; demulsifier selection guideline; relative solubility number (rsn) 1. abstract the most common method for resolving water-in-oil (w/o) emulsions is chemical demulsification. the bottle test is a recommended procedure to analyze a combination of essential parameters such as the demulsifier dosage, residence time, heat, degree of agitation to generate the emulsion and agitation effects after demulsifier injection. it is an extensive and time-consuming selection procedure. furthermore, the previous demulsifier selection guideline reported in the literature had limitations and was not suitable for the southeast asia region. this study describes the development of a new demulsifier selection guideline that relates the demulsifier properties to the crude oil characteristics and is more representative for resolving emulsions in the southeast asia environment. in developing the selection guideline, four types of synthetic crude were used, with the crude api ranging from 27˚ to 40˚. sixteen demulsifier s with a relative solubility number (rsn) ranging from 11 to 21 were evaluated comprising resin alkoxylate and modified polyol base demulsifiers. an emulsion test matrix was developed by creating emulsions with different wax contents, asphaltene content and solid contents in the crude oil; then, the demulsifier was screened for all the matrices. based on the demulsification bottle test completion for all the test matrices, the demulsifier selection guideline was developed and then validated with the blind test in resolving emulsions from the actual crude. the validation results achieved an 86.7% match rate between the guideline output and the lab experimental result. this proved that good agreement had been established between the demulsifier properties and the crude characteristics. 2. introduction the most common type of emulsions in the petroleum industry are water-in-oil (w/o) emulsion. once formed, w/o emulsion can adversely impact petroleum dehydration and desalination processes. they cause corrosion, scaling, and mechanical changes in gas–oil separation units, affect the operation of the pumping systems due to the elevated viscosity, influence raw material processing quality and increase energy consumption (binks and rocher, 2009). crude oil emulsions must be separated almost completely before the oil can be transported and processed further. w/o emulsion is strongly stabilized by native crude oil emulsifiers (surfactants), which tend to migrate and concentrate at the w/o interface, forming a film that reduces the interfacial tension between the phases, preventing droplet coalescence. asphaltenes, resins, waxes and fine solid particles are generally considered to be natural emulsifiers and are thought to be responsible for the emulsion stability (zaki et al., 2000). on the other hand, the use of chemicals such as alkali, surfactants, and polymers in the injected water in eor technologies not only interacts with rock to change the wettability conditions, but also reacts with oil to form emulsions that improve oil recovery. however, the natural oil–water interfacial properties are also altered, which possibly makes the w/o emulsions much more stable. thus, while oil field emulsion might possess beneficial effects for oil recovery during oil reservoir enhanced oil recovery (eor) flooding processes, they create challenging conditions in the subsequent oil processing operations and must be neutralized, reduced, or removed. therefore, for many decades, understanding their causes, both chemically and physically, an d predicting their formation and how to mitigate them, has been a very important technical development objective in the petroleum industries. chemical methods are the most common mitigation approach for emulsion resolution in both the oil fields and the refinery (angle, c.w., 2001). the application of chemicals designed to neutralize the effects of emulsifying agents has the great advantage of being able to break the interfacial film effectively without the addition of new equipment or modification of existing equipment. however, due to the great number of different types of crude oils and eor process conditions, development, and selection of effective demulsifiers for regional crude oils has become a serious challenge. currently, in the oil industry, the selection of a demulsifier is still based mainly on trial and error after some preliminary screening such as bottle testing (wu et al., 2003). normal bottle testing duration in screening the demulsifier raw chemicals is very time consuming as there are a lot of raw chemicals to be tested which sometimes can reach 40 to 50 types of raw chemical. there should be a systematic process for selecting a suitable demulsifier based on the increasing knowledge of demulsifier chemistry. marques-silva et al. developed a model that relates the crude oil acidity number, water salinity and demulsifier relative solubility number. correlation bet ween the crude oil nature, the associated water salinity and the demulsifier hydrophilicity (rsn) are described as per eq. (1) below (marquessilva et al., 1997): ln s = -0.77a – 0.28 rsn + 8.17 (1) where s is the associated water salinity and a is the crude oil acidity number. this model is proposed as a method for demulsifier selection of crude oil/ water systems in which the acidity number and water salinity are easy parameter to be measured in the laboratory. cooper et al. studied the hydrophilic–lipophilic balance (hlb) of the demulsifier used to break an emulsion of heavy oil, water, and clay. the degree of demulsification was found to correlate with the hlb of the surfactant. the most effective agents for dewatering had hlb values between either 4 and 6, or 13 and 15. for clay removal, the most useful surfactants had hlb values above 20 (cooper at al., 1980). grenoble and trabelsi agreed on the relationship of hlb with demulsifier performance by mentioning that the initial selection of the most suitable surfactant or surfactant combination based on the intrinsic hlb may be a valid starting point but should not be limiting for fine-tuning the system (grenoble and trabelsi, 2018). temple-heald et al. reported that because the rsn of a demulsifier is a measure of its solubility properties, it is a key factor in demulsifier selection because solubility properties dictate whether the chemical will perform effectively as a surface-active agent at the oil/water interface. demulsifier molecular weight, rsn and functional groups are the keys to provide good separation of the water from the oil emulsion for heavy oil applications. in terms of the rsn evaluation, all demulsifiers < 8 rsn did not exhibit any separation whilst surfactants with rsn > 11 showed an improvement in the emulsion separation. in terms of the level of alkoxylation levels, the products that had highly mixed alkoxylation levels had better demulsification properties than single alkoxylated products (temple-heald et al., 2014). al-sabagh and noor el-din stated that the optimum demulsification efficiency, with 80% water separation, was obtained by a demulsifier with a high rsn value of 22 (al-sabagh and noor el-din, 2014). many studies have been carried out to evaluate the stability and demulsification of crude oil emulsions. a.a. pena et al. carried out research on the effect of alkylphenol polyalkoxylated resins and polyurethanes on the stability and properties of brine-in-crude oil emulsions. the phenolic resins promoted coalescence of droplets, supplemented by the cross-linked polyurethanes, which may act as “bridges” between droplets, thus increasing the probability for collisions leading to successful coalescence events. a mixture of 200 ppm of polymer polyurethane and 40 ppm of phenolic resin managed to achieve complete water separation in less than 2 hours at 30 °c (pena et al., 2005). f. zhang et al. described that one of the main challenges in demulsifier research and application is the demulsification of alkali surfactant polymer (asp) flooding produced liquid, because the asp application induces oil-in-water, water-in-oil and multiple emulsions which are very complex. to tackle this, there is a need to study dual function demulsifiers which can provide demulsification of both o/w and w/o emulsions at the same time (zhang et al., 2017). about resin alkoxylate demulsifier application, the literature has reported that ethylene oxide: propylene oxide mixes and resin: alkoxylate ratios are more important for assessing demulsifier performance than the type of resin used. furthermore, the paper reported that nonylphenol resin alkoxylates were the best performing products for treating emulsions for heavy oil applications (mohammed et al. 1994). as reported in other literature, the efficiency of a surfactant to act as a demulsifier depends on a few factors related to the surfactant structure, namely, the distribution of the demulsifier molecules throughout the bulk volume of the emulsion, the partition of the demulsifier between the phases, the process temperature, ph, and the salt content of the aqueous phase (auflem, 2002). in other literature, molecular dynamic simulation software materials studio was used to determine the effectiveness of the demulsifier. the simulation results show that the demulsifier with ethylene oxide (eo) and propylene oxide (po) values of 21 (eo) and 44 (po) achieved the highest water removal amount of 7.21 ml with an overall error less than 1.83 in which the predicted results are consistent with the experimental screening results (gent et al., 2022). this paper will discuss the establishment of a demulsifier selection guideline based on the demulsifier characteristics of re lative solubility number (rsn) with the crude oil characteristics including asphaltene content, wax content, and solid content. these three elements are the emulsion stabilizing agents and the impact of them in the emulsion behavior is discussed further in this paper. the previous demulsifier selection guidelines were focusing on the crudes from northern america (canada), europe (uk and france) and middle east (egypt) whereas this study are meant for southeast asia region which the crudes have higher crude api but some of the fields may contain high wax and solid content as describes in table 1. nevertheless, the guideline can be used outside southeast asia boundary as well since the synthetic crude of api 27 included in this study resembles the heavy crude behavior which is not from this southeast asia region. table 1physical properties of southeast asia crude oil. no properties value 1 asphaltene 0.1 – 2 % 2 wax content 1 – 10 % 3 crude api 30 46° 4 solid content 0 – 0.2% relative solubility number (rsn) is an empirically determined value that characterizes water solubility and the hydrophobic – hydrophilic character of a surfactant. it is commonly used to distinguish demulsifiers from emulsifiers. a demulsifier with an rsn value < 13 is considered insoluble in water or hydrophobic, while 13 <rsn>17 is dispersible at low concentrations, demulsifiers with an rsn > 17 are soluble in water or hydrophilic (grenoble and trabelsi, 2018). rsn has similarities with hlb as such that it measures the combined affinity of the hydrophobic part and lipophilic part of the surfactants to oil or aqueous phase. rsn has been widely used by surfactant manufacturers due to the simplicity of the testing in determining the rsn value (wu et al., 2003). two demulsifier groups were studied, namely resin alkoxylate and a modified polyol type of demulsifiers. the resin alkoxylate demulsifier is a versatile demulsifier for covering all emulsion treatment aspects and is usually used as the major portion in demulsifier formulations. it is a fast water dropper, which separates the emulsion quickly, while modified polyol is a good demulsifier for treating emulsions from heavy oil or low api crude oil. in term of resin alkoxylate demulsifier application, mohammed et al. (1994) has evaluated that the ethylene oxide: propylene oxide mixes and resin: alkoxylate ratio are more important for assessing demulsifier performance than the type of resin used. from this paper as well, nonylphenol resin alkoxylates showed the best performing products in treating emulsion for heavy oil application. normal demulsifier screening may took 2 or 3 months to obtain the formulation. after the guideline has been developed, team took only around 2 weeks in average to obtain the suitable demulsifier formulation in resolving the emulsion. 3. materials and methods 3.1 materials as the basis for developing the demulsifier selection guideline for non eor emulsions, four types of synthetic crude oil were used in the demulsifier bottle test with crude oil api ranges from 26˚ to 40˚. lower api indicates a heavier crude oil. non eor emulsion means that the emulsion stabilization is not caused by the eor chemical surfactant. the synthetic crude oil recipe was developed based on the crude true boiling point (tbp) from the crude assay. light components would involve tbp from c5-150 °c, the intermediate components include tbp of 150-370°c distillate and the heavy components tbp ranging from 370-540°c. under light components of c5-150°c tbp, the components that need to be included were naphthene and aromatics solvent. for intermediate component, naphthalene needs to be introduced while under heavy components, asphaltene and wax were added into the synthetic crude oil. all these components need to be incorporated to a certain ratio to produce the four (4) types of synthetic crude. the physical properties of the synthetic crude oil are described in table 2 below. the synthetic crude oil was used to vary the amount of wax, resin, and solid particles in the crude oil in producing various kind of emulsion behaviors. table 2physical properties of synthetic crude oil. properties crude oil api 27 crude oil api 34 crude oil api 37 crude oil api 40 wax (wt%) 2.18 6 11.55 2.85 asphaltene (wt%) 1.6 0.18 0.72 0.36 saturate (wt%) 29.8 30.1 52.1 37.4 aromatic (wt%) 4.5 29.1 20.7 28.0 solid (wt%) 0.1 0.1 0.1 0.1 in the bottle test, 16 different base demulsifiers supplied by croda with rsn ranges from 11 to 21 were used, comprising resin alkoxylate and modified polyol groups. the chemical structures are illustrated in fig. 1 and fig. 2. for the resin alkoxylate demulsifier, the resins have some aromatic hydroxyl groups that react with ethylene oxide/propylene oxide. for the modified polyol demulsif ier, the alkoxylated polyol compound is modified by a quaternary amine capping unit to give the desired characteristics of demulsi fier (scheibel and menkhaus, 2005). fig. 1chemical structure of resin alkoxylate demulsifier. fig. 2. chemical structure of modified polyol demulsifier. for the emulsion-stabilizing agent, asphaltenes were introduced into the synthetic oil by adding vacuum residue in the range of 3 wt% to 26 wt% that had been collected from the distillation process at the petronas malaysian refining company sdn bhd (mrcsb). the vacuum residue contained 28% saturate, 37% aromatic, 29% resin and 6% asphaltene. for the effect of solid particles, this study used aerosil r974, a moderately hydrophobic solid nanoparticle, provided by evonik inc. for evaluating the effect of wax on the emulsion stability, 2 wt% to 12 wt% of paraffin wax, namely acros organic type, which has a melting point of 42 °c and boiling point of 370 °c, was incorporated into the synthetic oil. 3.2. emulsion tendency test for non-eor emulsion before performing the demulsification test, an emulsion tendency test was conducted for the blank sample without any demulsifier injected to evaluate the stability of the emulsion produced. the formation of the emulsion and observation of the emulsion stability of each synthetic crude oil was performed in the laboratory following the inhouse standardized protocol as below: 1. place 50 ml of synthetic crude oil and 50 ml of 2% nacl water and warm to 60 °c in a 100 ml centrifuge tube. 2. manually shake 100 times to create a homogeneous emulsion. 3. place the tube in a water bath maintained at 60 °c, except when taking photographic images. 4. observe, photograph, and record the volume of emulsion left at 5, 10, 15, 20 and 30 minutes. 5. record the appearance of the emulsion. 3.3. demulsification test for the demulsification bottle test to evaluate non-eor emulsion, 2% nacl was used as the synthetic water. this represents the average salinity of the produced water in malaysian offshore fields. the bottle test is conducted by mixing the crude oil and brine in a 50:50 ratio, because the emulsion behavior is usually at a maximum at this water to crude oil ratio. each sample was manually shake n 100 times to produce a homogeneous emulsion. a total of 100 ppm of each base demulsifier was dosed into the emulsion mixture. this is the baseline concentration that is normally applied during the demulsifier screening process. after dosing the demulsifier, the samples were shaken by hand for another 20 times before placing the tubes back in the water bath. monitoring of the emulsion separation was recorded at 30 minutes. the demulsifier bottle tests were performed at two different operating temperatures of 60 °c and 35 °c. these temperature points were selected in accordance with the operating temperature of the demulsifier injection in the malaysia offshore fields. table 3 presents the test matrix of the bottle tests that were conducted to study the relationship between the demulsifier performance and crude oil properties for a non-eor emulsion. table 3test matrix of non-eor demulsification test. parameter testing condition crude oil api (°) temperature (°c) asphaltene content (wt %) wax content (wt%) solid effect (wt%) 27, 34, 37 and 40 35 and 60 0.09–1.8 2.85–11.55 0.1 and 0.2 for the eor induced emulsion demulsification guideline development, crude oils from three eor fields were used, namely from field a, field d and field b. the test matrix of the eor demulsification test is illustrated in table 3. for field a, a chemical eor (ceor) application was implemented using a proprietary formulation of surfactant s which is an amphoteric type of surfactant. for field d and field b, an enhanced water alternate gas (ewag) application using surfactant e was implemented, which is a foam surfactant comprising a mixture of anionic and amphoteric surfactants. during the demulsification bottle testing, an amount of eor surfactant as shown in table 4 was mixed with the synthetic produced water following the water composition from each field. the low concentration (lc) of the surfactant refers to the probable case of the emulsion which will be produced at the surface facilities, allowing for some surfactant adsorption into the rock in the reservoir. the high concentration (hc) of surfactant considers the worst-case scenario of the produced emulsion. the water with surfactant was then mixed with the actual crude oil following the water cut for each field and a test was conducted as per the field process temperature. to produce the emulsion, the mixtures were manually shaken 100 times, and the demulsifiers were dosed at the concentration described in table 3. after 30 minutes of heating in a water bath, the emulsion separation for each sample was monitored. table 4test matrix of eor demulsification test. parameters field a field d field b eor method ceor ewag ewag eor surfactant amphoteric type mixture of anionic and amphoteric type mixture of anionic and amphoteric type eor surfactant concentration (ppm) 250 750 900 2700 900 2700 3.4. blind test for demulsifier validation once all the demulsification data sets were completed, the demulsifier selection guideline was established. in validating the guideline, a blind test was conducted in testing the demulsifier performance with the actual crude oil from during the development phase. for the blind test, 15 crude oil samples from 5 fields were tested with base demulsifiers in which their rsn were matched with their crude oil property data. the demulsifiers were tested using the bottle test method to evaluate whether they could resolve the emulsion from these actual crude oil samples. 4. result and discussion 4.1. emulsion tendency test (non-eor emulsion) when crude oil and water are mixed, there is an intrinsic risk that they will stabilize and create an emulsion. the purpose of this emulsion tendency test is to create a stable and robust emulsion in the middle phase of the prepared synthetic crude oil for each individual api. fig. 3 shows the emulsion produced from each of the synthetic crude oils when mixed with 2% nacl at 50:50 crude oil: water volume ratio after 30 minutes at 60 °c; and fig. 4 illustrates the emulsion separation times within the 30-minute time, with respect to different crude oil apis. as can be observed from the graph, for the low crude oil api of api 27 and api 34, the emulsion was stable, w hich means no separation at all after 30 minutes. the most stable emulsion was from the crude oil of api 27, and the least emulsion produced from the crude oil of api 40. this is due to the increasing amount of vacuum residue in the heavy crude oil of api 27. it contained the highest asphaltene and saturate content, which are the stabilizing agents for the emulsion. the content of the vacuum residue in each of the crude oil were 26.2% for crude oil of api 27, 5.5% for crude oil of api 34, 4.4% for crude oil of api 37 and 3% for crude oil of api 40. process temperature (°c) 65 55 40 watercut (%) 60 and 80 80 60 and 80 demulsifier concentration (ppm) 20—100 1000—3000 1000—3000 fig. 3test matrix of non-eor demulsification test. fig. 4emulsion separation time of crude oil api 27, api 34, api 37, and api. 4.2. demulsification test (non-eor emulsion) after completing the emulsion tendency test, the next step was to conduct the demulsification test by dosing a certain concentration of demulsifier into the emulsion. in this case, 100 ppm demulsifier concentration was used to resolve the produced emulsion. the effect of different crude api, wax content, asphaltene content and solid content to the emulsion and demulsification behavior are discussed further in each subsection. 4.2.1 effect of crude api and wax content from the demulsification test result, the most effective demulsifier in terms of their rsn for variation of crude oil api and wax content at 60 °c, are tabulated in fig. 5. the demulsifiers are defined as working when they can completely resolve the emulsion or there is 1% or less remaining in the solution. the demulsification result from the two demulsifier chemistry groups shows that on average, the demulsifier with the high rsn, which is from 19 to 21, works best in resolving the emulsion compared to the low rsn demulsifiers. increase in hlb/ rsn value increases the solubility of the demulsifier in the aqueous phase which is water. when the demulsifier is initially introduced to the water in oil emulsion, it will be thermodynamically stable at the interface of water droplets. accordingly, the surfactants possessing high rsn migrate faster to the interface than those having low rsn. as a result of such enhanced migra tion toward the interface, the surfactant forms a continuous hydrophilic pathway between the dispersed water droplets. this leads to a rapture of the interfacial film surrounding the water droplets (atta et al., 2009). the high rsn demulsifier is a water soluble demulsifier which worked well in resolving the water-in-oil emulsion of this emulsified synthetic crude oil. compared to this high rsn demulsifier, the demulsifier with rsn 19 was the most effective demulsifier in resolving the emulsion for all the crude oil apis except for crude oil api 37. the crude oil of api 37 had the highest wax content, 11.55%, and that required a higher rsn, of rsn 21, for it to work effectively. fig. 5most effective demulsifier based on the rsn for variation in crude oil api and wax content at 60 °c. fig. 6percentage (%) of working demulsifier at 60 °c based on different demulsifier chemistries. the demulsification data, based on each demulsifier chemistry group at 60 °c for all the crude oil apis are illustrated in fig. 6. as determined by the demulsifier chemistry trend, the resin alkoxylate type was better in dehydrating the crude oil compared to the modified polyol type especially for crude oil api 37 where the crude oil was a bit waxy and the wax content was high, up to 11.55%. th e percentage of the working demulsifier was higher for the resin alkoxylate which was about a 53% difference compared to the modified polyol type. 4.2.2 effect of temperature temperature plays an important role in the destabilization of emulsions. demulsification evaluation also was conducted at lower temperature of 35 °c to determine the demulsifier performance at lower process temperature, as per fig. 7. the test could not be conducted for crude oil at api 27 since this crude oil contains a high vacuum residue of 26.2% and comprises high asphaltene and saturates until it solidifies at this low temperature. referring to the results in fig. 7., the demulsifier performance was decreased at 35 °c, especially for crude oil at api 37, which had a high wax content. fig. 7most effective demulsifier based on the rsn for variation in crude oil api and wax content at 35 °c. at low temperatures, especially below the wax appearance temperature (wat), waxes precipitate and interact with water droplets, forming a physical network between the droplets (freitas et al., 2018). the formation of a network structure occurs by crystal aggregations through interand intramolecular non-covalent interactions in which wax concentration and crystal size affect the stabilization mechanism (ghosh and rousseau, 2011). this network can increase the emulsion stability (visintin et al., 2008). low temperature conditions hinder the collision of droplets thus increasing the oil viscosity. this increases the strength of the stabilizing agents at the droplets, thus providing low chances of settling. despite this, demulsifiers at rsn 19 continue to work with high efficiency even at low temperatures, which implies the robustness of these demulsifiers. 4.2.3 effect of asphaltene as mentioned in the introduction, asphaltene content and solid content stabilized the emulsion (zaki et al., 2000). these two parameters have been studied in detail regarding their demulsification, by varying both components in the synthetic crude oil. sara analysis of the vacuum residue shows the asphaltene content was 6%. this equated to the asphaltene content in the original synthetic crude oil being 1.6% (26.2/100*6%) in heavy crude oil of api 27, and 0.18% (3/100*6%) in the light crude oil, api 40. fig. 8 describes the demulsifier performance of each individual rsn upon varying the asphaltene content in the synthetic crude oil of the lowest and highest crude oil api. from the figure, the demulsifier performance reduced when the asphaltene content increased for both low and high crude oil api. (zaki et al., 2000) illustrated that the higher the concentration of asphaltene, the higher the emulsion stability, which caused the demulsifier performance to reduce. due to the large molecular weight of asphaltene, it forms a steric barrier to coalescence between two approaching water droplets which is considered the important factor in emulsion stabilization. for a heavy crude oil of api 27, demulsifiers with rsn 16 work best for all asphaltene content between 1.2% and 1.8%, while for a light crude oil of api 40, demulsifiers with rsn 19 work best for all asphaltene content between 0.36% and 0.72%. surfactant species that are available in the crude oil, such as asphaltenes and resins results in a hld > 0. hld is a dimensionless hydrophilic–lipophilic deviation from a reference state. the usual technique to dehydrate the crude oil is to break the w/o emulsion by adding a hydrophilic demulsifier surfactant that migrates at the drop interface and combines with the natural surfactants to attain an exact hld = 0 mixture formulation (salager and forgiarinni, 2012). grenoble and trabelsi, (2018) also supported this theory and mentioned that asphaltenes, which have a more lipophilic character, require a more hydrophilic demulsifier (oil soluble or less water soluble demulsifier) to shift the hydrophilic lipophilic deviation (hld) towards zero. the optimum condition for demulsification is when the hld is 0. both references support the result that a lower rsn (less water soluble) demulsifier works better than a demulsifier with high rsn in resolving the emulsion for a crude oil with high asphaltene content. to promote good destabilization at the interfacial phase, the demulsifier must competitively adsorb at the interface, remove, and break up the asphaltenic aggregates and reduce the interfacial tension between the hydrocarbon aqueous phases and hence facilitate the droplet coalescence kinetics (salager and forgiarinni, 2012). fig. 8most effective demulsifier based on the rsn for variation in crude oil api and asphaltene content. 4.2.4 effect of solid content evaluation was continued to observe the demulsification effect when solid content was varied in the mixture of synthetic crude oil and water. to study the solid content effect to the emulsion stabilization, 0.1 and 0.2 wt% of aerosil r974, a silica particle was mixed into the mixture of crude and water using a mechanical shaker. aerosil r974, is a moderate hydrophobic type which tend to stabilize water-in-oil emulsions (perino et al., 2013). this type of silica particle, with a contact angle of 143.7° helps water droplets disperse in oil phases, resulting in stabilization of water-in-oil emulsions (wu et al., 2020). table 5 illustrates the percentage of working demulsifier at different solid amounts for both crude oil apis. for crude oil api 27, because it had the highest amount of asphaltene at 1.6%, the combination of this asphaltene and solid caused the emulsion to become very stable, thus the percentage of working demulsifier was very low at about 16% compared to the high api crude oil that is easier to treat, and in which 63% of demulsifiers were still working to resolve the emulsion. small particles strongly enhance water–crude oil emulsion stability when interactions with asphaltenes promote particle adsorption at the oil–water interface (sullivan and kilpatrick, 2002). the higher emulsion stability observed in the presence of hydrophobic particles results from the addition of severel effects: the tendency to form a structure in the oil dispersed phase and the influence of the attached particles at the interface (perino et al., 2013). due to this tighter emulsion, the demulsifier to resolve the emulsion is limited, especially for low api crude oil of api 27. fig. 9 presents the results of the best demulsifier rsn when solid effect is the main factor in stabilizing the emulsion for the lowest and highest api crude oils. the results indicate that the demulsifier with rsn 19 worked best for all solid content except for the light crude oil of api 40%, which need a higher water soluble demulsifier, which is a demulsifier of rsn 21, to resolve the emulsion at the higher solid content of 0.2 wt%. 1.2 1.8 0.36 0.72 16 16 19 19 0 10 20 30 40 50 60 70 34 37 40 crude api (°) most effective demulsifier in term of rsn for variation of asphaltene content and crude api asphaltene content (wt%) rsn demulsifier effectiveness (%) table 5percentage of working demulsifier for both solid contents and different crude oil apis. crude oil api (°) solid content (wt%) working demulsifier (%) 27 0.1 31 27 0.2 16 40 0.1 63 40 0.2 38 fig. 9most effective demulsifier based on the rsn for variation in crude oil api and solid content. with respect to the different demulsifier chemistries, the chart in fig. 10 illustrates the comparison between the modified polyol and resin alkoxylate demulsifiers with the presence of solids in the synthetic crude oil emulsion. for heavy crude oil, modified polyol demulsifiers are good for resolving the emulsion with the presence of solids but for light crude oil, the performance of both demulsifier chemistries is comparable. in addition, polyol demulsifiers are claimed to work effectively in resolving bituminous emulsions in canada. this bituminous hydrocarbon is known to be very viscous or even non flowable under reservoir conditions, thus it produces highly stable emulsions which are made even more stable by the usual presence of clays (laberge and mccoy, 1982). fig. 10percentage of working demulsifier of different demulsifier chemistries with the variation in solid content. 10 12 14 16 18 20 22 0 0.1 0.2 0.3 0.4 0.5 27 27 40 40 r s n s o lid c o n te n t (w t% ) crude api (°) most effective demulsifier in term of rsn for variation of solid content and crude api solid content (wt%) rsn 4.3. emulsion tendency test (eor emulsion) the effect of amphoteric eor surfactant concentration on the emulsion separation was studied with the concentrations of 250 ppm and 750 ppm for field a ceor application. for field b ewag and field d ewag application, the ewag surfactant concentrations were 1000 ppm and 2700 ppm. for ewag surfactant, it comprises of a mixture of amphoteric and anionic type of surfactant. table 6 presents the eor induced emulsion due to ewag surfactant foam and ceor surfactant chemical. hc is defined as high surfactant concentration and lc is low surfactant concentration. the results showed a general increase in emulsion volume at the high surfactant concentration. for the field b ewag case, for the high surfactant concentration, the emulsion was worst at 60% water cut in which the emulsion is about 40% compared to the 80% water cut in which the emulsion is about 25%; however, the foam produced was higher for the 80% water cut. chen et al. showed that foam stability decreased when oil saturation increased (chen et al., 2020). however, for emulsions, the emulsion stability increases as the oil saturation rises. in another study, it was observed that as the water cut increased, the tendency of emulsion formation was reduced for foam assisted co2 wag applications (borhan et al., 2014). these results support the findings of the field b ewag emulsion tendency test for the high ewag surfactant concentration case. for the field d ewag case, the test was only conducted at the 80% water cut as that was the current water cut of that field. the emulsion was quite comparable between the low and high surfactant concentration except that it produced a higher foam height compared to the low surfactant concentration. for the emulsion induced by the ceor application of injecting amphoteric surfactant in field a, it seems that the emulsion was worse for the 60% water cut compared to 80% water cut. at this water cut, the emulsion behavior can be either the oil-in-water or waterin-oil type (borhan et al., 2014). however, due to the nature of this ceor amphoteric surfactant, which is a less water-soluble type of surfactant, it tends to produce a water-in-oil emulsion which is why a higher volume of crude oil is needed to produce a more stable emulsion. furthermore, from the observation the higher ceor surfactant concentration produced a more severe emulsion than the lower ceor surfactant concentration. nguyen et al., (2012) showed that the eor surfactant decreased the size of oil droplets, increased the surface charge of oil droplets and increased the film elasticity, thus making the oil–water separation more difficult, which was depicted in a ceor emulsion tendency test. table 6emulsion behavior of eor induced emulsion. no field emulsion behavior 1 field b ewag field b ewag emulsion at 60% and 80% water cut for low and high surfactant concentrations 2 field d ewag field d ewag emulsion at 80% water cut for low and high surfactant concentrations. 3 field a ceor field a ceor emulsion at 60% and 80% water cut for low and high surfactant concentrations. 4.4 demulsification test (eor emulsion) a demulsification system was then formulated to address the emulsion formed by this eor application. a demulsifier in the range 20 ppm to 100 ppm was used for treating the field a ceor application, and a 1000 ppm to 3000 ppm demulsifier concentration was used to treat the ewag emulsion. this demulsifier can be further optimized as this screening is only referring to a single base demulsifier without combining with other demulsifiers or solvents, thus becoming a formulation. table 7 describes the recommended demulsifier rsn for each eor demulsification case with respect to the different fields, water cuts and surfactant type and concentration breakthrough. table 7eor demulsification result. field process temperature (°c) water cut (%) surfactant type surfactant breakthrough (wt%) workable rsn 0.075 19 and 20 0.025 17 to 21 0.075 19 to 21 0.025 17 and 20 0.27 11 to 16 0.09 11 to 17 0.27 16 to 17 0.09 16 to 17 0.27 11 to 16 0.09 11 to 16 ceor surfactant 80 field b 40 60 ewag foam surfactant 80 field d 55 80 field a 65 60 wc the eor demulsification is mostly impacted by the eor surfactant properties and its concentration thus the eor demulsification guideline was developed based on the eor surfactant being the causative factor in eor emulsion stability. for the field d ewag application, the effective demulsifiers had an rsn of 11 to 16, which was a lower rsn than the high rsn demulsifiers used for resolving non-eor emulsions. the ewag surfactant e was highly water soluble which means it is highly hydrophilic thus it tends to produce an oil-in-water emulsion. this emulsion needs an oil soluble or less water-soluble demulsifier with a low rsn to resolve the emulsion. for the field b ewag application, the workable demulsifier rsn range was larger, being from 11 to 17 (low to medium rsn range) even though they were using a similar ewag surfactant. field b crude oil which is lighter than the field d waxy crude oil may make the workable demulsifier rsn range bigger compared to field d. at 80% water cut, the emulsion was more severe and the workable rsns were between 16 and 17 only. for field a ceor application, generally the effective demulsifiers had the rsn from 17 to 21. properties of the ceor surfactant s which is less water-soluble (less hydrophilic) than foam surfactant, tends to produce the water-in-oil emulsion. this emulsion needs a highly water-soluble demulsifier that has a high rsn to resolve the emulsion. in one study, decreasing the extent of the interfacial tension acted on by the water solubility demulsifiers was bigger than the oil solubility demulsifiers for the surfactant polymer flooding application. with the increase in the demulsifier concentration for these demulsifiers, the interfacial tension decreased, and the dewatering rate increased (yimei, 2014). (zhang et al., 2006) revealed that a non-ionic water-soluble mixed demulsifier was used successfully to treat the produced liquid from asp flooding. the demulsifier increased the zeta potential and interfacial tension (ift) and reduced the water content from 30.5 to 7.6%, at a 50 mg/kg dose. this demulsifier also managed to reduce the oil concentration in the water phase from 1623 mg/l to 530 mg/l which was about a 67% reduction. fig. 11 illustrates the comparison of the demulsifier performances between the resin alkoxylate and the modified polyol for eor demulsification. the performance was comparable between the two demulsifier groups for all three eor applications except for the field b ewag demulsification where the resin alkoxylate demulsifier worked better than the modified polyol. the results also showed that not many demulsifiers effectively resolved the ewag emulsion compared to the ceor emulsion, as the effect of foam really increased the emulsion severity. fig.11percentage (%) of working demulsifier based on different demulsifier chemistries for eor demulsification. 4.5. demulsifier selection from demulsification guideline based on the demulsification database that was developed earlier, the demulsifier selection guideline is summarized as below: 1. for a non-eor emulsion, generally the best demulsifier ranges that work for all api crude oil are high, which is between 19 to 21. 2. the demulsifier with rsn 19 works for wax content 6% and below. 3. for a higher wax content, the demulsifier rsn needs to be higher, which is 21, for the demulsifier to work. 4. the demulsifier with rsn 19 works best at low process temperature of 35 °c. 5. for heavy crude oil, demulsifiers with rsn 16 work best for all asphaltene content between 1.2% to 1.8%; while for light crude oil, demulsifiers with rsn 19 work best for all asphaltene content between 0.36% to 0.72%. 6. on the solid effect, for heavy crude oil, demulsifiers of rsn 19 performed the best in resolving the emulsion at all solid content. for light crude oil, demulsifiers worked at rsn 19 for solid content of lesser than 0.2%. for higher solid content of more th an 0.2%, they need a higher water soluble demulsifier which is demulsifiers of 21 to resolve the emulsion. 7. for field b ewag application, demulsifier with rsn 16 and 17 work best and for field d ewag application, demulsifier with rsn 11 and 16 work best in resolving the ewag emulsion. 8. for field a ceor application, the effective demulsifiers have an rsn from 17 to 21. 4.6. demulsifier blind test after the demulsifier selection guideline was developed, a blind test was conducted to test the demulsifier performance with the actual crude oil. the most important parameters when applying the selection guideline are asphaltene content, wax content, solid content and api gravity, and the crude oil properties are presented in table 8. for the blind test, 15 crude oil samples from 5 fields were tested with base demulsifiers, and their rsn was matched with their crude oil property data. the results of the blind test are depicted in table 7 and some of the bottle test images are illustrated in fig. 12. table 8demulsifier blind test result. no crude oil crude oil properties demulsifier properties no. of working demulsifier of similar rsn matching rate (%) api wax (%) solid (%) asph (%) rsn 1 d1 34 13 0.29 1.19 21 2 out of 3 66 2 g2 46 6 0.2 1.2 21 1 out of 2 50 3 b3 39 2.7 0.14 0.1 19 2 out of 2 100 4 b4 35 4.3 0.12 0.1 19 2 out of 2 100 5 b5 37 3 0.1 0.04 19 2 out of 2 100 6 d6 31 4.7 0.1 0.53 19 2 out of 2 100 7 b7 44 2 0.01 1.78 19 2 out of 2 100 8 s8 36 4.8 0.09 0.09 19 2 out of 2 100 9 t9 24 6.9 0.08 2.19 19 2 out of 2 100 10 t10 23 1.3 0.06 1.25 19 2 out of 2 100 11 t11 25 3.3 0.09 2 19 2 out of 2 100 12 t12 26 1.3 0.04 3.6 19 2 out of 2 100 13 d13 33 25 0.4 0.1 19 2 out of 2 100 14 b14 41 4 0.2 0.1 19 2 out of 2 100 15 s15 19 2.1 0.17 1.25 16 1 out of 1 100 fig. 12blind test image of b3 and d1 crudes before and after addition of base demulsifier. for b3 crude oil, based on the crude oil properties data in table 7, it was a high-api type of crude oil, which is close to 40°. the wax content was quite low, about 2.7%. based on this data, because the wax content is lesser than 6%, the demulsifiers chosen should be under rsn 19. in terms of the solid’s relationship, b3 crude oil had a solid content of 0.14% which was less than 0.2%, and based on this, rsn 19 also worked best. for the d1 crude oil, it was a bit waxy, and the solid content was also higher than b3 crude oil. because the wax content was 13% and the solid content was 0.29%, base demulsifiers from the rsn 21 group were chosen for testing. in addition to this, the blind test results in table 8 show that almost recommended demulsifiers worked efficiently in resolving the emulsion except for d1 and g2 crude oils. this led to a high matching rate of 86.7% based on the number of working demulsifiers between the guideline output and the experimental lab results. 5. conclusion this paper establishes a demulsifier selection guideline in resolving w/o emulsions based on the relationship of demulsifier properties with the crude oil characteristics. based on the bottle test completion for all the test matrices, the demulsifier selection guideline was developed and then validated with the blind test in resolving the emulsion from the actual crude oil. the high matching rate of 86.7% between the selection guideline outputs versus laboratory test proved that good agreement was established between the demulsifier properties and the crude oil characteristics. statements and declarations on behalf of all authors, the corresponding author states that there is no conflict of interest. abbreviation rsn eor ceor ewag relative solubility number enhanced oil recovery chemical enhanced oil recovery enhanced water alternate gas w/o water-in-oil o/w oil-in-water hlb hld sara hydrophilic–lipophilic balance hydrophilic–lipophilic deviation saturate aromatic resin asphaltene asp alkaline surfactant polymer api hc lc ift american petroleum institute high surfactant concentration low surfactant concentration interfacial tension tbp true boiling point references [1] b.p. binks, a. rocher. 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[24] colin l. laberge and david r. mccoy (1982) “demulsification of bitumen emulsions with a high molecular weight polyol containing discrete blocks of ethylene and propylene oxide,” 4,321,147. [25] d. chen, h. zhao, k. liu, y. huang, and b. li (2021) “the effect of emulsion and foam on anti-water coning during nitrogen foam injection in bottom-water reservoirs,” j. pet. sci. eng., vol. 196, p. 107766, doi: 10.1016/j.petrol.2020.107766. [26] n. borhan, n. h. halim, and j. m. b. m. ibrahim (2014) “an investigation of micro-emulsion and fine foams induced by eor application in malaysian fields,” soc. pet. eng. int. pet. technol. conf. 2014, iptc 2014 innov. collab. keys to afford. energy, vol. 1, pp. 548–562, 2014, doi: 10.2523/iptc-17762-ms. [27] d. nguyen, n. sadeghi, c. houston. chemical interactions and demulsifier characteristics for enhanced oil recovery applications. energy & fuels, 12th international conference on petroleum phase behaviour and fouling, 2012. [28] m. yimei (2014) “research on demulsification mechanism of polymer surfactant flooding produced fluid,” vol. 6, no. 1, pp. 15–21. [29] r. zhang, c. liang, d. wu, and s. deng. (2006) “characterization and demulsification of produced liquid from weak base asp flooding,” colloids surfaces a physicochem. eng. asp., doi: 10.1016/j.colsurfa.2006.05.023. 3.2. emulsion tendency test for non-eor emulsion 3.3. demulsification test 3.4. blind test for demulsifier validation 4.1. emulsion tendency test (non-eor emulsion) 4.2. demulsification test (non-eor emulsion) 4.2.1 effect of crude api and wax content 4.2.2 effect of temperature 4.2.3 effect of asphaltene 4.2.4 effect of solid content 4.3. emulsion tendency test (eor emulsion) 4.4 demulsification test (eor emulsion) 4.5. demulsifier selection from demulsification guideline 4.6. demulsifier blind test [1] b.p. binks, a. rocher. (2009) effects of temperature on water-in-oil emulsions stabilized solely by wax microparticles, j. colloid interface sci. 335 (1), pp 94-104. substantia. an international journal of the history of chemistry 3(2) suppl. 4: 101-114, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-502 citation: a. zambon (2019) periodicity trees in a secondary criterion of periodic classification: its implications for science teaching and communication. substantia 3(2) suppl. 4: 101-114. doi: 10.13128/substantia-502 copyright: © 2019 a. zambon. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. periodicity trees in a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon universidad nacional de la patagonia san juan bosco, argentina e-mail: alfiozambon@gmail.com abstract. in this work, i will present a proposal for introductory courses in chemistry. after the topics of atomic structure, chemical periodicity and chemical bonding, this proposal addresses the study of the periodic system based on triads, which has closed structures called periodicity trees as a secondary periodic criterion. this table was designed from a classical chemical perspective, with the purpose of integrating traditional topics and of supplying a conceptual basis for new ones, and, mainly, to privilege the chemical over the physical approach in the process of teaching-learning chemistry in initial courses. keywords. periodicity tree, chemical element, periodic system, teaching and communication in chemistry. no sólo le costaba comprender que el símbolo genérico “perro” abarcara tantos individuos dispares de diversos tamaños y diversa forma; le molestaba que el “perro” de las tres y catorce (visto de perfil) tuviera el mismo nombre que el “perro” de las tres y cuarto (visto de frente).1 jorge luis borges 1. introduction borges’s quote, presented as an epigraph, is included in the short story “funes, his memory”, and serves as a trigger to the purpose of this work : not only was it difficult for him to see that the generic symbol “ dog” took in all the dissimilar individuals of all shapes and sizes, it irritated him that the “ dog” of three-fourteen in the afternoon, seen in profile, should be indicated by the same noun as the dog of three-fifteen, seen frontally.2 just as the generic symbol ‘dog’ comprises many different individuals, of various sizes and diverse forms, the generic symbol ‘chemical element’ comprises a multiplicity of species in the same locker of the periodic tables. for example, one box of the usual periodic tables includes all the isotopes 102 alfio zambon of an element, all the simple ions of all the isotopes of that element, all the ions combined to each other, and therefore all the isotopes of all the elements that make up each combined ion, in turn, in all possible combinations. it furthermore also encompasses all the molecules, from the simplest that the element can form, as oxides or hydrides, going through those of more complex structures, like most organic molecules, to all polymers, both natural and synthetic, in which that element can be part of, etc.3 in addition, a single locker includes all those species in all possible contexts in which they can be presented, for example, solutions with subtle variations in concentration or ph. the context, although usually neglected, is a however fundamental aspect in chemistry, since small variations, which can be considered insignificant −as the difference between the dog of three fourteen (seen from the side) with the dog of three fifteen (seen from the front)− may induce large changes in some particular reactions such as the case of saturated solutions or metastable systems. ireneo funes, the character of borges’s short story, found it hard to comprehend that the generic symbol ‘dog’ covers many different individuals in size and in shape. by contrast, most students of initial chemistry courses experience no difficulty to approach the complexity of the concept of chemical element, as they simply do not become aware of that complexity, of that conceptual labyrinth. to them, the concept of element coincides with the concept of atom, and an atom is a cluster of protons and neutrons in the nucleus and electrons in the periphery, which are organized in a “quasi-military” way in “decreed” energy levels; in turn, molecules are simply conceived as sums of atoms. the purpose of this contribution is to present an alternative view that could be used in the educational context, in order to help the student to become aware of the complexity involved in the term ‘chemical element’, and of the importance and limitations of the periodic classification of elements. the acknowledgement of the complexity of this problem and of all the problems derived from the concept of element − basically all chemistry −, far from discouraging the students, should stimulate them to approach the exciting task of studying chemistry. let us recall that the standard periodic table (spt) is organized by a primary criterion, which orders the elements by increasing atomic number, and a secondary criterion, which allows grouping elements in chemically similar families according to the electronic configuration of the last layer. in contrast we suggest the following alternative. after teaching the initial topics of the regular course − atomic structure, periodic table and chemical bonding, the table based on atomic number triads (hereafter called tbt, table based on triads) is introduced, in order to integrate those topics from a purely chemical perspective.4 the tbt maintains the primary criterion but, as a secondary criterion, it proposes to organize the elements in a series of closed structures called ‘periodicity trees’ (pt’s). the peculiarity of this periodic table is to dispense with all consideration of electronic configurations. this is a fundamental point of the proposal, since it shows an alternative way of organizing the elements without using a concept that, although it is very relevant in chemistry, comes from a physical theory as quantum mechanics.5,6 moreover, this approach shakes two common “beliefs” by showing, on the one hand, that the concept of element is not as simple as usually believed, and, on the other hand, that classifications are never unique: there are very different ways of classifying, each useful in its own field or application. in the case of tbt, the secondary criterion of classification is periodicity tree (pt), which focuses on the classification of the elements from a chemical and non-physical perspective: the criterion is based on macroscopic chemical similarities among elements and not on quantum features of atoms (see sections 4 and 5). with this goal in sight, the article is structured as follows. the next section provides a brief historical overview on the development of the concept of element. section 3 sketches the path towards periodic classification. section 4 describes the proposal of the periodic system based on triads (tbt). by section 5 we will be described focusing on the structures called ‘periodicity trees’ (pt). section 6 will introduce the implications in the context of teaching and communication of chemistry; in this section the main proposal of this work will be explained and the treatment of some relevant issues in this context will be discussed. finally, the conclusions of this work will be presented. 2. the roots of the notion of element from pre-socratic philosophy to modern times, the concept of element was mainly philosophical, designing the originating principle of everything real: it referred to what is primary, fundamental and persistent, in opposition to what is secondary, derivative and transitory. it was only in the eighteenth century that antoine lavoisier (1743-1794) proposed an operational definition of element that had a strong influence up to now: elements are the ultimate product of chemical analysis. dimitri mendeleev (1834-1907) replaced the lavoisier program, based on the relationship between simple body and compound, by the relationship between 103periodicity trees as a secondary criterion of periodic classification element and simple or composite body.7 simple body ceases to be an explanatory principle and becomes an appearance. only elements, hidden in simple and composite bodies and remaining in spite of change, can be an explanatory principle. this motion from the concrete reality of simple bodies to the abstract reality of elements, is what allowed mendeleev to conceive a general system of elements that goes far beyond a mere grouping of chemical families.8 with the advent of quantum physics in the early twentieth century, the atomic theory pervades the field of chemistry, and the concept of element is assimilated to that of atom. however, after the discovery of isotopes by frederick soddy (1877-1956) in 1913, elements seemed to “multiply” and the doubts about whether or not there were new elements triggered what eric scerri calls as the “periodic table crisis”.9 it is in the context of this crisis that friedrich paneth (1887-1958), in 1931 proposes the dual nature of the concept of element, distinguishing between elements as simple substances according to their phenomenological manifestations, and elements considered in an abstract sense as basic substances, whose only property was no longer their atomic weight, as in mendeleev’s, but their atomic number, in consonance with the new quantum mechanics.10 for paneth simple and basic substances are not two descriptions of the same entity, product of an epistemic limitation to be overcome in the future; for him, the very concept of chemical element embodies a double nature. the epistemological status of the basic substance is part of the current discussions about the nature of the concept of element among historians, chemists, educators and philosophers of chemistry. these discussions show that, although there is a broad consensus about the extension of the concept, there are strong disagreements with respect to its intention (cf., for example, bent, hendry, schwarz, earley, ruthenberg, scerri).11,12,13,14,15,16. 3. the road toward a periodic classification according to van spronsen and scerri, two notions led to the evolution of the periodic system: the prout hypothesis and the döbereiner triads.17,18 the idea that all simple bodies must derive from hydrogen was formulated by the scottish physicist william prout (17851850), who noted that many of the atomic weights determined for the elements were integer multiples of the atomic weight of hydrogen. prout concluded that hydrogen could be the fundamental element, and that all other elements would be formed from this element by a condensation phenomenon. this hypothesis implied that all the elements had to have whole atomic weights, which was in contradiction with many experimental data of the time. prout’s hypothesis played a double role in the history of the classification of the elements: on the one hand, it stimulated research aimed at the exact determination of atomic weights, and on the other hand, it also weakened the tendency to systematize the elements through its phenomenological properties, imposing the primacy of classification by atomic weight.15 in 1817 the german chemist johann wolfgang döbereiner (1786-1849) reported that certain elements associated in groups of three, presented chemical similarity and a particular arithmetic relationship: the atomic weight (or equivalent weight) of the second element was almost exactly the average of the other two. he called these groups ‘triads’. for instance, döbereiner found that selenium in the triad of sulfur, selenium, and tellurium had an atomic weight that was the approximate average of the weights of the other two elements. the importance of this discovery lies in the association of qualitative chemical properties, such as the kind and the degree of reactivity, with numerical properties of the elements. this suggested that there could be some underlying numerical order that could serve to relate the elements to each other in a systematic way. döbereiner also discovered other triads, such as calcium, strontium and barium, and lithium, sodium and potassium. other chemists discovered still more triads and began to elaborate tables that tried to relate the triads to each other.15 among the precursors of the periodic system, william odling (1829-1921) classified the then 45 known elements into 13 groups.19 also noteworthy is the contribution made by the british chemist john newlands (1837-1898), who in 1864 published a table of 24 elements subdivided into five groups.20 he noticed that in the table there was a repetition of some properties of the elements every certain regular interval. then he placed the elements in increasing order of atomic weights, giving each one an order number. in 1865 he published another table containing the numbered elements arranged in eight columns.21 he observed that when counting from any element, the eighth had similar properties. he called this relationship “the law of octaves”. in turn, in 1864 the german chemist julius lothar meyer (1830-1895) presented a table of 28 elements, arranged horizontally according to their valence (see also boeck’s article on meyer in this special issue).22,23 in 1868 he proposes another periodic table with the atomic weight as criterion of order. this new table had 55 elements arranged vertically in 15 columns, being classified in families located horizontally.24 by then clearly the ordering of the elements was linked to the atomic weights and the 104 alfio zambon analogy in their chemical behavior, which went beyond döbereiner’s concept of triads but definitely built on it. when he had to dictate his chemistry course, mendeleev considered that he lacked appropriate teaching material and decided, like many of his colleagues, to develop his own manual.25,26 one of the first difficulties that he found was how to organize the huge set of chemical knowledge, accumulated over decades, about thousands of known chemical substances. from the time of lavoisier, the mostly adopted solution for teaching consisted in relating the properties of a composite substance with the properties of its component simple substances. by contrast, mendeleev adopted a pluralist position. from his perspective, phenomenal properties are nothing else than external manifestations of more abstract entities, the elements: he considered that elements had a more fundamental status, of a metaphysical nature, and that their only attribute is atomic weight. in this way, mendeleev introduced a clear differentiation between simple body or simple substance and element. the notion of simple body or substance, which from lavoisier had become the key concept of chemistry, is thus replaced by that of element, understood in an abstract or metaphysical sense. according to mendeleev, the simple body is something material, and remains relegated to the world of appearances. the element is the only explanatory principle, the substratum of everything observable. the elements have no phenomenal existence, they are always “hidden” in a simple or compound body. it is that “something” that is conserved in chemical reactions. it is a fundamental reality, clearly abstract, which explains the conservation and permanence of individual properties despite chemical changes.5 mendeleev was a strong defender of the individuality of the chemical elements, and therefore, a critic hostile to the hypothesis of prout, which he considered contrary to the periodic law. it is on the basis of this conception of element that mendeleev organized his classification endeavor; reaching that level of abstraction appeared was indeed an essential requirement for a successful classification. he was then able to consider that the properties of simple and compound bodies came as a periodic function of the atomic weights of the elements.5 the periodic classification marked the apogee of a chemistry centered on the elements: it recapitulated the facts, organized the laws, systematized the acquired knowledge and motivated the program of the theoretical development of chemistry from the notion of element. it was not the isolated discovery of an isolated individual, endowed with enough knowledge to be in the scientific vanguard of his time; on the contrary, it was the answer to a specific problem of nineteenth-century chemistry, and the culmination of a long history marked by evidence and errors.5 in the second decade of the twentieth century, the british physicist henry moseley (1887-1915) conducted experiments with discharge tubes, in which the rays collided with metal sheets of different elements. moseley found that the x-ray spectra so obtained depended on the used metal, and that the lines of the spectra changed uniformly, maintaining a harmonic pattern, when moving from one element to the next of the periodic classification.27 from his work, a new property was defined: the atomic number.28,29 in 1913, niels bohr (1885-1962) postulated a new atomic model for the hydrogen atom, based on the first quantum theories. later, other researchers such as arnold sommerfeld (1868-1951), pieter zeemann (1865-1943) and wolfgang pauli (1900-1958) developed the theory and formulated the quantum numbers. the atomic model of bohr, initially proposed for monoelectronic atoms, was then generalized to any multielectronic atom and the arrangement of electrons in these systems began to be studied, giving rise to the concept of electronic configuration, in whose development was fundamental the contribution of other scientists, mainly charles bury (1890-1968).29 it is noteworthy that bohr’s approach was not based on any mathematical basis, nor explicitly resorted to quantum theory to assign the electrons in the different shells, but was guided by the chemical characteristics of the elements to assign them electronic configurations.14,15 chemists accepted the bohr model, because it provided a surprisingly intuitive version of the concept of atomic number, which indicated the position of the element in the periodic system. this number is equal to the number of electrons, and also to the number of positive charges that characterize the nucleus. each successive element in the usual periodic table has one more electron that its predecessor, and the periodic changes of the valence observed in the table could be explained by the successive occupation of the orbits. in this way, a research program was initiated, which erased the traditional boundaries between chemical reactions and physical interactions.31 the present way of teaching chemistry is the consequence of that program. 4. the periodic system based on triads of atomic number32 as shown in the previous section, one of the early systematisation from which the periodic system was built was the concept of triad concept proposed by 105periodicity trees as a secondary criterion of periodic classification döbereiner; we regard the concept of triad as one of the pilar of the periodic system. at the beginning of the current century, eric scerri reformulated the concept of the triad, by defining them as based on atomic numbers; so, triads resulted from integer numbers.33,34 scerri also suggested the use of triads of atomic numbers as a possible secondary criterion for the periodic system. although in the spt (and in the representations directly derived from it) there is a large number of triads −which can be increased with the displacement of hydrogen to the group of halogens−, the formation of triads cannot be considered as a secondary criterion of periodic classification since it does not relate systematically to all elements. in tbt, the primary criterion is given by the increasing atomic numbers, and the secondary criterion is established by the formation of triads of atomic numbers, which in turn form closed structures of 20 elements called ‘periodicity trees’ (pt’s). the representation is based on three factors that act as criteria for the construction of the table: the conception of the elements in their character of basic substances, the triads of atomic numbers, and the chemical information on the behavior of the elements as simple substances.3 the fact that the three elements necessarily have similar macroscopic properties is no longer required in tbt, as was the case with döbereiner. for instance, two of the elements of the triad may belong to consecutive periods with the same length, that is, of the same block, while the third may come from a different block, and thus belongs to a period of different length. in this approach, the elements of the same block have similar chemical properties, and the third element, also called “connecting element”, performs the function of linking consecutive blocks. the idea of connecting element only makes sense when elements are considered as basic substances. the branches in the pt’s are formed by those connecting elements (see the next section). this way of conceiving triads shows that chemical elements can be organized without appealing to electronic configurations, and without relying exclusively on the macroscopic properties of simple substances. chemical periodicity can be characterized in a formal and abstract way, but, at the same time, it turns out to be compatible with the empirical knowledge accumulated in chemical experience. this proposal is inspired in the conciliation between the conceptions of element as basic and simple substance, in the sense recommended by scerri: “paneth’s insistence that the periodic system only classifies elements as basic substances invites the obvious question of how we might learn about these elements, especially as they are said to have no properties. admittedly atomic number provides an ordering criterion but periodic classification is also about group similarities which are recognized through the properties of elements as both simple substances and as combined simple substances. it is difficult to see how focusing on elements as ‘basic substances’ can provide any indication of the second dimension of the periodic table, namely the grouping of elements into vertical columns.35 in the proposal of tbt, elements are grouped so that all are involved in at least one triad; it is for this reason that formation of triads can be adequately considered as the basis of a secondary classification criterion. the table is structured as follows: (i) periods result from organizing the elements according to the increase in atomic number; (ii) in each period, a new generation of triads is formed, and each generation will have as many triads as the period has (see figure 1, where all the triads are shown).3 the fist 8 periods contain: 1, 1, 8, 8, 18, 18, 32 and 32 elements, respectively. if the series were extrapolated for the construction of the table, the ninth period should contain 50 elements. however, due to anomalies in some elements of the eigth period, a reversal of the sequence is proposed.3 finally, it is interesting to notice that the tpt preserves several aspects present in the mendeleev classification: the abstract perspective on the nature of elements to allow the structure that classifies them, and also the individuality of the chemical elements as a fundamental and objective feature of nature. 5. periodicity trees the system introduced in the previous section is based on the idea that triads manifest the abstract relations between elements, which only make sense at the level of basic substances, but not necessarily in that of simple substances. thus, each triad in this system should not be thought of individually, but within a pt, that is, a set of nested triads. in other words, each triad is conceived as a part of a tree, in such a way that it becomes meaningful only within this set of relationships. the concept of pt is proposed as an alternative to the traditional concept of group in the spt.36 a pt is a symmetric structure where the elements are related by triads: there are 9 structures of this type (see figure 2). since they make up the architecture of the table, they manifest the secondary criterion of classification in tbt. there are two types of pt: 8 lateral trees of 20 elements, and a central tree also of 20 elements, which is 106 alfio zambon figure 1. periodic table bases in triads: in green the triads corresponding to even generations, in orange those corresponding to odd generations. observe that in each period, a new generation of triads is formed. 107periodicity trees as a secondary criterion of periodic classification formed from the elements not included in the lateral pt’s. the main branch is the branch that starts with the first two elements and continues with those located at the left in the first 4 trees, and the branch that starts with the first two elements and continues with those located at the right in the second 4 trees. the opposite complementary branch is the yellow branch in the first 4 trees, and the orange branch in the second 4 trees (see figure 2). the 8 lateral pt’s include, as their first element, those elements that start the representative groups of the series a (with the exception of hydrogen, which is a very special element, see next section). each one of them contains 20 elements, connected through a succession of concatenated triads. in order to give an idea of the structure of the pt’s, let us consider the features of the lateral tree t1 and of the central tree.3 the tree t0 begins with the triad 2-10-18 (hene-ar). then, it continues to the right with the triad 10-28-46 (ne-ni-pd), where ne acts as a connector element where the first bifurcation occurs. then, the triads 18-36-54 (ar-kr-xe) and 28-46-64 (ni-pd-gd) follow in the construction. in this way, in the laterals of the tree, the group viii a of the noble gases appears as a left main branch, and the third column of group viii b of the stp appears as a right complementary branch in the same structure.37 in turn, in the one of the central branches of the tree, the first lanthanide (gd) is included, in the next generation the triads 36-68-100 (kr-er-fm) and 46-78110 (pd-gd-cm). the first actinides (fm and cm), and the second lanthanide (er) appear. the next generation is composed of the triads 54-86-118 (xe-rn-og) and 64-96-128 (kr-er-fm), which complete the elements known up to the present in t0. the tree continues with triads formed some hypothetical elements: the triads 100-118-136 (fm-og-136) and 96-128-146 (cm-128-146), then the triad 118-136-154 (og-136-154) comes, and finally the triad 146-154-162 which closes the tree.3 the pt’s t1 to t7 are constructed by following the same procedure, by adding 1 to the number of each element. in turn, the central pt includes the elements not contained in the lateral pt’s, beginning by 26 and 27 (fe and co). the central tree allows to reconstruct the first 2 columns of the spt by means of triads. the central tree also includes the first 2 elements (0 and 1) and the last 2 (170 and 171).3 figure 3 shows the complete tbt. 6. implications for the teaching and communication of chemistry in higher secondary education and university courses of chemistry of introductory level, the teaching of the periodic relationships among chemical elements generally follows the study of the electronic structure of atoms and precedes the basic concepts of chemical bond. in this way, the most frequent strategy (without considering the different possible approaches whose analysis is not the purpose of the present work) begins by studyfigure 2. the nine periodicity trees make up the tbt. 108 alfio zambon figure 3. periodic table based in triads, in the same color the elements that must present relations of periodicity. 109periodicity trees as a secondary criterion of periodic classification ing the electromagnetic radiation and the atom from the quantum-mechanical point of view, on the basis of the uncertainty principle, an introduction to the wave functions, the quantum numbers and the characteristics of the atomic orbitals. then, the chemical periodicity is approached from the point of view of the quantum numbers and the electronic configurations of the neutral atoms, the electronic configurations of the ions, and the variation of the periodic properties, such as ionization energy, electronic affinity, and atomic and ionic radio. after this, covalent and ionic bonds, the rule of the octet and its exceptions, the lewis structures, the load distribution, and the formal charge are introduced. finally, the theory of repulsion of valence orbitals and an introduction to the theory of molecular orbitals are explained.38 this way of presenting the topics in chemistry courses is the result of the uncritical acceptance, by most of the current chemical community, of the quantum tools as potential solutions and comprehensive explanations of all the problems and challenges posed by chemistry. this, in turn, derives from the great influence of the so-called “dictum” of dirac: “the fundamental physical laws necessary for the mathematical theory of a large part of physics and the totality of chemistry [are] completely known from quantum mechanics.”38 in recent years, many works in the field of the philosophy of chemistry addressed the problem of reduction, focusing on logical, ontological, epistemological and historical aspects and questioning the validity of dirac’s dictum. the present work is part of this trend: it is based on the assimilation of new philosophical research, or rather, the part of that new research that is relevant to chemistry.40 from this perspective, i propose, as a didactic strategy, to teach the periodic system on the basis of tbt and the concept of pt, immediately after the treatment of the notions of atomic structure, chemical periodicity and chemical bond.41 it is important to introduce tbt after chemical bond, and not in conjunction with the standard study of chemical periodicity, in order to emphasize the chemical approach over the physical one. this table can be used as a tool to integrate the preceding topics, and in this way to consolidate their conceptual bases; this facilitates the approach to the later topics with a fundamentally chemical approach, and not, as usually happens, from a physical perspective. the tbt, given its foundations, might have been contemporary to the lewis’s proposals at the first decades of the last century, since it is conceptually independent of the quantum-mechanical description of the atom. in fact, for the elaboration of tbt, i relied on a deliberate anachronism, by “rewriting” the periodic system with an approach that rescues the essential aspects of the chemical perspective of the late nineteenth and early twentieth centuries. at that time, chemistry boasted of being an active, autonomous, and academic science, self-reliant.42 on this basis, i tried to accommodate the later developments of the discipline from a chemical perspective, that is, from a classical way of understanding chemistry. this view does not intend in any way to conflict with the quantum perspective, whose study is fundamental especially for university students of chemical-based careers. the aim here is to complement and enrich that physical point of view, and to reassess the chemical approach over the physical for the process of learning chemistry in the initial courses. the concepts and aspects that can be enriched by this proposal are: (1) the concept of chemical element; (2) the concept of “valence shell” and, in a certain sense, also the treatment of the notion of electronic configuration; (3) the relations between the groups of the series a and b of the spt, which appear naturally in the pt’s; 4) the concept of metal element; (5) the debate about the elements difficult to be classified according to the standard view; and (6) some considerations on the foundations of the periodic system under discussion. while the latter issues are still debated among specialists, the four first are integral to the teaching of chemistry from the secondary school on. i will expand briefly on each of them in the subsequent sub-sections. 6.1 the concept of chemical element it is very common that students, especially in the initial courses of chemistry, but also in the advanced courses, consider the concept of element as equivalent to the concept of atom.43 the concept of element is even introduced in terms of its electronic configuration, as if there were almost nothing else than electronic configuration as relevant for chemistry. every element is usually represented in terms of the closest noble gas, to which the missing part of the electronic configuration is added. thus the chlorine element, for example, is usually represented as [ne] 3s2 3p5. more than an individual entity, a chemical element is considered the result of the sum of elementary particles, which in some sense (perhaps not too indirect) implies an allegorical return to the hypothesis of prout. this view equates the concept of the element to that of the atom, and the concept of molecule to that of a simple set of atoms; chemistry is thus understood as the study of the interactions between molecules in those terms. such a view is a barrier that prevents students from understanding the high relevance of the 110 alfio zambon context in chemistry. for instance, it is common that students conceive regulatory systems of ph as something alien to the solution they are regulating, something external to the solution: the multiplicity of chemical interactions involved are not usually analyzed; they are perceived as a kind of thermostat in a refrigeration system. similar situations occur when studying solutions in states close to the saturation point, heterogeneous systems, etc., in which the importance of context is crucial. students are exclusively anchored in the perspective of the individual, or of the form, instead of taking into account the perspective of matter or stuff, specific of chemistry.44,45 the distinction between simple substance and basic substance is not perceived, except in exceptional cases. thus, it can be said that the practice and teaching of chemistry, in some sense, has brought the chemical teaching back to the conceptual framework previous to the work of mendeleev. our proposal (or the tbt) aims at contributing to recover the distinction between simple and basic substance, and to emphasize the importance of context in chemistry. this would help the student to become aware of the complexity of the concepts of element, compound, basic substance and simple substance. 6.2 the concept of “valence shell” in general, the traditional approach to explain the place of elements in groups and periods of spt is based on describing sequentially the electronic configurations by means of combinations of quantum numbers. as a consequence, the valence shell (the outermost shell of an atom, containing the electrons that can be transferred to or shared with another atom), which is the relevant notion for chemists, appears at the end of this sequential process. therefore, students commonly direct their effort in memorizing the sequence of the diagram of construction (aufbau principle, madelung rule), and lose sight of the importance of the valence shell. they do not interpret, for example, the reason why the sublevels s and p are “mixed” to form the valence shell of the so-called elements of the p-block in the spt, among many other difficulties. moreover, since they arrive to the valence shell after a long procedure, errors are frequent. in the approach of the tbt based on pt’s, in the 8 lateral pt’s the number of electrons in the valence shell coincides with the tree number (except in tree t0 and in the complementary branches of t1 and t2). in figure 3, it is possible to observe that, in trees 3 to 7, the number of electrons in the valence shell of the elements that make up the main and complementary branches (which in the spt integrate the groups a and b, see next sub-section) coincides with the number of the tree. for instance, in tree t4, the elements c, si, ge, sn, ti, zr, pb and hf have 4 electrons in their last shell (adding the s with the p or d as appropriate). moreover, in neutral atoms the number of internal electrons can be computed by subtracting the number of electrons in the valence shell from the atomic number; so, the diagram of construction is applied only to the internal levels.45 this strategy introduces the electronic configurations of the elements “in reverse”, that is, from the valence shell to the inner shells, emphasizing the concept of valence shell, one of the most relevant in chemistry.47 moreover, the frequent errors in the application of the construction diagram remain confined to the inner shells, with few chemical consequences, at least at the level of teaching. it is also important to note that tbt, based on a simple arithmetic relationship such as the triad, allows the student, once the logic of generation of triads is interpreted, to easily locate each element, by its atomic number in its corresponding pt, know the number of electrons in the valence shell, and make inferences about its chemical behavior. for example, with the logic of generation of triads, the elements of any tree can be reconstructed. and once the elements are located in the corresponding trees, it is possible to make inferences about the chemical behavior of the elements and the relationships between them; this is particularly important to relate the elements of the series a and b (see the next sub-section). this way of introducing the concept of valence shell actually recovers lewis’s structures, with all their didactic virtues. lewis used cubes to represent atoms, in such a way that the electrons of the valence shell in the 2nd period of the spt are placed in the 8 vertices of the cube. the practice in the formation of the lewis structures is particularly productive −but often underestimated− in representing chemical bond, becoming a useful resource for the student who begins the study of chemistry. in fact, this practice allows representing chemical bond in a “classical” way, with the union of 2 points, and not with a line, as currently recommended. now, if the number of electrons in the valence shell can be obtained in the tbt without relying on electronic configurations, the student can concentrate his attention on those electrons and use lewis’s structures to analyze chemical bonds.48 6.3 the relations between the elements of the same groups of the series a and b in the first tables of mendeleev, the series a and b do not appear. in later mendeleev’s tables, those series 111periodicity trees as a secondary criterion of periodic classification are distinguished, with the relationships between the elements belonging to them.49 precisely due to the fact that the series a and b cannot be explained in quantummechanical terms, they have disappeared from the contemporary tables, and its use is explicitly discouraged by iupac.50 however, this strategy hides important chemical analogies between elements. some of these relationships are very relevant, and usually go unnoticed by students, especially those linking groups 2 and 3, such as the chemical similarity between mg and zn, and between al and sc. other similarities regarding reactivity naturally arise among ti, si and ge, among v, p and as, and among cr, s and se, among others. the tbt based on pt’s recovers the classification in series a and b in a natural way since it represents the elements the series a by the lateral branches of the pt’s, and the elements of the series b −the so-called ‘transition metals’− by the complementary branches of the trees. it is also interesting to notice that, in general, the elements belonging to the main branch and those of the complementary branch in a lateral tree have the same number of electrons. the exceptions of this regularity are t0, t1, and t2. however, these exceptions are the manifestations of chemical particularities of the involved elements. for instance, in t0, pd and pt (belonging to the complementary branch) are not very reactive, but their reactivity is a degree greater than the almost zero reactivity of noble gases (belonging to the main branch); in this way, the less reactive metals are related with the less reactive non-metals in the same tree. 6.4 metallic elements traditionally, it is taught that the essential feature of transition metals is that their d sub-level remains incomplete; this allows explaining the variation of the periodic properties between these elements. however, this explanation produces in the student the false idea that the metallic elements are very similar to each other and even that they are “essentially equal”. by contrast, the chemical differences between these elements, which are all part of the b series in the spt, are clear within the tbt, because the transition metals appear in the different pt’s that constitute the table. lanthanides and actinides, also known as internal transition metals, are traditionally presented as having an incomplete sub-level f. so, even more intensely than in the case of transition metals, students have the idea that they are all alike, an idea that persists even in advanced courses. it is true that internal transition metals are chemically very similar to each other, but ignoring their differences leads the students not noticing very chemically important elements, such as ce, pr, nd, and dy in the first series, and u, np, and pu in the second series, for instance. in the present proposal, although internal transition metals appear all together in the tbt, they belong to different pt’s which clearly expresses their differences. 6.5 classification of elements the tbt provides a criterion about the relative position of the elements that are difficult to be classified, a topic currently under discussion in the studies on the foundations of the periodic system. while these topics do not appear in the teaching program, these discussions can nevertheless be interesting and informative if presented in introductory chemistry courses. the first debate refers to the position of h and he. hydrogen as membership of group 1 is under discussion: the question is whether it should be placed with alkaline elements or with the group of halogens in the spt. it has also been proposed that h must appear floating on the top of the table due to its peculiarities.51 according to tbt, the particularity of h is manifested by the fact that it belongs to the central tree, and it is the single member of its period. nevertheless, h is connected with the rest of the tbt through its participation in two triads (0-hhe and h-f-cl). the central position of h in tbt thus naturally manifests the importance and the multiple aspects of its chemical behavior. in the case of helium, the discussion is whether it must be included in the group of the noble gases (for its chemical properties) or in group ii with the alkaline earths (for its valence electrons). if we evaluate the question from the standpoint of the tbt there can be no doubt: he belongs to the triad he-ne-ar, which integrates the main branch of t0. this position characterizes he as a noble gas, in agreement with the spt. in addition to the positions presented, about this controversy, other alternatives have been proposed, presented with interesting arguments and discussions. 52,53,54,55,56 another controversy is related to the position of the elements of group 3 of the spt. in particular, the disagreement refers to which elements have to be placed under sc and y: some tables place the pair la and ac, and others the pair lu and lr.57,58,59,60,61 the tbt shows that, in a certain sense, both pairs are “below” sc and y. this is particularly evident in the t3: sc and y form a triad with la; but, on the other hand, y forms a triad with lu and lr (see figure 4). in this way, the structure of trees leading to interconnected triads allows to conclude that there are good reasons for the two solutions, 112 alfio zambon although both are partial manifestations of a more complex relationship. 6.6 other considerations about the foundations of the periodic system at present, other points are debated: the existence of the element 0, the existence of a final element, and the multiplicity of possible representations, among others. though not compulsory, a basic presentation of these topics in introductory courses might be interesting and motivational for students. it also invites them to think more deeply about the periodic system and the elements. the tbt allows accommodating the element 0, which forms a triad with hydrogen and helium and initiates the system of triad generation. this element is conceived as an undifferentiated substance, which in a certain sense persists in all the elements: the neutron might be conceived as an empirical manifestation of the element 0. in this aspect, the tbt agrees with some recent views, such as that of philip stewart, who proposed a representation of the periodic system in spiral form, known as “chemical galaxy”: the chemical element number zero is placed in the center of the galaxy, and its “atoms” are the neutrons.62,63,64 the idea of element 0 sounds strange if chemical elements are considered only as simple substances, but is natural when elements are viewed also as basic substances. in the tbt, which admits the double nature of elements, the element 0 is defined in a theoretical way by following the same progression that orders all elements: it is the element with zero electrons and zero protons, and one of its manifestations as a simple substance is the neutron, which corresponds to the element with atomic number 0, mass number 1 and null electronic configuration. regarding the existence of a final element, a point that is left open in spt, the proposal of tbt takes a definite position. on the basis of the conjecture that leads to the reversal of the growth trend in the central period, the periodic system has a final element with number 171. this view suggestively agrees with some very recent quantum-mechanical model.65,66 finally, the tbt represents a favorable contribution to acknowledging the multiplicity of possible representations for classifications of the elements. in fact, it is based on a secondary criterion completely different from that used in the spt, and this fact allows it to highlight different features of the classification. as jorge luis borges asserts in his short story “the analytical language of john wilkins”: “… it is clear that there is no classification of the universe not being arbitrary and full of conjectures. the reason for this is very simple: we do not know what thing the universe is.”67 7. conclusions and final thoughts the presentation of the periodic system in the introductory chemistry courses usually follows the teaching of the atomic structure, and the relations of periodicity among elements are based on the combination of the corresponding quantum numbers. this way of teaching often leaves out, or confines to a secondary place, the chemical perspective about elements. moreover, as bernadette bensaude-vincent stresses, mendeleev is usually presented as a precursor of those theories, ignoring that, far from being a prophet, he was a chemist of his time, who reorganized the body of existing knowledge around the concept of element, and not around merely empirical properties of substances.5 after describing how the historical roots of the periodic system were erased by the quantum understanding of elements and the reorganization of the periodic system through the atomic number instead of the atomic weight, this paper presents a proposal for teaching the periodic system differently, based on analyzing the chemical relationships among chemical elements on the basis of the tbt. this table, being conceived from a chemical perspective, can be a plausifigure 4. the periodicity tree 3. 113periodicity trees as a secondary criterion of periodic classification ble option to integrate not only the study of the periodic system, but also the concepts of element, atom, molecule, mole, as well as the concepts of valence shell, chemical bond, and reactivity, among others. this novel perspective offers an approach very different from that offered by the currently predominant physical viewpoint. of course, the quantum mechanical perspective is nevertheless important in higher courses, and clearly it must be studied in the first courses to be able to address those challenges. however, basing teaching exclusively on the physics perspective leaves aside the chemical view of the elements, and this causes great difficulties in the understanding of many chemical topics; in this way, the perspective of classical chemistry turns out to be merely anecdotal. but this is paradoxical, especially when the objective is precisely to train professionals in chemistry. indeed the nowadays way of teaching the classification of the elements is not only disconnected from the historical development of the periodic system, it is also disconnected from a large part of the practice of chemistry. the tbt highlights the chemical perspective of the second half of the nineteenth century, and goes beyond the mere historical interest. that was a chemistry which, as isabelle stengers expressed “not only achieved its status as an autonomous science, but the science of the avant-garde, science queen, positive science model , illustrating a conception in the effective practice of pragmatic and empirical science.41 the tbt aims to rescue that spirit, and from that position seeks to assimilate and structure the chemical knowledge about chemical elements. in particular, the aim is to recover both the individuality and the dual meaning of the concept of a chemical element, beyond of the idea of atoms and molecules as constituents of matter. on this basis, this work looks towards the future for teaching, but also, to forthcoming theoretical and empirical research in the realm of chemistry. a future full of challenges and full of difficulties, whose approach will bring us successes, but also errors, unforeseen difficulties, failures and unforeseen complications. in short, a future that is worth living. acknowledgements i want to acknowledge especially prof. olimpia lombardi for her persistent support, and dr. brigitte van tiggelen for her acute remarks on a previous version of this work. i also thank lic. andrea blengini for the translation of the original paper written in spanish, prof. graciela pinto vitorino for her valuable comments, dcv. agostina alassia for the preparation of the figures and anonymous reviewers for valuable suggestions. this works was possible thanks to the support of the grant pict-2014-2812 by the agencia nacional de promoción científica y tecnológica of argentina and the universidad nacional de la patagonia san juan bosco. references 1. j. l. borges, obras completas. emecé, buenos aires, 2005, p. 524. 2. j. l. borges, fictions, penguin books, 2000, translated by a. hurley, pp. 91-99. 3. in the case of a compound formed by several elements, which refer to different boxes of the periodic table, it is possible to link the compound itself with those boxes. 4. a. zambon, found. chem. 2018, 20 (1), 51. 5. electronic configurations, quantum numbers and, in general, the quantum perspective, are very important for current chemistry. however, it is worth to emphasize that not all chemical knowledge can be based on quantum mechanics. in this sense, this work defends the ontological autonomy of chemistry in the line proposed by olimpia lombardi and martín labarca, see reference 4. 6. o. lombardi, m. labarca, found. chem. 2005, 7, 125. 7. from the definition of element proposed by lavoisier, element and simple body are considered synonyms and interchangeably concepts. mendeleev, on the other hand, classifies elements in an abstract sense, and differentiates them between simple and compound bodies. for details see references [5, 14 and 15]. 8. b. bensaude-vincent, “mendeleev”in élements d’histoire des sciences, (ed.: m. serres), bordas, paris, 1989, pp. 447-468. 9. e. scerri, hyle. 2005, 11, 127. 10. f. a. paneth, [reprinted in found. chem. 2003, 5, 113]. 11. h. bent, new ideas in chemistry from fresh energy for the periodic law, author house. bloomington, 2006, pp.10-46. 12. r. hendry, stud. hist. philos. sci. 2006, 37, 322. 13. e. schwarz, found. chem. 2007, 9, 139. 14. j. earley, found. chem. 2009, 11, 65. 15. k. ruthenberg, found. chem. 2009, 11, 79. 16. e. scerri, found. chem. 2012, 14, 69. 17. j. van spronsen, the periodic system of chemical elements a history of the first hundred years, elsevier publishing company, amsterdam, 1969, pp. 22-63. 18. e. scerri, the periodic table – its story and its significance, oxford university press, new york, 2007, pp. 29-62. 114 alfio zambon 19. w. odling, quarterly journal of science, 1864, p. 643. 20. j.a.r. newlands, chemical news, 1864, p. 59. 21. j.a.r. newlands, chemical news, 1866, p. 113. 22. j.l. meyer, die modern thoerien und ihre bedeutung fur die chemissche statisik, breslau (wroclaw), 1864, p. 135. 23. g. boeck, substantia 2019, 3(2) suppl. 4, 13. 24. e. scerri, the periodic table – its story and its significance, oxford university press, new york, 2007, pp. 98-99. 25. scerri observes that leopold gmelin was probably the first in using a system of elements as the organizing principle for a textbook in 1843, see reference 21. 26. e. scerri, the periodic table. a very short introduction, oxford university press, new york, 2011, p. 64. 27. e. scerri, the periodic table – its story and its significance, oxford university press, new york, 2007, pp. 169-173. 28. scerri observes that the dutch amateur scientist anton van den broek, anticipated the concept of atomic number in a series of papers published between 1907 and 1913, see reference 23. 29. e. scerri, the periodic table – its story and its significance, oxford university press, new york, 2007, pp. 165-168. 30. e. scerri, the periodic table – its story and its significance, oxford university press, new york, 2007, p. 192. 31. b. bensaude-vincent, i. stengers, historia de la química, addison wesley universidad autónoma de madrid, madrid, 1997, pp. 195-198. 32. a full description of the building of the tbt can be found in reference 3. 33. e. scerri, j. chem. educ. 2008, 85, 585. 34. e. scerri, found. chem. 2010, 12, 69. 35. e. scerri, found. chem. 2012, 14, 72. 36. iupac recommends naming groups from 1 to 18 instead of series a and b. in this paper, i use the previous convention, because i highlight relations between groups a and b. 37. an antecedent of these united groups can be found in the periodic table of langmuir of 1919, where both have the maximum number of electrons in their last level (see https://www.meta-synthesis.com/webbook/35_pt/pt_database.php?pt_id=434). 38. a. caamaño, educ. quím. 2006, 17,195. 39. p. dirac, proc r. soc. lond. 1919, a338, 714. 40. an exhaustive discussion of these matters might be the subject of a further work. 41. the view about the difficulties in the teaching-learning of chemistry expressed in the present work comes from the experience of the author, who teaches chemistry since 1991 at the high-school level and since 1999 at the university level in different courses. 42. i. stengers, l’affinité ambiguë: le rêve newtonien de la chimie du dix-huitième siècle in élements d’histoire des sciences, (ed.: m. serres), paris, bordas, 1989, 361 43. g. papageorgiu, a. markos and n. zarkadis, sci. educ. int. 2016, 27(4), 464. 44. l. lewowicz, o. lombardi, found. chem. 2013, 15, 65. 45. j. schummer, “matter versus form and beyond” in stuff – the nature of chemical substances (eds.: j. van brakel, k. ruthenberg), würzburg: königshauen & neumann, 2008, pp. 3-18. 46. the concept of atomic number in the periodic system based on triads has only an ordinal sense. the atomic number in this abstract sense agrees numerically with the number of protons, but this is not relevant in the present framework. 47. although the proposal does not use quantum numbers, it may be interesting to relate the exceptions to the rule (n+l) in the transition metals (cr, cu, mo, ru, pd, among others) with the location of the elements, since there are no exceptions in the sum of the s and d electrons that locate each element in the corresponding tree. 48. in my teaching practice, i devised a strategy of teaching the formation of lewis structures by combining cubes and icosahedrons (that, with their 12 vertices, allow representing the electrons of the metallic elements) with molecular models of balls and sticks and with pencil and paper exercises. 49. in mendeleev’s table of 1879 he uses the terms “typical” for the first elements, and “even” and “odd” elements for the rest. 50. see robinson in this issue. 51. p. atkins, h. kaesz, chem. int. 2003, 25, 14. 52. m. cronyn, j. chem. educ. 2003, 80, 947. 53. g. katz, chem. educator. 2001, 6, 324. 54. m. labarca, a. srivarths, bjsep, 2016, 25, 514. 55. r. rich, m. laig . educ. quím. 2011, 22, 162. 56. r. sanderson, j. chem. educ. 1964, 41, 187. 57. e. scerri, j. chem. educ. 2009, 86, 1188. 58. w. jensen, found. chem. 2015, 17/1: 23. 59. l. lavelle, j. chem. educ. 2008, 85/11: 1482-1483. 60. e. scerri, chem. int. 2019, 41(1): 16. 61. w. xu, p. pyykkö, phys. chem. chem. phys. 2016,18: 17351. 62. p. stewart, educ. chem. 2004, 41, 156. 63. p. stewart, found. chem. 2007, 9, 235. 64. m. labarca, new j. chem. 2016, 40, 9002. 65. p. a. pyykko, chem. phys. 2011, 13, 161. 66. p. indelicato and a. karpov, nature. 2013, 498, 40. 67. j. l. borges, other inquisitions 1937-1952, university of texas press, 1993. translated by l.vázquez, pp. 101-106. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo substantia. an international journal of the history of chemistry 3(2) suppl. 5: 125-138, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-267 citation: s. c. rasmussen (2019) a brief history of early silica glass: impact on science and society. substantia 3(2) suppl. 5: 125-138. doi: 10.13128/substantia-267 copyright: © 2019 s. c. rasmussen. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. a brief history of early silica glass: impact on science and society seth c. rasmussen department of chemistry and biochemistry, north dakota state university, ndsu dept. 2735, p.o. box 6050, fargo, nd 58108-6050, usa e-mail: seth.rasmussen@ndsu.edu abstract. silicon in the form of silica is the basis of common glass and its uses predate recorded history. the production of synthetic glass, however, is thought to date back to no earlier than 3000 bce. this glass technology was not discovered fully fashioned, but grew slowly through continued development of both chemical composition and techniques for its production, manipulation, and material applications. this development had become fairly advanced by the roman period, resulting in a wide variety of glass vessels and the initial use of glass windows. following the fall of the roman empire, glass grew to new heights in venice and murano, where improvements in composition and production resulted in both more chemically stable and clearer forms. the quality of this new glass ushered in the development of lenses and eyeglasses, as well as the greater use of glass as a material for chemical apparatus, both of which changed society and the pursuit of science. finally, glass in the north developed along different lines to ultimately result in a new form of glass that eventually replaced venetian glass. this bohemian glass became the glass of choice for chemical glassware and dominated the chemical laboratory until the final advent of borosilicate glass in the 1880s. a brief overview of the early history of silica glasses from their origins to the development of borosilicate glasses will be presented. keywords. soda-lime glass, potash-lime glass, glassblowing, chemical glassware, eyeglasses, windows. introduction silicon is one of the most abundant elements of the periodic table, comprising the eighth most common element in the universe by mass and the second most abundant element in the earth’s crust after oxygen (ca. 28% by mass). in nature, silicon occurs almost exclusively in combination with oxygen. silicon dioxide, sio2, occurs in a variety of forms in nature and is known as silica. one form of silica is α-quartz, a major constituent of common sand, sandstone, and granite, as well as the timekeeper in most watches. silicon also occurs in many minerals as silicates (consisting of compounds in which sio4 units may be fused by sharing corners, edges, or faces) or aluminosilicates. for the discussion here, silica also plays a critical role as the major component of common glass.1-4 126 seth c. rasmussen while quartz is a crystalline solid with a regular repeating lattice as shown in fig. 1,5,6 glass has no regular repetition in its macromolecular structure and exhibits a disordered structure similar to substances in the liquid state as illustrated in fig. 2.3,7 due to the extent of disorder in amorphous structures, the glass state of a material is higher in energy than its crystalline state and thus glasses can suffer from devitrification (i.e. frosting and loss of transparency as a result of crystallization).1 as a result, stable glasses are those that can form a highly disordered state that is of comparable energy to the corresponding crystalline state.8 glass as a material shares the properties of both solids and liquids. as such, glass at room temperature is commonly described as either a supercooled liquid or an amorphous solid,1-3,7-9 although these can both be viewed as oversimplifications.9 thus, a glass is a solid, but due to its highly disordered nature, it exhibits properties much like a liquid that is too viscous to flow at room temperature. this dichotomy has led to the commonly cited myth that glass is really a highly viscous liquid and thus observable flow can be detected in objects of a sufficient age. this belief originates from the observation that stained-glass windows of 12th century cathedrals are thicker at the bottom than the top.2,10-14 it has been verified via theoretical calculations, however, that the compositions used in either medieval or contemporary windows would not exhibit measurable flow at room temperature within the time scales of humanity,10,12,14 and physical measurements have confirmed that unless sufficient compressive stress is applied, glass does not flow below 400 °c.11,13 in truth, the uneven nature of medieval windows is the result of the limited technological methods used in their manufacture, and because of the resulting variable thickness, the thicker edges of the panes were logically mounted at the bottom of the window.10-12 glass is unlike any other early material and its production required some of the most advanced methods of any of the chemical technologies originating in antiquity. in terms of material properties, the closest modern analogues of silicate glasses are the organic plastics ubiquitous in modern society.1 molten glass could be poured into almost any shape and would retain that shape upon cooling. in addition, preformed pieces of glass could be thermally fused together to produce either air-tight seals or more complex structures. furthermore, chemically stable glasses are relatively inert and can be produced in a wide range of color, opacity, or transparency. as such, this made glass a broadly versatile material for a vast range of applications. composition and production of ealry silicate glasses although it is possible to produce a glass from silica alone, the temperature needed to melt silica (~1710 °c) is too high to have been achieved through methods available during the formative years of glass production.6,15-19 sometime during the 3rd millennium bce,18 however, it was discovered that the use of a flux (from the latin fluxus “flow”), such as soda (sodium carbonate, na2co3), could lower the fusion temperature of silica sources to below 1000 °c.6,16-19 while this approach successfully reduced the temperature needed to profigure 1. x-ray structure of quartz viewed down the a-axis. figure 2. simplified two-dimensional silicate structures: sio4 tetrahedron (a); oligomeric structure (b); crystalline structure (c); amorphous structure (d). 127a brief history of early silica glass: impact on science and society duce molten glass, the sodium contained in the resulting glass is highly soluble and thus susceptible to attack by water. as a result, the glass produced via the application of soda as a flux is of low chemical stability.1 in order to produce viable glass materials, a third component is thus required that acts as a stabilizer for the final glass product.17,18 such stabilizing species generally contribute less soluble cations, with calcium or magnesium compounds the most commonly applied. while potential sources of these ions could be lime, shells, or other mineral additives,17,20,21 the critical nature of these stabilizing species was not initially recognized and it is believed that calcium was not intentionally added as a major constituent until the end of the 17th century.20-22 as such, the calcium and magnesium content of all early glasses is thought to have been introduced via impurities in the silica or soda sources utilized.1,2,21-23 the glasses produced through the addition of soda and calcium species to silica are typically referred to as sodalime glass and it was these soda-lime formulations that made up the majority of all early glasses in the western world.1,2,16,19-24 early glass was produced from a silica source (such as beach sand) and a crude source of soda, with both components containing enough lime and/or magnesia to provide some chemical stability.1,2,23 heating this mixture would initiate fusion of the soda and other salt species, which would then start reacting with the sand to generate various sodium silicates and initial formation of liquid material. lime and other basic species would then begin to react with the fusing mixture of silica and silicates to join the growing melt.21,25 as the melt temperature increased, the viscosity of the mixture was reduced and any remaining silica would be incorporated into the melt.25 throughout the generation of the melt, gases would be liberated as the various carbonate, nitrate, and sulfate components were converted to their corresponding oxides,15 resulting in violent agitation of the fusing mixture and significant bubbles in the final molten glass.25,26 in order to minimize the effect of these escaping gases, glass production was often carried out in two distinct stages. the silica-soda mixture would first be heated in shallow pans at a temperature to allow the reaction of the silica with soda and lime, but below that required to achieve homogenous fusion. the majority of the gaseous byproducts would thus be liberated in the process, after which the mixture would be cooled to give an intermediate product commonly referred to as a frit.2,17,21,27 this frit would then be crushed to enhance more intimate mixing and then heated a second time at higher temperatures in order to achieve complete fusion.17 via this process, a final glass could be produced that was relatively free of bubbles.27 although commonly known as soda-lime glass, the chemical composition of these materials was really more complex than suggested by this simple designation. besides the three primary components (silica, flux, and stabilizer), glasses also contained colorants (table 1) and/or decolorizing agents, as well as a variety of unintended impurities introduced along with the primary reagents. as a consequence, the composition and structure of the resulting glasses could be quite complex and extremely variable, resulting in a range of physical and chemical properties. furthermore, the nature of a particular glass depends not only on its chemical composition, but also the manner and degree of heating, as well as the rate the hot glass is cooled (i.e. annealing of the glass).15,26,27 origin and intial development the origin of synthetic glass is unknown and its discovery has been attributed to the syrians, the egyptians, and even the chinese.2,31-33 of course, various legends have developed around the discovery of glassmaking,2,32-35 the most famous of which was recorded by the 1st century roman author pliny the elder.32 pliny’s account gives the story of a ship moored along the belus river in phoenicia, whose merchants used blocks of soda to support their cooking pots. as the combination of the sand and soda were heated by the cooking fire, it was stated that streams of liquid glass poured forth. while attempts to reproduce this legend have shown that glass cannot be produced in this fashion,2,33,35 this story continues to be repeated into the present. in contrast, scholars believe glass resulted as either a byproduct of metallurgy, where fluxes were first utilized to convert rock table 1. colorants commonly employed in early silica glasses. color transition or main group metal coloring oxides references white calcium/antimony, or tin ca2sb2o7; sno2 2,7,16,18,28 yellow lead/antimony, or iron pb2sb2o3; fe2o3 2,6,7,16,18,28 red copper and/or lead cu2o; cua; pb3o4 2,7,16,19,29 purple manganese mn2o3 2,6,7,16,19,28 blue cobalt or copper coo; cuo 2,6,7,15-19 blue-green iron feo 2,6,7,15-18 green chromium cr2o3 2,6,19,30 a metallic copper nanoparticles can result in a ruby red color. 128 seth c. rasmussen impurities into liquid slag during the smelting of metals, or via an evolutionary sequence in the development of silica-based ceramic materials.1,2,16,18,31,35-38 regard less of t he specif ic developmenta l pat h, glass as an independent material is not believed to predate 3000 bce.2,39-42 reports have claimed the analysis of glass beads that date back to as early as 2600 bce, but at least some of these dates are questionable.7 glass objects have been found in syria that date to 2500 bce, and by 2450 bce, glass beads were believed to be plentiful in mesopotamia.23,43 some glass objects were also produced in eg y pt during the 3rd millennium bce,38,40 but the oldest egyptian glass of undisputed age is believed to date to only ~2200 bce.43 as such, historians have revised the original belief that glass was an eg y ptian discovery and current views place the most likely development of the earliest glass in the mitannian or hurrian regions of mesopotamia.39,4 4 furthermore, there is little doubt that glass was made from an early period in both babylonia and assyria45 and routine mesopotamian glass production is thought to have started ca. 1550 bce.41 the first glass objects included beads, plaques, inlays and eventually small vessels,23,39,40,46 although such glass vessels did not become prevalent until after the middle of the 2nd millennium bce.47 it is generally thought that introduction of glass technology into egypt occurred during the reign of tuthmosis iii (1479-1425 bce) via glass objects and ingots being imported as tribute37,38,40,41 and the import of mesopotamian glassmakers around 1480 bce.37,38,41 as such, this ultimately resulted in the local egyptian production of glass by the time of amenophis iii (ca. 1388 ca. 1350 bce)40 with evidence supporting onsite glass production in the egyptian city of amarna around 1350 bce. glass objects exhibiting genuine egyptian style were made soon after, supporting their manufacture within egypt. archaeological evidence further supports this through the identification of several glass workshops in egypt.41 glass manufacture soon became a major industry and was spread throughout the mediterranean for the next 300 years.4 glass objects of this early period (1500 ca. 800 bce) are characterized as a typical soda-lime glass with a high magnesia (3-7%) and potash (1-4%) content,2,16,24,28,38,40,44,45 which is thought to be representative of glass produced or used throughout the mediterranean area.24 these vitreous materials were commonly produced from a mixture of silica and a crude source of alkali. both the silica and alkali could then act as sources of lime or magnesia to give the resulting glass some chemical stability.23 in terms of the specific raw materials used during this early period, crushed quartzite pebbles and sand are usually cited as the two most common sources of silica.2,21,28 however, the analysis of glasses of this time period reveal very low alumina content (~1.3% or less)37,38 which is inconsistent with the high alumina content found in the majority of analyzed sands. as such, it is generally believed that these early glasses utilized crushed quartzite pebbles as the source of silica, an interpretation supported by the fact that large angular quartz particles have been found to survive in frits analyzed from amarna.38 for the alkali source, the two primary sources for early glassmaking were natron, a naturally occurring mineral source of soda, and various types of plant ash.7,16,21,27,28,48-52 while both sources were used during this initial period, glass throughout the eastern mediterranean, egypt and mesopotamia was characterized by high magnesia (3-7%) and potash (1-4%) content.16,23,24,40 this increased magnesia and potash content has been linked by many authors with the nature of the alkali used in the glass, and as glasses made with natron usually contain less than 1% of either mgo or k2o,43,64 this has led to the common view that plant ash was the predominant alkali source during this period.16,40 in addition to the necessary soda flux, the plant ash also provided calcium and magnesium as chemical stabilizers for the resulting glass.37 however, sea shells and calcinated corals have been mentioned in mesopotamian tablets as reagents for glass production, both of which could have acted as additional sources of calcium.7,27 processing methods for the formation of glass objects were fairly rudimentary during this early time period, consisting of either core-molding or cast glass2. the first of these dates to ~1500 bce and was the earliest known technique for the production of hollow glass vessels.24,46,53,54 as is outlined in fig. 3, this involved the shaping of a form or core onto the end of a wooden or metal rod,16,54-56 after which it could then be heated to help set its shape (fig. 3c), and then glass layers were built up around the central set core. the most commonly cited methods for adding the glass layers involved treating the core with an organic binder (egg white or honey) and then by rolling it in crushed glass (fig. 3d);16,56 winding hot strands of glass around the core (fig. 3d’);40,55,56 or immersing the core in molten glass not much above the softening temperature (fig. 3d”).7,40,43,54-56 the assembly would then be heated to generate a uniform layer of glass (fig. 3e), cooled, and another layer applied. via such a repetitive process, the glass walls would be built up iteratively until the desired thickness was achieved.54,56 the exterior of the object 129a brief history of early silica glass: impact on science and society could then be worked and the object cooled (fig. 3f), after which the rod was removed from the vessel so that the core material could be carefully dug from its center to give the final hollow vessel (fig. 3g, fig. 4). the next significant advancement in glass forming was then made in ca. 1200 bce, when the egyptians learned to press softened or molten glass into open molds,2,31,54 which allowed the production of simple shapes such as bowls, dishes, and cups not possible via the previous core molding methods. as outlined in fig. 5, casting involved melting glass pieces into a mold which provided the simple, crude shape of the desired object.55,57 after the glass had cooled, the mold could then be removed57 and carved or polished to give the final product.55 decline and the rise to roman glass after this period of initial development, the glass industry declined for a time until a revival in production beginning in mesopotamia during 900-700 bce.4,7,16 this was followed by the growth of an apparently independent glass industry in syria and along the palestinian coast in 800-500 bce7 and a revival in egypt in ca. 500 bce.4 this overall resurgence in glass technology is viewed as part of the iron age revival that followed the period of turmoil in the mediterranean in 1200-1000 bce. centers of glass production then continued to develop in egypt, syria, and other countries along the eastern shore of the mediterranean sea,9 with the egyptian industry ultimately becoming centralized at alexandria.16,56 during this second period of ca. 6th century bce to ca. 4th century ce, glass was characterized by lower potassium (0.1-1.0 %) and magnesium (0.5-1.5%) content, along with a consistent high concentration of antimony.16,24,40 many authors have linked the decreased figure 3. production of core-molded vessels: (a) metal or wooden rod; (b) formation of core form; (c) firing the core; (d) glass application via rolling in crushed glass; (e) firing of applied layer; (f) completed object; (g) vessel after removal of rod/core. alternate methods for glass application: (d’) coiling strands of softened glass around the mold or (d”) dipping the core in molten glass [adapted from reference 42 with permission from springer nature]. figure 4. core-formed glass alabastron (6th 4th century bce) [m.88.129.10; courtesy of the los angeles county museum of art]. figure 5. fuse-casting of glass objects: (a) production of black mold; (b) glass pieces added, heated to fuse and fill mold; (c) metal rod inserted; (d) mold removed; (e) piece ground and polished to finish [adapted from reference 42 with permission from springer nature]. 130 seth c. rasmussen magnesia and potash content with a change from plant ash to that of natron as the alkali source.16,40,50,58 another major change during this period was a shift in emphasis from opaque to clear glass production, with the move to clear and translucent colored glass thought to be due to a shift in viewpoint as much as any specific new advances in technology.39 colorless glass was produced via the careful selection of a silica source of low iron content, coupled with the addition of antimony as a decolorizing agent.18,31 the use of antimony as an additive was not new and was previously important for the production of opaque glasses. the colorless glasses achieved via the use of antimony are very similar in composition to the previous white opaque glasses, differing only in higher antimony levels (1.95% on average) for the opaque glasses.28 although such colorless glass was relatively transparent, the final object may still exhibit a slight yellow tint depending on the extent of fe(iii) content. in addition, the majority of ancient glass contained various undissolved materials and was therefore not as transparent as modern glass. the conquests of alexander the great (d. 323 bce) during the 4th century bce brought the greeks in contact with the cultures of the near east as far as india.39,59 as a result, the greeks began to amass the technological knowledge of the middle east, as well as that of the egyptians, indians, and chinese.42 rome then conquered greece in the 2nd century bce, with the entire mediterranean basin united under roman rule by 30 bce.39 the culture and natural philosophy of the greeks was thus absorbed by the romans, including the collected knowledge and technology of glassmaking. the term “roman glass” is used to describe the normal composition of glass of the period 4th century bce to 9th century ce that was produced throughout syria, egypt, italy, and the western provinces.24 such glass consists of a composition similar to that of the previous antimony-rich group, although with a large drop in the amount of antimony and significantly higher manganese content. this has led to the conclusion that the primary distinction between roman glass and the previous antimony-rich glass is the choice of decolorant used to achieve colorless glass.16,24,60 however, this is somewhat of an oversimplification as it is generally believed that the roman period is also distinguished by other changes in the raw materials applied to glass production.37 the primary alkali source for roman glass is generally held to be natron, most probably obtained from the wadi natrun in egypt.16,36,37,40,58,61,62 the romans extensively imported natron from egypt and it remained the alkali of choice for glass production for the duration of the roman empire.40 in contrast, the silica source of roman glass is now thought to consist primarily of sand, based on increased alumina (al2o3, 2.3% average), tio2 (0.07% average), and fe2o3 (0.5% average) content.37,62 furthermore, pliny the elder confirms the use of sand in roman glass in his natural history63 and this sandnatron glass formulation remained as the standard glass formulation throughout the roman and byzantine periods until ca. 850 ce37. in addition to the use of manganese as a decolorant, roman glass also utilized lead salts and other components as additives to the glass formulation.7,18,36,63 the primary use of lead was as a colorant in the production of yellow opaque glasses,28 but lead salts were also sometimes intentionally added to either improve the working properties of the melt36 or to enhance the brightness of the resulting glass.18 it has also been claimed by some that the uniform calcium content found in the analysis of roman glasses is evidence of the intentional addition of lime to glass formulations.7 to support this reasoning, authors have pointed to passages of pliny the elder that mention the addition of shells and fossil sand to glass,63 as well as suggesting chalk or other forms of limestone (caco3) that could have acted as convenient sources of lime in addition to burned shells (primarily a mixture of chitin and caco3).7 still, it has also been pointed out by others that the distinct lack of substantial amounts of such additives in known glass recipes does not really support such claims.2 furthermore, as these potential calcium-based additives are not mentioned in the known glassmaking treatises of the medieval and renaissance periods, it is generally believed that the role of lime in glass was not yet recognized during the roman period.20 it should be pointed out, however, that analysis of the sands used as the roman silica sources have shown higher calcium content and thus these sands are believed to have acted as a source of lime as well as silica.37,60,61 advanced processing methods and new applications the roman empire presented a ready market for high-quality glass objects, which thus encouraged the development of new methods for the manipulation of glass and a more centralized approach to glassmaking.2 for the first time, the mass production of similar glass objects became an economic goal and new fabrication methods were required to meet this demand. such efforts began with bending (fig. 6), a method also known as sagging or slumping.2,55 the formation of slumped objects began with pouring hot glass onto a flat surface (fig. 6a), which was then pressed with a flat, 131a brief history of early silica glass: impact on science and society disc-shaped tool (fig. 6b) to create a glass disc (fig. 6c). the resulting disc was then transferred onto a “former” mold (fig. 6d) and the system was reheated to soften the glass disc to the point that the combination of heat and gravity would cause the disc to sag over the mold to give a bowl-shaped glass object (fig. 6e, fig. 7). the formed piece was then finished by grinding and polishing in order to remove mold markings or tool marks.55,64 the large-scale production of slumped objects has been dated to ca. 400 bce39 with one of the most common objects made in this way being the distinctive ribbed bowls often referred to as pillar-molded bowls. such bowls were popular from the 1st century bce to the 1st century ce and modern glassmakers have illustrated that this is a viable, easily repeatable, and relatively fast method which reproduces all of the characteristics of roman-era ribbed bowls.64 of course, the most significant new advancement was the introduction of glassblowing during the 1st century bce,2,7,23,31,37,53,56,65 a technique now commonly viewed as synonymous with the general working of glass. although it has been proposed by some to have been invented as early as 250 bce, there is far too little evidence to support the application of glassblowing at this earlier date.65 sometime after 50 bce, however, blown glass objects had become common and thus the genesis of glassblowing is typically dated to the time period of 50 bce 20 ce.31,65 the origin and development of this technique is typically attributed to craftsmen somewhere in syria or phoenicia,23,39,54,56,65,66 with many scholars favoring the phoenician city of sidon (on the coast of syria) as its point of origin.31,66 glassblowing is then thought to have migrated to rome via craftsmen and slaves after roman annexation of the area in 63 bce.16 the introduction of the revolutionary technique now made possible the creation of an almost endless variety of hollow glass objects.56 this method allowed the production of very thin, transparent glass, increased the overall versatility of glass significantly, and opened up potentially new applications for glass.46 in addition, glassblowing could be combined with previous methods to result in new variants such as mold-blowing (fig. 8),65 in which glass was blown into a twoor three-piece hollow mold. the product of this method was a hollow, thin-walled vessel and the molds could be re-used indefinitely to allow the mass production of such objects.65 as a consequence of such advances, the whole character of glass objects changed, with the heavier forms of earlier periods being gradually replaced by thin-walled vessels.37 furthermore, the scale of glass production increased dramatically such that it was now possible for the rapid production of simple utilitarian vessels in large quantities, and glass transitioned from prestige objects to household commodities.7,37 figure 6. the formation of open-form bowls by sagging glass over convex “former” molds: (a) molten glass is poured onto a flat surface; (b) pressed with a flat, disc-shaped former; (c) cooled to create a glass disc; (d) transferred onto a “former” mold; (e) heated to cause the disc to sag over the mold giving the final bowl shape [adapted from reference 42 with permission from springer nature]. figure 7. ribbed bowl (1st century ce) [81.10.39; courtesy of the metropolitan museum of art, www.metmuseum.org]. figure 8. blow-molding with a two-piece mold: : (a) hollow glass blank; (b) glass blank inserted into mold; (c) mold fastened together and softened glass blown to fill mold; (d) mold disassembled and hollow vessel isolated [reprinted with permission from reference 2. copyright 2015, american chemical society]. 132 seth c. rasmussen one of the new applications of glass introduced by the romans was the construction of glass window panes as early as the 1st century ce.67-70 the date of this innovation is supported by window glass in pompeii structures built or restored after the earthquake of 62 ce, yet preceding the eruption of vesuvius in 79 ce,68 with additional examples commonly found in roman sites in britain.69,70 for the most part, however, such early glass windows were quite small, of irregular thickness, and not truly clear or transparent (fig. 9).67 larger glazed windows comprised of multiple glass panes were known, however, such as those used for solar heating of roman bath houses.71 early window panes were fabricated via a variety of different processes,2,62,67-70,72 the oldest of which was the production of “cast glass” which produced panes of uneven thickness, with one side exhibiting a smooth texture and the other side a pitted, rough finish.68-70 this seems to have been the prevailing technique up to the 3rd century ce, after which the technique fell into disuse and thus the exact details of making cast glass have been lost.62,69,70,72 the production of blown window glass (cylinder and crown glass) appeared sometime after the 2nd century ce, with both the cylinder and crown techniques starting to become widespread by the beginning of the 4th century ce.62,72 it is thought that cylinder-blown glass windows initially existed alongside windows fabricated via the older casting technique.72 it is also during the roman period that the development of chemical apparatus began sometime towards the end of the 1st century ce.73-76 specific known examples at this point in time include the initial distillation apparatus (fig. 10), the water-bath, and the kerotakis apparatus, all credited to the alchemist maria the jewess.73-76 although glass did find some application in such chemical apparatus, the majority were fabricated from either earthenware (with the interior glazed) or copper.73,76 rather, glass was limited to the objects such as the receiving flasks for stills (bikos) or other initial types of flasks known as phials and urinals.73,76 as glass technology was rising to its initial heights during this time period, it is somewhat surprising that glass-based apparatus for the chemical arts do not seem to have been developed to any significant degree during the roman period.22,46,73 the late use of glass for such applications was largely due to the fact that typical soda-lime glasses of this period lacked sufficient chemical durability to be practical for such use.6 laboratory glassware must often withstand severe temperature changes in the presence of strong reagents. thus, for such glassware to be useful, it must not only be resistant to chemical attack, but must also be durable under thermal stress.22,73 the combination of poor quality, low thermal stability, and the figure 9. modern reproduction of roman window glass (~5 mm thick) [copyright mark taylor and david hill, used with permission]. figure 10. basic components of the early still [adapted from reference 75 with permission from springer nature]. 133a brief history of early silica glass: impact on science and society irregular nature of early glasses resulted in the frequent breaking of vessels when used under heat.77 venetian glass centralized glass production came to an end following the fragmentation of the roman empire in the 4th century ce, with glassmaking shifting from urban centers to rural locations closer to raw materials and critical sources of fuel. as a consequence, glassmakers became isolated and eastern and western glassware gradually acquired distinct characteristics. in addition, this resulted in the loss of more specialized and sophisticated decoration techniques (cutting, polishing, and enameling) and critical techniques such as glassblowing were simplified to their basic essentials.39 the path of glass in the east continued in the byzantine empire long enough to ensure its survival, and aspects of glassmaking that died out in the west were thus kept alive. furthermore, contact between the byzantine empire and the new empire of islam allowed islamic glassmakers to add known roman and byzantine techniques to their glassmaking activities.39 as with many chemical arts, this cumulative glassmaking knowledge was then preserved by the world of islam until the coming of the renaissance in the west. after the initial crusades in the 11th century, the center of glass manufacture gradually shifted from glassmakers in the islamic empire to the growing glass industry of venice.7,56,78 venice developed into a city state during the 9th century and grew in importance during the 11th to 13th centuries by exploiting its strategic position at the head of the adriatic.39 the strength of the venetian fleet allowed it to make the most of its advantageous trading position, achieving a virtual dominance of trade with the east. it is believed that the tradition of glassmaking never completely died out in italy after the fall of rome and the manufacture of glass had been revived in venice by the time of the crusades.4,46,79 this simple industry was well established by the 9th century and was soon operating on such a remarkably grand scale that it was prospering by 1200.39,56,80 it is believed that the venetians then gained additional glassmaking knowledge via an influx of eastern expertise, beginning with information transfer from byzantine glassmakers after the sack of constantinople in 1204 and enhanced by a critical treaty signed in 1277 between venice and the prince of antioch to facilitate the transfer of technology between the two centers.39,78,79 this included the transfer of syrian glassmaking, thus allowing many secrets to be brought to venice, and a continuous supply of low-cost plant ash for the venetian glass industry was established in 1366.81 these factors provided key components that led to the flowering of glass in 14th to 16th century venice.78 as the glass industry grew, the venetian glassmakers established their own guild in 1268 with a more elaborate guild system to follow in 1279.39,56 the center of venice ultimately became dominated by furnaces, the control of which was lost far too often, the resulting fires causing destruction of both critical glasshouses and adjacent neighborhoods. as a solution, the glass industry was ordered to be moved to the island of murano in 1291, about a mile from venice.56,79,80 the glasshouses of murano are said to have extended for an unbroken mile where thousands of workers toiled to make the glass objects for which venice became famous (fig. 11).56,80 until the beginning of the 14th century, the primary source of silica used by the venetian glassmakers was various local sands.82,83 in addition to silica, these sands figure 11. venetian wineglass (murano, 16th century ce) [91.1.1458; courtesy of the metropolitan museum of art, www. metmuseum.org]. 134 seth c. rasmussen are thought to have provided considerable alumina, as well as iron oxide, lime, magnesia, and small amounts of manganese.23 however, it had long been known that the cleaner and whiter the source of silica, the clearer the resulting glass. as a result, these sands were gradually replaced with flint pebbles (a form of the mineral quartz) obtained from nearby river beds. before use, these pebbles were calcined (heated red-hot in an oxidizing atmosphere), ground, and sieved to form a fine quartz powder that was purer than the sands previously used.23,39,79,82-85 the resulting material was ~98% silica and became the near exclusive silica source of the venetian glassmakers for the next several centuries.82,85 in terms of the alkali source, the venetians favored the use of plant ashes imported from the levant (modern syria, israel, lebanon, and the sinai in egypt) as discussed above.21,82-87 the soda ash imported from the levant originated from the burning of plants thought to have belonged to the large family of the chenopodiaceae, in particular the plant salsola kali.21,82-87 these levantine ashes, referred to in venice and murano as allume catino, were in common use by 128582 and were used almost exclusively in murano until the end of the 1600s.86 such ash had high soda content (as much as 30-40%), as well as large quantities of potassium, calcium, and magnesium carbonates.21,82,85-87 the exclusive use of these ashes was even dictated by the venetian government, with the use of other plant ashes expressly prohibited,87 thus highlighting the importance of these ashes to the venetian glass industry. in addition to specific changes in the raw materials utilized, another significant contribution to the success of venetian glass was the introduction of new processes for the preparation of the alkali raw materials.86 the plant ash was shipped to venice as hard pieces of calcined residue, after which it was pulverized and purified by a series of sieving, filtering, and/or recrystallization steps. these methods removed non-fusible material that would act as particulate matter in the resulting glass, as well as removing other unwanted impurities such as iron and aluminum-containing species.21,23,84 the choice of raw materials used by the venetian glassmakers, coupled with their innovative purification methods, resulted in significantly improved glasses that dominated the industry for hundreds of years. the preparation and purification methods utilized removed unwanted colorants, as well as insoluble, nonfusible components from the resulting glass products. not only did this result in much clearer glass, but this also removed particles that would have acted as stress points during rapid heating. in addition, the reduced soda content combined with the higher amounts of the stabilizing oxides would result in a material that exhibited both higher chemical durability and less thermal expansion.18,22,73 as a result, the improved venetian glass would therefore be more resistant to the action of water, acids, and bases, and would be less affected by rapid temperature changes, thus making it much more favorable for laboratory glassware in comparison to the previous roman glass. as such, it is not surprising that this time period also exhibited a gradual shift of chemical apparatus from pottery and metal to the greater application of glass.22,73,76 mirrors, eyeglasses, and lenses in addition to the production of higher quality glass, the venetians also introduced a number of innovations for the production of novel forms of glass objects, beginning with advances in glass mirrors.88 although the production of glass mirrors was known to the romans, these were limited to very small sizes and thus polished metal mirrors were preferred.46 critical factors that limited the previous development of glass mirrors was insufficient methods for producing flat, smooth glass that was still clear and relatively thin, as well as the fact that the initial metal backing was commonly lead or tin, and the application of hot metal onto glass typically resulted in thermal shock and cracking or breaking of the underlying glass substrate.46,89 this latter limitation was overcome with the innovation of metallic leaf, rather than molten metal, a discovery credited to the venetians.80 this was then further advanced in the 13th century, when the venetians started to use a slow grinding process in order to produce highly polished mirrors.88 the grinding and polishing needed to create a large, distortion-free surface, however, required the mirror glass to be made thicker than possible using conventional methods for the fabrication of windows. as a solution, panels of the desired thickness were typically produced by a modification of the original “cast glass” method of producing glass panes, after which the glass sheets were painstakingly ground and polished. finally, the reflecting metal foil was then fixed to one surface to give very high-quality mirrors, although prohibitively expensive. a superior method of coating glass with a tin-mercury amalgam was then developed during the 14th-15th centuries, again typically credited to venetian glassmakers. venice had become a center of mirror production by the 16th century and was viewed to produce the best mirrors in the world.89 of course, mirrors were a crucial feature in the later development of optics and their application had significant 135a brief history of early silica glass: impact on science and society effects on the developing sciences of physics, chemistry, and astronomy. it has been said that without mirrors, the renaissance and the scientific revolution might not have occurred.90 once the venetian polishing techniques became more common, the manufacture of spherical glass surfaces became much easier, ultimately resulting in the production of eyeglasses.88 although various people have been credited with their invention over time,91-93 available historical evidence has shown all of these to be false attributions and the inventor of eyeglasses is still unknown.91,92 available sources support their appearance in italy sometime between 1286 and 1292,91,92,94,95 with pisa typically given as the most likely site of origin.92-94 eyeglasses were being produced in venice by 1300 and were repeatedly referenced in guild regulations during the first two decades of the 14th century.92,93,96 in fact, venice became such an important production center for eyeglasses that venetian spectacle makers left the glassmakers’ guild to form their own guild in 1320.93 the earliest eyeglasses were comprised of two separate lenses and frames, held together with a central rivet (fig. 12a).93,94 these initial spectacles utilized convex lenses (fig. 12b),95,96 thus improving vision for the farsighted and used primarily for reading.92,93 concave lenses, for the nearsighted, were more difficult to work and did not arrive until the mid-15th century.94-96 it has been stated that eyeglasses are one of mankind’s most beneficial material inventions. without them, people born with poor vision would be illiterate or have insufficient vision for a skilled trade. even most people born with normal vision typically lose the ability to focus by their mid-40s.93,95 as a consequence, it is believed that this single invention effectively doubled the intellectual life span of the average person beginning in the 13th century, significantly impacting society as a whole. of course, as with mirrors, high-quality lenses were critical for the development of optics, as well as allowing later discoveries such as the microscope and telescope.88 from waldglas to bohemian glass glass in the west followed a different path following the fragmentation of the roman empire.78 under roman rule, glasshouses had been established in the western provinces of gaul and britannia prior to the 3rd century ce, including sites at boulogne, trier, cologne, manchester, and leicester.7,16,56 by ~500 ce, the western empire fell to german tribes and although glassmaking essentially ceased in the west for a period, the established glasshouses survived and the knowledge of glass production was not completely lost. reduced access to raw materials unavoidably produced glass exhibiting the character of the local silica and flux used and made it no longer possible to achieve colorless glass.39 such northern glass produced in the middle ages was sometimes referred to as waldglas (forest glass), and was commonly dark green or brown due to contained impurities.23,97 a critical raw material for the production of highquality soda lime glass was the natron imported from egypt. however, without suitable access to the previously imported soda, several northern glasshouses started to use the ash of wood logs as the primary flux for glass production as early as 800 ce.16,18,98,99 beech was most commonly used for this purpose, although other species such oak, spruce, and birch were also used.98,100 in comparison to the previously discussed soda-rich ashes obtained from plants grown near the sea or in salty soil, inland species typically provide ash higher in potash (k2co3).23 thus, the ash of the various trees used was very low in soda, but all exhibited significant potash content (up to 37%) along with very high levels of calcium.21,99 thus by the 10th century ce, glass in the northern glasshouses was produced from a combination of the tree ash and local sands to give a potash-lime formula.16,18,24,100 chemical analysis of northern glasses of this time period have revealed high potassium and calcium content (11.8 and 17.9%, respectively) coupled with low sodium (1.63%), although potash-lime glass produced from 780-1000 ce was also quite variable and not as consistent as later glasses.99 in comparison to soda-lime glass, potash-lime glasses exhibited significantly different physical properties. for example, the application of potash as the flux figure 12. early eyeglasses design (a) and convex versus concave lenses (b) [adapted from reference 87 with permission from springer nature]. 136 seth c. rasmussen could reduce the melting point of the silica to low as 750 °c, compared to the value of ca. 1000 °c achieved with soda.101 in addition, potash-lime glass was heavier and harder than soda-lime glasses, which made it better for cutting and engraving, although it was also typically not as clear. due to its lower melting temperature and the simple availability of trees in the northern european forests, potash-lime glass could be inexpensively massproduced, making it very desirable, particularly for the production of windows.99,100 such northern potash-lime glass is often viewed as reaching its greatest heights with the material known as bohemian glass. although it is named after the bohemian forests where it was developed, it is typically viewed as a german glass, as its origin stems from efforts by rudolph ii, emperor of germany and king of bohemia, to start an establishment in prague to make cut glass in imitation of rock-crystal.97,102 as such, he recruited famous engravers of rock-crystal to prague in the late 16th century, most critical of which was a german named lehmann who came to prague in 1590.97 glassworks had been established in the bohemian and silesian forests as early as the 15th century, but the glass produced was typical of other northern glasshouses and primarily copied venetian glass forms.97,98,102 lehmann, however, developed a new style of glass-cutting and engraving that served as the basis of bohemian forms. to facilitate the cut glass, heavier and thicker forms were developed, with the first such bohemian glasses being white glass cut in facets and engraved with images. at a later period, both colored and colorless glass were also made.97,102 a new bohemian glass was then introduced in 1683 under the name of kreideglas (chalk glass), which is the first verified glass that used lime as a significant component. this reputedly improved glass is ascribed to michael müller, developed in his factory in southwest bohemia,20 and the analyses of bohemian glasses dated to the end of the 17th century are consistent with the use of lime.98 it was not long before bohemian glass competed successfully with venetian glass and, by 1730, it had completely supplanted venetian glass in terms of artistic form.97,102 furthermore, it was in the early period of the 19th century that the chemical laboratory underwent what has been described as the “glassware revolution”.103 as such, what started with the gradual replacement of other materials (copper and pottery) with venetian glass had now transitioned to a laboratory consisting primarily of chemical glassware, the majority of which was now produced from bohemian glass. conclusion the introduction of borosilicate glass in the 1880s ultimately ended the reign of the simpler soda-lime and potash-lime glasses, with brands such as pyrex offering greater thermal and chemical stability and thus dominating most practical applications of glass.104 still, many of the everyday innovations commonly associated with glass began with these simpler formulations, including windows, glass mirrors, eyeglasses and lenses, and of course, chemical glassware. needless to say, silicon in the guise of such silica-based glasses had unimagined impact on science 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its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna chemical demulsification of oil-in-water emulsion from gas condensate field habineswaran rajan1,2 , nur’aini raman yusuf2 , dzeti farhah mohsim1, nor hadhirah bt halim3 1 department of petroleum engineering, universiti teknologi petronas, 32610, seri iskandar, perak, malaysia 2 center of enhanced oil recovery, institute of hydrocarbon recovery, universiti teknologi petronas, 32610 bandar seri iskandar, perak darul ridzuan, malaysia 3 petronas research sdn bhd, jln ayer hitam, kawasan institusi bangi, 43000 bandar baru bangi, selangor, malaysia keywords: emulsion; produced water; demulsifier; demulsification; oil-in-water content (oiw); demulsifier oa-kx received: feb 05, 2023 revised: apr 19, 2023 just accepted online: apr 20, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: h. rajan, n. r. yusuf, d. f. mohsim, n. h. b. halim, (2023) chemical demulsification of oil-in-water emulsion from gas condensate field. substantia. just accepted. doi: 10.36253/substantia-2035 1. abstract produced water, also known as oily wastewater, is one of the major wastes in the oil and gas industry. during the hydrocarbon production, formation of emulsion takes place such as oil-in-water emulsion which has a huge financial effect on the sector. oil and gas industry seeks highly effective and reasonable demulsifying chemicals to separate the oil-in-water emulsions into water and crude oil. thus, in this publication, resin alkoxylate, cationic polyamine, cationic surfactant and ethylene oxide/propylene oxide (eo/po) block copolymers are utilized to resolve the oil-in-water emulsion from a gas condensate field. according to the findings of preliminary screening, a unique demulsifier db was formulated by incorporating resin alkoxylate and cationic surfactant at an optimal weight percentage ratio. demulsification efficiency (de) of 96 % based on measurement of turbidity was attained after treating the oil-in-water (o/w) emulsion with demulsifier db at a dosage of 7 ppm. to determine the demulsifier's efficiency further, the oil-in-water content (oiw) of the produced water was evaluated after the treatment with demulsifier db. oil removal efficiency (ore) of 90% was achieved as the formulated demulsifier db reduced the oil-in-water content (oiw) of o/w emulsion from 1008.3 ppm to 97.1 ppm within 15 minutes at the dosage of 7 ppm. furthermore, interfacial tension (ift) and turbiscan analysis were performed to further study the demulsification process of blank sample and the addition of the demulsifier db at the optimized dosage of 7 ppm. at demulsifier db dosage of 7 ppm, the interfacial tension between oil and water reduced significantly compared to blank sample from 24.98 mn/m to 9.38 mn/m. the produced water sample after treatment with 7 ppm of demulsifier db resulted in a significant increase of turbiscan stability index (tsi) value of 8 which indicates the rate at which the separation of oil and water occurred. the attained results of ift and turbiscan analysis further validate that mixed surfactant system is more efficient than single surfactant system. by combining surfactants with different functional groups, mixed surfactant systems can exhibit greater surface activity than single surfactants. 2. introduction the development of alternative energy sources is a significant challenge in today's world, given environmental contamination and the constant need for fresh water. nevertheless, petroleum is still one of the prominent sources of energy for transportation fuels in most countries. therefore, there is a steady need to supply the continuous demand for the oil and gas industry. as a result of exploration and development activities, excessive amount of water known as produced water is lifted from the subsurface formations to the earth surface (veil et al., 2004). produced water can be present in the form of emulsions which can be harmful to the aquatic organism if it was discharged untreated into the sea. in order to preserve the environment from contamination, these excessive amounts of water should be treated before it can be discharged into the environment. when economically feasible, it is recommended to recycle produced water within the upstream oil and gas sector as it offers several benefits, such as minimizing the need for external water sources, reducing liability concerns associated with managing produced water, and limiting the overall management of produced water. prior to recycling, specific substances like insoluble oil, microorganisms, iron, and boron are typically removed using fit-for-purpose treatment trains consisting of oil-water separations, solids separation, disinfection, and iron removal methods (liden et al., 2017). conventional oil and gas wells are drilled into geological formations where oil and natural gas flow easily to the wellbore. in contrast, unconventional oil and gas wells are drilled into previously unconventional geological sources, such as coalbed methane (cbm), shale gas, tight oil, shale oil, and oil sands. with conventional production, the produced water is often recycled by injecting back into medium-to-high permeability reservoirs to maintain pressure of the reservoir or enhanced oil recovery (eor) (scanlon et al., 2019). however, in the case of unconventional production, the excessive produced water cannot be injected back into the low-permeability reservoirs. therefore, treating produced water is a practical approach for managing the large volumes of water generated during oil and gas exploration and production. the primary objectives of produced water treatment are to remove dispersed oil and grease, desalinate the water, remove suspended solids, eliminate soluble organics, remove dissolved gases, reduce naturally occurring radioactive materials (norm), disinfect the water, and soften it (liden et al., 2019). de-oiling is a process of removing any remaining oil and grease that can be harmful to the environment if discharged untreated. desalination process done using desalters removes any salt from the water to prevent damage to the environment and equipment. generally, combination of two non-miscible liquid phases is known as emulsion in which one phase is dispersed in the other phase (tadros, 2013). an emulsion contains a continuous phase and a dispersed phase which are also known as external and internal phase respectively. the oil droplets are the dispersed phase in the continuous phase which is water or vice versa. regardless of the phase volume ratio, dispersed phase always has the smaller phase volume compared to the other phase (schramm, 1992). a water-in-oil (w/o) emulsion is a type of emulsion in which the dispersed and continuous phase is water and oil respectively. oil-in-water (o/w) emulsion is a form of emulsion in which continuous phase or the dispersion medium is water and the dispersed phase is oil (auflem, 2002). multiple emulsions have a more complicated structure, with microscopic droplets suspended in large droplets in a continuous phase. oil-in-water-in-oil (o/w/o) and water-oil-in-water (w/o/w) emulsions are two types of multiple emulsions (israelachvili, 1994; sjoblom, 2001) as shown in the fig. 1. fig. 1–types of emulsions oil refining, also known as petroleum refining, is the process of transforming crude oil into a range of useful products such as gasoline, diesel, jet fuel, heating oil, lubricants, and various other chemicals. crude oil is a complex mixture of hydrocarbons, impurities, and contaminants, and refining is necessary to convert this raw material into usable products that meet specific quality and performance standards. the refining process typically involves several stages of processing, each of which is designed to remove different impurities and contaminants from the crude oil. desalination process done using desalters removes any salt from the water to prevent damage to the environment and equipment. de-oiling is a process of removing any remaining oil and grease that can be harmful to the environment if discharged untreated. these processes of oil refinery are often aided by demulsifier where it helps to separate water and other impurities from the oil more effectively, reducing the amount of contaminants in the final products. demulsifiers involve desalters and deoilers, which is considered to be about 40% approximately the world oilfield production chemicals market. demulsification is the process of segregating an emulsion into two different phases which are water and crude oil. crude oil can be sent directly to refineries utilising less complex emulsion breakers and chemical technology when crude oil had little to no water during its production in oil and gas industry. emulsion droplets can range in size from rather big (visible) to sub-micron. some emulsions are extremely stable and require a demulsification technique to be treated. destabilization of emulsion is carried out by using either four main methods such as mechanical, chemical, thermal, or electrical (coca et al., 2011). chemical method is one of the common approaches applied in the process of demulsification where demulsifiers are added into the emulsion to assist the emulsion breaking process (razi et al., 2011). chemical additives' primary role is to counteract the stabilizing impact of emulsifying agents which are asphaltenes and resins (daniel-david et al., 2008). demulsifiers are surfactants that helps to separate o/w and w/o emulsions into two phases respectively at low concentrations of dosage. produced water include a significant amount of oil droplets during the production of hydrocarbon. to minimise complications during the refining process, these oil droplets should be removed from the produced water or viceversa. asphaltenes and resins are naturally occurring compound of crude oil which can form a stabilizing layer around the water droplets, preventing them from coalescing and separating from the oil (feitosa et al., 2019). the surface-active chemicals known as demulsifier are absorbed to the oil/water interface and it weaken the rigid film of the droplets. addition of demulsifier reduces the surface tension of the droplets, which in turn destabilizes the emulsion particles (or droplets). eventually, it leads to the rupturing of rigid film and enhance coalescence of water droplet (mhatre et al., 2018). as a result, the particles within the emulsion have a natural tendency to agglomerate and form larger masses which leads to the separation of oil and water. demulsifiers or surfactants are organic particles comprising of two parts: the polar portion that is attractive to the water phase (hydrophilic) and the non-polar portion that is attractive to the oil phase (hydrophobic) as shown in fig. 2. effective emulsion breaking using a demulsifier needs a chemical that is appropriately selected for the specific emulsion, a suitable amount of dosage, appropriate stirring of chemical in the emulsion, and an adequate time for the droplets to settle down (yi et al., 2017). it may also be necessary to rise the temperature of the system to aid the demulsification process, however, it might increase the cost of treatment. fig. 2 – basic structure of demulsifier (porter, 1991) there are previous study and research on the types of demulsifiers tested which is important for improving the understanding of emulsions, developing more effective treatments, optimizing their usage, and minimizing their environmental impact. poly aluminium chloride and quaternary ammonium salt (pac-qas), polyamine (pa), and the compound of polyamine and poly aluminium chloride (pa-pac) were investigated for the treatment of oily produced water in 2020 (shu et al., 2021). shu discovered that pa and pa-pac at 60 mg/l and 90 mg/l respectively showed better performance than pac-qas in terms of oil removal efficiency, achieving around 60% and 70%. due to the cationic polyamine’s high positive charge, the stability of emulsified oil droplets was disrupted as the negatively charged oil droplets was counteracted by the chemical and making it surface active (shu et al., 2021).wang et al. examined the demulsification of o/w emulsions using block copolymers of ethylene oxide (eo) and propylene oxide (po), which has amphiphilic characteristics in aqueous solution (wang et al., 2010). when the concentration of pae82 and pae102, which are dendritic copolymers and synthesised by propylene oxide and ethylene oxide reactions, reached 150 mg/l, their demulsification ratios were 91.92% and 91.23% at 15 minutes respectively. this shows that eo/po block copolymers is capable of a good demulsifier for o/w emulsion. furthermore, according to the study conducted by acostal et al., a member of the resin alkoxylate family, c6 have demonstrated remarkable performance in accordance with industrial norms when tested for the demulsification of w/o emulsion, enabling more than 80% water separation (acosta et al., 2020). a feasible substitute to the hydrophilic–lipophilic balance (hlb) approach for evaluating the hydrophilic-lipophilic balance of surfactants is the relative solubility number (rsn). rsn has found extensive applications in the surfactant chemical industry for aiding in product selection, quality control, and formulation. it is also beneficial in emulsion research as it facilitates the choice of demulsifiers and stabilizers (wu et al., 2004). the demulsifier c6 has a relative solubility number (rsn) value of 11. this constant, which is frequently used for screening and benchmarking, categorises demulsifiers as water or oil-soluble. high rsn numbers (>13) are associated as water-soluble demulsifier, whereas low rsn numbers (< 13) numbers are associated with oil-soluble demulsifiers (marquez-silva et al., 1997). intriguingly, c6 lies in the region close to the region of oil-soluble demulsifier which shows that it could be effective in resolving in o/w emulsion. for the o/w emulsions demulsification, water-soluble demulsifiers are typically utilized whereas oil-soluble demulsifiers are commonly utilized to destabilise water-in-oil emulsions (raya et al., 2020). hirasaki et al. observed that certain amphoteric and cationic surfactants were efficient at segregating o/w emulsions, which were produced when surfactant/polymer (sp) method was used for enhanced oil recovery (hirasaki et al., 2011). in his study, adding roughly 200 ppm of cationic surfactant, n-octyltrimethylammonium bromide (c8tab) caused a distinct segregation of the oil and water phase. the cationic surfactant decreased electrostatic repulsion between droplets and altered system phase behaviour leading to a balanced state of lipophilic and hydrophilic effects which reduces the emulsion stability. in this article, various types demulsifiers such as resin alkoxylate, cationic polyamine, cationic surfactant and eo/po block copolymers were evaluated for the demulsifcation of o/w emulsion. the impact of various demulsifiers on the o/w emulsion was investigated based on the turbidity and oiw content of the treated sample. the main objective of this work is to minimize the oiw content of the o/w emulsion from gas condensate field by developing a new formulation using selected effective demulsifiers based on the screening conducted. 3. materials and methods 3.1 materials petronas research sdn. bhd. (prsb) provided the essential materials for the experiment purpose from gas condensate field such as produced water and condensate. they were selected for the preparation of emulsion as they were raw material obtained from a gas condensate field without undergoing any treatment. the characteristics of the condensate and produced water are shown in table 1 and table 2. several types of chemicals were provided by petronas research sdn. bhd. (prsb) were used for the treatment of o/w emulsion of gas condensate field are shown in table 3. demulsifier a, b, c and d are used in this experiment and the chemicals are industrial grade. characteristics value density @15°c 0.8857 g/cm3 api gravity @15°c 28.2° wax appearance temperature (wat) 10.7 °c kinematic viscosity @60 °c 1.438 mm2/s saturates 52.77 % aromatics 46.77 % resins 0.41 % asphaltenes 0.12 % table 1– characteristics of the condensate characteristics value salinity 100 mg/l ph 3.7 table 2– characteristics of produced water demulsifier type a cationic polyamine b resin alkoxylate c eo/po block copolymers d cationic surfactant table 3– types of demulsifier 3.2 emulsion preparation for the preparation of o/w emulsion, the condensate and produced water from gas condensate field were used as oil and water phases respectively. the o/w emulsion was prepared by using the produced water and condensate at a volume ratio of 85:15. using a 100 ml beaker, produced water and condensate were added into the beaker at a volume of 34 ml and 6 ml respectively. the total mixture of condensate and produced water was 40 ml in the beaker. in order to form a stable o/w emulsion, the produced water and condensate was then homogenized for 10 mins at 4000 rpm using ika ultra-turrax t-50 homogenizer. 3.3 emulsion characterization the type of emulsions whether o/w or w/o emulsion and the typical size was confirmed visually using a leica dm lb2 microscope at 40x magnifications. furthermore, zeta potential (z-potential) gives more information on the o/w emulsion stability, and it is measured by measuring the charged droplets or colloids’ velocity in a specified electrical potential field. zeta-potential of the emulsion were measured to study the electrical charge of any droplet present in the emulsion. malvern zetasizer nano-zsp was used to test the zetapotential of emulsion that had no chemical compounds added. 3.4 bottle test screening the prepared emulsion according to the experimental procedure mentioned above was then transferred to a bottle. in order to stimulate the real field condition, the bottle containing the emulsion was then immersed in water bath for 30 minutes at 60 °c. after that, the demulsifiers was injected into the bottle using pipette at various dosages and the bottles were shaken 100 times by hand to ensure that the demulsifier was uniformly distributed throughout the emulsion. for the segregation of oil and water to take place, the emulsion was then allowed to settle down for 15 minutes by placing the bottles in water bath. the water sample from the bottom of the bottle was obtained at the end of the retention time. the water sample's turbidity and oiw content were also determined. 3.5 turbidity measurement turbidity is a liquid's relative clarity measurement that has long been used as a fundamental and straightforward indication of water quality. it is an optical property of water in which the amount of light scattered by material in the water is measured when a light is shone on a water sample. the turbidity of the emulsion and treated sample was measured with hach 2000 turbidimeter at 0.001 ntu, maximum sensitivity. the efficiency of the demulsifier was determined by calculating the demulsification efficiency, de (%), using the formula below: 𝐷𝑒𝑚𝑢𝑙𝑠𝑖𝑓𝑖𝑐𝑎𝑡𝑖𝑎𝑛 𝑒𝑓𝑓𝑖𝑐𝑒𝑛𝑐𝑦, 𝐷𝑒 (%) = 𝑇𝑜 − 𝑇 𝑇𝑜 × 100 (1) where to and t are the initial and final turbidities of the produced water. 3.6 oil-in-water content (oiw) measurement for the measurement of oil concentration of the sample, td-500d handheld oil in water meter from hma instrumentation was utilized. using infrared detection, the td-500d handheld oil in water analyzer determines solvent extractable substances (hydrocarbons, oil, and grease) in water or wastewater. the standard procedure to measure oil concentration is by transferring the produced water to a tube and add hexane solution at a volume of 10% to the total amount of produced added initially. the tube was then shaken for 2 minutes and the top layer of the tube was taken using a pipette. the solution will be then injected on the surface of the oil analyzer to measure the oiw content. the amount of oil removed from the produced water was evaluated based on the oil removal efficiency, ore (%), calculated using the formula below: 𝑂𝑖𝑙 𝑟𝑒𝑚𝑜𝑣𝑎𝑙 𝑒𝑓𝑓𝑖𝑐𝑒𝑛𝑐𝑦, 𝑂𝑅𝑒 (%) = 𝑂𝑖𝑊𝑜 − 𝑂𝑖𝑊 𝑂𝑖𝑊𝑜 × 100 (2) where oiwo and oiw are the initial and final oiw contents of produced water sample. 3.7 interfacial tension (ift) measurement the force between two distinct phases that can be liquid-solid, liquid-liquid, gas-solid or gas-liquid contact is known as interfacial tension (ift). the interfacial tension of two non-miscible liquids, oil and produced water, was measured at 60°c using the rame hart model 260 by the pendant drop method. pendant drop is an optical method to measure interfacial and surface tensions of fluid system. they are determined through the drop shape using the following equation: 𝑆𝑢𝑟𝑓𝑎𝑐𝑒 𝑡𝑒𝑛𝑠𝑖𝑜𝑛, 𝛾 = ∆𝜌𝑔𝑅0 2 𝛽 (3) where γ is the surface tension, g is the gravitational constant, δρ is the difference of densities between liquid, r0 is the curvature’s drop radius at the apex, and β is the shape factor. β is defined as three dimensionless first-order equations through the young-laplace equation expressed. 3.8 turbiscan lab® expert demulsification analysis turbiscan™ ags high throughput stability analyzer from formulaction (france) is intended for examining destabilization mechanisms of emulsions and dispersions. besides, it characterizes physical properties of substances, or identifies the particle size and concentration in a sample more importantly (mengual et al., 1999; paweł et al., 2020). the turbiscan apparatus utilizes a near-infrared light source with a wavelength (λ) of 880 nm, emitting pulsed signals, in combination with synchronized dual detectors a transmission (t) detector and a backscattering (bs) detector to aid in the optical evaluation of dispersion destabilization. at a degree of 0° from the incident beam, the transmission (t) detector detects light that passes through the sample. the light will be then reflected back by the sample at degree of 135° from the incident beam and it will be detected by the back scattering (bs) detector (celia et al., 2009). this equipment can detect destabilisation by creaming before it is apparent to the human eye. emulsion destabilisation was investigated utilising profiles of transmission (t) and backscattering (bs) by scanning the sample of emulsion at a wavelength of 880 nm every 5 minutes for 1 hour at 60 °c. it analyses all variances in each sample and generates a unique number that indicates a specific sample's destabilization. turbisoft lab can be utilised to compute the turbiscan stability index (tsi) and analyse any quantity of samples. this will provide an analysis of the sample's stability. this coefficient, tsi is calculated as follows (zheng et al., 2018; zhu et al., 2015): 𝑇𝑢𝑟𝑏𝑖𝑠𝑐𝑎𝑛 𝑠𝑡𝑎𝑏𝑖𝑙𝑖𝑡𝑦 𝑖𝑛𝑑𝑒𝑥, 𝑇𝑆𝐼 = √ ∑ (𝑥𝑖 − 𝑥𝑏𝑠 ) 2𝑛 𝑖=1 𝑛 − 1 (4) where n is the scans number, 𝒙𝒊 is the mean backscattering measurement for every minute and 𝒙𝒃𝒔 is the average value of 𝒙𝒊. 4. result and discussion 4.1 emulsion characterization the microscopy image of the prepared emulsion is shown in fig. 3. based on the observation, the continuous phase occupies most of the area which indicates that the phase with the smaller volume is the dispersed phase. therefore, o/w emulsions were formed based on the emulsion preparation procedure which involved mixing produced water and condensate in a volume ratio of 85:15. the surface charge of particle is linked to the zeta potential. large readings of z-potential (negative or positive) improve emulsion stability and signify difficulties in droplet coalescence, although z-potential is often ph-dependent, and other important parameters must be addressed for coalescence prediction (coca et al., 2011). this is a vital parameter for studying the chemistry taken place in evaluating whether an emulsion will remain stable in its intended environment. the prepared emulsion recorded a zeta potential measurement of -29.8 mv that represent a stable emulsion has formed. when the zeta potential in the range of +5 m to -5 mv, colloidal particles are quite unstable due to agglomeration and it is highly stable when the zeta potential reading is around -30 mv or more negative (schramm, 1992). a zerozeta potential implies that the conditions for flocculation of emulsion droplet are at optimum meaning it has a potential for easier emulsion separation. emulsions are classified as macro-, micro-, and nano-emulsions based on size of droplet and its stability (komaiko & mcclements, 2016). based on visual observation obtained under microscope, the average size of oil droplets ranges from 20 μm to 5 μm. this shows that the prepared emulsion is a macroemulsion which is also known as conventional emulsion. the typical droplet size of macro-emulsion ranges from 1 – 100 μm and it has a turbid optical property which is the same as the prepared emulsion. micro and nano-emulsions has a droplet size of 10 – 100 nm and < 200 nm respectively (aswathanarayan & vittal, 2019). macro-emulsions will lead to a separation of two-phase over time as it is thermodynamically unstable (yao et al., 2021). fig. 3–photography of prepared emulsion under microscope 4.2 impact of demulsifier on produced water turbidity the bottle test screening was conducted according to the experimental procedures on the prepared emulsion. the dosage of demulsifier used are 7 ppm, 10 ppm and 20 ppm. fig. 4 illustrate the results obtained from the experiment after the injection of chemicals and immersed in water bath for 15 minutes at 60 °c. the impact of demulsifier on the changes in the turbidity reading of the treated produced water sample was studied. the turbidity of the produced water is mainly caused by the presence of oil droplets dispersed in the produced water. the greater the turbidity reading, the greater the intensity of scattered light. as a result, clear water has a low turbidity value, indicating that there are less oil droplets suspended in the produced water. based on the results shown in table 4, demulsifier a showed no impact on the turbidity of the produced water as a constant 1000 ntu reading were recorded. as for demulsifier c, a slight change in the turbidity reading of 966 ntu recorded at a dosage of 10 ppm. the impact of demulsifier c is not significant as the reading of turbidity is still high. it can be said that the cationic polyamine and eo/po block copolymers demulsifer are ineffective in treating o/w emulsion of the gas condensate field. however, as compared to the blank sample, the demulsifiers d and b significantly reduced the turbidity reading of the treated sample. the addition of demulsifier b resulted in a constant decrement of turbidity reading as the dosage increased from 7ppm to 20ppm where the lowest reading of turbidity reading of 210 ntu at 20 ppm. a slight increment in the turbidity reading was recorded as the dosage increased to 30 ppm which is unfavourable. besides, at a dosage of 7ppm, demulsifier d had the lowest turbidity reading (181 ntu) with the least dosage of demulsifier. the reading of turbidity started to increase when the dosage of demulsifier was increased to 20 ppm where a turbidity measurement of 593 ntu was recorded. the significant reduction in turbidity reading of demulsifiers d is due to the highly active molecules of the demulsifier which can attach to the oil/water interface and lower the stability of dispersed oil droplets. at a dosage of 7 ppm, the adsorption behaviour of demulsifier d molecules on the oil/water interface was remarkable which resulted in a low turbidity reading. further increase of the dosage of demulsifier d has caused the turbidity reading to increase as the demulsifier d has reached the saturation or optimal point at 7 ppm. the molecules of demulsifier starts to form micelles due to aggregation when the demulsifier dosage exceeded the micelle concentration (cmc) which increased the turbidity of treated produced water sample (huang et al., 2019). the demulsification efficiency (de) of the demulsifiers were calculated based on eq. 1. based on the results, demulsifier d recorded the highest demulsifcation efficiency up to 82 % at a minimum dosage of demulsifier which is 7ppm. demulsifier b was able to achieve a demulsification efficiency of 79 % at a dosage of 20ppm. therefore, demulsifier d and demulsifier b were further optimized to treat the o/w emulsion of produced water from the gas condensate field. chemical dosage (ppm) type of demulsifer 0 7 10 20 30 turbidity (ntu) demulsifier a 1000 1000 1000 1000 1000 demulsifier b 1000 421 386 210 325 demulsifier c 1000 1000 966 1000 1000 demulsifier d 1000 181 194 593 756 table 4–turbidity result of various demulsifiers fig. 4–impact of demulsifier on the turbidity of treated produced water sample at 60 °c 4.3 development of demulsifier (db) formulation a unique demulsifier was formulated by incorporating demulsifier d with demulsifier b. the unique demulsifier is prepared by adding 10 ml of demulsifier d and 10 ml of demulsifier b into a tube. the mixture is then stirred at 1200 rpm for 10 minutes using barnstead thermolyne maxi mix ii vortex mixer as shown in fig.5. the unique demulsifier db was then used to conduct bottle test screening at dosage of 7ppm, 10ppm and 20 ppm for treating the o/w emulsion. fig. 6 illustrate the turbidity results obtained after addition of demulsifier db. according to the outcome of the testing, the newly formulated demulsifier db decreased the turbidity reading of treated produced water sample to 45 ntu which is lesser than results attained by the addition of demulsifier d alone (181 ntu). based on eq.2, the demulsification efficiency (de) of 96 % was attained at 7 ppm of demulsifier db. the water clarity of the produced water sample is much clearer after the addition of demulsifier db when compared with blank sample which is very turbid as shown in fig. 7. fig. 5preparation of demulsifier db using barnstead thermolyne maxi mix ii vortex mixer 1000 1000 1000 1000 10001000 421 386 210 325 1000 1000 966 1000 10001000 181 194 593 756 0 200 400 600 800 1000 1200 0 7 10 20 30 t u rb id ty ( n t u ) dosage of demulsifier (ppm) demulsifier a demulsifier b demulsifier c demulsifier d fig. 6–impact of demulsifier db on the turbidity of treated produced water sample at 60 °c fig. 7–produced water after the addition of demulsifier db 4.4 impact of demulsifier db on oil-in-water content (oiw) the oiw content of the treated produced water sample with demulsifier db were measured using td-500 td-500d handheld oil in water analyser and the results are shown in fig. 8. based on the results obtained, the blank sample without any addition of demulsifier recorded an oiw content of 1008.3ppm. at a dosage of 7ppm, oiw content reading of 97.1 ppm which is the lowest reading was obtained with demulsifier db. when the unique demulsifier db was applied, the results demonstrate a substantial drop in oiw content at an oil removal efficiency (ore) of 90%. as the dosage of demulsifier was increased after 7 ppm, the oiw content gradually increased. demulsifier db helps to neutralise the negatively charge oil droplets and reduce zeta potential, lowering repulsion and weakening the oil droplets stability. however, excessive amounts of demulsifier db may cause the flocs to become positively charged, preventing the production of big flocs from tiny ones. as a result, an excess of the demulsifier db impedes the oil removal from wastewater which can be seen by the increase of oiw content from 97.1 ppm to 200 ppm as the dosage increase to 20 ppm. therefore, the optimum dosage of demulsifer db is 7ppm to achieve the lowest reading of oiw content. the treated produced water sample is further validated with interfacial measurement and turbiscan analysis to show that the demulsifier db helps in the demulsification of o/w emulsion. 981.7 45.0 45.6 65.3 0.0 200.0 400.0 600.0 800.0 1000.0 1200.0 0 7 10 20 t u rb id ty ( n t u ) dosage of demulsifier (ppm) fig. 8–impact of demulsifier db on the oiw content of treated produced water sample at 60 °c 4.5 impact of demulsifier db on interfacial tension (ift) produced water was the aqueous phase and condensate was the drop phase in this ift analysis. the blank sample without additio n of chemical has a high ift value (24.98 mn/m) indicates that a steady emulsion is still present as shown in fig. 9. a high ift results indicates a highly stable emulsion (kumar & mandal, 2018). with the addition of demulsifier db, it can be seen that the newly formulated demulsifier was able to minimize the interfacial tension at oil/water interface. the interfacial tension between oil and water reduced significantly from 24.98 mn/m to 9.38 mn/m at demulsifier db dosage of 7ppm. demulsifiers can significantly lower interfacial tension, which weakens the oil droplets’ stability as the rigid film surrounding the oil droplets tends to breakdown readily. the oil droplet with the addition of demulsifier db has a smaller shape compared to the untreated sample as the demulsifier db neutralize the natural surfactant present on the oil droplet film. minimizing the droplets’ stability leads to the coalescence of oil droplets which leads to the separation of condensate and produced water (huang et al., 2019). demulsifier db was able to decrease the ift at the oil/water interface, leading to an increased separation rate of oil and water via enhanced flocculation and coalescence process. 4.6 demulsification analysis using turbiscan lab® expert in order to demonstrate how the emulsion ageing process influences the oil droplets, the sample can be be optically analysed by the turbiscan equipment. the turbiscan stability index (tsi), which is used to characterise physical stability, is determined by adding 1008.3 97.1 177.5 200 0.0 200.0 400.0 600.0 800.0 1000.0 1200.0 0 7 10 20 o il -i n -w a te r c o n te n t (p p m ) dosage of demulsifier (ppm) fig. 9–image of oil droplet without demulsifier db (a) and after the addition of demulsifier db dosage at 7ppm (b) (a) (b) changes in transmission (t) or backscattering (bs) of light over the course of several measurements as a function of sample height (paweł et al., 2020). the main advantages of tsi measurement are the ability to analyse opaque systems (such as crude oil emulsions) over a short period of time and the samples are undisturbed during tsi measurement from transmission/backscattering data as no dilution is required. tsi measurement has the advantages over several typical stability determination techniques, such as conductivity measurements, and ageing tests (xu et al., 2013). the tsi value will trend upward for any destabilization occurrence, including coalescence, creaming, sedimentation, flocculation, or ostwald ripening, because the back-scattered signal and the photon transport mean free route are inversely related (bs ≈ 1/√λ*) (acosta et al., 2020). in short, turbiscan stability index (tsi) measurements are utilized to determine how stable an emulsion is. based on fig. 10a and 10b, it can be observed that there is a rise in the slope and tsi value after the addition of demulsifier db compared to blank sample. over the period of 30 minutes, the slope of the treated sample with demulsifier db showed a rapid increase which indicates a steady increase of tsi values. the rate of slope change indicates how quickly separation occurs in which higher instability is implied by higher tsi value. (liu et al., 2011; mengual, 1999). compared to tsi value of blank sample without the addition of demulsifier db which is 1.6, the treated produced water sample with 7 ppm of demulsifier db resulted in a significant increase of tsi value of 8 as shown in table 5. the emulsion’s stability is considered weaker when the tsi value is high (li et al., 2019). this shows that the demulsifier db helps in the demulsification of the emulsion efficiently in a short period of time compared to the blank sample without any chemical additives. dosage of demulsifier db (ppm) tsi value 0 1.6 7 8 table 5–turbiscan analysis of db demulsifier conducted at 60 °c (a) (b) fig. 10–comparison of turbiscan analysis of sample without demulsifier db (a) and after the addition of demulsifier db dosage at 7ppm (b) conducted at 60 °c 4.7 demulsification mechanism of o/w emulsion using mixed surfactant system generally, chemical demulsification, as performed in this study, is a process in which an optimum amount of demulsifier is added to emulsions and the emulsion is rapidly agitated to separate the oil and water. ostwald ripening happens when the dispersed phase which is the oil droplets may readily diffuse in a continuous phase which is the water to come together for flocculation. the demulsifier molecules of a mixed surfactant solution will be absorbed to the oil droplets’ surface, thus lowering interfacial tension and rupturing interfacial film strength which holds the oil in droplets form. this will indirectly minimize the oil droplets’ stability and allow the oil droplets to accumulate. the accumulation of oil droplets is referred to as the flocculation process in which the oil droplets cluster together in the water continuous phase. this causes the droplets of oil to coalesce and form larger droplets. finally, depending on the phase density of emulsion's dispersed, the creaming or sedimentation processes take place when the denser phase settles down below the less dense phase (abdulredha et al., 2020). since combinations of various surfactant types typically demonstrate synergism in their impact on the characteristics of the system, utilising a mixed surfactant system is more effective than using conventional method of single surfactant (holland & rubingh, 1992). mixed surfactant demulsifiers have been shown to be more effective than single-surfactant demulsifiers in breaking oil-water emulsions. by combining different surfactants with different mechanisms of action, mixed surfactant demulsifiers can more effectively reduce the interfacial tension, provide steric hindrance, and neutralize electrostatic repulsion between the droplets (kronberg et al., 2014). besides, mixed surfactant demulsifiers can improve the stability of the demulsification process by providing a broader range of surface activity and surface coverage (kronberg et al., 2014). this leads to a more complete destabilization of the emulsion, resulting in faster and more efficient separation of the oil and water phases. after analysing the experimental data, considerable impacts at interfaces with the solution can be noticed even at low concentrations of mixed surfactants in the emulsion sample. the most noticeable result is a reduction in interfacial tension caused by adsorption of surfactant molecules at oil droplets interface, as seen in fig. 11. fig. 11–occurrence in a mixed surfactant system of two surfactant types 5. conclusion the o/w emulsion of gas condensate field was treated through demulsification in the present study. various types of demulsifiers were studied by bottle test and based on the study, the demulsifiers d and b reduced turbidity substantially higher when in comparison with demulsifier a and c. therefore, an unique demulsifier db was formulated at an optimal weight percentage ratio of d/b. the unique demulsifier db exhibited the highest efficiency in removing the dispersed oil droplets of the produced water compared to single demulsifier use. the demulsifier db was able to neutralize the charge around the dispersed oil droplets leading to coalesces of oil droplets and reduced the oiw content in the produced water. at a temperature of 60 °c, the optimum dosage of demulsifier db was determined at 7 ppm. an oil removal efficiency (ore) of 90% was achieved where the oiw content of the treated produced water sample reduced from 1008.3 ppm to 97.1 ppm under 15 minutes. moreover, the ift and turbiscan analysis exhibited that the utilization of demulsifier db further validates the results obtained for the oiw content measurements in which the demulsifier helps in minimizing the interfacial tension at oil/water interface and reduce the stability of the produced water sample for the separation of water and condensate to occur. this shows that the resin alkoxylate (demulsifier b) and cationic surfactants (demulsifier d) work together well to treat the o/w emulsion from gas condensate field. statements and declarations on behalf of all authors, the corresponding author states that there is no conflict of interest. nomenclature 𝐷𝑒 [%] demulsification effieciency 𝑇𝑜 [ntu] intial turbidity 𝑇 [ntu] final turbidity 𝑂𝑅𝑒 [%] oil removal efficency 𝑂𝑖𝑊𝑜 [ppm] initial oil-in-water content 𝑂𝑖𝑊 [ppm] final oil-in-water content suband superscripts o initial e efficiency abbreviation oiw oil-in-water content ift interfacial tension w/o water-in-oil o/w oil-in-water w/o/w water-oil-in-water tsi turbiscan stability index hlb hydrophilic–lipophilic balance references abdulredha, m. m., siti aslina, h., & luqman, c. a. 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(2015). development of stable water-in-oil emulsions using polyglycerol polyricinoleate and whey protein isolate and the impact on the quality of bittern-tofu. journal of dispersion science and technology, 36(11), 1548–1555. https://doi.org/10.1080/01932691.2014.964360 substantia. an international journal of the history of chemistry 3(2) suppl. 2: 55-67, 2019 firenze university press www.fupress.com/substantia citation: f. fitzroy (2019) a green new deal: the economic benefits of energy transition. substantia 3(2) suppl. 2: 55-67. doi: 10.13128/substantia-276 copyright: © 2019 f. fitzroy. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-276 a green new deal: the economic benefits of energy transition felix fitzroy school of economics and finance, university of st. andrews, fife, uk, ky16 9al e-mail: frf@st-andrews.ac.uk abstract. after explaining the current climate emergency, this survey article summarises financial cost estimates for transition to zero carbon by 2050, which even in the medium term, neglecting catastrophic climate collapse, are much less than the cost of ‘business as usual’ (bau). standard economic modelling of continued gdp growth with only minor costs of climate change and limited mitigation investment which still guides policy is shown to be completely unrealistic, simply ignoring current climate science, health costs and the welfare economics of economic growth. the global health benefits from phasing out fossil fuels will also exceed the costs of transition to renewable energy in the medium term, and these co-benefits are widely neglected. the major investment and fiscal expansion required for rapid transition will help to attain full employment, further reducing the net financial cost of the policies necessary for energy transition to avoid catastrophic climate change, policies often summarised as a ‘green new deal’. keywords. climate catastrophe, energy transition, renewable energy, fossil fuel, pollution. 1. introduction atmospheric co2 concentrations have been rising steadily, with a 23 ppm increase p.a., reaching a record 415 ppm in may 2019 (the highest for about 3 million years), although estimated carbon emissions from fossil fuels (ff) remained roughly constant for 3 years, mainly due to the substitution of cleaner gas for coal, 1 before increasing again in 2017. emissions of greenhouse gases from land use change and biomass burning are more difficult to estimate and probably account for the steady growth of atmospheric co2. 1 uk emissions in 2017 were 42% below 1990 levels due mainly to replacing coal by gas, according to official accounts, but neglecting the outsourcing of ‘dirty’ production to china and other developing countries, as well aviation and shipping. including these factors means that consumption-related emissions have declined by only about 10%, as pointed out by climate activist greta thunberg (carbon brief, 2019; anderson, 2019). china remains the world’s largest emitter and user of coal by a wide margin, as well as being the largest investor in re, and though coal production seems to have peaked, there is no sign yet of the rapid reduction needed to reduce even appalling local pollution with health costs from 9 – 13 % of gdp , let alone mitigate climate change (lse, 2018). 56 felix fitzroy the really bad news is that the arctic is warming twice as fast as the temperate zones, under the influence of positive feedbacks – albedo effects as ice and snow cover recede, and growing methane emissions from rapidly thawing permafrost – thus threatening eventually irreversible, runaway warming without drastic and rapid mitigating action. otherwise the result could be a largely uninhabitable, ‘hothouse earth’ with much higher temperatures than previously predicted, or experienced for millions of years, and resulting collapse of current civilization (steffen et al, 2018; berners-lee, 2019; mckibben, 2019; wallace-wells, 2019). ‘the only rational response to the  scientific evidence  on climate change, is to declare a global emergency – to mobilise all of society to do whatever it takes to fix it’ (paul gilding, 2018). mean global temperature is already more than 1 degree c above the pre-industrial level, and ‘… paleoclimatology has revealed that in the longer run each 1°c of warming will result in 10 to 20 metres of sea-level rise and that the current level of greenhouse gases is sufficient to produce warming that would likely end human civilisation as we know it…’ (spratt, 2019) yet the latest, 2018 report by the intergovernmental panel on climate change, global warming of 1.5°c: an ipcc special report, warns of serious consequences from exceeding 1.5°c, but neglects the major threats already posed by current warming, not to mention further warming triggered by arctic methane release and other positive feedback effects. loss of arctic and antarctic ice has been accelerating in recent years, and only a rapid drawdown of existing atmospheric co2 has a chance of averting major, long term sea level rise. lack of policy recommendations follows the conservative tradition of official un reports, which have all failed to call for the required emergency, wwii-scale mobilisation of investment to phase out ff as rapidly as technically possible (spratt, 2019). since the cost of energy transition varies considerably between nations, and there are also incentives for national governments to ‘free-ride’ or rely on mitigation by others, strong international agreements for cost sharing and meaningful sanctions are essential to accelerate the process. such agreements would have to go far beyond the ineffective united nations framework convention on climate change (unfccc) paris agreement, or the badly designed eu emissions trading system, neither of which have had much success in facilitating energy transition. ironically, swedish schoolgirl greta thunberg’s fridays for future, school strike campaign and other movements such as extinction rebellion, have done much more to focus public opinion on the climate emergency in many countries, with a widespread upsurge in green party votes and a first commitment by new eu commission president ursula von der leyen to attain carbon neutrality by 2050. to avoid widespread collapse of water supplies and agriculture in populous regions, which is most likely to be the first major climate related disaster if emergency policies are not rapidly implemented, other measures are also needed. reducing food waste, deforestation and meat consumption, and transition from industrial factory farming to sustainable eco-agriculture, are all urgently required for food security, which includes halting the parallel emergency of accelerating biodiversity loss (sdg, 2019).2 the 1.5°c-target is arbitrary, and evolving temperatures cannot be predicted at all precisely from actual emissions paths and policy measures. the target is likely to be exceeded, at least temporarily, even if all emissions were suddenly stopped, due to the thermal inertia of the large ocean mass, which takes a long time to reach equilibrium temperature with relatively slow circulation from the surface down to the depths. eliminating aerosol air pollution from biomass and ff burning, which has a substantial cooling effect, would actually accelerate warming in the short run, and require further drawdown of atmospheric co2. much faster warming of the critical arctic region also reduces the relevance of mean global temperatures. a co2 concentration of 350 ppm is considered to be the maximum ‘safe’ level and is thus a much more relevant target (though the pre-industrial level was only 280 ppm), since the current warming trend began at about this level in the 1970s. nearly half of current emissions are sequestered by natural sinks. however, ending deforestation, and additional carbon sequestration through reforestation and a switch from industrial monocultures, which promote soil carbon loss, to regenerative eco-agriculture and agro-forestry will be needed, in addition to rapid transition from ff to re, to reduce the atmospheric carbon concentration to 350 ppm by 2050. industrial hemp can sequester 10 tonnes of carbon per hectare per year, in poor soil with little water and no need for fertilizers, so is much more effective than slow growing tree plantation. (hawken, 2018; rumpel et al, 2018). these policies have already been shown to be highly cost-effective at local levels, and are much more promising than carbon capture and storage (ccs), which has proved to be very costly and ineffective in several discontinued tri2 whether political response will be rapid enough to avert disaster remains an open question, with plenty of grounds for pessimistic scepticism in spite of a surge of ‘green votes’ in the 2019 european parliament elections, but with strong right wing populist support forclimate science denial as well. 57a green new deal: the economic benefits of energy transition als in the us (grandia, 2018). sgouridis et al (2019) show in detail that re investment is much more cost-effective that any likely development of ccs, though of course technological breakthroughs cannot be ruled out. it is ironic that the dangers of climate change had already been clearly identified by 1989, when pioneering scientist james hansen testified before the us congress, and the first ipcc had been constituted, with little progress over the intervening 30 years, or indeed at the latest, december 2018 cop24 conference at katowice (revkin, 2018). new research by yu et al (2018) provides strong evidence that 1.5°c of average warming will be reached by about 2030 on present trends or ‘business as usual’ (bau), 10 years earlier than predicted by the 2018 ipcc special report. one estimated global carbon budget of cumulative emissions for not exceeding 1.5°c will exhausted by 2020 under bau, underlining the urgency of radical mitigation and ‘drawdown’ policies for which only the political will is lacking (hawken, 2018; hickel, 2017). the good news is that solar and wind power costs have been declining much faster than only recently predicted, to reach or fall below parity with ff generation costs in favourable locations, but this development is rather overwhelmed by the still limited share of wind and solar (ws) in global primary energy consumption (only about 1.5%, though estimates vary), and totally inadequate investment. nuclear remains the most expensive new power source, but closing down existing nuclear power for purely party-political reasons, while only planning to phase out heavily subsidised coal by 2038, as in germany’s expensive but ineffective ‘energiewende’, will remain one of chancellor angela merkel’s worst legacies (der spiegel, 2019). estimated ws capacity is just over 1 trillion watts (tw), currently growing at about 17% p.a. with investment under $300 billion pa (and recently declining in monetary terms). jacobson et al (2017) estimate about 50 tw of new wind, water and solar (wws) capacity would be needed by mid-century for a zero carbon economy, which would thus require an average expansion of about 1.6 tw p.a. over the next 30 years to attain, more than 10 times the current annual ws3 addition! of course, this could only be achievable with initially still higher growth rates, underlining the catastrophic inadequacy of current ‘business as usual’ climate and energy policy (bau), which will generate only a slow decline of the ff primary energy share of about 80%, as well as a rapid overrun of the ‘safe’ global carbon budget, and a probable ‘hothouse earth’. sgouridis et al (2016) investigated the dynamics of a complete transition to renew3 most of the new capacity would be ws, since there is only limited scope for expanding (mainly small scale) hydro power. able energy including storage from a net energy perspective while staying within the carbon budget. to achieve this, installation rates would peak at around 8tw p.a. in 2035, and emissions could be cut by more than half by 2030 with major energy savings and parallel ‘drawdown’ of atmospheric carbon through eco-agriculture and industrial hemp plantation. jacobson et al (2017, 2018, 2019) analyse several technically feasible models of decarbonisation. one estimate gives a total gross investment cost for transition by 2050, at about $125 trillion or an average annual cost of just over $4 trillion,4 which, as we argue below, represents a less demanding policy shift for the rich countries that will have to bear most of the cost than the wwii mobilisation which finally ended the great depression in the us (mckibben, 2015; tooze, 2019). this estimate is quite conservative, neglecting likely major further improvements in ws or any other, new re technologies, but does assume large scale efficiency gains and savings through electrification. these numbers are of course only a rough guide to gross costs, and neglect the extensive co-benefits of transition discussed below. hawken (2018) provides detailed discussion of many different technologies to ‘drawdown’ carbon and transition to re, with similar overall conclusions. a comprehensive new report by ram et al (2019) estimates a much lower cost of global transition to 100% re by 2050. behavioural changes such as much higher cycle and public transport shares in urban areas, less flying, meat consumption, deforestation and material use in an economy based on repair and recycling rather than obsolescence and disposal, will also be necessary to ensure rapid enough transition and avoid shortages of crucial materials. in the next section 2, we offer a brief account of traditional neglect and fundamental misunderstanding of the climate emergency by prominent economists. in section 3 we then summarise the evidence that mobilising society for energy transition would yield enormous medium term financial, health and employment ‘co-benefits’ that would more than pay for transition, in addition to averting catastrophic climate change as the ultimate long term ‘bonus’. section 4 explains the macroeconomic and distributional benefits of the ‘green new deal’ (gnd) or mobilisation for energy transition, all the more urgent after decades of neoliberal austerity. a detailed discussion of the main policies for a gnd follows in section 5, while section 6 relates these policies to the ‘growth or de-growth’ debate. conclusions are summarised in a final section 7. 4 presumably in constant, current dollars, roughly 5% of current global gdp. 58 felix fitzroy 2. traditional economics of climate change and energy transition long after the threats of unmitigated climate change, pollution and environmental destruction had been recognised by environmentalists and scientists, these issues were ignored by most economists. the 2018 nobel laureate economist, william nordhaus, was an exception who did make early attempts to quantify the ‘optimal’ carbon tax with the help of long-term models of gdp growth and possible climate damage known as ‘integrated assessment models’ (iams), but nevertheless assumed growth to be much more important than climate damage and essentially unlimited.5 future damages are reduced to trivial present values using unreasonably high discount rates, and future generations are assumed to be so much richer that they can easily cope with climate change! his latest attempt (nordhaus, 2017), estimates the welfare maximising ‘social cost of carbon’ or optimal tax rate at $31 per ton, rising by about 3% p.a., which would only slightly reduce the bau emissions path. he predicts ‘mean warming of 3.1°c for an equilibrium co2 doubling’ by 2100, without considering the methane and other feedbacks which would almost certainly generate much higher temperatures and a largely uninhabitable ‘hothouse earth’ under such a policy. with average annual real per capita growth predicted to be about 2%, mainly due to exogenous technological change, climate damage is claimed to be only about 2% of gdp by 2100, though much of the world’s population might not survive this bau programme! all these model predictions are decisively contradicted by the climate science which is never mentioned by nordhaus. it is now clear, as steffen et al (2018) and others have shown, that even the old ‘political’ target of 2°c average warming, let alone 3.1°c, would decimate global food production, and trigger irreversible methane and other feedbacks to leave much of the world uninhabitable in the long run, with warming ultimately far beyond 3.1°c. ‘what is more, nordhaus reasons that the sectors most vulnerable to global warming—agricultural, forestry, and fishing—contribute relatively little to global gdp, only about 4 percent. so even if the entire global agricultural system were to collapse in the future, the costs, in terms of world gdp, would be minimal’ (hickel, 2018). on this logic, billions of the world’s poorest inhabitants contribute relatively little to global gdp, so their death from starvation would also hardly mat5 bardi (2018, 2011) discusses nordhaus’s repeated failure to understand ‘complex systems’ of ecology and economy, as modelled in the club of rome’s limits to growth and various updates (meadows and randers, 2004). ter. furthermore, water and products of the vulnerable sectors are universally under-priced, neglecting externalities and sustainability, and encouraging overuse and exploitation. in addition to the moral repugnance of these conclusions, they are also based on elementary economic errors. if agriculture was devastated by climate change, most of the rest of the global economy would collapse, and food prices would explode, so while billions of the poorest inhabitants would starve, what was left of the agricultural sector would actually dominate global gdp because inflated spending on food would exhaust most budgets even in rich countries! this is likely to be the first really major global impact of climate change, long before rising sea levels have flooded many of the world’s biggest cities, because modern industrial agriculture in general and many of the most important food growing areas in china, india, and africa, as well as the wheat belt of the north american great plains are particularly vulnerable to increasing aridity, falling water tables, rising temperature and extreme weather events as climate change progresses. a major reduction of meat consumption and food waste could feed the current population with a much smaller total output, as well as greatly reducing ff use and emissions, and providing healthier diets, but in addition, large scale conversion to regenerative ecoagriculture, and ending deforestation are necessary for long term sustainability. this incorporates mixed farming, low-till cover-cropping and controlled animal grazing, to reverse accelerating soil carbon loss, degradation and desertification under current destructive and unhealthy industrial agriculture, with its reliance on intensive factory farming and large-scale, vulnerable monocultures, to sequester a substantial share of carbon emissions (holt-jimenez, 2019; hawken, 2018; rumpel et al, 2018; fitzroy and papyrakis, 2016; montgomery, 2016). while nordhaus’s ideas seem to have provided academic respectability for policy makers’ obsession with growth and neglect of food security and climate mitigation measures, other prominent economists,6 never cited by nordhaus (2017), have clearly recognised the possibility of catastrophic climate change and the impossibility of any meaningful cost-benefit analysis of, for example, the destruction of much of human and other terres6 see stern (2015), and wagner and weitzman (2016). these studies as well as the latest climate and environmental science and the threat to global food production are all ignored by nordhaus (2017), although they clearly show that all his central assumptions are completely unrealistic. however these and most other economists have neglected the cobenefits of transition discussed below. 59a green new deal: the economic benefits of energy transition trial life, so that policy priority should just be the fastest politically ‘feasible’ transition to zero carbon. such a policy will minimise the expected cost of ongoing climate change as well as the risk of more distant disastrous outcomes. in this respect, these economists follow the lead of climate scientists, but like nordhaus, neglect the much earlier, pioneering work of ecological economists such as daly (1973, 1992) and environmentalists such as mckibben (1989), who have long recognised that drastic reduction of emissions with a mobilisation of resources almost comparable to that of wwii (but lasting for decades), represents the only safe and viable climate policy, which would also provide many co-benefits. indeed, full employment after the great depression was only restored by war time mobilisation in the us. as gilding (2018) remarks, ‘the only rational response …is to do whatever it takes’, which must again mean the fastest ‘feasible’ transition, where the constraint is how rapidly behavioural changes such as less driving, flying and meat-eating can be implemented in the wider population with help of ‘nudges’ and persuasion in a democratic framework. what is not widely realised, due to the well-funded efforts of the ff lobby to exaggerate the costs of transition to re, as well as denying the costs of climate change, is just how small – actually negative – the real overall net costs of transition are likely to be, though of course the ff sector will be the main loser with all their ‘stranded assets’ left in the ground.7 3. the cost-reducing and health-improving co-benefits of energy transition in addition to the obvious benefit of saving the natural world and human civilization from irreversible and catastrophic climate change in the long run, transition to re offers three additional major co-benefits in the medium term (hawken, 2018; fitzroy and papyrakis, 2016; smith, 2013). the most obvious is perhaps the reduction of expenditure on ffs as they are replaced by re, thus reducing the net cost of transition. the iea (2019) estimates world ff energy investment of about $1.5 trillion in 2018, about 2% of global gdp, so the average annual total direct cost of bau could be nearly 7 see mcglade and ekins, 2014; rogeli et al, 2015. an alternative is compensation or a public sector buyout of ff assets in order to reduce opposition with a pareto improvement for all (broome, 2018; smith, 2019), not an appealing policy after decades of deception and disinformation, a campaign which was clearly contradicted by exxonmobil’s own early research results. smith (2019) emphasises that displaced ffaffected workers do need to be given alternative employment and training. half of the average annual $4 trillion cost of complete transition in the next 30 years, following jacobson et al (2017). they also estimate that nearly 13% of total enduse energy world-wide is used to produce the refined ff and uranium that provide most of the current energy supply. all ff costs are likely to rise substantially as the most easily exploited resources are declining and reliance on unconventional, ‘tight’ oil and gas and costly fracking increases. total ff cost savings will depend on the precise path of re expansion, but should be substantial, at least in the later stages, though rapidly expanding re and efficiency investment will initially raise ff demand which is a necessary component of what was termed the sower’s way – the use of ff for building the re infrastructure (bardi, et al, 2016). the second co-benefit or cost saving has recently been highlighted by the imf, where coady et al (2017) estimate the current global costs of air pollution from ff, including about 4 million annual fatalities from outdoor air pollution, at around $4 trillion in 2015, roughly equal to the projected average cost of transition! however burnet et al (2018) and lelieveld et al (2019) find 9 million – twice as many – fatalities p.a. from ambient (outdoor) fine particulate, or pm2.5, and ozone pollution, with much improved data and estimates, greater than the 7 million annual deaths from smoking found by the who. indoor air pollution from cooking with solid fuels and traditional stoves are a major additional source of mortality and morbidity in developing countries, but with less quantitative data. all this obviously implies much higher costs, at least double the imf estimate, depending on how the morbidity and mortality of poor individuals is evaluated. over 90% of the fatalities are in poor countries, which is why the imputed value of a statistical life (vsl) of about $1 million, or less with morbidity costs included, is only a small fraction of the vsl in advanced economies. thus following the new studies, $10 trillion or about 13% of global annual gdp would seem to be a very conservative, rough estimate of annual health and well-being costs from ff pollution.8 these costs have two components – the direct, financial or resource costs of lost output, disability and extra costs of care and medical services, and the intan8 most of the fatalities are among vulnerable individuals with a much lower life expectancy than the average, but this is often the result of a long history of exposure. pollution also directly reduces happiness of all who are affected, as well as the future health, life expectancy and iq of children who suffer exposure. huge health costs from indoor air pollution due to biomass burning for cooking in developing countries should be added, and could also be largely eliminated with cheap solar energy and clean cookers, adding substantially to the benefits from transition to renewable energy. scovronick et al (2019) estimate that ‘the global health benefits from climate policy could reach trillions of dollars annually…’. 60 felix fitzroy gible, welfare costs of premature mortality and morbidity, as well as directly reduced life satisfaction for most people affected. these latter costs are usually estimated as the vsl, and the value of qalys – quality adjusted life years – by willingness to pay for a marginal reduction in the probability of fatality or morbidity, or for a cleaner environment, which in turn implies dependence on income and hence large differences between rich and poor countries, an ethically dubious distinction. we do not have separate estimates of the intangible and tangible components, but even just the latter are likely to exceed the approximately $4 trillion estimated average annual cost of complete transition to a zero carbon economy by 2050. coady et al. (2017) refer to the total imputed cost as ‘post-tax subsidies’, which are much greater than direct or pre-tax financial ff subsidies of less than $1 trillion p.a. economists usually refer to external costs of pollution rather than subsidies, but not accounting for these costs with an appropriate ‘pigouvian’ tax on ff does amount to an implicit subsidy which has substantially increased ff consumption and consequent environmental and health damage. pollution costs have been steadily increasing under bau, and some health damage from pollution will continue to emerge after the pollution is reduced or eliminated. nevertheless, avoiding a growing share of at least $(2+10 = 12) trillion direct and indirect or external annual costs of ff as re grows and replaces ff suggests a very approximate average annual saving of half the total, or $6 trillion.9 this is much larger than the jacobson et al (2017) estimate of annual average cost of transition, leaving a huge co-benefit in addition to averting irreversible and catastrophic climate change as the ultimate ‘bonus’. of course, health and other costs of pollution would increase rapidly under continued bau, well beyond 2050, until the industrial global economy collapsed under the impact of climate change, and most of the global population died, so these ‘estimates’ are very conservative, rough guides to orders of magnitude. furthermore, the health benefits from a zero carbon economy would continue indefinitely after 2050, so even in terms of discounted present values, the surplus of cost savings or benefits over the actual expected costs of transition to re would be still further increased, a huge reward over and above the essentially incalculable benefit from averting catastrophic climate change.10 9 summarises for simplicity a linear increase of savings from initially 0% to finally 100% of projected total ff costs of at least $14 trillion p.a. as noted above, some of the health costs and hence savings are intangible. 10 hawken (2018) summarises of savings from complete decarbonisation by 2050 of $74 trillion with a very different methodology, but 4. green new deal various co-benefits of ‘steady state economics’ and energy transition have long been emphasized by environmentalists such as mckibben (2016, 2006, 1989) and progressive economists, such as daly (1973, 1977), and recently by the green new deal group and new economics foundation in their ‘green new deal’ proposal (nef, 2008; murphy and hines, 2019).11 after the financial crash of 2007/8, ‘quantitative easing’ (qe) – the purchase of government bonds by central banks – helped to fuel an asset price boom, making mainly the rich even richer and contributing to growing inequality, with little effect on employment. austerity then inflicted huge losses on the majority, as most wages have stagnated and welfare spending cut, particularly in the uk and us, while unand particularly under-employment remain serious problems everywhere (storm, 2017; blanchflower, 2019). the keynesian alternative would have been a major fiscal expansion to fund labour-intensive investment in infrastructure and energy transition in a green new deal, creating jobs for genuine full employment, and a start to averting irreversible climate change. ecb expenditure of €2.4 trillion on qe, ending in 2018, was a gigantic missed opportunity, as were similar qe programmes in the uk and us (tooze, 2019). the keynesian ‘multiplier’ effect results as increasing employment reduces the need for welfare and unemployment benefit payments, so the formerly unemployed will start to pay taxes, while their greater spending will in turn stimulate the rest of the economy and further raise tax receipts. thus some of the original extra public expenditure will be recouped, further reducing the net cost of re and other public investment before the economy reaches full employment, with little danger of increasing inflation in the current environment of very low interest rates and inflation. prospects of ‘secular stagnation’ advanced by prominent economists strengthen the case for further fiscal stimulus (eggertsson et al, 2018; tily, 2017). launching a programme of rapidly expanding re and related investment will require initially increasing without distinguishing between pecuniary and non-pecuniary components, and using the outdated coady et al (2017) health cost estimates, which could explain why the total is somewhat lower than the estimates reported here. it is not clear whether the total represents final accumulated savings or a present discounted value. however the similar orders of magnitude from such disparate approaches are quite reassuring. 11 the idea is receiving increasing attention from progressive democrats such as alexandria ocasio-cortez, the uk labour party and green party supporters in the us and europe, though neoliberal media disinformation and neglect have so far hindered any broader public understanding or acceptance (roberts, 2018; klein, 2019; rifkin, 2019). 61a green new deal: the economic benefits of energy transition public expenditure and funding requirements before the multiplier effect begins to generate rising revenue and reduce welfare claims. while the dysfunctional euro system raises serious legal obstacles to such necessary policies (mody, 2018), there are no real problems for countries with sovereign currencies such as the uk, where central banks can simply create necessary funds without causing inflation, as long there are underutilised resources, and governments can borrow or raise taxes on high earners. as tooze (2019) puts it, ‘a decade after the world bailed out finance, it’s time for finance to bail out the world’. however, conservatives obsessed with the neoliberal ideology of smaller government, lower taxes for the rich, less welfare for the ‘undeserving’ poor, and ‘debt fetishism’, have imposed austerity in the uk and much of the eu since 2010 at enormous cost in both human and economic terms. they continue to oppose fiscal expansion, neglect infrastructure and underfund the nhs and care services, while completely failing to understand the urgency of climate change mitigation (cooper and whyte, 2017). and more broadly, the ad hoc maastricht criteria for eurozone members place all emphasis on debt and budget deficits, ignoring employment, poverty or any environmental/cc targets. the official uk climate change committee (ccc, 2019) has published detailed plans for zero carbon by 2050, now also an officially legislated target, but there are currently no signs of needed policies. conservatives in the us including most of the republicans in congress and the trump administration generally deny basic climate science12 (as well as modern economics and even evolution), as do vladimir putin in russia and brazil’s new president jair bolsonaro, so the political prospects for rapid implementation of serious climate policy even in europe, let alone in other major polluters, are still extremely dim. china leads in re investment but also in emissions and coal consumption by a wide margin, and while coal use may have peaked, appalling pollution problems remain, and the urgently needed, rapid reduction of coal powered generation has not yet been addressed, while china continues to support new coal power in many developing countries. 5. policies for energy transition the co-benefits outlined above are all medium to long term, and so major additional initial expenditure remains necessary. economists agree that substantial and rising carbon taxes should be part of any climate 12 even those who claim to accept the evidence for climate change generally still deny the need for urgent policy measures to reduce ff use. policy, but to gain public acceptance and avoid adverse distributional effects, at least some of the revenue should be returned, either as an equal per capita ‘dividend’ to all citizens as part of a universal basic income, or targeted to the most disadvantaged. while redistributive in aggregate because the rich generally use more ffcarbon per head than the poor,13 there are always some low income households with a high ff consumption, e.g.in rural areas, who would need additional compensation (boyce, 2018; stiglitz and stern, 2017). subsidised electric cars for low income individuals with long commutes and lacking access to public transport would have obvious benefits to mitigate the distributional impact of a carbon tax, as would the expansion of low cost or free public transport (as recently introduced in luxembourg). banning most cars from cities would greatly facilitate cycling, socialising and public transport with major health and welfare benefits, and be much more effective than current plans just to replace petrol and diesel cars with still very expensive e-cars, or indeed with any motorised individual transport. extensive and sometimes violent, ‘gilet jaunes’ protests erupted in france in late 2018 in opposition to rising fuel taxes, initially announced without any compensation or redistribution of revenues, thus illustrating the importance of distributional equity, and finally forcing the macron government into cancelling the fuel tax hike and several neoliberal policies which also reduced the incomes of low earners. as mehling (2018) explains, subsidies for re are also needed to accelerate development and gain broad acceptance, and higher taxes which impact low income households need to include appropriate compensation, in contrast to purely redistributive taxes on high earners, which should then be used to benefit the poorer majority of the population. under such appropriate conditions there is actually widespread support for a global carbon tax (carattini et al, 2019). unfortunately some commentators such as martin wolf in the financial times (5 nov, 2019) claim without evidence that large scale public investment in mitigation implies abandoning markets in favour of a ‘planned economy’ with disastrous effects. he fails to understand that it is far too late to rely exclusively on carbon taxation. to alleviate the inevitable disruptions of transition to re, as well as problems already being caused by the growth of non-standard and precarious employment 13 in the us, the top 10% of the income distribution emit over 4 times as much carbon per head as the bottom 10%, and globally they are responsible for about half of total emissions. however boyce (2018) shows that a $200 / t co2 us fee-and-dividend would leave 12% of the lowest income quintile, and 23% of the 2nd quintile worse off, so the need for additional compensation is clear, some of which could come from a universal basic income. 62 felix fitzroy for many, a modest universal basic income for all citizens, combined with a public sector job offer or guarantee, seems to be the most effective policy to supplement existing and unco-ordinated, targeted welfare measures (fitzroy and jin, 2018) a carbon tax or ‘fee-and-dividend’ which is not too high to be disruptive initially, but rises on a preannounced path to ultimately capture the full external costs of ff use, and thus undo the existing implicit subsidies discussed above, should provide the appropriate incentives for the private sector to invest in energy saving and re. however direct government and central bank intervention, ‘green bonds’ and subsidies will surely be required for rapid change on the required scale, less than wwii mobilization when military spending peaked at 41% of gdp, but lasting for decades (tooze, 2019). in particular because the very fast growth of re capacity needed to achieve largely complete decarbonisation by mid-century will impose initially rising costs, supply-side bottlenecks and shortages. certainly to build the continental -scale smart grids and storage and backup facilities needed to ‘smooth’ the natural intermittency of local re production will require major public investment and international political coordination in europe and elsewhere. smith (2019) and others argue in detail that only ‘eco-socialism’ with public ownership of large corporations can manage rapid transition, though it is difficult to see why appropriate regulation and other policies cannot achieve the same goal. contrary to frequent claims, higher taxes are not necessary initially, though reducing growing inequality with more progressive, redistributive taxes on high incomes would have many political and welfare benefits, but obviously faces strong opposition. instead, as long as there are underutilised resources in the economy, sovereign governments and their central banks can create new money, or borrow without risk of generating inflation or default, to fund the vital and productive investment of a green new deal. as the additional expenditure is re-spent by the initial recipients and thus raises other incomes, this keynesian multiplier mechanism will increase government tax revenues and over time can offset much of the initial investment cost. the first stages of a massive expansion of re will also require additional ff energy, which may even require a temporary increase of ff production if energy saving elsewhere does not proceed fast enough. sgouridis et al (2016) have estimated that ff supplies should be adequate for transition with the growth of unconventional or ‘tight’ oil and gas, in spite of the decline in easily recoverable reserves and the ‘energy return on energy invested’ (eroei). the intermittency of ws is frequently claimed to be a major obstacle to complete decarbonisation. however jacobson et al (2017, 2018), breyer et al (2018), brown et al (2018) and ram et al (2017) have shown in detail that an appropriate combination of continental-scale smart grids, feasible storage technologies and closed cycle gas turbine backup generating capacity, using bio-gas or even natural gas, can smooth supply and solve the intermittency problem at a cost which is dwarfed by the value of the energy savings from almost complete electrification. since the back-up will only be required during very rare, extreme weather conditions persisting over large areas, the average annual emissions from use of natural gas during such events will be negligible. in europe, for example, the sunny mediterranean periphery would be optimal for solar, and could be linked to the windy north for night time wind power generation by a high voltage, direct current, ‘smart grid’ with very low transmission losses, and additional savings potential when coupled with smart metering and household appliances. an important but neglected point is that moving from ‘low’ to zero emissions is the most expensive phase of transition. particularly since existing natural sinks would be substantially augmented by adoption of eco-agriculture and large scale reforestation, a small, remaining share of flexible natural gas for power generation, as a backup to variable renewables, could greatly reduce storage and other costs and still allow a steady reduction in the stock of atmospheric co2 concentration to the target of 350 ppm. complete decarbonisation may thus be an unnecessarily ambitious and expensive goal, though the final trade-offs will need careful calculation and monitoring. the main priority must be the initially rapid reduction of emissions through energy saving and expansion of re while phasing out coal consumption, and cutting globaal emissions by at least half by 2030. 6. green growth, de-growth or both? there is a long standing debate about the feasibility of continuing (greener) gdp growth on the transition path to a zero carbon economy and subsequently, or whether radical reduction of currently wasteful and polluting production and consumption will be required, and if so, how the costs of such de-growth should be distributed (antal and van den bergh, 2017; jackson, 2018; semieniuk et al, 2018; schröder and storm, 2018). there does seem to be general agreement, at least among environmental economists, that complete decoupling of gdp growth from environmental damage is an illusion (ward et al, 2016). however, this debate sometimes diverts 63a green new deal: the economic benefits of energy transition attention away from the crucial supply-and-demand synergy of expanding re, replacing first coal, and then other ff power as rapidly as possible, and simultaneously reducing energy demand by investment in energy efficiency and saving. thus there is extensive scope to retrofit buildings for greater energy efficiency, and replacing ice vehicles with evs, including public transport, and bicycles.14 much of this activity is labour intensive, and under a green new deal full employment should be attainable, with rising incomes for the formerly unand-underemployed, and increasing public expenditure, so that gdp would certainly grow in the initial stage of transition. however this growth would be mainly in investment, though with some consumption growth for the newly employed and low income households who benefit from redistributive carbon fee-and-dividend payments and a universal basic income, as well as more progressive taxes on the rich. clearly developing countries need green growth to attain the sustainable development goals, but equally obviously, the developed economies cannot continue material growth indefinitely, with ever more and ever larger cars and houses which use many other scarce resources in addition to energy. indeed, radical conservation and savings policies will be needed, including repair and maintenance of durable goods instead of the ‘throwaway culture’ of planned obsolescence. in the long run the ‘levelized cost of electricity’ (lcoe),15 after transition to re is estimated to be lower than the bau lcoe largely powered by ffs in the many studies referenced above, but it will not be zero (though the marginal cost of re up to capacity limits is very low with no ff use). thus there will continue to be limits to the recycling of non-renewable resources, and hence to sustainable material (and population) growth. on the other hand, declining it costs facilitate the ‘weightless’ growth of human knowledge, though the resulting power of digital ‘natural monopolies’, the proliferation of ‘fake news’, and the potential for intrusive surveillance, abuse and addiction in digital social networks remain serious threats, still far from being effectively regulated (zuboff, 2019). though ignored by policy makers and academic gdp growth proponents such as nordhaus (2017) and friedman (2006), but emphasised by nobel laureate economist joseph stiglitz (2009; 2019), kubiszewski et 14 such policies have already dramatically improved the quality of urban air and life in cities such as copenhagen, freiburg, and, remarkably, in curitiba, brazil (fitzroy and papyrakis, 2016). 15 the net present value of the unit-cost of electricity over the lifetime of a generating asset, including both investment cost and operating cost, equal to the break-even average price. aghahosseini et al (2019) find that complete transition of power generation to re in the americas by 2030 would already reduce the lcoe compared to bau al (2013) and many others, it has long been known that gdp is a poor measure of welfare, and that ‘[c]hasing gdp growth results in lower living standards. better indicators are needed to capture well-being and sustainability.’ (stiglitz, 2009). since the pioneering work of easterlin (1974, 2013), a large and expanding body of survey evidence shows that subjective wellbeing, life satisfaction or happiness are unrelated to economic growth in the long run in developed economies, though short-term f luctuations are positively correlated. this is mainly because unemployment and loss of income are major causes of unhappiness, and also because relative income is an important determinant of happiness above the poverty level, which does not change when all incomes are growing simultaneously (kaiser and vendrik, 2018). though income is correlated with well-being in cross sections at any time, the effect is weak for income above the poverty level. the main determinants of happiness are satisfying work, health and family and social relationships, as well as environmental quality. even worse, growing inequality in recent decades has eroded both well-being for the majority who have not benefitted from economic growth, and the basic institutions of democracy (atkinson, 2015; dorling, 2017; stiglitz, 2013; wilkinson and pickett, 2010, 2018). in the uk, only the minority with higher education and earnings reported increasing life satisfaction over the last two decades, while in the us average happiness has declined since the 1970s, with greatest decline for the poor (fitzroy and nolan, 2018; graham, 2017). in an egalitarian society with minimal poverty and deprivation, technological progress can be used to reduce working time and improve work-life balance following practice in social democratic denmark and other nordic economies, which also regularly yield the highest life satisfaction or happiness rankings (gustavson, 2011; radcliff, 2013; lakey, 2016). in addition to transition to re, another, complementary, transition, from neoliberal obsession with gdp growth to priority for well-being and sustainability is urgently required (laurent, 2017). as jackson (2016) and many others have emphasised, ‘prosperity without (material) growth’ is then the only sustainable, long run alternative in advanced economies to currently prevailing ‘growth fetishism’ and environmental destruction, though of course knowledge should continue to grow, and poor countries still need to overcome poverty with aid for green growth. 7. conclusions concern about climate change is increasing in populations around the world as the effects become 64 felix fitzroy increasingly evident. however, the perception that complete transition to re would be inordinately expensive remains widespread, a perception which is not only the result of intensive ff lobbying and disinformation efforts. proponents of re remain preoccupied with the undoubtedly spectacular technical progress and falling costs of re, but have generally failed to make the economic case that rapid global energy transition under the necessary massive mobilisation with a green new deal would provide a financial and welfare bonanza. much of the world’s advanced economies remain mired in ‘secular stagnation’ a decade after the great recession, with high levels of underemployment and declining labour force participation, not captured in official unemployment statistics. at the start of wwii, the us was suffering from even worse problems from the legacy of the great depression in the early 1930s, with over 14% unemployment, which was reduced to about 1% by 1944, while gdp doubled with military spending that peaked at 41% of gdp. a green new deal of similar magnitude today could also generate truly full employment to save the environment and reverse ‘global heating’, with immense and immediate benefits for the most deprived, un-and-under-employed who are currently suffering from neoliberal policies and shrinking welfare. it is these and other short to medium term cobenefits of energy transition and climate change mitigation which are most likely attract widespread political support from electorates whose immediate survival concerns tend to crowd out warnings of apparently distant climate catastrophe. thanks in particular to the pioneering work of stanford’s mark jacobson and his co-authors we now know that average annual costs of energy transition by 2050 are of similar magnitude to the financial savings from phasing out ff and averting just the local health costs of ff pollution, in addition to the welfare benefits of ultimately avoiding the more that 9 million current fatalities from outdoor air pollution alone and the associated morbidity. in addition, of course, the benefits from rapid action to avert irreversible 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license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article mechanistic trends in chemistry louis caruana sj faculty of philosophy, pontificia università gregoriana, rome, italy e-mail: caruana@unigre.it abstract. during the twentieth century, the mechanistic worldview came under attack mainly because of the rise of quantum mechanics but some of its basic characteristics survived and are still evident within current science in some form or other. many scholars have produced interesting studies of such significant mechanistic trends within current physics and biology but very few have bothered to explore the effects of this worldview on current chemistry. this paper makes a contribution to fill this gap. it presents first a brief historical overview of the mechanistic worldview and then examines the present situation within chemistry by referring to current studies in the philosophy of chemistry and determining which trends are still mechanistic in spirit and which are not. keywords. mechanism, descartes, atomism, substance, teleology. chemistry can be described as the study of how matter adopts different forms and of how it changes from one form to another. within this discipline, various conceptual issues arise. they are of interest to philosophers, to historians and sometimes to chemists themselves, especially to those chemists who seek greater clarity about the deeper assumptions of their work. one of the most interesting conceptual issues has to do with mechanism. to account for the way matter changes from one form to another, chemists often use mechanistic explanations. for instance, they may explain a chemical reaction in terms of a small number of steps from the initial reactants to the final products, the intermediates being conceived of as somewhat stable molecular combinations. the mechanistic explanation in these cases is like a set of snapshots taken at different stages of the transformation. the basic assumption is that the world functions like a complex machine and that every process can be analysed into definite steps that involve simple reconfiguration of parts and transfer of energy. chemists tend to see a chemical reaction as a kind of sub-device within the larger machine of nature and tend to see their task as a kind of reverse engineering.1 1 the clearest example of this method is probably e. j. corey’s retrosynthetic analysis. “retrosynthetic (or antithetic) analysis is a problem-solving technique for transforming the structure of a synthetic target (tgt) molecule to a sequence of progressively simpler structures along a pathway which ultimately leads to simple or commercially available starting materials for chemical synthesis.” e. j. corey and xue-min cheng, the logic of chemical analysis (new york: john wiley & sons, 1989), p. 6. 30 louis caruana sj the fascination with mechanisms has an interesting history. the origin of the so-called mechanistic worldview is often associated with galileo galilei and with the beginning of the scientific revolution. even before his time, however, the proliferation of machines had been a distinctive feature of the intellectual milieu of the renaissance. about a hundred years before galileo, leonardo da vinci had filled notebook after notebook with designs of various contraptions intended to satisfy all kinds of human needs. leonardo’s contraptions qualify as machines because he proposed them as artefacts made up of components that function together for an overall positive effect. the most rudimentary machines, like levers and pulleys, have been with us since the dawn of civilization but, in the course of european history, from the renaissance onwards, we see the importance of machines increasing at an accelerating rate, with human society becoming progressively dependent upon them. the rise of mechanistic thinking left a significant mark on the wider cultural, philosophical, and religious contexts. it affected the way people understood the world and their place within it, and it gave rise to a distinctive worldview, a cosmology in which god became increasing seen as the chief engineer responsible for the greatest and most intricate machine of them all, the entire universe. the specific philosophical features and assumptions of this worldview were not completely clear from the start. it took philosophers and scientists of the early modern period many generations to explore and articulate such assumptions often after lengthy disputes with theologians. during the twentieth century, the major features of this worldview came under attack mainly through the rise of quantum mechanics but some of the basic characteristics still survive today in some form or other. for example, it is arguable that the research programme of reductive physicalism within the brain sciences is a direct descendant of the mechanistic materialism of the late seventeenth century. many scholars have produced interesting studies of such significant mechanistic trends within current physics and biology but very few have bothered to explore the effects of this worldview on current chemistry. in this paper, i intend to make a contribution precisely in this neglected area, primarily by seeking an answer to the question, “how mechanistic is current chemistry?” in the first section, i will present a brief historical overview of the mechanistic worldview with the aim of extracting its main philosophical characteristics. in the second section then, i will examine the present situation by referring to current studies in the philosophy of chemistry and determining which trends are still mechanistic in spirit and which are not. 1. the mechanistic view in history the rise of a distinctively mechanistic worldview would not have been possible without the position often called corpuscularianism, according to which macroscopic bodies should be described, and their behaviour explained, in terms of microscopic corpuscles — a view not very different from traditional atomism.2 the novelty of corpuscularianism arose from the conviction of fifteenth and sixteenth century thinkers that the aristotelianism of the middle ages needed urgent revision. these thinkers were convinced moreover that a revision could only come about by using mathematics to quantify in some way the various attributes of the ultimate constituents of the world. such insights pointed towards something that would be definitely new. in spite of this novelty, however, some affinity between the emerging, new mechanistic paradigm and the old scholastic aristotelianism remained. elements of continuity were especially evident in the way major proponents of the new paradigm justified their project. they adopted an attitude that corresponds exactly to what one would expect from an aristotelian scholastic thinker: they referred to an underlying essence. aristotle had constructed his entire edifice of natural philosophy on the idea of substance. descartes, one of the paradigmatic mechanistic philosophers, adopted a similar approach: he constructed the entire edifice of his mechanistic view upon the idea that the essence of matter was extension. it is clear therefore that, since the change from the old to the new paradigm included elements of both discontinuity and continuity, a responsible historiography needs to be sensitive to both.3 to determine those features of the new worldview that affected chemistry, we need to investigate such complex conceptual transformations and legacies with special attention. let us start by considering the contribution of three prominent protagonists of the mechanistic worldview. pierre gassendi (1592-1655) left his mark on the history of philosophy because he not only endorsed and developed the atomistic philosophy of epicurus but also attempted to produce a christianized version of it. with his competence in both philosophy and theology, he managed to produce a sophisticated natural philosophy that was on a par with the cartesian proposal. 2 ancient greek philosophers used to assume that atoms were indivisible; corpuscles however were assumed microscopic building blocks of everyday objects, just like atoms, but without the condition of indivisibility. 3 see r. ariew, “descartes and scholasticism: the intellectual background to descartes’ thought,” in the cambridge companion to descartes, edited by j. cottingham, cambridge university press, 1992, pp. 58–90. 31mechanistic trends in chemistry now, many features of epicureanism seem, at first sight, completely irreconcilable with religious belief, especially christianity. for instance, the kind of atomism defended by epicurus denies creation and divine providence, assumes the infinity and eternity of atoms, rejects final causes, and gives a central role to chance. gassendi knew this well. nevertheless, he engaged in reconciliatory work by launching a critical evaluation of aristotle’s objections to this kind of natural philosophy. gassendi was convinced that what aristotle had attacked was not the genuine version of atomism but a caricature of it. the genuine epicurean philosophy was indeed reconcilable with religious belief primarily because it included an element of wisdom. like many other ancient greek philosophers, epicurus had produced his theoretical proposal ultimately as an ethical way of life, his main aim being that of grasping the correct structure of the world so as to do away with imaginary fears arising from animistic cosmology. this element was certainly reconcilable with christianity. gassendi was aware of this point but did not limit his defence of epicurus to these considerations. he turned his attention to other aspects as well. according to gassendi, epicurus and christianity were opposed primarily as regards materialism and divine providence. unlike democritus, epicurus had accepted as real not only the atoms themselves, but also the complex compounds that these atoms constitute when combined in various configurations. epicurus had not insisted however that, by perceiving the macroscopic object, in other words, the combination of atoms, we have access to that object’s essence, as aristotle was to do after him. for epicurus, in cognition we do not grasp the hidden essence of things but merely their appearances. gassendi’s first move was therefore to try to retrieve and defend this pre-aristotelian epicurean position. epicurus had also insisted that all physical processes, including those of perceivable macroscopic objects, are nothing more than interaction between atoms. he had complicated his picture however by assuming that all atomic motion was downwards, if not disturbed by swerving. in this somewhat strange assumption, gassendi found his opportunity to introduce the element of divine providence. he argued that god provides atoms with different initial attributes: different motions and different sizes. thus god gives the atoms the ability “to disentangle themselves, to leap away, to knock against other atoms, to turn them away, to move away from them, and similarly the capacity to take hold of each other, to attach themselves to each other, to join together, to bind each other fast, and the like, all this to the degree that he [god] foresaw would be necessary for every purpose and effect that he destined them for”.4 with such a proposal, gassendi seemed to distort epicurean thinking considerably. he was effectively replacing the fundamental idea of chance with goal-directed atomic behaviour. in this move, we see why gassendi represents a radical departure from both epicureanism and aristotelianism. he brought god’s action into epicurean atomism and he also removed aristotelian final causes from within nature. he ceased seeing goal-directed behaviours or final causes as intrinsic to the nature of things. instead, he started to treat goal-directedness as an extrinsic factor, deriving not from nature but from god. with such an idea of providence, gassendi had to respond to the problem of personal freedom. how could an externally goal-directed universe leave space for freewill? the answer for him involved the idea of flexibility: he argued that the intellect is precisely that kind of complex combination of atoms that produces a flexible nature, one that can judge various aspects of the same object, and can evaluate different future possibilities. this proposal does account for what we observe but seems ad hoc. overall, we can say that gassendi’s attempt to arrive at a synthesis of epicureanism and religious belief was brave but not without its own problems. we move on now to another defender of the mechanistic worldview, thomas hobbes (1588-1689) who proceeded in gassendi’s steps but was not concerned as much as gassendi with retaining consistency with religious belief. hobbes embraced materialism and determinism, and consequently expressed an overall view that nowadays we would call a materialist theory of the mind. he developed a comprehensive version of mechanistic philosophy that aspires to explain the entire universe in terms of matter and motion only, without reference to other features or forces, not even space and time. within this picture, there is place neither for spiritual substance nor for religious belief in the traditional sense. in his book de corpore, which contains most of his ideas on the workings of nature, he adopts an overall reductive approach. for him, any object’s capacity to produce motion is nothing more than the motion of the constituent corpuscles. space for him is neither substantial, enjoying a separate existence, nor a container, as plato had suggested. it is merely a subjective frame of refer4 p. gassendi, opera omnia, lugduni: 1658 (sumpt. laurentii anisson, & ioan b. bapt. devenet), volume i, page 280: “congruam sese movendi, ciendi, evolvendi; et consequenter sese extricandi, emergendi, prosiliendi, impingendi, retundendi, regrediendi; itemque ses invicem apprehendendi, complectendi, continendi, revinciendi, et cetera quasenus ad omneis fineis effectusque quos tum destinabat necessarium providit.” such anthropomorphic language seems inevitable and is still present in chemistry today. in current literature, molecules attack each other, nuclear spins “flip,” and electrons push other electrons. 32 louis caruana sj ence, a mental abstraction. to explain an object’s tendency to move, hobbes developed the notion of conatus, which roughly refers to the object’s inherent directionality or vectorial aspect. he developed also the correlative notion of impetus, which roughly refers to the measured conatus of any given object.5 he used these two notions to describe not only any given object’s motion but also its capacity to produce sensation in rational creatures. overall, his worldview was clearly materialistic, but most commentators agree that the arguments he put forward to defend his materialism were never very strong. it seems likely that what convinced him of materialism was not sustained reflection or a knockdown argument but confidence in the new method of empirical inquiry, which was making fast progress during his time. there is no doubt that religious belief played a significant role in his philosophy, especially in his political philosophy, but this does not mean that he was an orthodox believer. some surprising ideas that he expressed, for instance that god could be material, suggest that he was an outright atheist. the issue however remains unclear. the best way of seeing him is probably as a heavy-handed, revisionist, religious believer, a sceptic about much that organized religion proposed; in other words, a very critical theist.6 compared to gassendi and hobbes, rené descartes (1596-1650) stands out as the one who produced the most characteristic expression of the mechanistic worldview of the modern period, influencing nearly all areas of culture. he presented his views for the first time in the book principia philosophiae of 1644, where he focused on the nature of human cognition. for him, the very nature of natural philosophy obliges us to see the characteristics of mind, and of god, as essentially distinct from the physical world. this affirmation for him was a typical “clear and distinct idea”, something that can offer guidance to inquiry because we perceive it with the mind rather than with the senses. a non-deceiving god who is responsible for all existence will ensure that what we perceive by the mind clearly and distinctly is in general true rather than systematically misleading. this principle throws light also on the essential features of substances that make up the world. the two basic attributes of substances are extension and thought. extension can show variations, for instance when an object is now in one position and later in another. simi5 for further details, see h. bernstein, “conatus, hobbes, and the young leibniz”, studies in history and philosophy of science, 11 (1980): 25–37. 6 for a specific study of hobbes’s mechanistic philosophy, see f. brandt, thomas hobbes’ mechanical conception of nature (copenhagen; london, 1928); c. leijenhorst, the mechanisation of aristotelianism: the late aristotelian setting of thomas hobbes’ natural philosophy (leiden: brill, 2002). larly, thought can show variations, for instance when the mind remembers one thing and then another. such variations constitute what he calls modes. for him therefore, motion is a mode; and so is the lack of it, the state of rest. we notice here some fundamental novelties with respect to aristotelian thinking. for aristotle, there was an asymmetry between motion and rest, at least when the motion is not heavenly. for non-celestial objects, all motion showed a natural tendency to come to rest. the motion of such non-celestial objects therefore needed an explanation, while their state of rest did not. as opposed to this, descartes sees a symmetry between uniform motion and rest. both are modes. for him therefore, uniform motion does not need an explanation in terms of a force. he follows aristotle and says that god is the primary cause of motion but adds that god maintains a constant quantity of motion within the entire universe. what may change is the distribution of motion and of rest within the universe. the overall amount of motion, however, remains the same. this is a law of conservation, justified just like all genuine laws of nature, by god’s immutability. descartes concludes that “in general, we evidently cannot see this otherwise than as follows: that god himself, who set the parts of matter in motion or at rest when he first created them, now, through his sole ordinary attention, preserves in all of it the same quantity of both motion and rest”.7 another important novelty with respect to aristotelian physics concerns the laws of nature. for descartes, laws are causes: “from god’s immutability, we can also know certain rules or laws of nature, which are the secondary and particular causes of the various motions we observe in individual bodies.”8 consequently, the natural regularities we discover and formulate in mathematical form are not, as aristotelians had assumed, descriptions of the intrinsic activity of the various substances. they are rather extrinsic causes affecting extended substance that, on its own, is inert. a third innovation worth mentioning here deals with the idea of a vacuum. for descartes, the idea of a vacuum is mistaken. motion is not movement across empty space but displacement of one part of the universe by another. 7 r. descartes, principia philosophiae, part ii, sec. 36: “et generalem quod attinet, manifestum mihi videtur illam non aliam esse, quam deum ipsum, qui materiam simul cum motu & quiete in principio creavit, jamque, per solum suum concursum ordinarium, tantundem motus & quietis in ea tota quantum tunc posuit conservat.” see oeuvres de descartes, ed. c. adam and p. tannery, paris: vrin, 1996, volume viii, p. 61, my translation. 8 ibid., sec. 37: “atque ex hac eadem immutabilitate dei, regulae quaedam sive leges naturae cognosci possunt, quae sunt causae secundarae ac particulares diversorum motuum, quos in singulis corporibus advertimus.” oeuvres de descartes, ed. c. adam and p. tannery, paris: vrin, 1996, volume viii, p. 62, my translation. 33mechanistic trends in chemistry for any part of the universe to move, other parts need to squeeze out of the way accordingly. this is the direct consequence of descartes’s idea that the entire cosmos is a plenum. this means that, at any point, there is either a body or the fluid medium that fills up the space between bodies. this f luid medium causes bodies to move or come to rest. it reconfigures the overall distribution of motion and rest within the universe, which, on the large scale, is therefore a system of adjacent whirlpools carrying planets around their respective centres that are occupied by a central star. the sun is just one of these central stars. this cartesian cosmology is often referred to as a vortex theory, because it is modelled on what we see when a liquid moves round in a whirlpool. he argues that “the matter of the heavens, in which the planets are situated, revolves unceasingly, like a vortex having the sun as its centre, and that those of its parts that are close to the sun move more quickly than those further away.”9 descartes thus offers a serious contender to aristotle’s cosmological system, which had assumed that the sub-lunar region is essentially different from the supra-lunar regions. some historians highlight the fact that descartes was not conceptually innovative on all counts. as i mentioned briefly before, he remained committed to giving explanatory priority to deductive arguments and essentialist thinking. nevertheless, his original cosmological system had an enormous impact and remained the major point of reference for many generations of thinkers, even after the publication of newton’s principia mathematica. the three philosophers mentioned up to now are by no means the only defenders of the mechanistic worldview. for a full list of philosophers who contributed to the detailed articulation of this worldview, we need to include people who were more directly associated with the new methods of empirical inquiry, figures like galileo galilei, isaac newton, and pierre-simon de laplace.10 it may be interesting to note that, even if we add all these, the list will not contain the name of anyone who was definitely against religious belief. in some form or other, religion was never completely absent in the work and life of these mechanistic thinkers.11 9 ibid., part iii, sec. 30. the fuller explanation is as follows. “sic itaque sublato omni serupulo de terrae motu, putemus totam materiam coeli in qua planetae versantur, in modum cuiusdam vortices, in cuius centro est sol, assidue gyrare, ac eius partes soli viciniores celerius moveri quam remotiores, planetasque omnes (e quorum numero est terra) inter easdem istius coelestis materiae partes semper versari. ex quo solo, fine ullis machinamentis, omnia ipsorum phaenomena facillime intelligentur.” 10 for a fuller historical treatment of the mechanistic worldview, see e.j. dijksterhuis, the mechanization of the world picture, oxford 1961. 11 admittedly, some historians today present laplace as a champion of religious unbelief. he showed mathematically that the solar system is with the hindsight we enjoy today, after about four centuries since the emergence of the mechanistic worldview, what can we say about its basic conceptual ingredients? to answer this question, some scholars adopt the method of first identifying an ideal type of mechanistic philosophy, and then seeing the major sixteenth and seventeenth century thinkers as expressing some specific aspect or aspects of this ideal type. for instance, according to stephen gaukroger, the ideal mechanistic philosophy is one that reduces all physical processes to the motion of inert particles, fully describable in mechanistic and geometric terms.12 the ideal mechanistic worldview assumes that we can fully explain any macroscopic object and its behaviour in terms of such particle motion only. the solid corpuscles are all of the same shape and size, while causation occurs between them only on contact. what we call matter is space that is full to capacity with such solid corpuscles. all macroscopic features of matter, such as observable variations in density, arise because of variations in the distribution of the constitutive corpuscles in space. the universe is causally closed, with no possibility of processes beginning or ending spontaneously. given this basic picture, the main research programme of a mechanistic natural philosopher is to determine the laws of nature that allow a mathematical explanation of all observable changes. of course, within such an explanation, corpuscles have passive attributes only. they are driven around according to the laws of nature. this modest list of assumptions is all we need to produce an exhaustive account of all kinds of motion and change, whether organic or inorganic. an important consequence here is that such a worldview has no place for aristotelian final causes. it involves no intrinsic goals or purposes: neither within the corpuscles themselves nor within the complex composites. this last point may give the impression that the mechanistic worldview represents a clear breach from ancient and medieval cosmology, but this is not completely true. some important features of the old style of explanation did remain, as manifested by the example already mentioned, namely the recourse to first principles within the explanation. descartes resorted to precisely this kind of explanatory strategy when deriving stable on its own, without the need of the occasional divine readjustment as newton had proposed, and he famously affirmed that he had no use of the “divine hypothesis”. he thus produced the complete mechanistic worldview and allegedly pushed god out of a causally closed universe. this interpretation however neglects the fact that even laplace retained a form of deism and endorsed the idea that we should consider god the supreme being responsible for the laws of nature. 12 s. gaukroger, the emergence of a scientific culture: science and the shaping of modernity 1210-1685, oxford university press, 2006. i am drawing especially from chapters 8 and 9. 34 louis caruana sj observations from his basic principle of matter as res extensa. is this strong element of deduction an essential ingredient of the mechanistic worldview? some historians distinguish between a mechanistic philosophy that is highly dependent on deduction from another kind that is less dependent. this second kind of mechanistic philosophy highlights observation and experiment, and minimizes the role of speculation about what might lie hidden. gaukroger argues that these two kinds of methods of approaching nature depend on whether one gives explanatory priority to the formal element of the explanation or to the observations themselves. the mechanistic style of natural philosophy described so far puts the emphasis on first principles, which it then considers the building blocks of the new worldview. it then interprets the phenomena to fit that logical structure. as opposed to this, the experimental style of natural philosophy gives the priority to the observations and experiments, highlighting the importance of empirical evidence and reliability. in this latter style, first principles are not the engine of inquiry. they do not play the role they had within the cartesian mechanistic philosophy, the role of ensuring the organization and unity of knowledge. in the experimental style of mechanistic explanation, what drives the inquiry is rather the effort to arrive at piecemeal, local explanations of the phenomena at hand. an interesting example is the explanation of colour. descartes, as a typical mechanistic philosopher of the deductive style, produced a theory rationally grounded on his geometrical optics and microscopic corpuscles, whereby he explained white light as a homogenous collection of corpuscles whose spin could be differentially affected by passing through a prism. this explains our sensation of seeing different colours. isaac newton, on the contrary, did not feel constrained to start his explanation from an alleged underlying hidden principle, from which the observations could be derived. he concentrated exclusively on the relations between observable aspects at the phenomenal level. he thereby arrived at the idea that white light is indeed heterogeneous, composed of different colours that can be separated by passing through a prism. descartes therefore had looked for underlying causal links while newton looked for manifest causal links at the phenomenal level without the need for foundational assumptions regarding the hidden dimension of reality. newton realized that, if he focused on the phenomenal relations only, he had to suspend judgment as regards the correctness of the theory of corpuscles. this introduced a new attitude within the mechanistic philosophy, an attitude that newton excellently summarized in his famous comment regarding the origin of gravity: i have not as yet been able to discover the reason for these properties of gravity from phenomena, and i do not feign hypotheses. for whatever is not deduced from the phenomena must be called a hypothesis; and hypotheses, whether metaphysical or physical, or based on occult qualities, or mechanical, have no place in experimental philosophy. in this philosophy particular propositions are inferred from the phenomena, and afterwards rendered general by induction.13 we note here how newton distinguishes his views from mainstream mechanistic ideas by calling his own philosophy experimental.14 in spite of this new terminology, however, there is much that keeps all mechanistic natural philosophers together. the cartesian style and the newtonian style are therefore better seen as two versions of the same worldview rather than as two different worldviews. it may be interesting to add here that, as regards consistency with religious belief, there was no significant difference between descartes’ deductive style and newton’s experimental style. both versions were open to belief in god more or less in line with the standard western religious tradition.15 13 newton wrote this in the general scholium, which was an appendix to his book philosophae naturalis principia mathematica. the final version of this scholium appeared in the 1726 edition of the principia. “rationem vero harum gravitatis proprietatum ex phaenomenis nondum potui deducere, et hypotheses non fingo. quicquid enim ex phaenomenis non deducitur, hypothesis vocanda est; et hypotheses seu metaphysicae, seu physicae, seu qualitatum occultarum, seu mechanicae, in philosophia experimentali locum non habent. in hac philosophia propositiones deducuntur ex phaenomenis, et redduntur generales per inductionem.” the translation used here is from i. newton, the principia: mathematical principles of natural philosophy, trans. i. b. cohen and a. whitman, berkeley: university of california press, 1999, p. 943. 14 m. ben-chaim, “the discovery of natural goods: newton’s vocation as an ‘experimental philosopher’” the british journal for the history of science 34 (2001): 395-416. 15 descartes presented and justified his most famous work, the meditations, as a way of defending the catholic faith: “i have always considered the two questions, the one regarding god and the other the soul, to be the main ones that ought to be answered by the help of philosophy rather than of theology. for, although to us, the faithful, faith is enough to believe that the human soul does not cease to exist with the body, and that god exists, it surely seems impossible ever to convince infidels of the reality of any religion, or almost even any moral virtue, unless, first of all, those two things be proved to them by natural reason.” (semper existimavi duas quaestiones, de deo et de anima, praecipuas esse ex iis quae philosophiae potius quam theologiae ope sunt demonstrandae: nam quamvis nobis fidelibus animam humanam cum corpore non interire, deumque existere, fide credere sufficiat; certe infidelibus nulla religio, nec fere etiam ulla moralis virtus, videtur posse persuaderi, nisi prius illis ista duo ratione naturali probentur.) r. descartes, “sapientissimis clarissimisque viris sacrae facultatis theologiae parisiensis decano & doctoribus” (letter of dedication to the very sage and illustrious, the dean and doctors of the sacred faculty of theology of paris), in oeuvres de descartes, ed. c. adam and p. tannery, paris: vrin, 1996, vol. vii, pp. 1-2, my translation. newton justified his major work just as descartes had done before him, by referring to its 35mechanistic trends in chemistry so far, i have tried to show how the mechanistic worldview emerged slowly, how it remained in step with the new empirical methods of the natural sciences, and how it then eventually took definite shape towards the end of the seventeenth and early eighteenth centuries. most of its fundamental tenets enjoyed considerable popularity during the nineteenth century but started to experience serious setbacks during the twentieth century. scientific advances, especially in the area of quantum mechanics, obliged physicists to abandon the idea of elementary particles as tiny blobs of matter. the new paradigm in physics became incompatible with most of the features of classical mechanistic thinking. one of the most surprising novelties was the way in which the new physics undermined the materialistic basis of the mechanistic worldview. it brought about what n. r. hanson called the “dematerialization of matter”.16 this expression does not mean that we should now reject the word “matter” as useless. it means rather that we need to retrieve its original philosophical sense: matter as a principle of individuation. the new paradigm obliges us to refrain from assuming that “matter” refers to some elemental stuff situated in space and time. this and other relevant shifts of meaning regarding fundamental terms show that, in the course of the twentieth century, the support that the mechanistic worldview used to receive from physics decreased considerably. it seems fair to say that, compared to what this support used to be in the seventeenth and eighteenth centuries, it is at present of minor importance.17 value as an apology for religion: “when i wrote my treatise about our [solar] system, i had an eye upon such principles as might work with considering men, for the belief of a deity, and nothing can rejoice me more than to find it useful for that purpose. […] to make this system therefore, with all its motions, required a cause which understood and compared together the quantities of matter in the several bodies of the sun and planets, and the gravitating powers resulting from thence; the several distances of the primary planets from the sun, and of the secondary ones from saturn, jupiter, and the earth; and the velocities with which these planets could revolve about those quantities of matter in the central bodies; and to compare and adjust all these things together in so great a variety of bodies, argues that cause to be not blind and fortuitous but very well skilled in mechanics and geometry.” i. newton, four letters from sir isaac newton to doctor bentley, containing some arguments in proof of a deity, london: r. & j. dodsley, 1756, digitized 2007, letter i, p. 1; p. 7-8. 16 n. r. hanson, “the dematerialization of matter,” philosophy of science 29 (1962): 27-38. 17 as regards the fundamental constituents of nature, the present majority-view seems to involve a version of structural realism according to which what scientific theories ultimately refer to are not objects in space and time but patterns of relations expressed in the form of mathematical equations. see for instance anjan chakravartty, a metaphysics for scientific realism: knowing the unobservable (cambridge university press, 2007). 2. the mechanistic view within chemistry how has this mechanistic worldview affected chemistry? does the present state of this discipline still show traces of mechanistic thinking? to answer these questions, we can first prepare the ground by considering the two fundamental concepts at work here, namely the concept of nature and the concept of mechanism, as they appear in chemistry. for many centuries before the rise of natural science, the concept of nature was determined by aristotelian philosophy and included a strong element of teleology or finality. moreover, the distinction between natural and artificial, between physis and technē, was clear and important for the understanding of the world and of our place within it. with the christian assimilation of these aristotelian ideas, “natural” started to mean “in line with god’s will”, but, when the mechanistic view took over, final causes lost much of their importance, god was sidelined, and nature itself started being seen as the ultimate basis of explanation. these shifts caused some prominent thinkers to examine carefully how god should be referred to by the new science. the first book-length study of the concept of nature, written by robert boyle in 1682 and entitled a free inquiry into the received notion of nature, argued against the replacement of god by nature. for boyle, it was a mistake to see nature as an agent. what scientists call the laws of nature should really be called the laws of god.18 in line with this understanding, going against the laws of nature, or doing the unnatural, becomes sinful. when chemists create substances that are not found in nature, they therefore seem to transgress god’s will, because, if god had wanted such substances to exist, he would have included them in creation. this kind of argument is obviously simplistic. chemists could indeed be held responsible for going against god’s will but their transgression would not lie in their having added something new, which god had not created before. it would lie rather in their intention to cause harm via the use of that new substance. since humans are themselves part of nature, created by god like the rest of creation, their chemical ingenuity is not in itself something that goes against god’s will. the chemists’ endeavor to bring out, to actualize, the hidden potentialities of creation is perfectly natural. these considerations show how the dis18 see joachim schummer, “the notion of nature in chemistry,” studies in the history and philosophy of science 34 (2003): 705–736. this paper presents a good overview of how chemistry resisted some of the fundamental assumptions of the mechanistic worldview. it is important to add however that the way the author identifies the christian worldview with an odd narrative that he extracts from the non-canonical book of enoch shows considerable ignorance in this area. 36 louis caruana sj tinction between natural and artificial can be misleading. in fact, we can observe that, from newton onwards, the distinction starts losing its significance in philosophical and theological works about science and technology. if we can say that the aristotelian heritage regarding the pair physis-technē loses its importance, we cannot say the same thing as regards final causes. the literature about modern chemistry, especially during the interesting period of the artificial production of organic substances (roughly between the 1840s and the 1870s) shows that chemists increasingly assumed a teleological notion of nature and thereby distanced themselves more and more from physicists. chemists readily made use of expressions like “imitating nature” and “learning from nature”. of course, the meaning of such expressions can oscillate between two extremes. the meaning may be that chemists see themselves as apprentices of nature or as its rivals. in spite of this possible semantic ambiguity however, we can safely conclude that, especially with the discovery of how to produce organic compounds artificially, chemists started seeing nature as active, as doing something. they thus reinstated some elements of teleology within the notion of nature, liberating themselves from the strictures of the classical mechanistic worldview. in this respect therefore, the chemists’ idea of nature lies apparently midway between the finality-free mechanistic worldview and the teleologically rich, biological worldview. current chemical literature confirms this point. a recent study affirms that, “the fact that we can so easily attribute the old metaphors to each of the branches [of current drug research] – learning from nature, imitating nature, improving nature, competing with nature, and controlling nature – is hardly pure chance. it is more likely that these metaphors have actually been effective in shaping research traditions until today.”19 like the concept of nature, that of mechanism has had significant recent developments, some of which are relevant for chemistry. for lack of space, i will highlight two main features only. the first one deals with the idea of mechanism as corresponding to the form of acceptable explanations. basically, a mechanism is an explanation that has the form of “nested hierarchies”.20 in line with the classic mechanistic worldview, the explanatory style i am referring to here assumes that objects are complex arrangements of smaller units, which are themselves made up of even smaller units, and so on. for current chemists, this should sound familiar. the explanation of a given phenomenon consists in supplying a description 19 schummer, “the notion of nature in chemistry”, p. 726. 20 peter machamer, lindley darden and carl f. craver, “thinking about mechanisms,” philosophy of science 67/1 (2000): 1-25; the quote is from p. 13. of a lower-level set of objects together with the push-pull relations between them and then supplying another evenlower-level set of smaller objects and their relations, and so on until we bottom out at the level of fundamental non-reducible elements. we support the entire explanatory ladder by assuming that the fundamental elements have some dispositions that do not need any further explanation. we affirm, for instance, that the electron has a negative charge, period. in such an explanatory process, the challenge is to reduce the number of inexplicable dispositions to a minimum. of course, to arrive at a satisfactory set of nested hierarchies in this sense, we are entitled to use all the knowledge at our disposal. we can use previous knowledge of other systems and subsystems. we can use also knowledge that we may have acquired from situations that have nothing to do with the phenomenon that we are trying to explain. moreover, the particularity of the phenomenon we are studying could be a stepping-stone for broader understanding. if we manage to extract the abstract form of the mechanism, if we manage to extract it out of the particularity of the one phenomenon we are studying, we could then use it for understanding other similar phenomena.21 this is one feature of mechanism within current chemistry. another important feature is the mechanism’s inherent directionality. the hempel-inspired discussions on the structure of explanation of the late 1960s and 70s supported the idea that to explain a phenomenon is to provide some information about general laws and about its causal history. given this background, we can conceive of a mechanism simply as a particular subset of causal relations that contribute to the appearance of the phenomenon. for any given phenomenon, the entire causal history is a vast network of mutually interacting cause-effect relations. the subset of this network that deserves to be called a mechanism is, according to this view, that subset that researchers consider relevant for their discipline. this understanding of mechanism, however, remains unsatisfactory. it seems too subjective. different researchers would carve up the causal history in different ways. some philosophers therefore have defended the claim that a mechanism is not just any sub21 the abstract version of a mechanism, usually in a diagrammatic form, is sometimes called a mechanism schema. such schemas help in the effort to unify the knowledge that we derive from different situations, regarding both macroscopic properties and microstructure. “higher level entities and activities are thus essential to the intelligibility of those at lower levels, just as much as those at lower levels are essential for understanding those at higher levels. it is the integration of different levels into productive relations that renders the phenomenon intelligible and thereby explains its.” machamer et al., p. 23. see also james a. overton, “mechanisms, types, and abstractions,” philosophy of science, 78/5 (2011): 941-954. 37mechanistic trends in chemistry set of the causal history. something more is needed. a causal subset deserves to be called a mechanism when it is clearly directional, when it is clearly productive of the specific effect that we are investigating. the causal subset needs to be a complex system consisting of mutually interacting sub-systems that function together to produce the specific effect. the specific effect, in this case, would be what the mechanism is for.22 on this view therefore, we are not entitled to call a set of nested hierarchies of systems a mechanism if we do not know what it is for. we notice immediately here the affinity with the biological concept of function. these developments therefore are suggesting that the concept of mechanism in chemistry should depend on that of function, just as in biology.23 when explaining living organisms, we can talk about the mechanism involved in a specific organ only when we know the function of that organ within that living thing. the simple causal-role view of mechanism therefore is not enough. we do not pick any set of events that have a causal role within the production of an effect. to refer to a biological mechanism, we first determine the specific task that the effect represents, in other words, we determine its function, and then spell out, step by step, how that function is realized. not every change in a living organism is associated with a function. changes can be accidental or even pathological. we do not take a pathology to be a mechanism. we take it to be a mechanism that has broken down. a malfunction is, as the word implies, a mechanism that went wrong. this shows how intimately related is the idea of mechanism to that of function. now, the functional view of mechanism is typical of biology. in physics, the situation is different. here, final causes have no significant role and the causal-role view of mechanism is therefore the only one available. what about chemistry? as one would expect, chemistry lies somewhere between these two positions. in the course of the seventeenth and eighteenth centuries, the mechanistic worldview gave priority to physics over the other sciences, it emphasized the causal-role view of mechanism, and it convinced many scientists to apply the causal-role view without alterations to chemistry and even to biology. the indispensable role of functional explanations within biology however, together with the onset of organic chemistry, has persuaded recent philosophers of science that the functional view of mechanism is indispensable not only for biology but for chemistry as well. the present situation therefore is interesting because, within the one dis22 stuart glennan, “rethinking mechanistic explanation,” philosophy of science 69/s3 (2002): s342-s353. 23 justin garson, “the functional sense of mechanism,” philosophy of science 80/3 (2013): 317-333. cipline of chemistry, we find features that are definitely mechanistic and others that are not.24 let us consider one current feature that is definitely mechanistic in character, namely the way chemists espouse atomism in some form or other. just as the early mechanistic philosophers had their version of atomism, according to which all things were made up of small corpuscles, so nowadays chemists have their own version. they think of substances as combinations of smaller units and these units as combinations of even smaller units, and so on. the basic idea of postulating building blocks or elements to explain the great variety of things in the world has a long history going back to the ancient greek philosophers for whom there were only four elements: earth, water, fire and air.25 in the course of history, alchemists adopted this assumption of the four elements and used it extensively in their somewhat confused talk about the transformation of substances. subsequent studies became more systematic and started to involve the categorization of substances and the study of controlled changes, especially through the invention and betterment of the distillation apparatus. no doubt, technological advances continued to increase our knowledge of how substances react but the deeper mechanisms behind the observed changes remained indefinite. sometimes, alchemists referred to animistic powers or occult forces to explain the hidden mechanisms, but such explanations were never a substitute for the basic idea of the four elements. as innovation progressed, interest in uncovering what lay hidden waned. metallurgical manuals of the mid 1500s adopted an instrumentalist view, concentrating on how-to-do rather than on the underlying mechanisms that might explain the production of useful materials like glass, acids and gunpowder.26 when natural philosophers started formulating the mechanistic worldview in terms of corpuscles, early chemists tended to combine the doctrine of the four elements with the new atomism, postulating the existence of four kinds of atoms, one for each element. on this view, the transformation of substances became a reconfigura24 the functional view of mechanism and the idea of “nested hierarchies” are not the only important features of current philosophical research concerning mechanism. for other features, see for instance stuart glennan, the new mechanical philosophy (oxford university press, 2017); carl craver and james tabery, “mechanisms in science”, the stanford encyclopedia of philosophy (spring 2017 online edition), edward n. zalta (ed.). these studies deal with the broad picture including all the sciences. in my paper, i focus on chemistry. 25 for more on how ancient greek philosophy paved the way for modern theories about atoms, see andrew g. van melsen, from atomos to atom: the history of the concept atom, trans. h. j. koren (pittsburg: duquesne university press, 1952). 26 aaron j. ihde, the development of modern chemistry (new york; evanston; london: harper and row, 1964), p. 24. 38 louis caruana sj tion of these four types of atoms.27 the fact that the atomic theory continued to develop, to receive empirical confirmation and to arrive finally at the remarkable achievement of the periodic table did not change the basic explanatory strategy. the idea that chemists should reduce every process to a mechanistic picture that involves nothing more than motion of electrons, atoms or molecules, together with energy-transfer between states, continued well into the twentieth century and is still dominant today, even as regards organic chemistry. this explanatory strategy gained considerable support within organic chemistry through the discovery of the dna structure in 1953, a discovery that refreshed hopes that chemists would soon be able to explain the reproduction of cells via a mechanism in the classical sense.28 the twentieth century formulation of quantum mechanics did affected research strategies in chemistry but it did not eliminate all traces of the mechanistic and reductive style that this discipline had inherited from atomism. at this point, we need to consider an important conceptual issue that lies behind the entire approach, an issue that arises whenever we seek to explain a phenomenon by referring to some lower-level microstructure. the problem arises because of the relation between parts and wholes. in general, we can say that there are different ways for parts to be together to form a whole. we can have loosely associated agglomerations, likes heaps. we can have mixtures. we can have compounds. and we can have strongly associated agglomerations like living cells. we can even have very intricately associated agglomerations that reiterate themselves, forming a whole of wholes, as in the case of the human body made up of organs, each of which is constituted of living tissue. what is the difference between these degrees of unity? philosophers have discussed this question since ancient times. it is certainly not a new question resulting from the mechanistic worldview or from modern chemistry.29 in nature, we find examples of all these kinds of combinations. as regards chemical thinking, a strictly mechanistic attitude would imply that the behav27 this was defended especially by the seventeenth century wittenberg professor of medicine, daniel sennert (1572-1637). 28 for a useful historical study of how the mechanistic worldview had a role in the emergence of molecular biology, especially in the contrasting explanatory strategies of microbiologist oswald t. avery and theoretical physicist max delbrück, see ute deichmann, “different methods and metaphysics in early molecular genetics — a case of disparity of research?” history and philosophy of the life sciences 30/1 (2008): 53-78. 29 see, for instance, aristotle, metaphysics 1040 b, 5-10; on generation and corruption, book i, chapter 10. a more recent study worth mentioning is pierre duhem, le mixte et la combinaison chimique. essai sur l’évolution d’une idée (paris, 1902). see also paul a. bogaard, “after substance: how aristotle’s question still bears on the philosophy of chemistry,” philosophy of science 73/5 (2006): 853-863. ior of a chemical compound is exhaustively explainable in terms of our knowledge of the constituent atoms. current knowledge however does not seem to support this view. obviously, a compound like h2o is not just a mixture of hydrogen and oxygen. it represents a specific state of togetherness that is different from that of mixtures. it is also different from that of organisms. its state lies somewhere between these two grades of constitution. the individual elements, hydrogen and oxygen, can indeed exist separately, and, when combined, they are not destroyed. in philosophical terms, we can say that their ontological identity is not annihilated by the identity of the whole of which they are now part. we need to add however that they do not have any longer all of the attributes that they had before the formation of the compound. we do not seem capable of explaining all of the properties of the compound in terms of those of the constituents. some philosophers argue that, with the formation of the compound, the individual elements undergo a kind of ontological promotion. the hydrogen atom in its combined state is not primarily a hydrogen atom any longer; it is now primarily a part of the water molecule. these last decades, philosophers have been exploring these issues in terms of emergent properties but we need not stray too far away from our main argument in this paper.30 suffice it to say that current explanatory strategies within chemistry include some persistent conceptual issues but, in spite of this, still show some traces of the classic mechanistic philosophy especially as regards the trend to explain marco-properties in terms of micro-properties.31 30 the philosophical literature on emergent properties is considerable. i offer a short overview with special attention to the concept of nature in chapter 7 of nature: its conceptual architecture (peter lang, 2014). what i am calling ontological promotion is more evident in the case of a biological whole. when i eat a loaf of bread, i am not adding bread as such to myself. nevertheless, some parts of the bread do indeed became part of me. what used to be part of an inanimate thing becomes part of a living thing. if we accept the idea of higher and lower forms of unity, higher and lower kinds of wholes, then we should take the chemical example of h and o combining into h2o as analogous to the organic example. for the specific question of how major biologists ernst mayr, theodosius dobzhansky, and george gaylord simpson defended biology from the encroachment of the physics-inspired mechanistic approach, see erika lorraine milam, “the equally wonderful field: ernst mayr and organismic biology,” historical studies in the natural sciences, 40/3 (2010): 279-317. 31 my insistence on persistent atomistic assumptions within chemical thinking might suggest that the way chemists resort to explanations in terms of micro-attributes is diametrically opposed to the way physicists do so. when chemistry resorts to the microscopic, it reveals itself as mechanistic while, when physics resorts to the microscopic, it reveals itself as non-mechanistic, especially because of its indeterminism, nonlocality and wave-particle duality. it is good to recall however that this is correct only to the extent that chemistry focuses mainly on what happens from the level of electrons, protons and neutrons upwards, and 39mechanistic trends in chemistry what about other features that seem diametrically opposed to the mechanistic worldview? i will focus on three points only. consider first the way chemistry as a discipline is related to physics. there is, of course, the trend to see chemistry as part of the far-reaching physicalist research program that seeks to reduce all objects and all motion to the fundamental interactions now acknowledged in physics, namely the electromagnetic, strong, weak and gravitational interactions.32 in current chemistry, some reduction of this kind is always present, as is most evident in the sub-discipline of computational quantum chemistry. the results of using computers instead of chemicals have been important but we cannot take these methods to be a substitute for practical, experimental work. computational chemistry is the theoretical counterpart of concrete practice, accounting for what is already known and exploring new possibilities, but always in need of calibration with reference to experimentally observed data. for the theory to be useful, approximations are inevitable. as the complexity of the system increases, so also the need to make approximations. for heuristic reasons therefore, it seems better not to limit chemistry to strictly reductionist explanatory methods but to assume that chemical explanation enjoys a certain degree of autonomy with respect to physics. the forms of explanation in both camps show similarities but remain distinct. for instance, a theory in physics may include theoretical entities whose existence is justified because of the theory’s explanatory success. this occurs also in chemistry. chemical theories have their own theoretical entities, entities like atomic and molecular orbitals, but these entities are different from anything that physics deals with.33 we have here, rarely considers elementary particles. physics, on the contrary, had to abandon its mechanistic foundations precisely because of its tackling phenomena at the level of elementary particles. the relatively recent sub-discipline of quantum chemistry reduces this opposition to some extent because it uncovers quantum effects at the atomic and sometimes even at the molecular level. the overall point is that there are areas of chemistry that are not influenced by quantum mechanics. these retains a mechanistic character. 32 the way physics dominates other disciplines, and the reasons behind this phenomenon, constitute an interesting area of study; for more about this effect on chemistry in the early 1900s, see kostas gavroglu, “philosophical issues in the history of chemistry,” synthese 111/3 (1997): 283-304. 33 in philosophy of science, the term “theoretical entity” refers to an unobservable thing that scientists assume to exist so that their theory predicts observations successfully. for further discussion on this point as regards chemistry, see eric r. scerri and lee mcintyre, “the case for the philosophy of chemistry,” synthese 111/3 (1997): 213-232. a typical theoretical entity in current physics is the electron. in chemistry, molecular orbitals were first stipulated as a mathematical construct to help solve a particular set of quantum mechanical problems. they were then co-opted by organic chemists as an explanatory framework, and are now said to have been “observed” via the visualization of electron density. therefore, a feature of current chemistry that is opposed to the classical mechanistic worldview. the point can be summarized as follows. if we take the classical mechanistic worldview as equivalent to today’s physicalism and if we take physicalism as the idea that all scientific disciplines are reducible to physics, then chemistry today, even in its computational form, is not straightforwardly mechanistic. it is no wonder that some current philosophers working in this area are convinced that we “must abandon the a priori assumptions and ontological commitments of traditional mechanistic epistemology and go beyond the physicalistic reference frame […]. mechanistic doctrine is even a barrier for understanding the epistemology of chemistry.”34 a second novel feature worth mentioning here is the shift of interest from the internal microstructure of substances to relations. the classical mechanistic worldview suggests that we should see chemistry as the study of substances and their constitution. the interest of current chemists however is not primary in substances as such but in relations between them. the emphasis is on the rules that govern the combinatorial possibilities of substances. these rules are comparable to the rules of grammar that determine how language can function properly. some philosophers of chemistry call them “semiotic rules” and equate them to reaction mechanisms.35 on this view, chemistry is “the science of the rules of possible chemical substances”.36 the term “mechanism” therefore is changing its meaning. according to these philosophers, a mechanism for chemistry is not a physical system of particles in motion but the set of signs and their rules of combination. for instance, the valence of an element, as the measure of its combining power, serves as a rule within the writing of a chemical equation. revising the meaning of mechanism in this way implies a major shift from the classical stance. previously, we used to assume that the highest form of understanding of a given phenomenon was the determination of the primary qualities of the entities involved and, when possible, the determination of its accurate pictorial representation. this attitude apparently implies that a direct photograph of a molecule, as we can sometimes obtain via x-ray crystallography, would be the best that chemistry could achieve. such a photograph however would be useless for modern chemistry because what constitutes the important focus of chemical mechanisms is the set of rules of combination. a significant transformation is happening here within the very concept 34 joachim schummer, “towards a philosophy of chemistry,” journal for general philosophy of science / zeitschrift für allgemeinewissenschaftstheorie 28/2 (1997): 307-336; the quoted text is from pp.308-309. 35 e.g. j. schummer. see ibid. p. 324. 36 ibid. p. 327. 40 louis caruana sj of mechanism. from the idea of a faithful pictorial representation of material elemental objects and the pushpull relations between them, mechanism has become the abstract idea of a set of rules. although we use the same term “mechanism”, the way chemists today use this word would hardly be recognizable by the mechanistic natural scientists of the modern period. the third point of departure of modern chemistry from the mechanistic worldview concerns the persistent importance of macro-properties with respect to microstructural explanation. the classical mechanistic view, as has been shown in the first part of this paper, emphasized the importance of microstructure. it emphasized the way the corpuscles were configured in a specific way. it deconstructed the idea of substance inherited from ancient and medieval philosophy, substances as persistent macro-objects, and substituted it with that of a combination of elemental units. this is what the classic mechanistic philosophers defended. does modern chemistry still depend upon this kind of deconstruction? it seems not. modern chemistry, of course, still considers atomic structure of capital importance. nevertheless, we have some clear indications that it does not make the idea of substance redundant. it does not substitute the idea of substance by a discourse about atoms. philosopher jaap van brakel argues persuasively that at least two chemical definitions of pure substance remain fully operational within current chemistry. they are in fact independent of one’s convictions regarding atoms or quantum mechanics. first, “a pure substance is a substance of which the macro-properties (of one of its phases), such as temperature, density and electric conductivity, do not change during a phase-conversion (as in boiling a liquid or melting a solid)”. second, “pure chemical substances are the relatively stable products of chemical analysis and synthesis: nodes in a network of chemical reactions”.37 the plausibility of such definitions shows that, for chemistry, the way we quantify and understand the macroscopic world remains indispensable. we need not resort always to the microscopic world. the macroscopic world, in fact, remains indispensable for calibrating the microscopic. the macroscopic world guides the explanation in terms of microstructure and not the other way round, as reductionists sometimes assume. this point recalls the crucial distinction between what philosophers call the manifest image of the world, which refers to what i am here calling the macroscopic world, and the scientific image of the world, which refers to microstructure. for chemistry, the manifest image remains indispensable. we are entitled to say this because, as van brakel puts it, “if quantum mechan37 j. van brakel, “chemistry as the science of the transformation of substances,” synthese 111/3, (1997): 253-282; the quote is from p. 253. ics turns out to be wrong, it would not affect all chemical knowledge […] what there is, are chemical and physical descriptions of macroscopic entities, whose identity conditions are grounded in the end in the manifest image”.38 conclusion my original aim was to determine the extent to which current chemistry is still mechanistic in spirit. through my initial historical overview, i illustrated that the mechanistic worldview involved some basic ingredients, such as the assumption that we can fully explain any macroscopic object and its behaviour in terms of corpuscular motion only, that the scientist’s task is to determine the laws of nature, that the universe is causally closed, and that there are no final causes. this set of assumptions experienced some setbacks during the twentieth century but some of its explanatory maxims remained. in the second part of my paper, i focused on chemistry, analysed the notion of nature and that of mechanism within this discipline and determined which trends in current chemistry are still mechanistic in spirit and which are not. the results show that, as regards the urge to explain phenomena by resorting to lower-level ontological units, chemistry is still in line with some of the major tenets of the mechanistic worldview. it is not mechanistic, however, as regards its acceptance of higher-level properties that are not fully reducible to lowerlevel properties, as regards its assumption of some form of finality within nature, as regards its heightened focus on rules of combination, and as regards its notion of substance that is primarily associated with macroscopic attributes. of course, much more can be said about many of the points i discuss in this paper. moreover, my evaluation of the current situation has probably not considered all the significant trends in current chemical thinking. i hope however that what i did present here is enough to support the conclusion that current chemistry still involves some traces of mechanistic thinking but it does so without adopting the entire philosophical baggage of the seventeenth and eighteenth centuries. today, chemists seem to use mechanistic explanatory strategies just like any other instrument. in their overall project of studying substances and their properties, they use this instrument when it helps and reject it when it hinders.39 38 ibid. p. 273. the distinction between manifest and scientific images of the world is, and has been, the object of sustained philosophical study. the most prominent philosophers in this area are probably edmund husserl and wilfred sellars. 39 thanks to prof. michelle francl-donnay and to an anonymous reviewer for substantia for helpful comments to a previous version of this paper. substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi substantia. an international journal of the history of chemistry 3(2) suppl. 5: 91-107, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-404 citation: g. löffler (2019) carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics. substantia 3(2) suppl. 5: 91-107. doi: 10.13128/substantia-404 copyright: © 2019 g. löffler. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a-9201 krumpendorf (6/2019) e-mail: gerd.loeffler@aon.at abstract. carl auer von welsbach (1858-1929) was a chemist and entrepreneur famous beyond the borders of austria, with good contacts to well-known chemists and physicists in europe. this is evidenced by his extensive correspondence and the shipment of his rare earth preparations to known researchers. in 1895 he discovered the elements neodymium and praseodymium and in 1905 the elements ytterbium and lutetium. in his time he was considered a specialist for the rare earth elements (ree). he received his doctorate from robert bunsen in heidelberg (1880-1882). spectral analysis was his domain. his ability to neatly separate the chemically very similar se elements from the minerals (e.g. monazite sand) to the then-known and further developed principle of “fractional crystallization” also made relatively accurate investigations of the magnetic properties of these elements possible. in particular, the chemists and physicists were interested in the question of whether or not the series of ree elements is complete with lutetium. the famous quantum physicist niels bohr had made a statement with his atomic model that lutetium must be the last element of this sequence in the periodic table of the elements and predicted the magnetic properties. they were confirmed by the experiments with the auer von welsbach preparations in particular of lutetium by the physicist stefan meyer (1842-1949) in vienna. in 1925 the physicist and theoretician friedrich hund (1886-1997) from göttingen then succeeded to set up a first quantum mechanical model (hund’s rule), which achieved good agreement with the experimental results from vienna. this was an advance in early quantum mechanics, which is also due to the highly pure se preparations of the chemist carl auer von welsbach. keywords. carl auer welsbach, rare earth elements, magnetic properties, niels bohr, friedrich hund, quantum mechanics. 1. introduction. carl auer von welsbach – the most important stages of his life as a research scientist carl auer von welsbach was born on september 1st 1858 in wels (austria) and later especially known for the invention of the incandescent gas mantle. his father alois welsbach was already famous as chief of the imperial court printing house and well-known beyond austrian borders. 92 gerd löffler auer von welsbach was born into a wealthy family. this meant that even though he lost his father at a young age, after completion of his military service year (lieutenant patent 1878) he was still able to attend the technical university of vienna to study mathematics, chemistry, and physics. there he became acquainted with adolf lieben (1836 – 1914), a professor of chemistry, who, as a member of the imperial academy of sciences and later as a member of the radium commission, supported auer von welsbach ś research projects. initially auer von welsbach switched to the university of heidelburg. this university, where famous chemists and physicists such as robert wilhelm bunsen (1811 – 1899) and gustav robert kirchhoff (1824 – 1887) taught, was a mecca for many young scientists at the time. even the famous physicist and physiologist hermann helmholtz (1821 – 1894) was working there from 1858. under the guidance of bunsen, auer von welsbach soon occupied himself with the technique of chemical spectral analysis, which bunsen and kirchhoff had developed, in order to research rare earth metals. these were little known, sparingly researched and were of complex formulation. here, he distinguished himself quickly in experimental chemistry and physics, completing his doctorate (without any written work) with “in insignis cum laude”, and had acquired trust and recognition from bunsen.1 in 1882, auer von welsbach returned to vienna and worked as an unpaid assistant to professor adolf lieben in the basement of the university of vienna’s institute of chemistry. in 1885, with the help of spectral analysis, he succeeded in proving that the rare earth element didymium in fact consisted of two elements, namely of neodymium and praseodymium.2 then followed an almost unparalleled period of discoveries as a chemist and technician and success as an entrepreneur, namely through the development of the thorium und cerium incandescent gas mantle (patented 1891) and the development of the first metal-filament lightbulb with osmium as the base material (patented 1898) and the marketing of this innovation from 1902 (auer os-light, later osram). the residual material from the production of the illuminants, namely the cerium oxide, was reused as a raw material in his firm in treibach-althofen (carinthia, austria). the product, flint (auer metal/ferrocerium), has been (and is still today) produced and sold by the billions. in 1905 he was once again successful in his laboratory at welsbach castle (near althofen) but now as a private scholar, who slowly withdrew from his economic activities. he separated the rare earth element ytterbium into the elements aldebaranium (today ytterbium) and cassiopeium (today lutetium).3 20 years later the physical properties of cassopeium were to play an important role in the further development and confirmation of quantum mechanics. with the beginning of the first decade of the 20th century, auer von welsbach devoted himself to the new phenomenon of radioactivity. in his firm in atzgersdorf, vienna, the first radium preparations in austria were produced from the residues of a pitchblende ore outside of jáchymov, czech republic. he personally examined these residues (“hydrates”) at welsbach castle, separated ionium, polonium and actinium preparations, and provided them to the university of vienna’s institute of physics and the institute of radium research in vienna, which opened in 1910, for further research.4,5 at the same time, the examination of rare earth metals proceeded and he provided their preparations to scientists, many of them later nobel prize laureates, all over europe. with this, he had supported the classification of the rare earth metals in the periodic table of elements and nuclear and quantum physics in the critical early stages. these activities, which were naturally hindered during the first world war, can be seen in figures 1 – 3. measured by his research activities, auer von welsbach published relatively little. he was more devoted to his experiments than the documentation and explanation of his research outcomes. perhaps that can be attributed to the influence of robert bunsen in heidelburg. he was an experimental chemist, experimental physicist and technician. if you look closely however, you can determine that he indeed followed developments in the fields of chemistry and physics, and consciously wanted figure 1. frequency of contact through eversand compound. source13 : gerd löffler, carl auer von welsbach und sein beitrag zur frühen radioaktivitätsforschung und quantentheorie, isbn 978-3200-04400-5, 2015, p. 125. 93carl auer von welsbach (1858-1929) to assist these developments and their representatives, such as ernest rutherford and niels bohr for example. he strove to preserve science institutes with considerable donations where the need after the first world war was greatest, such as the radium institute of vienna.6 in 1926, he published the results of his search for the rare earth element no. 61 (atomic number 61).7 with the experimental methods at the time, there was nothing that could be detected. von welsbach was to be proved right. this gap in the periodic table of elements was able to be filled only in 1945 by producing 61 (promethium) using the nuclear reactor at oak ridge, usa. it is evident that a stable element (isotope) does not exist.8 auer von welsbach was distinguished in his lifetime with many honors. he was recognized not only in austria, but also throughout germany for his many achievements, such as, for example, with the “siemens-ring” (1921) which was unofficially designated as the german version of the nobel prize. he enjoyed an exceptionally high reputation with the gesellschaft deutscher chemiker (gdch), who also hailed him and his accomplishments as a researcher and as a businessman on the 150th anniversary of his birthday in 2008.9,10 auer von welsbach was a member of various academies in europe, e.g. from 191111 he was a full member of the kaiserliche akademie der wissenschaften in austria, and from 191312 – appointed by max planck – he was a corresponding member of the preußische akademie der wissenschaften in germany. carl auer von welsbach passed away in welsbach castle, near althofen, on 4th august 1929, and was buried in vienna. 2. collaboration with and support of niels bohr’s work it is little known that auer von welsbach carried out pioneering work in the field of early quantum theory and made a considerable contribution as an experimental chemist to the slowly developing quantum theory of max planck from 1900, and then from 1910 to 1913 to that of niels bohr, culminating in an initial high point. he made numerous preparations of the rare earth elements for the physicists and chemists in europe at that time in his laboratory in carinthia in particular, in order to test the new theory in copenhagen and cambridge. the gratitude expressed by niels bohr to auer von welsbach in 1923 (see fig. 4) was made at a time when george von hevesy and dirk coster had discovered the long sought-after element hafnium in a zirconium mineral at the end of 1922, following previous extensive x-ray spectroscopic investigations, as well as the welsbach preparations. this rare document underlines the connection between the carinthian physicist and early quantum theory at that time. 2.1 carl auer von welsbach’s incandescent gas mantle and max planck’s radiation formula. forgotten details from the beginnings of quantum theory chemists and physicists, who do not or have not concerned themselves in particular with quantum physics, are mostly unaware why carl auer von welsbach was so closely linked in the early phases of quantum theory with researchers in this field. fig. 1 gives a short insight when names such as bohr, rutherford, hevesy, figure 2. auer von welsbach – correspondence with chemists and physicists in europe. source14 : gerd löffler, carl auer von welsbach und sein beitrag zur frühen radioaktivitätsforschung und quantentheorie, isbn 978-3-200-04400-5, 2015, p. 127, figure 3. an overview of the compounds of the rare earth metals, which carl auer von welsbach made available to other researchers. number of compounds (element as a salt or oxide). source15: gerd löffler, carl auer von welsbach und sein beitrag zur frühen radioaktivitätsforschung und quantentheorie, isbn 978-3-200-04400-5, 2015, p. 126. 94 gerd löffler coster, aston, and siegbahn arise as recipients of von welsbach preparations. who remembers today that even the “father” of japanese nuclear physics, yoshio nishina (1869-1951), investigated rare earth element preparations from carl auer von welsbach by x-ray spectroscopy during his studies in copenhagen with niels bohr from 1923 onwards?16,17 the discoveries of the planck radiation formula in 1900 and of the photoelectric effect (einstein, 1905) can be considered turning points in our concept of the world of physics at that time. the rare earth elements and their final classification in the periodic system of the elements was a “real test” for the further development of nuclear and quantum physics at the beginning of the 20th century. if it had not been for the achievements of the chemists, who had specialized in the discovery and isolation of these “rare” metals – including in particular carl auer von welsbach – quantum physics would not have been able to take the well-known dramatic developments in the first two decades of the last century. as one example for many other documents, this assessment arises from the letter from niels bohr to carl auer von welsbach dated may 13, 1923 (see fig. 4). 2.1.1 the interest of quantum physicists in the auer light the step taken by the natural sciences in the field of quantum physics was not very straightforward. it started in retrospect with the radiation laws of the physicist gustav kirchhoff governing the radiating properties of solid bodies. together with robert w. bunsen, kirchhoff established heidelberg‘s reputation as a research center, where the scientific career of carl auer von welsbach also began. in 1860, kirchhoff recognized that the ratio of the emissivity to the absorption capacity for all types of radiation, independent of the material properties of the body and for a certain wavelength, only depends on the temperature of the body. in 1875, kirchhoff was appointed professor of theoretical physics in berlin, which later became the center for quantum physics. kirchhoff ’s radiation law, with which theoretical physics introduced the term “black body,” as an ideal state, which a body approaches with increasing temperature,18 was the starting point for further considerations and experiments of physicists to describe the energy emitted by a body with a comprehensive law, which was finally presented on december 14, 1900 as the radiation formula at a convention of the german physical society by max planck. kirchhoff himself sensed the fundamental significance of his findings and/or his radiation law and knew in which direction further research would have to be carried out in order to find a generally valid radiation law. in 1860, he wrote in this respect: “it is a task of great importance to find this function.19 not until we have solved this problem, will we be able to reap all the fruits of our labors.”20 the time span of about 40 years alone exemplifies the efforts, struggles and aberrations which had been experienced in order to come to a conclusive result. starting with kirchhoff, several physicists, such as wilhelm wien (1864-1928), friedrich paschen (1865), otto lummer (1860-1925) and heinrich rubens (1865-1922), were involved. max planck was also not immune to making errors until he decided “in an act of desperation”21 to introduce two natural constants: namely, the boltzmann constant k 22 and the action quantum h, which had already been described in 1900, into the previously unsatisfactory drafts for a radiation formula and as such open the door to quantum physics. the main problem was to bring experiment and theory into agreement with one another in the infrared range. if, however, kirchhoff had not introduced the “black body” and its physical properties (see above) in 1860, most certainly years, if not decades would have passed before this era of physics would have come up with the breakthrough insight created a completely new world view from 1900 onwards. producing a body which came closest to the “black body” postulated by kirchhoff, was by no means trivial. there were many failed attempts in this respect. in parfigure 4. niels bohr to carl auer von welsbach (05/13/1923). source: archives auer-von-welsbach research institute, file: correspondence; location: auer-von-welsbach museum, althofen (carinthia). 95carl auer von welsbach (1858-1929) ticular, wilhelm wien and otto lummer attempted to find a solution at the physical-technical imperial institute in berlin. the same applied from an experimental point of view to the development of a photometer, which could measure the wavelengths of radiating bodies with sufficient accuracy. thermally insulated (heated) platinum tubing was finally used as a black body and as of 1889 a newly developed photometer was used, the socalled “lummer-brodhun cube”.23 as a radiating body emits electromagnetic waves in the ultraviolet to the ultra-red range, it was also necessary to filter out the wavelengths from this spectrum with sufficient precision and intensity. in the development of this technology, the physicist heinrich rubens distinguished himself in particular with the residual radiation method. the aim was to clarify the discrepancies between theory and experiment in the ultra-red range. the method developed by rubens was particularly suitable for this purpose. in the experiments, light sources and temperatures were necessary which could provide an ultra-red range with sufficient intensity. for this purpose, rubens used the auer light, i.e. the incandescent gas mantle.24,25 the auer light is an excellent source of radiation in that only a small part of the emitted energy is in the visible range. most of the energy is emitted in the ultraviolet and in particular in the infrared and the ultra-red range – which in this case was of great interest. fig. 5 shows the principle of selective electromagnetic radiation for a certain wavelength starting from an emitter. fig. 6 shows why the auer incandescent mantle possesses suitable radiation capacity especially in the ultra-red range. the residual radiation method is based on the fact that some crystals have a selective reflectivity, such as e.g. rock salt, fluorspar and quartz. by positioning several plates of these crystals behind one another (multiple reflectivity), stray rays are suppressed and only electromagnetic waves of a certain wavelength are forwarded with a high degree of reflectivity (to a thermocouple). with an auer light, one can thus create very precise radiation with a wavelength of λ=43 μm with sufficient intensity. optical grids were not suitable for this purpose.26 in order to underscore the advantage of the auer light using the residual radiation method, heinrich rubens is quoted as follows (extract): “as i explained earlier, one already obtains very pure residual rays after three-fold reflection of the radiation emitted by the auer burner in a strength which amounts to 1.7 % of the entire radiation. a perfect black body at 1800 degrees abs. would result in less than 1 per mille of residual radiation under the same circumstances.”27 the significance of the “radiation physicists” in berlin, in particular heinrich rubens, and the experimental physics advanced by them cannot be praised highly enough for the acceptance of quantum physics, which gave rise to a completely new way of looking at processes on an atomic scale. 2.2 quantum theory and magnetism of the rare earth elements a short introduction to the subject of “magnetism” it is general knowledge today that the earth possesses a magnetic field and that anyone can navigate themselves through the earth’s magnetic field with the help of a figure 5. the residual radiation method according to heinrich rubens. a: emitters, e.g. auer incandescent mantle, h.sp: concave mirror, th.s: thermal column, crystal plates 1, 2, 3, 4. source: gerthsen, christian; kneser, h. o.: “physics”, textbook, (berlin 1969), 371. figure 6. the emissivity of the auer incandescent mantle relative to a black body (=1). wellenlänge = wavelength 10-6 m. source: rubens, heinrich: “the emission spectrum of the auer incandescent mantle”, in: proceedings of the german physical society 7 (1905), table, 349. 96 gerd löffler compass using the direction given by the magnetic needle. in the same manner, it is general knowledge that a magnetic field can be created using simple means with a current flowing through a coil, whereby the coil likewise behaves as a magnetic needle in the earth’s magnetic field if it is freely suspended. it is also known for objects of everyday life, e.g. in electronic products (televisions, computers), from food processors to cars, as well as in large manufacturing components, such as machines in all branches of industry, not least of all in power generating plants such as those utilizing atomic, thermal, water and wind energy, that all of the above use magnets and/ or metals and metal alloys with magnetic properties. there are four types of magnetism which can be differentiated: diamagnetism, paramagnetism, ferromagnetism and ferrimagnetism,28 depending on the different physical properties of the metal compounds which occur in nature, or artificially manufactured metal oxides and metal alloys. for a long time, the causes of the different magnetic behavior of substances, i.e. the elements and their compounds, was not known. the technical applications were far ahead of an understanding of the actual physics.29 up until today, magnetism is a special field of solid state physics and the subject of further developments in quantum mechanics. at this point in time, ferromagnetism, which is a characteristic of the substances iron, cobalt, nickel as well as the rare earth element gadolinium, and in which a magnetic force can also be determined without any external influence (without an additional external magnetic field), will not be further discussed here, as early quantum theory could not provide any conclusive explanation for this. the same applies for ferrimagnetism.30 the situation is different with the diamagnetism of the elements, characterized by diamagnetic substances which are crowded out of an existing external magnetic field (µ < 0; κ < 1).31 paramagnetic substances are drawn into an existing magnetic field (µ > 0; κ > 1). experimentally, in the first case, there is attenuation of the existing magnetic field and in the second case it is intensified. since the causes of this were not being pursued at that time (i.e. quantum physics was not a topic of interest), the differing behavior of diamagnetic and paramagnetic substances was described as “lenz’s principle”,32 whereby it should be mentioned that both element types cannot be differentiated in their magnetic behavior if no external magnetic field is present. however, there is a further characteristic difference: diamagnetism is independent of temperature, whereas paramagnetism decreases with increasing temperature (curie’s law). further, it should be remembered that some paramagnetic substances (compounds) have a characteristic color. besides the elements of the iron group, the rare earth elements can also be included with those in the periodic system that are characterized by their special magnetic behavior (see above), with which carl auer von welsbach had worked on so intensively and/or was decisively involved in their preparation in a pure state. the understanding of magnetism only changed slowly and stepwise when the french physicist paul langevin (1872-1946) assumed from an atomic model in 1905 that an electron gas is a prerequisite for non-magnetic substances, whereby the quotient of the charge of the electrons to their mass is more than one thousandfold greater than that of the compensating positive particles. both particle types ensure external electrical neutrality. according to the classical theory, the electrons move in a circular motion (larmor frequency) around an external magnetic field. these circular motions produce a magnetic moment. from this, the magnetic susceptibility for diamagnetism can be derived, as it still applies in principle today. it became apparent that the assumption of langevin in this form was not tenable, as the properties of an electron gas residing around a positive charge had not been completely described. such a model assumed by langevin creates an opposite dipolar moment by the (spherically shaped) surface of the electron gas, so that the entire magnetic moment is zero. niels bohr referred to this in his dissertation in the year 1911.33 further steps in the development of nuclear and quantum physics were needed (bohr-rutherford, bohr-sommerfield atomic model) as well as the step to quantum mechanics by werner heisenberg, max born, amongst others, in the mid 1920’s. however, langevin still deserves credit for his attempts and his conclusion that the magnetic behavior of the elements can be attributed in principle to that of the electrons. 2.3 the long road to a first quantum physical model for the magnetic behavior of the ree despite the progress that quantum theory had made, thanks to the famous theorists such as bohr, sommerfield and heisenberg, until the middle of the 1920‘s the abnormal zeeman effect (splitting of the spectral lines in a strong magnetic field into more than 3 terms),34 the paschen-back effect (multiple splitting of the spectral lines in a strong electrical field)35 and the complicated spectra of the rare earth elements had not yet been disentangled. it was thus appropriate to understand the magnetic properties of these elements, starting with the previous findings about the numbers of occupied electrons according to the different main quantum numbers (= “electron shells”) of the lighter elements and the empiri97carl auer von welsbach (1858-1929) cally obtained magnetization numbers (or magnetic susceptibility).36 the physicist friedrich hund (1886-1997) in göttingen, a student of the theorist max born (18821970), was particularly specialized in this field. hund published the results of his work in 1925 (see below).37 it was a long road which had to be taken until this point in time was finally reached: bohr had already ascertained in his dissertation in 1910,38 that the magnetic properties of the elements known then could not be explained using classical theory (with free electrons or those bound to atoms). according to classical theory (langevin’s theory of paramagnetism), it could be derived that all elements must have paramagnetic properties. in reality, however, the situation was and still is very different: most elements are diamagnetic.39 the supporters of quantum theory were thus challenged again, and further development of quantum theory was urgently needed. this process concerned researchers, both opponents and advocates of quantum theory, for many years to come. this discrepancy was addressed by niels bohr in several stages. in 1913, he went one step further by establishing a fundamental postulate. his solution to the further development of quantum theory was to assert the consistency of the angular momentum of an electron in an orbit, also in the presence of an external magnetic field. it can be shown using perturbation theory (in principle a mathematical process) that under this assumption one individual electron (of an atom) performs work against the external field,40 i.e. the diamagnetic substances are crowded out of the (external) magnetic field. physics only allows this explanation for the occurrence of diamagnetism, however, if the external magnetic field is vertical to the circular electron level. in other words, a theoretical model was only imaginable for one special case. bohr’s quantum theory had reached its limits.41 progress in quantum physics was needed. this work was essentially carried out by sommerfeld and subsequently by max born (1882-1970)42 and his students werner heisenberg, pascal jordan, friedrich hund (scientist for theoretical physics in göttingen) as well as by the austrian wolfgang pauli.43,44 from 1925 onwards, the step from quantum theory to quantum mechanics had been fulfilled. besides copenhagen, göttingen became a center for theoretical physics.45 the sterngerlach experiment and that of samuel goudsmit and george eugene uhlenbeck were correctly interpreted in the course of this development. a difficult process from theory and experiment now led to the belief that a halfintegral angular momentum (= ½ h/2π) and thus a magnetic moment had to be attributed to an electron. this was in no way to be taken as a matter of course, as up until then electrons and protons were still considered to be the building blocks of the atomic nucleus (thomson’s atomic model). 2.4 comparison of the magnetic properties of rre: theory versus experiment as already mentioned, carl auer von welsbach discovered the rare earth element cassiopeium (called lutetium today) with the atomic number 71. in addition to other preparations, auer von welsbach also sent this preparation to the institute for radium research in vienna, where the head stefan meyer was working on the measurement of the magnetic properties of different elements, amongst other things.46 on 2/29/1924, meyer wrote to auer von welsbach:47 institute for radium research” vienna, 2/29/1924 ix., boltzmanngasse 3. dear doctor! as i already wrote to you, your pure cp2 (so4)3 x 8 h2o is diamagnetic, which is of great interest. likewise, hfo2 is diamagnetic.48 with kindest regards and greetings, yours faithfully, stefan meyer a few days later, on 3/6/1924, carl auer von welsbach replied: it will greatly please bohr to hear that his prediction about the diamagnetism of cp has been confirmed.49 the letter from auer von welsbach to bohr is one of the few direct pieces of evidence amongst the documents still remaining which shows that auer von welsbach was aware of the significance of the explanation of magnetism by quantum theory. following this, stefan meyer published one year later the magnetization numbers of the other rare earth elements starting with atomic number 57 (lanthanum) up to atomic number 71 (cassiopeium = lutetium). meyer compared the measurements with the results of the famous spanish physicist blas cabrera (18781945), who can also be included in this small circle of specialists in this area. the results concurred well, if one takes into account the state of measurement technology available at that time (see fig. 7). remarks: regarding the magnetization numbers (weiss’s magnetons)51 of the rare earth elements (lanthanum la to cassiopeium cp), see the following footnotes.52,53 98 gerd löffler stefan meyer (1925) wrote in the introduction: since the discovery of the unusual magnetic properties (18991) of the rare earths, i have always had the opportunity to measure their magnetization numbers thanks to the kindness of c. auer-welsbach and have repeatedly reported about this.2 1) vienna. ber, (iia), 108, 861, 1899 2) vienna. ber. (iia), 109, 403, 1900; 110, 541, 1901; 111, 38, 1902; 117, 995, 190 8) meyer continues: “at the beginning of 1924, i informed the interested parties, especially the bohr institute in copenhagen, that both cassiopeium (71) as well as hafnium (72) are diamagnetic, and that in the first instance this information referred to cp preparations from 1915 and 1924.”54 niels bohr had already recognized the significance of the welsbach preparations in 1923, when he classified them as “inestimable” for atomic research (see the letter from bohr to auer von welsbach dated 05/13/1923, fig. 4). experimentally obtained data on the magnetic behavior of the rare earth metals were now available and could be considered essentially verified according to the state of measurement technology at that time. however, the theoretical explanation was still missing. in 1925, the physicist friedrich hund succeeded in essentially explaining theoretically the experimental data which had been collected up until then about the magnetic behavior of the above-mentioned metals on the basis of the work of the afore-mentioned physicists in göttingen, the assumptions of niels bohr about the successive occupation of the subjacent electron shells (today described as the 4f-electrons),55 furthermore taking the pauli principle and especially the preliminary work of heisenberg into consideration.56,57 hund described his theoretical model in an abridged form, as follows: “shortly thereafter, he [hund] was able to explain the magnetic behavior of the rare earths by giving the basic state of their trivalent ions using the rule that from the possible multiplets with the deepest energetic configuration, the multiplets with the highest multiplicity lie deepest and that which is the deepest is the one with the highest angular momentum.”58 hund established the bohr magneton numbers (for the trivalent ions of the rare earth elements lanthanum and subsequently) and then converted these into weiss’s magneton numbers.59 in this way, he could compare his theoretically established values with the data determined experimentally by blas cabrera and stefan meyer. the comparison with the data from stefan meyer is shown in fig. 8.60 the level of agreement between theory and experimental results was astoundingly good considering the experimental techniques used by stefan meyer and the state of quantum theory at that time. in particular, the occurrence of two maxima by hund could be comprehended using one of the theories based on quantum physics. both lanthanum and lutetium ions are clearly diamagnetic. there is, however, a noticeable deviation between theor y and experiment for the europium ion. stefan meyer explained that the europium preparation used must have still contained 5-6  % gadolinium, in other words it was slightly impure. he states that for this reason, weiss’s magneton number would have to be 15.5 instead of 18.5.61 according to this, the difference between theory and experiment would then be reduced, although for the europium ion it would still be significant.62 the comments from meyer, however, also show that through the advances made in measurement techniques the investigations of magnetic properties were suitable to identify the rare earth elements in substances and/or to establish their degree of impurity. the actual objective to disentangle the spectral lines of the rare earth elements came one step closer by an understanding of their magnetic properties, namely by quantum theoretical specifications for the permissible energy states of an atom and/or these elements. in fig. 7 the magnetization numbers (weiss’s magnetons) of the rare earth elements (lanthanum 57la to cassiopeium 71cp). n: weiss’s magnetons; z = atomic number (= number of protons). source50: stefan meyer, magnetization numbers of the rare earths, physikalischezeitschrift, 1925, 26, p. 53. 99carl auer von welsbach (1858-1929) this respect, the quality and purity of the preparations of these elements (mostly sulfates) which were also supplied by carl auer von welsbach played an important role. however, it must be brought to mind here that the arc and spark spectra, e.g. of dysprosium and yttrium compounds exhibited more than 3,000 and/or more than 2,000 lines, respectively.64 however, the spectra of the rare earth elements were not fully explained during the lifetime of carl auer von welsbach. further advances were linked to continued developments in quantum mechanics and achieved after his death in the 1930’s.65 today, rare earth elements are used in numerous industrial products (in the form of complex metal compounds) due to their magnetic properties, in particular in the electronics industry. this is referred to as an inherent “magnetic technology”. this rapid development was unimaginable at that time up to the end of the 1920’s. however, it shows the true significance of basic research work which was carried out almost 100 years ago. 3. the determination of the atomic weights of ytterbium and lutetium the two elements ytterbium and lutetium conclude the lanthanide series. these findings and the properties of these two elements still have an important significance for chemists and physicists today. the discovery and the following chemical-physical investigations commencing with ytterbium by jean charles de marignac (1817-1894)66 in a mineral obtained from the area around the swedish town of ytterby near stockholm (1878) and finally the separation of this element by auer von welsbach commencing 1905-1914 – almost at the same time as the french chemist georges urbain – into ytterbium as it is known today (called aldebaranium at that time) and lutetium (called cassiopeium at that time) has given today’s table of the elements its definitive structure through modern chemistry and physics. auer von welsbach had already worked on ytterbium relatively early on, as can be seen from the records of his most important employee, ludwig haitinger (1860-1945).67 here it is briefly described how he separated the original ytterbium from the elements scandium and erbium contained in the starting mineral. auer was also aware of the weak basicity of ytterbium before 1893. he also knew that the oxalate of this supposed element (a white powder) was almost insoluble in water and dilute hydrochloric acid. besides the knowledge of the spectrum, these findings served him later on in his further work to determine the atomic weight of the actual elements, namely ytterbium and lutetium. the procedure used for the separation of ytterbium (old) into ytterbium (aldebaranium) and lutetium (cassiopeium), starting from half a ton of crude ytteroxalate in 190668 is described in detail in the sitzungsberichte der kaiserliche akademie der wissenschaften. the “birth” of the new element, in this case the discovery of the element lutetium, can best be described by the discoverer in his own words, and therefore his description of this moment and/or the time at the beginning of 1905 should be reproduced verbatim, similarly his description of the first atomic weight determinations in 1906 should be quoted. these were repeated in la ce pr nd pm sm eu gd tb dy ho er tu yb lu fig. 8 magnetic properties of the rare earth elements (trivalent ions of 57 lanthanum to 71lutetium). source63: friedrich hund, atomtheoretische deutung des magnetismus der seltenen erden (= theoretical atomic signification of magnetism of the rare earths), zeitschrift für physik, 1925, 33, table 1, p. 857. table 1. (to fig. 8). atomic number 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 mg. number cabrera 0.0 12.5 17.8 17.8 13.4 4.2 0.0 39.4 48.3 52.8 52.8 47.7 37.6 22.5 0.0 mg. number meyer 0.0 13.8 17.3 17.5 13.4 7.0 18.0 40.2 44.8 53.0 51.9 46.7 37.5 22.5 0.0 mg. number = weiss’s magneton number 100 gerd löffler the years to follow. several records from 1912 about the determination of the atomic weights of ytterbium (aldebaranium) and lutetium can be found in handwritten documents, which are archived in the carl auer von welsbach museum (see fig. 9, fig. 10 and the literature references below). the earliest announcement of this discovery of the composition of the old ytterbium from two elements results from the notification of these findings by auer von welsbach with the imperial academy of sciences in vienna in 1905. however, this did not yet include the atomic weights and spectra of the two elements. for this reason, however, we know that mainly the spectral findings at this point in time supported these results.69 in 1906 and 1907, he then described how he proceeded exactly and his results (spectra, atomic weights of the newly discovered elements, in this respect see also below). in 1906, readers were informed in a separate treatise via the journal ‘justus liebig ś annalen der chemie’ about the exciting situation in his laboratory at the time of the discovery.70 here he wrote: during the investigation of ytterbium ammonium oxalate, i noticed some strange phenomena which suggested that ytterbium is not a uniform body. i first compared the different fractions (remark of the author: fractionated crystallization) amongst themselves and also using pure ytterbium from earlier presentations, but could not find any indications for the correctness of my assumption despite careful comparison. nevertheless, i continued the fractionation. after a longer period of time, i obtained a preparation which demonstrated quite distinct changes in intensity, which in the case of weak arcing showed up by all means in some of the characteristic lines in the red of ytterbium in comparison to other ytterbium preparations. when this separation process was continued, these changes became even more striking. individual lines in the red started to become paler, others became more pronounced with all the more radiance. now the change in the intensity of the lines became noticeable also in the remaining parts of the spectrum. when i then compared the ytterbium fractions which were farthest apart later on, after protracted continuation of the separation process, the distinct differences of the two spectra came to light. with the continuation of the separation process, i realized that the purest preparations did not have any common lines any longer even with strong arcing in the optical part of the spectrum. i now photographed the spectra which had been produced with the help of a concave grid under fully identical experimental conditions in the range λ = 4500-2600 (å).71 the glass-clear, very high-contrasting negatives gave, when compared directly, an extremely interesting picture. almost all lines were very precise upon moderate enlargement … following a short description of the spectra, he continued thanks to these explanations which were most certainly needed, the exact scientific proof of the successful separation of ytterbium into two bodies had been provided. auer von welsbach then established that he “had already informed anyone who had asked in the year 1906”, and that he had informed them about the approximate wavelengths and the approximate atomic weights. he had determined the atomic weights for ad= 172.52 g/ mol (ytterbium) and cp= 174.28 g/mol (lutetium). the separation method he used was fractional crystallization (appendix). this method was also suitable, amongst other things, as the rare earth elements all crystallize isomorphically. his particular contribution to the further development was that he used the different solubility of ammonium binoxalate of the rare earths in ammonium oxalate (intentionally mixed with some ammonia so that no turbidity occurred)72 during fractionation and was thus able to follow in many hundreds of steps the slow separation by continuous analysis of his (arc) spectra,73 until no change in the spectra of the elements ytterbium (new) and lutetium could be observed. in the years that followed up until 1914, very exact spectra and atomic weights which had been determined by further experiments were published. the publications not only appeared in the communications of the imperial academy of sciences but also partly in other scientific journals.74 the rare earth elements which are discussed here were certainly available to him in 1903 through the basic maceration of the raw material monazite (using sodium hydroxide)75 as oxides and/or as salts, even though he did not expressly mention this. monazite was the starting material for the extraction of thorium, which was on the one hand the main constituent of the incandescent mantles of his gas lights which were sold and used on a worldwide basis. during their production, different mixtures of the rare earths, amongst other things, accumulated copiously as a “waste product”. the french chemist marginac (who had previously also discovered gadolinium and was very well known) succeeded in extracting the old ytterbium from these mixtures in 1878, as already mentioned above. in 1907, auer von welsbach published a comprehensive paper and determined thereby the atomic weights of ytterbium (aldebaranium) and lutetium (cassiopeium) as 172.90 and 174.23 on the basis o=16 according to the bunsen method. in the same publication, he also published the corresponding spectra.76 101carl auer von welsbach (1858-1929) in 1912, auer von welsbach made a further attempt to determine the atomic weight of the elements ytterbium (new) and lutetium, which he had extracted from the old ytterbium in 1905, apparently in order to improve the accuracy of his procedure and thus the result. the route that he took is to be looked at more closely here: after conclusion of the fractional crystallization, which extended as far as the 320th series, he still had various ytterbium and lutetium preparations from 1903 in the form of solid substances (oxalates, oxides) and (not further fractionated) lyes. in a renewed spectroscopic examination, he noticed that some spectra of these preparations still showed slight traces of calcium (ca), sodium (na), zinc (zn) manganese (mn) and thorium (th) as well as several traces of silicic acids (sio2). for the determination of the atomic weights, auer von welsbach concentrated on the cp (lutetium) preparations which were still slightly impure with silicic acid amounting to 18.2 grams and which originated from the end fractions from the 147th – 319th series. the elimination of k and na succeeded by the skillful addition of nitric acid and hydrogen sulfide. finally, a few steps later, a cpnitrate solution was produced which was precipitated with ammonia. a part of the hydrate was dissolved in nitric acid, the other part was smelted. the oxide cp2o3 (lu2o3) was obtained. the k and na traces had been eliminated in this cp preparation.77 in order to remove the traces of silicic acid, the purification process had to be extended and continued with other substances. the cp oxide obtained in the first step was dissolved again in nitric acid. the solution was concentrated and heated until the evolution of nitric oxide. the smelt was partially dissolved in water. in addition to the turbidity of the water, a flaky precipitate occurred in a small amount, which did not dissolve after the renewed addition of nitric acid or water, and no turbidity of the liquids could be observed. it could be proven that the sio2 traces (and also thorium traces) had been at least partly removed with the precipitate. finally, auer von welsbach used oxalic acid to which nitric acid had been added twice in a row while heating the precipitate to incandescence, with precipitation of the respective mother liquor. by “vigorous” heating to incandescence of the last oxalate precipitate in a platinum crucible, he obtained cp oxide as a white powder. “contrary to expectations”, however, the silicic acid had not entirely disappeared. at this time, auer von welsbach had a platinum crucible, which he had used for “more than 30 years“, but the impurities in the platinum itself could not be completely excluded. by weighing the crucible before and after heating to incandescence, he could exclude such an effect. the accuracy of his weighing activities must have amounted to approx. + 0.001 grams. the cp oxides were now dissolved in nitric acid. this clear solution was mixed with sulfuric acid in a slight overage and slowly concentrated. “crystal clear” and “nice-looking” sulfate crystals were formed. these were then dissolved in a little water so that a completely clear solution was obtained. in the last step, oxalic acid “free of ash residues” was added to this solution. the cp oxalate was precipitated, was washed and finally heated to incandescence. the result was cp2o3 (lu2o3) as an oxide which had been purified several times from the traces of other elements. auer von welsbach had now produced lutetium (cp) in different compound forms starting from a defined amount, namely as a defined amount of hydroxide, sulfate and as oxide. the last two compounds alone, whose exact amounts he determined gravimetrically, would have sufficed in order to determine the atomic weight of lutetium (lu) by a simple calculation. in a similar manner, he continued experimentally with the original ytterbium (new) that he had produced in 1905. in 1912/1913 he repeated these experiments a total of three times with essentially the same results. the details of the atomic weight refer to the atomic weight for oxygen o= 16. on average, these experiments resulted in 173.00 for ytterbium and 175.00 for lutetium.78 the handwritten laboratory records used for the determination of the lu atomic weight from the year 1912 are still mostly available and are archived in the auer von welsbach museum. these are to be considered according to the sources given as an obvious preliminary result of the final results, which were published in june 1913 in the monthly edition of the chemie mitteilungen (chemical communications)79. it is apparent here, amongst other things, that auer von welsbach had gradually come closer to the final result through his corrections, using as an example the element lutetium, (cassiopeium = cp), (see fig. 9 and fig. 10) compared to the current values used today for yb= 173.045(10), lu= 174.9668, this is to be considered an outstanding result considering the technology available to chemists at that time in 1910.80 one of the highlights of the exhibits in the auer of welsbach museum is that there is still a sealed test tube with a lutetium preparation (cp2o3) originally produced by auer (see fig. 11) 102 gerd löffler appendix: fractional crystallization the principal procedure used in the separation of substance mixtures by “fractional crystallization”: a method to separate the rare earth elements and mixtures of radioactive substances. mu lt icomponent mi x t u res, d issolved at a n increased temperature until saturation, e.g. in distilled water, nitric acid or in other solvents, can be separated into individual components, i.e. for example, into oxides or salts of the individual elements of the mixtures of these substances, in which this heated solution is cooled down (e.g. by allowing it to stand). as the components of this mixture of substances as a rule possess differences in solubility, depending on the temperature, these element compounds crystallize at different points in time. if the crystallization process is interrupted at the right time and the alkaline solution (mother liquor) is removed, one obtains the first fraction (top fraction) of an element – e.g. as a salt – which has become more concentrated and is relatively free of the other components of the original mixture. this precipitate is then redissolved and the procedure is repeated. the respective mother liquors are evaporated again and then cooled down as in the first step. through the skillful combination of crystallization, dissolution and evaporation, the most hardly soluble element becomes increasingly concentrated and as such separates from the original mixture of substances. the sequence of this procedure can be seen schematically in fig. 12. the greater the number of crystallization steps, the purer the presentation of the individual components will figure 9. lutetium (cp), atomic weight determination, second to last step 1912. figure 10. lutetium (cp), atomic weight determination 1912 (last step). figure 11. test tube with a lutetium preparation (cp2o3) originally produced by carl auer von welsbach. 103carl auer von welsbach (1858-1929) become (as salts of the element). the least soluble elements crystallize at the beginning, and the most easily soluble components at the end.82 the rare earth metals almost always occur in nature as similar mixtures of such substances. chemists then speak about a “socialization” of the elements, which however is only observed with the rare earth metals. auer von welsbach developed this separation method which had originally already been used by dimitri iwanowitsch mendelejew (1834 – 1907) to perfection when investigating the rare earth metals and the elements of this series that he discovered. however, for this purpose many thousands of crystallization steps were necessary in each single case. auer von welsbach’s procedure for the separation of didymium into neodymium and praseodymium in 1905 using a double nitrate salt of ammonium (1885) was briefly described by hevesy83. the separation of ytterbium in 1905 was performed by auer von welsbach using the double oxalate of ammonium by the same method. the different separation experiments to concentrate actinium during his research into radioactivity also took place using fractional crystallization.84 in principle, the method of fractional crystallization was used, e.g. by madame curie in the discovery (isolation) of radium and by otto hahn in the discovery of nuclear fission (the separation of radium from barium chloride and identification of the rare earth metals as nuclear fragments). these elaborate procedures for the separation of mixtures of substances have been extensively replaced today by chromatographic and ion exchange processes. the true complexity of the method used by auer von welsbach at that time (from around 1895 onwards) is to be seen in the light of more recent research, e.g. in the paper by rosmanith85. bibliography and comments 1. http://www.althofen.at/welsbach.htm (22/03/2019). 2. carl auer von welsbach, die zerlegung des didyms in seine elemente, chemical monthly, 1885, 6, 447-491. 3. carl auer von welsbach, die zerlegung des ytterbiums in seine elemente, chemical monthly, 1907, 29, 181-225. 4. carl auer von welsbach, über die chemische untersuchung der actinium enthaltenden rückstände der radiumgewinnung (1. teil). mitteilungen der radium-kommission 6, in: proceedings of the imperial academy of sciences in vienna, division for mathematics and natural sciences sect. 2a, 119,1910, pp. 1-44; chemical monthly, 1910, 31, 1159-1202. 5. there are indications that auer von welsbach did not knowingly observe neutron activation in these studies. georg steinhauser,gerd löffler, roland adunka, eine unentdeckte entdeckung ?, nachrichten aus der chemie, 2014, 62, 1074-1076. 6. handwritten letter from stefan meyer to carl auer von welsbach dated 11/29/1923, archives auer-vonwelsbach research institute, file: correspondence; location: auer-von-welsbach museum, althofen, carinthia. 7. carl auer von welsbach, über einige versuche zur auffindung des elementes nr. 61, chemie.-zeitung, 1926, 50, 990. 8. hans-jürgen quadbeck-seeger, die elemente der welt, weinheim 2007,p. 61. 9. gerd löffler, pionier der seltenen erden, nachrichten aus der chemie, 2008, 56, 889-892. 10. roland adunka, entdecker – erfinder – unternehmensgründer, nachrichten aus der chemie, 2008, 56, 959-962. 11. congratulatory telegram from adolf lieben to carl auer von welsbach dated 05/31/1911, archives auer-von-welsbach research institute, file: correspondence; location: auer-von-welsbach museum, althofen, carinthia. 12. certificate of appointment (copy) to corresponding member of the prussian academy of sciences (22/05/1913), archives auer-von-welsbach research institute, file: other documents; location: auervon-welsbach museum, althofen (carinthia). 13. gerd löffler, carl auer von welsbach und sein beitrag zur frühen radioaktivitätsforschung und quantentheorie, isbn 978-3-200-04400-5, 2015, p. 125. 14. ibid p. 127. 15. ibid p. 126. 16. letter from georg hevesy to carl auer von welsbach dated 10/19/1923, archives auer-von-welsbach ← sparingly soluble easily soluble → [lösung = solution; kristalle = crystals; mutterlauge = mother liquor] figure 12. schematic sequence used in fractional crystallization.81 104 gerd löffler research institute, file: correspondence; location: auer-von-welsbach museum, althofen (carinthia). 17. yoshio, nishina, on the l-absorption spectra of the elements from sn(50) to w(74) and their relation to the atomic constitution, philosophical magazine and journal, 1925, 49, 522 f. 18. in practice, hollow spheres and cylinders from fireproof materials with circular openings of a few millimeters were used. these objects were kept at a constant temperature. the (electromagnetic) radiation coming from the opening was then analyzed in relation to the temperature. one analytic method (german: reststrahlenmethode “residual rays method”) is shown in schematic form in fig. 5. 19. the increasing industrialization of the economy was another driving force to gain a clear understanding of the processes of heat and light generation. for example, in 1860, there was no safe, i.e. continuingly glowing, illuminant yet. the gas mantle that was developed by carl auer von welsbach was not patented until 1885 and was only introduced on the market in series production as a safe light source around 1891. source: see online http://www.althofen. at/welsbach.htm (03/04/2019). 20. wilfried, hauser, strahlungsphysiker ebnen in berlin den weg zur quantentheorie – vienna, paschen, lummer, rubens, in: wilhelm treue; gerhard hildebrandt, berlinische lebensbilder “naturwissenschaftler”, berlin, 1987, p. 92. 21. armin hermann, max planck. vorträge und erinnerungen, see online: http://www.zeit.de/1984/08/vortraege-und-erinnerungen (24/03/2019). 22. max planck finally decided, after some hesitation, to build on the work of austrian physicist ludwig boltzmann in the area of thermodynamics for the development of his radiation formula. boltzmann was seen to be a proponent of “atomism.” 23. see online https://physicsmuseum.uq.edu.au/lummer-brodhun-photometer (23.04.2014) 24. dieter meschede, gerthsen physik, berlin/heidelberg, 2006, p. 588. 25. heinrich rubens; friedrich kurlbaum, anwendung der methode der reststrahlen zur prüfung des strahlungsgesetzes, annalen der physik, 1901, 4, 649-666. 26. meschede, 2006, p. 588. 27. heinrich rubens, über das emissionsverhalten des auerbrenners”, annalen der physik 1905, 14, 734. 28. horst, stöcker, taschenbuch der physik, frankfurt/ main, 2010, pp. 441-447. 29. carl auer von welsbach built his first hydroelectric power plant in 1898 for generating electricity for the production of osmium lamps and the production of rare earth elements in his factory in althofen-treibach. for his construction of power plants in carinthia, see roland adunka, carl auer von welsbach. entdecker – erfinder – firmengründer, 2015, 64-67. 30. ferrimagnetism is the characteristic of crystals that have partial grids with opposing magnetization. they only compensate each other in part and are therefore only slightly ferromagnetic. source: horst stöcker, taschenbuch der physik, 2010, pp. 956 f. 31. µ = κ 1 applies, whereby µ indicates magnetic susceptibility and κ indicates magnetic permeability – which is the relationship of magnetic flux density b (in the material) to the outer magnetic field strength h. the magnetic susceptibility µ is identical or rather proportional to the rate of magnetization used by many researchers. 32. fachredaktion für naturwissenschaften und technik des bibliografischen instituts (ed.), meyers physiklexikon, 1973, p. 525. 33. dieter wagner, das rätsel des magnetismus, physik journal, 2005, 4/3, 23 f. 34. the normal zeeman effect (division of a spectral line into 3 sections) has already been explained by means of the classical electrodynamics and early quantum theory, as the spin of electrons was not known at this time. 35. both the physicists friedrich paschen (1865-197) and ernst back (1851-1959) discovered the paschen-back effect in 1921. 36. m = ϫ x h0 : → ϫ = m/h0 magnetic susceptibility, m= magnetic moment, h0 = outer magnetic field 37. friedrich, hund, atomtheoretische deutung des magnetismus der seltenen erden, zeitschrift für physik (1925), 33, 855-859. 38. niels bohr, studies on the electron theory of metals, (diss.), 1911, p. 395. 39. ulrich, hoyer, die geschichte der bohr’schen atomtheorie”, 1974, p.150. 40. ibid., p. 153. 41. ibid., p. 160. 42. max born, mein leben, 1975, pp. 288-304. 43. wolfgang pauli, über den einfluß der geschwindigkeitsabhängigkeit der elektronenmasse auf den zeeman-effekt, zeitschrift für physik, 1925, 31, 373-385. 44. wokfgang pauli, über den zusammenhang des abschlusses der elektronengruppen im atom mit der komplexstruktur der spektren, zeitschrift für physik, 1925, 31, 765-783. 45. werner heisenberg, über quantentheoretische umdeutungen kinematischer und mechanischer beziehungen, zeitschrift für physik, 1925, 33, pp. 879-893 and max born; pascal jordan, zur quan105carl auer von welsbach (1858-1929) tenmechanik, zeitschrift für physik, 1925, 34, 858888. max born; werner heisenberg; pascal jordan, zur quantenmechanik. ii., zeitschrift für physik, 1926, 35, pp. 557-615. in 1933 heisenberg, along with erwin schrödinger and paul dirac, received the nobel prize for physics for the formulation and presentation of the “new” quantum mechanics. 46. the physicists stefan meyer and egon v. schweidler in vienna were experimentally perfectly equipped for this. in 1899/1900, at around the same time as the french h. becquerel and german chemist f. giesel, they proved through the deflection of magnetic and electric fields, that radium rays (β-rays) behaved as though they were negatively charged (electrons). through an attempt at deflecting the polynomial rays it was determined that they were twofold positively charge helium atoms, which were identified as αrays. 47. letter from stefan meyer to carl auer von welsbach dated 02/29/1924, archives auer-von-welsbach research institute, file: correspondence; location: auer-von-welsbach museum, althofen (carinthia). 48. cp is the abbreviation for the rare earth element cassiopeium, called lutetium (lu) today. hf is the abbreviation for the element hafnium, which will be dealt with later. 49. letter from carl auer von welsbach to stefan meyer dated 03/06/1924, archives auer-von-welsbach research institute, file: correspondence; location: auer-von-welsbach museum, althofen (carinthia). 50. stefan meyer, magnetization numbers of the rare earths, physikalische zeitschrift, 1925, 26, p. 53. 51. the french physicist pierre-ernest weiß (1865-1940) had studied metals and their compounds (e.g. iron, cobalt, nickel, magnetite) intensively even before the beginnings of bohr’s quantum theory. see: “über die rationalen verhältnisse der magnetischen momente der moleküle und das magneton”, in: physikalische zeitschrift 12 (1911), 935-952. they demonstrated a strong magnetic attraction without an outer field, thus were ferromagnetic. his investigations led to the conclusion that in such bodies, small microscopic dipoles must exist, which are also equally aligned in very small areas (max. 1mm diameter). these areas are called weiß’sche bereiche (magnetic domains). through external influences, for example through a magnetic field, a multitude of these dipoles can be aligned in different areas. in doing so we get to magnets used in electronics, dynamos and other propulsion machinery. the correct explanation for this characteristic was provided not till modern quantum mechanics. rare earth elements play an important role in producing magnets of this kind. above the so-called ferromagnetic curie-temperature, which is a material constant, the magnets slowly lose their characteristics and become paramagnetic. source: 52. horst stöcker, 2010, p.445, p. 661. 53. stefan meyer measured the anhydrous sulfates of rare earth elements. in this compound the elements were trivalent, which is the preferred valency. source: see holleman; wiberg, lehrbuch der anorganischen chemie, 2007, p. 1939. (nomenclature by stefan meyer e.g. for the lanthanum cation: la). the sulfate anions provide no contribution to magnetization. the cations la and cp are diamagnetic. according to stefan meyer the remaining cations are paramagnetic. for the element with the atomic number 61 (promethium) no rate of magnetism could be determined, because this element in its extreme rarity was impossible to determine. see also carl auer von welsbach, über einige versuche zur auffindung des elements nr. 61, chemiker-zeitung,1926,118, p. 990. here magnetic susceptibility means the specification of magnetization (on the ordinate in fig. 7), the value of the so-called weiß magnetons. stefan meyer chose this measuring unit in order to be able to compare his results with those of cabrera. 54. blas cabrera had also received rare earth compounds from carl auer von welsbach via the institute for radium research in vienna. this emerges from a letter from stefan meyer to auer von welsbach from 1924. cabrera paid the institute 300 pesetas for this compound. stefan meyer thanked auer von welsbach. source: letter from stefan meyer to auer von welsbach dated 07/25/1924. archives auer-von-welsbach research institute, file: correspondence; location: auer-von-welsbach museum, althofen (carinthia). 55. stefan meyer, magnetisierungszahlen der seltenen erden, physikalische zeitschrift, 1925, 26, 51 f. 56. the head of the radium institute in vienna, stefan meyer, who had been working mostly with preparations from carl auer von welsbach during his research on magnetic behaviors of rare earth elements since 1899, pointed out that he had already in 1915 expressed the assumption that the magnetism of these elements could not be explained solely by the valence electrons (in the outer shell of the atom) but that electrons in the inner shells had to play a role. source: meyer, 1925, 52. 57. werner, heisenberg, zur quantentheorie der multiplettstruktur und der anormalen zeemaneffekte, zeitschrift für physik, 1925, 32, 841-860. 58. friedrich hund, atomtheoretische deutung des magnetismus der seltenen erden, zeitschrift für physik 33 1925, 33, 855-859. 106 gerd löffler 59. friedrich hund, geschichte der quantentheorie, 1975, p,117. these selection rules became referred to as hund’s rules. they are explained as follows: when adhering to the pauli principal in an atom l equals the sum of all orbital angular momentum, s equals the sum of all electron spins and j=l+s, it can be concluded that: 1. the basic state takes the maximum possible total spin s -à smax, d. h., it possesses the maximum possible total symmetry 2. the basic state also possesses, along with rule 1, the maximal possible orbital angular momentum, l -à lmax 3. the total angular momentum j takes on the lowest horizontal state of worth: j = ӏl – sӏ with less than half full shell j = ӏl + sӏ with more than half full shell cf. dieter meschede, gerthsen physik, 2005, p, 853. these rules can be deduced from quantum mechanics. a basic principle is that every atom takes the lowest possible energy state. rule number three makes it also plausible, that in fig. 7 two characteristic curbed lines occur. 60. hund, 1925, p. 857 f. 61. ibid., p, 858. 62. meyer, 1925, p.478 f. 63. in this respect, it should be noted that in 1925 it was not yet usual to determine measuring errors in an experiment in either systematic and statistical errors and publish them accordingly. in the present case besides contamination, other systematic errors could have had occurred. 64. friedrich hund, atomtheoretische deutung des magnetismus der seltenen erden (= theoretical atomic significance of magnetism of the rare earths), zeitschrift für physik, 1925, 33, table 1, p. 857. 65. roughly cited from georg hevesy, die seltenen erden vom standpunkte des atombaues”, 1927, p. 80 f. 66. vleck assessed the presented explanation for the magnetic behavior of the rare earth elements by friedrich hund in 1925 (s. o.) in his nobel prize speech in 1977 as follows “in 1925 hund (…) wrote a paper on the magnetic susceptibilities of rare earth compounds which was the crowning achievement of empiricism of the old quantum theory.”. see: j.h. vleck, quantum mechanics. the key to understand magnetism, sience, 1978, 201,4341, p.115. 67. ludwig haitinger, handbuch der anorganischen chemie, 1893, iii, p. 53. 68. ibid. 69. auer von welsbach, carl, über die elemente der yttergruppe, (erster teil), proceedings of the imperial academy of sciences, sect. ii b, 1906, 115, pp. 737747. 70. carl auer von welsbach, vorläufiger bericht über die zerlegung des ytterbiums, gazette of the imperial academy of sciences, 1905, 42, p. 122. 71. commemorative publication adolf lieben and liebig´s annalen der chemi,1906, 351, pp. 464-465., also cited in: carl auer von welsbach, zur zerlegung des ytterbiums, chemie-heft ,1909, 9, p. 49. 72. auer von welsbach does not give a unit of measurement. since his spectral analytical research was conducted in the visible area, only å = 10-10 m is a possible unit of measurement. 73. carl auer von welsbach, über die elemente der yttergruppe, (1. teil), proceedings of the imperial academy of sciences, sect. ii b, 1906, 115, pp. 737747. 74. auer von welsbach published the spectroscopical technology that was further developed by him in 1922: carl auer von welsbach, spektroskopische methoden der analytischen chemie, proceedings of the imperial academy of sciences, sect. ii b, 1922, 131, pp. 387-408. 75. carl auer von welsbach, über die elemente der yttergruppe, (1. teil), proceedings of the imperial academy of sciences, vol. cxv, sect. ii b, 1906, 115, pp. 737-447. carl auer von welsbach, die zerlegung des ytterbiums in seine elemente, proceedings of the imperial academy of sciences, vol. cxvi, sect. ii b, 1907, pp. 1425-1469. carl auer von welsbach, zur zerlegung des ytterbiums, proceedings of the imperial academy of sciences, sect. ii b, supplement, 1909, 118, pp. 307-312. carl auer auer von welsbach, zeitschrift für anorganische chemie, 1911, 86, pp. 58-70. 76. see online: https://commons.wikimedia.org/wiki/ file:monazit_behandlung_basischer_aufschluss.svg (02/04/2019) 77. carl auer von welsbach, die zerlegung des ytterbiums in seine elemente, proceedings of the imperial academy of sciences, sect. ii b, 1907, 116, pp. 14251469. 78. auer von welsbach was always in close contact with experts f. exner, j.m. eder and e. valenta in vienna, making his preparations available to them for further spectral analytical research. see e.g. j.m. eder; e. valenta, wellenlängenmessungen im sichtbaren bereich der bogenspektren der von auer von welsbach entdeckten elemente aldebaranium und cassiopeium, zeitschrift der anorganischen und allgemeinen chemie, 1910, 67, pp. 102-106. 79. chemical monthly, 1913, 84, 1713-1728. 107carl auer von welsbach (1858-1929) 80. there are hints in literature that point to the results also having been published in july 1913 in the proceedings of the imperial academy of sciences sect. ii b, 1913, 22. this seems likely as carl auer von welsbach generally published his publications in the academy first. however, these proceedings cannot be found today in the library of the austrian academy in vienna. 81. see online: http://www.ciaaw.org/atomic-weights.htm (02/04/2019) 82. eugen schmahl, carl auer von welsbach, abhandlungen und berichte (deutsches museum), 1952,1, p. 4. 83. see online: http://www.chemieunterricht.de/dc2/lanthan/trennung.htm (11/11/2018) 84. george von hevesy, die seltenen erden vom standpunkte des atombaus, 1927, pp. 95-101. 85. carl auer von welsbach, über die chemischen untersuchung der actinium enthaltenen rückstände der radiumgewinnung, announcements of the radium committe of the imperial academy of sciences, part 1, 1910, 6, pp. 1011-1054. 86. kurt rossmanith, fraktionierte kristallisation von ammoniumund magnesiumdoppelnitraten der ceriterden“, chemical monthly, 1995, 126, pp. 543547. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna substantia. an international journal of the history of chemistry 3(2) suppl. 1: 57-71, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-281 citation: n. balasubramanian, k. f. steward (2019) biodiesel: history of plant based oil usage and modern innovations. substantia 3(2) suppl. 1: 57-71. doi: 10.13128/substantia-281 copyright: © 2019 n. balasubramanian, k. f. steward. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. biodiesel: history of plant based oil usage and modern innovations narayanaganesh balasubramanian*, katherine f. steward dept. of chemistry and biochemistry, montana state university, bozeman, mt 59717 *corresponding author: b.narayanaganesh@gmail.com abstract. the history of biodiesel dates back to mid-19th century when transesterification of vegetable oils was discovered. it took another half century for the world to realize its potential as fuel. through the 20th century, two world wars and other regional turmoil increased the quest for energy security among nations. this chapter presents the history of biodiesels from the perspective of its development from vegetable oils, and animal fats. usage of biodiesel and straight vegetable oil before world war, and how the energy crises sparked the intense development of these fuels around the globe towards the end of 20th century. keywords. biodiesel, biofuels, vegetable oils, transesterification, energy policy, food or fuel. introduction modern society relies heavily on fossil fuel-based engines to achieve various tasks and work.1 the rate of consumption of fossil fuels over the last two centuries has increased dramatically. a valuable alternative to diesel and related fossil fuels is biodiesel: a liquid fuel derived from fats and oils of plants, animals, and other sources. biodiesel can be produced from pure vegetable oil, algal cultures, oils from animal fats, tallow, grease, and waste cooking oil.2 the term vegetable oil covers a number of oil sources, such as nuts, seeds, vegetables and other plants. this chapter will discuss the history of biodiesel, from conception and development to industrial scale production. also detailed here is the historical use of plant oils and their adaptation to biodiesel. over the past century, the global political climate, war, socio-economic conditions, government policies and various other factors have shaped the development and use of biodiesel. generally, diesel is a c8 to c25 hydrocarbon mixture produced from the distillation of crude oil. chemically, the term biodiesel signifies monoalkyl esters of fatty acids from oils and fats.3 although utilized since the late nineteenth century, the term biodiesel wasn’t used in the mainstream until the 1980s. in 1984, the word “bio-diesel” appeared in power farming magazine out of sydney, australia. the term has become more common in the 58 narayanaganesh balasubramanian*, katherine f. steward58 narayanaganesh balasubramanian, katherine f. steward literature subsequently. with the exception of a few nontechnical reports, most articles use the term “biodiesel” without the hyphenation. the definition of biodiesel in the present day is often confusing. with us regulations differentiating biodiesel and biomass based biodiesel, the eu regulatory requirements are based on meeting the standards outlined in the definition of biodiesel. biodiesel’s fuel quality is measured by astm (usa) and designated as d6751 and in europe (eu is en 14214).2 the qualities that define a biodiesel are completion of the transesterification reaction, complete removal of the catalyst, removal of glycerin, sulfur content, trace amounts of alcohol, and any free fatty acids present.4 the u.s. department of energy defines “biodiesel” as “renewable, biodegradable fuel manufactured from vegetable oils, animal fats of recycled restaurant grease. it is a liquid fuel often referred to as b100 or neat biodiesel in its pure form”.5 the process of obtaining fuel from fat is an ancient one. several civilizations have used straight vegetable oil (svo) and oils derived from animal fat and other sources for fuels.6 in the seventeenth and eighteenth century, whale oil was used as a major fuel source throughout europe and the us. in 1853, e. duffy and j. patrick reported transesterification of oils.7 transesterification is a process of using triglycerides in the presence of a base or acid to chemically break the molecule and produce methyl or ethyl esters of the fatty acids.8 this was not utilized for production of biodiesel until 1937 however, when a belgium engineer patented the use of this process for producing fuels. several countries explored the opportunity to use vegetable oils as fuels for diesel engines, as it gave some self-sufficiency to countries that had access to oil producing crops and other feedstock materials.9 modern day demands for alternative energy and fuel sources is high. svo usage in biofuels has increased over the 20th century globally, with major producers such as the european union, south east asia and the americas.10 biodiesel can be produced from a variety of feedstocks, including edible and non-edible oils. different countries utilize different plant based oils, but more than 95% of the world’s biodiesel comes from edible oils. the popularity of some non-edible oils as feedstock is growing however, with easy to grow plants like jatropha11. multiple studies have been conducted on the use of biodiesel versus svo outlining the cost-benefit to the consumer and the type of engine.10–12 the use and production of svo and biodiesels from edible oils has been shown to improve not only emissions and renewability, but can help local economies that are producing these fuels.12 the use of biofuels and the evolution of biodiesel can be separated into four time periods: 1) use of straight vegetable oils (svo) as a lamp fuel from times before antiquity to the mid-19th century; 2) the use of svos in internal combustion engines and esterification of svos to produce biodiesel during the 1930s and 40s 3) as replacement for petroleum during oil shortages in the 1970s; and 4) present day need for alternative fuels including global energy needs, and sustainable agriculture and environmental impacts. chemistry of biodiesel transesterification of oils in 1853, irish chemists patrick and duffy reported transesterification of oils (scheme 1). transesterification is an important reaction in industry, not only for biodiesel, but is crucial for the production of numerous household products, soaps and detergents. all biodiesel around the globe is produced through this process.3,13,14 triglycerides are molecules with a glycerol molecule head group and three fatty scheme 1. transesterification of triglycerides with methanol. triglyceride 3 molecules of methyl esters glycerol 59biodiesel: history of plant based oil usage and modern innovations 59biodiesel: history of plant based oil usage and modern innovations acids attached to the three hydroxyl groups. in general, characteristics of the fat are determined by the chemical nature of the fatty acids attached to the glycerol. vegetable and nut oils contain mostly triacyl glycerols or triglycerides, which is why they are often the precursors for biodiesels.15 when triacyl glycerols (triglyceride) are combined with a base and an alcohol (eg. methanol), they produce methyl esters of fatty acids and the byproduct glycerol. this class of reaction is known as transesterification.8 the previous scheme shows the chemical process for fatty acid methyl estersbiodiesel production. the reaction between the triglyceride and the alcohol is a reversible reaction, so the alcohol must be added in excess to ensure complete conversation of the reactants.16 it was not until 1937, when georges chavanne patented the production of fuel through this process, that the utility of bio-diesel was realized.2 production and properties of biodiesel biodiesel is produced from moisture-free vegetable oil. the oil is pre-heated to 60°c and sodium methoxide in methanol is added in a closed reactor. the reaction usually takes about two hours for completion. the alcohol reacts with the fatty acids to form the mono-alkyl ester, the glycerol by-product of the reaction deposits on the bottom of the reactor due to its density and is removed. industrial scale production of biodiesel is described in scheme 2. in most production, methanol or ethanol is the alcohol used (methanol produces methyl esters, ethanol produces ethyl esters) and is base catalyzed by either potassium or sodium hydroxide. potassium hydroxide is more suitable for the ethyl ester biodiesel production, but either base can be used for methyl ester production.14,16–18 various research has been performed over the years on enhancing the chemical stability of biodiesel. as they are derived from fatty acids, the oxidative stability has always been of concern.19 this has been addressed mainly by modifying the fatty acid composition of the feedstock oil. usually polyunsaturated fatty acids are avoided in the production of biodiesel. literature reports suggest that carbon chain-lengths up to c16 and c18 show good oxidative stability. in permitted situations, the biodiesel produced will be fractionally distilled to separate saturated and unsaturated fractions.20,21 other than a transesterification reaction, the alternate two ways to produce biodiesel include: hydro processing or deoxygenation and microemulsion or co-solvent blending. the biodiesel production facility at amsterdam (figure 1) in netherlands, producing 150,000 tons of biodiesel annually along with 50,000 tons of pharma grade glycerin.22 biodiesel is bio-renewable in all aspects: the feedstock, the product and the byproducts are all renewable. for this reason, it is often termed as carbon neutral. properties of biodiesel such as biodegradability and its high flash points makes it safer in the event of crash or spills. the present technology enables the production of biodiesel from any plant or animal derived oil. however as discussed above, some oils produce benefits upon conversion to biodiesel compared to others.8,23 around the globe various vegetable oils and other fat sources have been used as feedstock materials for years. ultimately there was a need for suitable starting material that provides a high-quality lipid for transesterification and subsequent biodiesel product. the source material is composed of triglycerides, which contain three long scheme 2. schematic representation of biodiesel production process from vegetable oil. figure 1. biodiesel production facility at port amsterdam. 60 narayanaganesh balasubramanian*, katherine f. steward60 narayanaganesh balasubramanian, katherine f. steward strings of fatty acids attached to a glycerin molecule. the fatty acids can differ in their length and degree of unsaturation. the overall fatty acid content differs in each oil source material.15 table 1 shows the percentage composition of fatty acids in common oils used for biodiesel production. the nomenclature of fatty acid is as follows, the number on the left represents the number of carbon atoms and the number after the colon represents the number of double bonds in the fatty acids. based on the number of carbon atoms and number of double bonds, each fatty acid has different freezing point, ability to polymerize and overall energy content.24 the fatty acid composition can also affect important physical properties of biodiesel such as viscosity (fluidity), ignition point and caking at low temperatures. degree of unsaturation also effects the performance of biodiesel produced from vegetable oils.22,25,26 the overall saturation levels of many biodiesel oils are given in table 2. oils with maximum amounts of saturated fat content yield biodiesel that has a lower gel point. biodiesels derived from oils with more unsaturation oxidize sooner than oils with less unsaturation. for example, biodiesel derived from walnut oil, poppy oil and linseed oil degrades relatively quickly.25 currently, biodiesels derived from cooking oils perform well comparatively to other source materials. most of these oils contain one or two double bonds per fatty acid. this gives optimum shelf life for the biodiesel as well as desired properties.15,26 based on the performance, canola oil is reported to perform well when converted to biodiesel. historically this has increased the cost of canola oil in the us market. olive oil has also been an option for producing biodiesel. the advantage of canola oil is it is genetically modifiable to produce increased amount of polyunsaturated rather than saturated content. hydrogenated vegetable oils have not been significant in biodiesel production as they yield a fuel with undesired qualities. used cooking oils, especially the ones with high free fatty acids are attractive for biodiesel production.13,22,23,27,28 waste vegetable oil (wvo), which is high in free fatty acids cannot be converted into biodiesel in the most preferred method of production: the base catalyzed. the use of base results in conversion of the free fatty acids to soaps. the acid catalyzed esterification process is better suited to wvo. the soaps formed as impurities from oils with high free fatty acid content during biodiesel conversion, can lead to accumulation of water due to the hygroscopic nature. this results in biodiesel with more water content than normal and an undesirable product.16,29 the viscosities of svos are an order of magnitude higher than that of the biodiesels derived from them. the derivatives of svo, methyl and ethyl esters also have different viscosities. various biodiesel producing countries resort to methanol as the alcohol partner in transesterification, due to the low cost of methanol.30 the viscosity of biodiesel is similar to petroleum diesel, in cases where biodiesel is mixed with petroleum diesel the lubricity of the fuel is increased.8,26 biodiesel and petroleum-based fuels are highly miscible and are available and utilized around the world in many markets. biodiesel can be used as such in present day modified diesel engine vehicles (b100). blends of 20% biodiesel with 80% petroleum diesel (b20) are used in unmodified diesel engines. some drawbacks occur with the use of biodiesel, it will degrade natural rubber parts in vehicles manufactured table 1. fatty acid composition of common oils and fats. fat or oil 12:0 14:0 16:0 18:0 18:1 18:2 18:3 20:0 20:1 22:1 soybean . 8 5 25 55 11 corn 2 10 4 19-49 34-62 . peanut . 9 2-3 50-65 20-30 . olive . 10 2-3 73-84 10-12 . cottonseed 0-2 23 1-2 23-35 40-50 . butter 7-10 25 10-13 28-31 1-2.5 .2-.5 lard 1-2 30 12-18 40-50 7-13 0-1 tallow 3-6 26 20-25 37-43 2-3 . linseed oil . 6 2-4 25-40 35-40 25-60 pongamina pinnata 2 6 8 45-71 11-18 4 11 5 coconut oil 45-53 17-21 10 2-4 5-10 1-3 . palm oil . . 44 5 39 10 . palm kernel oil 48 16 8 . 15 3 . 61biodiesel: history of plant based oil usage and modern innovations 61biodiesel: history of plant based oil usage and modern innovations before 1992 and emissions of nitrogen oxide and ozone precursors are higher than in petroleum diesel. however, there are many benefits, the use of biodiesel has been found to breakdown the residues and deposits in fuel lines. biodiesel burns cleanly with 80% less co2 emissions and 100% less sulfur dioxide than regular diesel. the octane number, measure of fuel’s ignition quality for biodiesel is 100, for petroleum diesel it is 40. the energy content of biodiesel (average) is 35mj per liter, close to petroleum diesel at 38.3mj per liter.31 the us federal trade commission distinguishes biodiesel based on the starting material. although it is not in the scope of the current report to discuss in detail regarding the differences and similarities between biodiesel and biomass-based diesel (bbd). it is important to distinguish between the two.32 the federal trade commission defines bbd as “a diesel fuel substitute produced from non-petroleum renewable resources that meets the registration requirements for fuels and fuel additive established by the environmental protection agency under 42 u.s.c. 7545, and includes fuel derived from animal wastes, including poultry fats and poultry wastes and other wastes materials, or from municipal solid waste and sludge’s and oils derived from wastewater and treatment of wastewater, except that the term does not include biodiesel”. whereas biodiesel is simply defined as “the mono alkyl esters of long chain fatty acids derived from plant or animal matter that meet the astm standard d6751 requirement and registration requirements for fuel and fuel additive”. 31–33 scheme 1 and 2 clearly shows that during the production of biodiesel, glycerol is produced as a byproduct. with the global increase in production of biodiesel, there has been an increase in crude glycerol production. for every 9 kilograms of biodiesel, about 1 kilogram of glycerol is produced as by-product. although glycerol is a valuable material to produce industrial chemica ls, intermediates, cosmetics and poly mers, purifying this amount of crude glycerol poses a challenging problem from a sustainabilit y standpoint. the average consumption of glycerol in the us in the past decade was 200 million kg. the amount of glycerol entering the us market was 20 billion kg in 2010. since the early 2000s, methods for converting glycerol into other useful products have been explored. one approach is to convert glycerol to ethanol, co2 and hydrogen using e.coli. in work from 2005, dharmadi et al. reported the use of e.coli to consume glycerol resulted in 75% theoretical yield ethanol. one drawback to this process is that it produced more than 50% carbon dioxide. historical use of vegetable oils plant and seed oils have documented use as far back as 1500 bce. oils and fats were not only historically used for light and heat fuel, but ancient egyptians used perfumed oils for beauty routines, religious ceremonies and medicine as well. additionally, these oils have long been part of the food supply. recent archeological work has shown that as early as 6000 bce olive oil was being extracted for a food source in galilee, israel.34,35 cultivation of olive trees dates to 3500 bce in the eastern mediterranean. ancient greeks utilized olive oil for food, religious ceremonies, fuel for oil lamps, and medicinal treatments. it was one of the regions chief exports and continues to be a commodity in modern italy and greece. other ancient civilizations also utilized plant and natural oils in similar ways.36 the use of castor oil was extensive in ancient egypt and is documented in the ebers papyrus. the historic text outlines the use of multiple parts of the plant and extracted oil for headache, respiration, digestion, skin treatments, and hair growth. the oil was also used for fuel and ceremonies. almond oil mixtures for skin and anti-aging treatments are also described in the smith papyrus.37,38 early greece was also a consumer of plant oils, herodotus recorded the use of castor oil for lamp table 2. fatty acid nature (saturation) level in common oils and fats. oil saturated monounsat. polyunsat. butter 63% 26% 4% canola oil 7% 62% 31% coconut oil 90% 6% 2% camelina oil 10% 33% 54% chufa oil 20% 67% 12% corn oil 13% 24% 59% olive oil 14% 73% 11% soybean oil 16% 23% 58% peanut oil 17% 46% 32% cottonseed oil 26% 18% 52% chicken fat 30% 45% 21% lard 39% 45% 11% palm oil 49% 37% 9% palm kernal oil 81% 11% 2% sunflower oil 10% 20% 66% safflower oil 7% 14% 79% * notethe values are averaged. actual values may vary based on the region of growth, genetic modification made, and method of extraction. 62 narayanaganesh balasubramanian*, katherine f. steward62 narayanaganesh balasubramanian, katherine f. steward light, and as a hair and skin treatment. the greek expanded on the egyptian knowledge of medicine that influenced care until the middle ages. the greek physician hippocrates recommended the use of olive oil for sports injuries and to warm the body39. as international exploration continued the varied uses of these oils spread to china and india. these societies also utilized plant oils for fuel, beauty, medicine and religious ceremonies.38 linseed, or flax oil was used for waterproof clothing, luggage, carriages and shelter fabric in the 18th century, as documented by louis franquet, a french explorer. “they (canadians) name prelart a large and heav y cloth, oil-painted in red, […] to keep oneself from the rain” louis franquet, 1752.40 canvas or linen was boiled with a combination of oil and paint in order to achieve the waterproofing.41 oilcloth remained popular through the late 1950s, until rubberized and plasticized fabrics became more available. in the 1870s, procter and gamble endeavored to make individually sized bars of soap to sell. in order to achieve this, they revolutionized the use of palm and coconut oil rather than animal fat for soap. around this time, the us cotton industry was producing tons of oil as byproduct from the industrial process. consumption of the cottonseed oil eventually led to production at such high rates, that this byproduct was later industrialized and converted to a food product that is now highly consumed in the us.42,43 during the late 19th and early 20th centuries, the use of natural medicinal oils fell out of favor due to growing advances in synthetic pharmaceutical chemistry.44 in recent history, there has been a renewed interest in natural, plant and essential oils for their use as homeopathic remedies and eastern-based medicine. for example, a recent study tested the efficacy of lemongrass, pine and clove oil compared to deet. these oils were found to be up to 98% as effective as the common insecticide.45 as with ancient times, modern use of these plant oils includes food, beauty and medicinal purposes. they are also still used for heat and lamp oil in developing countries and in generators during emergencies. during the mid-nineteenth these plant oils were being utilized as fuel for combustion engines. diesel, otto and other inventors of the time designed engines that would run off pure oil, mixed petroleum and plant oils or other combinations of fuels.14 biodiesel is also an effective cleanup solvent for petroleum based oil spills, as shown in lab tests with simulated shorelines.46 modern day awareness for the environment have re-invigorated international policies encouraging the use of alternative fuels like plant-based biodiesel. the transition to a fuel: nineteenth century utilization of the internal combustion engine and choice of fuels internal combustion engines played a crucial role in shaping up the development and use of biodiesel. prior to the invention of the diesel engine there were many attempts throughout the seventeenth century to develop an internal combustion engine.47 historian lyle cummins recorded the detailed history of these attempts in his book. in 1893, rudolf diesel, a german engineer (figure 2) wrote an essay on theory and construction of a heat motor. historical reports indicate the first biofuel powered vehicle is diesel’s oil powered 10 iron cylinder with a flywheel in the base. this ran on peanut oil for the first time in augsburg, germany on august 10th, 1893.48 diesel had a strong desire to develop alternatives to conventional fuel engines.49 in 1912, a year before his death, he gave a speech in which he mentioned that, “the use of vegetable oils for engine fuels may seem insignificant today, but such oils may become, in the course of time, as important as petroleum and the coal-tar products of the present time.” in the following years he filed a patent for his design. at the time of diesel’s invention, steam engines were common, even with a relatively low efficiency at only about 10%. diesel’s invention came as a breakthrough during this era. in his internal-combustion engine design, the combustion of the fuel and the piston movement occurred through an isothermal reaction. although revolutionary to the field, the initial models of diesel’s engine were bulky and could not be moved easily, so were not ideal for automobiles or trains.47,48 throughout the time that diesel was working on his engine, other engines with alternative fuel sources were being developed despite low gasoline prices. alcohol fueled engines, coal gas, kerosene and gasoline engines were all advanced during this time. kerosene was of particular interest, as the byproduct of gasoline fractionation, but multiple alternative sources were being utilized and explored at this time.2,3,13,50 these other alternative combustion engines were capable of running on different fuels and fuel mixtures. prior to diesel’s invention, in 1860, german engineer nicholas august otto developed an engine utilizing ethanol. just like vegetable oil used for burning lamps in eighteenth and nineteenth century europe, ethanol lamps or spirit lamps were also common. hence, otto conceptualized an engine burning ethanol as fuel. with funding from eugen langen, owner of a sugar refining company, they launched the otto & langen company which produced stationary piston engines in the 1870s. these engines were powered 63biodiesel: history of plant based oil usage and modern innovations 63biodiesel: history of plant based oil usage and modern innovations by coal gas. later in the1880s, he came out with a fourstroke “otto-cycle” engine that used gasoline.47,50 in 1900, at the paris exhibition, the french otto company had four diesel engines including one from diesel’s own son eugen diesel. out of the five engines, one engine ran entirely on peanut oil; although not many of the visitors realized this according to diesel.51 he mentions that, “the engine was built for petroleum (mineral oil) and was used for the plant oil without any change. in this case also the consumption experiments resulted in heat utilization identical to petroleum”. the french government did take notice of the engine running on peanut oil. diesel notes that the french had interests in testing the efficiency of arachide (earthnut or in this case peanut oil). the availability of large quantities of ground nuts and other sources of vegetable oils in the french african colonies prompted the french government to encourage the cultivation of these food sources.47,50 thus, using these vegetable oils as possible fuel source in engines. from an engineer’s perspective, this was made possible mainly because diesel engines developed around 1900s had complex injection system to accommodate various fuels. from kerosene, coal dust, oils and petroleum mixtures early diesel engines ran on various fuels. the major implementation of diesel’s internal combustion engine (or diesel engine) did not start until almost two decades after diesel’s patent expired in 1908. numerous varieties of diesel engines were introduced, to the extent that diesel felt he was not accredited properly for his invention. even though in histories of biodiesel, the first use of a bio-fueled engine is mistakenly attributed to rudolf diesel in 1900 at the world expo in paris. while it is true that there was an engine displayed at world’s expo that ran completely on peanut oil, it was demonstrated by nicolas otto.47,48 diesel engines quickly gained attention in early the 20th century due to their power, reliability and fuel economy. numerous versions of rudolf diesel’s engine were developed within a short span during this time. from diesel’s statements and speeches, it is evident that he envisioned the use of reliable svos to assist the fuel power of developing and underdeveloped nations such as african and asian countries where petroleum-based fuels did not reach. diesel had interest in creating an efficient engine.47,52 from his book die entstehung des dieselmotors (translation: the emergence of the diesel engine) in his own words he mentions his motivation, “the desire to realize the ideal carnot process determined my existence”. rudolf diesel died in 1913, before his vision of developing efficient engines that could utilize svos was realized. during the decade following diesel’s death, the petroleum industry developed a by-product that was able to power the modified diesel engine, they termed it “diesel fuel”. it was around this time that the industry shifted towards petroleum-based fuels and the focus on alternative fuels was lost. diesel engine manufacturers of the 1920s altered engines to better suit low viscosity fuels rather than the viscous fuels such as svo or biodiesel. august 10, the day rudolf diesel demonstrated his internal combustion engine using svo is presently observed as international biodiesel day.31,47 the fluidity of svos creates problems in present day diesel engines that are made to run on less viscous diesel. preheated peanut oil, animal fat and other oils have been successfully used to power diesel engines, but this requires modifications to the engine.53 when the shortage of petroleum-based fuels occurred in 1970’s, the existing engines were only able to run specifically on diesel and issues occurred when other fuels were attempted. petroleum industries have monopolized the automobile industry, as they have been able to produce fuels at much lower costs compared to biomass derived fuels. this has resulted in a century of added pollution and increased carbon emissions from the use of petroleum fuels. the research, infrastructure and technological advancements of biomass-based fuels such as biodiesel were suppressed for many decades due to the monopoly of petroleum-based fuels.54 world wars and the effect on development during world war ii, the demand for biofuels increased, as importing petroleum-based fuels was becoming difficult. germany was experiencing a fuel figure 2. early portrait of rudolf diesel. 64 narayanaganesh balasubramanian*, katherine f. steward64 narayanaganesh balasubramanian, katherine f. steward shortage, which led to another phase in alternative fuel engine development. mixing gasoline with alcohol derived from potatoes came into practice.55 following germany, the uk implemented the use of mixing grain alcohol with gasoline. at the same time, brazil prohibited the export of cottonseed oil so that it could be utilized as a substitute for diesel. in china, tung oil and other svos were used to produce a fuel similar in performance to kerosene.50 american automobile entrepreneur henry ford also had great interests in alternative fuels. his interest and the fact that up to world war ii, soybean crops in the us were mainly used for oil production, he developed the “soybean car” in 1941. during world war ii, ford built a single experimental soybean car, but due to the war activities it never saw the production line. the soybean car weighed 2,000 pounds; 1,000 pounds lighter than other cars in production in 1941. after world war ii, the development of the soybean car did not resume.56 after world war i and ii, america, france and the uk had the advantage of access to petroleum-based fuels, resulting in the common saying “they floated to victory on a wave of oil”. germany had become self-sufficient in ethanol-based fuels as early as 1910, as ethanol production was a major part of their economy.57 in 1942, germany reached a peak in synthetic fuel production at 1.7 billion liters from coal. in the same year, germany produced 267 million liters of fuel grade ethanol from potatoes. in sum, germany made 54% of their fuels from non-petroleum-based sources.58 the war in the western hemisphere created different pressures in india and china. since much of the fuel was imported by the allied nations, it sparked an interest in substitutes for petroleum-based fuels in these areas. vegetable oils were not readily available due to the large populations of these countries, which were dependent on the land. one crop that proved viable as an alternative fuel source however, was sugar cane. molasses from sugar cane was used as raw material for alcohol production. in china, benzonite, a mixture of 55% ethanol, 40% benzene and 5% kerosene was sold after world war i. sugarcane plants demand huge volumes of water for growth, hence india and china slowly made their shift away from sugarcane bioethanol to alternative plant based biodiesel.59 the plantations moved to cheaper and drought resistant crops such as jatropha. there are also reports that indicate that the use of biodiesel produced from peanuts, tea leaves, tung, cotton seed and cabbage seed was implemented during this time.53 despite all of international advancements in the biodiesel industry, when peace returned to much of the world, the oil prices from the middle east region dropped again reducing the demand for alternative fuel research.13 the rise and fall of biodiesel innovation, how the global market shaped the industry from the 1950s through 1970s the 1950s was a prosperous time for the us, and petroleum-based fuel was readily available. in the 30 years following the end of world war ii, consumption of oil on the global scale had grown six times60. at this time the us was a top producer of soybean oil and europe produced large amounts of canola oil. although demand for biodiesel was low, these crops determined the type of biodiesel that would be developed and used in these countries. in 1951, us researchers reported the efficient use of cotton seed oil as diesel fuel.61 in the 1970s, the unstable political situation of the middle east shook the global availability of petroleum fuel. this lack of supply propelled countries to search for alternate fuel sources once again. in the us and europe, a major consumer of petroleum fuel was agricultural machinery and heavy vehicles.52,57 from the period of 1973 to 1979, a serious supply deficit occurred all around the globe due to the growing conflict in the middle east. the opec (oil producing and exporting countries) nations reduced the supply of fuels to non-opec nations, which increased the motivation to develop biodiesel. a second energy crisis occurred in october 1978, when iranian oil refineries were attacked, effectively shutting down five percent of the world’s oil exports. the conflict lasted until january 1979, increasing the cost per barrel twice in a time span of six months.32 the oil crisis of the 1970s primarily impacted the united states. on october 6th, 1973, egypt, saudi arabia and other arabian countries attacked israel in an attempt to regain lost land from the 1967 war. us aids were flown to israel on october 17th, but on the same day arab oil ministers met in kuwait and signed an agreement for an oil embargo against the united states and its allies. the agreement pledged to reduce oil production by five percent every month, which had immediate effects on the us oil market. the price of crude oil went up by four times. after these conflicts were resolved, the supply of petroleum-based fuels was restored. diesel production and the improvement of supply chain infrastructure increased the accessibility of petroleum fuels. with these shifts in petroleum fuel availability, the concept of biodiesel research, development and production was not actively pursued and fell by the wayside once again.51 65biodiesel: history of plant based oil usage and modern innovations 65biodiesel: history of plant based oil usage and modern innovations the twenty first century has seen a bigger push for alternatives to petroleum based fuels as growing concerns over climate change, carbon emissions and sustainability push politics towards subsidies and incentives for the biofuel industry.62 biodiesel initiatives around the globe have been implemented in which blends of diesel and biodiesel are sanctioned.63 however, using svo as a diesel engine fuel hasn’t experienced the same uptick. multiple studies have reviewed the usage of svo in diesel and combustion engines with overall mixed conclusions about engine performance.12,64 while the future of biodiesel and svo as alternative fuel sources is promising, there are still many challenges to overcome. biodiesel production globally, international energy policy and regulations: shaping the history of biodiesel us in the united states, biodiesel programs rapidly developed and commercialized after 1980. it was difficult for the advancement of biodiesel to gain traction, as us oil industries propagated myths about alternative fuels.65 some of which espoused that ethanol is an inferior fuel, which creates technical issues, and that blending biodiesel and gasoline creates inferior quality fuel that doesn’t have the same power output as petroleumdiesel. in addition, the us automobile industry historically backed the oil industry claims. on the other hand, the farming industry which relied heavily on diesel for heavy equipment operations, supported biodiesel production. during the 1980s, the brazilian alcohol expansion program worked with the nebraska corn products utilization committee to initiate road tests with corn ethanol to prove that the efficiency and power claims were completely true.66 following the second world war, the united states faced a shortage of petroleum-based fuels for a short time. this inspired the start of the “dual fuel” project, at ohio state university (columbus, oh).67 extensive exploration was carried out on cottonseed oil, corn oil and various blended oils as a substitute diesel fuel. although the use of vegetable oils has resulted in satisfactory performance with engines, the power output consistently remained lower than conventional petrol engines. after the oil crisis of the 1970s, in 1978 us president jimmy carter created a 25-million-dollar program called ‘aquatic species program’ to investigate high-oil from algae, focusing on biodiesel production. in 1980, he signed another bill giving a $0.54 per gallon ethanol tax incentive. this legislation sealed the developmental path of the us biofuel and biodiesel programs. the us biodiesel industry slowed to a crawl in the 1990s, due to lower costs of petroleum-based fuels.51,55 despite this, in 1996 pacific biodiesel, the nation’s first biodiesel plant was established on the island of maui, hawaii. it focused on recycling cooking oil into biodiesel. this plant, through its waste conversion to biodiesel, produced over 49,000 liters of biodiesel per day as of 2016 and was certified as a “sustainable plant” that same year.54 legislation in the us regarding biofuels started in the early 1990s in an effort to reduce market demands for foreign oil. the energy policy act of 1992 was one of the pieces of legislature aimed at increasing research on biofuels and how federal programs should be constructed to increase biofuel implementation. it was the first time that requirements were put on the department of energy to increase biofuel utilization in their own vehicle fleets and to collect data on the efficiency, use and supply of biofuels and environmental effects of biofuels.68 oil prices rose following the events of 9/11/2001, which again renewed interest in biodiesel production ventures. the energy policy act of 2005 introduced a biodiesel tax credit which allowed blended fuel producers to claim a one-dollar credit per gallon. it also expanded research and development of alternative fuels to include expanded agricultural supplies of biofuel and additional bio-power energy systems.69 this furthered the production and growth of the biodiesel industry. in the same year, minnesota became the first state to make it mandatory for all diesel fuels sold in the state to have a minimum of 2% biodiesel. additional legislation in 2007, 2008 and 2009 to help liberate the us market from dependence on foreign oil and crashes in commodities were put in place via presidential order, and stimulus packages from congress. these laws helped protect troubled assets and gave tax credits to biodiesel and incentivize environmentally friendly energy practices.70 these policies helped grow the biofuel industry in the us, providing innovation and furthered the reach and implementation of these alternatives. the use of biodiesel in the continental united states has increased over the past decade. in 2017, the us produced 7.38 billion liters of biodiesel and imported 1.1 billion liters.71 biodiesel has been increasingly used as the fuel of choice for university and college campus transportations across the us. biodiesel is biodegradable, nontoxic, and has significantly fewer emissions than petroleum-based diesel when burned. this makes it the fuel of choice in delicate eco-systems. in 1995, yellow66 narayanaganesh balasubramanian*, katherine f. steward66 narayanaganesh balasubramanian, katherine f. steward stone national park launched the “truck-in-the park ” project in collaboration with the university of idaho and several other partners. the project featured a pickup truck with a direct injected diesel engine that ran on canola ethyl ester. when an engine check was performed at 92,000 miles, the impact of emissions was far less than that of a regular diesel engine. over the next decade, the national park system started using solely biodiesel blends and by 2006 had completely converted to these blended fuels. as of 2016, a total of 163,000 liters of blended biodiesel had been consumed by trucks, graders, front-end loaders and other heavy vehicles utilized in the parks. this has reduced the carbon and sulfur dioxide emissions and particulate matter released into the air. other pilot programs were introduced which utilized biodiesel for public transportation infrastructure, such as community buses and heavy equipment. the us made a pledge of achieving production of 120 metric tons of biofuels by 2022.72 europe much of the present-day european biodiesel industry was developed in the 1980s. the fuel crisis that hit the us hard in the 1970s was also a detriment to supplies in europe. in europe and south africa, pioneering work on biodiesel was conducted by researchers such as martin mittelbach who advanced the production processes and the storage stability of biodiesels.73,74 this propelled the development of the biodiesel industry into the 1990s. in 1990, france launched a program named “diester” aimed at the production of biodiesel from rapeseed oil.75 specifically, the methyl ester derivative of rapeseed oil was sold as biodiesel in france, austria, germany, sweden, italy, belgium, hungary and the czech republic around 1988. germany established specific criteria for rapeseed biodiesel to be sold using standards based on the density, viscosity, iodine value and residual catalyst.57,65 the european union proposed a 90% tax reduction for biodiesel in 1997, leading to an increase in the production of biodiesel. the estimated amount produced was 660,000 tons per year in the following years. as of 2005, worldwide biodiesel production crossed 4.1 billion liters with the eu being the largest producer. the european legislation has had requirements in place since 2008 for the use and expansion of biofuel which has led to the production of over 10.6 billion liters of biodiesel as of 2017. their work will continue into the 2020s, with directives to ban palm oil and increase energy efficiency in public transport and consumption.76 india, china and southeast asia shortly after world war ii, india gained independence. in 1948, nine million liters of alcohol was produced for fuel and two million liters of alcohol blended fuel was used. although there was a dire need for alternate fuels, the issue of “food vs fuel” prevented the use of grains for oil production. hence, the expansion of biodiesel did not occur in these regions until after 1980. since alcohol was also produced from sugar cane wastes, the indian alcohol act of 1948 mandated the use of 20% alcohol blending in fuels.77 this law was repealed in 2000, but an ethanol blending program was mandated in 2002. unfortunately, it has been impossible to enforce this ethanol blended biofuel due to lack of supply and bureaucracy delays.67 in 1990, india established biodiesel production with a goal of reducing imported oil and improving energy security. due to the vast amount of non-agricultural land available, the drought resistant jatropha plant was chosen for biodiesel production. in 2003, the indian government launched the national biodiesel mission in order to improve technology and extraction of biodiesel and to allocate land and the implementation of the industrialization of jatropha to biofuel.78 in 2011 and 2012, india’s total biodiesel production was projected to grow to 3.6 million tons. although economic development has made automobiles affordable for much of the population in india, it comes hand in hand with pollution, increased greenhouse gases and total carbon emissions. in the philippines the first use of biofuel dates to 1914, when alcohol was used as an engine fuel on calamba sugar estate, an american-operated sugar plantation. on august 22nd 1922, the philippine motor alcohol corporation was founded, with a goal of experimenting with and producing alternative fuels. during world war ii, ethanol production stumbled in the philippines, but soon regained momentum and reached 30 million liters by 195079. again, the years to come provided cheap oil availability, and alternative fuel sources were abandoned. a philippine representative spoke at the united nations on this issue stating that “the use of blended motor fuel was abandoned, for the simple reason that the gasoline interests fought hard to kill it. after such a very sad experience, we fully realize that proper legislation similar to that in india should be adopted in the philippines”. many asian countries faced the dilemma of increasing availability of cheap middle east petroleum-based fuels versus their alternative fuel programs. due to this inexpensive, readily available petroleum fuel and lack of sustainability for the programs, biofuel initiatives were abandoned in these regions after the 1950s. 67biodiesel: history of plant based oil usage and modern innovations 67biodiesel: history of plant based oil usage and modern innovations in 2006, the philippines established a biofuel usage mandate that required 5% ethanol blended gasoline distribution. in 2007 legislation regarding biofuel use and consumption was enacted, the first of its kind in southeast asia.80 ethanol production in the region has continued to increase over the past ten years to current day. nine percent ethanol blended fuel is the current standard in the country, with an aim of 20% ethanol by 2020, which isn’t projected to succeed. biodiesel production and consumption has stayed stagnant since 2009 at a 2.5% blend rate. brazil brazil made several efforts in 1931 to encourage the use of alternative fuels like ethanol, this trend continued and eventually lead to the nation’s efforts in the field of biodiesel production. in 1933, brazil established instituto do assucar e do alcool for sugarcane ethanol production. during the global oil crisis in the 1970s, brazil pushed the production of ethanol blended fuel as well as vehicles which required it. legislation for the reduction in sales tax for the use of pure alcohol fuels and blended fuels was introduced. this set the stage for brazil to be one of the global leaders in production and innovation in the biofuel and biodiesel industry. brazil is the only country where the production of biofuel is profitable without tax incentives and subsidies.81 in 2005, based on the success of their ethanol biofuel, brazil invested in biodiesel with legislation requiring replacement of two percent of the petroleum diesel and an increase over the next seven years to five percent. the feedstock material for biodiesel in brazil is soy beans. brazil also uses palm and castor beans as well. unfortunately, the development of biodiesel production has come at the cost of the rain forests of brazil. at the urging of the brazilian government, drier regions of the country are encouraged to use other sources: like jathropha in india.65,67,82 biodiesel production in brazil is projected to reach 4 billion liters. unlike ethanol biofuel, brazil’s biodiesel production is not profitable for the country and like the rest of the international markets, requires subsidies and tax incentives. these government supports have helped maintain biodiesel production and demand, especially for local farmers and the region where the feedstock is produced.83 other biodiesel programs in 1932, 30 industrial nations introduced tax incentives for an ethanol-petroleum fuel blending program. from these 30 nations only a few graduated to establishing sustainable methods for biodiesel production.53 argentina was one of the pioneer nations to utilize biofuel from oils for diesel engines. the first diesel engine was imported to argentina in 1916. the same year, r.j. gutierrez of buenos aires university tested castor oil on the engine. biofuel is produced in argentina from soybeans, and despite a mandate in 2010 for five percent blended fuel, most of their biofuel is exported and isn’t supported through tax reimbursements.84 cuba and panama have been able to produce 20% ethanol mixed gasoline since 1922. this is in part due to the fact that raw ethanol was cheaper than gasoline. unfortunately, these nations efforts towards ethanol were not matched in their biodiesel efforts. failure to subsidize biodiesel production, and political obstacles historically prevented these nations from cultivating biofuel production and consumption.67 canada has gotten on board with the biofuel movement, the canadian renewable fuels association promotes the use of ethanol and biodiesel. in 2008, the production of ethanol for use as a biofuel was incentivized through the ecoenergy for biofuels program. this tax reimbursement was decreased annually however, and there are few trade protections on biofuel as compared to the international market. this has resulted in the cost of blended biodiesel in canada being 10 cents higher than the cost of petroleum diesel.84 biodiesel an ethical dilemma? food v. fuel and the ecological impacts in countries where fossil fuels are not available, biodiesel was found to be a practical and sustainable means to meet the fuel demands. although numerous crops and plants have been added to the list of feedstocks for biodiesel production, it is important to realize that crops abundant in a specific region are likely needed for food supply rather than biodiesel demands.85 currently, only a fraction of biodiesel comes from waste products. the majority of the biodiesel is produced from sources such as seed and other vegetable oil. this in combination with the production of other biofuels such as corn-ethanol has sparked a controversy of ‘food vs fuel’. the diversion in the use of the crops from fuel purposes has added pressure to food prices. in 2007, this issue was raised at the un food and agricultural organization, with some reporters calling the use of food sources as fuel a “crime against humanity”. 1 this ‘feed, food and fuel’ debate has raised serious question about the impact of biofuels such as biodiesel on climate 68 narayanaganesh balasubramanian*, katherine f. steward68 narayanaganesh balasubramanian, katherine f. steward change, sustainability and biodiversity.86 since the early 2000s, when this debate began, studies have shown differing results supporting opposing sides of the food or fuel argument: depending on how the studies are carried out and the statistical analysis methods utilized. in addition to strains on the food supply, growing non-food biofuel feedstock can also have ecological and environmental implications. clearing of forest lands to grow fuel in addition to rising food demands results in higher amounts of carbon dioxide being released into the atmosphere.87 presently, sugar cane is the largest cultivated crop along with soybean, palm and jatropha for biofuel production. palm oil is the infamous biodiesel crop held responsible for destroying large areas of tropical rain forests in the amazon.88 the growth of plants and trees for biodiesel production in south america has presented a large ecological concern. although the growth of the biodiesel industry in countries such as brazil will benefit the economy and lessen the dependence on fossil fuels, the land abuse has created environmental problems that reach beyond pollution caused by fossil fuel usage. millennia-old rain forests continue to be destroyed since the push for biodiesel production in the 1980s. palm oil is the most infamous source for biodiesel, as rain forest clear cutting in order to grow this crop has recently been publicized. for the same reason, rainforests in indonesia and malaysia are being destroyed and raising further concerns of sustainability.89 despite the great risk to amazon forests, there is an argument that well planned palm oil use can replace pastureland and reduce the global threat on the extinction of rainforests. compared to any biofuel, palm oil yields the highest amount of fuel per hectare. brazil introduced a biofuels policy where 80% of the palm plantations land should count towards forest area. following brazil’s example, smaller countries like colombia and ecuador are also growing the size of their palm plantations. these developing nations argue that palm plantations create more jobs compared to soy or cattle farming while sustaining biodiesel production.90 conclusion: what does the future hold for biodiesel? biodiesel’s inception started with the discovery of transesterification of vegetable oils. german engineer rudolf diesel envisioned the efficient use of vegetable oils in his engines and was also well ahead of his time in his foresight into the challenges and potentials of renewable sources. in his 1912 book he talks about alternative power sources, “in any case, they make it certain that motor-power can still be produced from the heat of the sun, which is always available for agricultural purposes, even when all our natural stores of solid and liquid fuels are exhausted”.51 there is no recorded history of the use of mono alkyl esters of fatty acids from vegetable oils as fuels documented in the literature until george chavanne’s patent in 1937. although not a major producer of the feedstock oil crops, countries like france, belgium, and the uk showed great interests in biodiesel manufactured from vegetable and plant oil. this interest was primarily based on the availability of the raw materials from their colonies. as the global political environment changed, priorities and energy policies changed. interest and investment into biofuel research and production ebbed and flowed depending on the global market until it gained real traction in the early 1970s when the industrial process for the production of biodiesel was developed. in 1977 brazilian scientist expedito parente patented the production. it was over a decade later when the first commercial biodiesel plant started production in austria in 1989.47,48,50 the success of the biofuel industry has always hinged on geography, political climate, economics of the feedstock material and regional regulations. countries must navigate these obstacles in order to grow their alternative energy programs. the global petroleum fuel market has historically been the driving force behind nations’ quest for energy security and the subsequent use of biodiesel and alternative fuels. in order to drive the development and production of biofuels, petroleum-based fuels have historically needed to be scarce in the market, only recently have the challenges facing humanity been motivational for this industry. challenges like species extinction, ecosystem collapse and resource sustainability have sparked debates on climate change, energy policy and food rights. many of these debates are aimed at constructing an optimal and sustainable energy system. biodiesel is a good candidate to lessen the world’s reliance on fossil fuels and increase energy safety, with its clean emission profile. however, with minimal subsidies allocated to biodiesel and the long argued “food v. fuel” argument, the future of biodiesel will become increasingly unstable. production of 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clearing and the biofuel carbon debt. science (80-. ). 319, 1235–1238 (2008). https://www.ftc.gov/enforcement/statutes/energy-policy-act-2005 https://www.eia.gov/biofuels/biodiesel/production/ substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 3(1) suppl.: 45-48, 2019 firenze university press www.fupress.com/substantia citation: f. frasca, a. garuti, g.l. calzoni (2019) “antichi strumenti orafi” of the garuti collection – the virtual exhibition. substantia 3(1) suppl.: 45-48. doi: 10.13128/substantia-604 copyright: © 2019 f. frasca, a. garuti, g.l. calzoni. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-604 “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 1 sapienza, university of rome, department of classics, rome, italy 2 goldsmith in retirement, owner of the garuti collection, sasso marconi, bologna, italy 3 university of bologna, department of biology, via irnerio, 42, bologna, italy abstract. the “antichi strumenti orafi” virtual exhibition is a multidisciplinary project developed by the department of history and cultures of the university of bologna in collaboration with the garuti collection’s owner, adelmo garuti. garuti, a goldsmith in retirement, has been collecting tools and machineries related to his profession for years, and has placed them in sasso marconi (bologna, italy). this unique collection shows the inside of the old goldsmiths’ workshops, giving us the opportunity to rediscover a world that has changed dramatically since the coming of information technology and 3d computer graphics in the gold working industry. this virtual exhibition (www.antichistrumentiorafi.it) (fig. 1) shows the most relevant objects of the garuti collection and describes their functioning, so the visitor can follow each step of the precious metals working process. the objects can also speak on their own about the workshops they belonged and about their producers. that gives the visitor the opportunity to know something more about goldsmithing in bologna the main city represented in the collection – and in general about this sector in italy between the 19th and 20th century. keywords. virtual exhibition, ancient goldsmithing, ancient tools, industrial heritage, industrial archaeology. the realization of this virtual exhibition has requested over three and half years of documentation and study of the huge and heterogeneous collection set by adelmo garuti. probably there is no such an exhibition in italy, and maybe in europe, for the quantity and quality of objects and documents included. they belong different workshops and refer to different ages and come from the 18th century to the second half of the 20th century. all the objects have been captured in high resolution, classified and dated, including all the hardcopy archive of the collection, made up of sheets and technical notes from the workshops (fig. 2), ancient photos, old catalogues, and much more. researches in historical archives have been performed to collect information on single workshops or factories, in order to dedicate a special session of the exhibition to the industrial archaeology. the importance of this virtual platform was clear since the early stages of the work. it has the pur46 francesca frasca, adelmo garuti, gian lorenzo calzoni pose of dissemination to the public, including non-specialist visitors, and also to give the academics new perspectives in the studies concerning ancient metallurgy. it also gives the opportunity to visit the collection from different parts of the world, without physical barriers and limitations of time. another purpose of this project is to get in touch with other exhibitions or collections like this around the world, to discuss and share knowledge and experiences. very often old workshops definitively close down and all their equipment are sent to dump. most of the objects and tools of the garuti collection have been donated to garuti through the decades by goldsmiths in retirement or by their families. many of these objects have also been restored by garuti himself. he likes to talk about his collection, about the circumstances of the recovery of the objects and, above all, about his profession. he started as apprentice in bologna, in the workshop of a goldsmith, romano degli esposti, in 1960 (fig. 3). his job became his life and even now he dedicates himself to it, preserving the knowledge of the past and trying to pass it down to the new generations. considering how this technical and artistic knowledge was handed down, from one generation to another, during the years of practice, the risk to lose all this heritage with the current industrial progress is real. the platform chosen for this virtual exhibition is a cms software (content management system) that allows to handle different kind of contents, like photos, videos and more. the exhibition is designed to guide the visitor through a main path, that starts with the first steps of gold manufacturing. the main menu, at the top, has several sections, including the one that leads to the heart of the exhibition: the “virtual tour” (visita virtuale) (fig. 4). this one is dedicated to the working stages of precious metals and starts from the melting of gold, going on with rolling, drawing, engraving and so on. a multi-level menu shows the user how the tour is structured, step by step, so he can choose to follow this fil rouge or not. every working stage is explained in detail, focusing on the tools and machineries employed, with particular attention to those from the collection. some of them have also dedicated pages, because of their importance in the working process or for their rarity (fig. 5). after each explanation there is a gallery of figure 1. home page of “antichi strumenti orafi” the virtual exhibition. figure 2. technical sheet and its mould from ditta oreste guidi. figure 3. the “history of the collection” (la storia della collezione) page, and a picture of young adelmo garuti in the romano degli esposti’s workshop. 47“antichi strumenti orafi” of the garuti collection – the virtual exhibition all the objects referring to the page. the user can watch them one by one, with a slide show. at the end of each section visitors can go on with the guided tour or jump to another section at their will. many of the machineries are manually operated and for some of them videos have been provided to show their functioning. more videos will be recorded in the next future to increase that kind of contents. every page has links to specific contents, that send back to other sections of the exhibition, or lead to other external contents shared by on-line museums or digital archives. a dedicated tool gives the visitor the opportunity to look closely into every object with a special lens. it allows the observation of specific details on the surface of the objects, like dates, brands, colours and signs of use (fig. 6). concerning brands, as previously said, there is a special section dedicated to the history of the workshops and producers of the objects exhibited. this section is called “factory brands and workshops” (marchi e botteghe) and leads to three different sub-sections (fig. 7). one is dedicated to the ditta oreste guidi, established in bologna in 1898 and closed before the early 2000s. the second one is about another important workshop in bologna, established in 1909 by enea stefani. stefani mainly worked silver objects that are still highly renowned and appreciated even after the closing of his shop, occurred in 2015. figure 4. the multi-level menu of the “virtual tour”. figure 5. the multi-level menu and one of its pages, dedicated to relevant objects. figure 6. the “lens” tool at work, a square window to see details on the surface. figure 7. the “factory brands and workshops” page and its related sub-sections. 48 francesca frasca, adelmo garuti, gian lorenzo calzoni the third subsection is dedicated to an italian factory – established in alessandria in 1840 by giovanni battista mino – and therefore called g. b. mino & figli. the mino factory produced machineries and tools for goldsmiths and silversmiths and received awards from the italian government for its innovations in this sector. the garuti collection has numerous objects from mino, especially rolling mills and drawing plates. there are also machineries from foreign countries like germany, france, united kingdom and from the u.s.a. the “antichi strumenti orafi” virtual exhibition is still improving its contents, with researches and new relevant acquisitions. this project cannot be considered completed, it’s still in progress and our purpose is to offer the public new sections and increase the current ones. sharing and dissemination are as important as preserving objects, because we now live in a transition era. some professions are now referring more and more to machines, therefore we are losing some techniques and know-how that are not reachable in books but are learned from every day practice and from the voice of old artisans. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe substantia. an international journal of the history of chemistry 3(2) suppl. 4: 83-99, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-498 citation: a. e. robinson (2019) order from confusion: international chemical standardization and the elements, 1947-1990. substantia 3(2) suppl. 4: 83-99. doi: 10.13128/substantia-498 copyright: © 2019 a. e. robinson. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson widener library, harvard university, cambridge, ma 02138, usa e-mail: ann_robinson@harvard.edu abstract. the international union of pure and applied chemistry (iupac) is the international standards making body for chemistry whose goal is to create a common language for the global chemistry community. the iupac governs the use and creation of names, symbols, and terminology. it also establishes criteria for the discovery of new elements and assesses discovery claims, develops rules for naming new elements, and defines group numbering and collective names. this paper examines a series of episodes in which the commission on nomenclature of inorganic chemistry (cnic) made changes in the nomenclature of the elements and to the periodic table. they faced protests in their attempts to harmonize the names of elements, create a systematic nomenclature for elements with an atomic number greater than 100, and changed the group numbering on the periodic table, dropping the use of a and b sub-group labels in favor of arabic numbers 1 through 18. by allowing for difference while advocating for uniformity, cnic persevered in creating order out of confusion through standardized nomenclature. keywords. chemical elements, periodic table, iupac, nomenclature. 1. introduction the need for standardization in chemical terminology, symbols, and nomenclature was well-recognized in the nineteenth century. the first international chemical conference held at karlsruhe in 1860 made some attempt at this.1 a congress was held at geneva in 1892 to create a standardized nomenclature for organic chemistry. this nomenclature did not cover the entirety of organic chemistry and it failed to be adopted, although it did later form the basis for today’s standardized nomenclature.2 international chemical conferences in the first decades of the twentieth century made gestures towards standardization but little was accomplished. a notable exception was the international committee on atomic weights (iacw), formed in 1900 after a mail ballot found overwhelming acceptance of o=16 as the basis for the determination of atomic weights, rather than h=1.3 although it took several years for the o=16 standard to be fully accepted, the iacw continues to carry out its mandate regarding atomic weights. the international association of chemical societies (iacs) was formed in 1911 with the intention of developing international chemical standards in 84 ann e. robinson the areas of nomenclature and notation, classification, atomic weights, and information related activities such as the indexing of chemical literature. commissions were created to study the nomenclature of organic and inorganic chemistry and the standardization of symbols for physical constants.4 the proposed work of the iacs was “promethean” and questions were raised regarding its funding and membership.5 before these could be resolved, world war i intervened and the iacs was dissolved in its wake. the international union of pure and applied chemistry (iupac) was formed in 1919 to replace the iacs. its purpose is to organize cooperation between scientific societies around the world, to coordinate their activities, and to contribute to the advancement of chemistry as a whole.6 the iupac is the international standards making body for chemistry whose goal is to “create a common language for the global chemistry community.”7 the common language for chemistry is largely a standardized one. the iupac publishes several books of nomenclature rules, known as the color books, that cover the many subdisciplines of chemistry. these rules govern the use and creation of names, symbols, and terminology. many of the iupac’s standardization activities are related to the elements and thus to the periodic table. the iupac reviews atomic weights, establishes criteria for the discovery of new elements and assesses discovery claims, develops rules for naming new elements and coordinates their naming, and defines group numbering and collective names. however, the iupac does not recommend the use of a specific form of the periodic table.8 much of the standardization work regarding the elements and the periodic table fell to two commissions within the iupac’s inorganic division.9 the commission on atomic weights, the continuation of the iacw, was responsible for the regular evaluation and dissemination of the atomic weights of the elements. it was also responsible for officially naming new elements until after world war ii when that duty was shifted to the commission on nomenclature of inorganic chemistry (cnic). the cnic was responsible for the development, maintenance, and publication of rules relating to the names of inorganic substances, including the elements. the cnic, in particular, was responsible for several major changes in the nomenclature of the elements and to the periodic table during the second half of the twentieth century. this paper examines several episodes associated with these changes. the first set of changes regarded the elimination of alternate names for the elements, in which the cnic opted for the adoption of “good names” over the wishes of chemists in france, the united states, and elsewhere (sections 2 and 3). the second set of changes occurred in the wake of new elements being synthesized in accelerators rather than being isolated from materials found in the earth. in their attempt to name these elements, the cnic came up against the belief in the traditional right of discoverers to name that which they discovered (sections 4 and 5). the final set of changes examined in this paper are associated with the group numbering found on the periodic table. although the use of a and b sub-group labels with the traditional roman numeral group numbering was pedagogically useful, the cnic insisted on changing the group numbers to resolve confusion that was perceived to be important for the chemical literature (sections 6 and 7). as i will show, these episodes reveal that the cnic walked a line between uniformity and the allowance of difference as they persisted in making changes they believed were necessary to achieve order from confusion through standardized nomenclature. 2. the need for internationalized element names the elements are the foundation of the periodic table. their names are the cornerstone of inorganic chemical nomenclature, the basis on which the names of compounds, minerals, and other substances are derived. standardized element names are the cornerstone of a common language for chemistry. atherton seidell (18781961),10 a chemist with the u.s. public health service, argued in 1929 that “one of the most urgently needed improvements is probably the unification of the names of the earliest recognized elements.”11 at that time, there were 80 known elements. thirty-eight of those elements had the same names in english, french, and german, and all but five ended with the suffix -ium. another 24 elements had names that differed only in spelling in the three languages. a further four elements were generally comparable and would be easy to modify for the sake of uniformity. the remaining 14 elements, however, had a great variety of names (fig. 1). chemists were required to learn all of these names in order to read the literature, particularly with regard to compounds. seidell surveyed 150 chemists who had attended meetings of the iupac and who were otherwise known to be interested in nomenclature matters.12 he sent a letter outlining the advantages of having uniformity in chemical terminology, as well as a list of five questions regarding the unification of nomenclature in general and the unification of the names of the elements in particu85order from confusion: international chemical standardization and the elements, 1947-1990 lar. among the questions seidell asked was, “will the advantages resulting from a unification of the names of the more common elements repay the effort to accomplish this end?”13 more than half of the responses were opposed to the unification of the names of the elements. among the reasons given were the belief that atomic numbers and internationalized symbols should be used rather than internationalized names, the belief that universal approval of new names would not be possible, as well as concern that confusion would result if the names of the most commonly known elements were to be changed and that relations between chemists and the public would be strained. the survey, seidell concluded, showed “that efforts to improve the nomenclature of chemistry must be confined to new names and to the harmonizing of variations in usage which do not conflict with fundamental language differences.”14 seidell had also asked if a permanent international committee should be responsible for the formulation and promulgation of rules for chemical nomenclature. about two-thirds responded favorably to this idea and half of the survey respondents thought any standardization attempts should be handled by the iupac. in fact, the iupac committee for the reform of inorganic chemical nomenclature was already at work. their 1926 report noted that all of the “very diverse propositions” that had been submitted to date could be divided into roughly ten categories, none of which included the names of elements.15 draft rules were issued in 1940, although this draft was only published in germany, britain, and the united states. the aim of these rules was “the unification of inorganic chemical nomenclature and the removal of names which are out of date or incorrect.”16 however, the names of the elements were not considered. this was because the iupac committee on atomic weights was in charge of naming new elements. it was not until after world war ii that the responsibility for element names was shifted to the commission on nomenclature of inorganic chemistry (cnic).17 a more comprehensive set of nomenclature rules for inorganic chemistry was developed in the early 1950s. before the 1951 iupac meeting in new york city, a chemical nomenclature symposium was held at which several members of the cnic presented papers. these papers reflected many of the same views that seidell’s survey brought to the fore. henry bassett (1881-1965) noted that it was desirable for nomenclature to differ as little as possible as chemistry was an international pursuit. but he also allowed that some differences were inevitable, particularly in areas “where chemistry touches the lives of people,” as in the case of commonly used elements such as silver or lead.18 kai a. jensen (19081992), on the other hand, saw “no fundamental reason for not introducing a much more radical unification of chemical terms.”19 reaching a middle ground between these two perspectives would be the task of the cnic when it came to the naming of the elements, both old and new. 3. elements with more than one name the cnic held their first post-war meeting in london in 1947 where they returned to the draft rules that had been drawn up in the late 1930s. they recognized that “a prerequisite of any international system of nomenclature was the acceptance, in all countries adhering to the union, of the same list of names and (particularly) symbols for the elements themselves.”20 towards this end, they resolved to obtain a set of symbols for the elements that was internationally acceptable. they also asked that the responsibility of naming new elements should be shared by the commission on atomic weights and by the cnic.21 this was an important step in the process of harmonizing the names of all of the elements. much of the discussion at the cnic’s 1949 meeting in amsterdam revolved around the names of elements. the cnic recommended names for eight recently discovered or synthesized elements (fig. 2). they also recommended names for six elements that were known by more than one name (fig. 3).22 little controversy was expected at the recommendation for three of the elements. element 91 was known as both protoactinium symbol french name german name english name early name ag argent silber silver argentum au or gold gold aurum c carbone kohlenstoff carbon carbon cu cuivre kupfer copper cuprum fe fer eisen iron ferrum h hydrogene wasserstoff hydrogen hydrogen hg mercure quecksilber mercury hydrargyrum k potassium kalium potassium kalium n azote stickstoff nitrogen nitrogen na sodium natrium sodium natrium o oxygene sauerstoff oxygen oxygen pb plomb blei lead plumbum sa etain zinn tim stannum s soufre schwefel sulfur sulfur figure 1. the 14 elements with the greatest variety of names according to seidell (1929). 86 ann e. robinson and protactinium, and it was decided that protactinium was more convenient. element 72 had been known as both hafnium and celtium. although the differing names were the result of a now settled priority dispute,23 hafnium was the more generally accepted name. element 71 also had two names stemming from a resolved priority controversy,24 lutecium and cassiopium, but lutecium was more widely used. the cnic changed the spelling from lutecium to lutetium. the cnic anticipated that the remaining three elements would be more controversial. the first of these three elements was element 4, which had been known as glucinium, glucinum, and beryllium. the conflicting names were the product of a tangled history, as well as a question of priority and a conflict in language.25 glucinium fairly quickly fell out of use in favor of glucinum, which was used in both english and french. germanic languages tended to use beryllium. the two names coexisted fairly peaceably although the question of which should be used was regularly raised at the turn of the twentieth century. the american association on the spelling and pronunciation of chemical terms approved the use of glucinum, largely on the basis of priority, but despite the decision it was still a matter of debate in the united states and elsewhere.26 in 1949, the cnic recommended the use of beryllium. by this time the name was widely accepted although glucinum continued to be used in french-language journals into the 1980s. element 41 was the second element with multiple names that the cnic felt could be controversial. it was known as both columbium and niobium. this element also had a somewhat complicated history and both names co-existed for many years.27 in 1913, the iasc, the iupac’s precursor, endorsed the name niobium.28 this decision did not go over well in the united states as the mineral in which the element had been discovered, columbite, was found in america. the english chemist who isolated the element named it columbium, after columbia, a historic as well as poetic name for america (fig. 4). the cnic likewise recommended the use of niobium in 1949 with a similar outcry from american chemists. evan j. crane (1889-1966), an american member of the cnic, argued that cooperation was more important than selfishness and noted, “our french colleagues made a similar concession in giving up ‘glucinum’ in favor of ‘beryllium.’”29 much like their french colleagues, american chemists were reluctant to give up the name columbium and it continued to be used for many years after the 1949 recommendation. the last of the three elements that was thought to be controversial was element 74. it had been known from the late eighteenth century as both wolfram and tungsten. wolfram was generally preferred in germanic and scandinavian countries while other countries preferred to use tungsten, although here, too, there were priority issues.30 the first attempt to harmonize these names was undertaken by the cnic in 1949. they recommended the use of wolfram, although they allowed that tungsten could be used for commercial purposes. there were atomic number name & symbol 41 technetium, tc 61 promethium, pm 85 astatine, at 87 francium, fr 93 neptunium, np 94 plutonium, pu 95 americium, am 96 curium, cm figure 2. newly synthesized elements named by the cnic in 1949. atomic number official name (1949) alternate name 4 beryllium glucinum 41 niobium columbium 71 lutetium cassiopium 72 hafnium celtium 74 wolfram tungsten 91 protactinium prototactinium figure 3. elements whose names were changed by the cnic in 1949. figure 4. detail from the 1947 edition of the periodic chart of the atoms (welch scientific company) showing element 41 with the name columbium, as well element 74 with the symbol w and the name tungsten (photo taken by the author; table in author’s personal collection). 87order from confusion: international chemical standardization and the elements, 1947-1990 objections to this recommendation and the matter was taken up again at the 1951 meeting. an erroneous report appeared in the press that the cnic was abolishing the use of tungsten which “provoked a storm of protest from all over the world.”31 although no other recommendation was made, future editions of the rules for inorganic chemical nomenclature almost exclusively used the name tungsten, albeit with the symbol w which required a note explaining its origin.32 protests, however quiet, continued to be made. it was not until 2009 that the iupac’s division on chemical nomenclature and structure representation33 declared that “the case was now closed” – tungsten was the only recommended name for element 74.34 there was a traditional belief that the person who discovered an element was the person to name it, therefore the name chosen by the person with priority should be the one used. however, the names chosen by the cnic did not always follow this tradition, one reason why the alternate names for elements 4, 41, and 74 continued to linger after the 1949 recommendation. one of the important – and controversial – stances taken by the cnic in 1949 was antithetical to this tradition. no importance was placed on priority, rather, as bassett, the cnic chair, stated at the time, “a good name was always preferable to a bad one.”35 (what constituted a “good” name was not explained.) this decision was enshrined as a part of rule 1.12 in the official nomenclature of inorganic chemistry: “it should be emphasized that their selection carries no implication regarding priority of discovery.”36 the cnic would fall back on this rule frequently in the following decades as they struggled to prevent confusion in element names while confronted with discoverers demanding their traditional right to name their discovery. 4. the challenges of synthetic elements the first official inorganic nomenclature rules, known as the red book, were published in 1957. at the same time, the cnic was faced with new challenges as a result of the discovery of new synthetic elements. these elements were different in several ways. in regard to nomenclature, a new trend arose in naming elements after people rather than after characteristics, places, or mythological figures, which created new difficulties in standardizing names across languages. scientifically, these elements were different as they were created in accelerators. as the elements get heavier, it becomes possible to create only one or a handful of atoms at a time. they had very short half-lives. they were generally detected through physical rather than chemical methods. although there were only a handful of laboratories in the world that synthesized new elements, they frequently criticized each other’s discoveries, leading to priority disputes. the cnic’s stance that element names had no implication regarding priority of discovery was put to the test. with the increasing importance of physics in the detection of new elements, the iupac would need to cooperate with the international union of pure and applied physics (iupap). similar to the iupac, the iupap was founded in 1922 to promote international cooperation in physics; create standards in the areas of symbols, units, and nomenclature; and prepare and publish tables of physical constants and abstracts of papers.37 the iupap has a commission on symbols, units, nomenclature, atomic masses, and fundamental constants (sun-amco), founded in 1931, who also publishes a so-called red book that provides authoritative guidance on the matters in its name.38 despite its interest in nomenclature, the responsibility for the naming of new elements resides with the iupac, not the iupap. however, due to the iupac’s lack of expertise in physics, a series of joint working groups was instituted to deal with the priority issues arising from the discovery of new synthetic elements. the first synthetic element that would highlight the iupac’s lack of expertise was element 102. at their 1957 meeting in paris, the cnic received word from the nobel institute in stockholm that a new element had been synthesized. element 102 was the result of a collaboration between argonne national laboratory in the united states, the harwell atomic energy research establishment in england, and the nobel institute. the meeting minutes reflect a sense of excitement at the news, as well as a sense of urgency.39 if the report could be confirmed while the cnic was meeting, the proposed name could be considered immediately rather than waiting until their next meeting two years hence. the nobel institute was contacted and news reports of the discovery were confirmed. the name, nobelium, was approved for element 102. the hasty naming of element 102 was unfortunate. when the commission on atomic weights had been in charge of naming new elements, they had waited to accept an element until a measurable amount had been separated and its atomic weight determined, a process that could take years.40 the cnic, however, did not wait for another lab to reproduce and confirm the nobel institute’s results. in 1963, they were informed by glenn t. seaborg (1912-1999) that his group at the lawrence berkeley laboratory (lbl) in the united states had 88 ann e. robinson been unable to reproduce the stockholm results. however, they had been able to synthesize a different isotope of element 102 and therefore objected to the use of the name nobelium. the cnic reiterated rule 1.12 and suggested that as the name nobelium was already in use, it would remain.41 they were in part concerned that a change in element names could cause confusion, particularly for indexing services as chemical abstracts, but they also did not want to set a precedent that element names could be changed upon request. in 1968, the cnic learned that georgi n. flerov (1913-1990) and his group at the joint institute for nuclear research (jinr) in dubna, russia, had obtained different isotopes of element 102 and called into question the results of both the original experiment in stockholm and the lbl experiments. at their meeting in copenhagen that year, the cnic “unanimously decided that it could not re-open discussion concerning the name of an element on which a definitive decision had already been taken.” they again reiterated rule 1.12, that an element’s name had little to do with priority of discovery. the cnic also noted that priority could be difficult to determine and, as a nomenclature committee, they “had no special competence to judge” in matters of priority. 42 in short, determination of priority was not a matter of nomenclature. element 102 was not the only element whose discovery was under dispute. in 1961, lbl announced the discovery of element 103. the cnic confirmed the suggested name, lawrencium, at their meeting in brighton in 1963. but again in 1968, jinr announced that the results obtained at lbl were incorrect and that they had discovered element 103, for which they suggested a different name. the cnic received this notification during their meeting in copenhagen and their stance on the name of element 102 was also applied to the situation with element 103. the name lawrencium was reconfirmed.43 another issue arose when the name for element 103 was proposed by lbl in 1963. the name lawrencium was derived from ernest o. lawrence (1901-1958), the founder of lbl and the inventor of the cyclotron. the proposed symbol for lawrencium was lw. heinrich remy (1890-1974), a member of the cnic, observed that the letter w was “an uncommon letter in many languages and difficult to pronounce.” he suggested that the spelling of the lawrencium be changed to laurentium. after discussion, jensen, the chair, remarked that they had “no right to modify the spelling” of a proper name but in order “to make the name more acceptable,” the symbol was changed from lw to lr.44 this was not the first element for which the symbol was modified. in 1955, the cnic approved the name mendelevium for element 101 with the symbol mv, after dmitrii mendeleev (1834-1907). at the 1957 meeting in paris, however, the cnic voted to change the symbol to md. no reason was given in the minutes, but as later explained this was done because “it is not customary to choose one of the last letters of the name as the second letter of a two-letter symbol” and because not all transliterations of mendeleev’s name use the letter v.45 another element whose proposed symbol was changed was element 99. the name einsteinium was proposed, with symbol e, after albert einstein (1879-1955). at their meeting in reading in 1956, the cnic approved the name but expressed concern at having an element with a single letter symbol. two letter symbols were preferred so as to avoid any confusion with the symbols of physical quantities.46 they suggested the symbol es and it was officially recommended at the 1957 meeting. the challenges faced by the cnic in regards to the names and symbols of new synthetic elements were the result of several factors. one was the desire for a truly global chemical nomenclature. although standardization was the goal, the realities of language could put the achievement of that goal into question. the increasing use of personal names as the basis for element names, such as those of lawrence and mendeleev, prevented the ability of the cnic to attain true standardization for both element names and symbols. another factor was the insistence of discoverers exercising what they perceived to be their traditional right to name the element they discovered. competing names offered by competing laboratories was a step back from the harmonization in element names the cnic began to achieve in 1949. although the cnic reiterated rule 1.12, their insistence that names had little to do with discovery was a roadblock on the path to a standardized nomenclature. 5. the tension between chemistry and physics elements on the periodic table have only one name and symbol. even those elements that have lingering alternate names, such as wolfram and tungsten, are shown with only one name and symbol. the cnic had refrained from renaming elements 102 and 103 when new claims about their discovery were reported, citing the confusion that could be caused by changing their names. in reiterating rule 1.12, they reinforced their position that element names had little to do with priority of discovery. however, elements 104 and 105 presented a new test of their resolve as the discoverers frequently 89order from confusion: international chemical standardization and the elements, 1947-1990 – and increasingly publicly and vitriolically – presented their claims while denigrating the claims of others.47 the first claim for the discovery of element 104 came in 1964. flerov’s group at jinr announced they had identified an isotope of element 104 but found it “quite desirable to conduct chemical experiments for additional identification.”48 this announcement was followed in 1966 by publication of chemical studies of element 104. flerov then sent a letter to the iupac claiming the discovery of element 104 and suggesting a name, kurchatovium. this name was in honor of igor v. kurchatov (1903-1960), who was widely regarded as the founder of the soviet atomic bomb program and had recently passed away. the group at lbl was also attempting to synthesize element 104. they had not been able to confirm the results of jinr’s experiments but, after running a different experiment, announced in 1969 they had synthesized two isotopes of element 104.49 a name was not proposed in the initial announcement, however in a paper given at the welch foundation conference later that year, albert ghiorso (1915-2010) proposed the name rutherfordium in honor of ernest rutherford (1871-1937), “the great pioneer of nuclear science.”50 ghiorso and the lbl group then notified the cnic of this suggestion. ghiorso’s letter also included the news that lbl had discovered element 105. they proposed the name hahnium, in honor of german chemist otto hahn (1879-1968).51 in much the same manner, flerov’s group wrote to the cnic in the summer of 1969 announcing they had discovered element 105. they proposed to name the element after niels bohr (1885-1962).52 though they left the name and symbol unspecified at the time, they later suggested nielsbohrium (fig. 5). this situation was not tolerable to the cnic. an element having two unofficial names in use ran contrary to the goal of a standardized international chemical nomenclature. the use of multiple names for these new elements was a potential source of confusion, not only in publications but also in indexing. at their 1969 meeting in cortina d’ampezzo, they had discussed the matter with the commission on atomic weights. the cnic ultimately recommended that elements should not be named for a period of five years after the initial announcement of their discovery. this would allow for confirmation of the discovery to occur, preferably at another laboratory and in another country.53 the cnic also once again reiterated their position on element names having little to do with priority of discovery. at the 1968 meeting in copenhagen, the cnic had raised the possibility of a systematic nomenclature for the elements. this would, they believed, end the “needless controversy” that had arisen.58 the idea was again raised in 1969. at the 1971 meeting in washington, d.c., it was unanimously recommended that a systematic nomenclature be devised for elements beyond 105. (they still hoped that lbl and jinr would solve the problems regarding elements 104 and 105 themselves.) this systematic nomenclature was to be a numerically derived system based on atomic number.55 with this nomenclature in place, all elements claimed to have been discovered would have a name ready to be used until priority could be determined and a new name proposed by the discoverer (fig. 6). in 1971, the cnic chair w. conard fernelius (19051986) wrote a position paper on the naming of the elements. it began, “communication among chemists and between chemists and other professionals has been greatly aided through the years by the existence of a logical, systematic, and generally agreed-upon nomenclature practice.” however, there were still “real problems that require the vigilance, vision, and persuasion of nomenclature committees and commissions to establish order in their use, to secure agreement among users and to avoid duplicate names and patterns.”56 it was by these means that a common language for chemistry would be achieved, a part of which was the recognition of a single name for each element. figure 5. detail from a 1985 german periodic table (vch verlagsgesellschaft) showing multiple names for elements 104 and 105 (original courtesy of the science history institute, philadelphia, pa, https://digital.sciencehistory.org/works/k3569525k). figure 6. detail from a 1988 periodic table wallchart (central scientific company) showing the iupac systematic nomenclature for elements with an atomic number greater than 100 (photo taken by the author at wellesley college, september 2016). 90 ann e. robinson a systematic nomenclature ensured that names be ready for use upon discovery, preventing the use of multiple, unofficial, names in publications as well as in indexing services such as chemical abstracts. it had long been acknowledged that these services were vital to chemists. the development of a standard international nomenclature was meant, in part, to facilitate their creation and use. among the responses seidell had received to his survey in 1929 were recommendations for the use of symbols and latin names for the elements, amid other suggestions, in indexes and compendia if names could not be harmonized (see section 2). the systematic nomenclature was a major topic of discussion at the cnic’s meeting in munich in 1973. they agreed that the names used should be short, related to atomic number, and end in the suffix -ium, while the symbols should be three letters rather than the usual two. the names would be derived from a standard set of numerical roots, based on a mixture of latin and greek on the grounds that they were easily recognizable by chemists.57 thus, for example, the name of element 106 would be unnilhexium (un + nil + hex) with the symbol unh, and 116 would be ununhexium (un + un + hex) with symbol uuh. the system was able to accommodate elements up to number 999. although this system would be in place, the cnic did not want to deny the right of discoverers to name new elements.58 although there was no expectation that the systematic names for elements 101 through 103 would be used, the cnic’s system was expanded to begin with element 101 after a “virtually unanimous” vote by the bureau, one of the iupac’s executive bodies.59 the systematic nomenclature was eventually published as an official iupac recommendation in 1979.60 even then the system was not welcomed. the iupap’s sun-amco commission expressed dismay that its proposal, as well as that of the iupap’s commission on nuclear physics, were seemingly not taken into consideration by the cnic. both preferred a system in which the atomic number took the place of a lettered symbol.61 in a letter regarding another controversy (see sections 6 and 7), one chemical educator wrote, “i don’t really care if all the new elements are named after soviets, germans, or martians, so long as they are named after someone, someplace, or something.”62 chemical and physical researchers described the systematic nomenclature as “artificial and ugly” and “utterly ridiculous,” and one physicist commented that he doubted anyone would use it.63 this may not have been the reaction the cnic was hoping for when they developed the systematic nomenclature. however, it served its intended purpose. elements that were claimed to have been newly discovered had placeholder names that allowed them to be discussed in the literature and located in indexing services and reference works without the confusion of multiple names. the systematic names avoided the appearance of official acceptance of one discovery claim over another. in order to solve the priority disputes over the synthetic elements, a joint iupap-iupac group, the transfermium working group (twg), was formed in 1986 at the behest of the iupap. the twg formulated a set of criteria that needed to be satisfied in order to determine if an element had been developed and then applied those criteria to the claims for elements 101 through 109.64 once discovery had been assigned by the twg, discoverers were asked to suggest names and symbols to the cnic for official approval. by way of the systematic nomenclature and the creation of the twg, the cnic adroitly escaped from adjudicating discovery claims and instituted a standardized chemical nomenclature that furthered their goal of a common language for chemistry. 6. confusion in group numbering the names and symbols of the elements are one of the important aspects of the periodic table. another is the group numbers which run across the top of the table, one number for each column. group numbers are used to refer to a set of elements which have similar characteristics and propertiers. these group numbers have been the subject of confusion for many years. until the 1980s, most group numbers on periodic tables consisted of eight roman numerals, with some of these having sub-group labels of a and b, such iiia or ivb. these labels were considered an important pedagogical device as they made a clear distinction between main group elements and the transition elements. the main, or major, group elements comprise the s-block and p-block, referring to their electron configuration. the transition elements, often called the transition metals, comprise the d-block. without a and b sub-group labels on a periodic table, the distinction would need to be made through the use of mnemonics or a visual cue, such as different colors as seen in fig. 7. the periodic table developed by horace g. deming (1885-1970), first published in 1923 and widely adopted in the following decades, gave the main group elements the sub-group label a and the transition elements the sub-group label b. another popular table in the united states, the periodic chart of the atoms, created by 91order from confusion: international chemical standardization and the elements, 1947-1990 henry d. hubbard (1870-1943), gave the sub-group labels in the opposite manner of deming.65 unlike hubbard ’s table, many short-form tables popular in the soviet bloc as well as in europe well into the 1960s, did not use the a and b labels. when the long form table began to become popular in europe, the a and b subgroup labels were applied somewhat arbitrarily. a survey of publications found that “in more than 10% of the articles it was nearly impossible, from the wording of the text, to recognize which elements were being discussed.”66 confusion could also be caused in the classroom. british chemist joseph chatt (1914-1994) noted of wall charts purchased from american companies, “in england students are usually told that the chart is wrong and in some universities i have seen sticky labels with the correct sub-group numbering stuck over the [other] numbers.”67 early on, in 1958, the question of group names was first raised by lamberto malatesta (1912-2007), a member of the cnic. the first edition of the red book had been sent to the publisher and it was too late to make any changes. it was decided to consider the question for the second edition, work on which was just beginning.68 at their next meeting in munich in 1959, the cnic discussed the topics of the form of the periodic table, the confusion in group numbering, the need for a definition of transition elements, and the group names used for the rare earth elements. it was decided that “no firm rules should be laid down” but nonetheless the cnic should issue a statement. a small sub-committee was appointed to examine these matters and make a recommendation regarding the use of a/b sub-group labels and group names for the elements.69 k. a. jensen, a member of the sub-committee, prepared a report on these issues. the majority of this report – six of the eight pages – concerned solely the form of the periodic table. he stated: “there are so many types that a standardization seems highly desirable. even if the commission can not [sic] agree on one standard table we could perhaps agree on a small number of different tables which could be recommended for different purposes.”70 the report then examined three main figure 7. a russian short-form periodic table that uses colors to denote the elements belonging to different blocks (khimia, moscow, 1987) (photo taken by the author; table in author’s personal collection). 92 ann e. robinson types of tables: short tables with eight groups and no sub-groups, short tables with sub-groups, and medium and long tables. jensen concluded that “the most satisfactory – i should even say the only satisfactory – periodic system is a slightly modified form of the old von richter table.”71 the table used in victor von richter’s (1841-1891) popular nineteenth century textbook was a short-form table with no sub-groups (fig. 8).72 the sub-committee discussed this report at a meeting in elsinore in 1962. it was agreed to begin with “the least controversial matters” and move towards the most controversial. given that the majority of the report was about the form of the periodic table, the minutes do not reflect any discussion of which, if any, forms should be recommended as a standard. there was a decision that the inert gases should be on the left-hand side of the table as group 0, although placing them on both sides would be permissible. the committee also agreed to accept the neutron as the first element, with atomic number 0, and placed in group 0 with the inert gases. a definition of transition elements was agreed upon, as well as names for the rare earths series.73 it was decided to use sub-group labels a/b. these sub-groups would apply only to periods 4 through 7. in order to prevent confusion, the first of the sub-groups in each group was to be given the label a while the second would be b. sub-groups labeled a were those headed by the elements k, ca, sc, ti, v, cr, and mn. sub-groups labeled b were those headed by the elements cu, zn, ga, ge, as, se, and br.74 these a and b groups would become the ones officially recommended in the iupac red book.75 a sample table was drawn and the sub-committee chair asked the members to privately inquire if the table would be acceptable. this was a standard practice for the iupac nomenclature commissions who preferred to “test the water” before issuing official recommendations.76 in this case, it was a particularly prudent precaution. some reactions to the proposals were moderate. marguerite perey (1909-1975) agreed with the placement of the inert gases on the left-hand side but questioned the inclusion of the neutron in the periodic table.77 kazuo yamazaki (1911-2010) presented the thoughts of japanese chemists who likewise were against the inclusion of the neutron but were divided over the location of the inert gases, they also believed that the placement of the a and b sub-group labels within the sample table needed further consideration.78 the chemical society relayed the comments of british chemists to the cnic. their comments focused more on the form of the sample periodic table that was enclosed with the sub-committee’s recommendations. their reactions ranged from astonishment to dread. the chemical society argued that all chemical education was based on the long-form table, not the short-form which was considered to be obsolete.79 as one british chemist put it, “if we must have a party line about the periodic table, let us at least base it on the ideas of 1963, and not those of 1863.”80 another was less sanguine, stating he had read the proposals “with a feeling little short of complete horror” and was distressed to find the iupac recommending a return to the shortform table.81 there was nothing in the nomenclature sub-comfigure 8. von richter’s periodic table (1885) which used no a/b sub-group labels. 93order from confusion: international chemical standardization and the elements, 1947-1990 mittee’s proposals about the form of the periodic table. however, they sent only one sample table and it was a short-form. many asked to comment on the proposals justifiably assumed the committee was recommending that specific form of the periodic table. chatt, member of the sub-committee, stated that he strongly recommended a long-form table be used to illustrate their proposals as it was “so much more useful in teaching chemistry that we should take care that we do not create the impression that the short form has i.u.p.a.c. preference.”82 despite t his warning, he was voted down.83 at their 1963 meeting in brighton, the cnic discussed the sub-committee’s proposals as well as the responses that had been received. after deliberations, they decided that whether or not the neutron was an element was a matter of definition rather than nomenclature, so it was dropped. it does not seem they discussed the position of the inert gases in the periodic table. following some discussion, they recommended that if subgroup labels a/b were used, they should be capitalized. otherwise, the cnic decided they did “not wish to encourage the use of these letters or of any particular form of the periodic table.”84 the second edition of the red book was issued in 1970. it included a recommendation for sub-groups for those who wished to use them, but no recommendation that they must be used. there is no mention of the form of periodic table nor is there a periodic table printed anywhere in the text.85 the reactions of chemists, particularly those who were educators, were likely a shocking and unwelcome surprise to the cnic. in response, the minutes of their 1975 meeting in santiago de compostella contain a statement that it is “desirable” that a periodic table “portray groups, periods of differing lengths, a and b subgroups, transition elements, and the accepted chemical families.” a “policy decision” reflected their new belief that, “approval of an[y] particular form of the periodic table is not a problem of nomenclature.”86 7. renumbering the groups the cnic’s recommendation for the use of a/b sub-group labeling had consequences they likely did not expect. scientific supply companies in the united states took note of their recommendations and began selling periodic tables with the new recommended labeling. however, they placed these labels in a different place than usual, sparking even more confusion.87 the committee on nomenclature of the american chemical society (acs) attempted to solve the confusion and in 1984 approved a recommended format for the periodic table (fig. 9). it was a long-form table with group numbers 1-18, groups 3-12 had a sub-label of d to denote the d-block elements, and the lanthanides and actinides below the table were given the label 3f. this new table was published in the journal of chemical education and in chemistry in britain,88 where it sparked a series of letters about the use (or lack thereof ) of a/b labels and the advisability of moving to the 1-18 group numbering. the chair of the royal society of chemistry’s educational publications committee, wrote that they had “recommended that the rsc should not adopt the 18-group formulation.”89 another letter writer expressed the hope that “all enlightened non-teaching members of the rsc will add their weight of protest along with the teachers.”90 a different writer had at first wondered whether “this was one of the more elegant spoofs perpetrated by the quality press on all fools’ day,” but he was disabused of that notion by checking the date and concluded, “there is no valid reason for falling into line with the acs model and the iupac recommendation unless it really does aid learning and understanding and avoid confusion.”91 a year later, a member of the cnic, g. jeffery leigh (1934), published a short article in chemistry international that proposed the use of the long-form table with the group numbers 1-18.92 meanwhile, chemical & engineering news published a brief story titled, figure 9. periodic table recommended by the acs in 1984 (courtesy of the american chemical society). 94 ann e. robinson “group notation revised in periodic table,” that erroneously stated an iupac recommendation for the use of group numbers 1-18 was “working its way through iupac approval procedures.”93 this article also sparked a storm of letters.94 one chemistry professor wrote, “unfortunately, the recommended numbering system … represents a giant step backward from a pedagogical standpoint” as it destroyed the relationship between group number and atomic structure.95 another argued that, “this revision ‘to remove ambiguities’ between the u.s. and european practices seems to be one of those compromises in which chemical education in the u.s. loses – again.”96 reactions in other countries varied. the portuguese chemical society requested more information “on the appropriateness of enforcing the new numbering scheme for the periodic table … in secondary school education,” particularly “given the strong controversy that this iupac ruling has provoked.”97 in response, the chair of the cnic, daryle h. busch (1928), stated that the ducth ministry for education “has advised the use of numbering scheme and has accepted it for state examinations” and the state of new york had done similarly. “the system appears to be well used in france … and in sweden.” busch also noted that “special versions” of the periodic table using the 1-18 numbering had been published for display in germany, the netherlands, and the united states.98 one of the “special versions” was published in a german chemistry magazine which sparked astonishment in klaus brodersen (1926-1997), chair of the aduc, a society of german chemistry professors. in a letter to nachrichten aus chemie, technik und laboratorium titled “save the 8-group periodic table,” he stated, “the 18-group periodic table will certainly do a disservice to chemistry.” he noted that “many rules of the behavior of the elements, which are easy to learn for every student, are now made more difficult or dull.” this included the loss of relationships between valence and group numbers as well a variety of mnemonics.99 ekkehard fluck (1931), a member of the cnic, and karl rumpf (1908-1997) laid out the case for the 18-group table and stated that it would be easy enough to create new mnemonics.100 the west german deutscher zentralausschuß für chemie raised “a formal objection” to the 1-18 recommendation. the proposal, they wrote, “does not make sense and should be rejected since it will create great confusion in chemistry lessons.”101 this confusion would in part be due to a unique situation in west germany. “while universities are usually free to use whatever nomenclature they want, schools in the federal republic are bound to follow iupac recommendations.” this could potentially cause great confusion as students moved from elementary and secondary schools into universities where they would be confronted with an unfafigure 10. a periodic table wallchart (sargent-welch) on which the a/b group numbers have been taped above the 1-18 group numbers (photo taken by the author at the university of massachusetts amherst, june 2016). 95order from confusion: international chemical standardization and the elements, 1947-1990 miliar group number system. most textbooks would also need to be revised “because much information about chemical behaviour is usually inferred from the site an element occupies in an 8 group periodic system.” ursula a. hofacker (? ) concluded that, “a recommendation of the inorganic nomenclature committee to use both forms of the periodic system would be most desirable.”102 the national committee of soviet chemists strongly objected to the recommendation to drop the a and b sub-group labels and use group numbers 1-18 instead. unlike the majority of countries, russia and many members of the soviet bloc continued to use the shortform table. the table was considered to be an important part of russian history, given the role played by dmitrii mendeleev in the discovery of the periodic law. the chairman of the national committee wrote to the iupac president noting, “we feel it particularly important to keep table’s traditional form … and to reject all groundless attempts to renounce the generally accepted … 8-groups form of periodic table.” they also objected to the change on pedagogical grounds.103 as these letters were f looding into the chemical news magazines and the iupac, the cnic was well underway with work on a new version of the red book. at their 1982 meeting in paris, they unanimously agreed to the provisional dropping of the a/b sub-group labels. there was also an agreement for a system based on the long-form periodic table.104 after the publication of the acs recommended periodic table and the articles in both chemical & engineering news and chemistry international, the iupac became alarmed by “the storm of concern” that ranged “from severe criticism, to tacit approval.” the iupac president, chintamani n. r. rao (1934), rather unusually wrote to the cnic expressing his concern and wondering “how the problem will be settled.” further, kazuo saito (1923-1998), the president of the inorganic division, attended the cnic meeting in heidelberg in 1986 – also an unusual event – to impress upon them the importance of the issue.105 as most of the objections related to pedagogy, one way to “settle” the problem might have been for the cnic to consult the iupac committee on teaching of chemistry (ctc).106 however, they apparently did not do so. in a letter to the iupac’s executive secretary, david j. waddington (1932), the chair of the ctc, remarked on the “considerable disquiet” regarding the proposed 18-group periodic table. he had “received several unfavourable comments” at the most recent ctc meeting. members, he said, “were concerned on two counts. one was on the elementary point about consultation within the iupac family. the second was on the difficulties foreseen in teaching the new form.”107 if the ctc’s objections were made known to the cnic, they were not enough to change their intentions to move ahead. after extensive debate, the cnic acknowledged “the reluctance of some users of the periodic table, mainly teachers” to drop the use of a/b labelling. however, they wished to bring an end to the confusion that was to be found in the literature and in indexing services. while they did not wish to “legislate,” they noted that in many countries there was already a tendency to use the longform table, thereby making the use of group numbers 1-18 easier.108 as a result of this meeting, busch, the chair of the cnic, published an article in chemistry international which laid out their reasons for the recommendation to use the 18-group periodic table. he noted that “it is neither the purpose nor the intent of cnic arbitrarily to set the format of the periodic table to be used in all parts of the world,” however, “it is a reasonable mission for cnic to offer broadly useful solutions when direct conflicts in usage occur.”109 in response to the many protests, the cnic continued to state that they were not legislating the adoption of a particular form of the periodic table. indeed, the new edition of the red book contained four periodic tables. the table on the frontispiece was a long-form table using the 1-18 group numbering. an appendix contained a short-form table that used the recommended a/b subgroup numbers, a long-form table that used both systems, and a 32-column table that also used both systems of numbering. the cnic stated that “common worldwide practice in teaching and research overwhelmingly supports the eighteen-column format,” however they “did not wish to deprecate any specific periodic table format.”110 regarding a/b sub-groups, the text stated “this usage is to be avoided.”111 however, three of the four tables included in the appendix used this system. the new edition of the red book was published in 1990 with little fanfare. an article was published in chemical & engineering news announcing its release112 but unlike the article in 1985 about the periodic table, it was not followed by months of letters to the editor. that did not mean there was whole-hearted acceptance of the new numbering system. scientific supply companies began printing periodic tables with group numbers 1-18 but a long tradition of educators modifying commercial products to suit their purposes continued. much as english chemists had once placed sticky labels over the “wrong” group labels, some have stuck the old group labels orver or above the new 1-18 labels as in fig. 10. once again, the cnic recommended uniformity to end perceived confusion while also leaving the door open for the continuation of difference. 96 ann e. robinson 8. conclusion one of the many letters published in the midst of the controversy over the use of a and b sub-group letters noted, “the progression of scientific thought toward worldwide unification of terms, as evidenced by the acceptance of si units and iupac naming conventions, meets an obdurate foe when faced with the periodic table of the elements.”113 the iupac commission on nomenclature of inorganic chemistry (cnic) ran into this obdurate foe in their attempts to further develop a common language for chemistry. as fernelius had written in his position paper on the naming of elements, “vigilance, vision, and persuasion” was necessary for establishing order out of confusion. the episodes examined in this paper illustrate the persistence of the cnic in walking the line between a radical unification of chemical terms and the inevitability of differences, a persistence that caused even the obdurate foe to give way. this line was a difficult one when it came to the names of the elements. as the cnic discovered when harmonizing the names of the elements after world war ii, their perception of what constituted “a good name” was not necessarily welcomed. the lingering use of alternate names for elements 4 and 41 was a case of the inevitability of differences that eventually turned into the acceptance of standardization. the “storm of protest” over the name of element 74 – tungsten or wolfram? – on the other hand was an example of the inevitability of difference not gracefully giving in to the goal of unification. the cnic’s insistence on divorcing priority of discovery from the naming of an element, rule 1.12, engendered more than a storm of protest. in the face of decades of continual protest from berkeley and dubna demanding that the traditional right of discoverers be upheld, the cnic persisted in putting off making decisions they argued were not matters of nomenclature. in response, they developed a systematic nomenclature for elements with an atomic weight greater than 100. although this system was met with scorn by chemists and physicists alike, the recommendation was welcomed by indexing services such as chemical abstracts and found its way onto periodic tables worldwide. the protests that arose of the change of group numbering were perhaps more contentious than those over the naming of synthetic elements. the non-standard use of the a and b sub-group labels were perceived by the cnic to be a source of confusion, one that could be readily solved by the use of standardized nomenclature. they did not seem to realize the pedagogical importance of the labels, even if they were not standard across the world, and when faced with protest, they did not consult within the iupac family. the committee on teaching of chemistry could have been a source of information, if not a partner in how best to approach a change, but even their objections went unheeded. and again, despite the protests that arose, the cnic was successful in walking the line between radical unification and allowing difference. on the whole, as these episodes illustrate, the periodic table and the elements were an “obdurate foe” but one that gave way to persistence. their belief in the power of standardized nomenclature to resolve perceived confusion allowed the cnic to persevere in the face of protests from multiple directions. in the end, they were responsible for changes to the periodic table and the nomenclature of the elements that advanced the goal of developing a common language for chemistry based on “the existence of a logical, systematic, and generally agreed-upon nomenclature practice.” acknowledgments my thanks to annette lykknes, brigitte van tiggelen, luis moreno-martínez, and two anonymous reviewers for their helpful comments on earlier versions of this paper. references 1. c. wurtz, in the question of the atom: from the karlsruhe conference to the first solvay conference, 1860-1911, (ed. m. j. nye), tomash, los angeles, 1984, pp. 5-28. 2. e. hepler-smith, ambix 2015, 62, 1. 3. j. l. howe, science, n.s. 1900, 12, 246. for more on the iacw, see n. e. holden, chem. int. 2004, 26(1), 4. 4. r. fennell, history of iupac 1919-1987, blackwell, london, 1994. 5. b. van tiggelen and d. fauque, chem. int. 2012, 34(1), 9. 6. ref. 4. not all member societies, called national adhering organizations (nao), are chemical societies; for example, the nao for the united states is the national research council not the american chemical society. 7. https://iupac.org/what-we-do/, last accessed on 06/03/2019. 8. https://iupac.org/what-we-do/periodic-table-of-elements/, last accessed on 04/03/2019. 9. the iupac underwent an organizational restructuring that took effect in 2002; see j. jortner, chem. int. 1999, 21, 129. 97order from confusion: international chemical standardization and the elements, 1947-1990 10. seidell was a leader in the field of international documentation and a proponent of the use of microfilm to deal with information overload in chemistry and other fields; see p. hirtle, j. am. soc. inf. sci. 1989, 40, 424. 11. a. seidell, j. chem. educ. 1929, 6, 721. 12. it is unclear if seidell did this under the auspices of a particular organization or if he did it solely on his own discretion. 13. ref. 11, 724. 14. ref. 11, 729. 15. m. delépine, chem. weekbl. 1926, 23, 86. 16. w. p. jorissen, h. basset, a. damiens, f. fichter, h. remy, j. am. chem. soc. 1941, 63, 889. 17. ref. 3 (holden). 18. h. bassett, adv. chem. 1951, 8, 5. 19. k. a. jensen, adv. chem. 1951, 8, 38. 20. commission of inorganic nomenclature, july 1947, records of the international union of pure and applied science, science history institute, philadelphia, box 38 folder 1. (hereafter cited as iupac archive.) 21. c. r. conf. union int. chim. pure appl., 14th, iupac, 1948, p. 73. 22. c. r. conf. union int. chim. pure appl., 15th, iupac, 1950, p. 58. 23. h. kragh, centaurus 1980, 23, 275. 24. h. kragh in episodes from the history of the rare earths, (ed. c. h. evans), kluwer, dordrecht, 1996, pp. 67-89. 25. c. l. parsons, science, n.s. 1904, 20, 809. 26. j. l. howe, science, n.s. 1905, 21, 35; ref. 20. 27. m. e weeks, discovery of the elements, 7th ed., journal of chemical education, easton, 1968, pp. 323344. 28. f. w. clarke, chem. news 1914, 109, 5. 29. a. m. patterson, chem. eng. news 1953, 31, 1576. 30. n. e. holden, element 74, the wolfram versus tungsten controversy, brookhaven national laboratory, bnl-81324-2008-cp, 2008. 31. ref. 30. 32. t. damhus, chem. int. 2005, 27(4), 27. 33. the division on chemical nomenclature and structure representation was created in 2002 to oversee iupac nomenclature and computer standards across chemistry-related disciplines after the dissolution of the cnic and other commissions in 2001; see a. mcnaught, chem. int. 2002, 24(2), 12. 34. minutes, division viii committee meeting, glasgow, 2009, http://iupac.org/who-we-are/divisions/divisiondetails/?body-code=800. 35. inorganic nomenclature commission, 7 september 1949, iupac archive, box 38 folder 5. 36. iupac, nomenclature of inorganic chemistry, butterworths, london, 1957, p. 6. 37. http://iupap.org/ab out-us/, last accessed on 28/05/2019 38. the iupap’s red book is one of the primary reference sources for the iupac’s green book, quantities, units and symbols in physical chemistry. 39. inorganic nomenclature commission, july 1957, iupac archive, box 41 folder 4. 40. ref. 30. 41. c. r. conf. union int. chim. pure appl., 22nd, butterworths, london, 1963, p. 206; commission on the nomenclature of inorganic chemistry, 30 june – 4 july 1969, iupac archive, box 48 folder 3. 42. commission on the nomenclature of inorganic chemistry, 26-31 august 1968, iupac archive, box 48 folder 2. 43. ref. 42. 44. ref. 15 (c. r. conf.), 207. 45. ref. 39; k. a. jensen to g. h. bixler, 6 july 1966, iupac archive, box 47 folder 4. 46. inorganic nomenclature commission, 12 april 1956, iupac archive, box 41 folder 1. 47. for an overview of the scientific controversies, see h. kragh, from transuranic to superheavy elements, springer, cham, 2018, chapter 5. 48. g. n. flerov, et al., phys. lett. 1964, 13, 75. 49. a. ghiorso, et al., phys. rev. lett. 1969, 22, 1317. 50. a. ghiorso in proc. robert a. welch found. conf. chem. res., welch foundation, houston, 1969, pp.107-150. 51. a. ghiorso to k. a. jensen, 11 june 1970, iupac archive, box 49 folder 3. 52. g. n. flerov, et al., to k. a. jensen, 23 july 1970, addenda to the records of the international union of pure and applied chemistry, science history institute, philadelphia, box 202 folder 5. (hereafter cited as iupac addenda.) 53. c. r. conf. union int. chim. pure appl., 25th, iupac, 1970, pp. 111-112. 54. ref. 42. 55. c. r. conf. union int. chim. pure appl., 26th, iupac, 1972, p. 137. 56. [w. c. fernelius], naming the chemical elements: historical and prospective, 10 december 1971, iupac addenda, box 106 folder 5. 57. several systems were suggested, including ones based solely on latin roots, but they were unwieldy, particularly when it came to symbols. see w. c. fernelius to titular and associate members of commission ii.2, 22 june 1973, iupac addenda, box 107 folder 3. 98 ann e. robinson 58. c. r. conf. union int. chim. pure appl., 27th, iupac, 1974, pp. 149-150. 59. 36th bureau (strasbourg, 1976), iupac addenda, box 202 folder 1. 60. j. chatt, pure appl. chem. 1979, 51, 381. 61. iupap sun-amco commission, 27 may 1980, iupac addenda, box 110 folder 4. 62. m. j. albinak, chem. eng. news 1985, 63(14), 5. 63. g, zu pulitz to m. williams, 28 mar 1983, iupac addenda, box 111 folder 1; r. dagani, chem. eng. news 1992, 70(37), 5. 64. a. h. wapstra, pure appl. chem. 1991, 63, 879; d. h. wilkinson, et al., pure appl. chem. 1993, 65, 1757. joint iupap-iupac working groups have continued to examine discovery claims for the elements beyond 109. 65. for more on deming’s table and the periodic chart of the atoms, see a. e. robinson, creating a symbol of science, university of massachusetts amherst, usa, 2018, pp. 258-263, 269-273. 66. w. c. fernelius and w. h. powell, j. chem. educ. 1982, 52, 504; e. fluck, pure appl. chem. 1988, 60, 432. 67. j. chatt to g. glaros, 6 march 1979, iupac addenda, box 109 folder 4. 68. l. malatesta to a. silverman, 11 december 1958, iupac archive, box 43 folder 4. 69. c. r. conf. union int. chim. pure appl., 20th, butterworths, london, 1960, p. 214. 70. k. a. jensen, nomenclature of group names etc., iupac archive, box 45 folder 3. 71. ref. 70, emphasis in original. 72. v. von richter, a text-book of inorganic chemistry, p.244, p. blakiston, son & co., philadelphia, 1885, p. 244. 73. sub-commission on the nomenclature of group names, 1 july 1962, iupac archive, box 45 folder 3. 74. ref. 73. 75. the 1990 red book discouraged the use of a/b subgroup labels, however it included two periodic tables that used them, whereas the 2005 red book does not mention a/b sub-group labels at all. 76. e. w. godly in chemical nomenclature, (ed. k. j. thurlow), kluwer, dordrecht, 1998, p. 13. 77. m. perey, commentaire sur les propositions de la commission de nomenclature, 6 april 1963, iupac archive, box 45 folder 4. 78. k. yamasaki, comments of japanese chemists on the nomenclature of group names and others, iupac archive, box 45 folder 4. 79. the chemical society, the i.u.p.a.c. commissioner’s periodic table, iupac archive, box 45 folder 4 80. h. c. longuet-higgins to a. g. sharpe, 4 march 1963, iupac archive, box 45 folder 4. 81. c. c. addison to a. g. sharpe, 4 march 1963, iupac archive, box 45 folder 4. 82. j. chatt to e. j. crane, 27 march 1963, iupac archive, box 45 folder 4. 83. j. chatt to a. g. sharpe, 30 march 1963, iupac archive, box 45 folder 4. 84. commission on the nomenclature of inorganic chemistry, 27 june – 5 july 1963, iupac archive, box 46 folder 1. 85. iupac, nomenclature of inorganic chemistry, 2nd ed., butterworths, london, 1971. 86. commission on the nomenclature of inorganic chemistry, 27 august – 2 september 1975, iupac addenda, box 108 folder 3. 87. ref. 66. 88. k. l. loening, j. chem. educ. 1984, 61, 136; anon., chem. br. 1984, 20, 390. 89. m. berry, chem. br. 1985, 21, 447. 90. a. j. roberts, chem. br. 1985, 21, 350. 91. f. m. garforth, chem. br. 1985, 21, 914. 92. g. j. leigh, chem. int. 1985, 7(3), 26. 93. anon., chem. eng. news, 1985, 63(5), 26. 94. an overview of the multitude of letters can be found in r. rawls, chem. eng. news 1986, 64(4), 22. 95. r. t. sanderson, chem. eng. news 1985, 63(10), 4. 95. r. f. drake, chem. eng. news 1985, 63(11), 2. 97. a. r. dias to m. williams, 7 december 1987, iupac addenda, box 111 folder 4. 98. d. h. busch to a. r. dias, 16 march 1988, iupac addenda, box 111 folder 4. for more on the state of new york’s decision, see a. saturnelli, the sci. teacher, 1985, 52(5), 46. the cnic’s 1-18 system was based on a proposal from the swedish national committee; see swedish national committee to interdivisional committee on nomenclature and symbols and the commission on nomenclature of inorganic chemistry, [may 1973], iupac addenda, box 107 folder 3. 99. k. brodersen, nachr. chem. tech. lab. 1986, 34(1), 34. 100. e. fluck and k. rumpf, chem. unserer zeit 1986, 20, 111. 101. w. fritsche to c. n. r. rao, 27 march 1986, iupac addenda, box 111 folder 4. 102. u. hofacker to j. d. waddington, 24 january 1986, iupac addenda, box 111 folder 4. 103. a. v. fokin to c. n. r. rao, june 1986, iupac addenda, box 111 folder 4. 104. commission on nomenclature of inorganic chemistry, 28 august – 1 september 1982, iupac addenda, box 111 folder 1. 99order from confusion: international chemical standardization and the elements, 1947-1990 105. commission on the nomenclature of inorganic chemistry, 15-22 august 1986, iupac addenda, box 111 folder 3. 106. for more on the ctc, see b. t. newbold and d. j. waddington, j. chem. ed. 1982, 59, 107. the ctc was superseded in 2002 by the committee on chemistry education; see p. atkins, chem. int. 2003, 25(1), 4. 107. d. j. waddington to m. williams, 27 january 1986, iupac addenda, box 111 folder 4. 108. ref. 103. 109. d. h. busch, chem. int. 1987, 9(2), 49. 110. iupac, nomenclature of inorganic chemistry, recommendations 1990, blackwell, oxford, 1990, p. 280. 111. ref. 110, 43. 112. d. o’sullivan, chem. eng. news 1990, 68(52), 22. 113. l. m. daniels, chem. eng. news 1986, 64(51), 3. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo martin heinrich klaproth (1743-1817), a great, somewhat forgotten, chemist as much as i worried about meeting the obligations that the chemist owes to science, for whose progress he responds to, and the audience, to whom he reports the fruits of his labor; as much as i myself committed to imprinting on my analyses the greatest possible degree of accuracy and truth; many were the occasions when i realised how difficult this goal is. (martin heinrich klaproth) juergen heinrich maar retired, department of chemistry, federal university of santa catarina, florianópolis, sc, brazil. e-mail: juergen.maar@gmail.com received: apr 26, 2023 revised: jun 25, 2023 just accepted online: jul 03, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: j. h. maar (2023) martin heinrich klaproth (1743-1817), a great, somewhat forgotten, chemist. substantia. just accepted. doi: 10.36253/substantia-2125 abstract for various reasons, some of them linked to the evolution of the historiography of chemistry, many recognized and important chemists in their time – and in ours, because of the legacy they left – are relegated to some degree of oblivion. one of these chemists, dead just over 200 years ago, is martin heinrich klaproth (1743-1817), a key figure in the transition from phlogiston theory to lavoisier’s new chemistry and one of the creators of modern analytical chemistry, an empiricist who discovered many elements and mailto:juergen.maar@gmail.com polymorphism, author of remarkable chemical and mineralogical analyses and creator of archaeometry. this article presents the life, training and scientific production of a great, but less remembered, chemist, crossing the frontiers of chemistry in many cases. key words: history of chemistry. martin heinrich klaproth. history of analytical chemistry. history of the discovery of the elements. mineral and mineral water analyses. archaeometry. forgetfulness. a little more than two hundred years ago, on january 1, 1817, died martin heinrich klaproth, one of the most important, respected and productive chemists of his time. in the posthumous opinion of august wilhelm von hofmann (1818-1892), klaproth was “for all times a model of the true scientist”1, and yet today he is not remembered as deserved. despite his great importance for the consolidation of lavoisier's new chemistry, especially in the german-speaking academic world, even with the discovery or confirmation of new elements (uranium, zirconium, cerium, tellurium, titanium, strontium, chromium), with a systematic work in the fields of analytical chemistry (gravimetry, data processing) and of inorganic chemistry, with the creation of archaeometry (application of chemical procedures in archaeology), klaproth’s name is now not very common even among chemists. how is it possible that a researcher of enormous importance and influence in his own time is now somewhat forgotten? forgetting would even be understandable if his proposals were currently not valid, or their empirical data wrong, but this is not the case. georg edmund dann (1898-1979), historian of pharmacy and professor of history of pharmacy at the university of kiel, biographer of klaproth, wrote about it in 1958: “no chemical law, no theory, much less a hypothesis are associated with klaproth's name. with his exact works of investigation he participated personally like few others in the establishment or confirmation of the bases of the new chemistry. but from the results of his researches he did not develop any regularity or general law, he did not himself develop any theory from his data”2 . brita engel adds that klaproth did not leave any longer text exposing in an integrated way his ideas and conceptions about the new antiphlogistic chemistry, to whose dissemination he contributed so much. he did not even write a textbook, which could offer an idea of his lectures, which can, however, be evaluated through an extensive manuscript of 588 pages, left by arthur schopenhauer (1788-1860), who studied at the university of berlin in 1811/1812, not only with fichte and schleiermacher, but also with klaproth. another manuscript, by the physician stephan ferdinand barez (1790-1858), complements schopenhauer’s. both were transcribed and studied by b. engel in 1987/19893. a law. or theory, or reaction or reagent linked to the name of a chemist certainly perpetuates his memory along with the application that is made, to this day, of his law, theory, reaction, or reagent, even if the researcher who created them occupies a less prominent place in the general context of our science. every chemist, and probably researchers from other areas, will know the names of guldberg and waage, proust, fehling or mohr, but the aforementioned klaproth, or torbern bergman, or wollaston are less remembered. although present in almost all histories of chemistry, cited and quoted in papers, the real importance of his work should, in our opinion, be the subject of more detailed discussion. pharmacist, chemist and member of the berlin academy, klaproth was self-taught. has this fact contributed to some marginalization? this seems unlikely, considering dalton, davy and faraday were self-taught, and obligatorily figure in all history of science texts, irrespective of ideologies. on the other hand, the academic community seems to value graduates from the academy itself: mitscherlich, klaproth's successor, coming from göttingen and from berzelius' laboratory, deserved a statue at the university of berlin, but not klaproth, whose contribution to chemistry, however, far surpasses mitscherlich’s. there may be extra scientific motivations minimizing klaproth's contribution to the whole history of chemistry. perhaps the most obvious case of forgetting and excluding scientists for unscientific reasons is the ostracism to which brilliant austrian chemists were condemned after austria's political and economic downturn in 1918: where do we still find figures such as loschmidt, rochleder, lieben, hlasivetz, pfaundler, redtenbach, authors of extensive empirical and theoretical work? the scientific isolation of germany and austria after the first world war (1914/1918) may have contributed to the ostracism or even oblivion of many scientists. needless to say, opinions fluctuate with time and context, and sometimes the version is worth, not the objective fact. there are reasons for some marginalization which are inherent to the scientific activity, and as such justifiable. but there are also reasons unrelated to science, arising from historical-political contexts, and thus not always justifiable. what matters is keeping, within the limits where this is possible, the historical records of a great man, and that is what we intend to do succinctly in this article. it does not intend, and should not be, a hagiography, but klaproth’s scientific activity and practice are such that few criticisms can be made. of course there are controversies and questions of priorities, but these are normal in periods of great expansion of scientific knowledge. but there are other, much deeper – and more dangerous – motivations for the ostracism to which klaproth and many other chemists were relegated, which we will present at the end of this essay; the importance of uranium, which klaproth discovered in 1789, for nuclear energy, contributes to preserve his memory. the origins and formation of klaproth. of humble origins, martin heinrich klaproth was born on december 1, 1743 in the small town of wernigerode, in the mountains of the harz, the second son of the tailor johann julius klaproth ( ? – 1767). the medieval town of wernigerode was nominally part of the county of stolberg-wernigerode, but count christian ernst of stolberg-wernigerode (1691-1771) ceded his lands in 1714 to the kingdom of prussia. the modest birthplace, narrow and 3 meters wide, was rebuilt after a great fire that devastated a large part of the town in 1751. with the destruction of his family's house, he moved to the home of relatives. his childhood was unhappy. of his four brothers, one died young; julius christoph (1739-....) studied theology and was a lutheran pastor and teacher, and christian august (1757-1812) held a public office. from 1755 to 1758 martin heinrich klaproth attended the gymnasium (lateinschule), but abandoned it before completing his studies, because of the rigor observed by some teachers. in dann and schwedt's current critique, instruction at the gymnasium was comprehensive and modern, similar to halle's famous franckesche stiftung. for c. friedrich, the professor johann christian meier (1732-1815), from the gymnasium, aroused klaproth's interest in figure 1. valentin roses’s pharmacy ‘zum weissen schwan’, in the nikolaiviertel, in berlin, lithograph, c. 1840, where klaproth was assistant. (edgar fahs smith collection, university of pennsylvania, philadelphia). pharmacy. to ensure his livelihood, he participated in the church choir (chorus symphonicus), giving rise to the deep religiosity that accompanied him throughout his life. even with little education, from 1759 to 1766 he was apprenticed in pharmacy at the adler und ratsapotheke (founded in 1575), with the pharmacist friedrich victor bollmann (1712-1789), in the nearby city of quedlinburg, becoming a pharmacist in 1766, at the age of 23. between 1766 and 1771 he went to work as a pharmacy assistant at the hofapotheke (court pharmacy) in hannover, at gabriel heinrich wendland’s (1730-1796) pharmacy zum engel (located on mohrenstrasse and now disappeared) in berlin, and at the ratsapotheke in danzig (present-day gdansk, poland), then owned by the physician johann alexander hevelke (1731-1806). he decided in 1771 to return to berlin, to study with johann heinrich pott (1792-1777) at the collegium medico-chirurgicum, with andreas sigismund marggraf (1709-1782) at the academy of sciences, and with the pharmacist valentin rose the elder (1736-1771), with whom he learned not only chemistry, but also latin and greek. the year 1771 marked klaproth's professional life: he became valentin rose's assistant at his zum weissen schwan (to the white swan) pharmacy in berlin, located on spandauerstrasse, no longer in existence today. rose, who had been a student of marggraf and versed not only in pharmacy but also in chemistry (inventor of rose's metal, a low melting point alloy) and in metallurgy, acquired the pharmacy in 1761. there worked and studied not only klaproth, but also sigismund friedrich hermbstaedt (17601833), who would take over the pharmacy in 1783, conrad heinrich soltmann (17821859), johann daniel riedel (1786-1843). rose's pharmacy was a sought-after center of research and study. still with wilhelm rose (1792-1876), grandson of valentin the elder, came to study pharmacy (1836/1840) the novelist theodor fontane (1819-1898), fellow countryman of valentin rose (in his novel “effi briest”, from 1896, fontane speaks of figure 2. martin heinrich klaproth (1743-1817). engraving by ambroise tardieu (1788-1841), after a portrait by eberhard siegfried henne. public domain. carl wilhelm scheele and the discovery of oxygen, in the wake of manuscripts from scheele's time then discovered by adolf erik nordenskiöld). in his biographical writings “von zwanzig bis dreissig” (1894), fontane tells in a casual way his formation with wilhelm rose. the pharmacy, which in 1802 gained a new building designed by karl friedrich schinkel (1781-1841), an exponent of classicist architecture that would characterize berlin. the pharmacy was completely destroyed in 19454. with the death of valentin rose the elder in 1771, klaproth took over the “white swan” pharmacy, and the education of valentin's four children, including valentin rose the younger (1762-1807), later an important chemist and co-author with klaproth of several articles. he also took care of the education of the children of valentin the younger, who died of cholera in 1807, heinrich rose (1796-1864) and gustav rose (1798-1873), later professors of chemistry and mineralogy, respectively, at the university of berlin. in 1780, klaproth carried out the rigorous examinations required for the profession of pharmacist, with a paper entitled “treaty on phosphorus, plus an annex on the preparation of the best distilled waters” (published in 1782). the year 1780 was another decisive year in klaproth's career: in february he married christine sophie lehmann (1748-1803), daughter of the famous mineralogist johann gottlob lehmann (1719-1767), active in saint petersburg, and marggraf’s niece. klaproth thus entered the academy's innermost circle. in the same year, klaproth bought the pharmacy zum goldenen bären (to the golden bear) or simply bärenapotheke (bear's pharmacy) pharmacy, located on the same street as the white swan pharmacy, right next to old nikolaikirche. klaproth renovated the pharmacy and installed a private laboratory there, in which he analysed dozens of minerals and discovered uranium. a plaque shows today the location where this discovery, so crucial in the future and for the future of humanity, took place. klaproth sold the pharmacy in 1800. the building was replaced in 1898 by a modern one, which in turn was destroyed in 1945. the complex of houses was restored to recall, although not reproduce, its original appearance in the popular nikolaiviertel.5 in 1787 klaproth was admitted to the berlin academy of sciences, succeeding in 1802 franz carl achard (1753-1821) as director of the laboratory. he began teaching at the collegium medico-chirurgicum (1782), at the mining school (1784), at the military academy (1787), and finally, in 1810, self-taught in chemistry and without a university degree, he was chosen to be the first professor of chemistry at the new university of berlin, on the recommendation of wilhelm von humboldt (1767-1835), the founder of the university. his colleagues were the physicists paul ermann (1764-1851) and karl tourte (1776-1847), the mathematician johann georg tralles (1763-1822), the zoologist martin lichtenstein (1780-1857), the botanist karl willdenow (17651812) and the mineralogist christian s. weiss (1780-1856)6. klaproth's renown had crossed borders: he was a member of the royal society (1795), the paris academy (1804), the stockholm academy (1804), and the st. petersburg academy (1805). fortnightly, he taught public chemistry classes, in the spirit of the enlightenment, approaching current topics, and spoke about chemical subjects at meetings and private events. after successive attacks of apoplexy (he had already suffered a heart attack in 1814) he died in the modest residence reserved for him at the academy, on january 1, 1817, at the age of 74. he was buried in dorotheenstadt cemetery, but his tomb, for which schinkel had drawn a cross cast in iron, has not been preserved. in 1993, on the 150th anniversary of his birth, a plaque was placed in the cemetery. his successor at the university was eilhard mitscherlich (1794-1863), recommended by berzelius (who had refused the post to which he himself had been invited). the university honors mitscherlich with a bronze statue by carl ferdinand hartzer in front of the side façade (1894), but does not honor klaproth. signs of an (almost) forgetting. many of the places where klaproth worked no longer exist – another factor that leads to oblivion – but other important places of interest for the scientist’s life interested admirers can still be visited: the university, wernigerode, quedlinburg. the site of the old academy building (on dorotheenstrasse), built in 1711 and destroyed in 1944, today is occupied by a parking building. in 1996, an iron monument by ralf sander (*1963) in homage to klaproth, in the form of a stele, was installed next to the main building of the technical university in berlin. johann friedrich john (1782-1847) called klaprothium the element cadmium, discovered as an impurity of zinc (1817, stromeyer; klaproth had died shortly before). a crater on the moon was named klaproth. the infrequent citing of klaproth is, perhaps, only paralleled by that of marggraf – but in this case the sunset can be attributed to the fact that marggraf was a phlogistonist, swept away (unfairly) by the ‘house cleaning’ proposed by some historians7. martin and christiane klaproth had a son and four daughters, two died in early infancy. klaproth’s son julius klaproth (1783-1835) studied oriental languages against his father’s wishes, travelled through siberia and the caucasus, was a member of the st. petersburg academy and settled finally in paris. by the end of the 19th century his work was hopelessly outdated. johanna wilhelmine (*1787) married the bergrat heinrich wilhelm abich (1772-1844), and charlotte ernestine (1790-1868) married the prussian general moritz von bardeleben (1777-1868). the work – the theory. considering the stage of development of chemistry at his time, klaproth's work is quite comprehensive and diverse. as we have seen, he left few general texts, but his view of chemistry can be reconstructed from the notes of others (barez, schopenhauer), from his 218 articles, and his participation in several collective works, with other researchers, such as the five volumes from the “chemisches wörterbuch” (“chemical dictionary”) written in partnership with friedrich benjamin wolff (1765-1845). he left aside the french and latin of the academy's publications, writing exclusively in german. klaproth's theoretical contributions to chemistry are two and they are interconnected: his general conceptions in the field of chemistry and the necessary replacement of the phlogistonist theory by a more convincing antiphlogistonist theory, essentially that of lavoisier. the clash provoked by the introduction of lavoisier's antiphlogistonist theory in germany is known8, not a heated clash as is sometimes made to believe, but a clash anyway, using rational and scientific arguments, but also extra-scientific arguments of nationalist inspiration (after all, it was the period of the napoleonic wars, the occupation of part of german territory by french troops and the dissolution of the empire by napoleon in 1806). the first defenders of the new antiphlogistonist theory in germany were johann friedrich august göttling (1755-1809), thanks to goethe professor of chemistry at the university of jena, and sigismund friedrich hermbstaedt (1760-1833), professor at the collegium medico-chirurgicum. göttling not only defended the new theory, but published a positive critique in 1794, “contribution to the corrections of antiphlogistic theory”, while hermbstaedt translated lavoisier's “traité” into german (1792). klaproth read hermbstaedt's manuscript, studied it, and repeated several of the experiments. klaproth's position would be fundamental, since after becoming convinced of the validity and usefulness of lavoisier's theory, he led the berlin academy in 1792 to officially adopt it. klaproth was not content with theoretical considerations and the observations of others, but remade part of lavoisier's experiments (despite the difficulty in acquiring the equipment), for example, the famous “pelican experiment”, with which lavoisier showed that there is no transformation of water into earth (the experiment seems anachronistic in the 18th century, but is linked to several natural observations, for example, rain and its effects on plant growth and nutrition). the experiment was remade, and klaproth wrote: “the formerly accepted belief in the conversion of water into earth is unfounded: analyzing the experiments which were intended to prove it, it was found that the supposed earth was glass, detached from the retort by the effect of friction and heat”9. converted, he wrote in 1792: “the ease with which it was believed to be able to give from the phlogiston theory a satisfactory explanation for the most important chemical phenomena, led to forgetting that phlogiston is also a hypothetical entity, and that the system built on this theory would be solid and unshakable. with the almost daily increase in the sum of chemical knowledge, and especially in view of the discovery of gaseous species, there should finally be a review of this part of chemistry. among the researchers who are responsible for the greatest merits in this regard, lavoisier is at the forefront, having convinced himself, after years of experience, of the insufficiency of stahl's theory, overturning it entirely and introducing the current and new system, which it is also called antiphlogistic”10 . accepting the new theory, the concept of element was also accepted, as proposed by lavoisier, an element defined a posteriori, as the ultimate result of an analysis (boyle's element was defined a priori). klaproth mentions 51 elemente or unzerlegbare stoffe ( = indecomposable substances), including among them light (lichtstoff), heat (wärmestoff) and ‘electrical matter’ (elektrische materie). there were 28 metals, 11 of which discovered while he himself was acting as a chemist (lavoisier's table contained 33 elements, also including light and caloric)11. an original contribution by klaproth to theoretical chemistry was the discovery in 1788 of polymorphism: the same compound can present itself in several different crystalline forms. klaproth described two crystalline states for calcium carbonate (caco3), calcite (trigonal, hardness 3, density 2.7) and aragonite (orthorhombic, hardness 3.5-4, density 2.95). (the hardness and density values are not from klaproth's times; and the name “aragonite” was coined only in 1797 by abraham gottlob werner [1749-1817] in freiberg). given the above, the idea that klaproth was averse to theoretical considerations cannot be maintained, and as a proof, b. engel describes the theoretical conceptions of klaproth's chemistry as follows12: he intends in his lectures to explain, clarify, fighting the view of chemistry as a “secret science”; chemistry is not a rigid system, but an evolutionary path destined to approach the truth; the guideline of his work is clear objectivity, simplicity and accuracy – only experiments that can be repeated are of value as a proof; his own contributions are important to him as steps towards the apprehension of reality; his work is always descriptive, and whenever possible, quantitative. seen today, it is an almost positivist recipe, and certainly an empirical one, averse to unverifiable theorizations – it is in this sense that klaproth is averse to theories. consistent with its scientific beliefs, he abhors alchemy, and unmasks many of the miraculous "elixirs" then in vogue. for example, he called into question the alleged alchemical transmutations in the famous case of johann semler (1725-1791), professor of theology at the university of halle, who claimed to have been successful in obtaining gold: without knowing the “aid” of his servant, who had added traces of the precious metal to the jars. the mysterious “elixir” unmasked were the “bestuscheff drops” (tincture ferri chlorati aetherea) for “evils of the nervous system”, which were just a solution of fecl3 in ether dissolved in alcohol... the belief in miracle drugs is not of today. klaproth's theoretical stance can be understood from the way he converted from the phlogiston theory to the oxygen theory, but it can still be followed in all his “scientific genealogy”, in which we can go back to the paracelsian daniel sennert (1572-1637) , putting us in front of a current question: does the evolution and modification of chemical theory necessarily lead, in the creation of chemical knowledge, to ruptures (or new “paradigms”, in the kuhnian nomenclature)? or, as we have said before, the development of new experimental techniques and methodologies (such as replacing the idea that chemical analysis is a 'comparison of samples' by 'searching for sample components') would not more likely lead to new 'paradigms'? sennert → rolfinck → wedel → stahl → neumann → marggraf → v. rose → klaproth klaproth’s scientific genealogy in klaproth's case, the adoption of a new theoretical model did not change his laboratory procedures, but it did change the causality and interpretation of the empirical facts studied, excluding a priori experiments considered to be meaningless, and including others that his predecessors considered unnecessary. klaproth became a phlogistonist not only with his teacher valentin rose the elder, but with readings from his apprenticeship as a pharmacist, such as the texts of johann friedrich cartheuser (1704-1777) and jakob reinhold spielmann (1722-1783), and the option for the new theory did not change his practices: uranium and zirconium were discovered in the context of the phlogiston theory, cerium and tellurium already under lavoisier's theory, without changing laboratory methods. at the time, there was a tendency to consider, alongside “theoretical chemistry” (the analyses referring to the 'system of chemistry'), also a “rational chemistry”, which dealt with all aspects capable of 'converting chemistry into science'. the search for rational chemistry dates back to the times of georg ernst stahl's theory of phlogiston (1660-1734) – the theory of phlogiston was a rational theory, albeit based on false premises – and klaproth’s and his contemporaries strong opposition to alchemy is also owed to the phlogistonists. klaproth is directly associated with the discovery or confirmation of the discovery of seven elements. uranium and zirconium are unanimously mentioned as discovered by klaproth, in 1789. in the other cases – cerium (discovery simultaneously with berzelius), titanium, tellurium, strontium, chromium – questions arise about priorities, but it is up to him to confirm the discovery and the characterization of the element. klaproth's generosity made him give up many disputes, leaving to his colleagues the credit for the discovery. he had only had to confirm it, because, as james marshall mentions, his articles were in any case appreciated, for the guarantee of a good analysis. klaproth's righteous character did not want to anticipate henry de montherlant's (1895-1972) saying that the glory of the great corrodes and destroys that of the small. at a time of great expansion of chemical knowledge, the simultaneity of discoveries is inevitable, giving rise to the consequent disputes over priorities. klaproth's work with the elements is closely related to the improvements he introduced in analytical chemistry, and by extension in chemical analysis. table 1. elements discovered or confirmed by klaproth. element discovery independent discovery or confirmation 1782 tellurium müller v. reichenstein klaproth (1788), kitaibel (1789) 1789 uranium klaproth 1789 zirconia klaproth 1790 strontium crawford, cruikshank t.c. hope, klaproth 1791 titanium gregor klaproth 1797 chromium vauquelin klaproth 1803 cerium klaproth berzelius the work – the elements. of all these discoveries, the one with the greatest repercussion – not only in the history of chemistry, but in the history of humankind – was the discovery of uranium. the prehistory of uranium begins in the 16th century, when in the inhospitable and sparsely inhabited mountains and forests of the metalliferous mountains (erzgebirge), on the border between saxony (germany) and bohemia (czech republic) began an intense mining activity, of silver, tin and other metals, which quickly turned the region into europe's largest mining center (freiberg, annaberg, aue, johanngeorgenstadt in saxony, joachimstal [jachymov] in bohemia). despite depleted silver veins and competition from silver from the new world, the mines (then owned by the austrian crown) continued to be explored in the 18th century, producing mainly cobalt and bismuth. there was in these mines a black mineral, which apparently had nothing to do with the silver ores, which the miners called pechblende (from the german pech = pitch, blende = ore, literally 'pitchcolored ore'). the first to describe pitchblende was the naturalist franz ernst brückmann (1697-1753) in 1727. axel frederick cronstedt (1722-1765) considered it a silver mineral (1758), and abraham gottlieb werner (1749-1817), a mineral associated with iron (eisenpecherz). klaproth, using new analytical procedures he had developed, analysed a johanngeorgenstadt mineral in the laboratory of his “bear pharmacy” (july 1789), and found it to be a compound of a new element, which he called uranite, later uranium, in honor of the discovery of the planet uranus, in 1781 by sir william herschel (17381822), his compatriot living in england since 1757. altogether klaproth analysed about 300 samples of minerals from johanngeorgenstadt, today exhibited at the museum of natural history in berlin, which also preserves the more than 4800 pieces from klaproth's mineralogical collection. briefly, he dissolved pitchblende (some say it was a sample of torbernite, phosphate of uranyl and copper, cu(uo2)2(po4)2,) in nitric acid, and treated the solution thus obtained with potash (k2co3), obtaining a “yellow precipitate”, which redissolves with a new amount of potash. heating the yellow precipitate with linseed oil gives rise to a black mass, which on further heating turns into a black powder; this, when heated in an oven with coal, leads to a brittle black powder, which klaproth considered to be the new metal (uranium), but was actually its oxide uo2. no other element known to klaproth presented such properties, hence his conclusion that pitchblende contained a new element. the results of his experiments were reported by klaproth to the academy of sciences at the session of september 24, 178913. at a scientific meeting in a building that no longer existed, the atomic age was born, and as i have written elsewhere14, “in the year of the fall of the bastille, when humanity began to glimpse the spirit of freedom, equality, fraternity, the first seed of a spectrum that more than a century and a half later seriously threatened the future of humanity was also (innocently) planted. and if, to our unhappiness, the dream of freedom, equality, fraternity has not yet materialized, we are consoled by the fact that the specter is also dead or at least asleep”. klaproth isolated the oxide from a new metal, and obtained several of its compounds, such as uranium acetate (1793). metallic uranium was only isolated in 1841 by eugène melchior peligot (1811-1890), reducing ucl4 with potassium (ucl4 was also synthesized by peligot). it was necessary to await the discovery of a stronger reductant than those known at the time, like potassium (davy, 1807), to reduce certain metal oxides to the corresponding metal (berzelius developed a reduction procedure with potassium). for most historians, two conditions are necessary to consider a “discovery” of a new compound: obtaining it in pure state, and its perfect characterization by analysis. i add a third observation: the existence of resources that allow obtaining chemically the element. in klaproth's time there were no resources to chemically obtain metallic uranium, so klaproth is its discoverer. (lavoisier considered the “earths” as elementary – lime, magnesia, soda, potash, barite – as there were no resources to isolate the metal from them, but he suggested the possibility that in the future they would prove to be composed). there is a controversy between klaproth and the hungarian chemist antal ruprecht (1748-1814) about the conversion of oxides into metals, the “metallization” or thermal reduction of the “earths”15. considering that the calces are metal oxides, and given the then-known possibility of obtaining the metals manganese (gahn, 1774) and molybdenum (hjelm, 1781) by reduction with coal, ruprecht, a professor at the schemnitz school of mines, intended to be this reaction a general reaction of metal oxides. he built a furnace with which he obtained temperatures of 1600 °c, and claimed to have reduced barite, lime and magnesia to their respective metals (1790). klaproth was unable to repeat ruprecht's experiments, and the analysis showed that the supposed metals released in the three cases were impure iron fragments, probably released by the equipment. klaproth considered the “metallization” as the “schemnitz illusion”, schemnitzer illusion, and it would be “impossible in principle” to obtain the metals from these earths (1791). szabadváry draws attention to the care that we must take in science with statements such as “impossible in principle”, because by electrolysis sir humphry davy (1778-1829) managed to obtain the metals from the aforementioned earths, a result that klaproth, somewhat grudgingly, ended up accepting. the controversy is an example of a dispute in which both sides are right: ruprecht was right because the “earth” actually contains a metal, klaproth was right because it is really impossible to get the metal with chemical resources. at the time of the clash, klaproth's empiricism had won. pitchblende is an emblematic mineral in the history of science. in the same pitchblende, now from joachimstal (provided by the vienna academy, through its president eduard suess [1838-1914]), pierre (1859-1906) and marie curie (1867-1934) isolated in 1898 polonium and radium. another element discovered by klaproth in 1789, again as its oxide form and again in his pharmacy, was zirconium. after platinum, it was the first element to be isolated from a non-european mineral, zirconite (zirconium silicate, zrsio4), a semi-precious stone from ceylon (present-day sri lanka), already mentioned in the bible. it was not the first time that an eminent chemist had studied zirconite: torbern bergman (1735-1784) isolated from it an “earth”, which actually was a mixture of alumina, iron oxide and lime. klaproth analysed the zirconite, noting that 70% of the mineral was constituted by a new “earth”, the zirkonerde or zirconia, zro2. isolation was quite difficult, especially separating the contaminating iron. although klaproth believed he had obtained an element, metallic zirconium was only obtained by berzelius in 1824, by potassium reduction of k2[zrf6]. the discovery of cerium16 (or cererium, as suggested by klaproth) in 1803, simultaneously and independently by the teams of klaproth and jöns jacob berzelius (1779-1848), led to the single most serious controversy in klaproth's career, leading to a harsh exchange of correspondence between the two, interrupted by klaproth, as it was not leading to anything positive. the incident had a banal origin: when berzelius and his collaborator vilhelm hisinger (1766-1852) sent the journal neues allgemeines journal für chemie, edited by adolf ferdinand gehlen (1775-1815), their article communicating the discovery of the new element, the editor replied that he had already received an identical communication from klaproth and valentin rose, and that, for reasons of chronology, he would first publish klaproth's work in the current issue of the magazine, and berzelius' in the next edition. gehlen's correct decision (although he attributed the discovery of cerium to berzelius) angered berzelius' disciples active in paris, who started a fierce controversy, finally appeased by louis nicolas vauquelin (1763-1829): klaproth, a man of righteous character and already an experienced and famous scientist, had no need to appropriate the discoveries of others, and from what he had been able to observe during the controversy, berzelius and klaproth independently discovered the new earth, practically at the same time. in his view the two researchers should to be considered the discoverers of the earth “ceria”, an opinion today accepted by most historians of chemistry. klaproth himself calmly accepted the priority given to the swede. the element's name is an allusion to the asteroid ceres, discovered in 1801 in palermo by giuseppe piazzi (1746-1826). both berzelius and klaproth isolated the ceria earth from bastnaesite (name given by berzelius, klaproth called it ochroite), a mineral found by frederick cronstedt (17221765) in 1751 in the bastnaes mines, which belonged to the hisinger family. for the history of chemistry, more important than assigning the priority of the discovery to klaproth or berzelius, is the finding that both ceria and yttria, the latter discovered by johan gadolin (1760-1852) in 1794 (from a mineral found in the ytterby feldspar mines, which klaproth named in 1801 gadolinite) are sources for the future discovery of new elements – real elements, such as the rare earths, elements never confirmed, discovered twice or more, spurious or non-existent, but nevertheless extremely valuable empirical searches in the historical context of chemistry. for the methodology of scientific work, error or failure can be as illustrative as success. of the other elements mentioned, the most complex case is that of tellurium. in 1782, austrian chemist franz joseph müller von reichenstein (1742-1824), mine inspector in transylvania (then part of hungary, now in romenia), among deposits of gold discovered a mysterious mineral he called (1795) aurum problematicum, possibly an antimony mineral (it is now known to be (ag,au)te2, telluride of gold and silver, silvanite). müller was averse to analyses, and the mineral was studied, among others, by antal ruprecht and torbern bergman, who also supported the thesis of an antimony mineral. finally müller von reichenstein sent samples of aurum problematicum to klaproth. in general terms, klaproth's analysis involves the dissolution of the mineral in nitric acid, the precipitation of gold and iron by adding potash, neutralization of the solution with hydrochloric acid: it precipitates the oxide of a new “semimetal”, as yet unknown; we know today that it is tellurium oxide, teo. in 1796 klaproth visited vienna, and there learned of the analyses of a mineral found by paul kitaibel (1757-1817) in 1789 in hungary (manuscript, the article was never published). klaproth, who was then busy with müller's samples, confirmed them, but did not realize at first that they were the same oxide that existed in the aurum problematicum sample. once confirmed the identity, klaproth called the new element tellurium, in 1798 (from tellus = the earth, “our dear mother earth”), and was a kind of godfather to the tellurium. the discoveries of the elements strontium (1790), titanium (1791) and chromium (1797) were confirmed by klaproth. klaproth was an independent discoverer of strontium in 1793, but he was not the first to obtain it (always in the oxide state, sro, metallic strontium was only obtained by davy in 1809, by electrolysis). klaproth prepared, however, several strontium compounds (chloride, nitrate, acetate, tartrate) and definitively differentiated baco3 from srco3, and consequently bao from sro. klaproth was studying at the same time the properties of baco3 and srco3. the name strontium is an allusion to the lead mines of strontian, scotland, where in 1787 william cruikshank (c.1745-1810), a chemist from the woolwich arsenal, found a new “earth”, so he is known, next to adair crawford (1748-1795), also from woolwich, as the discoverer of this element (1790). a more detailed study of the new species, even before klaproth, is that of thomas charles hope (1766-1844), professor at the university of edinburgh (successor to joseph black). hope obtained strontium oxide by heating the strontian mineral, srco3, which he named strontianite. klaproth confirmed in 1793/1794 the discovery of titanium, isolating titanium oxide, tio2, from rutile or schörl (a kind of tourmaline). in other analyses, in 1797, klaproth also isolated strontium from the mineral celestine, srso4. the original discovery of titanium, in 1791, is due to william gregor (1761-1817), in a cornish mineral, menachite or ilmenite, from which he isolated a new “earth”. the name “titanium” was given by klaproth, a tribute to the titans, children of titania, the earth goddess. the history of chromium begins with the discovery in 1766 of the mineral crocoite (lead chromate) in the lead mines of beresoff, near yekaterinburg in siberia, by johann gottlob lehmann (1719-1767) (klaproth's father-in-law). louis nicolas vauquelin (1763-1829) analysed the mineral in 1789, but discovered nothing new. only a further analysis by vauquelin in 1797 led to a new metal, chromium (the name was suggested by haüy and fourcroy). in the same year, klaproth isolated the same element from crocoite, but historiography generally attributes the discovery to vauquelin, because of his previous experiments; others, like gmelin and kopp, consider it a simultaneous and independent discovery. for dann, there is no reason to create a matter of priority vauquelin – klaproth about the discovery of chromium, as already in 1791 johann jakob bindheim (17401825), then in moscow, had analysed a siberian mineral (crocoite), in which would exist a metal, maybe molybdenum; vauquelin later identified the metal as chromium. as for beryllium, even before knowing the element beryllium or glucinium, discovered by vauquelin in 1802, klaproth had analysed chrysoberyl17, a mineral discovered in brazil, first described by christian august hoffmann (1760-1814) and dietrich ludwig karsten (1768-1810), both from freiberg. klaproth's (1795) analysis provided 71% alumina, 18% silica, 6% lime, 1.5% iron and 3% losses, total 99.95%. the current formula is beal2o4 (seybert’s analysis, 1824)18. beryl, a silicate of aluminum and beryllium (emerald and aquamarine are variants containing metallic impurities) was analysed by vauquelin, klaproth and bindheim. the work – analytical chemistry. anyone like this author who went through the banks and laboratories of chemistry courses in the 1960s will recognize in klaproth's discussion on analytical chemistry many of the operations he performed in practice, and much of the reasoning behind them. i think we are few survivors of an era of analytical chemistry in which exhausting manual labor performed the task of today's sophisticated instruments and techniques. i think – without nostalgia – that much of the magic of scientific practice has been lost... klaproth inherited an already reasonably well-structured analytical chemistry, fruit mainly of torbern bergman’s (1735-1784) activity in this field. after bergman, klaproth joined vauquelin as the greatest exponent of analytical chemistry of his time. according to bergman, chemical analysis has as its purpose the search for the truth, and the analyses must be carried out with the greatest possible rigor. analytical data already available should be reviewed with the utmost exemption. the analysis of the components of a compound should not be based on comparisons, but on independent identifications in each case. for that, the “wet route” methods are more indicated. here are the general lines of bergman's “philosophy of chemical analysis”, for which he developed scripts and introduced new reagents. bergman's conceptions in turn were influenced by earlier work by marggraf, and many of his reagents already come from boyle and friedrich hoffmann (1660-1742). following bergman, klaproth structured analytical chemistry on strong empirical bases, mainly gravimetry, which he structured as a scientific method of analysis. he emphasized some aspects he considered essential: to be subjected to analysis, chemical substances must be in the purest possible state; he emphasized the purity of reagents and developed procedures to purify them; the equipment must be chosen properly (he was perhaps the first to use agate and silica mortars). in the particular case of gravimetric analysis, he introduced: heating the precipitates to constant weight; the precipitate of the reaction is not always the most suitable compound for weighing, and if ignition results in a more stable product, this should be used to determine the weight. regarding data processing, klaproth was the first chemist to record exactly the data obtained, without the “corrections”, which even chemists like bergman and lavoisier did when the sum of the data did not reach 100%. precisely the reactions that do not reach 100% lead to the discovery or confirmation of new elements: the “correction” of the analytical data made the discovery of zirconium elude bergman. in the aforementioned analysis of chrysoberyl, among the “losses” is the element beryllium, later isolated by vauquelin (1802). in the qualitative analysis, he made intensive use of hydrogen sulphide (h2s) to obtain precipitates, a procedure later expanded by heinrich rose, and finally systematized by remigius fresenius (1818-1897). in analytical practice he introduced potash fusion in a platinum crucible to convert minerals difficult to decompose into suitable analytes (1802). the work – chemical analysis – minerals. having commented on klaproth's contributions to analytical chemistry, and considering that analytical chemistry and chemical analysis are distinct concepts, some comments on the analyses carried out by klaproth are also appropriate. according to paschoal ernesto senise (1917-2010), analytical chemistry is a branch of chemical science and as such deserves a study with all the methodological rigor that characterizes a science; chemical analysis, on the other hand, is the simple routine, “a set of methods and figure 3. martin heinrich klaproth. bust by eduard august lürssen (1840-1891), 1882. courtesy museum für naturkunde, berlin. operations necessary to arrive at the determination of the composition of a compound”. of course, chemical analysis does not dispense with rigor either, and klaproth writes about it in the preface to the manual “anweisung zur chemischen analyse” by the pharmacist johann friedrich john (1782-1847), professor at the university of frankfurt/oder until 1811 and later in berlin: “[...] it is not enough to follow in an analysis a theoretical procedure that gives a correct impression of the object [ = analyte] to be worked on, but the experiments must be such that in repetition by several chemists, all working with the same accuracy, they always get the same result. the acumen of a chemist can easily be seen by reading his works, but we can only assess the accuracy with which he performs his experiments if we are present when he performs them, or if we repeat them. the two qualities are not always present at the same time. there is no lack of chemists who easily know how to solve the most complex problems, without apparently having to confirm a priori; but if we direct our attention to his skills as an experimenter, things soon take on a different image”19 . here are the conditions that are still valid today for a correct chemical analysis, introduced as an obligatory systematic by klaproth, and also allowing us to foresee the verification by other analysts defended by the empirical science of the nineteenth century. the difference, for the chemist, between accuracy and precision is also explicit. klaproth analysed a large number of minerals, among them, in addition to the aforementioned chrysoberyl (from brazil), chrysolite20 (brought from the levante by his friend hawkins), criolite (originating in greenland, from where it came into the hands of professor peter abildgaard [1740-1801]; klaproth mentions the analyses of josé bonifácio de andrada e silva [1763-1838], who had received abildgaard's samples)21, olivine, alum, apatite, fluorite (previously studied by scheele, marggraf, wenzel and richter)22, lepidolite, emerald (from peru, a gift from prince dimitri gallitzin [17231803])23, topaz24, opal25, sapphire, garnet from bohemia and the orient26, dolomite27, lapis lazuli28, borax or tincal29, and mainly pitchblende. the samples were collected by klaproth himself on excursions through the dresden and freiberg region, to bohemia, to pomerania; others were sent to him from around the world by friends, such as geologist john hawkins (1761-1841), or researchers, like alexander von humboldt (1769-1859), and even by his son julius klaproth, who travelled the caucasus and in georgia. of klaproth's mineral analyses, the most famous is certainly that of pitchblende, mentioned above, not only for the future consequences of the uranium discovery, but for the chemical aspects of this analysis, in addition to theoretical aspects, such as the “schemnitz illusion”. the qualitative detection of uranium, as practiced until the 20th century, was, in general, klaproth's (little practiced in chemistry courses, not because of the risk, but because of the high cost of uranium). the various chemical treatments to which pitchblende was subjected resulted in a solution, identified in 1842 by eugène melchior peligot (1811-1890) as uranyl nitrate, uo2(no3)2; the addition of naoh leads to precipitation of sodium diuranate, na2u2o7, and h2s precipitates uranyl sulfide, uo2s. briefly, klaproth indicates the following composition of pitchblende, converted into percentage: table 2. composition of pitchblende according to klaproth uranium oxide 86,5% iron oxide 2,5% galena (lead sulfide) 6% silica 5% (total 100%) all these mineral analyses are described in “beiträge zur chemischen kenntnis der mineralkörper” (1795/1815), with a great wealth of experimental details, the repetition of which would be idle here. a patient reading of all these analytical works, however, shows not only the rigor of klaproth's work, but especially the ingenious use of the chemical and analytical resources then available. some of these mineral analyses are of special importance in the history of chemistry, for example, that of leucite, a volcanic mineral from italy, analysed in 1797. at the time, two “soft alkalis” were known, mineral mild alkali, or soda (na2co3), and vegetable mild alkali, potash (k2co3), the latter obtained exclusively from vegetable ashes (from algae or marine plants). although the elements sodium and potassium were only isolated in 1807 by electrolysis (sir humphry davy), chemists were able to distinguish perfectly between soda and potash (1736, duhamel de monceau), as well as between sodium salts and potassium salts (stahl). klaproth discovered potash in leucite, and obtained for the first time in a mineral the “white plant alkali” (leucite is an aluminum and potassium silicate, according to klaproth containing 53.750% silica, 24.625% alum and 21.350% of ' vegetable alkali')30. there is the curious case of siderite or hydrosiderite, a supposed element. in 1777/1778, torbern bergman in uppsala and johann karl friedrich meyer (1733-1811) in stettin were studying a curious variety of cast iron, which after being treated with sulfuric acid and further reduced, gave rise to a greyish-white powder, a possible element, siderite. the same variety of iron was also analysed by klaproth, who found in 1783 that it was an alloy of iron and phosphorus (as phosphoric acid or phosphide)31. another analysis of importance for the evolution of chemistry was that of guano, brought from south america by alexander von humboldt on his return to europe in 1804. humboldt entrusted samples for analysis to fourcroy and vauquelin in paris, and to klaproth. the french published their analysis in 1806, klaproth in 180732. klaproth found in guano 16% of ammonium urate, 12,75 % of calcium oxalate and 10% of calcium phosphate. the results were similar, but far from those of a modern analysis (klaproth found phosphates, oxalates, urea, ammonia). guano has been known since the 16th century, but the first more detailed descriptions are by amédée françois frézier (16821773), in his 1712/1714 travels, and by antonio de ulloa (1716-1795). in addition to klaproth, louis nicolas vauquelin (1723-1829) and wilhelm august lampadius (17721842) also chemically analysed guano. other exotic materials brought by humboldt were also subjected to analysis by klaproth, such as the “pacos” from peru (supposed silver mineral, actually 71% iron, 14% silver)33 and the “mocha” from quito, a volcanic material34. the work – chemical analysis – mineral waters. the analysis of mineral waters, especially those that present a supposed or real curative aspect, attracted the attention of analysts and assayers since the middle ages, and with the improvement of analytical techniques these analyses multiplied from the beginning of the 18th century, involving many chemists, from hoffmann and bergmann to berzelius, liebig and fresenius. oskar baudisch (1881-1950), an analytical chemist, dedicates an essay to the “magic and science of healing mineral waters”. the “magical” aspect of the “cure” is, on the one hand, psychological, involving the entire atmosphere reigning in the mineral resorts, and on the other, even scientific, with the discovery in the waters of chemical principles that could account for certain medicinal effects (iodides, sodium sulfate, lithium salts)35. klaproth also analysed mineral waters, two of which we will present here: the waters of karlsbad, in bohemia (today karlovy vary, in the czech republic), and the waters of the dead sea, the first due to the great importance of karlsbad in the cultural context of the 18th and 19th centuries, attended by the european elite (goethe, beethoven, berzelius, chopin, turgenev were regulars), and the second for the emblematic value for christianity of the waters of the jordan and the dead sea. the first analysis of karlsbad thermal waters is due to the spa's physician, david becher (1725-1792), in 1770. klaproth analysed them during his stay there in june 1789, in the company of his friend count carl friedrich von gessler (1752-1829). klaproth determined the following components of karlsbad water: 1000 parts by weight of water contains 5,478 parts of solids, distributed as per the table; the analysis generally confirms becher's. table 3. klaproth analysis of karlsbad mineral waters36. sodium sulfate (glauber's salt) 2,431 parts sodium bicarbonate 1,345 parts sodium chloride 1,198 parts calcium bicarbonate 0,414 parts silica 0,086 parts iron oxide 0,004 parts a new analysis was carried out in 1809 by the chemist ferdinand friedrich reuss (17781852), professor at the university of moscow. as early as 1802, klaproth had published a recipe for making 'artificial karlsbad water'. the production of artificial mineral waters was described in 1783 by johann carl friedrich meyer (1739-1811), a pharmacist in stettin (now szczecin, poland), but even earlier priestley and bergman had already produced artificial waters. berzelius published in 1823 a long article discussing the analysis of the waters of karlsbad, in which he criticizes aspects of klaproth's analysis, despite the usual rigorous procedure of the latter37. the dead sea is par excellence a sacred place for judaism and christianity, and its waters have a high symbolic value for western christian-jewish civilization: their analyses combine the history of humanity, the presence of mythical and transcendental values, the ‘magic’ side of science, and chemical analysis figures as a kind of 'centralizer' of the discussion. for centuries, pilgrims and explorers visiting the holy land brought back bottles with water from the dead sea and the jordan river, and a first qualitative analysis of these waters was carried out by the english physician charles perry (1698-1780) in 1742. the first quantitative analysis was that of pierre macquer (1718-1784), in 1781 (it is the second quantitative analysis of natural waters, preceded only by seawater). after macquer, many chemists occupied themselves with the emblematic water: alexandre marcet (1807 and 1813), klaproth (1809, 1813), gay-lussac (1819), hermbstädt (1822), christian gmelin (1827), boussingault (1856)38. table 4 shows klaproth's data from 1813: table 4. klaproth analysis of dead sea waters chloride 206,5 g/liter sodium 38,2 magnesium 35,9 calcium 24,3 potassium traces klaproth's data broadly confirm macquer's, but they were contested by marcet. in 1792/1793 klaproth analysed the waters of iceland's hot springs. john thomas stanley (1766-1850) had brought bottles of these waters from his expedition to the faroe islands and iceland in 1789 and forwarded the samples for analysis to klaproth and joseph black. the results of both are almost coincident (presence mainly of silica, sodium chloride, sodium sulphate)39. the work – archaeometry40. analyst that he was, it did not take long for klaproth to apply chemical analysis to antiquities and archaeological objects: coins, metals, bronze and other metallic alloys, glass, ceramics, pigments, dyes, an applied branch of chemistry known today as archaeometry. the term ‘archaeology’ is not klaproth’s, it was used for the first time in 1953, in a journal published by the research laboratory for archaeology and the history of art in oxford. there are some analyses prior to klaproth, e. g. the analysis of chinese paktong by gustav von engeström (1738-1813) in 1776, and some ‘archaeometallurgical’ studies mentioned by t. pownall in 177541. archaeometry is one of klaproth's most figure 4. cover page of klaproth’s most important publication, ‘beiträge zur chemischen kenntnis der mineralkörper’. interesting contributions, not only to science, but to history itself42. archaeology, erected in science essentially thanks to the efforts of johann joachim winckelmann (1717-1768) in understanding classical antiquity, had an auxiliary arm in archaeometry, which allows not only to study the technological resources available to the ancients, but also to make inferences, such as determining trade routes, cultural influences, colonization start dates and others. knowing the composition of ancient objects, it is also possible to restore works of art from the antiquity. klaproth had a special interest in history, and had a valuable collection of antiquities, thus being interested in the analysis mainly of metals (coins, weapons), but also of glass and medieval metallic objects. klaproth began these analyses in 1785, and earle caley (1900-1984), a modern authority on the subject, considered them of great importance, as never before had anyone analysed such objects from a chemical, scientific point of view, nor was there a script until then, for the analysis, for example, of old coins43. it is no longer possible to confirm klaproth's data, but modern analyses of coins from the same time and place confirms his results: for example, for a roman coin from the times of emperor claudius, klaproth found a composition of 77.9% of cu and 21.1% zn, and in 1869 the self-taught writer and chemist ernst von bibra (1806-1876), also interested in this subject, found for a coin of the same period the values 77,44% cu and 21.50% zn (the difference corresponds to traces of metals that escape the analytical procedures of klaproth and bibra)44. it is thus known, thanks to archaeometry, that the roman coins of the 1st century were minted in brass and not in bronze. josef riederer (1939-2017), a chemist from the berlin museums, repeated some analyses of roman coins (1974), with results very similar to those of klaproth. table 5 shows some of the results. table 5. analyses of roman coins by klaproth and riederer45 elements klaproth (1795) riederer (1974) (sample 1) (sample 2) (sample 1) (sample 2) copper 77,9 83,0 77,5 83,0 tin 1,9 0,7 lead 0,62 zinc 15,5 15,15 22,1 14,45 [sample [1]: coins from the times of claudius (41/54); sample [2]: coins from the times of vespasian (98/117)] table 6 compares the data of the analysis of an ancient mirror by klaproth and bibra. table 6. analyses of the metal of an ancient metal mirror, by klaproth and bibra46 elements klaproth bibra copper 62 64,46 tin 32 28,36 lead 6 7,13 iron traces nickel 0,05 in the case of studying old glasses, the weight of the sum of the weights of the components found does not match the original weight of the sample, a fact that klaproth does not explain, although he knew the fundamental aspects of glass technology since antiquity. it is now known that the difference is due to the presence of sodium and potassium oxides, compounds not known in klaproth's time. the importance of the knowledge of the basic theoretical aspects for correct chemical practice is evidenced in klaproth's analysis of glass: for him copper was responsible for the color of red and green glasses, but different “forms” of copper. we would say today, different oxidation states of copper, cu(+ii) in red, cu(+i) in green glass. table 7 shows data from klaproth’s analyses47. table 7. composition of old glass according to klaproth components (grains) red green blue silica 142 130 163 lead oxide 28 15 copper oxide 15 20 1 iron oxide 2 7 19 alumina 5 11 3 limestone 3 13 0,5 in 1798 klaproth published more detailed glass analyses, from glasses collected at the villa of emperor tiberius in capri. compounds in bold were in klaproth’s opinion responsible for the color of the glass. klaproth found out that different ‘kinds’ of copper are responsible for both red and green color, a fact we explain today considering different oxidation states of copper. table 8. analyses of roman glasses from capri (klaproth, 1798)48. color sio2 pbo cu2o cuo fe2o3 al2o3 cao red 72,8 14,4 7,7 1,0 2,6 1,5 green 66,3 7,7 10,2 3,6 5,6 6,6 blue 87,4 0,5 10,2 1,6 0,3 it is worth mentioning the analysis of the ancients' electrum (in this case, a mineral sample from siberia)49, and, in the course of the analysis of many “earths”, the analysis of the “earth of lemnos” (lemnia sphragis), used by the ancient greeks as antidote for poisons, and whose composition is, according to klaproth: 66% silica, 14.5% alum, 6% iron oxide, 3.5% soda, 0.25% lime, 0.25% talc and 8% water50. other early 19th-century chemists were concerned with archaeometry: jean antoine chaptal (1756-1832) analysed pigments found in pompeii (1809), and sir humphry davy (1778-1829) analysed the pigments used by the ancients in paintings51. and as we said, archaeometry ended up leading to the possibility of restoration and conservation of archeological objects and ancient works of art, today a routine in the laboratories of specialized museums. the first laboratory along these lines was that of friedrich rathgen (1862-1942), the “father of modern archaeological conservation”, in the berlin museums (1888)52. the work – organic chemistry. most of the history of chemistry treatises consider klaproth's contribution to organic chemistry to be minimal. they limit themselves to mentioning the discovery, in the mineral mellite (mellit, honigstein), of mellitic acid (honigsteinsäure), c6(cooh)6, in 1799 (mellite is the aluminum salt of mellitic acid, [al(h2o)6]2c6(cooh)6, discovered in artern, germany, in 1789 by dietrich ludwig gustav karsten [1768-1810])53. mellytic acid is obtained by treating mellite with ammonium carbonate and precipitating alumina with ammonia. in 1776, klaproth examined copal, a vegetable resin of various origins, used in the manufacture of varnishes. copal was considered sometimes as a mineral, sometimes as a semi-fossilized resin (succinum vegetabile indicum) similar to amber54. in fact, klaproth's interest was great not only in organic chemistry, but also in physiological chemistry, but as both were still taking their first steps, they hardly appear in his writings. however, they occupy an appreciable space in his lectures, as b. engel discovered to her surprise when transcribing the aforementioned manuscripts by barez and schopenhauer. surprising is the space given to the “components of organic bodies”, almost 28% of the manuscript, almost the same extent as that devoted to minerals (30%), klaproth’s main field of research. "organic bodies" include "flammable substances" and "substances from the animal kingdom". it is clear, according to engel, that klaproth not only taught his students inorganic chemistry, but also the knowledge taken as fundamental requirements for understanding organic chemistry and physiological chemistry that were beginning to develop, a particularly important aspect in courses that prepared physicians and pharmacists, still in the opinion of b. engel55. the work – publications. in addition to the routine publication of the results of his investigations – mainly chemical analyses – in various scientific journals, such as crell’s annalen der chemie, in scherer's allgemeines journal der chemie and in rose’s and gehlen’s neues allgemeines journal der chemie, there are also more comprehensive publications, some in partnership with other chemists. the most important of these works is undoubtedly “beiträge zur chemischen kenntnis der mineralkörper” (contributions to the chemical knowledge of minerals), in six volumes, published between 1795 and 1815 in berlin, devoted the first five volumes successively to john hawkins, dietrich ludwig g. karsten, vauquelin, berthollet and a. von humboldt. also important is "chemische abhandlungen gemischten inhalts"56 (chemical communications on various contents), berlin 1815. in this book he describes, for example, the analyses of ancient coins57 and glasses, belustscheff’s dye58, analyses of minerals and products of plant origin, analysis of salt, ozokerite, meteorites59, sugars and many other subjects. in 1797 the king of prussia frederick william iii (1777-1840) commissioned a new pharmacopoeia, the pharmacopoeia borussica, which was developed by klaproth, with the collaboration of valentin rose the younger and sigismund friedrich hermbstaedt (1760-1833). the pharmacopoeia was developed according to the lavoisierian theory, including nomenclature. chr. friedrich notes that the new pharmacopoeia already contains data on the chemical composition of the simplices as well as quality tests. klaproth wrote in partnership with friedrich benjamin wolff (1765-1843) the “chemisches wörterbuch” (dictionary of chemistry), in five volumes (1807/1810), dedicated to tsar alexander i (1777-1825), translated in 1812 into french by heinrich august vogel (1778-1867), professor at the lycée napoléon in paris; later four volumes of “supplements” (1815/1819) were added. wolff was kant's student in königsberg and for a long time taught mathematics and physics at the joachimstaler gymnasium in berlin, and also wrote a didactic “handbook of chemistry”. the “systematisches handbuch der chemie” (systematic handbook of chemistry) by friedrich albrecht carl gren (1760-1798), published in 1787/1794, merited a new revised edition by klaproth in 1805 (gren was an ardent advocate of phlogiston, but convinced of the assertion of lavoisier's theories, sought to reconcile the two theories). the students. raised to the university chair at the age of 67, klaproth had there few students (we mentioned arthur schopenhauer before), but many studied with him at the collegium medicum, and in what aaron ihde considered the “best place to learn chemistry” in the 18th century, the pharmacy60. klaproth did not form a school, but his biographer dann mentions 32 names he considers of some relevance who were his students, starting with heinrich rose and gustav rose, sons of valentin rose the younger and later professors at the university of berlin. important was adolf ferdinand gehlen (1775-1815), editor of several scientific periodicals and, since 1807, chemist at the bavarian academy of sciences in munich (where he died of intoxication while researching arsenic compounds). johann jakob bindheim (1740-1825), about whom little is known, studied with klaproth in the white swan pharmacy, and later worked in russia (1795/1804). also should be mentioned carl willdenow (1765-1812), later professor of botany at the university of berlin, the pharmacists johann heinrich julius staberoh (1785-1858) and johann christian schrader (1768-1826), active in the public health service in berlin, and jacques peschier (1769-1832), the latter from geneva61. a tentative evaluation looking at the life and work of the pharmacist and chemist klaproth, it remains for us to assess the figure of the scientist at the time he was active. in hufbauer's opinion, at the end of the 18th century the situation in german chemistry was chaotic, and we can say that in the midst of this chaos, klaproth's figure is a lone star62. in the 18th century there were outstanding and influential personalities in german chemistry, coming essentially from pharmacy and medicine: the theorist stahl, the empiricists friedrich hoffmann and andreas sigismund marggraf, the technologist johann beckmann, but the situation deteriorated at the end of the century, not only because of the controversy between the "french chemistry" (read lavoisier) and "german chemistry" (read stahl’s followers), a controversy fueled not only by scientific arguments, since it was predictable that the german chemists defended first the theory of theirs countryman stahl. one cannot forget the influence of nationalist factors and especially the reflection of the decadence of academic chemistry, exhausted and without perspectives, revived in the end by the adhesion of hermbstaedt and klaproth to the new lavoisierian theory, and, in homburg's opinion, also by the radical reformulation of university laboratories. if at the end of the 18th century there were undoubtedly competent chemists such as georg ludwig claudius rousseau (1724-1794) or heinrich august vogel (1778-1867), there were also exotic characters such as gottfried christian beireis (1730-1809) in helmstedt, and ferdinand wurzer (1765-1844) in bonn. thanks to the rationality and empiricism that he imprinted on his scientific activities, klaproth reversed the situation, just when the chemical community in germany was beginning to organize itself, around 1790. after a youth of “suffering and hope”, in his own words, the self-taught klaproth raised all the steps of the prussian medical bureaucracy and academic activity; as an internationally recognized scientist, he gave a new start to the chemical activity in germany and influenced the pharmaceutical activity for 30 years. we conclude with the assessment that the chemist and historian of chemistry thomas thomson (1778-1842) made of his legacy63: “among the outstanding traits of his character is the incorruptible respect he had for all that was true, honorable and good; his pure love of science, without any reference to feelings of selfishness, ambition or avarice; his rare modesty, unaffected by the slightest boasting or arrogance. he was benevolent to all men, and he never uttered a word of spite or even offense directed at anyone around him. when forced to censure, he did so quickly and without bitterness, for his criticism was always directed at facts, never at people. his friendships were never the result of selfish calculation, but were based on his opinion of each individual's personal worth. […] to all this we can add a true religious feeling […] of the obligations of love and charity […] demonstrated, for example, in the commendable care he devoted to the education of valentin rose's children”. here is the life, character, and work of our somewhat forgotten honoree. epilogue a necessary finding. why was klaproth forgotten? the evils that affect historiography in general today also affect the historiography of science: a refusal to accept causality, the gradual replacement of the philosophy of science by a sociology of science, the abandonment of a logically ordered method, the neglect of primary sources (which could lead to a historiography that is too “positivist”, or even rankean). in the case of the historiography of science, there are also two dangerous trends: the mistaken belief that scientific creation is socially conditioned, and not by the logic underlying a method, and the appreciation of facts not for what they mean in terms of advances in scientific knowledge, but for the importance attributed to them in the social context. many "theorists" of the history of science, in their practice, no longer differentiate between objective science and subjective "doing science", are ignorant of the very notion of "science", and often forget that chemistry is, after all, an experimental science. and many “theorists” of science defend more and more the idea that knowledge is a “social construction” and not the consequence of the rigorous application of a pre-established scientific methodology that is periodically tested through the results obtained. thus, they open the doors for the return of pseudo-sciences and for the emergence of themes that do not exist at all, such as a supposed “pre-columbian science” (there were pre-columbian techniques), or others that should already be buried, such as “occult chemistry”. the necessary integration of scientific culture to the culture of humanity as a whole is unfortunately done at the expense of scientific knowledge. thus, names like klaproth, like bergman, gadolin, trommsdorff, runge or kolbe, all empiricists, left the scene. they are all deserving of a return. and in this regard “[history] can help to better understand the scientific discovery itself, verifying the factors that acted in it, the figures that remained behind the scenes. perhaps this way scientists and historians can rectify many glories and unearth many forgotten skeletons”64. and the biographies serve as a backdrop against which all the events that led to a particular scientific discovery unfold, going beyond the limits of science itself. biographies, far from hagiographies, make it possible to establish contacts between people – scientists and non-scientists – places and times, assess the spread of ideas and theories, in addition to allowing the identification of influences and scientific schools65. . references. 1 .bugge, g;. “das buch der grossen chemiker”, verlag chemie, weinheim, 1979 [berlin, 1929], vol. 1. 2 . dann, g. e., “martin heinrich klaproth (1743-1817). ein deutscher apotheker und chemiker. sein weg und seine leistungen”, akademie verlag, berlin, 1958, p. 72. 3 . engel, b., “martin heinrich klaproth: chemie, nach den abschriften von stephan friedrich barez und arthur schopenhauer”, mitteilungen, gesellschaft deutscher chemiker. fachgruppe geschichte der chemie, 1989, 3, 27-37. 4 . schwedt, g., “vom harz nach berlin – martin heinrich klaproth”, booksondemand, 2016. 5 . kraft, a., jahrbuch des vereins für die geschichte berlins, 2008, 58, 9-24; 6 . scurla, h., “wilhelm von humboldt”, heyne-verlag, munich, 1984, p. 349. 7 . ihde, a., “the development of modern chemistry”. dover publications, new york, 1984, pp. 25-32. 8 . homburg, e., “the rise of analytical chemistry and its consequences for the development of the german chemical profession (1780-1860)”, ambix, 1999, 46, 1-32; 9 . klaproth, m. h., from the notes of a. schopenhauer, apud engel, b., op. cit., p. 35. 10 . klaproth, m. h., from the notes of s. barez, apud engel, b., op. cit., p. 35. 11 . engel, b., op. cit., 30-31. 12 . engel, b., op. cit., 34-35. 13 . klaproth, m. h., “chemische untersuchung des uranits, einer neuentdeckten metallischen substanz”, ann. chem., part 2, 1789, pp. 387-403. 14 . maar, j, h., “história da química”, volume i, conceito editorial, florianópolis, 2008, p. 537. 15 . szabadváry, f., periodica polytechnica chem. eng.,, 1982, 26, 143-147. 16 .klaproth, m. h., “beiträge zur chemischen kenntnis der mineralkörper”, decker & co., h. a. rottmann, posen and berlin, 1796-1815, vol. iv, pp. 140-154. 17 . klaproth, m. h., beiträge, vol. i, pp. 97-102. 18 . seybert, h., annals of philosophy, 1824, 7, 427-432. 19 . klaproth, m. h., apud schwedt, g., p. 94. 20 . klaproth, m. h., beiträge, vol. i, pp. 103-111. 21 . klaproth, m. h., beiträge, vol. iii, pp. 207-214. 22 . klaproth, m. h., beiträge, vol. iv, pp. 360-365. 23 . klaproth, m. h., beiträge, vol. ii, pp. 12-15. 24 . klaproth, m. h., beiträge, vol. iv, pp. 160-178. 25 . klaproth, m. h., beiträge vol. ii, 151-154. 26 . klaproth, m. h., beiträge, vol. ii, pp. 22-24. 27 . klaproth, m. h., beiträge, vol. iv, pp. 204-223. 28 . klaproth, m. h., beiträge, vol. i, pp. 189-196 29. klaproth, m. h., beiträge, vol. iv, pp. 350-353 30 . klaproth, m. h., beiträge, vol. ii, pp. 39-51. 31 . fontani, m., costa, m., orna, m., “the lost elements”, oxford university press, 2015, pp. 3-4. 32 . klaproth, m. h., “untersuchung des guanos von den peruanischen inseln”, beiträge, vol. iv, pp. 299 313. 33 . klaproth, m. h., “untersuchung der ‘pacos’ aus peru”, beiträge, vol. iv, pp. 4-9. 34 . klaproth, m. h., “untersuchung des ‘moya’ aus quito”, beiträge, vol. iv, pp. 289-298. 35 . baudisch, o., “magic and science of natural healing waters”, j. chem. educ., 1939, 16, 440-448. 36 . klaproth, m. h., beiträge, vol. i, p. 322 37 . berzelius, j. j., annalen der physik (gilbert), 1823, 74, 113-211; 38 . nissenbaum, a., “chemical analyses of dead sea and jordan river water”,israel journal of chemistry, 1970, 8, 281-287. oren, a., “qualitative and quantitative chemical analyses of dead sea water in the 18th and 19th century”, israel journal of chemistry, 2006, 46, 69-77. 39 . gliemann, t., “geographische beschreibung von island”, j. hämmerich, altona, 1824, pp. 59-60. 40 . bartel, h., “martin heinrich klaproth und die archäometrie”, berliner beiträge zur archäometrie, 25, 119-136 (2017). 41 . pollard, a., “the first hundred years of archaeometallurgical chemistry: pownall (1775) to von bibra (1869)”, historical metallurgy, 2015, 49, 37-49. 42 . schütt, h. w., ”martin heinrich klaproth als archäometer”, chemie in unserer zeit, 1989, 23, 50-52. caley, e.,” the early history of chemistry in service of archaeology”, j. chem. educ., 1967, 44, 120 127. 43 . caley, e., “klaproth as a pioneer in the chemical investigation of antiquities”, j. chem. educ., 1949, 26, 251-257. 44 . bibra, e. v., “die bronzen und kupferlegierungen der alten und ältesten völker”, ferdinand enke, erlangen, 1869, pp. 52-58. 45 . data adapted from bartels, op. cit., p. 127. 46 . data from bartels, op. cit., p. 46. 47 . schütt, h. w., op. cit., p. 51. 48 . klaproth, m. h., “über antike glaspasten”, abhand. königl. akad. wiss., 1798, pp. 34, 35, 37. 49 . klaproth, m. h., beiträge, vol. iv, pp. 1-3. 50 . klaproth, m. h., beiträge, vol. iv, pp. 327-333. 51 . caley, e., “the early history of chemistry in the service of archaeology”, j. chem. educ., 1967, 44, 120-127. 52 . gilman, m., “friedrich rathgen: the father of modern archaeological conservation”, journal of the american institute of conservation, 1987, 26, 105-120. 53 . klaproth, m. h., beiträge, vol. iii, pp. 114-134. 54 . krünitz, j. g., oekonomische encyclopaedie, part 43, joseph trassler, brünn, 1790, pp. 710-760. 55 . engel, b., op. cit., pp. 30-31. 56 . klaproth, m. h., “chemische abhandlungen gemischten inhalts”, nikolaische buchhandlung, berlin and stettin, 1815. 57 . klaproth, m. h., chemische abhandlungen, pp. 21-60 (five papers) 58 . klaproth, m. h., chemische abhandlungen, pp. 1-15. 59 . klaproth, m. h., chemische abhandlungen, pp. 209-308. 60 . ihde, a. “the development of modern chemistry”, dover publications, new york, 1964, pp.290-291. 61 . friedrich, c., pharmazeutische zeitung, 2016, 51/52 62 . hufbauer, k., “the formation of the german chemical community”, university of california, 1970. 63 . thomson, t., “the history of chemistry”, vol. ii (reprint of the 1830/1831 edition), h. coburn & r. bentley, london, pp. 135-136. 64. reis, j., “a história e o ensino da ciência”, revista de história, 1967, 34, 3-13. 65 . ledermann, e., “les pharmaciens suisses et la science: une autre histoire de la pharmacie helvétique”, anal. real acad. farm., 2000, 66 doi: https://doi.org/10.36253/substantia-1115 received: oct 13, 2020 revised: dec 02, 2020 just accepted online: dec 04, 2020 published: mar 01, 2021 https://doi.org/10.36253/substantia-1115 substantia. an international journal of the history of chemistry 2(1): 51-76, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-41 citation: b.d. hughes, b.w. ninham (2018) a correspondence principle. substantia 2(1): 51-76. doi: 10.13128/ substantia-41 copyright: © 2018 b.d. hughes, b.w. ninham. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. permission to reproduce. republished from physica a, 2016, 443, 495517. with permission from elsevier. copyright 2016. research article a correspondence principle barry d. hughes1,* and barry w. ninham2 1 school of mathematics and statistics, university of melbourne, victoria 3010 australia. ∗corresponding author 2 department of applied mathematics, research school of physical sciences and engineering, australian national university, act 0200, australia e-mail: barrydh@unimelb.edu.au (barry d. hughes), barry.ninham@anu.edu.au (barry w. ninham) abstract. a single mathematical theme underpins disparate physical phenomena in classical, quantum and statistical mechanical contexts. this mathematical “correspondence principle”, a kind of wave–particle duality with glorious realizations in classical and modern mathematical analysis, embodies fundamental geometrical and physical order, and yet in some sense sits on the edge of chaos. illustrative cases discussed are drawn from classical and anomalous diffusion, quantum mechanics of single particles and ideal gases, quasicrystals and casimir forces. keywords. classical analysis, quantum mechanics, statistical mechanics, random walks and lévy flights, quasicrystals, casimir forces. physics is not just concerning the natures of things, but concerning the interconnectedness of all the natures of things [1] 1. introduction one of the more insightful critics of relatively recent mathematics–from inside the profession–is morris kline, who has made the following observation [2]. “it behooves us to learn why, despite its uncertain foundations and despite the conflicting theories of mathematicians, mathematics has proved so incredibly effective”. the views of wigner [3] and hamming [4] on the “unreasonable effectiveness of mathematics” are perhaps better known, are warmer towards the mathematical profession, and have likely been better received. philosophers of mathematics have perhaps placed undue emphasis on the apparent rightness of mathematics for the formulation of physical theories. the essential point of this article is that there is a single theme–though one which can be recast in many superficially distinct ways–that reappears in a bewildering array of mathematical and physical contexts. its appearance is seldom in the direct formulation of models, but rather arises in the working out of the implications of those formulations. we venture to suggest, though with some diffidence, that this mathematics internal to theories may itself 52 barry d. hughes and barry w. ninham contain some measure of physical insight, and perhaps even of physical reality. some of the ways in which the theme presents itself are collected in table 1. it is particularly striking that the formulae in table 1 vary from highly specific results about particular mathematical functions to results involving arbitrary functions, and include formulae that make sense in relatively elementary calculus, formulae that necessarily involve the theory of functions of a complex variable, and formulae that make no sense in classical real or complex analysis and need to be interpreted in the sense of generalized functions. the mathematical equivalence of the results in table 1 has been addressed twenty years ago in a paper of ninham, hughes, frankel and glasser [5], and the reader may refer to that paper for a fuller account of the mathematical inter-relations and some relevant references that are not repeated here. what we offer here is a more compelling case for centrality of these relations to physics, rather than to mathematics. in the context of physics, the “correspondence principle”, first enunciated by bohr [6], requires quantum mechanics to be consistent with classical mechanics in an appropriate limit, initially in bohr’s case in the limit of large quantum numbers, but now interpreted more broadly [7]. the “complementarity principle”, also due to bohr [8], was enunciated in the context of the problem of measurement in quantum mechanics, and its consequence of most interest in the present paper (loosely expressed as “wave–particle duality”) is the requirement that quantum mechanical systems exhibit both wave and corpuscular characteristics, though never both at the same time. echoes of these principles may be discerned in the discussion that follows. in section 2.1 we discuss various perspectives on the common theme underlying the entries in table 1, which we regard, perhaps controversially, as the deepest “correspondence principle” in mathematical physics. there is an elegance and a tidiness in the formulae of table 1, but these formulae are in some sense at the edge of chaos, as we discuss in section 2.2. moving towards specific physical contexts, we discuss time-evolving classical and quantum processes (section 3), before turning our attention to questions of dilatational symmetry motivated by scattering data from quasicrystals (section 4). the examples in sections 3 and 4 all involve intrinsically linear, non-cooperative phenomena and there is no explicit temperature dependence. in section 5 we consider problems of quantum statistical mechanics, before concluding with perhaps the most elegant and intriguing appearance of our common theme in the context of casimir forces (section 6). a collection of useful formulae for the theta functions is given in appendix a. the variety of contexts from which our examples are drawn have their own popular notations and characteristic terminologies. for the most part we are able to avoid different uses of the same symbol, however force of habit and prevailing idiom oblige us to use τ in two different ways: as a complex number in the upper half-plane for the theory of theta functions and (in section 4 and appendix b) as the golden ratio (1 + √5)/2. for brevity we use the usual notations ℤ, ℕ, ℝ and ℂ for the integers, natural numbers (i.e., the strictly positive integers), real numbers and complex numbers, respectively. all computations were performed with mathematica. 2. the mathematical context 2.1. variations on a theme an infinite sum of periodically spaced delta functions, , corresponding to equally spaced “points” or “atoms” on a line, is one of the simplest conceptualizations of the atomic-scale granularity of real matter. finite segments of such a function, stacked in two and three dimensions form visualizations of elementary crystals and at large scales, where the granularity cannot be resolved, produce apparently smooth structures. by purely formal fourier analysis–though a proper derivation within the theory of generalized functions is available [9]–we shall represent as a (classically divergent) series of classical functions. as is periodic, computing its fourier expansion in the usual manner using (1) yields (2) although eq. (2) is valid only in the sense of generalized functions, it arises very cleanly as an extrapolation from a very classical result. where (3) 53a correspondence principle denotes the third of the jacobi theta functions [10] (see appendix a) in what is now the traditional notation [11], the jacobi theta function transformation (4) is valid for all z ∈ ℂ and for im{τ} > 0. if we divide eq. (4) by 2l and set τ = iε (ε > 0) and z = πx/(2l), we find that (5) for each fixed value of x, every term in the sum converges rapidly to zero as ε → 0, unless we have x = nl, in which case the nth term diverges, but we have showing that the right-hand side converges in an appropriate sense to . we show the series (5) for ε = 1/16, 1/4, 1 and 4 in fig. 1. the elegant identity (5) equates two conceptually distinct viewpoints: a sum of smooth waves and a sum of pulses that may be identified as individual particles [12]. the particle interpretation becomes increasingly more attractive as ε is reduced. the three other jacobi theta functions have analogous transformations that connect classically divergent trigonometric series to periodically spaced delta functions [5]. indeed a more general result can be obtained by writing (6) (so, for example, θ3(z|τ) = θ0,0(z/π |τ)) and noting that the generalization of jacobi’s transformation, (7) leads to (8) the periodic delta function structures associated with the standard jacobi theta functions θ1 θ2, θ3 and table 1. five essentially equivalent results, identifiable as a single theme that is central to a broad range of problems in classical and quantum physics. the correspondence principle or wave–particle duality theta function transformations (many equivalent or related forms) (classical) poisson summation formula riemann relation for the analytic continuation of transformation of euler’s product 54 barry d. hughes and barry w. ninham θ4 are recovered by replacing (a, b) with (1/2, 1/2), (1/2, 0), (0, 0) and (0, 1/2), respectively. some of these choices yield coefficients with alternating plus or minus signs in the string of delta functions, and so can represent microscopically charged but macroscopically neutral matter. the generalized function is sometimes called a (or the) “dirac comb” and its implications on the interpretation of diffraction data from solid crystals have received some attention [13, 14], especially in the context of its invariance (up to dilation and multiplication) under fourier transformation: (9) the generalized function identity (2) is sometimes called the poisson summation formula, a forgivable appropriation of terminology [15] that we shall not adopt. for us the poisson summation formula is [16] (10) this follows immediately from the observation that jacobi’s transformations, which we have seen produce such things as generalized function identity (2), can also be regarded as consequences of eq. (10). for example, by taking f (x) = exp(–πx2ε) in eq. (10), we obtain θ3(0|iε) = ε−1/2θ3(0|iε−1). riemann [17, 18] used this relationship to establish his famous functional relationship (11) where the riemann zeta function ζ(s) and the gamma function γ(s) are defined initially by (12) and (13) and extend by analytic continuation to functions holomorphic except for simple poles at s = 1 and at s = 0, 1, 2, …, respectively [11, 17, 19]. the riemann zeta function is profoundly important in number theory, but surprisingly frequently encountered also in physics [20]. although a rigorous account of those of its properties that are rigorously established requires serious work [11, 19], some results fall out very simply [21]. since inserting the binomial expansion and interchanging orders of summation (the double series is absolutely convergent for re{s} > 1) we find after a little algebra that (14) analy tic continuation of this result, which we obtained initially on the assumption that re{s} > 1, shows immediately that figure 1. the series (5) interpolates between a uniformly flat profile (ε → ∞), a continuous wave (finite ε) and a train of particles (ε → 0). we illustrate this with the cases ε = 1/16 (highest peaks), 1/4, 1 and 4 (nearly flat). −3 −2 −1 0 1 2 3 ε = 1/16 ε = 1/4 x/l 55a correspondence principle and so on, and the riemann relation (11) then yields ζ(2) = π2/6, ζ(4) = π4/90, …, although closed-form elementary evaluations of ζ(3), ζ(5), … have never been found. some of the known simple exact values of the zeta function will be needed in section 6, as will the equation (15) that results from writing t = nx in eq. (13) and summing over n. as noted in the introduction, but worth emphasising again, the five results collected in table 1–four of which we have already discussed, with the fifth (an infinite product transformation)–are essentially a single result [5]. it is possible to obtain all of the results from any one of them, and they establish a link between many substantial fields of mathematics, including complex analysis, number theory, harmonic analysis and numerical analysis [5, 22, 23]. it is the centrality of this common theme to physics that we begin to address in section 3. 2.2. analytical irregularity there is surprising irregularity and complexity lurking behind the five equivalent identities in table 1. we illustrate this first by considering the special case of the theta function θ3(z|τ) with z = 0. if we write for brevity θ(τ) = θ3(0|τ), then θ(τ) is well-defined as a holomorphic (that is, complex-differentiable) function of the complex variable τ in the upper half plane im{τ} > 0. from eqs (3) and (4) we find that (16) both of the transformations τ → τ + 1 and τ → –τ−1 are bijections of the upper half plane (that is, one-to-one correspondences between two copies of the upper half plane). these two fundamental transformations are the generators of a group of transformations of the upper half-plane known as the modular group [24]. modular transformations have the form τ ↦ (aτ + b)/(cτ + d), where a, b, c, d ∈ ℤ and ad − bc = 1. figure 2(a) shows a subset 𝕄 of the upper halfplane known as the fundamental region for the modular group. every point in the upper half-plane is the image of a point in 𝕄 under a modular transformation, but there is no modular transformation connecting any two points of 𝕄. figure 2(b) shows the remarkable way in which successive applications of simple modular transformations carry m into regions of progressively smaller total area, located closer and closer to the real τ axis. it follows that along the line segment defined by τ = σ + iε, with –1 ≤ σ ≤ 1 and 0 < ε ≪ 1, there is enormous variation in θ(σ + iε), as shown in fig. 3. if we write q = eiπτ, the upper half-plane re{τ} > 0 corresponds to the disk |q| < 1 and we have τ = −2 τ = 1τ = 0τ = −1 τ = 2 (a) (b) τ = −1 τ = 1 |τ| = 1e −2πi/3 e +2πi/3 figure 2. (a) the shaded region shows the fundamental set 𝕄 for the modular group. we include only the right half of the boundary, that is, boundary points with 0 ≤ re ≤ {τ} ≤ ½, shown as a dark curve. there are no modular transformations connecting any pair of distinct points in 𝕄. (b) the images of the fundamental set 𝕄 under the modular group tessellate the plane. we have shaded the right half of 𝕄 and all its images, while the left half of 𝕄 and all its images are left white, though their boundaries are drawn in gray. the images of 𝕄 shown here were obtained from those modular transformations with a = 0, b = –1, c = 1 and –2 ≤ d ≤ 2 (corresponding to τ' = τ + d, followed by τ'' = –1/τ'), or these transformations followed by a translation. the region close to the real axis is progressively filled as further transformations of 𝕄 are considered, but it become increasingly hard to portray the images without increasing the magnification of the figure. 56 barry d. hughes and barry w. ninham (17) this is a power series in q, with the unit circle as its circle of convergence, and gaps of rapidly increasing length between powers of q with nonzero coefficients. indeed, for fixed z, all of the theta functions θk(z|τ), k ∈ {1, 2, 3, 4}, have the form (18) where κ ∈ {0, 1/2} and either λn = n2 or λn = n(n + 1), with the series always convergent for |q| < 1 and always divergent for |q| > 1. more generally, if λn is a strictly increasing sequence of non-negative integers, then ∑n anqλn is a power series in the complex variable q. if λn/n → ∞ as n → ∞ the power series is called a “lacunary series”, the name referring to the gaps between powers of q that have nonzero coefficients. a beautiful theorem of fabry [25, 26] states that if ∑n anqλn is a lacunary power series with radius of convergence 1, then the function defined by f (q) = ∑n anqλn for |q| < 1 cannot be continued analytically beyond |q| = 1. as functions of q, the theta functions meet the conditions of fabry’s theorem. analytic continuation across the unit circle |q| = 1 is prevented by the presence of a dense fence of singular points on this circle. figure 3 manifests the existence of this fence. it is interesting that the five equivalent identities in table 1, which involve either smooth functions or periodic functions, are the gateway to revealing dense, nonsmooth behavior. 3. time-evolving classical and quantum processes our point of departure in section 2.1 was already associated with physical concepts, namely periodically spaced point masses or point charges, but no physical models or processes have really been addressed. 3.1. classical diffusion for –∞ < z < ∞ and im{τ} > 0, all four jacobi theta functions satisfy the partial differential equation (19) as indeed does the more general function θa,b(z/π |τ). if we take τ = (4d/π)it with t real, replace z by x, and write u(x, τ) = v(x, t), eq. (19) reduces to the one-dimensional diffusion equation (20) the theta function transformations connect optimally structured short-time and long-time solutions of one-dimensional diffusion problems in finite domains, with one theta function expression corresponding to an expansion of the solution in spatial trigonometric functions with exponentially decaying time-dependent coefficients (a good solution from at long times) and the other corresponding to a “method of images” solution constructed from gaussian propagators (a good solution at short times) [22]. for example, if we write ε = πdt/l2, then eq. (5) equates these two solutions in the case of impenetrable reflecting boundaries (zero flux: –d∂v/∂x = 0) at x = ±l, and initial condition v(x, 0) = δ(x): figure 3. we show the real part (blue curves) and the imaginary part (red curves) of θ3(σ + iε) for –1 ≤ σ ≤ 1: (a) ε = 0.1; (b) ε = 0.01; (c) ε = 0.001. 1 1 10 10 1 1 10 10 1 1 20 10 10 20 (a) (b) (c) 57a correspondence principle (21) 3.2. anomalous diffusion in one dimension and in the absence of boundaries, the mean-square displacement for the diffusion process (20) grows linearly with time [27]: (22) the study of diffusion processes based on eq. (20) was initiated by fick [28] in 1855. much more recently there has been intense interest in transport processes that are not diffusive in character [29, 30, 31, 32]. in onedimensional unbiased non-diffusive processes the meansquare displacement may grow more slowly that linearly with time (sub-diffusive processes), or faster than linearly (super-diffusive processes). an extreme case of onedimensional super-diffusion has an infinite mean-square displacement and this can lead to a statistically self-similar or fractal [33] footprint structure (the set of points visited has a fractal dimension less than 1). hughes, shlesinger and montroll [34] considered a random walk model in which the random displacement made at any step has the probability density function (23) with a > 1 and b > 1. since motions on the length scale ∆bn are a times more abundant than motions on the next shortest length scale ∆bn+1, the stepping law has fractal character built in (with fractal dimension µ = ln(a)/ ln(b)), and the only question is whether fractal footprints are left visible at long times, or the legacy of the walk is smeared. if µ < 2 the mean-square displacement per step is infinite, the central limit theorem fails, and the continuum limit of the process does not have the standard gaussian propagator familiar from classical diffusion [30, 35]. the walk is transient if µ < 1 (any interval is visited only finitely many times with probability 1) and fractal footprints are left. to analyze features of this model, it is necessary to understand the behavior near the origin of the fourier transform of the probability density function (23), and this is equivalent to requiring the small-k behavior of (24) it is easy to see that λ(k) satisfies the rather simplelooking functional equation (25) which is reminiscent of equations obtained in real-space renormalization treatments of lattice spin systems [36, 37]. the apparent simplicity of the functional equation is illusory. hughes et al. [34] were able to show using the poisson summation formula (10) that for k > 0 and ln(a)/ ln(b) ∉ {2, 4, 6, · · · }, (26) where [38] (27) and we have written for brevity sn = –µ + 2nπi/ ln b. the appearance in q(k) of “log–periodic oscillations” (periodic in ln k with period ln b) is striking (see fig. 4). similar oscillations occur in real-space renormalisation group transformations for lattice spin systems [39], in a model for the distribution of family names in a society [40] and in a variety of other systems that exhibit a form of discrete scale invariance [41]. figure 4. the structure function (24) of the weierstrass random walk step probability density function (23). in each case, b = 2, and we choose a values so that so that µ = ln(a)/ ln(b) takes the values 0.5 [blue (most irregular) curve], 1.5 (red curve) and 2.5 (gold curve). 1 2 −0.5 0 0.5 1 μ = 2.5 μ = 1.5 μ = 0.5 k/π λ(k) 58 barry d. hughes and barry w. ninham if b is a positive integer and b ≥ 2 then we can recognize λ(k) as a constant multiple of the real part of the lacunary power series evaluated on its circle of convergence (|z| = 1), so a dense set of singular points must be present and indeed for appropriate values of a and b the series for λ(k) is the celebrated nowhere-differentiable function of weierstrass [42]. there is a second perspective on eq. (23) that is also worth considering [30, 34]. by considering the contour integral of e–zzs−1 around a simple closed contour in the z-plane consisting of the arc of the circle |z| = r within the first quadrant, and straight lines along the real and imaginary axis linking the ends of the arc to the origin, it is easy to prove that for 0 < re{s} < 1, (28) adding this equation and its complex conjugate we find that for 0 < re{s} < 1, (29) the definition of the mellin transform and the associated inversion formula [16], (30) (31) with the bromwich contour re {s} = c placed inside a strip in which the mellin transform integral converges, are another manifestation of the relations collected in table 1, since they can be used to obtain both the riemann relation and the theta function transformation in relatively straightforward ways. using eqs (29) and (31) we can write (32) for k > 0 and 0 < c < 1. inserting this representation into eq. (24), interchanging the order of integration and summation and recognizing a geometric series, we find [30, 34] that (33) translating the contour of integration to the left and taking account of the residues at the poles crossed, we recover eqs (26) and (27). the power series arises from the simple poles along the real axis at s = 0, –2, –4, …, while kµq(k) comes from the line of poles at sn = –µ + 2nπi/ ln b. the small-k behavior, which governs the limiting behavior of the random walk, is dominated by which pole or poles the contour next encounters after we have translated it past the origin. for µ > 2 the next pole encountered is a simple pole at s = –2, so that 1 λ(k) ∝ k2 as k → 0 (ensuring a diffusive limit). however for 0 < µ < 2 we meet the line of poles at s = sn, and this is how the term kµq(k) arises, precluding diffusion. these kinds of calculations using mellin transforms are closely connected to the powerful role of mellin transforms in asymptotic analysis [43] and also give one link between several identities in table 1. whichever approach is used to reveal the small-k behavior of λ(k), the simplest limiting behavior is obtained as ∆ → 0 and t0 → 0 (where t0 is the time between successive steps) if we also make a → 1 and b → 1, while holding both µ = ln a/ ln b and ∆µ/t0 constant. then if µ < 2, the evolution of the random position xt of the moving agent satisfies (34) where c is a positive real constant, q ∈ ℝ, and e denotes mathematical expectation or averaging. the “characteristic function” e{exp(iqxt)} is just a spatial fourier transform of the probability density function for the agent’s location at time t. solving the evolution equation (34) with the initial condition x0 = 0 gives e{exp(iqxt)} = exp(-c|q|µt) and inverting the fourier transform gives the celebrated symmetric stable densites [29, 30] of lévy [44], (35) the borderline case µ = 2 corresponds to the gaussian density, while for µ < 2, the density decays algebraically rather than exponentially, with pr{xt > x} ∝ x–µ as x → ∞. the only other case where the symmetric stable density has a simple closed form expression [45] is µ = 1, which is the cauchy density (c/π)(x2 + c2)–1. super-diffusive processes, such as the stable density, are naturally formulated in unbounded space, but it may be of interest to seek solutions in finite intervals. appropriate boundary conditions for ref lecting boundaries are debatable (for µ < 1 the path is discontinuous), but we can use method of images arguments [cf. eq. (21)] 59a correspondence principle to obtain a solution which conserves probability in the interval (–l, l). the following analysis is very much in the sense of generalised functions, as we work with classically divergent series and use the identity (2): (36) it is perhaps curious that for this system, the relaxation to the uniform density 1/(2l) on the interval is a simple exponential, rather than some form of stretched exponential, despite the transport process being highly super-diffusive. clearly there are many subtleties that can arise when stochastic ideas intersect with self-similarity. for another manifestation of this, see appendix b. 3.3. one quantum particle let h denote planck ’s constant and = h/(2π). if we write τ = –2 t/(πm) with t complex (with a negative imaginary part) and u(z, τ) = ψ(z, t), we obtain from eq. (19) the one-dimensional schrödinger equation in free space, (37) thus linear combinations of theta functions with the complex time extrapolated to the real axis should be able to be used to construct non-trivial time-dependent solutions of schrödinger equation. although we are aware of no systematic study of this, for an investigation of some cognate issues the reader may consult the beautiful paper of fulling and güntürk [46] on the one-dimensional schrödinger equation with periodic boundary conditions. less direct applications of theta functions to solving schrödinger’s equation have been considered by gaveau and schulman [47]. the formal connection between theta functions and schrödinger’s equation (obtained by letting the artificial negative imaginary part of the time approach 0) corresponds to moving radially outwards towards the circle of convergence of a lacunary series, as discussed in section 2.2. the highly irregular form of the propagator discussed by fulling and güntürk should therefore come as no surprise. if we don’t observe the connection to theta functions, and instead use an energy eigenfunction approach to solve the d-dimensiona l schrödinger equation in the box (0, l)d (with the wave function vanishing on the boundary) we obtain the general solution (38) where n = (n1, n2, … , nd) and (39) if we take the initial condition ψ(x, t') = δ(x – x') with x' ∈ (0, l)d , we obtain the (never classically convergent) generalized function propagator × (40) perhaps the connection to theta functions makes the strangeness of this result easier to comprehend. despite the irregular propagator for finite intervals, the free-space schrödinger equation does have some comparatively simple, well-behaved normalizable solutions on the real line, such as the spreading gaussian wave packet found by darwin [48] and kennard [49] and the airy function solution of lekner [50]. 4. quasicrystals diffraction experiments probe the structure of condensed matter using electrons, neutrons or x rays. in systems with longrange order, this order is revealed by observed intensity distributions exhibiting sharp peaks [51, 52]. experimental realities and the finiteness 60 barry d. hughes and barry w. ninham of the atoms scattering the incident radiation broaden the peaks, but basically in an idealized but substantially correct way, the observed density in many cases is a set of delta functions, whose locations encode information about the atomic locations, which are also delta functions. this picture is clearest and most apt for crystals, where the diffraction data corresponds to the fourier transform of the crystal [53]. for the one-dimensional case with equal spacing between atoms, eq. (9) shows that the fourier transform is simply the original lattice structure with a changed lattice spacing (the fourier transform of the dirac comb is a dirac comb). similar results hold in two and three dimensions [54]. the discovery in 1984 by shechtman et al. [55] of a metallic phase with long-range orientational order but no translational symmetry challenged established paradigms in crystallography, which assume that crystals consist of unit cells of atoms of various species arranged periodically. within six weeks, levine and steinhardt [56] had dubbed these structures “quasicrystals”–a name the structures have retained [57]–and suggested analogies to nonperiodic tilings of space with local pentagonal symmetry previously studied by penrose [58]. shechtman received the 2011 nobel prize in chemistry for the discovery of quasicrystals. the appearance in a physical context of long-range order without translational symmetry naturally motivated a number of fundamental studies of a purely mathematical character, including a careful definition of diffraction on aperiodic structures [59]. many important observations concerning cognate mathematical issues can be found in senechal [60, 61], senechal and taylor [62, 63] and baake and grimm [64]. when translational invariance breaks down in the observed crystallographic data, the unambiguous connection to the original lattice is lost. how is the structure of a quasicrystal to be inferred? to begin, the attempt to fit the diffraction data (k) to delta functions with a non-zero minimal spacing and recover wellspaced delta functions for ρ(r) is doomed to failure [65]. ninham and lidin [66] suggested the possible relevance to quasicrystals of dilatational rather than translational symmetry, using the following example, which has interesting historical antecedents. the gnomon (γνὡµων) is the shadow-casting blade on a sundial, but also refers to triangles or rectangles produced by internal subdivision of triangles or rectangles in a special way. in particular, if an isosceles triangle with two sides of length τ > 1 and third side of length 1 is subdivided by drawing a straight line from one of the equal angles to the opposite face to create an isosceles triangle with two sides of length 1, the other triangle created in this subdivision is the gnomon. a simple argument based on similar triangles establishes that the gnomon is itself an isosceles triangle if and only if τ2 – τ – 1 = 0, (41) from which it follows that τ = (1 + √5)/2 ≈ 1.618 (42) (see fig. 5(a), in which the gnomon is shaded in gray). for this special choice of τ, the internal angles of the triangles produced in the subdivision are all integer multiples of π/5, as shown. in fig. 5(b) we take the scaled replica of the original triangle produced by the subdivision, subdivide it in a similar manner, and repeat this process several times, always producing isosceles triangles with the same angles, but with the lengths of sides diminishing by a factor of τ at each stage. the number τ is the famous golden mean, golden ratio or golden number, which figures prominently in aesthetics [67] and in nature [68]. the logarithmic spirals (43) are shown as grey curves in fig. 5(c). their intersections generate a distribution of points with five-fold rotational symmetry about the origin. the logarithmic spiral ln r/ ln τ = θ/(3π/5) passes through these points of intersection, with the distance from the origin increasing by a factor of τ between any two consecutive intersections. with suitable scaling and rotation, the inscribed triangles shown in fig. 5(b) can be placed with their vertices located at the intersection points [66, 69]. we consider the fourier-space signature of the mass distribution × (44) which places all mass on rays through the origin, with angular separation π/5 between rays, and on each ray, we have dilational invariance in the locations of the masses, with a scaling factor τ. the convergence factor a–|m| (with a > 1) is present to keep finite total mass in the system. we find that where k = (k1, k2), 61a correspondence principle (45) we show |ρ(k)| for a = 1.1 in fig. 6. it is not surprising that the rotational symmetry in the mass distribution is reflected in the fourier transform domain: this is clear from eq. (45). what is more interesting, and more beautiful, is that in the fourier transform domain, where the signal is continuous (rather than localized on lines, as in the original space domain), we see a rich structure with local intensity maxima occurring at many points in the sectors between the ten lines on which the brightest peaks are located. also, it is by no means obvious from the formula (45) where the intensity maxima on the bright lines will occur. in fig. 7, we show |ρ(k)| on the vertical axis in the k-plane. there are many local maxima, but a sequence of locally outstanding maxima can be identified at the k2 values 4.775, 7.732, 12.51, 20.25, 32.77. the successive ratios of these k2 values are all close to (but not exactly) 1.618, and we see the golden ratio from physical space recurring (to a decent approximation) in intensity maxima in fourier space. the convergence factor a|m| in eq. (45) stops | (k)| from having exact dilatational symmetry. if we were able to set a = 1, then we would recover | (k)| = | (τk)|. berry and lewis [70] have considered what they call the weierstrass–mandelbrot fractal function (46) where ϕn represents a constant phase added onto each term. the series is convergent and, if ϕn is constant, has perfect self-similarity: w(γt) = γ2−dw(t). ninham and lidin [66] have considered another way of overcoming the problem of infinite mass accumulating in the neighborhood of the origin by using the formal series figure 5. (a) with τ given by eq. (42), an isosceles triangle with side lengths ratios τ : τ : 1, can be subdivided into two isosceles triangles, one of which (white interior) has side length ratios τ : τ : 1 but side lengths a factor τ smaller than those in the original triangle. (b) we can continue the process of subdivision to generate a nested set of isosceles triangles with side length ratios τ : τ : 1, but at each step of the process, the side length of the triangle just produced is reduced from that of its parent by a factor of τ. (c) the intersections of the logarithmic spirals (43) generate a distribution of points with five-fold rotational symmetry about the origin. the logarithmic spiral ln r/ ln τ = θ/(3π/5), shown in red, passes through these points of intersection, with the distance from the origin increasing by a factor of τ between any two consecutive intersections. with suitable scaling and rotation, the inscribed triangles shown in diagram (b) can be placed with their vertices located at the intersection points (figure adapted from ninham and lidin [66]). (b) (a) τ π/5π/5 π/5 2π/5 1 1 1/τ τ − 1/τ = 1 (c) 62 barry d. hughes and barry w. ninham for the mass distribution along a ray through the origin, where r is the distance from the origin. quasicrystals are not the only context in which wild oscillations and apparent self-similar structure arise in the amplitude of diffracted light. berry [71] gives a beautiful example, in which theta functions play a key role. 5. quantum statistical mechanics we consider several models from quantum statistical mechanics, for which we use standard notation and terminology [72, 73], so that k is boltzmann’s constant and t is the absolute temperature. 5.1. the harmonic oscillator the free energy g(ω) associated with a harmonic oscillator of frequency ω and energy levels (n + 1/2) ω (n = 0, 1, 2, …) is given in terms of the canonical partition function (ω) by (47) (48) for brevity, we have suppressed in the notation the dependence of the free energy on the temperature. hence (49) figure 7. we show | (k)| on the line k = (0, k2), where the fourier transform (k), given by eq. (45) arises from the mass distribution (44). for the convergence factor a–|m| we have taken a = 1.1. 10 5 0 −5 −10 4 2 0 −2 −4 1050−5−10 420−2−4 (a) (b) figure 6. the k-plane is colored (with 20 levels) to show | (k)|, where the fourier transform (k), given by eq. (45), arises from the mass distribution (44). lighter shades represent larger values of | (k)|. (a) –10 ≤ k1, k2 ≤ 10; (b) –4 ≤ k1, k2 ≤ 4. for the convergence factor a|m| we have taken a = 1.1. 10 20 30 40 20 40 60 80 k 2 |ρ(k)| 63a correspondence principle leading to the formal identification [74] (50) this superficially bizarre result connecting the oscillator free energy to a string of delta functions, arising from the mathematical correspondence principle, proves surprisingly useful. if the modes of oscillation of a system are given by a secular equation of the form d(ω) = 0, then the free energy can be computed as a sum over the contributions from the various modes by the contour integral (51) the contour integral being taken over a simple closed contour that surrounds all zeros of d(ω) on the positive real axis. if there are infinitely many such zeros with the spacing bounded below as ω → ∞, an appropriate limiting construction is made. integrating by parts, deforming the contour and making formal use of eq. (50) enables the free energy to be computed conveniently [74, 75]. this is especially convenient in the calculation of dispersion (van der waals) forces between dielectric media [74, 75]. 5.2. particle in a box using the energy eigenvalues (39), the free energy associated with a single (non-elementary [76]) particle of mass m in the d-dimensional box [0, l]d is given by (52) here we adopt the usual notational convenience of writing θk(z|τ) = θk(z, q), where q = eiπτ. if we consider n identical non-interacting particles in the same box, eq. (52) becomes the equation for the free energy per particle. fixing t, the right-hand side can be evaluated asymptotically in the limit l → ∞, using the jacobi theta function transformation (4), which in the special case z = 0 and τ = it (t ∈ ℝ, with t > 0) becomes θ3(0, it) = t–1/2θ3(0|it–1). we find that (53) (54) where for brevity in notation we have introduced the thermal wavelength λt = h(2πmkt)–1/2. the single-term approximation (54) is well known [73], but the theta function representations (52) and (53) enable us to compute and the associated thermodynamic observables to high precision for any value of l/λt. 5.3. ideal gas of elementary particles consider now ideal gases of elementary particles, which may be bosons (such as photons or mesons, for which an arbitrary number of particles can occupy any state) or fermions (such as electrons or neutrinos, for which any state may be occupied by at most one particle). it is more convenient to work with the grand partition function = πn n, where n is the canonical partition function for occupancy of the nth state, in which each particle present has energy εn and chemical potential µ. thus we have (bosons); (fermions). if we define the fugacity as usual by z = exp[µ/(kt)] we obtain [77] (bosons); (fermions). consider the case of fugacity z = 1. if zero point energy is neglected and we write εn = n ω as in blackbody radiation, then on writing x = exp[– ω/(kt)] we find [5] that 64 barry d. hughes and barry w. ninham (55) where euler’s product φ(x) = , intimately related to the jacobi theta functions, is discussed in appendix a and has the transformation formula (56) which is one of the mathematical correspondence principle relations from table 1. the original expressions for the grand partition function are able to be used for computation for high temperatures, but are useless at low temperatures. however, eq. (56) gives immediate access to low temperature expansions, since we can eliminate φ(exp[– ω/(kt)]) in favor of φ(exp[-4π2kt/( ω)]). planat [78] has pursued the implications of the relation between euler’s product and the theory of partitions [79] in the context of the massless bose gas. if we retain the zero point energy and consider a general value of the fugacity, we can represent the grand partition functions in terms of the q-pochhammer function [80] (57) building on the work of rogers and ramanujan [81], there is now an impressive corpus of transformations and identities related to theta functions and q-pochhammer functions, and they arise frequently in mathematical physics [82]. 6. casimir forces the famous prediction of casimir [83, 84] that the zero temperature energy of interaction of two perfectly conducting plates a distance apart in vacuum provides an attractive force per unit area π2 c/(240 4) between the plates was a landmark result. direct experimental verification was challenging, with sparnaay [85] in 1958 finding that “the attractive interactions do not contradict casimir’s theoretical prediction” (the experiments had problematically large uncertainty). finally, in 1997, lamoreaux [86] effectively settled the basic issue [87]: “we have given an unambiguous demonstration of the casimir force with accuracy of order 5%. our data is not of sufficient accuracy to demonstrate the finite temperature correction …”. (casimir’s original discussion did not address either finite temperature nor limitations on conductivity.) crudely described, the casimir effect demonstrates the consequences of geometrically constraining free oscillations of a system (here, the electromagnetic field) compared to the unconstrained state. entirely classical analogues of the casimir effect in macroscopic physics have been identified in a maritime context [88], and in an acoustic system suitable for lecture demonstrations [89]. the literature related to the casimir effect is already voluminous and connections of papers with apparently cognate keywords to physics can be highly tenuous. at one extreme end of the literature [90, 91], since the evaluations of ζ(–1) and ζ(–3) are needed in the discussion of the physical casimir effect (depending on the geometry), the evaluation for s = –1 of the analytic continuation of a series of the form z(s) = ∑λλ–s, where λ runs through a set of values with an interpretation related to energy levels, has been called the “casimir energy”. the sign of z(–1) “reflects certain dynamical and arithmetical properties” [91] and formulae related to the so-called casimir energy can be obtained for compact riemann surfaces of genus g ≥ 2. of greater physical interest is the embedding of the original casimir effect in a broader context that admits predictions of interactions between more general classes of matter than perfect conductors at zero temperature [75, 92]. profoundly important papers by lifshitz [93, 94, 95] and his subsequent work with dzyaloshinskii and pitaevskii [96, 97], also appearing in a later textbook [98], replaced perfect conductors in vacuum by dielectric materials separated by an intervening dielectric material. by permitting the dielectrics to have a frequencydependent dielectric susceptibility, a wide variety of physical (and even biological) systems could be discussed, and subsequent work of ninham and parsegian [99, 100] showed how the required dielectric properties could be determined from spectroscopic data, leading to the ability to make quantitative predictions in experimentally accessible systems. the original casimir problem arises as an extreme limit of the lifshitz theory approach, and lifshitz theory permits the computation of temperature-dependent effects [74, 75, 101]. experimental validation of the predictions of lifshitz theory has been obtained in many cases [102]. we focus on the original casimir problem–plates separated by vacuum–because it exhibits most simply 65a correspondence principle the importance of the mathematical correspondence principle. let f( , t ) denote the free energy of interaction per unit area between two infinite parallel conducting plates separated by a distance , in vacuum, at finite temperature t. it is instructive to see how extensive use of results of classical analysis such as the riemann relation for the zeta function and various properties of the gamma function enable the free energy to be expressed in a highly informative way that enables dangerous issues concerning non-uniformity of asymptotic expansions to be dealt with [103]. where we have already set the dielectric constant of the region between the plates to be unity, then from lifshitz theory [75] we have (58) where the prime on the sum indicates that the n = 0 term is to be weighted with a factor of 1/2, the parameter ξn is defined by (59) and (60) to avoid an indeterminacy [104] in the case n = 0, we evaluate i(ξn, ) for small positive real n by use of the change of variables y = 2pξn /c and then take the limit n → 0. the riemann zeta function first arises from the n = 0 contribution from the s = 3 case of the integral (15). for convenience in the asymptotic analysis we write (61) the coupling between the temperature t and the plate spacing is very important. the limit x → 0 corresponds to the low-temperature limit, provided that the plate separation is constrained, or to the small-spacing limit, provided that the temperature is not too high. the analysis of ninham and daicic [103] to this point has (62) to evaluate the sum over n we may begin by expanding the logarithm using the series since eq. (13) shows that the gamma function is the mellin transform [43] of the decaying exponential, using the mellin inversion theorem [eqs (30) and (31)] we have the contour integral representation with the positive constant κ that places the vertical bromwich contour re(s) = κ selected to secure convergence in the subsequent analysis based on this integral (κ > 3 suffices). we now have so we can eliminate the logarithm factor from the integrand in eq. (62), evaluate the resulting elementary integral over p and recognize the sums over m and n as series for the riemann zeta function [eq. (12)]. in this way one arrives at the scaled free energy (63) (64) the integrand has only four singularities, namely the simple poles at s = –1, 0, 2 and 3. to see this, we note that the gamma function has simple poles of residue (–1)j/j! at s = –j(j = 0, 1, 2, 3, …), while ζ(s – 2)ζ(s + 1) has a simple pole at s = 3 and simple zeros at s = –2, –3, –4, … (noting that ζ(z) has a simple pole at z = 1 and simple zeros at z = –2, -4, –6, …). the bromwich contour may be translated an arbitrary finite distance, provided that we account correctly for the residues at poles across which the contour is dragged. if we move the contour to re(s) = 1, then the term that must be added to account for the pole at s = 2 is easily shown to cancel with the first term on the right in eq. (64). the pole at s = 3 leads to a term proportional to 1/x2, whose coefficient can be evaluated by recalling that ζ(0) = –1/2 and ζ(4) = π4/90. we find that 66 barry d. hughes and barry w. ninham (65) since ζ(s – 2) = –2s−2πs−3sin(πs/2)γ(3 – s)ζ(3 – s) from the riemann relation (11) and (66) we deduce that (67) where the first term on the right corresponds to the casimir formula, while (68) the change of variables s = 1 + it produces (69) since ln(x) = −ln(1/x), eq. (69) reveals the remarkable inversion symmetry j(x) = j(x–1). (70) the casimir term is temperature-independent when one returns to the original variables, but the function j(x) encapsulates genuine temperature dependence. the riemann relation, one avatar of our central theme summarized in table 1, has been used to expose the inversion symmetry (a previously observed result [107, 108]), but is also crucial for an efficient extraction of the x dependence. it may be noted in passing that a computer algebra software (such as mathematica) is very helpful in checking that the intricate manipulations involved are correct, but is presently (and in the foreseeable future may well continue to be) unable to offer much help in guiding the analysis. we digress for a moment. the function ζ(2 + it)ζ(2 –it) in the integrand in eq. (69) is easily shown to be realvalued, but is by no means simple in structure: see fig. 8. in qualitative terms, it appears roughly periodic, but the amplitudes of successive peaks and troughs and their spacing vary in an apparently random manner. more generally, for real σ and t, we have ζ(σ + it)ζ(σ – it) = |ζ(σ + it)|2. (71) and the strange behavior of |ζ(2 + it)|2 revealed in fig. 8 arises also for other values of σ. when studying the response to changes in σ it is helpful to consider |ζ(σ + it)| rather than |ζ(σ + it)|2 to reduce the height of the maxima. we plot |ζ(σ + it)| in fig. 9 for σ = 2, σ = 1 and σ = 0.5. it may be observed that the spacing of the peaks and troughs hardly changes, but the peak heights grow and the trough heights fall as σ decreases. it is relatively easy to prove that ζ(σ + it) is nonzero whenever σ > 1. that ζ(σ + it) is also never 0 for σ = 1 is much more difficult to prove. establishing this was an essential ingredient of the proofs in 1896 by hadamard [105] and de la vallée 20 40 60 80 100 0.5 1.0 1.5 2.0 2.5 t ζ(2+it)ζ(2−it) 10 20 30 40 50 60 70 80 90 100 1 2 3 4 5 σ = 0.5 σ = 1 σ = 2 t |ζ| figure 8. the function ζ(2 + it)ζ(2 – it) in the integrand in eq. (69): 0 < ζ(2 + it)ζ(2 – it) ≤ ζ(2)2 = π4/36 ≈ 2.7 for all t ∈ ℝ. figure 9. |ζ(σ + it)| = for σ ∈ {1/2, 1, 2}, 0 < t < 100. 67a correspondence principle poussin [106] that the number of prime numbers less than or equal to n has the asymptotic form n/ln n as n → ∞. in the context of our discussion, the still-unresolved riemann hypothesis [17, 19], asserts that ζ(σ + it) ≠ 0 for σ > 1/2. it is strangely beautiful that the mathematics of the casimir effect comes so close to such subtle matters. returning to matters more overtly connected to physics, if fcasimir denotes the original single-term casimir energy prediction for the energy per unit area, we have (72) in assessing the accuracy of the casimir term, the role of the composite parameter x is crucial. we note that with measured in metres and t in kelvin, we have (73) in principle the numerical evaluation of the integral (69) requires some care because of the rapid oscillation of the cosine factor when x ≫ 1 or 0 < x ≪ 1 and the erratic behavior of the real-valued function ζ(2 + it)ζ(2 – it) (see fig. 8). however, the riemann–lebesgue lemma ensures that j(x) → 0 as x → 0 or as x → ∞ and for the region where j(x) differs perceptibly from zero, mathematica is up to the task. we show j(x) for 10–2 ≤ x ≤ 102 in fig. 10. the fractional error η in the one-term casimir formula, defined in eq. (72), exceeds 1 for x > 1.14 but is less than 5 × 10–5 for x ≤ 0.03. in applications of the casimir formula to experimental situations, relative errors associated with finite conductivity, departure of the real geometry from infinite parallel plates and other practical realities may dominate over the errors arising from the finiteness of the temperature that we have quantified through η(x). having acknowledged that caveat, we note that the case x ≈ 0.5 arises for atomic dimensions ( ≈ 10-10m) when t ≈ 6 × 106 k, within the range of estimated temperatures for the sun (≈ 4 × 103k at the surface, 1.6 × 107k at the center [109]). the analytic structures that have been revealed with the techniques illustrated above have a number of interesting consequences for the casimir problem in vacuum and for analogous problems involving dielectric or conducting films. some of these, including connections with nuclear and particle physics, have been explored elsewhere [110, 111]. the point to be made is that viewing physical problems from a mathematical perspective in the spirit of table 1 leads both to efficient practical analysis and to new insights, though deep and subtle mathematical exotica are seldom far away. 7. conclusions we opened this paper with a reference to the conundrum of the surprising effectiveness of mathematics in physics. berry has proposed one possible explanation [112]. we are beings of finite intelligence in an infinite inscrutable universe. in science, our individual intelligences cooperate, and we can understand more. but still, we are able to comprehend only those structures in the natural world that mirror our mental constructs. and at any stage of humanity’s development, the most sophisticated constructs are those of our mathematics. therefore our deepest penetration into the natural world is limited by our latest mathematics. as mathematics develops, more subtle features of –2 –1 1 2 – 0.04 – 0.03 – 0.02 – 0.01 log (x) 10 j(x) 0.2 0.4 0.6 0.8 1.0 0.2 0.4 0.6 0.8 1.0 x η(x) figure 10. the function j(x) computed from the integral (69) by numerical integration. figure 11. the fractional error η(x) in the single-term casimir formula, defined by eq. (72), inferred from the numerically evaluated integral (69). 68 barry d. hughes and barry w. ninham the universe become accessible to our understanding… so, ‘the unreasonable effectiveness of mathematics in the natural sciences’ is not unreasonable at all; on the contrary, it is inevitable. this is not the only possible explanation, and in some areas, there are credible alternatives. we have shown that what is essentially one grand mathematical idea, which comes expressed in various ways, such as those collected in table 1, underlies a wide range of apparently disparate physical phenomena. if one is a mathematical platonist–that is, a believer in the existence of abstract mathematical objects that are independent of intelligent agents and their language, thought and practices [113]–it is perhaps not such a leap of faith to conceive of a profound connection between some of these mathematical objects and physical reality. amongst a charming collection of pithy quotes and witticisms relevant to science collected by berry [114] one finds what he calls “three laws of discovery”. 1. discoveries are rarely attributed to the correct person [115]. 2. nothing is ever discovered for the first time [116]. 3. everything of importance has been said before by someone who did not discover it [117]. the existence of a common underlying mathematical theme in many contexts may be an explanation for the applicability of berry’s laws in the sociology of physics. most physicists will wisely choose to limit their pondering of metaphysical questions to the bar or coffee shop, but the contemplation of what may be the most natural mathematical framework for physical theory and the pursuit of the implications of the mathematics is a more defensible use of one’s office hours. while physical intuition and accumulated conventional wisdom are always worthy of respect, careful analyses with appropriate mathematical insight can yield surprising results. recently, lekner [118] has shown that at small separations, charged conducting spheres always attract each other, even when the charges on the spheres are of the same sign, except when the spheres have charges in the ratio that would make them an equipotential surface on contact. this refutation of the rule that “like charges repel” in classical physics is indeed striking. in quantum mechanics, where physical intuition is a more contentious matter (and in the view of many, not even appropriate), accumulated conventional wisdom has still developed, but as noted recently by ball [119] it is by no means a settled matter that we have either the optimal perspective on the subject or the optimal formulation. what is the appropriate mathematical training for the modern physicist may be hotly debated, but what we have styled a correspondence principle (embodied in table 1) and the associated treasures of classical real and complex analysis have legitimate claim for inclusion. acknowledgments we are grateful to the referees for helpful comments, and for bringing several important references to our attention. appendix a. jacobi theta functions where im{τ} > 0 to secure convergence in the sense of classical analysis and q = eiπτ (so that |q| < 1), the four jacobi theta functions θk(z|τ) = θk(z, q) are 69a correspondence principle here and euler’s product φ(x) = (1 – xn) has the remarkable property [5] that where 0 < arg(τ) < π, the jacobi transformation formulae are we observe that in a formal sense, if not within classical analysis (with the limits taken under the restrictions that |q| < 1 or re{τ} > 0, respectively) that appendix b. diffusion with increasing lethargy there is another interesting model for a kind of anomalous diffusion that raises mathematical questions that are at least as subtle as those discussed in section 3.2 and partly related to them [120]. consider a random walk in one dimension, for which steps to the left and right are equally likely at each stage, but the length of the nth step is cn, where cn > 0 and . the walker exhibits increasing lethargy, and asymptotically comes to rest at a random position x relative to the starting location, where x = , the random variables {εn} are independent, and pr{εn = 1} = pr{εn = –1} = 1/2. in the probability literature, the random variable x is described as an “infinite bernoulli convolution” and it can be proved [121] that provided that < ∞, the characteristic function (fourier transform) associated with the distribution of this random variable exists, and is given by e{exp(iqx)} = . the case cn = αn−1, where 0 < α < 1, for which e{exp(iqx)} = , is especially fascinating [122, 123, 124, 125]. this model builds in self-similarity in a way reminiscent of, but different to, section 3.2. we have x = ε1 + αx1, where x and x1 are identically distributed random variables, while ε1 and x1 are independent. since = (1 – α)−1, we know that –(1 – α)−1 ≤ x ≤ (1 – α)−1. for the case α = 1/2, it can be proved [127] that x is uniformly distributed on [–2, 2], but for many other values of α ∈ (0, 1) the distribution of x does not apportion the probability so smoothly. in general [126], the cumulative distribution function f(x) = pr{x ≤ x} of a real random variable x consists of either a single one, or a linear combination of both, of the following components: (i) an “absolutely continuous” component, corresponding to classical probability density function; (ii) a “singular” component, in which the probability all resides on a set of measure zero. for the increasingly lethargic walk with 0 < α < 1/2, x has a singular distribution: the nonzero probability all resides on a cantor set of measure zero [123]. the rapid attenuation of the step lengths prevents the walker from exploring the apparent support decently. for 1/2 < α < 1, it has been proved [122] that the distribution of x for any given value of α is either entirely absolutely continuous or entirely singular. the simplicity of the case α = 1/2 might suggest that absolute continuity always prevails for 1/2 < α < 1, and it has been proven that the set of values of α ∈ (1/2, 1) for which the distribution is singular has measure zero [128], but a countable number of values of α ∈ (1/2, 1) for which the distribution is singular were found by erdös [124] and the search for other anomalous α values continues. diffusion with accumulating lethargy also has interesting connections to the discussion of section 4, where the golden ratio τ = (1 + √5)/2 plays a significant role. hu [129] has shown that for α = 1/τ = (√5 − 1)/2 and for −(1 − α)−1 < x < (1 − α)−1, the local fractal dimension d(x) = limr→0+ + log[pr{x – r ≤ x ≤ x + r}]/ log(r) of the distribution of the random variable has maximum value log(2)/log(τ) ≈ 1.4404 and minimum value log(2)/log(τ) – 1/2 ≈ 0.9404. for additional related results see lau and ngai [130]. 70 barry d. hughes and barry w. ninham references [1] the quotation is from the retirement speech given by sir charles frank (1911–1998) at the university of bristol in 1976, as recorded by m.v. berry, “bristol anholonomy calendar”, in sir charles frank obe frs, an eightieth birthday tribute, edited by r.g. chambers, j.e. enderby, a. keller, a.r. lang, and j.w. steeds (adam hilger, bristol, 1991), pp. 207-219. [2] m. kline, mathematics: the loss of certainty (oxford university press, new york, 1980). [3] e.p. wigner, “the unreasonable effectiveness of mathematics in the natural sciences”, richard courant lecture in mathematical sciences delivered at new york university, may 11, 1959, communications on pure and applied mathematics 13(1), 1–14 (1960). [4] r.w. hamming, “the unreasonable effectiveness of mathematics,” american mathematical monthly 87(2) 81–90 (1980). [5] b.w. ninham, b.d. hughes, n.e. frankel, and m.l. glasser, “möbius, mellin, and mathematical physics,” physica a 186, 441–481 (1992). [6] n. bohr, “über die serienspektra der element,” zeitschrift für physik 2 423–478 (1920). english translation in l. rosenfeld and j. rud nielsen (editors), niels bohr, collected works, volume 3, the correspondence principle (1918–1923), pp. 241–282 (north-holland, amsterdam, 1976). [7] w.h. cropper, the quantum physicists (oxford university press, new york, 1970) notes that ‘although the correspondence principle became increasingly elaborate in later work, it was always based on one simple concept: that when the scale is suitably adjusted, classical physics and quantum physics must merge.’ [8] n. bohr, “the quantum postulate and the recent development of atomic theory,” nature 121, 580– 590 (1928). bohr writes (p. 580) ‘… if in order to make observation possible we permit certain interactions with suitable agencies of measurement, not belonging to the system, an unambiguous description of the state of the system is no longer possible, and there can be no sense of causality in the ordinary sense of the word. the very nature of the quantum theory thus forces us to regard the spacetime coordination and the claim of causality, the union of which characterises the classical theories, as complementary but exclusive features of the description…’. see also n. bohr, “discussions with einstein on epistemological problems in atomic physics,” in p. schilpp (editor), albert einstein: philosopher-scientist (open court, chicago, 1949). [9] m.j. lighthill, introduction to fourier analysis and generalised functions (cambridge university press, cambridge, u.k., 1958). [10] c.g.j. jacobi, “theorie der elliptischen functionen aus den eigenschaften der thetareihen abgeleitet”, in gesammelte werke, band 1, pp. 497–538 (reimer, berlin, 1881; reprinted chelsea, new york, 1969). [11] e.t. whittaker and g.n. watson, a course of modern analysis, 4th edition (cambridge university press, cambridge, u.k.,1927). [12] the wave-particle duality aspect of our central theme can be embedded in a somewhat broader context that we only touch on here. (the authors are grateful to one of the referees for suggesting that we address this, and referring us to relevant literature). poisson’s summation formula, in both the guises (2) and (10), relates spectral information (eigenvalues) to a discrete geometry (a regular lattice). this hints at a class of relations between spectral sums and geometrical or topological sums. perhaps the simplest manifestation of this is the relation between the ray and mode descriptions of waveguides, which represent complementary perspectives: see c.l. pekeris, “ray theory vs normal mode theory in wave propagation problems”, proceedings of symposia in applied mathematics 2, 71–75 (1950). however, there are many examples, such as: (i) scattering from spheres, with spectral sums over angular momentum vs rays winding different numbers of times round the scattering center (m.v. berry and k.e. mount, “semiclassical approximations in wave mechanics”, reports on progress in physics 35, 315–397 (1972)); (ii) electron diffraction in crystals, with spectral sums over bloch waves vs classical trajectories winding through the lattice (m.v. berry, “diffraction in crystals at high energies”, journal of physics c 4, 697–722 (1971)); and (iii) complementary approximate solution methods for the energy eigenvalue problem of quantum mechanics when separation of variables is not available (m.c. gutzwiller, “periodic orbits and classical quantization conditions”, journal of mathematical physics.12, 343–358 (1971)). [13] a. córdoba, “la formule sommatoire de poisson,” comptes rendus de l’académie des sciences. série 1, mathématique 306 (no 8) 373–376 (1988). [14] a. córdoba, “dirac combs”, letters in mathematical physics 17, 191–196 (1989). 71a correspondence principle [15] see p.l. butzer, p.j.s.g. ferreira, g. schmeisser and r.l. stens, “the summation formulae of euler–maclaurin, abel–plana, poisson, and their interconnections with the approximate sampling formula of signal analysis,” results in mathematics 59, 359–400 (2012). these authors note that eq. (10) was first produced by gauss. the results such as (4) are usually called jacobi’s transformation after their appearance in several of jacobi’s works [c.g.j. jacobi, “suite des notices sur les fonctions elliptiques,” journal für die reine und angewandte mathematik (crelle’s journal) 3, 403–404 (1828); c.g.j. jacobi, “über die differentialgleichung, welcher die reihen 1 ± 2q ± 2q4 ± 2q9+ etc., + etc. genüge leisten,” journal für die reine und angewandte mathematik (crelle’s journal) 36, 97–112 (1848). however if gauss did not produce them earlier, they are certainly present in work of poisson, which jacobi has acknowledged [s.d. poisson, “suite du mémoire sur les intégrales définies et sur la sommation des séries, inséré dans les précédens volumes de ce journal”, journal de l’école royale polytechnique 12 (19), 404–509 (1823)]. [16] e.c. titchmarsh, introduction to the theory of fourier integrals, 2nd edition, (oxford university press, oxford, u.k., 1948; reprinted chelsea, new york, 1986). [17] b. riemann, “ueber die anzahl der primzahlen unter einer gegebenen grösse,” monatsberichte der königliche preußische akademie der wissenschaften zu berlin aus der jahre 1859, 671–680 (1860). [18] riemann shows that where ψ(x) = and re{s} > 1, we have ζ(s)π−s/2γ(s/2) = xs/2−1ψ(x)dx. he uses the transformation formula for θ3(0|ix) to construct an analytic continuation for ζ(s) π−s/2γ(s/2) that is symmetric under replacement of s by 1 – s, and the riemann relation follows. [19] e.c. titchmarsh, the theory of the riemann zetafunction, 2nd edition, revised by d.r. heathbrown (oxford university press, oxford, u.k., 1986). [20] d. schumayer and d.a.w. hutchinson, “physics of the riemann hypothesis”, reviews of modern physics 83, 307–330 (2011). [21] a shorter formal argument based on a binomial expansion of (n + a)−s with a ∈ (0, 1) and subsequent use of the limit a → 1 yields the formal expression [5] from which the same conclusions about simple known values of ζ(–m) for m a non-negative integer be drawn. the method given in the present paper is classically rigorous. for an alternative rigorous approach, leading to the identity see §68 of e. landau, handbuch der lehre von der verteilung der primzahlen (1st edition, leipzig and berlin, teubner, 1909; 3rd edition, providence, rhode island, ams chelsea, 1974). [22] r. bellman, a brief introduction to theta functions (holt, rinehart and winston, new york, 1961). [23] although we have produced eq. (2) from eq. (1), the process is quite reversible. they are essentially equivalent results. j.n. lyness and b.w. ninham [“numerical quadrature and asymptotic expansions”, mathematics of computation 21, 162–178 (1967)] have shown how eq. (1) can be used to deduce a very broad class of quadrature rules for numerical integration on finite intervals, with useful asymptotic expansions for the quadrature error. further developments of this approach lead to practical techniques for computing analytic continuations of functions defined by parametrized integrals, by direct computation of the integrals even for parameter ranges where the integral diverges. see b.w. ninham, “generalised functions and divergent integrals”, numerische mathematik 8, 444–457 (1966). [24] for properties of the modular group and proofs of results discussed in section 2.2 see the following texts: w. magnus, noneuclidean tesselations and their groups (academic press, new york, 1974); j.p. serre, a course in arithmetic (springer-verlag, new york, 1973); and b. schoeneberg, elliptic modular functions (springer-verlag, berlin, 1974). [25] e. fabry, “sur les pointes singuliers d’une fonction donnée par son développement en série et sur l’impossibilité du prolongement analitique dans les cas très généaux”, annales de ’école normale supérieure (3) 13, 107–114 (1896). [26] p. dienes, the taylor series: an introduction to the theory of functions of a complex variable (oxford university press, oxford, u. k., 1931). [27] for an easy proof, multiply eq. (20) by x2 and integrate by parts twice. we have normalized the total mass to unity, so that v(x, t) can be interpreted as a probability density function. 72 barry d. hughes and barry w. ninham [28] a. fick, “ueber diffusion”, annalen der physik 94, 59–86 (1855), translated as a. fick, “on liquid diffusion”, philosophical magazine 10, 30–39 (1855). [29] e.w. montroll and b.j. west, “on an enriched collection of stochastic processes”, in e.w. montroll and j.l. lebowitz (editors), fluctuation phenomena, pp. 61–173 (north-holland, amsterdam, 1979). [30] b.d. hughes, random walks and random environments, vol. 1 (oxford university press, oxford, u.k., 1995). [31] r. kutner, a. pękalski, and k. sznajd-weron (editors), anomalous diffusion: from basics to applications (springer, berlin, 1999). [32] r. klages, g. radons, and i.m. sokolov (editors), anomalous transport: foundations and applications (wiley-vch, weinheim, germany, 2008). [33] b.b. mandelbrot, the fractal geometry of nature (w.h. freeman, san francisco, 1982). [34] b.d. hughes, m.f. shlesinger, and e.w. montroll, “random walks with self-similar clusters”, proceedings of the national academy of sciences (u.s.a.) 78, 3287–3291 (1981). [35] when µ > 2 there is a standard diffusive limit when the time-step t0 and spatial scale ∆ are sent to zero with ∆2/t0 held constant. for µ = 2 it is necessary to take ∆2 ln(1/∆)/t0 constant to recover diffusion, and for 0 < µ < 2 diffusion is never attained. [36] l.p. kadanoff, “scaling laws for ising models near tc”, physics (long island city, n.y.) 2, 263–272 (1966). [37] t. niemeijer and j.m.j. van leeuwen, (1976). “renormalization: ising-like spin systems”, in c. domb and m.s. green (editors), phase transitions and critical phenomena, vol. 6, pp. 425–505. (academic press, london, 1976). [38] for µ ≤ 1/2 the series for q needs to be summed by abelian means, with a convergence factor e−δ|m| inserted and the limit δ → 0 taken after evaluation of the sum. [39] m.f. shlesinger and b.d. hughes, “analogs of renormalization group transformations in random processes”, physica a 109, 597–608 (1981). [40] w.j. reed and b.d. hughes, “on the distribution of family names”, physica a 319, 579–590 (2003). [41] d. sornette, “discrete-scale invariance and complex dimensions”, physics reports 297 (5), 239– 270 (1998). [42] g.h. hardy, “weierstrass’ non-differentiable function”, transactions of the american mathematical society 17, 301–325 (1916). 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[45] although we have discussed here only the symmetric densities with fourier transforms exp(–c|q|µt), there is a more general theory of stable densities, containing additional parameters. in this more general context, simple closed form expressions for densities are usually not available, but there have been some interesting developments since 2010. see k.a. penson and k. górska, “exact and explicit probability densities for onesided lévy stable distributions”, physical review letters 105, 210604 (2010); and k. górska and k.a. penson, “lévy stable two-sided distributions: exact and explicit densities for asymmetric case”, physical review e 83, 061125 (2011). [46] s.a. fulling and k. s. güntürk, “exploring the propagator of a particle in a box,” american journal of physics 71, 55–63 (2003). [47] b. gaveau and l.s. schulman, “explicit timedependent schrödinger propagators,” journal of physics a 19 1833–1846 (1986). [48] c.g. darwin, “free motion in the wave mechanics”, proc. r. soc. lond. a 117 (1927) 258–293. [49] e.h. kennard, “zur quantenmechanik einfacher bewegungstypen”, zeitschrift für physik 44 (1927) 326-352. [50] j. lekner, “airy wavepacket solution of the schrödinger equation,” european journal of physics 30, l43–l46 (2009). [51] w.h. zachariasen, theory of x-ray diffraction in crystals (wiley, new york, 1945). [52] e. zolotoyabko, basic concepts of crystallography (wiley-vch, weinheim, germany, 2011). [53] this is a slight over-simplification from the experimental perspective. the amplitude of the fourier transform can be measured experimentally, but its phase is not directly available. [54] let be a d-dimensional lattice, that is, a set of points with position vectors , where mj ∈ ℤ and the vectors {a1, … ad} are a linearly independent set. the dual lattice or reciprocal lattice consists of these points whose potion vectors have integer-valued dot products with every position vector of a point in . then (see, for example, theorem 3.2 in senechal[61]) the fou73a correspondence principle rier transform of the mass distribution ρ(r) = defined by placing unit mass at each point of is given by (k) = . more general results which essentially account for all simple cases have been established by córdoba [13], who has shown that if µ and ν are two discrete subsets of ℝd (this requires the existence of a nonzero lower bound for the spacing between pairs of points) and c(s) > 0 for all s ∈ µ then the relations between a mass distribution ρ(r) and its fourier transform can hold simultaneously if and only if the following conditions hold: c(s) = 1 and there exists a linear transformation a of ℝd with determinant 1 such that µ = aℤd and ν = (a−1)tℤd, where t denotes the transpose. it may be noted that because the definitions of the fourier transform and its inverse are simply complex conjugates, the factor of c(s) can be placed in either one of the sums over µ and ν without altering the result. we have used this in rephrasing córdoba’s result to suit our notation and our application of interest, where it is more natural to assert that all masses are the same in physical space and allow position dependent coefficients in the sum obtained on taking the fourier transform. 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[62] m. senechal and j. taylor, “quasicrystals: the view from les houches,” mathematical intelligencer 12 (2), 54–64 (1990). [63] m. senechal and j. taylor, “quasicrystals: the view from stockholm,” mathematical intelligencer 35 (2), 1–9 (2013). [64] m. baake and u. grimm, aperiodic order, volume 1, a mathematical invitation (cambridge university press, cambridge, u.k., 2013). [65] in view of córdoba’s observations [54]. [66] b.w. ninham and s. lidin, “some remarks on quasicrystal structure”, acta crystallographica a 48, 640–650 (1992) . [67] these considerations have ancient antecedents among the greeks and arabs, and were certainly prominent in renaissance italy: see, for example, luca pacioli, de divina proportione (venice, 1509), available at https://archive.org/details/divinaproportion00paci. [68] d.w. thompson, on growth and form, complete revised edition (new york, dover, 1992). 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[87] actually, lamoreaux’s experimental system is not one based on parallel plates, but instead uses a flat plate and a sphere, with the force on this system being expressed in terms of the law to be verified for parallel plates using the proximity force theorem of blocki et al. [j. blocki, j. randrup, w.j. swiatecki, and c.f. tsang, “proximity forces”, annals of physics (n.y.) 105, 427–462 (1977)]. the proximity force theorem is essentially the famous derjaguin approximation of colloid science [b.v. derjaguin, “untersuchungen über die reibung und adhäsion. iv. theorie des anhaftens kleiner teilchen”, kolloid-zeitschrift 69, 155–164 (1934)]. for subsequent independent verifications of the casimir force, with a 1% root-mean-square average deviation between theory and experiment at the smallest measured separations, see: u. mohideen and a. roy, “precision measurement of the casimir force from 0.1 to 0.9µmm”, physical review letters 81 (1998) 4549–4552; and a. roy, c-y. lin and u. mohideen, “improved precision measurement of the casimir force”, physical review d 60 111101 (1999). [88] s.l. boersma, “a maritime analogy of the casimir effect”, american journal of physics 64, 539–541 (1996); boersma writes “the old tales were true. rolling ships do attract each other. two ships on a rolling sea attract each other as two atoms do in the sea of vacuum fluctuations.” [89] a. larraza, “a demonstration apparatus for an acoustic analog to the casimir effect”, american journal of physics 67, 1028–1030 (1999). [90] s. koyama and n. kurokawa, “casimir effects on riemann surfaces”, indagationes mathematicae 13, 63–75 (2002). [91] s. koyama and n. kurokawa, “absolute zeta functions, absolute riemann hypothesis and absolute casimir energies”, in g. van dijk and m. wakayama (editors), casimir force, casimir operators and the riemann hypothesis: mathematics for innovation in industry and science (de gruyter, berlin, 2010). [92] e.m. lifshitz and l.p. pitaevski, course of theoretical physics: statistical physics, part 2 (pergamon, oxford, u.k., 1980). [93] e . m . 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[97] i.e. dzyaloshinskii, e.m. lifshitz and l.p. pitaevskii, “general theory of van der waals forces”, soviet physics uspekhi 4, 153–176 (1961); translation from the russian original in uspekhi fizicheskikh nauk 73, 381–422 (1961). the same paper, prepared by a different translator, also appears as “the general theory of van der waals forces”, advances in physics 10 165–209 (1961). [98] see §81–82 of lifshitz and pitaevski [92]. [99] b.w. ninham and v.a. parsegian, “van der waals forces across triple-layer films”, journal of chemical physics 52, 4578–4583 (1970). [100] b.w. ninham and v.a. parsegian, “van der waals forces: special characteristics in lipid-water systems and a general method of calculation based on the lifshitz theory”, biophysical journal 10, 646–663 (1970). [101] v.a. parsegian and b.w. ninham, “temperaturedependent van der waals forces”, biophysical journal 10, 664–674 (1970). [102] e. elizalde and a. romeo, “essentials of the casimir effect and its computation”, american journal of physics 59, 711–719 (1991). [103] b.w. ninham and j. daicic, “lifshitz theory of casimir forces at finite temperature”, physical review a 57, 1870–1879 (1998). [104] it seems that all derivations of the casimir effect require at least one formal argument to resolve an indeterminacy. [105] j. hadamard, “sur la distribution des zéros de la fonction ζ(s) et ses conséquences arithmétiques”, bulletin de la société mathématique de france 24, 199–220 (1896). [106] c. de la vallée poussin, “recherches analytiques sur la théorie des nombres premiers. première partie: la fonction ζ(s) de riemann et les nombres premiers en général”, annales de la société scientifique de bruxelles 20 (2), 183–256 (1896). [107] l.s. brown and g.j. maclay, “vacuum stress between conducting plates: an image solution”, physical review 184, 1272–1279 (1969). 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[115] attributed by berry to arnold, “implied by statements in his many letters disputing priority, usually in response to what he sees as neglect of russian mathematicians”. priority for this observation may, however, be due to s. stigler, “stigler’s law of epynomy”, transactions of the new york academy of sciences 39, 147–158 (1980). [116] modestly attributed by berry to himself, though there is a certain recursively to this assertion. a more modest precursor, viz. that most discoveries of interest have significant precursors, seems worthy of the status of an axiom for human culture. 76 barry d. hughes and barry w. ninham [117] quoted by m. dresden, h.a. kramers: between tradition and revolution (springer, new york, 1987). [118] j. lekner, “electrostatics of two charged conducting spheres”, proceedings of the royal society of london, series a 468, 2829–2848 (2012). 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[130] k.-s. lau and s.-m. ngai, “lq-spectrum of the bernoulli convolution associated with the golden ratio”, studia mathematica 131, 225–251 (1998). substantia an international journal of the history of chemistry vol. 2, n. 1 march 2018 firenze university press why chemists need philosophy, history, and ethics emulsion stability and thermodynamics: in from the cold stig e. friberg finding na,k-atpase hans-jürgen apell mechanistic trends in chemistry louis caruana sj cognition and reality f. tito arecchi a correspondence principle barry d. hughes1,* and barry w. ninham2 from idea to acoustics and back again: the creation and analysis of information in music1 joe wolfe snapshots of chemical practices in ancient egypt jehane ragai the “bitul b’shishim (one part in sixty)”: is a jewish conditional prohibition of the talmud the oldest-known testimony of quantitative analytical chemistry? federico maria rubino michael faraday: a virtuous life dedicated to science franco bagnoli and roberto livi substantia. an international journal of the history of chemistry 7(1): 113-119, 2023 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-2039 citation: crabtree r.h., greenberg a., rasmussen s.c. (2023) review of a cultural history of chemistry. peter j. t. morris and alan rocke, eds. substantia 7(1): 113-119. doi: 10.36253/ substantia-2039 copyright: © 2023 crabtree r.h., greenberg a., rasmussen s.c. this is an open access, peer-reviewed article published by firenze university press ( h t t p: // w w w.f u p r e s s .c o m /s u b s t a n tia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. book reviews review of a cultural history of chemistry. peter j. t. morris and alan rocke, eds., bloomsbury academic: london, 2022 robert h. crabtree1, arthur greenberg2, seth c. rasmussen3 1 department of chemistry, yale university, new haven ct 06520 usa 2 department of chemistry, university of new hampshire, durham, nh 03824 usa 3 department of chemistry and biochemistry, north dakota state university, fargo, nd 58108 usa e-mail: robert.crabtree@yale.edu, art.greenberg@unh.edu, seth.rasmussen@ndsu.edu when presented with a new multivolume series on the history of chemistry, one cannot help but compare it to j. r. partington’s masterful fourvolume a history of chemistry. the new six-volume a cultural history of chemistry reviewed here, however, is really a different beast and should not be viewed as a simple attempt to update partington’s previous series. as highlighted by series editors peter morris and alan rocke in the series preface that begins each volume, “this is not a conventional history of chemistry, but a first attempt at creating a cultural history of the science.” as such, this series brings together 50 contributors in an effort to present the first detailed and authoritative survey of the impact of chemistry on society, as well as how society has influenced and impacted chemical practice and thought. spanning from the earliest applications of the chemical arts in antiquity up through the present, this cultural history is split into six volumes, each covering a specific time period, with the structure of each volume consistent throughout the series. as such, each volume begins with an introduction, followed by the identical chapter titles: theory and concepts; practice and experiment; sites and technology; culture and knowledge; society and environment; trade and industry; learning and institutions; art and representation. as a result, this gives the reader the choice of focusing on a specific time period within a single volume, or following a chosen theme across history by reading the corresponding chapter in each of the six volumes. each volume concludes with both a bibliography and an index, with all six volumes providing a combined 1728 pages of material. separate reviews for each of the six volumes are given below, followed by some concluding remarks about the overall six-volume effort. http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 114 robert h. crabtree, arthur greenberg, seth c. rasmussen volume 1: a cultural history of chemistry in antiquity. marco beretta, ed. (review by s. c. rasmussen) the initial volume covers by far the largest timespan, tackling nearly 4000 years over the period from 3000 bce to 600 ce. the challenge of this task is highlighted by editor marco beretta in the introduction, particularly considering the limited surviving written sources from this period of history. beretta argues that it is this scarcity of literary sources, in comparison to the wealth of archaeological objects, that has led to the focus on the material background of the chemical arts in previous attempts to cover this period by authors such as partington. still, in addition to the many practical achievements evidenced during antiquity, beretta gives a good overview of the literary genre available that can be used as a lens into this period of time. the following chapters are then collaborations between the four contributors of this volume, with each author covering one of the primary cultures of focus: egypt by sydney aufrère; mesopotamia by cale johnson; greco-roman by matteo martelli, with beretta providing overarching conclusions. this uniform structure for each chapter thus provides additional consistency throughout the various subjects discussed. chapter one attempts to make connections between mythology and chemical theory, particularly within the egyptian civilization. while the natural philosophies of the greeks and romans were more independent of such my thological inf luences, they did incorporate ideas and concepts from the older civilizations. chapter two then delves into the technical practices during this period, including the wealth of chemical species applied, with discussion of the names and symbols used to distinguish the reagents, species, and products involved. chapter three goes on to analyze the state of laboratories and the technological advances found within antiquity. for those that have studied the history of chemical technology of this period, this chapter is perhaps the most traditional of those offered in the volume, and offers a good overview of technical workshops and their products. chapter four then reflects on the influence of religion on chemical practices, with focus on connections between the gods of a given culture and various activities of the craftsman. chapter five then discusses the impact of the growing chemical technology on the local environments, both in terms of overexploitation of resources and the effects of toxic byproducts released during various operations. for a topic so prevalent in the discussion of modern chemical practice, it was very eye-opening to see these relationships mapped onto practices in antiquity. chapter six covers the processes of trade between neighboring societies as a result of progresses made in the production of goods via chemical processes. this of course included not only the products themselves, but minerals, ores, and other reagents needed for their production. chapter seven then discusses the development of recipes and the production of recipe books, which served the dual purpose of transmitting knowledge to future generations, as well as providing better control to the access of this knowledge. the final chapter then discusses the relationship between various practices and their artistic representation, both visually and in words (poems, songs, etc.). as illustrated by the quick summary given above, this volume brings much that is new to the study of this period of chemistry, providing new context to consider when reflecting on the processes and technologies developed during antiquity. while it would have been nice to have included aspects of the far east, beretta makes good arguments for why this was not included in the current effort. regardless, this volume is highly recommended for anyone with an interest in this earliest period of chemical practice. volume 2: a cultural history of chemistry in the middle ages. charles burnett and sébastien moureau, eds. (review by r. h. crabtree) sébastien moureau’s introductory chapter sets out the geographic scope of volume 2 as the islamic south, the orthodox east and the latin west over the period 400-1500 c.e. it also outlines the grave difficulties facing students of the period, such as widespread pseudepigraphy, shifting nomenclature, allegorical symbolism and coded language. applications to medicine, dying and transmutation are discussed and linked to alchemical principles and classifications, such as the familiar four element theory. the operations chapter that follows highlights the difference between craft and alchemy: both sought useful products but the latter also sought theoretical understanding. various types of distillation, calcination, dissolution, coagulation and sublimation are also covered along with the equipment needed for each. difficulties arise in interpreting the texts because they embody unstated ‘know-how’ that is hard to reconstruct. the third chapter on laboratories contrasts the abundance of relevant images in latin sources with their paucity from arabic ones, and even where they do exist in the latter they are often allegorical. there is also a useful extended discussion of archaeological finds with diagrams and images. another avenue for exploration of the topic, although still too rarely used, is experimental, by design of historical replications. as for laboratories, 115review of a cultural history of chemistry domestic spaces seem to have been most common, but artists’ depictions of them may owe more to invention than to reality. archaeology indicates that abbeys may have housed workshops for preparation of inks for the scriptorium although this may have been a craft rather than a true alchemical tradition. castles and noble urban dwellings have also provided similar evidence. various specific tools, types of furnace and items of apparatus are listed or described, with the helpful addition of their arabic and latin names. chapter 4 provides an interesting discussion of alchemy’s relations with other natural philosophic efforts along with contemporary criticism of the practice. already in arabic mss., alchemy is not always listed among the sciences and its validity can be disputed. because it had not existed in aristotle’s time, so not discussed by him, this had the effect of giving alchemy a secondary standing. its relationship to the occult sciences of astrology and magic also hurt its standing, although many continued to hold the occult sciences as authentic. the close association of alchemy with medicine, especially in connection with paracelsian doctrines and the analogy between an elixir curing people and the philosophers stone ‘curing’ metals is noted. the interconnection with religious ideas, so important in the period, is not neglected, as in the discussion of the quintessence and the special affinity of alchemy with shiite islam. in the latin west, both detractors and supporters of alchemy are found among religious scholars, roger bacon being a notable adherent, ramon llull taking the opposite position. mary the jewess is identified as a rare female adept, remembered today in the french term ‘bain marie’ for an aqueous heating bath. chapter 5 discusses the place of alchemy and the alchemist in society. for example, as a supposedly purely practical art without theoretical underpinning, buridan thought it had no place in a monastery, but some monasteries did have alchemical connections. numerous arabic and european royal courts also encouraged alchemical efforts. a major concern was economic: currency minted with false alchemical gold would be equivalent to counterfeiting. the next chapter discusses medieval chemical technologies with case studies on metal and glass production, thus going beyond pure alchemy into trade and commercial concerns. educational concerns follow next with a discussion of oral and manuscript transmission of the art, noting the problems posed by semantic fluidity of alchemical terms and the problems with later alchemists composing alchemical texts falsely attributed to well-known scholars, such as llull, who in reality opposed the art. perhaps the most original chapter is the final one on art, in which the images, often allegorical, found in the manuscripts are discussed and illustrated. in summary, this volume will be a valuable addition to institutional and personal scholarly libraries. volume 3: a cultural history of chemistry in the early modern age. bruce t. moran, ed. (review by a. greenberg) the third volume traverses the sixteenth and seventeenth centuries. paracelsus, born in 1493, revolutionized the medical paradigm; in 1597, libavius published the first chemistry textbook; in 1697 stahl published the phlogiston theory of combustion. the introduction, by volume editor bruce t. moran, outlines historical and technical upheavals during the renaissance. the cabinet of medicines enriched by discovery of new world plants and animals; luther and the protestant reformation; dutch east india company and economic growth of europe; becher, chemist, and commercial advisor to the holy roman emperor. chapter one (theory and concepts…), by lawrence m. principe, seemingly “squares the circle” by accessibly contextualizing the four chemical theories of this era: aristotle’s hylomorphism: “forms” imposed upon “prime matter”; four elements; mercury and sulfur; and a “quasi-particulate conception of the structure of matter”. to add to complexity, principe describes variations and overlaps of these theories. william newman and principe reintroduced the archaic term “chymistry” to remove the artificial barrier between serious alchemy and chemistry. practice and experiment… by joel a. klein emphasizes the development of chymistry as a practice and theory of analysis and synthesis. beginning with pseudo-geber, continuing with the sixteenth-century works of agricola and brunschwig, technologies of assaying and distillation became widely available to artisans and adepts. indeed, paracelsus considered the human body as a process of spagyria, a disassembly and reassembly of the tria prima (mercury, sulfur, salt). sennert chemically separated gold-silver alloy, precipitating a silver salt and then recovering the pure metal. the gravimetric work of van helmont began to make analysis quantitative. laboratories and technology…, by donna bilak, beautifully describes and illustrates the laboratory technology of the mid-seventeenth century with woodcuts of apparatus from lefèvre’s compendious body of chemistry (1662) and a painting by david teniers the younger. but the foibles, failures and road to poverty of gold makers are illustrated by bruegel painting engraved by galle, and allegorical secrets illustrated in atalanta fugiens (1618), by the musical alchemist maier, in which a washerwoman launders philosophical matter to remove impurities. 116 robert h. crabtree, arthur greenberg, seth c. rasmussen culture and science…, by andrew sparling, describes the communication of chymical information by peripatetic chymists, including paracelsus and kunckel, a century later. during this period books and pamphlets found avid readership. boyle described, in print, witnessing transmutations and newton was an avid reader of the harvard-trained alchemist starkey. chemistry and environment…, by william eamon, is a very ambitious, wide-ranging chapter emphasizing the role of distillation, from purely commercial to charitable, pigments, mining, domains of women, the exponentiallyincreasing role of books including books of secrets, chemical imagery, warfare, the environment among topics. trade and industry…, by tilmann taape, returns to the economies of distillation, including woodcuts of apparatus from the fifteenth and sixteenth centuries. plat’s jewell house of art and nature (1594) is cited for the clarity of presentation of works culled from many sources. in learning and institutions…, margaret d. garber offers examples of the roles of european noble courts and universities, in fostering theory and practice. physicians played an important role as liaisons between the courts and universities such as those in prague, jena, wittenberg, and leiden as well as in france and england. arts and representation…, by elisabeth berry drago, employs a woodcut, an engraving and eleven paintings (in black and white), as well as excerpts of poems in order to illustrate the chymical mysteries, glories, foibles, and frauds, as imagined by the artists of the period. this third volume, although replete with names, theories, processes and historical perspective, is a must for any institutional collection as well as for individual libraries of those interested in a truly interdisciplinary approach to the history of chemistry. volume 4: a cultural history of chemistry in the eighteenth century. matthew eddy and ursula klein, eds. (review by a. greenberg) according to its cover, this fourth volume in the series covers the period from 1700 to 1815. emerging as a modern science, chemistry achieves respect in cultural and academic circles and contributes to material wealth as laboratory and workplace skills improve agriculture, pharmacy, medicine, manufacture, and the fine arts. the introduction, by the editors, describes the institutionalization of chemistry in eighteenth-century europe in the context of the enlightenment. a major school of thought attributes the chemical revolution largely to lavoisier and his contemporaries. another school conceives lavoisier’s breakthroughs in a wider context that developed gradually throughout the eighteenth century. chapter one (theory and concepts…), by ursula klein, navigates readers through the complexities of the earliest chemical theories which maintained their hold into the eighteenth century: greek atomists, aristotelian philosophers, and paracelsians. stahl is a crucial link blending mechanical-corpuscular theories with theories based upon four principles comprising matter, transforming becher’s seventeenth century theory into phlogiston explaining combustion and calx formation as one. stahl linked his chemistry with affinity tables. the concept of the chemical element was critical and macquer (1753) was an important pioneer anticipating lavoisier’s definition of a chemical element. even so, lavoisier conceived of gaseous oxygen containing the element oxygen with the imponderable element caloric, the latter released as heat when oxygen combined with, say, mercury. in chapter two (practice and experiment…), victor d. boantza defines eighteenth-century terms of chemical operations, most still familiar but some obscure (e.g., collature, filtration through a hair sieve) and illustrates apparatus from the 1757 edition of lemery’s cours de chymie. plants were exploited using “wet chemistry”, e.g., solvent extraction, and more often by “dry chemistry”, e.g., distillation, to produce medicines. mineral chemistry led to geoffroy’s affinity table (1718), devoid of theory but the first ordering of chemical (and some physical) properties. pneumatic chemistry, pioneered by hales, brownrigg, cavendish and priestley “set the table” for lavoisier. chapter three (laboratories and technology…), by marco beretta, makes the important point that even university laboratories started with close ties to artisans, businesses and industries. pharmacies had the greatest initial impact on laboratory techniques. a plate from the 1763 encyclopédie depicts a mid-eighteenth-century laboratory. beretta emphasizes macquer’s impact on theory and experiment including his 1766 dictionnaire. the remainder of this chapter is devoted to pneumatic chemistry including illustration of lavoisier’s complex gasometer. beretta describes scheele’s contributions, surprisingly little mentioned elsewhere in this volume. chapter four (culture and science…) by bernadette bensaude-vincent describes the increasing fascination of professionals and the lay public with chemical demonstrations (no longer “the mere province of ‘sooty empirics’”) and lectures by shaw, g.-f. rouelle, and cullen. venel’s essay and the illustrations in the encyclopédie further popularized chemistry. at edinburgh, cullen’s successor black trained a generation of chemistry professors including those at the best american universities. the concluding section examines chemistryinspired philosophies. in exploring chemistry and daily 117review of a cultural history of chemistry life, matthew daniel eddy (society and environment…) takes an amazingly inclusive approach describing patronage, sociability, consumerism, politics, the environment and ecology. particularly illuminating was the discussion of the interplay between chemistry and consumerism in european attempts to uncover the secrets of chinese porcelain. pott’s unsuccessful attempts to crack the meissen company’s formulation of porcelain led to the first widely-recognized chemical classifications of the earths. chapter six (trade and industry…) by leslie tomory begins with the mechanization of textile production during the industrial revolution, increasing the demand for innovation in and production of chemicals for bleaching, dying and fixing dyes to fabrics (salts termed mordants). in the section on metallurgy, we learn that europe was initially dependent and eventually inspired by indian technology as a source of high-quality zinc for making brass. a section on domestic goods is followed by one on chemical industries including gunpowder buoyed by lavoisier’s encyclopedic research on saltpeter. john c. powers (learning and institutions…) describes the evolution of didactic chemistry from artisan chemists in the early eighteenth century toward university professors, noting that in 1720 there only six chemistry professorships in german universities that increased to twenty-eight in 1780. apprenticeships were common in the early eighteenth century, but the quality of training was highly variable, and the increasing sophistication of chemical science demanded sounder didactics including theory. there were public lectures, for example g.-f. rouelle, at the jardin du roi, that were often open free to the public and private instruction for those who could afford it. boerhaave, at leiden, presented a fairly modest course for university students but a more comprehensive course for paying customers. throughout the eighteenth century, textbooks evolved from purely practical to incorporate theory, culminating in lavoisier’s 1789 traité. art and representation…, by john r.r. christie, illustrates the growing fascination among growing urbane middle and upper classes, depicting fascination with the science as well as opportunities for satire from such as gillray. perhaps the apex in chemical artwork is the very large, much-analyzed portrait by david of the lavoisiers in the metropolitan museum of art. among literary representations, considerable emphasis is placed on the radical english poet anna letitia barbauld, who remained priestley’s correspondent well beyond his emigration to america following the 1791 “priestley riots” in birmingham. as christie comments: “priestley’s appearances in barbauld’s poetry received gentler and more positive handling than from the carricaturists of the 1790s.” volume 5: a cultural history of chemistry in the nineteenth century. (edited by peter j. ramberg, ed. (review by r. h. crabtree) the introduction to volume 5 notes the high points of a century, the ‘long’ 19th, that may mark the high point for chemistry as a whole. this takes us from debates on atomism to the puzzling phenomenon of radioactivity. whether dalton’s atoms were real, as he thought, or merely useful concepts, remained a continuing debate throughout. the middle of the century saw both mendeleev’s periodic table and the rise of organic chemistry and the dyestuff industry dependent on it. by the end of the century, professionalisation of the field was far advanced with universities creating laboratories for teaching and research, especially in germany where the chemical industry also flourished, for example in dye production. a theory chapter follows that traces the development of the ideas of atoms, equivalents and formulas and argues that berzelius and davy were the most influential figures of the early period. the finding that liebig’s silver fulminate and wöhler’s silver cyanate had the same chemical composition led berzelius to coin the term isomerism and explain this result in terms of a differing atomic arrangement. the rise of physical chemistry in the same period is discussed, including such figures as gibbs, foreshadowing the rise of the us as a scientific power in the next century. ostwald, denying physical atoms, used thermodynamics as a replacement scaffold for discussion of the experimental facts. spectroscopy came into being with an early application of elemental analysis of the solar atmosphere by comparison of the solar spectrum with laboratory standards. chapter two charts the development of experimental practice, including analysis, lab equipment, the representation of molecules, a section that includes an image of kekulé’s own molecular models. the next chapter contrasts the relative simplicity of the chemical laboratory in 1800, often in a private space, with the vastly more complicated situation by the end of the century when labs were almost always institutional and used not just for research but also for teaching, germany taking the lead. oxford resisted adding experimental sciences to its curriculum perhaps because most of its graduates took up clerical appointments. chemistry, it was also felt, did not fit with the intellectual activities of the university. activity also spread to the americas: by the end of the period, harvard had a chemistry department with 14 teaching staff and more than 300 students engaged either in undergraduate or graduate studies, thus approaching closely to the modern pattern. the next chapter more directly justifies the cultural history 118 robert h. crabtree, arthur greenberg, seth c. rasmussen orientation of the whole work by looking at the influence of chemistry on the wider world. jane marcet’s ‘conversations on chemistry’ popularized chemistry in 16 british editions from 1805 to 1853; public lectures, such as ones by tyndall, frankland and faraday, were very well attended, including by marcet herself. faraday published his ‘chemical history of a candle’ in 1861, a work that, remarkably, is said to have never been out of print since. applications to agriculture were the topic of several books in the period intended to encourage scientific farming, such as liebig’s ‘agricultural chemistry’. anaethesia in medicine also depended on chemistry, for example queen victoria much appreciated being given chloroform in her last two confinements. advances in forensic medicine included the celebrated marsh test for arsenic and orfila’s test for blood stains. religious influences were still evident--prout, for example, pointed to dalton’s laws as examples of divine wisdom. mary shelley’s celebrated novel, ‘frankenstein’, published as early as 1818, includes references to then-current popular science. the rise of photography from the 1840s relied on chemistry for development of the images and of course the dye industry led to much brighter clothing becoming available. the next chapter continues the theme of the influence of chemistry on society with a discussion of the numerous ways in which this was felt. for example, how the supply of clean water, and pure food and drugs was assisted by analytical chemistry. as for industry, we are told that chemists were only employed in significant numbers after 1870, because prior industrial practice differed little from traditional craft procedures. chemical industry was strongly represented in the trade fairs that followed the great exhibition of 1851. explosive manufacture was perfected in the same period, an advance that was to have a big impact in both peace and war. thanks to the the foundation of women’s colleges, such as girton at cambridge in 1869 and vassar in 1865, women made significant contributions to research late in the century, but were sadly still excluded from many professional bodies. chapter 6 covers chemical industry, with a close look at pharmaceuticals and fertilizers. the next chapter covers learning and institutions, with special attention to popularization and the role of chemical societies and their journals. the final chapter takes the ‘mad scientist’ as its theme, not a particularly appealing one to this reviewer. as a general point, a common problem with edited volumes is evident here: some material is duplicated in different chapters but otherwise this work provides a view of chemical history from an original viewpoint and will be a valuable addition to institutional and personal scholarly libraries. volume 6: a cultural history of chemistry in the modern age. peter j.t. morris, ed. (review by r. h. crabtree) the final volume has the formidable challenge of covering the period from 1914 to the present. some of the themes include the rise of mechanism and of computational chemistry in explaining the course of reactions and of x-ray diffraction and of the common spectroscopic techniques for determining structures. the development of oral contraceptives influenced cultural behavior and demography and the rise of chemical engineering and green chemistry had a direct influence on industrial practice. links with biology and physics were formed with the rise of molecular biology and chemical physics and links with industry came from natural products, polymers, silicones, solid state chemistry and catalysis. isotope dating gave human development an absolute timescale and even determined the age of the earth. some of the themes of prior volumes are taken up again here, such as professionalization and internationalization. adverse trends are also noted in the closure of some uk chemistry departments, and the possibility that the field might be largely absorbed by neighboring disciplines. the major theoretical advance of the early period, the understanding of bonding and reactivity, led to mechanistic thinking that in turn fed into structure and synthesis with such advances as the hemoglobin structure and the coenzyme b12 synthesis. late in the period, nanoscience came to the fore with such novelties as bucky ball and carbon nanotubes. research, education and policy form the core of chapter two, with emphasis on numerous advances, many of which affected the wider world. the next chapter examines the evolution of the laboratory over the period. a radical shift that started in the 1950s involved the introduction of major electronic instrumentation on a grand scale that displaced prior practices such as organic structure determination by chemical means. the advent of these costly machines greatly increased the costs of research but enhanced its output. mass spectroscopy, gas chromatography and nmr spectroscopy are discussed in detail and the importance of timely books is illustrated by roberts’ ‘nuclear magnetic resonance’ of 1959 that made nmr sufficiently understandable so the general bench chemist could use it. one point that could have had greater emphasis in this series as a whole is the importance of textbooks as both influencers of the field as well as providing evidence of its evolution over time. chapter four shows how chemistry’s earlier good public reputation was put in question in the 1970s by rising attention to such negative outcomes as industrial pollution and the 119review of a cultural history of chemistry undesired side-effects of pesticides and drugs; items later added to the list include halocarbon refrigerants and perfluorinated ‘forever chemicals’. chapter 5 continues the same theme with the international regulation of pollution, climate change and efforts to ban chemical weapons, and introduces a new one with the rise of women in the field. chapter 6 traces the rise of the chemical industry with special reference to its globalization and internationalization during the century. beginning with japan in the 1950s and more recently with china, the rise of east asia as a scientific center is documented but the 1990s are considered to bring in an era of global science, facilitated by the new methods of communication across the globe. the final chapter on art and representation continues the theme of the ‘mad scientist’, mentioned in the last volume, as well as tracing the representation of scientists in general literature such as children’s comics. in summary, this volume does a fine job of selecting telling aspects of the century’s development in the field and providing a useful bibliography for further study. summary of the reviewers in conclusion, we collectively believe that the cultural history covered in the six volumes presented above provides a fresh view of the history of chemistry, with analysis and discussion that surpasses the frequent presentation of notable individuals, chemical processes, and discoveries. by considering the full impact and interplay of society with chemical practice, a much more complete representation is achieved. as such, this series marks a valuable addition to the study and knowledge of the history of chemistry. substantia an international journal of the history of chemistry vol. 7, n. 1 – 2023 firenze university press superbugged pierandrea lo nostro equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the π0 meson, its mass and lifetime barry w. ninham1, iver brevik2, mathias boström3,4 the rate constant – reaction free energy dependence for the electron transfer reactions in solutions. the way to interpret the experimental data correctly lev i. krishtalik1,† training of future chemistry teachers by a historical / steam approach starting from the visit to an historical science museum valentina domenici a new response to wray and an attempt to widen the conversation eric scerri boxing partula: 25 years after stephen t. hyde surface inactivation of bacterial viruses and of proteins mark h. adams johann beckmann (1739-1811) and modern chemical technology juergen heinrich maar kuroda chika (1884-1968) – pioneer woman chemist in twentieth century japan yona siderer review of a cultural history of chemistry. peter j. t. morris and alan rocke, eds., bloomsbury academic: london, 2022 robert h. crabtree1, arthur greenberg2, seth c. rasmussen3 substantia. an international journal of the history of chemistry 7(1): 5-6, 2023 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-2038 editorial superbugged pierandrea lo nostro department of chemistry “ugo schiff ” and csgi, university of florence, 50019 sesto fiorentino (firenze), italy e-mail: pierandrea.lonostro@unifi.it we thought that with the decline of the covid-19 pandemic the worst had gone and that we could go back to normal life, maybe keeping one eye open on the evolution of the virus variants from time to time. suddenly almost any news on tv about the pandemic has disappeared. but we are not aware of the threatening risk of a super-pandemic for which we won’t have powerful weapons: antimicrobial resistance (amr). the phenomenon is well known in the scientific community but citizens are not informed that they can play a crucial role in avoiding this disaster. briefly, bacteria produce natural antibiotics to fight against other strains, and some develop resistance. when we use antibiotics without a real need, they kill good and bad bacteria, but those that develop resistance are free to proliferate. amr can be transferred to deadly pathogens and we will not have any tool to control or limit infections. at the end, humans will not have efficient bullets against superbugs as they will have already mutated and become resistant to the most powerful antibiotics. we (humans) are responsible for amr. the wrong use of antibiotics is a common practice all over the world, in all countries. often people take these drugs even in the case of diseases that are not related to bacteria, e.g. cold, flu and other infections like dengue and malaria. in other cases the patient stops assuming the antibiotic before the sickness and the infection are totally eradicated, with a potential relapse of the illness. we must not forget that expired antibiotics are often dispersed in the environment and not disposed of in the proper way. another terrific source of amr comes from large livestock farms, where the animals are administered huge amounts of antibiotics to “improve” their health. while urban sites possess sewer ducts to collect waste waters and bring them to the treatment plants, the waste waters in animal farms are dispersed in the soil and can reach the groundwater streams without any control. in general, amr in soils represents a serious risk to human health through the food chain and human–nature contact.1 some data. a recent world health organization (who) document reports high levels of amr in 87 countries in 2020. the study concerns both bacteria that cause infections in the bloodstream, for example klebsiella pneumoniae and acinetobacter spp that become insensitive to carbapenems.2 the same phenomenon occurs with more common bacteria, in fact more than 60% of neisseria gonorrhoea isolates, a common sexually transmitted disease, have shown resistance to ciprofloxacin and more than 20% of e.coli isolates – the most common pathogen in urinary tract infections – became resistant to first-line drugs (ampicillin and co-trimoxazole) and to secondline treatments (fluoroquinolones). in the past four years most amr trends have remained stable, but bloodstream infections due to resistant escherichia coli and salmonella spp. and resistant gonorrhoea infections increased by at least 15% compared to 2017. more research is needed to identify the reasons behind the observed amr increase and to what extent it is related to raised hospitalizations and increased antibiotic treatments during the covid-19 pandemic. 1 h.-z. li, k. yang, h. liao, y.-g. zhu. active antibiotic resistome in soils unraveled by single-cell isotope probing and targeted metagenomics. pnas 119 (2022) e2201473119. 2 report signals increasing resistance to antibiotics in bacterial infections in humans and need for better data. https://www.who.int/news/ item/09-12-2022-report-signals-increasing-resistance-to-antibiotics-inbacterial-infections-in-humans-and-need-for-better-data (last accessed: 25/02/2023). http://www.fupress.com/substantia 6 pierandrea lo nostro antibiotics continue to be prescribed for diarrheal diseases and upper respiratory infections for which they have limited value. during the chaotic treatment of covid-19, patients were treated with antibiotics which resulted in more adverse effects. a recent study carried out at the indian council of medical research showed that out of about 17,000 patients in indian hospitals, more than half of them who acquired drug-resistant infections died.3 the problem is extremely serious and is affecting western countries as well. in spite of all these warnings, broad-spectrum antibiotics – i.e. drugs that should be reserved for tackling the hard-to-treat bacterial infections – represent 75% of all prescriptions issued in india’s hospitals.4 of course, the environmental regulations that every single country adopt (or should do so) play another crucial role. recently it was reported that several big pharmaceutical industries delocalized their plants in china and in india for the production of antibiotics, including the generic brands. well, it was found that – astonishingly – the industrial waste waters carrying antibiotics and byproducts discarded their junk in the same stream where untreated raw sewage was released! nobody could ever build a better bioreactor for the production of antibiotic resistance bacteria! in this case the responsibility of the companies to press and obtain from the governmental agencies the respect of the procedure to properly treat the industrial and urban wastes is clear.5 even more recently scientists confirmed or realized that other chemicals can induce resistance in pathogens. this is the case of cationic surfactants,6,7 often used as antimicrobial agents for example in household detergents, and antidepressants.8 3 s. vijay, n. bansal, b. k. rao, b. veeraraghavan, c. rodrigues, c. wattal, j. p. goyal, k. tadepalli, p. mathur, r. venkateswaran, r. venkatasubramanian, s. khadanga, s. bhattacharya, s. mukherjee, s. baveja, s. sistla, s. panda, k. walia. secondary infections in hospitalized covid-19 patients: indian experience. infect drug resist. 14 (2021) 18931903. 4 india facing a pandemic of antibiotics-resistant superbugs. https://www.bbc.com/news/world-asia-india-63059585 (last accessed: 25/02/2023). 5 waste from pharmaceutical plants in india and china promotes antibiotic-resistant superbugs. https://www.statnews.com/2016/10/14/superbugs-antibiotic-resistance-india-china/ (last accessed: 25/02/2023). 6 c. zhou, y. wang. structure–activity relationship of cationic surfactants as antimicrobial agents. curr. op. colloid & interface sci. 45 (2020) 28-43. 7 s. ishikawa, y. matsumura, f. yoshizako, t. tsuchido. characterization of a cationic surfactant-resistant mutant isolated spontaneously from escherichia coli. j. appl. microbiol. 92 (2002) 261-8. 8 how antidepressants help bacteria resist antibiotics. https://www. nature.com/articles/d41586-023-00186-y (last accessed: 25/02/2023). the goal of this brief document is to recall how the problem is serious and to show that it must be treated efficiently and rapidly.9 the nex t (super)pa ndemic has a lready been announced, the perfect storm is approaching. 9 c. lübbert, c. baars, a. dayakar, n. lippmann, a. c. rodloff, m. kinzig, f. sörgel. environmental pollution with antimicrobial agents from bulk drug manufacturing industries in hyderabad, south india, is associated with dissemination of extended-spectrum beta-lactamase and carbapenemase-producing pathogens. infections 45 (2017) 479-491. substantia an international journal of the history of chemistry vol. 7, n. 1 – 2023 firenze university press superbugged pierandrea lo nostro equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the π0 meson, its mass and lifetime barry w. ninham1, iver brevik2, mathias boström3,4 the rate constant – reaction free energy dependence for the electron transfer reactions in solutions. the way to interpret the experimental data correctly lev i. krishtalik1,† training of future chemistry teachers by a historical / steam approach starting from the visit to an historical science museum valentina domenici a new response to wray and an attempt to widen the conversation eric scerri boxing partula: 25 years after stephen t. hyde surface inactivation of bacterial viruses and of proteins mark h. adams johann beckmann (1739-1811) and modern chemical technology juergen heinrich maar kuroda chika (1884-1968) – pioneer woman chemist in twentieth century japan yona siderer review of a cultural history of chemistry. peter j. t. morris and alan rocke, eds., bloomsbury academic: london, 2022 robert h. crabtree1, arthur greenberg2, seth c. rasmussen3 substantia. an international journal of the history of chemistry 3(2) suppl. 1: 73-82, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-280 citation: c. l. heth (2019) energy on demand: a brief history of the development of the battery. substantia 3(2) suppl. 1: 73-82. doi: 10.13128/substantia-280 copyright: © 2019 c. l. heth. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. energy on demand: a brief history of the development of the battery christopher l. heth minot state university, 500 university ave. w, minot, nd 58707 e-mail: christopher.heth@minotstateu.edu abstract. portable, readily available electrical energy provided by batteries is ubiquitous in modern society and can easily be taken for granted. from the early voltaic piles to modern lithium ion cells, batteries have been powering scientific and technological advancement for over two centuries. a survey of select notable developments leading to modern batteries commercially available today are presented, with emphasis on early technologies and also including some of the advancements made within the last few decades. a brief discussion of the chemistry utilized by battery technology is also included. keywords. battery, electrochemical cell, voltaic pile, daniell cell. introduction in the modern industrialized world, it can be difficult to imagine life without ready access to on-demand electricity. massive electrical infrastructures have been built allowing for safe, reliable, and constant delivery of electrical energy to households, businesses, and industrial complexes throughout much of the globe. by 1950, electric power consumption in the united states was reported at 291 billion kilowatt hours.1 by the mid 1990’s usage topped 3,000 billion kilowatt hours, and demand has continued to increase with consumption of 3,946 billion kilowatt hours reported for 2018, the bulk of which is split between residential (37%) and commercial (35%) usage.1 while this infrastructure effectively provides fixed access to electrical energy within relatively easy reach in homes, workplaces, and other locations, batteries are used as a source of power for a myriad of devices. from cell phones to flashlights, wall clocks to children’s toys, more and more electronic devices utilize battery power. medical devices, whether implanted such as a pacemaker or external like an insulin pump, also require lightweight mobile power sources, as do fully electric automobiles on an even larger scale. with a ready supply of electrical energy ubiquitous in industrialized society, it can be easy to take this valuable resource for granted without consideration for the process by which the development of the battery occurred, 74 christopher l. heth74 christopher l. heth or the technological advancements that followed. a complete and exhaustive accounting of all these advances would be an undertaking beyond the scope of this work and may well be out-of-date prior to publication, as work currently continues to design and produce smaller, lighter, and longer lasting batteries for mobile electronics. as such, this work will focus on the earliest battery developments as well as the more significant general developments within the past several decades. the electrochemical cell the term “battery” has several different meanings which may at first glance appear unrelated.2 the common thread within these varied definitions is the reference to multiple parts working in concert, whether artillery pieces, a pitcher and a catcher in baseball, or a collection of electrochemical cells. benjamin franklin is attributed with one of the first uses of the term “electrical battery”, included in a letter describing his work with static electricity using leyden jars to english naturalist peter collinson in 1749: upon this we made what we call’ d an electric battery, consisting of eleven panes of large sash glass, arm’ d with thin leaden plates,…with hooks of thick leaden wire one from each side standing upright, distant from each other; and convenient communications of wire and chain from the giving side of one pane to the receiving side of the other; that so the whole might be charg’ d together, and with the same labour as one single pane;…3 over time, the term “battery” has come to refer to both a collection of connected electrochemical cells and a single working cell, and will be generally used without specificity throughout this work.4 batteries produce electrical energy through oxidation-reduction (redox) processes, wherein one substance loses electrons through oxidation while another substance gains electrons through reduction. it is sometimes convenient to examine the oxidation and reduction processes independently as half reactions, an example of which is shown below. however, it is important to note that oxidation cannot occur without a corresponding reduction process also occurring and vice versa, although the two processes do not necessarily need to occur at the same physical location. oxidation: zn(s) → zn2+(aq) + 2 ereduction: cu2+(aq) + 2 e→ cu(s) overall: zn(s) + cu2+(aq) → zn2+(aq) + cu(s) in simple electrochemical cells (figure 1), these processes occur at the surface of electronic conductors, termed electrodes. these electrodes may be composed of a redox-active material or more electrochemically inert materials such as platinum, mercury, gold, or graphite.5 oxidation occurs at the anode, while the reduction process occurs at the cathode. between the electrodes is an electrolyte, an ionic conductor necessary to reduce polarization and allow current to flow. wire or another electrically conducting material connects the two electrodes to a load, completing the circuit, allowing the battery to discharge and work to be done. the overall system must remain charge-neutral in order to continue functioning. if a build up of charge occurs, polarization results and the electric current is reduced and ultimately stopped completely. batteries are often classified as either primary or secondary batteries. in both cases, chemical potential energy is converted to electrical energy. for primary batteries, the chemical reactants are consumed in a process which is not easily reversible, resulting in a battery which can only be discharged a single time. examples of primary batteries include common alkaline batteries, silver button cells and watch batteries, and the homemade “lemon battery” consisting of pieces of iron and copper stuck into the flesh of the acidic citrus fruit. secondary batteries also convert chemical potential energy to electrical energy, but do so through reversible chemical process which render the resulting battery rechargeable. application of electrical energy from an external source such as a generator or another battery can regenerate the initial chemical reactants, restoring the battery’s charge and allowing repeated charge/ discharge cycles. because of this ability to store energy, these types of cells are also known as “storage batteries”. common examples of storage batteries include lead-acid figure 1. a simple electrochemical cell. 75energy on demand: 75energy on demand: a brief history of the development of the battery batteries used in most automobiles and lithium-ion batteries found in mobile consumer electronics. the voltaic pile prior to 1800, studies of electricity were limited to what could be achieved through collection and discharge of static electricity.6–8 while arcs with rather large voltages could be achieved, their application was limited by the small current and extremely short duration of the discharge.6 despite this limitation, the study of electrical phenomenon spanned from attempts to split water through electrolysis, to studies with frogs predating luigi galvani’s well-known work, to franklin’s famous lightning experiments.9–13 in march of 1800, alessandro volta (figure 2), professor of natural philosophy at the university of pavia in lombardy, italy, in a correspondence to joseph banks, president of the royal society of london, described a device which could provide a continuous supply of electrical power.8,14 this apparatus (figure 3), later known as the “voltaic pile” consisted of discs of tin or zinc paired with discs of copper, brass, or silver, with layers of water-soaked paper, fiber board, or leather between the disc pairs. wire contacts with the discs on the top and bottom of the pile allowed the experimenter access to a constant electric current. also included was a description of what volta termed a “crown of cups”, a series of what would modernly be described as simple wet cells.14 discharging volta’s pile resulted in visible corrosion occurring on the zinc (or tin) discs, the result of oxidation of the anode. a slight corrosion was also sometimes noted on the silver (or copper) cathode discs, but not to the same extent as seen on the anode. at the time this led him to believe the current was solely the result of the anodic reaction. considering it is now known that oxidation cannot occur without reduction, and with volta and others noting problematic polarization resulting from bubbles of hydrogen gas adhering to the electrode surfaces, it seems evident that the corresponding reduction process in volta’s pile was the reduction of hydrogen from water, as seen in the overall electrochemical reaction below. zn(s) + 2h2o(l) → zn2+(aq) + h2(g) + 2oh-(aq) it should be noted that the reduction process is often incorrectly attributed to reduction of the cathode material (half reactions seen below for silver and copper). however, this would require ions of the cathode material to be already present in order to occur. while it is possible some advantageous oxidized cathode material may figure 2. alessandro volta (1745-1827) (public domain). figure 3. volta’s crown of cups and several piles (public domain). 76 christopher l. heth76 christopher l. heth have been present, it is unlikely there would be enough to support much electric current out of the device. cu2+(aq) + 2 e→ cu(s) ag+ + e→ ag(s) volta’s description of his pile was quite complete and its design was elegant yet simple, allowing experimentalists to very quickly build replicas in their laboratories for application to their own work. volta in this same letter described experiments where he applied the leads from his pile to his lips and tongue, describing the results: in fact, once the circuit is closed in a convenient manner, one will excite simultaneously…a sensation of light in the eyes, a convulsion on the lips and even in the tongue, a painful prick at the point of the tongue, finally followed by a sensation of taste.15 impact of volta’s pile this new development had an almost immediate impact on the study of electricity. possibly due to hostilities between france and england at the time, volta sent the first four pages of the letter to banks in march, with the remainder sent several months later.8 as a result, volta’s letter was not formally read into the society until june 26, 1800.14 however, banks shared the contents of the first four pages with a number of the members of the society, allowing them to build devices for their own work prior to the paper’s reading. william nicholson specifically mentions these circumstances in his accounts of this new “electrical or galvanic apparatus” published in july, 1800, indicating he felt it proper to delay publication of his own work until volta’s entire paper had been read to the society.16 in this same paper, nicholson describes work he performed with anthony carlisle which included the electrolysis of water, with application of electric current for a period of 13 hours to produce 1.17 cubic inches of gas.16 this was a significant improvement in both yield and efficiency from earlier works using static discharge. for comparison, george pearson reported collecting one third of a cubic inch of gas utilizing over 14,600 static discharges.9 while times for that specific experiment are not given by pearson, based upon times given for other experiments in the same paper, the process likely took approximately 18 hours to complete. later that same year, humphry davy produced isolated hydrogen and oxygen gases from samples of water in separate glasses using a voltaic pile, completing the circuit through his own body by inserting a finger in each glass of water.17 further advances rapidly followed. electrodeposition of metals was reported by nicholson and carlisle along with william cruickshank in england, and independently by j.w. ritter in bavaria in 1800.18–20 in 1805, ritter was reported to have developed a modified pile utilizing a single metal which could be charged, a precursor to the storage battery.21 humphry davy confirmed that charcoal could substituted for the wires connected to the pile (a phenomenon originally reported by volta), and is reported to have used charcoal to produce impressive sparks as early as 1802.22 by 1808, davy had used the voltaic pile to discover and isolate several of the alkali and alkaline-earth elements, including sodium, potassium, barium, calcium, strontium, and magnesium.23,24 eary improvements to the battery while undoubtedly a monumental improvement over static discharge collecting devices of the time, the voltaic pile was not without its imitations. the useful lifetime of the pile was limited, as corrosion of the metal discs, while a necessary result of the chemical processes driving the output, would occur quite rapidly and require the pile to be rebuilt.25 in addition, polarization of the electrodes would result in a decrease in output over time. within a year, numerous attempts to improve the voltaic pile were made. one such modification was the trough battery developed by cruickshank (figure 4).25 a grooved wooden trough was used, with soldered pairs of zinc and silver plates affixed in the grooves with rosin or wax to create a number of sealed chambers. these chambers were then filled with a solution of ammonium nitrate, effectively replacing the wetted paper discs of the pile with a fluid solution. this ensured a more ready supply of electrolyte at the surface of the plates, and allowed the plates to be more easily cleaned as corrosion occurred through treatment with hydrochloric acid solution.25 charles wilkinson modified cruickshank ’s trough battery, using wooden partitions instead of metal plates, and attached wires to separated zinc and copper plates, allowing the plates to be removed at the conclusion of the battery’s daily usage while leaving the electrolyte in the trough.26 wilkinson had previously noted the power of the device was not related to the contact area between the copper or silver plate and the zinc plate, and proposed an increase in available zinc surface area resulted in increased output.27 with the zinc and copper plates completely separated, wilkinson reported his plungetype device with four inch plates was the equal of a cruickshank-type trough battery with six inch plates.26 77energy on demand: 77energy on demand: a brief history of the development of the battery as previously mentioned, corrosion of the anode material was recognized to occur during discharge of a battery. however, corrosion would also occur, albeit more slowly, even when the battery was left idle or stored for a period of time. while removal of the anode metal from the electrolyte solution as seen in plungetype batteries was an effective means to halt this secondary corrosion, the two-fluid cell would prove to be another approach with historical significance.6 the daniell cell while aspects of a two-fluid cell had previously been described independently by becquerel and wach, the successful invention is generally credited to j. frederic daniell.6,28 in letters to michael faraday, daniell describes a cell composed of a copper cylinder with a membrane tube “formed of a part of the gullet of an ox” suspended by collars inside (figure 5).29–31 within the membrane was contained a zinc rod as well as a solution of either sulfuric acid or zinc sulfate, with the copper cylinder filled with a copper(ii) sulfate solution. additionally, a siphon tube was included to allow removal of saturated zinc sulfate solution from the bottom of the membrane tube. thus, fresh acid and copper(ii) sulfate could be added as needed. later other materials such as paper dividers or porous ceramic were used to separate the two solutions.6,32,33 the presence of copper ions in the outer solution, and the need to occasionally add copper(ii) sulfate to the cell, indicate the reduction reaction for the daniell cell was not hydrogen reduction as seen in the voltaic pile and the trough battery, but rather the reduction of copper ion, resulting in the following overall reaction. zn(s) + cu2+(aq) → zn2+(aq) + cu(s) one particularly noteworthy modification of the daniell cell was developed by william grove.34,35 while investigating the action of a mixture of nitric and hydrochloric (muriatic) acids on gold foil, he discovered connecting the gold foil to an isolated pool of nitric acid via a wire resulted in the dissolution of the gold foil.34 he also proposed that using nitric acid and an inactive cathode such as platinum in one chamber of a daniell cell, with a zinc anode in the other, should produce a greater electric current than the standard configuration.34 while nitric acid had been used as an electrolyte previously, this is believed to be the first time nitric acid was recognized as a cathodic reactant.6 the half reactions, as well as the combined overall redox reaction, can be seen below. oxidation: zn(s) → zn2+(aq) + 2 ereduction: 2 h+(aq) + 2 hno3(aq) + 2 e→ 2 h2o(l) + 2 no2(g) overall: zn(s) + 2 h+(aq) + 2 hno3(aq) → zn2+(aq) + 2 h2o(l) + 2 no2(g) further improvement of the grove cell occurred through the inclusion of carbon as an inert electrode material.6 while many investigators, including volta and davy, had already explored charcoal and graphfigure 4. 19th century illustration of a trough battery (public domain). figure 5. a drawing of a daniell cell. this later design utilizes a ceramic cell container and paper divider, with copper sheet and zinc rod electrodes. 78 christopher l. heth78 christopher l. heth ite for charge collection or as electrical conductors, it is robert bunsen who is commonly credited with initiating its widespread use in batteries.6 the replacement of the expensive platinum cathode with carbon helped reduce the cost of grove-type batteries, which undoubtedly increased their usage. however, the disadvantages inherent to the use of nitric acid were still present, particularly the production of noxious nitrogen oxides (no, n2o4). eventually oxidants other than nitric acid were explored, including chromic acid, permanganate, and chlorates, and modified grove cells were used for the next several decades for certain applications.6 however, the greatest value in both the daniell and grove cells may have been in laying the groundwork for what would eventually become the modern dry cell battery. toward the modern dry cell one significant downside to the cruickshank, daniell, and grove batteries, as well as their derivatives, was the need for liquid electrolytes, often times corrosive acid solutions. these solutions resulted in batteries that were quite heavy, prone to spillage if moved, and susceptible to messy leaks. this combination of factors was especially problematic for applications requiring a mobile source of power, such as on railroads, street cars, or eventually for carriage lighting. a significant step toward a solution to this problem occurred with the design of a cell by georges leclanché, patented in france in 1866.36 the leclanché cell continued to utilize a zinc rod as the anode, but made use of a porous ceramic pot filled with a mixture of manganese(iv) oxide and carbon with a carbon rod current collector as the cathode (figure 6). reduction of the manganese from +4 to +3 occurred at the cathode, and can be seen below.7 a solution of saturated ammonium chloride was used as the electrolyte.6 oxidation: zn(s) → zn2+(aq) + 2 ereduction: 2 h+(aq) + 2 mno2(s) + 2 e→ 2 mno(oh)(s) overall: zn(s) + 2 h+(aq) + 2 mno2(s) → zn2+(aq) + 2 mno(oh)(s) while still a wet cell, and thus still suffering from some of the same limitations of its predecessors, the elimination of acid served to improve the stability of the cell, and reduced the hazards associated with leaks and spills. unfortunately, current outputs were limited under prolonged use, with only a slight improvement over the daniell cell, possibly due to the limited redox availability of the mno2 residing in microdomains within the carbon matrix.6 as with the daniell and grove cells, the leclanché cell also served as an important stepping stone toward the eventual development of the dry cell battery. numerous attempts were made through the years to immobilize the electrolyte and create a “dry cell”, thus reducing or eliminating risk of leaking or spillage. volta’s original pile immobilized the electrolyte by absorbing it in paper or leather.14 attempts with other materials were reported, including starch pastes, sand, asbestos, wool, and gelatin.6,36 in 1887, carl gassner, jr. filed a patent in the united states outlining the use of zinc oxide mixed with plaster surrounding a mno2/c cathode inside a zinc cylinder, which served as both anode and cell container for a battery.37 while this approach was not particularly successful, likely due to extremely limited ion mobility within the solid plaster, it does bear a striking resemblance to the modern dry cell configuration. alkaline electrolytes were reported in a french patent in 1881, followed by a u.s. patent in 1883, by felix de lalande and georges chaperon, although it is likely the use of alkaline solutions was investigated far earlier.38 lalande and chaperon used caustic potash or caustic soda with zinc anodes and copper oxide as the cathode material to good effect, and in 1889 a manufacturing plant was producing alkaline zinc and copper oxide cells in the united states.38,39 figure 6. leclanché wet cell (public domain). 79energy on demand: 79energy on demand: a brief history of the development of the battery the modern alkaline battery can be considered a culmination of many of the advances described above, although 50 years would pass before its invention. a zinc casing serves as the anode as used by gassner. contained within the cell is a cathode composed of the carbon rod collector made popular by bunsen surrounded by a mno2/c paste similar to that found in the leclanché cell. a caustic soda paste serves as the electrolyte as described by de lalande and chaperon. the alkaline electrolyte and the cathode materials are separated with a layer of paper, reminiscent of the separators used in volta’s original pile. patents were granted for this configuration to lewis urry, paul marsal, and karl kordesch in 1947 in great britain, and in the united states over a decade later in 1960.40 one additional development to improve safety was the use of small amounts of mercury to suppress hydrogen gas production inside the cell which could cause the cell to rupture.41 due to the toxicity of mercury, its use eventually fell out of favor, and there is now a worldwide ban on the use of mercury in commercial batteries. lead-acid battery while ritter’s “charging pile” should be recognized as the first storage battery, its application did not gain traction at the time.21 the first widely utilized secondary battery was the lead-acid battery. the use of lead plates to store electrical charge was first described by w.j. sinsteden in 1854.42 however, it was gaston planté several years later who would develop a version which would be viable on a useful scale, although its usefulness was still limited and it could be considered to be ahead of its time.43 sinsteden, for unknown reasons, used lead plates to connect batteries to a voltammeter instead of using silver, platinum, or copper wires as was commonly done.42,43 he noted a small secondary current that could be measured, which increased with subsequent charge/ discharge cycles. he also noted the formation of lead oxides on one of the plates. planté looked at this phenomenon more closely, comparing the results of a number of different metals including aluminum, silver, copper, lead, iron, and gold.43 he also compared electrolyte acidified with sulfuric acid to other options. the modern lead-acid battery utilizes a series of cells, each containing a lead-alloy grid as one electrode, and a lead(iv) oxide-coated lead plate or grid as the other electrode (figure 7). the overall redox process results in both oxidation and reduction of lead, as seen below. pb(s) + pbo2(s) + 2h2so4(aq) → 2pbso4(s) + 2 h2o(l) the increased surface area of the lead grid allows for a greater current output than could be achieved using similar sized plates. a solution of 20-30% aqueous sulfuric acid serves as the electrolyte. a lt hough t he bat ter y was capable of being recharged, the technology needed to generate the current to efficiently charge it had not yet been developed, and as such the only way to recharge a lead acid battery was to exhaust a number of primary batteries such as daniell or grove cells. it wasn’t until the 1880’s when large scale electrical power production allowed storage batteries to flourish.6 even today, the lead-acid battery holds a worldwide market share of over $35 billion usd annually, with automotive batteries as the primary market.44 nickel storage batteries while the lead-acid battery was (and continues to be) quite serviceable for many static applications, its weight and acidic electrolyte made it less-than-ideal for more portable purposes. the first secondary battery to successfully compete with the lead-acid battery was developed by e.w. jungner. in a patent filed in his native sweden, jungner first described a nickel-iron cell in 1897, followed in 1901 by a patent replacing iron with cadmium.45,46 in 1901, thomas edison also obtained a united states patent for a nickel-iron secondary battery.47 it is unclear if edison was aware of the work of jungner at the time. owning to the lower density of nickel and cadmium (7.81 and 8.00 g/cm3, respectively) versus that of lead (10.66 g/cm3), these cells showed a significant decrease in weight when compared to their lead-acid counterparts.48 jungner also utilized an alkaline electrolyte rather than acid, which would eventually allow for dry cell development. however, mass production of nicd (sometimes figure 7. diagram of a lead-acid battery. 80 christopher l. heth80 christopher l. heth figure 8. intercalation of lithium ions. termed “nicad”) batteries did not occur until the middle of the 20th century, upon development of a means of dealing with gases that can be produced during the redox processes, allowing for creation of a completely sealed battery.49 while quite popular in the second half of the 20th century, nicd cells had several downsides. first, they were prone to memory effects, requiring a full discharge prior to recharging to avoid loss of charge capacity. additionally, the toxic nature of the cadmium cathode was a disposal concern, and in 2009 the european union prohibited their use in most applications.7 improvements to nicd batteries were investigated as early as the 1960’s. efforts to improve the capacity of the nickel hydroxide electrode through inclusion of didymium hydrate (a mixture of rare-earth oxides, primarily lanthanum and neodymium) were granted a united states patent in 1967.50 development of what would become known as nickel-metal hydride batteries occurred in the 1990’s, when stanford ovshinsky and coworkers expanded the scope of additives to include many rare-earth and transition metals.51,52 these additives allowed the cadmium cathode to be replaced with a nickel-metal alloy. these cathodes allowed for the storage and discharge of hydrogen (as hydride) through charge/discharge cycles, increasing the charge capacity and greatly reducing memory effects compared to standard nicd batteries.7 having led the work that directly allowed commercialization of nickel-metal hydride batteries, ovshinsky, a prolific inventor, is often referred to as the inventor of the nickel-metal hydride battery.53 the rise of lithium while zinc was the predominant anode material for almost two centuries, potential was seen for lithium as a replacement. lithium has a higher activity and a lower density than zinc, which would allow for lighter batteries with increased voltage output than zinc cells. gilbert lewis and frederick keys successfully measured the potential of the lithium electrode as early as 1913.54 unfortunately lithium, like the rest of the alkali metals, reacts with water, rendering it unusable with aqueous electrolytes. additionally, lithium metal reacts readily with atmospheric nitrogen at ambient temperatures to produce a surface coating of lithium nitride, generally with some amount of lithium oxide as well, thereby requires inconvenient inert atmosphere conditions to successfully work with lithium metal. in was not until 1965 when a patent for a secondary battery utilizing lithium (as well as sodium, potassium, magnesium, beryllium, and aluminum) was obtained, although the patent application was filed in 1961.55 an organic solvent with salts of the anode material is specified, avoiding the problems associated with aqueous electrolyte solutions. also mentioned are cathodes composed of redox-active organic polymers including polymers of quinones, sulfoxides, hydroxylamines, and azo compounds. another approach was described by d.a.j. swinkels in 1966, wherein a molten lithium chloride electrolyte was used.56 unfortunately, this system required a minimum operating temperature of 650 °c, making it impractical for widespread use. one practical application of lithium metal anodes was the lithium-iodine battery.57 its development had a significant positive impact in medicine, improving the performance of pacemakers implanted in cardiac patients by decreasing the weight and increasing the battery life compared to previous battery options of the time.58 while not necessarily a problem for pacemaker applications, the lithium-iodine battery was a primary battery, and could not be effectively recharged. with pure metal anodes, ions produced through oxidation upon discharge must be reduced and redeposited onto the anode when the cell is recharged. unfortunately, for several reasons, lithium often does not redeposit evenly on the electrode surface but instead can form dendrites which can grow to sufficient length to short circuit the cell.58 in the mid 1970’s, intercalation of ions, including lithium ions, into a host framework had been recognized and described.59 rather than relying upon a pure lithium metal electrode with the inherent risks associated with it, electrodes composed of materials capable of accepting lithium ion insertion within its solid structure (figure 8) were explored. attempts to develop cells based upon intercalating electrodes proceeded through the 1980’s.58 the most successful of these, which would form the basis for the lithium ion batteries now common, utilized a lithium cobalt oxide (licoo2) material developed by j.b. goodenough and coworkers in 1981.60 other materials were also found to support lithium ion insertion, including tis2, v4o10, and graphite.61 intercalating elec81energy on demand: 81energy on demand: a brief history of the development of the battery trodes are now commonly used for both the anode and the cathode in lithium ion batteries, with lithium ions shuttled between them during charge or discharge processes.62 conclusions as society relies more and more on portable electric power, there is little doubt that significant effort will be expended to further improve battery technology. the desire for increased charge capacity, better thermal stability, longer functional lifetimes with more charge/discharge cycles, faster recharge rates, and decreased size and mass will continue to drive exploration and innovation. for example, efforts are currently underway to improve the performance of gel electrolytes in lithium ion batteries for mobile electronics and electric automobiles. it seems likely that increased efforts to develop ultra-high capacity, large scale stationary batteries to store renewable energy sources such as wind and solar to stabilize a greener energy grid is also on the horizon. one can only guess at what alessandro volta would think if he were to see the impact his device ultimately had on the world. acknowledgments thanks to minot state university and the staff of the gordon b. olson library for assistance obtaining materials. thanks also to prof. seth c. rasmussen for valuable advice and encouragement. references 1. u.s. energy information administration, monthly energy review, u.s. doe, washington, dc, april 2019. 2. new oxford american dictionary, 3rd 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(eds.: a. stevenson, c.a. lindberg), oxford university press, new york, 2010. 3. b. franklin, franklin papers 1749, 3, 352. 4. k.b. oldham, j.c. myland, fundamentals of electrochemical science, academic press, san diego, ca, 1994. 5. a.j. bard, l.r. faulkner, electrochemical methods, 2nd ed., john wiley & sons, hoboken, nj, 2001. 6. g. w. heise in the primary battery, vol 1 (eds. g.w. heise, n.c. cahoon), john wiley & sons, new york, 1971, 1-58. 7. m. nentwich, b. störr, j. hanzig in electrochemical storage materials: from crystallography to manufacturing technology (t. leisegang, m. zschornak, h. stöcker), de gruyter, boston, ma, 2018, 41-74. 8. b. dibner, alessandro volta and the electric battery, franklin watts, new york, 1964. 9. g. pearson, philos. trans. r. soc. london 1779, 87, 142. 10. a. p. van troostwijk, j. r. deiman, obs. sur la phys. 1789, 35, 369. 11. h.a.m. snelders, ambix 1979, 26, 116. 12. a. stuart philos. trans. r. soc. london 1732, 37, 327. 13. b. franklin, franklin papers 1752, 4, 360. 14. a. volta, philos trans. r. soc. london 1800, 90, 403. 15. p.a. abetti, electr. eng. 1952, 71, 773. 16. w. nicholson, j. nat. philos. chem. arts 1800, 4, 179. 17. h. davy, j. nat. philos. chem. arts 1800, 5, 275. 18. w. nicholson, a. carlisle, w. cruickshank, philos. mag. 1800, 7, 337. 19. d. gilbert, ann. phys. 1800, 6, 470. 20. w.m. sudduth, the electrical decomposition of water: a case study in chemical and electrical science, university of oklahoma, united states, 1977. 21. j.w. ritter, philos. mag. 1805, 23, 51. 22. h. davy, j. nat. philos. chem. arts 1800, 5, 326. 23. h. davy, philos. trans. r. soc. london 1808, 98, 1. 24. h. davy, phil. trans. r. soc. london 1808, 98, 333. 25. w. cruickshank, j. nat. philos. chem. arts 1800, 4, 254. 26. c.h. wilkinson, philos. mag. 1807, 29, 243. 27. c.h. wilkinson, j. nat. philos. chem. arts 1804, 8, 1. 28. d. owen, ambix 2001, 48, 25. 29. j.f. daniell, philos. trans. r. soc. london 1836, 126, 107. 30. j.f. daniell, philos. trans. r. soc. london 1836, 126, 125. 31. j.f. daniell, philos. trans. r. soc. london 1837, 127, 141. 32. j.p. gassiot, philos. mag. iii 1838, 13, 436. 33. w. r. grove, philos. mag. iii 1838, 13, 430. 34. w. r. grove, philos. mag. iii 1839, 14, 388. 35. w. r. grove, philos. mag. iii 1839, 15, 287. 36. g. leclanché, 71865, 1866. 37. c.j. gassner, 373064, 1887. 38. f. de lalande, g. chaperon, 274110, 1883. 39. e.a. schumacher in the primary battery, vol 1 (eds. g.w. heise, n.c. cahoon), john wiley & sons, new york, 1971, 1-58. 40. p.a. marsal, k. kordesch, l.f. urry, 2960558, 1960. 41. s. ruben, 2422046, 1947. 82 christopher l. heth82 christopher l. heth 42. w.j. sinsteden, ann. der phys. und chemie 1854, 92, 1. 43. g. planté, the storage of electrical energy, whittaker, london, 1887. 44. g.j. may, a. davidson, b. monahov, j. energy storage 2018, 15, 145. 45. e.w. jungner, 8558, 1897. 46. e.w. jungner, 15567, 1901. 47. t.a. edison, 678722, 1901. 48. handbook of chemistry and physics, 79th ed (ed. d.r. lide), crc press, new york, 1998. 49. g. neumann, u. gottesmann, 2571927, 1951. 50. w.n.j. carson, 3311502, 1967. 51. s.r. ovshinsky, m.a. fetcenko, c. fierro, p.r. gifford, d.a. corrigan, p. benson, f.j. martin, 5523182, 1996. 52. s.r. ovshinsky, b. aladjov, s. venkatesan, b. tekkanat, m. vijan, h. wang, s.k. dhar, 2004/0175615a1, 2004. 53. available online, last accessed on 05/31/2019. 54. g.n. lewis, f.g. keyes, j. am. chem. soc. 1913, 35, 340. 55. s.w. mayer, d.e. mckenzie, 3185590, 1965. 56. d.a. swinkels, j. electrochem. soc. 1966, 113, 6. 57. j.b. phipps, t.g. hayes, p.m. skarstad, d.f. unereker, solid state ionics 1986, 18-19, 1073. 58. b. scrosati, j. solid state electrochem 2011, 15, 1623. 59. m.s. whittingham, prog. solid state chem. 1978, 12, 41. 60. k. mizushima, p.c. jones, p.j. wiseman, j.b. goodenough, solid state ionics 1981, 3-4, 171. 61. m.s. whittingham, proc. ieee 2012, 100, 1518. 62. m.s. whittingham, j. electrochem. soc. 1976, 123, 315. https://www.nytimes.com/2012/10/19/technology/stanford-ovshinsky-an-inventor-compared-to-edison-dies-at-89.html substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 3(2) suppl. 5: 59-77, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-193 citation: m. v. orna, m. fontani (2019) mendeleev’s “family:” the actinides. substantia 3(2) suppl. 5: 59-77. doi: 10.13128/substantia-193 copyright: © 2019 m. v. orna, m. fontani. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 1 chemsource, inc., 39 willow drive, new rochelle, ny 10805, usa 2 dipartimento di chimica “ugo schiff ”, università degli studi di firenze, via della lastruccia, 13 sesto fiorentino (fi) italy e-mail: maryvirginiaorna@gmail.com, marco.fontani@unifi.it abstract. when dmitri mendeleev laid out his ordered grid of the then-known elements in 1869, he could not have predicted the overwhelming and all-encompassing effect that his idea would have on scientific theory for the next 150 years. nevertheless, he knew, presciently and from the start that he had conceived and laid claim to a powerful predictive tool that would bring some kind of order to a seemingly random set of fundamental substances. it is not within the scope of this paper to detail how the thought currents of his day were converging, little by little, on the realization that the universe was an intrinsically ordered one, nor is it our purpose to award to mendeleev the title of sole “discoverer” of the periodic system. we wish merely to point out that he now occupies a well-deserved place within the system under the title of “mendelevium,” element 101, and that, by this attribution, he belongs to a special “family,” the actinides. how this family was uncovered, grew, and developed is the topic of this essay. keywords. discovery, fission, intergroup accommodation, priority, radioactivity. introduction one glance at any modern periodic table (figure 1) will superficially show that the actinides belong to a group of elements, from atomic numbers 89 to 103, that occupy the “southern plateau” offset from the main body of the periodic table and directly under the rare earths. how and why this “geography” came about is a tale to be told, fraught with both theoretical and experimental implications. the first caveat is that this form of the table is one that mendeleev himself never saw, nor even dreamed of. his table1 took form from a set of cards on which mendeleev had written the names and properties of all 63 of the then-known elements. arranging them in order of increasing atomic weight, many of which were erroneous, he began nevertheless to see a pattern.2 the genius of the arrangement was (1) spaces were presciently left open for presumed missing elements based upon obvious large gaps in atomic weights and physical properties; (2) anomalous pairs that threw the atomic weights out of order were retained in groups with similar valences instead; (3) as an afterthought, mendeleev flipped his chart 90 degrees to the right, giving us 60 mary virginia orna, marco fontani the arrangement that persists to this day. by acknowledging an implied motif known only to nature, he conferred a predictive quality on his table that bore fruit in the discovery of three of the missing elements within the following 20 years. his acceptance of the anomalous order of some elements left wiggle room for attempts to determine more accurate atomic weights and at the same time to allow this mystery to unfold into the discovery of isotopes many years later. his 90-degree “flip” eventually made the elemental groupings and trends in their properties more visible. since this first table appeared, more than 700 others have found their way into print.3 the table shown in figure 1 has headings with group numbers. group numbers have been a bone of contention for years, leading to confusion for both practicing chemists and for students. in 1983, the american chemical society decreed the now-familiar 18-column numbered sequence version4 and in 1988 the international union of pure and applied chemistry (iupac) followed suit, acknowledging that the system actually had been proposed as long ago as 1956 by stockholm chemistry professor arne ölander (1902-1984).5 over the course of the sixty years following mendeleev’s attempt,6 a series of discoveries were made that began to reveal the modern picture of the structure of the atom. in chronological order these were cathode rays, emission spectra, canal rays, x-rays, radioactivity, the electron, α, β, and γ rays, planck’s law, the photoelectric effect, the atomic nucleus, isotopes, bohr model of atomic structure, atomic number, and the neutron. it gradually became clear that the number of nuclear protons equaled the nuclear charge and conferred on each atom its unique identity. this allowed scientists to determine how many elements existed in nature, theoretically 92. it also allowed them to devise experiments to push the envelope beyond 92 – to actually create new elements by bombarding and combining existing atomic nuclei, thus expanding the original periodic table to 118 elements. the impact of these discoveries has changed the course of history. the story of debierne’s discovery, actinium, and the fourteen elements that follow it are the subject of this article. what are the actinides? “discovery is new beginning. it is the origin of new rules that supplement, or even supplant, the old…were there rules for discovery, then discoveries would be mere conclusions.”7 the history of the discovery of the actinides, the 15 elements that comprise the second f-block row of the present periodic table of the elements, is pepfigure 1. the standard medium-long form of the periodic table. 61mendeleev’s “family:” the actinides pered with rules: new rules, old rules transformed, new rules broken and remade – not necessarily by those doing the research, but often by nature itself. furthermore, if we consider the ways in which discoveries are made, they often fall into the categories of planned research, trial and error, or accidental discovery. add to this a creative and observing mind8 and you can encompass virtually all of the discoveries, and the methods used to further understand and gain more information about how the discovery can be exploited. it would be useful to analyze the following story for these characteristics for this is the discovery that set in motion the train of events that would expand and change the periodic table forever. as our exploration continues, we will discover that the actinides themselves, just like any family, have their share of rugged individuals, lawlessness, disruptive behavior, problem children, nonconformists, and law-abiding citizens. in 1896, henri becquerel (1852-1908) reported that the double sulfate of potassium and uranium, formulated by him as [so4(uo)k·h2o] using the superscript notation common at the time, emitted radiation capable of penetrating light-opaque paper to expose silver salts. he realized that the so-called phosphorescent material was emitting this radiation by its very nature and not because of becoming phosphorescent by exposure to light.9,10 subsequent work showed that the radiation could also penetrate thin sheets of aluminum and copper. becquerel realized at this stage that the radiation was analogous to the newly-discovered roentgen rays.11 five additional notes in the same volume of the journal follow the course of his further experiments to show, beyond doubt, that the radiation was spontaneous and due to the uranium component of the salt. this conclusion is succinctly summarized in becquerel’s nobel lecture: the phenomenon could be ascribed to a transformation of solar energy, like phosphorescence, but i soon recognized that the emission was independent of any familiar source of excitation...we were thus faced with a spontaneous phenomenon of a new order...[my experiments] showed that all uranium salts, whatever their origin, emitted radiation of the same type, [and] that this property was an atomic property connected with the element uranium.12 it was marie curie (1867-1934) who eventually named the new phenomenon “radioactivity.” radioactivity, discovered in a uranium salt, was to dominate the scientific, political, economic, and social scenes of the first half of the 20th century. and during that century, all the rest of the actinides were to be discovered. using radioactivity as the signature by which radioactive atoms could be detected, scientists began to bombard targets with particles such as α-particles and neutrons as they became available, and then to identify the products of these reactions. they gradually surpassed the limit of atomic number 92 imposed by nature to venture onto an unknown sea, not knowing where it would lead. so far, the journey has led to the discovery of 26 elements beyond uranium, completing the seventh row of the periodic table. this has involved massive amounts of funding, dedicated and persevering work on the part of genius-level individuals, and a surprising degree of international cooperation even during the cold war. it has led to spectacular discoveries, overturned assumptions and theories, and given glimpses of a nature full of unexpected surprises. a simple definition of the actinides is: the elements beginning with actinium, with atomic number 89, and ending with lawrencium, element number 103. none of these elements possesses a stable isotope; every actinide is radioactive with half-lives that vary from billions of years, like thorium, 232th, with a half-life of 1.41 × 1010 y, to microseconds, like polonium, 214po, with a half-life of 1.62 × 10-4 s. the electronic structures of the actinide elements are complicated and still a subject of both theoretical and experimental research, although the latter is hindered due to the nature and scarcity of the atoms being studied. they are thought to all have a 7s2 outer electronic configuration, with variable and irregular occupancy of the 5f and 6d subshells. table 1 lists these 15 elements (occupying about 12.7% of the periodic table) in order of atomic number. however, the chronology of discovery does not follow from this order. the first actinide to be discovered, in 1789 by martin heinrich klaproth (1743-1817), was uranium; a century later it was, as well, the first element recognized to be radioactive. klaproth’s alertness to detail accompanied by his pure love of science13 no doubt prepared him to recognize a new substance when he dissolved the mineral pitchblende in nitric acid, and then neutralized the solution with a strong base and observed the formation of a yellow precipitate. using the tried and true method of heating the precipitate in the presence of a reducing agent, he obtained a black powder that he took for the element, which he named uranium in honor of the newly-discovered planet, uranus.14 a glance at table 1 is quite informative regarding discovery. the first three actinides to be discovered were “lone wolf ” affairs: a single discoverer is named, and that brings us to the end of the 19th century. it is an entirely different matter for the entire 20th century: discovery is a team affair, often with long lists of multi62 mary virginia orna, marco fontani ple authors: we have entered the age of “big chemistry,” characterized by specialized and expensive equipment in a national laboratory. it is easy to see that the lawrence berkeley national laboratory (lbnl) exercised a monopoly on actinide discoveries, completing the list with element number 103, lawrencium, in 1961. the place of the actinides in the periodic table the modern periodic table is a grid consisting of seven rows (periods) and eighteen columns (groups). periods 6 and 7 exceed the 18-column model with thirty-two groups each in the long form, and two offset rows of fifteen elements each in the traditional, or mediumlong, configuration, used for convenience so that the table will fit on a normal printed page, as shown in figure 1. the grid, originally arranged in order of increasing atomic weights of the elements, is now arranged in order of increasing atomic number (the number of protons in the nucleus of an atom, often abbreviated z) in one dimension, and in order of similar chemical properties in the second dimension to form the groups. this grid actually defines the way electrons arrange themselves in atoms in terms of principal energy levels and sublevels that they occupy, the so-called s, p, d, and f blocks. not only has it brought order out of the chaos of so many elements with so many different properties, but it also functions as a theoretical tool, a “marvelous map of the whole geography of the elements.”15 the two rows offset as “footnotes” from the main body of the periodic table each consists of fifteen elements. the top row, from lanthanum (z = 57) to lutetium (z = 71), along with two elements in the main body of the table, scandium and yttrium, are termed the “rare earths.” the fifteen rare earths in the offset sit below yttrium with properties so similar to one another that the czech chemist, bohuslav brauner (1855-1935), once proposed that they should all occupy the same space.16 today, we take the placement of the actinides in the table for granted. however, initially, the first-discovered members of this group were placed in the main body of the table with actinium in the yttrium group, thorium under hafnium, protactinium under tantalum, and uranium under tungsten. any transuranium elements to be yet discovered were expected to fall into place to complete period 6, with the last element in the row, z = 104, fitting under radon. the differences in chemical properties between, say, tungsten and uranium, soon made this assumption untenable. it was alfred werner (1866-1919) who first suggested that the heavier elements beyond uratable 1. discovery of the actinides. atomic number symbol name/symbol discoverer date of discovery place of discovery 89 ac actinium a. debierne 1899 paris, france 90 th thorium j. j. berzelius 1829 stockholm, sweden 91 pa protactinium o. hahn, l. meitner, k. fajans f. soddy, j. a. cranston, a. fleck 1917 berlin, germany karlsruhe glasgow, scotland 92 u uranium m. h. klaproth 1789 berlin, germany 93 np neptunium e. mcmillan, p. abelson 1940 lbnl*, usa 94 pu plutonium g. t. seaborg, a. c. wahl, j. w. kennedy 1940 lbnl, usa 95 am americium g. t. seaborg, l. o. morgan, r. a. james, a. ghiorso 1944 lbnl, usa 96 cm curium g. t. seaborg, r. a. james, a. ghiorso 1944 lbnl, usa 97 bk berkelium s. g. thompson, a. ghiorso, g. t. seaborg 1949 lbnl, usa 98 cf californium s. g. thompson, k. street, jr., a. ghiorso, g. t. seaborg 1950 lbnl, usa 99 es einsteinium g. choppin, s. g. thompson, a. ghiorso, b. g. harvey 1952 lbnl, usa 100 fm fermium g. choppin, s. g. thompson, a. ghiorso, b. g. harvey 1952 lbnl, usa 101 md mendelevium g. choppin, s. g. thompson, a. ghiorso, b. g. harvey, g. t. seaborg 1955 lbnl, usa 102 no nobelium g. flerov & others 1958 jinr*, russia 103 lr lawrencium a. ghiorso, a. e. larsh, t. sikkeland, r. m. latimer 1961 lbnl, usa jinr, russia *lbnl = lawrence berkeley national laboratory; jinr = joint institute for nuclear research. 63mendeleev’s “family:” the actinides nium might need an intergroup accommodation similar to that of the rare earths.17 decades later, in 1940, when edwin mcmillan (1907-91) and philip abelson (1913-2004) discovered element 93, and shortly afterward, glenn seaborg (1912-99) and his team discovered element 94, they had a surprise waiting. chemical tests revealed that the properties of both new elements were more similar to those of uranium than to their supposed homologs, rhenium and osmium.18 at this point in the group’s struggle to place the new elements in the periodic table, its extreme utility became spectacularly evident as both a flexible and predictive theoretical tool: seaborg took up werner’s old idea and made it his own: “i began to believe it was correct to propose a second lanthanide-style series of elements …[starting]…with element number 89, actinium, the element directly below lanthanum in the periodic table. perhaps there was another inner electron shell being filled. this would make the series directly analogous to the lanthanides, which would make sense, but it would require a radical change in the periodic table…[i was told] that such an outlandish proposal would ruin my scientific reputation. fortunately, that was no deterrent because at the time i had no scientific reputation to lose.”19 so the initial stages of discovery of the transuranium elements gave rise to a reconfiguration of the periodic table. the two new elements were appropriately named neptunium and plutonium after the two planets that lay beyond uranus in the solar system. the rest of the actinides, as they were discovered, fell right into place under their rare earth homologs, and the transactinides, from atomic numbers 104 to 118 populated period 7 to its completion. it remains to be seen how the future treats the super-actinides beginning with atomic number 121. the pre-uranium actinides: actinium, protactinium, and thorium the discovery of thorium element number 90, thorium, was the first of this trio to be discovered in 1829. one of the most famous chemists of the time, jöns jacob berzelius (1779-1848), professor at the karolinska university, stockholm, in examining a curious mineral sent to him by jens esmark (1763-1839), a norwegian mineralogist, thought he could discern the presence of a new element. he isolated the impure metal by reducing its fluoride salt with elemental potassium, and named it thorium, after the scandinavian god, thor. the mineral subsequently was called thorite.20 in 1898, working independently, marie curie and gerhard c. schmidt (1865-1949) reported almost simultaneously that thorium, like uranium, was radioactive.21,22 the discovery of actinium seventy years were to pass before the announcement of the discovery of actinium (z = 89), the element that gives its name to the entire actinide series.23 parisian andré-louis debierne (1874-1949) began his studies at the école de physique et de chemie and began to study mineral chemistry following the death of his mentor, charles friedel (1832-99). welcomed into the curies’ laboratory, he began to treat the enormous quantities of pitchblende they supplied to him until he soon discovered a new element; he was one of the youngest chemists ever to do so.24 he called it actinium from the ancient greek word, aktinos, meaning beam or ray. the year 1913 was a landmark one for science: in that year h. g. j. moseley (1887-1915) conferred a number and identity on every atom by reason of its number of nuclear protons, and frederick soddy (1877-1956) discovered isotopes, atoms with differing neutron numbers in atoms with like atomic numbers. he also formulated the law of chemical displacement: α-emitters produce a daughter product two atomic numbers lower and β-emitters one atomic number higher. moseley’s work defined the list of elements still missing in the periodic table, namely elements 43, 61, 72, 75, 85, 87, and 91.25 soddy’s work solved the puzzle of the myriad of new “elements” spawned by radioactive decay and his chemical displacement law had predictive properties. all of these facts figured weightily in the discovery of protactinium over the period from 1913 to 1917. the discovery of protactinium the hunt was now on for the missing element 91. kasimir fajans (1887-1975) and ostwald helmuth göhring (1889-1915?) took up the challenge. fajans was the first to succeed in deciphering the radioactive decay cascade of 238u as the following: u1 α ux1 β ux2 β uii α io [eq. 1] which translates in modern terminology to: 238u α 234th β 234pam β 234u α 230th [eq. 2] they found that the substance ux2, a β-emitter with a very short half-life of about one minute, did not correspond to any radioisotope already known, realizing that 64 mary virginia orna, marco fontani it should occupy a vacant space in the periodic table. due to its short half-life, they named this new element brevium. soon after fajans’s announcement, otto hahn (18791968) and lise meitner (1878-1968), working in berlin, began to search for longer-lived isotopes of this same element. hampered by the outbreak of world war i, especially by hahn’s conscription, meitner carried on alone with a miniscule sample (21 g) of pitchblende, doing preliminary separations. it was only a year later that she received a kilogram sample of radioactive salts from which she was able to isolate an isotope of element 23191 with a half-life of about 32,700 y.26 they named it protoactinium (later changed to protactinium by iupac in 1949), recognizing it as the mother substance of actinium. in june of that same year, frederick soddy and his young student, john arnold cranston (1891-1972), published the results27 of their heat treatments of pitchblende that yielded small sublimated amounts of protactinium for which they were unable to characterize the decay scheme. obviously, the case of protactinium, with multiple publications claiming priority over a period of several years, was a complicated one. eventually the priority was awarded, by custom, to the team that had discovered the isotope with the longest half-life, hahn and meitner,28 but not without dealing delicately with the aggressive character and imperious temperament of kasimir fajans, who eventually withdrew his claim.29 cranston and soddy, having published their papers three months after those of hahn and meitner, immediately recognized their priority.30,31 while it is beyond the scope of this paper to single out one element on which to discourse on chemical properties, we beg this little exception. because protactinium’s electron configuration is such that an energy crossover between its 6d and 5f orbitals results in nearly degenerate states, its bonding characteristics deviate drastically from its neighboring actinides. for this reason, protactinium’s chemistry has been described as puzzling, peculiar, mysterious, and even smacking of witchcraft!32 this little protactinium story was told at some length because it presages the multiple contentious priority disputes to follow: who gets the recognition for the discovery, and who gets to name the new element? the naming, in the end, came to be the most controversial issue, for as paleobotanist hope jahren (b. 1969) observes: the scientific rights to naming a new species, a new mineral, a new atomic particle, a new compound, or a new galaxy are considered the highest honor and the grandest task to which any scientist may aspire.33 discovery of uranium fission enrico fermi’s neutron bombardment experiments the facts that uranium was discovered in 1789 and its radioactivity was recognized in 1896 seem almost trivial in light of the shattering discovery of its most important, and most all-encompassing property: its ability to undergo nuclear fission with the consequent release of immense amounts of energy. this property was undreamed of, and in fact dismissed, when enrico fermi (1901-54) and his team, the legendary “ragazzi di via panisperna,” began to bombard uranium with neutrons. fermi, convinced that knowledge of the atom was in large part complete, decided to investigate the properties of the atomic nucleus. he was one of the first to recognize the tremendous importance of artificial radioactivity, discovered by frédéric joliot (1900-58) and irène joliot-curie (1897-1956), and for which they received the nobel prize in chemistry in 1935.34 not possessing a cyclotron, and therefore lacking sufficient irradiated material, he decided to attack the atom with neutrons, discovered only two years previously by james chadwick (1891-1974), instead of with α-particles. since neutrons had no electric charge, fermi reasoned, they would not be repulsed by the nuclear charge and might easily penetrate the nucleus itself. but since neutrons are not spontaneously emitted by radioactive isotopes, he had to obtain them by bombarding lighter elements, like beryllium, with α-particles emitted by natural substances, like radium. the neutron yield was low: just one per every 100,000 α-particles emitted, but undeterred, fermi personally built the detectors necessary for counting atomic disintegrations. success only came when, after bombarding all the lighter elements, fluorine and aluminum exhibited neutron-induced radiation.35 after that, the list of nuclei susceptible to neutron irradiation grew.36, 37, 38 seven months later, in october, fermi announced a second crucial discovery: the braking effect of hydrogenous substances, like water, on the radioactivity induced by neutrons. this amounted to the first step towards the utilization of nuclear energy. meanwhile at rome, fermi procured a very precious treasure, 1.6 grams of radium chloride from which he could extract emanation (or radon) that would be necessary for the production of neutrons. further work by fermi and his team led to seemingly two new elements with atomic numbers 93 and 9439 due to neutron absorption by 238u, and subsequent double-β-emission according to the following schemes: 239u 23993 + β 23994 + β[eq. 3] 65mendeleev’s “family:” the actinides radiochemical tests showed that the activity of 239u produced particles with properties that did not belong to any elements that preceded them in the periodic table. believed to be eka-rhenium and eka-iridium, they were placed in period 7 of the table. criticism of the fermi group’s interpretation of results the fermi group’s announcement raised sharp criticism in scientific circles. in addition to the two “transuranic elements” they thought they had identified, they had found a good half-dozen others with a variety of chemical properties difficult to place in the periodic table since they had to be untangled from uranium’s ongoing normal decay producing its own short-lived daughter products.40 in fact, a chemist at the university of fribourg, ida tacke noddack (1896-1978), criticized fermi’s experimental judgment in only searching for elements in the neighborhood of element 92. she said that all elements should be searched for, even lighter ones. she did not hesitate to declare that she strongly doubted that the products fermi identified were transuranium elements, but suggested nuclear fission instead.41 this idea was unacceptable in the physics world, deemed highly speculative and lacking a theoretical basis. “everyone knew” that atoms just did not fly apart in such a manner! things remained unresolved. a year later, otto hahn and lise meitner repeated fermi’s experiments using better facilities and they confirmed fermi’s results. furthermore, according to them, they were also able to observe traces of elements 95, 96 and 97 that they provisionally called eka-iridium, eka-platinum, and ekaaurum.42 however, as time went on, irène joliot-curie and her yugoslavian co-worker, pavle savić (1909-1994), published some papers documenting their concentration on only one of the products of neutron irradiation, that with a half-life of 3.5 hours, and after a few false starts conclusively stated that the product in question strangely resembled lanthanum, an already known element lodged in the middle of the periodic table. however, they never declared that they had actually found lanthanum, only a possible transuranic element that resembled lanthanum!43, 44 they could not imagine that they actually had lanthanum. reality was hidden in plain sight! fission at last! the last of these papers made hahn sit up and take notice: perhaps the almost forgotten suggestion by ida noddack was right after all. so later in 1938, after more experimentation and re-thinking, hahn and his colleague fritz strassmann (1902-80) finally admitted that, as chemists, they realized they were dealing with radiobarium and radiolanthanum, but as physicists they added, “we cannot bring ourselves to take such a drastic step, which goes against all previous laws (a word that hahn later changed to “experiences”) of nuclear physics.”45 hahn communicated his conclusions by letter to lise meitner who was in exile in sweden, fleeing the nazi racial persecution, and she, with her nephew otto frisch (1904-79), in their famous walk in the woods, worked out a theory whereby the positive charge of the uranium nucleus was large enough to overcome the effect of the nuclear surface tension almost completely, allowing the nucleus to fall apart at the slightest provocation. they also worked out the fact that the mass loss on nuclear division would be about one-fifth the mass of a proton, exactly equivalent to the correct and enormous energy predicted by albert einstein’s (1879-1955) relationship, e = mc2.46, 47 meanwhile, enrico fermi had already received his nobel prize in physics for 1938, awarded for his demonstrations of the existence of new radioactive elements produced by neutron irradiation, and for his related discovery of nuclear reactions brought about by slow neutrons.”48 the citation is very cautious in using the words “new radioactive elements,” initially interpreted erroneously by fermi as transuranium elements. but in the light of subsequent interpretations, he had actually discovered nuclear fission without knowing it, and actually produced new radioactive isotopes of elements previously known! the impact of uranium fission on the modern world by the irony of fate (or, some would say, of blindness), enrico fermi, in looking for transuranium elements, found nuclear fission. at the about the same time, physicist paul scherrer (1890-1969), working in zurich, had an even closer encounter with fission. he bombarded thorium…with neutrons and saw the fission fragments that meitner and frisch had identified. but scherrer wouldn’t believe his eyes. he thought his geiger counter was malfunctioning. what wasn’t expected wasn’t seen.49 fermi, working in fascist rome in 1933, or scherrer working in switzerland, could have handed (or have seized from them) the information the nazis would need 66 mary virginia orna, marco fontani to build a super-weapon six years earlier than the actual recognition of fission and its potential had they realized the evidence that was right before their eyes. their “slight oversights” had a profound and beneficial effect on the rest of the world. when word of the reality of nuclear fission broke upon the world, niels bohr (1885-1962) in copenhagen struck his head with his fist and exclaimed. “oh, what fools we were that we did not see this before.”50 and in paris, irène joliot-curie cried out, “what fools we were!”51 in 1941, just two years after the discovery of fission, hans von halban (1908-64) and lew kowarski (190779), two french exiles from the curie institute working in cambridge but under the mentorship of frédéric joliot in france, were the first to establish that it was possible to sustain a chain reaction starting with uranium.52 simultaneously, two other cambridge physicists, norman feather (1904-78) and egon bretscher (1901-73), hypothesized that the chain reaction could have military applications. by now it was recognized that the fissionable nucleus was the 235u isotope of element 92, only seven parts in 1,000 in naturally occurring uranium. they also hypothesized that the more abundant isotope, 238u, could be transmuted by neutron absorption into a new, hitherto unknown, element which would not only be fissionable, but would also have a long half-life according to a pathway almost identical to eq. 3: 238u + n 239u 23993 + β 23994 + β[eq. 4] what would follow from these discoveries was an international race for the ultimate weapon carried on in wartime under the shroud of utmost secrecy. although research on the peaceful uses of atomic energy was also on the docket, it had low priority when it came to building the atom bomb. heavy water, deemed essential for the propagation of a chain reaction due to its moderating (slowing down) properties on neutrons, was in short supply. the largest production plant, norsk hydro, was in the hands of nazi germany. although many top scientists abhorred the idea of such a weapon, the allied governments knew that they could not allow germany to beat them in the race and use this weapon for world domination. as frederick soddy remarked presciently in 1904: the man who put his hand on the lever by which a parsimonious nature regulates so jealously the output of this store of energy would possess a weapon by which he could destroy the earth if he chose.53 the berkeley hegemony to understand how the university of california at berkeley eventually became the epicenter of discovery of the transuranium elements, it is necessary to describe some institutional facilities and historical events that came together to form a collaborative whole which led to the completion of the actinide series at this single and unique location. the invention of the cyclotron it is often said that the three landmark scientific inventions that gave the impetus to discovery of new elements, in chronological order, were the voltaic pile, the spectroscope, and the cyclotron. the voltaic pile, devised by alessandro volta (1745-1827), began the age of electricity, the energy source that drives the modern world, as well as the disciplines of electrodynamics and electromagnetism.54 its use by humphry davy (17781829) led to the discovery of numerous elements such as sodium, potassium, magnesium, calcium, strontium, barium, and boron. similarly, the spectroscope, invented by gustav kirchhoff (1824-87) and robert bunsen (1811-99), changed the face of analytical chemistry, making possible the myriad instruments available today for purposes as varied as archaeological characterizations and medical diagnoses.55 it also was the instrumental method in the discovery of thallium, indium, rubidium, and cesium. perhaps the cyclotron (see figure 2), invented in 1929 by ernest orlando lawrence (1901-58) and figure 2. m. stanley livingston (l) and ernest o. lawrence in front of the 27-inch cyclotron at the old radiation laboratory at the university of california, berkeley. 67mendeleev’s “family:” the actinides m. stanley livingston (1905-86), was the most prolific invention of all in terms of element discovery: 25 new elements and still counting! with his ever-larger and more powerful cyclotrons, lawrence pioneered what is now known as “big science,” an approach that required large and expensive instrumentation, teams of researchers, interdisciplinary (chemistry, medicine, engineering, physics) collaboration, and consequently, a rather complex bureaucracy. he not only probed and illuminated some of the darkest mysteries held by nature but also invented a new approach to the problem of studying nature. when lawrence traveled to the centers of science in europe during a belated “studienreise,” he was astounded at the groundbreaking discoveries european scientists, such as marie curie and ernest rutherford (1871-1937), were making with the most rudimentary equipment. he did not realize that high quality research and solid theoretical reasoning were the key to scientific advances – not necessarily glitzy equipment. as if to give the lie to the “small science” approach he had witnessed, lawrence experienced a seminal moment in 1929 when he read an article in the obscure archiv f ür elektrotechnik which outlined a general approach on how to accelerate ions. by 1930 he was up and running, empirical trial and error running ahead of theory as well, until he discovered the two fundamental principles that would make his ideas work: the “cyclotron principle,” as particles gain speed their paths spiral wider, and the “resonance principle,” that protons keep time with the oscillator even as they accelerate. putting these principles together accompanied by lots of hard work with prototypes eventually led to success.56 eventually, with his cyclotrons running around the clock, lawrence was a sort of overseer of workers, each one focused on bombarding only one element’s nucleus to see what secrets it would reveal. he attracted great talent and enormous funding with a panache that would soon attract a nobel prize, for physics, in 1939 with the citation: for the invention and development of the cyclotron and for results obtained with it, especially with regard to artificial radioactive elements.57 world-class theoreticians and experimentalists in 1912, gilbert newton (g. n.) lewis (1875-1946) moved from m.i.t. to take up the chairmanship of the chemistry department at berkeley, at that time viewed by the eastern establishment as a scientific backwater. of the five chemistry faculty in the department, lewis retained three and managed adroitly to purge the other two. he then began to populate the department with people of his choice beginning with joel hildebrand (1881-1983), kenneth pitzer (1914-97), and wendell latimer (1893-1955). some of his recruits went on to win nobel prizes, such as william giauque (18951982), willard libby (1908-80), melvin calvin (1911-97), and glenn seaborg. lewis imprinted his educational philosophy on his faculty: educate for chemical understanding and not rote learning. he required every faculty member to run undergraduate labs as part of their departmental duties; he promoted research, especially in physical chemistry, and eventually in nuclear chemistry. much of lewis’s own work, especially on thermodynamics, and acids and bases, is still taught in undergraduate courses today.58 gilman hall, the seat of berkeley’s chemistry department, was named a national historic chemical landmark by the american chemical society in 1997. across the road in the physics department, a similar trajectory was in progress: game-changing research, pioneer scientists, and world-class students. in addition to ernest lawrence, recruited from yale to run the radiation laboratory, such notables as emilio segrè (1905-89), owen chamberlain (1920-2006), j. robert oppenheimer (1904-67), charles townes (1915-2015), and luis alvarez (1911-88) were changing the world as we know it by their historic discoveries. what motivated the research? in addition to scientific curiosity and national pride, there were three other reasons for pursuing heavy ion research with a view to extending the periodic table. the first was to verify the validity of the perio dic table itself as a theoretical tool. by forming elements of higher atomic number one by one and by examining their chemical properties, one could see examples of the trends predicted for the naturally occurring elements among the artificial ones. the second reason was to reach the theoretically predicted “magic island of stability” in which, in the contest between half-life and spontaneous fission, half-life wins out. the third reason, which took pride of place during the years of world war ii, was military and commercial exploitation of atomic energy. 68 mary virginia orna, marco fontani the first transuranics: neptunium, plutonium, americium, curium, berkelium, and californium neptunium although it turned out to be upstaged by its longlived and f issile daughter, plutonium, neptunium remains the first synthetic transuranium element. it is somewhat ironic that it was discovered accidentally during an experiment to study nuclear fission. working with berkeley’s 37-inch cyclotron, edwin mcmillan bombarded uranium with neutrons and began to examine what he thought were the fission products. he detected two interesting ones, the first with a half-life of 2.3 d and the other with a half-life of 23 m. he was able to identify the latter as 239u, but the longer-lived product was puzzling. mcmillan, working later in partnership with philip abelson, realized that the isotope did not resemble any known element and that it had chemical properties similar to those of uranium. this was the first definitive proof that the new element, and presumably those to follow, would behave like the rare earths rather than its supposed homolog, rhenium, in the main body of the periodic table. theoretically interpreted, there was an inner 5f electron shell that was being filled in, with the outer shells remaining the same, thus explaining the similar chemical properties. they published their results immediately, but only later named it neptunium, after the next planet out in the solar system. since mcmillan and abelson were the only discoverers, there was no controversy over either the discovery or the name.59 element 94, about to make its debut, turned out to be completely unique. to appreciate its uniqueness, it is important to digress on two additional topics: a theoretical model of the atomic nucleus and the criteria for the discovery of new chemical elements. the liquid drop model ever since people began to believe in the existence of atoms, prior to dalton, as a matter of fact, the idea of an atom was that of an impenetrable, hard sphere. newton, in his treatise opticks expressed this model of the atom in this way: “it seems probable to me that god, in the beginning, form’d matter in solid, massy, impenetrable particles…even so hard as never to wear or to break into pieces, no ordinary power being able to divide what god himself made one.”60 with this model fixed in mind for centuries, it was a great break with tradition when, in the late 1920s, the theoretical physicist, george gamow (1904-68) advanced a simplified liquid-drop model of the nucleus; it was extended in the mid-1930s by wilfrid wefelmeier (1909-1945), a student at berlin-dahlem, who proposed the idea of a nonspherical lump, or kernwurst, with more exposed surface area to allow for the ejection of nuclear particles.61 otto frisch found this model helpful in determining the parameters of fissile (fissionable) nuclei, especially the concept of nuclear surface energy, es, as a stabilizing force which was crucial to understanding it. there are two antithetical forces that determine the conditions under which an atomic nucleus will be fissile: the coulomb energy, ecoul and the surface energy, es. the model predicts that when ecoul exceeds twice the value of es, a nucleus will undergo fission. when a liquid drop is perturbed by a little energy, it will just jiggle; there is a threshold energy that will engender a split between roughly two equal halves of the drop to give a bi-lobar, or dumbbell-shaped drop; applying the critical energy, ec, exceeds the threshold energy and results in fission. ec is directly proportional to the product of the atomic numbers of the separating nuclei, and inversely proportional to the sum of their radii. a potential energy vs. reaction coordinate diagram similar to those used to track ordinary chemical reactions (figure 3) can be used to illustrate this effect. as the mass number and atomic number increase, ec generally decreases, but since this is a complex term, other factors such as odd or even numbers of nucleons, also determine the value. table 2 illustrates this with some selected nuclei. since the isotope 235u is known to be fissile, any nuclides with ec values lower than 6.5 mev would also be fissile. figure 3. model illustrating conditions for nuclear fission.62 69mendeleev’s “family:” the actinides criteria for the discovery of new chemical elements now that it is evident that the periodic table can undergo expansion, it becomes necessary to define what forms of experimental proof must be offered to establish one’s claim to having discovered a new element. an international group of scientists identified these criteria in a 1979 paper drawing upon the experience of many members of the group.63 the most important criterion for asserting discovery is to confirm, without doubt, that the element possesses a unique atomic number, z, different from all other elements known. at the same time, it is not necessary to establish the mass number unless evidence for it is directly related to the means by which the atomic number was determined. establishing z can be done in a variety of ways, and preferably using multiple ways: chemical identification, which is an ideal proof if the chemical procedure is appropriate, such as ion-exchange adsorption and elution; identification of characteristic x-rays that accompany the new element’s decay, determination of the half-life, and measurement of the precise, unique energies of the emitted α-particles; or proof of a genetic decay relationship through an α-particle decay chain in which the isotope of the new element is identified by the observation of previously known decay products. these criteria would prove to be extremely important in adjudicating competing claims in the decades that followed. these criteria, despite the claim by neil rowley that physicists alone were responsible for expanding the periodic table beyond element 92,64 left room for either chemists or physicists to establish the identity of a new element. plutonium the creation of neptunium turned out to be the stepping-stone to plutonium. the team involved did not include abelson, who was only temporarily working at berkeley, nor mcmillan, who was called away for “war work,” although he received co-authorship on the first paper announcing the discovery. this time, using the radiation laboratory’s 60-inch cyclotron (referring to the diameter of the poles of the electromagnet), glenn seaborg, joseph w. kennedy (1916-57), and arthur c. wahl (1917-2006) bombarded uranium with deuterons (2h) and succeeded in replacing one of uranium’s neutrons with a proton to yield neptunium which in turn decayed by β-emission to yield an isotope of element 94 with a half-life of about 90 y: 238u + 2h 238np + 2 1n 23894 + β [eq. 5] this work was done in 1941, but was not published until 194665 due to wartime secrecy, in force at the time. the content of the paper is much understated since the researchers did not feel that they had sufficient proof to say they had discovered a new element. chemical characterization proved to be the most difficult part because the element was not susceptible to the ordinary oxidizing agents. they finally used the strongest oxidizing agent known, peroxydisulfate with a silver ion catalyst, and finally obtained proof that the material they had made was different from all other known elements.66 the isotope signaling the existence of plutonium for the first time, not yet named, was 238pu, which, due to its even number of protons and neutrons, was not fissile. the isotope of interest in this regard was 239pu which was identified and characterized as a nuclear energy source in the spring of 1941 – cloaked in secrecy due to the military potential of fission. however, microgram quantities, invisible and almost immeasurable, were all that could be produced after weeks of bombardment of a uranium target in the cyclotron. glenn seaborg estimated that at that rate, it would take 20,000 years to produce a kilogram of plutonium! on august 20, 1942, a several-microgram sample of plutonium was isolated and for the first time, a synthetic element was visible to the human eye. it was up to the physicists to figure out how to do a billion-fold scale-up, a task that got an excellent start by enrico fermi when he built the first atomic “pile” with 400 tons of graphite, 6 tons of elemental uranium, and 50 tons of uranium oxide. and it was up to the chemists to separate out purified plutonium from the many other products in the mix – a very daunting task that required not only perseverance but creativity and clever ideas in dealing with problems never encountered before. after u.s. scientists succeeded in producing enough 235u and 239pu to make the bombs that would eventually be dropped on hiroshima and nagasaki respectively, the world as a whole fell into a period of horror mixed with anger, recrimination, and reflection. russia stepped up its nuclear program and had a working bomb within a few years; other countries wanted to join the nuclear club immediately. it soon became apparent that this tertable 2. critical energies of some representative nuclei. nucleus 232th 238u 235u 233u 239pu ec 7.5 mev 7.0 mev 6.5 mev 6.0 mev 5.0 mev 70 mary virginia orna, marco fontani rible weapon of mass destruction was here to stay and everyone wanted it, if only to use it as a deterrent against aggression. it had “drastically reordered the global hierarchy after world war ii and continued to amplify some of the darker pulls of humanity: greed, vanity, xenophobia, arrogance, and a certain suicidal glee.”67 eventually terrorist groups and rogue states discovered that one did not need to do years of research to develop explosive fissile material – one only needed the black market to obtain some grams of uranium, perhaps slightly enriched in 235u, but not necessarily, to create a “dirty” bomb – one with the impact of an ordinary bomb that would scatter long-lived radioactive material over a wide area, rendering it uninhabitable for years, or perhaps centuries. no matter how this two-edged sword would be used in the future, it was clear that there was no turning back. actinide discoveries changed the course of history forever. americium and curium once the berkeley scientists had learned the trick of producing elements 93 and 94, they felt that numbers 95 and 96 would soon follow – but such was not the case. the working assumption was that these elements should behave chemically like plutonium, but it took two years of work for the team to realize that their assumptions were off base. any new element in the series, unlike plutonium, had a stable +3 oxidation state and could not be oxidized further. the breakthrough occurred in midsummer, 1944, when 239pu was bombarded with 32-mev helium ions: 239pu + 4he 24296 + 1n [eq. 6] the new element, 96, an α-emitter, was identified by detecting its decay daughter, 238pu with a half-life of 162.9 d. element 95 followed shortly thereafter, in late 1944 and early 1945, when the transplanted berkeley team, now working in chicago as part of the war effort, produced it by successive bombardment and neutron capture by 239pu, 239pu + 1n 240pu + γ [eq. 7] 240pu + 1n 241pu + γ [eq. 8] followed by βdecay to yield element 95 with a half-life of 432.7 y: 241pu 24195 + β[eq. 9] subsequent characterization of both elements determined that they chemically resembled their rare earth homologs, europium and gadolinium, named respectively in honor of the european continent and of the pioneer chemist, johan gadolin (1760-1852), who discovered the first rare earth element. so it was only deemed fitting that the two new elements be named americium, in honor of the american continents, and curium, in honor of marie and pierre curie, the pioneers of radioactivity.68 the existence of both of these elements was “published” informally in a most unusual way: in a question-and-answer session between glenn seaborg and a young participant on the nationally broadcast radio show, “the quiz kids.” berkelium and californium production of the next two elements was simple enough, although this depended upon a supply of fairly large amounts of americium and curium to use as targets. element 97 showed up in late 1949 as the product of α-particle bombardment of 241am: 241am + 4he 24397 + 2 1n [eq. 10] then in early 1950, bombardment of a few micrograms of 242cm with high-energy α-particles yielded element 98: 242cm + 4he 24598 + 1n [eq. 11] what makes these two elements unusual is that there was so little of them, estimated at under 10,000 atoms and with very short half-lives, that classical chemical means of identification could not be used. in each case, separation and detection methods had to be vastly improved, work that took years to develop. eventually, both elements were detected by ion-exchange techniques, a first in transuranium element methodology. naming these elements proceeded along the logical lines of naming americium and curium. element 97’s rare earth homolog was terbium, one of four elements named after the swedish hamlet near the ytterby mine, where the rare earth ores were first extracted. although by this time, berkeley was not exactly a hamlet, it seemed appropriate to name 97 after a town, and hence it became berkelium. the homolog for element 98, dysprosium, presented some difficulties. the name, meaning “difficult to get” in greek, was certainly also appropriate for 98. so in deciding to call element 98 californium, the researchers pointed out “that the searchers for another element (au) a century ago found it difficult to get to california.”69, 70 71mendeleev’s “family:” the actinides in 1950, a challenge from a russian group headed by a. p. znoyko (1907-1988) and v. i. semishin signaled that the lbnl was not alone in claiming discoveries among the actinides. the soviets claimed that they had the right to name element 97 on the basis of their prediction of its radioactive decay products, and proposed calling it mendelevium in honor of the father of the periodic table.71 although their “discovery by speculation” was rejected as having no merit, the americans realized that they were no longer the only players in the field. einsteinium and fermium: children of a blast elements 99 and 100 burst on the scene “full blown from the head of zeus,” so to speak.72 both were unexpectedly found in debris from a thermonuclear blast that took place at the eniwetok atoll in the pacific in late 1952. this incredible unplanned event73 revealed that uranium was capable of absorbing numerous neutrons when subjected to a high enough neutron flux. scientists immediately began searching the debris for transcalifornium elements and immediately found element 99, 25399, an α-emitter with a half-life of 20 d. a few weeks later, element 100 appeared in the coral that had been mined from the test site in sufficient quantity to identify such a short-lived isotope: 255100, an α-emitter with a halflife of 22 h. the method of identification once again was ion-exchange.74 75 subsequent to the initial discoveries, it was clear that the amounts found in the bomb debris were not sufficient, so scientists mined tons of coral reefs that surrounded the explosion site in a pilot-plant operation. credit for all this work goes to scientists participating in a large cooperative project at lbnl, argonne national laboratory (anl), and los alamos national laboratory (lanl). when it came time to name the elements, for element 99, the groups suggested the name einsteinium in honor of albert einstein, whose famous equation supplied the theory behind nuclear power. enrico fermi’s turn came and appropriately so since he had ushered in the atomic age. when he was on his deathbed suffering with stomach cancer, al ghiorso (1915-2010) failed to communicate directly his intention to name element 100 after him. in april, 1955, five months after fermi’s death, he wrote a letter to mrs. fermi conveying the good news.76 the two names were also a symbol of the openness of the research groups: any number of american scientists could have been chosen to be honored. although einstein and fermi were both american citizens, both had been naturalized from countries that were at war with the united states. in addition, these names did not come without a certain amount of discord. the lanl people pushed hard for recognition by suggesting the name losalium (after los alamos), among many others, and the argonne group proposed the name anlium (after their acronym, anl). many other suggestions came from other sites, even from places and publications that had nothing to do with the initial discoveries. a great deal of mediation was required to settle the matter, a premonition of the naming rights and priority disputes that would occur with virtually every other element soon to be discovered. the halcyon days of lbnl would soon be over. another ending of consequence was the fact that fermium would be the last element that it was possible to synthesize by utilizing neutron capture reactions. it was also clear that if fermium could only be produced in the amount of about 200 atoms; the heavier elements soon to come would require much more than large neutron fluxes or small particle bombardment of a given target. it would soon be necessary to devise reactions using heavier bombarding particles and to produce larger quantities of target material in order to move beyond the necessity of characterizing newer elements one atom at a time. and ever more powerful accelerators! the first transfermium elements or the last of the actinides: mendelevium, nobelium, and lawrencium mendelevium a first for mendelevium, element 101, was its production and identification one atom at a time. the exciting story is told in the first person by the discovery team of albert ghiorso, bernard g. harvey (1919-2016), gregory r. choppin (1927-2015), and stanley g. thompson (1912-76). they started out by bombarding element 99, einsteinium, with helium nuclei, producing element 101 plus a neutron: 253es + 4he 256101 + 1n [eq. 12] the target was very small, not more than about 3 x 109 atoms, and any atoms of element 101 formed were caught on a gold foil placed directly behind the target. once caught, a relay race of sorts took place: to first separate the one or two atoms of element 101 from the billions of atoms of einsteinium, and then to record the pulse of current from the detector as the atom decayed – all within about a half-hour, which was the estimated half-life of the isotope. the team remarked, 72 mary virginia orna, marco fontani it is typical of these elusive heavy elements that we cannot positively identify an atom until the moment that it ceases to be that element and disintegrates into something else. it’s rather like the man who only counts his money as he spends it. they continued, in the first experiment, we waited more than an hour before the pen shot to mid-scale and dropped back, marking a line that meant the disintegration of the first known atom of mendelevium. since this was quite an event…we connected a fire bell in the hallway to the counters so that the alarm would go off every time an atom of element 101 disintegrated. this was a most effective way of signaling the occurrence of a nuclear event, but quieter means of communication were soon substituted, following a suggestion put forth by the fire department. we found only about one atom of mendelevium in each of our first experiments, we repeated the experiment perhaps a dozen times, and our grand total was seventeen atoms of the new element.77 we think mendeleev himself would have approved of the fire bell. surprisingly, mendelevium was a maverick in a group of well-behaved newcomers to the periodic table (also a mendeleev characteristic?). it exhibited electron capture, a process intuited by al ghiorso, and subsequently verified, which enabled the group to identify it by its fissile daughter, 256fm: 256md ec 256fm spontaneous fission [eq. 13] in naming the new element mendelevium, the discoverers had obviously revisited the reasons put forth by the russians five years earlier, but also proved to be very open and accommodating given the fact of the cold war. selecting a russian to be honored certainly went against the grain of conventional attitudes at the time, but it brought unexpected political capital as well. at the september 1958 atoms for peace conference in geneva, the french chemist moïse haïssinsky (1898-1976), who had often had combative disagreements with glenn seaborg, pulled him aside and confided in him that his choice of the name mendelevium did more for international relations than everything that the u.s. secretary of state had done in his entire career.78 the convoluted history of nobelium by 1956, in order to overcome the barrier presented by the small masses of bombarding particles used up to this time, only three particle accelerators able to accelerate heavy ions existed: lbnl, kurchatov institute in moscow (later jinr), and the nobel institute for physics, stockholm. all three were hard at work, and in that same year, a team in moscow led by georgy nikolayevich flerov (1913-90) produced element 102 by bombarding 241pu with 16o. they proposed naming the element joliotium after irène joliot-curie, although flerov himself noted that the data were inconclusive and thus not widely disseminated. then, in the following year, the nobel institute for physics, in collaboration with anl and the atomic energy research establishment, harwell, uk, announced the production of either 251102 or 253102 (they were not sure) by bombarding 244cm with 13c.79 they immediately proposed the name nobelium in honor of the great swedish philanthropist, alfred nobel (1833-96), and the name stuck because it received immediate approval by iupac. however, within the year, the group at lbnl were able to show that the swedish claim was erroneous and in new experiments reported success by fusing 244cm and 12c to produce 254102.80 now it was the soviets’ turn to disparage the lbnl results, claiming that they had erred in their half-life and isotope assignments, and therefore could not have produced element 102. and they continued to insist on their choice of name, joliotium. spurred by the criticism, the lbnl group re-examined their data and realized their errors. their revised analysis supported the data from the soviet group, but continued to agitate for “naming rights” even though they allowed that they would be satisfied with the name nobelium.81 the soviets ignored all the claims made and continued to insist on their rights. it should at this point be recognized that everyone involved in heavy ion nuclear research was feeling their way along a path that they were creating themselves. it is important to remember that the methods used for nuclear identification at this time were still being developed so that it was not unusual for mistakes of interpretation to be made by all groups working in the field.82 this standoff lasted for decades, prompted iupac to finally re-evaluate the discovery of all transfermium elements to date, and finally, in 1993, they attributed priority to the flerov group at jinr,83, 84 which had in the meanwhile published their own version of events.85 flerov and his group insisted that the expenditure of material and personal resources in the discovery of elements should result in the group’s right to name the discovery. they also criticized the make-up of the iupac committee, peopled with persons without the expertise to judge the validity of claims. they cited as well a lack 73mendeleev’s “family:” the actinides of objectivity in developing the criteria for judging the claims.86 lbnl stubbornly rejected the jinr objections and the iupac decision, but the berkeley hegemony was finally over. in retrospect, berkeley repeated the stock holm method for producing number 102 (244cm + 13c), using an identical reaction, and yet each group came up with different half-lives for what was presumably the same isotope. add to this mystery the fact that the stockholm group was assuming that 102 exhibited a preferred 3+ oxidation state, whereas in reality, it is more thermodynamically stable as the 2+ ion, so they would have missed it in their ion-exchange elution protocol.87 despite all the controversy, the one fixed fact is that the name nobelium is here to stay: in 1997, the iupac confirmed the name nobelium with the symbol no. lawrencium in 1958, lbnl lost its director and founder, ernest orlando lawrence, following a brief illness. it fell to glenn seaborg, who, by now, was chancellor of the university of california at berkeley, to select a new director. luis alvarez pre-empted seaborg’s choice by first, indicating that he was not a candidate, and secondly, that he would highly recommend edwin mcmillan for the post. seaborg happily accepted alvarez’s intervention, and mcmillan took over soon afterwards. a few years later, in 1961, element 103 was identified in the following fashion: about 3 μg of a mix of californium isotopes were bombarded with heavy ion beams of 10b and 11b at the berkeley hilac. an α-emitter with a half-life of 4.3 s due to 258103 was detected, and immediately named it lawrencium in the title of the publication announcing the discovery.88 the new element, given the symbol lw (later changed to lr by iupac), honored the inventor of the cyclotron, the machine that had led to the discovery of so many new elements. although the berkeley team was acknowledged as the discoverers, in 1965 the jinr at dubna identified the longest lived isotope, 256lr with a half-life of 28s, and established the genetic decay sequence as well. in its review of the decade-long efforts of both groups, and their substantial contributions to the correct identification and the properties of element 103, the transfermium working group (twg), in 1992, recommended that the two groups share credit for the discovery. it also reconfirmed the name, lawrencium, and the symbol, lr. some characteristics and uses of the actinides electronic structure of the actinide elements due to the radioactivity, toxicity, and lack of large numbers of sample atoms for many of these elements, theoretical calculations of atomic characteristics play an important role. however, due to spin-orbit and scalar relativistic effects, open-shell electronic structures, and likely covalent bonding of the 5f shells, among other considerations, ordinary crystal field calculations are unsuitable. the relativistic effects, particularly, are most important because the velocity of the electrons is directly proportional to increasing atomic number; these effects, in fact, overshadow the periodic trends that are characteristic of the lighter elements. ab initio quantum chemical calculations utilizing relativistic multireference wavefunctions can help enormously in understanding the actinide elements’ complicated electronic structures.89 actinides in medicine the use of radioactivity in medicine got its start when henri becquerel realized that uranium was capable of producing images on a photographic film. this discovery was almost simultaneous with the discovery of x-rays by wilhelm conrad röntgen (1845-1923) who, with them, produced an image of his wife’s left hand. thus, diagnostic imaging with high energy electromagnetic radiation became the first application of actinides in medicine. radiotherapy came next, both external, and internal by brachytherapy and targeted radionuclide therapy (trnt). the chief actinides in use were naturally occurring uranium and thorium and reactor-generated isotopes of actinium, thorium, and uranium, useful as radionuclide generators for the production of lighter elements such as 99mtc. cost and availability of the actinides severely limit development of their use in clinical applications.90 actinides in catalysis developments in organoactinide chemistry have spurred the use of these compounds as potential catalysts in areas calling for chemoselectivity on sterically demanding substrates. most catalytic studies have centered on th4+ and u4+, but u6+ has recently come into the limelight. one feature of organoactinides is the possibility of forming high coordination number complexes 74 mary virginia orna, marco fontani due to the large ionic radii of the actinides’ 5f orbitals. determination of bond disruption enthalpies to understand the thermodynamic factors responsible for catalytic turnover utilizing organoactinides has been found useful. this is a rapidly developing field.91 conclusion we can comfortably assert that the actinides and the rare earths share some similarities, both chemical and historical, but there are also some significant differences between the two groups. they are both set apart from the main body of the periodic table, chiefly for spatial convenience in accommodating their 4f and 5f orbital representations. they both take their group names, lanthanides and actinides, from the name of the first member of each group. four of the actinides, am, cm, bk, and cf, received names analogous to those of their lanthanide homologs, eu, gd, tb, and dy. discovery stories for both groups are peppered with priority disputes and contention over naming rights. however, we cannot discern many other points of likeness. it took almost 150 years to discover all of the rare earths; if we exclude uranium and thorium, the completion of “mendeleev’s family” took only 40 years of purpose-driven research. historically, we observe that the american contribution to lanthanide discoveries was marginal, as in the case charles james (1880-1928),92,93 and if not even fallacious, as in the case of john lawrence smith (18181883).94 on the contrary, with respect to the actinides, the american laboratories exercised a hegemony for several decades that was not easily challenged. using the enormous resources of their federal budget, they invented new ways of producing and identifying radioisotopes, resulting in almost routine new element discovery every couple of years. eventually, their absolute domination of the field crumbled in the face of russian, swedish, japanese and german expertise, ushering in a new age of collaboration, rather than of competition. for mendeleev, a scientist who formed the nexus between ancient greek philosophy and the new 19th century discoveries, his periodic arrangement was a kantian “categorical imperative.” he was constrained to dismiss julius lothar meyer’s (1830-1895) notion of the unity of matter wherein all the elements were multiples of hydrogen (or possibly of some simpler entity) as simply a relic of classical thought.95 mendeleev based his own table on the idea of the “plurality of matter,” by which all the elements are different, and yet are connected. he recognized “the existence of multiple elements as the basis of material reality. he never accepted the idea of “prime matter” maintained by prout, and the possibility of reducing all the elements to a single element, hydrogen.”96 in his 1976 analysis of mendeleev’s thought,97 yuri solov’ev makes it clear that the exact formulation of the periodic law did not spring forth suddenly from mendeleev’s head (as from the “head of zeus”), but only after he had processed and clarified the fundamental concept of his system of the elements.98 he says that there can be no doubt that the fundamental content of the law (the principle of periodicity) was quite clear to mendeleev from february 17, 1869, and that it served as a guide to expand upon the system of the elements. by 1871, two fundamental concepts on the theory of periodicity had been definitively established and announced by mendeleev. he emphasized that “every natural law gains its particular scientific significance when it is possible to derive practical consequences from it, that is, logical conclusions that explain what has not yet been explained, pointing out phenomena unknown from the beginning, and above all by the possibility of carrying out controllable predictions by experiment.” the results of particular significance in the promulgation of the law was the prediction of the existence of “eka-aluminum” (gallium, discovered by boisbaudran in 1875), “eka-boron” (scandium, nilson, 1879) and “ekasilicon” (germanium, winkler, 1885). the discoveries of these elements, and first of all that of gallium, decisively changed the attitude of the scientific world with respect to the periodic system of the elements. in 1879, in his letter to g.a. quesneville,99 mendeleev had every right to affirm: “it is now evident that the periodic law leads to consequences that preceding systems did not dare to predict. at first there was only a scheme, a grouping according to determined facts, while the periodic law renders the facts subsidiary to itself as the principle, and aims at understanding more deeply the philosophical principle that governs the mysterious nature of the elements.” mendeleev states further “this trend is in the same category prout’s law, but with this essential difference: that prout’s law relies on mere numbers, whereas the periodic law draws its authority from a series of mechanical and philosophical laws which constitute the character and brilliance of the present impetus of the exact sciences.” he later stated that the periodic law is a direct outcome of a collection of experimental data and that experiment must take precedence above all else, seemingly a categorical dismissal of the idea of the unity of matter, an idea that comes not from experiment but from speculation.100 as mendeleev’s work marks the beginning of the modern chemical world, so the actinides mark the start75mendeleev’s “family:” the actinides ing point for the expansion of periodic table chemistry, whose end, even up to today, it seems impossible to fix with any certainty.101 this is a trajectory that doubly fascinates chemists: firstly as scientists, and secondly for the iconic meaning that the periodic table represents for them. as we have already demonstrated, the early actinides are a subgroup unique among the elements. all radioactive, some naturally occurring, and in great abundance, and many fissionable, they have been the backbone of the nuclear energy industry, both in war and in peace. but, as far as their chemistry is concerned, actinide research fell into the doldrums in the late 20th century. a surprisingly recent resurgence of interest in actinide chemistry can be attributed to the realization that nuclear power can help to curtail carbon emissions and understanding actinide chemistry is vital in dealing with nuclear waste. in addition, the lighter actinides are increasingly being scrutinized, as noted above, for possible catalytic and medical applications, especially in terms of indirectly delivering hard-to-get radioisotopes as part of their decay chain. the mid-actinides pose another problem: availability. unless more than a few milligrams of these cyclotron-produced elements can be available long enough for 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pp. 603-604. the accounts on these pages seem to give the reader the idea that lothar meyer is uncertain about the validity of prout’s law on the unity of matter, but is reluctant to dismiss it. 96. f. calascibetta, l’evoluzione delle idee di d. mendeleev rispetto all’ipotesi di prout, 1869-1889, in g. michelon, ed. atti del iv convegno nazionale di storia e fondamenti della chimica (venezia, 7-9 novembre 1991), accademia nazionale delle scienze detta dei xl, roma, 1991, pp. 301-312. authors’ translation. 97. d. i. mendeleev, periodičeskij zakon. osnovnye staťi. klassiki nauki, b. m. kedrov, ed., izd. an sssr, moscow, 1958, also published in german in zeitschrift für chemie, 1869, 12, 405. 98. y. solov’ev, l’evoluzione del pensiero chimico dal ‘600 ai giorni nostri, mondadori, milano, 1976, pp. 270271. authors’ translation. 99. d. i. mendeleev, le moniteur scientifique, 1879, 21, 691. authors’ translation. 100. d. mendeléeff, j. chem. soc. (london), 1889, 55, 634. 101. p. j. karol in elements old and new: discoveries, developments, challenges, and environmental implications (eds. m. a. benvenuto, t. williamson), american chemical society symposium series volume no. 1263, american chemical society, washington, dc, 2017, pp. 41-66. 102. m. peplow, chem. eng. news 2019, 97(9), 22. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna substantia. an international journal of the history of chemistry 3(2) suppl. 3: 57-63, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-546 citation: j. teixeira (2019) the puzzling problem of water properties at low temperature. an experimentalist view. substantia 3(2) suppl. 3: 57-63. doi: 10.13128/substantia-546 copyright: © 2019 j. teixeira. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. the puzzling problem of water properties at low temperature. an experimentalist view josé teixeira laboratoire léon brillouin (cea/cnrs) cea saclay 91191 gif-sur-yvette cedex france e-mail: jose.teixeira@cea.fr abstract. water is at once the most familiar substance, the one for which we have the most data, and a liquid with anomalous properties that make it unique. many theoretical models provide explanations for the abnormal behaviour of water. the most recent ones are based on numerical simulations of molecular dynamics made from effective potentials that reproduce the tetrahedral geometry of hydrogen bonds. from the experimental side, homogeneous nucleation of hexagonal ice limits the range of temperature accessible to experiments. there is therefore no experimental data at atmospheric pressure in a wide temperature range extending from the homogeneous nucleation temperature (230 k) to the glass transition (135 k). however, water anomalies are the most important in the supercooled domain. therefore, a large number of theoretical models, often based on extrapolations of data or analogies, have been developed without being able to be compared to non-existent experimental data. in all cases, the temperature domain where homogeneous nucleation takes place plays a crucial role in the anomalies observed at low temperature. here, we present shortly structural models that predict the existence of a low-temperature critical point and a liquid-liquid transition between two phases of different structures by comparing them with experimental data. other models are based on dynamic transitions or the existence of two types of relaxation, at the molecular and hydrogen bonding levels, which may correspond to two glass transitions. keywords. supercooled water, critical point, water anomalies, neutron scattering. introduction water is virtually the only natural liquid on the surface of the planet earth. the solid and vapour phases are present as well in large quantities, which is unique on earth and rare on other planets. the importance in the biosphere, the climate and many physical and chemical processes make water the best-known substance for which the most accurate data are available. however, at the level of the fundamental physics, water is an “anomalous liquid”, i.e. whose properties are very different from those of an “ideal” liquid described by the statistical physics. among the “anomalies” of the properties of liquid water are the wellknown lower density of the ice or the maximum density of the liquid at 58 josé teixeira about 4 °c even if, in reality, their banality is not currently associated with abnormal behaviour. indeed, it is at the molecular scale that it is difficult to explain why the ordered molecules in ice occupy a larger volume than in the disordered liquid state. essentially all the thermodynamic and transport properties of liquid water (compressibility, specific heat, viscosity…) depend anomalously on temperature and pressure, especially at low temperature. to find plausible models and explanations, it is therefore essential to study the properties of water at the lowest possible temperatures. measurements of the thermodynamic properties of water can be made below tm = 0 °c, the melting point of ice, since water, like other liquids, can remain liquid below the melting point as long as there are no nuclei that initiate the heterogeneous nucleation of ice. there is however a limit to this “supercooled” state, that of the homogeneous nucleation which, at atmospheric pressure, takes place at tn = 230 k = -43 °c. therefore, for many properties, we have measurements that extend to -25, sometimes -30 °c. in all cases, it is found that the anomalous behaviour accelerates as the temperature decreases. thus, the density decreases by 1.6 % between 4 °c and -30 °c while the decay is only 0.7 % in the same temperature interval between 4 °c and 38 °c. isothermal compressibility, specific heat and other properties have similar behaviour. figure 1 depicts the temperature dependence of isothermal compressibility at ambient pressure. there a minimum at 46 °c and an anomalous sharp increase on the low temperature side. numerical extrapolations are consistent with a divergence although the numerical values remain far from those measured near a critical point. to describe the properties of a liquid, semi-empirical equations of state based on numerical fits of the data are established. in the case of water, these equations of state lead to apparent divergences of several properties at temperatures a little below tn, which raises the problem of the existence or not of a true divergence, similar to that which one would observe near a critical point or a spinodal line. thus, for example, the remarkable equations of g.s. kell,1 which reproduces the density and the isothermal compressibility of water with an accuracy of 10-5 between -30 and 150 °c, but extrapolates to infinite for t = -56 °c and -51 °c, respectively. equations of state describe more accurately properties of liquid water in domains of temperature and pressure covered by experiment but their extrapolations cannot be reliable, i.e. several extrapolations are numerically compatible with existing data.2 in this context, one of the first conjectures 3 were based on fits of thermodynamic properties by power laws diverging at -42 °c, which postulated the existence of a re-entrant spinodal line that, passing through negative pressures would impose a stability limit in the liquid state at low temperature.4 despite the fact that formation of a glassy state by quenching does not exclude the existence of a re-entrant spinodal,5 the experiments of j. dubochet et al.6 showing that the amorphous state of water can be reached by rapid quenching of the liquid, that is to say crossing the region of the postulated spinodal line, had a great impact in discussions on extrapolations. the amorphous state obtained by quenching, glassy water, has a structure identical to that of the amorphous form obtained by deposition on a support at very low temperature. the glass transition temperature is of the order of 135 k, i.e. more than 100 °c below the supercooled domain accessible to the experiments. the temperature dependence in this vast temperature range, sometimes called “no man’s land”,7 is unknown. yet it is not trivial since the numerical divergences are only apparent. the “no man’s land” is therefore a territory of speculation! several models have been proposed to describe the temperature dependence of the properties of water, without ever reaching discriminant tests. figure 1. isothermal compressibility of liquid water at atmospheric pressure. there is a minimum at 46 °c. 59the puzzling problem of water properties at low temperature. an experimentalist view an experimental fact occupies an important place in the arguments developed on this temperature domain inaccessible to the experiment. this is the discovery in 1984 of a form of high-density amorphous (hda) ice,8 obtained by compression at very low temperature of the crystalline ice. its density (1.17 g.cm-3 at 77 k) is much higher than that of amorphous ice, which is obtained by quenching (0.94 g.cm-3 at 77 k, so close to that of ice). the structural study9 shows that interstitial sites between the first and second neighbours are occupied, which corresponds to strong distortions of the hydrogen bond network, probably due to the collapse of a network of very directional links as well as the weak coordination of the water molecules, barely higher than 4 in the liquid phase. following the discovery of hda ice, some models of supercooled water postulate the existence of a high density liquid that would correspond to the melting of hda ice, therefore to the existence of two forms of liquid water, having very different densities and structures, though similar to those of high and low density amorphous ice respectively.10 if, despite their metastability, the amorphous states are represented in a pseudo-phase diagram, the transition line separating the two forms of amorphous ices of different densities would be prolonged by a line separating the two liquids and a liquid-liquid transition would be the pendant of the transition between the two forms of amorphous ices. this idea consists to consider hda as a glass, just like the amorphous form of low density, lda is the glassy form of liquid water. the line of separation of the two liquid phases would end at a critical point where a certain number of thermodynamic properties would have a singular behaviour. this model is supported by the fact that some numerical simulations of the molecular dynamics of water do indeed predict the existence of one critical point at low temperature and high pressure. however, such numerical simulations are based on effective potentials that try to reproduce at best the thermodynamic properties and the molecular structure in a pressure and temperature range not too far from the ambient conditions.11 of the many potentials,12 st2 and tip4p potentials actually predict a singular behaviour of isothermal compressibility near a critical point around 200 k and 0.1 gpa, so deep inside the no man’s land.13 this critical point would be the extreme point of the transition line separating high and low density liquids, itself an extension of the line separating the two forms of amorphous ice, hda and lda, as mentioned above. it can therefore be seen either as a demixtion point of two liquids, or as a critical point identical to that, liquidvapour, on the high temperature side of the phase diagram of water. both interpretations exist in the literature. they correspond to different interpretations of certain structural measurements. in the context of the existence of a critical point at high pressure and low temperature, anomalies observed experimentally at atmospheric pressure and at low temperature are explained by another analytical extension of the same line of separation of liquid phases beyond the critical point, line often called “widom line”.14 as a result, the thermodynamic properties would only present “bumps” when crossing the widom line. a problem remains open: how to explain that the anomalies are reduced under pressure? concretely, starting from the ambient pressure side, a high pressure point of the phase diagram is closer to the critical point than another point at the same temperature and lower pressure. therefore, anomalies should be larger for the second point conditions, what is not the case. on the other hand, it is important to note that the widom line deduced from the numerical models almost coincides with the homogenous nucleation line of ice. other models neglect the structural aspects and postulate rather a dynamic transition taking place also in the same field of pressure and temperature, or near the homogeneous nucleation line. in this article, we discuss, in a non-exhaustive way, the consequences of the most popular models by comparing them with the experimental results available for supercooled water. mixture models the idea that liquid water can be a mixture of two liquids is not new. this is even one of the first conjectures formulated to explain the maximum density at 4 °c. w. röntgen in 1892 conjectured the existence of different types of water molecules.15 other mixing models have been proposed, including the elaborated one by g. némethy and h.a. scheraga,16 never confirmed by experience. mixing models envisage either different types of molecules,17 or molecular arrangements such as two types of dimers or pentamers18 or the coexistence of two liquids of very different structures and densities coexisting in the form of clusters, one of the two phases immersed in the second.19 all these models are hardly compatible with measurements of the structure of liquid water. indeed, the pair correlation function, g(r), shows the existence of a single very narrow peak at 2.8 å, representative of the 60 josé teixeira distance between close neighbours, perfectly defined by the intermolecular links.20 the existence of aggregates of different densities is equally incompatible with x-ray scattering measurements,21-22 which show that smallangle scattering is due solely to the number fluctuations at the origin of isothermal compressibility. moreover, the isothermal compressibility, so the small angle scattering of water, are very weak compared to those of other liquids. as well, if one limits oneself to the known thermodynamic data, it is impossible to explain the maximum of density or the minimum of compressibility by the mixture of two liquids whose density would differ by about 10%.23 about these models, one can note the ambiguity of the definition of the critical point at low temperature. if it is a demixing point, nucleation of one of the two phases should be detected but there would be no anomaly in the isothermal compressibility. in contrast, density fluctuations with increasing coherence length explain the increase in compressibility observed at low temperatures. in a recent experiment, x-ray and neutron scattering at very low temperature and high pressure24 measured the water-lithium chloride eutectic mixture. no anomalies were observed what excludes enhanced density fluctuations or nucleation of a distinct phase. therefore, solid polyamorphism does not imply liquid poly-amorphism. nevertheless, it is important to note that measurements made on aqueous solutions can only provide additional information on the behaviour of bulk water. indeed, the addition of small amounts of any solute decreases or eliminates abnormalities of pure water, as for example in the case of ethanol25 even in the presence of hydrogen bonds. in fact, the breaking of the tetrahedral structure is sufficient to make the behaviour of water similar to that of other associated liquids. the same applies to samples of water confined in small pores. there is a very significant reduction in the melting temperature, or even its suppression,26 but the thermodynamic anomalies are also suppressed. dynamic models in other approaches, the abnormal behaviour of water was attributed to purely dynamic transitions. thus, measurements of the molecular dynamics of hydration water on lysozyme protein,27 can be interpreted by a discontinuity of the temperature dependence of the relaxation time associated with diffusion. at high temperature this time varies very strongly with temperature (sometimes called “fragile” liquid behaviour) while at low temperature, the temperature dependence is of the arrhenius type (“strong” liquid). the fit of the experimental neutron quasi-elastic neutron scattering27 data sets the transition to 220 k at atmospheric pressure, so very close to the homogeneous nucleation temperature tn and the postulated widom line. this may actually correspond to a dynamic transition. in addition, the measurements made on samples of bulk water demonstrate the coexistence of two times characterizing the molecular dynamics, 28, 29 which depends on time in a very different way. the residence time, a measure of the time during which a molecule is inside the cage formed by neighbouring molecules, follows the anomalous temperature dependence of other transport properties, such as viscosity. a much shorter time, of the order of the ps, is related to the lifetime of the intermolecular bonds and its dependence of the temperature is of the arrhenius type even at the lowest temperatures accessible to this type of experiments, that is to say -20 °c. spin echo relaxation time measurements, with momentum transfers selected in order to be able to discriminate these two times,30 as well as measurements of the imaginary part of the susceptibility by x spectroscopy,31 also show the existence of two relaxation times. finally, it is remarkable that in the analysis of the quasielastic spectrum of neutrons on the melting line of the ice vii, one always finds this short time, which characterizes the dynamics of the hydrogen bonds.32 the strong directionality of the intermolecular potential due to the hydrogen bonds is at the origin of a very short life time if one takes into account the energy, which is of the order of 8 kj / mol, thus greater than 1000 k. we speak here of the time during which a hydrogen atom remains inside the cone where the bond can be established, whose opening is of the order of 30°. this is the time of allegiance defined by f. stillinger.33,34 otherwise, a bond can break and reform between the same neighbouring molecules. this often happens at low temperatures when the number of “intact” hydrogen bonds is very large, which generates a gel-like structure with residence times that increase very rapidly with temperature. figure 2 shows the residence times and lifetime of the hydrogen bonds as a function of temperature in a arrhenius plot. the apparent divergence of the first should correspond to the formation of a macroscopic gel. yet, as we have seen, the homogenous nucleation of ice takes place around -43 °c, when the liquid is still very fluid. in addition, the structure of the supercooled liquid changes rapidly as the temperature decreases. it is remarkable that, also towards -25 °c, the position of the first peak of the structure function, s(k), decreases approaching that of the amorphous ice.35 this means 61the puzzling problem of water properties at low temperature. an experimentalist view that, between this limit temperature of possible measurements and tg, thus in all the extension of the no man’s land, there is practically no structural changes. only hydrogen bonds maintain a fast dynamic over this wide temperature range because of the smooth arrhenius temperature dependence of its characteristic time. this amounts to admitting the existence of two glass transitions. the first, occurring near -43°c, corresponds to the arrest of the molecular diffusion. indeed, the structure measured at the lowest accessible temperatures (-30 °c) is practically identical to that of the low-density amorphous ice, lda, however 100 ° above tg.35 near the homogeneous nucleation temperature, it is the hydrogen bonds, which keep a sufficiently fast dynamic to prevent the formation of the amorphous phase. between tn and tg, small displacements of the hydrogen atoms are sufficient to form the crystalline phase. it is only at 135 k that the hydrogen bonds are frozen and that the lda phase is formed with a small change of enthalpy. this type of behaviour is the analogue of the alpha and beta dynamics that characterize the dynamics of many polymers. however, in the case of water, it is the beta dynamics, that of the hydrogen bonds, that determines the thermodynamic properties and the existence of a vast no man’s land. it remains to explain the existence of several amorphous phases, including that of high density (hda) that can be obtained by compression of hexagonal ice or compression of low-density amorphous ice (lda). on the one hand, there is not exactly one line of coexistence of these two forms of amorphous ice. in fact, one goes from lda to hda only by compression, while the transition hda towards lda results from the heating of hda above 120 k. thus, hda is stable at atmospheric pressure if the temperature is sufficiently low. more important is the question of whether there is a liquid with the hda ice structure, i.e. if hda is a symmetrical glass of glass having the lda structure. recent results of c.a. tulk et al.36 show that hda is rather a kinetically arrested transformation between lowdensity ice i and high-density ice xv. as a result, the water anomalies must actually go through bumps near the temperature tn of nucleation of ice. for example, the compressibility must reach a maximum value towards tn and remain practically constant between tn and tg. therefore, the line that defines the homogeneous nucleation in the plane (p, t) plays a capital role, formally analogous to that of line widom but in the absence of a critical point and liquid-liquid transition. as far as compressibility is concerned, one can try to evaluate a coherence length of density fluctuations. there is no exact method to do this because it is a very small effect but we can say that it is a very small value, certainly less than 1 nm21,37 which can be explained by the formation of the gel phase. this does not exclude the fact that, in certain situations of confinement, water can have a high apparent density. this is the case of hydration water at hydrophilic sites of proteins.38 conclusion from the large amount of data available, it can be said that liquid water is a homogeneous liquid at all temperatures and pressures. the various theories that have been proposed agree on the existence of anomalies of the temperature dependence of most thermodynamic and transport properties near the line that defines the nucleation of hexagonal ice, i.e. around -43 °c at atmospheric pressure. computer simulations of molecular dynamics predict divergences in response properties, including isothermal compressibility and specific heat. two actual potentials even foresee the existence of a critical point situated towards 200 k and a few kbar of pressure, in spite of the fact that the anomalies of the water at ambient temperature decrease quickly under pressure. given the intrinsic difficulty of entering the “no man’s land”, it is possible that extrapolations, analogies and speculations continue to be made on the behaviour of deeply supercooled liquid water. nevertheless, recent figure 2. schematic representation of the two times that characterize dynamics of liquid water. squares represent experimental evaluations of the molecular residence time showing the anomalous super-arrhenius temperature dependence. the red line is an extrapolation of the hydrogen bond lifetime evaluated at temperatures above -20 °c.28 tm, th ang tg are the melting, homogeneous nucleation and glass transition temperatures, respectively. 62 josé teixeira results show that high-density amorphous ice is not a glass, what eliminates the possibility of a high density liquid. also, the consideration of two characteristic times (that of the molecular dynamics and the one of the hydrogen bonding) makes it possible to reach relatively classical explanations of the unusual behaviour of the water. probably, future studies should look more in detail at the nature of the hydrogen bond, which implies approaches beyond the thermodynamic scale. in fine, a complete knowledge of hydrogen bonds in water could lead to the determination of the 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from coherent and incoherent neutron scattering, phys. rev. lett. 117, 185501 (2016). 32. l. e. bove, s. klotz, th. strässle, m. koza, j. teixeira and a.m. saitta, translational and rotational diffusion in water in the gigapascal range, phys. rev. lett. 111, 185901 (2013). 33. f.h. stillinger, water revisited, science 209, 451-457 (1980). 34. a. luzar and d. chandler, hydrogen-bond kinetics in liquid water, nature 379, 55-57 (1996). 35. m.-c. bellissent-funel, l. bosio, j. dore, j. teixeira and p. chieux, spatial correlations in deeply supercooled water, europhys. lett. 2, 241-245 (1986). 36. c.a. tulk, j.j. molaison, a.r. makhluf, c.e. manning and d.d. klug, absence of amorphous forms when ice is compressed at low temperature, nature 569, 542-545 (2019). 37. g.n.i. clark, g.l. hura, j. teixeira, a.k. soper and t. head-gordon, small-angle scattering and the structure of ambient liquid water, proc. nat. acad. sci. (usa) 107, 14003-14007 (2010). 38. d. russo and j. teixeira, mapping water dynamics in defined local environment: from hindered rotation to vibrational modes, journal of non-crystalline solids 407, 459-464 (2015). substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 3(2) suppl. 6: 39-47, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-587 citation: s. tortorella, a. zanelli, v. domenici (2019) chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity. substantia 3(2) suppl. 6: 39-47. doi: 10.13128/substantia-587 copyright: © 2019 s. tortorella, a. zanelli, v. domenici. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity sara tortorella1,2,*, alberto zanelli2,3, valentina domenici2,4 1 molecular horizon srl, via montelino 30, 06084 bettona (pg), italy 2 gruppo interdivisionale “diffusione della cultura chimica”, società chimica italiana, viale liegi 48c, 00198 roma, italy 3 consiglio nazionale delle ricerche, istituto per la sintesi organica e la fotoreattività, via p. gobetti 101, 40129 bologna, italy 4 dipartimento di chimica e chimica industriale, università di pisa, via moruzzi 13, 56124 pisa, italy *corresponding author: saratortorella4@gmail.com abstract. several scientific channels on tv, crowded scientific fairs, and many serious scientific board games on the market demonstrate that people are curious about science. however, when asked about the perception of scientific subjects, chemistry in the first place, general public still shows rejection toward “too complicated”, “abstract”, and “far from everyday life” topics. unarguably, every chemist would not recognize chemistry as neither “abstract” nor “far from everyday life”: actually chemistry, the so-called central science, is all around us. where is the gap to fill, then? why are not we able to convert that innate curiosity, which makes people stepping out from their houses to join public engagement activities, into genuine, time-persistent, passion about chemistry? such questions will be addressed herein, giving practical examples of possible approaches to address the problem. special emphasis will be given to new learning means, generically referred as “open learning” ones, and interactive teaching approaches typical of non-formal environments, such as science festivals. real examples of activities beyond the formal curricula of chemical study, some carried out by us in the framework of the “diffusione della cultura chimica – società chimica italiana” (dissemination of chemical culture italian chemical society) mission and vision, will be discussed underlining their role in enhancing learning and inspiring confidence and passion toward chemistry. keywords. open learning, chemistry, society, gamification, science festival, didactics, interactive teaching approaches. introduction the ideenexpo 2019 in hannover (germany) had about four hundred thousands visitors in eight days,1 the 30th edition of the edinburgh international science festival (ireland) in 2018 had about one hundred seventy five thousands visitors in two weeks2 and the 16th edition of the science festival 40 sara tortorella, alberto zanelli, valentina domenici in genoa (italy)3 in 2018 reached about one hundred fifty thousands people in ten days. these are just few examples of recent big scientific events promoted by scientists and scientific organizations to increase the public engagement and the public understanding of the crucial role of science in the modern society.4 science festivals are typical non-formal contexts, where different scientific and technological aspects, innovations and even new scientific concepts, are shown in a spectacular way with several purposes: impressing people about the beauty of science, increasing their interest and curiosity through science, giving the sense of the pervasive presence of science in every-day life. among different scientific disciplines, chemistry is usually present in science festival, even if not predominant, except in few cases (see, for instance, the italian festival of chemistry organized by the university of basilicata, since 2009).5,6 despite chemistry is recognized from the scientific community as a “central science”, since it connects different disciplines and most of the basic chemical concepts are fundamental in biology and medicine, nanoscience and material science,7 the general public perception of chemistry is quite far from this idea.8 chemists have defined a specific word, chemophobia, to describe an “irrational aversion to or prejudice against chemicals or chemistry”.9 “more specifically it refers to the growing tendency for the public to be suspicious and critical of the presence of any man-made (synthetic) chemicals in foods or products that they make use of ”.10 while demonstrating the various origins of chemophobia, as a quite complex human attitude, goes far beyond the scope of the present work, it is worth noticing that several recent studies have systematically investigated the public attitude toward chemists and chemistry giving rise to interesting results.11-14 according to the survey proposed by the royal society of chemistry (rsc) in u.k., chemistry is often perceived as “abstract”, “difficult” and “far from everyday life”.14 however, most of the interviewers did not declare any pre-conceptual aversion or any chemophobic attitude towards chemicals and chemists, so the general perception of chemistry among the lay public is more positive than what expected by chemists themselves. although the rsc study paints a better picture than the chemists themselves had expected, it also revealed a sort of “emotional neutrality” and a “lack of engagement with” chemistry.12 another interesting result coming from these studies is related to the interviewers’ school experiences about chemistry;12,13 most of them declared that their experiences at school were indeed crucial in determining their ideas about chemistry. these are some of the interviewers’ statements concerning how chemistry was taught at school, based on their own experience: “chemical concepts were too abstract”, “ few examples about every-day life applications of chemistry were done”, and “the utility of chemistry was not addressed”. 12,13 the evidence of a link between the formal and traditional teaching of chemistry and the diffuse perception of a distance between chemical concepts learned at school and the role of chemistry in the society could be a good starting point to rethink the teaching approaches to chemistry. moreover, as suggested by rsc, instead of focusing on the minority of negative views, the scientific community, and in particular the chemists, should try to address the substantial indifference or lack of engagement in order to improve the image of chemistry. according to these indications, the biggest challenge seems to be how to convince students and the general public on the relevance and the utility of chemistry. we need to foster public excitement in chemistry by making the public aware of the extent to which chemistry is indeed all around them. however, this ambitious objective can only be reached by working on different parallel targets: 1. changing the way chemistry is taught at school; 2. establishing stronger connections between the research in chemistry and the society; 3. talking more about applications of chemistry than theory and abstract concepts; 4. using the digital tools, by exploiting their potentialities to increase the knowledge of chemistry; 5. enhance the communication skills among young chemists and take advantages from the non-formal learning environments.15,16 a possible mean to achieve these tasks is the so-called open learning, concept with a broad meaning usually referred to activities and teaching strategies that enhance learning opportunities beyond formal education systems. open learning is just an appendix of the broader open science movement, the ongoing transition promoted by the european union (eu) in how research, knowledge and scientific culture is performed and disseminated by using digital technologies and new collaborative tools.17 on the other hand, open learning is related to the so called life-long learning strategy, which became central in the eu program for the education of new european citizens since 1985.18 several studies have indeed underlined how the learning of science, and of chemistry in particular, is a complex process extended to the whole life, resulting from a continuous interplay among learning in formal, non-formal and informal contexts.19 the role of non-formal and informal contexts in learning chemis41chemistry beyond the book try, such as the experiences of interactive laboratories in science museums and science festivals or activities about chemistry through mobile devices (m-learning), internet (e-learning), wikipedia and other digital tools, has been recently overviewed by several authors.20-22 in this paper, we will focus on some experiences related to different open learning strategies, divided in two subsections: i. chemistry in the arena and ii. chemistry, new media and gamification. in particular, we will describe and comment real examples on how different open learning approaches have been successfully applied to foster trust in the essential role of chemistry for our society and ultimately inspire passion and curiosity toward this subject. open chemistry and open learning in chemistry open science is a comprehensive reform proposed and promoted by the eu on how science can be practiced in an accessible, transparent and reusable way in the current digital age.17 considerations about which technological changes can we expect from this reform and which impact will open science, and in particular open chemistry, have on both society and the research community have been extensively discussed elsewhere.23 among the open-components enabling such historical transition in science, we find the promotion of free access to scientific literature and data sets (i.e. open access and open data, respectively), as well as freely available teaching and learning materials, which hold the promise of reducing financial and structural barriers and bridging the gap between the less and more developed countries, especially in fields where small investments can have relevant social impacts, as chemistry is (see, for instance, the open educational resources24-27). as a consequence, such shift also impacts teaching and learning activities, which are being redefined under the concept of open learning. open learning, grounded on the work of pedagogues and educational reformers like célestin freinet and maria montessori among others, emerged as teaching method in the late ‘70s. starting from the statement that students of the same age have vast differences in experiences, interests, and competencies, and that such differences play a crucial role in the learning process, the key concept of open learning pedagogy is an “independent and interest-guided” learning.28 this can be achieved by means of interactive learning, interdisciplinary focus activities, hands-on experiences, group-based dialog formats, evidence-based problem analysis, and by developing and using open educational resources. beside the chosen mean, the final goal is to enable each individual learner to be self-determined, confident, thus genuinely inspired by the learning process. from the scientists’ perspective, this translates into moving away from what has been defined as the “deficit model” of public attitudes towards science.29 the traditional idea that public scepticism about science is the result of a lack of understanding, and can only be filled by providing information, is nowadays replaced by a “dialogue model” that engages publics in two-way communication aimed at disseminating the social implications of science.15-17, 30, 31 in this context, science festivals, open-lab activities, science gamification using new media and similar learning opportunities beyond formal education systems can be applied to bring back the public perception of chemistry as central science for the development of our society. these aspects will be discussed in details in the following sections. focusing on chemistry, several examples of open learning teaching approaches successfully proposed to students are those related to new open digital environments and platforms, such as the so called schnaps,32 which was developed to help students to approach chemistry with the problem-solving method. similar strategies have also been explored related to specific topics in chemistry, such as environmental applications of analytical chemistry.33 the use of virtual laboratories and digital tools to teach chemistry has also been object of intense research about the effectiveness of mooc (massive open online courses), which were developed for the first time in the 2002, by the massachusetts institute of technology with the opencourseware («mit ocw») project. despite of the first official mooc were open in 2012 by the major american scientific universities and research institutes, the number of mooc about chemistry represents less than 5% of all online courses. nowadays, several studies have been published putting in evidence the role of such interactive and participating learning platforms to enhance the learning of chemistry among undergraduate and high school students.34-36 besides assessing how interactive and participating learning platforms impact on students, another question arises: are teachers ready and minded to embrace this cultural transition? luckily, for teachers passionate about and who wants to get trained on such open learning and innovative didactics, dedicated initiatives have been proposed in recent years. for instance, “playing with protons” is an education initiative led by the cms experiment at cern bringing together primary 42 sara tortorella, alberto zanelli, valentina domenici school teachers, science education specialists and cern researchers to develop creative approaches, learning activities, hands-on experiments with everyday materials to help all primary students engage effectively in science, discovery and innovation.37 this growing community of passionate, innovative and creative primary school teachers get free access to learning resources, share classroom activities with like-minded colleagues and create opportunities for school-to-school collaboration, paving the way for a full exploitation of open learning. i. chemistry in the arena science festivals, nowadays taking place all over the world1-7, aim at disclosing and disseminating the role of science in the society and the relationship of science with different aspects of everyday life. this effort in bringing science “out of the laboratory” and in engaging with the public in a constructive dialogue is the key of the success of such “creative, playful and surprising celebration of science”.4 a typical science festival comprises a wide variety of events ranging from hands-on activities, spectacular demonstrations, workshops and conferences up to the involvement of arts. the presence of chemistry in science festival, although rarely predominant5, is pervasive and undoubtedly among the most spectacular for the general public. indeed, at first sight, solutions suddenly changing colours or matter changing its state appear as magic and almost unbelievable phenomena. also simple laboratory equipment, like a magnetic plate with a bar stirring a methylene blue-containing solution, inspires curiosity in the public by evoking a charming world disclosed to only few people. this is also the reason why the ancestors of modern chemists, the “alchemists”, were considered halfway between philosophers and magicians. indeed, chemistry became a science only in the middle of the 17th century. before this date, it was a wide cluster of practical knowledge as leather tanning, metallurgy, fabric dyeing, and many other craft activities. more or less everywhere, several centuries before christ, the carbonate rocks were heated and milled to produce lime to built houses. the famous painters like leonardo da vinci (1452-1519) or michelangelo buonarroti (1475-1564), started their careers by preparing pigments for example by roasting and milling teeth (black), or earths (terra di siena) and mixing them with rock powders, such as the orange cinnabar or the light blue lapis lazuli, and binders in the laboratory of their masters. on the other hand, one century ago, every woman was able to produce soap from grease and ash. those are just few examples of chemical reactions! so, science festivals are the perfect occasion to make the general public aware of the central role of chemistry in our society and remembering them how pervasive it has been for human life and culture throughout history. even with ver y simple chemical concepts and means, one can inspire interest about chemistry and research, fascinate kids, and motivate teens to start looking at chemistry as a key to open the secret behind the technology they are using on a daily basis. in other words, such activities in science festivals increase critical thinking and implicitly communicate that chemistry is not just a bunch of formulas and numbers wrote on a book, but is a mean to interpret the world around us. for instance, members of the group diffusione della cultura chimica – società chimica italiana attended multiple editions of the “festival della scienza di genova”, where several didactic laboratories were proposed, such as the laboratory about visible absorption spectroscopy(“fare chimica con la luce” – “doing chemistry with light” – 2017 edition, theme: contact). more recently the group itself promoted and realized a didactic laboratory using new technology as an appendage of analytical techniques to enable to “see” chemical reactions (“ciak: (re)azione!” – “ciak: (re)action!”2018 edition, theme: transformations).4 in both cases, visitors were offered the possibility to engage with chemistry by means of simple, but real experiments in a very interactive environment (figure 1). for instance, the laboratory “fare chimica con la luce” was a very effective activity to introduce students of the secondary school to a quite complicate subject of figure 1. typical setting of didactic laboratories at the “festival della scienza di genova”, 2018 edition. 43chemistry beyond the book physical chemistry: molecular spectroscopy.38-40 this particular “format” was also tested with students visiting the university under the educational orientation programs, such as “pls” (piano lauree scientifiche), with the aim to get students interested in scientific studies.41 the use of portable spectrophotometers developed for educational purposes or the development of prototypes of colorimeter to measure coloured solutions directly by the students provided to enhance the understanding of some basic concepts of molecular spectroscopy.38-41 “ciak: (re)azione!”, designed by members of the group diffusione della cultura chimica – società chimica italiana, was another good example of interactive activity related to the concept of “chemical transformations” and the interplay between chemistry and technology, where kids (and adults, too!) were captured by the phenomenological changes occurring during a chemical reaction.42,43 people who participated to the lab was helped in understanding the basic of why and how matters change colours or state of matter, and choose the most appropriate mean to visualize such changings thanks to the digital devices (i.e. tablet or smartphone, figure 2). in all cases, after a first feeling of surprise and amusement, we notice that students and general visitors focused on what was happening under their eyes and started somehow interiorize the scientific method by making hypothesis, testing, discussing the results and deciding how to proceed. similarly, open-lab activities are organized to establish stronger connections between research in chemistry and the society and talk about applications of chemistry in every-day life. for instance, the “european night of researchers” is an event organized by the european commission with the aim of celebrating the work of the researchers.44 every year, in the same day in september, every country proposes different communication, dissemination and public engagement activities organized by local universities, research centres, museums and schools. perfect occasion also to enhance communication skills among scientists, such in-formal learning environments offer the unique opportunity to let the people enter real laboratories, meet researchers in person and feel free to ask them everything about their research (figure 3). as reported on the official web-site44, “ from 2018-2019, 55 projects have been implemented in 371 cities across europe and beyond. during the 2018 night, over 1.5 million of visitors attended!”. these numbers give the idea of the social impact of these activities and the high demand from the european citizen to participate and get involved in the science processes. noteworthy, the goal of such activities is not to transfer information, rather to seed confidence and knowledge on how chemistry could be useful to tackle different real-world challenges. figure 2. primary school students performing and filming in slowmotion the synthesis of prussian blue during the laboratory “ciak: (re)azione!” at the “festival della scienza di genova”, 2018 edition. figure 3. activities during the european researcher night 2018 at the university of pisa. 44 sara tortorella, alberto zanelli, valentina domenici to summarize, with the aim of addressing the already discussed issue about the underestimated perception of the role of chemistry in our everyday life, bringing “chemistry in the arena” with science festivals and open-laboratories activities fulfil the open learning vision and mission. ii. chemistry, new media and gamification knowledge can be considered as static, while the way in which information is transferred and then hopefully converted into knowledge is fluid and, nowadays, incredibly fast. according to a recent study on the italian citizens habits, the 95% of italians use smartphone and internet on a daily base, the 32% for most than 5 hours per day (even for longer if we consider teenagers).45 such scenario can be perceived in two opposite ways: either as a treat to the traditional, book-based teaching and learning approach, or as an exceptional opportunity for its enhancement. indeed, trying to convey the interest of such users toward scientific discipline could be an opportunity. undoubtedly, the use of technology can help to increase science lesson engagement. today’s technology can provide an immersive experience and make learning a more active experience, stimulating students at a deeper level. strictly related to this, we find the concept of “science gamification”: an approach for improving students’ attitudes toward learning traditionally challenging subjects by proposing games, which increases engagement by means of rewards and feedback.46 far from being a simplified version of traditional education methods, the research agenda for the field of science gamification concerns with central aspects of research methodology, including psychometric measurement, experimental design, and generalizability, in order to maximize its trustworthiness and real-world value, as comprehensively discussed elsewhere.47 “gamif ication” in education and “cooperative learning”, where most of the activity is related to a team game, have proven successful in many contests.48,49 serious games about chemistry have always existed and seem to be one of the more appealing and prone to popular marketization: in fact, “the laboratory of crystals”, “science and lip-sticks” and “chemistry lab” are only a few we can find in toy-shops. nowadays, with the diffusion of technology and the wide engagement of pupils and teenagers with new media and technology, science gamification is moving from the shelf to the smartphone. an example is the popular kahoot!50 game-based platform. with the claim “make learning fun, inclusive and engaging in all contexts”, kahoot! not only fully embraces the principles of open learning, but it also exquisitely merges the benefit of using new media (e.g., tablets, smartphones) for teaching and learning activities. with kahoot! a teacher can create learning games (kahoots) by typing a series of multiple choice questions and optionally adding videos, images and diagrams to amplify engagement. then, players (ideally, a class) answer the questions on their own devices, while games are displayed on a shared screen to unite the lesson. this cooperative learning creates what the kahoot!’s authors define as “campfire moment, encouraging players to look up and celebrate together”. whether players are in the same room or on the other side of the globe, such game-based learning platforms also allow to search among millions of existing games and share results, thus enabling “social learning” which promotes discussion, pedagogical impact, and encourage players to deepen understanding, mastery and purpose, as well as engage in peer-led discussions.51,52 as reported by jack quinn, 5th grade teacher at withcomb elementary school (houston, tx, usa), using such game-based learning “got students more plugged into learning, helped them improve mastery of complex science topics, and, as a result, they did 11.4% better in their exams compared to last year and are projected to grow 75% above the district norm”.53 the diffusione della cultura chimica – società chimica italiana group recently used kahoot! to disseminata the unesco international year of the periodic table (iypt2019). in particular, a dedicated kahoot! quiz for high school students was created by the consiglio nazionale delle ricerche and proposed by the group during open days, career guidance, and pls activities (figure 4).54 for instance, during the “chemistry days”, a pls figure 4. the “human periodic table”, performed by students attending the cnr event celebrating the international year of the periodic table (iypt). 45chemistry beyond the book event organized by the university of palermo, the diffusione della cultura chimica group proposed the quiz to 31 students at the end of a traditional talk on the history and curiosity on the periodic table. questions ranged from simple notions (e.g., what is the surname of the scientist who first proposed the periodic table?) and curiosity on the origin of the elements or their names (e.g., which among these countries was named by an element?), up to questions related to the presence of elements in everyday life (e.g., which among these elements is not used to build a smartphone?). we noticed that by using their smartphones, even if for simply answering a question related to concepts they had just listened to or that were already aware of, students were fully engaged and almost anxious to give the right answer. noteworthy, at the end of every quiz session, a report summarizing statistics on the overall and question-specific performances is available (table 1). when the quiz is proposed after a lesson, such report can be used by teachers to evaluate the level of understanding of concepts proposed during the lesson. when the quiz is proposed before the lesson itself, in line with the “blind test” methodology which uses the feeling of initial failure as “cognitive need” (i.e., a stimulus to learn), the report can be used to finely tune the content of the lesson.55 another example of interactive and participative activities, where the good use of digital tools and devices is crucial, is represented by the so-called “citizen science” programs.56,57 these programs aim to reach a shared knowledge among citizens (of any age, culture and education) and about specific scientific topics, which are usually related to concrete everyday problems (such as environmental ones).58 for instance, in the recent years, several “citizen science” programs were promoted by arpat59, in tuscany (italy), to monitor the sea status during summer time. among these activities, people were invited to participate to the monitoring of a naturalistic area or an environmental phenomenon (such as the nesting of caretta caretta turtles), by recording data, sharing comments, observations, images and videos, but also measuring some significant chemical or physical properties, such as the temperature or humidity.60 in this way, everybody participating to the process, enhances its own responsibility and knowledge of the complexity and high interdisciplinarity of scientific “problems”. “ariapesa” is an example of “bottom-up citizen science” promoted by a network of free associations of citizens in bologna (italy) to monitor nitrogen oxides in the air near the schools through the installation of hundreds of passive samplers. these samplers have been, and will be, analyzed by specialized laboratories and the results compared to the data of three official monitoring stations, giving a punctual map of the pollution all over the school district.61 therefore we believe that, upon appropriate study and definition of shared procedures and metrics to assess the correctness of the information provided, chemistry should embrace these ways of digital communication and open learning. conclusions chemistry, the central science, is often perceived by the general public as “distant from everyday life” and “too abstract”. the reasons are manifold and partially addressed herein, however, it is clear that too traditional and content-focused teaching and learning approaches represent an important issue, which may justify the public attitude towards science and chemistry, in particular. in the current digital age, open science and, more specifically, open learning, offers new paradigms and tools to establish a synergic interaction among science, digital technology, and society worldwide. although the ambitious aim of creating a comprehensive list was beyond our scope, in the present manuscript we reported on successful examples of open chemistr y, hands-on laboratories during science festivals, and alternative teaching activities based on new media and on the gamification of chemistry. some of these activities were developed by us under the umbrella of the “diffusione della cultura chimica table 1. example of quiz report available in kahoot!, based on the “domande periodiche” (periodical questions) quiz proposed during the “chemistry days” at the university of palermo.54 quiz title periodical questions q1: what is the surname of the scientist who first proposed the periodic table? correct answer d. mendeleev players correct (%) 73.3% question duration (seconds) 30 seconds answer summary answer options mendel mandela mendeleev mandilei number of answers received 8 0 22 0 average time taken to answer (seconds) 8.39 6.77 46 sara tortorella, alberto zanelli, valentina domenici – società chimica italiana“ (dissemination of chemical culture italian chemical society) activities, others in the broader framework of the eu mission and vision on communication, dissemination and public engagement. moving from the “deficit” to the “dialogue” model of public attitudes towards science, we believe that such new way of promoting interaction between science and society holds the promise of triggering general public curiosity and fostering trust in the essential role of chemistry in our society. references 1. ideenexpo. https://www.ideenexpo.de/fuer-presse; accessed july 10th, 2019. 2. edinburgh international science festival. https:// www.sciencefestival.co.uk/medialibrary/other/english/43891.pdf; accessed july 10th, 2019. 3. festival della scienza di genova. http://www.festivalscienza.it/site/home/edizioni-precedenti.html; accessed july 10th, 2019. 4. v. domenici, i. dierking, liq. cryst. today 2018, 27(1): 2-6. doi: 10.1080/1358314x.2018.1438039. 5. festival della chimica di potenza (università della basilicata). from the web-site of the italian chemical society: 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http://www.arpat.toscana.it/notizie/ arpatnews/2019/059-19/il-mare-e-la-citizen-science: accessed july 24th, 2019. 60. l. marsili, s. ventrella, c. mancusi, g. terracciano, a. lenzi, p. piombanti, v. valentina domenici, nidificazione della caretta caretta e partecipazione pubblica al progresso della scienza: un esempio di citizen science, in codice armonico 2018, edizioni ets, isbn: 978-884675376-2. 61. https://ariapesa.org/; accessed septembder 23th, 2019. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 6 2019 firenze university press where does chemistry go? from mendeelev table of elements to the big data era luigi campanella1, laura teodori2,* visualizing solubilization by a realistic particle model in chemistry education antonella di vincenzo, michele a. floriano* chemistry as building block for a new knowledge and participation stefano cinti tissue engineering between click chemistry and green chemistry alessandra costaa#, bogdan walkowiakb, luigi campanellac, bhuvanesh guptad, maria cristina albertinie* and laura teodori a, f* chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity. sara tortorella,1,2,* alberto zanelli,2,3 valentina domenici2,4 substantia. an international journal of the history of chemistry 4(2) suppl.: 5-8, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1155 citation: b.w. ninham, r.m. pashley, (2020) overview. substantia 4(2) suppl.: 5-8. doi: 10.36253/substantia-1155 copyright: © 2020 b.w. ninham, r.m. pashley,. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. overview barry w. ninham1, richard m. pashley2,* 1 department of applied mathematics, research school of physical sciences, australian national university, canberra, australia 2 school of science, university of new south wales, northcott drive, campbell, canberra, australia *corresponding author: r.pashley@adfa.edu.au it is an indisputable observation, beyond climate change: that the urgent development of simple new technologies, to ensure the supply of quality fresh water for cities and towns, industry and agriculture, presents an existential challenge for humanity. several novel technologies that fill that need show that the job is not impossible. they are summarized in this volume. they are environmentally friendly and inexpensive. they include techniques for seawater desalination, wastewater sterilization – including viruses –, selective removal of heavy metals from industrial wastewater, efficient concentration of wastewater slimes to recycle water, and the prevention of water cavitation for much cheaper transport. other new techniques like high temperature reactions achieved in low temperature water, and low energy desalination are in the wings. borrowing from biology, new and edible class of surfactants is environmentally friendly, and can replace standard surfactants in present usage. the new technologies are cheap and scalable. they became possible once we realised that the theories of physical, colloid, surface and electrochemistry are deeply flawed due to sins of omission and commission. those of commission have to do with erroneous treatment of molecular forces in solution and their specificity (hofmeister effects). those of omission are due to neglect of effects of dissolved gas. both are ignored in classical and textbook theories. the greeks taught us there were 4 elements, earth (salt), water, fire (heat) and air. we forgot the air, even descartes, who might instead of his saying: “i think, therefore i am”, might have better said: “i breathe, therefore i am,” the inclusion of gas changes the world of physical chemistry and opens up new vistas. desalination seawater desalination offers an unlimited source of fresh water, the demand for which we are increasingly unable to meet. different desalination techniques are already commercially available. it is unlikely that they can be 6 barry w. ninham, richard m. pashley improved further in terms of energy efficiency as well as operational simplicity to meet the needs of an ever expanding industrial scale. some of these techniques have not been changed for half a century, reverse osmosis membranes being the most familiar. their limitations are well known. two novel desalination processes are described here. the first is the bubble column evaporator (bce), which is simple, scalable and requires low maintenance. the bce operates primarily by direct contact of the seawater with heated gas. in a further development, helium carrier gas consumes less energy than other processes and can be recycled in a closed system. high overall heatand mass transfer is achieved. the bce process can be used extensively in many applications such as desalination, water/ wastewater treatment and even for the thermolysis of solute decomposition (e.g. ammonium bicarbonate). a new way of decomposing and recycling ammonium bicarbonate in aqueous solution has been developed using a membrane-transport process with both dense and porous hollow-fiber membranes. the decomposition of ammonium bicarbonate solutions occurs via contact through a permeable membrane, of the solutions pre-heated to 80°c with a continuous counter-flow of dehumidified air at room temperature. in this process, ammonia (nh3) and carbon dioxide (co2) gases permeate through the membrane and are thereby separated from the feed solution; they can then be collected into aqueous solution for recycling. the bce method also offers a fast and robust way to decompose ammonium bicarbonate solutions and readily meets industrial-scale requirements. combined with this, we have produced a novel, sustainable ion exchange desalination process based on low cost resin regeneration. it uses ammonium bicarbonate solution in place of the usual, and expensive, acid and base washing. regeneration using this salt further allows the use of novel ion exchange resins which contain the cation and anion exchanging groups in close proximity, that is, nanometers apart rather than millimeters apart. these resins are more efficient and can be regenerated in situ without exposure to either acid or base solutions. this offers a second energy-efficient desalination method. it is a serious competitor for, and indeed superior to reverse osmosis desalination on all fronts and is close to large scale implementation. water treatment the treatment of water contaminated with hazardous heavy metal ions, is also needed to supply clean water. these metal ions are produced naturally or through industrial processes, and can infiltrate water supplies for general or agricultural uses. naturally occurring arsenic is a massive problem for millions of people world-wide. new techniques are required to remove hazardous ions from drinking water, especially at low-level concentrations. one potential technique is ion flotation, and with environmentally friendly, meaning biodegradable, surfactants. in principle these should be highly efficient and specific absorbers of hazardous ions from aqueous solutions. in biology, enzymes have an exquisite capacity to select and bind specific ions. so taking that lesson from biology, we have taken cysteine, which is a natural amino acid, and has a high affinity to bind with a range of contaminant ions, to explore what can be done. as an example, the na+ salt of the n-octanoyl-cysteine surfactant showed highest efficiency in the ion flotation process. it has a high water solubility and exhibits extensive foaming in a typical flotation chamber over a wide ph range. in a batch ion-flotation process, this surfactant was able to remove 97‒99% of lanthanum, arsenic and various divalent heavy metals present at 5ppm levels in contaminated water, in a simple, single-stage physiochemical process. this surfactant showed significantly lower efficiency for the removal of iron, selenium and gold ions and hence these studies also show how the ion-flotation process could be used to remove specific ions selectively from mixed ion solutions. the most promising aspect of the selectivity achieved is probably for future developments involving rare earth separation and the treatment of nuclear wastes. the design of environmentally friendly surfactants that have specific ion binding properties is a long standing aim of the chemical industry, and something devoutly to be wished for. our “exhibit one” surfactant is such an environmentally acceptable compound. it can be readily decomposed into cysteine (an amino acid) and octanoic acid (or caprylic acid), both of which can be taken as a dietary supplement). the surfactant, as an efficient and specific collector, has the potential for wide usage in both ion and froth flotation. the surfactant has also been shown to have a high affinity to bind with ions like copper, lead, arsenic. it is promising in the treatment of mining wastewater sites contaminated by such ions worldwide. naturally occurring arsenic contamination in drinking water is a huge problem in various countries and this surfactant is a winner not yet harnessed for the task. a novel, efficient synthesis method has been developed to produce the n-octanoyl-cysteine surfactant. 7overview this gives cheap high product yields with a simple and straight forward method. the high synthesis yield of this product is important, as it offers an environmentally acceptable agent for the removal of a range of heavymetal ions from contaminated water and soil. more importantly, it could also be used in general household-detergent/personnel-cleaner formulations and even in toothpastes! replacement of standard surfactants like sodium dodecyl sulfate and a myriad quaternary ammonium or related cationic surfactants is urgent. their manufacture from petroleum products is a large part of industrial co2 production in europe. in addition, the surfactant could be used to facilitate the removal of pfas compounds from soils. the pfas surfactants are negatively charged, but often bind to negatively charged particles of sand, clay and humic acid-coated materials, and microorganisms via bridging multivalent cations. hence, it could be more environmentally acceptable to use this biodegradable surfactant, which would combine cation chelation properties with foam fractionation separation of surface-active (e.g. pfas) components in soils. sterilization, carbon dioxide and viruses inactivation of viruses has been an insuperable inhibition to the use of recycled water. hence the ubiquity of plastic bottled water in cities. current processes such as uv irradiation, chlorination, ozonolysis and even treatment with bacteriocides, such as quaternary ammonium surfactants, all produce varying levels of potentially toxic by-products and subsequent environmental issues. we have said goodbye to all that. in a surprising development, we found an environmentally friendly technology for sterilizing water by doing just that. the technology bubbles heated, un-pressurized carbon dioxide (or even exhaust gases) through contaminated wastewater in a bubble column. the process kills both waterborne bacteria and viruses close to 100%! the technique is extremely cost effective, with no by-products to bother about, and has already been successfully scaled-up industrially. substantial success so far achieved in solving the problem of pathogens is here extended. a novel technique based on the use of a continuous, high density flow of carbon dioxide bubbles, over a range of temperatures – depending on application, can effectively sterilize wastewater – without the risk of harmful byproducts. efficient use of hot, waste combustion gases can be used for wastewater sterilization and at the same time produce pure, condensed product water using a bubble column evaporator. in the near future, testing of covid-19 susceptibility may also prove interesting and might lead to further sterilization applications for this simple technique (see postscript for rapid progress here). de-watering slimes industrial wastewater slimes are currently treated in several ways, e.g. flocculation, filtration, hydrocyclone treatment, centrifugation, all of which raise issues and problems associated with each particular process. we have developed a novel method based on the use of hot gas bubbles which both fluidize slimes whilst at the same time efficiently removing water vapour which can then be condensed as a pure water product. the bubble column evaporator enables slime de-watering up to levels where the dispersions are only maintained in a fluid state by the continuous flow of hot gases. this facilitates the industrial use of this process via the continuous deposition into flat open drying trays where the material is deposited in solid form for ultimate evaporative drying and disposal. our surprising observations with heated helium gas might further dramatically improve the efficiency of the process, with the incorporation of helium recycling. at the end we found a good method to inhibit scaling in pipelines. and this has opened up new insights into the core of physical chemistry –the energy sources of reactivity in ordinary and biochemistry (see postscript). cavitation prevention another novel process has been developed which completely prevents the cavitation caused by the rapid rotation of a propeller in water. cavitation has a deleterious effect on the efficiency of fluid transmission, and generally leads to material degradation in hydraulic systems. a major part of transport costs by shipping is due to cavitation. currently, the main approaches by industry to reduce the effects of cavitation are to select operating conditions, use geometric designs that reduce the occurrence of cavitation, or use hard materials to resist wear caused by cavitation. for example, the maximum shaft speed of propellers is typically limited to ensure that cavitation does not occur at the blades. in the recent advance described here, a novel method of releasing de-gassed water towards the low-pressure side of a propeller was developed. this forms a boundary layer completely preventing cavitation. this is extraordinary, simple and has game changing implications. 8 barry w. ninham, richard m. pashley the prevention of cavitation and associated noise has widespread practical implications for commercial shipping and the navy; it improves energy efficiency and reduces propeller damage, and also can have a dramatic effect on the effective operating speed of ships and submarines. following proven laboratory scale tests, a multidisciplinary research approach involving fluid engineers, propeller designers, ship-makers with expertise in cavitation is now required to develop this innovation for large scale applications. we wish them well in the enterprise. the novel technologies presented in this volume offer promising new environmentally friendly processes for desalination, water treatment, water sterilization, and the total prevention of cavitation. some of these technologies have already been patented. each of these innovations has been brought to the stage where further development might lead to full commercialization with global implications. substantia. an international journal of the history of chemistry 2(2): 7-18, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-56 citation: h. kragh (2018) the lorenzlorentz formula: origin and early history. substantia 2(2): 7-18. doi: 10.13128/substantia-56 copyright: © 2018 h. kragh. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article the lorenz-lorentz formula: origin and early history helge kragh niels bohr institute, university of copenhagen, blegdamsvej 17, copenhagen, denmark e-mail: helge.kragh@nbi.ku.dk abstract. among the many eponymous formulae and laws met in textbooks in physics and chemistry, the lorenz-lorentz formula merits attention from a historical point of view. the somewhat curious name of this formula, which relates the refractive index of a substance to its density, reflects its dual origin in two areas of nineteenth-century physics, namely optics and electromagnetism. although usually dated to 1880, the formula was first established in 1869 by l. v. lorenz (optics) and subsequently in 1878 by h. a. lorentz (electromagnetism). apart from discussing the origin and priority of the lorenz-lorentz formula the paper outlines its early use in molecular physics and physical chemistry. during the late nineteenth century studies of molecular refractivity based on the formula proved important in a number of ways. for example, they led to estimates of the size of molecules and provided information about the structure of chemical compounds. keywords. l. lorenz, h. a. lorentz, optical refraction, clausius-mossotti formula, molecular refractivity. 1. introduction in 1902 the famous dutch physicist hendrik antoon lorentz (1853-1928) received the nobel prize in physics sharing it with his compatriot pieter zeeman. in his nobel lecture delivered in stockholm on “the theory of electrons and the propagation of light” he referred to the refraction of light and the recent insight that the phenomenon was due to vibrating electrical charges (electrons) in the refracting substance. many years earlier he had succeeded in explaining on the basis of electromagnetic theory “the approximate change in the refractive index with the increasing or decreasing density of the body.” lorentz continued: “when i drew up these formulae i did not know that lorenz at copenhagen had arrived at exactly the same result, even though he started from different viewpoints, independent of the electromagnetic theory of light. the equation has therefore often been referred to as the formula of lorenz and lorentz.”1 it is the early history of this formula, variously called the lorentz-lorenz and the lorenz-lorentz formula or law, which is the subject of the present paper. in brief, the formula dates from 1869, when it was first proposed by 8 helge kragh the relatively obscure danish physicist ludvig valentin lorenz (1829-1891) on the basis of experiments and optical theory. nine years later it was independently derived on a very different basis by 25-year-old lorentz in the netherlands, his first major scientific work. the lorenz-lorentz formula, as i shall call it (and justify later), soon became accepted as an important law not only in optics and electromagnetic theory but also as an eminently useful tool in the new field of physical chemistry. indeed, chemists embraced the formula at an early date, applying it in various ways to determine the molecular refractivity of chemical compounds and thereby to gain information on their constitution. ever since the 1880s the lorenz-lorentz formula has played a significant role in the physical sciences and it continues to do so. still today, about 150 years after it was first proposed, it is an active research area in branches of physical chemistry, crystal chemistry and materials science. the paper focuses on the period ca. 1870-1890 and in particular on the contributions of the little known lorenz. a specialist in the mathematical theory of optics, contrary to lorentz he never accepted maxwell’s electromagnetic theory and preferred to represent optical phenomena in terms of abstract wave equations with no particular physical interpretation. although lorenz, independently of maxwell, suggested an innovative electrodynamic theory of light in 1867, he did not apply it to either the refraction or the dispersion of light (but see the end of section 5).2 2. refractivity and density the general idea that the refractivity index n of a transparent body is related to its density d was far from new at the time when lorenz took up the subject. as early as in his revised edition of opticks from 1718, newton reported experiments on the refraction of light in a variety of substances ranging from air to olive oil and diamond (figure 1).3 on the basis of these experiments he discussed the possibility of a “refractive power” of the form (n2 – 1) that varied proportionally to the body’s density. about a century later pierre simon de laplace, in his famous mécanique céleste, derived on the basis of the corpuscular theory of light what became known as the “newton-laplace rule.” according to this rule n2 −1 d  ≅ constant  the newton-laplace rule was tested experimentally by j.-b. biot and f. arago in a work of 1806; the next year their investigations were continued by e. l. malus. although the formula agreed well with the experiments of the french scientists for gases, it failed miserably for liquid and solid bodies. nonetheless it remained in use for many years, even after the corpuscular theory had been replaced by the wave theory of light. a simpler and much better expression involving (n – 1) instead of (n2 – 1) was proposed by an extensive series of experiments performed during the period 1858-1865 by the leading british chemist john hall gladstone (figure 2) and his collaborator thomas dale.4 the two scientists established that for liquids, n−1( )v = n−1( ) d = constant , where the quantity v = 1/d is known as the body’s specific volume. gladstone and dale referred to the quantity rgd = (n – 1)/d as the “specific refraction energy.”5 figure 1. newton’s measurements of the “refractive power” (column 5) relating the refractive index (column 2) to the density relative to water (column 4). 9the lorenz-lorentz formula: origin and early history the relation was widely used for analyses of solutions, glasses and crystals, and determinations of the “gladstone-dale constant” are still part of modern mineralogy, geochemistry and materials science. however, the gladstone-dale constant is not a characteristic parameter of the refractive substance as it varies considerably with its physical state. moreover, the gladstonedale rule and other rules proposed in the mid-nineteenth century were basically empirical relations lacking a proper theoretical foundation. the rule was later provided with a theoretical justification, albeit this proved possible only by means of ad hoc hypotheses concerning the structure of the ether.6 it remained an empirical rule, practically useful but of limited scientific importance. during the latter half of the nineteenth century several other refractivity-density relations were proposed, but these had very restricted applicability and were little more than extrapolations from a limited number of experiments. to mention but one example, in 1883, after the lorenz-lorentz law had been generally accepted, the german chemist w. johst proposed that n −1 d = constant the formula was discussed for a brief period of time after which it was forgotten.7 ludvig v. lorenz, a physics teacher at the military high school in copenhagen, was trained as a chemical engineer at the city’s polytechnic college. in the early 1860s he established a general, phenomenological theory of light from which he claimed that all optical phenomena could be deduced.8 the basis of the theory was three partial differential equations for a so-called light vector propagating with a velocity equal to the velocity of light and satisfying the condition that the waves were only transversal, not longitudinal. lorenz had originally suggested that something similar to the newton-laplace rule would follow from his equations, but in 1869 he arrived at a different result.9 in a memoir of that year published by the royal danish academy of sciences and letters, of which lorenz had become a member three years earlier, he reported for the first time the lorenzlorentz formula (figure 3). 3. lorenz’s optical route from a series of elaborate experiments lorenz established in his 1869 memoir a number of empirical formufigure 2. j. h. gladstone (1827-1902). source: https://en.wikipedia. org/wiki/john_hall_gladstone. figure 3. lorenz’s 1869 memoir on “experimental and theoretical investigations on the refractivity of substances” published by the royal danish academy of sciences and letters. 10 helge kragh lae, for example by measuring the refractive index for the yellow sodium light passing water at different temperatures t. in the interval between 0 ˚c and 30 ˚c he found that n t( )= n 0( )+ 0.076t − 2.803t2 +0.002134t3⎡⎣ ⎤⎦10 −6 thus, at a change in temperature of 10 ˚c the observed change in refractivity was found to be only of the order 0.01 per cent. measurements of this kind had earlier been reported by the french physicist jules jamin in 1856, but lorenz’s data were more precise and in better agreement with later results.10 the refractive index depends on the wavelength and according to a.-l. cauchy’s semi-empirical dispersion formula of 1836 the dependency can be represented as n λ( )= m+ a1 λ2 + a2 λ4 + a3 λ6 …, where the symbols in the nominators are constants to be determined experimentally. the quantity m thus denotes the refractive index reduced to an infinite wavelength or zero frequency, n(λ) → m for λ → ∞. if only the two first terms on the right hand are used, we have n λ( )= m+ a1 λ2 then m can be calculated from measurements of two values of n corresponding to two wavelengths λ1 and λ2 with the result that m = λ1 2n1 − λ2 2n2 λ1 2 − λ2 2 having discussed his own data and those reported by other scientists, lorenz concluded that m only depends on the density and that the temperature merely enters indirectly, namely by changing the volume and hence the density. he ended up with the following expression for water: m t( )=1.3219+ 21.05t − 2.759t2 +0.02134t3⎡⎣ ⎤⎦10 −6 although lorenz’s experimental work was of unsurpassed precision (figure 4), it did not differ essentially from similar measurements made in german and french laboratories. what distinguished his work from investigations made elsewhere was its connection to theory, which he covered in the second part of his treatise. proceeding from his fundamental wave equation lorenz deduced in 1869 that the quantity (m2 – 1)v/ (m2 + 1) was given by a certain function that only depended on the distribution in space of the refractive substance. since it was known from the gladstone-dale rule that (m – 1)v was approximately constant, lorenz concluded that the correct law of refractivity was given by what he called the “refraction constant,” namely m2 −1 m2 + 2 v = constant  = rll( ) this result was independent of the form of the molecule, he argued. however, for reasons of simplicity he assumed the refractive medium to be composed of optically homogeneous spherical molecules with mi being their internal refractive index. with vi being the specific proper volume of the molecules lorenz could then write the law as m2 −1 m2 + 2 v = mi 2 −1 mi 2 + 2 vi figure 4. lorenz’s apparatus of 1869 for the determination of the refractivity-density relationship for liquids. in the tank c a thin tube with the liquid is enclosed between two mirror glasses l and l’. the two parts of the tank f and f’ and the two small containers h and h’ are filled with distilled water. the tank is mounted between two jamin mirrors b and a formed as cubes. one of the light rays passes the tube while the other ray passes the water in the tank with the result that the interference lines are displaced. by measuring the number of displaced lines and the weight of the liquid lorenz could relate the refractivity of the liquid to its density. 11the lorenz-lorentz formula: origin and early history he further argued that the reduced refractive index was approximately constant and for a mixture consisting of k non-interacting components could be expressed as m2 −1 m2 + 2 v = j=1 k ∑ mj 2 −1 mj 2 + 2 vj the observation turned out to have significant consequences for chemical investigations. for an isotropic substance consisting of only one kind of molecule he deduced the approximate relation m2 −1 m2 + 2 v = p 1− k2 v2 ⎛ ⎝⎜ ⎞ ⎠⎟ here p and k are two constants that depend on the molecular structure of the substance but not on its volume or temperature. for a gas, where v is large and m only slightly larger than 1, m2 −1≅ 2 m−1( )  and   m2 + 2 ≅ 3 lorenz noted that the expression above approximates to n−1( )v =   3 2 p in agreement with the gladstone-dale formula. moreover, the lorenz expression also accommodates the newton-laplace rule since n2 −1 d = rll n 2 + 2( )≅ 3rll only after a period of six years did lorenz return to his studies of refraction, this time in a predominantly experimental paper where he reported measurements on oxygen, hydrogen, water vapour, ethanol, ether and other volatile liquids.11 lorenz’s law of refractivity, derived as a theoretical consequence of his theory of light, received solid confirmation in 1880, when the danish physicist peter k. prytz published extensive measurements on the refractive constants of a variety of liquids and vapours. the measurements showed convincingly that lorenz’s law was superior to the gladstone-dale rule.12 prytz’s 1880 paper in annalen der physik und chemie was preceded by a paper in which lorenz presented a detailed summary of his two communications on optical refraction originally published in two sequels in the proceedings of the royal danish academy.13 using a new and simpler approach he derived the same expression for the relation between refractivity and density as in his earlier theory, namely a constant value of the ratio (n2 – 1)/d(n2 + 1). it was only on this occasion that the international community of physicists became aware of his extensive work on the refractivity-density law. since his memoirs of 1869 and 1875 were written in danish, they were known only by scientists in scandinavia. 4. optical refraction and molecular physics lorenz was convinced that optical research provided a method to obtain information about the size of molecules and their number in a volume or mass unit of a substance (figure 5). in his 1875 paper he derived that for a substance composed of spherical and optical homogeneous molecules, n2 −1 n2 + 2 v = ni 2 −1 ni 2 + 2 vi 1+δ( ), with β being a measure of the molecular radius, he stated the δ quantity as δ = 16 5 π 2 ni 2 −1 ni 2 + 2 β 2 λ2 according to lorenz, it followed from experiments that for λ = 589.3 nm (sodium light) the value of δ was approximately 0.22. lorenz used this result for two purposes. first, he pointed out that since δ = δ(λ-2) the expression explained dispersion, if only qualitatively, without relying on special assumptions about molecular forces or the structure of the ether. this contrasted with cauchy’s earlier theory of dispersion which relied on such assumptions and also was unable to explain why dispersion does not take place in void space. in lorenz’s very different theory, dispersion was a property of the heterogeneity of a substance and thus excluded dispersion in a vacuum. importantly and contrary to other optical theories at the time, lorenz’s theory did not assume the existence of an ethereal medium. the second use he made of his result was to estimate a lower limit to the size of molecules. in lorenz’s theo12 helge kragh ry the quantity β was not literally the molecular radius but what he cautiously called “the radius of the molecular sphere of action, meaning the sphere surrounding a molecule within which there is an appreciable effect of the molecule’s influence on the velocity of light propagation.” this quantity is greater than the actual or material radius of the molecule. since ni 2 −1 ni 2 + 2 <1 and with δ known, lorenz was able to conclude that β >1.5×10−8  m he was pleased to note that the german physicist georg hermann quincke from recent measurements of viscosity and capillarity had found molecular radii agreeing with the limit inferred from the optical method.14 using a different optical method based on the scattering of light on a small sphere, in an important memoir of 1890 lorenz refined his value of β. he also estimated a value for the number of molecules in one millilitre of a gas, a quantity known as loschmidt’s number (nl) and named after the austrian physicist and chemist josef loschmidt.16 the better known avogadro number na is given by na = 6.022 mole −1 ≅ 22.4103 × nl lorenz reported nl = 1.63×1019 while the modern value is nl = 2.688×1019. 5. lorentz’s electromagnetic route lorenz’s law of refractivity is today referred to as the lorenz-lorentz law, or more commonly the lorentzlorenz law, because h. a. lorentz (figure 6) derived the same result in 1878.17 just the year before, he had been appointed professor of theoretical physics at the university of leiden, at the tender age of 24. in his doctoral dissertation of 1875 lorentz referred to the refractive index of various substances as given by their dielectric constants.18 he briefly discussed the newton-laplace formula relating the refractive index to the density but at the time without suggesting an improved law based on the electromagnetic theory. contrary to the danish physicist, in his memoir of 1878 lorentz obtained the improved law by combining the clausius-mossotti formula (see below) with the electromagnetic theory of light. however, he did not rely primarily on maxwell’s theory but rather on an alternative action-at-a-distance theory proposed by hermann von helmholtz.19 at the time maxwell’s field theory was generally considered to be very difficult, almost impenetrable. although lorentz appreciated the theory, he thought that it depended too much on unconfirmed hypotheses. what is known as the clausius-mossotti formula was first proposed, if only implicitly, by the italian physicist ottaviano fabrizio mossotti in 1847. much later the formula was stated by rudolf clausius in 1879 in an attempt to explain the dielectric properties of insulators on an atomistic basis. from a historical point of view the order of names is perhaps unfortunate, but “mossotticlausius” is rarely used. with εr the material’s dielectric constant (or relative permittivity ε /ε0 and α denoting the polarizability of the molecule, the clausius-mossotti formula for a unit volume with n molecules is figure 5. ludvig v. lorenz. royal library, copenhagen, picture collection. 13the lorenz-lorentz formula: origin and early history εr −1 εr + 2 = 4π 3 nα in modern literature this expression, which for n = na is called the molar refractivity, is often used synonymously for the lorenz-lorentz formula. in a paper of 1910 on the theory of opalescence einstein appropriately referred to it as the clausius-mossotti-lorentz formula.20 modern physicists sometimes use the more cumbersome name clausius-mossotti-lorenz-lorentz (cmll) formula. the declared purpose of lorentz’s work was to construct a theory of the optical properties of matter, such as indicated by the title of his memoir, which in english reads “concerning the relation between the velocity of propagation of light and the density and composition of media.” contrary to his danish near-namesake, lorentz considered a molecular or atomic model in connection with his theory, namely that a molecule consists of an electric charge harmonically bound to the rest of the molecule and characterised by its electric polarizability. he thought of the material molecule as being situated at the centre of a sphere or cavity, an idea which can also be found in lorenz’s paper of 1875. lorentz thus pictured the molecules as embedded in an all-pervading ether, which he, much like maxwell, regarded as a dielectric substance. he emphasised the necessity of assuming inter-molecular space being filled with ether, a belief he stated was “not open to doubt.” lorenz, on the other hand, had dismissed the ether as superfluous and even “unscientific” in his electrical theory of light from 1867 and it played no role whatsoever in his optical theory two years later. after a series of complex calculations lorentz ended up with the following expression: n2 −1 n2 + 2( )d = 4π 3 ρ3 3+ 4πε0( )− 4πε0 ρ3 κ m 3+8πε0( ) ρ3 κ −8πε0 here ε0 denotes the dielectric constant of the free ether, m is the mass of a molecule, d the density of the body, and κ is the ether’s specific resistance according to helmholtz’s theory. the quantity on the right side of the equation is thus a constant for a particular transparent body. in the last part of his extensive 1878 memoir lorentz compared his theoretical law of refraction with available experimental data from the literature. unlike lorenz, he did not perform experiments of his own. in its modern formulation the lorenz-lorentz law is stated as a relation between the refractive index of a substance, a macroscopic quantity, and its polarizability α, a microscopic quantity: n2 −1 n2 + 2 = 4π 3 nα , when the polarizability is small, the equation reduces to n2 −1≅ 4πnα     or    n−1≅ 2πnα in agreement with the gladstone-dale formula, this expression is valid for gases at normal pressure. it follows from the lorenz-lorentz theory that the polarization of a molecule in a solid body under the influence of an external electric field is not only determined by the strength of the field and the number of molecules per volume. there is also an effect due to the polarized figure 6. hendrik a. lorentz in 1927. courtesy the niels bohr archive, copenhagen. 14 helge kragh neighbour molecules which produce an additional force. this force was in the earlier literature sometimes called the “lorentz-lorenz force,” a name which should not be confused with the well-known lorentz force acting on an electrical charge moving in a magnetic field.21 although lorenz never referred to the electromagnetic derivation of the lorenz-lorentz law in his publications, in an unpublished manuscript from 1887 he used his own electrodynamic theory to derive the law.22 based on his electrical theory of light from 1867 he found an expression for the refractive index and its dependence on the molecular currents elements (figure 7). in this way he concluded wholly independently of maxwell’s theory that the medium’s dielectric constant was given by the expression εr ≡ ε /ε0 = n 2 he thus arrived at the very same relationship as found by lorentz. 6. lorenz-lorentz or lorentz-lorenz? because h. a. lorentz originally published his paper in dutch, and l. v. lorenz published his two papers of 1869 and 1875 in danish, the lorenz-lorentz formula became generally known only when abridged and revised versions of their papers appeared in german in 1880. both of the papers were published in annalen der physik und chemie but in two different issues and with lorentz’s as the first. gustav heinrich wiedemann, the editor of annalen, had originally planned to have the two papers published consecutively, but for some reason this did not happen.23 apparently the two authors were at the time unaware of each other’s work. in the case of lorenz, he summarised and discussed the two danish articles whereas lorentz’s german paper was a substantially reduced and revised version of his 1878 memoir published in dutch in the proceedings of the amsterdam academy.24 in a series of lectures delivered at columbia university, new york, in 1906, lorentz called the double discovery “a curious case of coincidence.”25 referring to the annalen papers of 1880, the british physicist arthur schuster wrote a few years later that “two authors of similar name, h. a. lorentz of leyden, and l. lorenz of kopenhagen [sic], have almost simultaneously published investigations leading to the result that (μ2 – 1)/(μ2 + 2) d is constant.”26 again, when awarding lorentz the rumford medal in 1909, lord rayleigh said about the formula that it had been “reached simultaneously, along different special lines, by h. a. lorentz originally from helmholtz’s form of maxwell’s electric theory, and by l. lorenz, of copenhagen, from a general idea of propagation after the manner of elastic solids.”27 however, given that lorenz published his result as early as 1869 the curious coincidence does not constitute a proper case of simultaneous discovery. robert merton and other sociologists of science have long ago noted that discoveries in science are rarely made by a single scientist or group of scientists. discoveries are almost always “multiples,” meaning that the same or nearly the same discovery is made by two or more scientists (or groups of scientists) working independently of each other.28 multiple discoveries may be more or less simultaneous, but the important thing is not so much the chronology as it is that they are made independently. merton proposed, somewhat artificially, that even discoveries far removed from one another in time may be conceived as “simultaneous” in what he called “social and cultural time.”29 applying the notion of simultaneity in its ordinary meaning there is no doubt that priority to the lorenzlorentz law belongs to l. lorenz and, consequently, that it should not be referred to as the lorentz-lorenz law. on the other hand, the discovery was not lorenz’s alone, what merton called a “singleton.” it can be seen as a classic example of a multiple discovery, in this case a “doublet” separated in time by nine years. the order lorenz-lorentz can be found in the literature in the 1890s, but with the rising fame of the dutch physicist the order was soon reversed or lorenz simply left out. in an obituary article on lorentz, max planck referred to the formula relating refractivity and density, “which by accident had been established at the same time by his namesake, the danish physicist ludvig valentin lorenz, and for this reason has been assigned the curious double name lorentz-lorenz.”30 much later figure 7. lorenz’s unpublished derivation of the relationship between the dielectric constant (d) and the specific refractivity (n). 15the lorenz-lorentz formula: origin and early history we find the same usage in the authoritative textbook on optics written by max born and emil wolf: “by a remarkable coincidence, the relation was discovered independently and practically at the same time by two scientists of almost identical names, lorentz and lorenz, and is accordingly called the lorentz-lorenz formula.”31 as an illustration of the popularity of the two terms, google scholar gives ca. 14,900 results for “lorentz-lorenz” and ca. 3,700 results for “lorenz-lorentz.” the preference for the first eponymous term can be seen as an example of a general tendency to associate a discovery with the name of a famous scientist even in cases where priority belongs to someone else.32 the clausius-mossotti formula is another example. google scholar also lists the number of references to the two annalen papers of 1880, namely 192 references to lorenz’s paper and 644 references to lorentz’s. 7. a tool for physical chemistry after the refraction studies of lorenz and lorentz had become widely known they spurred a large number of experiments in molecular refractivity under various conditions. the overall result of this work was that the lorenz-lorentz law agreed far better with experimental data than competing formulae of an empirical nature. in a review paper of 1888 the british physicist arthur william rücker referred to the works of l. lorenz and h. a. lorentz as well as to prytz’s experimental confirmation of the law named after them. rücker found it of particular interest that the measurements of lorenz and prytz indicated that the value of (n2 – 1)/(n2 + 2) did not depend on whether the substance was in a liquid or a vaporous state (table 1). having reviewed the experimental data rücker concluded that “the results, on the whole, confirm the accuracy of the physical meaning of the expression (n2 – 1)/(n2 + 2) and tend to show that the diameter of the molecule is the same in the liquid and gaseous state.”33 this was also the conclusion of the austrian physicist franz exner, at the university of vienna, who in 1885 stated that the lorenz-lorentz law had been “completely confirmed.”34 as exner pointed out, the law served as a key instrument for obtaining information about the size and constitution of molecules and the range of the unknown molecular forces. for the diameter of gas molecules he suggested the formula d = c n2 −1 n2 + 2 ℓ , where c is an empirical constant and ℓ the mean free path of the molecules. combining refractivity and diffusion measurements exner found d = 10-10m for air molecules (n2, o2) and d = 2.7×10-10m for cs2 vapour. the subject of molecular refractivity belonged as much to chemistry as to physics. indeed, refractivity studies had been part of theoretical chemistry many years before the lorenz-lorentz formula. the new formula further stimulated this kind of work which played a most important role in the new discipline of physical chemistry that emerged during the 1880s. when lorenz and lorentz figure in books on the history of chemistry, and not only in those on the history of physics, it is principally because of their role in the lorenz-lorentz formula.35 by the turn of the century the formula and related refractivity studies had become a staple part of textbooks in physical chemistry.36 the leading swiss chemist hans heinrich landolt and his german colleagues wilhelm ostwald and julius wilhelm brühl were among those who applied the lorenz-lorentz formula to calculate the so-called molecular refractivity (or refractive power) of a particular substance. they defined this quantity as the product of the specific refractivity rll and the molecular weight m, that is, with n determined at a particular wavelength, mrll = n2 −1 n2 + 2 ⋅ m d   in cases where the gladstone-dale formula was used, the molecular refractivity was similarly given by mrgd = n−1( ) m d the monochromatic light used in most experiments was either the yellow sodium d line (λ = 589 nm) or the red hα line in the spectrum of hydrogen (λ = 656 nm). it turned out that in many cases the summation rule for mixtures could be carried over to chemical comtable 1. data for the quantity (n2 – 1)/(n2 + 2) obtained by lorenz and prytz. source: rücker (1888). substance formula work liquid vapour ethyl ether (c2h5)2o lorenz (1875) 0.30264 0.3068 ethanol c2h5oh lorenz (1875) 0.28042 0.2825 water h2o lorenz (1875) 0.20615 0.2068 methanol ch3oh prytz (1880) 0.2567 0.2559 methyl acetate (ch3)2coo prytz (1880) 0.2375 0.2399 ethyl formate c2h5cooh prytz (1880) 0.2437 0.2419 16 helge kragh pounds, such as suggested as early as 1863 in a paper by gladstone and dale.37 if a compound consists of q1, q1,… elements with atomic weights μ1, μ1,… then the molecular weight is m = q1µ1 +q2µ2 +… according to the summation rule the molecular refractivity r = rll is simply the weighted sum of the individual atomic refractivities given by ri = ni 2 −1 ni 2 + 2 ⋅ µi di that is, n2 −1 n2 + 2 ⋅ m d = q1µ1r1 +q2µ2r2 +… experiments showed that although the rule was approximately correct for many compounds it was not universally true. in several cases the molecular refractivity differed substantially from the sum of the constituent atomic refractivities or, differently phrased, a particular atomic refractivity did not always have the same value. it was soon recognised that the molecular refractivity is influenced also by the constitution of the molecule as given by the arrangement of atoms and the presence of double and triple bonds. the pioneer in this branch of optical chemistry was j. w. brühl, who employed the lorenz-lorentz formula in a series of elaborate studies of inorganic as well as organic substances. by considering the refractivity values of compounds in homologous series he derived the corresponding values for double and triple bonds in molecules. he applied this method to the vexed and much-discussed question of the constitution of benzene, c6h6. on the assumption of kekulé’s structural model with three single and three double bonds brühl found a theoretical value for benzene’s molecular refractivity that only differed 0.6% from the measured value. on the other hand, he concluded that alternative formulae suggested by h. armstrong, a. von baeyer, j. thomsen and others did not agree with benzene’s molecular refractivity (figure 8).38 while the lorenz-lorentz formula aroused great interest in the chemical community, none of the founders of the formula took much interest in the chemical applications. this is perhaps understandable in the case of lorentz, who had neither interest in nor knowledge of chemistry, but it is more surprising in the case of the chemically trained lorenz. in fact, at the end of his 1880 paper lorenz dealt with a number of chemical reactions during which the refractivity constant changed. from his own and others’ experiments he suggested that the change in refractivity might constitute a measure of the chemical affinity in the same way as the change in heat (q) did in the thermochemical thomsen-berthelot theory.39 lorenz suspected that exothermic processes were followed by a decrease in refractivity and endothermic processes by an increase. however, he admitted that the case of ammonia n2 +3h2 → 2nh3 +q was an exception to the rule. the molecular refractivity of nh3 was known to be 0.3266 and lorenz’s measurements of a mixture of n2 and h2 in the mass ratio μn : 3μh = 14 : 3 resulted in 0.3116. 8. conclusion the lorenz-lorentz law is a general, non-trivial relationship between the refractive index of a substance and its density. the origin of the eponymous law – or perhaps better formula – is traditionally dated 1880 and considered an example of a simultaneous discovery made independently by the two physicists after which it is named. however, although lorentz came to the law independently of lorenz and the discovery was thus a “doublet,” it is not a simultaneous discovery since figure 8. based on thermochemical arguments the danish chemist julius thomsen proposed in 1886 an octahedral model of benzene in which there were no double bonds. thomsen’s structural model was among those which brühl dismissed as incompatible with refractivity data based on the lorenz-lorentz formula. 17the lorenz-lorentz formula: origin and early history the danish co-discoverer formulated the law already in 1869, nine years before lorentz. for this reason i propose that the law should properly be called the lorenzlorentz law although most physicists and chemists prefer the other permutation.40 the routes of the two physicists to the refractivitydensity law were entirely different both as regards formalism and physical interpretation. and yet they arrived at exactly the same formula. in the physical sciences it is not unusual that the same result can be derived in different ways and therefore is not uniquely determined by the underlying theory. from a modern point of view the theory behind the lorenz-lorentz law is simply maxwell’s theory of electromagnetism, but lorenz’s original formulation had nothing to do with that theory. aware of the dual origins of the law, wilhelm ostwald commented that “this agreement between two completely different approaches increases the probability that the result has a more general significance than if it were based on one or the other of the theoretical foundations.”41 whatever its theoretical background and interpretation, the lorenz-lorentz law was eminently successful and instantly applied to the study of molecular refractivity and related branches of chemistry, physics and materials science. by the early twentieth century it was predominantly a resource for the new generation of physical chemists rather than a topic belonging to theoretical physics. acknowledgments my thanks to christian joas, the niels bohr archive, copenhagen, for helpful comments on an earlier version of the paper. references 1. https://www.nobelprize.org/nobel_prizes/physics/laureates/1902/lorentz-lecture.html. 2. l. lorenz, phil. mag. 1867, 34, 287. e. whittaker, a history of the theories of aether and electricity, pp. 267-270, nelson and sons, london, 1958; w. kaiser, theorien der elektrodynamik im 19. jahrhundert, pp. 157-162, gerstenberg verlag, hildesheim, 1981. 3. i. newton, opticks, pp. 270-276, william innys, london, 1718. 4. j. h. gladstone, t. dale, phil. trans. roy. soc. 1858, 148, 887. 5. j. h. gladstone, t. dale, phil. trans. roy. soc. 1863, 153, 317. 6. w. sutherland, phil. mag. 1889, 27, 141. 7. w. johst, ann. phys. chem. 1883, 20, 47. 8. l. lorenz, phil. mag. 1863, 26, 81. for lorenz’s contributions to optics, see h. kragh, appl. optics 1991, 30, 4688 and o. keller, progress in optics 2002, 43, 195. 9. l. lorenz, kgl. da. vid. selsk. skrifter 1869, 8, 205. french translation in h. valentiner, ed., oeuvres scientifiques de l. lorenz, 2 vols., royal danish academy of science, copenhagen, 1898-1904. 10. j. jamin, compt. rend. 1856, 43, 1191. 11. l. lorenz, kgl. da. vid. selsk. skrifter 1875, 10, 483. 12. p. k. prytz, ann. phys. chem. 1880, 11, 104. 13. l. lorenz, ann. phys. chem. 1880, 11, 70. 14. g. quincke, ann. phys. chem. 1869, 137, 402. 15. l. lorenz, kgl. da. vid. selsk. skrifter 1890, 6, 1. the paper is today recognized as the foundation of so-called mie-lorenz scattering theory. 16. r. m. hawthorne, j. chem. educ. 1970, 47, 751. 17. h. a. lorentz, collected papers, vol. 2, pp. 1-119, martinus nijhoff, the hague, 1934-1936. 18. h. a. lorentz, collected papers, vol. 1, pp. 193-383, martinus nijhoff, the hague, 1934-1936. 19. e. a. woodruf, isis 1968, 59, 300; t. hirosige, hist. stud. phys. sci. 1969, 1, 151. 20. a. einstein, ann. phys. 1910, 33, 1275. 21. handbuch der physik, vol. 20, pp. 503-505, j. springer, berlin, 1928. 22. manuscript dated 1 june 1887; lorenz papers, royal danish academy of science. 23. wiedemann to lorenz, 7 may 1880; lorenz papers, danish museum of science and technology. 24. h. a. lorentz, ann. phys. chem. 1880, 9, 641; l. lorenz, ann. phys. chem. 1880, 11, 70. 25. h. a. lorentz, the theory of electrons, dover publications, new york, 1909. 26. a. schuster, an introduction to the theory of optics, p. 284, edward arnold, london, 1909. 27. lord rayleigh, proc. roy. soc. a 1909, 82, 1. 28. w. f. ogburn, d. thomas, pol. sci. quart. 1922, 37, 83; r. k. merton, the sociology of science, pp. 343370, university of chicago press, chicago, 1973; d. lamb, s. m. easton, multiple discovery, avebury publishing, avebury uk, 1984. 29. ref. 28 (merton), 369. 30. m. planck, naturwissenschaften 1928, 16, 549. 31. m. born, e. wolf, principles of optics, p. 87, pergamon press, oxford, 1970; j. d. jackson, classical electrodynamics, p. 119, john wiley & sons, new york, 1962. 32. t. f. gieryn, ed., science and social structure, pp. 147-158, new york academy of sciences, new york, 18 helge kragh 1980; j. d. jackson, am. j. phys. 2008, 76, 704. 33. a. w. rücker, j. chem. soc. trans. 1888, 53, 222. 34. f. exner, sitzungsber. kais. akad. wiss. 1885, 91 (2), 850. 35. a. j. berry, from classical to modern chemistry, pp. 88-90, dover publications, new york, 1968; a. j. ihde, the development of modern chemistry, p. 393, dover publications, new york, 1984. 36. e.g., j. h. van’t hoff, vorlesungen über theoretische und physikalische chemie, part iii, pp. 75-76, vieweg und sohn, braunschweig, 1903; w. nernst, theoretical chemistry, pp. 306-313, macmillan and co., london, 1904. see also the comprehensive review in s. smiles, the relations between chemical constitution and some physical properties, pp. 239-324, longmans, green and co., london, 1910. 37. j. h. gladstone, t. dale, phil. trans. roy. soc. 1863, 153, 217. 38. j. w. brühl, zs. phys. chem. 1887, 1, 307; brühl, ber. deut. chem. gesselsch. 1891, 24, 1815. for the debate concerning the structure of benzene, see a. j. rocke, ann. sci. 1985, 42, 355 and s. g. brush, stud. hist. phil. sci. 1999, 30, 21. 39. h. kragh, brit. j. hist. sci. 1984, 17, 255. 40. the case for lorenz-lorentz over lorentz-lorenz was briefly argued in a. sihvola, ieee antennas prop. mag. 1991, 33, 56. 41. w. ostwald, grundriss der allgemeinen chemie, p. 133, w. engelmann, leipzig, 1899. ostwald mistakenly thought that lorenz’s optical theory belonged to the older tradition of elastic ether theories. substantia. an international journal of the history of chemistry 1(1): 25-36, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-11 citation: c.l. khetrapal, k.v. ramanathan (2017) title. substantia 1(1): 25-36. doi: 10.13128/substantia-11 copyright: © 2017 c.l. khetrapal, k.v. ramanathan.this is an open access, peer-reviewed article published by firenze university press (http:// www.fupress.com/substantia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the authors declare no competing interests. feature article developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 1centre for biomedical research, sanjay gandhi post graduate institute of medical sciences campus, raebareli road, lucknow 226 014, india 2nmr research centre, indian institute of science, bangalore 560012, india corresponding author. e-mail: clkhetrapal@hotmail.com abstract. nmr has made rapid progress in the last more than seven decades after its discovery. this article reviews the development of this field over the years with emphasis on some of the recent developments with interesting consequences for the study of mental health and human behaviour. keywords. nmr, mri, fmri, molecular structure, brain imaging introduction nuclear magnetic resonance (nmr) is perhaps the only field which has produced seven nobel laureates till date in all the disciplines of science in which the prize is given, in a short span of about seventy years from the discovery of the phenomenon. over this period, it has thus established itself as a full-fledged interdisciplinary science rather than being just an analytical technique. its utility has been fully exploited by physicists, chemists, biologists, clinicians, agriculturists, industrialists, computer scientists, psychologists and social scientists. the developments of the field up to 1996 are described in the eight-volume encyclopaedia of nmr1 published in the year 1996 to commemorate 50 years of the discovery of the phenomenon. the growth of the field has been so voluminous that a supplementary 9th volume of the encyclopaedia had to be published within 5 years of the initial publication.2 this presentation gives a brief description of the field over these years from the perspective of the authors. the articles published by the authors earlier have been liberally used. developments of the field ‘at a glance’ are presented in fig.1. nmr in bulk material purcell in mit/harvard and bloch in stanford became interested in experiments leading to accurate measurements of magnetic fields/magnetic 26 c.l. khetrapal and k.v. ramanathan moments. both the groups succeeded and nmr in bulk materials was born in 1945 and the results published in the same issue of the physical review.3,4 both the scientists got the nobel prize in physics in 1952. nmr in india started in 1951 with the first report of nmr experiments carried out in flowing liquids by suryan5 who demonstrated that the arrival of fresh polarized sample at the rf coil decreases saturation and results in a more intense nmr signal. he was able to estimate spin – lattice relaxation time (t1) from the flow rate and the geometrical parameters of the system. nmr in chemistry proton chemical shifts: dramatic observation6 of separate lines for non-equivalent protons in the same molecule, by arnold, dharmatti and packard in 1951 set the stage for most of the applications of nmr in various branches of sciences dealing with structural studies. the first molecule to be studied was acetic acid and then ethyl alcohol (fig. 2). this led to the discovery of ‘chemical shifts’ in protons and it formed the basis of most of the applications of nmr. indirect spin-spin couplings: this is another parameter which is of great significance in structural studies. figure 1. developments of nmr at a glance. developments of nmr – at a glance discovery in bul material 1945-1946 chemical shift 1950 coupling constant 1951 relaxation processes 1946 solids structure and motion 1948 chemical applications 1951 exchange processes 1953 pulse experiments: spin echoes 1950 quadrupole splittings 1950 interpretation of complex spectra 1953 nuclear overhauser effect 1953 magic angle spinning 1958-1959 new era nematic liquid crystals in nmr 1963 multipulses 1968 imaging 1973 ft-nmr 1966 new dimensions to molecular structures 1964 structure in the solid state: material science clinical applications multidimensional nmr 1971 membrane studies 1971 polymers functional imaging biomolecular structure metabolic studies direct relevance to society 3-dimensional structure of biomolecules future horizons: (1)  clinical applications (2)  mind reading (3)  ultra low field nmr figure 2. first reported proton nmr spectrum 1 spectrum of ethyl alcohol. reprinted from ref. 6, with the permission of aip publishing. 27developments of nmr from molecules to human behaviour and beyond unlike chemical shifts, it is field-independent. it is difficult to establish unequivocally the real discoverer of spinspin couplings; at least the following three groups can be considered independently responsible for its observation. 1. arnold, dharmatti and packard did get the indication of some fine structure as line-distortion particularly in the methyl peak in their original spectrum of ethyl alcohol (fig. 2) but this distortion went unnoticed. 2. gutowsky and hoffman observed 2 lines of comparable intensity in the 19f spectrum of pf3.7 3. hahn and maxwell observed the same effect in entirely different manner – as ‘slow-beats’ in the spin-echo envelope for non-equivalent protons8. in structural studies, the spin-spin couplings have been extensively employed to estimate the dihedral angles using karplus equations.9 the couplings for protons on adjacent saturated carbons (jvicinal) can be employed to estimate the dihedral angles within a precision of a few degrees using the following empirical equations: (jvicinal) = 8.5 cos2 j-0.28 hz (for 0°<j<90°) (jvicinal) = 9.5 cos2 j-0.28 hz (for 90°<j<180°) new era in nmr the following discoveries changed the destiny of nmr and the field entered a new era. 1. fourier transform nmr (1965-66) 2. two-dimensional nmr (1971-72) 3. magnetic resonance imaging (1973-74) fourier transform nmr: the development of fourier transform methods10 represents a turning point in the history of nmr. in an nmr experiment at a particular magnetic field strength (bo), the angular frequency of precession (ωo) of the nuclei is given by the larmor equation ωo = γbo where the proportionality constant γ is the magnetogyric ratio ( ratio of the magnetic moment to the angular momentum). in a conventional continuous wave nmr experiment, the resonance condition is arrived at either by keeping the frequency of irradiation fixed while varying the magnetic field fixed or vice versa. such slow scan experiments were of limited utility especially for studies of solutions with low concentrations of the nuclei of interest, nuclei with low natural abundance, larger molecules, fast dynamic processes and so on. even as efforts to improve the sensitivity of the nmr experiment were in progress, to speed up the experiment ernst and anderson10 suggested the use of the fourier transform method. herein, a short burst of radiofrequency (r.f.) excitation, called a pulse of r.f., excites nuclear spin resonances over a broad band of frequencies. the precession of nuclear spins having resonance frequencies falling in this band-width generates the nmr signal in the time domain. subsequent fourier transform of the signal provides the frequency domain nmr spectrum. this innovation changed nmr signal acquisition from frequencydomain to time-domain and thus on the one-hand made the nmr experiment faster by several-folds. on the other-hand, it opened up the flood-gates for innovation in nmr and the possibility of carrying out a whole lot of new experiments. thus a new era of research and applications of nmr was born. though difficult to publish the results at the time, the experiment formed the basis of the 1991 nobel prize in chemistry to richard ernst. two –dimensional nmr: the concept of twodimensional (2d) fourier transform nmr was given by the belgian physicist j. jeener who presented his results at ampere international summer school, in 1971.11 he proposed a simple sequence of two 90° pulses separated by a time period t1which is incremented between the experiments. this is followed by double fourier transformation of the signal acquired after the second pulse. a spectrum is thus obtained which has spread in two frequency dimensions and for homonuclear experiments has diagonal as well as cross peaks. the cross peaks carry important information as they result due to magnetization transferred from one nuclear spin species to another that has an indirect spin-spin coupling to it. the results were never published formally. the school was attended by thomas bauman of richard ernst’s group. when briefed by baumann, ernst was very excited but still did not pursue the idea for quite some time since firstly he considered it as “jeener’s property” and secondly he did not have a computer adequate to handle the two-dimensional data storage and processing. eventually, he applied the concept to a different area namely magnetic resonance imaging (vide below) initially and later on published a series of papers that formed the foundation of two-dimensional nmr as a methodology.12 magnetic resonance imaging (mri): paul lauterbur conceived the idea of using magnetic field gradients to obtain 2 and 3 dimensional spatial information about the distribution of magnetic nuclei in a sample placed inside nmr coil. he thus created the picture of the object by nmr and called the technique as zeugmatography. he published the work in nature13 in 1973 and also submitted it as a poster presentation at the triennial conference of the international society of magnetic resonance held in bombay in 1974. the presentation was however, converted into an invited plenary talk by the organizers. 28 c.l. khetrapal and k.v. ramanathan mri is based on the principles of nmr but instead of revealing structures of molecules, mri reveals the structure of an object, by mapping the distribution of a molecule (usually water) in the object. mri’s most successful and well known application is in the field of medicine where it is used to image organs of a human body in microscopic details. in human mri, a person lies inside a large hollow magnet. with a combination of magnetic field gradients and radio waves, signals are produced. a computer converts these signals into a series of 2-d images. the images can then be combined to create highresolution 3-d pictures of the subject. advancements in the area such as fourier imaging (by kumar et al.14) and echo planar imaging (epi) introduced by mansfield15 contributed to a rapid expansion of the use of the technique in a number of contexts. nuclear magnetic resonance and magnetic resonance imaging and spectroscopy have developed into valuable diagnostic tools during the past three decades. the radiologists and the clinicians have literally captured the technique during this period like what the chemists did about a half a century back. reasons for such a widespread growth are built into the origin of the phenomenon, which involves the use of low energy electromagnetic radiation. the effects produced are, however, large and easily detectable with the present day technology, leading to details of molecular structures obtained at the atomic level. applications of nmr and mri nmr is being used in a variety of areas. the range of application of nmr is illustrated in fig.3. leaving out some of the well known applications of nmr in chemistry, in bio-molecular structure determination and in material science, we highlight here applications in some of the other areas. nmr application in agriculture hydration in food stuffs: it is based on the fact that water molecules in many such products are more mobile than the protons in the host matrix. the proton spectra thus consist of sharp signals superimposed on broad background.16 the state of absorbed water: it has been investigated in meat, seeds, dairy products, and vegetables.17 the effect of storage: significant differences in the free and bound water on storage have been reported on potatoes, garlic and apples.18 rapid distinction between oil and water in agricultural products: nmr has been employed in rapid distinction of oil and water and dedicated instruments manufactured for such purposes. the instrument manufacturers with publicity such as “…. accurate moisture contents in seconds…. not in hours” became multi-billionaires.19 oil build-up as a function of time after flowering of the seeds: nmr has been used to examine the quality of the oil as a function of maturity of the seeds as well as the determination of percentages of individual saturated and unsaturated fatty acids in intact seeds .20 total oil content in individual seeds: nmr has found extensive utility for selecting the best seeds for plant breeding. such a fast and non-destructive method provides a means to increase the average oil content of corn 2.25 times when compared with traditional selection methods resulting in gains over five generations that would have otherwise taken 20-30 generations.21 spatial distribution of water and oil in intact seeds: the spatial distribution of oil and water in intact groundnut and sunflower seeds have been obtained.22 in the immature commercial groundnut seeds complementary oil and water distributions have been observed (fig.4). the two images exhibit distinctly different features indicative of different intracellular environments in the two cotyledons – oils is present predominantly in one the cotyledons and water in the other. in this immature groundnut seed, it has been interpreted as the incomplete oilbuild up with the result that the oil and water within the seed are preferentially localized in complementary manner. the water soluble sugars yet to be converted to storage lipids are confined in one of the cotyledons. a physiological disorder may be responsible for this differential micro environment in the two cotyledons. figure 3. major applications of nmr in different areas. 29developments of nmr from molecules to human behaviour and beyond some clinical problems investigated using nmr the objective has been to identify specific markers for the quick and non-invasive diagnosis of the diseases and to monitor the treatment. several problems related to human bile, liver graft dysfunction, fulminant hepatic failure, bacterial urinary tract infection, mal-absorption syndrome, obstructive jaundice, breast disorders, congenital heart disorders, benign and malignant gallbladders, alkaptonuria, and mitochondrial diseases have been reported.23-33 results on three typical studies are briefly mentioned below. for details, one may refer to the cited literature. human bile: human bile being a complex mixture of numerous metabolites provides highly overlapping and complex spectra requiring the need for the highest field nmr especially for quantification of the individual components. a typical 800 mhz is reproduced in fig.5. the figure 4. 1h nmr images of transverse section of a commercial variety of ground nut seed. left: water image and right: oil image. the extreme right shows the scale with the concentration increasing from top to bottom. permission in attesa figure 5. 1h nmr spectrum of human bile at 800 mhz. reproduced from ref. 26 with permission of springer. 30 c.l. khetrapal and k.v. ramanathan assignments of the resonances due to various metabolites are shown in the figure. nmr in fact, provides a novel, unique single step method to identify and quantify such a large number of metabolites present in a mixture. once this was achieved several problems related to human bile have been investigated.23-27 assessment of liver graft dysfunction: a study of patients who underwent liver transplant was carried out. it was noted that some of the patients died before they were discharged from the hospital though surgically all operations appeared satisfactory. in this study, the use of nmr has been made to find out the reason for the death. studies on serum and urine samples of patients before liver transplantation and every 24 hours after the liver transplantation, till the time they were discharged/ alive, were taken. high levels of glutamine in both serum and urine and concomitant reduced urea levels in urine were found to be evidence of impairment in urea cycles and compatible with abnormal graft function. increased glutamine levels lead to brain death, if untreated. this is medically useful information since it gives prior information on what is going to happen and one may take corrective measures in advance.28 prediction of therapeutic outcome in patients with fulminant hepatic failure: fulminant hepatic failures (fhf) are associated with severe liver injuries leading to impairment of hepatic function followed by hepatic encephalopathy within eight weeks of the onset of the illness. the mortality rate is as high as 80%. liver transplant for fhf patient appears to be the only effective answer to this. since the survival rates are low, rapid diagnosis is necessary to identify patients for transplantation. until today, there is no means to predict the spontaneous recovery or non-recovery for such patients. 1h nmr to quickly identify molecular markers such as glutamine in serum and urine and urea in urine promise a potential in quickly deciding on liver transplantation. nmr spectroscopy has been used to determine the molecular markers in serum and urine to distinguish between those recovered patients and those who did not. glutamine in serum and urine glutamine/creatinine ratios were higher in non-surviving patients compared with surviving patients. on the other hand, no significant differences were found in conventionally employed clinical parameters such as serum alanyl-amino transferase, aspartyl-aminotransferase and bilirubin.29 bacterial urinary tract infection: qualitative and quantitative estimations of metabolites produced as a result of bacterial infection in the urinary tract have been reported. absolute concentrations of the metabolites provide the severity of the infection and, are likely to be very valuable in patients on antibiotic therapy with negative urine cultures.major bacteria in uti are e.coli, k. penumoniae, p. aeruginods and p. mirabilis. they uniquely metabolize lactose to lactate, glycerol to 1, 3propanediol, nicotinic acid to 6 hydroxy nicotinic and methiofigure 6. distinction between real bacterial infection and contamination. reproduced from ref. 31 with permission from john wiley & sons, inc. 31developments of nmr from molecules to human behaviour and beyond nine to 4-methyl-oxobutyric acid, respectively.30-33 these properties have been exploited to identify and quantify specific bacteria responsible for the infections. the nmr technique has also been employed to distinguish between the real infection and contamination as shown in fig.6. this is in fact one of the major problems in the precise diagnosis of uti and nmr provides a solution. examples of applications of mri mri is especially valuable for detailed imaging of the brain and the spinal cord. nearly all brain disorders lead to alterations in water content, which is reflected in the mri picture. a difference in water content of less than a percent is enough to detect a pathological change. in multiple sclerosis, examination with mri is superior for diagnosis and follow-up of the disease.34 the symptoms associated with multiple sclerosis are caused by local inflammation in the brain and the spinal cord. with mri, it is possible to see the of the inflammation in the nervous system and how intense it is, and also how it is influenced by treatment. mri is an important preoperative, improved diagnostic and reduced suffering tool for patients. mri has been used to reveal the effects of yoga on brain. the results show that concentration of gamma amino butyric acid (gaba), increases by performing certain yoga exercises.35 it implies that yoga, and perhaps some other forms of exercise should be utilized as a complementary treatment for depression and anxiety disorders. the results have clear public health utility. yoga should be compared with other forms of exercise to determine whether or not it is the nature of yoga postures that results in raised gaba levels, or it is an effect of any exercise. functional mri (fmri) functional mri is based on the fact that oxyhemoglobin is diamagnetic but when oxygen is consumed in metabolism, the haemoglobin becomes paramagnetic. this permits visualization of the regions of the brain in which metabolic activity occurs in response to an external stimulus.36 it can characterize functions while brain processes thoughts, sensations, memories, and motor commands. functional mri makes it possible for neurologists to detect early signs of alzheimer’s disease and other disorders, to evaluate drug treatments, and pinpoint tissue housing critical abilities like speech before venturing into a patient’s brain with a scalpel. such results provide a basis for designing new intervention techniques. illustrative applications of fmri considering the importance of the subject and its direct societal relevance, numerous interdisciplinary groups and institutions in this field have been established all over the world during the past few years. basic and social scientists, psychologists and medical doctors are now joining hands to exploit the interdisciplinary nature of the field in order to diagnose and understand not only the molecular structure and the diseases in human beings but also to understand the metabolic and structural changes in them. some illustrative applications are briefly described below: the dyslexics and non-dyslexics: numerous groups all over the world are involved in investigating biological bases of learning and learning disorders essentially because of great societal need. it has been reported that the deficiencies in functional brain organization underlying dyslexia can be reversed after sufficiently intense intervention lasting as little as 2 months. the reading difficulties in many children represent a variation of normal development that can be altered by intensive intervention.37 such investigations are of great importance.immediate creation of an interdisciplinary school on child psychiatry, social science and fmri is the need of the hour in societal interest. alcoholism in young adult, female alcoholics: specific areas of the brain impaired by years of heavy drinking have been identified in young adult women. previously, investigators have relied on thinking and memory tests to gauge brain dysfunction in alcoholics, but no one had identified the actual brain sites where impairment occurs in young adults. even young and physically healthy individuals risk damaging their brains through chronic, heavy use of alcohol.38 pretty female faces: they trigger activity in men’s brains. a beautiful woman’s face is like chocolate, cash or cocaine to a young man’s brain.39 when men in the study were shown pictures of various faces, only the female faces deemed beautiful triggered activity in brain regions previously associated with food, drugs and money. sex differences in mental rotation and spatial working memory: behavioural and neural sex differences in sexspecific spatial abilities have been investigated.40 males typically surpass females on tasks dealing with mental rotation and spatial navigation, while females tend to excel males on tasks dealing with object location, relational object location memory or spatial working memory. 32 c.l. khetrapal and k.v. ramanathan crime and lie detection: during the past few years, the data on crime detection by nmr has become voluminous. several hundred thousand entries are found in ‘google search’ under this category. pathological liars have been found to have brain abnormalities. brain deformities have been observed in people who habitually lie, cheat and manipulate. the brain area just behind the forehead exhibits structural difference among pathological liars41 and their white matter content is more. the finding could be used in making clinical diagnosis and may find applications in daily life, criminal justice system and the business world. the fmri is bound to transform the societal values system, the security and the judicial processes. by mapping the neural circuit behind deception, fmri will provide a new kind of ‘lie detector’ that is more probing and accurate than the polygraph – the standard lie-detection tool being employed for nearly a century. fmri may change the entire judicial system. it will be useful in high-profile crimes like terrorism. it may appear that fmri is expensive, bulky, noisy and time consuming for such routine applications. however, if one thinks of the cost of judicial process taking years to discover the truth or the price of missing a terrorist, nations can certainly afford it as far as the present costs are concerned. with more advances in technology, many of the limitations may be overcome as discussed in the subsequent sections. enhancement of trust among humans: intranasal administration of oxytocin, a neuropeptide causes a substantial increase in trust among humans.42 oxytocin specifically affects an individual’s willingness to accept social risks arising through interpersonal interactions. an fmri study may throw light on biological basis and provide scientific evidence on the role of oxytocin or human behaviour.most charitable people show enhanced activity in the top and back of the brain – an area normally linked to processing incoming information, sorting out social relationships and controlling movements! understanding the function of this region may give clues on the origin of social behavior.43 science behind health benefits of yoga and meditation: though it is well known that yoga and meditation can reduce stress and cure many diseases, recent times have seen the emergence of scientific evidence to demonstrate these beneficial effects using modern scientific technologies such as fmri. these results are drawing worldwide attention. neuro-imaging and genomics technology have been employed to measure physiological changes in greater detail. some typical studies are outlined below: fmri study of neuro-cognitive effect of sound “om” on human brain: the sound “om” is of paramount importance and is supposed to relax human beings physically, mentally and emotionally. the fmri results delineate the exact brain area involved in response to om sound and reveal that listening om recruits areas of both left and right hemispheres including left prefrontal cortex. this corresponds to “om” as a pleasant melodic sound which increases attention and emotional quotient and creates intuitive feeling towards spirituality (fig. 7). such studies provide a unique idea to employ modern scientific technologies to demonstrate whether yoga pertains to a figure 7. neuro-cognitive effect of “om” sound. (supplementary motor area (sma):involved in motorcoordinationsuperior temporal gyrus (stg): auditory perceptioninferior frontal gyrus (ifg): perception of pleasant sounddorso-lateral pre-frontal cortex (dlpc): involved in monitoring of attention process.) 33developments of nmr from molecules to human behaviour and beyond particular faith or religion or it is universal. it may go a long way to establish religious harmony and world peace if such an idea is pursued. the observation of the international yoga day has generated hot debates particularly in india on whether yoga pertains to a particular religion or faith. the use of modern scientific technologies such as functional mri and other technologies can throw light on the issue in an unbiased manner and will go a long way to establish world peace and happiness and religious harmony. the functional mri studies reported above delineate the exact brain areas involved in response to om sound and reveal that listening to om sound recruits areas in the brain involved in increasing attention and emotional quotient and creates intuitive feelings of happiness.44-47 a question arises whether such studies can result in providing a scientific approach to achieve religious harmony and world peace? it would be interesting to see whether ‘om’ is faith specific or it affects similarly to all irrespective of the religion or faith. one could even study the effects of “mantras” preached by different religions. if all have similar effects, it will establish scientifically for the first time that all religions preach the same thing and if the effects are specific only to om, then it will establish that this sound is universal and is independent of the religion. if studies of the mantras preached by different religions demonstrate changes in different areas of the brain but they too have positive health benefits it will throw a challenge to scientists to discover a “universal mantra” which takes into accounts positive aspects of all faiths. the results will establish a correlation between spirituality and science. “soham” meditation: the parts of the brain that show activity during meditation in general in fmri is illustrated in fig. 8. in “soham” meditation one merely observes the breathing process even as one repeats the word  ”soham” in mind,  synchronising it with breath. therefore the process is when one inhales, one mentally repeats the sound “so” and while exhaling the sound “ham” is repeated. as one breathes in and out the sound “soham” is repeated. grey matter in the brain fills about 40 percent of the whole brain in humans and consumes 94 percent of oxygen. the senses of the body (speech, hearing, feelings, seeing and memory) and control of the muscles, are part of the grey matter’s functions. differences in grey matter are observed between “soham” meditators and non-meditators (fig. 9). three distinct regions show higher grey matter concentration in meditators . positive attitude insures happiness: the power of positive attitude or perception, meditation, reciting and listening mantras etc in coping up of the various stresses and strains in human daily life is well known and is widely practiced. however, it may have better impact on common man’s daily life if one can demonstrate this by a scifigure 8. effect of soham meditation on the brain. middle frontal cortex (mfc): this implies regulation of attention, which in the case of meditation is directed at the subjects own mental and bodily state.left inferior frontal gyrus (ifg): involved in the cognitive aspects of emotional processing , such as paying attention to emotion or the identification of emotion.precuneus: involved in the execution or preparation of spatially guided behaviors. reprinted from ref. 45, copyright 2013, with permission from elsevier. 34 c.l. khetrapal and k.v. ramanathan entific evidence. a preliminary fmri study (brain imaging and behavior, august 2012) demonstrates that negativity is perceived by different brain regions compared to positive perception. the experiments decode specific regions in human brain involved in positive and negative perceptions. a crucial finding was the activation of the bilateral temporal pole for negative sentences (indicating sadness, anxiety and stress). no such effects were observed in affirmative sentences (fig. 10). a study48 on mentally depressed and anxious individuals also shows activation pattern similar to that in subjects with negative thoughts (fig. 11). recent advances in nmr, mri and fmri technology nano particles and fmri: the new generation of nanoscale calcium contrast agents being developed will have applications in understanding learning, memory, and behaviour and will allow functional fmri to make transition from imaging gross properties of brain to a fine-tunes analysis based on information flow involving cells and circuits .49 a new low-cost, portable mri technology: a novel laser-based mri technique is being developed by the alex pines and his colleagues in berkeley. it provides a viable alternative for mri detection with substantially enhanced sensitivity and time resolution. it will result in the development of a low cost, compact, portable and battery-powered portable mri technology and an on-line analytical instrument for monitoring chemical reactions and biological processes.50 nmr: from k gm to pico gm: the quantity of the paraffin sample initially used by purcell when he discovered nmr in bulk material was 1 k gm in weight and with developments or organic molecules possessing electronic properties analogous to those of gallium arsenide, it seems likely that nmr spectra of pico gm quantities of proteins and nucleic acids could be recorded.51 nmr nanometer-scale device: nmr has received considerable attention in the context of quantum computation and information processing which require controlled coherent qubit operations. towards achieving this goal, a self-contained nmr semiconductor device has been implemented that can control nuclear spins in a nanometre-scale region. high sensitivity at the microscopic level has been demonstrated for probing materials whose nuclei contain multiple spin levels and thus form the basis of a versatile multiple qubit device.52 nmr on a chip: if a nanoscale gallium arsenide structure is excited with an oscillating magnetic field, figure 9. grey matter differences in “soham” meditators and non-meditators: three distinct regions show higher grey matter concentration in meditators. left image: brain stem regulates breathing and anxiety level. right image:ventral palladiumregulates positive mood and motivation. bottom bottom:motor area regulates motor aspects. figure 10. influence of negation on human brain. distinct neural regions for negative sentences: temporal pole: this region is associated with anxiety and depression. figure 11. brain activation (bright color) characterizing the functioning of anxious and depressed persons as they process emotional information and respond to various types of positive and negative stimuli. reproduced with permission of the stanford mood and anxiety disorder laboratory. 35developments of nmr from molecules to human behaviour and beyond superposition of nuclear spin states can be created and detected electrically. quantum computing could be the beneficiary.51 conclusions to the question “is there an end in sight for the new exciting developments in nmr?”, the answer is a simple “no”. if one just looks at the advances in technology and the possible applications outlined above, one may predict that the best is yet to come. if a young man wants to remain “young”, here is an opportunity to enter the “young” field and get assured enjoyment and excitement for the rest of the life. acknowledgement k v ramanathan would like to thank the council of scientific and industrial research, india for the grant of an emeritus scientist position to him. the authors would like to thank prof. anil kumar for a careful 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natl. acad. sci. usa 2006, 103, 14707. 50. s. xu, v. v. yashchuk, m. h. donaldson, s. m. rochester, d. budker, a. pines, proc. natl. acad. sci. usa 2006, 103, 12668. 51. r. tycko, nature 2005, 434, 966. 52. y. go, m. koji, t. kei, h. katsushi, h. yoshiro, nature 2005, 434, 1001. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments substantia. an international journal of the history of chemistry 7(1): 15-22, 2023 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1872 citation: krishtalik l.i. (2023) the rate constant – reaction free energy dependence for the electron transfer reactions in solutions. the way to interpret the experimental data correctly. substantia 7(1): 15-22. doi: 10.36253/substantia-1872 received: jul 03, 2022 revised: feb 05, 2022 just accepted online: feb 08, 2022 published: march 13, 2023 copyright: © 2023 krishtalik l.i. this is an open access, peer-reviewed article published by firenze university press ( h t t p: // w w w.f u p r e s s .c o m /s u b s t a n tia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article the rate constant – reaction free energy dependence for the electron transfer reactions in solutions. the way to interpret the experimental data correctly lev i. krishtalik†1 a.n. frumkin institute of physical chemistry and electrochemistry, russian academy of sciences, moscow for correspondence please contact dr. vasily ptushenko (ptush@mail.ru) 1lev i. krishtalik left a noticeable mark in electrochemistry and biophysics. his scientific career started in the mid-1940s, when the hardships of wartime were replaced first by hopes for the best, and then by persecution of the numerous segments of the population and many scientific schools in the ussr. † 23.11.1927–26.02.2022 lev i. krishtalik. courtesy of vasily ptushenko. http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 16 lev i. krishtalik fortunately, lev krishtalik survived these difficult years, although he had to work for 15 years in the industry, doing science only in his off-duty hours. even in these hard conditions, he managed to perform an outstanding work on the experimental detection of barrierless electrode reactions (discharge of hydrogen ions). later, he worked in the alexander n. frumkin institute and contributed substantially to the theory of charge transfer reactions developed by revaz r. dogonadze and alexander m. kuznetsov and to its experimental confirmation. this was a cutting-edge field in chemistry and led to rudolph a. marcus’ nobel prize in chemistry in 1992. a little later, lev krishtalik developed his views on the catalytical abilities of enzymes. the work of krishtalik was well known at the time and his efforts were rewarded with the frumkin prize of the international society of electrochemistry in 2001. note that he was a disciple and one of the closest colleagues of alexander n. frumkin, although he was never formally his student. along with his scientific interests, lev krishtalik also had interests and encyclopedic knowledge in different cultural fields, including poetry, music, painting, and architecture. one of his favorite cities was florence, and the painting “la catena” with the medieval/renaissance landscape of florence was always on his bookshelf. his personal memoirs have been recently published (in russian; https://7i.7iskusstv.com/avtory/krishtalik/). lev krishtalik was a radiant personality. even in the most difficult moments of his life, he remained friendly to people and grateful to fate. this is the last manuscript which he worked on in his two or three last years of his life. unfortunately, his illness did not allow him to publish the paper before his death. vasily ptushenko abstract. the relative influences of the reorganization energies of the classical and quantum modes on the maximum position of the rate constant – reaction free energy curve have been studied. in the framework of the continuum electrostatics, the electron transfer reorganization energies in methyltetrahydrofurane solutions for the system biphenylyl – spacer – acceptor were calculated. for different acceptors, the solvent reorganization energy varies from 1.0 to 1.1 ev. when added with the rather small reorganization energies for classical intra-molecular modes we obtain 1.13–1.34 ev. with account of possible errors this coincides practically with the experimental estimate of the energy at the maximum of the rate–free energy curve δgmax ≈ -1.2 ev. hence, we can conclude that the reorganization of quantum modes does not influence substantially the position of this maximum. to the contrary, in a non-polar solvent isooctane were the solvent reorganization does not play any role the reorganization of the quantum intrareactants modes becomes determinant. these conclusions agree fully with the results of the general theoretical analysis and should be accounted for in the experimental data interpretation. keywords: reorganization energy, medium reorganization, intra-molecular reorganization, rate maximum. list of abbreviations: a – acceptor, bph – biphenylyl, d – donor, mthf – metyltetrahydrofurane, py – pyrenyl, sp – spacer, q – benzoquinonyl. 1. introduction one of the fundamental problems of the chemical and electrochemical kinetics is the physical mechanism of the elementary act of the electron transfer, especially in condensed media. this question was intensively studied in many theoretical works (in particular [1-4]; a short review of them is given in section 2. 1). electron transfer is connected with some reorganization of the reactant’s polar surroundings and reorganization of the molecules inner structure. these two processes are characterized by the corresponding parameters – the medium (solvent) reorganization energy λs and the intramolecular reorganization energy λv. the relative contribution of these processes has been many times discussed. in liquid solutions the kinetics of the electron transfer proper can be distorted by kinetics of the mutual diffusion of the reactants. therefore, most suitable for the comparison of the experimental results with the theory are the systems in which the donor and the acceptor are connected by a rigid linker ensuring a constant distance between the reactants. in the present paper, a typical example of such a system will be considered. in many papers dealing with the problem in chemical and biochemical systems [5-9], it has been a priori accepted that both the parameters – λs and λv – contribute substantially to the final result. accordingly, both parameters were found by fitting the experimental data to the theoretical equation derived under the same assumption. the results of such a fitting are not quite unequivocal. therefore, it is highly desirable to estimate the reorganization energies, both λs and λv by independent methods. as a vivid illustration of the possible prob17the rate constant – reaction free energy dependence for the electron transfer reactions in solutions lem the data of [7] can be mentioned. in this paper, the fitting for the system porphyrines – c2h4 – quinones in benzene and toluene has been performed with two sets of parameters – the first one λs = 0.18 ev, λv = 0.60 ev and the second λs = 0.60 ev, λv = 0.20 ev. the second set which is physically quite unrealistic gives the results almost so good as the first one. this shows again that one should use parameters obtained from the independent data. to emphasize this conclusion is the aim of the present paper. section 2 deals with the theory (2.1) and calculations (2.2); in section 3, the results described and discussed; in section 4, the conclusion are presented. 2. theory and calculations. 2.1 theory in this subsection, a short description of the most important theoretical results used in this paper is presented. marcus [1] was the first who has given, in the framework of a semi-classical theory, the correct exponential dependence of the reaction rate on the reaction free energy δg and the reorganization energy λ. levich and dogonadze [2] have done a quantum–mechanical analysis of the problem. they have obtained the same exponent and a strict expression for the pre–exponential factor. the final result is (1) here k is the rate constant, v(r) – the distance r dependent electronic coupling matrix element, h – planck constant, kb – boltzmann constant, t temperature. this equation is valid only at the high-temperature limit, e.g. under condition ћw << kbt, where ћw is the energy of vibration coupled to the electron transfer. from eq.1 follows that the rate constant – reaction free energy dependence presents a symmetric parabola with maximum at -δgmax=λ (1a) for the purpose of qualitative treatment of results it is instructive to recall the marcus formula for the medium reorganization energy (2). (2) here e is the charge to be transferred, εo and εs are optical and static dielectric permittivities of the medium, a1 and a2 are the radii of the spherical reactants, and r is the inter-center distance. this simple analytical solution is obtained for the case of two spherical reactants in an infinite homogenous medium. at a more complex geometry and an inhomogeneous medium one employs the numerical methods of calculation (section 2.2) with the same physical rationale as for derivation of the marcus eq.2; hence the latter is suitable for the qualitative discussion. dogonadze et al. [3] have considered a more general case when different oscillators are present with a wide range of the frequencies. they have shown the principal difference in the behavior of the intramolecular vibrations that have a high frequency ћω>>kt, i.e. much more than own vibrations of liquid solvent (ћω<<kt). consequently, they are much faster, and hence cannot influence the reorganization energy. it should be noted that the condition of low frequency (condition of the classical behavior) can be fulfilled not only for the solvent but also for some intramolecular movements. jortner [4] has presented in an explicit form the expression for the rate constant in the case of the presence of different oscillators. (3) where v(r)is the electron tunneling matrix element, ћw is the energy of the nuclear vibration coupled to electron transfer, s is λ/hw. here λ is the total reorganization energy equal to the sum of intramolecular (vibrational) component λv and the medium (solvent) reorganization λs; n is [exp(hw/kb t) – l]-1 where t is the absolute temperature, kb is boltzmann constant (it is the thermal population of a mode with vibrational frequency w), ip(z) is the modified bessel function, and p is – δg/ћω. this expression calculates the thermally weighted contribution of the franck-condon overlap integral from each vibrational quantum level to the rate. jortner’s eq.3 also predicts a parabolic k – δg dependence but the asymmetric one: at larger δg the rate is enhanced due to involvement of exited vibrational levels. the maximum of the rate is determined by the condition -δgmax=λv+λs (3a) let us consider the high-temperature limit, e.g. under condition ћw << kbt, where ћw is the energy of vibration coupled to the electron transfer. this situation usually exists when the reorganization takes place due to 18 lev i. krishtalik the change of the polarization of the surrounding dielectric medium. the latter can be described as a set of the low-frequency phonons. hence, for this case the jortner’s eq.3 simplifies to eq.1 2.2 calculations calculations of the medium reorganization energies are performed in the framework of continuum electrostatics – the approach successfully used for the several intra-protein charge transfers [10]. for the numerical solution of the poisson–boltzmann equation the finite difference method was employed [11], the program delphi v.4 release 1.0. this program permits to account for the presence of several dielectrics with the different permittivities. to find the reorganization energy one should calculate the dielectric response energy (reaction field energy) upon the simultaneous charging of reactants by +1e and –1e in optical and static dielectric media. response in the optical medium (dielectric permittivity εo) corresponds to the inertialess polarization, and response in the static medium (permittivity εs) corresponds to sum of the inertialess and the inertial polarizations. the difference of these responses gives the effect of the inertial polarization, i.e. the reorganization energy. parameters the ±1e charge is supposed to be distributed equally among all of the aromatic hydrocarbons heavy atoms. for quinone molecules, the additional charge appearing upon their reduction were obtained from quantum– chemical calculation by density functional method at the b3lyp/6-311++g(d,p) level. the results are: -0.202e at each of carbonyl oxygen, -0.194e at carbon atoms connected with o, and -0.052e on other c atoms. it should be noted that variation of the charge distribution in reasonable limits result in changes of the reorganization energy by few millielectronvolts. electrostatic reorganization energy is often estimated using eq.2 which accepts the spherical shape of the reactants. in many cases, in particular for large flat molecules this leads to a drastic underestimation of the reorganization energy. for a more realistic description of the reactants’ size and shape, the pauling van der waals radii of atoms were employed (their more detailed list is given in the parse parameterization [12]). using these radii and partial charges the poison–boltzmann equation can be solved numerically. the probe radius implies the spherical shape (or somewhat similar to that) of solvent molecule. however, the mthf molecule is a flat one. therefore, one must use some approximations. as the minimal value the radii of o atom or ch2 group contacting immediately the reactants, i.e. 2å. as the approximate maximum effective radius, the radius of a sphere circumscribing the flat figure of tetrahydrofurane was accepted. it equals to 3.2 å. calculation of λs with these radii gives values differing by 10–12 mev. as the final result for each pair the average figure rounded up to one hundredth of electronvolt was chosen. its error due to uncertainty of radii hardly exceeds 5–6 mev. the calculations were performed with the grid size 0.15 å, box filling 80 %. the salt concentration was accepted formally as 10-4 m what allowed to neglect the reorganization of the ionic atmosphere. the experimental values of the dielectric permittivities, static and optical, for the solvent methyltetrahydrofurane (mthf) are εs=7.0 and εo = 1.98 [13]. the permittivities inside the reactants are εin = εs = εo = n2 (n is the refractive index). because there is no orientational polarization (dipoles reorientation) inside the molecules, the corresponding values for the reactants under study are absent in the literature. they were estimated by comparison with the data on εo for the following molecules: benzene 2.25, naphthalene 2.53, phenantrene 2.55. acetone 1.85, vinylmethylketone 1.98, acetylacetone 2.14. pyren is the next in the series of aromatic hydrocarbons, hence its εo can be estimated as ~2.6. for bph one should expect εo higher than for benzene due to the interaction of phenyl groups but this interaction should be substantially weaker than in naphthalene; the estimated εo is 2.35. q is not an aromatic compound but an unsaturated diketone. with the account of additional conjugation the estimate is εo ≈ 2.45. further, by computations reason it is more convenient to use a unique value of εo for each pair of reactants. these figures are 2.4 for bph–q pair, and 2.5 for bph–py pair. given the approximate nature of these values the calculations with various ε’s were performed. the variation in εo by 0.1 leads to change of λs not exceeding 6–7 mev. therefore, this approximation seems to be quite acceptable. 3. results and discussion among the entire systems donor (d) – spacer (sp) – acceptor (a), the most suitable for theoretical analysis is the system biphenyl – a spacer of steroidal type– different acceptors that is studied in detail by miller, closs, and their coauthors [5, 14–19]. the most data relates to spacer 5-a–androstane. they were used in our analysis. 19the rate constant – reaction free energy dependence for the electron transfer reactions in solutions the advantages of using this and similar spacers are, first, that it provides a constant inter-reactant distance and their orientation. the second advantage is that the long chain of s–bonds excludes any marked electron transfer between the reactants before the reaction starts. therefore, one can sure use in electrostatic calculations the full integer charges of reactants. the last remark. in the experiments of miller et al., reaction was initiated by the pulse of the high-energy electrons. the solutions were without the supporting electrolyte. hence, in these systems cannot be operative the effect discussed by kuznetsov [20] for weakly polar media, namely reorganization of ionic pairs formed between the reacting ions and the ions of the background electrolyte. below, two typical systems will be considered. 3.1. bph – sp – a in mthf. for calculations two acceptors were chosen – py, having the largest size, and q, having the smallest one; correspondingly, they have the smallest and the largest electrostatic energy of interaction with the dielectric medium. for all the other acceptors the medium reorganization energy has the intermediate value. as described in section 2.2 the calculations account for the real size and shape of reactants. the calculated λs are for bph–sp–py 1.00 ev, and for bph–sp–q 1.11 ev. besides medium reorganization there are some other practically classical degrees of freedom. the first of them is the torsional movement around s – bond connecting two phenyl fragments of bph; their frequency is estimated theoretically as 55-125 cm-1 (reviewed in [21]). hence, they are classical ones. the corresponding reorganization energy has been estimated experimentally by comparison of the reaction rates with bph and with 2-(9,9’dimethyl)fluorene having a similar energetics and electronic structures, but for the fluorene derivative the torsional component of λ is absent due to sterical hindrance. therefore, the difference in rates can be ascribed to λt = 0.13 ± 0.03 ev [18]. similar value has been obtained by quantum chemical calculation of two rotamers energy [18]. the second component is the intramolecular lowfrequency vibrations. borrelli and dormcke [23] have performed ab initio calculation of the full benzoquinone vibration spectrum. the main contribution to its reorganization energy is due to five modes with the frequencies near ~440, ~780, ~1140, ~1500, and ~1600 cm-1. the same frequencies were obtained by fischer and van duyne [24] from the data on raman spectroscopy. it is important that all they are connected with some shift of the polar co group. the total λv due to all vibrational modes is 0,45 ev. the mode with the frequency 440 cm-1 behaves practically classically and gives the reorganization energy λv= 0.10 ev. the behavior of the mode 780 cm-1 is intermediate between classical and quantum ones, nearer to quantum. fortunately, its full reorganization energy is only 0.01 ev, and hence its contribution to the total classical reorganization energy can be neglected. in [23], the full analysis of the mg-porphyrin spectrum was also given. the total vibrational reorganization is about 0.1 ev. classical vibrations give only 0.0003 ev. in this molecule, all the polar groups are incorporated in a rigid ring structure. therefore, it is reasonable to accept that in cyclic aromatic hydrocarbons containing no polar groups λv ≈ 0. in total, all the classical components give the λ = λs + λt + λv. for bph-sp-py λ = 1.13 ev, for bph-sp-q it equals to 1.34 ev. this is rather close to -δgmax = ~1.2 ev found experimentally from the k – δg curve. with account of the possible errors of two estimates one should conclude that the closeness of the calculated and experimental values is quite acceptable. thus, eq.3a does not describe the experiment satisfactorily while eq.1a does. this is especially clear for the system including q where the quantum contribution to the total λv equals to 0.35 ev, and the classical one only 0.1 ev. in other words, the reorganization of the solvent (plus other classical components) determines the total reorganization energy. this is fully consistent with the theoretical conclusion by dogonadze et al. [3]. jortner [22] also notes that in liquid solvents where exist lowfrequency phonons they exert the predominant effect on the reorganization energy. from this point of view it is interesting that the rates of electron transfer between anion – radical and the neutral reactant and from the neutral reactant and the cation – radical coincide [16] what shows that determining is an electrostatic effect. the fact that reorganization energy is determined by the solvent and other classical modes does not mean that intra-molecular vibration modes do not influence kinetics, and in particular the shape of the rate – free energy dependence. at |δg| > |δgmax|, e.g. in the inverted region, the excited vibration levels come into play making k – dg curve asymmetric. 3.2. bph–sp–a in isooctane. the data on this system are presented according to [14] at fig. 1. the dashed curve is tacked from [14]. it is calculated with the following parameters: λs = 0.15 ev 20 lev i. krishtalik and λv= 0.45ev. strictly speaking, in the nonpolar solvent isooctane λs = 0. however, with account of the torsional component the accepted value is reasonable for the classical reorganization energy. for the vibrational component the authors quite logical accepted the same value as was obtained previously by fitting the data for the same system in mthf. however, as it is clear from fig.1 the agreement of this calculation with the experiment can be hardly considered as satisfactory one. the deviation of the experimental points from the theoretical curve in some cases can be as large as ~ 4 orders of magnitude while for mthf there is only for one experimental point with the maximal deviation not exciding 0.3 orders. moreover, the experimental data cannot be described as a bell-shaped dependence. therefore, it is hardly possible to establish definitely the value of δgmax. the reason for that lies, most probably, just in the mechanism of the elementary act of the electron transfer. in absence or at quite small classical reorganization energy the initial and final electronic energy levels can be equalized only at the expense of the excitation of intra-molecular vibrations. just this idea is accounted for in jortner equation. however, this equation in fact does not imply the same λs and also the same total λv for all acceptors. however, as it is shown in section 3.2 for the different reactants λs and, especially, λv can be substantially different. this is very likely the reason of the discrepancies between experiment and calculations represented on fig. 1. two additional remarks seem to be proper. first, in the presence of several modes the total λv equals to the sum of the corresponding parameters for each mode (the model calculations of ulstrup and jortner [25]). second, there exists a wide set of less effective modes, forming a quasicontinual spectrum important at gradual excitation. note also that the difference in the intra-molecular quantum frequencies does not influence the data for mthf because in polar liquid solvent the location of the rate maximum is determined by the classical reorganization only. 4. conclusion nowadays, experimental data processing often uses jortner formula which implies a substantial contribution of both reorganization energies (of the intra-molecular quantum modes and the classical medium modes) into the total reorganization energy. the latter determines the reaction free energy corresponding to the maximum reaction rate. however, the values of the two reorganization energies are usually taken not from some independent sources but obtained by fitting the kinetic data to jortner equation. correspondingly, there is not any attempt to prove the basic condition of a comparable effect of the two reorganization energies. the specific feature of the approach advanced in this paper is determination of all the parameters not by fitting the kinetic data but basing on the independent experimental data. the medium reorganization energy has been calculated electrostatically. for this purpose, not the simplified marcus formula implying spherical shape of the reactants but the more general method of the numerical solution of the poisson–boltzmann equation was employed. this method allows accounting for the real shape and size of the reactants. the calculations performed for solutions in a polar solvent mthf show that the medium reorganization gives the predominant contribution to the total reorganization energy. to the contrary, in a non–polar isooctane, the medium reorganization does not play any substantial role, and the intra-molecular reorganization becomes predominant. in the latter case, the shape of the rate – free energy curve is rather complex due to differences in vibration spectra of various molecules. all these results are in agreement with the general theoretical conclusions. from the above, the algorithm for processing experimental data follows. in the case of reaction in polar solvent one should perform a strict electrostatic figure 1. system biphenylyl–spacer–acceptor in isooctane solutions. dashed line correspond to calculations [14] with the following parameters: λs = 0.15 ev, λv = 0.45 ev, ω = 1500 cm-1, v = 6.2 cm-1. dotted line is just a guide for eye that is drown according to the sequence of the reaction free energies. the symbols indicate experimental data: 1— 4-biphenylyl, 2— 2-naphthyl, 3— 9-phenanthryl, 4— 1-pyrenyl, 5— 2-(5,8,9,io-tetahydronaphthoquinonyl), 6— 2-naphthoquinonyl, 7— 2-benzoquinonyl, 8— 2(5-chlorobenzoquinonyi), 9— 2-(5,6-dichlorobenzoquinonyl). 21the rate constant – reaction free energy dependence for the electron transfer reactions in solutions calculation of the medium reorganization energy and try to analyze the other possible classical modes. for the reaction in a non-polar medium one should analyze the vibration spectra of the reactants and calculate the corresponding reorganization energies. acknowledgement i am indebted to prof. an.m. kuznetsov for providing me the quantum chemical data on the partial charges distribution in quinone, and to dr. v.v. ptushenko for his help in preparing the paper for publication. references [1] r.a. marcus (1956) on the theory of oxidationreduction reactions involving electron transfer. i. j chem phys 24 966–978. 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[20] a.m. kuznetsov (1986) a quantum mechanical theory of the proton and electron transfer in weakly polar solvents. j. eiectroanal. chem., 204 97-109. [21] d. kirin. (1988) torsional frequency of the biphenyl molecule. j. phys. chem., 92 3691–3692. 22 lev i. krishtalik [22] j. jortner (1980) dynamics of electron transfer in bacterial photosynthesis. biochim biophys acta 594 193–230. [23] r. borrelli, w. domcke (2010) first-principles study of photoinduced electron-transfer dynamics in a mg–porphyrin–quinone complex. chemical physics letters, 498 230–234. [24]. s.f. fischer, r.p. van duyne (1977) on the theory of electron transfer reactions. the naphtalene-./ tcnq system. chemical physics 26 9–16. [25] j. ulstrup, j. jortner (1975) the effect of intramolecular quantum modes on free energy relationships for electron transfer reactions. j. chemical physics 63 4358–4368. substantia an international journal of the history of chemistry vol. 7, n. 1 – 2023 firenze university press superbugged pierandrea lo nostro equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the π0 meson, its mass and lifetime barry w. ninham1, iver brevik2, mathias boström3,4 the rate constant – reaction free energy dependence for the electron transfer reactions in solutions. the way to interpret the experimental data correctly lev i. krishtalik1,† training of future chemistry teachers by a historical / steam approach starting from the visit to an historical science museum valentina domenici a new response to wray and an attempt to widen the conversation eric scerri boxing partula: 25 years after stephen t. hyde surface inactivation of bacterial viruses and of proteins mark h. adams johann beckmann (1739-1811) and modern chemical technology juergen heinrich maar kuroda chika (1884-1968) – pioneer woman chemist in twentieth century japan yona siderer review of a cultural history of chemistry. peter j. t. morris and alan rocke, eds., bloomsbury academic: london, 2022 robert h. crabtree1, arthur greenberg2, seth c. rasmussen3 substantia. an international journal of the history of chemistry 3(1) suppl.: 29-37, 2019 firenze university press www.fupress.com/substantia citation: m. innocenti, w. giurlani, m. passaponti, a. de luca, e. salvietti (2019) electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry. substantia 3(1) suppl.: 29-37. doi: 10.13128/substantia-602 copyright: © 2019 m. innocenti, w. giurlani, m. passaponti, a. de luca, e. salvietti. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-602 electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti department of chemistry “ugo schiff ”, university of florence, via della lastruccia 3, 50019 sesto fiorentino (fi), italy abstract. in recent years the idea that metals, oil and, more generally, natural resources are not endless has been firmed. furthermore, people become aware that humanity must not only increase the production of customer-goods, but they also must produce them with respect for the environment, trying to limit either dangerous processing techniques and hazardous materials. the elimination of many metals from alloys has also reduced the possibility to modify or to produce a wide range of precious jewels and new materials. for such reasons it is essential to develop new techniques for manipulation and preparation of precious jewellery products. nowadays this economic policy drives many companies and even the single craftsmen to a cultural innovation and technological growth. many small and medium-sized companies ask the university for a technological support, otherwise impossible to achieve alone for high costs. the basic research of university has become an important point for the development of the goldsmith sector and for the increase in production and variety of new jewels. this important collaboration between universities and industries is called “the third mission for the university”. this collaboration is important from a cultural, as well as from a productive point of view. nowadays, the symbiosis “research centre goldsmith company”, allows the company to expand internationally its market, thus making the whole industrial sector competitive and innovative. this union is extremely important not only for the goldsmith sector but for the entire national economy. keywords. electrodeposition, surface analysis, galvanic, jewel. introduction since several years, industrialists, politicians and scientists have become aware that the energy resources of our planet may sooner or later end since they are limited. awareness contributed to move towards the development of numerous renewable energy sources. alternative energies and new renewable sources supported by developing technologies are already a big market creating many, high quality jobs. national research on major societal challenges, such as renewable energies, synthesis of new materials or creation of technological poles, will have more impact if efforts would be combined at the 30 massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti european level. besides technological poles and innovation centres – widespread across european union – must help to improve networking and dissemination of experience with entrepreneurs in the industry, universities and civil society organisations. some problems have emerged in recent years for all precious metals starting from gold, platinum, silver, copper and even zinc. then, in 2010, the first official reports were published in europe [1] and america [2]: these documents highlight the scarce availability of the elements mentioned above, which in a few years will become even rarer [3,4]. in addition to this problem, which is not easy to solve, a second one has been added: the banning of numerous metals regularly used in the jewellery and fashion sectors: elimination of lead from brass alloys elimination of nickel from wearables the abolition of galvanic baths based on chromium (vi) the imminent elimination of cyanides from galvanic baths these legislative provisions have limited or even eliminated certain galvanic or synthetic processes. for this reason, many techniques employed for decades in the jewellery sector, have been abandoned. it has become necessary to invest in real applied research to find out new ways to meet the market demands. to accomplish this highly qualified and onerous task, a collaboration between the university and industry has arisen. at a local level as well as international one, this process of collaboration has exacerbated competition among companies: a scientific war has begun between those companies which have invested more or less in new technologies and the other which did not. the future industrial development will penalize countries in which this industry-university synergy has not yet been created. this costly commercial war left many italian companies unarmed. the few italian researchers employed by italian companies have often been forced to work in conditions of inferiority (in terms of financial resources): without appropriate structures and large-scale investment in research, it was impossible to face the fierce world competition. this led some companies to bankruptcy and has condemned others to remain at the edge of the global scene. the latter category of industries has undergone a much faster and more unexpected cultural aging than it could be imagined. some examples are the case of gold galvanic bath in which it is difficult to replace the cyanides with other less dangerous substances; sparing some metals as additives in castings is a major challenge; replacing nickel, with a fundamental metal preventing the diffusion in the solid solution of easily oxidized metals such as silver and copper, is a conceptually and economically titanic undertaking. not only that, but the scarce availability of gold has triggered the research to decrease the amount of this element in alloys. with low carat alloys of gold and the creation of alloys based on non-precious metals, a “precious-perceived” market has been created. if the economic problems can be limited in this way, the chemical and physical ones cannot be avoided at all, rather they are increased and new ones are added: the corrosion resistance worsens in alloys with a lower gold content. in addition to that also the evaluation of the colorimetric parameters needs some development as well as morphological characterization techniques and new techniques able to examine the composition of the new products. history of galvanic industry the history of electroplating begins in the early 18th century [5,6] when, in 1805, l. v. brugnatelli used the volta’s voltaic pile to plate silver with metallic gold from a gold solution. his discovery was not appreciated from the scientific community and only thirty years later the russian scientist b. jacobi devised a process similar to the brugnatelli’s work. jacobi used the more performing daniell cell for electroplating copper on metal plates thus rediscovering electroplating [7] and electroforming [8]. the first patent to perform gold and silver deposition were submitted in birmingham by henry and george elkington in 1840. their use of potassium cyanide as electrolyte led to establish birmingham as the industrial center for electroplating with the inauguration of the first large-scale plant in 1876. later, the stability of gold plating bath was improved with the use of ferrocyanides, thus providing the capability of depositing gold alloys containing silver and copper. from then on, electroplating quickly spread throughout the rest of the world and became a common process for depositing precious and non-precious metals. since then few improvements were made in the following decades, except for the large-scale electric power distribution; only after the second world war, in 1946, a. brenner and g. e. riddell discovered the first autocatalytic metal deposition by adding sodium hypophosphite to a nickel bath giving birth to the “electroless” deposition [9]. since the early 1950s some baths were implemented by replacing cyanides with acidic solutions obtaining a more manageable and sustainable working environment [10]. in recent years electrodeposition in non-aqueous solution was investigated leading to the development of electrodeposition in ionic liquids and electrophoretic deposition [11]. ionic liquids are used to 31electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry deposit metals with a nernst reduction potential more negative than the evolution of hydrogen in water, e.g. aluminum, [12]. in ionic liquids the electrolyte is composed of anionic and cationic organic species which are in the liquid phase at low temperature; this allows the salts of the metal precursor to solubilize by means of the electroreduction process. ionic liquids are very sensitive to moisture and therefore they must be employed in a special closed environment with a controlled atmosphere. the electrophoretic deposition process involves the reaction of organic monomeric precursors driven by an external electric potential [13]. differently from the aqueous-based electrodeposition, the organic molecules not only occur in a redox reaction, but they also form a network leading to the formation of a polymer. the resulting coatings are generally well-adhered and softer than the metal ones with fewer cracking issues. the final polymer could be either conducting or insulating materials. the organic-based coatings tend to be more degradable over time, another issue is the environmental toxicity in the production process due to their precursors. the impact of electroplating on our lives is huge: in 2015 electroplating represented 37 % of the total market share within the metal finishing sectors with applications in automotive, aerospace, building, jewelry and electronics [14,15]. the most commonly galvanically-deposited metals are zinc and zinc alloys (about 15 %), followed by nickel, copper, chromium, tin, and precious metals [16]. according to a recent study published by future market insights the global electroplating market is expected to increase at a compound annual growth rate (cagr) of 3.7% over the forecast period of 2016-2026, projecting revenues of over us $21 billion by the end of 2026 [17]. the main limit to an even larger expansion of electroplating is the strict environmental regulations: many plating processes involves toxic metals and dangerous chemicals. another issue facing industrial development is the price volatility of highly on-demand electroplated materials (e.g., gold, copper, and nickel). although significant technological and processing advancements occurred in the past forty years, industrial firms are still struggling to provide viable solutions to energy conservation, reduction of costs and toxic wastes, as well as strategic challenges such as product durability and corrosion protection [18,19]. today, a deeper knowledge of the electrochemical mechanisms and the research of new materials and emerging technologies are driving the traditional manufacturing process towards a more reliable, flexible and interconnected production [20]. by exploiting the natural affinity of some elements is possible to obtain a surface-limited reaction that spontaneously generates a single atomic layer. this behavior is very useful from a technological point of view and, therefore, widely studied by the scientific community. starting from this principle, many techniques have been developed during the last years: electrochemical atomic layer epitaxy (ecale) [21,22], electrochemical atomic layer deposition (e-ald) [23-25], selective electrodesorption-based atomic layer deposition (sebald) [26,27], electrochemical liquid-liquidsolid growth (ells) [28]. hubbert peak of precious metals the world gold council estimated that about 190,000 tons of gold have already been mined from earth [29]. almost half (48 %) of the total was manufactured in jewellery; almost a quarter (21 %) was channelled into private investments; 17 % in official sector and the remaining 14 % assigned to other sectors such as technology. it is difficult to answer to question of how much gold remains to be extracted. it has been observed that two thirds of the gold already extracted until now occurred after 1950. one might think that if we follow this trend for in the next 100 years we can expect to achieve more hundreds of thousands of tons. unfortunately, experts estimated that the current underground reserves amount to only 50,000 tons. it is understandable that this relatively modest picture is in contrast with the increasing production and use of gold in recent years. the idea of peak oil pushed up the price of petroleum, but now another peak theory has emerged, this time involving gold and all the other precious metals. hubbert’s peak, called also hubbert’s curve,  is a theory that approximates the production rate of a  resource  over a period of time. from a careful analysis of the hubbert’s curve we found that the initial production rate follows the increasfigure 1. hubbert peaks of gold (black) and platinum group metals (red): past production and future previsions. 32 massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti ing demand for the new resource, but then it is predicted a loss of correlation and a decreasing in production while the demand still grows up. during this fall, there may be dramatic differences in production and demand as demand continues to rise, but production falls overall. from the estimations of the remaining unmined gold and its increasing price, many analysts of precious metals and gold miners are taking a cue from the prediction of the hubbert’s theory, according to them the same concept can be applied equally well to the ingots, as well as to the oil, and can lead to outsized investment returns from the purchase of the yellow metal. in this context, the supporters of the golden peak claim that mining has a discrete number of similarities with oil extraction. just as the slowing of production and the diminishing reserves observed in the old oil wells, many of the best gold deposits exhibit the same kind of geriatric tendencies, with high quantities extracted long ago. however, after the peak, it was not observed a sustained decline as was the case of the model proposed by hubbert. the reason could be the evolution of new technologies that provided us the tools to extract oil from unconventional resources. then, a question arises: does the gold extraction follow this story? the answer is complex; the extraction of gold is connected to something more than just the technology. in fact, the price of the metal itself influences its extraction: it is observed that when gold becomes too cheap the extraction process stops. furthermore, gold ores becoming increasingly more difficult to access compared to previous decades, and the likelihood of a discovery leading to mine development is very low (less than 0.1% of the proposed sites will lead to a production mine), according to the research of the world gold council, even if the 10 % of global gold deposits contain sufficient gold to justify further development, the exploration alone could take up to 10 years and entail heavy costs in terms of geological investigations and chemical analysis. electrodeposition of low-carats gold galvanic baths containing considerable amount of toxic substances, such as cyanides, and heavy metals, which are also toxic and difficult to remove. for example, cadmium, in the matrix1 have been used for decades to get one gold alloy containing less than 75% by weight of gold metal (corresponding to a gold alloy of 18 carats or less). these baths allow to get effectively gold deposits having the desired carat value e considerable thickness. however, the presence in them of highly poisonous substances makes them virtually unacceptable for practical use. the alternatives in use, however, exploit products that have only partially solved known problems met with the use of previous galvanic baths and, in addition, do not demonstrate the same suitability for practical use and the same quality of results. in fact, these are generally formulations that only partially eliminate toxic products used and which have limited periods of use or with which an alloy is obtained characteristics of the value of carats, thickness or appearance that do not meet the needs of the intended use. however, baths of this type also include solutions that use cyanide in the matrix or that, though they do not contain cyanide in the matrix, contain other elements or compounds of a certain toxicity. a recent study [30] has opened the possibility to satisfy the above needs due to galvanic alkaline baths containing: gold salts, copper and indium salts, salts of polycarboxylic organic acids, organic amines, and possibly complexing agents, surfactants and other metals in smaller quantities, as gloss additives and refiners of deposits. it is noted that, in contrast to the antecedent technique, cyanide is not present in the bath matrix and its content in the electroplating the solution is caused by its counterion function in the gold salts alone. cyanide is therefore practically irrelevant, though necessary for the stability of gold in solution. characterization of electroplated coatings color measurements the determination of the color has a central role in the quality control of electroplated deposits. the color 1 matrix is an aqueous solution of organic and inorganic acids and their salts. figure 2. price of gold from 1970 to 2019. 33electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry measurement may seem a trivial task, but environmental factors and intrinsic properties of the objects might generate inconsistent data [31]. the formalism used for color assessment is the lab color space [32] in which the three coordinates l*, a*, and b* are considered. l* identifies the brightness with values from 0 to 100, a* the red-green component (a* > 0 red, a* < 0 green), and b* the yellow-blue component (b* > 0 yellow, b* < 0 blue). the coordinates a* and b* do not have fixed limits but are generally in the range of ±100. the color coordinates a* = b* = 0 represents grays. the color of a sample can be compared with a target with several metrics [33]. the simplest and most commonly used approach defines color difference (δe*) as the euclidean distance between the coordinates of two different colors. it is generally accepted that two colors, placed one next to the other, are not distinguishable δe* < 1 [34]. in practice, companies generally tend to give an acceptable range for the single colorimetric coordinates (l* ± dl; a* ± da; b* ± db), whose values are defined by the customer. colorimetric coordinates are obtained from the mathematical combination of the illuminant, sample reflectance spectra and the average of human eye sensitivity (tristimulus functions) [35]. the main problem in color determination is the inconsistence of the results, even from the same paint or metallic coating, due to instrumental differences (colorimeters are generally used instead of more expensive and accurate spectrophotometers) substrate polishing (reflective or matte), dimensions and irregular patterns and textures [36]. thickness evaluation the precise determination of the electrodeposited thickness is a fundamental parameter to characterize a galvanic coating. mechanical properties are influenced by the thickness, beyond the type of alloy and the succession of the underling layers. a thick deposit can have very high tensile stress and low adhesion. on the other hand, if the layer is too thin, gloss, diffusion, color, and corrosion problems might occur. the most common methods for measuring the thickness are through scanning electron microscopy (sem) of metallographic crosssections or using x-ray fluorescence (xrf). cross-sectional analysis allows acquiring a direct image of the layers’ sequence and then measure the thickness. therefore, quantification is very simple, for thick deposit the cross section can be also measured with an optical microscope. the main disadvantages of this approach are the high cost of the instrument (60,000-200,000 €) and the slow and destructive sample preparation. on the other hand, xrf allows for non-destructive and fast measurements, with an instrumental price of around 40,000-60,000 €. knowing the composition and sequence of the metallic layers an appropriate calibration curve is made, then the thickness of all the layers can be measured, with a typical 10% standard deviation. the researchers should be knowledgeable about the sample under investigation and the impossibility of measuring layers in which a certain element is repeated: for example, in a typical deposition bronze/copper/brass, the copper layer cannot be measured because it is present in both the deposits and brass, while bronze can be evaluated by analyzing the tin and correcting the result based on its percentage in the alloy. figure 3. measured reflectance spectrum (left) and the calculated colorimetric coordinates (right) of a gold sample. 34 massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti a new methodology based on energy dispersive x-ray (edx) spectroscopy for the determination of the thickness and the composition of electrodeposited thin films was developed in the last year [37]. the proposed method employed a combination of edx spectra acquisition and monte carlo simulation. this method has better lateral resolution than the xrf technique and allows reliable measurement of the thickness on thin metal films, with the capability to determine also the composition of the film in the 1% concentration range. the approach was validated by the analysis of electrodeposited plates with known metal thickness using various approaches and custom-made software. the results were compared with other techniques showing an uncertainty of 9%, which is consistent with the literature data obtained using real standards [38]. the method has been validated on copper-based substrates covered by a layer of nickel, palladium and gold. corrosion and mechanical strain product durability is a fundamental aspect which a producer must deal with, therefore mechanical and corrosion test must also be evaluated. the methods for examining the coatings’ adhesion are describe by international standards by the qualitative examinations with thermal shock astm b571-97:2008, the network of cuts method iso 2819:2017 and iso 11644:2009, and the tape test under iso 11644:2009. the formation of blisters or exfoliations indicates weak adhesion. the effects of time and environment on a sample is simulated with accelerated aging. the corrosion test can be carried out on a new sample or after mechanical tests in order to obtain a more pronounced effect. the most common international corrosion tests are: the effects of exposure to damp heat with or without leather iso 4611:2010 and iso 17228:2015, resistance to synthetic sweat iso 3160-2:2015, salt spray test iso 9227:2017, and tests with chemicals derived from atmospheric pollution, such as thioacetamide iso 4538:1978, sulfur dioxide, and nitric acid iso 4524:2000. corrosion test generally takes long time (hours to days) to obtain a result and are intrinsically destructive. for these reasons, efforts have recently been made to find faster and non-destructive, or micro/ semi-destructive, systems. a probable evolution in this sense could come from electrochemical measurements of open circuit potential (ocp) and electrochemical impedance spectroscopy (eis). florentine applied electrochemistry laboratory in the florentine laboratory of applied electrochemistry, 20 people (professors, researchers, technicians and phd students) are working. all of them are specialized in the various fields of chemistry and electrochemistry, engineering and materials science. the laboratory is affiliated with the chemistry department of the university of florence. the academic research sectors in which the attention has been focused mainly concern: 1) study of electrified interfaces with particular attention to the adsorption of electroactive organic substances and inorganic ions on different metals. 2) study of nanomaterials obtained electrochemically. 3) morphological and compositional characterization exploiting many technique: scanning electron microscopy (sem), energy dispersive x-ray spectroscopy (edx), x-ray photoemission spectroscopy (xps), scanning probe microscopy (spm) with parfigure 4. cross section of typical galvanic deposition analyzed with optical microscope. from left to right it is possible to distinguish: brass substrate, copper, nickel and gold finishing. before the cut of the sample an additional layer of nickel was deposited on gold to preserve its integrity and sharp edge during the lapping process. figure 5. corrosion test of a gold-plated sample, before (left) and after (right) 12 hours under syntenic sweat test. 35electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry ticular regard to atomic force microscopy (afm). in this field the attention has turned to the morphological characterization of substrates of technological, environmental and biological interest. 4) microcontact printing and electrodeposition on a nanometric scale. 5) preparation of modified surfaces of catalytic or technological interest by confined metal electrodeposition. 6) electrodeposition of ternary or quaternary sulfides for the preparation of surfaces of technological interest in the field of solar cells. 7) design and implementation of devices in the energy sector with natural materials with low environmental impact and with low energy consumption preparation techniques. in recent years the laboratory has also been involved in applied research in the industrial field, for the development of sensors in medical use, low-cost instrumentation for oil and wine analysis, absorbent materials for acid spills courses of basic microscopy and galvanic baths. as previously reported, the florentine applied electrochemistry laboratory shared the project of the university’s third mission activity. the “third mission” of the university addresses the growing societal economic challenges. in reality the term “third mission” is ambiguous because it is used to indicate a multiplicity of activities that relate university research and society. a first fundamental typology is that of technological transfer activities aimed at the evaluation, protection, marketing and marketing of technologies developed in the field of research projects conducted by the academic world and, more generally, for the management of intellectual property in relation with the same projects. in this context laboratory’s research activity has been carried out in a very important way, placing the applied electrochemistry laboratory directed by prof. innocenti massimo to a central role in the transfer of knowledge from the university to the industry and vice versa. in addition, the numerous contracts obtained have allowed an exponential growth of this group acquiring high-level instruments, of great impact in the regional production sector. thanks to the various research activities, the applied electrochemistry laboratory has been able to boast numerous research funds and above all to play a central role for high-level training and the introduction into the working world of numerous graduates and post-doctoral graduates in chemistry. miur projects financed: 1) prin 2004 project financed by the title “integrated study on the national territory for the characterization and control of atmospheric pollutants (sitecos)” of which professor innocenti was responsible of the operative unit of florence 2) prin 2008 project financed by the title “platinumfree electrocatalytic materials for direct fuel-based fuel cells” of which professor innocenti was deputy manager projects funded: monte dei paschi di siena foundation 1) monte dei paschi di siena foundation 2006-2007 he financed the project entitled “design synthesis and characterization of nano-structured composite materials with pre-selected functional characteristics” tuscany region: 1) gabbrielli 2013 regional project 1.3b of the por creo 2007-2013  “eco-sol”. research project “eco-sustainable and low-cost production of sulphides for photovoltaic applications” 2) esa 2016, participant project tuscany region, por erdf 2014-2020 call 2: research and development projects of smes, “new electrolytes for electroforming of yellow gold alloys with low environmental impact” present and research manager of the subcontractor. 3) regione toscana spettrox project, por erdf 20142020 call 2: research and development projects for smes, present as researcher instm. 4) gadget project call for por creo 2014-2020 dd 3048 of 21/02/18, call for proposals 2: research and development projects for smes, “silver, galvanic, ecological and technological jewelry” 5) el4all project bando por creo 2014-2020 dd 3048 of 21/02/18, call 2: research and development projects of smes, “new aluminum electrodeposition process on fashion accessories through the development of des and next coloring “ 6) thin fashion project bando por creo 20142020 dd 3048 of 21/02/18, call 2: research and development projects for smes, “plasma technologies for the luxury industry: 4.0 approach to additive manufacturing”. instm . appropriation 1.995.704,55 euro (classified 61, head of industry, texts) 7) galvatron project call for por creo 2014-2020 dd 3048 of 21/02/18, call 2: research and development projects for smes, my research group is present as a subcontractor. project approved but admitted to the funding with resource reserve (probable 36 massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti project start by 2018) budget 469.302,45 euro (classified 108, head of industry eco-tech finish) references 1. commission of the european communities (ec) tackling the challenges in commodity markets and on raw materials. brussels eur. comm. 2011, 1–22, doi:com(2011) 25 final. 2. bauer, d.; diamond, d.; li, j.; sandalow, d.; telleen, p.; wanner, b. us department of energy: critical materiasl strategy, december 2010. agenda 2010, 1–166, doi:10.2172/1000846. 3. commission, e. comm. from the commission to the european parliament, the council, the european economic and social committee and the committee of the regions: on the review of the list of crms for the eu and the implementation of the raw materials initiative. 2014. 4. european commission communication from the commission to the european 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doi:10.1111/j.1520-6378.1994.tb00070.x. 35. capitán-vallvey, l. f.; lópez-ruiz, n.; martínezolmos, a.; erenas, m. m.; palma, a. j. recent developments in computer vision-based analytical chemistry: a tutorial review. anal. chim. acta 2015, 899, 23–56, doi:https://doi.org/10.1016/j.aca.2015.10.009. 36. giurlani, w.; gambinossi, f.; salvietti, e.; passaponti, m.; innocenti, m. color measurements in electroplating industry: implications for product quality control. ecs trans. 2017, 80, 757–766, doi:10.1149/08010.0757ecst. 37. giurlani, w.; innocenti, m.; lavacchi, a. x-ray microanalysis of precious metal thin films: thickness and composition determination. coatings 2018, 8, 84, doi:10.3390/coatings8020084. 38. zhuang, l.; bao, s.; wang, r.; li, s.; ma, l.; lv, d. thin film thickness measurement using electron probe microanalyzer. 2009 int. conf. appl. supercond. electromagn. devices 2009, 142–144, doi:10.1109/ asemd.2009.5306671. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe doi: https://doi.org/10.36253/substantia-1121 received: sep 27, 2020 revised: nov 22, 2020 just accepted online: nov 23, 2020 published: mar 01, 2021 https://doi.org/10.36253/substantia-1121 substantia. an international journal of the history of chemistry 3(2) suppl. 3: 29-56, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-324 citation: m. henry, l. schwartz (2019) entropy export as the driving force of evolution. substantia 3(2) suppl. 3: 29-56. doi: 10.13128/substantia-324 copyright: © 2019 m. henry, l. schwartz. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. entropy export as the driving force of evolution marc henry, laurent schwartz* assistance publique des hôpitaux de paris, paris, france *corresponding author: dr.laurentschwartz@gmail.com abstract. the entropy concept was forged by the middle of the nineteenth century to predict how a chemical system may undergo spontaneous evolution over time. at the dawn of the twentieth century, four principles of a new science called “thermodynamics” have been firmly established. concept of thermal equilibrium (zeroth law), conservation of energy (first law), spontaneous increase in entropy over time (second law) and vanishing entropy at the absolute zero of temperature (third law also called nernst’s theorem). among these principles, the most troublesome one was the second law that points to gases as the end final product of any evolution in a closed system. from direct observation, it seems that biological systems undergo spontaneous evolution from gases characterized by a maximum entropy to highly complex structures displaying considerably lower entropies, an apparent violation of the second law. however, it is also perfectly allowed to view the earth as an open system able to undergo a spontaneous (local) decrease of entropy, provided that the excess entropy could be efficiently exported towards the whole universe through invisible infrared photons. provided that the entropy exported as invisible infrared radiation is much higher than the entropy decrease observed on earth, life apparition on this planet becomes fully compliant with thermodynamics laws. the consequences of such an enlarged viewpoint taking into account all kinds of processes (reversible as well as irreversible ones) are studied in depth in this paper. here we advocate that the first requirement allowing spontaneous life apparition on earth is the existence of a metabolism, taking the form of thermodynamic cycles able to generate a large output of entropy by degrading low entropy molecular systems (food) into high entropy molecular compounds (waste). two possible cycles have been identified, relying on the very low entropy of earth’s metallic core for generating reducing gases (such as h2, co, nh3, h2s) coupled to the low entropy of sun’s radiation (food) and producing minerals (such as serpentine, metallic sulfide, magnetite, goethite) as well as high entropy gases (water, carbon dioxide) as waste. the large entropy flux generated by such processes can then be used to build low-entropy molecular systems based on reduced carbon species and soluble phosphates that are observed in any living cell. another consequence of this approach is stressing the ubiquitous role played by water in every feature of life, through the concept of “water activity”. keywords. entropy, life, water activity, irreversibility, thermodynamics, biology. 30 marc henry, laurent schwartz introduction the apparition of life is a deep rooted mystery. life appeared on earth over 3,6 billions years ago. life is a robust phenomenon with similar concentrations of sodium, potassium and chloride in every living cell. moreover, similar lipoproteins constitute the membranes and the nucleic acids are always built with the same bases. taking the problem from the biological side, focusing on protein-trafficking related to gene activation and transcription, as currently done is a daunting task. putting numbers on the table, a back of the envelope calculation leads to an average concentration of 3 millions of proteins per µm3 of cell.1 this translates into 3 millions of proteins for e. coli (v ≈ 1 f l), 150 millions for budding yeast s. cerevisiae (v ≈ 50 f l)2, and 3 billions for a mammalian cell (v ≈ 1 pl).3 concerning the human genome, we are facing about 18,000 genes4 able producing about 100,000 different types of proteins.5 nowadays, only super-computers are able to crawl in huge databases giving rise to new research domains such as genomics, proteomics or metabolomics, epigenomics, lipidomics, glycomics, etc. an alternative line of research is to admit that such a complexity accessible only through high-speed computers is sustained by laws deep-rooted in physics and chemistry. if this is the case, then identifying some key physicochemical variables should be enough to control cell growth and proliferation. in deep contrast with biology, physics does not look for detailed mechanisms, facts being the mere consequences of fundamental laws given a certain set of initial conditions. the goal of this paper is to suggest that the universality of only one form of life might be the simple consequence of the second law of thermodynamics. such an approach is obviously complementary to the –omics strategy and would allow physicians to act on diseases without the help of computers, would also considerably reduce the number of drugs for healing patient and most importantly would allow using very cheap chemicals instead of drugs characterized by sky-rocketing prices. the paper is organized as follows. in a first section we will go back to abiotic hadean times where only physical and chemical events were able to take place. this will allows us to identify key physicochemical parameters that should be still operational in modern cells. the second part of the paper will be the formulation of bioenergetics in terms of irreversible entropy variations instead of energy changes. in a third part, this new quite general formalism will be applied to prebiotic chemistry of lipids, aminoacids as well as phosphate-based compounds. finally, a last part will stress the important role played by the water activity in anabolism and catabolism processes. hadean times life seems to originate with the formation of liquid water on earth about 4,4 gyr ago.6 first forms of life as prokaryotes seem to appear about 3,8 gyr ago.7 during this first period covering 600 myr, we have to make a mapping between what we currently know about the last universal common ancestor of all cells (luca) and some basic chemistry. using phylogenetic trees for 6.1 million protein coding genes from sequenced prokaryotic genomes has allowed reconstructing the microbial ecology of luca.8 with its 355 identified genes, luca could be viewed as anaerobic, co2-fixing, h2-dependent (elimination of acetate via the reduction of acetyl-coa), n2-fixing and thermophilic. luca’s biochemistry was replete with fes clusters and radical reaction mechanisms. its cofactors reveal dependence upon transition metals, flavins, s-adenosyl methionine, coenzyme a, ferredoxin, molybdopterin, corrins and selenium. its genetic code required nucleoside modifications and s-adenosyl methionine-dependent methylations. our reasoning is based on the hypothesis that entropy-driven networks of small molecules ruled by thermodynamics afford better odds as the initiators of life than a set of highly complex molecules such as rna and proteins. among all the scenario proposed for life apparition on earth, it appears, as explained thereafter, that the geochemical rocky route is the only one compatible with luca’s portrait emerging from phylogenetic trees analysis. starting from geochemistry occurring at hot, reduced, alkaline hydrothermal vents, the route leads to a prebiotic era, followed by the successive development of rnas, rnps, dnas molecules as water becomes cooler, more oxidized and more acidic. this means that we may set aside the genetic definition of life to focus on a more water-based picture. the necessity of putting water at the front stage is well illustrated by figure 1 that describes the composition of the gram-negative prokaryote escherichia coli (e. coli). the key point here is to focus on the molar fraction scale for quantifying the amount of matter. on such a scale, it should be obvious that life is a water-based phenomenon (99.3 mol%) with inorganic ionic species playing the major role (0.5 mol%) over organic matter (0.2 mol%). basically, every event in a living cell appears to be orchestrated by water and ions, organic matter behavior being under the full control of these two kinds of chemical species. 31entropy export as the driving force of evolution shapiro stated five requirements for the emergence of life:10 1. existence of a membrane allowing defining compartments able to sustain ionic concentration gradients. 2. existence of an external energy source to drive the increase in complexity and biodiversity. 3. existence of a growing and splitting mechanism for the network allowing information duplication. 4. existence of a chemical network able to sustain circular transformations (cycles) permitting adaptation and evolution. 5. existence of coupling mechanisms linking the release of energy with entropy exports. in fact some of these points have already been answered. point #1 is by no means mandatory, as it has been demonstrated that water adjacent to hydrophilic surfaces and submitted to radiant energy from the sun or from a geothermal vent, is perfectly able to produce coalescence, order, and even function at multiple levels of organization without any enclosing membrane.11 point #2 is thus automatically solved. point #3 is based on the trivial fact that a physical collection of small items holds the same information as a list that describes the items formally with a code. in other words there is no difference in terms of information between holding ten real metallic gold coins in your pocket and holding them virtually in a bank account. in both cases, you will be able to take the same decisions on how to spend such an amount of money despite the fact that one set is purely material and the other one is completely dematerialized. there is thus no need to store information in a single molecule such as dna (playing in the cell the role of the bank account) that have to be duplicated and passed to the descendants as observed in a modern cell. self-replicating reverse micelles12 or mere aggregates of iron sulfide bubbles13 are perfectly able to do such a job (equivalent of gold coins). concerning point #4, it should be clear that one cannot rely on the citric acid cycle or on its reverse version owing to the difficulty of achieving all of the required reactions using only mineral catalysts.14 accordingly, there is so many side reactions in the citric acid cycle that a large number of different mineral surfaces would be needed to close the cycle. a much simpler version with fewer steps is then required. fortunately, the existence of a proto-metabolic analog of the tca involving two linked cycles, which convert glyoxylate into co2 has been recently evidenced.15 to initiate the two cycles, only glyoxylate h-co-cooand pyruvate ch3-co-cooare needed with the help of hydrogen peroxide h2o2 all reactions proceeding under figure 1. molecular composition and basic energetic needs for the gram-negative prokaryote escherichia coli according to the cybercell database (ccdb).9 32 marc henry, laurent schwartz neutral aqueous conditions and at mild temperatures (figure 2). here, the molecule oxaloacetate or 2-oxosuccinate (2-os) is acting as a central hub allowing continuous production of either malonate (upper part) or 4-hydroxy-oxo-glutarate (lower part). so one, could speak of an 2os-cycle fed by a gph-flux.it was also shown that aspartic acid, a crucial aminoacid, might be produced by reacting malonate with α-hydroxy-glycine (α-hg). moreover, the conversion of malate to oxaloacetate is an elementary step of the citric acid cycle. the problem now boils down to the emergence of only three chemicals: glyoxylate, pyruvate and hydrogen peroxide from inorganic species. as explained below, hydrogen peroxide is continuously produced using solar radiations, while glyoxylate and pyruvate precursors are continuously produced at the mouth of hydrothermal vents. hydrogen peroxide plays here the role of the very first electron acceptor and glyoxylate and pyruvate, the very first electron donors. please notice that there is no need here to invoke negative loops and regulation signals that occur in modern biological systems. our point is that for the most primitive living cell, a few cycles and the laws of kinetics are all is needed for starting chemical oscillations, as shown by the work of ilya prigogine.16 we should thus at this point speak a little bit of bioenergetics in order to write a plausible scenario in order to discuss point #5 more deeply. here is a summary of the proposed reformulation of shapiro’s conditions: 1. lipid membranes replaced by polarized multilayers of water (ez-water) as proposed by gilbert ling in 1962 and gerald h. pollack in 2013. 2. external energy source may be of two kinds, sun or earth, as only ir radiations matter for ez-water creation. 3. no mechanism for information duplication as only brute copying of a full set of molecules is needed. 4. identification of a 2os-cycle based on glyoxylate, pyruvate and hydrogen peroxide precursors (gphflux) for the first chemical oscillations. 5. coupling mechanisms concerns only entropy exports as only one kind of energy (ir radiations) is used by the cell for building water layers. bioenergetics: the key role of entropy bioenergetics is a domain based on thermodynamics, a science that is often misinterpreted. the name “bioenergetics” is by itself quite misleading as it could make believe that evolution is ruled by energy exchanges with states of high energy evolving spontaneously into states of low energy. in fact, this cannot be, as energy being a conserved quantity has nothing to say about spontaneous evolution. the entity giving a preferential direction to energy fluxes is in fact entropy, a state variable characterizing how energy may spread among all the available degrees of freedom. accordingly, the second law states that entropy should always increase or remain constant in any spontaneous chemical reaction. so, faced with any chemical reaction, we should always refer to entropy variations. but referring to entropy and not to energy is not the attitude adopted by most scientists. in order to speak only in terms of energy and never refer explicitly to entropy, scientists have masqueraded the entropy concept under various expressions such as “internal energy” for adiabatic and isochoric processes, “enthalpy” for adiabatic and isobaric changes, “helmholtz’s free energy” for isothermal and isochoric changes and “gibbs’s free energy” for isothermal and isobaric processes. for open systems able to exchange both heat and matter, it is necessary to introduce chemical potentials, yet another masqueraded form of entropy. if electrons are exchanged during a transformation, entropy is again masqueraded as a redox potential. as stated by the second law of thermodynamics, any spontaneous irreversible evolution corresponds always to an increase in entropy inside the system. however, the price to be paid for any internal increase in entropy is always a loss of structure. the reason behind such a loss of structure is merely that energy may be spread either on positions of matter particles (potential energy) or on the velocities of these matter particles (kinetic energy). in such a context, increasing its entropy means that the system spread its energy more on velocities (more kinetic energy) than on positions (less potential energy). when kinetic energies becomes larger than potential energies, chemical bonds responsible for the existence of solid as well as liquid structures break down, the volume occupied by the system becoming delimited by the container and no more by the chemical bonds. here, another pitfall should be avoided by speaking of loss of structure upon any entropy increase and not of a loss of order. a liquid has always a much smaller entropy than a gas despite the fact that both systems are completely disordered. the lower entropy of the liquid comes from the fact, positions above the liquid/gas interface are accessible only to a very small number of the constituting matter particles (vapor pressure). similarly, a solid will always have an entropy smaller than a liquid, as constituting matter particles are doomed to remain at fixed points in space, thus being unable to occupy all the available positions in the proper volume. in a liquid, any constituting particles may be found everywhere in the proper volume, meaning a much greater entropy. conse33entropy export as the driving force of evolution quently, there is absolutely no need to invoke order/disorder arguments for discussing entropy changes. recognizing that thermodynamic potentials are in fact masqueraded irreversible entropies of variation and definitively not energies, leads to a considerable simplification of thermodynamics. accordingly, instead of dealing with a multitude of different kind of energies (mechanical, thermal, chemical, electrical, magnetic…), it remains only two basic types of real energies. first, the energy stored in electromagnetic waves or in massless photons (radiant energy). second, the energy associated to particles having a non-zero rest mass (gravitational, kinetic and nuclear energies). all the other forms of “energies” are in fact irreversible entropy variations ∆si that can be translated into energetic equivalents after multiplication by the temperature at which the transformation occurs. one may thus formally write, ∆g = -t·∆si, with a criterion of spontaneous evolution ∆g ≤ 0 owing to the fact that according to the second law one should always have ∆si ≥ 0. as explained above, one is thus obliged to add the term “free” to the term “energy” to remember that we are dealing here with an irreversible entropy change and not with an energy change. we thus propose here to adopt such a very convenient convention sticking closely to what is in fact really occurring during a spontaneous evolution within a system. the only fundamental law is thus that everything proceeds from a state of low entropy towards a state of high entropy. if the system is not able to export this excess of entropy towards its surroundings the entropy irreversibly grows inside the structure and at some point, the structure breaks down. such a behavior is typical of transformations occurring in a beaker or in the universe where inert structures are doomed to disappear irreversibly after breaking down into smaller and smaller units of matter. at the end, solids and liquids evaporates leaving only a gas, which is always the state having the largest entropy for a given composition. the situation is different, if it exists inside the system a mechanism able to export entropy from its interior towards its exterior: this means that the various components of the system should now cooperate in order to absorb compounds having the lowest possible entropies and reject in its environment compounds having the highest possible entropies. as shown by the laws of irreversible phenomena, any system being crossed by figure 2. two abiotic cycles each oxidizing glyoxylate into carbon dioxide co2 with the regeneration of oxaloacetate, a key intermediate of the modern tricarboxylic acid cycle. such reactions progress significantly in hours at ph values 7–8.5 at 50 °c (red arrows) or 23 °c without the help of enzymes.15 34 marc henry, laurent schwartz an irreversible flow of entropy, becomes automatically self-organized.16 the higher the entropy flux, the higher the number of functional links between different the parts of the system. the key point here is the unavoidable existence of fluctuations that could be organized into spatial and temporal coherent behavior (dissipative structures) when the system is brought far enough from equilibrium. mathematically speaking, one may write the following fundamental equation for entropy variations, ds = dis + des, where des is the variation of entropy due to exchanges with the surroundings and dis the entropy increase due to irreversible processes occurring inside the system, such as diffusion, chemical reactions, heat conduction and so on. basically, one has des = 0 for an isolated system, meaning that ds = dis ≥ 0, according to the second law. this means that if a system in evolution is not able to export any irreversible internal increase in entropy towards its surroundings, it is doomed to land in a state of maximum entropy, where all available energy is spread among all the possible degrees of freedom (positions and velocities). in other words, any kind of structural arrangement observed at a given time is doomed to become a gas at an infinite time. this is what is expected for any kind of inert matter. the situation is completely different as soon as a mechanism is available for exporting the newly generated entropy in order to avoid entropy accumulation. the most interesting case occurs for open systems that are allowed to exchange both heat and matter towards their surroundings. here, during evolution, ejection of wastes of sufficiently high entropies or release of a sufficient amount of heat, allow reaching a state where entropy is smaller than at the beginning, meaning that des ≤ 0. such a state which is highly improbable from a statistical viewpoint and doomed to disappear in a closed or isolated system, could in this case survive indefinitely in a steady state (dissipative structure) provided that ds = 0 or des = -dis ≤ 0. this basically means that highly improbable states need just highly efficient mechanisms of entropy export, and that there is no upper limit in complexity. the price to pay for being quite complex is that the higher the entropy export, the higher the destruction of the surroundings that have to sustain such a huge flow of entropy coming from the complex system. it is worth noticing that here we are considering the whole earth as a living system exporting entropy towards the whole universe through infrared radiations centered on a wavelength of about 10 µm. the fact is that the universe has very few structures by itself and is in continuous expansion, meaning that it is able to absorb an almost infinite amount of entropy from the earth. and if we have so many structures on earth, it is precisely because the universe is almost totally devoid of structures. this obviously does not apply to the earth that is not in expansion. being on earth, living systems should export their entropy first to the earth putting the burden on the earth for exporting entropy towards the universe, the ultimate garbage. however, the rate of export towards the universe is finite: ∆s ≈ 1 w·m-2·k-1. if living systems release entropy in their immediate surroundings at a rate higher than this critical value, the earth will begin to accumulate entropy with the immediate consequence of breaking down structures. natural means for such breakdowns are tornadoes, hurricanes, floods, fires, volcanoes and earthquakes. consequently, when the surroundings becomes saturated with wastes, entropy export is doomed to be reduced, leading to the disappearance of the dissipative structure with a breaking down into smaller components as explained above. here is the thermodynamic basis for aging and death of any kind of living system. obviously one of the most efficient ways of exporting entropy is to release gases, explaining why most complex living systems always hold an internal machinery for manipulating gases. another very efficient way of exporting entropy, is by releasing heat (i.e. infrared radiation), explaining why complex living systems are systematically warmer that their surroundings. a basic equation for life should then be: foods (in) = biomass (in) + heat (out) + wastes (out), where “in” and “out” refer to a system surrounded by a containment able to exchange heat and matter between the inside and the outside. now in the following, we will assume that each substance carries within its structure a certain amount of a so-called irreversibility potential noted πi hereafter. such a new term is here introduced for stressing the fundamental role played by irreversible processes and also stressing the fact that it is a thermodynamic entity ruling a possible evolution that may occur or not depending on kinetic factors. its main role is to put on a quantitative basis the ability of substance of being a food (low irreversibility or entropy-poor substance) or a waste (high irreversibility potential or entropy-rich substance). as shown below, for systems evolving at constant temperature and pressure, the irreversibility potential is measured by the ratio of the opposite chemical potential -µ divided by the constant temperature t, that is to say πi = -µ/t. the irreversibility potential has thus the dimension of an entropy. the reason for changing the name is that such a correspondence between irreversibility potential and chemical potential exists only if pressure and temperature remain constant during the evolution. for other experimental conditions, the numerical values 35entropy export as the driving force of evolution are changed, but the rule remains the same. for instance for an isolated system unable to exchange heat and matter with its surroundings πi may now be identified directly with entropy and no more with the chemical potential. consequently, for a system absorbing one type of food f having an irreversibility potential πif, used to create one type of molecule m having an irreversibility potential πim and generating an amount of heat q with ejection of one type of waste w having an irreversibility potential πew, a fundamental law of existence should be: ds dt = dis dt + des dt = −π i f · dnf dt + sπ i m · dnm dt + 1 t · dq dt +πe w · dnw dt ≥ 0         1( ) ds dt = dis dt + des dt = −π i f · dnf dt + sπ i m · dnm dt + 1 t · dq dt +πe w · dnw dt ≥ 0         1( ) (1) if several types of foods are needed or several types of wastes produced, one should subtract a term πi(k)·dnk/dt or add a term πe(j)·dnj/dt for each type of food (k) or waste (j), n being the number of entities absorbed (food), created (biomass) or ejected (wastes) by the system. systems with a low ds/dt are simple, complexity increasing rapidly with any increase in ds/dt. figure 3 gives an illustration of such a relationship.17 according to such a law, in order to have the largest ds/ dt, one should have on input foods of very low irreversibility potentials (πif ≈ 0) that should be metabolized at the smallest possible rate (dnf/dt ≈ 0) in order to create large entities (πim >> 0) at the highest possible rate (dnm/dt >> 0). on output, one should evacuate the largest amount of heat at the lowest temperature and/or eject wastes having the highest irreversibility potentials (πew >> 0) at the highest admissible rate (dnw/dt >> 0). any increase in dnf/dt (overfeeding), decrease in dnm/ dt (starvation), increase in temperature surroundings (heating) or decrease in dnw/dt (clogging) would, below a critical threshold, lower ds/dt and brings the system closer to its death. figure 3. the exponential rise in complexity as a function of irreversible energy flux (left). top-right: arrow of time and major evolutionary phases that have produced the visible universe. bottom-right: the crossover between evolution in time of radiation energy density (stefanboltzmann σ·t4 law) and matter energy density (ρm·c2) leading to neutral atoms formation some ≈ 105 years after the big-bang. adapted from eric j. chaisson’s work.17 36 marc henry, laurent schwartz it is worth noting that these are very general rules that apply to any kind of living system whatever its internal machinery and complexity. more particularly, the higher is ds/dt, the higher the complexity and the higher the dependence on the surroundings for survival. we will now apply such a universal recipe to prebiotic life as represented in figure 2. to do this, we have to know reasonable values measuring irreversibility potentials. in fact, as explained above, for systems evolving at constant temperature and pressure, we should have –t·πi = µ, where µ is gibbs ‘s chemical potential, or partial molar gibbs free energy. so, all the data we need are contained in tables of gibbs’s free energies. as such tables give data for a particular reference state (usually t° = 298.15 k and p° = 100 kpa), it is worth knowing how the chemical potential varies with temperature, pressure and composition. we will use the following expression easily derivable from the definition of a chemical potential:18 π i m, t , p, n( )= π i0 m( )+ sm0 m( )· t t° −1⎡ ⎣⎢ ⎤ ⎦⎥ −vm 0 m( )· p t° − p° t° ⎡ ⎣⎢ ⎤ ⎦⎥ − r·lna m( )     2( ) π i m, t , p, n( )= π i0 m( )+ sm0 m( )· t t° −1⎡ ⎣⎢ ⎤ ⎦⎥ −vm 0 m( )· p t° − p° t° ⎡ ⎣⎢ ⎤ ⎦⎥ − r·lna m( )     2( ) (2) here, sm°(m) and vm°(m) are the molar absolute entropy and molar volume of substance m respectively while a(m) is the activity of the substance when not in pure state, that is to say mixed with other substances. for a pure substance a(m) = 1 by definition, meaning that si°(m) is the standard irreversibility potential at t = t°, p = p° of the pure substance, a(m) = 1. choosing the elements in their standard state as setting the level zero of irreversibility potential leads to πi°(m) = -∆fg°(m)/t. table 1 gives some selected values that we should use to follow the irreversible flux of entropies associated to a possible abiotic metabolism represented formally in figure 2. concerning units, the usual choice for energy in to use kilojoule per mole (kj·mol-1) in chemistry and electron-volt (ev) in physics. in fact, these two units have been arbitrarily chosen as respectively convenient for calorimetry where heat fluxes are expressed in joules and for electrochemistry or nuclear physics where charges are measured in coulombs and potentials in volts. in order to switch from the macroscopic world (joules, volts) to a microscopic world, one uses respectively the avogadro constant na = 6.02214129×1023 mol-1 and the elementary charge e = 1.602176565×1019 c. the drawback of such units is that they are not related to biological conditions that are centered on a characteristic temperature t ≈ 300 k. a much better unit of energy for biology should thus be e = kb·t ≈ 4 zj, where kb = 0.013806488 zj·k-1, is boltzmann’s constant and 1 zepto-joule (zj) = 10-21 j. this explains why table 1 uses the zepto-joule as a fundamental unit of energy, with 1 kj·mol-1 = 1.66 zj and 1 ev = 160.2 zj as conversion factors between the new unit (zj) and the old ones. similarly, the standard volumes are directly expressed in nm3 (1 nm3 = 10-21 cm3) in order to compare the standard entropy s° with a state where all atoms are just mixed together without making any chemical bonds. for such an “ideal” state where the only source of entropy increase sid is diffusion through translation in space , one may use the sackur-tetrode equation allowing establishing a direct link between sid and elementary quantum processes:19 sid kb = 0.83+1.5·ln{ m /da( )· t / k( )}+ ln v /nm3( )         3( ) (3) prebiotic chemistry let’s now show how such a table should be used for understanding what is happening during any irreversible evolution. first, the table has been organized by ascending order of standard irreversibility potential πi° in order to see at once what substance could be a food (top of the table) and what substance would be a waste (bottom of the table). one thus immediately see that metals and gases are the most interesting foods, while liquids and solids are better qualified as wastes. this explains the basic scheme of most complex living systems: breathing gases (air) and rejecting liquids (urine) and solids (feces). a fundamental point of living systems is that even a waste can be used as a food by rejecting another waste, provided that such a waste has a higher irreversibility potential than the waste used as a food. a good example is provided by the bacteria shewanella oneidensis, that is able to “respire” from goethite α-feooh, the iron ore responsible for the brown color of the soil, and reject black magnetite fe3o4 as a waste.20 as can be seen in table 1, this is possible because the irreversibility potential of magnetite is higher than the one of goethite. this shows that when speaking of living system, solids minerals should not be discarded as possible source for food. this explains, why after its apparition, life may be found in different ecological niches. on such a ground, metallic iron or nickel owing to their very small irreversibility potentials should be 37entropy export as the driving force of evolution considered as the ultimate source of all foods on earth. this stems from the fact that these two elements are formed from the four most tightly bound nuclides in the universe, with an average binding energy decreasing in the order 62ni > 58fe > 56fe > 60ni.21 both species form the core of any telluric planet such as the earth. consequently, any substance on earth is to doomed to encounter sooner or later metallic nickel or iron during its recycling by the plate tectonics. the importance of nickel and iron for early forms of life is represented nowadays by two crucial metallo-enzymes.22 first, carbon monoxide dehydrogenase (codh) using nife3s4 and fe4s4 clusters for transforming carbon dioxide co2 into carbon monoxide co. second, acetyl-coa synthase (acs) combining the co generated by codh with a methyl group to form the key metabolite intermediate acetyl-coa using a ni2-fe4s4 cluster. table 2 shows other important (ni,fe)-based metallo-enzymes demonstrating the crucial role played by these two metals in biology,23 in geochemistry and in astronomy. accordingly, ni-glx(i) protects the bacteria e. coli against the damages made by methylglyoxal, a reduced form of pyruvic acid, to the arginine-bearing proteins and to nucleic acids. ard is an enzyme involved in the ubiquitous methionine salvage pathway. urease protects bacteria, archaea, plants, algae and fungi against harmful acidification of the living medium. ni-sod is an enzyme that protects cells from an excess of the superoxide ion, a free radical byproduct of aerobic metabolism. (ni-fe)-hydrogenase manage the reversible interconversion of hydrogen gas with protons and electrons in archaea, bacteria and selected eukaryotes. mcr play table 1. irreversible standard potentials πi° (t = 298.15 k, p = 100 kpa), standard absolute entropies s° and standard molecular volume v° for some selected compounds involved in the prebiotic metabolic cycle shown in figure 2. values being given per molecule or motif, the unit of energy corresponds to the zepto-joule (zj), with 1 zj = 10-21 joules and 1 kj·mol-1 = 1,66 zj. see annex for the derivation of this table from literature data. (s) = solid, (liq) = liquid, (g) = gas and (aq) = aqueous solution. substance (state) formule πi° / zj·k-1 s° / zj·k-1 v° / nm3 nickel (g) ni -2.14146 0.30255 41.164 iron (g) fe -2.06460 0.29973 41.164 iron (liq) fe -0.55808 0.16550 0.01321 iron (s) ε-fe (hcp) -0.02507 0.05525 0.01132 iron (s) γ-fe (fcc) -0.02490 0.05694 0.01151 iron (s) α-fe (bcc) 0 0.04533 0.01178 nickel (s) ni 0 0.04965 0.01094 sulfur (s) s 0 0.05322 0.02576 dihydrogen (g) h2 0 0.21700 41.164 dinitrogen (g) n2 0 0.31816 41.164 di-oxygen (g) o2 0 0.34066 41.164 ammonia (g) nh3 0.09134 0.32010 41.164 hydrogen sulfide (g) h2s 0.18602 0.34174 41.164 troilite (s) fes 0.56419 0.10013 0.03022 hydrogen peroxide (aq) h2o2 0.74648 0.23895 carbon monoxide (g) co 0.76358 0.32762 41.164 pyrite (s) fes2 0.89167 0.08784 0.03975 water (g) h2o 1.27386 0.31351 41.164 ice ih (s) h2o 1.31769 0.07434 0.03193 water (liq) h2o 1.32097 0.11624 0.03000 carbon dioxide (g) co2 2.19660 0.35502 41.164 goethite (s) α-feooh 2.73907 0.10030 0.03457 carbonic acid (aq) h2co3 3.47090 0.30670 hematite (s) α-fe2o3 4.14592 0.14513 0.05027 magnetite (s) fe3o4 5.64021 0.24267 0.07393 fayalite (s) fe2sio4 7.68086 0.25074 0.07690 forsterite (s) mg2sio4 11.43747 0.15626 0.07248 serpentine (s) mg3si2o5(oh)4 22.45835 0.36748 0.17851 apatite (s) ca5(po4)3oh 35.29432 0.64827 0.26502 38 marc henry, laurent schwartz a major role in the global carbon cycle by controlling the biological emission of methane. finally lactic acid (l and d-isomers) is an important and versatile compound produced by microbial fermentation being involved in the energy metabolism of many prokaryotic species, as a product of sugar fermentation or as a carbon and electron source to sustain growth.24 in other words, if something is complex relative to its inner constituents, this means that it is the result of a huge flow of outgoing entropy. wastes are to be found in its immediate surroundings. if not, the waste may have been exported far away, for example in the form of far-infrared photons that may have escaped towards the intergalactic space. this distant export of entropy may give the false impression, at first glance, that such a complex thing having an incredible low probability of formation from simpler elements apparently violates the second law. in fact, there is no violation at all, the point being that wastes are just invisible photons, i.e. heat for instance. another possibility is that wastes generated by a given species have been used as foods for another one, the observable result being a large increase in chemical as well as biological diversity. this is exactly what happens when plants generate o2, a waste then breathed by animals. owing to recycling, the amount of waste may appear, at first glance, to be lower that what it really is. figure 2 show that the two purely abiotic spontaneous cycles can synthesize complex molecules such as glyoxylate, pyruvate and hydrogen peroxide. in accordance with the second law, a spontaneous process is such that the total irreversibility potential after reaction (b) should have increased relative to its initial value (a), or ∆πi° = σni·πi°(b) σni·πi°(a) > 0. spontaneous formation of reduced carbon, nitrogen and sulfur species it is highly probable that life begins with water encountering a hot magma made of olivine somewhere on the oceanic floor.25 upon mixing, olivine will reduce water into hydrogen h2 leaving as wastes serpentine. assuming that olivine is made as 75% of forsterite mg2sio4 and 25% of fayalite fe2sio4 we will assume from table 1 that πi°(olivine) = 0.75×11.43747 + 0.25×7.68086 = 10.49832 zj·k-1. before transformation, the total irreversibility potential is thus πi°(a) = 6×10.49832 + 7×1.32097 = 72.23671 zj·k-1, while after transformation we get πi°(b) = 3×22.45835 + 5.64021 = 73.01526 zj·k-1. the difference ∆πi° = πi°(b) πi°(a) = +0.77855 zj·k-1 being positive, this explains the great amount of hydrogen gas escaping from the hydrothermal vent on the oceanic floor where the waste, magnetite, accumulates with time, the other waste, serpentine, remaining within the oceanic crust. in fact, the vent should be viewed a very powerful entity able transforming a waste h2o (low position in table 1) into a valuable food (high position in table 1). such a reduction that corresponds to a strong decrease in entropy from water’s viewpoint is nevertheless possible because wastes high in entropy (serpentine and magnetite) have been produced simultaneously, pushing the overall entropy balance in the good direction. however, in order to make organic matter, one should also dispose of a valuable source of carbon able to act as a food. carbon dioxide, which was an abundant molecule in early earth’s atmosphere being a waste rather than a food, one should again makes use of the powerful regenerating power of earth’s core containing metallic iron in order to transform it into carbon monoxide. after hydration by a water molecule to form carbonic acid h2co3, we have πi°(a) = 3×3.47090 + 0 = 10.4127 zj·k-1. after transformation into carbon monoxide producing goethite and water as wastes, we get πi°(b) = 2×2.73907 + 3×0.76358 + 2×1.32097 = 10.4108 zj·k-1. with a difference ∆πi° = -0.0019 zj·k-1, we have an almost equal repartition of carbon between carbontable 2. the “two” most tightly bound nuclides in the universe, nickel (ni) and iron (fe), are at the heart of many crucial biological processes involving at least nine different ni-based enzymes used by 80% of the archaea and 60% of the eubacteria. glx = glyoxalase, ard = acidreductase dioxygenase, sod = superoxide dismutase, hyd = hydrogenase, codh = co dehydrogenase, acs = acetylcoa synthase, mcr = methyl-coenzymem reductase, lar = lactate racemase, dhk-mtpene = 1,2-dihydroxy-3-keto-5-methylthiopentene, kmtb = 2-keto-4methylthiobutyrate, fesp = corrinoid/fe–s protein. enzyme metals reaction ni-glxi 2 ni2+ me-co-cho + ½ o2 = me-choh-coo+ h+ ard fe2+ or ni2+ dhk-mtpene + o2 = kmtb + hcoo+ 2h+ urease 2 ni2+ co(nh2)2 + 2 h2o = 2 nh4+ + co32ni-sod ni3+ 2 o2•+ 2 h+ = o2 + h2o2 [ni-fe]-hyd nifes2 h2 = 2 h+ + 2 ecodh nife3s4 co2 + 2 h+ + 2 e-= co + h2o acs ni2-fe4s4 me-co(iii)-fesp + co + coash = meco-scoa + co(i)-fesp mcr ni(i) me-scom + cob-sh = ch4 + com-s-s-cob lar ni2+ (d)-me-choh-coo= (l)-me-choh-coo39entropy export as the driving force of evolution ic acid and carbon monoxide in such a transformation. however, carbon monoxide being a gas is able to escape from the location of the transformation provoking by its departure more transformation of carbonic acid into carbon monoxide in order to restore the equilibrium fixed by the relative irreversibility potentials in presence. concerning nitrogen, a mandatory element for synthesizing aminoacids, table 1 shows that it may already be classified as a food, being in higher position than carbon monoxide and at equal level with hydrogen. however, dinitrogen is a completely apolar molecule with nitrogen atoms engaged into very a stable triple bond that is very difficult to break spontaneously. but table 1 shows that another nitrogen-based molecule, ammonia nh3, is almost at the same level of irreversibility potential without the problem of the triple bond. here one may use again earth’s core to perform the transformation of n2 into ammonia nh3 with as always the help of the ubiquitous water molecule. before transformation we have πi°(a) = 4×1.32097 + 0 + 0 = 5.28388 zj·k-1, while after transformation into ammonia producing goethite as a waste, we get πi°(b) = 2×2.73907 + 2×0.09134 = 5.66082 zj·k-1. with a difference ∆πi° = +0.37694 zj·k-1, the reaction thus proceeds quite easily. accordingly, in the laboratory it was possible to convert 17 mol% of nitrogen gas into ammonia by reaction with iron and water at a temperature of 700°c and a pressure of 0.1 gpa according to: 3(1-x) fe + n2 + 3 h2o = 3 fe(1-x)o + 2 nh3.26 ammonia was also obtained by with a mixture of nitrogen and formic acid at the surface of magnetite. what have been said for n2, applies also to sulfur that exists as a solid and not as a gas under standard conditions. here also, transformation of sulfur into hydrogen sulfide having a position rather close to sulfur in table 1 could be envisaged with the help of water as before and of a previous waste, magnetite, acting now as a food. this would allow disposing of the last important organic element necessary for building living matter as a gas and not as a solid. accordingly, before transformation we have πi°(a) = 2×5.64021 + 0 + 4×1.32097 = 16.5643 zj·k-1, while after transformation into h2s producing goethite as a waste, we get πi°(b) = 6×2.73907 + 0.18602 = 16.62044 zj·k-1. with a difference ∆πi° = +0.05614 zj·k-1, the reaction is thus in favor of h2s over a mixture of water and sulfur. accord ing to t he prev ious considerat ions we understand that a hydrothermal vent could be viewed as a powerful source of foods in the form of h2, co, nh3 and h2s gases. however, these gases are released in water, a protic solvent, they may exist under several forms depending on the ph of water. for instance, at ph = 7, hydrogen sulfide exists as a 50-50 mixture of h2s and hsspecies. for ammonia, it is the ammonium form nh4+ that is the predominant species at ph ≈ 7. it follows that a given irreversible process may be represented by several chemical reactions involving species differing by their number of h-atoms and that can bear a non-zero electrical charge. in order to deal with such situations, one should use an apparent irreversible potential π’i°(ph, i) that reflects all the possible protonated forms of a chemical species in water existing at a given ph at a specified ionic strength i. specif ic procedures have been designed to retrieve such apparent potentials from thermodynamic data of each chemical species at ph = 0 and i = 0 m.27 when the necessar y thermodynamic data is not available, one may decompose a given chemica l species into various characteristic functional groups and add all the contribution to retrieve the corresponding apparent potential.28 table 3 gives such group contributions for ph = 7 and three ionic strength, i = 0 m, 100 mm and 250 mm adapted to our entropy units (zj·k-1). as with table 1, we have listed irreversibility potentials in ascending order in order distinguishing between potential foods (top of the table) and potential wastes (bottom of the table). in order to convince of the usefulness of such a table, we will try to see if fatty acids may synthesized inside the mouth of a hydrothermal vent: table 3. group contributions to aqueous irreversibility potentials π’i° at a pressure of 100 kpa, ph = 7 and three different ionic strengths i. this table is based on the convention that πi° = 0 for species h+, adenosine, nadand nadp3at zero ionic strength. group i = 0 m i = 0.1 m i = 0.25 m adenosine -2.89295 -2.93729 -2.95160 c-ch2-nh3+ -0.94837 -0.96876 -0.97538 c2-ch-nh3+ -0.88070 -0.89780 -0.90326 methyl: c–ch3 -0.56235 -0.57254 -0.57588 methylene: c-ch2-c -0.47396 -0.47736 -0.47842 ammonium: c-nh3+ -0.38602 -0.39621 -0.39950 -ch2-oh 0.23876 0.22852 0.22517 c2-ch-oh 0.37594 0.36909 0.36692 aldehyde: c-cho 0.44634 0.44294 0.44183 c3-c-oh 0.45915 0.46706 0.47006 amide 0.59248 0.57889 0.57438 keto: -co0.67892 0.67324 0.67886 ol: c-oh 0.80111 0.80106 0.80106 carboxyl: c-coo1.95160 1.95500 1.95606 c-o-p-o-p-o-po34.81002 4.82640 4.83302 c-o-p-o-po34.82796 4.83976 4.84450 c-o-po34.93973 4.95338 4.95823 40 marc henry, laurent schwartz n co + 2(n-1) h2,aq = ch3-(ch2)n-2-coo-aq + h+aq + (n-2) h2o the resulting fatty acid being composed of 1 methyl, 1 carboxyl groups and (n-2) methylene groups, one should expect from table 3 for an ionic strength i = 0.25 m the following irreversibility potential: π’i°(cnh2n+2) = 1.95606 -0.57588 – (n-2)×0.47842 = (2.33702 0.47842×n) zj·k-1 the prime symbol is a remainder that such a value is an apparent irreversibility potential valid for ph = 7 and i = 0.25 m. its negative value above n ≈ 5 means that formation of fatty acids with long hydrocarbon tails involves a large decrease in entropy relative to its constituting elements (carbon c and hydrogen gas h2). consequently, the higher n, the less the probability of seeing such a species forms spontaneously. however, we are not interested here by the formation from the constituting elements, but rather by the formation from carbon monoxide (food) reacting with hydrogen to produce the fatty acid with elimination of water as a waste. for the small molecules, we will use π’i°(co) = 0.66778 zj·k-1, π’i°(h2) = -0.55210 zj·k-1 and π’i°(h2o) = 0.86695 zj·k-1 valid for ph = 7 and i = 0.25 m,28 leading to: ∆π’i° = (n-2)×0.86695 + (2.33702 – 0.47842×n) – 0.66778×n + 0.55210×(2n-2) = (0.82495×n – 0.50108) zj·k-1 this now shows that fatty acid formation is always a spontaneous process (∆π’i° > 0) for all values of n larger than n = 1. self-assembly of lipids into micelles this is an important result, as every living cell has a membrane made of long-chain fatty acids. a crucial point, here, is that as soon as the number of carbon atoms becomes large enough, such fatty acids are able to self-assemble spontaneously into micelles, vesicles and membranes. accordingly, a long-chain fatty acid is basically a small rigid pinhead welded on a flexible whip strap. in water, these long chain fatty acid assembles to form cavities not accessible to water molecules. this translates into a prohibitive entropy cost explaining the very low solubility of such species. however, provided that the hydrocarbon tail is long enough, it becomes possible to have a large gain in entropy by creating in water large cavities holding several tails instead of a single one.29 for instance, for a spherical cavity of radius r able holding n tails of volume v of a fatty acid, one should have n·v = 4π·r3/3. but the fatty acid has also a head-group sweeping an area a, so that one has simultaneously n·a = 4π·r2, leading to r·a = 3·v. now, r cannot be greater than the maximal length l of the fully stretched hydrocarbon chain. with r = 3v/a ≤ l, it comes that a criterion for making a spherical micelle is to have a packing parameter pp = v/(l·a) ≤ 1/3. fatty acids having a packing parameter such that pp > 1/3 should then look for another less curved topology. let us then consider a cylinder of arbitrary length d and radius r. here, one should have n·v = π·r2×d and n·a = 2π·r×d, leading to r·a = 2·v or r = 2v/a ≤ l as before. it follows that a criterion for making a cylindrical micelle is to have a packing parameter pp = v/(l·a) ≤ 1/2. if pp > ½, the fatty acid is not able to aggregate as a cylinder and should look again for another topology. a possibility is to make closed spherical bilayers having a radius equal to twice the hydrocarbon chain length r. for such a vesicle one may write that n·v = 4π·(2r)3/3 to be compared to n·a = 4π·(2r)2, leading to r = 3v/2a ≤ l that is to say pp = v/ (l·a) ≤ 2/3. finally, if pp > 2/3, the solution is to make a planar double layer having a thickness equal to 2r. for a square having an arbitrary area equal to d2, one may the write that n·v = 2r×d2 and n·a = 2d2, leading to r = v/a ≤ l that is to say pp = v/(l·a) ≤ 1. finally, if pp > 1, the area of the head-group is too small to pack into bilayers and inverse micellar structures are formed (figure 4). figure 4. spontaneous self-assembly in water of fatty acids characterized by the volume v of the hydrocarbon tail, the area a of the head-group, the maximum chain length l and observed topologies as a function of the packing parameter pp. 41entropy export as the driving force of evolution the final topology of the self-assembly process is thus controlled by a simple geometric criterion pp = v/ (a·l). now, for saturated hydrocarbon chains cnh2n+1, one has v ≈ (0.0274 + 0.0269×n) nm3 and l = (0.150 + 0.1265×n) nm, leaving only the area of the head-group a as a variable. depending on the number of water molecules associated with the head-group, a given fatty acid may adopt any of the topologies represented in figure 3. the head-group area in the bilayer phase may be measured from force-area isotherms of squeezed monolayers giving an average value a0 = 0.247 nm2 for fatty acids (n = 16-22).30 now, the average volume vw occupied by a single water molecule may be computed from the observed density of liquid water ρ ≈ 1 g·cm-3, water’s molecular weight mw = 18.0015 da and avogadro’s constant na = 0.602214129×1024 mol,1 leading to vw = mw×10-3/(na×ρ) ≈ 0.03 nm3. it follows that hydrating the carboxyl head-group with n water molecules would lead to an effective area a = (a03/2 + k×n×vw)2/3, with k a shape factor equal to 6×π1/2 ≈ 10.635 for spherical head-groups. for instance, for stearic acid (n = 18), we get v = 0.5116 nm3 and l = 2.427 nm. with two water molecules per head-group (n = 2), we get an effective area a = 0.833 nm2, leading to pp = 0.25 < 1/3, pointing to spherical micelles formation when ordinary soap is dissolved in water. for n = 1, the area is reduced to a = 0.580 nm2, leading to pp = 0.36 > 1/3, that is to say formation of worm-like micelles responsible for the high viscosity of concentrated soap solutions. finally, for a fully dehydrated head-group a = a0 = 0.247 nm2, leading to pp = 0.85 > 2/3, that is to say formation of stacked planar bilayers typical of solid soap. this shows that the same fatty acids are able to form spherical, worm-like or planar bilayers depending on the fatty acid molar fraction relative to water. in other words, the shape of a cell is dictated by the amount of water molecules available in the medium. obviously, the trouble with fatty acids is that they form bilayers only when the polar carboxylate head-group is not solvated by water molecules. in order to get stable bilayers in a large amount of water, it is mandatory to select a polar head-group not heavily solvated by water molecules and find a trick to increase the hydrocarbon volume v without increasing too much the chain length l. for the polar head-group a smart solution was to use a quaternary ammonium moiety, such as -nme3+, as methyl groups are not able to be hydrogen-bonded with water molecules, explaining the ubiquitous choline head-group ho-ch2-ch2-nme3+, in modern living membranes. as shown in table 4 giving irreversibility potentials at ph = 7 as a function of ionic strength for prebiotic species, choline is a most valuable low entropy food with a quite negative irreversibility potential. reaction (a) and (b) in table 5 shows that its abiotic synthesis within a hydrothermal vent may occur spontaneously by reducing carbon monoxide or dioxide with hydrogen gas in the presence of ammonia and with an appropriate mineral surface for catalyzing the reaction. concerning the chain length, the trick was to use 2 fatty-acids chains instead of one, allowing doubling the volume without changing the length of the hydrocarbon tail. in order to get a molecule with 2 tails and one head-group welded together to form a single entity, an obvious choice was to select glycerol molecules hoch2-choh-ch2-oh having three oh groups available for esterification. as ether-links -c-o-care much more difficult to synthesize than ester links –c(o)-o-c-, it was necessary for welding choline to glycerol to recruit a divalent weak inorganic acid for bridging two alcohol moieties together. sulfuric acid h2so4 being a strong acid and carbonic acid h2co3 being too instable, a good candidate was phosphoric acid h3po4 existing in aqueous solution around ph ≈ 7 under a di-hydroxy form h2po4-. a convenient source of phosphate on earth is hydroxyapatite ca5(po4)3(oh), but this mineral appears to be definitively a waste and not a food as it is found at the very bottom of table 4. to realize the difficulty of extracting phosphate groups from apatite by water, we see that reaction (c) in table 5 leads to a negative irreversibility potential variation ∆πi°, meaning that such a transformation cannot occur spontaneously. it should thus be coupled with another transformation releasing enough entropy to compensate for such a large decrease. as explained below, this is precisely the role of a metabolism to furnish such entropic compensation. abiotic organic chemistry concerning the formation of glycerol, another mandatory ingredient for having a double chain phospholipid, reactions (d) and (e) in table 5 shows that such a molecule may be formed spontaneously by reducing carbon monoxide or dioxide by hydrogen gas, as was the case for fatty acids or choline. taking into account the fact that phosphate groups were not available for welding using a choline head-group, a possibility could be to use glycerate, ho-ch2-choh-coo-, obtained according to reactions (f ) or (g) in table 5. this shows that abiotic glycerate synthesis is less favorable than that of glycerol but nevertheless still possible. the apparition of double chain amphiphiles was an important step for evolution because it has make pos42 marc henry, laurent schwartz sible the appearance of endocytosis and exocytosis. we will take the example of egg lecithin, that have the following geometrical parameters: v = 1.063 nm3, a = 0.717 nm2, l = 1.75 nm,31 leading to pp = 0.84 favoring planar bilayers. however, by mixing such lecithin molecules with a fat such as stearic acid we get for a 50:50 mixture an average pp-value of (0.30 + 0.84)/2 = 0.57, i.e. formation of a closed spherical double layer. for a lecithin/fat ratio of 75:25, it comes <pp> = (0.30 + 3×0.84)/4 = 0.705 and now we are back again with a planar bilayer. we have thus here a very basic mechanism of exocytosis (pp < 2/3) or endocytosis (pp > 2/3) allowing such micelles to absorb foods and reject wastes. another quite important molecule for membranes was cholesterol that have the following geometrical parameters: v = 0.630 nm3,31 a = 0.41 nm2,32 l = 1.03 nm,33 leading to pp = 1.49 favoring inverse closed spherical double layer, allowing transport of water in oil and not oil in water as with direct micelles. owing to such a property cholesterol may be used to favor very stable planar bilayers for molecules having a packing parameter not close to 1, the optimal value for such a topology. for instance by mixing egg-lecithin with cholesterol in a 75:25 ratio, one get <pp> = (1.49 + 3×0.84)/4 = 1,00. now, we should understand that extracting phosphate group from apatite was a crucial problem that has to be solved before the spreading of life on earth. when a transformation is not thermodynamically allowed owing to a decrease of the total entropy (∆πi° < 0), a good solution is usually to make a coupling with radiant energy coming from the sun as visible light or from the earth as infrared radiation. characterizing radiations by their wavelengths λ, such a coupling may be expressed by the following relationship: -λ·t·∆πi° = h·c = 198.645 zj·µm (4) thus, for reaction (c) in table 5 characterized by ∆πi° = -2.32000 zj·k-1, one should use at t = 298.15 k a photon having a wavelength less than λ = 287 nm. the problem is that apatite is a solid that could be used for storing radioactive nuclides generated by nuclear power table 4. aqueous irreversibility potentials π’i° (zj·k-1) at a pressure of 100 kpa, ph = 7 and three different ionic strengths i. this table is based on the convention that πi° = 0 for species h+, adenosine, nadand nadp3at zero ionic strength. compound i = 0 m i = 0.1 m i = 0.25 m nadh -6.13461 -6.21303 -6.23831 nad+ -5.78590 -5.87117 -5.89867 choline (c5h14no+) -3.39955 -3.44411 -3.45820 adenine (c5h5n5) -2.84297 -2.85942 -2.86550 cyanide -0.88917 -0.89251 -0.89357 adenosine -1.80969 -1.85402 -1.86834 methane-thiol -0.84734 -0.86099 -0.86539 dihydrogen -0.54308 -0.54993 -0.55210 ammonia -0.44845 -0.45865 -0.46193 valine -0.45040 -0.48789 -0.50003 proline -0.28861 -0.31930 -0.32921 sulfide -0.28037 -0.28338 -0.28416 dinitrogen -0.10128 -0.10128 -0.10128 dioxygen -0.09134 -0.09134 -0.09134 thioacetate 0.08442 0.07742 0.07519 hydrogen peroxide 0.30142 0.29418 0.29240 formaldehyde 0.34470 0.33784 0.33567 alanylglycine 0.49758 0.46349 0.45246 alanine 0.50855 0.48467 0.47697 carbon monoxide 0.66778 0.66778 0.66778 glyceraldehyde 0.68510 0.67146 0.66700 methane 0.69897 0.71256 0.71696 water 0.87597 0.86912 0.86695 glycylglycine 0.94848 0.92125 0.91239 glycerol 0.99042 0.96313 0.95433 acetate 1.38925 1.38246 1.38023 compound i = 0 m i = 0.1 m i = 0.25 m formate 1.73233 1.73233 1.73233 α-hg 1.80434 1.78730 1.78173 ribose (c5h10o5) 1.88933 1.85525 1.84422 pyruvate (2-op) 1.96268 1.95589 1.95366 glutamate 2.10426 2.08042 2.07268 glyoxylate (2-oa) 2.38730 2.38730 2.38730 aspartate (asp) 2.54052 2.52347 2.51796 glycerate 2.56630 2.55260 2.54815 carbonate 3.04817 3.04734 3.04706 amp 3.13027 3.09958 3.09011 malonate (2-ca) 3.38556 3.43263 3.43369 malate (2-hs) 3.80301 3.80301 3.80301 2-os 3.97310 3.97995 3.98212 4-hog 4.48410 4.47463 4.47947 portlandite ca(oh)2 4.55633 5.54948 4.54731 3-cas 4.58852 4.58502 4.58396 3-cm 5.84516 5.85190 5.85413 phosphate pi 5.89562 5.89902 5.90080 3-cos 6.14363 6.15605 6.16608 3-om 6.52408 6.52514 6.52787 ribose-5-phosphate 6.81676 6.79654 6.79025 adp 7.95839 7.93957 7.93483 pyrophosphate ppi 10.7767 10.7999 10.8085 atp 12.7686 12.7661 12.7680 triphosphate pppi 15.6178 15.6665 15.6838 hydroxyapatite 34.9609 34.9575 34.9564 43entropy export as the driving force of evolution plants during a geological period of time.34 consequently, if apatite remains stable upon heavy irradiation with gamma photons, there is no chance that a uv-c photon will be able to extract phosphate from apatite. it is at this point that a metabolic cycle being a perpetual source of entropy alimented by earth plate tectonics and emerging at the mouth of hydrothermal vents could be very useful. from, figure 2 we know that to start the cycle, three ingredients should be able to meet upon a mineral surface: glyoxylate, pyruvate and hydrogen peroxide. a look at table 4 immediately shows that the most critical food will be hydrogen peroxide h2o2, as it is the compound that displays the smallest irreversibility potential. the problem is then how to reduce water h2o into hydrogen peroxide h2o2. a possible solution is to consider that there was on the primitive earth probably a lot of pyrite fes2 that could react according to the scheme (h) in table 5 and illustrated in figure 2. such a reaction is characterized by a large decrease in total entropy, but could be compensated according to (6), by a uv-a photon having a wavelength less than λ = 325 nm, using pyrite’s surface as a photo-electrode (figure 2). here, the solid reacts only by its surface and does not need to be solubilized as in the case of apatite. the fact that all form of life uses extensively ferredoxins containing iron-sulfur clusters as source of electrons is thus probably a vestige of these hadean times where pyrite and sun was the sole source of hydrogen peroxide. such a reaction has been tested in the laboratory and it was shown that upon uv-irradiation water could be decomposed into hydrogen peroxide with steady-state concentration of 34 µm.35 it was also shown that pyrite was not the most efficient photo-catalytic surface as a concentration of 400 µm was obtained in the presence of vaesite nis2, pointing to the crucial role played by nickel and iron for the apparition of life on a primitive earth. on the other hand, it was also found that fes and zns surfaces were not able to catalyze such a reaction. with the help of the sun and pyrite, hydrogen peroxide could be absorbed by the primitive oceans and reach the mouth of hydrothermal vents located upon the oceanic floor. now, the problem is to explain how α-keto-acids such as glyoxylate and pyruvate could also be present here in order to react with hydrogen peroxide. in fact, laboratory experiments has shown that metal sulfides could acts as catalysts for hydrocarboxytable 5. thermodynamic analysis of some abiotic reactions generating important compounds for the emergence of life on earth. (a,b) choline; (c) phosphate; (d,e) glycerol; (f,g) glycerate; (h) hydrogen peroxide; (i,j) formate; (k,l) acetate; (m,n) methanethiol; (o,p) thioacetic acid; (q,r,s) glyoxylate; (t,u,v) pyruvate. all values are given at ph = 7 and i = 0.25 m and reported in zj·k-1. reaction σ πi° (left) σ πi° (right) ∆πi° (a) 5 co + nh4+ + 9 h2 = c5h14no+ + 4 h2o -2.09193 0.0096 +2.10153 (b) 5 h2co3 + nh4+ + 14 h2 = c5h14no+ + 14 h2o 7.04397 8.6791 +1.63513 (c) ca5(po4)3oh + 9 h2o = 5 ca(oh)2 + 3 pi 42.75895 40.43895 -2.32000 (d) 3 co + 4 h2 = c3h8o3 -0.20506 0.95433 +1.15939 (e) 3 h2co3 + 7 h2 = c3h8o3 + 6 h2o 5.27648 6.15603 +0.87955 (f ) 3 co + 2 h2 + h2o = c3h5o41.76615 2.54815 +0.78200 (g) hco3+ 2 h2co3 + 5 h2 = c3h5o4+ 5 h2o 6.38068 6.88290 +0.50222 (h) 2 h2o + fes2 = h2o2 + h2s + fes 2.62557 0.57243 -2.05314 (i) co + h2o = hcoo+ h+ 1.53473 1.73233 +0.19760 (j) hco3+ h2 = hcoo+ h2o -2.49496 2.59928 +0.10432 (k) 2 co + 2 h2 = ch3coo+ h+ 0.23136 1.38023 +1.14887 (l) hco3+ h2co3 + 4 h2 = ch3coo+ 4 h2o 3.88572 4.84803 +0.96231 (m) co + 2 h2 + h2s = ch3-sh + h2o -0.72058 0.00156 +0.72214 (n) h2co3 + 3 h2 + h2s = ch3-sh + 3 h2o 1.10660 1.73546 +0.62886 (o) co + ch3-sh = ch3cos+ h+ -0.19761 0.07519 +0.27280 (p) hco3+ h2 + ch3-sh = ch3cos+ 2 h2o 1.62957 1.80909 +0.17952 (q) hcoo+ co = c2ho32.40001 2.38730 -0.01281 (r) hco3+ h2co3 + 2 h2 = c2ho3-+ 3 h2o 4.98992 4.98815 -0.00177 (s) hco3+ co + h2 = c2ho3-+ h2o 3.16274 3.25425 +0.09151 (t) ch3coo+ co = c3h3o32.04801 1.95366 -0.09435 (u) hco3+ 2 h2co3 + 5 h2 = c3h3o3+ 6 h2o 6.38068 7.15536 +0.77468 (v) 3 co + 2 h2 = c3h3o3+ h+ 0.89914 1.95366 +1.05452 44 marc henry, laurent schwartz lation (koch’s reaction) where a α-keto-acid is obtained via carbonyl insertion at a metal-sulfide-bound alkyl group in the absence of peptide-based enzymes.36 it was found that the sulfides of nickel, cobalt, iron and zinc were able to catalyze such an insertion but not copper sulfides. glyoxylate would thus be the result of inserting carbon monoxide into formate, while pyruvate would be the result of inserting carbon monoxide into acetate. as shown in table 5, formate could be formed according to scheme (i) or (j) and acetate according to scheme (j) and (k) with a moderate increase in entropy in the case of formate and a substantial one in the case of acetate. table 5 also shows that formation of methane-thiol through reactions (l) or (m) and thioacetate through reactions (n) or (o) proceeds with a neat increase of entropy, larger for the thiol derivative than the thiolate one. this basically means that alkyl sulfides were available around hydrothermal vents. however, scheme (p) in table 5 shows that direct insertion of carbon monoxide into formate yielding glyoxylate, proceeds with a slight decease in total entropy. the direct reduction of a mixture of carbon monoxide and dioxide by hydrogen gas according to scheme (q) is a better solution. however, the best way to form glyoxylate leading to a an increase in total entropy is scheme (r) proceeding by insertion of carbon monoxide into bicarbonate followed by reduction with hydrogen gas. the abiotic synthesis of pyruvate by insertion of carbon monoxide into acetate according to scheme (t) in table 5 appears to be not favorable. direct reduction of bicarbonate by hydrogen gas according to scheme (u) is a much better solution, the best one being direct reduction of carbon monoxide following scheme v). having checked the avaibility of glyoxylate, pyruvate and hydrogen peroxide, we should now focus on the 4-hydroxy-oxo-glutarate cycle shown at the bottom of figure 2 and analyzed for its feasibility in table 6. the result is impressive and shows that such a cycle is a totally abiotic “respiration” relying on carbon monoxide and hydrogen gas that are precursors of glyoxylate and pyruvate generated by the earth that are burned by hydrogen peroxide generated by the sun, rejecting as waste carbon dioxide and water. on such a ground, there is no major difference between such a purely abiotic respiration supported transition metal sulfides and a plant capturing the energy from the sun to make organic matter that would be burned away releasing entropy at night. moreover, by coupling the 4-hydroxy-2-oxoglutarate cycle generating a large amount of entropy with the solubilization of apatite reaction (c) in table 5, it becomes possible extracting inorganic phosphate and release simultaneously 537 zj of heat. these inorganic phosphate would be used to create phospholipids during the hadean period, then coenzyme-a and its derivatives (nadh, nadph, fad, fmn, etc…) and most importantly nucleotides. we could also have a look at the upper malonic cycle (table 7), that starts from 2-oxo-succinate (also called oxalo-acetate), an intermediate molecule synthesized during the revolving of the 4-hog cycle. this cycle is not so efficient as the first one, but it also leads to the burning of glyoxylate by hydrogen peroxide with a large entropy increase available for coupling with a process associated to a decrease in entropy together with the eventual release of any excess entropy as heat. one may notice that a critical step in this cycle is the decarboxylation of 3-carboxy-2-oxo-succinate, which is the only step with a negative entropic contribution. however, as most of the irreversibility potentials for such intermediates has been estimated using alberty’s group contribution table 6. thermodynamic analysis of the 4-hydroxy-2-oxo-glutarate cycle represented at the bottom of figure 2. such a cycle consume one glyoxylate molecule that is oxidized into carbon dioxide and water with an overall largely positive increase in entropy all values are given at ph = 7 and i = 0.25 m and reported in zj·k-1. reaction σ πi° (left) σ πi° (right) ∆πi° 2-op + 2-oa = 4-hog 4.34096 4.47947 +0.13851 4-hog + h2o2 = 2-hs + carbonate 4.77187 6.85007 +2.07820 2-hs + h2o2 = 2-os + 2 h2o 4.09541 5.71602 +1.62061 2-os + 2-oa = 3-om 6.36942 6.52514 +0.15572 3-om + h2o = 4-hog + carbonate 7.39482 7.52653 +0.13171 c2ho3+ 2 h2o2 = h2co3 + hco3+ h2o 26.97248 31.09723 +4.12475 table 7. thermodynamic analysis of the malonate cycle represented at the top of figure 2. such a cycle consume one glyoxylate molecule that is oxidized into carbon dioxide and water with an overall largely positive increase in entropy. all values are given at ph = 7 and i = 0.25 m and reported in zj·k-1. reaction σ πi° (left) σ πi° (right) ∆πi° 2-os + h2o2 = 2-ca + h2co3 4.27452 6.48075 +2.20623 2-ca + 2-oa = 3-cm 5.82099 5.85413 +0.03314 3-cm + h2o2 = 3-cos + 2 h2o 6.14563 7.89998 +1.75435 3-cos + h2o = 2-os + hco37.03303 7.02918 -0.00385 c2ho3+ 2 h2o2 = h2co3 + hco3+ h2o 23.27417 27.26404 +3.98987 45entropy export as the driving force of evolution method,28 such a very small value is within the errors of the algorithm. but again, this does not really matters as there is enough entropy release in the other steps for keeping the cycle into a permanent running state. as shown in figure 2, the malonate cycle is of crucial importance because as it allows formation of the important aminoacid aspartate by reacting malonate with alpha-hydroxy-glycine (see table 8).15 abiotic aminoacid synthesis as shown in figure 5, five other aminoacids may be derived from aspartate: lysine, asparagine, threonine, isoleucine and methionine. another important precursor of aminoacids, sugars, cofactors and lipids is pyruvate, that is an important hub metabolite that have been obtained from fes surfaces.37 another study has shown that pyruvate could be transformed readily in the presence of transition metal sulfide minerals under simulated hydrothermal fluids at temperature t = 25-110°c.38 depending on the relative concentration of h2s (3-110 mm), h2 (0.150 mm), alanine could be obtained among nine other species with yields ranging from 0.1% to 60%. with 100 mm h2, 100 mm co2 and 20 mm h2s at t = 25°c on fes pyrrhotite, it was also possible to perform aldol condensation of pyruvate to 2-hydroxy-2-methyl-4-oxo-pentane-dioate with a yield of 13%. on such surfaces, it was also possible to form various thio-derivatives. now experimental studies have shown that the full sequence complexity of naturally occurring proteins is not required to generate rapidly folding and functional proteins, i.e. proteins can be designed with fewer than 20 letters.39 using combinatorial mutagenesis in an table 8. thermodynamic analysis of the abiotic synthesis of the aspartate aminoacid from malonate –ooc-ch2-coo-, carbon monoxide, ammonia and hydrogen gas. all values are given at ph = 7 and i = 0.25 m and reported in zj·k-1. reaction σ πi° (before) σ πi° (after) ∆πi° hco3+ co + h2 + nh4+ = α-hg + h2o 2.70081 2.64868 -0.05213 α-hg + 2-ca = 3-cas + h2o 5.21542 5.45091 +0.23549 3-cas + h2o = c4h6o4n + hco35.45091 5.56502 +0.11411 c3h2o4+ co + h2 + nh4+ = c4h6o4n + h2o 13.36714 13.66461 +0.29247 figure 5. relationships between the twenty aminoacid within their 3-letters and 1-letter codes, possible substitutions in proteins and secondary structure (helix or sheet) preference. primary organic precursors are highlighted in blue, secondary aminoacid precursors of other aminoacids are highlighted in yellow. aminoacids added lately to the universal genetic code under oxic conditions are highlighted in green. 46 marc henry, laurent schwartz enzyme of the bacterium e. coli, it has thus been shown that it was possible grouping the 20 aminoacids to a reduced set of 7 groups: asp (asn, glu, gln); ala (gly, ser, thr, cys); val (met, leu, ile); arg (lys, his); tyr (phe), trp and pro.40 among these groups the four aromatic aminoacids (his, tyr, phe, trp) and met are characterized by an homo-lumo gap smaller than 10 ev.41 this indicates that in demanding building blocks with more versatile redox chemistry, biospheric molecular oxygen triggered the selective fixation of these last amino acids in the genetic code. similarly, arginine may be discarded on the ground that it is essential only for catalytic activity and not for conformational stability.42 consequently, one may retain only four critical aminoacids for building prebiotic peptides precursors of proteins: asp, ala, val, and pro. in such a minimal set, we find a strong former of α-helix (ala) and a strong former of β-sheet (val). we have also a breaker of helices and sheets (pro) and an indifferent aminoacid (asp) bringing acidic properties. the next aminoacid that will be logically recruited upon evolution is also an indifferent aminoacid (arg) bringing basic properties. table 9 shows that alanine, valine and proline may be formed from pyruvate with an increase in entropy in all cases. we have also considered the formation of glutamate, which is expected to be an important intermediate for the synthesis of arginine. accordingly, glutamate has also been obtained under hydrothermal conditions at a concentration of about 4 µm.43 table 8 also shows that condensation of two amino acids to form a dipeptide is a non-spontaneous process that requires coupling with another process releasing at least +0.2 zj·k-1 of entropy. as there is plenty of entropy release in the two abiotic cycles represented in figure 2, oligomerization of amino acids into polypeptides just needs an adequate mineral surface. accordingly, it is a well-established fact that amino acids concentrate and polymerize on clay minerals or apatite to form small, protein-like molecules containing up to 12 amino-acids.44 for instance, the sanidine feldspar not only favors the peptide bond formation from both a thermodynamic and kinetic viewpoint but also prevents their hydrolysis.45 moreover, some mineral surfaces are known to be chiral, an important requirement for explaining the chirality of biomolecules. it has also be demonstrated that formation of a dipeptide from two amino acids is about eight times more difficult than subsequent condensations of an amino acid to a dipeptide or longer chain.46 the same study has shown that adding an amino acid to a peptide of any size is five times more difficult than joining small peptides together. this demonstrates that the rather small entropy decrease associated to formation of a peptide bond is not a real problem and could be easily overcome. according to (4), one could for instance make a coupling with the absorption of an infrared photon having a wavelength λ = 4.8 µm. according to wien’s displacement law the light emitted by a black body, 4.9651·λmax·(kbt) = h·c i.e. λmax·t = 2898 µm·k, such photons are emitted in great amount by any surface heated to a temperature t ≈ 600 k ≈ 330°c. such a temperature is typical of hydrothermal vents and experiments have confirmed that peptide synthesis was indeed favored in hydrothermal fluids.47 abiotic phosphate-based compounds our last concern will be the exact role played by atp, a molecule intimately associated with any kind of table 9. thermodynamic analysis of the abiotic synthesis of the some aminoacid from pyruvate and their condensation into di-peptides. alanine = c3h7no2; valine = c5h11no2; proline = c5h9no2; glutamate = c5h9no4; glycine = c2h5no2; glycylglycine = c4h8n2o3; alanylglycine = c5h10n2o3. also shown the analysis for the formation of inorganic as well as organic polyphosphates and polymers of formaldehyde (sugars) or cyanhydric acid (purine base). ribose = c5h10o5; glyceraldehyde = c2h4o2; adenine = c5h10o5. all values are given at ph = 7, i = 0.25 m and reported in zj·k-1. reaction σ πi° (left) σ πi° (right) ∆πi° c3h3o3+ h2 + nh4+ = alanine + h2o 0.93963 1.34392 +0.40429 c3h3o3+ 2 co + 5 h2 + nh4+ = valine + 3 h2o 0.06679 2.10082 +2.03403 c3h3o3+ 2 co + 4 h2 + nh4+ = proline + 3 h2o 0.61889 2.27164 +1.65275 c3h3o3+ 2 co + 2 h2 + nh4+ = glutamate + h2o 1.72309 2.93963 +1.21654 hco3+ h2co3 + 3 h2 + nh4+ = glycine + 4 h2o 3.97589 4.44847 +0.47258 gly + gly = gly-gly + h2o 1.96134 1.77934 -0.18200 ala + gly = ala-gly + h2o 1.45764 1.31941 -0.13823 2 pi = ppi + h2o 11.8016 11.6755 -0.1261 amp + pi = adp + h2o 8.99091 8.80178 -0.18913 3 pi = pppi + 2 h2o 17.7024 17.4177 -0.2847 pi + ppi = pppi + h2o 16.7093 16.5508 -0.1585 adp + pi = atp + h2o 13.8356 13.6350 -0.2006 2 h2co3 + 4 h2 = glyceradehyde + 4 h2o 3.88572 4.13480 +0.24908 5 h2co = ribose 1.67835 1.84835 +0.17000 5 hcn = adenine 4.46785 -2.86655 +1.60130 ribose + pi = ribose-5-phosphate + h2o 7.74502 7.65720 -0.08782 ribose + adenine = adenosine + h2o -1.02128 -1.00139 +0.01989 47entropy export as the driving force of evolution life process. as shown in figure 6, this molecule is made of three main parts: a triphosphate, a c5-sugar and a heterocyclic base named adenine. table 8 shows that formation of polyphosphates, whether inorganic or organic is always associated to a decrease of the total entropy. consequently, such reaction should be coupled with an entropy-generating process. here, coupling with an infrared photon is unlikely as this would require a wavelength λ ≈ 3.3 µm generated by surfaces heated at t = 870k ≈ 600°c, a temperature much too hot for hydrothermal vents. here coupling with a metabolic cycle seems thus mandatory for the synthesis of such polyphosphate species. the same conclusion obviously applies to other phosphate-based species such as rna or dna. the abiotic synthesis of the ribose and adenine moieties poses no particular problems, as a sugar is just an addition polymer of formaldehyde (h2c=o)5, while adenine is an addition polymer of cyanhydric acid (hcn)5. table 8 shows that formation of these polymers is associated to a significant increase in total entropy in both cases and may thus proceed without the need for an extra source of entropy. obviously, such reactions need to be catalyzed by serpentinizing olivine and borate minerals for the formation of ribose from formaldehyde and small quantities of glycolaldehyde.48 this last compound is necessary for catalyzing the first step of dimerization of formaldehyde that requires a high energy of activation. as shown in table 8, it could be easily formed in hydrothermal vents or derived from surface hydrogenation of co molecules in interstellar dark cloud regions of the universe.49 similarly, the mechanism of formation of adenine, a hcn pentamer, under prebiotic conditions has been studied, and it seems that catalysis by water and ammonia molecules is needed.50 from table 8, one may see that the condensation of the ribose moiety with an inorganic phosphate is associated with a small decrease of entropy. for the condensation between adenine and ribose to yield adenosine, we are within the errors (±0.02 zj·k-1) of the method and nothing can be said about such a process. figure 5 also shows that the atp molecule has a particularly good geometry for chelating divalent metallic ions51 and has in particular a quite high affinity for magnesium ions.52 consequently, one should be cautious when computing irreversibility potential differences involving species bearing a strong negative charge such as atp. but, the most interesting aspect of atp is its position at the very bottom of table 4 giving irreversibility potentials in ascending order. one can see that the overall effect of phosphorylation is to strongly increase the irreversibility potential. it follows that atp should be more assimilated to a waste than to a food. moreover, one can see from table 8 that the energy released upon hydrolysis of atp, about 60 zj, is of the order of magnitude of at most two hydrogen bonds (about 40 zj between two water molecules in liquid water). speaking of the p-o-p linkage as a “high energy” bond seems thus quite exaggerated. one may also compare such an energy with the energy released by one turn of the two abiotic cycles shown in figure 2 that are 1330 zj for the 4-hydroxy-2-glutarate cycle and 1190 zj for the malonate cycle. this means that about 20-22 molecules of atp would be needed for storing the energy liberated by the combustion of glyoxylate. the question is thus why configure 6. lewis structure of adenosine triphosphate (atp) shown here chelating a magnesium ion. 48 marc henry, laurent schwartz sidering a waste as a ubiquitous agent for storing energy? table 4, shows that much better agents would be nad+ or nadh that are at the very top of the table. such a position is perfect for “high energy” molecules and accordingly the nad+/(nadh,h+) couple is the universal energy pool in any kind of respiratory chain. one of the reasons for focusing attention on atp is merely that without a continuous production of such a compound, a cell is not able to survive. as a consequence, “high-energy” molecules such as nadh that are basically foods are systematically degraded to produce atp, a very valuable waste indeed for the cell. a recent publication on the real role of atp in the cell gives a clue.53 it was shown that atp at physiological concentrations 5-10 mm has properties of a biological hydrotrope, preventing the formation of protein aggregates and dissolving them if they happen to be formed. in other words, without atp the intracellular medium is doomed to precipitate owing to its very high molecular crowding. such a property of maintaining solubility is more in line with the position of atp in table 4 and points to the importance of a systematically neglected factor, water activity aw. water activity aw to understand this crucial point, we have to go back to equation (2) and see that an irreversibility potential for a given substance depends on temperature t, pressure p and on the activity a of this substance. let’s us recall that a = 1 for a species in a pure state and that a < 1 as soon as the substance is mixed with other substances. for condensed states such as liquids or solids, activity may be written as a product of two terms, a = γ·x, where x is the molar fraction of the substance in the mixture and γ an activity coefficient taking into the deviations from ideal behavior of the mixture. basically, an ideal mixture is a medium where constituents do not interact with each other. in other words, by considering an ideal mixture we implicitly assume that it exists only a single form of energy: kinetic energy. in such a case, one has γ = 1 and the activity is essentially ruled by molar fractions x, that is to say molecular composition. however, as soon as the constituents interact through potential energy, one has γ ≠ 1 and activity is no more ruled by molar fractions alone. a situation where the molecular interactions between constituents are repulsive would lead to γ > 1, meaning that activity is increased relative to the ideal non-interacting case. now, if molecular interactions are attractive then γ < 1, meaning that activity is decreased relative to the ideal non-interacting case. from a practical viewpoint, for species having a sufficiently high vapor pressure, activities may be defined as the ratio a = pvap(t)/p°vap(t), where pvap(t) and p°vap(t) are the vapor pressure measured at saturation and temperature t for the mixture and the species in a pure state respectively. as a substance ubiquitous in the cell, water has its own activity that depends on the composition and of the interactions between water molecules and all the species in contact with water. a common assumption is that in a cell one should have aw ≈ 1, on the ground that the molar fraction of water xw is very high (xw > 0.99) relative to all other constituents (see figure 1). by doing this, one automatically assume that γw ≈ 1, meaning that water molecules do not interact at all with the solutes. such an assumption is obviously utterly wrong, as water is a solvent that always interacts quite strongly with any kind of solute, meaning that one has necessarily γw < 1. as soon as this is posed, the immediate question is to quantify the deviation from unity for the activity coefficient of water. obviously, there will be some substances provoking a large decrease of γw even at very low molar fraction and other substances needing high molar fractions to significantly decrease γw. a direct proof of the crucial importance of water activity for life is given by the fact that no microbial growth is possible below aw < 0.6 for the three domains of life (prokaryotes, archaea and eucaryotes).54 in fact most microbes living at room temperature and ambient pressure are able to grow only if aw > 0.9. such a finding is clear evidence of the importance of water activity for life processes. norrish’s equation is the best approach to understand how water activity changes upon adding a solute:55 k = (kbiww + kbiss – 2·kbisw)/2vw = aw = xw·exp(k·xs) here kbiww, kbiss and kbisw are kirkwood-buff integrals (kbi) that are function of the radial distribution functions of water-water (ww), solute-solute (ss) and water-solute (sw) interactions. in practice, norrish’s equation applies up to moderate solute concentrations (ca 60 wt%, 5-10 m or 0.1-0.2 mole fraction) and may thus be applied to any kind of living cell. as norrish’s constant k is generally negative, it follows that water activity always decreases when molar fraction of solutes increases. however, the variation of water activity with xs appears to be modulated by the value of k that strongly depends on the chemical nature of the solute. in fact, owing to its very small size (ca 0.3 nm in diameter), it follows that the water-water integral kbiww does not change very much upon adding a sol49entropy export as the driving force of evolution ute. this is not the case of the two other integrals that are generally both negative owing to the existence of large excluded volumes. generally speaking, the larger the solute species, the larger the exclusion volume and the more negative the kirkwood-buff integral. it thus follows that as a glucose molecule is bigger than a glycerol molecule, the decrease in water activity is stronger at the same concentration for glucose than for glycerol. this explains the phenomenon of cryptobiose where a cell produces a large amount of sucrose (k = -6.47) in order to protect itself against freezing, dehydration, osmotic stress or low pressure. by strongly lowering its water activity, the cell is no more able to grow but can survive under very harsh conditions waiting eagerly for better conditions. as soon as water activity rises again, the sucrose is exchanged for water and the cell become able to grow again, as soon as aw > 0.9. now, we are in the position of understanding that atp owing to its very large negative charge and its big size is in fact an agent able to strongly decrease water activity. table 10 gives the water activity calculated at xw = 0.91 for different substances soluble in water.56 values for na3adp and na2atp were derived from measurements of hydration isotherms of the solids.57 it should be clear that the water activity coefficient γw is never equal to 1 and is strongly dependent on the nature of the solute. the water activity coefficient is in most cases less than one, pointing to attractive solute-water interactions. the smaller the activity coefficient, the stronger is the attraction. the only exception is urea that has an activity coefficient greater than one pointing to repulsive interactions with water molecules. we have also indicated in table 10, the equivalent temperature that should be applied to supercooled water to get the same water activity value.58 the lower the temperature, the stronger is the interaction. values in table 9 are sorted in ascending order in order to highlight the fact that na3adp and na2atp salts are quite efficient in decreasing significantly water activity for a concentration below 2m. all other compounds require concentrations higher than 2m. it is worth recalling that as shown in figure 7, no life is possible below aw ≈ 0.6 corresponding to an osmotic pressure p ≈ 70 mpa ≈ 0.7 kbar and to a temperature less than -40°c. the fact that na3adp leads to a larger decrease in water activity than na2atp at the same molar fraction comes from the fact that na3adp has one additional negative charge relative na2atp. one may then expect that the decrease in water activity for the salt na4atp will be much larger than for na3adp. similarly, it may be expected that the complexation of atp4by magnesium ions, yielding mgatp2will be associated to large increase in water activity, allowing inducing conformational changes of many proteins. accordingly, it was shown that the f1 part of the atp synthase present in the inner mitochondrial membrane was strongly dependent on water activity, the reaction figure 7. water activity and growth of several kinds or microorganisms in relation woth food preservation. 50 marc henry, laurent schwartz f1·adp + pi = f1·atp being shifted to the right by adding dmso, a molecule able to decrease water activity below aw = 0.80 at a concentration of 40 vol%.59 similarly, it was observed that reduction in water activity upon addition of dmso greatly retards the phosphoryl transfer from atp to enzyme protein in the catalytic cycle of sarcoplasmic reticulum ca2+-atpase.60 finally, synthesis of atp after a single catalytic cycle of the same enzyme was promoted by water activity jumps.61 it follows that a cyclic activity of many enzymes could be related to cyclic variations in water activity. this is in fact quite logical when it is realized that most reactions in a living cell corresponds to the following reaction: x-oh + h-y = x-o-y + h2o where x and y may be c, co or p and y may be o, s or nh. proceeding to the right, we have anabolism, while proceeding to the left we have catabolism. in both cases, the presence of the water molecule means that changing water activity could easily shift such equilibria. as shown in table 9, any variations in salt concentrations or in small organic solutes (sugars, polyols, carboxylic acids or urea) will change more or less water activity and shift the above equilibrium either to the left if aw increases or to the right if aw decreases. as this concerns water, the most abundant species in a living cell, we have here a quite general binary code. more importantly, any cyclic variation in aw could be associated to the existence of a clock, a prerequisite for having coherent movements in a living cell. conclusion the main result of our approach is the crucial role played by the entropy for understanding any kind of table 10. water activity aw, water activity coefficient γw and equivalent equilibrium temperature t relative to supercooled water for a constant molar fraction xw = 0.91 of common solutes. one may convert water activities to equivalent osmotic pressures at t = 298.15 k through the relationship p(mpa) = -137.15×ln(aw). substance s m.w. / da concentration / m aw γw t / °c peg600 400.00 2.28 0.578 0.635 < -40 na3adp 493.15 1.85 0.606 0.666 < -40 nacl 58.44 15.57 0.790 0.868 -24 kcl 74.55 12.21 0.834 0.917 -19 na2atp 551.14 1.65 0.838 0.921 -18 lactose 342.30 2.66 0.838 0.921 -18 lactulose 342.30 2.66 0.853 0.937 -16 trehalose 342.30 2.66 0.862 0.947 -15 sucrose 342.30 2.66 0.864 0.950 -15 citric acid 192.12 4.74 0.866 0.952 -15 tartaric acid 150.09 6.06 0.876 0.963 -14 maltose 342.30 2.66 0.877 0.964 -14 propylene glycol 76.09 11.96 0.881 0.968 -13 fructose 180.16 5.05 0.889 0.977 -12 dmso 78.13 11.65 0.889 0.977 -12 glucose 180.16 5.05 0.894 0.982 -12 galactose 180.16 5.05 0.894 0.982 -12 malic acid 134.09 6.79 0.897 0.986 -11 xylitol 152.15 5.98 0.898 0.987 -11 sorbitol 182.17 5.00 0.898 0.987 -11 lactic acid 90.08 10.10 0.898 0.987 -11 xylose 150.13 6.06 0.899 0.988 -11 arabinol 152.14 5.98 0.900 0.989 -10 erythritol 122.12 7.45 0.900 0.989 -10 glycerol 92.09 9.88 0.901 0.990 -10 mannitol 182.17 5.00 0.903 0.992 -10 urea 60.06 15.16 0.925 1.017 -8 51entropy export as the driving force of evolution biological transformation. most previous publications focused on energy not on entropy. energy applies to the first law of thermodynamics, entropy to the second law. our analysis is based on the second law and therefore on entropy. such a distinction between energy and entropy becomes obvious when one tries to understand the physical origin of the entropy concept. from boltzmann’s formulation of entropy, s = -kb·σi pi·ln pi, we may link this concept to the number of indistinguishable microscopic configurations of a system corresponding to a single macroscopic state. here, a clear link could then be established with shannon’s information content, h = -σi pi·ln pi, of a message as both expression differs only by a universal scaling constant. in other words, if energy has something to do with mass or frequency (times a universal constant), entropy has something to do with information. as far as evolution is concerned, knowledge of the involved masses and frequencies is useless, relative to the information content. accordingly, as energy should never increase or decrease during any evolution, the focus should be put on information that can be created at will and once created will never be destroyed. variations of information contents (entropy) is the real driving force for any kind of evolution, available energy being here to set up the speed at which such an evolution may occur. as shown above, it is possible to describe the bioenergetics principles in terms of irreversibility potentials, leaving energy considerations to kinetics. on such a ground, one accounts for a fundamental splitting of the bioenergetics field into two distinct fields: biothermodynamics on one hand ruling evolution and focusing on entropy variations, and biokinetics on the other hand focusing on energy flux. such a splitting is fully coherent with the fact that thermodynamics considerations are useless for discussing kinetics problems and vice-versa. the main consequence of such a formulation is the existence of a single criterion of evolution in terms of irreversibility potentials ∆π ≥ 0, instead of five different ones ∆s ≥ 0 (evolution for an isolated system), ∆u ≤ 0 (evolution at constant entropy and volume), ∆h ≤ 0 (evolution at constant entropy and pressure), ∆f ≤ 0 (evolution at constant temperature and volume) and ∆g ≤ 0 (evolution at constant temperature and pressure) when focusing on the energy/entropy duality. in other words, instead of putting experimental constraints on the thermodynamic potentials, a simpler approach is to have a single thermodynamic potential measuring irreversible power and distinct numerical tables according to the experimental constraints. for instance, the values of the π°i potentials used here applies to transformations occurring at constant temperature and pressure and they should thus not be used for transformations occurring at constant entropy and volume for instance. for such transformations, other tables with different numerical values have to be used. in other words, the revolution for biologists is not the data (they are unchanged), but simply, putting entropy at the center of the equations. life could be summarizing as able to export a large amount of entropy from the inside to the outside (∆s >> 0). it is the progressive decrease in entropy export ability that causes aging (∆s > 0), death (∆s = 0) and finally dispersion (∆s < 0) when entropy becomes imported from the surroundings, instead of being exported towards the surrounding (∆s >0). by putting entropy at the forefront, the quest for survival is deep-rooted in the ability for exporting entropy rather than in the ability of finding energy that is always available. on such a ground, existence of a metabolism based on a food/waste balance appears to be a prerequisite for any form of life, even the most rudimentary ones. defining life by entropy export establishes a natural link with information quest. a system could then be qualified as ‘living” as soon as it is able to export information towards its environment, keeping the useful and pertinent one for maintaining its internal structure. as demonstrated by the dna molecule, an information content of about 1 gb is enough to encode in all details a whole human being. another advantage of the proposed approach is to qualify the whole earth as a living system through its plate tectonics allowing mixing of the high entropy upper materials in the atmosphere and the crust with the low entropy lower materials in the mantle and the core. having a self-assembled membrane lipidic bilayer is thus not a mandatory condition for being qualified as a living system. any rocky system could be a potential living entity as soon as an exporting mechanism of entropy becomes available. again, the differentiation between a living rocking system and a living biological cell is just a matter of kinetics with a time scale of billions years for the rocks and of a few years for cells. finally, such a reformulation of the emergence of life has deep implications in medicine where illness could now be viewed by a decrease of the ability for exporting entropy. restoring the entropy export ability at its optimum level, or preventing entropy importation could be very valuable tools for healing. the main characteristics of such new healing methods would be treat the body as a whole and to use very simple chemical compounds able to restore compromised entropy outputs (breath, sweat, urine, feces, heat for instance) by changing water activity. time seems then to be ripe for stopping discussing biological events in terms of energy variations. 52 marc henry, laurent schwartz any “energy” variation should be reformulated as an irreversible entropy increase, by changing the sign of the involved energy and dividing the result by the temperature of the medium. this is not at all just a mathematical game, but rather the clear acknowledgment that what drives evolution is entropy and not energy. without a clear recognition that an expression such as “chemical energy” is meaningless, evolution of biology as a science will be deeply hampered. appendix a at the root of the development of thermodynamics, two notions are usually introduced: energy that is always conserved (first law) and entropy that should never decrease (second law). such a dichotomy has led to much confusion, with an opposition between processes occurring in inert matter piloted by an increase in entropy and processes occurring in living matter supposed to proceed with a decrease in entropy. it is thus quite strange that the notion of chemical potential introduced at the beginning of the xx century by john willard gibbs is seldom used in chemistry and biology. one of the big advantage of considering chemical potential rather than energy or entropy is that there is a single fundamental law stating that a spontaneous transformation is always associated to a decrease of the total chemical potential µ. accordingly moving a weight up, increasing a speed, heating a body, decreasing volume of gases, increasing an area, increasing concentration of a solution, increasing an electrical potential difference are not processes occurring spontaneously. in our universe, weights always fall down, speeds always decrease, hot bodies always cool down, gases always expands, areas always decrease, solutions becomes always diluted, and potential differences always decrease. the fundamental reason behind such phenomena is always the same: a decrease in each case of an entity having the dimension of a mass times an area times the square of a frequency. in the previous examples, such an entity was the product of a force by a height, the product of a linear momentum by a speed, the product of an entropy by a temperature, the product of a volume by a pressure, the product of a number of moles by a chemical potential and the product of an amount of electrical charge by a voltage. confusion immediately arises as soon as such an entity is called “energy”. this stems from the fact that in physics energy is defined as mass (m) times the square of the velocity of light in vacuum c (theory of relativity) or as frequency (f) times planck’s constant h (quantum theory). so, even if the propensity to spontaneous evolution in thermodynamics and energy in physics are quantified by the same physical unit (joule), they should not be confused. the consecrated name “gibbs free energy” (symbol g) for measuring propensity for spontaneous evolution in thermodynamics is a first step, but has the drawback of still making a link with the energy concept of physics (e). we will use the symbol u and write according to the first law: ∆u = ∆q – p·∆v, where ∆q is the amount of heat, p the pressure and ∆v the variation in volume. for energy we have on the other hand, ∆e = ∆m·c2 from relativity theory or ∆e = h·f, from quantum theory. one should easily understand that setting ∆e = ∆u is quite absurd, despite the fact that both quantities share the same physical unit. the absurdity is that mass is assumed to be conserved in ∆u, but is allowed to change in ∆e. similarly, ∆u refers to systems made of matter whereas ∆e = h·f refers to photons that have no mass. in order to unveil the real significance of ∆u, one may consider that pressure p is a kind “mechanical potential” associated to variations in volume. this fundamentally means that spontaneous changes are expected as soon as it exists pressure differences in a system, mechanical equilibrium being reached when pressure is the same everywhere (no more changes in volume). it was a quite brilliant idea of rudolf clausius, to introduce a state function named “entropy” s ruling reversible infinitesimal heat transfers between a system and its surroundings, associated to a “thermal potential”, measured by the temperature t, dq = t·des. as with pressure, this fundamentally means that spontaneous changes are expected as soon as it exists temperature differences in a system, thermal equilibrium being reached when temperature is the same everywhere (no more changes in entropy). but, it was also realized by clausius, that entropy exchanges dis could also occur inside a system with the constraint that dis ≥ 0. in other words, if des is perfectly allowed to increase (des > 0) or decrease (des < 0), dis has the unique property of being a quantity that should always increase or remain constant. taking into account these two laws and writing the total entropy variation as ds = des + dis, leads to du = t·des – p·dv = t·ds – p·dv –t·dis. it follows that for any evolution occurring at constant entropy and volume (ds = dv = 0), one should have du = -t·dis ≤ 0 as t and dis are both positive quantities. the drawback of such a formulation is that most transformations occurs at constant pressure (dp = 0) and constant temperature (dt = 0). however, one may introduce a new potential g = u + p·v – t·s, leading to dg = du + v·dp + p·dv – t·ds – s·dt = v·dp – s·dt -t·dis. now, for any isobaric (dp = 0) and isothermal (dt = 0) evolution, we get dg = -t·dis ≤ 0. it is an easy matter to check that the same criterion 53entropy export as the driving force of evolution of evolution could also be written dh = -t·dis ≤ 0 for isobaric (dp = 0) and adiabatic (ds = 0) evolution and df = -t·dis ≤ 0 for isochoric (dv = 0) and isothermal (dt = 0) evolution. it thus appears that there is a single universal criterion of evolution, dis ≥ 0, whatever the pair of variable chosen for controlling the system. consequently, any spontaneous evolution always corresponds to an irreversible increase in entropy. for chemistry, one speaks of irreversible transformation while for biology one speaks of irreversible aging. in all cases, the thing that is decreasing has nothing to do with the energy of physicists related to mass content for material systems or to frequency of oscillations for radiations. the above considerations apply rigorously for a closed system allowed to exchange only heat with its surroundings. if exchange of matter are also allowed, one may introduce a “chemical potential” µ in addition to the mechanical potential p and the thermal potential t and writes that dg = v·dp – s·dt + µ·dn – t·dis. consequently, any substance is characterized by a set of three thermodynamic properties, a molar volume vm = (∂g/∂p)t, n, a molar entropy sm = -(∂g/∂t)p,n and a chemical potential µ = (∂g/∂n)t,p. choosing a standard reference state t° = 298.15 k, p° = 100 kpa allows writing the chemical potential as µ(p,t) = µ° – s°m·(t – t°) + v°m·(p – p°). a universal rule is then that if a substance is able to exist under different states, the observed state will always be the state having the lowest chemical potential. as s°m(gas) > s°m(solid) and v°m(gas) > v°m(solid), it directly follows that any pure substance should vaporize at a sufficiently high temperature(∆t > 0) or low pressure (∆p < 0). similarly one should expect a solid at a sufficiently high pressure (∆p > 0) or low temperature (∆t < 0). if a solid substance exists under several polymorphs, the observed polymorph at high temperature and pressure will be the one displaying respectively the highest entropy and the lowest molar volume. chemical potentials may also be defined for mixtures of substances, as µi(p,t,ni) = µi(p,t) + rt·lnai, where 0 < ai ≤ 1 measures the “activity” of each substance in the mixture. by definition, ai = 1 for a pure substance. for mixture of liquids containing n molecules, the activity of each component is given by the product of the molar fraction xi = ni/n by an activity coefficient γi characterizing how the various molecules interact together either trough attractive (γi < 1) or through repulsive (γi > 1) forces: ai = γi·xi. for solutions, the activity corresponds to a molarity ratio, ci/ c°, or molality ratio, mi/m°, times an activity coefficient γi : ai = γi·ci/c° or ai = γi·mi/m°. here, c° and m° refer to a reference state such that c° = 1m or m° = 1 mol·kg-1. for gases, the activity is function of the partial pressure pi = p·xi relative to a standard pressure p° times an activity coefficient γi : ai = γi·pi/p°, the reference pressure being p° = 100 kpa. concerning activity coefficients, a general rule is that for low molar fraction xi << 1, highly diluted solution ci << c° and low partial pressure pi << p° one may safely assume that γi ≈ 1. appendix b as the existence of irreversibility potentials should be quite new for most of the readers, we will give here some clues for decoding its physical significance. it should first be realized that such potentials results from the competition between two antagonistic kind of energies, the first one being kinetic energy favoring expansion and repulsion, the second one being electrical potential energy of attraction between positively charged nuclei and negatively charged electronic clouds. the stronger this attraction, the lower the irreversibility potential of the substance. but this is not the whole story, as these potentials are also dependent on the ability to liberate a large number of different kinds of chemical species during any transformation. this explains why elements, substances able to generate only a single kind of atom upon reaction and making strong covalent bonds under standard conditions, have the lowest πi° values and may thus be considered as primitive foods. this also explain why complex substances made of a large number of different atoms have higher πi° values. the larger the number of different constituting atoms, the larger the πi° values. taking for instance the case of carbon dioxide co2 that appears from table 1 to be rather close to solid wastes, despite the fact that it is a gas. this stems from the fact that electrical interactions between co2 molecules are here very weak (absence of permanent dipole moment owing to a very high symmetry) and that carbon dioxide may be cleaved into 2 different chemical species carbon monoxide co on the one hand and dioxygen o2 on the other hand. carbon monoxide co, being more polar than co2 owing to its asymmetric structure and being more reluctant to give off its oxygen owing a triple bond between carbon and oxygen has logically a much lower πi°-value. finally dioxygen o2 and dinitrogen n2 molecules are still less polar than co and may give off upon dissociation only a single kind of atom, explaining their position near the top of the table. water h2o, which is able as co2 to be cleaved into two gases (here h2 and o2), but is also a highly polar substance has thus a πi°-value intermediate between that 54 marc henry, laurent schwartz of co and co2. on the other hand hydrogen sulfide h2s which is a gas and which may be also cleaved into two different substance, sulfur s and h2, has a much lower πi°-value because one of these substance, sulfur, is made of molecules s8 that display attractive interactions strong enough to form a solid under standard conditions. as irreversibility potentials for compounds are all measured relative to the irreversibility potentials of the constituting elements, these elements all have the same zero πi°-value. in order to distinguish between them, one may use their absolute standard entropy s° or their volume v° under standard conditions of pressure and temperature. here, the lower s°, the tighter the organization of atoms in space. for gases, the sackur-tetrode equation (3) shows that the higher the molecular weight, the higher the entropy. consequently, one gets s°(o2) > s°(n2) > s°(h2) as m(o2) = 31.999 da, m(n2) = 28.013 da and m(h2) = 2.016 da. for condensed phases such as solids and liquids, it becomes more difficult to interpret changes in absolute entropy. however, the sackur-tetrode equation (3) shows that entropy always increases with temperature, meaning that we should always expect the order: s°(g) > s°(liq) > s°(s). now, a general rule is that if a substance is able to exist under different phases the phase observed at given temperature and pressure will always be the one with the largest irreversibility potential. consequently, from the definition of πi°-values given in equation 2, it follows that at sufficiently high temperature every substance should exist as a gas, as entropy is always maximized in the gaseous state. similarly, if a solid substance may exist under several distinct crystalline polymorphs, the polymorph observed at high temperature below melting temperature would be the one with largest s°. for iron, for instance, we see from table 1 that fe(bcc) is expected to transform into fe(fcc) or fe(hcp) as temperature is increased. the sackur-tetrode equation predicts that entropy s° should also increases with volume, meaning that one may expect: v°(s) < v°(liq) < v°(g). from equation (2) it follows that at sufficiently high pressure any substance should be transformed into a solid, as owing to the negative sign before v°, it is phases with the smallest volume that would have the largest irreversibility potentials. for iron, this means again that fe(bcc) is expected to transform into fe(fcc) or fe(hcp) as pressure is increased. one should also understand that with v°(liq) < v°(s) < v°(g), water appears as a quite strange substance, as it displays a lower volume than ice despite having a larger entropy. basically, this means that upon heating, an increase in kinetic energy leads to a decrease in volume leading to a liquid being more dense than ice, the solid form of water. similarly, by applying pressure on ice, one should get a liquid. such “anomalies” for water has deep consequences for life on earth. the fact that ice floats upon water, means that it is impossible to transform a large mass of liquid water into a block of ice. this is because below 4°c, the liquid always sink at the bottom of the container, thus escaping from the freezing. the fact that ice melts upon applying a pressure means that large masses of ice cannot remain static but should always flow downwards as observed with glaciers. being able to break down rocks by its increase in volume upon freezing and to abrade them away by flowing under an icy form, water is thus the main shaper of earth with time. it is also worth noting that irreversibility potentials given in table 1 applies to a single particle of each concerned species. consequently, if one has in one part of the system n(a) particles characterized by an irreversibility potential πi(a) and in another part n(b) particles having irreversibility potential πi(b), the irreversibility potentials of both parts should be p(a) = n(a)·πi(a) and p(b) = n(b)·πi(b) respectively. if both part are allowed to exchange particles and if p(a) = p(b), the system is said to be in equilibrium. in such a case the number n(a) and n(b) does not change with time. but if p(a) ≠ p(b), the system becomes out of equilibrium and changes in n(a) and n(b) will be observed until restoration of the equilibrium p(a) = p(b). a direct consequence is then that if n(a)·πi(a) = n(b)·πi(b), then n(a)/n(b) = πi(b)/πi(a). one may thus compute relative populations from the knowledge of irreversibility potentials. applying such considerations to a pure substance (a = 1) assumed to exist under two phases a and b means that equilibrium between both phases is expected as soon as n(a) = n(b) or πi(a) = πi(b). at constant pressure (p = p° = 0.1 mpa), it comes from (2) that: πi°(a) + s°(a)·(t – t°) = πi°(b) + s°(b)·(t – t°), leading to: t =t°· 1+ π i 0 a( )−π i0 b( ) s° b( )− s° a( ) ⎡ ⎣ ⎢ ⎤ ⎦ ⎥         b1( ) (b1) using equation (2) and table 1, it is thus possible to approximate melting (tm) and vaporization (tvap) temperatures of pure substances. for instance one may understand the very high cohesive energy of metallic iron as with a = solid phase (bcc) and b = liquid, (4) predicts that tm = 1682 k versus tm(exp) = 1811 k, while with a = liquid and b = gas, it comes that tvap = 3644 k versus tvap(exp) = 3343 k. the differences with experimental values may be accounted for by the fact that in (4) we have used s°-values at t = 298.15 k and neglected the variation of these standard entropies with tempera55entropy export as the driving force of evolution ture. nevertheless, this clearly shows that iron atoms are in strong attractive interactions in the solid or in the liquid. one may also use table 1 to predict that upon heating α-fe(bcc) should be transformed into γ-fe(fcc) and not into ε-fe(hcp). now, applying (4) to water with a = ice and b = liquid leads to tm = 275 k = 2°c, while with a = liquid and b = gas, it comes tvap = 369 k = 96°c. again, this shows the ability of irreversibility potentials to account approximately for observed melting and ebullition temperatures. one may also consider what happens at constant temperature (t = t° = 298.15 k) with (2) giving a new equilibrium condition as function of applied pressure πi°(a) – v°(a)·(p – p°)/t° = πi°(b) – v°(b)·(p – p°)/t° and leading to: p mpa( )= p°+ π i 0 b( )−π i0 a( ) v° b( )−v° a( ) ·t°       b2( ) (b2) consequently, one predicts that the transformation of a = α-fe(bcc) into b = ε-fe(hcp) should be observed at about p = 16.3 gpa, in good agreement with 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university press substantia. an international journal of the history of chemistry 3(2) suppl. 2: 75-89, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-576 citation: f. monti, a. barbieri, n. armaroli (2019) battery electric vehicles: perspectives and challenges. substantia 3(2) suppl. 2: 75-89. doi: 10.13128/substantia-576 copyright: © 2019 f. monti, a. barbieri, n. armaroli. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. battery electric vehicles: perspectives and challenges filippo monti, andrea barbieri, nicola armaroli* istituto per la sintesi organica e la fotoreattività, consiglio nazionale delle ricerche, via gobetti 101, bologna, italy *e-mail: nicola.armaroli@isof.cnr.it abstract. in the early decades of the car industry (1880-1920), battery electric vehicles (bevs) got a remarkable popularity. eventually, they fell into oblivion for nearly a century, leaving the stage to internal combustion vehicles (icvs), which enabled longdistance driving thanks to the superior energy density of liquid fuels. the invention of the lithium-ion battery (lib, 1991), characterized by unprecedented energy density and steeply decreasing costs, set the stage to reverse this century-long trend, making nowadays bevs a competitive alternative to icvs. in this paper, we analyze the perspectives of battery electric cars, quantitively assessing their performance in terms of energy efficiency and consumption versus icv counterparts. an examination of material requirements for manufacturing each battery component is made, with focus on critical resources such as cobalt, dysprosium, lithium and graphite. based on quantitative data, we conclude that the transition to electric powertrains for light-duty vehicles is not only desirable but also doable. however, this must be accomplished by following circular economy principles across the whole industrial chain, in the frame of a wider, radical transformation of the mobility system towards more sustainable models. keywords. battery electric vehicles, lithium ion batteries, cobalt, dysprosium, critical materials, energy efficiency, circular economy. the rise, fall and rebirth of the electric car the widespread notion that electric cars are a new technological concept is incorrect. the first battery-powered electric vehicle (ev) was made in 1834, i.e., over 50 years before the first internal combustion vehicle (icv) powered by gasoline went onroad.1 notably, the first examples of machines for personal transportation were based on steam engines and dates back to the very beginning of the 19th century. a century later, at the turn of the 20th century, the share of registered us cars was as follows: 40% powered by steam, 38% by electricity, 22% by gasoline (figure 1).1 therefore, as weird as it may sound nowadays, the fight for predominance among the three car concepts was far from over in 1900, when refined oil products were still scarcely available, electricity was a luxury for (some) city dwellers, and roads were far from being developed and paved outside the main urban centers. 76 filippo monti, andrea barbieri, nicola armaroli in the early 20th century, cars were only used by wealthy people within metropolitan areas, where distances were very short. this is why electric cars were still an attractive option. moreover, evs were silent, did not produce any smoke or smell and – most remarkably – did not require hand crank to be turned on. however, within a few years, the situation dramatically changed in favor of icvs,2 whose dominance in road transportation was poised to last for over one century. the main drivers for the triumph of icvs were (i) the invention of the electric starter in 1912, (ii) the start of the industrial production of the ford model t in 1908 (though henry ford continued to use his luxury electric car); (iii) the oil boom in texas that made gasoline increasingly available at affordable prices, (iv) the development of road networks that required cars with increasingly long mileage.2 the last ev of the pioneering times was produced in detroit in 19261 and the idea was (ephemerally) resurrected only in the 1970s in the aftermath of the first oil crisis. waves of interest occurred in the last part of the 20th century, but times were not mature, primarily because battery technologies (typically based on leadacid systems) were not capable of providing acceptable mileage at an affordable price and overall weight. in 1997 toyota released prius, the first hybrid car (figure 2).3 it combined an ice with electric propulsion, which enabled a decrease of fuel consumption in urban settings. nowadays, hybrid cars are the preferred choice for taxi drivers in many cities worldwide. the success of prius and of some other hybrid models (almost exclusively from japanese firms) marked the slow rebirth of electric mobility. the first prius used a nickel-metal hydride (nimh) battery pack.4 the technological game changer that made at last possible the dream of thomas edison – the pioneer of the electric transportation – is the rechargeable lithiumion battery (lib), which was introduced in the market by sony corporation in 1991 to power laptops.5,6 the progressive introduction of portable devices on a large scale (mp3 players, mobile phones, etc.) and also of systems requiring bigger battery packs (home appliances, bikes) offered a formidable opportunity to boost the development of libs and widely expand the market. this trend was timely pinpointed by two american engineers, martin eberhard and mark tarpenning, who realized that libs could be the long-awaited solution to enable battery vehicles with long ranges. they founded tesla motors in 2003 and were soon joined by elon musk, a f lamboyant south african immigrant and entrepreneur, who became the ceo and product architect of the company. since then, tesla has become one of the most noteworthy, controversial and debated companies in the world. whatever will be its future destiny it will be historically remembered as the company which challenged the most gigantic industrial conglomerate of human industry – oil & automotive – and forced it to change its century-old trajectory.7 there are three types of cars equipped with a battery pack: hybrid electric vehicles (hevs), plug-in hybrid electric vehicles (phevs) and battery electric vehicles (bevs). hev batteries are charged only by the thermal engine or via regenerative braking, whereas in phev these processes can be integrated by direct charging on the electric grid. bev have only an electric motor and can be powered exclusively by electricity. this article will primarily deal with bevs, often indicated simply as electric vehicles (evs). the key components of battery electric vehicles bevs are easier to assemble and cheaper to maintain than icvs simply because they contain a much smaller number of moving parts.8 hybrid, instead, are by far the most complex and materials intensive automobiles, as figure 1. from left to right, examples of electric, steam and internal combustion engine cars of the early 20th century (1906, 1908, 1925, respectively). 77battery electric vehicles: perspectives and challenges they contain both electric and traditional components. key constituents of bevs are: the battery, the electric machine, the power electronics and the charging device.9 a schematic representation of the key components of an electric car are depicted in figure 3. battery. it determines the key technical attributes of an ev, such as driving range and also performance. in the past, evs were equipped with lead-acid or nickel hydride batteries, but nowadays lithium ion batteries (libs, see also next paragraph) are by far the dominant technology and their role is not expected to fade even in the medium-long term, due to the unique (electro)chemical and physical properties of lithium.6 the most important parameters that define the quality of a battery are the mass and volume energy densities, the former being expressed in mj/kg (or more often in wh/kg and indicated as “specific energy”) and the latter in mj/l or wh/l;10 the volume energy density is particularly relevant for vehicles, due to obvious space constraints. in figure 4 are depicted energy densities of some types of batteries, along with those of the liquid fuels used in transportation. it must be emphasized that data in figure 4 refer to cells, but car batteries operate as packs. these include the control circuitry that warrants the car performance under any conditions and the robust casing that protects the cells (vide infra). therefore, at pack level, the battery energy density is smaller by 30-50% compared to bare cells. on the long term, the accessory parts of the battery appear to be the main limit for increasing energy density. the energy density of the most performing libs for evs are presently close to 250 wh/kg (tesla model 3), or 710 wh/l.11 this value unfavorably compares with gasoline or diesel fuels, which is nearly 15-fold higher at ca. 10,000 wh/l. however, this comparison is partly misleading because the energy packed in the storage unit must be converted into mechanical movement. for this job an electrical motor is 3-4 times more efficient than a combustion engine and, at the same time, is substantially lighter. therefore, power densities should be normalized accordingly.12 a 75 kwh lithium ion battery pack (tesla model 3) weights about 478 kg, whereas an equivalent ice car requires the burning of only 25 kg of gasoline to deliver the same energy to the wheels.4 however, it must be emphasized that an ev is a closed figure 2. the slow rebirth of electric vehicles: the first hybrid toyota prius (1997, top) and the tesla roadster (2008, bottom). figure 3. the key components of a battery electric vehicle (bev). figure 4. volume and mass energy densities of some selected batteries and liquid fuels. both mj and wh are reported in the diagram as energy units (on opposite sides), as both are largely diffused in the literature and technical documents. 78 filippo monti, andrea barbieri, nicola armaroli system which exchanges only (electric) energy with the external environment, whereas icvs are open systems undergoing a constant inbound flow of fuels and an outbound flux of gaseous chemicals at tailpipe. after 250,000 km, an average diesel car running at 18 km/l, has burnt 13,900 l of fuel, i.e., over 10 tons corresponding to about 8 times the weight of the whole ice car and over 20 times the weight of a 75 kwh ev battery. when the electricity is produced by solar panels (an increasingly frequent case) the flux of matter that moves an electric car is reduced to zero across the entire supply chain. in other words, comparisons of energy density and material intensity of batteries vs. traditional fuels is less straightforward than it may appear at first sight. electric machine. this term defines the combination of the electric motor, converting the electrical in mechanical energy, and the power generator coupled to it, which recovers kinetic energy from braking and deceleration and convert it into electricity for recharging the battery. electric machines are characterized by an high starting torque (up to 1,000 nm), high efficiency (up to over 90% battery-to-wheels), robustness, negligible noise, long life and low maintenance costs. electric machines can run with both direct (dc) and alternating (ac) current. traditionally, series wound dc motors have been used, but today modern bevs can also be powered by ac. the alternating current generates a rotating magnetic field that causes rotational movement inside the motor (made up by a stator and a rotor) via electromagnetic induction. in turn, the motor is coupled to a gearbox that brings the power directly to the wheels; the speed of the vehicle depends on the pulse width modulation (pwm) frequency of the power converter. in principle, in a bev, the electric motor can be directly incorporated into the wheel (as e.g., in the michelin active wheel), removing the need for a complex and intrinsically inefficient transmission system of icvs that converts the linear and noisy motion of cylinders into the circular motion of the wheels. power electronics. the power electronic module oversees all the functions that control the efficiency and economy of the vehicle, such as torque and efficiency of the motor, and regeneration of the battery charge. the main function is to convert the dc output of the battery into an ac feed for the motor through an inverter (or viceversa during recuperation). it also controls the different levels of voltage, depending on the power demand and specific device to run. it is also very important for the charging process. charging device. it is the interface between the vehicle and the electric grid. modern electric cars can be typically charged both with ac and dc. the ac charging mode is controlled via an onboard system which operates during slow garage-based operations (2-3 kw, standard socket) or in small-medium size recharging stations up to 22 kw. if one wants to charge faster, the ac/dc converter needs to be bigger and heavier, taking up more space and increasing the complexity and cost of the vehicle. therefore, off-board dc fast-charging systems are typically used to charge the battery with higher power (≥ 50 kw).4 fast dc charging stations up to 300 kw are now being introduced by some companies. this poses relevant challenges for the long-term integrity of the battery (a very efficient cooling systems is required) and for the electric grid as a whole. in fact, with a high market penetration of bevs, the stability of the grid may in principle be endangered not only by extensive networks of high-power fast charging stations with high peak demands,13 but also by uncoordinated ev charging at the residential level at low-medium power.14 accordingly, the diffusion of the electric car must be accompanied by an upgrade and strengthening of the electric grid, i.e., the so-called smart grid.15 in this scenario, a large share of electric vehicles should be ideally charged around midday, when the peak of photovoltaic production occurs. this can be facilitated by a larger diffusion of parking lots equipped with charging stations at workplaces. the core of bevs: the lithium ion battery the basic idea of this device (whose concept dates back to 1970s)6 is the reversible, alternate intercalation of li+ in a lithium oxide material at the cathode and in graphite at the anode, upon redox processes. j. b. goodenough, m. s. whittingham and a. yoshino were awarded the nobel prize in chemistry 2019 for the development of lithium-ion batteries. lithium is the smallest and lightest metal ion, hence libs exhibit intrinsically high mass energy density and are particularly suitable for fast recharging. moreover, it has excellent cycling performance and exhibits one of the highest electrochemical potential among metals, which enables devices with high voltage. a lib is made of anode, cathode, separator, electrolyte and two metallic current collectors at each terminal; it is schematically depicted in figure 5. upon battery charging, the li+ ions are forced to move away from the cathode (where cobalt/nichel oxidation occurs) and nest inside the graphite layers (which gets reduced) of the anode; upon discharging, they go back to the cathode at their equilibrium position. in 79battery electric vehicles: perspectives and challenges parallel, electrons move back and forth along the external circuit and are conveyed to the al and cu terminals on the cathode and anode side, respectively. upon battery discharge, the electric current powers the external device. when shuttling between electrodes, li+ ions passes through a plastic polymer separator that prevents the flow of electrons inside the battery. the cathode of libs is made of layered oxides of general formula limo2, where m indicates some combination of co, ni, al, and mn; nowadays anodes are made of carbonaceous materials, particularly natural and artificial graphites.16 non-layered cathodes can be made of less precious li oxide materials (e.g., lifepo4), but their energy density is not comparable with layered systems and cannot be used in highly performing libs. the electrolyte is typically a lithium salt in an organic solvent or gel. the replacement of the latter media with solid matrices would be a substantial breakthrough of the lib technology, particularly in terms of durability and safety.17 the features of the three main families of libs currently on the market are reported in table 1. cobalt is omnipresent, due to the unique electronic configuration of co3+ with 6d electrons in a low spin state, which makes it particularly small and capable of affording batteries with high energy density. big efforts are being made to reduce as much as possible the cobalt content, due to supply concerns (vide infra). for instance, the nichel-manganese-cobalt batteries (nmc) have progressively evolved as, for instance, nmc111, nmc622 and then nmc811, where the numbers designate the specific ratio of each metal.18 the element requirements of some common electrodes (in kg/kwh) are reported in table 2.18 from these data it can be inferred that a medium sized 40 kwh battery nmc 111 contains in the cathode about 5.5 kg of lithium (without considering the electrolyte), 15.7 kg of ni, 14.7 kg of mn and 15.8 kg of co (to be reduced to 8.6 and 3.8 kg with nmc 622 and nmc811, respectively). a battery of a 40 kwh bev also contains nearly 50 kg of graphite, irrespective of the cathode composition. efforts to increase the energy density of batteries are now also addressed to the improvement of the standard graphite anode, with focus of silicon-based materials.20 these solutions are still far from large-scale market applications. real-life batteries for electric vehicles are made of hundreds or thousands of individual cells having the structure depicted in figure 5 and connected in a series and parallel combination. these cells may have three different shapes: cylindrical, prismatic and pouch, the latter being characterized by very small thickness (< 1 cm). different car manufacturers adopt different types of cells and related assemblies (figure 6). tesla uses cylindrical cells slightly longer and wider than conventional aa cells for home appliances, profiting from the large manufacturing experience of its partfigure 5. scheme of a lithium ion battery, where co4+/co3+ half reaction occurs at the cathode and redox-promoted intercalation of lithium in graphite takes place at the anode. table 1. key parameters and applications of the three main families of libs.19 name battery type lithium cobalt oxide (lco) lithium nickel cobalt aluminum oxide (nca) lithium nickel manganese cobalt oxide (nmc) cathode licoo2 linicoalo2 linimncoo2 voltage [v] 3.7 – 3.9 3.65 3.8 – 4.0 mass energy density [wh kg–1] 150 – 240 200 – 300 150 – 220 cycle life 500 – 1000 500 1000 – 2000 thermal runaway [°c] 150 150 210 applications mobile phones, tablets, laptops, cameras. medical devices, electric powertrains, industrial. e-bikes, medical devices, electric vehicles, industrial. 80 filippo monti, andrea barbieri, nicola armaroli ner panasonic, with whom it has developed the so called gigafactory 1 in the nevada desert. this enormous facility is planned to be energy self-reliant through a combination of photovoltaic, wind and geothermal energy. the projected capacity for 2020 amounts to 35 gwh/y of automobile cells and 50 gwh/y of battery packs for stationary backup of renewable power facilities, but it is not yet evident if these targets will be fully met. the idea is to demonstrate cradle-to-cradle handling of lithium ion batteries, all the way from raw materials to manufacturing and then recycling. the battery pack of the long-range tesla model 3 (75 kwh) contains 4416 cylindric batteries (70 mm length, 21 mm diameter; 66 g) arranged in 96 blocks of 46 parallel connected cells. the nissan leaf 2018 (40 kwh), has a battery pack made of 24 modules, each containing 8 pouch nmc cells. each of these 296 cells weights 914 g and have a size of 261x216x8 mm. all the battery packs in bevs are protected by robust metallic and plastic enclosures that protect the cells from external elements (e.g., dust, moisture, rain, debris) and must withstand severe crash tests to warrant the safety of passengers in case of accidents.21 last but not least, bevs are equipped with a battery management system (bms) which warrants integrity and best performance, for instance by avoiding damages due to anomalies in temperature or electricity supply. nowadays battery packs range typically from 20 up to 90 kwh; the driving range is rated between 150 and 500 km,16 but strongly depends on the weight of the vehicle, style of driving, speed and, quite remarkably, outside temperature.22 at 0 °c the mileage of an ev is shortened by about 30% and even more in harsher winter conditions, this is related to a lower intrinsic efficiency of the device at low temperature and to the energy needed to warm up the car interior. also hot temperatures have detrimental effects for similar (and opposite) reasons, but to a substantially lesser extent. as far as temperature is concerned, one may say that libs are like human beings: they perform best in the range 15-30 °c.22 (4) average consumptions of evs are about 12-14 kwh/100 km in mild and warm seasons and 15-17 kwh/100 km in cold weather. present targets for bevs to become fully competitive with conventional thermal cars concern: (i) faster charging capabilities in order to achieve 80% state of charge within 5-20 min. this target will become more challenging if the average battery capacity will grow bigger. for example, to charge a 60 kwh battery (350-400 km range) in 20 min would require at least 180 kw of charging power and a very efficient on-board temperature control management of the cells. nowadays standard fast charging stations are normally rated 50 kw. it must be emphasized again that the diffusion of fast charging stations requires a more rational management of electricity peak demand, to be ideally matched with the daily and seasonal production peaks of renewable electricity. (ii) higher battery energy density at about 240 wh/kg and 500 wh/l at pack level, in order to routinely reach driving ranges of 500 km.16 this is technically table 2. li, co, ni, mn, al requirements for common battery cathodes (kg/kwh).18 li co ni mn c lco 0.113 0.959 – – ≈ 1.2 nca 0.112 0.143 0.759 – nmc111 0.139 0.394 0.392 0.367 nmc622 0.126 0.214 0.641 0.200 nmc811 0.111 0.094 0.750 0.088 figure 6. individual cells for bevs and their final assembly in the pack: tesla (cylindrical, top) and nissan leaf (puch, bottom). 81battery electric vehicles: perspectives and challenges possible already, but only for models which, at present, are economically accessible to a limited fraction of consumers. (iii) price decrease down to 125 $/kwh at pack level to become fully competitive with icvs at the car showroom. present battery costs are placed at 100–170 $/ kwh and 220–250 $/kwh at the cell and pack level, respectively.16 regarding future perspectives, research on next generation batteries targets the development of new sensors to monitor complex reactions in the device, so as to enable self-healing and enhance battery performance and lifetime.23 critical raw materials in bevs since 2011 the european commission has compiled a list of “critical raw materials” (crm); the latest list has been issued in 2017 and contains 27 materials or classes of materials such as platinum group metals (pgm) or rare earth elements (ree).24 materials are defined critical after a thorough screening that quantitatively assesses (i) importance for the eu economy in terms of enduse applications and added value and (ii) risk of supply disruption for the eu. due to the ever-increasing number of road vehicles worldwide, the huge size of the market and the extensive use of materials of different sorts in automobiles (a lightweight duty vehicle weights between 1 and 3 tons) the car industry is the object of intensive studies to assess its materials sustainability.25 this issue is even more important nowadays, because this industrial sector is undergoing a technological shift from thermal to electric traction. the body and some auxiliary parts of bevs and icvs are virtually identical. the electric machine is much lighter than the conventional combustion engine, but this advantage is counterbalanced by the heav y battery pack, which can exceed 600 kg for the largest capacities (85-100 kwh).26 the weight of battery packs is almost linearly correlated with overall capacity, when the same cell technology is examined. on the other hand, icvs have a much larger number of parts, which impacts the mass of the automobile. all in all, bevs equipped with lithium ion batteries and icvs of comparable size have a similar weight, but bevs are more material intensive than conventional thermal cars. in other words, they contain substantial amounts of more “sophisticated” materials (particularly metals) some of which are considered critical.27 in figure 7, major raw materials utilized in electric cars are schematically indicated.27 as far as material criticality is concerned, battery is by far the most sensitive part of bevs, both in terms of number of materials involved and quantity utilized.18,27 as pointed out above, the battery pack of a bev contain some tens of kilograms of metals – in particular li, co, ni, mn and al (cathodes, electrolyte) – and graphite materials (anode). in batteries, cu is only used as anode collector (along with al on the cathode) in rather limited quantities. however, cu is a strategic metal for the electric mobility system as a whole, being widely employed in car circuitry and wiring, all the way to the electric grid. among the materials listed in figure 7, co, li, dy are the most critical in terms of potential availability risks, whereas graphite is critical because the production is highly concentrated in one country (china). let us briefly examine each of them. • lithium. at present, lithium is the most difficult component to replace in bevs. its mass, volume and electrochemical properties suggest that the role of lithium in this sector can be reduced only going beyond metalbased batteries, an unlikely scenario for the foreseeable future. in 2017, about two thirds of lithium was extracted from hard rocks,28 which are crushed to allow the separation and concentrations of lithium minerals and then chemically processed (e.g., by leaching) to obtain lithium hydroxide, carbonate or chloride. an easier, cheaper, but longer process is extracting lithium dissolved in highly concentrated underground saltwater solutions called continental brines. such brines are brought to the surface by drilling wells and then moved through a series of surface ponds to concentrate the lithium salts and remove impurities (figure 8). the last step is chemical treatment to make the final marketable product, such as dry lithium carbonate.28 extraction from brine was started in the salt lakes of the atacama desert in figure 7. most relevant materials used in different parts of battery electric vehicles. those defined as critical are highlighted in red. 82 filippo monti, andrea barbieri, nicola armaroli chile in 1980s. this technique is now dominant in the so-called “lithium triangle”, the region between chile, bolivia and argentina where the concomitance of geological, orographic and climate conditions have created several lakes very rich in lithium brines (figure 8). the largest lithium reserve in the world is the salar de uyuni in bolivia, for which extraction plans are conflicting with the need to preserve a place of unique environmental value and are challenged by the presence of high concentrations of magnesium, which needs to be separated.29 it has to be emphasized that lithium extraction from brines, though relatively easy, is a lengthy process that cannot quickly respond to the steep rises in demand that are expected in the years to come.27 according to the us geological survey (usgs), australia (from hard rocks) and chile (from brines) currently dominate lithium production with 60% and 31% of global output in 2018, respectively.30 the production of this highly valuable metal has been on a steep rise in recent years (+ 23% in 2018), due to enhanced demand for all types of electric vehicles. the largest known untapped resources (i.e., identified deposits) are concentrated in the lithium triangle, but their upgrade to reserves (i.e., technically and economically exploitable stocks) is still uncertain in bolivia and argentina.28 the search for new lithium reserves is a relatively recent trend, hence it is reasonable to expect the discovery of relevant deposits in new geographic areas such as afghanistan, where effective exploitation may be extremely challenging for a variety of technical and political issues.31 in 2018, over 80 million new cars were sold. on the other hand, we can approximately assume that an average bev contains about 10 kg of lithium in the battery.32 therefore, if all the cars presently sold worldwide were bevs, the annual lithium demand would be 800,000 tons. this is about 10 times the current world production,30 half of which goes to the battery market, the rest being used in ceramics, glass, lubricants and other minor applications.28 these data also suggest that the present production of lithium for the manufacturing of batteries (about 40,000 tons/y) can in principle sustain only a 5% share of ev in the present global annual car market. the substantial increase in resource and reserve estimates in recent years does not indicate risks of lithium shortages up to the medium term (10-20 years).18 recently, there have been a supply deficit for refined products and an oversupply of mined minerals. spot prices of lithium carbonate have fallen 60% from early 2018 to mid-2019, but long-term contract prices (over 75% of lithium trade globally) were rather stable in the same period. forecasting on the longer term on such a complex and evolving market is difficult. price trends depends on multiple factors such as the evolution of the market in road vehicles,8,33 the availability of new lithium reserves and, last but not least, the establishment of recycling practices in a circular economy perspective. at present, lithium recovery is technically possible through a variety of pyrolytic, hydrothermal as well as pyroand hydrometallurgic methods.27 despite some companies have implemented industrial processes for recycling libs,34 the recovery and recycling of lithium from batteries remains scarcely attractive at the present cost of virgin mineral products.18 the economic attractiveness of recycling will improve when the number of end-of-life evs will substantially increase. libs in cars are considered exhausted when they can recharge at 80% of the initial rate, a level allowing excellent performance in some second-life applications such as accumulators for renewable electric generation facilities powered by intermittent sources (wind, photovoltaics). some companies have implemented this practice in flagship sites such as the amsterdam stadium (3 mw),35 showing that car libs can fruitfully serve well beyond the performance guaranteed by car manufacturers which is between 150000 and 200000 km. longer mileages can be achieved by a thorough daily management, especially in the recharging phase.36 for instance, it is advisable to not keep them above 80% or below 20% of their capacity for very long times. this means that batteries of higher capacity (> 60 kwh) can in principle last longer, as the number charge/discharge cycles across their lifetime tends to be lower. • cobalt. cobalt is considered the most serious potential obstacle for the expansion of the lib market for electric mobility.18 as already pointed out, cobalt is the best choice among transition metals to get laminated cathodes with very high energy density; so far, it could figure 8. lithium brine ponds in the lithium triangle, south america (bottom right map). 83battery electric vehicles: perspectives and challenges be only partially substituted with ni or mn. in the last decade (2009-2018) the world mine production of cobalt has increased by 125%, from 62 to 140 kton/year;37 in comparison ni production has increased by “only” 64%, (from 1.4 to 2.3 mt).38 by assuming 10 million bev cars sold yearly by 2025 (about 10% of the global car market) – with an average battery pack of 75 kwh (about 400 km driving range) and under the assumption of a mixed cathode chemistry relative to the present technologies – the global demand for cobalt in libs would increase up to almost 600% (from 50 to 330 kt, 2016-2025).18 at present, it is not evident if supply can keep up with such a steep demand, in the absence of substantial technological advancements to reduce the use of cobalt in libs, even if demand trend will be less disrupting, as projected by other studies.39 besides impending constraints in material availability, cobalt is critical for other aspects. first of all, most of it is obtained as a byproduct of the extraction of ni and cu (about 60% of the world cobalt production comes from copper ores),40 which means that its production is dictated by the market trends of its parent “attractor metals”, potentially generating uncertainty and price volatility.41 moreover, cobalt production is concentrated (around 60%) in a politically unstable country such as the democratic republic of congo (drc), where violation of human rights in small uncontrolled mines is well documented.42 to give an idea of the economic value of cobalt, it is interesting to note that one of the largest mines in congo (mutanda) produces about 250 kt/y of cu and 25 kton/y of co, but the latter generates about 40% of the revenues.18 cobalt refining is also a matter of concern because most of it is done in china. the trade flow of ni-co and cu-co ores from drc and other countries to china is a multibillion affair that feeds the chinese manufacturers of lib cathodes.18 this is one of the (many) strategic activities behind the ongoing “trade wars” between china and the usa. the benefits and concepts related to the reuse and recycling of libs discussed for lithium fully applies – and even more strongly so – to the more critical cobalt. indeed, at present, lib recycling is much more attractive for cobalt than lithium due to its higher economic and material value. at any rate, the extensive use of libs is a relatively recent trend, therefore large-scale recycling can be effectively accomplished not earlier than 2025, with eu possibly obtaining about 10% of its co supply for the ev sector from end-of-life batteries in 2030.39 • graphite. the dominant material for libs anodes is graphite, sometimes added with small amounts of silicon oxides. both synthetic graphites (sgs) and natural graphites (ngs) are normally utilized, with an almost equal market share. ngs tend to be less performing, but they are about 50% cheaper than sgs.16 ngs occurs in several forms (amorphous, flake and vein) and its quality is dictated by the carbon content and the grain size; battery grade ng must have a very high carbon content (> 99.95%) and particles sizes in the range 10-25 µm for optimal operations.43 availability of natural graphite is not a matter of concern in itself because the annual world demand is around 1 mt and estimated world reserves are currently placed at 300 mt.44 new extraction projects are under development in several parts of the world, particularly in africa (tanzania, mozambique), north america and australia; reserves in europe appear to be very limited.43 presently, the issue with natural graphites is that over 60% are produced in china (the rest primarily in brazil and india), which makes this anode material the most geographically concentrated component of libs in terms of supply, even more than cobalt.18,45 however, less than 10% of graphite is used for batteries, the primary application being refractories, due to its high temperature stability and chemical inertness, and steel making.43 the share of graphites used in lib manufacturing is expected to increase dramatically in the next decade.45 • dysprosium. the most widely used motors in electric vehicles are based on permanent magnets (pm) which are made of the neodymium-iron-boron (ndfeb) alloy,46 primarily in a nd2fe14b tetragonal crystalline structure. at present, ndfeb is the dominant high-performance permanent magnet material due to its superior magnetic flux output per unit volume, which is almost ten times as much compared to ferrite. besides electric motors, ndfeb is used in several applications such as wind turbines, computer drives and headphones. the ndfeb alloy is made in different variants, with minor concentrations of other rare earths (dysprosium, praseodymium, terbium) or transition metals (copper, cobalt, niobium) capable of optimizing the alloy’s properties for specific applications. dysprosium is used to enhance the performance of ndfeb magnets at high temperatures (up to about 7% in weight), such as those reached inside electric motors.47 about 90% of bevs presently sold have permanent magnet motors, whereas induction motors, which do not require rare earth elements (ree), cover most of the rest. pm motors are up to 15% more efficient and the combined weight of metals used in pm motors is also 15% smaller than induction motors, despite the presence of ree. the latter account for a tiny percentage of the overall motor weight, which is mainly dictated by laminated steel and copper.47 84 filippo monti, andrea barbieri, nicola armaroli ree are not rare on the earth’s crust, but they are rarely found at concentrations making extraction viable from the technical and economic point of view. accordingly, rare earth mines are very few worldwide and prices are highly volatile. dysprosium makes less than 1% of the global production of rare earth oxides, while neodymium is about 16% and is substantially cheaper (figure 9).48,49 this physical and economic constraint has prompted technological improvements leading to a decrease in the use of dysprosium by 50% (from about 120 to 60 g) in the average ev.47 this allowed a stabilization of the global demand of dysprosium oxide, which is almost completely covered by china. in the years to come, a large expansion of the ev market is expected and, in spite of an enhanced efficiency in the use of dysprosium in permanent magnets, it is expected that its demand will increase to such an extent that china alone will no longer be able to cover it with legal production (illegal mining of ree in china is common).47a number of new mining projects of rare earths are under development in several countries, including australia, canada, chile, namibia and greenland.47 therefore, a relieve on the supply of dysprosium and, more generally, of rare earth elements is expected, also in light of the increasing efforts aiming at recycling ree41 and replacing the most rare ones in new magnet formulations.50,51 efficiency, electricity, consumption and environmental impact of battery electric vehicles level 1 – tank-to-wheel vs. battery-to-wheel and the overall electricity consumption of bevs the average consumption of a modern 150 hp car is around 6 liters of gasoline for 100 km, which corresponds to about 60 kwh in terms of thermal energy content of the fuel. an equally rated electric car (e.g., nissan leaf 2018) runs at least 250 km with its fully charged nominal 40 kwh ni-mn-co lithium ion battery (actual: 38 kwh). in a nutshell, the energy consumption of the gasoline car is 0.60 kwh/km, i.e., four times higher than a bev (0.15 kwh/km). if one considers losses due to battery charging and discharging (5-20%, depending on specific conditions of temperature, current intensity, etc.) a bev is still over three times more efficient than an icv of comparable power. assuming a yearly mileage of 15,000 km, a medium-size ev (0.15 kwh/km) consumes 2,250 kwh/y, i.e., less than the average eu household (3,500 kwh/y). it has been assessed that if 80% of eu cars were electric by 2050, the eu electricity demand would increase by only about 10%.53 the desirable scenario of an overall decrease of the number of cars in the eu in the next decades would make electricity demand for personal car transportation nearly insignificant. let us put these consumption numbers in a specific national context. in italy there are 37 million cars, running an average 12,000 km/y. if they were all electric – assuming 0.18 kwh/km by including charging/discharging losses – they would require 80 twh/y of electricity. italy already produces over 110 twh/y only by renewable sources (hydro, pv, wind, biomass, geothermal). therefore, by increasing 70% only renewable electricity production with respect to current levels, all italian cars could in principle be powered by renewables. the target is very ambitious but not unrealistic in a 20-year time window, particularly in the perspective of a very likely climate crisis that may foster drastic political decisions and, hopefully, bring about a more moderate use of individual transportation. it must be emphasized that a strong expansion of the ev market in the next 20 years would be fully sustainable in terms of electricity demand, but might find bottlenecks regarding the availability of critical materials such as cobalt (see above). level 2 – the influence of the electricity production mix on greenhouse gas (ghg) emissions of bevs this issue has been examined in many studies, and there is a general consensus that greenhouse gas emissions (primarily co2) associated with the use of bevs are lower compared to icvs, when the electricity production stage is factored in.27 in figure 10 are reported the results of a recent study where ghg emissions of gasoline and diesel cars vs. bevs are thoroughly analyzed, in relation to the electricity mix of every eu country and taking into account upstream emissions (extraction, transport, refining of fossil fuels) and crossborder electricity trade among different countries.54 figure 9. production of rare earth oxides in 2017.52 85battery electric vehicles: perspectives and challenges small/medium-size bevs (14.5 kwh/ 100 km) entail a lower ghg emissions than gasoline icvs in every eu country and perform worse vs. diesel only in two countries (latvia and malta) in which electricity production is strongly based on coal and oil (malta is now switching to gas). on the other hand, the ghg emission of bevs is much lower than icvs in countries with a strongly decarbonized electricity portfolio such as sweden, france, finland, austria and denmark, which primarily rely on nuclear, hydro, wind and biomass. it is noteworthy the good performance of bevs in italy, a big exporting industrial economy with a renewable electricity production close to 40%. it must be emphasized that all of these data can be considered a superior limit, as they do not take into account a simple fact. at least in this initial stage, bev owners are typically more environmentally concerned than the average citizen and often feed their cars with self-produced pv electricity or sign contracts with utilities that sell renewable electricity packages. such a bargaining power, which of course cannot be exerted at the gasoline pump with icvs, can speed up the “greening” of the electric system in a bottom-up fashion. level 3 – overall life-cycle assessment of battery electric vehicles assessing the environmental impact of bevs over the entire lifecycle is a complex exercise that depends on several factors, such as the size of the vehicle considered, the electricity production mix, the location of the mineral resources for batteries and whether the comparison is made with diesel or gasoline cars. the european environment agency has recently released an excellent report on the state of the art in the field, where details on impacts assessed at the different stages of the industrial chain are reported: raw materials extraction, production, use, end-of-life.27 the component that makes the biggest difference between bevs and icvs is of course the battery. it has been consistently reported that the extraction of battery materials has a substantial impact in terms of human, freshwater and terrestrial ecotoxicity, as well as freshwater eutrophication. in this domain, the comparison with icvs may be presently unfavourable55 and the single most important factor leading to this result is the use of electricity produced from fossil fuels in raw materials extraction and battery manufacturing.27 besides the use of renewable electricity at every stage of lib production, use and disposal, other relevant factors that can improve the life-cycle environmental performance of bevs vs. icvs are (i) using them for at least 150,000 km and (ii) better transparency of car firms through the implementation of traceability protocols along the whole raw materials supply chain, so as to constantly monitor social and environmental impacts. finally, putting the bev industrial supply chain in the context of circular economy is crucial for the endof-life management.27 to this end, legislations around the world must promote as much as possible the implementation of extended producer responsibility (epr) practices, which make product manufacturers responsible for the entire life-cycle of their products and especially for the take-back, recycling and final disposal. in the last decades, several governance mechanisms have been introduced on waste disposal and mineral recycling processes for electronics and batteries. recycling practices related to bevs are already and will continue to be shaped by these national and international regulations, which will become stricter as electric mobility will expand.56 the number of bev to recycle is presently insignificant, but companies and legislators must be ready for the first wave of end-of-life bevs which will occur in the 2020s. conclusion after one century of undisputed dominance of the internal combustion engine, the road transportation sector is slowly undergoing an epochal transformation towards electric powertrains. this trend is dictated by two main factors: the quest for enhancing the energy efficiency of vehicles and the need of improving air qualfigure 10. greenhouse gas (ghg) emissions of electric vehicles in the countries of the european union vs. gasoline and diesel cars, taking into account the electricity generation mix and cross-border electricity exchange.54 86 filippo monti, andrea barbieri, nicola armaroli ity in urban areas for the sake of public health. another factor that may foster the market expansion of evs is the supply and/or price of oil in the long term. at present, oil is cheap and plentiful,57 but it is increasingly obtained from unconventional resources58 (e.g., shale rocks, tar sands, conventional wells in extreme environments), which are characterized by stronger carbon footprints, heavy environmental impacts, questionable economic returns, poor energy return on energy invested (eroi).59 on the other hand, the constant increase of renewable electricity production and the possibility to deploy vehicle fleets which are intrinsically less dissipative (batteries are far easier to recycle than co2) can ultimately be a major driver for the transformation of the car sector. there is debate on which extent electrification will permeate the way of moving persons and goods in the next decades. in our opinion, bev will be dominant for personal transportation (cars, suvs, motorbikes, bikes) because the ubiquity of the recharging infrastructure (i.e., the electric grid) is a formidable asset versus potential competitors lacking an energy distribution base (e.g., hydrogen).60 on the contrary, we believe that batterybased transportation will be far less relevant for trucks and buses, due to the huge material demand this would imply for manufacturing batteries. since heav y duty vehicles are often collected in large parking lots and run more predictable routes, it is reasonable to expect that they may be preferentially electrified via fuel cells,61 fed by hydrogen or liquid fuels produced in large centralized facilities. in this regard, it is needless to say that an even more rational solution for freight transport is shifting as much as possible to railways, which are largely existing and often underutilized in several countries. lithium ion battery is the key enabling technology for the development of road electric transportation, with a number of different chemistries now available for the cathode, but less practical solutions for the anode, beyond graphite materials. it can be reasonably expected that no practical alternatives to libs will be found in the next decade and perhaps even beyond, also because the huge ongoing investments in libs manufacturing make it harder for potential alternatives (e.g., lithium-sulphur, lithium-air or sodium/magnesium based batteries)62 to become economically or technically competitive.16 unfortunately, the energy sector is afflicted by frequent claims of “revolutionary” inventions or discoveries, with scientists sometimes too bold in communicating results to the general public, without properly highlighting the limits of their work for commercially viable applications.63 the road transportation sector claims about 50% of the world oil supply and emits about 18% of global co2 emissions,64 therefore the electrification of road vehicles is a key milestone of the global energy transition, because almost 30% of the world electricity supply is already generated by renewable wws technologies (water, wind, solar)65 and will grow further in the years to come, due to massive investments worldwide, with china as leader.66 however, in order to make this process truly beneficial for society, it is necessary that the global industrial supply chain of libs – all the way from raw materials extraction (concentrated in south america, africa and oceania) to battery manufacturing (primarily in china, japan and south korea) to usage (mainly in north america, europe, china, japan) – is made environmentally and economically sustainable. regarding physical availability of materials, cobalt represents a real risk, whereas lithium appears to be of lower concern. at any rate, integral recycling of libs at the industrial scale is becoming mandatory because it is presently projected that there will be 140 million evs on the road by 2030 (10-15% of the global share), with 11 million tons of libs reaching their end-of-life service throughout the next decade.67 the biggest obstacle in this direction is the fact that batteries are manufactured in several forms, sizes, and chemistries, hence a variety of disassembly/recycling protocols needs to be established, increasing technical and economic costs. ultimately, failure in addressing the recycling issue could endanger the expansion itself of the bev market, as availability of some virgin raw materials (particularly cobalt) could turn out to be an insurmountable physical limit, also in view of the rise of another potentially huge market such as backup battery packs for intermittent renewable technologies. in principle, electric vehicles might be an integral part of smart electric grids, serving as two-way electricity dispatchers on demand (v2g, i.e., vehicle-to-grid concept)68 thus helping to shelve peak demand. this approach has several pros and cons, for instance the car owner could make a profit of his/her “mobile storage system”, but the lifetime of the battery would be negatively impacted. the rational of this idea is compelling: 97% of their lifetime vehicles are idle. however, an effective implementation of v2g require substantial advancements at the grid and battery level. presently, the car battery industry is focusing on three priorities to be fully competitive with traditional thermal cars: a price of 125 $/kwh for lib packs,16 higher energy densities (up to 500 wh/l, pack level)16 to extend driving ranges beyond 500 km, and the consolidation of fast charging networks. a relevant issue to address is the modernization of the commercial network of car companies, which is unprepared (if not unwilling) to offer electric models to customers.69 87battery electric vehicles: perspectives and challenges it must be emphasized that the final objective of the electric revolution should not be the replication of the presently inefficient and unsustainable system heavily based on individual mobility, with an increasing urban population trapped in traffic jams, albeit “electric”. the great transition to be possibly 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research agenda”, annu. rev. environ. resour., 2017, 42, 377. 69. g. zarazua de rubens, l. noel, b. k. sovacool, “dismissive and deceptive car dealerships create barriers to electric vehicle adoption at the point of sale”, nat. energy, 2018, 3, 501. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 4(2) suppl.: 9-17, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1123 citation: b.w. ninham, r.m. pashley (2020) introduction and background. about water: novel water technologies in the new millennium. substantia 4(2) suppl.: 9-17. doi: 10.36253/substantia-1123 copyright: © 2020 b.w. ninham, r.m. pashley. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. introduction and background about water: novel water technologies in the new millennium barry w. ninham1, richard m. pashley2,* 1 department of applied mathematics, research school of physical sciences, australian national university, canberra, australia 2 school of science, university of new south wales, northcott drive, campbell, canberra, australia *corresponding author: r.pashley@adfa.edu.au a year ago, may 24, 2019 was the 500th anniversary of the death of leonardo da vinci. visionary water projects on a grand scale were one of his lifelong passions. they were never fulfilled. substantia offers this volume on new water technologies that work, in celebration of the life of da vinci, the artist and genius of florence. these technologies are simple and cheap. they embrace desalination, sterilization of wastewater, including killing of viruses, selective heavy metal ion removal and harvesting. and a simple solution to a major world economic problem. that of cavitation in ship propellers. our claims are startling and apply to real world conditions, that is, in concentrated and complex environments. they are not restricted to ideal, dilute solutions. they are presently inexplicable within the confines and boundaries of classical physical and colloid chemistry. it has been increasingly apparent that this venerable enabling discipline that underpins chemical engineering and biology suffers from sins of omission and commission. once those strictures are removed whole new opportunities open up. examples of these we want to exhibit here. about water in the early centuries of our christian-roman civilisation it is reported by gibbon in decline and fall of the roman empire, that the bazaars of byzantium, alexandria and antioch all buzzed with debate on the nature of the trinity. the matter was settled by the guidance of constantine himself at the council of nicea in 351 ad and, as we know, against the heresy of arius. at the present time the corresponding, though godless, debate concerns the anticipated catastrophe of climate change. regardless of which creed tri10 barry w. ninham, richard m. pashley umphs here, pro climate change or sceptic, it is apparent that without clean water mankind is in for a terrible time. the motivation is indisputable. without clean water our future prospects, recalling the biblical ten plagues of egypt1, are dire. 1. the history of water in civilisations has been documented with elegance and erudition by mark henry. we defer to his exceptional paper.1 2. water and climate change in prehistory what is missing in henry’s paper are some sobering water related catastrophes of prehistory. it has recently been discovered that the blue nile did not flood for 30 years, during the middle kingdom of egypt. the disaster was one from which egyptian civilisation never quite recovered, not to speak of cannibalism, the loss of many cities and nile tributaries. similar events consumed civilisations of the middle east on the euphrates and tigris. the mighty oxus of antiquity it now seems might even have been so large that it passed through the then sea of aral to the caspian and on to the black sea. its banks were lined with lost cities all the way to afghanistan. alexander’s army it seems might have been able to row all the way to central asia.2 the sea of aral has dried up permanently in the last 50 years due to soviet exploitation of the oxus for irrigating second grade cotton. the darling river in australia, that country’s longest river dried up this year for the same reason. the british aswan dam, massively expanded by the soviets has stopped the nile from flooding – a catastrophe for egypt and the 500 km dam so formed, for the sudan. the blue nile is now dammed in ethiopia with who knows what catastrophes are to follow in egypt, as for turkey’s dam at the head of the euphrates. the black sea only filled up about 8000 years ago, taking out an entire civilisation in the process. 3. a perennial problem with water why ice floats on water, without which life could not have evolved, was the subject of celebrated debate commissioned by cosimo ii de’ medici. it took place in florence for a few days around nov 5, 1611, between galileo and an aristotelian professor. galileo lost the 1 god’s punishment of the egyptians from whom the enslaved israelites who escaped across the red sea is given in the jewish passover services. they consisted of ten plagues: blood, boils, frogs, hail, vermin, locusts, murrain (an infection of mucous membrane of intestines of sheep and cattle (substitute swine flu) pestilence, slaying of first born, darkness. debate, although he never admitted it. in almost a role reversal, a hubris-filled galileo argued as an aristo-platonist, while his opponent appealed to experiment.3 the occasion was marked again 400 years later in florence with an international conference.4 the matter remains unresolved. the only work that comes close to solving the problem is the little-known paper.5 this is not accepted, as it is unconventional and not understood by a too conservative clientele obsessed with simulation as a valid occupation, and not familiar with older theories. 4. water and oil the first experiment published was on clay tablets that dates back to the time of hammurabi (a famous akkadian ruler from the area which is now iraq) around 18th century before christ. the priests studying oil on water spreading (pouring water in oil and oil in water) were among other things interested in predicting the future. for instance, if one small and one large drop emerged a male child would be born. there were lots of scientifically interesting results in this early publication such as a study on spreading and retraction; the formation of droplets and globules; and interference colors. the clay tablet is one of the first scientific publications known.6 the other experiment relevant was also reported by tabor and also published in the journal of colloid & interface science paper. it was a translation of an experiment published on cuneiform clay tablets found in the library of the ruined palace at nineveh of the king asshurnabanipal around 750 bc.  the tablets were brought back to oxford by george smith who discovered also the story of noah and the flood and of gilgamesh there. the priests studying oil on water spreading were more interested in applications to necromancy than present fashionable pursuits. more recently, and on a stronger scientific footing, lord rayleigh re-did benjamin franklin’s studies of oleic acid spreading on the surface of a south london pond to make the first quite accurate estimate of molecular size. franklin started the experiment but got bored and went off to a house of ill repute. 5. carbon dioxide and natron the oldest technology. temperature a factor after sodium chloride, natron, sodium bicarbonate, is probably the first industrial scale chemical used by mankind. natron, in ancient egypt was essential for mummification. the still little understood, peculiar hydration properties of the bicarbonate ion, in contact with air, affects both tissue dehydration and preserves by sterilization against bacterial degradation. 11about water: novel water technologies in the new millennium the magic of the bicarbonate ion has remained, a long with the likewise unexplained problems of roman and other cements. the foundation of physical chemistry can arguably be marked by berthollot’s observation that reactions are temperature dependent.7 he saw soda lime instead of the expected calcium carbonate on the banks of the nile river during napoleon’s scientific expedition to egypt in 1792.7 this was and is very surprising. under the high temperature of the sun (> 60 °c) when the salt is precipitated from a mix of na+, ca2+, cl-, and hco3ions in the flood waters the hydration is different from that at 25 °c. but at the very high temperatures in excess of 60 °c the natural precipitate is sodium bicarbonate. this profoundly important obser vation is still universally forgotten, and seems never to have been repeated. wet sodium bicarbonate is extremely effective in cleaning surfaces. it cuts peptide bonds of proteins bound to saucepans. carbon dioxide bubbles in a salt water column are extremely effective in killing viruses as well as bacteria!8-10 this is the key to sterilizing and recycling water as is amply illustrated further in papers that follow. the technique is developing fast and successfully for commercial use. 6. water, country clubs and the british empire for over two centuries the third largest contributor to the economy of the state of massachusetts was ice from a small lake in the village of wenham, south of boston. very pure water from a small lake froze gradually in winter, so slowly that the ice contained no trapped air and was crystal clear. the ice was sawn up into blocks, covered with hessian bags, and transported by sailing ship around the british empire from london to the colonies, from india to jamaica. during the journey, 2/3 of the ice melted. no selfrespecting englishman would ever drink his gin and tonic without wenham ice. this affectation persists. it is claimed that gas free water tastes differently. perhaps it does. the same can today be achieved using a freezethaw vacuum system but is perhaps somewhat less exotic. 7. the 4 h’s: in search of hydration the words hydration, hydrophobic, hydrophilic, hydrogen bond are as elusive to pin down as they are universally used. so are other words that are part of the fabric of physical chemistry. the meaning of the four h words, and others like ph, buffers, surface potentials, water structure are not something a researcher wants to delve into too much. yet delve into them we must. the 12 member ipac commission on ph, for example, recommends that one cannot place any faith in a ph measurement in a salt solution above 0.1 molar concentration. similarly any biologist knows that once a protocol is working, you never play around with the buffer. such facts are well known but ignored, and with justification. because if we do ask questions outside the classical canon we enter a perfect storm. at the other extreme, and for different reasons, ph measurements on ultra-pure water are also very difficult to make. to make that explicit: 7a. water “structure”: bernal’s ideas the perennial debate on very long ranged water structure vs short range order – hydration – is of long standing. there is no molecular theory of liquids like that underlying statistical mechanical theories of gases or solids. for gases the molecular distribution function is uniform. for solids, the distribution function which is the basis for perturbation is a periodic distribution function (crystal lattice). bernal’s ideas on the dynamic zeolite-like topology of structures with many membered hydrogen bonded water molecule rings perhaps comes closest to capturing the essence.11 7b. water structure and hydration while we cannot yet define what we mean by “water structure” the soda lime phenomenon of # 5 is a clear demonstration that it exists. the specific “affinity” of hydrated cations and anions is different at low and high temperatures. indeed, it turns out that water in not “hydrogen bonded” above about 89-90 °c. if we change water structure by adding an indifferent background electrolyte or sugars or urea, then precipitation of salt crystals, e.g. mg(oh)2 can be made to vary from microns to nanoparticles to zero in size, as water structure imposed by the background solute changes.12 changing hydration (water structure) with temperature or surfactants affects protein structure and function.13, 14 other explicit examples of water structure show up in micellar and microemulsion phase diagrams and with gels.15-17 7c. young, laplace, vs poisson and maxwell and hydration interfacial tensions and colloidal particle interactions both involve surface induced hydration (or surface water structure). that is a matter of thermodynamics, quantified in principle by gibbs. thomas young’s classic work ignored this. debates about this have continued, 12 barry w. ninham, richard m. pashley starting with laplace vs. poisson (1832) and a definitive article by j clerk maxwell,18 (1876) to the present day. at soft surfaces, rough or dynamic on a molecular scale, like phospholipid membranes, these “hydration” forces are repulsive and decay exponentially with a range of the order of the size of a molecule, for water about 3 å.17 at hard surfaces “depletion” forces due to molecular granularity are oscillatory and also repulsive. molecular granularity includes, for example, micelles that can stabilise emulsions. the periodicity is here of the order of the size of the “pseudo molecules”, here micelles.19 similar effects occur with proteins in solution. our confidence in what we know about water is tempered by the fact that we do not know and cannot predict even the sign of the potential at the air-water interface due to the hydronium vs. hydroxide disposition at the air-water interface.20 7d. hydrogen bonding and other heresies the concept of a hydrogen bond derives from a perturbation calculation of the interaction between two hydrogen atoms. this has been extended to apply to interactions between two atoms in a sea of its neighbours, an inherently many body problem. evidently it is nonsense. the strength of what is assigned to a “hydrogen bond” can vary between 0.1 to 10 kt! the same confusion has become standard for “dipole–dipole” interactions. thus, the “keesom force” between two rotating water or protein molecule dipoles is inversely proportional to temperature t. but in a condensed medium it is proportional to temperature due to many body effects. the distinction made between hydrogen bonding, hydration, van der waals, permanent dipole or ion dipole forces is completely artificial and erroneous. it is an artefact of the (mathematical) expansion of an arbitrary distribution of mass or charge into a multipolar taylor series. 8. very long ranged hydrophobic interactions very long ranged hydrophobic interactions between similar surfaces were first measured and reported by israelachvili and pashley in 198221, 22 based on their experiments using the surface forces apparatus (sfa), which was developed by israelachvili. two symmetrical, cleaved and smooth mica surfaces were coated with a hydrophobic surfactant monolayer and the forces between them was measured in various aqueous electrolyte solutions. comparing these measured forces with the expected van der waals attractive forces, indicated that there was an additional attractive force, acting over a range of several nanometers, which was identified as a ‘long range hydrophobic attraction.’ since then, these attractive forces have been measured at separations up to several hundred nms. the origin of these forces has generated much debate, with the likelihood that their unexpectedly long range is probably related to dissolved gas cavitation created between the hydrophobic surfaces, evidence for which was also observed in the original studies.22, 23 there are other mechanisms all lumped together in this single mysterious word. some are due to capillary action.24 some are due to co-operative electrostatic surface molecular correlations and some due to permanent dipolar surface correlations between zwitterionic lipids.25 and some are due to polymer bridging between surfaces. some are due to nanobubbles. to confuse matters all depend on dissolved atmospheric gas. many of these forces disappear when dissolved gas is removed from water!26 9. deconstructing colloid science, physical chemistry and electrochemistry as is evident above, the classical theories, even in the continuum solvent approximation are fundamentally flawed. this is due to sins of omission and commission, about which much has been revealed over these past 20 years. see26 and references therein. classical theory begins with an ansatz that treats electrostatics and dispersion forces separately. double layer forces are treated by a nonlinear theory poisson boltzmann or hnc say, while dispersion forces are treated by a linear theory (lifshitz, hamaker). see ref. 4. this ansatz violates thermodynamics, both the gibbs adsorption isotherm and the gauge condition on the electromagnetic field. a consequence is that hofmeister, “specific ion” effects, are ignored. (when the theory is done correctly, they are not.) the result is that practically all force measurements (with the exception of those measured at long range and in very dilute solution) are incorrect and inferences on hydration are also wrong. subtracting two partial incorrect theories, double layer and dispersion (van der waals) forces from an experimental measurement means that the assignment of the residual to “hydration” or specific ion effects is meaningless. so all measurements based on the incorrect theory like ph, pkas, zeta potentials, membrane potentials, ion pumps, activities and interfacial potentials can be incorrect and can be badly so. 10. dissolved gas a hidden variable. cavitation there is worse to come. it turns out that dissolved atmospheric gas, we mean not just oxygen or co2, but 13about water: novel water technologies in the new millennium nitrogen too, has a profound effect. remove the gas and “hydrophobic” forces go away. emulsions become stable.26 hofmeister effects reverse and we enter a new world. simulation does not help and is very misleading. this is because it cannot handle dissolved gas in water. it compares model, gas-free, water or electrolytes or proteins with real water and solutions that do contain dissolved gas. newton tried to measure molecular forces but gave up, in art 31 of the principia, i think, saying “surface combinations were owing”. this is not the main problem for us. 11. why not simulation? it is impossible to find an answer by computer simulation. the reason will recur. it has nothing to do with the inadequacy and incorrect nature of the molecular potentials used. the reason is that real water contains dissolved gas. this changes the physico-chemical properties of water drastically. so any computer simulation that does not include dissolved gas is not appropriate to, and does not apply to, real water which does. if it does claim agreement with experimental properties, it is comparing apples with oranges and is wrong. it is reasonable to think that dissolved atmospheric gas could be ignored. consider that the total number of gas molecules in air at 20 °c and 1 atm is 0.041 moles/l = 2.5x1019 molecules /ml. the dissolved gas content in water in equilibrium with normal atmospheric pressure at 20 °c is: oxygen: 0.0093 g/l = 0.00029 moles/l =1.75 x 1017 molecules /ml. nitrogen: 0.0148 g/l = 0.00053 moles/l = 3.17 x 1017 molecules /ml. total gas molecules in water is 0.00085 moles/l = 5.1 x 1017 molecules /ml. the number of water molecules in liquid water is 55 moles/l. hence, they differ by a factor of about 105. such a small number of impurity molecules would be impossible to deal with in a simulation. (this is around the cmc of a surfactant like sds in 0.3 m salt). but it really does matter! in another important example: acceptable or potable water has to be at least 99.99% pure, that is less than 1.0 mm nacl! small ‘contaminants’ matter but so can drinking ultra-pure water, which can cause death by hyponatremia or water poisoning by reducing sodium levels in your blood. sports electrolyte drinks prevent this. the famous medical doctor paracelsus told us this about too much water. as already remarked, the origins of long ranged hydrophobic interactions most likely lie with the presence of dissolved gas also. the tensile strength of water depends on ‘inert’ dissolved atmospheric gas molecules. they act in the same way as impurities in a solid to reduce its strength according to a well known theory of griffiths. the tensile strength of water is two orders of magnitude less than that we would calculate from molecular forces. it gives rise to cavitation, which only occurs because of the presence of dissolved gases. the energy cost of cavitation on shipping is a huge economic impost on society. so control by removal of gas will yield enormous energy savings. we will see how it can be accomplished in what follows. 12. water, salt and bubbles the debacle has hardly begun. this, perhaps simplest of all experiments remains unexplained:27 gas passed through a porous frit ascends as bubbles in a column of water. they collide, and fuse to form bigger bubbles. the column stays clear (like a fish tank). if a salt like nacl is added, above a critical concentration centred around 0.17 m the bubbles do not fuse. the column becomes a densely packed foam of tiny bubbles. the critical concentration is the same ionic strength as that of the blood of land animals and that of the permian ocean from which we emerged. the reason is not incidental and irrelevant. to make matters worse, for some salts no such effect is observed. bubbles happily fuse in salt solutions up to 6 m. there are rules without exceptions that show which ion pairs give rise to fusion and which do not, and also rules for mixtures. this is still a complete mystery that has defied explanation and has been ignored for over 30 years. it is a phenomenon that the new technologies of this volume exploit. 12. nanobubbles and bubble fusion a history of nanobubbles is given in reference 29. by these we mean gas filled entities of the order of a nanometer in size or above. they are if we like the analogue of micelles. it was argued until recently that they could not exist as stable entities, although what “stable” meant is unclear. that consensus was arrived at by applying macroscopic concepts to nanometric objects to which macroscopic arguments cannot apply. it is now agreed that nanobubbles do exist in salt water regardless of theory.28-30 gas containing small bubble structures have been much studied by laser spectroscopy and appear to be involved in enzyme catalysis via cavitation, in the active sites of enzymes.31 their formation and stability in elec14 barry w. ninham, richard m. pashley trolytes is long lived above 0.17 m and probably explains the bubble-bubble fusion inhibition phenomenon. 13. jellyfish just as old as the problem of why ice floats on water, or why bubbles do not fuse in salt water is that of the very existence of jellyfish, and other soft bodied multicelled animals. these emerged in the ediacaran era 570 million years ago before the cambrian era. it was first raised by gorter and dismissed by the establishment at a faraday conference in 1930.1 the problem is that jellyfish contain <<1-2% non-aqueous matter. any such matter is confined to digestive and reproductive regions. if that is so the jellyfish carapace must be essentially pure water. this rubbery solid matter exists surrounded by an ocean that contains at least 3% salts. its existence – chinese people preserve and eat it – defies the laws of osmotic pressure; and the diffusion equation.1 on the face of it, there is little to answer the inference that here is a new state of water with very long ranged macrostructure. that could be resolved by some straightforward experiments. like measurement of conductivity and careful elemental composition studies. the existence of jellyfish – for 600 million years defies conventional wisdom and yet the problem continues to be ignored except by brave souls like j. pollack. (see however remarks below on very long range forces between conducting polymers.) 14. the polywater debacle the jellyfish conundrum is resolved by some by postulating the existence of a new state of water structures over tens of thousands of nanometers. such a “solution” is a tautology. it was a trap into which the renowned russian colloid scientist fell into with the discovery of the much derided “polywater”. for an account of this and associated events see ref 32. polywater does exist but is due to polymeric impurities. between conducting thin linear charged polymers there are very long range, many body interactions, which are a hidden driver of organisation and recognition.26,33-35 the same forces occur for polyelectrolytes and also for dna.36 they have been known almost since the discovery of van der waals dispersion forces and ignored. 15. problems and solutions we can continue in this mould, listing words without limit that remind us that the foundations are insecure – chirality, magnetic fields, clouds and rain, for a start. the surface tension of water? forget it. the problems associated with water seem to have become deeper with the increasing reliance on, and now dominance of unreasonable aristo-platonic approaches to chemistry. these abjure experiment in favour of simulation with fixed concepts that assign insight to mindless computer games. these can sometimes fit data but never predict. it is a curious constraining and lazy reversion to medievalism. we can consider this reversion a catastrophe or an opportunity. awareness of the defects of present theory allows us to throw off the shackles. the major source of hubris and of omission in theories is that of air, the fourth telement of the greeks. in retrospect, descartes might better have said: “i breathe; therefore i am” instead of his famous impotent platonic assertion: “i think: therefore i am”. thales of miletus, the oldest known greek scientist, thought the world consisted in two parts: water and god. 16. desalination and aristotle the technology is not new. aristotle described a desalination technique in the 4th century bc in meteorologica. there’s even a mention of desalination (although vague) in the bible (exodus 15:22-26). “desalination has been around for millennia if you count the evaporation techniques pioneered by the ancient greek. sailors in the 4th century bc boiled salt water and then captured the steam. when cooled, steam condenses into distilled water that’s free of virtually all contaminants.” https://ideas.ted.com/would-you-drink-desalinatedseawater-recycled-sewage-water-get-ready-to-find-out/ plans for desalination—removing salt from seawater—date back to 4th century b.c. from ancient greek philosopher aristotle, according to livescience.com. action was put into place around 200 a.d. when sailors desalinated seawater with boilers on their ships. https://w w w.pumpsandsystems.com/desalinationprojects-picking-challenges-remain 17. leonardo da vinci’s view it is impossible to assert with confidence what people meant by words written in a different world 500 years ago. leonardo’s science seems to have been sniffily dismissed because he did not know latin and greek, plato and aristotle, the mantles of the renaissance cogniscenti. but he seems to have been of the same view as roger bacon and kant. and as d’arcy thompson said: kant said of the chemistry of his day and generation that it was a science but not a science – in that the criterion of true science lay in its relation to mathematics.37 15about water: novel water technologies in the new millennium (by that he included physics too). he tells us too that leonardo da vinci (1452 – 1519) who died 500 years ago thought the same:38 nissuna umana investigazione si pò dimandare vera scienzia s’essa non passa per le matematiche dimostrazioni, e se tu dirai che le scienzie, che principiano e finiscono nella mente, abbiano verità, questo non si concede, ma si niega, per molte ragioni, e prima, che in tali discorsi mentali non accade esperienzia, sanza la quale nulla dà di sé certezza. (no human enquiry can call itself a true science unless it proceeds by means of mathematical demonstrations, and if you claim that the sciences that begin and end in the mind possess some truth, this is not conceded, but is denied for several reasons, the first being that in such mental arguments no experience occurs, without which nothing is certain). and xenophanes said: the gods have not revealed all things from the beginning. but men seek and so find out better in time, let us suppose these things are like the truth. but surely no man knows or ever will know the truth about the gods and all i speak of. but even if he happens to tell the perfect truth, he does not know it, but appearance is fashioned over everything. we borrowed xenophanes words of motivation and inspiration from morris klines’ marvellous book ‘mathematics: the loss of certainty.’ this present volume takes air with salts and water and puts them to work for novel water technologies, regardless of theory. we take that as our text and so to work. postscript since this essay was written the very long range forces between conducting cylinders, or polyelectrolytes have begun to surface as serious hidden variables, in phenomena associated with physiology in the previously mysterious endothelial surface layer28 and other anomalous properties that occur with the fuel cell polymer nafion.39-40 these developments, connected to chinese acupuncture confirm the perpetual fact that water always surprises. references 1. m. henry, the state of water in living systems: from the liquid to the jellyfish in aqua incognita. why ice floats on water and galileo 400 years on, pp 51-99 connor court publishing pty ltd. copyright 2014 pierandrea lo nostro and barry w ninham eds. 2. the route of the ancient shipping route from greece through the karakum desert of turkmenistan and beyond to the lost city of alexandria on the old oxus in afghaistan has been explored and rediscovered by australian photo journalist david adams. 3. s. j. louis caruana in aqua incognita from water to the stars: a reinterpretation of galileo’s style and dava sobel, galileo’s daughter. 4. aqua incognita why ice floats on water and galileo 400 years on. editors: p. lo nostro and b. w. ninham, 2014, 516 pp. connor court publishers ballarat, victoria. 5. s. andersson, b. w. ninham, why ice floats on water, solid state science, 2003, 5 (5), 683-693. 6. d. tabor, quotes from british museum, cuneiform texts from babylonian tablets in british museum, vol. 5, plate iv, 22446, london, 1898, j. colloid interface sci., 1980, 75, 240 – 245 7. scientific aspects of the french egyptian expedition 1798-1801 author(s): charles coulston gillispie source: proceedings of the american philosophical society, vol. 133, no. 4 (dec, 1989), pp. 447474, published by: american philosophical society stable, accessed: 07-01-2016 12:50 utc. 8. a. g. sanchis, r.m. pashley, b.w. ninham, water sterilisation using different hot gases in a bubble column reactor, j. environ. chem. eng., 2018, 6, 26512659. 9. a. g. snachis, r. m. pashley, b. w. ninham, low temperature ms2 (atcc15597-b1) virus inactivation using a hot bubble column evaporator (hbce), colloids surf. b biointerfaces, 2016, 151, 1-10. 10. a. g. sanchis, r. m. pashley, b. w. ninham, virus and bacteria inactivation by co2 bubbles in solution, npj clean water, 2019, v2 number 1. 11. s. t. hyde, aqua reticulata: topology of liquid water networks, in aqua incognita, 145-175. 12. r. giorgi, c. bozzi, l. dei, c. gabbiani, b. w. ninham, p. baglioni, nanoparticles of mg(oh)2: synthesis and application to paper conservation, langmuir, 2005, 21 (18), 8495-8501. 13. a. e. voinescu, p. bauduin, c. pinna, d. touraud, b. w. ninham, w. kunz, similarity of salt influences on the ph of buffers, polyelectrolytes and proteins, j. phy. chem. b, 2006, 110 (17), 8870-8876. 16 barry w. ninham, richard m. pashley 14. r. waninge, m. paulsson, t. nylander, b. w. ninham, p. sellers, binding of sodium dodecyl sulphate and dodecyl trimethyl ammonium chloride to beta –lactoglobulin: a calorimetric study, int. dairy j., 1998, 18 (2), 141-148. 15. i. lisiechi, m. b. orling, l. motte, b. w. ninham, m. p. pileni, synthesis of copper nanosize particles in anionic reverse micelles: effect of the addition of a cationic surfactant on the size of the crystallites, langmuir, 1995, 11 (7), 2385-2392. 16. p. andre, a. filankembo, i. lisiecki, c. petit, t. gulik-krzywicki, b.w. ninham, m. p. pileni, supraaggregation: microphase formation in complex fluids, adv. mater., 2000, 12, 119-123. 17. the literature on hydration and controlled nanoparticle synthesis in cationc microemulsions is very large now. the authors’ book provides an entry point molecular forces and self assembly in colloid, nano sciences and biology, cambridge up, 2010, b. w. ninham and p. lo nostro. 18. j. clerk maxwell: capillary action. encyclopaedia britannica, 9th ed.; 1876. see also his “collected works”. 19. r. m. pashley, b. w. ninham, double-layer forces in ionic micellar solutions, j. phy. chem., 1987, 91 (11), 2902-2904. 20. t. duignan, d. f. parsons and b. w. ninham hydronium and hydroxide at the air–water interface with a continuum solvent model, chem. phys. lett, 2015, 635, 1-12. 21. j. n. israelachvili, r. m. pashley, the hydrophobic interaction is long-range, decaying exponentially with distance, nature, 1982, 300, 341-342. 22. j. n. israelachvili, r. m. pashley, measurement of the hydrophobic interaction between two hydrophobic surfaces in aqueous electrolyte solutions, j. colloid interface sci., 1984, 98, 500-514. 23. r. m. pashley, p. m. mcguiggan, b. w. ninham, d. f. evans, attractive forces between uncharged hydrophobic surfaces: direct measurements in aqueous solutions, sci., 1985, 229, 1088-1089. 24. v. v. yaminsky, s. ohnishi, b. w. ninham. long range hydrophobic forces are due to capillary bridging. in: handbook of surfaces and interfaces of materials, academic press: new york, 2001, 4, 131227. 25. p. kekicheff. adv. coll. interface sci, 2019, 270, 191215. 26. b. w. ninham, r. m. pashley, p. lo nostro, surface forces: changing concepts and complexity with dissolved gas, bubbles, salt and heat, curr.  opin. colloid interface sci., 2016, 27, 25-32. 27. v. s. j. craig, b. w. ninham, r. m. pashley, the effect of electrolytes on bubble coalescence in water, j. phy. chem., 1993, 97 (39), 10192-10197. 28. b. p. reines, b. w. ninham, structure and function of the endothelial surface layer: unraveling the nanoarchitecture of biological surfaces, quarterly reviews of biophy., 2019, 52, 1–11. 29. m. alheshibri, j. qian, m. jehannin, v. s. craig, a history of nanobubbles, langmuir, 2016, 32(43), 11086-11100. 30. n. f. bunkin, , b. w. ninham, p. s. ignatiev, v. a. kozlov, a. v. shkirin, a. v. starosvetskij, long living nanobubbles of dissolved gas in aqueous solutions of salts and erythrocyte suspensions, j. biophotonics, 2011, 4(3), 150-164. 31. kim, h.-k., e. tuite, b. norden, b. w. ninham, coion dependence of dna nuclease activity suggests hydrophobic cavitation as a potential source of activation energy, eur. phys. j., 2001, 4, 411-417. 32. b. v. derjaguin, j. theo, g. overbeek, their times, and ours, barry w. ninham, substantia, 2019, 3(2), 65-72. p. lo nostro, b. w. ninham, after dlvo: hans lyklema and the keepers of the faith, adv. colloid interface sci., 2020, 276, 102082. 33. b. davies, b. w. ninham, p. richmond, van der waals forces between thin cylinders: new features due to conduction processes, j. chem. phys., 1973, 58(2), 744-750. 34. n. f. bunkin, p. n. bolotskova, s. v. gudkov, y. juraev, m. s. kiryanova, v. a. kozlov, b. w. ninham, r. s. safronenkov, a. v. shkirin, e. v. uspenskaya, structure and properties of the exclusion zone of nafion: swelling in a constrained volume, acs omega, 2020. 35. n. f. bunkin, a. v. shkirin, v. a. kozlov, b. w. ninham, e. v. uspenskaya, s. v. gudkov, near-surface structure of nafion in deuterated water, j. chem. phys., 2018, 149, 164901. 36. k. l. jimenez-monroy, n. renaud, j. drijkoningen, d. cortens, c. van haesendonck, w. j. guedens, j. v. manca, l. d. a. siebbeles, f. c. grozema, p. h. wagner, high electronic conductance through double-helix dna molecules with fullerene anchoring groups, j. phys. chem. a, 2017, 121, 1182-1188. 37. d. w. thompson, growth and form. cambridge university press, 1917. 38. l. da vinci, treatise on painting, codex rurbinas latinus, transl. and annotated by p. p. mcmachon, princeton university press, 1956. 39. n. f. bunkin, p. n. bolotskova, s. v. gudkov, y. juraev, m. s. kiryanova, v. a. kozlov, b. w. ninham, r. s. safronenkov, a. v. shkirin, e. v. uspenskaya, 17about water: novel water technologies in the new millennium structure and properties of the exclusion zone of nafion: swelling in a constrained volume, acs omega, 2020. 40. n. f. bunkin, a. v. shkirin, v. a. kozlov, b. w. ninham, e. v. uspenskaya, s. v. gudkov, near-surface structure of nafion in deuterated water, j. chem. phys., 2018, 149, 164901. substantia. an international journal of the history of chemistry 5(2): 85-95, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1256 citation: cohen j. s. (2021) the revolution in science in america, 1900-1950. substantia 5(2): 85-95. doi: 10.36253/ substantia-1256 received: mar 22, 2021 revised: jun 04, 2021 just accepted online: jun 04, 2021 published: sep 10, 2021 copyright: © 2021 cohen j. s. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles the revolution in science in america, 19001950 jack s. cohen chemistry department, ben gurion university, be’er sheva, israel e-mail: cohenjk@post.bgu.ac.il abstract. the us lagged behind the european powers, germany, britain and france, in scientific research and development at the beginning of the 20th century. why this occurred and how germany and britain supported their flourishing scientific research cultures are discussed. the first serious expansion in basic scientific research in the us occurred with the influx of european jewish scientists fleeing nazism in the 1930’s. they specifically brought with them knowledge of atomic physics. the influence of vannevar bush, who was director of the office of scientific research and development during world war two proved crucial for the expansion of civilian research and development after the war, supported by the federal government. also after the war, operation paperclip brought german scientists to the us and they had significant influence on developments in aeronautics, rocketry and space exploration. keywords: history of science, american science, european science, nobel prizes, basic research. 1. introduction americans are used to thinking of their country as the greatest in the world, both in terms of economic clout and military strength. but few know how it got that way. the fact is that the us became the greatest industrial power, out-performing the uk, its parent country, in industrial output (measured as gdp per capita, to correct for different sized populations) around 1890,1 and has been estimated to have out-produced all of europe around 1917, during world war one.2 but in military terms the us had no “regular” army as generally understood until 1913, when secretary of war henry l. stimson organized one, in the form of four divisions assigned to protect each geographical region of the usa.3 at this time, the uk had a large military force both fighting in and occupying colonies throughout the world. for example, at the battle of waterloo in 1813, the british army, consisting of regular and conscripted forces, numbered around 250,000 men. but, at least until world war one, and more generally until world war two, the us was still a secondary power, especially in scientific terms. most of the great discoveries and basic research that revolutionized western socihttp://www.fupress.com/substantia http://www.fupress.com/substantia 86 jack s. cohen ety were made in europe, in the uk, germany and france. but eventually the us out-stripped its european rivals in science too. how this happened is a unique and intriguing story. the first organized attempt to improve us scientific standing was made in 1903 with the formation of the carnegie institute of washington (ciw), founded by andrew carnegie, the scottish immigrant steel magnate.4 he specifically envisaged that the ciw would engage in basic research (without specific applications) in all areas of science. but, over time, the ciw’s impact was limited. the next great attempt to expand american science was made during and after world war two by vannevar bush, an extraordinary intellect, who envisaged an early version of the internet, and who was appointed adviser for science and development by president roosevelt.5 his influence caused a revolution in how science was thought of in america, both by the government and its people. most people would be shocked to discover that the us became the great scientific and technological power it is today by ironically exploiting two groups of germans, first german (and other european) jewish émigré scientists before world war two and then german scientists, particularly german rocket and aeronautical engineers, after world war two. i endeavor to tell the story of how america became the world’s scientific superpower through these developments in science and technology. 2. america lags behind europe in science at the beginning of the 20th century it was the end of one century and the beginning of another. at city hall in new york city, electric lights formed giant letters that spelled out “welcome 20th century.” thousands of smaller lights studded the exterior of the building, forming delicate strands of red, white and blue. thousands of us flags hung everywhere, and the entire city was ablaze with lights. if anything could be gauged from this display it was that electricity that had only recently been invented, was here to stay.6 as the hands of the big clock on city hall reached midnight, all the lights suddenly went out. the city was plunged into darkness. it was a moment’s silence that signified the ending of the old century, and when the lights returned, it was the signal that the new century had begun. the crowds began to sing again, bells pealed, and fireworks exploded in the sky. it was the beginning of a new century, 1900 had begun. no-one could have imagined what incredible and amazing discoveries lay ahead that would revolutionize society and everyone’s life. already, the telegraph that had been invented by samuel morse in 1844 had revolutionized long-distance communication. thomas edison invented an improved carbon telephone transmitter for telephones in 1877 and the phonograph in 1878. but, it was the development of the first successful light bulb in 1879 that ensured he would be famous.7 in search of a way to light up the city he formed the edison electric light company in ny city and he said “we will make electricity so cheap that only the rich will burn candles.”8 to do this he invested in what became known as direct current (dc) electricity, ignoring the invention of one of his assistants, nicola tesla, an immigrant from croatia, of alternating current (ac), a decision he would later regret. the competition between dc and ac is a well-known story,9 but ac was found to be by far the best for transmission over long distances and the less dangerous, and when it was chosen to light the pan-american exposition in chicago in 1895,10 the stage was set for the electrification of america and the world. the future looked bright. but, notwithstanding these developments pioneered by edison and a few other inventors, there was a problem in america that few people foresaw. as scientific developments proceeded at a rapid pace in the early years of the 20th century, the us fell behind. notwithstanding the development of heavy industry, including steel production and extensive railway systems, there was no organized attempt to foster basic research in america. by contrast, in europe, germany and the uk had active and already traditional frameworks of fostering basic research at many famous universities and industrial laboratories. one can see from the ratio of nobel prizes that america lagged behind the european nations.11 nobel prizes for such important work in physics as the discovery of radioactivity, the nature of the electron and the atom, in chemistry the development of dyes and drugs, in physiology the understanding of hemoglobin and the function of proteins and enzymes. in all these areas the research level and competition were much more intense in europe than in america at that time (figure 1).12 here is a partial list of some early german nobel prize winners: in physics; roentgen (1901), lenard (1905), von laue (1914), planck (1918), stark (1919), einstein (1921), hertz (1925), franck (1925), heisenberg (1932). in chemistry; fischer (1902), von baeyer (1905), buchner (1907), ostwald (1909), wallach (1910), willstatter (1915), nernst (1920), wieland (1927), fischer 87the revolution in science in america, 1900-1950 (1930), bosch (1931). these names are of the highest possible caliber and were responsible for establishing the highest level of these scientific subjects at the time. by comparison during this period the us had the following nobel prize winners: physics; michelson (german jewish immigrant, 1907), millikan (1923), compton (1927), davisson (1937), lawrence (1939); chemistry, richards (1914), langmuir (1932), urey (1934). frankly, there is no comparison. the same could be said of comparison of uk and us nobel prize winners during the same period 1901-1939. what is the origin of these differences? in the uk, government funding of science started in 1675 when the  royal observatory  was established in  greenwich. this was continued in the 19th century with the creation of the  british geological survey  in 1832, and the allocation of funds in 1850 to the  royal society  to award individual grants.13 by the  first world war  in 1915, claims about the poor state of british manufacturing compared to germany, led to the  department of scientific and industrial research  (dsir) being founded. it was a part of the uk government, staffed by civil servants who distributed grants, operated laboratories, and made policy. examples included the  radio research station, established in ditton park in 1924. in 1918, richard haldane produced an official report on the machinery of government that recommended that government departments undertake more research before making policy. it was recommended that they should oversee that specific, policy-minded research was carried out, governed by autonomous councils free from political pressure. following the haldane report’s recommendations, the  medical research council (mrc) was created in 1920 from a previous body called the medical research committee that had been established in 1913 to distribute funds collected under the  national insurance act of 1911. in contrast to dsir, the mrc was not a government department, its staff were not civil servants, and its resources were concentrated in a small number of central laboratories and a large number of research units associated with universities and hospitals.13 this is still the pattern today. in berlin in 1909, professor adolf von harnack, a close adviser to the kaiser and a member of the academy of sciences, wrote a memorandum to kaiser wilhelm ii in which he outlined a reform of the german science system. he proposed the establishment of independent research institutes conducting specialized basic research. he wrote that the rapid pace of industrialization had demonstrated the need for greater knowledge of basic sciences. harnack proposed the foundation of a new type of research association for the advancement of science to be known as the kaiser wilhelm society. harnack’s memorandum paved the way for a reorganization and the establishment of research institutes that still characterize the german science system today.14 the kaiser wilhelm gesellschaft (kwg) was founded in 1911 for the advancement of science and was formally independent of the german state. some 30 research institutes and testing stations were founded all over germany in specific areas of science. the kwg had presidents such as adolf von harnack, fritz haber,  otto hahn and max planck, and each institute had its own scientific director. funding was obtained from inside and outside germany. after wwii the kwg became the max planck geselleschaft. 15 after the first world war the financial situation of the universities and scientific institutions was dire. their budgets had not been increased since before the war and inflation was rapidly increasing. however, it was precisely in this period following the war that an increase in funding was most needed. the war had been responsible for the interruption of scientific and research activities, young researchers had been called up for military service and research projects had been interrupted. in addition, basic research had been almost completely discontinued in favor of research critical to the war. this situation was further exacerbated by the international isolation of german research, as a result of the treaty of versailles, which ascribed sole guilt to germany for the first world war. figure 1. the cumulative number of physics, chemistry and medicine nobel prizes per country. prizes are attributed to the respective country according to the nationality of the recipients at the time of the announcement, with prizes obtained by more than one recipient accordingly divided. note that the us population increased from 76 to 327 million during 1901–2017.12 88 jack s. cohen in 1920, leading representatives of science and scholarship in germany established a working committee, which subsequently adopted the name notgemeinschaft (“emergency foundation”). its task was to coordinate joint action and proposals to the parliaments, governments and also potential sponsors in industry, in order to secure the provision of the necessary financial resources to continue basic research. friedrich schmidtott, adolf von harnack and fritz haber played leading roles in this working committee, and also in lobbying the government for funding. 16, 17 friedrich schmidt-ott (figure 2) was elected president of the notgemeinschaft at the inaugural meeting in 1920. adolf von harnack was the president of the kaiser wilhelm society (kwg, later the max planck institutes) founded in 1911. fritz haber was director of the kaiser wilhelm institute of physical chemistry and electrochemistry in dahlem. he was awarded the nobel prize for chemistry in 1919 for the fixation of nitrogen from the air. he and adolf von harnack became members of the executive committee of the notgemeinschaft in 1920. the concerns of the notgemeinschaft fell on sympathetic ears in government and in society; a decline in the standard of german research compared with other nations was seen as a loss of national honor. in addition, there were concerns about a negative impact on germany’s future economic development. in an application by the notgemeinschaft for financial support from the reich government in 1920, adolf von harnack stressed the importance of science and research for germany’s overall development: the vital necessities of the nation include the preservation of the few assets that it still possesses. among these assets, german science and research occupy a prominent position. they are the most important prerequisite not only for the preservation of education in the nation and for germany’s technology and industry, but also for germany’s reputation and its position in the world, on which in turn prestige and credit rely. following debates on the allocation of reich funds to the nascent notgemeinschaft in the reichstag,18 in october 1920 the reich ministry of the interior made 20 million marks available in the 1921 budget year “for the advancement of the goals pursued by the notgemeinschaft der deutschen wissenschaft.” funding continued in this manner until 1934, when the committee of the notgemeinschaft were forced to resign and were replaced by nazi party control. haber who was born jewish, had converted to christianity and was a german nationalist, was nevertheless dismissed from all his positions and left germany and died in poverty in basle, switzerland in 1934. the notgemeinschaft was the precursor of the deutsch forschungsgemeinschaft (dfg) the german research foundation after world war two, that was founded officially in 1951 and became the federal organization for the support of basic research in the federal republic of germany. by comparison with the european powers, the fact is that in the us at the beginning of the 20th century there was no federal government support for basic research, there were no institutions that were funded to carry out basic research and no committees existed to foster such research. it is no wonder then that the us fell behind europe in the early period in the advancement of science and the advantages that could bring for industry and society. in the us at the turn of the century, many so-called “robber barons” had made huge fortunes in such industries as iron, steel, coal, railways and automobiles. several of them in later life turned to philanthropy and established institutes in their name. thus there is the frick institute on the mall in washington dc, established by henry clay frick, who made his fortune in steel and railroads, that holds a wonderful art collection. leland figure 2. left, friedrich schmidt-ott, president of the notgemeinschaft from 1920 to 1934; middle, adolf von harnack; right, fritz haber. 89the revolution in science in america, 1900-1950 stanford in california, who made his fortune in railroads, chose to establish a famous university. two of these luminaries chose to establish institutions that support the concept of basic research, john d. rockefeller, who made his fortune in oil refining and was reputed to be the wealthiest american, established the rockefeller institute in new york city in 1901 for biomedical research.19 andrew carnegie, who had made his fortune in iron and steel production, realized the need for basic research in america and founded the carnegie institute of washington (ciw).20 his initial donation of m$10 for this purpose was given with the stipulation that only research without any applied objectives should be conducted there. he hoped that this would engender a commitment to basic research throughout america. once established in 1903, the ciw engaged in many areas of research, including physics, chemistry, genetics and astronomy. this included edwin hubble who revolutionized astronomy in 1929 with his discovery that the universe is expanding, and barbara mcclintock, who won the nobel prize in 1983 for her work on genetics in maize. although the ciw did make important contributions in all these areas it is interesting to note that while the director of the ciw, robert s. woodward, was himself a physicist, the major project in physics that the ciw undertook to pursue was the construction of a wooden-copper boat the carnegie, to sail the seas of the world and establish the earth’s magnetic field.21, 22 this could not be done obviously in a regular iron ship. but the ciw missed the boat as it were in physics, they chose not to work on the frontline in physics research that was taking place in europe, where such notables as rutherford in britain, neils bohr in denmark, werner heisenberg and albert einstein in germany, were grappling with the structure of the atom and its properties. if they had initiated a program of research into the atom, the us might not have had to depend on the immigration of european jewish scientists in the 1930’s to initiate the manhatten project to build an a-bomb. although the ciw did some notable basic research, its influence was not so great as to bring america in line with its european competitors. during the early part of the 20th century it was expected that any phd candidate in science in the us would spend at least some time in post-doctoral studies at one of the great european universities. also, at the time german was considered the scientific language. andrew carnegie’s hope that ciw would bring about a revolution in support for basic science in america was not realized at that time. 3. development of military technology during wwi and the inter-war years it is a well-known truism that warfare results in advances in science and technology that have tremendous consequences. this is certainly true of the main development in military technology that resulted from wwi, namely the tank. originally ideas of a mobile armored vehicle were conceived by leonardo da vinci and h. g. wells. wells called them “land ironclads” and described their successful use in his story of that name published originally in 1903.23 but, in reality it took a lot longer to develop them. at first an american company named holt of stockton ca developed caterpillar tractors, that were used to tow heavy equipment around behind the lines of the uk forces in wwi. their potential as actual fighting vehicles was foreseen by the british who developed a version called the mark-1 tank that was mainly seen as a means to cross trenches to overcome the stagnant warfare of wwi. many subsequent versions were produced by many countries and rejected, but tanks were first used effectively by col. george patton, in the battle of amiens under the command of us general pershing, that effectively was the last major battle of wwi.24 during the 1920’s many improvements were proposed, but mostly rejected by traditionally thinking military commands. however, one innovation that proved significant was that of independent suspension of all wheels of the track proposed by an american transportation engineer named j. walter christie in 1928.25 this allowed the tank to move much faster over rough terrain, precisely what a tank was needed to do. this idea too was rejected by us and british army ordnance officials. but, the germans, who had been defeated at amiens by tanks, realized their military significance and took up this idea and incorporated it into their panzer tanks. this was one of the main reasons for the defeat of the french and the british expeditionary force at dunkirk at the beginning of world war two. they were stunned by the speed with which the german tank corps raced ahead and overpowered them. the russians too took this idea and incorporated it into their tanks and eventually the americans and british followed suit. incidentally, one reason that germany lost world war two was that although they produced the “best” tank, the famed tiger tank, they were over-engineered and were so heavy that they had to stop to fire, and germany produced only 1,350 of these, while the us produced 49,324 sherman tanks, that were more mobile, more easily repaired and cheaper.26 90 jack s. cohen as well as the development of the tank, parallel advances were made in the areas of automobile technology and in airplanes, from the wright brothers first flight in 1903 in north carolina. wwi catapulted the airplane into prominence, first for reconnaissance of enemy positions and then as fighters facing each other. detailed analysis of the developments in car engine technology and aeronautics is considered beyond the scope of this work. 4. the influence of european jewish emigres in the period 1930-39 before world war two, as the wave of anti-semitism engulfing europe developed, there was a positive tsunami of jewish scientists of german, austrian, hungarian and other nationalities emigrating from europe to the us. their estimated number by 1944 was 133,000, and they contributed enormously to the development of basic sciences in the us, including increases in patents and expansion of scientific networks.27 among them was a large proportion of highlevel scientists, particularly physicists and chemists, some of whom were helped in various ways by us officials, such a varian fry28 and hiram bingham iii.29 while the majority of jews were denied visas and prevented from entering the us, due largely to anti-semitism among state department officials,30 the cream of the crop of the scientists were facilitated. among them were the physicists, albert einstein from germany, leo szilard from hungary, enrico fermi from italy, and many others whose names would become synonymous with the leap in american ability in the crucial area for the future war effort of nuclear physics. many of these physicists were familiar with the developments being made in nuclear physics in europe during the period 1900-1930. they knew of the work of ernest rutherford in england on the splitting of the atom, of hans bethe and lise meitner in germany on the energy produced when splitting the atom, and of neils bohr in denmark on the structure of the atom and his german student werner heisenberg, who enunciated the famous “uncertainty principle” and who was later to become the director of the german nuclear program during world war two. each of these individuals contributed significantly to the knowledge and understanding of the atom and of its potential to produce enormous amounts of energy. however, this culture of scientific achievement in the area of nuclear physics was not present in the us. in fact, the most famous american physicist, robert millikan, who had won the nobel prize in 1923 for measurement of the electron, was quoted as saying in 1929, “there is no likelihood to me that man can ever tap the power of the atom, there is no appreciable energy available to man through atomic disintegration.”31 however, ernest rutherford himself also was skeptical that splitting the atom would result in large amounts of available energy. following their arrival in the us, several of these german jewish emigres played very important roles in atomic research in america. einstein was accommodated at princeton, where he played a role in the institute for advanced studies in expanding knowledge of atomic theory. fermi went to the university of chicago, where he famously built the first nuclear reactor core pile-1 under the stadium of the chicago university and szilard worked with fermi. szilard authored the famous letter which einstein sent under his signature to pres. roosevelt warning him of the possibility of the development of an atomic bomb with enormous potential.32 this led to the establishment of the manhattan project in new mexico, which was under the scientific direction of robert oppenheimer, an american-born jew. it is well-known that they did indeed develop the atomic fission bomb and contrary to the original intentions of some of the scientists, two were dropped on the cities of hiroshima and nagasaki in order to force the surrender of the japanese without needing to carry out an invasion of the japanese home islands. what would have happened if these jewish scientific immigrants had not arrived in the us before world war two, had they not pursued their research on the atom and had not directly persuaded president roosevelt to initiate a major and huge commitment to study atomic fission that resulted in the manhattan project that led to the atomic bomb? there would never have been the a-bombs that were dropped on hiroshima and nagasaki by order of pres. truman and the war would not have ended in august 1945 (vj day was aug 15, 1945), but the us would have had to mount an invasion of japan itself and there would have been an estimated 1 million us casualties.33 it is not generally known that an attempt at a coup against the emperor was tried by elements of the japanese army in order to prevent him broadcasting his message of surrender to the japanese people.34 although some 120,000 people were killed by the bombing of hiroshima and another 65, 000 in nagasaki, given the amount of resistance encountered in the invasion of okinawa, and the suicides carried out by large numbers of japanese, particularly women, it can be estimated that there would have been millions of japanese casualties 91the revolution in science in america, 1900-1950 resulting from an invasion of the home islands. so ironically in effect the dropping of the atomic bombs saved lives, both american and japanese, although there is some controversy about whether or not the second bomb on nagasaki was indeed necessary. 5. vannevar bush, and the office of scientific research and development if any one man could be regarded as instrumental as the initiator and proponent of support for basic research in the usa, that man would be vannevar bush (figure 3). he was born in everett, massachusetts, in 1890 and went to tufts university and mit. bush played a role in many engineering developments in circuit design and radio technology that led to the development of the raytheon company in 1922 that became a large electronics company and defense contractor. at mit in 1932 he became vice-president and dean of engineering. in 1938 he was appointed president of the carnegie institute of washington, which brough him in close contact with the government of the usa. he was an engineer, inventor and science administrator, who from its inception in 1941 and during world war two was director of the us office of scientific research and development, and was the first science adviser to a us president, president roosevelt. although many scientists made contributions towards the development of scientific research in the usa, vannevar bush was pre-eminent among them.5 in 1940, prior to the us joining the war, the british revealed to the us that they had made significant strides in developing radar to detect approaching german airplanes. realizing the significance of this technology bush arranged for mit to develop airborne radar that was available by 1941. bush’s developments in circuit design had enabled him to effectively develop an analog computer. in 1940, norbert weiner approached bush with a proposal to develop an electronic computer. bush declined to provide funding because he thought it could not be completed before the end of the war. in this he was correct, but nevertheless, weiner approached the army and they provided funding to build what would be known as eniac, the world’s first electronic computer. bush was considered short-sighted by many, he refused to provide support for social sciences and also refused to support the development of rockets or missiles. for this he was later criticized. one of the first applications of science to military technology that bush oversaw was the proximity fuse, that was developed by merle tuve and james van allen. this was designed to ensure that bombs would explode even if they did not directly hit their target, they only had to be in the proximity of their target. this was not only advantageous because it increased the likelihood of an effective explosion, but also the damage caused by blast was also very significant. when these proximity fuses were used in american ordnance in the first involvement of american forces in north africa in 1942, sir solly zuckerman, who was to become the british equivalent to bush, who was an expert in the effects of bombing, discovered that the american bombs were more efficient at taking out german emplacements than the british ones. when he discovered why, he immediately recommended that the british adopt a similar proximity fuse.35 perhaps bush’s most significant initiative was his role in persuading the us government to undertake a program to create an atomic bomb that would become the manhattan project. bush met with pres. roosevelt in 1941, and following the initiative of the german jewish émigré nuclear scientists szilard and einstein in 1939 and the british program in atomic development, roosevelt gave his go-ahead for a crash program. the manhattan project was to be run by the us army under the direction of secretary of war henry stimson and of brigadier gen. leslie groves and under the scientific direction of robert oppenheimer. he had carried out calculations that estimated that for a uranium-235 bomb to achieve criticality would require 2.5-5 kg. if we are to believe the evidence of werner heisenberg, who was in charge of the german nuclear program, the germans made mistakes in their calculations and thought that it would require much figure 3. vannevar bush seated at his desk (library of congress). 92 jack s. cohen more, as portrayed in the historical drama “copenhagen,” involving niels bohr and heisenberg.36 6. the american revolution in science after world war two after the war, the office of scientific research and development was no longer needed and was disbanded. but vannevar bush realized that there was a great need for a peacetime agency to replace the function of osrd in promoting science and technology for the national interest. he wrote an essay in 1945 that is considered the most influential paper relating to science and technology every produced in the usa. it was entitled “science, the endless frontier,” that was a report to pres. roosevelt,37 urging the establishment and funding of such a peacetime organization. note there was 36 years between vannevar bush’s report to pres. roosevelt and the similar memorandum of adolf von harnack to kaiser wilhelm ii, a measure of the lag in us understanding of the significance of basic scientific research. the change from president roosevelt, who died in 1945, to president truman, resulted in a significant loss of influence for vannevar bush. through many political changes and compromises bush’s report finally resulted in congress establishing the national science foundation (nsf) in 1950 that funds basic research in the usa. one other significant influence that vannevar bush exerted on science in the us after world war two was his concept of large-scale data manipulation needed for the pursuit of science, something that he called memex. he had thought about this since the 1930’s and he crystallized his ideas in an article entitled “as we may think,” that was published in the atlantic magazine in 1945. it consisted of a data storage device in the form of microfilm that could be rapidly switched to enable rapid access to different information. this paper was a forerunner of what we call “the information age,” and was extremely influential in the thinking of people who set about using electronic means to develop the mouse, the computer and the internet.38 apart from their singular influence on the developments in nuclear physics which resulted in the atomic bomb, european jewish immigrant scientists had a widespread salutary effect on american science. this is attested to by the general increase in scientifically based patents produced in subsequent years following their immigration and the development of a much wider range of research on basic scientific subjects.27 note that jews have won 26% of nobels in physics, 20% in chemistry, 27% in physiology or medicine and 41% in economics. although jews are only 0.25% of the world’s population they have won a staggering 24% of all nobel prizes in science (physics, chemistry and physiology or medicine). if we take the period 1901-1939 jews won 15% of german nobel prizes while being less than 1% of the german population. from 1939 onwards, when there were no longer any jews in germany, the number of nobels won by germans did not increase significantly for some time (figure 1), but this is not surprising since germany had lost the war and was devastated. similarly after world war two the increase in number of nobels in the uk, which had won the war but was similarly devastated, grew only very slowly. but the us experienced a sharp increase in nobels following world war two and surpassed the individual european nations after 1960 (figure 1), as both its population and expenditure on research and development significantly increased. countries with increased research and development expenditures demonstrate higher growth performance with higher levels of gdp per capita than other countries.39-41 this salient fact indicates that apart from the influence of the european émigré scientists and the subsequent influence after world war two of german scientists transferred to the us, particularly in the area of rockets and aeronautics, it was the decision of the us to expend a large amount of funding on research and development after the war that led to its accumulating wealth in that period. after world war two, it was perhaps a shock to the western allies to find that the germans had been so far ahead in various areas relating to military technology. for example, in the development of rockets, such as the v2, that could be fired into the stratosphere and then crash into a city far away and cause enormous damage. the allies had no such weapons. also, the germans developed the first functioning jet airplane, the me 262 (called the schwalbe or swallow), that was used in combat at the end of the war. it could easily outfly the propellor planes of the allies, although it was developed in 1942, not enough of them were produced to affect the outcome of the war. to obtain the secrets of german research on these and other technologies, there was a race between the us and the ussr as the war came to an end to capture and use the expertise of the german scientists. those who were caught and transferred to the us were, of course, quite happy not to share the fate of the rest of the nazi apparatus they had served. this us operation was called operation paperclip and resulted in ca. 1,600 german scientists and engineers being transferred to the us.42 werner von braun, the head of the german rocket 93the revolution in science in america, 1900-1950 program under the nazis, whose products, including the v2, that killed tens of thousands of slave laborers in their construction and londoners as their targets, was never charged with any war crime. instead, he was appointed head of the us army’s ballistic missile program and then head of the national aeronautics and space administration (nasa) space program. the reason was, of course, to try to beat the ussr in the development of rockets and in space exploration. he received the us national medal of science in 1975. the origin of the national institutes of health (nih) can be traced to the  marine hospital service started in the late 1790s that provided medical relief to sick and disabled men in the u.s. navy. by the 1870’s a network of marine hospitals was developed and congress allocated funds to investigate the causes of epidemics like cholera and yellow fever. the national board of health was also created, making  medical research  an official government initiative. in 1887 the hygienic laboratory was established at the marine hospital in new york for the study of bacteria. in the early 1900s congress began appropriating funds for the marine hospital service. in 1922, this organization changed its name to public health services and established a special cancer investigations laboratory at  harvard medical school. in 1930, the hygienic laboratory was re-designated as the national institute of health by the  ransdell act, and was given $750,000 to construct two nih buildings in bethesda md.43 over the next decades congress would markedly increase funding of the nih until today it is in the billions of dollars, and various institutes and centers within the nih were created for specific research programs. in 1944, the  public health service act  was approved, and the  national cancer institute  became a division of nih. in 1948, the name changed from singular national institute of health to plural national institutes of health. the nih’s functions were divided into two, the intramural research program, and the extramural grant program. each institute has its own separate intramural and extramural programs designed to advance knowledge and understanding of disease and therapy in each of the major disease categories and to support research through competitive grants at universities and medical schools throughout the usa and the world. in the period up to the end of world war two the us relied primarily  upon a laissez-faire  approach to scientific research and development.  in 1950 president harry s. truman  signed public law 507  creating the national science foundation (nsf), which provided for a  national science board  of twenty-four part-time members. the nsf began its first full year of operations with an appropriation from congress of $3.5  million, with which 28 research grants were awarded. after the 1957 soviet union orbited  sputnik 1, the first ever man-made satellite, national self-appraisal questioned american education, scientific, technical and industrial strength and congress increased the nsf appropriation for 1958 to $40 million.44  between them nih and nsf funding account for most of the biomedical and scientific research carried out in the usa, and constitute the largest commitment of any country around the world to the funding of basic research (figure 4).45 the significant increase in scientific research in the us after world war two parallels the increase in the number of nobel prizes won (figure 1). 7. america becomes world leader in science and technology the tremendous increases in expenditures in support for basic scientific research that occurred in the us after world war two resulted in a veritable explosion of notable accomplishments. the nih and nsf that fronted the support for research in the health-related medical sciences and the basic sciences respectively, brought extensive advances in understanding of both the biological and the physical world. these advances in knowledge and understanding also resulted in inventions and applications that have revolutionized our world. these include the transistor that was developed by william shockley and his team at bell labs in 1947, that triggered the development of electronics; the printed circuit that was developed by the us army during the war and released for commercial use in 1948, key to miniaturization of electronics; the key development of the computer, both hardware by steve jobs and steve wozniak and dos software by bill gates; the internet, that was first developed as the arpanet in california in the 1960’s; and then of course there was the smartphone in biology, advances in genetics resulted mainly from the ability to sequence large segments of dna, figure 4. us federal government spending on research (in billions of 2017 dollars).45 94 jack s. cohen including the human genome. and this led to the understanding of genetic function. it is tempting to conclude that all these developments could only have occurred in the us at that time. clearly the european nations were not only devastated by the war, but also lacked the necessary funds and expertise to continue along the path that could have been projected from before the war. the other victorious allies, britain and russia, were both forced into a long period of recovery. only the us had the largesse and the industrial potential of exploit the commercial possibilities brought about by this revolution in thinking about science in the us. acknowledgement i thank franklin h. portugal for helpful discussions and dr. niklas hebing and mechthild koehler, librarian, of the dfg for their help. references 1. david greasley, les oxley, comparing british and american economic and industrial performance 1860–1993: a time series perspective, explorations in economic history 35 171-95, 1998. 2. gavin wright, the origins of american industrial success, 1879-1940, the american economic review 80 651-68 1990. 3. david f. schmitz, henry l. stimson: the first wise man. rowman and littlefield, 2000. 4. https://carnegiescience.edu/about/history 5. g. p. zachary, endless frontier: vannevar bush, engineer of the american century. free press, 2018. 6. in book the new century, ed., ed. by editor, city, chap. chapter.1900 7. paul israel, edison: a life of invention. wiley, new york: , 1998. 8. t h o m a s e d i s o n , ht t p s : / / q u o t e i nv e s t i g at o r. com/2012/04/10/, 1880. 9. tom mcnichol, ac/dc: the savage tale of the first standards war. john wiley, 2006. 10. erik larson, devil in the white city. crown publisher, 2003. 11. https://en.wikipedia.org/wiki/list_of_nobel_laureates_by_country. 12. claudius gros, an empirical study of the per capita yield of science nobel prizes: is the us era coming to an end?, r soc open sci. 5, 2018. 13. philip gummet, scientists in whitehall. manchester univ. press, 1980. 14. history of the kaiser wilhelm society. 15. margit szöllösi-janze, science and social space: transformations in the institutions of “wissenschaft” from the wilhelmine empire to the weimar republic, minerva 43 339-60, 2005. 16. the origins of the notgemeinschaft, https://www.dfg. de/en/dfg_profile/history/notgemeinschaft/index.html, 2014. 17. mark walker, karin orth, ulrich herbert, rudiger vom bruch, the german research foundation 19201970: funding poised between science and politics. franz steiner verlag, 2013. 18. https://www.reichstagsprotokolle.de/en_index.html 19. report, the rockefeller institute for medical research, journal of the american medical association xxxvi 1630, 1901. 20. https://carnegiescience.edu/about/history 21. https://carnegiescience.edu/news/cliffs-mercur ynamed-carnegie-research-ship 22. f.h. portugal, unpublished ms 23. h.g. wells, the land ironclads, in the short stories of h.g. wells, ernest benn, pp. 115-38.1974, 24. james mcwilliams, amiens: dawn of victory. dundurn, 2001. 25. https://en.wikipedia.org/wiki/history_of_the_tank 26. https://en.wikipedia.org/wiki/military_production_ during_world_war_ii 27. petra moser, alessandra voena, fabian waldinger, german-jewish emigres and u.s. invention, social science res. network https://papers.ssrn.com/abstract_ id=1910247, 2013. 28. andy marino, a quiet american: the secret war of varian fry. st. martin’s press, new york, 1999. 29. peter eisner, saving the jews of nazi france, smithsonian magazine march, 2009. 30. daniel a. gross, the u.s. government turned away thousands of jewish refugees, fearing that they were nazi spies, smithsonian mag. nov. 18, 2015. 31. robert millikan, presentation in the biltmore hotel to the society of arts and sciences, brooklyn life, 1929. 32. https://www.atomicheritage.org/key-documents/einstein-szilard-letter. 33. carol a. clark, what if the u.s. had invaded japan on nov. 1, 1945?, los alamos daily post oct. 27, 2019. 34. william craig, the fall of japan: the final weeks of world war ii in the pacific. openroad media, 2015. 35. john peyton, solly zuckerman: a scientist out of the ordinary. j. murray, london, 2001. 36. michael frayn, historical drama, copenhagen, 1998. 37. vannevar bush, science the endless frontier: a report to the president by vannevar bush, director 95the revolution in science in america, 1900-1950 of the office of scientific research and development, national science foundation. , july 1945. 38. b. johnston, s. webber, as we may think: information literacy in the information age, research strategies 20 108-21, 2006. 39. m. ildirar, m. osmen, e. iskan, the effect of research and development expenditures on economic growth: new evidences, international conference on asian economies 36-43, 2016. 40. d. lederman, l. saenz, innovation and development around the world, 1960-2000, world bank policy research working paper 3774, 2005. 41. o. ozden, evaluating the impact of r&d expenditures on gdp per capita, a panel data study for oecd countries 2017. 42. annie jacobsen, operation paperclip: the secret intelligence program that brought nazi scientists to america. back bay books, 2015. 43. victoria a. harden, wwi and the ransdell act of 1930: a short history of the national institutes of health, office of history national institutes of health, 2011. 44. george t. mazuzan, the national science foundation: a brief history, nsf publication 8816. 45. gj. hather, w. haynes, r. higdon, n. kolker, ea. stewart, et al, the united states of america and scientific research, plos one 5 e12203, 2010. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 3(2) suppl. 3: 71-83, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-507 citation: e. zürcher (2019) water in trees an essay on astonishing processes, structures and periodicities. substantia 3(2) suppl. 3: 71-83. doi: 10.13128/substantia-507 copyright: © 2019 e. zürcher. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. water in trees an essay on astonishing processes, structures and periodicities ernst zürcher dr. sc. nat., forestry engineer ethz, professor em. for wood science bachelor & master wood, bern university of applied sciences, architecture, wood and civil engineering solothurnstrasse 102, p.o. box, ch-2500 biel-bienne 6 e-mail: ernst.zuercher@bfh.ch abstract. this essay shows that the relations between water and trees have far-reaching, unexpected aspects and consequences. the local and the global terrestrial water cycles are directly or indirectly linked to the presence of trees and forests. a more precise consideration of photosynthesis reveals that this process is not only producing biomass and oxygen, but is also the place of water synthesis. this newly formed water probably shows properties according to the new water-paradigma proposed by g. pollack (2013). this must also be the case for the water absorbed in the soil and flowing upwards through capillar wood structures, forming vortices at the microscopic cellular and at the macroscopic tree level. another lesser-known phenomenon is linked to periodical changes in the wood-water relation, according not only to the solar influence (photoperiodism, seasonality), but also to more subtle lunar rythmicities having an effect on wood properties. this last aspect represents a kind of rehabilitation of traditional practices often considered as mere superstitions. keywords. water cycle, photosynthesis, water synthesis, wood structure, vortices, lunar rythmicities. water at the center of the fundamental process of life photosynthesis is the common process to all plants, but trees, due to their outreaching dimensions and to the formation of forests in specific multispecies associations, perform 2/3 of the global photosynthesis on earth. a closer study of this process reveals that there is a hidden face of photosynthesis. in many textbooks or even dictionaries, an uncomplete equation of photosynthesis is still usual, which is misleading for a correct understanding of the most important physiological process making life possible on earth. effectively, following equation is often figuring: “6 molecules of carbon dioxide + 6 molecules of water + light → 1 molecule glucose + 6 molecules oxygen” 72 ernst zürcher 6co2 + 6h2o ------> c6h12o6 + 6o2 sunlight energy where: co2 = carbon dioxide h2o = water light energy is required c6h12o6 = glucose o2 = oxygen the researcher who finally refutes this incomplete and tenacious portrayal is the microbiologist cornelis van niel (1897–1985) of stanford university, following work as a young student on the photosynthetic activities of various types of bacteria. one particular group of these – the purple sulphurous bacteria (thiorhodobacteria) – is capable of reducing the co2 into carbohydrates, in an atmosphere devoid of oxygen (anaerobic conditions) and without emission of oxygen. the substrate necessary here is not water h2o, but hydrogen sulphide h2s. what is released by the process, on the other hand, in addition to the carbohydrates, is water h2o and elemental sulphur s2 accumulated in the globules within the bacteria and identifiable under a microscope. van niel did not stop here and he extrapolated his discovery by proposing a generalised equation for photosynthesis. this came down to affirming that the source of the oxygen produced by chlorophyllian photosynthesis was in fact the water and not the carbon dioxide. this brilliant speculation put for ward in the 1930’s received its proof in the following decade when researchers from berkeley used a heavy isotope of oxygen (18o) to mark the water molecule entering the reaction. result: the oxygen released comes exclusively from the h2o molecule. in terms of process, this comes down to understanding that the primary action of the sun’s rays in photosynthesis consists of the splitting or photolysis of water. the newly produced water takes its oxygen from the carbon dioxide absorbed (ray 1972; lance 2013). the complete and balanced equation for the production of glucose by photosynthesis, within a living system without which nothing can happen, thus includes an extra constituent. the destination of the atoms of the water molecules taking part in the reaction can be shown by using colours and bold type: 6 co2 + 12 h2o + light energy & living system  c6h12o6 + 6 o2 + 6 h2o glucose 6 co2 + 12 h2o + light energy & living system  c6h12o6 + 6 o2 + 6 h2o glucose by converting into moles (molecule-grammes, according to chemists’ terminology), it is possible to illustrate the flows of matter by weight (in grammes), with indication of the energy required (in kilo-joules): 6 mol co2 + 12 mol h2o + light & life  1 mol c6h12o6 + 6 mol o2 + 6 mol h2o 264 g 216 g 2897 kj 180 g 192 g 108 g 6 mol co2 + 12 mol h2o + light & life  1 mol c6h12o6 + 6 mol o2 + 6 mol h2o 264 g 216 g 2897 kj 180 g 192 g 108 g figure 1 also presents the values corresponding to the synthesis of wood, originally based on glucose, but characterised by a slightly different formula used by physiologists (zimmer and wegener, 1996). some remarkable facts emerge from this new vision of the process: • for each dry tonne of wood made by the tree, a mass of 1.851 tonnes of gaseous co2 is removed from the atmosphere, reducing by that amount the greenhouse effect and global warming which preoccupy humanity at present. we have here a ‘carbon sink’, persisting as long as the wood is not burned or decomposed releasing an analogous quantity of co2 into the atmosphere. it will therefore be important in the future to incorporate wood on a long-term basis either into buildings as a material or into soils in order to increase the content of stable organic matter. • each anhydrous tonne of wood made by the tree is accompanied by a mass of 1.392 tonnes of newlyformed oxygen, coming from the photolysis of water. this represents a considerable volume: 973 m3 of pure oxygen, or 4,636 m3 mixed at a proportion of 21% into the air we breathe to stay alive. a rather unorthodox question, coming from a quality point of view: does newly-formed oxygen of this kind, entering the biosphere for the first time in this form, have different properties from “old” oxygen? could this possibly be one of the reasons why forest air has always been felt to be particularly beneficial to health? • each anhydrous tonne of wood made by the tree is accompanied by a mass of 541 kilos of newly-formed water. as for the preceding component, we have here perfectly pure water, which has never before entered into the great cycle “evapotranspiration – cloud formation – condensation / precipitation – runningoff / percolating – accumulation – resurgence”. it is likely that this new water soaks the green parts of the plants and circulates with the elaborated (phloem) sap down to their lower organs, contributing to their growth. here too arises the question of qualities, properties or specific virtues of such water, especially given the many forms of pollution to which the external water cycle is subjected. such a question can be placed in a modern scientific debate, very con73water in trees – an essay on astonishing processes, structures and periodicities troversial at the outset, but finding more and more renowned defenders: that of the ‘memory of water’, as developed by pioneers such as jacques benveniste, xy vinh luu, marc henry, luc montagnier or gerald pollack. we should mention here, to underline the credibility of the protagonists and the importance of the subject, that professor luc montagnier received the nobel prize for medicine in 2008. trees and the latest findings about water the emergence of a new understanding of water allows us to adjust our view of the structures and functioning of trees. a chance observation made in a japanese laboratory followed by a series of experiments starting at the beginning of this century has led to a progressive confirmation of a hitherto-unknown property of water. in the presence of hydrophilic membranes (natural or synthetic) and over a distance reaching sometimes several tenths of a millimetre, water acquires a state which seems both liquid and solid at once, a fact which suggested to the discoverer, a researcher and professor of bioengineering already well-known for his book ‘cells, gels and the engines of life (pollack 2001), the expressions of ‘exclusion zones, ez’ (ez water / linked to its particularly pure state) and ‘fourth phase of water’. in addition to the solid, liquid and vapour phases. the research on the subject which continues to this day has recently received a coherent overall structure in the form of a publication which did not go unnoticed by the scientific community: ‘the fourth phase of water – beyond solid, liquid and vapor’ (pollack 2013). the anatomical structures of plants and trees in particular, composed of a complex system of membranes and cells with hydrophilic walls showing dielectric properties (as postulated by pollack) and the mechanisms of transport of water towards the crown and the metabolism linked to photosynthesis can, through this new concept, be interpreted more precisely. it should be mentioned that this water close to hydrophilic membranes can be distinguished from ‘normal’ water by many criteria such as level of purity, ph, viscosity, refraction index, the absorption of light energy, electrical charge, oxygen content or again the formation of a supramolecular network. the formation of ‘new’ water resulting from photosynthesis, in addition to the carbohydrates and oxygen, thus gains additional significance, since it occurs within complex membrane systems, corresponding to the criteria of formation of water of the ‘ez’ type. the fact that this new water takes 89% of its mass from part of the oxygen of the atmospheric co2 is already remarkable in itself, making the plant – and in a particular way the tree – both a consumer and a producer of water. it is recognised that carbohydrates and oxygen are necessary for life. we may now ask whether new water with its special properties (which still need analysing) might not also be of fundamental importance. structures a functional approach / xylem as water conducting system the function of conducting water requires bringing water from the root system to the crown, where the assimilation takes place. this occurs through a conducting system made of cells called tracheids in conifers and connecting alignments of cells called vessels in broadleaved species. the first engineering problem is: how to bring cold water (heavy) up to the high parts exposed to heat, sometimes more than 100 metres for the largest trees? how can the physical law of gravity be overcome? the solution is proposed by the physiologists with the ‘theory of cohesion – tension’: water is sucked up, with its diluted mineral salts, along the cellular channels by the ‘negative pressure’ resulting from the foliar transpiration of the tree (zimmermann 1989; koch et al. 2004; johnson 2013). to go beyond the critical height figure 1. complete general equation of photosynthesis, with an indication of the destination of components (above) and average proportions accepted for wood, with indication of weight ratios compared to the dry matter of wood, according to zimmer and wegener (1996) (below) [drawing d. rambert]. 74 ernst zürcher of 10 metres (linked to the atmospheric pressure), the water must contain absolutely no gas bubbles and thus have access to the totality of its internal cohesive forces (which allow, for example, two glass plates to stick together). this state of liquid purity is made possible in conifers by bordered pits. these are mobile contact structures between a tracheid and its neighbour with an effect simultaneously of valve and sieve in order to avoid any embolism due to air bubbles which could accumulate. this system of water transport with special specifications functions at the periphery of the bole’s section, in the xylem, the living part of the wood characterised by bio-electric fields. gerald pollack’s recent discovery (mentioned above) reveals that water running through tracheids or vessels the most directly in contact with the hydrophilic cell wall acquires a particular structure (‘liquid crystals’) and unexpected physical, chemical and electrical properties, probably essential to the physiological exploits of trees. running through capillary systems allows the water to stay liquid down to low temperatures, around – 15°c for certain species, instead of damaging the structures by the formation of ice crystals in winter. as for the electrophysiologists, they observe that the differences in electrical potential generated by the living tissues stimulate the flow of raw sap. these observations follow on logically from old experiments testing the effect of glass capillaries on the fluidity and sensibility of water (maag 1928). this function of conducting water in an upward direction is fulfilled in conifers by tracheids of earlywood (formed in the spring and the beginning of summer) containing many bordered pits. the latter represent the points where water passes from one cell to its neighbour during its flow towards the crown, site of photosynthesis. comparatively, the tracheids of late wood (formed towards the end of the vegetative period) possess a much thicker cell wall endowed with fewer pits; their function is no longer conducting raw sap, but primarily the support of the whole structure. the functioning of a bordered pit, a local cell wall modification essential to the security of the conduction system, is presented in figure 2: we have here an efficient and ‘ingenious’ system, a characteristic component of the functional anatomy of conifers. compared to conifers, the anatomy of broad-leaved trees is much more complex, with its forms of functional specialisation. depending on the tree species, we find generally two types of arrangement of vessels: in porous zones in the case of a marked contrast between early and late wood, or in diffuse pores, when the vessels are of practically constant diameter, spread regularly over the whole of the annual ring. spirality and the golden ratio the helical arrangement observed in the needles of a young scots pine shoot follows a general principle of pronounced geometrical nature, which goethe (1749– 1832) considered as fundamental and called “spiral tendency, which reigns in nature”, and which is always found in combination with the “vertical tendency”. it was shown by a philosopher and naturalist from geneva, charles bonnet (1720–1793), that the position of leaves or needles along a stem (subject of phyllotaxy) or the figure 2. diagramme of the workings of a bordered pit: when functioning normally (top), the water skirts the central impermeable zone of the shared membrane and enters the neighbouring tracheid; in the case of a wound with air bubbles (accidental entry of air), the relative increase in pressure causes the membrane to be flattened, by suction, against the inside of the opposite pit (bottom), blocking the flow of water in the damaged part [modifies after zimmermann 1983]. the recent discoveries about water encourage the supposition that this forced passage through the fibrillar weave of the peripheral membrane confer on the water an additional proportion in the ‘cristalline-liquid’ phase with high viscosity and lowered freezing point, an essential characteristic for species growing in cold regions. 75water in trees – an essay on astonishing processes, structures and periodicities structure of a fir-cone or pine-cone, or indeed that of a thistle flower head, follow a series of crossed spirals. these are subject to a particular relationship: the golden ratio. this ratio, originally defined by euclid (325– 265 bc), is found among others in the famous number sequence developed by leonardo of pisa, also called fibonacci (approx. 1170 – 1250) : 1 – 1 – 2 – 3 – 5 – 8 – 13 – 21 – 34 – 55 – 89 – 144 … , where each element is the sum of the two preceding ones. this series allows the constitution of a set of rational ratios 2/1, 3/2, 5/3, 8/5, 13/8, … 144/89, … , which tend towards the number phi ( ф ) = 1.61803 … . similarly, the series 1/2, 2/3, 3/5, 5/8, … etc. converges towards the number phi (ϕ) = 0.61803 … (ϕ = ф 1). a cone of the scots pine (pinus sylvestris) observed from its base shows an arrangement of scales (also called bracts) according to two spiral systems: a group of 13 rightward (clockwise) spirals and a group of 8 leftward (anti-clockwise) spirals. an eastern white (weymouth) pine (pinus strobus) is also formed according to the golden ratio, but with a ratio of 8/5. these arrangements are illustrated by the example of a maritime pine in fig. 3. analysis of a specimen of spear thistle (cirsium vulgare), an annual plant, shows the seeds on a dried head to be arranged according to a double spiral system with a ratio of 26/16, which can also be written 13*2 / 8*2, thus is part of the fibonacci series. interestingly and to make a link with the 2019 international year of the periodic table of chemical elements – the elements of the mendeleyev’s table can be geometrically arranged according to a spiral following the fibonacci pattern (morton 1977). where life surges up usually (as was the case in figure 3), the right-handed and left-handed spiral patterns (also called parastiches) are counted from the base either clockwise or anticlockwise, which corresponds to an upwards direction for the axis of the cone or for the stem carrying leaves or buds. but we could also consider, like the famous austrian forester-hydrologist viktor schauberger (1885-1958), that in the genesis of plant organs, series of upward spirals cross downward spirals. in his vision of the living world, he talks of female upward energies which are fertilised by male downward energies moving in the opposite direction. in practice, the axillary buds arranged along the shoot and the seeds developing at the receptacle or along the axis of the cone (at the base of the scales) could be understood as germs of life appearing within a “flow – counterflow” system according to the precise mathematical-geometrical ratios of the golden ratio. in a conception of the plant as interacting with the astronomical rhythms modulating among others gravitational forces, these germs of life would thus appear at the points where terrestrial and cosmic ‘force lines’ meet and cross-fertilise (fig. 4). figure 3. cone of a maritime pine (pinus pinaster) growing in the western mediterranean (above), showing an arrangement of the scales according to two series of spirals with a ratio 13 / 8 (below). figure 4. left: diagrammatic representation of two “energy flows (male downwards / female upwards)” intersecting in a helical fashion (in coats 1996). right: spatial arrangement of the seed location at the intersections of the spiral patterns characteristic of the species; the seed represent dormant meristematic points, destined to develop as new specimen. drawing d. rambert. 76 ernst zürcher viktor schauberger (1885–1958) austrian forester remaining voluntarily outside university circles, viktor schauberger was a hydrologist and inventor who stupefied the technical and academic circles of his time. his first achievement was making channels for floating wood of a revolutionary type, seeming to defy the laws of physics of the time. a great observer of natural phenomena, he explored the diverse properties of water and drew from them technical applications including regeneration systems. he saw water as the basis not only of all life, but also of the whole of the ‘terrestrial consciousness’. his thoughts and discoveries led him to direct applications in forestry, agriculture and hydrology (waterways, dams, vitalising water, organisation of forest areas). he designed an ecology in symbiosis with nature well before the contemporary approach (alexandersson 2002; bartholomew 2014). this concept of special places for life to surge up where two flows meet can also be applied to the first cambial cells separating the conducting bundles of young stems, and to the widened ‘secondary’ cambium forming a closed cylindrical meristematic layer, in charge of the growth in thickness of the trunk: both are placed exactly between the upward xylem flow (in the wood) of raw sap and the downward phloem flow of phloem sap. vortex flows revealed by means of injections of liquid colourings into the sapwood at the base of the trunk, some physiologists (see bosshard 1974; harris 1989 on this subject) found that the upward flow of raw sap does not occur in a straight line, but in a manner which is generally helical, in a progression around the axis of the tree. according to the species, but also according to their growth conditions, five ways of transporting water up to the branches were described, of which four were clearly not straight, in the form of upward spirals turning towards the right, or towards the left, or even swinging from one direction to the other (fig. 5). these flows are linked to the anatomical structure of the wood, presenting a ‘spiral grain’, with conducting cells deviating from the axis to a greater or lesser extent, including radical changes in direction during the change from juvenile to adult status in many conifers. these phenomena serve to guarantee that each root can provide water to each branch or nearly, with priority given to the apex, the most essential part of the crown. an analogous experiment remains to be carried out with the downward flow in the phloem: will we find downward spirals in the opposite direction? this elucidation of the upward flow of raw sap using dye solutions injected at the base of the stem showed the paths to the crown were not direct but helical (in a vortex) compared to the axis of the trunk. an interesting similarity underlining the coherence of biological systems: the flow of blood in the large vessels and in the human heart, studied using doppler echocardiography and cardiac magnetic resonance, also form vortexes (day 1998; sengupta et al. 2012; caro et al. 2013). in the more recent development of research on water, based on the discovery of a “fourth phase of water’, particularly in contact with organic hydrophilic membranes, the part played by vortex flows appears in a new light. one of the particularities is that the vortexes increase the oxygenation of the water and its amount of energy-rich hydrogen bonds (ignatov et al. 2015). simultaneously, the emission of energy by radiation is reduced, while significantly decreasing the temperature when before and after vortexing is compared (pollack 2013). this last feature had been discovered by viktor schauberger mentioned above, who considered it very important for the health figure 5. ascent of dye solutions in stems of standing trees, after injections radially at the base of the stem. a: sectorial straight; b: sectorial winding; c: interlocked; d: spiral turning left; e: spiral turning right (in harris 1989, after vité 1967). 77water in trees – an essay on astonishing processes, structures and periodicities of ‘biological systems’ such as trees or even waterways. figure 6 may illustrate the phenomenon at the anatomical level. periodicities chronobiological studies on felling dates of trees and properties of wood related to water the exact moment when a tree is felled to harvest the wood, or simply the moment when samples are taken, has an importance which is generally ignored or underestimated. indeed, we should think of this material as a dense tissue of organic matter saturated with water by forces and to an extent which fluctuate in a cyclic manner. the behaviour when drying (loss of water, shrinkage) and the resulting final density, as well as mechanical resistance (to compression for example) and even resistance to decomposing agents such as fungi or insects, will all be influenced one way or the other by the date of harvesting. traditional practices which are still very much alive still today, ma xims about felling linked to the moon are applied by certain workers of wood. an interesting fact: these rules come from traditions which persist in many regions of the world where links remain with ancestral culture. here we will not deal with the multiple “lunar calendars”, very trendy nowadays, covering numerous areas fairly comprehensively, without any experimental basis. the examples which follow concern cases known directly to the author, or taken from scientifically documented sources; their aim is to illustrate the great variety of uses of wood for which the moon factor is considered important for obtaining certain exceptional properties. it should be pointed out that in most cases this factor comes only in second or third position, the most important being in general the time of year, with a high value placed on “winter wood”, and the situation in terms of the growing conditions, mountain wood from slow-growing natural forest stands being particularly appreciated. sometimes winds are mentioned, such as the foehn in the alps, which could negatively impact certain properties of the wood. large-scale research in order to tackle the question more fundamentally and with a large data base, a new trial was carried out simultaneously on 4 sites in switzerland, with 48 successive fellings (each monday and each thursday) – not linked to any experimental hypothesis – of 3 trees per site over 5 ½ months, representing a total of more than 600 trees felled over the winter of 2003-2004 (zürcher et al. 2010). the species were spruce (picea abies) and sweet chestnut (castanea sativa). before the beginning of the experiment, a reference sample was taken the same day from each of the trees which were later felled (a prismatic sample at chest level). each tree provided at different levels of the trunk a series of samples of sapwood and a series of samples of heartwood. the drying behaviour of this material was followed under standardised laboratory conditions. among the different rhythmicities first observed and then confirmed statistically for three principal criteria, let us mention here the water loss, which varied systematically in spruce, particularly between the fellings immediately preceding the full moon and those following it. the type of variation is probably due not to differences in initial water content, but to the fact that the forces binding the water to the cell wall of the ligneous tissues could be subject to fluctuations. the ratio between the water easily extractable from the wood, designated ‘free’, and the water extracted below the saturation point of the fibres, or ‘bound’ water, fluctuates according to lunar cycles, and probably also according to the seasons, the ‘lunar’ variations being more marked during the period from october to february (zürcher et al. 2012). moreover, the rhythmicities are manifested differently according to the species: the chestnut also figure 6. the clematis (clematis vitalba) is a woody plant which is not self-supporting, belonging to the group of lianas, which have the highest-known speeds of transport of the raw sap. a maximum of 222 metres per hour was measured by kucera and bossard (1981). the strongly helical structure of the vessel walls probably plays here an essential role (photo t. volkmer). 78 ernst zürcher shows statistically significant lunar variations, but distinct from those of the spruce. these systematic variations in water loss cause a variation in the density of the wood after drying: for the case of spruce, it confirms what the previous studies mentioned had already observed (fig. 7 – lower). drying wood felled around the full moon in the spruce samples (picea abies; sapwood and heartwood together), a systematic and statistically significant variation of water loss is detectable. this fluctuation occurs according to the synodic lunar cycle on felling, subdivided into 8 periods of 3.7 days, beginning with the moment of the new moon. the most marked variations occur during the passage from the period preceding the full moon (high water loss) to the one beginning with the full moon (minimal water loss) then the one preceding the last quarter (high water loss). [zürcher et al. 2010] the statistical analysis indicates unexpectedly not only rhythms of a synodic type, but also a marked sidereal rhythmicity. scientific research is thus able to affirm that behind the ‘lunar’ phytopractices of foresters resides a kernel of objective observations. this the case both for synodic lunar phases (the cycle new moon – full moon linked to the position of our satellite relative to the sun) and for the sidereal cycle (position of the moon compared to fixed constellations), also mentioned in a roundabout and somewhat curious way in certain felling rules. note that these results, while confirming the existence of the ‘moon’ factor as mentioned in country lore, appear in a much more complex form than imagined at the start of this research, theophrastus’s rule seeming to be very close to the synodic phenomena observed in spruce (see below). focus on a representative site the systematic variations over the course of the synodic lunar month can be illustrated in another fashion with the graph of variation around the general mean of this same criterion ‘water loss’ for the 48 successive felling dates, using a representative series: the sapwood samples of the site of château-d’oex (zürcher et al. 2012). this material is relatively homogeneous because all the trees are of the same age, belonging to an even-age-managed mountain forest deriving from a plantation. figure 8 a shows the visible change which occurred around the full moons of november, december and january. even if the february full moon is included, where there was almost no difference between the values before and after the full moon, the respective variations around the full moon for this winter period of four months are not insignificant, the general mean indicating a reduction in water loss of 4.5%. tests of water absorption (after drying) one of wood’s most important physical properties, decisive for its bad-weather behaviour and its resistance to rot, is its hygroscopic nature – a very hygroscopic wood is more prone to rot than one which is less hygroscopic. this property is generally expressed by the equilibrium state in a given atmosphere, with a given temperature and relative humidity. when they are completely waterlogged, the cell walls are in a state designated ‘fibre saturation point’, below which the loss of bound water following the drying process causes deformations (shrinkage). the test method chosen for estimating the hygroscopic variations due to felling date was to expose the samples to a direct contact with water (zürcher et al. 2012). a series of measurements was made using small rods from felled trees, previously air-dried under controlled conditions. they were all fixed (12 x 48 = 576 samples per site) by one end to a slab, the other end being immerged over a length of 5mm for 9 minutes in figure 7. variation of dry (andhydrous) densities of wood (sapwood) of spruce (picea abies) with felling period and moon phases, according to research done in different places and years. upper: tharandt 1996-97 (triebel 1998); freiburg i.br., 1997-98 (seeling and herz 1998, 2000); zürich, 1998-99 (bariska and rösch 2000) / lower: château-d’oex 2003-04 (zürcher et al. 2012) means waxing moon – waning, resp. château-d’oex 2003-04 around the full moon – before / after). waxing moon dates 1, 3, 5, 7; waning moon dates 2, 4, 6, 8. similar variations can be observed especially in the second half of the trial period, from december onwards (4). reminder: most of the technological properties of wood are closely linked to its density. 79water in trees – an essay on astonishing processes, structures and periodicities a bowl of water with ink as a dye. figure 8b shows the variations in absorption of water by capillarity in the samples taken during this experimental period. both the limitation of the lunar effect to the 4 winter months and the systematic and marked decrease in water absorption directly after the full moon are very similar to what was observed concerning initial water loss described above at figure 8a. it is noteworthy that for the reabsorption of water by capillarity, the mean amplitude of the decrease (25.9%) for the samples taken just after the full moon is comparatively much more pronounced than for water loss and is evident even for february. the second test method for quantifying the degree of hygroscopicity was applied by immersion of samples previously used for the determination of the density. in the same way, 576 cubic samples for each site (4 per tree, 12 for the felling date) were immersed in water at 20°c for 7 days. the absorption is expressed in this case as the percentage increase in mass. there too, systematic lunar variations in hygroscopicity occur, in obvious coherence with the loss of water. for the four months from november to february, the mean reduction between the days before the full moon and the days immediately after is 12.6%, half the value obtained for absorption of water by capillarity. these results show us that the reversible variations linked to the moon are not limited to the loss of water and the relative density (and shrinkage) in the course of drying: the phenomenon is even more marked for the absorption of water (by capillarity and by immersion) of previously dried wood samples. it should however be pointed out that these hygroscopic variations linked to the lunar cycles are much weaker than the differences due to the site and the type of forestry, since spruce samples from a naturally-regenerating mountain forest show much lower water absorption than those from a plantation. these encouraging results have to be confirmed by tests of durability before definitive conclusions can be made about spruce wood for outdoor use. it could nevertheless be expected that differences in the resistance to decay of spruce wood might follow the following rule: “low durability of wood cut not long before the full moon, because very hygroscopic; higher durability of less hygroscopic wood cut immediately after the full moon between november and february” – which would correspond to the oldest documented rule, written by the greek naturalist theophrastus (371–287 b.c), stipulating that the best construction timber is obtained when trees are felled in winter, in the first days after full moon. indeed, it is well known that woods whose fibres can be highly saturated by water are more easily attacked by fungi and xylophagous insects than woods with a comparatively low saturation level of their cell walls. implications and perspectives concerning periodicities this insight into lunar cycles detected in the plant world, and in particular in trees and their wood, shows a real phenomenon, which is additional to the exogenous rhythms of mostly solar origin whose action is well known, both on a daily and a seasonal level, and linked over the longer term to the cycle of sunspot activity, varying over an 11 year period. the moon modulates this principal exogenous rhythm on an hourly basis, through the gravimetric tides occurring with two high and two low tides per day, as well as over the week and the lunar figure 8a. variation of water loss during drying of spruce (picea abies) samples, comparing the felling dates occurring in the 3.5 days running up to the full moon (vvm), with those of felling occurring during the 3.5 days after the full moon (nvm), for the months of november 2003 (1), december (2), january 2004 (3) and february (4). the samples from before the full moon of november, december and january lost slightly more water than those from fellings performed after the full moon. values calculated from the general mean. figure 8b. variation of capillary water absorption by the dried spruce (picea abies) samples, comparing the felling dates occurring in the 3.5 days running up to the full moon (vvm), with those of felling occurring during the 3.5 days after the full moon (nvm), for the months of november 2003 (1), december (2), january 2004 (3) and february (4). the samples from before the full moon of november, december, january and february absorbed considerably more water than those coming from fellings performed after the full moon. values calculated from the general mean. 80 ernst zürcher month, according to the synodic, tropical, sidereal or anomalistic (perigee and apogee) cycle. it seems that the lunar rhythms become apparent when the influence of the sun is reduced, either naturally or due to an experimental set-up. what kind of forces are involved here? where the synodic and anomalistic rhythms are concerned, the gravitational force causing tides is too weak to explain even a tiny part of the lunar phenomena observed in plants: it is not more than 0.08 millionths of the force exerted by gravity on a mass situated at the surface of the earth. for the largest tree measured in europe, described by klein in 1908, a silver fir abies alba in the black forest (height 68m, diameter 380cm, bole volume 140 m3, weight estimated at 100 t), the tidal (gravitational) lunar force represents a light daily pull then relaxation of 8 grammes only – the weight of two sugar lumps! the variations of the geomagnetic field, weak but distinct, with a period of half a lunar day (12 hours 25 minutes), due to the gravimetric tides, present a similar situation. the french chronobiologist lucien baillaud (2004) points out quite rightly: “where the moon is concerned, the supporter […] wants to be shown the basis of the link between the moon and the living being, with a breakdown of how the phenomena fit together – or at least wishes us to suggest a hypothesis”. it seems to us more and more obvious, as has been mentioned several times, that this basis is none other than the essential element for every organic process: water. this was the direction of the conclusions of researchers working on the cyclic variations of certain chemical reactions in aqueous medium in controlled laboratory conditions, such as giorgio piccardi, joseph eichmeier or soco tromp. we should mention also the work of vladimir voeikov and emilio del giudice (2009) on the fluctuations of water in its electronic charge and its capacity to react with oxygen, bringing them to the concept of “ water respiration”. already in the 1920s, experiments had been performed on the variations in surface tension of water using extremely fine glass capillary tubes, where the frequency of drop formation was observed (maag 1928). they demonstrated lunar rhythmicities (monthly, but also daily) appearing as soon as the capillaries became fine enough, showing then the effect of certain planetary conjunctions. meanwhile, it was observed that when it is in capillary systems, either of glass or organic like plant cells (with their vacuole and their partially porous membrane), water undergoes an important change in its properties, like for example the ability to remain liquid at temperatures as low as – 15°c. it would be interesting to analyse again the effect of the ‘time’ factor on these essential properties of water using modern technologies. a relatively recent double publication in theoretical physics by gerhard dorda (2004), co-author with von klitzing of the discovery of the “quantum hall effect”, winner of the nobel prize for physics 1985, puts forward a new astro-geophysical model of the role of gravitation in living processes. this model integrates static and dynamic aspects of gravitation according to the orbital movement of celestial bodies, leads to a ‘quantisation’ of gravitation and of time, and demonstrates a reversible effect linked to the sun on one hand and to the moon on the other, on the supra-molecular structure of water. this model leads to the determination of reversible states of aggregation or coherence (‘clusters’) of water, in a quantitative ratio of a considerable size, from 1 to 2200, according to whether the interaction involved is sun-earth or moon-earth, the latter being modulated by the lunar day, but also according to the waxing/waning phase. dorda considers that this rhythmic fluctuation of water in a system with 3 celestial bodies, constitutes the biological clock sought up to now in organic structures. this model was validated independently thanks to experimental measurements already published by mario cantiani et al. (1994) and interpreted in keeping with lunar chronobiology by e. zürcher, m.-g. cantiani, f. sorbetti-guerri and d. michel in 1998. martial rossignol and his colleagues, some years before (1990), highlighted the role of electromagnetic phenomena linked to lunar cycles (polarisation of light, modulation of wavelength, ionisation of the atmosphere, atmospheric pressure) and considered a possible link with the induction of bio-electric potentials at the cell level. not long after, in 2004, philippe vallée devised a new experimental method for proving in a reproducible manner that weak, low-frequency electromagnetic fields have a durable effect on water. this researcher stresses the importance of interfaces between water and its solid or gaseous inclusions: an essential aspect, since interfacial water plays a fundamental role in the organic world. and now, a new scientific sensation has just come out, and brings an essential component to reinforce the hypotheses formulated here: ‘the fourth phase of water’ (pollack 2013). the discovery and the demonstration of a “liquid crystal” phase of water in contact with hydrophilic membranes with dielectrical properties (wood corresponds to these criteria) allows pollack to explain a whole series of ‘anomalies’ of water which were until now unexplained, and to open horizons beyond expectation. 81water in trees – an essay on astonishing processes, structures and periodicities all these discoveries and interpretations on a purely physical level do not however provide a reply to the question of why differences are observed between certain living plant species, both annual and woody, in their physiological reactions to lunar cycles and the behaviour of their wood. indeed, trials on germination and initial growth have shown that simultaneously growing plants of different species are actually impacted by the factor “moon”, but in counterphase, some species being positively stimulated of days before the new moon, while others start their growth better in days before full moon (zürcher 1992). endangered global context the described processes, structures and periodicities probably play a major role in the water cycles activated by forests, especially in equatorial zones. the last ones are probably of much higher existential importance for the life on earth than commonly admitted. trees produce clouds, but forests make also their own rain. be it above the amazonian tropical forest or boreal coniferous forests, the formation of clouds and the rainfall that follows happen thanks to a form of ‘seeding’ by micro-particles of organic origin. the gaseous substances given off by the trees, volatile organic compounds, undergo a photochemical condensation caused by light and behave as ‘cloud condensation nuclei’. mushroom spores, pollen grains and microscopic vegetable debris which are also given off into the atmosphere have the same effect (pöschl et al. 2010; ehn et al. 2014). it is then easy to imagine that the rain regime could dramatically change if the forest cover should be reduced, not only because of then lacking “cloud producers”, but also because of the absence of “rain provokers”. in his description of the geoclimatic role of the amazonian forest, peter bunyard (editor of the british journal the ecologist, 2015) draws attention to the new geoclimatic model developed by victor gorshkov and anastassia makarieva, of the department of theoretical physics of the institute of nuclear physics of saintpetersburg (2007, 2014). the analysis of the climatological and hydrological data leads them to the conclusion that it is not the movement of air masses which set off the hydrological cycle (the generally accepted model up to now), but on the contrary the changes in phase of the water in the atmosphere above forests which bring about the movement of air masses. indeed, water needs considerable energy to evaporate from forests (around 600 calories per gramme, depending on temperature and atmospheric pressure), and it returns this energy as heat in the high atmosphere when it condenses to form rain. thus, the extreme impact of solar radiation around the equator is absorbed, thanks to the ecosystems rich in water and biomass found in these zones of the globe. in parallel, the rapidity of the condensation process compared to the slowness of the evapo-transpiration creates a pressure difference with a suction effect. the amazonian forest thus acts like a gigantic hydrological heart (‘biotic pump’), attracting air masses from the atlantic and enriching them in water, performing half a dozen cycles of evapo-transpiration – precipitation, moving from east to west, and finally rising in the andes and moving north (central and north america) and south (argentina) giving rise to warm rains in latitudes far from the equator. the tropical forests can therefore be seen as components of the biosphere ensuring both the functioning and the stability of the great geoclimatic water cycle. in this context, the researchers bring to light another essential phenomenon: if a coastal zone is deforested over a width of 600 km or more, the masses of humid ocean air can no longer move inland, thus condemning their forests to perish. references alexandersson, o. 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(2012): reversible variations in some wood properties of norway spruce (picea abies karst.), depending on the tree felling date. in: spruce: ecology, management and conservation. eds. nowak ki and strybel hf. nova science publishers, hauppauge, new york 2012; 75-94. zürcher, e., schlaepfer, r., conedera, m., giudici, f. (2010): looking for differences in wood properties as a function of the felling date: lunar phase-correlated variations in the drying behavior of norway spruce (picea abies karst.) and sweet chestnut (castanea sativa mill.). trees (2010) 24: 31-41. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 3(1): 139-152, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-211 citation: b.f. ronalds (2019) bringing together academic and industrial chemistry: edmund ronalds’ contribution. substantia 3(1): 139-152. doi: 10.13128/substantia-211 copyright: © 2019 b.f. ronalds. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds university of western australia, australia e-mail: beverley.ronalds@gmail.com abstract. born 200 years ago, edmund ronalds (1819–1889) obtained his doctorate in germany under liebig, became a professor at queen’s college galway and ran the little-studied but significant bonnington chemical works in edinburgh. his few mentions in the modern literature relate generally to the legacies of his actual and assumed academic supervisors of renown, yet his hitherto unknown mentors included family members and the important chemists graham, magnus, tennant and tennent. the novelty of his shift from university to manufacture has also been noted. with the aid of little-known primary sources, this biography details the evolution of ronalds’ career, exploring the context and influences for his diverse accomplishments and in particular the new and successful ways he bridged academia and industry through technological education and industrial research. keywords. chemical technology, coal-tar processing. upbringing and education (1819-1842) edmund ronalds, the eldest of at least twelve children, was born on 18 june 1819 at “no 1 canonbury square islington”, which then denoted the house on the west end of the partially-completed square (figure 1).1 his father edmund sr had lived his early years just down the road in canonbury place and now ran the family’s large wholesale cheesemonger business in upper thames street, london.2 edmund’s mother eliza jemima was the only daughter of james anderson,3 a scot who graduated from the university of edinburgh and was awarded a doctor of laws there in 1794.4 he ran a respected academy at mansion house in hammersmith offering a broadbased and vocationally-oriented curriculum.5 1 the address of the house is given in ronalds’ birth registration at dr williams’s library (now in the national archives) and its location can be discerned from the extended series of rate books held at the islington local history centre. 2 b. f. ronalds, sir francis ronalds: father of the electric telegraph, imperial college press, london, 2016. 3 gentleman’s mag. 1818, 88:2, 178. 4 register of laureations in the university of edinburgh m.dlxxxvii–m.dccc. 5 n. hans, new trends in education in the eighteenth century, routledge, london, 2001, p. 111. 140 beverley f. ronalds the family soon after moved to brixton hill, “nearly opposite the telegraph”,6 where edmund fell seriously ill7 and a number of his siblings died. as a result, his surviving brothers were more than thirteen years his junior. despite the spread of ages, it was a close and happy family, with later letters reminiscing of their “merry and boisterous” evenings.8 they sang and played music together and conversation was informed by well-rounded education and their parents’ friendships. christmas day was often spent with the martineau family:9 edmund’s aunt had married peter martineau, through whom they met his cousin, the sociologist harriet martineau. edmund sr and eliza’s associates included the early socialists and educational reformers robert owen and fanny wright. edmund’s brothers attended from about age five an “admirably-kept” preparatory boarding school10 and his own education would have commenced in a similar manner, while his sisters were described by associates as “well educated” and read several languages.11 the ronalds family being dissenters – of the unitarian faith – could not graduate from the english universities cambridge and oxford. students of the first secular institution, university college london, were not awarded degrees until 1839. any continuation of edmund’s studies of this kind would necessarily be undertaken elsewhere. his obituaries noted that he spent 6 e. ronalds to r. owen, 7 september 1829(?), robert owen collection, national co-operative archive, manchester, roc/17/31/1. 7 j. lawe to e. ronalds, 24 october 1834, ronalds family papers, harris family fonds, western archives, western university, london, ontario, canada (hereafter wu), b1450. 8 h. ronalds to e. ronalds, 28 march 1854, alexander turnbull library, wellington, new zealand, qms-1719 (hereafter atl). 9 s. flower, great aunt sarah’s diary 1846–1892, printed privately, 1964, p. 45. 10 england census, 1841; edmund yates: his recollections and experiences, vol. 1, richard bentley, london, 1884, p. 35. 11 g. h. scholefield, ed., richmond-atkinson papers, vol. 1, nz government printers, wellington, 1961, p. 473. time in “giessen, jena, berlin, heidelberg, zurich, and paris”,12 a list that would have been provided by someone who knew him well. his entry in the dictionary of national biography and all but one of these obituaries (that written by his friend john young buchanan who lived near his widow and children) prefixed the descriptor “successively” to the names and, as a result, inaccurate assumptions have been made as to the identity and timing of his professors. the list is actually in a decreasing order of importance, based on such factors as stage in his education and length of attendance, and thus largely in reverse chronological order. edmund probably commenced his university studies in paris as, like others in the family, he was most comfortable in french. years later he edited a booklet for his uncle sir francis ronalds in that language; sir francis – who was knighted for developing the first working electric telegraph – was a key influence for him and the two were always close and mutually supportive.13 once edmund was sufficiently confident living abroad, and had shown his potential, he headed to the german regions and their renowned academics. his teacher at heidelberg could not have been robert bunsen as has on occasion been presumed,14 as bunsen was then elsewhere and ronalds would still have been taking general courses. in late 1838 a family associate, the unitarian diarist henry crabb robinson, organised a letter of introduction to his botanist friend professor friedrich siegmund voigt at the university of jena. ronalds matriculated at this university on 29 april 1839 and remained three semesters, his major subject being philosophy with jakob friedrich fries.15 he had a break at home in april 1840, during which he was invited to breakfast with robinson. his host, although admitting he did not understand science, noted in his diary that he “was pleased with him”.16 ronalds moved to the university of berlin later in 1840 for the next three semesters.17 he told his uncle sir francis that there it was gustav “magnus the professor of physicks & technology in whose laboratory i worked or rather idled a good deal of time”, although he did 12 proc. r. soc. edinburgh 1889–1890, 17, xxviii; j. chem. soc. trans. 1890, 57, 456; proc. inst. chem. 1890, 14, 53. 13 ronalds, sir francis ronalds. 14 george ronalds (unrelated to edmund) studied with bunsen at heidelberg in the 1850s. see j. t. krumpelmann, jahrbuch für amerikastudien 1969, 14, 167. 15 university archives jena, bestand ba, no. 815/9; bestand g, abt. 1, no. 67–72. 16 h. c. robinson, diaries, 29 april 1840, dr williams’s library, london, with permission from the trustees. 17 amtliches verzeichnis des personals und der studierenden der königlichen friedrich-wilhelms-universität zu berlin, berlin, 1840–1841, 1841, 1841–1842. figure 1. locations of ronalds’ two homes in canonbury, islington. source: titheable lands in the parish of saint mary islington, 1849, london metropolitan archives dl/ti/a/029/a. by permission of the bishop of london and the london diocesan fund. 141bringing together academic and industrial chemistry: edmund ronalds’ contribution not neglect magnus’ colleague heinrich rose, whom he called “the great analytical chemist of the age”.18 it is of note that he was now orienting towards “technology”; this was already an academic field in germany, associated with cameralism – administrative sciences promoting efficient stewardship of economic activity for the benefit of the state.19 a short stay with magnus’ friend justus liebig at the university of giessen formed the capstone of his formal education: he enrolled on 7 may 1842 and was awarded the degree of doctor of philosophy less than three months later on 2 august 1842.20 he mentioned just these last two professors – liebig and magnus – and their laboratories in a brief statement of experience on his later professorial appointment.21 ronalds’ thesis, which contributed to liebig’s agricultural and physiological chemistry studies, addressed the analysis of wax by oxidation. he found that a crystalline material was produced after an extended reaction time with nitric acid; this proved to be succinic acid, which has biological functions. the work was published immediately in liebig’s journal under ronalds’ name, abstracted in pharmaceutisches central-blatt, and quickly referenced by charles gerhardt, bernhardt lewy and liebig himself in subsequent papers.22 the extent of his education and its subject matter indicate the family’s affluence. when he embarked on his university training, there were few academic positions in chemistry in britain (and even fewer for dissenters) and these were not always salaried. it was largely his share of the family’s accumulated wealth that would enable him to pursue his scientific interests while supporting a sizable future family and maintaining his accustomed lifestyle. sir francis had chosen this life of “gentleman scientist”, determining his own research priorities and only taking on roles in an honorary capacity. sir francis’ “chief amusement” in his youth had been chemistry.23 the family’s religious and moral values in addition emphasised the application of knowledge acquired 18 e. ronalds to f. ronalds, 19 june 1858, institution of engineering and technology archives (hereafter iet), 1.9.1. see: a. w. hofmann, allgemeine deutsche biographie 1884, 20, 77. 19 e. schatzberg, technology: critical history of a concept, ucp, chicago, 2018, p. 77–81. 20 f. kössler, register zu den matrikeln und inscriptionsbüchern der universität giessen 1807/08–1850, universitätsbibliothek, giessen, 1976, p. 155; kössler, verzeichnis der doktorpromotionen an der universität giessen von 1801–1884, universitätsbibliothek, giessen, 1970, p. 84. 21 galway vindicator, 11 august 1849, 2. 22 e. ronalds, ann. chem. 1842, 43, 356. summarised in pharmaceutisches central-blatt 1842, 2, 926. 23 f. ronalds to s. carter, 21 february 1860, university college london (ucl) special collections, gb 0103 ms add 206. to bring benefit for society;24 this ethos is apparent throughout ronalds’ career and is a central theme of this paper. the last two supervisors he chose were known for their laboratory-based teaching and gave him a strong grounding in practical science. aided by his doctorate, a path in analytical consulting was thus also open to him. by way of example, edmund sr’s cousin silvanus ronalds was chemical operator and a consultant with the society of apothecaries.25 another possible avenue was the growing manufacturing sector. various members of his extended family were largescale industrialists – his uncle peter martineau owned and ran a sugar refinery.26 ronalds was to pursue all these options in the course of his career. academia (1842-1856) in london immediately after completing his thesis, ronalds returned home to his family, who were now living at a property of three acres called the grove at the east end of canonbury place; its location is shown in figure 1. liebig visited him there right away – in mid-august 1842 – at the commencement of a trip around england, and kept his luggage there.27 liebig then met up with thomas graham, chemistry professor at university college, before heading to the regions. a cousin reported the next step very soon afterwards. ronalds had “most fortunately met with a situation exactly suited to him as assistant to a mr graham the first chemist in london which will occupy him from 11 oclock to 5 every day and be the means of introducing him to become a popular man himself if he makes good use of the advantages he now enjoys”.28 liebig must have been complimentary about ronalds’ abilities. sir francis could also have provided a recommendation to graham: they knew each other quite well,29 in part through their shared interest in the kew observatory that sir francis was beginning to set up for the british association for the advancement of science (baas). just as his cousin recommended, ronalds used every opportunity to meet other chemists and be helpful. graham having begun his career in glasgow, there 24 ronalds, sir francis ronalds, pp. 53–54, 93–94. 25 a. e. simmons, the chemical and pharmaceutical trading activities of the society of apothecaries, 1822 to 1922, ph.d. thesis, the open university, uk, 2004. 26 b. f. ronalds, martineau society newsletter 2018, no. 41, 10. 27 j. volhard, justus von liebig, vol. 1, verlag, leipzig, 1909, p. 160. 28 m. ronalds to h. ronalds, 12 october 1842, wu, b2284. 29 ronalds, sir francis ronalds, p. 546. 142 beverley f. ronalds was a steady stream of scots to his laboratory. he was the founding president of the chemical society of london and the cavendish society,30 and ronalds joined both immediately, becoming a council member of the latter. another original member of these organisations was john tennent, denoted erroneously at times as “tennant”.31 both johns – tennent and tennant – had grown up in the glasgow area, studied chemistry under thomas thomson (as had graham)32 and became chemical manufacturers, and both would be prominent in ronalds’ future. the two men have been confounded over the years. for example, the chemical society’s jubilee album featuring its founding members contains tennant’s rather than tennent’s portrait.33 tennant (1796-1878) was the managing director of the “gigantic” charles tennant & company established by his father, with its st rollox chemical works that made bleaching powder.34 tennent (1813–1862) was the son of barbara née graham and hugh tennent, who helped run the famous tennent brewery. it was apparently the tennent family who sold the land for st rollox to the tennants.35 john tennent and john tennant partnered in the bonnington chemical company in 1847, with the former being the manager of the facility.36 there was in addition a strong network of alumni from the universities ronalds had attended. former giessen students edward frankland and robert angus smith both asked him to be a referee when they applied for the professorship at owens college, manchester.37 ronalds also hosted numerous visitors that he had met abroad. within weeks of arriving home, he had as guests “2 young hungarians who could not speak one word of english but they were very animated & agreeable, both professors”.38 fortunately several family members could contribute to the conversation in german. liebig visited again in 1844. it was graham who took him to visit sir francis at the kew observatory on 4 september39 and both also went to the baas annual 30 w. h. brock, ann. sci. 1978, 35, 599. 31 see for example: proc. chem. soc. 1842, 1, 1. 32 r. d. thomson, edinburgh new philosophical j. 1853, 54, 86. 33 jubilee of the chemical society of london, chem. soc., london, 1896, p. 24. 34 glasgow herald, 18 april 1878, 4. 35 tennent family trees, university of glasgow archive services, gb 248 t 13/1; g. stewart, curiosities of glasgow citizenship, james maclehose, glasgow, 1881, p. 239. 36 j. a. anderson, bonnington chemical works, 1851, national records of scotland (hereafter nrs), cs313/946; proc. chem. soc. 1868, 21, xxix. 37 e. ronalds to e. frankland, 10 may 1850, papers of sir edward frankland, special collections, university of manchester, rfa ou mf 01.03.0900. 38 e. ronalds to h. ronalds, 2 october 1842, wu, b558. 39 kew observatory diary and accounts, 1844, national meteorological meeting at york. this was the first baas conference that ronalds and his uncle attended,40 and he would have been proud to be associated with these mentors while meeting more of their associates. in 1851 liebig visited him in galway.41 ronalds became a member of the baas in 184642 and, slowly gaining confidence, contributed increasingly to the technical discussions there.43 he served as secretary of the chemical science section at the 1852 meeting held in belfast and later as section vice-president at edinburgh in 1871 and sheffield in 1879. this was perhaps one of the ways he kept in touch with magnus, who also visited him, his uncle and the kew observatory on a trip to england.44 ronalds in addition translated and summarised papers by his colleagues (as well as liebig’s) for publication in english journals.45 already he had mix of experiences relevant for his later career path across academia and industry. he had started with a sojourn in germany, where he received the best practical chemistry training in a culture of science utilisation, along with numerous contacts and associated kudos. he was now active in the overall chemical profession at its hub in his london hometown, with its links to commerce and government. he had friends and family from glasgow and edinburgh, important industrial centres that had close connection with their universities, and he was interacting with other chemists and industrialists at the baas. these built on the foundation of his unitarian circle with its accent on societal benefit through education. although the groupings overlapped significantly, as bud and roberts have illustrated through lyon playfair and others, ronalds was unusual in having the influence of all of these education-practice networks early in his academic career.46 he now determined to develop his teaching skills and was soon giving lectures in london and further afield. on 19 february 1845, for example, he lectured on “chemical principles of gas manufacture” at the derby mechanics’ institution and he taught at a school in worksop, near sheffield, that had a chemical laboratory.47 beginning in october 1845 he gave lectures at the library and archive, exeter. 40 ronalds, sir francis ronalds, p. 336. 41 e. k. muspratt, my life and work, john lane, london, 1917, p. 36. 42 report of the 59th meeting of the british association for the advancement of science, john murray, london, 1890. 43 for example: annual of scientific discovery: or, year-book of facts in science and art, gould and lincoln, boston, 1850, pp. 207–08; daily news, 9 september 1852, 3. 44 e. ronalds to f. ronalds, 19 june 1858. 45 for example: philos. mag. 1846, 28, 161, and 29, 25, 31. 46 r. bud, g. k. roberts, science versus practice: chemistry in victorian britain, mup, manchester, 1984. 47 derby mercury, 15 january 1845, 2; muspratt, my life and work, p. 143bringing together academic and industrial chemistry: edmund ronalds’ contribution aldersgate school of medicine through the winter session and offered practical classes three days per week – this increased to four days the following year.48 he was additionally lecturing regularly at the middlesex hospital school of medicine and offering “private instruction in chemical manipulation and analysis… at the laboratory of the hospital school” there.49 the latter was affiliated with the nearby university college. his role as “lecturer on chemistry at the middlesex hospital” was a continuing appointment and he began to use it as his affiliation for publications and in societies. the chemical laboratory was available to him to conduct consulting activities and research. he quantified the copper content of ores provided by the australian mining company from their proposed tungkillo mine near adelaide, and published the results in the literature.50 mining continued there for some years. he also devised and performed tests to assist medical questions. he discovered taurine in human bile, which was announced in the chemical gazette by his giessen friend william francis (who was later a partner in taylor and francis publishers).51 links between the impurities in water and its utility were beginning to be considered in this period and he undertook water quality analyses in several locations. these included the water supply for the new railway town of wolverton, to help determine the best treatment for ailments experienced by residents, and spring water from the colne valley near watford that was proposed to be pumped to hampstead.52 he also studied how the amount of organic matter taken up by water from peat increased with its temperature.53 on 18 june 1846 golding bird, a physician at guy’s hospital, read a paper by ronalds to the royal society. he had shown in what was viewed as “a series of welldevised experiments”54 that urine contained sulphur and phosphorus in both unoxidised and oxidised states and quantified the amounts in 24-hour urine tests. the higher unoxidised sulphur in a diabetic patient illustrated the potential use of the results in diagnosis. the article was included in the philosophical transactions and repub36. the school was founded on johann pestalozzi’s educational philosophy, with which ronalds’ aunts had strong links, and the principal dr benjamin heldenmaier was active in the derby mechanics’ institution. 48 morning chronicle, 22 september 1845, 5; lancet 1845, 46, 339; lancet 1846, 48, 345. 49 exeter gazette, 19 september 1846, 2; athenæum 1846, 1009; lancet 1847, 50, 361. 50 e. ronalds, chemical gazette 1846, 4, 463. 51 chemical gazette, 1846, 4, 281, 295; lancet, 1848, 52, 335. 52 g. corfe, pharmaceutical journal and transactions 1849, 8, 30, 71; morning post, 11 january 1850, 5. 53 q. rev. 1850, 87, 479. 54 g. day, half-yearly abstract of the medical sciences 1847, 5, 285. lished in the philosophical magazine and german journals.55 the results were quickly picked up in summaries of medical advances and in pathology lectures and continued to be referenced into the twentieth century.56 with his reputation growing, ronalds (figure 2) was given the opportunity to undertake two significant projects. becoming secretary of the chemical society, he was the inaugural editor of its first journal. he was responsible for the first two volumes of the quarterly 55 e. ronalds, philos. trans. r. soc. london 1846, 136, 461. also in: philos. mag. s3 1847, 30, 253; journal prakt. chem. 1847, 41, 185; notizen aus dem gebiete der naturund heilkunde 1847, 3, 214. 56 for example: a. b. garrod, lancet 1848, 52, 441, 469, 599; sci. am. 1869, 21, 249; j. j. rae, biochem. j. 1937, 31, 1622. figure 2. edmund ronalds, photographed in may 1878 by george shaw in edinburgh. source: sir george grey special collections, auckland library, new zealand, nzms 1235. 144 beverley f. ronalds journal published in 1849 and 1850, and received an honorarium of £50 each year. he incorporated a list of all papers published in chemistry locally and overseas and prepared abstracts of interesting papers appearing in foreign language journals.57 when he retired to move to galway, henry watts was employed as a paid editor but, unlike ronalds, his name did not appear on the title page. chemical technology the other project was a large book. friedrich ludwig knapp, professor of technology at the university of giessen, was preparing a text called lehrbuch der chemischen technologie and it would have been his brother-in-law liebig who invited two of his past students, ronalds and thomas richardson, to translate it into english. the preface to the first volume of their edition bore the same date of 1847 as knapp’s work and so they must all have been working in concert. in the english publication, entitled chemical technology; or, chemistry applied to the arts and to manufactures, knapp was denoted as the author and it was “edited with numerous notes and additions” by ronalds and richardson; it was of credit to ronalds to be the first-named of these two authors so early in his career. their additions to the book included “excellent” figures58 to give a total of over 550 illustrations. knapp’s first volume covering fuel, alkalies and earths was split into two, both appearing in 1848, and their third volume on food was completed in 1851.59 they formed part of a new library of illustrated standard scientific works published by hippolyte bailliere in london. although ronalds downplayed the academic rigour of the book, calling it before it appeared “a merely popular treatise”,60 its research would have deepened his technical knowhow across the breadth of british chemical manufacture. colleagues and family members like tennent, tennant and martineau who owned processing plants offered assistance and in return benefited from the resulting amalgamation of current scientific thinking with industry best practice and trends. reviews in the press were very positive. the opinion of the athenæum was that “to the manufacturer this publication must prove eminently useful” and it is also 57 r. s. cahn, proc. chem. soc. 1958, 157. 58 sci. am. 1855, 11, 112. 59 f. knapp, e. ronalds, t. richardson, chemical technology; or, chemistry applied to the arts and to manufactures, bailliere, london, 1848– 1851. 60 e. ronalds to l. l. dillwyn, 20 september 1848, swansea university archives, gb 217 lac/26/d/55. “most valuable as one of general reference”.61 the economist highlighted “the good judgment of the translators, who have… done a great service to the public”. “scientific knowledge… is explained in a simple manner” while “scientific men will hail with delight the quantity of practical information”. “it is a book for everybody”.62 even the lancet gave a page-long review. overseas, scientific american called it a “great work” while the journal of the franklin institute wrote that “the english editors have also performed their task with talent and faithfulness, as is evidenced by the large and judicious additions which they have made, describing british inventions and improvements, and giving us the latest results of british science and ingenuity”.63 an american edition of the first two volumes was quickly published in which walter rogers johnson made further additions emphasising us industry.64 there was initially little mention of the potential value of the book in formal education. the authors had lamented in their preface the lack of higher education establishments with a technical emphasis. chemist george wilson was the first professor of technology in britain and he explained in his inaugural lecture in edinburgh in 1855 that “the word technology has been introduced into our language” through the book.65 subsequent assessments suggest comparable conclusions on the text’s novelty and significance.66 “technology” has a greek etymology and, because it was then in few dictionaries, was described by the authors as “the systematic definition (λογος) of the rational principles upon which all processes employed in the arts (τεχνης) are based”; (after coming into use its meaning altered in the twentieth century as described by schatzberg).67 their focus was thus a framework to aid understanding, use and development of plant processes, equipment etc. chemical technology can be considered to be a key early emphasis outside western europe on a distinct educational discipline of chemistry application for industry.68 ronalds and richardson soon began work on an updated edition of chemical technology. this became 61 athenæum 1849, 321. 62 economist, 2 december 1848, 1364. 63 sci. am. 1852, 7, 221; j. franklin inst. s3 1848, 15, 449. 64 johnson’s career is described in: g. e. pettengil, j. franklin inst. 1950, 250, 93. 65 g. wilson, what is technology? sutherland and knox, edinburgh, 1855. see also: r. g. w. anderson, br. j. hist. sci. 1992, 25, 169. 66 schatzberg, technology, pp. 81–82, 91–94; j. m. van der laan, narratives of technology, springer, new york, 2016, pp. 25–27; r. p. multhauf, the history of chemical technology: an annotated bibliography, garland, new york, 1984; bud, roberts, science versus practice, p. 108. 67 e. schatzberg, technology and culture 2006, 47, 486. 68 w. schneider, neue deutsche biographie 1979, 12, 151. schatzberg, technology, p. 81. 145bringing together academic and industrial chemistry: edmund ronalds’ contribution essentially a new work, much rewritten and enlarged. they were now the named authors, but noted that it “incorporated a revision of dr knapp’s “technology””. the text needed to be further divided, and the first two volumes covering fuel and its applications were published in 1855. they also received strong reviews, the american journal of science calling it “by far the most full, scientific and satisfactory exposition of the subjects of fuel and illumination to be found”.69 ronalds’ priorities changed abruptly in this period, as explained below, and he stepped aside after these two volumes. richardson and his new co-author henry watts completed the material on acids, alkalies, and salts in 1867, which is the year richardson died.70 that it took twelve years to issue these later books hints at the scale of ronalds’ contribution to the earlier ones. the volume on food was not updated. the overa ll book “ became a standard work ” internationally;71 it was still advertised for sale in the chemical news in the 1870s. material was commonly quoted in other texts72 and is referenced today in histories of the chemical industry to explain nineteenth-century processes.73 it stood the test of time for over thirty years. watts had begun preparing an update before his death in 1884 and charles edward groves, who replaced him as editor of the chemical society’s journal, then took on the role of general editor for a new edition with oversight of numerous authors.74 the first volume emerged in 1889 – the year ronalds died – followed by three more in the period to 1903. the preface erroneously described them as being founded on richardson and watts’ work but in fact they covered only fuel and lighting and thus used ronalds and richardson’s volumes as their basis. this edition also received good reviews and maintained the strong reputation of the title. it is of interest that editors of the chemical society journals played a leading role in all the versions. chemical technology featured increasingly in university education over time. it was included in the rec69 am. j. sci. arts s2 1856, 22, 149. 70 e. ronalds, t. richardson, h. watts, chemical technology; or, chemistry in its applications to the arts and manufactures, bailliere, london, 1855–1867. 71 “richardson, thomas (1816–1867)”, oxford dictionary of national biography. 72 muspratt, for example, referred to “the valuable treatise” numerous times in his chemistry, theoretical, practical & analytical, william mackenzie, glasgow, 1860. 73 for example: c. a. russell, chemistry, society and environment: a new history of the british chemical industry, royal society of chemistry, cambridge, 2000. 74 w. h. brock, the case of the poisonous socks: tales from chemistry, royal society of chemistry, london, 2011, p. 247. ommended library list published by the canadian journal of education as early as march 1854.75 ronalds presented the 1848–1851 edition to the queen’s college galway library and subsequent versions were acquired by the college as well. the 1855–1867 and 1899–1903 editions are held by innumerable universities around the world and kikuchi has outlined how they would have been used in teaching.76 putting this progression into context, university chairs in chemical engineering were only established in the early twentieth century.77 in galway non-denominational higher education had commenced in ireland in 1849 with the creation of the queen’s university of ireland, which awarded degrees for the new queen’s colleges of belfast, cork and galway. these offered academic positions for which a dissenter like ronalds was eligible and he was appointed as the inaugural chemistry professor at galway at age thirty. his salary would be £200 plus additional student fees.78 he asked sir francis to dine with him in canonbury on 14 october 1849 to say farewell, along with graham, and also thomas andrews, who was the first vice-president of queen’s college belfast. he suggested his uncle’s “advice about the purchases of physical apparatus would be of service to the irish colleges”.79 ronalds and his sister left london immediately afterwards and were in galway in a week.80 he gave his introductory chemistry lecture on 11 december.81 impatient to begin in earnest, he complained to sir francis the next february that “the intolerably dawdling habits of all workmen in this place has prevented me from yet getting to work in the laboratory. i do not think i shall be able to begin my course for some weeks”.82 once up and running, he delivered up to 140 lectures each year at the college, around 40 being in practical chemistry in the laboratory,83 and “he was 75 journal of education for upper canada, 1854, 7, 33. 76 y. kikuchi, history of science 2012, 50, 289. see also: anglo-american connections in japanese chemistry: the lab as contact zone, palgrave macmillan, new york, 2013, p. 44. 77 c. divall, s. f. johnston, scaling up: the institution of chemical engineers and the rise of a new profession, kluwer, dordrecht, 2000. 78 a. j. ryder, an irishman of note: george johnstone stoney, printed privately, 2012, pp. 89–92. 79 e. ronalds to f. ronalds, 12 october 1849, iet, 1.3.332. 80 freeman’s journal, 23 october 1849, 2. 81 galway vindicator, 28 november 1849, 3. 82 e. ronalds to f. ronalds, 9 february 1850, iet, 1.3.362. 83 see for example: report of the president of queen’s college, galway, for the academic year 1852–53, hmso, dublin, 1854, p. 7; and, for the year 1856, 1857, p. 4. 146 beverley f. ronalds remembered as a successful and inspiring teacher”.84 his first course outline and examination questions survive in the college calendar.85 in 1854 he was able to take on edward divers as an assistant to help with the demonstrations. giving his new affiliation on the title page of chemical technology would have been a welcome boost to the reputation of the embryonic university. it was formally listed as a course textbook by ronalds’ successor.86 teaching of “chemistry applied to the arts and to manufactures” began to receive attention at various colleges from around mid-century, and galway is an early example that has gone unnoticed in previous analyses of this curricular development. with his authorship and german education, ronalds’ approach was presumably more rational and balanced than efforts elsewhere in britain, which matured only very slowly as alluded to above. donnelly and others have discussed how this was in part because academics argued that their preferred “pure” chemistry was what industry needed, hinting at an academic elitism that appears again below. the technology chair at edinburgh lapsed with wilson’s death in 1859 for similar reasons.87 ronalds suffered the disadvantage however of galway having limited manufacturing industry and thus needing to rely on the book to illustrate how different chemical processes could be deployed at scale.88 he pursued other teaching opportunities as well. he gave a course of nine public lectures illustrated by “a series of beautiful and highly-successful experiments” under the auspices of the board of trade and the royal galway institution. the press was most complementary about “the able and talented lecturer” – “we have never attended any lectures with more pleasure”. one commentator did regret however that he “does not avail himself of the opportunities… of directing the attention of the hearers to that great and almighty being”.89 this was a reflection of widespread antipathy towards the new “godless colleges”.90 84 dictionary of irish biography, vol. 8, cup, cambridge, 2009, pp. 597– 98. 85 calendar of queen’s college, galway, hodges and smith, dublin, 1851. 86 see for example: report of the president of queen’s college, galway, for the academic year 1863–64, hmso, dublin, 1865, p. 22; and, for the year ending 31st march, 1867, 1867, p. 24. 87 j. f. donnelly, social studies of science 1986, 16:2, 195; j. f. donnelly, history of education 1997, 26:2, 125; bud, roberts, science versus practice; schatzberg, technology, pp. 64–65; j. f. donnelly, chemical education and the chemical industry in england from the mid-nineteenth to the early twentieth century, ph.d. thesis, university of leeds, uk, 1987; anderson, br. j. hist. sci. 88 kikuchi, history of science. 89 galway vindicator, 10 february 1855, 2; 5 may 1855, 2. 90 j. o. ranelagh, a short history of ireland, 3rd ed. cup, cambridge, 2012, p. 141. he quickly adopted a priority of investigating local natural resources with a view to possible new and enhanced industries for the area, which had suffered terribly during the recent potato famine; the results would also have informed his lectures. he analysed peat found in different situations in galway, including the quantity and composition of its ash and how the water content varied with drying method, both of which affected its value. the results were summarised in chemical technology (1855), repeated almost verbatim in the 1889 edition and continued to be quoted into the next century.91 he had earlier studied the ash of several coals and these data were included in both editions of the book as well. he also analysed a peat fertiliser and fungicide for a new company.92 he later donated “specimens illustrative of the products of the destructive distillation of wood, bones, and coal, &c” to the museum of irish history in dublin.93 the irish press was delighted to announce in september 1852 that “the eminent authoress” harriet martineau was “on a visit with dr. ronalds”.94 she described in the national daily news and in her subsequent book that the “professor of chemistry” attempted to demonstrate how the local red seaweed could be burnt to produce iodine and potash salts to supplement its traditional use as a fertiliser.95 the locals, after accepting his advance payment to conduct a trial, apparently declined to participate. the new industry did develop however and continued into the twentieth century.96 she also highlighted work he presented to the 1852 baas meeting on the oil of the basking shark, which was found off the bay of galway. the fish contained large quantities of a very light oil and ronalds emphasised its unusual and valuable properties, including its bright flame and possible medicinal uses, in the hope that the fishermen might obtain a higher price for it in new applications. the results were summarised in the athenæum, published in the chemical gazette and included in chemical technology and other texts.97 he also advised sir francis in this period on oil lighting for the continuously-recording cameras he had developed. in return he later teased his uncle that he “may possi91 w. a. kerr, peat and its products, begg, kennedy & elder, glasgow, 1905, p. 27. 92 galway vindicator, 28 august 1852, 3. 93 fourth report of the department of science and art, hmso, london, 1857, p. 94. 94 freeman’s journal, 3 september 1852, 2. 95 daily news, 3 september 1852, 4; h. martineau, letters from ireland, john chapman, london, 1852, pp. 82–91. 96 g. h. kinahan, q. j. sci. 1869, 6, 331. 97 e. ronalds, chemical gazette 1852, 10, 420. also in: athenæum 1852, 1042. summarised in: h. watts, dictionary of chemistry and the allied branches of other sciences, vol. 5, longmans, london, 1868, p. 404. 147bringing together academic and industrial chemistry: edmund ronalds’ contribution bly… find time to make me that glass float wh has been five & twenty years in process”.98 ronalds was presumably wanting a better hydrometer. from university towards industry the 1850 baas meeting had been held in edinburgh. on 23 december that year ronalds married his friend tennent’s sister barbara christian at her mother’s home: 128 wellington street, glasgow.99 the couple went on to have three daughters followed by three sons. not long afterwards, the ronalds family suffered a major change of fortune. with edmund sr’s younger sons now completing their schooling, he wished to fund their establishment in life. he had borrowed £12,000 from his elderly mother during the economic recession of the late 1840s and, on her death in 1852, the family cheesemonger business was sold and he invested his inheritance in a large silk mill in derby that was in debt. the idea was that his son hugh would learn the business and then start running it. instead the current managers apparently absconded with the money.100 a cousin summed up the outcome for edmund sr: “he must be much reduced in circumstances as two of his daughters have been obliged to go out as governesses”.101 one went on to establish a respected school and another became a nursing sister. their brother hugh later reminisced about “the careless way i thought of money and time… no care or anxiety for the future” in the years before “the smash”.102 another of the sons had attended queen’s college galway for a year, but did not continue his studies.103 the three young men, aged eighteen, nineteen and twenty, set sail for new zealand in february 1853 with their fares and early subsistence funded by uncle martineau. it was intended that the rest of the family would follow once they were settled as it was “mother’s wish… to fly from all society” and escape her embarrassment. after arriving, however, hugh quickly warned her not “to induce edmund to come out, the settlement is too young and poor to attempt any experiments… i suppose there is no chance of his thinking of giving up his chymistry”.104 in the meantime edmund sr and eli98 e. ronalds to f. ronalds, 30 march 1858, iet, 1.9.1. 99 glasgow herald, 27 december 1850, 2. 100 derby mercury, 27 april 1853, 4. 101 h. ronalds, diary, 1851–1854, wu, b1462. 102 h. ronalds to m. ronalds, 14 november 1854, anl; e. ronalds to j. greg, 7 october 1928, ronalds family papers, sydney, australia. 103 queen’s colleges (ireland), return to an order of the house of commons dated 25 may 1857, p. 22. 104 h. ronalds to m. ronalds, 14 november 1854, h. ronalds to e. za joined ronalds in galway. eliza’s death there altered plans – two of ronalds’ sisters joined their brothers but the rest of the family remained in britain. the brothers took labouring work to support themselves while clearing a farm in the bush outside new plymouth. ronalds tried to help as he could, sending money and practical agriculture books. he was elected examiner across the three queen’s colleges, which supplemented his income by £100, and became dean of science and a member of the galway college council.105 this same year, 1853, his brother-in-law tennent became a partner in charles tennant & company and manager of the st rollox works.106 ronalds had the opportunity to move into a much more remunerative role running the bonnington chemical works. with him having other commitments however, tennent’s brother hugh brown tennent, the assistant manager, cared for the facility until his death two years later. chemical manufacture (1856-1878) in march 1856 ronalds and barbara were able to leave their home at nun’s island in galway and relocate to bonnington:107 he had extricated himself from his academic duties, the two chemical technology volumes were printed, and their new baby was three months old. tennant, tennent and ronalds had all been on the chemical science committee for the baas meeting in glasgow the previous september (with liebig also being an attendee),108 which is perhaps where the handover was organised. ronalds became a partner in the bonnington chemical company, with his contribution being the management of the facility. tennant and tennent remained non-active partners, the company being under the tennant corporate umbrella.109 that ronalds’ career change was aty pical has been noted by fox and guagnini in their discussion of applied science, but without comment on the context.110 there were many interactions between universities and industry in his education-practice networks outlined earlier, and elsewhere, but it was very rare to swap secronalds, 19 september 1853, atl. 105 cork examiner, 26 june 1854, 2; nenagh guardian, 29 october 1853, 1. 106 one hundred and forty years of the tennant companies 1797-1937, tennant companies, london, 1937, p. 2. 107 galway mercury, 15 march 1856, 3. 108 athenaeum 1855, 1092. 109 bonnington chemical company v. gibson and walker, 1868, and 1874, nrs, cs242/203, cs242/208. 110 r. fox, a. guagnini, hist. stud. phys. biol. sci. 1998, 29, 55, esp. 75–76. 148 beverley f. ronalds tors and integrate an academic experience base into the running of an established manufacturing business. generally in such interactions the academic passed across scientific knowledge while ensuring their distinctive position: “they presented themselves above all as the theorists of industry… without becoming wholly assimilated in the industrial world”; they were the “elite”.111 indeed, it has been presumed on occasion that ronalds must have been “a chemist” or “consultant” at bonnington rather than the managing partner.112 his closest university associates adopted comparable approaches, even in germany with its cameralist links between state, commerce and science. magnus supported “technology” through university teaching and research in experimental science, by visiting factories and advising government. in enthusiastically promoting industrial application of his research ideas, liebig provided scientific guidance (often through his assistants), while also seeking commercial returns to supplement his academic income. knapp aided liebig in several of these endeavours and held the position of technical director at a government porcelain manufactory for a time – together with his professorship. richardson’s career was the other way round: he specialised in industrial chemistry at several different plants, and after a few years also took an appointment as a lecturer. another giessen associate, august wilhelm hofmann, director of the royal college of chemistry, proudly associated himself with a further and oft-quoted model of technology transfer – his student william perkin discovered the coal-tar dye mauveine in 1856; perkin became what homburg has called an “inventor-entrepreneur” when he established a factory and entered into production.113 as a final example, kranakis has identified academics who melded theory and practice in noteworthy “hybrid careers”, but they did so while remaining attached to the university.114 ronalds contrasts with these and other cases in that he moved at top level and permanently from academia to an operating manufacturing firm where he had lit111 fox, guagnini, hist. stud. phys. biol. sci. 79; see also: bud, roberts, science versus practice; e. homburg, isis 2018, 109, 565; e. schatzberg, isis 2012, 103, 555; technological development and science in the industrial age: new perspectives on the science-technology relationship, (eds.: p. kroes, m. bakker), kluwer, dordrecht, 1992, pp. 1–15. 112 w. h. brock, ambix 2013, 60, 203; w. h. brock, justus von liebig: the chemical gatekeeper, cup, cambridge, 1997, p. 349. 113 hofmann, allgemeine deutsche biographie ; brock, justus von liebig; schneider, neue deutsche biographie ; “richardson, thomas”, oxford dictionary of national biography; l. f. haber, the chemical industry during the nineteenth century, oup, oxford, 1958, pp. 80–87; donnelly, social studies of science; e. homburg, br. j. hist. sci. 1992, 25, 91. 114 e. kranakis in technological development and science in the industrial age, pp. 177–204. tle first-hand experience, and took responsibility overall rather than for technical aspects. sharing scientific knowledge was part of his role but the imperative was to quickly acquire quite different skills while building credibility as the manager. universities and manufacturing facilities were highly disparate entities in this era, which made the transfer demanding and risky. it was only later when industrial companies had research laboratories, universities became businesses, and the class structure changed that advantages could be seen in senior staff cross-fertilisation.115 an early ramification of ronalds’ move was an altered standing in the community in comparison with being a professor: he quipped to sir francis that he was now “completely ignored, as a tradesman, by the entire society”.116 fortunately, as outlined below, status was of little concern to him. in the same light-hearted vein, he explained: “i have entirely changed my mode of life & have (with a view to the future of the bairns) taken seriously to money grubbing, an occupation sufficiently disgusting & only tolerable in consideration of the results which i hope may be successful”. like his uncle, he was unaccustomed to the marketing, sales and negotiation side of business and also ill-suited to it with his retiring nature. more importantly, there was a lot to learn about the plant and he admitted (with some self-deprecation) that he had “been kept & am still very hard at work, having hardly had time to master the details of manufacture & trade”. despite these challenges, he welcomed his new opportunity. not only could he now better support the ronalds family, but he was responsible himself for the type of largescale manufacture he had before only written about and could trial ideas suggested by his studies. barbara would also have enjoyed returning to family and friends in scotland. it can be surmised however that without the trigger of financial distress he would not have taken on the job and also that its risks would have been too great if he not researched chemical technology and had the support of his relationship with tennent. his partners, having studied at university, would also have appreciated that his alternative skillset could bring plant innovations. a career change from the academic to the manufacturing world at that time almost certainly required special circumstances, notwithstanding the potential benefits it brought. the bonnington chemical works was located close 115 on when and how manufacturing firms developed research arms, and their links with academia, see for example: homburg, br. j. hist. sci., and d. a. hounshell and j. k. smith, jr., science and corporate strategy: du pont r&d, 1902–1980, cup, cambridge, 1995. 116 e. ronalds to f. ronalds, 30 march 1858. 149bringing together academic and industrial chemistry: edmund ronalds’ contribution to the water of leith on newhaven road, edinburgh. it was a pioneer coal-tar processing facility established around 1822 to distil naphtha from the residues of the edinburgh gasworks for charles macintosh’s eponymous waterproof fabrics; macintosh’s firm was a special customer for two decades and probably longer.117 the plenteous residues were transported from the gasworks to bonnington by a dedicated pipeline over calton hill. in the words of ronalds’ giessen friend professor frederick penny, the processing works were “so extensive and so important” and were now run by “a distinguished scientific and practical chemist”.118 within months of arriving, ronalds donated a large series of specimens to the industrial museum of scotland showing the numerous intermediate, final and byproducts created from gasworks waste.119 the collection formed a valuable companion to the descriptions and illustrations of coal-tar processing in chemical technology and was used by the museum director (technology professor wilson) as a teaching aid. from ronalds’ perspective, by looking outward to support technological education he was seemingly already in command of his role, which indicates both his prior understanding of industry practices and his adaptability. his detailed summary of plant operations was published in the cyclopædia of useful arts.120 bonnington’s most important products were rectified naphtha, creosote, sal ammoniac (ammonium chloride), ammonium sulphate, and anticlor (sodium thiosulphate). he noted that “we have a good deal of business with the owners of the steamers”121 exporting these commodities around the world and indeed george seater, the director of the leith, hull & hamburg steam packet company, christened his son “edmund ronalds”. he also made all his sulphuric, hydrochloric and sulphurous acid requirements and a new acid plant was the first facility he commissioned. figure 3 shows the plan of the facility from the 1876 ordnance survey map. comparing this with the first survey in 1852 indicates the extent of his alterations, with the facility’s footprint increasing from two to approaching three acres. one of the motivations for the enhancements he made (including waste-gas cap117 b. f. ronalds, “bonnington chemical works (1822–1878): pioneer coal tar company”, submitted. the bonnington works is not listed in p. j. t. morris, c a. russell, archives of the british chemical industry 1750–1914, bshs, faringdon, 1988, but considerable archival material has now been identified. 118 f. penny, report to the provost, magistrates, & council of leith on the bonnington chemical works, 1865, edinburgh city archives, e32, mybn u140g box 00 01 20. 119 fourth report of the department of science and art, pp. 162–63. 120 c. tomlinson, cyclopædia of useful arts, vol. 1, james virtue, london, 1862, pp. 751–52. 121 e. ronalds to f. ronalds, 19 june 1858. ture equipment and a large new chimney) was to reduce emissions, which was an emphasis in chemical technology. the gamble of his appointment had paid off. ronalds and richardson had noted in the preface to the second edition of their book that “the valuable constituents of coal-tar [have not] yet been fully worked up into a merchantable form” and the chance to be part of a rapidly developing sector was another inducement to come to bonnington. his longer-term aim would have been to build on the current efforts of hofmann and others in fossil fuel chemistry and its applications by conducting in-house research. in the early years he had little time “for prosecuting my chemical enquiries connected with the manufacture which, however, exist in sufficient abundance & would well repay the time expended upon them, could it only be afforded by the more pressing demands of everyday business”.122 unfortunately details are relatively scant on the science he was able to oversee when circumstances allowed, and how it was utilised in plant operations. he was however elected a fellow of the royal society of edinburgh in 1862, proposed by professor peter guthrie tait,123 and quickly served on the council. interested to explore both the composition and handling risks of the light petroleum recently discovered in pennsylvania in comparison with coal tar, he read a non-proprietary research paper to the society on its volatile components in february 1864. he discovered several lower members of the methane series dissolved in the crude: ethane, propane and butane. he described the proper122 e. ronalds to f. ronalds, 30 march 1858. 123 royal society of edinburgh, biographical index of former fellows of the royal society of edinburgh 1783–2002, 2006. figure 3. bonnington chemical works near edinburgh. bonnington house is at the southeast corner of the overall site. source: ordnance survey, edinburgh, sheet 16, 1876, national library of scotland. 150 beverley f. ronalds ties of the last, also for the first time124 – with a specific gravity of 0.600 at zero degrees celsius, it was the lightest liquid known and it began boiling at that temperature. the paper was included in the society’s transactions, reprinted in the chemical society’s journal and the german literature, and was referenced numerous times as petroleum research progressed.125 he presented product samples to the industrial museum in edinburgh.126 another aim was to investigate the properties of the pyridine series, which were very minor constituents of coal tar. he prepared a significant quantity of these bases by repeated fractionation but, perhaps due to time constraints, he then gave the various fractions to james dewar. dewar’s analyses of this “liberal supply” enabled him publish the proposal that pyridine had a ring formula.127 ronalds was able to determine that the tar he received from the gasworks contained almost no anthracene, and its relatively little benzene was often uneconomic to separate from the methane series of compounds also in the naphtha. this precluded him from contributing to the new synthetic dyestuff industry that was commencing to manufacture the dyes alizarin and mauveine from these components following perkin’s discovery. he also ascertained how the detailed properties of his coal tar varied with the coal mix and retort temperature being used at the gasworks. when bonnington was closed he provided the results for lunge’s respected treatise on coal-tar processing.128 these examples suggest that ronalds had succeeded in building up advanced research capability, with experimental apparatus that was unusually sophisticated for a manufacturing environment. in the meantime, his brothers and sisters in new zealand had become embroiled in the maori wars in 1860 and their timber cottage and farm were destroyed. he encouraged hugh, the most despondent and unsettled of the siblings, to return to britain129 and he became a partner in the firm in 1867 after ronalds had trained him in the business.130 ronalds’ eldest son edmund 124 ronalds’ discoveries are noted, for example, in: watts, dictionary of chemistry, vol. 4, p. 385; h. e. roscoe, c. schorlemmer, treatise on chemistry, vol. 3, macmillan, london, 1881, pp. 144–45; w. t. brannt, petroleum, henry carey baird, philadelphia, 1895, pp. 56–80; c. f. maybery, proc. am. acad. arts sci. 1896, 31, 1. 125 e. ronalds, trans. r. soc. edinburgh 1864, 23, 491. also in: j. chem. soc. 1865, 18, 54; j. prakt. chem 1865, 94, 420. 126 edinburgh museum of science and art, catalogue of industrial department, neill, edinburgh, 1869, p. 94. 127 j. dewar, trans. r. soc. edinburgh 1872, 26, 189. 128 g. lunge, treatise on the distillation of coal-tar and ammoniacal liquor, john van voorst, london, 1882, pp. 12–13. 129 h. ronalds to e. ronalds, 25 september 1860, atl. 130 inquirer 1911, 821. hugh later became an assistant chemist.131 his other sons, christened tennent and frank, became respectively a fellow of the edinburgh obstetrical society132 and a merchant. his daughters attended the respected rowdon house school for ladies in london until their late teens, continuing the family’s emphasis on education.133 last years (1878-1889) the bonnington chemical works closed in 1878. tennent and tennant were dead, ronalds had been “afflicted with very bad health” for some years that a spell on the north berwick coast did not alleviate,134 and his family members did not wish to take on the management responsibility. since 1868 he had lived in the “beautiful” bonnington house (figure 4) with large ornamental gardens close to the works.135 it and several smaller houses had been purchased by the chemical company before he joined and now became his personal property.136 hugh lived nearby at another “good house” called hillhousefield. this part of the family had become very wealthy – ronalds had assets to the value of £136,000, exclusive of his recent real estate acquisition.137 in addition to his portion of bonnington’s worth over two decades, barbara and the children had been the major beneficiary of her brother tennent’s estate, which included his £54,000 share of st rollox, an £8,300 contribution from bonnington, plus real estate.138 hugh had married into samuel greg’s family, renowned for their large cotton spinning mills. ronalds repaid his good fortune by continuing to support other siblings through trust funds. he occupied his last years in an “admirably appointed laboratory” he established,139 denoting himself as a “scientific chemist”.140 it was a lifelong goal to pursue science of interest in a private facility in the mould of magnus’ teaching and research laboratory in ber131 scotland census, 1881. 132 trans. edinburgh obstetrical society 1888–1889, 14, xiii. 133 barbara, eliza and emily ronalds, england census, 1871. 134 proc. inst. chem. 1890, 14, 53. 135 property descriptions are in the midlothian ordnance survey name books 1852–1853, scotlandsplaces, os1/11/87. 136 ground belonging to the trustees of the late dr. ronalds, bonnington, historic environment scotland, edd 804/1–3; valuation rolls, 1885–1886, scotlandspeople, vr005500031-/386–387. 137 edmund ronalds, inventory, 1889, scotlandspeople, sc70/1/278. 138 john tennent, will and testament, 1867, scotlandspeople, sc36/48/58, sc36/51/52. 139 proc. r. soc. edinburgh 1889–1890, 17, xxviii. 140 scotland census, 1881. in the 1861 and 1871 censuses ronalds called himself a “manufacturing chemist” and a “chemist and manufacturer”, respectively. 151bringing together academic and industrial chemistry: edmund ronalds’ contribution lin and the well-equipped workshop that sir francis set up at each of his homes.141 he had come full circle and was now enjoying the life he had imagined he would lead when he was studying. “[h]e made any chemist welcome”142 in the laboratory and, according to his obituary, was well known and remembered “with affection” by all chemists who had resided in edinburgh. little is known of the work conducted there, although his son’s analyses aided george beilby in the production of ammonia from shale and coal.143 in 1875 he was appointed a foundation trustee of the ronalds library at the institution of electrical engineers bequeathed by sir francis – he had always cherished his copy of sir francis’ 1823 booklet describing his telegraph.144 he joined the new society of chemical industry, became a fellow of the institute of chemistry of great britain and ireland when it was formed,145 and along with other former professors was awarded the honorary d.sc. degree by the queen’s university of ireland in 1882.146 “he was a constant attendant at the meetings” of the royal society of edinburgh and “always took a live141 c. jungnickel, r. mccormmach, mastery of nature: the torch of mathematics 1800–1870, ucp, chicago, 1986, pp. 107–10; ronalds, sir francis ronalds, p. 95. 142 j. chem. soc. trans. 1890, 57, 456. 143 g. beilby, j. soc. arts 33 (1885): 313; also j. soc. chem. ind. 1884, 3, 216. 144 trust deed of the ronalds library, 1875, iet; e. ronalds to j. fahie, 26 april 1882, iet, 1.9.2.119. 145 proc. inst. chem. 1878, 2, 13. 146 belfast newsletter, 2 february 1882, 8. ly interest in everything”, “although he rarely took an active part in its proceedings”.147 similarly, when tait invited him to help found a new learned club, he replied that he would be “be delighted to join if smoking & good listening without much talk will qualify”.148 like sir francis and other members of his unitarian family, he was an introvert, with no interest in status or recognition and avoiding public roles. he was motivated in his work simply by the personal knowledge of achieving scientific and technical goals. there are therefore few institutional records of his contributions and this, together with his small portfolio of academic papers, helps to explain his comparative absence in the history of science literature. never recovering his health, he died on 9 september 1889 and was buried in rosebank cemetery diagonally opposite bonnington house.149 conclusion ronalds had a highly advantageous entry to his lifelong field of chemistry through his international education and initial work experience and he brought significant talent and energy to his subsequent career. from his relative obscurity today it could be construed that he did not fulfil this early promise. he has been categorised in studies of the students of liebig (and bunsen) as an academic and his traditional metrics of science output are not strong.150 he himself found that his focus on industrial interests equated in britain to a lowered status, and even today dual academic and industrial achievement is not commonly embraced and quantified, despite the culture of science utilisation these students were exposed to in germany. ronalds in fact had an unconventional two-stage career, spending fourteen years in academia and then twenty-two years in the quite different setting of largescale manufacture. his change was abrupt but cogent because he always linked scientific insight and industry practice. as an academic, his research and teaching addressed local problems and facilitated the study of chemical technology through a seminal book that synthesised theory and application. he then put his advanced knowledge of technology into practice while also bringing research into a manufacturing firm, and 147 proc. r. soc. edinburgh 1889–1890, 17, xxviii. 148 e. ronalds to p. tait, 25 october 1869, national library of scotland, archives & manuscript collections, ms.1704 f.74 v1. 149 c. napier, scottish genealogist 2012, 59, 176. 150 for example: j. s. fruton, proc. am. philos. soc. 1988, 132, 1; brock, ambix. figure 4. bonnington house, ronalds’ home in the period 18681889. source: j. grant, cassell’s old and new edinburgh: its history, its people, and its places, vol. 3, cassell, petter, galpin, london, 1887, p. 93. 152 beverley f. ronalds this resulted in new discoveries, plant improvements, business expansion and significant profits. these two cross-sector unions – technological education and industrial research – were then very novel but presaged what became key trends into the twentieth century, yet his accomplishments have been largely overlooked by historians. substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 5(1): 5-7, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1183 editorial giving credit where it’s due – the complicated practice of scientific authorship seth c. rasmussen department of chemistry and biochemistry, north dakota state university, fargo, nd 58108 usa e-mail: seth.rasmussen@ndsu.edu anyone who has participated in modern scientific publishing has experienced the potentially complex issue of coauthors, both in terms of who merits to be included on a particular paper and in what order should they be listed. during the early years of serial scientific publications in the 17th and 18th centuries,1 nearly all papers consisted of just a single author. in contrast, the growing complexity of most present-day studies has required collaborative teams to accomplish the work needed to present a suitable report meriting publication.2 some have attempted to tie this move to multiple-author papers with the introduction of large-scale government funding following world war ii.3,4 while valid arguments can be made about the expansion of the scientific enterprise at this point in history,4 simply browsing the contents of prominent journals shows that papers with two or more authors predated this event and were somewhat common by the second decade of the 20th century. of course, one can now easily find papers with 10 or more coauthors, further complicating the ability to properly recognize each author’s specific contribution. as such, it is not surprising that the history of science includes various cases of authors not receiving sufficient credit for their contributions, and it was recent research into one such controversial case5 that has led to the current discussion. unfortunately, there exists no firm, uniform rules for determining authorship6 and current practices can vary significantly,7 even to the point that the literature is now plagued with ethically questionable practices such as coercive authorship4,7 (senior officials requiring authorship on the work of subordinates without any contribution), gift/honorary authorship4,6,8 (the addition of authors that did not actually contribute to the work out of respect or friendship), or the opposite case where actual contributors are given no credit whatsoever (sometimes referred to as ghost authorship4). as such, the goal here is to present various best practices in terms of both determining valid authorship, as well as addressing the related issue of author order on a given publication. for most researchers, the baseline requirement for authorship is that the researcher should have provided a real contribution to the reported work. of course, this does not mean that all contributors should be authors and the sticking point is often determining what merits authorship over a simple acknowledgement. one of the earliest attempts to define scientific authorship has been quoted as2 …someone who has made significant contribution to the project through planning, conceptualization, or research design; providing, collecting, or recording data; analyzing or interpreting data; or writing and editing the manuscript. the american chemical society (acs) then introduced their own take on a definition in 1985 as a part of the society’s ethical guidelines to publication of chemical research. as outlined by the acs:9 the co-authors of a paper should be all those persons who have made significant scientific contributions to the work reported and who share responsibility and accountability for the results. other contributions should be indicated in a footnote or an “acknowledgments” section. this definition has been retained nearly unchanged in each of the society’s revised ethical guidelines since. of the currently available best practices, the international committee of medical journal editors (icmhttp://www.fupress.com/substantia 6 seth c. rasmussen je) included much of the acs definition, while also attempting to provide more specific parameters. as such, the icmje recommended that to merit authorship, researchers must meet all of the following conditions:10 i) substantial contributions to the study’s conception/ design, data acquisition, or analysis/interpretation; ii) drafting the manuscript or critical revision for intellectual content; iii) approval of the final manuscript to be published; iv) accountability for the accuracy/integrity of the work. thus, per icmje guidelines, contributors that meet all four of these conditions should be authors, while those that meet three or less should only be given a suitable acknowledgement. of course, while this provides a simple rubric for deciding authorship, the actual threshold for meeting points i and ii is still somewhat vague. for instance, what exactly qualifies as a substantial contribution? such standards can vary from one discipline or research group to another.7 furthermore, the icmje guidelines reinforce the very traditional definition of an author as one who contributed to the actual writing of the manuscript and does not always allow credit for less traditional types of contributions to the published study. a n a lternate, a nd somewhat more deta i led, approach is the contributor roles taxonomy (credit) introduced in 2014 and now adopted by a number of scientific publishers.11 as outlined in table 1, this consists of 14 various roles for potential contributions to a given publication, with each author assigned appropriate roles upon submission of the manuscript. while no guidelines are provided in terms of the extent of contribution expected of each author, this approach does provide a practical way to acknowledge the diversity of researchers’ contributions to published papers, particularly in large teams, as well as the ability to clearly document how each author contributed to the work. still, it does become easier to justify authorship over a simple acknowledgement when it is clear that a researcher has contributed via multiple different roles. furthermore, this new taxonomy attempts to move away from the traditional author role to the broader, and more realistic, role of contributor (even if still commonly referred to as a paper author in practice).11,12 even if publishers have not explicitly adopted credit, many journals are now requiring that each author’s contribution be explicitly described in a dedicated section of the published paper, which effectively accomplishes the same overall goal. overall, application of at least the spirit of these best practices should help avoid the ethically questionable practices referenced above. once decisions have been made concerning which contributors merit authorship, there is still the thorny issue of author order, particularly in publications with a significant number of authors. by far the most common practice is to list authors according to their relative contributions to the work. that is, the author with the greatest contribution is given first author status, with others ranked in descending order of contribution. the only exception to this is typically the placement of the principle investigator (pi), who is most commonly listed last and designated as the corresponding author. however, even the placement of the pi can vary and sometimes the pi can be given first author status, either as the result of providing the bulk of the contributions (as in review articles, etc.), as the result of discipline traditions or convention, or in an attempt to increase the paper’s perceived exposure. as the number of first author publications can play a critical role in job applications, extramural funding, etc.,3,4 deciding who merits first author status can be a tricky and contentious process, particularly in cases where multiple authors have provided somewhat similar contributions to the work. as a potential solution to this issue, the practice of designating multiple first authors has started to become common, in which footnotes are used to specify that each author contributed equally to the work.13 even here, however, the first of the two “equal” authors still tends to receive greater recognition, table 1. contributor roles taxonomy (credit). role description conceptualization formulation of research goals and aims methodology development or design of methodology used software programming, implementation of computer code, or testing of existing code validation verification of the replication/reproducibility of results/experiments formal analysis use of formal techniques to analyze study data investigation performance of experiments or data collection resources provision of materials, reagents, samples, etc. data curation management activities to annotate and maintain data for research and later re-use writing – original draft preparation/presentation of the published work, specifically writing the initial draft writing-review/ editing critical review, commentary, or revision of the published work visualization preparation of data presentation/visualization supervision oversight and responsibility for the research project administration management and coordination of the research activity and execution funding acquisition acquisition of financial support for the project 7giving credit where it’s due – the complicated practice of scientific authorship particularly where only a single author is used to refer to the work. although less common, similar practice can also be applied to the last/corresponding author, for those studies that involve multiple pis. in reality, however, most collaborations (at least informally) have one pi that takes the lead responsibilities on each paper, thus removing the need for multiple corresponding authors. as a way to remove the issues of author order, some fields have adopted the practice of listing authors in alphabetical order. the problem here is that unless this is made explicitly clear to the reader, most will still assume authors are listed in terms of relative contribution, as this is the far more common practice. another compromise is the practice of what is sometimes referred to as negotiated order. that is, to come to some consensus or mutual agreement between authors on the listed order. for example, in cases where two researchers have provided near equal contributions, it is likely that the people in question will both contribute to more than one publication from the same project. therefore, the order of first and second author on one publication can then be reversed on the next publication, thus providing an avenue of giving balanced credit across the total scope of the project. needless to say, while this discussion has attempted to present best practices, none of these approaches are perfect and there are still plenty of opportunities of argument and contention. in the end, for everyone involved (students and advisors, alike), the best practice is to have open and transparent discussions about these issues and try to come to agreement about these decisions prior to drafting the manuscript for publication. in addition, if the author order needs to be modified due to changes in team composition or relative contributions of authors, make sure that all authors understand the reasoning behind the applied changes. in the end, open communication is the only way to limit unwanted disputes related to the authorship of a given publication. references and notes 1. d. a. kronick, a history of scientific and technical periodicals. the origins and development of the scientific and technological press 1665-1790. the scarecrow press, inc., new york, 1962. 2. m. m. jennings, i. h. el-adaway, j. prof. issues eng. educ. pract. 2012, 138, 37-47. 3. d. s. price, science 1981, 212, 986. 4. k. strange, am. j. physiol. cell physiol. 2008, 295, c567-c575. 5. s. c. rasmussen, substantia 2021, 5, 91-97. 6. v. venkatraman, science 2010, 10.1126/science. caredit.a1000039. 7. m. hosseini, l. consoli, h. a. e. zwart, m. a. van den hoven, sci. eng. ethics 2020, 26, 597-617. 8. m. biagioli, trends in chemistry 2019, 1, 3-5. 9. acs books and journals division, environ. sci. technol. 1986, 20, 559-560. 10. defining the role of authors and contributors, icmje, http://www.icmje.org/recommendations/ browse/roles-and-responsibilities/defining-the-roleof-authors-and-contributors.html (accessed december 3, 2020). 11. l. allen, a. o’connell, v. kiermer, learned publishing 2019, 32, 71–74 12. a. holcombe, nature 2019, 571, 147. 13. m. hosseini, sci. eng. ethics 2020, 26, 1133-1148. substantia an international journal of the history of chemistry vol. 5, n. 1 2021 firenze university press giving credit where it’s due – the complicated practice of scientific authorship seth c. rasmussen history of research on antisense oligonucleotide analogs jack s. cohen chemistry, cyclophosphamide, cancer chemotherapy, and serendipity: sixty years on gerald zon thermodynamics of life marc henry darwin and inequality enrico bonatti loren eiseley’s substitution bart kahr new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors yona siderer capillary electrophores is and its basic principles in historical retrospect 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis ernst kenndler1,*, marek minárik2,3 the eminent russian – german chemist –friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries aleksander sztejnberg review of what is a chemical element? by eric scerri and elena ghibaudi, eds. oxford: oxford university press, 2020 helge kragh substantia. an international journal of the history of chemistry 2(2): 27-41, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-59 citation: j.h. maar (2018) almost a discovery – henri gorceix, the mining school of ouro preto, the monazite sand of bahia and the chemistry of didymium. substantia 2(2): 27-41. doi: 10.13128/substantia-59 copyright: © 2018 j.h. maar. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article almost a discovery – henri gorceix, the mining school of ouro preto, the monazite sand of bahia and the chemistry of didymium juergen heinrich maar retired, chemistry department, universidade federal de santa catarina, florianópolis, sc, brazil e-mail: jhmaar@yahoo.com.br abstract. the chemical history of the supposed element didymium may well be characterised as a case of collecting empirical data in a period of “normal” science. but this element’s history also reveals little known facts of the history of chemistry in south america, such as the exploration and smuggling of monazite sands, and the difficult beginnings of scientific research and higher education in brazil. didymium is also a curious case: even after it was shown to be a mixture, it continued to be regarded as an element. this fact alone raises questions about the adequacy of scientific methodology at the time. in this paper, we consider the history of didymium, and determine how this history’s different facts and stories, set in brazil’s rather unique historical and scientific context, intertwine thanks to the work of claude henri gorceix. keywords. history of didymium, claude henri gorceix, ouro preto mining school, monazite sands. it is absolutely necessary to study the facts, to observe phenomena. henri gorceix whatever the aim man establishes for himself to reach, whatever the idea he chooses to develop, they cause a great feeling of pleasure when he succeeds, a great happiness when turned reality.1 henri gorceix to discover an element for the layman, more than for the scientist, the discovery of a new element marks a great event in the history of chemistry. indeed, discoveries or isolations of elements signify a great scientific advance, even from a theoretical point of view: the discovery of oxygen, of the first noble gas, of the elements foreseen by mendeleev in his periodic system. the discovery of an 28 juergen heinrich maar element is also one of the most “democratic” aspects of the history of chemistry. while some elements were discovered by the most respected scientific authorities – scheele, berzelius, klaproth, vauquelin, wollaston, davy – others were found by diligent and industrious practitioners of a “normal” science (in kuhnian terminology) – mosander or marignac. some of these elements perpetuate the names of their discoverers: gregor and titanium (1791), courtois and iodine (1811), balard and bromine (1826).2 the discovery, isolation and physical and chemical characterisations of rare earth elements constitute an apparently unbounded harvest for historians of chemistry. in this endeavor, the marvels of science and the aesthetic pleasure of discovery are painted in the best possible light. isolation and perfect characterization are necessary requirements for defining a “discovery” of a new element. in the case of the elements of the rare earths, all were derived from two pioneering discoveries: gadolin’s yttria (1794) and berzelius’ and klaproth’s ceria (1803). experimental problems were, however, particularly difficult: their physical and chemical properties are so similar that chemical separations proved extremely burdensome and laborious (thousands of recrystallizations are often required). such difficulties led chemical annals to occasionally record the same discovery twice or announce discoveries of nonexistent ‘elements’ that were, in reality, mixtures or already known elements. many such situations are discussed in karpenkò s paper on s̀purious elements̀ .3 for most of the 19th century, chemistry lacked a theoretical framework that could guide a targeted or systematic search for new elements. experimental complexity was later reduced by the introduction of a new analytical tool – spectroscopy (bunsen, kirchhoff, 1859). but the spectra of alleged newly discovered elements can easily be mistaken for either combinations of the spectra of already known elements or an impure element. for this reason, many ‘discoveries’ of new elements in the realm of rare earths were made, much to the perplexity of the scientific community. in 1880, the anonymous editor of the manufacturer and builder observed that the chemists of recent decades had discovered an enormous number of new ‘elements’. but, even if one only considers the last few years, the number of ‘discoveries’ and accumulation of unconfirmed empirical facts was simply beyond belief.4 the editor correctly identified why: chemists considered evidence from spectroscopic analyses sufficient to warrant the report of a new discovery, ignoring that such evidence could well be a mixture of rare earth elements, or a re-discovery. the desire and haste to claim priority over a new discovery sometimes prevented the discoverer from carefully isolating the new element from mixtures of elements or already known elements. the discoveries of only three elements have been associated with scientific practice in latin america: platinum – discovered in gold deposits in colombia by the spaniard antonio de ulloa (1716-1795); vanadium – discovered as “eritrônio” in a lead mineral from zimapán (mexico) by the spanish mineralogist andrés manuel del rio (1764-1849), professor at the real seminario de minería in mexico; and tungsten, whose spanish discoverers fausto de elhuyar (1755-1833) and juan josé de elhuyar (1754-1796) were later key personalities in the scientific communities of mexico and colombia, respectively. in this paper, we will shed light on the little-known aspects of two stories that are intertwined by the works of an important figure within the history of chemistry in south america: the french mineralogist and chemist henri gorceix (1842-1919). the first of these stories is the foundation of the mining school of ouro preto, where gorceix acted as director for several years. the second is the curious case of the didymium (mosander, 1841), a supposed rare earth element that continued to be the subject of much research – especially at the chemical laboratory of the mining school of ouro preto – even after it had been shown to be a mixture of neodymium and praseodymium, and not an element after all.5 the mining school of ouro preto in contrast to hispanic america, where the first universities were founded in the 16th century, portuguese america was only granted access to higher education beginning in the 19th century – unless we consider the hispanic universities as mere colleges and some of the luso american institutions, such as the jesuit college in salvador (1557), the seminario in olinda (1800)6, and the military school of fortifications in rio de janeiro (1792) as institutions of higher learning.7 the transfer of the portuguese royal family from the capital lisbon to rio de janeiro (1808) brought freedom and favoured the growth of brazil’s practical and applied sciences, which evolved in line with the pragmatism established by the marquis de pombal (1699-1782) at the university of coimbra. but it was only brazil’s political independence (1822) which enabled the foundation of the first faculties stricto sensu: the law schools in são paulo and in olinda (1827), the medical schools in rio de janeiro and bahia (1832), pharmacy courses in rio de janeiro (1832), bahia (1832) and ouro preto (1835), and 29almost a discovery the polytechnical school in rio de janeiro (1874), which was separated as institution from the escola central (1848), successor of the military school and a cradle of positivist thinking in brazil. these institutions created an intellectual elite in brazil and provided higher level education – but only in a practical and pragmatic sense. proper scientific research in brazil was the odd exception, not the rule, and brazilian universities were created as predominantly anachronic institutions.8 in this context, the mining school of ouro preto occupies a position entirely sui generis. since its conception and foundation, the school’s day-to-day life involved not only teaching, but also much international-level research in its first decades of existence. according to s. figueirôa, the first proposal for the creation of a mining school in brazil was made in 1804 by manuel ferreira da câmara (1764-1835), who took his alma mater, the mining school of freiberg as a model.9 the first attempt to create a mining school in ouro preto, minas gerais, dates back to 1832, during the period of the regência – which governed brazil from the abdication of pedro i (1831) until the majority of pedro ii (1840). but why ouro preto? ouro preto was chosen to host a new mining school thanks in great part to the efforts of bernardo pereira de vasconcelos (1795-1850), who argued before the brazilian parliament for a law able to facilitate the economic recovery of minas gerais, which had been stagnant since 1780. this law was also meant to compensate for the fact that the province had received none of the schools created after brazilian independence. but the law would only be made a reality 43 years later. located at the center of a region rich in ores and geological interest, ouro preto proved an obvious choice for a mining school. potosi, in bolivia, centralizing immense silver ore extraction, hosted since 1756 the first mining school of the americas, perhaps the first worldwide.10 after 1699, when the adventurer antonio dias discovered the first gold deposits around what is now ouro preto, the original village grew very quickly. it became a municipality in 1711 and was suggestively named vila rica (rich village); in 1720 the village became the capital of the new captaincy of minas gerais. during the 18th century, vila rica was responsible for most of the americas’ gold production, which is reflected in the rich religious and profane architecture preserved to our days (included by unesco in the world heritage in 1980), as well as a rich literary and artistic activity. a timid reflex of the enlightenment can also be detected in a movement for political emancipation in 1789 in ouro preto, which was the capital city of the province and state of minas gerais until 1897. the mining school of ouro preto was finally founded in 1875, during alfredo correia de oliveira’s (18351919) tenure as minister of the empire. a personal decision, almost an imposition, of emperor pedro ii, in the words of the historian josé murilo de carvalho, “the creation of the school was, after all, an act of political will, directed in great part by ideological rather than economic reasons”11. in a nation with a slave-based society and an economy based on agriculture and export with “a very incipient industrial activity”, there was no real need to train geologists or mining engineers. the country had no tradition of geological or mineralogical research. it is therefore difficult to imagine the creation of the mining school as a requirement mandated by society, the lower classes, or even as a necessary step for the country’s economic, social and scientific development. pedro ii (18251891), constitutional monarch at the tender age of 15, was educated by his tutors, josé bonifácio de andrada e silva (1763-1838), the “patriarch of independence”, and the marquis de itanhaém, manuel inácio de andrade (1782-1867), mentors responsible for awakening, besides his ever mentioned interests in literature and arts, a strong interest in science, particularly chemistry.12 there are well preserved notes from pedro ii on mendeleev’s periodic system (the evolution of which he documented through scientific journals), and on scientific subjects he personally taught his daughters. during his trips to europe, the emperor visited many chemists: chevreul, liebig, berthelot, pasteur, kelvin, van’t hoff. the emperor was also a member of the royal society and of the academies of paris, berlin, st. petersburg and munich.13 we shall not occupy ourselves with well-known controfigure 1. emeric marcier (1916-1990), “ouro preto”, 1952. oil on canvas, 64 x 90 cm. museu de arte de santa catarina/masc, florianópolis, brazil. 30 juergen heinrich maar versies surrounding his lack of commitment to matters of state in favour of his pursuit of personal interests14 – matters possibly made worse by the longevity of his reign. we will, however, focus on his interest in science. on his second voyage to europe (1870/1871), pedro ii visited the paris academy (he would be elected a member in 1875), and upon his return, he invited gabriel auguste daubrée (1814-1896), a former student of the école polytechnique and then director of the mining school in paris, to visit brazil – not only to research our mineral kingdom, but to help with the foundation of a mining school. daubrée had no interest in leaving europe, and suggested claude henri gorceix for this task. as we will see, gorceix was the perfect man, in all respects, for this work. a sincere friendship linked gorceix and the emperor, as demonstrated by the surviving, prolific correspondence between them. the emperor and empress teresa cristina (1822-1889) became godparents to gorceix’s daughter, cécile pierrete therèse gorceix (professor christiano barbosa da silva would later say that gorceix’s “first daughter was the school of mines”). claude henri gorceix (1842-1919) several foreign scientists exerted a long-lasting influence on the evolution of chemistry in brazil. we may begin by remembering the italian general carlos antônio napion (1757-1814), professor of chemistry at the military academy, or the frenchman félix d’arcet (1814-1847), who attempted to produce sulfuric acid in rio de janeiro but died in a laboratory fire. those who had the most enduring influence on brazilian chemistry were the german phytochemist theodor peckoldt (18221912), pharmacist of the emperor, and analyst henri gorceix, a pioneer of geochemistry in brazil. claude henri gorceix was born on october 19th, 1842, in the small village of saint-denis-des-murs, district of st. léonard, department of haute-vienne (which is also the native region of gay-lussac, a distant relative of gorceix) and fathered by antoine gorceix and cécile-valérie beaure la mareille.15 gorceix concluded his studies at the lycées in limoges and douai, graduated in 1866 at the école normale, and obtained a diploma of a “generalist in physical sciences and mathematics”. gorceix lectured at the french school in athens while exploring the geology and mineralogy of greece. daubrée found him in athens after pedro ii’s invitation, and in march 1874, gorceix signed a contract with the brazilian government at the brazilian embassy in paris. the contract mandated he “to organize teaching of mineralogy and geology in brazil”. article 12 of the contract states, ipsis litteris: “mr. gorceix promises to go to rio de janeiro, at the services of the imperial government to organize the teaching of mineralogy and geology”. resolute, severe and ill-tempered, rough and rude according to contemporaries, and arrogant in the opinion of s. figueirôa16, gorceix was a man tailored to his new functions: teaching and research in mineralogy and geology. multiple administrative and bureaucratic difficulties also awaited him – not to mention envy, enmity, unfair sponsorship and competition, lack of recognition and understanding. while still in europe, gorceix organized equipment and materials for teaching and laboratory activities. after the school was installed, he had to hire and engage teachers, assistants and other staff members, as well as ascertain financial assistance for poor students arriving from other provinces. about the installation of the laboratory, dutra comments: for us today it is practically impossible to evaluate the immense difficulties associated with the installation and maintenance of a chemical laboratory in the tropics at the end of the 19th century. how was it possible to find in europe and take to ouro preto the necessary chemicals, figure 2. claude henri gorceix (1842-1919). lythography by unknown artist. (courtesy oesper collection for the history of chemistry, university of cincinnati). 31almost a discovery glassware, stoves, distillation apparatus, equipment for preparing samples, and all kinds of paraphernalia? how to hire skilled labour necessary for scientific and technical activities? [ … ] . we can affirm with certainty that during many and many years the laboratory supplied the incipient demand for analyses, in a country just beginning to know its immense mineral possibilities, and also that the laboratory created a basis for future development of geochemistry in our country.17 with respect to equipment, the laboratory owned a small spectroscope (a detail important for our discussion) that may have been considered a novelty in laboratories and was certainly a rarity in latin america. in july 1874, gorceix arrived in rio de janeiro to a country that lacked any tradition in mineralogy and geology. once there, he was tasked with organizing teaching and research ex nihilo. brazil’s supposed and often hailed mineral richness is in great part a myth.18 geologist daniel atêncio of são paulo university notes that of more than 5000 mineral species known today, only 65 are native to brazil (23 of them discovered by atêncio himself ). the first to be discovered was chrysoberyl (beal2o4), described in 1789 by christian august s. hoffmann (1760-1814) and dietrich ludwig karsten (1768-1810), both students of abraham werner in freiberg. chrysoberyl was analyzed by martin h. klaproth (1795, before characterization of beryllium as an element). josé bonifácio de andrada e silva (17631838), also a former student at freiberg and discoverer of several new mineral species in scandinavia (1799/1801), could have contributed to the creation of a brazilian mineralogical tradition, but he instead devoted himself exclusively to the cause of brazilian political independence. gorceix’s first assignment in brazil was a visit to the province of rio grande sul with the botanist ladislau neto (1838-1894), director of the national museum. near the end of the same year, gorceix travelled to minas gerais to determine the location of the mining school. he opted for ouro preto. in the midst of 1875, he presented his proposals for the school, which included his “teaching philosophy”, to the governor. finally, on october 12th, 1876, the mining school of ouro preto was formally established. gorceix was named the director (until 1891) and was responsible for various disciplines. with the fall of the monarchy and the proclamation of a republic in 1889, gorceix and the school lost their great protector, pedro ii. in the face of this new political context, gorceix departed as director of the school in 1891 and named professor archias medrado (1851-1906) as interim director. gorceix returned to france, but his long absence made it difficult for him to return to academic and scientific activities. so, instead, he decided to finish his research career and engage in politics. he became mayor of le mont par bujaleuf. gorceix only returned once to brazil, in 1896, when he was invited as a teaching consultant. he died in limoges at september 6th, 1919. in 1926, on the 50th anniversary of the school, a bronze bust was erected in the internal yard of the building. in 1970, his remains were transferred to the mausoléu gorceix in ouro preto. besides his continuous efforts to ensure the survival and quality of the school, several examples of his own scientific research were published during his time in ouro preto, including analyses of minerals and the discovery of xenotime-y (ypo4). these research papers were published in part in the journal he founded in 1881, anais da escola de minas (since 1936 revista da escola de minas, and since 2016 international journal of engineering), and also in part in the comptes rendus of the french academy and in the bulletin de la société figure 3. bust of henri gorceix by an unknown sculptor in the inner yard of the former  escola de minas, erected 1926 at the 50th anniversary of the mining school, copyright and photograph by rené & peter van der krogt, delft, netherlands. (courtesy rené & peter van der krogt, delft). 32 juergen heinrich maar minéralogique de france. gorceix was responsible for the section “geology in brazil” at universal expositions such as the exposition universelle de paris (1889) and the south american exposition in berlin (1886).19 the mining school of ouro preto. cum mente et malleo once the location of ouro preto had been selected, the mining school was installed in the old governor’s palace, a partially fortified building erected in 1741 under the orders of governor gomes freire de andrade (1685-1763). the building shares a location with the former casa de fundição, designed by portuguese architect manuel francisco lisboa (17…-1767) on the basis of a project by general and military engineer josé fernandes pinto alpoim (1700-1765), an important figure in the development of brazilian mathematics.20 in ouro preto, gorceix had to choose between two models: the paris mining school and the saint etienne mining school. he was also, of course, influenced by his own course at the école normale.21 practical reasons led him to choose the st. etienne model, which proved easier to adapt to local conditions. gorceix’s project differed substantially from all other higher education courses in imperial brazil. murilo de carvalho lists the proposed facets of gorceix’s institution: free-of-charge education, full time classes (including saturdays and sundays) for students and teachers, a ten-month long school term (seven months was the norm in brazil) followed by two months of fieldwork, valuation of creativity and laboratory work, entrance examinations and frequent tests throughout the year, limited enrollments, grants for qualified students (for further studies in europe), and financial assistance to students in need.22 in gorceix’s own words: time for frivolous discussions about concepts and theories, simple speculations of the mind, a legacy from the middle ages and abandoned by the old world since a long time, are over [ … ] mines and metallurgical plants will be the best books in our libraries.23 gorceix’s project was not only innovative, but also almost an affront to brazilian academic traditions. the project was submitted to the appreciation of a commission of the rio de janeiro polytechnic school, and although approval was granted in the end, many sharp criticisms arose, marking the beginning of a famous rivalry between the two schools. the approval of his plans confirms gorceix’s political strength during the imperial period. gorceix defeated the arguments of influential people, including the viscount of rio branco, josé maria da silva paranhos (1819-1880), who was a former prime-minister (1871/1875) and very close to the polytechnic, where he served as dean and professor. gorceix’s plan remained in effect, with minor adjustments, until 1893 – substantial revisions occurred only in 1936, when the school became part of the universidade do brasil. since 1969, the school has been part of the federal university of ouro preto. it proved difficult to attract teachers and students to ouro preto. although a provincial capital, the town was still relatively small (circa 12.500 inhabitants in 1872). ouro preto was also far from rio de janeiro, and the school’s admission examinations and coursework itself were rigorous (at least compared to the country’s poor secondary schooling). graduates also faced poor prospects when searching for work in brazil.24 for the disciplines of physics, chemistry, mathematics, geology, mineralogy, foreign teachers were hired: armand de paul bovet, arthur charles thiré (18531924), paul ferrand (1855-1895); brazilian instructors included archias medrado (1851-1906), leônidas botelho damásio, and francisco van erven (1851-1936).25 s. figueirôa highlights that gorceix’s letters expose his contempt for brazilian teachers, who in his judgement were bad teachers teaching bad students. brazil’s general political and intellectual context must be considered when discussing the importance of the mining school. unlike what occurred at the polytechnical and medical schools in rio de janeiro, positivism had no influence in ouro preto. murilo de carvalho describes gorceix as a catholic, and his fellows as materialists or evolutionists.26 provincial and isolated, ouro preto was the right place for study and research: students and teachers interacted more than in other schools, and both remained longer at the school, the principal point of social life in the city. student life was much different from other schools, and interest in the nation’s economic and political future led to strong nationalist thought. many former students ascended to high posts in science, technology and government. carvalho observes that “it was essential for the ‘gorceix spirit’ the concern in translating scientific knowledge in developmental policies”. similarly, in 1970, djalma guimarães (1894-1973), pioneer of geochemistry and former ouro preto student, said: probably former students of the school of mines exercised a great influence during the first two decades of this century, when political context was not yet prepared to discuss issues related to scientific and technological knowledge. calógeras,27 pires do rio,28 francisco de sá,29 and other 33almost a discovery eminent former students of the ouro preto mining school entered the political scenario armed with objective knowledge of our natural resources [ … ].30 however, the state government assigned the planning and supervision of construction of the new capital belo horizonte (1897) to engineer aarão reis (18531936), a rio de janeiro polytechnic graduate. orville adalbert derby (1851-1915), an american geologist active in brazil, highlighted the quality of research done in ouro preto and its international recognition in an 1883 paper published in science: at present, the national museum and observatory in rio, and the school of mines in ouro preto, are the principal centres of scientific activity. the latter, being a comparatively new establishment, remote from the centralizing tendencies of the capital, organized on european models, and controlled by an able corps of french specialists, has escaped many of the vices of the older institutions.31 monazite sands from bahia on the southern coast of the province/state of bahia, in the municipalities of caravelas and prado, dark and heavy sand extends in long strips. known today as monazite sand, these strips are rich in rare earth minerals, and, in the case of sands from bahia, thorium minerals. ludwig camillo haitinger (18601945) and k. peters discovered the presence of radium in these sands in 1904.32 later, other deposits of monazite sands were discovered in espírito santo (1896) and rio de janeiro. orville derby, director of the geology section of the national museum in rio de janeiro, sent samples of sand from the beach of cumuruxatiba (municipality of prado) to gorceix in ouro preto (1883). this heavy brown sand he received from john gordon, an englishman (or american?), a manager of the north-american coffee exporting company e. johnstone & co. gorceix analyzed the samples from 1883 to 1885 and realized they contained phosphates and oxides of cerium, lanthanum and didymium (then still believed to be an element). at the same time, gordon, in partnership with english and german merchants, had exported 3000 tons of monazite sand by 1888. by 1890, the endeavor had “exported” a total of 15.000 tons to hamburg and was supplying rare earth processing industries in vienna and berlin.33 although there is no confirming evidence, it is believed gordon personally negotiated with carl auer von welsbach (1858-1929) and collected a fortune with this not entirely legal “trade”. the remnants of the wooden pier built on cumuruxatiba beach can still be seen today. the ruin advances hundreds of meters into the sea and facilitated the transfer of the “ballast of brazilian ships” into ship holds. inhabitants and tourists in cumuruxatiba, today a summer resort, remain predominantly unaware of the history and purpose of this derelict construction project, which has withstood the forces of the ocean, the mercilessness of time and decay, and even vandalism. after the pier was intentionally set on fire in 2005, only its row of pillars survives. in 1890, the government of bahia forbade “export” of the sands. but the trade was liberated again in 1895, though this time it was at least nominally under the control of state authorities. in 1900, a record-breaking 7120 tons were exported. afterward, the brazilian government finally forbade any export of this valuable raw material. international interest in the illegal extraction and smuggling of rare earth can be seen in alfred hitchcock’s 1946’s production “notorious” (launched in brazil as “interlúdio”).34 didymium and the chemical analyses of gorceix the supposed element didymium was first espoused to exist in 1841, when carl gustaf mosander (1797-1858) isolated it as an impurity of lanthanum, an element he had discovered as a contamination of cerium in 1839. didymium remained an element (symbol di) until 1879, when paul émile lecoq de boisbaudran (1838-1912) discovered a fraction of samarium in didymium, and as such didymium was included in periodic tables (gmefigure 4. didymium was incorporated in many periodic classifications, like this draft by hugo schiff (1834-1915) (courtesy  museo di storia della scienza, florence, reproduced with permission). 34 juergen heinrich maar lin, 1843, newlands, 1865, kremers, 1869, mendeleev, 1869). didymium possessed elemental status from 1841 to 1885, when carl auer von welsbach (1858-1929) split the mixture into two elements: neodymium and praseodymium. didymium’s story is not a simple one, and other researchers, like georges urbain and henri gorceix, came to the same conclusion; in his work on the subject, gorceix made no claim for a priority, and his effort was virtually ignored in the “central” scientific scenario as well as in the country where he lived and worked. to the best of our knowledge, dutra (2002) was the first to draw attention to gorceix’s ‘decomposition’ of didymium. we brought this information to the attention of colleagues abroad, who mentioned it in recent publications. didymium, as well as six ‘authentic’ elements (lanthanum, neodymium, praseodymium, gadolinium, samarium, europium) were obtained from cerium, discovered in 1803 by berzelius, and independently by klaproth in bastnaesite, a mineral found in the mines of bastnaes in sweden (bastnaesite was described for the first time by vilhelm hisinger [1766-1852]). with reference to the great amount of data on the chemistry of didymium, arthur comings langmuir (1872-1941) wrote in 1903: “the voluminous literature of didymium affords a striking illustration of the pursuit of science for its own sake, and with no reward beyond the satisfaction of having advanced the cause of truth”.35 moreover, adding to this “science for science”, to paraphrase parnassiens’ “l’art pour l’art ”, the enormous quantity of publications on didymium can now be found in a. c. langmuir’s “index to the literature of didymium (1842-1893)”, which was published in 1903 by the smithsonian institution after the initiative of henry carrington bolton (1843-1903). we may suggest a thought provoking question: to what extent is chemical practice an exact science, considering the many publications on the extraction, isolation, purification, chemical and physical properties of compounds of an element which does not exist? should we not consider the scientific methodology in place to be questionable or inappropriate? has the data been intersubjectively verified? should we accept the sometimes incoherent and inconsistent data, and the buildup of information, which would later be rejected, as a ‘normal’ step for any scientific investigation? or should we explain away such anomalies by appealing to “anthropogenic factors” centered on the shortcomings of our instruments and research techniques? in fact, until 1885, didymium was widely accepted to be a real element. however, many experiments showed contradictory results, which sometimes differed in samples with different origins, were sometimes impossible to replicate, or offered inconclusive results (such problems are not exclusive to didymium). since the discovery of didymium, there have been doubts about its elementary nature – this is clear in publications by hans rudolph hermann (1805-1875) as early as 1845, o. popp in 1864 (erbium and terbium as mixtures of didymium and yttrium), per theodor cleve (1840-1905) in 1885 after a series of experiments done since 1874, marc delafontaine (1838-1911) in 1878, and bohuslav brauner (18551935) in 1885. when, in 1879, lecoq de boisbaudran discovered samarium as an impurity in didymium, these doubts seemed to be clarified in part. among the chemists that systematically completed research on didymium, we cite jean charles galissard de marignac (1817-1894), h. r. hermann, f. frerichs, per t. cleve, karl friedrich a. rammelsberg (1813-1899), and many others. none of these chemists used unorthodox research strategies. no less than nine methods were proposed (and published) to separate lanthanum from didymium, by hermann, robert bunsen (1811-1899) and zschiesche, augustin damour (1808-1902) and deville, f. frerichs, auer von welsbach, auguste victor verneuil (1856-1913) and grigory wyrouboff (1843-1913), p. mengel, witt, paul gerard drossbach (1866-1903). at the same time, william crookes (1832-1919), octave leopold boudouard (1872-1923), eugène demarçay (1852-1903), georges urbain (1872-1938) and g. dimmer expressed views on the probable decomposition of didymium, retaining this opinion even after failing to prove it experimentally (not confirming brauner’s publication from 1885).36 adding 35almost a discovery to the uncertainties about rare earths, boudouard, from the conservatoire national des arts et métiers, suggested that even mosander’s cerium from 1839 could be a mixture of two elements (1895).37 our purpose here is to provide detail on gorceix’s chemical experiments with monazite sand and the didymium it supposedly contained. these experiments were performed in ouro preto from 1883 to 1886, a place distant from “central” scientific research institutions. although the findings were presented at the paris academy and published in french journals known worldwide, they did not attract the deserved attention, perhaps because gorceix lived and worked at the fringe of international academic life and at the “periphery” of the academic world. it is interesting to observe that, among the hundreds of scientific communications and papers published by langmuir in 1903, there is not a single reference to gorceix. the so-called “official” science solemnly ignored scientific productions from outside its geographic limits. the exhaustive two volume texts of richard böhm, “die darstellung der seltenen erden” (1905) make no reference to gorceix’s work on monazite sand.38 before coming to gorceix, it is interesting to see past research on the rare earth “didymia” since its “discovery” by mosander in 1841. marignac (1848, 1854), hermann (1853), cleve (1875, 1883), delafontaine (1878), kopp (1879), and clarke (1881) determined the “atomic weight” of didymium. mendeleev admitted the value 138 in his table. rammelsberg (1861) found the isomorphisms of didymium sulfate and other sulfates (“the isomorphism of the three cerite metals is beyond question”), marignac (1856) determined the theoretical crystalline form of didymium sulfate, and nordenskiöld (1861) determined the crystalline structure of didymium oxide, dio (rammelsberg proposed dio2). american chemists francis william hillebrand (1853-1925) and thomas norton (1851-1941) believed to have isolated metallic didymium in 1875 via electrolytic reduction of dicl2, thus obtaining cerium und lanthanum in accordance with a method developed by bunsen shortly after the development of the bunsen cell.39 using electrolysis, bunsen obtained y ttrium, cerium, lanthanum, didymium, thorium, zirconium, calcium and strontium in a “free state”. bunsen’s process converts oxides into sulfates, sulfates in chlorides (via oxalates), which were finally submitted to electrolysis. the authors remark that, of the three metals, didymium is the most difficult to obtain: didymium reacts with oxygen from the air to regenerate as an oxide. they further mention that the physical properties of didymium are more similar to those of lanthanum, rather than cerium. hillebrand and norton were looking for a very pure sample of didymium, like ‘pure didymium chloride’, which is necessary for electrolysis, and supposedly used the entire supply of lanthanum sulfate and didymium sulfate available at the laboratories of heidelberg university (hillebrand was a student and later an assistant of bunsen; norton was also a graduate student of bunsen). in the electrochemical series, didymium is located between cerium and magnesium. numerous contemporary papers discuss the separation of didymium from lanthanum and cerium (marignac, 1849; bunsen, 1875) or independently from cerium (popp, 1864) or lanthanum (frerichs, 1874), or from still other species, such as gallium (lecoq de boisbaudran, 1882), thorium (hermann, 1864), and zirconium (hermann, 1864). the separation of ‘didymium’ from cerium or lanthanum is not an absurdity; it could be a separation of a ‘mixture (neodymium + praseodymium)’ from its neighbours. didymium’s place in the periodic table was also a contentious matter (schiff, 1879; piccini, 1885). the paradox of an experimental investigation of a non-existent element will be discussed later. the figure shows a drawing of the periodic system by ugo schiff (1834-1915), which included didymium as an element.40 by way of example, let us discuss the procedure developed by f. frerichs for separating lanthanum from didymium (1874).41 a mixture of lanthanum and didymium oxides is heated in a flow of chlorine, then water is added to the resultant mixture of the oxichlorides, and the solution is allowed to stand for a while – la and di proportions in the solution are 3:6. lanthanum chloride remains dissolved, and didymium chloride precipitates. with higher concentrations of lanthanum, the procedure must be repeated. other methods suggested by frerichs consist of dissolving the oxides in nitric acid, adding sulfuric acid, and allowing the solution to stand for several days. the sulfuric acid combines with lanthanum, creating lanthanum sulfate. in order to obtain pure didymium compounds, sulfuric acid is added to the oxides until all the lanthanum and some of the didymium is converted in sulfates. after evaporation and ignition, a white mass is obtained, from which water extracts the lanthanum and part of the didymium. pure didymium oxide is obtained by dissolving the residue in sulfuric acid. this example illustrates how the lack of appropriate experimental (in this case, analytical) methods may result in false conclusions in chemical practices. in the case of gorceix, our interests lie in one aspect of didymium’s chemistry: its occurrence in monazite and monazite sand. gorceix had already completed some research on monazite before receiving the samples of caravelas from orville derby in 1883.42 the first men36 juergen heinrich maar tions of monazite in brazil came from gorceix himself (1883), when he “tentatively” considered the yellow sand grains from fazenda quebra-galho (são paulo)to be monazite. he was later informed that the sand was actually from caravelas (1884). gorceix mentions the occurrence of monazite in other places in minas gerais: the diamond-containing depositions in diamantina43 (1884, 188544), gold places in casca on the rio doce (1885),45 and finally in salobro, bahia (1884).46 in possession of the sands remitted by derby, gorceix worked on separations. in 1885, in the bulletin de la société minéralogique de france, he writes the following: “the samples [from caravelas sands] are found in form of yellow bright grains, mixed with some ferro-titanium”.47 once the iron is completely removed, microscopic examination of the sands reveals a homogeneous aspect containing crystals. some of these crystals resemble monazite and others suggest the presence of another species of mineral. the density of the mixture is 5,1. the sand is then ground into a fine powder, heated with sulfuric acid, dried and dissolved again in a weak acid solution. the insoluble fraction in the resultant sulfuric acid contains silica and zircona, and the soluble fraction contains cerium and didymium oxides, which are precipitated with oxalic acid. oxalates are heated and converted into nitrates. fusion with potassium nitrate at 360°c separates cerium from didymium. gorceix’s analysis suggests the following composition for the monazite sand from caravelas: (a) (b) sio2 3.4% zro2 6.3 9.7% cao 1.1 phosphate 25.7 ceo 28.0 dio + lao (?) 35.8 total: 100.3 (a) insoluble fraction; (b) soluble fraction. fraction solubilised by sulfuric acid contains: phosphate 28.7 % ceo 31.3 dio + lao (?) 39.9 total: 99.9 hence, the formula is po3.3[ceo,dio,lao],where 30% is phosphate and 70% are oxides of the three rare earths. gorceix emphasizes that his analysis revealed greater didymium content in the caravelas sands when compared with similar sands found in slatoust (russia) and arendal (norway). sands from slatoust were analysed by debray at the école normale. gorceix’s paper was also published in the comptes rendus of the paris academy,48 where it was presented by jules henri debray (1827-1888), which should have given it a greater visibility among scientists. however, its relative obscurity may be due to its provenance from the distant and unfamiliar ouro preto. in 1913, richard böhm published a more detailed analysis of monazite sand from bahia, showing the elements neodymium and praseodymium to be decomposition products of didymium49: cerium dioxide 31.5 % phosphoric acid 26.0 lanthanum oxide 17.52 neodymium oxide 10.52 praseodymium oxide 4.9 thorium oxide 1.0 other rare earths 9.6 in the same year, 1885, as gorceix’s publication, bohuslav brauner (1885-1935) in prague and carl auer von welsbach (1858-1929) in vienna analyzed didymium due to the well-founded suspicion about the possible divisibility of didymium. brauner was initially interested in finding new evidence for the periodic system of his friend mendeleev, as well as confirming p. cleve’s work signaling the decomposition of didymium into three elements (including lecoq’s samarium there where indeed three elements).50 auer decomposed didymium into two elements, neodymium and praseodymium, and after many recrystallizations, finally obtained the elements as double nitrates of ammonium – with slight differences in solubility and with different colours.51 former attempts were unsuccessful, lacking fractional recrystallizations of other salts, like double sulfates. brauner did not obtain neodymium and praseodymium compounds, but rather obtained different spectral data for the two new elements. six weeks before auer’s publica37almost a discovery tion, gorceix obtained the same spectral lines as those shown later by auer’s compounds. gorceix found no sustainable explanation for his experimental results, and did not claim priority over the “discovery” of a new element. we found no reference to any testing or repetition of gorceix’s experiments by other researchers. it seems, judging from his publications, that gorceix was primarily interested in confirming the existence of didymium in monazite sands. brauner and gorceix based their findings on the decomposition of didymium on spectral data, but in the case of didymium, as robert bunsen observed in 1866, the occurrence of “unusually narrow” spectral lines makes for a difficult interpretation. william crookes (1832-1919), in 1886 and again in 1889, discussed the possibility of an even greater divisibility of didymium than that predicted by auer.52 modern chemists may find it surprising that even after didymium was found to be a mixture of neodymium and praseodymium, some chemists persevered in studying didymium as an “element”. even more surprising, many chemists still believed, in late 19th / early 20th centuries, that neodymium and praseodymium could be divided into new “elements” on the basis of empirical (mostly spectral) data. richard böhm’s book, mentioned above, presents useful data for that purpose. further, many orthodox chemists investigated new “simple compounds” as elements. carl von scheele, in 1901, after many analyses, asserted that praseodymium has in fact an elemental nature.53 konstantin von chroustschoff (1852-1912) announced in 1897 a third component of didymium, the supposed “element” glaucodidymium, although this was never confirmed. for eugene demarçay (1852-1903), the discoverer of europium (1901), neodymium was, without a doubt, an element (1898).54 against current and almost universally accepted emerging chemical facts, some chemists insisted on the divisibility of the two new elements isolated from didymium. in 1892, paul albert schottländer (18431897), who earned a doctorate in würzburg and was an amateur chemist in berlin (1886/1896), published observations of the crystallization of double nitrate of praseodymium and ammonium: from the components of praseodymium, one element considered to be a metal presented only one absorption line (λ 468,9) [ … ]. the other praseodymium components constitute two groups, which seem to suffer separation during the crystallization process. one of them we call prα [ … ] and the other prβ.55 also, for the americans, louis monroe dennis (1863-1936), from cornell university, and his student emile monnin chamot (1868-1950), praseodymium was supposedly divisible (1897).56 the same opinion was expressed in 1899 by friedrich w. muthmann (18611913).57 richard böhm, in 1902, interpreted the spectral lines of praseodymium as pertaining to three “components” of the metal: prα (λ 596,8 and 589,6), prβ (λ 481,1 and 440,0, announced by cleve in 1878), and prγ (λ 469,0), identical to diη described earlier by gerhard krüss (1859-1895) and lars nilson (1840-1899).58 a possible explanation for a paradox in 1885, the empirical observation that didymium did not exist as an element, being confirmed as a mixture of neodymium and praseodymium, was insufficient to immediately remove it from the practices and activities of many chemists. we have thus another example of the persistence in science of ideas and facts that are no longer acceptable. such persistence is perhaps better understood as the resistance of some chemists to altering the body of data and beliefs guiding their practices. it is also an example of how scientific methodologies may justify anachronisms. “even formally excluded from the row of elements – wrote böhm in his text from 1905 – exclusively practical motivations led to a discussion about its preparation since for obtaining its components chemists frequently use materials rich in didymium as a raw material.”59 an 1898 paper by andré job (18701928),60 professor at the conservatoire national des arts et métiers, which described “new chemical compounds derived from cerite metals”, registers the preparation of oxalochloride of lanthanum obtained from lanthanum sulfate, for which he suggests the formula (c2o4) cl2la2. dissolved in hot water, this salt decomposes into lanthanum oxalate and lanthanum chloride. so far, this is nothing unusual. however, job also mentions that it is necessary to start with very pure lanthanum that is free from cerium and didymium (this in 1898), with the “spectroscope showing no more any signs of didymium”, and various new analytical methods developed by job himself showing no signs of cerium. in the same paper, job refers to the preparation of the same type of salt with cerium and with didymium, alluding to the didymium oxalonitrate prepared previously by cleve. richard böhm suggests that this situation could be explained by the evolution of chemistry itself: since older scientists studied very little or nothing about spectra, lacking therefore a resource to confirm the absence of lanthanum, they took for didymium oxide all products which precipitate as oxalate in an acid solution containing didymium and lanthanum, but not cerium.61 38 juergen heinrich maar the situation just described is not unique to the field of chemistry. but how is it possible for an exact, methodologically structured and practiced science to continue to operate on obsolete data? even though there may be a practical justification for the reluctance to reject falsified beliefs, is this not a case of bad science? or bad scientists? was there an excessive emphasis on empirical facts? or was practice too distant from theory? a possible explanation would be a general unawareness of the latest research results on didymium. however, this is not the case here; the international chemical bibliography had already incorporated neodymium and praseodymium, while excluding didymium from the series of elements. alternatively, this could be the result of an isolated group of researchers studying the “cerite metals” unaware of the newest literature, and therefore continuing to work on outdated data. this situation is often observed in the scientific practice of the so-called (geographically) “peripheral science”, where the diffusion of new information is often slower. there may be other explanations originating from the theoretical frameworks prevalent in different countries. we know from history that the anti-atomist thinking of positivists like jean-baptiste dumas (1800-1884) and marcelin berthelot (1827-1907) had a negative influence on the evolution of several aspects of french science. but disbelief in the existence of atoms as real and concrete entities did not prevent chemists from discovering new elements, as is proved by mendelevian eca-elements gallium (1875, lecoq de boisbaudran), scandium (1880, nilson) and germanium (1886, winkler). in other words, science may progress in the sense of making discoveries, despite false beliefs or wrong theories. this fact could in turn psychologically explain why we experience a kind of inertia or resistance from the scientific community when promptly revising beliefs or theoretical frameworks in the face of anomalies, as it may not be necessary to do so to make new discoveries. in this case, the high level of complexity in the experimental study of rare earths elements adds to this inertia. revising theoretical frameworks in light of anomalies conflicts with the desire to prioritize new discoveries, which in turns explains why scientists may choose to ignore such anomalies and carry on with their research programs. the desire for priority also explains the hasty communication of new rare earths discoveries that were later found to be just mixtures, or rediscoveries. physicists and chemists know all too well max planck’s quote on the triumph of new theories: it is not caused by the strength of their arguments, but by the death of the defenders of the older views. the best example of this in chemistry is the rapid triumph of lavoisier’s oxygen theory: after the death of its most prominent opponent, joseph priestley (1804), adherents of the old theory rapidly left the scene. the “old chemistry” then ceased to exist with the death of its last representative, anders retzius (1742-1821). in the case of the “element” didymium, we are not discussing theories, but rather the reluctance to accept the fact that it is a mixture and not an element. its falsification occurred during a period of “normal science” (in kuhnian sense) in chemistry. the general theoretical framework of chemistry is not being called into question, but we may identify some problematic methodological aspects of laboratorial work, such as overreliance on spectral data. due to the prolific amount of work on rare earths, we can find many situations resembling the case of didymium, or cases where scientists were reluctant to accept well documented falsification. and we also find amongst the history of rare earths discoveries examples situated at the other end of the spectrum; cases where elements were well confirmed and widely believed to exist, and yet some were reluctant to accept them (not only for scientific reasons). george de hevesy’s (1885-1966) and dirk coster’s (1889-1950) hafnium (1923) was unanimously accepted only after george urbain’s celtium, discovered six months before, was shown to be the same as lutetium, discovered by urbain himself in 1913, from another mineral, samarskite. when discussing rare earths elements, it is important to consider the enormous difficulties faced by chemists. the properties of rare earths elements are so similar that identification, isolation and purification are extremely difficult. chemists often misinterpreted mistakes, sometimes thinking a mixture to be a “new” element, and sometimes concluding that different samples of the same element were different elements. franco calascibetta points to theoretical and experimental problems: the vast number in the family, their appearance, multiplication and then disappearance, have several times been linked, in both the last and the current century, to important theoretical aspects of chemistry, including mendeleev’s periodic system and later moseley’s discovery and the new definition of atomic number.62 before the invention of spectroscopy, notably that of bunsen and kirchhoff (1859),63 chemists had at their disposal very difficult, troublesome and labour-intensive methods for identification and characterization of these elements. notwithstanding, experimented chemists like brauner, auer, marignac or urbain were still able to 39almost a discovery characterize new elements using only “classical” analytic methods. an initial limit to an apparently unlimited number of possible elements was mendeleev’s number of empty spaces (elements still unknown) in his periodic table, which indicated that there is indeed a limit to the number of possible rare earth elements (1869). convinced mendelevians suggested new graphical representations of the table that allowed the correct location of the elements still to be found, as in the tables of brauner (1902)64 and of alfred werner (1905)65. brauner included 19 rare earth elements in his table, seven of which were still unknown at the time. werner proposed 15 rare earth elements, two of them (between neodymium and samarium) not yet discovered. after henry g. j. moseley’s (1887-1915) studies with x-ray spectroscopy in oxford (1913) it was finally possible to define the “atomic number” of elements and conclude that the maximum theoretically possible number of rare earth elements is 14. two of these were not yet known: atomic number 43 (technetium, 1937) and atomic number 61 (promethium, 1945). finally, by combining empirical knowledge with theory, it was possible to determine which ones exist in the vast universe of possible rare earth elements – exhaustively described by marco fontani and coworkers.66 in other words, elements confirmed based on empirical facts alone, but in disagreement with theory, could finally be discarded. joseph william mellor (1869-1938), in his extensive treatise on inorganic chemistry, presents a table with 73 supposed rare earth elements discovered between 1794 and 1920.67 out of these, 15 were mixtures and 25 were never confirmed. empiricism without proper theoretical foundations leads to error. this explanation, of course, does not apply just to the case of didymium. still other (non-scientific) motivations exist for didymium’s persistence, and these are exclusive to didymium. didymium, when still believed to be an element, was used in the production of special glasses for the protective goggles of glassblowers. even after its falsification, the term didymium continued to be used, meaning the fraction remaining after the removal of all cerium content from monazite (this fraction contains 46% lanthanum, 34% neodymium, 11% praseodymium, and some samarium and gadolinium). mixtures of neodymium and praseodymium, like a ‘false didymium’, were used as catalysts and in the glass industry. ludwig moser (1833-1916) founded a factory that produces glassware (josef moser & söhne) in 1857 in karlsbad (bohemia), now karlovy vary, which used neodymium and praseodymium salts to obtain a great variety of iridescent colours, producing objects much appreciated during the art nouveau and art déco periods. in the 1920s, the chemists of karlovy vary again mixed neodymium and praseodymium salts, a kind of ‘synthesis’ of didymium, obtaining several pigments. one more reason has been presented to explain didymium’s longevity. f. szabadváry and c. evans (1996) offered a fanciful explanation for the permanence of the term “didymium” in the chemical literature: that auer published his paper on the isolation of neodymium and praseodymium from didymium in an obscure chemical journal, the monatshefte für chemie.68 but in auer’s time, and for many decades, this journal was all but obscure. epilogue – rudiments of an industry unfortunately, rare earths constitute an additional example of underused brazilian natural resources, thanks to lack of strategic policies of management69 is the sad conclusion of chemist osvaldo serra (*1943) on these resources, which are known for their history, occurrence and prospection, but were never really considered seriously by the academy and industry. at the same time, serra mentions a phenomenon that is not restricted to brazil, but that occurs worldwide: the dismantling of mineral processing industries not only causes unemployment, but also the disappearance of knowledge and rare skills and abilities necessary for mineral processing procedures. the recent resumption of extraction, separation and purification of rare earths in brazil is actually a new start, as all that was previously known about these procedures was lost. until 1914, brazil was the world leader of rare earth extraction, but it brought no benefit to the country: “the ballast of brazilian ships” created richness elsewhere. decades later, brazil began a timid industrial exploration of monazite sand with the foundation, in 1942, of the orquima s.a. (organo-química, later indústrias químicas reunidas) in são paulo, with a factory in santo amaro/são paulo.70 in 1946, orquima began to process monazite sand not from bahia (because of the long distance) but from the states of espírito santo (where it was discovered in 1896 and has been processed since 1906 by mibra –société miniére et industrielle franco-brésilienne) and rio de janeiro. orquima company developed and used with perfection all the know-how necessary for the extraction, processing, isolation and purification of rare earths – especially during the 20 years in which the polish chemist pawel krumholz (1909-1973), a former assistant of fritz feigl (1891-1971) in vienna, was in charge as tech40 juergen heinrich maar nical director. krumholz, along with an accomplished group of coworkers, produced at orquima an internationally acclaimed work on rare earths.71 orquima processed 2000 tons of monazite annually, producing compounds of cerium, lanthanum, neodymium, samarium, thorium, zirconium, with a purity of up to 99.99%. it was nationalized in 1949 and acquired by the comissão nacional de energia nuclear – cnen – in 1960, during the nationalistic and state-centralizing policies of the governments of that period, and transferred later to the nuclemon (nuclebrás areias monazíticas). all orquima’s activities were sadly paralyzed in 2002; lacking the deserved support, the enterprise failed. aknowledgements the author wishes to express his gratitude to the following: rené and peter van der krogt, delft, netherlands; william jensen, university of cincinnati and oesper collection for the history of chemistry; organic chemistry department ‘ugo schiff ’, university of florence; marco fontani, university of florence; laura colli and  museo di storia della scienza, florence;  museu de arte de santa catarina/masc, florianópolis, brazil. references 1. gorceix, h., inaugural speech, ouro preto mining school, october 12th, 1876. 2. maar, j. h., “história da química, vol.ii, de lavoisier ao sistema periódico”, papa-livro, florianópolis, 2012, 544. 3. karpenko, v., ambix, 27, 77-102 (1980). 4. anonymous, manufacturer & builder, 122 (7), nº 976, 84. 5. cláudio vieira dutra, professor at the federal university of ouro preto, was the first to draw attention to these facts, in 2002, and to him pertains the priority of including this novelty into the history of chemistry. dutra, c. v., revista da escola de minas, ouro preto, 55, 185-192 (2002). 6. alves, g. l., “o pensamento burguês no seminário de olinda”, editora da universidade federal de mato grosso do sul/editora autores associados, campo grande e campinas, 2001. 7. maar, j. h., scientiae studia, 2, 33-84 (2004). 8. cunha, l., “a universidade temporã”, editora civilização brasileira, rio de janeiro, 1980. 9. figueirôa, s., “um olhar sobre o passado”, editora da universidade estadual de campinas, campinas, 2000. manuel ferreira da câmara (1762-1835), member of the national assembly, proposed in 1823 the creation of an university in rio de janeiro, the “instituto brasílico” (campos, e. s., “história da universidade de são paulo”, editora da universidade de são paulo, 2004, p.27). 10. habashi, f., bulletin of the canadian institute of mines, 90, 103-114 (1997). 11. carvalho, j. m. de, “a escola de minas de ouro preto – o peso da glória”, editora da universidade federal de minas gerais, belo horizonte, 2002. 12. schwarcz, l., “as barbas do imperador”, cia. das letras, são paulo, 1998. 13. santos, n. p. dos, revista da sbhc, 2, 54-64 (2004); 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all had technological training as engineers and exert41almost a discovery ed strong influence on economic questions. 30. guimarães, d., apud carvalho, j. m., op. cit., p. 132. djalma guimarães (1894-1973), emeritus professor of the universidade federal de ouro preto, was perhaps the most important brazilian geologist, discoverer of the great niobium reserves near araxá/minas gerais (1931/1932). 31. derby, o., science, 1 (8), 211-214 (1883). 32. haitinger, l., peters, k., sitzungsberichte akademie wien, 1904, 159-160. 33. leonardos, o., “a monazita do estado da bahia”, departamento nacional de produção mineral, rio de janeiro, 1937. 34. for a critical review and production history of “notorious”, see “notorious” (1946): hitchcock’s mature and intricate espionage masterpiece”, https:// cinephiliaandbeyond.org. the screenplay was written by ben hecht (1894-1964). 35. langmuir, a., “index to the literature of didymium”, smithsonian miscellaneous collections, washington, 1893. 36. herzfeld, o., korn, o., “chemie der seltenen erden”, springer, berlin, 1901. 37. fontani, m., costa, m., orma, m., “the lost elements”, oxford university press, 2015, 40. 38. böhm, r., “die darstellung der seltenen erden”, 2 volumes, veit & co., leipzig, 1905. 39. hillebrand, w., norton, j., annalen der physik (pogg.), 155, 633-639 (1875); ibid., 156. 456-474 (1876). 40. selleri, s., fontani, m., “cent’anni dalla scomparsa di ugo schiff ”, consiglio regionale, florence, 2016, 63-80. 41. frerichs, f., berichte, 7, 331-366 (1878). 42. gorceix, h., anais da escola de minas de ouro preto, 4, 29-48 (1885). 43. gorceix, h., compt. rend., 98, 1446-1338 (1884). 44. gorceix, h., bull. soc. min. france, 7, 179-182 (1884). 45. gorceix, h., anais da escola de minas de ouro preto, 4, 29-48 (1885). 46. gorceix, h., compt. rend., 94, 1446-1448 (1884). 47. gorceix, h., bull. soc. min. france, 8, 32-35 (1885). 48. gorceix, h., compt. rend., 100, 356-358 (1885). 49. böhm, r., “die verwendung der seltenen erden”, veit & co., leipzig, 1913. 50. cleve, p., bull. soc. chim. france, 21, 196 (1874). 51. auer von welsbach, c., monatshefte für chemie, 6, 477-491 (1885). 52. crookes, w., chemical news, 60, 27 (1889) 53. scheele, c. von, z. anorg. allg. chem., 27, 53-57 (1901). 54. demarçay, e., compt. rend., 126, 1039-1041 (1898). 55. schottländer, p., berichte, 25, 378-394 (1892). 56. dennis, l., chamot, e., j. am. chem. soc., 19, 799809 (1897). 57. muthmann, w., stützel, l., berichte, 38, 2653-2677 (1899). 58. böhm, r., z. angew. chem., 15, 1282-1299 (1902). 59. böhm, r., op. cit (1905), 469. 60. job, a., compt. rend., 126, 246-248 (1898). 61. böhm, r., op. cit. (1905), 470. 62. calascibetta, f., vii convegno nazionale di storia e fondamenti della chimica, l’aquila, 1997, 259-272. 63. bunsen, r., kirchhoff, g., annalen der physik (pogg.), 110, 161-189 (1860). 64. brauner, b., zeitschr. anorg. chem., 32, 1-30 (1902). 65. werner, a., berichte, 38, 914-921 (1905). 66. fontani, m., costa, m., orma, m., “the lost elements”, oxford university press, 2015. 67. mellor, j., apud calascibetta, op. cit., p. 264. 68. szabadváry, f., evans, c., “episodes from the history of rare earth elements”, kluwer academic publishers, dordrecht, 1996, 64. 69. sousa filho, p., serra, o., química nova, 37, 753-760 (2014). 70. serra, o., j. braz. chem. soc., 22, 811-812 (2011). 71. vichi, e., química nova, 6, 152-156 (1983). doi: https://doi.org/10.36253/substantia-1040 received: jul 31, 2020 revised: oct 23, 2020 just accepted online: oct 26, 2020 published: mar 01, 2021 https://doi.org/10.36253/substantia-1040 substantia. an international journal of the history of chemistry 5(2): 19-34, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1224 citation: kessenikh a. (2021) spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983). substantia 5(2): 19-34. doi: 10.36253/substantia-1224 received: feb 19, 2021 revised: jul 05, 2021 just accepted online: jul 06, 2021 published: sep 10, 2021 copyright: © 2021 kessenikh a. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature articles spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh s.i. vavilov institute for history of science and technology, russian academy of science, moscow, russia e-mail: kessen32@mail.ru; orcid: 0000-0001-8727-4642 abstract. an attempt is undertaken to acquaint the reader with a history of research and applications of dynamic nuclear polarization (dnp) in the most concise form the main focus on the first three decades of dnp research, and the history of the discovery and development of multiparticle dnp and its relationship with the spin temperature approximation are outlined in some detail. the article emphasizes the role of such researchers as anatol abraham, maurice goldman, michel borghini, thomas wenckebach, vadim atsarkin, boris provotorov, maya rodak, mortko kozhushner, levan buishvili, givi khutsishvili. as far as possible, the contributions of many other scientists are considered. the establishment of a uniform temperature for nuclear spins due to the effect of spin diffusion was first proposed by nicholas blombergen in 1949. the content of the article is based on the bibliography available in the public domains, in particular on the memoirs of the research participants, and first of all on the materials of atsarkin’s 1978 review in sov. phys. uspekhi and on the oral history of the development of the multiparticle concept of dnp effects, collected from the speeches of the participants of the moscow seminar “problems of magnetic resonance” in 2001. a simplified description of the effects of dnp and a summary of the history of their discovery is given in section “introduction”. the brief biographical data and portraits of participants in the dnp study are given in appendix 1, and a selected bibliography on the problems of dnp and spin temperatures is given in appendix 2. the bibliography divided into four sections according to the time and type of publication (i historical research, memoirs; ii – monographs, reviews; iii original publications 1953 1983; iv – some original publications of a later time, mainly during the transformation of dnp into an method for the implementation of nuclear magnetic spectroscopy and tomography in the interests of chemistry, biochemistry and medicine). the widespread use of dnp methods is evidenced, for example, by the fact, that by now company bruker biospin has installed about 50 gyrotron based spectrometers for dnp operating up to 593 ghz worldwide to date. keywords: magnetic resonance, dynamic nuclear polarization, nuclear spin. http://www.fupress.com/substantia http://www.fupress.com/substantia 20 alexander kessenikh 1. introduction 1.1. general remarks the degree of polarization is determined by the relative excess among the spins of some type such a one with a lower energy of interaction with the magnetic field. therefore, this configuration is stable. the lower a lattice temperature tl is, the greater an excess of spins at the lowest quantum levels. the higher the induction of the magnetic field in which the sample is located, the higher the degree of polarization. the increasing of magnetic field’s induction b0 causes enhancement of polarization. this method of increasing polarization was once called the “brute force method”. the increase in polarization with decreasing lattice temperature is also natural. that is why experiments with polarized nuclei at low absolute temperatures tl ≤ 4.2 k are so widespread. the thermal polarization ps0 regardless of tl, for example, for spins s = ½ is equal to: ps0 = tanh (1) hereafter γs is the gyromagnetic ratio for electron spins, γi is the gyromagnetic ratio for nuclear spins, ħ = h / 2π is the planck constant, k is the boltzmann constant. the total paramagnetic moment of each type of spins i=½ with a total number n and gyromagnetic ratio γi and magnetic moment μi under conditions of interaction with lattice located at the absolute temperature tl is equal ( for μib0 <<ktl) to: m0 = = μi·pi (2) however, it turns out to be possible, using magnetic resonance and other “pumping” methods, to create quasi-equilibrium configurations with anomalous depletion of the lower levels or even with an excess of spins at higher energy levels. it is dynamic nuclear polarization (dnp). under conditions of continuous action of an alternating electromagnetic field with a frequency close to the esr resonance of paramagnetic centers (pc), the zeeman system of nuclear spins takes on a temperature ti that differs from the lattice temperature, and therefore: |m*| = ηm0 = (3) where η≤ is “the enhancement coefficient” or enhancement of nuclear polarization. the dynamic nuclear polarization for nuclei with γi may be of the order of thermal electron polarization for pc with γs. for an arbitrary spin number i, the corresponding values of the total magnetic moment and, therefore, the integrated intensity of the nmr signal are [abragam. ii.1961. chapter viii]: m0 = (2a) |m*| = (3a) anomalous polarization is characterized in conditions dnp (in the simplest case relatively high temperatures) by formula (3a), similar to (2a), but with the positive or negative inverse temperature of the nuclear zeeman system possibly much more in absolute value than the inverse lattice temperature) |ti|– 1>>(tl)– 1. methods of dynamic polarization of nuclei employing esr saturation began to develop in 1953. the mechanism of dnp was discovered and elementary magnetic resonance acts of one kind of electron spins s directly interacting with nuclear spins i was studied (overhauser effect (oe) [overhauser. iii. 1953a;1953b; carver and slichter. iii.1953]). the processes were discovered soon [abraham m., kedzie, jeffries iii.1957] with a saturation of the combined resonance a(±)(∓)s∓i± of the spins of two particles (an electron and one of the nuclei). in the so called solid effect (se), the result is achieved due to the microwave-induced forbidden electron-nuclear transitions a(z)(±)szi±, when each of the transitions two spins: s and i. the latter dnp mechanism is effective for solid dielectrics with a high density of polarized nuclei i (see below about nuclear spin diffusion) and was discovered by abragam [abragam, proctor. iii. 1958]. in previous formulas a(i)(k) are the components of hyperfine interaction tensor. later (1963-1967), the mechanisms were observed evidently with excitation of processes involving three spins (two electron and one nucleus, so called “electronnuclear cross-relaxation” (encr) or cross-effect (ce)) through saturation on the wings of the esr lines [kessenikh et al. iii.1963; hwang and hill. iii.1966a; 1966b]. the dnp mechanisms involving many electron spins were discovered almost simultaneously (1962 1968). in such mechanisms of nuclear polarization, the so-called thermal mixing (tm) and dynamic cooling (dc) dnp occurs due to the transfer of collective energy of electron spin-spin interactions, i.e., we are faced with an essentially multiparticle effects [abragam, borghini. iii.1962; provotorov, kozhushner. iii. 1967]. this was immediately confirmed in the important experiments performed by atsarkin, mefed, rodak [atsarkin et al. iii.1967], by dutch physicists [wenckebach et al. iii.1968; 1970], and by french physicists. the detailed analysis of the relationship between tm and ce is given 21spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) by wenckebach (see [wenckebach ii.2016; iv.2017; iv. 2019a;2019b]. the first steps of discovery and mastering of these two late dnp mechanisms were considered in the article [atsarkin, kessenikh. i.2012]. if we talk about dynamic polarization through the excitation of transitions between mixed electron-nuclear states, then this effect is provided usually by the nuclear spin diffusion inside the array of matrix nuclei (see for example [khutsishvili.iii. 1954; khutsishvili.ii.1968]), although it also manifests itself on the nuclei of the substance dissolved in the matrix. it should be noted that the diffusion mechanism of nuclear spins in a solid-state matrix was first suggested by n. blombergen before the discovery of dnp processes [blombergen. iii.1949]. when the dipole-dipole and exchange interactions in the system of electron spins of the paramagnetic centers (pc) are sufficiently large and their energy is at least comparable to the energy of effects leading to inhomogeneous esr broadening, the effects of dynamic cooling (thermal mixing) with a multiparticle transfer of polarization from the electron spin-spin reservoir to the nuclear zeeman system come to the fore in the dnp mechanisms. 2.the thermal mixing or dynamic cooling. under the sign of provotorov’s theory the mechanisms of dnp and related phenomena discovered or predicted earlier remained in the repertoire of researchers and were successfully developed further. the overhauser effect in nuclear spin systems with different resonant frequencies has become an almost routine method in nuclear magnetic resonance [noggle., schirmer. ii.1971.]. numerous studies in weak magnetic fields (up to the induction of earth’s magnetic field) have also been partially based on the overhauser effect. the “solid effect” discovered by a. abragam was successfully used for proton polarized targets. separate studies of the three-spin encr (ce) mechanism have also been performed. however, the main direction of research on dnp and related phenomena in the 1960s-1970s was the study of the effects of thermal mixing of the nuclear zeeman system with the subsystem of dipole-dipole interactions of electron spins discovered by boris provotorov. anyone who dealt with the problems of magnetic resonance in the 60s-70s will immediately remember what works [provotorov. iii.1961; provotorov. iii.1962] mean and what role they played in the development of this field of science. the essence of provotorov’s theory is that there exist an inverse temperature and one more inverse temperature, which are the inverse temperatures of the zeeman interaction and the dipole-dipole interaction. the concept of two temperatures is applicable both in a coordinate system rotating with the frequency of a radio-frequency field and in a laboratory coordinate system, and the schools of a. abragam m. goldman and a. redfield (see classical monographs [goldman.ii.1970; abragam and goldman.ii.1982]) predominantly use a rotating system coordinates. the relationship between the inverse temperatures of the two reservoirs is determined by provotorov’s equations. here is the record of provotorov’s equations in the classic monograph by m. goldman in the laboratory system: (4) where δ = ω0 ω (detuning the microwave frequency ω from resonance); d = γhl, – the average shift of the resonance frequency of each of the dipoles in the local field hl (that is, in the field caused by neighboring dipoles); factor proportional to the square of the amplitude of the resonant magnetic field w = πω12g(δ) – the probability of transition between spin magnetic sublevels under the influence of a rotating magnetic field with amplitude , where g(δ) – line shape function. the prime at a’= in goldman text corresponds to the zeeman temperature in the laboratory system, while the author of [goldman. ii.1970] and his immediate colleagues consider most of the problems in a rotating coordinate system. the value β = is a inverse temperature of spinspin reservoir introduced in provotorov’s works. it should be stressed for formal thermodynamics that the revolutionary idea of provotorov was to assign two temperatures to a single system of spins. this was theoretically a controversial innovation, especially because – except in the high temperature approximation—these two temperatures cannot be assigned to two separate energy reservoirs. j.philippot – [philippot. iii.1964], considered the inverse zeeman temperature as a chemical potential and the inverse dipolar interaction temperature as the real inverse temperature. the method of two reservoirs proposed by provotorov for a system consisting of one kind of spins turned out to be extremely fruitful. this method is suitable both for systems with several resonance lines, and for spin systems with spins of different types, with sharply differing values of gyromagnetic ratios. the case when the resonance frequency of spins with a low γi value is close to the width of the resonance line of spins with high γs is especially interesting. wenckebach in his article [wenckebach. iv.2019b] points out the approximation of the fluctuating field 22 alexander kessenikh introduced by buishvili [buishvili. iii.1965 – 1966], provotorov and kozhushner [provotorov and kozhushner. iii.1967; kozhushner. iii.1969] and subsequently further developed by goldman [goldman et al. iv.1974] — the case of generalized approach taking into account the interaction of nuclear spins with the whole dipole reservoir of electron spins. the version of the multiparticle dnp mechanism was the most popular in 1960s years. note that soviet researchers in the 60s and partly 70s accounted for at least 20% of that invisible college that dealt with the problems of spin temperatures and spin polarizations. of those who were directly involved in the development and experimental verification of provotorov’s theory, mention should be made primarily of mortko kozhushner, oleg olkhov from the institute of chemical physics, maya isaakovna rodak, vadim atsarkin, anatoly yegorovich mefeod, sergey morshnev et al from the institute of radio electronics of the ussr academy of sciences (ussr as), as well as georgian physicists givi khutsishvili, levan buishvili, mikhail zviadadze et al. the influence of both the above-cited and subsequent articles of boris provotorov on the development of theoretical and experimental work in the field of magnetic resonance in the 1960s and 1970s was very important and their significance has survived to this day. in 2001, the all-moscow seminar “problems of magnetic resonance” under the direction of v.a. atsarkin devoted his 158th meeting to the fortieth anniversary of provotorov’s first works (see the publication of the abridged transcript of the seminar [nmr, epr and theory of condensed systems of magnetic dipoles. i. 2004]). boris during the execution of his pioneer works was a young employee of the theoretical group headed by a.s. kompaneets at the institute of chemical physics of the ussr as. boris did not hide the fact that he was significantly influenced by the work of alfred redfield (usa) devoted to the saturation of magnetic resonance [redfield. iii.1955]. in continuation and development of the successes of french physicists, provotorov’s ideas were picked up and developed by maurice goldman and anatole abragham with michel borghini. already before 1964, abragam and borghini published the results of the implementation of the provotorov’s idea on existence of the electron spin-spin (ss) reservoirs and the implementation of a new dnp mechanism. in atsarkin’s article [atsarkin. 1978] the results of the application of provotorov’s theory included in the actually review work of abragam and borghini [abragam and borghini. ii.1964] are formulated as one of the options for thermal mixing (compare the fig.1): under conditions of microwave pumping at frequency ω  =  ω s +  δ p which saturates the esr line with a small offset δ p from the resonance, the values of βsz and βss become quite different. whereas the zeeman subsystem is heated (βsz decreases but remains positive), the inverse temperature |βss| value increases dramatically, reflecting strong change in the mean energy of the secular dipole–dipole interactions. the strong cooling of the ss reservoir is represented in fig.  1 by a steep boltzmann distribution of populations inside the ss band. in the frames of the quasi-equilibrium model, this phenomenon is explained by the transfer of the energy |ħδp|•ħδp to (at δ p >  0) or from (at δ p <  0) the ss reservoir at every act of quantum absorption. in the former case, particularly, the upper levels of the ss band are overpopulated and βss is negative, see fig.  1. here is a diagram of the induced thermal mixing mechanism. horizontal bars ref lect populations of corresponding energy levels in the electronic (left) and nuclear (right) systems. the arrows show transitions induced by the microwave pumping (black) and electron–nuclear dipolar interactions (light) . we add, using the valuable remark of the head of the 2001 seminar v.a. atsarkin (see [nmr, epr and theory of condensed systems of magnetic dipoles. 2004]), that the french physicists a year before the appearance of the work [provotorov. iii.1961] seemed to have anticipated provotorov’s ideas about two energy reservoirs in the spin system. atsarkin said: “their experiment [goldman and landesman. iii.1961] was carried out in such a way that in a weak field saturates the quadrupole resonance of chlorine isotopes (in paradichlorobenzene), thereby shifting the dipole temperature in the common dipole reservoir of chlorine and protons. then the field was introduced adiabatically, and a signal of protons was enhanced (a kind of dnp). goldman writes [goldman.i.1996] – he carried out the experiment figure 1. diagram of the mechanism of induced thermal mixing according to abragam – borghini [([atsarkin. ii.1978]). see text for explanation. 23spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) – writes that when they got this result, they still doubted how all this could be explained, but there was l. solomon, who explained this phenomenon to them in the mentioned way. i would not want a dispute about priorities to arise here, because in fact, i must honestly admit that abragam dealt with spin temperature much earlier than all of us put together. and, of course, people absent here at the seminar, french physicist, they have the same memories. therefore, when discussing priorities, one must understand all this. of course, abragam’s laboratory at saclay was the research engine of the spin temperature, and they thought a lot on this issue there”. french physicists evidently again proved to be at the forefront in mastering new approaches to the theory and method of dnp. but their soviet colleagues in this time did not fall behind them significantly. the idea of kozhushner and provotorov about the direct contact of an ss reservoir with a nuclear zeeman (iz) reservoir was formulated in 1964 at a conference on magnetic resonance in a solid, held in krasnoyarsk. the publication [kozhushner and provotorov.iii.1967] was, however, delayed due to purely technical reasons, but its result was already known and even actually experimentally confirmed in the works of rodak, atsarkin, mefeod, morshnev, ryabushkin ( see also [kozhushner. iii.1969]). intensive research towards the approval of the two-reservoir theory of spin temperatures including the study of systems with number of lines in esr spectrum [atsarkin et al. iii.1967] was initiated by maya rodak at the institute of radio electronics of the ussr academy of sciences (ussr as). let us to say a few words about the exceptional role of maya rodak in the development of provotorov’s theory. magnetic resonance data make it possible to measure not only the zeeman temperature, but also the spin-spin temperature, as was shown in the series of provotorov’s works. the integral intensity of the spectral line of magnetic resonance absorption serves as a measure of the zeeman spin temperature (this is well known), and the shape of the contour of the magnetic resonance absorption line makes it possible to establish the spin-spin temperature (this fact in itself and the algorithm for such determination were the subject of works by provotorov and his followers). but rodak first developed a detailed theory of the experimentally obser vable and wellexpressed effect (induced radiation in a part of esr line) under saturation conditions in 1964 [rodak. iii.1964]. at the same year provotorov and his disciple mortko kozhushner put forward the idea of thermal mixing of electron spin-spin and nuclear zeeman systems. due to this mixing, the inverse temperature of the nuclear zeeman reservoir will tend to the inverse temperature of the electron dipole-dipole reservoir (dynamic cooling). maya isaakovna recalled in 2001 at the seminar “problems of magnetic resonance” two conferences colloque ampere in ljubljana – 1966 and colloque ampere in grenoble – 1968, where she was a “scientific tourist”: “i brought to ljubljana a small calculation from a series of physical consequences of provotorov’s theory. here i should note that when boris nikitovich and i met at the beginning of 1963, i brought him a calculation just for cross-relaxation. it was simply striking that cross-relaxation draws energy from the dipole-dipole spin-spin reservoir. and in parallel with this, at saturation on the wing of the line, the same spin-spin reservoir is also touched, its temperature changes. these two processes can be somehow related and by changing the detuning and saturation on the wing, you can probably influence cross-relaxation. i was very happy when he accepted my calculation well. and then he immediately recommended my work at soviet jetp, and we established good relations. but by 1966, even in the fall of 1966, when the colloque ampere was in ljubljana, we did not have an experiment. and all these four years, quite a lot of effects were predicted, which, from the point of view of the experiment, seemed not at all easy. like provotorov, i was confronted with mistrust all the time … for this reason, this trip to ljubljana was very important for me, because i saw a completely different attitude of our foreign colleagues there. so, even on the eve of the congress, in the evening at such a cocktail party, where all the participants got to know each other, j. jeener came up to me. he was a professor at the university of brussels, a serious theorist of the prigozhin school and at the same time a skillful experimenter … so he came up, said that he was interested in provotorov’s theory, read my articles, requested me to send them. it was jeener who responded to provotorov’s very first publications with a large article entitled “thermodynamics of spin systems in solids”, which appeared in phys. rev. in 1964 [jeener et al. iii. 1964.], and he sent it to provotorov as a preprint back in 1963, this proves his benevolence. in this article, he not only brilliantly outlined the physical foundations of provotorov’s theory from a general standpoint, but also presented the data of his experiments. these experiments were on harmonic cross-relaxation of nuclear spins in lithium f luorine (lithium fluoride) and it turned out, contrary to old ideas, that the tendency of cross-relaxation is by no means the establishment of a single temperature. the temperatures turned out to be different, and the more volatile spin-spin temperature changed most sharply. after my report on the “theory of magnetic resonance” section [rodak. iii.1967], redfield approached 24 alexander kessenikh me. i was told that his classic work 1955 was his graduate thesis. and by the time of our meeting he was already an internationally recognized scientist. as you know, in this classic work of his, he described magnetic resonance in a solid at strong saturation. provotorov does not require saturation at all; he has a different criterion: the smallness of the alternating field in comparison with the local one. and redfield, therefore, rightly, back in 1963, noted that provotorov these are literally his (redfield’s) words – “…filled the gap that existed in the theory of magnetic resonance in solids – threw a bridge across the gap.” as far as i remember, in his famous book abragam even writes directly that for h1, for a variable field much smaller than the local one hloc, the question remains, so the theory is by no means complete. abragam actually opened the congress. he made the first plenary lecture on the dynamic polarization of nuclei [abragam. iii. 1967], by the way, he did it in french, apparently in opposition to the americans. half of the audience did not understand him. our entire delegation got to know him while walking around ljubljana, it was facilitated by the fact that he knows russian perfectly. afterwards, we talked more than once, and at the end i dared to complete the task that boris nikitovich gave me, he was very angry with abragam, and i decided to reconcile them. and so i just asked him why he had not responded in any way to the first work that boris had given him in the fall of 1961 in the form of typescript. abragam, as was typical for him, said that he did not understand anything. and then he noticed that he also did not understand and appreciate the classic work of redfield at first. i would also like to remind you that there were several physicists who by this time, although they were not represented at ampere, worked in the same direction as provotorov. they did conduct experiments, among them goldburg, work in 1962 [goldburg. iii.1962]. all of them referred to provotorov … franz and slichter later works of 1966 [franz and slichter. iii. 1966] and, of course, goldman, who in 1964 in the french journal de physique [goldman. iii.1964] introduced the term “provotorov theory”, and later used it many times. so, by 1966, our foreign colleagues recognized provotorov’s theory and were very interested in it, at a time when, as we know, and as it was said at our seminar, many of our russian colleagues had a lot of objections against provotorov’s theory, up to 1966». in 1968 maya isaakovna had already brought to the ampere meeting the results of the experimental work she initiated. rodak herself and their co-authors and colleague confirmed the effects expected from the results of provotorov. among the results reported in grenoble were data on an explicit connection between electronic cross-relaxation (and hence the temperature of the spinspin reservoir) and the dependence of the nuclear polarization enhancement on the frequency of microwave irradiation of a ruby sample, which has two well-resolved lines in the epr spectrum at frequencies close to 10 ghz. for these data see works [atsarkin et al. iii.1967; atsarkin et al. iii.1968] (see fig. 2) a group of dutch physicists began the dnp research [swanenburg et al.1967]. similar and very interesting results on induced thermal mixing of nuclear zeeman reservoir with dipole electron-electron reservoir in dnp were obtained at 1968 and later. the future classic of dnp w.t. wenckebach joined to this group and took part in verification of direct dc mechanism [wenckebach et al.iii.1968, wenckebach et al.iii.1969] too. they studied the so-called tutton salts znk2(so4)2. 6h2o with an admixture of paramagnetic copper-ii ions, where the esr spectra have a hyperfine structure due to the scalar interaction of electron spins with nuclei of isotopes 63.65cu. these studies were continued successfully ([hoogstraate et al. iii.1973; wenckebach et al. iii. 1974] etc). an interesting result was obtained by comparing the dnp pattern in such samples at 14 k and 1.5 k. this experiment was also described in the review [atsarkin. ii.1978] (see fig.3 from review). to some extent, the fig. 2. enhancement of polarization of 27al (η, here ej,open circles) and degree of ddr cooling βss/βl(here βd/β0, solid curve) as a function of the detuning δ12 between the two esr lines involved in the cross-relaxation (one of them is saturated by the high-frequency field) [atsarkin et al, iii 1969].]. a12o3 crystal with 0.03% of cr3+, to=1.9 °k, b0=0.33 tl. 25spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) averaging of the obtained polarization over all possible dipole cross-relaxation effects as the electron spin-lattice relaxation time increases with decreasing absolute temperature, which is obvious from the figure, reminds of a similar effect in irradiated polyethylenes. such an averaging (and there merge of maxima) leads to an effect that we call “spreading of the dnp maxima” [kessenikh. et al. iii.1964] and, of course, to a sharp decrease in the polarization enhancement. 3. some results of earlier period and further development of dnp research 3.1. results of the first three decades of research on the effects of dnp. leadership of french physicists and contribution of soviet researchers the first period of dnp research, in our opinion, ends by the early 1980s, but it makes no sense to indicate a more precise date than, say, the date of publication of a fundamental review [atsarkin. ii. 1978], and then a monograph [atsarkin. ii.1980], that, unfortunately was not translated into english. the 1970s, and early 1980s were also marked in the history of the dnp by the editions of more famous monographs [goldman. ii.1970] and [abragam & goldman. ii.1982]. in the soviet union, by the 1960s and early 1970s, there was a fairly significant cohort of researchers of dnp and other phenomena studied in the spin temperature approximation. the works of the scientific schools in field of magnetic resonance in the institute of radio engineering and electronics, the institute of chemical physics and the institute of physics of the georgian academy of sciences made a significant contribution to the development of ideas about dnp and are wide known. the important results of applications of the dnp method to the study of nuclear reactions were obtained at the joint institute for nuclear research in dubna. research on dnp in the late 1960s-1970s and up to the mid-1980s continued to be most successful in france. the saklay nuclear research center has become a real mecca for dnp specialists. as a remarkable example of the unif ication of scientif ic forces from different european countries under the auspices of the saclay center, we cite a link to the work of the ever-memorable for czechoslovakia 1968 with the coauthorship of the soviet specialist v.i. lushchikov and czech odehnal on the dnp of protons in lanthanummagnesium nitrate with a paramagnetic impurity of dysprosium ions [odehnal,  loutchikov  and  ezratty. iii.1968]. in the late 1960s and early 1970s, unique research led by abragam and goldman (partially with the participation of the dutch physicist wenckebach). these researches led to the achievement of almost 100% polarization of fluorine nuclei in a single crystal of lithium fluoride, which made it possible to observe phase transitions of the spin system of nuclei into magnetically ordered states nuclear ferromagnetism and nuclear antiferromagnetism [chapellier. goldman. chau. abragam. iii. 1969; jacquinot, wenckebach, chapellier, goldman, abragam. iii. 1974] etc. japanese an american physicist akira masaike recalls at 2014 the role of abragam’s disciple michel borghini in the development of dnp methods for high energy physics [masaike. i.2016]: «high energy spin physics began in early 1960s. it was pointed out that studying the spin dependent forces is one of the most important issues for particle physics. therefore, it became an urgent need to measure the spin parameters of particle reactions. in order to realize such an experiment, it was indispensable to polarize the target protons… the success of the dynamic polarization was amazing-event for high energy physicists, since it promised a new field of particle physics. at the international conference on polarized targets held at saclay in 1966, the known australian physicist r. h. dalitz pointed out that the polarized target may lead to especially illuminating information on three major areas in particle physics: fig. 3. enhancement of polarization of protons η (here est) in a crystal of zncs2(so4)2 · 6h2o with 0.5% of cu2+ as a function of the detuning δp of the high-frequency field relative to the center of gravity of the esr spectrum (b0 ≈0.3 tl) [wenckebach et al. 1974]: (a) to= 1.5 ok, (b) =14 °k, (c) esr spectrum of the cu2+ion. 26 alexander kessenikh (i) high energy scattering where regge-pole exchange is dominant. (ii) tests of time-reversal invariance for electromagnetic processes. (iii) hadron spectroscopy. many resonant states had been observed for mesonic and baryonic states. in the attempt to classify and understand these hadronic states, the first need is for the determination of the spin and the parity for each state. the first experiment with the polarized target was performed to measure the correlation parameter cnn for p-p scattering at 20mev by abragam, borghini, catillon p., coustham j., roubeau p. and thirion j. at saclay in 1962 [a. abragam et al. iii. 1962]. the experiment was done with a polarized beam on polarized protons in lmn. the first pion-proton scattering experiment was performed at berkeley (bevatron) by chamberlain, jeffries, schutz, shapiro, and van rossum in 1963 [chamberlain o. et al. iii. 1963.] in this experiment it was necessary to measure both angles of pion and proton in order to check the coplanarity, since the background from complex nuclei were enormous. neutron transmitted through polarized protons are polarized, since neutrons with spin anti-parallel to the proton spin are scattered away. l. shapiro at dubna proposed to make a polarized slow neutron beam using an lmn filter in 1966.1 ishimoto et al. made a polarized neutron beam using an ethylene glycol filter at kek in 1976 [deregel et al. iv.1980.]. the method was used for parity violation experiments with polarized neutrons of 0.02 1 ev at dubna [dragichesku et al. iii.1964], kek and los alamos in 1980s». 3.2. renaissance of methods of dynamic polarization at the turn of the millennium research on dy namic polarization continued throughout the 1980s and 1990s in the uk, usa, switzerland, japan, and elsewhere. however, in the ussr in the mid-1980s, these studies receded into the background, at the lebedev institute and in one of its heirs, the institute of general physics of the ussr as, such studies were no longer resumed, at the joint institute for nuclear research they dropped to a minimum, at other institutes they were occasional character. due to the difficulties in the development of instrumental methods and the limited possibilities for the further growth of human and financial resources for fundamental research, these works began to gradually curtail. meanwhile, in the west, another revolution in experimental technology was taking place. although gyrotron generators of millimeter and submillimeter electromagnetic waves appeared in the ussr, they were widely developed and applied only in western europe and in the usa. at the same time, a tendency arose to apply jointly the methods of dnp and sample rotation at a magic angle (mas) to study a solid. the capability of getting higher induction of magnetic fields continued to grow steadily thanks to the application of superconducting solenoids available for the experiment (see the first dnp research with use of girotron microwave generator of terahertz frequencies in laboratory of robert griffin [becerra et al. iv. 1993]), and the search for new solutions in preparing a sample with a paramagnetic impurity and in setting up the experiment did not stop. methods for obtaining ultra-low temperatures (for example, using a solution of helium-3 in helium-4) were also improved. the last possibilities were also available in the ussr (in dubna and kazan, for example), but the fact is that in europe and the usa all the numerous new achievements of experimental technology could be used jointly, while in soviet laboratories they remained available separately. therefore, at the next stage, scientists from russia and georgia could no longer be at the forefront of dnp, and they could only recall their past achievements in studying the problems of spin temperatures and dnp [nmr, epr and theory of condensed systems of magnetic dipoles. i. 2004]. along with the growth of experimental possibilities, the dnp method has a powerful and solvent consumer high-resolution nmr of rare isotopes of organogenic elements carbon and nitrogen, in the first place, as well as of course nmr of protons and phosphorus-31 nuclei in biochemically important substations. specialists in nmr of complex organic compounds were already backed by their customers – chemical enterprises, pharmaceutical companies and medical institutions. in particular, the idea arose to use the instantaneous melting of a sample with enhanced in 104 and more times polarization nuclei using a laser and transfer the sample to a high-resolution nmr spectrometer (“dissolution dnp” [ardenkjaer-larsen et al.  iv.2003]), then, after the operations of multidimensional nmr spectra recording, which were usual by the 2000s, it was necessary to return the sample to the installation to obtain dnp and repeat this field cycling or “shuttle” procedure a sufficient number of times to accumulate signals with a good signal-to-noise ratio. finally, at the beginning of the new century, the research team of the francis bitter magnetic laboratory (fbml) at the massachusetts institute of technology (usa) grew stronger. since 1992 robert griffin has been the head of this laboratory. in 2004, an article [hu, grif27spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) fin et al. iv. 2004] appeared in which the problem of the influence on the dnp mechanisms of the inhomogeneity of the distribution of paramagnetic centers was solved in the simplest and demonstrable way. the authors were the first to use tempo-type biradicals as a paramagnetic impurity to excite dnp. since then, the arsenal of dnp mechanisms has firmly included the pairwise paramagnetic impurities – biradicals and, accordingly, the mechanism of electron-nuclear cross-relaxation (encr), briefly called the cross-effect (ce). 4.conclusion in conclusion, let us recall the main findings from atsarkin’s fundamental review concerning the general state of dnp research in the late 1970s and early 1980s (see also monograph [atsarkin. ii.1980] and, of course, the well-known monograph [abragam and goldman. ii. 1982]). 1) the spin-spin reservoir model (provotorov’s two-reservoir model) was confirmed. experiments on dynamic nuclear polarization played an important role in this. 2) a high and in some experiments almost one hundred percent nuclear polarization was obtained, which made it possible to study the dependence on the spins of particles of scattering by protons and deuterons of polarized beams of protons, neutrons and hadrons. 3) extremely high nuclear polarization made it possible to observe magnetically ordered states of nuclear spins (nuclear ferromagnetism and antiferromagnetism). we also point out that in early years only in the review and monograph by atsarkin a special type of dnp mechanism electron-nuclear cross-relaxation (encr) cross-effect (ce) was discussed. studies of this mechanism were not completed by that time. in the works of that time, the effects of the spatial inhomogenity of the distribution of paramagnetic centers in the specimen were neglected. hence, it was unclear what the possible reason for the predominance of this mechanism was. also, in those years, and perhaps even later, the effect of a bottleneck in dnp, caused by long spin-lattice esr relaxation times at low temperatures, was not studied in detail. aknowledgments i would like to express my sincere gratitude to the secretary of the editorial board of the journal physics uspekhi, maria aksentyeva, for sending the english version of the review article by vadim atsarkin and permission to use the illustrations for this article. thanks to dr. w. t. wenckebach for kindly providing the full texts of his latest published works and photograph. i express my gratitude to dr.v. v. ptushenko for the many correction of my article, which serves as a supplement to our joint monograph. i thank in advance the readers who can forgive me for the incompleteness of the information due to technical difficulties and possible errors of the author. i thank dr. e.b. feldman for proposition to write this article and dr. v.a. atsarkin for extensive help during my scientific work. notes 1. some authors believe that in this case there is no actual thermal mixing. however, we will adhere to the concept of v. atsarkin set out in the text, according to which this is a variant of induced thermal mixing. 2. the transcription of the russian surname “lushchikov” (“loutchikov”) causes difficulties (see link below). 3. japan: kek-ko: enerugi: kasokuki kenkyu.kiko: “high energy accelerator research organization”. kek exists from 1950. 28 alexander kessenikh appendix i gallery of portraits. some leading researches which studied the phenomena connected with spin temperature and dynamic nuclear polarization from left to right: alfred overhauser (usa, 1925-2011); charles slichter (usa, 1929-2019); carson jeffries (usa, 1922-1995); jean jeener (belgium, 1933-2016). from left to right: anatole abragam (france, 1914-2011); maurice goldman (france, 1933); michel borghini (france, 1934-2012); vadim atsarkin (ussr (russia). 1936); w.t. wenckebach (netherland, usa, 1943) from left to right: boris provotorov (ussr (russia). 1931-2001); maya rodak (ussr (russia.). 1923-2015); mortko kozhushner (ussr (russia). 1937-2020); givi khutsishvili (ussr (georgia). 1921-1969); levan buishvili (ussr (georgia). 1933-1996). 29spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) appendix ii. selected bibliography considered works devoted investigations and applications of dnp and spin temperature model references (structured by topics and time) i. some abbreviations: journal of experimental and theoretical physics: zhetf – zhurnal eksperimentalnoy i teoreticheskoy fiziki [soviet journal of theoretic and experimental physics – soviet jetp] advances in physical sciences: ufn – uspekhi fizicheskikh nauk [soviet physics uspekhi ; later physics uspekhi] journal “solid state physics”: ftt fizika tverdogo tela [sov.phys. solid state] i. historical researches and memoires 1983-1991 abragam a. vremya vspyat (ili fizik, fizik, gde ty byl?) < backward time (or physicist, physicist where have you been?)> moskow: nauka. main redaction of physical and mathematical sciences 1991. 392 s. (russian variant of abragam a. réflexions d’un physicien. paris: hermann, 1983.152 р. isbn: 2-7056-5960-9; isbn: 978-2-7056-5960-8) 1996 goldman m. the time when spin temperature was hot stuff//encyclopedia of nmr. 1996. — chichester– new york–brisbane–toronto–singaporo: john wiley & sohns. v.1. p. 338–341 1998 knight w., reinolds j., hahn e., portis a. carson dunning jeffries (march 22, 1922 – october 18, 1995). biographical memoir copyright 1998 national academies press washington d.c. 15 p. volume 73 | the national academies press (nap.edu). https://nap.edu/ read/9650/chapter/14 2004 epr, yamr i teoriya kondensirovannogo sostoyaniya magnitnykh dipoley (opyt ustnoy istorii teorii provotorova). //nauchnoe soobshchestvo fizikov sssr v 1950-e – 1960-e gg. editors: vizgin vl.p.& kessenikh a.v. vyp.1. spb.: izd-vo russian christian humanitarian institute (rkhgi). 2004. s. 300 – 385 [epr, nmr and the theory of the condensed state of magnetic dipoles (experience of the oral history of provotorov’s theory)]. scientific community of physicists of the ussr in the 1950s 1960s. (russian, recorded by kessenikh a.v.) 2009 kessenikh a.v. magnetic resonance: discovery, investigations, and applications (from the history of physics).// physics uspekhi. v. 52, no 7. p. 695–722 2012 slichter ch. p.  in memory of albert w. overhauser (1925–2011) applied magnetic resonance  2012 volume 43, issue 1-2. p.3–6. [http://researchgate.net]. atsarkin v. a. & kessenikh a. v. dynamic nuclear polarization in solids: the birth and development of the many-particle concept. applied magnetic resonance,2012. vol. 43. issue 1-2. pp. 7–19 [http:// researchgate.net]. 2016 masaike akira. dawn of high energy spin physics — in memory of michel borghini spin physics (spin 2014) international journal of modern physics: conference series vol. 40 (2016) 1660114 (9 pages). (proceedings of the 21st international symposium on spin physics (spin2014); peking university, china, 20–24 october 2014; editors: haiyan gao and bo-qiang ma — memorial session https://doi. org/10.1142/s2010194516601149) 2017 goldman m. “anatole abragam. 15 december 1914 — 8 june 2011”.  biographical memoirs of fellows of the royal society.2017. vol.  63. p.7–21.  doi:10.1098/ rsbm.2017.0026. issn 0080-4606 2018 illinois physics. charles p. slichter (1924-2018) https:// physics.illinois.edu/people/memoriale/charles-slichter ii. monographs and reviews 1961 abragam a. principles of nuclear magnetism. oxford: clarendon press. 1961. 599 p 1964 bilenkiy s.m., lapidus l.i., ryndin r.m. polyarizovannaya protonnaya mishen v opytakh s chastitsami vysokikh energiy //ufn. 1964. t. 84, vyp. 2. s. 243–301. 1965 bilen’kii s.m., lapidus l.i.  , ryndin r.m.  sov. phys. uspekhi. polarized proton target in  experiments with high-energy particles. 1965. vol.7. p.721–754. 1966 khutsishvili g.r. spin diffusion sov. phys. uspekhi, 1966, p. 743-769. 1968 khutsishvili g.r. spinovaya diffuziya i yadernaya magnitnaya relaksatsiya v kristalle, soderzhashchem magnitnuyu primes. ufn. 1968.vol. 96. p. 441–466. 30 alexander kessenikh 1969 khutsishvili g.r. spin diffusion and nuclear magnetic relaxation in a crystal containing a magnetic impurity. sov.phys. uspekhi 1969,  vol.11  (6), p.802–815 https://doi.org/10.1070/pu1969v011n06abeh003776]. hill d.a., ketterson j.b., miller r.c., moretti a., niemann r.c., windmiller l.r., yokosawa a., hwang c.f. dynamic proton polarization in butanol water below 1 k. phys. rev. lett. 1969. v. 23. no 9. p. 460–462. 1971 noggle j.h., schirmer r. e. the nuclear oe. chemical applications. n. y.l. academic press. 1971. 259 pp 1972 atsarkin v.a., rodak m.i. “temperature of  spin-spin interactions in  electron spin resonance”  soviet phys. uspekhi 1972, vol.15, p. 251–265 1974 v.a.  atsarkin “achievements and current, problems of  solid-state radiospectroscopy”. soviet phys. uspekhi. 1974. vol. 16. p.  747–749 (based on the materials of the xvii ampere congress, turku, finland, august 21-26, 1972) 1977 goldman m., «  nuclear dipolar magnetic ordering », phys. rep., 1977. vol.32, p. 1-67 1978 m. goldman, a. abragam, principles of dynamic nuclear polarisation, rep. progr. phys. 1978 vol.41. p.395–467, https://doi. org/10.1088/0034-4885/41/3/002. atsarkin v. a. dynamic nuclear polarization in solids. sov. phys.usp. 1978. 21(9), p. 725 -746. 1979 pokazanev v.g., skrotskiy g.v. psevdomagnetizm [pseudomagnetism]. ufn. 1979. vol. 129. № 4. pp. 615–644. pokazan’ev  v  g, skrotskii  g  v “pseudomagnetism” sov. phys. usp. 1979.vol.22. p. 943–959. 1980 atsarkin v.a. dinamicheskaya polyarizatsiya yader v tverdykh dielektrikakh [dynamic nuclear polarization in solid dielelectrics]. (russian). moskow: nauka. 1980. 195 p. 1982 abragam a. & goldman m.nuclear magnetism. order & disorder. oxford: clarendon press 2016 wenckebach t. essentials of dynamic nuclear polarization. 2016. the netherlands. spindrift publications.308 p. 2019 jannin s., dumez j.-n., giraudeau p., and kurzbach d., application and methodology of dissolution dynamic nuclear polarization in physical, chemical and biological contexts. j magn reson. 2019 june 4; vol.305: p.41–50. doi:10.1016/j.jmr.2019.06.001. iii. original researches 1949-1983 1949 bloembergen n., “on the interaction of nuclear spins in a crystalline lattice,” physica 1949 vol.15, p. 386–426 1953 carver t. r., slichter c.p. polarization of nuclear spins in metals. phys. rev. 1953. vol. 92. № 1. pp. 212, 213. a) overhauser a. w. paramagnetic relaxation in metals // physical review. 1953. vol. 89. no. 4. p. 689-700. b) overhauser a.w. polarization of nuclei in metals. physical review. 1953. vol. 92. № 2. pp. 411–415. portis a.m. electronic structure of f-centers: saturation of the electron spin resonance // phys. rev.1953. v. 91, no 5. p. 1071–1078. 1954 beljers h. g. l., van der kint l., van wieringen j.s. overhauser effect in free radical. phys. rev. 1954. vol. 95. № 6. p.1683. khutsishvili g.r. spinovaya diffuziya [spin diffusion]. tr. in-ta fi z. an gruzssr. [proceedings of institute for physics georgian as] 1954. vol. 2. p. 115. 1955 solomon i. relaxation processes in a system of two spins. // physical review. 1955. vol. 99. no. 2. p. 559-565. redfield ag. nuclear magnetic resonance saturation and rotary saturation in solids.  physical review. 1956. vol.98. p. 1787-1809. doi: 10.1103/physrev.98.1787  feher g.method of polarizing nuclei in paramagnetic substances. phys. rev. 1956. vol. 103.no 2. p. 500 – 501 feher g., gere e. a. polarization of phosphorous nuclei in silicon. phys. rev. 1956. vol. 103.no 3. pp. 834 – 835 solomon i., bloembergen n. nuclear magnetic interactions in the hf molecule j. chem. phys.  1956.vol. 25, p.261 266. https://doi.org/10.1063/1.1742867 carver t. r. and slichter ch. p. experimental verification of the overhauser nuclear polarization effect. phys. rev. 1956. vol.102, p.975 – 981 1957 abragam a., combrisson a., solomon i. polarisation nucléaire par effet overhauser dans les solutions d’ions paramagnétiques. c. r. acad. sci. 1957. t. 245, p.157–160. jeffries c.d. polarization of nuclei by resonance saturation in paramagnetic crystals phys.rev.  1957. vol.106. p. 164-165. doi: 10.1103/physrev.106.164 31spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) abraham m., kedzie r.w. , jeffries c.d . γ-ray anisotropy of co60  nuclei polarized by paramagnetic resonance saturation. phys. rev., 1957. vol.106, p. 165-166 1958 abragam a., proctor w.g. spin temperature. phys rev 1958, vol.109, no 5. p.1441 1457 abragam, a ., proctor w une novelle methode de polarization dynamique des noyaux atomiques dans les solides. comptes rendus de l’academie des sciences. 1958.t. 246. № 14. pp. 2253–2255. de gennes p.g. sur la relaxation nucleaire dans les cristaux ioniques j. phys. chem. solids,  1958. vol.7. p. 345-350 erb e., motchane j.-l., uebersfeld j. sur une nuvelle méthode de polarization nucléaire dans les fluidesadsorbés sur les charbons. extension aux solides et en particulier aux substances organiques irradiées// compt. rend. 1958. t. 246, no 21. p. 3050–3052. 1959 de m.m. borghini, a. abragam polarisation dynamique des protons a de basse temperature comptes rendus 1959.t. 248 no 12 pp. 1803 – 1805 1960 müller-warmuth w. and parikh p.notizen: overhauser–abragam-effekt am (so3)2no--radikal in mittleren magnetfeldern.  zeitschrift für naturforschung 1960.a volume 15: no 1 s. 86 – 87 tchao y.h., herve j.polarisation dynamique des protons d’un radical libre par saturation de la resonance electronique. compte rendu 1960. t.250. p. 700 – 706 1961 borghini m. et abragam a.. polarisation dynamique de noyaux (rapport comissariat de energie atomique n° 1894). 1961. p. 5 (french) leifson o. s. and jeffries c. d. dynamic polarization of nuclei by electron-nuclear dipolar coupling in crystals phys. rev. 1961. vol. 122, p.1781 – 1795 goldman m., landesman a., «  polarisation dynamique nucléaire par contact thermique entre des systèmes de spins », c.r. acad. sci. 1961, t.252, (), p.263-265 provotorov b.n. o magnitnom rezonansnom nasyshchenii v kristallakh. zhetf 1961. vol. 41. vyp.5. pp. 1582–1591. 1962 provotorov b.n. magnetic resonance saturation in crystals. soviet physics jetp. 1962. vol. 14. № 5. pp. 1126–1131 abragam a., borghini m., catillon p., coustham j., roubeau p., thirion j., diffusion de protons polarises de 20 mev par une cible de protons polarises et mesure preliminaire du parametre cnn, phys. lett. 1962. t. 2. p. 310–311. provotorov b.n. kvantovostatisticheskaya teoriya perekrestnoy relaksatsii // zhetf. 1962.t. 42, vyp. 3. s. 882–888. provotorov b. n. a quantum statistical theory of cross relaxation //soviet physics jetp 1962. v. 15, no 3. p. 611–614. khutsishvili, spin diffusion and magnetic relaxation of nuclei, sov. phys. jetp 1962. vol.15 () p.909–913 goldburg w. j. static spin temperature experiments and the approach to thermal equilibrium in the rotating reference frame. phys. rev. 1962. vol.128. № 4. p.1554–1561. 1963 m. goldman and a. landesman dynamic polarization by thermal mixing between two spin systems phys. rev. 1963. vol.132, p.610 kessenikh a.v., lushchikov v.i., manenkov a.a., taran yu.v. relaksatsiya i dinamicheskaya polyarizatsiya protonov v polietilenakh. 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g.  kwiatkowski,  w.  köckenberger quantum mechanical simulation of cross effect dnp 34 alexander kessenikh using krylov-bogolyubov averaging. appl. magn. reson., 2012. vol. 43. p. 43-58 2017 wenckebach w.t., dynamic nuclear polarization via thermal mixing: beyond the high temperature approximation, j. magn. res. 277 (2017) 68–78, doi. org/10.1016/j.jmr.2017.01.020. pylaeva s., ivanov k.l., baldus m., sebastiani d., elgabarty h. molecular mechanism of overhauser dynamic nuclear polarization in insulating solids. j. phys. chem. lett., 2017. vol.8 , p. 2137-2142 2019 wenckebach w.th. dynamic nuclear polarization via the cross effect and thermal mixing: a. the role of triple spin flips journal of magnetic resonance. 2019. vol.299. p. 124–134 w.th. wenckebach dynamic nuclear polarization via the cross effect and thermal mixing: b. energy transport journal of magnetic resonance 2019. vol.299. p. 151–167 substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 3(2) suppl. 1: 43-55, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-270 citation: s. c. rasmussen (2019) from aqua vitae to e85: the history of ethanol as a fuel. substantia 3(2) suppl. 1: 43-55. doi: 10.13128/substantia-270 copyright: © 2019 s. c. rasmussen. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article from aqua vitae to e85: the history of ethanol as fuel seth c. rasmussen department of chemistry and biochemistry, north dakota state university, ndsu dept. 2735, p.o. box 6050, fargo, nd 58108-6050, usa e-mail: seth.rasmussen@ndsu.edu abstract. ethyl alcohol, or ethanol, is one of the most ubiquitous chemical compounds in the history of the chemical sciences. the generation of alcohol via fermentation is also one of the oldest forms of chemical technology, with the production of fermented beverages predating the smelting of metals. by the 12th century, the ability to isolate alcohol from wine had moved this chemical species from a simple component of alcoholic beverages to both a new medicine and a powerful new solvent. the use of alcohol as a fuel, however, did not occur until significantly later periods, the history of which is generally presented as a separate narrative from its initial applications as intoxicating beverages, medicines, or chemical reagents. the current report aims to more firmly connect these two disparate historical accounts, presenting an overview of the history of ethanol from its initial isolation in the 12th century through its current application as a fuel additive for most automotive vehicles in the united states. keywords. ethanol, distillation, combustion, spirit lamps, alcohol stoves, engine fuel. introduction there is no doubt that ethyl alcohol (or ethanol, ch3ch2oh) can be considered one of the most ubiquitous chemical compounds in the history of the chemical sciences. in the chemical laboratory, it is commonly used as a quite versatile solvent that is not only miscible with both water and wide variety of other organic solvents, but can also solubilize a broad range of analytes. as such, it still remains one of the most common chemical media for a wide range of solution-based chemical processes. historically, ethanol represents one of the earliest nonaqueous solvents and it is most certainly the very first such solvent of high polarity.1 beyond its laboratory use as both a solvent and chemical reagent, the antibacterial and antifungal properties of ethanol provide an effective medium for the preservation of organic matter and well as a highly useful disinfectant in medical applications.1-4 of course, ethanol predates its eventual isolation in the 12th century1-3,5-10 and dates back as far as ca. 10,000 bce2 as the psychoactive component of various fermented beverages (i.e. mead, wine, beer), resulting in euphoria and other mind-altering effects. as such, the alcohol content of such ferduccio rectangle 44 seth c. rasmussen44 seth c. rasmussen mented beverages is one of the oldest known recreational drugs, and is still the most widely accepted of such drugs in most cultures. ethanol has thus played, and continues to play, a central role in the history of society in general.1,2 more recently, the f lammable nature of ethanol has led to its use as a fuel for a variety of applications. while such early uses were limited to sources of light and heating, ethanol has now become a common fuel or fuel additive for the combustion engine. in these latter applications, the ability to produce ethanol from the fermentation of biomass provides the attractive promise of renewable alternatives to our current dependence on petroleum fuels. as such, the current report aims to present an overview of the history of ethanol as a fuel, starting with its initial isolation from wine in the 12th century through its current application as a fuel additive for most automotive vehicles in the united states. brief history of early distillation as discussed above, the production of alcoholic beverages via fermentation is thought to date back to sometime before 6000 bce,2,10-13 yet the isolation and application of ethanol as a distinct chemical species did not occur until the 12th century ce.3,5-10 as such, it is natural to wonder why its isolation took so very long. the simple answer to this is that distillation, the primary method for the separation of alcohol from such fermented beverages, was not really developed until the 1st century ce14-22. even so, it still took essentially another thousand years for ethanol’s successful isolation. in order to understand this additional delay, we first need to briefly review the history of distillation before returning to its use in the isolation of alcohol. distillation is considered an ancient art and its physical apparatus, commonly referred to as a still, is thought to be the earliest known specifically chemical instrument.14-16,21,22 distilling equipment was first described by the late first century ce alchemist known as maria the jewess. as her writings already illustrated a fairly advanced state of development, she is generally given credit for its invention.14-22 unfortunately, very little is known about maria other than writings ascribed to her, which survive only in quotations by the later alchemist zosimos.14,15,19,22 as shown in fig. 1, the early still consisted of three components: the distillation vessel (cucurbit), the stillhead (ambix) with an attached delivery tube (solen), and the receiving vessel (bikos).9,16-18,22,23 such early stills were constructed from a mixture of materials, primarily earthenware (with a glazed interior), copper, and glass, that were fixed together using a plastic material known as a lute to seal the joints between the individual components.6,16-18,22,24,25 glass, however, was initially limited to just the receiving vessels,6,15,16,18,22,23 where its transparency allowed the distiller to observe the collecting product. as glass technology evolved, glass later began to be also used for the ambix, and eventually for both the ambix and cucurbit.6,16,22,23 a difficulty encountered with the early use of glass in such applications, however, was the instability of glass vessels under heat. this can be seen in instructions from maria the jewess as quoted by zosimos:15,19 ...place at the ends of the tubes glass flasks, large and strong so that they may not break with the heat coming from the water... pliny the elder later warned of similar issues, stating:26 glass is unable to stand heat unless a cold liquid is first poured in. up through the roman period, early glasses primarily utilized a simple soda-lime-silica composition that varied depending on the specific raw materials applied.22,27,28 here, the calcium of the lime acted as a stabilizer to counteract the high solubility of the sodium contained within the glass. unfortunately, however, lime was not intentionally added as a major constituent before the end of the 17th century and all calcium content prior to that time was a result of impurities in either the sources of silica (sio2) or soda (na2co3). 22,27 31 because of this, early glasses consisted of a high soda figure 1. basic components of the early still [reprinted from reference 22 with permission from springer nature]. 45from aqua vitae to e85: 45from aqua vitae to e85: the history of ethanol as fuel and low calcium content which resulted in overall poor chemical resistance.16,23,32,33 furthermore, the thermal expansion of the such glasses increases with soda content,34 so the high soda content coupled with the physical defects common in early glass caused high thermal expansion and low thermal durability, which had a tendency to break under rapid heating.22,23,34 in an effort to overcome the limited stability of glass vessels under heat, heavy-walled flasks were typically used, the exterior of which was then coated with clay (layers up to 2-3 fingers width). 6,16,17,22, 23,35 this helped reduce breaking, but the poor heat transmission of the clay coatings resulted in long preheating periods and limited control of the cucurbit temperature, which when combined with the inefficient cooling of early still heads, made it difficult to distill volatile liquids such as alcohol.16,22,24 as the knowledge of distillation apparatus was transmitted to islamic philosophers during the 7th-8th centuries ce, the term ambix was transformed through the addition of the arabic article alto become alanbîq, which eventually became alembicus and alembic.15-18,20,22,23 by the 10th century, the terms ambix and alembic were commonly used to refer to both the stillhead and the still as a whole.6,15-18,20,22 because of the arabic contribution to the word alembic, some authors have mistakenly attributed the discovery of distillation methods to islamic philosophers.10 as discussed above, distillation efforts prior to the 12th century were limited by both the poor quality of glass and ineffective cooling methods for the collection the condensing material.7 initial methods to improve cooling were to cool the delivery tube (solen) with wet sponges or rags. as this tube was now generally cooler than the still-head, condensation would occur primarily in the solen rather than collecting the condensate within the still-head. as such, the typical medieval alembic no longer contained an inner rim to collect and transfer the collecting liquid to the solen.6,16,22,23 as one of the earliest references to distilled alcohol is found in the writings of magister salernus,6,9,22,24 it is believed that he may have pioneered the cooling of the solen to effect condensation outside the still-head22,23,25. beginning in the 13th century, the prospering venetian glass industry began blending roman and syrian glassmaking methods to produce a significantly improved glass.23,36-39 this improvement in glass technology was largely due to a change in the soda source used, as well as the introduction of new processes for the purification of both silica and soda sources prior to their use in glassmaking.39 the soda utilized exclusively by the venetians was a plant ash imported from the levant that contained large amounts of magnesium and calcium in addition to the desired na2co3 and its use in glassmaking resulted in a new glass that exhibited both higher chemical durability and reduced thermal expansion.32-34,39 furthermore, the venetians’ innovative purification methods removed insoluble, non-fusible components from the resulting glass, which would have acted as stress points during heating. with the introduction of the improved venetian glass, both glass cucurbits and alembics then became more common.6,16,23 the common fabrication of still components from glass then allowed the investigation of more versatile approaches to still design, particularly for improved cooling. however, the most revolutionary and critical of these advances, the modern cooling coil, was initially fabricated from copper.40 this design was introduced during the late 13th century by taddeo alderotti of florence (ca. 1210-1295, fig. 2), who is commonly viewed to be its inventor3.,6,16,18,22-24 in his de virtutibus aquae vitae, alderotti describes the distillation of wine using an alembic with an elongated solen consisting of a canalem serpentinum (“serpentine channel”), along with a cooling trough and regular supply of fresh cooling water.24,40 the earliest known pictorial representation of this new cooling method (fig. 3a) was not given until ca. 1420 by johann wenod, a physician in prague.6,16,41-43 unfortunately, wenod provides very little detail and only gives the notation vas cum aqua (vessel with water) above the cooling tub.43 based on alderotti’s description of a serpentine channel, however, it was thought that his cooling figure 2. engraving of taddeo alderotti of florence (ca. 12101295) [the national library of medicine]. 46 seth c. rasmussen46 seth c. rasmussen apparatus wound ‘worm-like’ through the cooling trough as shown by many later pictures (fig. 3b & 3c)6,8 and is thus commonly referred to as a “wormcooler”. the impact of the improved venetian glass and the growing glass industry on the evolution of distillation apparatus led not only to the development of new, improved glass-based components, but also to new stills fabricated completely from glass.16 as it became more common to utilize all-glass distillation apparatus, the cucurbit and alembic were eventually combined into a single piece. this new form of still (fig. 4) was called the retort (from latin retortus, “bent back ”) and was introduced in the early 14th century.6 the retort was especially well-suited for high temperature distillations when the lute sealing together a typical multi-component alembic would begin to fail.42 distillation via a retort was often referred to as destillatio ad latus (“sidewards distillation”).6 two later still designs both focused on the stillhead, rather than the solen, in order to increase effective cooling during distillation6,48,45. the rosenhut (german) or rozenhoed (dutch, both literally meaning “rose hat”) (fig. 5a) is thought to be the earlier design, as it was illustrated in its fully developed form in 1478,6 but essentially disappeared by the end of the 16th century.44 the still consisted of a high conical, air-cooled alembic and was a common form used for making early liqueurs.6,45 this modified alembic was typically fitted to a wide-mouthed cucurbit and, although never shown in illustrations, is thought to have been built with an inner rim to collect the distillate.6 while glass was now the commonly utilized for distillation components, the rosenhut was often constructed from metals such as lead and copper as the high thermal conductivity of the metals resulted in superior air cooling.6,45 in contrast, the mohrenkopf (“moor’s head ”) enclosed the still-head in a basin or container which was filled with cooling water (fig. 5b). the moor’s head was typically made of glass (although pottery is also said to have been used) and is thought to be an invention of the later 15th century.6,45 it has been suggested that it may have been influenced by the chinese still, which also utilized a water-cooled head,3 and was viewed to give lower quality distillates than those obtained via the wormcooler.46 early isolation of ethanol based on available evidence, the current view is that the initial isolation of alcohol occurred in southern italy during the 12th century, most likely at the school figure 3. external cooling trough as depicted in the treatise of johann wenod (a) and illustrations of the worm-like nature of the “wormcooler” cooling coil from: (a) philipp ulstadt’s coelum philosophorum seu de secretis naturae liber, 1525 (b) and walter ryff ’s neu gross destillierbuch, 1556 (c). figure 4. illustration of a basic early retort. 47from aqua vitae to e85: 47from aqua vitae to e85: the history of ethanol as fuel of salerno.3,5-10,14,22,24,47 some authors argue for an earlier discovery by muslim philosophers and it is possible that the alcohol could have been isolated prior to the 12th century.48 however, while it is believed that arab alchemists distilled wine prior to the 12th century,3,48 no convincing evidence has been presented that they isolated ethanol prior to that of the known western sources.6,49 in fact, the common view is that the arabs did not find the distillates obtained from wine very interesting,3 which would make sense if the distillates still contained high water content, as would be expected from the ineffective isolation of the volatile alcohol products. this assignment to 12th century italy is supported by the fact that one of the earliest direct recipes for the isolation of alcohol is found in the writings of magister salernus.5-7,24 earlier school of salerno treatises from 1100-1150 ce discuss the preparation of “beneficial waters” by distillation,3,6,9 but his writings were the first to directly mention alcohol.6 another recipe from the same time period is found in the mappae clavicula, which may predate that of salernus.3,5,7,47 this medieval latin text is thought to date to ~820 ce, but only later 10th and 12th century versions are currently available and the alcohol recipe is only found in the 12th century version.3,7,47 a third recipe is also said to have been found in a 12th century parchment recovered from weissenau, a south german monastery. further recipes for preparing alcohol are frequently found in the available literature after the 13th century.7 the late discovery of alcohol is viewed to be primarily due to inefficient cooling during distillation coupled with the use of materials with poor heat transmission, thus requiring long preheating periods and limited temperature control.22 some authors have linked the dependence of alcohol’s isolation on improvements in cooling methods3 and the evolution in still design most certainly improved the ability to isolate alcohol. unfortunately, none of the early recipes discussed above include details on the distillation methods used, particularly the nature of any cooling methods. as such, it is unknown if these initial successes utilized any methods for cooling the solen. it has been proposed that it could have been possible to distill alcohol in the ancient cucurbit and alembic without cooling the solen, but only if the heating could be carefully regulated.6 however, such temperature control would not have been possible through the common use of earthenware or clay-coated glass curcurbits, which usually resulted in long digestion periods before distillation and excessive temperatures that drove off the low boiling fractions, thus making it difficult to isolate volatile liquids such as alcohol.6,16,22,23,25 as such, the successful distillation of alcohol would necessitate either more effective cooling or curcurbits constructed of materials with more effective heat transmission, with the best results involving a combination of the two. if not, alcoholic distillates separated by the early stills would contain so much water that they would not burn, thus making it difficult to differentiate such distillates from normal water.3,6 figure 5. illustrations of the rosenhut from michael puff von schrick’s hienach volget ein nüczliche materi von manigerley ausgepranten wasser, 1478 (a) and the moor’s head from hieronymus brunschwyck’s liber de arte distillandi de compositis, 1512 (b). 48 seth c. rasmussen48 seth c. rasmussen another factor that contributed to the success of these early isolations was the addition of a variety of salt substances (nacl, potassium tartrate, k2co3, etc.) as detailed in the recipes discussed above. these added salts acted by absorbing some of the water content of the wine, thus increasing the alcohol concentration and making it easier to isolate via distillation.6,7 it is thought that this practice may have been influenced by the view of islamic philosophers that something to absorb one nature should be added in attempting to purify another nature.7 distillations of such wine-salt mixtures gave solutions referred to as either aqua ardens (burning water)3,7,9,50,51 or aqua flamens (flaming water), which typically had such low alcohol content that they burned without producing significant heat.3,5,6,8,50 the combination of pretreatment with salts along with more efficient cooling methods ultimately produced alcoholic distillates containing less than 35% water and repetitive fractional distillation was said to allow the isolation of “absolute” alcohol.6 after the introduction of aderotti’s wormcooler, the use of the salt pretreatments were no longer necessary and it is thought that it should have been possible for him to obtain 90% alcohol by fractional distillation.3,6,18 strong alcohol distillates were referred to as aqua vitae (water of life)3,7 by authors such as aderotti40 and arnald of villanova (ca. 1240-ca. 1312)6,8,52, the latter who stated: this name is remarkably suitable, since it is really a water of immortality. it prolongs life, clears away ill-humours, revives the heart, and maintains youth. it should be stressed that although the description of aqua vitae is sometimes given as absolute alcohol, the highest alcohol concentration that can achieved by the simple distillation of aqueous solutions is 95%. this is due to the fact that the 95% ethanol:5% water mixture represents a minimum-boiling azeotrope that cannot be separated by distillation. such an azeotrope has a fixed composition, a fixed boiling point, and in all respects acts as a pure liquid. in order to generate true absolute (99-100%) alcohol, the ethanol needs to be distilled from an ethanol-benzene-water mixture, or the water must be removed though the use of a dehydrating agents such calcium oxide (cao). 53 from aqua vitae to ethyl alcohol as introduced above, the original names for ethanol were aqua ardens, aqua flamens, and aqua vitae, with the last of these terms still surviving in the modern words aquavit (scandinavian), eau-de-vie (french), whiskey (scottish), and vodka (slavic). an additional later reference to ethanol was spirit of wine, as the separation of alcohol from wine was viewed to be analogous to the separation of the soul from an impure body. thus, alcohol was viewed to be the “spirit” of the wine and the remaining residue was called the caput mortum (dead body). 22 this is also the origin of the term spirits to refer to various forms of strong alcoholic beverages. the modern term alcohol, however, was not used to refer to these distillation products until the 16th century, with the development of the word an amazing example of the complexities of etymology. the word alcohol finds its origin in the word kohl (or kuhl), which referred to a finely powdered form of the mineral stibnite, or antimony trisulphide (sb2s3). 5,6,54-56 kohl can vary in color from dark-grey to black and was used in antiquity as a cosmetic, particularly to color the upper eyelid in egypt. its use has been documented back to at least the 15th century bce.56 as greek and roman knowledge was eventually transmitted to the islamic empire, kohl was modified with the arabic prefix alto become al-kohl (or al-kuhl) in a similar fashion to alembic as discussed above.5-7,53,54,56 the meaning of the word then changed over time, first transitioning from the simple black powder of kohl to refer to any very fine powder6-8,53,54,56 and then further extended to mean the most fine or subtle part of something.5,6,55 as a result, al-kohl figure 6. philippus aureolus theophrastus bombastus von hohenheim (1493-1541), commonly known as paracelsus [edgar fahs smith collection, university of pennsylvania libraries]. 49from aqua vitae to e85: 49from aqua vitae to e85: the history of ethanol as fuel or al-kohol became generally used for any substance refined by pulverization, distillation, or sublimation.57 by the 16th century, paracelsus (fig. 6) in his von offenen schaden and other writings referred to aqueous solutions distilled from wines as alcool vini or alkohol vini (i.e. the subtle part of wine). over time, vini was then eventually dropped to become first alkohol and then finally the modern alcohol.5,7,56 even into the 18th century, alcohol was still often defined first as powders of the finest form and only secondly as the spirit of wine.54 the use and meaning of the term alcohol then changed again, beginning with the discovery of methyl alcohol (ch3oh) in 1834 by jean baptiste dumas (18001884) and eugène peligot (1811-1890). 58,59 as a result, jöns jacob berzelius (1779-1848) proposed alcohol as the general name for these compounds, with ethanol referred to as wine alcohol (wein-alkohol) and methanol as wood alcohol (holzalkohol).58 shortly thereafter, dumas and peligot revealed that a compound previously discovered by michel chevreul (1746-1889) was cetyl alcohol (c16h33oh)58,59 and the fact that the family now consisted of three known examples suggested that a series of such alcohols were waiting to be discovered. for the discussion herein, any use of the general family name alcohol will refer specifically to ethyl alcohol, the modern name of which had become accepted, and was in formal use, by the second half of the 19th century. initial applications in heat and lighting the combustible nature of alcohol was discovered almost as soon as it was first isolated in the 12th century, as evidenced in its initial names aqua ardens and aqua flamens. such early studies revealed that although it looked like water, alcohol burned with a blue, gemlike flame, a perplexing contradiction for the time as everyone knew that the nature of water was to extinguish fire. given this early knowledge, however, there is no evidence that alcohol was used to any extent as a fuel in its first 500 years.60 this may have been due to the fact that it was too highly prized as a consumable and medicine, as well as for its various uses in the chemical and medical arts to solubilize other reagents.61 by at least the end of the 15th century, however, high-alcohol mashes could now be produced via the fermentation of a wide variety of common crops (grains, potatoes, corn, sugar beets, etc.).53,60,62 this wide variety of potential sources, coupled with the previously discussed advances in distillation methods by this period, should have thus allowed the production of ethanol on large enough scales that additional applications were only a matter of time. the earliest such use referenced are for alcoholbased spirit lamps, which consisted of small burners that could be used to heat food or other objects. it is thought by some that the use of such spirit lamps date as far back as the 17th century, but they were most certainly in widespread use by the beginning of the 19th century. by the 1830s, such alcohol-fueled sprit lamps (fig. 7a) were an important laboratory device for the application of heat and served as a useful alternative to more powerful heating sources such as gas flames, fires, or furnaces.63 such lamps were popular in france and germany, where alcohol was inexpensive. in england, however, the taxes on alcohol made its use for this purpose cost prohibitive such that labs were typically forced to rely on oil lamps. at the same time, the 1830s witnessed the introduction of high-proof alcohol as a solvent for illumination. in 1833, augustus van horn webb introduced a substitute in the united states (us) for the existing candles and whale-oil commonly used throughout the country.64 webb called this substance “spirit gas,” which consisted of a mixture of alcohol and spirits of turpentine. subsequent experiments resulted in the additional ingredients, whereupon he changed the name of the mixture to “camphorated gas”. a limitation, however, was that the spirits of turpentine were too resinous and thus he worked to further refine it, the product of which was given the name camphene (also known as camphine65).64 this led to his final composition of what was now called figure 7. a simple spirit lamp, circa 1830 (a) and an incandescent alcohol lamp, circa 1900 (b).63,64 50 seth c. rasmussen50 seth c. rasmussen “burning fluid”, consisting of one-part camphene and 4.5 parts 95% ethanol.64 from 1840 to 1860, camphene and burning fluid were emphatically the “lights of the world,” the former for fixed lamps, the latter for portable lamps. from 1850 to the outbreak of the civil war the business of distilling alcohol and camphene, and the manufacture and sale of burning fluid, became a distinct and very extensive business, with the market for alcoholbased solvents and fuels exceeding 25 million gallons per year by 1860.65 the dominance of burning fluid in the us was short-lived, however, due to the introduction of low-cost kerosene from refined petroleum in the early 1860s, coupled with increased taxes on alcohol in 1861.64,65 the introduction of the incandescent alcohol lamp (fig. 7b) at the end of the 19th century then led to a resurgence of alcohol for lighting.64 the success of this lamp was the incandescent mantle developed by carl auer von welsbach (1858-1929) in the mid-1880s.66 in attempts to maximize the emission of rare earth elements, welsbach had conceived of the idea of saturating a cotton fiber with a solution of the rare earth salts, after which he burned out the cotton, leaving behind a structure of metal oxides (originally a mixture of magnesium, lanthanum, and yttrium).64,66,67 this mantle would incandesce brightly when a flame was applied to it to emit a soft, intensely white light66,67 and its adaptation for use with alcohol lamps marked a notable improvement in the efficiency of the lamp such that it no longer required camphene or burning fluid to produce a luminous flame and simple alcohol alone was all that was needed.64,68 furthermore, comparative tests on the illuminance of alcohol in the new lamp showed that it outperformed kerosene by more than a factor of two.53,64,67 from this point, alcohol found widespread use for both indoor and outdoor lighting.64,67 in addition to lighting, the initial simple spirit lamps eventually developed into an assortment of more specific alcohol-fueled devices. this included a wide range of more sophisticated stoves for the heating and cooking of food, as well as hot water heaters, tea kettles, coffee percolators, coffee roasters, and flatirons.67,68 this last is particularly interesting, as such alcohol-fueled flatirons (fig. 8) appear to be the first example of a “self-heating” flatiron in comparison to a device that needed to be heated on an external heat source such as a stove or fire. as a result, this should have provided more consistent temperature control. lastly, various alcohol-burning stoves had also been developed for heating internal living spaces. a limitation here is that the alcohol flame itself radiates very little heat outward, with nearly all of the heat traveling upward from the tip of the flame. thus, in order to heat a room with an alcohol stove, the heat of the alcohol flame needed to be reflected out into the room. this was usually accomplished with a curved sheet of copper, as shown in the heaters depicted in fig. 9.67,68 the fluted arrangement of these sheets would further enhance the ability of the stove to throw out the heat in the largest possible quantities into the room.68 this is only one of the various types of heaters used for this purpose67,68 and other designs utilized a piece of non-combustible material, such as asbestos, which could be rendered redhot by the flame. germany in particular had developed many such alcohol-fueled heaters, where they were in common use by the early 20th century.67 denatured alcohol a primary issue that limited the use of alcohol as fuel was the frequent taxes and duties levied by governments upon distilled spirits. in the us, taxes were imposed on distilled spirits in 1791 to discourage its use as an intoxicant.65 these taxes were repealed in 1802,65 but were then reinstated in 1861 when the civil war figure 8. alcohol-fueled flatirons, circa 1900.67,68 figure 9. alcohol-fueled space heating stoves, circa 1900.67,68 51from aqua vitae to e85: 51from aqua vitae to e85: the history of ethanol as fuel made it necessary to raise money by every means possible. as early as 1864, however, the us government wanted to relieve the tax burden on the industrial uses of alcohol, while retaining taxes on alcohol beverages, but a path towards this goal was unclear.69,70 the us was not the only country struggling with the fact that the high taxes typically placed on consumable alcohol was limiting its possible uses as a fuel.60 as a potential solution, efforts began to produce a form of alcohol that could still be used for industrial uses, but would no longer be desirable to consume. this process of rendering alcohol unsuitable for drinking was referred to as “denaturing,” and essentially consisted of adding a soluble substance to the alcohol that generated a bad taste or odor of such intensity that it would render it impossible or impracticable to use the modified alcohol as a drink.62 furthermore, the substance added should be something that was quite difficult to remove from the modified alcohol by distillation. this modified alcohol was then commonly known as denatured alcohol or industrial alcohol.62,69,70 proposed denaturing agents included camphor, turpentine, acetic acid, met hanol, py ridine, acetone, methylene blue, aniline blue, naphthalene, castor oil, and benzene, among others.62 great britain was the first country to put the denaturing of alcohol into practice, with the duty-free use of denatured alcohol first authorized in 1855.53,69,70 the denaturing was accomplished via a mixture containing 10% commercial wood alcohol (a mixture of methanol and wood naphtha) and 90% ethanol, the combination of which was then referred to as methylated spirit. the acetone and other constituents of the wood naphtha were so difficult to remove that methylated spirit was considered permanently unfit for consumption and thus not subject to duty.69 france then followed suit, with the permitted use of denatured alcohol under benefit of reduced taxes in 1872.69 this was then revised in 1881 to make it impossible to use any methanol except that which possesses the characteristic odor to render any alcohol to which it has been added completely unfit for consumption. as with great britain, the french utilized commercial wood alcohol for the denaturing, although added benzene and either solid malachite or aniline green dye.67,69 this latter additive then gave the denatured alcohol a pale-green color to easily distinguish it from consumable alcohol.69 in germany, the use of tax-free alcohol was first permitted in 1879, using alcohol denatured with the addition of wood alcohol.69 this was then modified in 188769-71 through the addition of pyridine bases in order to permit greater general use. these pyridine bases are exceedingly repugnant in both taste and smell and were obtained as byproducts from the destructive distillation of coal.69 the german yearly consumption of denatured alcohol in 1904 was 26 million gallons.71 other countries soon followed suit, including austria-hungary (1888), italy (1889), sweden (1890), norway (1891), switzerland (1893), and belgium (1896). a law permitting the tax-free, domestic use of denatured alcohol for general purposes in the us was finally approved on june 7, 190653,62,65,70 and enacted january 1, 1907.69 in the us, denatured alcohol was required to consist of 100 parts ethanol (90% or greater), 10 parts methanol, and ½ part benzene.62,67 in the first year following the introduction of its tax-free use, 1.5 million gallons of denatured alcohol were used in the us.53 by 1918, this had grown to over 90 million gallons of denatured alcohol.60 solid alcohol in the beginning of the 20th century, another innovation was introduced in europe, which was called smaragdin.67 this was a solid gel that came in small cubes about one-third inch in size. the cubes were made via the addition of a little ether to ethanol, after which a small amount of gun cotton was dissolved into the liquid mixture. this mixture would then set into a jelly-like solid, which would keep for a year or more in a closed vessel, with little loss due to evaporation. fuel in this form could then be easily carried in small amounts and used as ordinary alcohol, leaving little residue. furthermore, it could be used for heating where no alcohol burner was available, as it could be burnt in any noncombustible receptacle.67 as of the 1920s, large quantities of industrial alcohol were used in the us in order to the make such solidified alcohol as a fuel for chafing dishes and small portable stoves.60 figure 10. solid alcohol cubes.67 52 seth c. rasmussen52 seth c. rasmussen alcohol in internal combustion engines the use of alcohol as a fuel in internal combustion engines dates to their early development. in 1826, samuel morey (1762-1843) published and patented in the us an internal combustion engine prototype that utilized vapor from a liquid fuel.72 although this work originated with the application of a fuel consisting of a mixture of water and spirt of turpentine, he reported that both alcohol-turpentine mixtures and pure alcohol were also successful.70,72 in 1876, german engineer nikolaus august otto (1832-1891) then perfected his four-stroke engine with compressed loading, that became known as the otto cycle engine. such otto engines were suitable for a range of fuels, including gasoline, kerosene, and alcohol.73 in 1902, deutz gas-engine works (deutz ag), the company originally founded by otto and eugen langen in 1864, began producing alcohol-fueled motors for portable uses in germany. these were then used extensively in tractors, harvesters, and railway engines.73 in 1907, the hart-parr company in the us then began adapting their gasoline traction engine for use with alcohol to be used as plowing-engines for agriculture65,70,73. at the time, it was viewed that the use of alcohol motors on the farm would become quite common as soon as such adaptations were completed. this included applications such as wagons, carriages, stationary motors, water pumps. mowing machines, and plows.68 by the 1890s, horseless carriages (automobiles) could be found in both europe and the us. in 1896, henry ford (1863-1947) completed his first automobile, which he called the quadricycle, powered by an ethanol-powered, two-cylinder engine (fig. 11).74 when ford later released the model t in 1908, it ran on gasoline, but it was equipped with an adjustable carburetor that could be adapted to run on pure alcohol.65,70,74,75 a competing manufacturer, the olds gas power company, soon followed suit to offer carburetor components that would allow their automobiles to run on either alcohol or gasoline.70 alcohol was then used to as an automotive fuel into the 1920s as efforts were made to build and sustain a us ethanol program.65,75,76 as reported by scientific american in 1921:60 the prospect is, indeed, that within the span of a very few years, alcohol or fuels with an alcohol base will largely or entirely replace gasoline as a fuel for motor cars. however, the us prohibition era then made it illegal to sell, manufacture, and transport alcohol, which made its use as automotive fuel nearly impossible.65,74 ethanol could still be sold when mixed with gasoline, but by the end of world war i, gasoline has become the most popular fuel in the us, as well as many other parts of the world.74 from gasohol to e85 although the use of pure alcohol never really found long-term success as an automotive fuel, decreases in the supply of gasoline, increasing fuel demand, and higher fuel prices all led to interest in replacing at least some of the gasoline in liquid fuel. the primary substitute in such efforts was alcohol, which had the benefits of lower cost and more efficient combustion, thus resulting in little formation of troublesome carbon deposits.53 in the 1930s, such gasoline-alcohol blends became popular in the us midwest, which grew the corn from which most us ethanol fuel was produced.74 by 1938, a plant in atchison, kansas, was producing 18 million gallons of ethanol a year, supplying more than 2,000 service stations in the midwest that sold alcohol blends (6-12% ethanol). 74,75 during world war ii, brazil enacted a wartime law that automotive fuel must be comprised of at least 50% ethanol.74 by the end of world war ii, however, fuels from petroleum and natural gas became available in large quantities at low cost, thus eliminating any economic incentives for alcohol fuels from crops. governments quickly lost interest in the production of alcohol fuels, resulting in the dismantling of many of the wartime distilleries.75 a few countries such as brazil, howfigure 11. henry ford (1863-1947) on his ethanol-powered quadricycle (wikimedia commons). 53from aqua vitae to e85: 53from aqua vitae to e85: the history of ethanol as fuel ever, still continued the production and development of ethanol fuels.74 interest in ethanol was renewed in the 1970s, when oil embargoes initiated in the middle east resulted in limited supply and increased prices for petroleum products.74,75,77 at the same time, the us began to phase out lead (an octane booster) from gasoline.75 in 1976, brazil then made it mandatory that gasoline contain ethanol.74 in the us, the energy tax act of 1978 introduced federal tax exemption for gasoline containing 10% alcohol in an effort to decrease the nation’s vulnerability to oil shortages.74,75,78 this subsidy brought the cost of ethanol down to near the wholesale price of gasoline, making alcohol blends economically viable.75 amoco then began to market fuels containing ethanol as both an octane booster and gasoline volume extender in 1979.75 other major oil companies, including texaco, beacon, ashland, and chevron, all soon followed suit.74,75 the resulting 10% alcohol blends were marketed as gasohol (now known as e10)74,75,78 and were available at 1200 fuel stations across the midwest by the end of 1979.78 by 1980, 25 states in the us had made ethanol at least partially exempt from gasoline excise taxes in order to promote consumption.75 at the same time, the us government introduced guaranteed loans for prospective ethanol producers to cover up to 90% of construction costs and then placed a tariff on imported ethanol in an effort to ensure that only local sources of alcohol were cost-effective.74 federal and state tax incentives then made ethanol economically attractive in the midwest, resulted in the production of 175 million gallons in 1980. the high cost and difficulty of transporting ethanol still limited consumption in other markets, however.75 ethanol received a boost from the us congress in 1990 with the passage of the clean air act amendments, which mandated the use of oxygenated fuels (minimum of 2.7% oxygen by volume) in specific regions of the us during the winter months to reduce carbon monoxide.75 this was commonly achieved by blending gasoline with either methyl tert-butyl ether (mtbe) or ethanol. however, the higher oxygen content of ethanol made it attractive, even when more expensive than mtbe. the higher volatility of ethanol did limit its use in hot weather, where evaporative emissions could contribute to ozone formation, but its expanded role as a clean-air additive allowed alcohol-blended fuels to penetrate markets outside the midwest.75 this was then followed with the energy policy act in 1992, which made it mandatory for certain car fleets to start buying vehicles capable of running on alternative fuels such as e85 (ca. 85% ethanol:15% gasoline). tax deductions are also given to promote the sale of such vehicles. however, the availability of e85 at this time was still low and generally limited to the midwest.74 between 1997 and 2002, 3 million cars and light trucks capable of running on e85 are produced. such vehicles, collectively known as flex-fuel vehicles, can run on gasoline or alcohol blends up to, and including, e85. such vehicles strengthened the demand for alcohol fuels in brazil74 and by 2005, over 4 million flex-fuel vehicles are on the road in the us. by this time e85 was now available at ca. 400 fuel stations, primarily in the midwest. after the eu adopted its first biofuels policy in 2003, ethanol blends have seen a steady increase, primarily as either e5 or e10 (5 and 10% ethanol, respectively), with e85 limited primarily to sweden, france, germany.79 by 2012, the number of flex-fuel vehicles in the us had risen to over 6 million,74 with more than 4600 stations offering e85 by 2019.80 conclusion the application of ethanol as a fuel for a variety of applications consists of a long history that dates back more than 200 years. of course, this is brief in comparison to the much longer history of ethanol as a solvent, disinfectant, medicine, and most importantly, intoxicating beverage. in fact, it is not unrealistic to say that it was due to the highly valued nature of these earlier applications that ethanol’s promise as a fuel was delayed by hundreds of years. although ethanol has a number of significant benefits as a fuel, its use has been limited throughout its history by such factors as insufficient supply, the availability of less expense alternatives, excessive taxation, and, to some extent, its stigma as an intoxicant. still, ethanol provides a promising alternative to petroleum fuels and its adaption as a standard, contemporary fuel seems to be on the rise. references 1. s. c. rasmussen, the quest for aqua vitae. the history and chemistry of alcohol from antiquity to the middle ages, springerbriefs in molecular science: history of chemistry, springer, heidelberg, 2014, pp. 1-12. 2. s. c. rasmussen in chemical technology in antiquity (ed.: s. c. rasmussen), acs symposium series 1211, american chemical society, washington, d.c., 2015, chapter 10, pp. 89-138. 3. l. gwei-djen, j. needham, d. needham, ambix 1972, 19, 69. 54 seth c. rasmussen54 seth c. rasmussen 4. g. broughton, j. e. janis, c. e. attinger, plast. reconstr. surg. 2006, 117 (suppl.), 6s. 5. j. m. stillman, the story of early chemistry, d. appleton and co., new york, 1924, pp 184-192. 6. r. j. forbes, a short history of the art of distillation, e. j. brill, leiden, 1970, pp 76-98. 7. h. m. leicester, the historical background of chemistry, dover publications, inc., new york, 1971, pp 76-77. 8. a. j. liebmann, j. chem. educ. 1956, 33, 166. 9. e. o. von lippmann, chem. ztg. 1920, 44, 625. 10. b. l. vallee, sci. am. 1998, 279(6), 80. 11. j. b. lambert, traces of the past. unraveling the secrets of archaeology through chemistry, addisonwesley, reading, ma, 1997, pp 134-136. 12. i. s. hornsey, a history of beer and brewing, the royal society of chemistry, cambrige, 2003, pp. 9-20. 13. p. e. mcgovern, u. hartung, v. r. badler, d. l. glusker, l. j. exner, expedition 1997, 39, 3. 14. f. s. talyor, ambix 1937, 1, 30. 15. f. s. taylor, ann. sci. 1945, 5, 185. 16. s. c. rasmussen, how glass changed the world. the history and chemistry of glass from antiquity to the 13th century, springerbriefs in molecular science: history of chemistry, springer, heidelberg, 2012, pp 51-65. 17. r. j. forbes, a short history of the art of distillation, e. j. brill, leiden, 1970, pp 17-24. 18. e. j. holmyard, alchemy, dover publications, new york, 1990, pp 47-54. 19. f. s. talyor, the alchemists, barnes & noble, new york, 1992, pp. 39-46. 20. e. j. holmyard in a history of technology, vol. 2 (ed.: c. singer), clarendon press, oxford, 1956. 21. j. m. stillman, the story of early chemistry, d. appleton and co., new 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2015, chapter 10, pp. 267-313. 29. j. b. lambert, bull. hist. chem. 2005, 30, 1. 30. w. e. s. turner, j. soc. glass technol. 1956, 40, 39t. 31. w. e. s. turner, j. soc. glass technol. 1956, 40, 277t. 32. c. j. philips, glass: the miracle maker, pitman publishing corporation, new york, 1941, pp 43-44. 33. v. dimbleby, w. e. s. turner, j. soc. glass technol. 1926, 10, 304. 34. s. english, w. e. s. turner, j. am. ceram. soc. 1927, 10, 551. 35. r. j. forbes, a short history of the art of distillation, e. j. brill, leiden, 1970, p 114. 36. k. cummings, a history of glassforming, a & c black, london, 2002, pp. 102-133. 37. g. sarton, introduction to the history of science, vol. iii, part i. the william & wilkins co., baltimore, 1947, pp. 170-173. 38. d. jacoby, j. glass studies 1993, 35, 65. 39. s. c. rasmussen, how glass changed the world. the history and chemistry of glass from antiquity to the 13th century, springerbriefs in molecular science: history of chemistry, springer, heidelberg, 2012, pp. 37-50. 40. e. o. von lippmann, arch. gesch. med. 1914, 7, 379. 41. k. sudhoff, arch. gesch. naturw. techn. 1914, 5, 282. 42. j. r. partington, a history of chemistry, martino publishing, mansfield centre, ct, 1998, vol. 2, p. 266. 43. k. sudhoff, arch. gesch. med. 1914, 7, 396. 44. r. j. forbes, a short history of the art of distillation, e. j. brill, leiden, 1970, pp. 108-112. 45. a. j. inde, the development of modern chemistry, harper & row, new york, 1964, pp. 13-18. 46. r. j. forbes, a short history of the art of distillation, e. j. brill, leiden, 1970, p. 217. 47. r. s. tubbs, a. n. bosmia, m. m. mortazavi, m. loukas, m. shoja, a. a. c. gadol, childs nerv. syst. 2012, 28, 629. 48. r. j. forbes, a short history of the art of distillation, e. j. brill, leiden, 1970, pp. 120-124,175-177. 49. m. p. crosland, historical studies in the language of chemistry, dover publications, inc., new york, 1978, pp. 285–286. 50. a. fleming, alcohol, the delightful poison, delacorte press, new york, 1975, p. 12. 51. d. j. s. thonpson, alchemy and alchemists, dover publications, inc., new york, 2002, pp. 79–83. 55from aqua vitae to e85: 55from aqua vitae to e85: the history of ethanol as fuel 52. j. f. benton, viator 1982, 13, 245. 53. c. c. pines, am. j. police sci. 1931, 2, 500. 54. m. p. crosland, historical studies in the language of chemistry, dover publications, inc., new york, 1978, pp. 107-108. 55. j. r. partington, a history of chemistry, martino publishing, mansfield centre, ct, 1998, vol. 2, p. 316. 56. e. o. von lippmann, angew. chem. 1912, 40, 2061. 57. r. j. forbes, a short history of the art of distillation, e. j. brill, leiden, 1970, pp. 47,107. 58. j. r. partington, a history of chemistry, martino publishing, mansfield centre, ct, 1998, vol. 4, p. 353. 59. a. j. inde, the development of modern chemistry, harper & row, new york, 1964, p. 189. 60. h. a. mount, sci. am. 1921, 125(10), 164. 61. s. c. rasmussen, the quest for aqua vitae. the history and chemistry of alcohol from antiquity to the middle ages, springerbriefs in molecular science: history of chemistry, springer, heidelberg, 2014, pp. 95-105. 62. h. w. wiley, industrial alcohol: sources and manufacture, farmer’s bulletin no. 268., u.s. department of agriculture, washington, 1906. 63. j. j. griffin, a compendium of experimental chemistry, part first, comprising chemical manipulation and analysis by the blowpipe, 8th ed. richard griffin and co., glasgow, 1838, pp. 17-21. 64. r. f. herrick, denatured or industrial alcohol, john wiley & sons, new york, 1907, pp. 207-238 65. h. bernton, w. kovarik, s. sklar, the forbidden fuel. a history of power alcohol, university of nebraska press, lincoln, 2010, pp. 8-13. 66. r. adunka, m. v. orna, carl auer von welsbach: chemist, inventor, entrepreneur, springerbriefs in molecular science: history of chemistry, springer, heidelberg, 2018, pp. 62-73. 67. j. k. brachvogel, industrial alcohol. its manufacture and uses, munn & company, new york, 1907, pp. 373-398. 68. w. l. c., iron age 1906, 78, 1273. 69. r. f. herrick, denatured or industrial alcohol, john wiley & sons, new york, 1907, pp. 1-16 70. m. s. carolan, soc. stud. sci. 2009, 39, 421. 71. j. k. brachvogel, industrial alcohol. its manufacture and uses, munn & company, new york, 1907, pp. 12-14. 72. s. morey, am. j. sci. arts 1826, 1, 104. 73. r. f. herrick, denatured or industrial alcohol, john wiley & sons, new york, 1907, pp. 277-328. 74. p. acharya, j. indian leather technol. assoc. 2012, 62, 997. 75. j. dipardo, outlook for biomass ethanol production and demand, united states department of energy, 2000. 76. r. g. skerrett, sci. am. 1920, 123(12), 274. 77. h. bernton, w. kovarik, s. sklar, the forbidden fuel. a history of power alcohol, university of nebraska press, lincoln, 2010, pp. 35-37. 78. h. bernton, w. kovarik, s. sklar, the forbidden fuel. a history of power alcohol, university of nebraska press, lincoln, 2010, pp. 59-70. 79. available online (accessed july 17, 2019). 80. available online (accessed may 27, 2019). https://www.epure.org/about-ethanol/fuel-market/fuel-blends https://e85prices.com substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 3(2) suppl. 5: 109-124, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-592 citation: g. s. girolami (2019) a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869. substantia 3(2) suppl. 5: 109-124. doi: 10.13128/substantia-592 copyright: © 2019 g. s. girolami. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami school of chemical sciences, 600 s. mathews ave., university of illinois at urbanachampaign, urbana, 61801, us e-mail: ggirolam@illinois.edu abstract. the present article identifies and discusses some of the books and scientific articles that played important roles in the development of the periodic law, before mendeleev published his periodic system in 1869. for each book, information is given about the edition in which the discovery was made, and for each scientific article, information is given about the form in which it was issued, such as whether offprints were printed in addition to the journal appearance. some observations of interest to book collectors are included, such as assessments of the availability of these documents on the rare book market. this paper may also be of use to those who wish to learn about (or to teach) the history of the periodic law from the original documents that first announced important advances toward its creation. keywords. periodic table, mendeleev, chemical elements, rare books, offprints, bibliography. introduction one of the most important unifying principles in all of science is the periodic law of the chemical elements. the history of the conception and development of the system and its associated periodic table is both rich and fascinating, and the books, monographs, and journal publications that led to its creation and improvement have been the subject of much study and commentary.1-5 the purpose of the present article is to identify and discuss, from a book collector’s perspective, some of publications that played important roles in the development of the periodic law. in the current paper, i will focus on those contributions that were made before mendeleev published his breakthrough ideas beginning in 1869. most of these documents appear only infrequently on the rare book market but can be acquired by the patient collector. this paper may also be of use to those who wish to learn about (or to teach) the history of the periodic law from the original documents that first announced important advances toward its creation. 110 gregory s. girolami boyle’s definition of an element (1661). the book the sceptical chymist: or chymico-physical doubts and paradoxes6 by the anglo-irish natural philosopher robert boyle (1627-1691) is an appropriate place to start because it contains early speculations about the basic particles of matter. in this book (fig. 1), boyle presented his theory that matter consists of a hierarchical arrangement of particles, and defined elements as “certain primitive and simple, or perfectly unmingled bodies; which not being made of any other bodies, or of one another, are the ingredients of which all those called perfectly mixt bodies are immediately compounded, and into which they are ultimately resolved.” of the books mentioned in the current paper, the sceptical chymist is one of the rarest. in a census carried out in 1960, only 27 copies of the first (1661) edition could be located, and 5 others previously known to be in private collections could not be traced.7 my own efforts to update the census suggests that perhaps 65 copies exist, of which perhaps six are privately held. these are very small numbers even for a seventeenth century book. some variants of the first edition of the sceptical chymist are known. the leaf bearing pages 243 and 244 is found in two states: about 20% of the known copies have the leaf in its original state (in which a part of a sentence is inadvertently printed twice) and most of the rest contain a replacement leaf that corrected the error. in addition, about 20% of the known copies lack the four-page list of errata that usually appears at the end of the text. copies without the errata more likely to have the original leaf, and copies with the errata are more likely to have replacement leaf. these correlations suggest that the addition of both the replacement leaf and the errata occurred sometime after the book was printed, but before all the copies had been bound and sold. the second english edition of the sceptical chymist (oxford, 1680) is nearly twice as long as the first edition because it contains much new material, under the subtitle experiments and notes about the producibleness of chymical principles. several latin editions of the sceptical chymist were also printed. all of these later editions are also scarce, although not as rare as the first english edition, which is today almost impossible to collect. lavoisier’s table of simple substances (1787 and 1789) in 1787, the french chemist antoine laurent lavoisier (1743-1794), along with three compatriots, louisbernard guyton de morveau (1737-1816), claude louis berthollet (1748-1822), and antoine françois de fourcroy (1755-1809), published an important book, méthode de nomenclature chimique,8 which grew out of a paper that had been written by guyton de morveau in 1782.9 this book introduced a new system of chemical nomenclature, still used today, in which names are based on the chemical content; for example, the substance the alchemists called “pompholix” is referred to instead as zinc oxide. in the context of the development of the periodic table, the méthode is notable for being one of the first to give a list of chemical elements, which the authors defined as substances that cannot be further decomposed. in table ii, the book gives a list that contains fifty-one “simple substances”. of these, twenty-one were elements as we recognize them today (n, h, c, s, p, au, pt, ag, hg, sn, cu, pb, fe, zn, mn, ni, bi, sb, as, mo, w), seven were elements that they suspected were combined with oxygen (k, na, ba, ca, mg, al, and si), and three others were radicals that had not yet been isolated from their acids (cl, b, and f). the remaining substances were the radicals of various organic acids, along with ether and alcohol. interestingly, two states of the first edition of the méthode have been identified: in one, pages 257-272 are misnumbered 241-256; in the other, only half of these figure 1. one of the two title pages in the first edition of boyle’s sceptical chymist, 1661. only about 65 copies of this book are known, perhaps six of which are owned privately, the rest being in institutional libraries 111a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 pages are misnumbered. these states were once considered to be different issues of the first edition, meaning that they were printed and sold by the publisher at different times.10 it is more likely, however, that all of the first edition copies stem from the same print run, and that some of the page numbers were corrected partway through the printing but before the books were bound. today, the two states of the méthode are of equal value. the second edition, which was a page-for-page reprinting dated the same year, can be recognized because it bears a different figure on the title page (a vase of flowers instead of a cherub supervising a distillation) and it lacks the printer’s colophon on p. 314. two years after the appearance of the méthode, lavoisier published his landmark textbook traité élémentaire de chimie, présenté dans un ordre nouveau et d’après les découvertes modernes… [elementary treatise on chemistry, presented according to a new order and after the modern discoveries…].11 in this book, lavoisier overthrew the phlogiston theory, emphasized the concept of the conservation of mass, and proved that the increase in the weight of calcined metals was due to something taken from the air, which had first been given the name “oxygen” in the méthode. the traité also contains a “tableau des substances simples,” which looks much more like a modern list of chemical elements: it repeats the list of simple substances given in the méthode, but omits the organic radicals, ether, and alcohol. lavoisier’s list also includes light and heat among these substances; interestingly, he omitted the “fixed alkalies” potash and soda from this list because he believed them to be compounds of unknown composition. the first edition of the traité élémentaire de chimie is a relatively common book, and copies are regularly available for purchase. most copies of the first edition consist of 653 pages, but before the publication of the full text of the first edition, lavoisier had a small number of copies of the book bound in one volume of only 558 pages.10 this version lacks the “tables à l’usage des chimistes,” the “table des matières,” and the approbation of the académie des sciences (dated 4 february 1789), which had not yet been printed. although the 558-page version has been referred to as a first edition, and the regular 653 page version as a second edition,12 they are more properly described as the first and second issues of the first edition.13 the first issue is most easily identified by the absence of the words “tome premier” on the half-title and title page; ten copies of the first issue are currently known. four of these are bound in calf, three of which are in institutional libraries: the national library of france (bnf, rebound), the mazarine library in paris, and cornell university (lavoisier’s personal copy). the fourth known copy in calf was sold at auction in paris in 2010. the six other known copies were given to the royal family and were sumptuously bound in red morocco bearing the arms of the recipient in the center of each of the boards (fig. 2). five of these are in institutional libraries: that of louis xvi at the library of versailles, that of marie antoinette at the bnf, that of louis stanislas xavier de bourbon, count of provence (later louis xviii) at the sainte geneviève library, that of charles philippe of france, count of artois (later charles x) at the library of the arsenal, and that of marie-thérèse de savoie, countess of artois at the institute of france. one other copy bound in red morocco was given to the eldest son of louis xvi and marie antoinette, the dauphin louis-joseph-françois-xavier de france, who died in june 1789 at the age of eight; this copy sold at auction in paris in 2005. several later editions of the traité élémentaire were published during lavoisier’s lifetime, and the book also appeared in english, spanish, german, italian, and dutch translations figure 2. one of ten known 558-page first issues of lavoisier’s traité élémentaire de chimie, 1789, in a presentation binding for the dauphin louis-joseph-françois-xavier de france, the eldest son of louis xvi and marie antoinette, who died in june 1789 at the age of eight. 112 gregory s. girolami dalton’s atomic weights (1805 and 1808). the english chemist john dalton (1766-1844) is well known for his atomic theory of matter, in which he proposed that all atoms of a given element are identical in mass and properties. dalton’s atomic theory is important for several reasons: one is that it made it possible for the first time to devise chemical formulas for pure substances, and another is that it provided the first way to list the elements in an order that (eventually) would be used to uncover periodic relationships. dalton first proposed the idea that atoms of an element had a characteristic weight in a journal article he published in 1805 entitled “the absorption of gases by water and other liquids.”14 dalton was led to this hypothesis during his research that showed that different gases were differently soluble in water: gases with low densities and only one kind of atom (such as hydrogen) were less soluble than gases with larger densities and more than one kind of atom (such as carbon dioxide). he proposed that the amount of gas that dissolves in water at a given gas pressure “depends upon the weight and number of the ultimate particles of the several gases, those whose particles are lightest and single being least absorbable and the others more, according as they increase in weight and complexity.” without any further discussion, dalton appended a table to his article, in which he listed his measurements of “the relative weights of the ultimate particles of gaseous and other bodies.” his list is (mostly) in order of increasing weight, beginning with hydrogen (which he assigned a relative weight of 1) and continuing with 20 other substances, the one with the largest relative weight being sulfuric acid. some of dalton’s numbers are molecular weights and some are atomic weights; among the latter are proposed values for h, n, c, o, p, and s, although none of the values matches modern atomic weights because dalton made mostly incorrect assumptions about combining ratios. although most early scientific discoveries were first announced in books, from the 18th century onward it became increasingly common for new ideas to be presented as papers in scientific journals. authors began requesting separate copies of their papers for them to distribute to scientific colleagues. such authors’ separates are known as “reprints” among practicing scientists but are called “offprints” in the book trade.15 as far as i know, however, no offprints of dalton’s 1805 article in the manchester memoirs exist; this document can be collected only as the journal issue or bound volume. dalton gave more information about his atomic ideas in his magnum opus, new system of chemical philosophy, published in three volumes between 1808 and 1827.16 the first of the three volumes was devoted almost entirely to a discussion of heat and the forces between chemical substances. only in the last four pages of the first volume did dalton turn to his atomic theory; he wrote, “now it is one great object of this work, to shew the importance and advantage of ascertaining the relative weights of the ultimate particles, both of simple and compound bodies…” (italics in original). in one of the figures that appears after the end of the text (fig. 3), figure 3. dalton’s table of elements and compounds from the first volume of his new system of chemical philosophy (top). this copy also contains experimental notes in dalton’s handwriting (partially visible at right) as well as dalton’s handwritten inscription presenting this copy to his personal physician, joseph a. ransome (bottom). 113a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 dalton gave for the first time a table of the then-known elements arranged in order of increasing atomic weight; remarkably, the atomic weights themselves appear only in the caption to this figure! complete sets of all three volumes of dalton’s new system are hard to find on the collector’s market, in part because few people who bought the first two volumes were persistent enough (and still alive) to purchase the third volume, which appeared nearly 20 years later. ampère’s attempt to classify elements (1816) one of the earliest attempts to classify elements according to their chemical properties was devised by the french physicist andré-marie ampère (1775-1836). in 1816, ampère published a journal article, “essai d’une classification naturelle pour les corps simples [essay on a natural classification of the elements],”17 in which he classified the elements according to their relative affinity for oxygen and the nature of the compounds they form with it. ampère’s system of classifying elements according to their chemical reactivity resembles the approach of étienne françois geoffroy (1672-1731), who published the first table of relative chemical affinities in 1718.18 like mendeleev’s periodic table, ampère’s system was intended to be an instrument of chemical research, and in fact it was still being used in the 1860s.19 ampère commissioned offprints of his 1816 journal article, which are identifiable by the repagination of the two parts as pages 1-44 and 1-35. these offprints are quite scarce, however, with perhaps five or so copies still extant. far more common is the 1816 journal volume of the annales de chimie et de physique in which ampère’s paper appears. dobereiner’s triads (1817 and 1829) in 1817, the german chemist johann wolfgang döbereiner (1780-1849) took one of the first steps towards the creation of the periodic table. in a letter sent in 1817 to annalen der physik, dobereiner’s colleague ferdinand wurzer (1765–1844) briefly reported döbereiner’s observation that the equivalent weight of strontia was almost exactly the arithmetic mean of those for lime and baria.20 by 1829, döbereiner had extended his initial observation by finding similar trends in certain properties of selected groups of elements.21 for example, lithium, sodium, and potassium were well known to have very similar chemical properties, and döbereiner pointed out the fact that the average of the equivalent weights of lithium and potassium was close to that of sodium. döbereiner found other triplets of chemically similar elements whose equivalent weights obeyed the same rule: one was calcium, strontium, and barium, another was sulfur, selenium, and tellurium, and a third was chlorine, bromine, and iodine. moreover, for some of these triads the gas or solid densities of the elements and “the intensity of chemical affinity” followed a similar pattern. these sets of elements became known as döbereiner’s triads. offprints of döbereiner’s 1829 paper seem not to exist (there is no evidence that any were printed) but one can find copies of the paper in the form of its appearance in the journal annalen der physik und chemie. gmelin’s network of elements (1843) in 1819, the german chemist leopold gmelin (17881853) published the first edition of his handbuch der theoretischen chemie [handbook of theoretical chemistry]. the second and third editions had similar titles and arrangements, but the fourth edition was intended to cover all types of chemistry, and gmelin chose a new title, handbuch der chemie.22 it is in this fourth edition that gmelin’s remarkable forerunner to the periodic table first appears: his “körpernetze” or network of elements. in volume 1 of his handbuch, gmelin presents a system, based on döbereiner’s triads, which established relationships between 55 chemical elements by arranging triads (or sometimes groups of four, five, or six elements) into an overall v-shape (fig. 4). gmelin states that, within the v, the triads are stacked vertically by electronegativity, with the most electronegative triad (f, cl, br, i) occupies the upper left of the v, the most electropositive (li, na, k) the upper right, and those with intermediate electronegativities (mostly what we now call the transition elements) are placed at the bottom. within figure 4. gmelin’s “körpernetze” from his handbuch der theoretischen chemie (1843). 114 gregory s. girolami each triad, the elements are ordered from left to right by increasing atomic weight. oxygen, nitrogen, and hydrogen are not placed into any of the triads, but instead are given privileged positions above the v. gmelin’s körpernetze arranged most of the thenknown main group elements in the same fashion (albeit rotated and slanted) as seen in a modern periodic table, despite the handicap of using “pre-cannizzaro” equivalent weights. although some of the elements are not arranged “correctly,” gmelin’s körpernetze is still a remarkable achievement.3 original multivolume sets of the fourth edition of gmelin’s handbuch are fairly readily available for purchase. the eight volumes were issued in nine parts (volume 7 being divided into two parts). volume 1 is dated 1843 and the following volumes were issued in subsequent years; volume 8 appeared in 1866. two supplementary volumes were issued in 1868. numerical regularities in the atomic weights common to different groups of elements (1850-1860) in the 20 years after gmelin published his körpernetze, several chemists tried to f ind mathematical regularities among the atomic weights of the elements. some of these, such as josiah parsons cooke (1827-1894), discussed only regularities that occur within individual groups.23 the first to propose that there might be regularities that pertain to more than one group of related elements was the german chemist max von pettenkofer (1818-1901), in his 1850 article “ueber die regelmässigen abstände der aequivalentzahlen der sogenannten einfachen radicale [on the regular spacings of the equivalent numbers of the socalled simple radicals].”24 after quoting the passages in gmelin’s handbuch that discuss döbereiner’s triads, pettenkofer made the observation that the differences in equivalent weights in the alkali metal, alkaline earth, and nitrogen groups (and a few other pairs of elements) are either 8 or a multiple of 8. he then commented, “the recurrence of differences between the cited equivalent numbers of such bodies that belong to a natural group, and which are nearly divisible by 8, is too frequent to be thought to be a mere coincidence in the size of the divisor.” pettenkofer went on to suggest that there the regularities in the equivalent weights of the elements might be analogous to those seen for the organic groups methyl, ethyl, butyryl (i.e., butyl), and amyl, for which the differences in equivalent weights were 14, 28, and 14. in 1853, in an article entitled “on the relations between the atomic weights of analogous elements,”25 the english chemist john h. gladstone (1827-1902) tried to fit the equivalent weights of several related groups of elements, as given in gmelin’s 1843 network, to formulas of the kind a + nx, where n is an integer. gladstone noted (as pettenkofer had, but without citing his paper) that similar formulas had recently been found to apply to series of organic compounds such as the methylethyl-amyl series. he went on to comment that there was a regularity that persisted across several groups of elements: the increment x in his formula was 24 for both the ca-sr-ba and s-se-te series, and also for the zn-cd pair. gladstone speculated (again, like pettenkofer) that these and similar regularities were unlikely to be due to chance, and suggested that they might reflect some regular aspect of the inner constitution of the elemental bodies. in 1858, in his three-part paper “mémoire sur les équivalents des corps simples [memoire on the equivalents of simple bodies],”26 the french chemist jean baptiste andré dumas (1800-1884) carried out an analysis of the equivalent weights of the elements in terms of algebraic formulas similar to those introduced by gladstone (although dumas cited cooke’s later paper23 of 1854 as the source of the idea). in particular, dumas fitted the weights to formulas of the type a + nd + md′ + d″. for some groups, however, fewer than four terms sufficed: the magnesium (i.e., alkaline earth) and oxygen groups, for example, required only the first two terms. dumas noted that the elements in the magnesium and oxygen groups could be paired up in such a way (oxygen with magnesium, sulfur with calcium, etc.) that the difference in equivalent weight within each pair was exactly 4; here, dumas’s weights for all these elements are half the modern values. he went on to point out that a similar relationship could be constructed for the halogens and pnictogens,27 except here the difference in equivalent weight between pairs was 5. dumas illustrated these relationships in a way that, in hindsight, clearly expresses the intergroup relationships of elements in the same period. for example, for the halogen and pnictogen elements, he wrote the atomic weights one below the other in two parallel rows: azote 14 phosphore 31 arsenic 75 antimoine 122 fluor 19 chlor 35.5 brome 80 iode 127 in 1859, the german chemist adolph strecker (1822-1871) published a small book entitled theorien und experimente zur bestimmung der atomgewichte der elemente [theories and experiments on the determina115a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 tion of atomic weights of the elements].28 strecker’s discussion of the numerical relationships among atomic weights occupies the last 10 pages of his book. much of this section consists of a critical analysis of dumas’s 1857 paper on this topic. but on page 145 strecker wrote, “if one doubles the atomic weight of the elements in the [carbon group], then the differences of each pair of atomic weights are all 22n except between carbon and silicon, where it is 16, i.e., approximately the same number that also is seen for nitrogen, fluorine, lithium and oxygen (if one doubles its atomic weight).” strecker’s statement is the first in the chemical literature that suggests the possibility of modifying the then-current atomic weights so as to create more regular numerical interrelationships with elements from other groups. this idea was to lie fallow until mendeleev resurrected it with great effect, most notably in 1870, when he multiplied cerium’s atomic weight of 92 by 1.5 so as place it in its proper location between barium and tantalum. mendeleev, who had brought strecker’s book with him when he returned from his study abroad in 18591861, credits the book with stimulating his interest in atomic weight relationships, an interest that led to his creation of his periodic system. years later, mendeleev wrote, “a. strecker, in his work theorien und experimente zur bestimmung der atomgewichte der elemente (braunschweig, 1859), after summarising the data relating to the subject, and pointing out the remarkable series of equivalents cr = 26.2, mn = 27.6, fe = 28, ni = 29, co = 30, cu = 31.7, zn = 32.5 remarks that: ‘it is hardly probable that all the above-mentioned relations between the atomic weights (or equivalents) of chemically analogous elements are merely accidental. we must, however, leave to the future the discovery of the law of the relations which appears in these figures.’”29 mendeleev’s great achievement was to do exactly that. another notable contribution in this area was made by the american chemist mathew carey lea (1823-1897). in his 1860 paper “on numerical relations existing between the equivalent numbers of elementary bodies,”30 (fig. 5), lea makes several remarkable observations: (1) the equivalent weights of elements with similar chemical properties often differ by 44 or 45; lea, however, fancifully finds additional pairs of elements related in this way by extending the algebra to negative equivalent weights, (2) the phenomenon of isomorphism is used to correct the equivalent weights of some elements, such as doubling copper’s atomic weight to 63.4 (the modern value), thus foreshadowing mendeleev, (3) the numerical regularities of equivalent weights are used to make some of the first predictions of the existence of undiscovered elements; lea predicts that an element of equivalent weight 164 should be intermediate between antimony and bismuth in the nitrogen group (although incorrect, mendeleev later made the same prediction), (5) the stoichiometries of recently discovered organometallic compounds, especially those of mercury and phosphorus, are employed to verify valence assignments and atomic weights, much as edward frankland (1825-1899) had done a few years earlier, and (6) correlations are sought between the equivalent weights and the atomic volumes of elements in the same group, thus foreshadowing lothar meyer’s (and mendeleev’s) work ten years later. the four papers by pettenkofer, gladstone, dumas, and lea are available to the collector as the journal article, with pettenkofer’s being the hardest to find. offprints are known only for the dumas and lea papers, which can be identified by the renumbering of the pages figure 5. one of two known copies of the offprint of carey lea’s 1860 paper “on numerical relations existing between the equivalent numbers of elementary bodies,” this particular copy was sent by lea to the american chemist franklin bache (1792-1864), greatgrandson of benjamin franklin. 116 gregory s. girolami beginning with page 1, and by the addition of a separate title page. both are scarce: slightly more than a dozen copies of the offprint of dumas’s paper are documented, and only two copies of the lea offprint can be traced. copies of strecker’s book are also scarce, and many years often separate the appearance of copies for sale. cannizzaro’s proposal of a single set of atomic weights (1858) before about 1860, all those who tried to find more universal relationships among the atomic weights of the elements (as opposed to relationships within individual triads) were handicapped by using equivalent weights that were sometimes true atomic weights and sometimes not; often, the equivalent weights in use in the 1850s and before differed from true atomic weights by a factor of two (and sometimes by other numbers such as 3 or 4 or 3/2). with such sets of equivalent weights, the construction of a periodic system that includes all (or even most) of the elements is essentially impossible. in 1858, the italian chemist stanislao cannizzaro (1826-1910) wrote two articles that played a decisive role in the formulation of modern atomic-molecular theory and the development of the periodic table. these two papers, which explained how he taught the atomic theory to his students at the university of genoa, covered both the fundamental concepts of the theory and how it could be used to determine which of the several existing (and incompatible) systems of atomic weights was physically most correct. cannizzaro’s ideas were not new, but instead he emphasized the value of combining the ideas of amedeo avogadro (1776-1856) and andrémarie ampère that equal volumes of gases contain equal numbers of particles, of pierre louis dulong (1785-1838) and alexis thérèse petit (1791-1820) on the constancy of the product of specific heat and equivalent weight (although cannizzaro does not mention their names), and the definitions of charles gerhardt (1816-1856) and marc antoine auguste gaudin (1804-1880) for the terms “atom” and “molecule.” one of these papers, “sunto di un corso di filosofia chimica [sketch of a course on chemical philosophy],”31 is well known to chemical historians: it was written in march 1858 and appeared in the may 1858 issue of the journal il nuovo cimento. the other paper, “lezioni sulla teoria atomica fatte nella r. università di genova [lessons on atomic theory given in the royal university of genoa],”32 (fig. 6), is almost unknown, but it is in fact the earlier of the two: it was published in the combined 15 march and 30 march 1858 issue of a genovese periodical, la liguria medica. as the earlier paper, it therefore is the form in which cannizzaro first introduced his ideas to the larger scientific community. cannizzaro’s description of the atomic theory in his lezioni article could be used essentially unchanged in modern textbooks: “examining the facts, we discover that there is limit to the division of the molecules of every simple body; … half a hydrogen molecule is the smallest quantity of this body that ever enters whole in the molecules of its compounds. we give to this smallest quantity the name of atom....” in addition to making the distinction between atoms and molecules fully clear, cannizzaro called attention in this paper to avogadro’s and ampère’s hypothesis and showed how one could use it to determine relative molecular (and atomic) weights from vapor densities. cannizzaro’s later sunto paper became far better known because copies of it were distributed at the 1860 karlsruhe congress, which was attended by many leaders and future leaders in the chemical profession. among those present were dmitri mendeleev and lothar meyer, both of whom were impressed by cannizfigure 6. one of five or six known copies of the offprint of cannizzaro’s 1858 paper “lezioni sulla teoria atomica. 117a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 zaro’s arguments and became converts to his views; both later cited cannizzaro’s work as a key enabler of their independent development of the periodic table in 1869. mendeleev wrote, “the decisive moment in the development of my theory of the periodic law was in 1860, at the conference of chemists in karlsruhe, in which i took part, and at which i heard the ideas of the italian chemist s. cannizzaro. i regard him as my immediate predecessor, because it was the atomic weights which he found, which gave me the necessary reference material for my work ”33 and lothar meyer commented, “i read [cannizzaro’s paper] again and again and was amazed at the clarity which that short treatise shed on the most important points of contention. scales fell from my eyes, doubts vanished, and the feeling of the most serene certainty took their place.”34 offprints of cannizzaro’s lezioni paper in la liguria medica exist but only about five or six are extant; these offprints are distinguishable from the periodical appearance by the repagination and renumbered signatures, by the absence of cannizzaro’s name in the reset title on the first page, and by the statement on the last page that the text was extracted from issues 5 and 6 of la liguria medica. the journal appearance is almost as scarce. cannizzaro’s sunto paper appeared in several different forms in the 19th century, including (i) the journal appearance in il nuovo cimento; (ii) an offprint from il nuovo cimento, which was distributed to the attendees at the karlsruhe conference in 1860. this 62 page pamphlet was printed in pisa and also contained the text of cannizzaro’s note on the condensation of vapor, which had appeared in the same issue of il nuovo cimento; (iii) an 1880 separate edition, in which the sunto paper was reprinted along with his “nota sulle condensazioni di vapore,” and with his 1858 lezione paper from la liguria medica. this 80 page pamphlet was printed in rome, possibly in commemoration of the 20th anniversary of the presentation of cannizzaro’s ideas at the karlsruhe conference; (iv) the 1896 book scritti intorno alla teoria molecolare ed atomica, which reprints the sunto, the nota, and the lezione papers, along with several other papers by cannizzaro on related topics. this 387 page text was printed in palermo to commemorate cannizzaro’s 70th birthday. two versions of this book are known, one with a frontispiece portrait of cannizzaro, and one without. the first three of these forms of cannizzaro’s paper are rare: the journal appearance can be found in libraries but is almost unknown in the book market, and fewer than 10 copies of the offprint and the 1880 separate are extant. only the 1896 book appears regularly for sale. béguyer de chancourtois’s telluric screw (1862-1863) the vis tellurique, or telluric screw, formulated in 1862 by the french geologist alexandre-émile béguyer de chancourtois (1820-1886), was an important precursor to the periodic table. in it, béguyer de chancourtois positioned the known chemical elements in order of increasing atomic weight on a slanted line wrapped around a cylinder, with 16 mass units per cylinder turn. when he did so, closely related elements lined up vertically. this regularity led him to state that “the properties of the elements are the properties of numbers.” he was the first to recognize that the properties of the elements, considered as an entire group and not just within individual triads, are periodic functions of their atomic weights. béguyer de chancourtois’s ideas were originally published in several parts35 in the comptes rendus in 1862 and 1863 but he was frustrated – and the impact of his ideas was blunted – because the journal refused to include a figure showing his helix. as a result, béguyer de chancourtois commissioned a combined offprint of his articles under the title vis tellurique. classement naturel des corps simples ou radicaux obtenu au moyen d’un système de classification hélicoïdal et numérique. [the telluric screw. natural grouping of simple bodies or radicals by means of a helical and numeric system of classification].36 the combined offprint was distributed with a privately-commissioned printing of the diagram of his helix; it is perhaps not too surprising that the journal did not print the diagram – printed in red, green, and black – because it is 1.45 meters long (fig. 7). the offprint of vis tellurique evidently was issued in at least two editions. the first edition, dating from 1862, was issued in paper wrappers and there is no mention of plates on the title page. a later (second) edition, probably dating from 1863, was issued in printed boards; the subtitle on the title page calls for two plates, the first being described as “tableau chromolithographié des caractères des corps [chromolithographed table of the characters of bodies]” and the second as “une seconde planche muette, du développement du cylindre disposée pour l’étude et l’extension du système [a second wordless illustration of the development of the cylinder arranged for the study and extension of the system].” the chromolithographed diagram of his telluric helix is always designated as “première esquisse” but there are at least three printings, the first dated 7 avril 1862 and the third dated 16 mars 1863. i do not know of a copy of the second printing. as far as i am aware, only four copies of the offprint of vis tellurique have been offered for sale in the last 118 gregory s. girolami 50+ years, and only about 10 copies of the offprint are documented in institutional libraries. the journal issues of the comptes rendus containing béguyer de chancourtois’s articles are more readily available, but these lack the all-important diagram. meyer’s first periodic table (1864) a significant advance is seen in the first edition of the book by the german chemist julius lothar meyer (1830-1895), die modernen theorien der chemie und ihre bedeutung für die chemische statik. [the modern theories of chemistry and their meaning for chemical statics],37 written beginning in 1862 and published in 1864. near the end of his book, meyer included a tabular arrangement of 28 elements, ordered by increasing atomic weight (except for the te/i inversion). this table (fig. 8) depicted the periodic relationships of the elements far more effectively than did béguyer de chancourtois’s telluric screw. meyer’s table, which arranged the then-known main group elements into six families, contained three important features, although none of these was explicitly discussed in the text: first, the table clearly shows that the valencies of the elements are correlated with atomic weight: the valency decreases from 4 to 3 to 2 to 1 when moving from the carbon group elements (which are at the left of his table) through the pnictogens and chalcogens to the halogens, and then the valency increases from 1 to 2 upon continuing from the alkali metals to the alkaline earths (which are at the right side). thus, meyer’s table implies that there are regular relationships between different groups of elements. a second important feature that is not explicitly discussed in his accompanying text is that the table includes gaps to denote presumably unknown elements. third, the table also contains information about the differences in the atomic weights between elements in the same group but different periods. the differences seen between elements in the first and second row, and between the second and third row, are all about 16, whereas the difference seen for elements in the third and fourth row, and fourth and fifth row, are all between 44 and 49. one of the gaps in the table is below silicon (atomic weight of 28.5) and above tin (117.6), corresponding to the then-unknown element germanium. meyer’s table implies (but does not state) that the atomic weight of this missing element should be about 44.55 larger than that of silicon, and about 44.55 smaller than that of tin. in addition to the table of main group elements, meyer presented two additional tables on the following page, the first showing intergroup relationships between six “early” transition metals, and the second showing intergroup relationships among sixteen “late” transition metals (speaking anachronistically). as for the main figure 7. one of about a dozen known copies of the table accompanying the offprint of béguyer de chancourtois’s 1862 paper vis tellurique. this figure shows only the upper 25 cm of the 145 cm long chart. this particular copy of the chart is the one that was owned by the italian chemist stanislao cannizzaro figure 8. mayer’s periodic table from his 1864 book die modernen theorien der chemie und ihre bedeutung für die chemische statik. 119a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 group elements, the tables illustrate trends in the valencies (oxidation states) across the groups. meyer’s transition metal triads are somewhat jumbled with respect to the modern placings, but he accurately put zn, cd, and hg into one triad, and cu, ag, and au into another, thus becoming the first to incorporate these triads into a general classification scheme of the elements. meyer’s book was issued in a very small edition and, as a result, it has long been a rarity in the rare book market. many well-known private collections of science or chemistry books did not include a copy. my investigations suggest that fewer than a half dozen copies have been sold at auction or by rare book dealers in the last 70 years. newlands’s law of octaves (1864-1866) in july 1864 the chemist john alexander reina newlands (1837-1898), born in london but the son of a scottish father and an italian mother, devised a table of 37 of the then-known elements, arranged (mostly) by increasing atomic weight and grouped into ten families. this paper, “relations between equivalents,” was one of a series of papers on his ideas about the relationships of the chemical elements that newlands submitted to the journal chemical news.38 in newland’s 1864 table, the main group elements are arranged exactly as in the modern table except that he is uncertain of the place of lithium, and (not too surprisingly given the stabilities of their lower oxidation states) thallium and lead are placed in the alkali metal and alkaline earth groups, respectively. eight transition elements are included in the table, and several of them are not placed as one would today: osmium is in the oxygen group, gold is in the boron group, zinc and cadmium are grouped with magnesium, and mo-v-w and pd-pt are placed in their own groups. newlands’s 1864 table leaves gaps in several places, such as those later to be occupied by gallium and germanium. although he does not discuss these gaps explicitly, he states “so frequently are relations to be met with among the equivalents of allied elements, that we may almost predict that the next equivalent determined, that of indium, for instance [which had been recently discovered], will be found to bear a simple relation to those of the group to which it will be assigned.” in 1865, newlands published a follow-up paper, “on the law of octaves,” and in 1866 he gave a talk at a meeting of the chemical society that was also abstracted in chemical news.38 in the 1865 paper, he wrote “if the elements are arranged in the order of their equivalents, with a few slight transpositions, as in the accompanying table, it will be observed that elements belonging to the same group usually appear in the same horizontal line. it will also be seen that the numbers of analogous elements generally differ either by 7 or by some multiple of seven; in other words, members of the same group stand to each other in the same relation as the extremities of one or more octaves of music.… this peculiar relationship i propose to provisionally call ‘the law of octaves.’” here, “the numbers of the analogous elements” are not atomic weights but rather the ordinal number that the element has in his sequence, i.e., akin to (but not) an atomic number. in his effort to find more regularity in the properties and interrelationships of the elements than he had been able to find in 1864, newlands forced the elements into seven families, eliminated the gaps from his previous table, and sometimes placed two elements in a single place; the net result is a distinct backward step. in the discussion after newlands’s 1866 talk, john h. gladstone – whose own contributions to this area are mentioned above – objected to the new table (quite appropriately, as later events showed) because it assumed that no elements remained to be discovered. offprints of articles from chemical news from this period do exist, but are unknown for newland’s papers and it is probable that they were never printed. newlands’s original papers in chemical news are readily available as the bound volumes for those years, however, often as library discards. in 1884, fifteen years after mendeleev announced his periodic system, newlands issued a collected reprinting of his articles from the chemical news as the book on the discovery of the periodic law, and on relations among the atomic weights.39 normally, presentation copies of books, i.e., those bearing a signed inscription from the author, are prized because so few exist, but newlands sent signed copies to a very large number of chemists and institutions. today, signed copies are frequently seen on the rare book market; unsigned copies are actually not as common. odling’s table of the elements (1864) in october 1864, the english chemist william odling (1829-1921) published a remarkable paper “on the proportional numbers of the elements,”40 which contained an important precursor to the periodic table. in this paper, odling succeeded in arranging 57 elements into a table that looks very much like mendeleev’s first periodic table of 1869 (fig. 9). odling stated in his article, “upon arranging the atomic weights or 120 gregory s. girolami proportional numbers of the sixty or so recognized elements in order of their several magnitudes, we observe a marked continuity in the resulting arithmetical series…. with what ease this purely arithmetical seriation may be made to accord with a horizontal arrangement of the elements according to their usually received groupings is shown in the following table, in the first three columns of which the numerical sequence is perfect, while in the other two the irregularities are but few and trivial.” odling’s table places the main group elements in the center, and the transition elements above and below them. odling, like meyer and newlands, independently introduced the inversion of the elements tellurium (129) and iodine (127) in order to associate these elements with their chemical relatives. the main group elements are arranged in groups that correspond exactly to the modern groups of elements; the relationships among the transition elements were more difficult to untangle, as they were to be even for mendeleev. odling noted that many pairs of chemically related elements have atomic weight differences that lie between 84.5 and 97 and that, of these pairs, about half are the first and third members of known triads. he added that, “the discovery of intermediate elements in the case of some or all of the other pairs is not altogether improbable.” it cannot be said that these predictions are based on a periodic law; instead, they are predictions based on individual incomplete triads. most of these predictions, however, didn’t pan out because most of the pairs odling cited had atomic weight differences that (as we now know) are affected by the interposition of the thenunrecognized lanthanide series of elements. odling incorporated a modified version of his table in the second (1865) edition of his book, a course of practical chemistry arranged for the use of medical students. a course of practical chemistry arranged for the use of medical students.41 starting on page 226 of that book, after the end of the text, are a series of appended tables. in the first of these, entitled “atomic weights and symbols,” 45 elements are arranged much as they are in the modern periodic table, with gaps for nine elements indicated by dashes. three of the gaps stem from not placing copper, silver, and gold into a triad, and another from not placing chromium, molybdenum, and tungsten together; it is interesting to note that odling had correctly placed silver and gold together, and chromium and molybdenum together, in his 1864 table. the remaining four gaps correspond to elements that had not yet been discovered: gallium, germanium, technetium, and indium. unfortunately, odling nowhere discusses this table in the text, nor does he comment on the gaps. mendeleev’s first paper on his periodic system42 included a footnote stating that, after his paper had been submitted, he had been informed that a very similar table of elements had appeared in odling’s practical chemistry. mendeleev emphasized that he had not been aware of odling’s table before this time. no offprints of odling’s 1864 paper are recorded, but it is available as the bound journal volume. the 1865 edition of odling’s practical chemistry is remarkably scarce and rarely appears for sale; the other editions (1854, 1869, 1876) seem to be more common but none contains odling’s table. hinrichs’s program of atomechanics (1867) the last of the contributions to the development of the periodic table that we will discuss in the present article were made by the chemist gustavus detlef hinrichs (1836-1923); hinrichs had been born in holstein, then part of denmark but now part of germany, but had immigrated to the united states in 1861. in 1867, he privately published a lithographed reproduction of a 44 page hand-written treatise, entitled figure 9. odling’s periodic table from his 1864 article “on the proportional numbers of the elements.” 121a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 programme der atomechanik, oder die chemie eine mechanik der panatome [program of atom mechanics, or chemistry a mechanics of panatoms].43 he also wrote an abstract in french and a 4 page abstract in english, the latter submitted in august 1867 to the american journal of mining.44 hinrichs, like many of those mentioned above, was passionately devoted to the challenge of finding deep meaning in the atomic weights of the elements (and other phenomena, such as the orbital radii of the moons of the outer planets and the wavelengths of the dark lines in the solar spectrum). he proposed that there was a unit of matter, which he called a panatom, which had an atomic weight equal to half of that of hydrogen. he further proposed that there were two kinds of atoms, which he called trigonoids and tetragonids; the former had inner structures consisting of stacks of trigonal/hexagonal arrays of panatoms, whereas the latter had inner structures consisting of stacks of square arrays of panatoms. his attempts to shoehorn the elements into these two classes are replete with ad hoc assumptions to account for the deviations of the atomic weights from the numbers that one would expect from such stacks. after presenting this proposal for atomic structure in his programme der atomechanik, hinrichs then proposed a spiral classification scheme for the elements in which those with larger atomic weights appear at larger distances from the center of the spiral (fig. 10). his scheme captures some of the intergroup relationships that are present in the modern periodic table, but there are many oddities. most notably, the nitrogen group elements are placed between the chalcogen and halogen groups. the transition elements are again mostly jumbled, although hinrichs (like lothar meyer before him) grouped copper, silver, and gold together. two years later, hinrichs published a revision of his classification system in two papers, one presented in august 1869 to the 18th annual meeting of the american association for the advancement of science, “on the classification and the atomic weights of the socalled chemical elements, with reference to stas’ determinations,”45 and the other the same summer to the journal the pharmacist, “natural classification of the elements”.46 in these two papers, the nitrogen group is now in its modern place relative to (i.e., between) the oxygen and chlorine groups. but other oddities are introduced; for example, the transition elements are listed in reverse order of their atomic weights. hinrichs’s tables of 1869 contain numerous gaps, but he gives no indication that the gaps are significant. hinrichs’s 1869 table is tabular instead of spiral: the elements within a period being listed in a vertical column, and elements within a group being arranged in rows from left to right. of all the early attempts to arrange the elements in tabular form, only odling’s table of 1864 and mendeleev’s first table of 1869 are arranged in this way. hinrichs clearly recognized the periodic interrelationships that are brought out by his tables: “[i]n this table the elements of like properties, or their compounds of like properties, form groups bounded by simple lines. thus a line drawn through c, as, te, separates the elements having metallic lustre from those not having such lustre. the gaseous elements form a small group by themselves,… so also the … heavy metals (specific gravity above five).… of great practical importance are the lines expressing certain properties of definite compounds [such as] solubilities … reactions in the wet way [and] blowpipe reactions….” to my knowledge, no copies of hinrichs’s 1867 programme der atomechanik have been available for purchase on the rare book market in the last 50 years. the american academy for the advancement of science printed a proceedings volume that contained the text of all the papers (including hinrichs’s) presented at their 1869 meeting; copies of this volume can occasionally be found for sale. hinrichs also reprinted this paper (using the same setting of type) as paper no. 4 of his contributions to molecular science, or atomechanics.47 i have not seen an original copy of this reprint available for sale in recent decades. figure 10. hinrichs’s spiral periodic table from his 1867 book programme der atomechanik. image reproduced with permission of the university of dresden. 122 gregory s. girolami concluding remarks with the contributions of hinrichs, the stage was set for the entrance of mendeleev into the story in 1869: in that year, mendeleev circulated a privately-printed periodic table and also published it in both a journal article42 and a textbook, osnovy khimii.48 it is important to point out, however, that the discussion above lists only some of the principal documents that led more or less directly to the concept of the periodic law. many other contributions, which either were important but peripheral or were later recognized as blind alleys, have been omitted for the sake of brevity. but this brevity necessarily paints a distorted picture of how this important and fascinating area of science actually developed. many of the books and papers mentioned above are quite rare: for some, fewer than a dozen copies exist, but others are more common and appear regularly for sale at auction or by rare book dealers. acquiring all of these foundational documents in a collection devoted to the history of the periodic table, in the original editions, would be a challenging but enjoyable pursuit. holding these documents in one’s hands conveys a real sense of connection with the great scientists of the past. this sense is especially keen if the pamphlet or book bears a handwritten inscription from the author, such as the copy of dalton’s new system shown in figure 3. such special copies, known as presentation copies among collectors, are very hard to find and are considerably more interesting (and valuable) than ordinary copies. in addition, the documents often contain the signatures of one or more former owners. although sometimes the previous owners are well known scientists, more often they are not. tracking down their identities can be a challenging puzzle that calls upon skills and methods similar to those employed when tracing family genealogies. as is true of all collecting hobbies, the hunt for and capture of suitable items to acquire is an endeavor of continual pleasure. the process affords opportunities to meet dealers and other collectors who share similar interests, and can result in long-lasting friendships. rare book dealers are often scholars themselves who not infrequently add to our understanding of history. without their unflagging passion to locate great books and find good homes for them, both private and public libraries would be much the poorer. but even if forming a collection is not one’s primary goal, these documents remain of great interest, and they can be viewed in person at major institutional libraries.49 by consulting them in their original forms, much can be learned about key parts of the path that led to the creation of the periodic law and its iconic table, one of the triumphs of modern science. acknowledgments i thank the william and janet lycan fund of the university of illinois for support, and vera mainz and an anonymous reviewer for valuable comments. references 1. f. p. venable, the development of the periodic law, chemical publishing co., easton, pa, 1896. 2. j. w. van spronsen, the periodic system of chemical elements, elsevier, amsterdam, 1969. 3. e. r. scerri, the periodic table, its story and significance, oxford university press, oxford, 2006. 4. m. d. gordin, a well-ordered thing: dmitrii mendeleev and the shadow of the periodic table, basic books, new york, 2004. revised edition, princeton university press: princeton, 2018. 5. m. kaji, h. kragh, g. palló, early responses to the periodic system, oxford university press, oxford, 2015. 6. r. boyle, the sceptical chymist: or chymico-physical doubts and paradoxes, printed for j. crooke, london, 1661. 7. j. f. fulton, bibliography of the honourable robert boyle, clarendon press, oxford, 1961. 8. de morveau, lavoisier, bertholet, de fourcroy, méthode de nomenclature chimique, chez cuchet, paris, 1787. 9. l.-b. guyton de morveau, obs. phys. l’hist. nat. arts 1782, 370-382. 10. d. i. duveen, h. s. klickstein, a bibliography of the works of antoine laurent lavoisier, 1743-1794, william dawson and sons, london, 1954. 11. a. l. lavoisier, traité élémentaire de chimie, présenté dans un ordre nouveau et d’après les découvertes modernes, chez cuchet, paris, 1789. 12. d. duveen, isis 1950, 41, 168-171. 13. e. weil, the library 1953, 8, 59-61. 14. j. dalton, mem. lit. phil. soc. manchester 1805, 1, 271-287. reprinted in phil. mag. 1806, 24, 14-24. 15. typically, an author would receive perhaps 50 copies of an offprint; of those, very few (and sometimes none) find their way to the rare book market. to many collectors, however, offprints are more desirable than the full printed journal in which the article appears for several reasons: unless the journal distributed them 123a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 directly, the offprints necessarily went through the author’s hands, they often bear presentation inscriptions, and they sometimes were printed days to years before the journal issue appeared, so that the offprint was often the form in which a scientific result was first made available to the world. owing to their direct physical connection with the author and their scarcity, offprints of significant articles (such as those discussed here) can be quite valuable. 16. j. dalton, a new system of chemical philosophy, manchester: s. russell for r. bickerstaff, london, 1808 (vol. i, part 1); manchester: russell and allen for r. bickerstaff, london, 1810 (vol. i, part 2); manchester: the executors of s. russell for george wilson, london, 1827 (vol. ii, part 1; all published). 17. a.-m. ampère, ann. chim. phys. 1816, 1, 295-308 and 373-394. 18. é. f. geoffroy, hist. l’acad. roy. sci. 1718, 202-212. 19. j. pelouze, e. frémy, traité de chimie générale, 3rd ed, vol. 2., victor masson et fils, paris, 1865, p. 4. 20. [j. w. dobereiner], ann. phys. 1817, 56, 331-334. several sources claim incorrectly that döbereiner published his ideas on triads in 1817, citing his paper in ann. phys. 1817, 57, 435-438, but this latter paper is on a completely different topic. 21. j. w. dobereiner, ann. phys. chem. 1829, 15, 301307. 22. l. gmelin, handbuch der chemie, universitäts-buchhandlung von karl winter, heidelberg, 1843-1866. 8 volumes in 9 (vol 7 in two parts); two supplementary volumes were issued later. gmelin’s körpernetze appears on p. 457 of volume 1. 23. j. p. cooke, am. j. sci. 1855, 17, 387-407. cooke’s paper was also printed in the mem. am. acad. arts sci. 1855, 5, 235-257 and 412. 24. m. pettenkofer, gelehrten anzeigen (münchen) 1850, 30, 261-272. pettenkofer reprinted his 1850 article in annalen der chemie 1858, 105, 187-202. 25. j. h. gladstone, phil. mag. 1853, 5, 313-320. 26. j. b. dumas, compt. rend. l’acad. sci. 1857, 45, 709731; 1858, 46, 951-953; 47, 1026-1034. 27. for convenience, i use here a modern term for the nitrogen group. see g. s. girolami, j. chem. educ. 2009, 86, 1200-1201. 28. a. strecker, theorien und experimente zur bestimmung der atomgewichte der elemente, f. vieweg und sohn, braunschweig, 1859. 29. d. i. mendeleev, j. chem. soc. 1889, 55, 634-656. 30. m. c. lea, am. j. sci. arts 1860, 29, 98-111. 31. s. cannizzaro, il nuovo cimento 1858, 7, 321-366. 32. s. cannizzaro, la liguria medica, giornale di scienze mediche e naturali 1858, 3, 113-142. 33. n. a. figurovskii, dmitrii ivanovich mendeleev, 18341907, 2nd ed., izdatel’stvo akademii nauk sssr, moscow, 1961, pp. 44-51. the quotation also appears in h. hartley, studies in the history of chemistry, clarendon press: oxford, 1971, p. 85. 34. [s. cannizzaro], abriss eines lehrganges der theoretischen chemie: vorgetragen an der k. universität genua, j. l. meyer, ed., verlag engelmann, leipzig, 1891. ostwald’s klassiker nr. 90. 35. a. e. chancourtois, compt. rend. l’acad. sci. 1862, 54, 757-761, 840-843, 967-971; 1863, 55, 600-601; 56, 479-482. 36. a.-e. beguyer de chancourtois, vis tellurique. classement naturel des corps simples ou radicaux obtenu au moyen d’un système de classification hélicoïdal et numérique, mallet-bachelier, paris, 1863. 37. j. l. meyer, die modernen theorien der chemie und ihre bedeutung für die chemische statik, maruschke & berendt, breslau, 1864. 38. j. a. r. newlands, chem. news. 1864, 10, 59-60; 94-95; 1865, 12, 83; 1866, 13, 113. 39. j. a. r. newlands, on the discovery of the periodic law, and on relations among the atomic weights, e. & f. n. spon, london, 1884. 40. w. odling, quart. j. sci. 1864, 1, 642-648. 41. w. odling, a course of practical chemistry arranged for the use of medical students, 2nd ed., longmans, green, and co., london, 1865. 42. d. i. mendeleev, zh. russ. khim. obshch. 1869, 1, 59-78. 43. g. hinrichs, programme der atomechanik oder die chemie eine mechanik der panatome, privately printed, iowa city, ia, 1867. 44. g. hinrichs, am. j. mining 1867, 4, 66, 82, 98, 114, and 116. this paper was also issued as an offprint, of which very few copies survive. 45. g. hinrichs, in proceedings of the american association for the advancement of science: eighteenth meeting, held in salem, massachusetts in august, 1869, joseph lovering, cambridge, ma, 1870, pp. 112-124. 46. g. hinrichs, the pharmacist (chicago college of pharmacy) 1869, 2, 10-12. 47. g. hinrichs, contributions to molecular science, or atomechanics, nos. 3, 4, essex institute press, salem, ma, 1870. 48. d. i. mendeleev, osnovy khimii [principles of chemistry], tovarishchestvo ‘obshchestvennaia pol’za’ for the author, st. petersburg, 1869. 49. of course, many of these documents can also be viewed as electronic copies online. in my experience, online copies often leave much to be desired; foldout plates or tables are often imaged only in their 124 gregory s. girolami folded form, and it can be very difficult to locate an electronic copy in which such plates can be viewed in full. google books has a large number of ebooks in their database, as do the hathitrust mobile digital library (https://www.hathitrust.org), the internet archive (http://www.archive.org/details/texts), and gallica, the digital library of the bibliothèque nationale de france (https://gallica.bnf.fr). other resources for electronic copies can be found at https://guides. library.harvard.edu/history/digital. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna sub-covid-805 1 citation: s. cinti (2020) covid-19: physical distancing will make science closer to citizen participation in decision making. substantia 4(1) suppl. 1: 900. doi: 10.13128/substantia-900 received: apr 07, 2020 revised: apr 08, 2020 just accepted online: apr 08, 2020 published: apr 09, 2020 copyright: © 2020 s. cinti. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia editorial covid-19: physical distancing will make science closer to citizen participation in decision making stefano cinti department of pharmacy, university of naples federico ii, via d. montesano 49, 80131 naples, italy dissemination of chemical culture interdivisional group of the italian chemical society email: stefano.cinti@unina.it nowadays, social distancing is mandatory in various countries worldwide. it is defined as a non-pharmaceutical intervention for preventing the spread of covid19, by maintaining a distance among people and reducing the frequency of contacts with each other. however, the correct definition, as reported somewhere, should be physical distancing. populations are “socially” close, citizens are experimenting novel approaches of communication, and novel way to help. of course, in the era of social networks, everybody is enabled to get in touch, even with people that have been missing for a while. the velocity of how life goes, the necessity of getting results, the demonstration of one’s own value and the invention of brand-new strategies to overcome the generic “everyday” issues, covering all the fields such as family, job, friends, etc., are facing with a pandemic monster. unfortunately, this is the situation in the presence of a widespread virus and in the absence of a vaccine. despite all the victims that have been counted, daily, the present emergency is teaching more than something to humankind, in all sectors. companies are trialing a forced smart-working: perhaps it will be partially consolidated when we will be “physically closer” after pandemic? schools and universities are facing the impossibilities to have students in classrooms. however, academy is exploiting e-learning approaches to make teaching possible. even final dissertation has being achieved by online graduation sessions. although the “in presence” teaching is and will continue to be the favorite way of exchange, by both students and professors, future students should not feel a prejudice towards the euniversities when choosing their growth path. again, people are being emotionally closer than before: plenty of charity actions, mainly directed to hospitals, are highlighting the tremendous social participation in opposing the emergency. being part of the scientific community, the pandemic should convince how life without vaccines look likes. hopefully, people far from science and scientific routes, should look at science from a diverse perspective, perhaps being suspicious from politicians’ slogan within scientific affairs, sometimes inaccurate and just (scientifically) erroneous: everyone, now, on her/his skin, knows that health is very fragile in such conditions. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 900, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-900 stefano cinti 2 looking at the various newscasts, listening to the radio and reading the newspapers, the presence and the authority of scientists are fundamental. the politicians’ decision to tackle this emergency are always taken following the “experts” recommendations. science has been often far from society, far from decisions, for long times. hopefully, life after pandemic will increase the sociality of science within life of lay audience. today, people are molecularly powerless against the sars-cov-2 spreading: the perception of how science represents the unique shield and the huge hope for vaccine development, represent common thoughts. it represents the past, present and future of humankind existence. moreover, tremendous limitations are encountered in low-resource countries, where the uneven distribution of care centers, the scarcity of specialists and financial restrictions do not allow for early diagnosis and/or improved access to monitoring and treatment. on the side of vaccine research and development, there is diagnostic. this is another very important character science is adopting. from the chemistry point of view, several approaches for creating easy to use and rapid diagnostic devices, at the point of care, have being developed and highlighted. the most sold market examples of glucose strips diabetes and pregnancy tests represent a solid concept of decentralized monitoring, thus physical distant. the use of such technologies, that allows non-specialists to take clinical decisions, is something recurrent in the present period and source of inspiration. point of care devices have been always associated to features like user-friendly, fast response, sensitive, specific and disposable. these keywords well fit with the current emergency. the pandemic is highlighting the role of researchers working in the field of analytical chemistry as extremely important. the necessity in developing portable devices, that avoid patients going to physicians or into hospitals, requiring very low amount of biological fluids, is the current challenge. it should be noted how governments are providing “non-ordinary” funds for this hot-topic research. however, to go beyond the state of the art, for providing advances in the diagnostic field, all the research branches cannot be distant: science progress needs to be exchanged in the vanguard of all the disciplines, merging chemistry, biology, biotechnology, physics, mathematics, engineering, telemedicine, etc. when the pandemic will be beaten, the take home message to all the populations and institutions will make scientific efforts shining again. it should be clear to everyone that science is fundamental to live towards progress and wellness: hopefully, the calamity we are living today will be the breakpoint towards the challenges of tomorrow, like environmental pollution, climate change and sustainability vision. substantia. an international journal of the history of chemistry 3(2) suppl. 5: 139-142, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-195 citation: m. v. orna (2019) mendeleev at home. substantia 3(2) suppl. 5: 139-142. doi: 10.13128/substantia-195 copyright: © 2019 m. v. orna. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. mendeleev at home1 mary virginia orna chemsource, inc., 39 willow drive, new rochelle, new york, usa e-mail: maryvirginiaorna@gmail.com abstract. dmitri mendeleev was “at home” at the st. petersburg state university for forty years. the museum set up in his former place of work/living quarters is well worth a visit. keywords. mendeleev museum, mendeleev archives, personal effects, memorabilia, laboratory equipment. introduction situated along the banks of the neva river is st. petersburg state university, just a short walk over the dvortsovyy bridge from the hermitage museum. founded in 1724 by decree of czar peter the great, the university still occupies the massive building designated by peter as the “twelve colleges.” and it is here, on the street now called mendeleevskaya liniya, that the mendeleev museum and archives (figure 1) is located. this remarkable museum was originally the apartment designated for the university’s professor of chemistry and laboratory curator. in that capacity, dmitri mendeleev (1834–1907) lived here with his wife, anna popovamendeleeva, during his professorial tenure from 1866 to 1890. it was here that he wrote many of his scientific papers.2 after his death in 1907 the university and the russian chemical society purchased his personal library, archives, and some furniture from his widow. these effects formed the basis of the museum that was established there only four years later in 1911. 1 this essay is reprinted (with added photographs and references) with the kind permission of the science history institute, philadelphia, pa, usa. https://www.sciencehistory.org/distillations/magazine/mendeleev-at-home, last accessed 12 march 2019. 2 mendeleev was never elected to the russian academy of sciences, which would have supplied the living quarters, research facilities, etc. for life. although he was, admittedly, the most famous russian scientist both at home and abroad, his nomination was turned down by the so-called “german party,” which, in 1881, elected friedrich konrad beilstein (1838-1906) instead. in response, the russian chemical society, of which mendeleev was one of the founders, drew up a statement that said, in part: “the indisputable value of the services of this candidate, whose equal cannot be found in russian science, and his reputation abroad, make his rejection entirely incomprehensible.” h. m. leicester, j. chem. educ. 1948, 25, 439. 140 mary virginia orna central attractions the central attractions of the museum are the three rooms that were originally mendeleev’s living room, dining room, and study. the first room contains memorabilia associated with his childhood and youth, as well as photographs of family members, artists, scientists, architects, and close colleagues who gathered for socializing and conversation each wednesday evening. (as a chemist, mendeleev acted as an adviser to artists and 3 translation courtesy of david lewis, university of wisconsin, eau claire, wi, usa architects on the composition of pigments and of building materials.) the second room, which in mendeleev’s lifetime served as a dining room, is devoted to recording mendeleev’s life before he came to st. petersburg university, including his study at the main pedagogical institute in st. petersburg from 1850 to 1855 and his work trip to heidelberg from 1859 to 1861. also recorded in the second room is his discovery of the periodic law in 1869. here the visitor can view his stand-up desk (he was a very tall man for the times) and some of his monographs on a variety of subjects, such as mineralogy, isomorphism, and specific volume. these monographs reflect mendeleev’s early interest in connecting internal properties to external form. there are also some examples from his mineral collection and the wooden models of crystalline forms that he constructed himself. the third, and most evocative room, is mendeleev’s reconstructed study, where everything remains as it was during the last years of his life. here one can see, among other items, a group of photographs of mendeleev with the discoverers of some of his “eka-elements” (elements whose future discovery mendeleev predicted in 1869): lars fredrik nilson (1840-1899), who discovered scandium in 1879;4 paul-émile lecoq de boisbaudran (18381912), who discovered gallium in 1875;5 and clemens winkler (1838-1904), who discovered germanium in 1886.6 mendeleev’s major contributions to chemistry the museum also conserves mendeleev’s personal archives. this famous collection has as its base a cataloging system developed by mendeleev himself and consists of over 35,000 titles, encompassing manuscripts, draft 4 nilson, l. c. r. chim. 1879, 88, 642. 5 p.-é. lecoq de boisbaudran, c. r. chim. 1875, 81, 493. 6 winkler, c., j. prakt. chem. 1887, 36, 177. figure 1. plaque at the entrance of the mendeleev museum and archives. courtesy of jan and mary kochansky. it reads: “here the great russian chemist dmitrii ivanovich mendeleev taught, worked and lived from 1850-1890.”3 figure 2. mendeleev photographs and memorabilia. photograph courtesy of roger rea. 141mendeleev at home documents, letters, telegrams, diaries, notebooks, laboratory registers, expenditure accounts, and correspondence with russian and foreign scientists. in addition, over 200 scientific instruments, many of them built specifically for mendeleev, are housed here. there is also a world map that shows all the places mendeleev visited (including northwestern pennsylvania) as part of his scientific travels. although mendeleev is best remembered for his discovery of the periodic law, his other major achievements were authorship of a major textbook, principles of figure 3. a russian periodic table showing elements 104 and 105 as kurchatovium and nielsbohrium respectively. courtesy of mary and jan kochansky. figure 4. mendeleev’s study. photograph courtesy of margaret comaskey. figure 5. mendeleev’s apparatus for measuring gas densities. photograph courtesy roger rea. 142 mary virginia orna chemistry (which included the periodic law), his studies on the elasticity of gases, and his studies of solutions as associations, to say nothing of his far-ranging eclectic interests in a variety of other fields. a visit to this museum evokes an appreciation for all of his interests in one small space. if the mendeleev aficionado’s curiosity has not been satisfied with this museum chock-full of memorabilia, a short subway ride to the technological institute (via line 1 or line 2) will bring him or her face to face with the famous cigar-smoking mendeleev statue at the foot of the giant periodic table built into the wall of one of the university buildings. from the viewpoint of this explorer, it is well worth the journey. 7 mendeleev’s “principles of chemistry.” https://archive.org/details/principlesofchem00menduoft/page/n4 , last accessed 21/03/2019. figure 6. title page of a 1901 american reprinting of the the english edition of mendeleev’s “principles of chemistry.”7 figure 7. mendeleev monument (ilya ginzburg, 1930). on the wall behind is the famous giant version of the periodic table. the building is the former bureau of weights and measures where mendeleev was director. it now houses the mendeleev all-russian institute of meteorological research. photograph: mary virginia orna. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna substantia. an international journal of the history of chemistry 3(2) suppl. 1: 83-97, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-277 citation: h. d. wallace, jr. (2019) fuel cells: a challenging history. substantia 3(2) suppl. 1: 83-97. doi: 10.13128/substantia-277 copyright: © 2019 h. d. wallace, jr. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. fuel cells: a challenging history harold d. wallace, jr. national museum of american history, room 5128, mrc 631, 12th st. & constitution ave., nw washington, dc 20013-0631 e-mail: wallaceh@si.edu abstract. professional and popular journals present fuel cells as the salvation of transportation and electric power infrastructures; the ultimate rechargeable battery. engineers and investors alike find them attractive as a modern and elegant alternative to other electrical generators. on three occasions since w. r. grove’s initial research around 1840, widespread adoption of fuel cells seemed imminent. each time, technical challenges in materials and systems integration, along with advances in other electrical technologies frustrated advocates’ hopes. despite successful development of several different types, commercialization remains limited to niche applications. after 180 years fuel cells remain outside the mainstream of power generation technology. this paper presents an overview of that history. the author discusses basic challenges that have faced developers, and suggests how present research may benefit from past experience. keywords. fuel cells, gas batteries, electrochemical technology. ...we concluded that the economical production of powerful currents for commercial purposes ... did not seem to be a problem likely to be readily solved.... —charles r. alder wright and charles thompson, 1889.1 introduction fuel cells have captivated and frustrated researchers and investors since 1839. a device that quietly combines hydrogen and oxygen to produce electricity and water would solve many problems in a world dependent on electric power. scientists spent decades learning how fuel cells generate electricity, and engineers built them into submarines, automobiles, a farm tractor, and other devices. humans traveled to the moon with fuel cells. yet after 180 years of work, wright and thompson’s conclusion remains valid. significant commercial adoption remains elusive due to high costs, intractable technical difficulties, and competition from other technologies. the seeming simplicity and potential benefits of fuel cells nurtures optimism rarely deterred by persistent obstacles.2 in the 1890s, the 1960s, and around 2000, technical journals and the popular press described fuel 84 harold d. wallace, jr.84 harold d. wallace, jr. cells as nearing commercial viability.3 on each occasion, development faltered and significant diffusion failed to occur. encouraging test results and occasional high-profile successes obscured vital facts: fuel cells come in non-interchangeable types that must function within larger technical and economic systems. today, a few are in low-rate production for automotive engines and stationary power. though prototypes proliferate, fuel cells remain niche products. perceived technical elegance does not convey success in the laboratory or in the marketplace. rather than a triumphal march from discovery to market, fuel cell history provides a sobering counter to progressive views of technology development. after a technical review, this article discusses four distinct periods of fuel cell work. examining the past brings perspective to current events by highlighting recurring factors that hindered adoption. the situation of fuel cells as components in technological systems—requiring other devices in order to operate, while meshing with existing infrastructures—served as one factor.4 another is the influence of public and professional perceptions on expectations, including the persistent myth that fuel cells are simple devices on the verge of mass production. the article also presents important differences in sociallydependent contexts, such as differing economic and technical circumstances of each period, so as to avoid the fallacy of cyclical history. setting the recurring factors in their changing contexts helps explain why fuel cells continue to fascinate despite many disappointments.5 an elegant technology engineers often refer to an especially efficient process or device as elegant. from the beginning, many admirers declared fuel cells (originally called gas batteries) elegant.6 like batteries, they generate direct current electricity through chemical action. several types exist and their operational details vary in important ways. figure 1 shows one type and depicts the general components and operating principle. fuel cells contain two electrodes, an anode and a cathode respectively, each treated with a catalyst, often platinum. hydrogen introduced at the anode and oxygen supplied to the cathode interact with the catalyst that facilitates the chemical action. an electrolyte separates the electrodes allowing passage of ions through the cell, while electrons routed externally provide electric power. recombination of gases generates waste heat and water. the operating process reverses electrolysis, in which an electric current separates water into hydrogen and oxygen. pure hydrogen can be pumped into a fuel cell directly or extracted from a hydrogen-containing fuel by a reformer. likewise, cells can use pure oxygen or air. engineers must manage waste water and heat, control reaction products that can damage catalysts, and prevent the internal leakage of gases and electrolytes. ideally cells emit no pollutants or greenhouse gases, though environmental challenges exist in mitigating the impact of cell fabrication and disposal, as well as in obtaining and delivering hydrogen fuel. individual cells yield only a modest amount of electricity. arranging cells in stacks boosts total output to as much as five megawatts. a power inverter changes the direct current to alternating current, if desired. fuel cells are typically classed by the form of their electrolyte. the principle types are: alkali, phosphoric acid, proton exchange membrane (pem), molten carbonate, and solid oxide. some types are more appropriate than others for certain applications, and each presents specific technical challenges. molten carbonate and solid oxide cells operate at relatively high temperatures and are usually classed together. high temperatures reduce the need for expensive catalysts and pure fuels. but cells and auxiliary equipment tend to be large and immobile, and reuse of waste heat can be critical to overall system efficiency. acid, alkali, and pem cells operate at lower temperatures and can be more compact and portable. but fuel purity becomes an issue and the power output is reduced.7 far from simple devices, each type’s history grew ever more distinct through time though some common features emerge. specific technical problems as well as figure 1. diagram showing basic fuel cell components. smithsonian image. 85fuel cells: a challenging history 85fuel cells: a challenging history general issues like making and distributing hydrogen fuel vexed generations of researchers. meanwhile, other researchers actively refined competing types of electrical generators.8 in a world of limited resources, societies typically made choices based on economics rather than technical elegance with the result that fuel cells remain marginalized. discovery of a puzzle in the 1790s, alessandro volta of italy (1745-1827) stacked discs of alternating metals such as zinc and silver to create “piles” that produced a steady, continuous electric current. his work inspired experimenters worldwide who improved on his discovery.9 advances came rapidly and in 1838, welsh jurist and scientist william robert grove (1811-1896, figure 2) devised an eponymous wet cell battery. he used a platinum electrode immersed in nitric acid and a zinc electrode in zinc sulfate. grove cells proved popular with early telegraphers; american samuel f. b. morse (1791-1872) used them to power his 1844 “what hath god wrought” demonstration.10 while experimenting with his new batteries, grove arranged two platinum electrodes such that one end of each was immersed in a container of sulfuric acid. he sealed the other ends separately in containers of oxygen and hydrogen, and then measured a constant current flowing between the electrodes. the sealed containers held water as well as the gases, and he noted that the water level rose in both tubes as the current flowed. christian schönbein of germany (1799-1868) independently noted a current in his experiments with platinum and various gases about the same time.11 grove decided to “effect the decomposition of water by means of its composition” and assembled several sets of electrodes in series, as seen in figure 3. energy lost as heat eventually stopped the process but grove’s experiment attracted attention. he named the new device a gas battery and published several papers on his experiments.12 he noted however, that “i have never thought of the gas battery as a practical means of generating voltaic power.”13 grove’s discovery challenged a scientific community still defining basic principles of chemistry, electricity, matter, and energy. gas batteries were, as wilhelm ostwald (1853-1932) of germany wrote, “a puzzle” for those struggling to understand what caused current to flow from some substances but not others.14 and it intensified a controversy between proponents of two competing theories. contact theory, proposed by volta to explain the pile and “defended” by johann poggendorff (1796-1877) and christoph pfaff, required physical contact between substances in order for current to flow.15 a rival theory supported by grove and schönbein held that a chemical reaction generated electricity. arguments between the two camps became quite acrimonious.16 figure 2. portrait of william robert grove. woodburytype by lock and whitfield. smithsonian institution libraries. figure 3. grove’s apparatus for “the decomposition of water...by means of its composition.” w. r. grove, trans. roy. soc. 1843, 133, plate v, p. 93. 86 harold d. wallace, jr.86 harold d. wallace, jr. the debate faded as knowledge advanced. concluding that the gas battery was “of no practical importance,” ostwald recounted the solution of the puzzle. “the answer is contained in the fact that oxidizing agents are always substances that form negative ions or make positive ions disappear; the reverse is true of reducing agents. oxygen and hydrogen are nothing more than oxidizing and reducing agents.”17 ironically both theories held some truth. later fuel cell researchers noted that chemical reactions in gas diffusion electrodes take place in “the contact zone where reactant, electrolyte and catalyst meet.”18 the controversy’s details are less important here than the fact of its existence. ostwald was correct. no practical device emerged from that era, despite several attempts. the primary importance of the gas battery in the mid-nineteenth century lay in spurring research that refined scientific theory. as scientific understanding improved, researchers shifted to making something useful. while that focus contributed to basic science—there was certainly more to be learned—research turned to developing better materials and more efficient designs. but by century’s end, ostwald’s countrymen ludwig mond (1839-1909) and carl langer (1859-1935) noted that “very little attention has been given by investigators to the [gas battery].”19 engineering and experiments public and professional interest in fuel cells briefly surged in the years around 1900 as several researchers looked for novel ways to produce electricity. mond and langer worked to increase gas batteries’ electrical output by means of an earthenware panel soaked with sulfuric acid and fueled with coal-derived “mond-gas.” but then they chanced to discover “the carbonyl process for refining and purifying nickel, and [their] attention was diverted away from fuel cells to the foundation of the great nickel industry.”20 this would not be the last time that fuel cell researchers turned to other work deemed more important or more amenable to success. englishmen charles r. alder wright (1844-1894) and charles thompson (18611892) developed a similar fuel cell about the same time. they made progress but reported that internal gas leaks interfered with attempts to increase voltage output, “even with only infinitesimal currents.” they concluded, our results were sufficiently good to convince us that if the expense of construction were no object, so that large coated plates could be employed, enabling currents of moderate magnitude to be obtained with but small current density, there would be no particular difficulty in constructing [cells] of this kind, competent to yield currents comparable with those derived from ordinary small laboratory batteries; although we concluded that the economical production of powerful currents for commercial purposes by the direct oxidation of combustible gases did not seem to be a problem likely to be readily solved, chiefly on account of the large appliances that would be requisite.21 their concern with “powerful currents for commercial purposes” ref lected the increasing inf luence of industrial age goals and organizations on electrical research. wright and thompson worked during a period of rapid electrification. they understood that producing “currents of moderate magnitude” held little attraction for industrialists who wanted to electrify factories and whole cities.22 after publishing their results, both turned to other work. thompson led research at a soap manufacturer. wright, a physician, is remembered as the inventor of heroin.23 neither returned to fuel cells. a few others did take an interest in fuel cells however, even one industrialist. steam research during the 1800s led to higher efficiencies in coal-fired electrical generating plants. a major driver of fuel cell development since the 1880s has been the desire to escape carnot heat-cycle limits in electrical plants. some researchers hoped that fuel cells might enable the direct conversion of coal into electricity. they pursued that goal vigorously, leading to a burst of research and publicity. american thomas a. edison (1847-1931), sought many ways to cut costs and improve the efficiency of generating electric power for his new lighting system. he spent over two years investigating the direct conversion of coal and received several patents, but found himself facing “an insurmountable obstacle.” he could not have been encouraged when the experiments resulted in “all the windows [being] blown out of his laboratory.”24 edison rarely wasted time on inventions that showed little profit potential and soon moved on to other work. in late 1894, the french team of louis paul cailletet (1832-1913) and louis j. e. colardeau (?-?) described a gas battery that used “precious metals” in sponge form to absorb gases, but deemed the process impractical.25 at the same time wilhelm borchers (1856-1925) of germany described an apparatus for “direct production of electricity from coal and combustible gases.”26 american charles j. reed (1858-1943) critiqued borchers’ work, then wrote two papers of his own on this “most promising” use of gas batteries.27 economic questions persisted, however. one editorial noted that given the low price of coal, even if borchers’ system gave 100% conversion efficiency consumers would see less than a 10% reduction in electricity prices. “[assuming] that the [techni87fuel cells: a challenging history 87fuel cells: a challenging history cal] problem were really solved, it does not follow, as is often asserted, that a revolution in the electrical industry would result.”28 that reminder of economic reality soon fell by the wayside. william w. jacques (1855-1932), an american electrical engineer and chemist, “startled the scientific world and general public,” in 1896, “by his broad assertion that he had invented a process of making electricity directly from coal.” jacques generated current via a “carbon battery” in which air injected into an alkali electrolyte reacted (or so he believed) with a carbon electrode. the apparatus, illustrated in a trade journal (figure 4) at the time, consisted of 100 cells arranged in series and placed on top of a furnace that kept the electrolyte temperature between 400-500 °c. jacques claimed 82 percent efficiency for his carbon battery, but critics soon pointed out that he had failed to account for the energy used heating the furnace or driving the air pump. they calculated an actual efficiency of only 8 percent. further research indicated that the current generated by his apparatus came not through electrochemical action, but rather through thermoelectric action.29 even had jacques’ battery worked as well as claimed it left unanswered the economic question raised by borchers’ critics. nonetheless, the desire to convert plentiful and inexpensive coal directly into electricity by way of an electrochemical process continued in the twentieth century.30 around this time, the use of fuel stocks like coal and manufactured gas gave the fuel cell its modern name. a follow-on article labeled borchers’ device a “fuel battery,” in recognition of the “combustible gas” he used.31 though the term gas battery remained in use for a time, newer generations came to call it a fuel cell. and experimenters in the years around 1900 found fuel cells to be far more complex than grove’s gas battery. despite the flurry of work, fuel cells faded from the scene for reasons modern developers would recognize: costly materials and unfavorable economics. competition ordinary batteries, for example, provided a less expensive alternative for important markets that needed low power devices. as with morse’s use of grove’s first battery, practical applications supported many battery producers, creating economies of scale. aside from telegraphy, alexander graham bell (1847-1922) and others used batteries to power telephone call stations and switchboards. the use of inexpensive materials like lead and the ease of refilling and refurbishing primary cell batteries also drove costs down. aside from single-unit applications such as telephones, electrical utilities in cities and towns connected large numbers of batteries into banks to buffer and regulate current on distribution grids. that application increased demand for batteries, attracted investment, and spurred research. in the larger scope however, most utilities required generators that produced bulk power, and neither batteries nor fuel cells could produce electricity at that scale.32 nor could either efficiently produce the alternating current that many utilities wanted for their electric light and power systems. though direct current proved useful for heavy motors and industrial applications, utility executives like samuel insull (18591938) of chicago’s commonwealth edison pushed equipment makers to improve ac generator technology. in 1904, insull opened fisk street station that featured new steam turbine generators rated at 5 mw each.33 the power industry’s focus on steam and hydroelectric generators left little interest in low-power devices like fuel cells, although it did ultimately boost battery development in a roundabout way. utilities struggled in the early years to find customers for electricity generated outside of evening or morning hours when lighting demand peaked. insull and others pushed daytime use of appliances like fans and irons, and equipment like pumps and elevators in order to keep generators spinning and improve return on invested capital. they identified automobiles as a potential market for so-called off-peak power. early internal combustion engines were noisy, dirty, and unreliable, and many people saw battery-powered electric vehicles figure 4. william jacques’ carbon battery apparatus showing the furnace at left with carbon cells on top, and air pump at center bottom. electr. rev. (london) 1898, 42, 128. 88 harold d. wallace, jr.88 harold d. wallace, jr. as the wave of the future. in the 1900s and 1910s, many utilities supported the idea of recharging electric vehicles overnight for urban use during the day. improvements in combustion engines and the creation of gasoline production and distribution infrastructures ultimately pushed electric vehicles aside, but that business model drove investment in battery research.34 edison developed his alkali batteries in hopes of entering the market via a route untapped by other inventors. not for the last time, utilities or auto makers determined that component expense and the need for a continuous fuel supply made fuel cells an inferior choice compared to batteries. no mass market developed and fuel cells faded from the scene. back to the lab laboratory work continued during the early decades of the twentieth century. karl siegl (?-?) of germany published a paper describing his gas battery work on the eve of the great war. after the war, john g. a. rhodin (1872-1941) of britain returned to the idea of direct conversion of coal by asking, “can the heat of combustion of coal be turned directly into electric energy?”35 while fuel cells generated less interest outside the lab than in the 1890s, scientists explored several novel designs, leading to the diversification of fuel cell types. emil baur (1873-1944) of switzerland (with students at braunschweig and zurich) conducted wide-ranging research into different types of fuel cells during the first half of the twentieth century.36 baur and hans preis experimented with solid oxide electrolytes using such materials as zirconium, yttrium, cerium, lanthanum, and tungsten. less electrically conductive than they hoped, their designs also experienced unwanted chemical reactions between the electrolytes and various gases, including carbon monoxide.37 in the 1940s, oganes k. davtyan (1911-1990) of the soviet union added monazite sand to a mix of sodium carbonate, tungsten trioxide, and soda glass “in order to increase [electrolyte] conductivity and mechanical strength.” this design also experienced unwanted chemical reactions and short life ratings, but work on high temperature devices by baur, davtyan and others paved the way for both molten carbonate and solid oxide fuel cells.38 fuel cells in general, however, remained a solution in search of a problem. as europe plunged toward the second world war, a suitable problem suggested itself to british scientist francis t. bacon (1904-1992). bacon suggested that fuel cells would be a good substitute for batteries on submarines, where hydrogen gas from damaged batteries could reach dangerous concentrations in the enclosed environment. bacon set to work at king’s college but after a short time the royal navy, battling german u-boats, reassigned him to a sonar project. although promising, fuel cell research again gave way to other priorities. no applications emerged during the war, but the research of bacon and others set the stage for a resurgence of interest in fuel cells afterwards.39 the onset of cold war competition between the us and the ussr spurred increased investment in many technologies with potential military use, including fuel cells. during the 1950s and 1960s designers tested cells containing different electrolytes in a range of applications. at the same time, research investment in competing technologies reduced or eliminated other prospective fuel cell applications. many possibilities after the war, bacon moved to cambridge and for the next twenty years experimented mostly with alkali electrolytes, settling on potassium hydroxide. koh performed as well as acid and was less corrosive to the porous gas-diffusion electrodes he used.40 bacon’s work showed good results, but nuclear energy better satisfied the power requirements for his original application. as demonstrated by uss nautilus in 1954, compact nuclear reactors allowed submarines to stay submerged for extended periods without refueling. the new technology provided far more electric power than fuel cells and by 1960 the navy deemed nuclear a superior alternative. at the time, that seemed only an isolated example with little impact on fuel cell development. a post-war economic boom in the us unleashed a flood of ideas for civilian applications that leveraged cold war military research. the popular press reported many fuel cell prototypes under development, from desoto’s “cella 1” concept car (figure 5) and exide battery’s “racer” to electric boat’s submersible.41 in 1959 allischalmers demonstrated a farm tractor powered by a stack of 1,008 alkali cells based on bacon’s work (figure 6). generating 15 kw, the tractor could pull about 1400 kg (3000 lb.). supported by the us air force, allis-chalmers pursued fuel cell research for some years, also testing a golf cart and a fork lift.42 battery maker union carbide also experimented with alkali cells in this period. karl kordesch (19222011) and colleagues built on 1930s work by george w. heise (1888-1972) and erwin a. schumacher (1901-1981), to make alkali cells with carbon gas-diffusion electrodes. 89fuel cells: a challenging history 89fuel cells: a challenging history they demonstrated a mobile radar set for the us army and designed fuel cells to run an undersea base. kordesch turned heads in cleveland, ohio by driving around in a converted austin a40 automobile powered by batteries and an alkali fuel cell.43 union carbide also provided cells for general motors’ experimental “electrovan” (figure 7).44 amid the work on alkali cells researchers did not abandon acid electrolytes, and many turned to phosphoric acid. in 1961, glenn v. elmore (1916-2009) and howard a. tanner tested an electrolyte of 35 percent phosphoric acid and 65 percent silica powder pasted into a teflon gasket. “unlike sulfuric [acid],” they noted, “phosphoric acid is not reduced electrochemically under cell operating conditions.”45 the us army explored the potential of phosphoric acid cells that ran common fuels like diesel as well as unusual fuels like hydrazine (figure 8). an industrial partnership known as the team to advance research for gas energy transformation, inc. supported research in phosphoric acid cells for the electric power industry, and developed a series of power plants ranging from about 15 kw in 1969 to nearly 5 mw in 1983.46 unfortunately phosphoric acid proved a poor conductor of electricity. that among other issues slowed the pace of development. interest in high temperature fuel cells resurged after wwii due to their greater tolerance for fuel impurities. dutch scientists gerard h. j. broers (1920-2003) and jan a. a. ketelaar (1908-2001) began building on the prewar research of baur and preis, and davtyan. they decided that limits on solid oxide conductivity and life expectancy made short-term progress unlikely so focused instead on electrolytes of molten carbonate salts. by 1960, they demonstrated a cell that ran for six months using an electrolyte “mixture of lithium-, sodiumand/or potassium carbonate, impregnated in a porous sintered disk of magnesium oxide.” however, they found that the molten electrolyte was slowly lost, partly through reactions with gasket materials.47 francis bacon also began working with a molten cell, using two-layer electrodes on either side of a “free molten” electrolyte.48 other groups tested semisolid or “paste” electrolytes, and investigated diffusion electrodes rather than solid ones. texas instruments made molten carbonate cells for the army that ranged in output from 100 w to 1 kw (figure 9). the promise of a cell with a stable solid electrolyte that could tolerate a variety of fuels sustained modest interest in solid oxides. researchfigure 5. desoto “cella 1” concept model, ca. 1959. from the science service historical images collection, courtesy de soto. figure 6. allis-chalmers fuel cell tractor, 1959. from the science service historical images collection, courtesy allis-chalmers figure 7. sample union carbide koh fuel cell for general motors “electrovan.” nmah catalog no. 2007.3061.01. smithsonian image. 90 harold d. wallace, jr.90 harold d. wallace, jr. ers at westinghouse experimented with a cell using zirconium oxide and calcium oxide in 1962.49 when price is no object the post-wwii work produced prototypes and conference papers, but little in the way of practical devices. fabrication costs continued to run high and substitute power sources existed for most potential applications. only in the mid-1960s did an application emerge that took advantage of fuel cells: the us space program. batteries sufficed for the first piloted spacecraft, the soviet union’s vostok and us’ mercury. but national aeronautics and space administration (nasa) planners knew that batteries would be too heavy for lunar expeditions, and fuel cells gave the added advantage of producing potable water. when reaching the moon became a political priority, concerns about costs receded. nasa ultimately used two types of fuel cells, a novel design from general electric (ge), and a derivative of bacon’s cell made by pratt & whitney. w. thomas grubb (1923-1994) and leonard niedrach (1921-1995) at ge developed a polymer electrolyte in the form of a thin, permeable sheet. in 1962, the company introduced the proton exchange membrane (pem) fuel cell, proposing small units for the military. the unit ran on hydrogen made by mixing water and lithium hydride contained in disposable canisters. though compact and portable, the cells’ platinum catalysts were expensive.50 the expense did not deter nasa officials who liked the compact size and chose pem cells for project gemini. missions lasting up to fourteen days would test in earth orbit equipment and procedures needed for lunar flights. unfortunately for ge, their model pb2 unit experienced problems including internal cell contamination and oxygen leakage through the membrane. the first four short duration gemini flights used batteries while ge hurriedly fixed the problems. their new model p3 performed poorly in gemini 5 but served adequately on six later flights.51 the pem cells’ problems boded ill for nasa’s very fast schedule to reach the moon. rather than risk additional delays, the agency chose pratt & whitney’s alkali cells for project apollo’s service module. the company had licensed francis bacon’s patents in the early 1960s and moved into production (figure 10). the alkali cells performed well for apollo, and a decade later space shuttle designers chose an updated version. ultimately five shuttles made 135 flights between 1981 and 2011 with electrical power provided by alkali cells. powering spacecraft allowed researchers to gain operational experience with fuel cells. they could accept figure 8. a soldier refuels a 300 w hydrazine fuel cell, ca. 1964. courtesy of the us army mobility equipment r&d center. figure 9. texas instruments 1 kw molten carbonate fuel cell. nmah catalog no. 330031. smithsonian image. 91fuel cells: a challenging history 91fuel cells: a challenging history high costs since few practical alternatives existed. driven by politics, scientists and engineers spent the money needed to improve cell performance. but space applications proved too limited a market to support that level of research. technical hurdles remained intractable and researchers struggled to find a replacement for expensive platinum catalysts. fuel cells still could not compete with other power sources in markets where costs mattered. another factor became clear during the post-wwii period: fuel cells were just one component in holistic power systems. figure 11 shows a representative example. as eisler points out, though bacon and others chose to ignore this issue, fuel cells required ancillary equipment like reformers, hydrogen storage tanks, and inverters.52 all those pieces, themselves complex, had to function compatibly when interconnected. modifications to one affected the others, increasing costs and complicating integration into the host device. if the application required the fuel cell assembly to function within a greater system, such as an electric power or transportation infrastructure, an external layer of compatibility issues arose. all power sources face these systems issues, but they add another disincentive to the high costs of adopting fuel cells. in the 1960s, specialty markets proved too small to generate the economies of scale necessary to reduce fuel cell production costs. potential mass markets took advantage of less expensive alternatives. internal combustion engines could power cars, tractors, and motorbikes more economically than fuel cells. gas turbine engines for aircraft were adapted for electric power stations; one was even displayed next to a fuel cell at the 1964 world’s fair (figure 12).53 propane engines could power fork lifts, batteries could run small submersibles and golf carts. military users liked the idea of fuel cells but not well enough to add hydrogen fuels to their logistic supply chains.54 they also grew wary of unfulfilled promises when technical and operational difficulties persisted.55 some companies (allis-chalmers, desoto), failed while others (texas instruments, philco) ceased fuel cell research. public and corporate interest waned and fuel cells’ prospects again faded. energy & environment after the 1973 oil embargo, interest in new power sources rebounded and kept money f lowing into fuel cell research. two potential markets attracted significant investment: stationary electric power and automobiles. utilities and auto makers faced the challenge of satisfying customers who demanded lower costs and less pollution. attempts to meet those demands led to another round of fuel cell prototypes and demonstrations during the 1990s and early 2000s. press releases promised near figure 10. apollo fuel cell assembly at pratt & whitney. from the science service historical images collection, courtesy pratt & whitney. figure 11. diagram of fuel cell system. courtesy of us army engineer research & development laboratories. 92 harold d. wallace, jr.92 harold d. wallace, jr. term availability of commercial products, and indeed a few did emerge for backup and auxiliary power. however, as before, investment in competing technologies resulted in advances to alternatives that made fuel cells less attractive, hindering widespread adoption.56 electric power utilities faced many difficulties beginning in the 1960s, including blackouts and soaring construction expenses.57 high oil prices led utilities to abandon that fuel where possible but replacements often seemed no better. nuclear technology faltered in the aftermath of the three mile island meltdown and the chernobyl disaster. coal plants needed to install expensive equipment to control emissions that created acid rain and smog, offsetting the low cost of fuel. renewable sources like solar and wind power were intermittent and expensive, while few acceptable sites remained for new hydroelectric plants. also, a backlash against large scale technical infrastructures led many people to question the basic concept of centralized power systems. plans to expand high voltage transmission grids became politically contentious, especially near scenic or historically sensitive areas. advocates of decentralized systems argued that small generating plants situated near users would reduce transmission losses, be less expensive to build, and limit the impact of malfunctions.58 that idea came to be known as distributed generation. fuel cells held promise for distributed generation in two ways: as additions to localized power grids, and as stand-alone generators. manufactured in relatively small, modular units, fuel cells’ cleanliness made them especially attractive to pollution conscious urban planners. nearly 200 fuel cells had been installed in japan by 2001, including phosphoric acid units of up to 200 kw capacity, similar to the unit in figure 13.59 in the late 1990s, the us department of energy worked with industry groups on several demonstration projects. one cogeneration unit coupled a solid oxide fuel cell with a microturbine, while a demonstration plant in santa clara, california, tested a molten carbonate stack.60 one urban plant demonstrated how non-technical problems could disrupt fuel cell adoption. using mostly public and some private funding, consolidated edison built a 4.8 mw molten carbonate power plant in new york’s bedford–stuyvesant neighborhood (figure 14). an extended period of inspections and reviews, spurred by local residents’ fears about the underground storage of naphtha fuel, delayed the plant’s opening date beyond the life of the fuel cells. faced with the need to replace the expensive cells, con ed instead demolished the plant.61 increased adoption of computer information systems led users to demand more electricity and better system reliability. power fluctuations and outages created expensive service interruptions in commercial and industrial operations. generating power onsite, fuel cells reduced demand on electric grids and provided backup power during blackouts. police in new york city’s central park were at first unaware of a 2003 blackout when their stafigure 12. fuel cell and gas turbine at the 1964 world’s fair. from the science service historical images collection, courtesy american gas association. figure 13. utc 40 kw model pc-18 phosphoric acid fuel cell, 1979. courtesy of the us department of energy. 93fuel cells: a challenging history 93fuel cells: a challenging history tion’s fuel cell kept lights and computers on. seeking to tap the residential market, a company called plug power in 1998 demonstrated a stationary pem unit in the albany, new york house seen in figure 15. promoted as the “first permanent home installation,” the 5 kw power plant powered the home for about two years. the company partnered with ge and detroit edison with the goal of marketing a residential fuel cell by 2002.62 it seemed in the early 2000s that fuel cells might finally be finding a practical niche in stationary power, as several companies began selling commercial units. advances in other technologies upset those plans, however. a substantial boost in natural gas supplies due to fracking led utilities to install more gas turbine power plants. cost competitive wind turbines gave them yet another option to replace coal and nuclear plants. breakthroughs in photovoltaics coupled with mass production dramatically cut the cost of solar cells. utilities began installing solar farms for local use or to feed the grid. many people installed solar panels to generate electricity for use or sale to local utilities during the day, while taking grid power in sunless times. manufacturers integrated small solar panels on equipment like road signs, replacing combustion generators and eliminating the need for either petroleum or hydrogen fuel. automotive cells like electric companies, car makers also needed to cut pollution and improve fuel efficiency. unable to quickly adopt alternative fuels, they designed lighter cars with smaller engines, while pushing national governments to maintain oil supplies.63 they also began to experiment, often under duress, with possible replacements for internal combustion engines. a compact fuel cell that emitted only water vapor held obvious attraction. though high temperature and alkali cells would be ill-suited for cars, pem cells looked promising. by 2002, major manufacturers were testing prototype fuel cell cars—and making grandiose promises, as hultman and nordlund noted.64 transporting some form of hydrogen fuel constituted a major challenge. few people would tolerate cars with exposed hydrogen tanks like kordesch’s austin. one either needed a reformer to extract hydrogen from a fuel that existing stations could sell or to create a hydrogen distribution infrastructure. either option would be difficult and expensive. making, compressing, and storing hydrogen entailed high energy costs, cutting overall system efficiency.65 reforming fuel onboard the vehicle, as with a methanol fuel cell, provided one way to address the issue. however, byproducts of the reforming process poisoned cell catalysts, a familiar problem, and corrosion problems required use of an acid electrolyte.66 the byproducts also belied claims of a nonpolluting engine.67 centralized refueling stations for urban trucks and buses, like the battery recharging stations of the early 1900s, seemed a reasonable first step. h-power, georgetown university, and the energy department adapted a 50 kw fuji electric phosphoric acid cell for transit buses and began test runs in 1994 (figure 16). phosphoric acid cells require an extended warm-up period, making them better suited for commercial vehicles than for personal cars. four years later, georgetown, nova bus, and the us transportation department began tests of a bus powered by a 100 kw cell from a joint venture of toshiba and united technologies.68 figure 14. artist’s rendering of the 4.8 mw bedford–stuyvesant fuel cell power plant. nmah catalog no. 2008.0006.03. smithsonian image. figure 15. plug power house with pem fuel cell in attached enclosure, 2001. smithsonian image. 94 harold d. wallace, jr.94 harold d. wallace, jr. during this time an unexpected cost hurdle emerged. one of the most expensive materials in many fuel cells, platinum, also proved critical for the catalytic converters that car makers needed to control engine emissions. increased demand for platinum raised the price of the already expensive metal. replacing an internal combustion engine with a fuel cell might eventually remove the need for catalytic converters and substitute one platinum containing product for another. but such a shift might take decades, and that pushed cost reductions too far out for most investors, reducing the attraction of automotive fuel cells. another option was to find a bridge technology that could work with the existing petroleum infrastructure. in 1997, major auto makers began to promote gas-electric hybrid vehicles that used a small gasoline motor in combination with an electrical generator to recharge batteries or power electric motors. they also invested at least as much in battery research as in fuel cells. the tesla electric automobile in 2003 along with the company’s massive battery factory in nevada shows how sustained research and investment in both product and power source might lead to economies of scale. commercially available hybrids and battery powered cars began moving a market that might have supported mass production of fuel cells in a different direction. advances in battery technolog y also disrupted another potential market: portable electronics. several companies experimented with micro fuel cells they hoped could replace rechargeable batteries in cell phones, laptop computers, and portable audio players (figure 17). millions of small electronic devices created environmental concerns about the disposal of used batteries containing toxic materials like cadmium and mercury.69 a motorola engineer at a 2001 conference reported problems with water transport in cells for phones, but claimed progress on a cell for laptop computers.70 before commercial products could be introduced though, new nickel-metal hydride and then lithium-ion batteries changed the market. despite the latter’s thermal problems, batteries were easier to integrate into electronic devices than micro fuel cells. one 2013 study found 109 firms in nine countries engaged in fuel cell research partnerships.71 despite all that effort and publicity, by the early 2010s fuel cells again fell out of favor. plug power demolished their test house in 2002 and shelved plans for residential pem fuel cells. the tennessee valley authority reactivated a closed nuclear facility instead of installing a regenerative fuel cell system. auto makers, who promised affordable fuel cell vehicles in showrooms by 2004, quietly pulled back from all but a few high-priced models. us government funding for fuel cells was cut in 2008, with one official citing “four miracles” needed to bring the technology to market.72 even in spacecraft like the international space station, high efficiency solar panels rather than fuel cells provided power. lessons of non-cyclical history nearly two centuries after grove’s discovery, fuel cell researchers have made significant advances even while the basic concept remains unchanged. thrice during that period fuel cells seemed on the verge of widespread adoption only to fade from view. history never repeats, despite the tired old adage. so how are we to take lessons from an account that seems to do just that? one key is to look for changes in the larger societal contexts within which technologies exist, especially economic and political changes, while remembering that human nature tends to persist. understanding context helps explain historical differences. understanding people helps explain historical similarities. figure 16. h power phosphoric acid fuel cell bus, 1996. courtesy of the us department of energy. figure 17. micro-fuel cell by fraunise ise for mobile phone. courtesy of fuel cells 2000. 95fuel cells: a challenging history 95fuel cells: a challenging history one lesson is to look beyond functional elegance to mundane economics. since 1839 people have been captivated by the idea of combining hydrogen and oxygen to generate electricity and water. there simply must be a way to use that idea, so fuel cells have always been a solution in search of a problem. yet technical elegance is neither necessary nor sufficient to produce a return on investment. every time engineers found a seemingly realistic use for fuel cells, a competitor better met users’ needs. internal combustion engines, steam turbines, photovoltaics, and batteries all set technical and economic challenges for developers. but each of those power sources attracted additional investment that advanced their capabilities when a compatible application proved commercially successful. advocates should pay close attention to alternate technologies and business models because there are no uncompetitive applications for fuel cells. nineteenth century researchers would recognize many difficulties their descendants struggle with. the need for expensive rare earths, especially platinum, is one; the need for readily available pure gases is another. yet the technical environs within which those difficulties exist have changed. inexpensive solar cells may enable efficient production of pure hydrogen. recent experiments with aqueous fuels based on recyclable boron hydride may offer a sustainable fuel distribution infrastructure without the energy loss of compressing hydrogen.73 still, the basic material costs must be dramatically reduced for fuel cells to become commercially competitive. today’s researchers do face hurdles many of their predecessors did not. for one, the need to design equipment that meets established standards. whether those are electrical, manufacturing, or safety standards, once in place new devices must operate within those set parameters. standards can advance quality and promote efficiency. setting standards is an act of control that can eliminate some competitors and raise costs for others.74 standards internal to fuel cell technology have been crafted, but engineers must also account for external standards like building codes that affect other power sources as well.75 a related difference is the need for economic compatibility with associated system components. fuel cells must work with power inverters and control equipment; ideally those should already exist in manufacturers’ product catalogs. special versions of those components can be made, but that introduces additional design, testing, fabrication, and certification costs that are counterproductive. incompatible variations between fuel cell types exacerbates the problem. fuel cell researchers today enjoy advantages their predecessors could only dream of, such as computeraided design and fabrication tools. the ability to model physical and chemical interactions before making experimental devices speeds research. additive manufacturing may permit economical production of complex component designs. researchers today also have the internet, a high-speed global communications system that permits far-f lung collaborations. access to searchable digital archives makes the results of ongoing and past research readily available. changes in information technology shift the basic nature of scientific and engineering research in ways that should not be underestimated. one of the most enduring human features of fuel cells is the feeling among advocates that solutions are close. in 1884, edison gave himself five years to find an answer, and expected some “lucky” person would succeed.76 in 1960, two ge engineers felt that use in “special applications...within the next five years” was “likely.”77 in 2010, a penn state engineer commented on the “fickle” nature of us government support, giving another fiveyear estimate “to make hydrogen technologies consumerready.”78 in 2013, a policy analyst recognized that companies, “always believed things could be fixed with a little more time and a little more money;” and then proposed a major national research program “to uncover the secrets of the fuel cell.”79 in part those feelings stem from technical naiveté conflating fuel cells that run on pure hydrogen with those that run on other fuels, a definitional difference that eisler noted.80 the economic and energy problems that made pure hydrogen a poor fuel choice have not been solved by research on reforming coal, gas, or petroleum fuels. technical advances provided a dose of positive reinforcement but failed to meet users’ immediate needs as well as other technologies. a cold accounting for recurring optimism may indeed be “disheartening for young [engineers],” but it is also essential to avoid another round of wasted money and dashed hopes.81 practical fuel cells will not emerge from the lab unless they can be produced and operated sustainably in both environmental and economic terms. other similarities and differences exist, and we cannot predict how this story will unfold. perhaps fuel cells are doomed to perpetual impracticality. perhaps persistence will finally lead to mass adoption. few people doubt the unsustainability of fossil fuels, only the timing of when they will run out or be abandoned to mitigate climate change. so demand for clean, low-cost power sources seems assured. perhaps batteries and renewables will meet that demand. perhaps a politically-driven shift away from combustion engines coupled with low-cost hydrogen generated using cheap solar 96 harold d. wallace, jr.96 harold d. wallace, jr. power will radically alter energy costs in favor of fuel 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0000-0001-8572-7070 received: apr 11, 2023 revised: may 24, 2023 just accepted online: may 30, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: a. kraft, (2023) animal oil, wound balm, prussian blue, the fire and light principium and the philosophers’ stone made from phosphorus: on the 350th birthday of the chymist johann conrad dippel (1673-1734). substantia. just accepted. doi: 10.36253/substantia-2107 abstract on the basis of many newly found archival sources and a close study of his relevant books, the life story of the chymist johann conrad dippel is re-described. the preparation of his most important chymical products, i.e. animal oil, wound balm, and prussian blue, is described. his own chymical theory was build around a fire and light principium. for decades, dippel tried to find a process for the preparation of the philosophers’ stone. he was convinced that phosphorus was the right starting material for this. this article does not deal with his theological and philosophical views and undertakings or his medical practice, but is focused on dippel the chymist. keywords: alchemy, chymistry, prussian blue, phosphorus, philosophers’ stone mailto:ak@kraftconsult.de alexander kraft manuscript for substantia page 2 introduction on august 10, 1673, johann conrad dippel was born at castle frankenstein near darmstadt in hesse, germany. therefore, in 2023 we celebrate the 350th birthday of this fascinating personality. during his lifetime, dippel, whose portrait is shown in figure 1, was a well-known but highly controversial theologian, as well as a physician and chymist. although born in germany, he lived a transnational life with longer stays in the netherlands, denmark and sweden.1 figure 1: johann conrad dippel (1673-1734), radical pietist theologian, physician and chymist. (source: justus-liebig-universität giessen) today, johann conrad dippel is mainly known as one of the two discoverers of the pigment prussian blue in 1706 and as the alleged model for mary shelley’s character victor frankenstein in her novel frankenstein or the new prometheus from 1818.1 the latter speculation is based on radu florescu’s (1925-2014) book in search of frankenstein from 1975.2 but there are no sources that support florescu’s hypothesis. quite the contrary, it has been shown convincingly that florescu’s speculation has no basis.3 the fact that very little is known about dippel’s activities as a chymist has certainly encouraged this kind of speculation, such as that of radu florescu or the even more ridiculous of the german journalist walter scheele.4 but in the last 15 years, several new archival sources have been discovered or rediscovered which shed a new and much brighter light on dippel’s acitivities as a chymist. among these archival sources from archives in berlin, frankfurt am main, hamburg, bad laasphe and münster are many previously unknown letters written by dippel, extensive notes of dippel’s young admirer johann christian senckenberg (1707–1772) about talks he had with dippel and last but not least several recipes concerning the preparation of the philosophers’ stone which can be attributed directly or indirectly to dippel. together with a close reading of some of the books he published during his lifetime, a much more detailed picture of dippel as a chymist emerges from the fog of unreliable internet sources which depict him as a mad scientist5, 6 and creator of monsters who experimented with nitroglycerin and dead human bodies. 1 see the recent conference: ein transnationales leben: bausteine zur biographie von johann konrad dippel (1673–1734) on 26.–27. january 2023 at forschungszentrum gotha of the university erfurt, germany, organisation: martin mulsow (erfurt/gotha), vera faßhauer (erfurt/gotha). alexander kraft manuscript for substantia page 3 in the following chapters of this article i will present a short biography of dippel the chymist, structured mainly according to the sources used. dippel’s biography of his first 25 years: 1673-1698 johann philipp dippel (1636-1704), the local pastor, had registered the birth and baptism of his son johann conrad on august 10, 1673 in the church register of nieder-beerbach,7 a village in the northern part of the odenwald mountain range. according to this church book entry, the family had fled to nearby frankenstein castle (figure 2) because of french soldiers (“französische völcker”) who were active in the area. it was the far-reaching franco-dutch war (1672-1678), during which french troops also attacked allies of the republic of the netherlands on the territory of the german empire, leading a french army into southern hesse. because he was sickly and frail, johann conrad dippel was baptized just one hour after his birth. johann conrad’s mother was anna eleonora münchmeyer (ca. 1640-1710). figure 2: view of the ruins of frankenstein castle in 1818 by johann georg primavesi (1774-1855). (source: hessian state archive darmstadt, signature r 4 no. 30788) before he went to nieder-beerbach as a pastor in 1672, johann conrad’s father had been a teacher in zwingenberg. in 1678 he moved from nieder-beerbach to the nearby somewhat larger niederramstadt as a pastor. these three places, zwingenberg, nieder-beerbach and nieder-ramstadt, were in the southern part of the landgraviate of hesse-darmstadt, a protestant lutheran state of the holy roman empire (hrr), the german empire of the time. two different calendars were used in germany between 1582 and 1700. catholic states used the more modern gregorian calendar, which is still in use today, while protestant territories, whether lutheran or reformed, used the older and less accurate julian calendar. at the time of johann conrad dippel’s birth the difference was 10 days. therefore, according to the gregorian calendar, he was born on august 20, 1673. in his excellent study from 2001, stephan goldschmidt presented a detailed biography of johann conrad dippel up to the year 1700.8 therefore, for the brief description of this period, we should follow his study, also because no new sources have been found for this period after goldschmidt’s study was published. alexander kraft manuscript for substantia page 4 figure 3: old school house in nieder-ramstadt. (source: photo by the author 2018) goldschmidt assumed that dippel attended the small latin school in nieder-ramstadt between 1679 and 1685. the building of this school still exists today. it is shown in figure 3. however, a modern commemorative plaque on the former school building indicates that it was a kind of elementary school for the town and the surrounding area, which cannot be described as a latin school as in the dippel literature. dippel then went to the paedagogium darmstadium, a higher school in darmstadt, the capital of the landgraviate of hesse-darmstadt. dippel completed his schooling there in 1691. on may 9, 1691, dippel was enrolled in the register of the university in giessen. his latin language entry read: “joh. con. dippelius, straetaemontano-francostenensis”, that means “johannes conradus dippelius from frankenstein on the bergstrasse”. the bergstrasse, literally mountain road, is an ancient travel route parallel to the rhine, but situated higher on the edge of the odenwald to avoid flooding in the rhine valley. the university of giessen was the only university of the landgraviate of hesse-darmstadt located in the northern part of this state. dippel finished the prescribed basic philosophical studies in giessen in 1693 with obtaining the “magister” degree. the thesis for his disputation was entitled “de nihilo”, i.e. “about nothing”. dippel then started to study theology in giessen until the middle or end of 1694. at that point, he had to interrupt his studies because of financial problems. for about one year, dippel earned money as a private teacher for the children of a nobleman in the odenwald forest. then he decided to continue his studies in theology. for this purpose he enrolled at the university of strasbourg in alsace. for centuries, strasbourg had been a free imperial city of the german empire. it was only annexed by france in 1681, 14 years before dippel came to study here. therefore, at that time, strasbourg still had the character of a german protestant city and not that of a french catholic city. on august 2, 1695, dippel was enrolled in the register of the university of strasbourg as “m. johannes conradus dippelius, darmstadiohassus”. so this time he stated that he came from darmstadt in hesse, perhaps because frankenstein castle on the bergstrasse was not well known in alsace. in addition to studying theology, dippel began to give first public sermons in strasbourg. besides that, he dealt with chiromancy and began first medical studies. a tutor position provided him with additional financial means. but dippel was also active in student associations, there were brawls and trouble with the alexander kraft manuscript for substantia page 5 city authorities, so that in august 1696 he fled head over heels from strasbourg to his hessian homeland. dippel continued his study of theology in giessen from spring 1697. at the same time he worked for one year as a prince’s tutor for one of the sons of the landgrave of hesse-darmstadt, which brought in a good income. if he wanted to give lectures at the university himself as a private lecturer, he still had to take an exam. after some quarrels with his professors, dippel held his habilitation disputation on july 8, 1697. he was now allowed to lecture in the field of theology at the university and his aim was either to become a pastor like his father and others of his ancestors or to get a permanent position at the university. but he, still a magister not a doctor, was not to achieve either goal. in order to explain this, it is important to know that dippel had switched from strictly orthodox lutheranism to pietism during his time as an aspiring theologian in strasbourg. he quickly made a name for himself as a radical pietist, mainly through two printed pamphlets in 1697 and 1698. in these two books and later in almost all other publications, he used the author’s pseudonym christianus democritus. the first book was entitled orcodoxia orthodoxorum (= the hellish doctrine of orthodoxy), the second one papismus protestantium vapulans (= the beaten papacy of the protestants). despite the latin titles, these were german-language treatises. with these two writings, which harshly opposed the orthodox lutheran variant of protestant christianity, dippel ended his prospects of a career in the protestant church for good. the government of hessedarmstadt began an investigation against him and his time at giessen university was over. in the next few years until 1704, dippel lived again with his parents in nieder-ramstadt, but he also traveled a lot in the hessian area and began to work together with various church dissenters such as johann henrich reitz (1665-1720). dippel’s book weg-weiser zum licht und recht (= guide to light and justice) in 1704 dippel published the first edition of the two volumes of his book weg-weiser zum licht und recht (= guide to light and justice).9 a third volume was announced, but never appeared in print. in an addendum at the end of the second volume it is stated that this addendum was written on march 23, 1704. so we can assume that dippel completed this work in the first half of 1704, the time when he was still living in his native hesse. dippel moved to berlin in late autumn of that year. the second edition of these two volumes was published in 1705. at that time, dippel had already established himself in berlin. the second volume of this work with the title weg-weiser zum licht und recht in der äußern natur (= guide to light and justice in outer nature) contains two sections which are of special interest if we study dippel’s activities as a chymist. the first section is fata chymica, the preface of the second volume of the guide to light and justice. in this text, dippel told the story of how he became a chymist. the second section of interest is chapter 7 of the second volume entitled kurtze anatomie derer in so weit unspecificirten cörpern der eusseren natur als des feuers, des wassers, der erden, und der lufft. und was endlich unter dem namen, licht und recht, in der natur zu verstehen sey (= brief anatomy of the unspecified bodies of external nature, i.e. fire, water, earth and air. and finally what is to be understood under the name of light and justice in nature). close reading shows that in this text and at a few places in the other chapters of this volume dippel’s chymical theory from that time is explained in great detail. dippel’s beginning as a chymist according to his fata chymica alexander kraft manuscript for substantia page 6 in most of his writings, dippel did not refer to himself as an “alchemist”, but as a "chymist" and he usually called the corresponding natural science "chymie" not “alchemie”. so he was, in his german mother tongue, already in line with the modern so-called "new historiography of alchemy".10 according to his fata chymica, he had a lot of time after he had published his highly controversial theological book papismus protestantium vapulans. this book appeared in print in mid-1698, perhaps in june. in the following time, in the second half of 1698, he received an alchemical book from a pastor who was a friend of his, in which the experimenta of raymundus lullus, the twelve keys of basilius valentinus and other classics of alchemy were printed. dippel mainly studied lullii’s experimenta and decided to try his hand at alchemy at the next opportunity. he reported about what happened some time later: in secret, i came across a chymical manuscript, which opened the way to a tincture in a very laborious way; which i resolved to follow at the earliest opportunity because both the method and the first matter were somewhat simpler than what i had found in lullio.11 it was a text written by “a certain medicus from montpellier” called “faber”, i.e. pierre-jean fabre (1588–1658). that was the process that he then successfully reworked, during which time he had to change his place of residence several times: to put it briefly, among all this incommodity i prepared within 8 months a tincture which, as soon as it was received, transmuted 50 parts of ☽ or ☿ into gold; which made me not a little happy and amazed.12 so dippel informed us here that he had produced the tincture, i.e. the philosophers’ stone, within 8 months and that he was able to convert 50 times the amount of silver or mercury into gold. can we believe him? certainly not. however, dippel then went on to report that he was from now on very liberal with his money. he bought an estate for 50,000 fl. from a “certain baron” at a place where there was a glassworks and other necessary “requisitis”. there he wanted, together some friends, further investigate chymistry. at first, dippel was only able to make a small down payment for the estate. to pay off this sum all the more conveniently, i wanted to increase and enhance the remaining quantum of my prepared tincture by multiplication. but unfavorable fate and an oversight in the preservation of fire shattered my glass in the process of this work, and what had taken so long to prepare perished in a moment. especially since a strange and unfavorable salt from the ashes in which the glass had stood had completely altered and separated the tincture, parts of which i could otherwise have salvaged.13 by multiplication, so the alchemists believed, the potency of the tincture could be increased. so obviously dippel worked on such a process when he lost the tincture altogether. dippel now had to put off the baron to a new payment date. dippel then attempted to make the tincture again. however, he wanted to achieve this in a faster way in just two instead of eight months. in order to make some money during this time, dippel sold various chymical particular recipes and thus made some money, 4,500 guilders. of this he paid the baron a sum of 1,500 fl., the rest melted between his fingers. but crucially, he failed to reproduce the tincture again. dippel reported: in my precipitated work i gradually learned that in chymistry all haste and shortening of time is an infallible dispendium and the shortest way from one error to another. i wanted to force nature and burned my fingers in all the work i did.14 alexander kraft manuscript for substantia page 7 with this unsuccessful work three years passed. dippel got more and more problems with his creditors and became the ridicule of his neighbors and his relatives. for example, they called him a great fool or arch-deceiver. dippel continued: but some felt sorry for me, and could scarcely believe how it could have been possible that so clever a mind could have been so presumptuously implicated in the follies and messes of the wretched laboratory workers. others thought it a strange judgment upon me, for speaking blasphemous words against the holy places, and confusing the world with my theological writings. others even believed that i was playing an adventurous comedy with diligence, in order to draw people’s minds into the light the better, and to hide my things, which were already quite obvious, with such chimeras.15 according to dippel, he had now in fact learned that in addition to knowledge and diligent work in such matters, a higher hand was at the helm, without whose direction the desired end could never be found. he could now easily see the reason why so many lovers of gold lose all their goods over the lapide; since even he, as an “adeptus”, had roamed about for so long in vain. so this is what dippel himself told about his beginnings in chymistry. it is interesting that dippel referred to himself as an adeptus, meaning someone who knows how to make and use the lapis philosophorum. therefore, this foreword from 1704 could also be seen as a kind of advertisement for the gold maker dippel. perhaps it helped him to be summoned to berlin towards the end of 1704 as a promising alchemist? dippel’s chymical theory according to his guide to light and justice in outer nature if studied by a chemist-historian, dippel’s book guide to light and justice in outer nature and especially it’s 7th chapter gives us new insight into his chymical theory. but what is interesting for us begins with a statement in the first chapter in which we can read: so let us confidently say that all currently existing hypotheses, of the old and new natural researchers, such as epicuri and cartesii atomi, of aristotelis and his successors 4 elements; of the paracelsists, and of the chymists in general three principia sal, sulphur, and mercurius, the more recent alcali and acidum, ... are proving as much as nothing.16 so dippel rejected the established teachings, particularly those of the four aristotelian elements (fire 🜂, water 🜄, earth 🜃, air 🜁) and the three paracelsian principles (sulphur 🜍, mercury ☿, salt 🜔). regarding the latter, he also remarked in chapter 7: the illusion “of three visible principiis”, namely “sale, sulphure, and mercurio” only arose in the “philosophers and chymists” “due to a lack of more thorough knowledge.”17 but what does he want to put in their place? this is explained in various places in the second part of the guide to light and justice, for example in one place dippel wrote that the whole basis of true chymistry, which noble and correct art is concerned solely with drawing out the pure form of fire and light and elevating it to permanence in fire. ... so chymistry is generally content with this purpose, when it can, through a thorough separation, separate out the pure form of light and fire ... and make it permanent in the fire through purer added matrices;18 elsewhere he stated: for it is, according to my experience, all about separating the light and fire form, and nothing else, from the natural bodies. plants and animals easily give off such principia, solely through the alexander kraft manuscript for substantia page 8 motum of the kitchen fire, but metals and other earthly, firmly closed bodies require a wet fire and appropriate solvents, through which the light form is freed of the bands of the dark matricis.19 dippel developed the idea of a “light and fire principium” from the aristotelian element fire.20 basically, as early as 1704 he tried to replace the three established alchemical principles with the new “light and fire principle”. superficially, this points somewhat in the direction of georg ernst stahl’s (1659-1734) emerging phlogiston theory, but also to wilhelm homberg’s (1652–1715) matière de la lumière21 and, as we will see later, to dippel’s preference for phosphorus as the starting point for the production of the philosophers’ stone. however, the difference between stahl’s phlogiston principle and dippel’s “light and fire principle” is enormous. while stahl postulated an immutable principle which would be exchanged between the reactants in chemical reactions, dippel’s principle was to be released from substances by separation, but then “raised to perfect permanence in fire”. then it is the philosophers’ stone, the “lapis philosophorum”. with this “tincture” it is then possible “to make gold and silver out of base metals”. this “lapidis” would also be suitable for “medicine, in the human body” because it has “along with the highest subtlety also the highest fixity”. so this was nothing more than another theory of the philosophers’ stone, the lapis philosophorum. dippel’s chymical theory further explained in a letter extract in the mellon collection of alchemy and the occult in the mellon collection of alchemy and the occult we can read an extract from a german language letter written by dippel and dated march 1716.22 it is interesting for the present study that this letter also contains fragments of dippel’s chymical theory. so he wrote that for the tincture “the substance of the 🜂 itself, which must really grasp itself as the principium agens in a matter” would be necessary. so there is dippel’s fire and light principle again. furthermore, dippel explained in the text that the “substance from the 🜂” would pass through the walls of the vessels standing in the fire, also through glass walls, and then “unite” with the contents of the vessels “intimo with it”. according to dippel, it is a saline substance from the fire that would permeate the walls of the vessel. mercury would be used in the process only to facilitate the “ingress” of the substance of fire. these are again interesting insights into dippel’s chymical world of thought. it has to be added, that an english translation of this letter extract can be found in the manly palmer hall collection of alchemical manuscripts.23 however, this is not a literal translation, but rather a free one, which does not always correctly capture the meaning of the original german text. dippeliana in the archival collection of count august zu wittgenstein in bad laasphe today’s bad laasphe was only laasphe in dippel’s time, the small capital of one of the two small counties of wittgenstein. in the private princely archive of sayn-wittgenstein-hohenstein in the rentkammer wittgenstein near castle wittgenstein in bad laasphe two folders are kept which deal with johann conrad dippel’s connection to count august david zu sayn-wittgenstein-hohenstein (short: count august zu wittgenstein) roughly for the time of dippel’s stay in berlin since 1704 until his death 1734 and a few years later surrounding questions of dippel’s heritage.24 the majority of the material is however from the time in which dippel lived in the wittgenstein counties (1729 to 1734). this dippeliana collection also contains 10 letters written by dippel himself between 1727 and 1734. we will come back to this collection in due time. alexander kraft manuscript for substantia page 9 the area of the former county of wittgenstein is now part of the german federal state of north rhine-westphalia, but is located directly on the border to the federal state of hesse. in the early modern period, the county of wittgenstein was under dominating hessian influence. since 1357 the county of wittgenstein was ruled by the counts of sayn, therefore the name sayn-wittgenstein for the ruling family. in 1603, the county of wittgenstein was divided into the northern berleburg and the southern wittgenstein halves. these two counties, sayn-wittgenstein-berleburg and saynwittgenstein-hohenstein existed until the french period in germany in the beginning of the 19th century. count august david zu sayn-wittgenstein-hohenstein (1663-1735) was an almost life-long friend of dippel from 1701 to his death. he came from the line of the counts zu sayn-wittgenstein-hohenstein residing in laasphe. from 1698 his older brother henrich albrecht zu sayn-wittgenstein-hohenstein (1658-1723) ruled the small county, while count august zu wittgenstein sought foreign services. we find him in january 1701 as a privy councilor and envoyé extraordinaire of the electoral palatinate at the coronation of friedrich i as the first king in prussia in königsberg (today kaliningrad, russia). from december 1701 he was oberhofmarschall at the prussian royal court in berlin, a very influential and well-paid position. in december 1710, however, he was relieved of his offices as part of the disempowerment of count johann kasimir kolbe von wartenberg (1643–1712), who had been in charge of government affairs up to that point. wittgenstein was temporarily imprisoned in the spandau citadel and then expelled from the country after paying a large sum. this meant severe humiliation for an imperial count. after that he was again in the service of the electorate of the palatinate until in 1719 he was placed alongside his brother as co-regent and finally, after his brother’s death in 1723, became the sole regent of the small county of sayn-wittgensteinhohenstein. while his brother was strongly influenced by pietism and opened the county to and sponsored all possible and impossible radical pietists, separatists, mystics, inspired and other sectarians, count august zu wittgenstein was a staunch opponent of such ecclesiastical dissenters. assuming the regency of the county, he ruled with an iron fist, driving out the separatists and being merciless to the old-established population as well. this led to countless lawsuits that were conducted by him or against him. but count august zu wittgenstein, who by his own admission had known dippel since 1701, was also a passionate alchemist. he was not alone in this at the berlin court. on the contrary, in the first decade of the 18th century, numerous more or less well-known alchemists were drawn to the royal prussian residence city on the spree to try their luck there. and the leading figures of the berlin court, the king himself, counts wartenberg, wittgenstein and wartensleben and many others were very much interested in the alchemical production of gold. dippel’s letters to baron geuder genannt rabensteiner in utrecht in the state archives of north rhine-westphalia, unit westphalia in münster a collection of 22 letters from johann conrad dippel to his friend baron von geuder, genannt rabensteiner2 in utrecht are preserved.25 these letters were written in german or latin between 1706 and 1715 and sent from berlin, amsterdam, warmond or hamburg to utrecht. these letters are full of valuable information on dippel’s life at that time. but also new insights in his acitivities as a chymist and physician result from reading these letters. 2 literally translated: baron de geuder named rabensteiner alexander kraft manuscript for substantia page 10 baron friedrich philipp von geuder, genannt rabensteiner (1659-1727), came from the aristocratic von geuder family, which had lived in the german region of franconia for centuries, especially in nuremberg and heroldsberg. he was a pietist nobleman and secretly married to the widowed duchess ernestine charlotte von nassau-siegen (1662-1732). the couple lived in utrecht in the netherlands and was part of an international pietist network. von geuder and dippel were close friends as can be seen from the letters dippel wrote to von geuder. the first of these letters was sent by dippel from berlin to utrecht in june 1706. this was apparently the letter accompanying a medicine that dippel had sent at the request of the addressee. it is not clear what this medicine was, but the baron could use it in “all current and future diseases”, especially “in head diseases, and in women’s diseases” as well. the dose was “from 60 to 80 drops in all [diseases] in distilled water.” the second letter of july 27, 1706 contains two medical recipes, that of dippel’s wound balm including a description of a drastic animal experiment with a dog and a nail, and that of a “medicina ex martialis”. the latter is perhaps the remedy that the first letter in this collection of letters was about. dippel’s wound balm let’s have a closer look at dippel’s wound balm, because although forgotten today it was thought to be an important remedy during his lifetime! dippel told baron von geuder in the letter from july 1706: it is a wonder-worthy spiritus as shown by the test that i myself made on various animals at my lodge. and now i believe with certainty that no wound is fatal per se, even if it goes right through the heart, if only it were possible to leave the weapon in the wound for so long until someone would be present to apply this spiritum through a syringe, the blood would certainly be staunched and the wound would soon be consolidated. he followed with a detailed description of one of his animal experiments: we drove a nail through the head of a young dog, in the presence of a medici, who, as a good anatomicus, had to show where the principal ventricali of the brain are located and the wound would be most fatal: the one who had driven the nail through and through, so that the dog was nailed properly, could not get the nail out again without using the greatest force and desordre, so that the dog’s brains had not been stirred up in the head, but it was quite ex animis, nevertheless we appilorated several drops into the wound, and poured half a spoonful down his throat: the animal recovered in momento, the blood stopped, and before half an hour had passed, the dog barked at the chickens, that had endured the same fate, it also ate bread and whatever was served to it. dippel also stated in this letter that the recipe did not come from him at all, but from a french medicus who had immigrated to berlin. nevertheless, this medicine became known under dippel’s name. the physician johann christian kundmann (1684-1751) in breslau (today wroclaw, poland), who received his doctorate from stahl in halle in 1708, reported in 1716 in his book kurtze abhandlung vom verstande des menschen vor und nach dem falle about the "dippelian wound balm".26 he mentioned that dippel had given a sample of it to the licentiate johann samuel carl (1677-1757) in berlin. carl would have traveled to halle with it and the drastic animal experiment with a dog and a nail would have been successfully repeated by the halle medical professor friedrich hoffmann (16601742). as a result, hoffmann’s colleague stahl also carried out this experiment.27 alexander kraft manuscript for substantia page 11 the recipe for the wound balm, which was given by both, by dippel in his letter to baron geuder and by kundmann in his book, was quite simple: you had to prepare the squeezed-out juice of fresh herbs from 1) betonica (betony): 1 pound, 2) cerefolio (chervil): 1 pound and 3) sanicula (wood sanicle): 1 pound. you had to mix these liquids and add 4 pounds of aceti vini destillati rectificati (rectified wine vinegar, i.e. highly concentrated acetic acid) and further add 1 pound of rock salt (nacl). this would be distilled together from a flask in a water bath and the wound balm is ready, more of a tincture from today’s perspective. dippel added: “you can add other herbar vulnerarias [wound herbs] if you like, but the basis are the first three.” around 1730 in berleburg, a list of dippel’s medicines was printed in two quite similar versions.28 as number 5, this list also contained a tinctura vulneraria, i.e. dippel’s wound balm. it was remarked in this rare print: otherwise it is known that all brain wounds in animals are cured by this tincture, and if you drive a nail through their head and just pour some of it into the wound and also half a spoonful down its throat, the animal will soon recover to be salvaged. so roughly 25 years after the letter to baron von geuder, dippel or one of his followers still told the same improbable, hardly to believe story. according to the print, the price of dippel’s tinctura vulneraria was 22 kreutzer per ounce (= 29.23 g). johann conrad dippel in the diary of senckenberg in the early 1730s, johann christian senckenberg (1707-1772), later a physician in frankfurt am main who was more than 30 years younger than dippel, was an admirer of the radical pietist theologian, physician and chymist. in his later years, the wealthy senckenberg whose children had all died before him was the founder of several charitable and scholarly foundations. he is famous for his extensive diaries. 53 volumes of diaries and 600 folders with further entries comprise approx. 40,000 pages. in the last decade the first volumes of his diaries have been transcribed by vera faßhauer29 and veronika marschall. through these efforts, much valuable information has become available to the research community. in april and august 1732, senckenberg visited dippel two times in berleburg, the last place of residence of the old dippel. the long conversations that senckenberg had with dippel himself and with others about dippel were recorded in his diary. they give us many previously unknown details of dippel’s life including his activities as a chymist. in addition to that, also in later diary entries after his return to frankfurt, dippel remained an important topic for senckenberg. this new or additional chymical information include a slightly different narrative of the discovery of the pigment prussian blue in berlin in 1706, dippel’s preference for phosphorus as the starting material for the philosophers’ stone and last but not least dippel’s chymical activities during his time in berleburg. the discovery of prussian blue according to senckenberg’s notes of dippel’s own report on august 22, 1732 dippel told senckenberg the story of the discovery of prussian blue in berlin.30 dippel’s story is slightly different from what georg ernst stahl had reported in his 1731 book experimenta, observationes, animadversiones, ccc numero, chymicae et physicae.31 for a long time stahl’s account was the basis for the written history of the discovery of prussian blue. 32 but since alexander kraft manuscript for substantia page 12 dippel was part of the discovery team, we can believe his story more than stahl’s who was not even living in berlin at the time of the discovery of this blue pigment.33 dippel wanted to prepare sal volatile, so his story begins. for this purpose, he calcined tartar, mixed the potash thus produced with dried ox blood and distilled sal volatile from this mixture and perhaps also his infamous animal oil. potash is potassium carbonate k2co3 and sal volatile is (nh4)2co3. sal volatile was a chymical product of the time and was used as a smelling salt. dippel wanted to throw away the six pounds of residual “sal” or caput mortuum from this process. but his young laboratory assistant rösser collected it, extracted the salt from the residue and, after drying, stored this salt in a sugar glass labeled as “sal tartari”, i.e. potash. we call it “rösser’s potash”, because this potash was contaminated. today we know that it also contained cyanide cn-, perhaps also some hexacyanoferrate(ii) [fe(cn)6]4-. some time later, after rösser had meanwhile left the laboratory, the following happened: a certain “lieutenant diesbach” also worked in dippel’s laboratory. according to dippel, diesbach usually prepared florentine lake and other colors. on that day, he wanted to produce florentine lake again by using, among other chemicals, potash and alum. diesbach, whose full name was actually johann jacob von diesbach (ca. 1670-1748) according to the berlin church records,34 produced the red florentine lake from a carminic acid extract. for this purpose, dried and pulverized cochineal insects were extracted in a warm, slightly acidic aqueous alum solution. by adding the right amount of alkaline potash solution, aluminum hydroxide precipitates in the neutralized aqueous solution, on which the carminic acid molecules adsorb. after filtering off and drying, the red florentine lacquer pigment is obtained. if the aqueous alum solution contains additional metal salts, a pigment with a different color is formed. the addition of ferrous ion, for example, shifts the color from red to violet. that is exactly what diesbach had done that day. however, things turned out very differently than diesbach had expected. senckenberg noted what happened according to dippel: diesbach picked up the glass which rösser, who had already left dippel, had only labelled as sal tartari. but he got loco rubri coloris, caeruleum berolinense, made an agreement with the painters behind dippel’s back to deliver them so and so much, but got caught out because after the glass was empty there was no more paint that looked blue with the common sal tartari. he came to dippel and reported it to him, who knew, told him to take sal tartari with sanguine bovino so he would get it, and it worked.35 let us summarize: dippel’s sal volatile production led to the formation of cyanide which remained in the residue of the process. because dippel’s assistant rösser wrongly labeled it as potash only, diesbach used it for his florentine lake preparation. but the cyanide in the potash led, together with the iron diesbach had added, to the formation of blue iron(iii) hexacyanoferrate(ii), i.e. prussian blue, besides the florentine lake. the reaction scheme of the first prussian blue synthesis is shown in figure 4. alexander kraft manuscript for substantia page 13 figure 4: reaction scheme of the first serendipituous preparation of prussian blue by diesbach using potash contaminated by dippel and wrongly labeled by rösser. diesbach sold this blue pigment to painters, but could not reproduce the process, after the source of contaminated potash (rösser’s potash) was gone. he had to ask dippel what was special with this potash and dippel told him to calcine potash with dried ox blood and the preparation of prussian blue could be reproduced. therefore, we can consider both, diesbach and dippel, as the discoverers of prussian blue. this discovery happened in berlin in the year 1706. we know this from an entry in a handwritten chronicle by joachim ernst berger (1666-1734), lutheran preacher in berlin’s friedrichstadt district in which he recorded the first preparation of the “prussian ultra-marine” by the “swiss” diesbach for this year.36 dippel’s flight from berlin in 1707 according to archival material in berlin in the secret state archives of the prussian cultural heritage foundation in berlin we can study a folder from which the events around dippel’s flight from berlin in late february 1707 become clear.37 not much about chymistry can be found there, though. but let’s tell the story: the first thing we can learn from the material in this folder is that dippel came to berlin around early november 1704. in a letter he described that “i soon had to realize that because of alchemy, everyone was staring at me from all corners” and that “this pursuit meant that not only did i not do anything real in alchymices, but i also resolved not to waste much time here.” roughly six months after dippel came to berlin he was so disappointed that he thought about leaving the city and try his luck elsewhere. therefore he wrote a letter in latin to the swedish king karl xii (1682-1718). among other things, he wrote to the swedish king that he wanted “to reveal his arcanum in alchemy to him as an inexhaustible source of wealth.”38 in addition, there was harsh criticism of the king and government of prussia. so dippel wrote: alexander kraft manuscript for substantia page 14 i see their monstrous crimes, in which court and government are completely immersed, as a divine sign, they impel me daily to promote my departure, and even if i alternately allied with one of the firsts around the king, they would betray me for their meanness, i can predict that with certainty.39 and another example: nor have i any confidence in the king’s foul servants, who surround him on all sides, when he binds himself by solemn promises to any demands what they impede, known to the king or not, for i have already witnessed the machinationes of some of them. dippel did not send this letter directly to the swedish king, but sent his servant to the swedish “envoyé” in berlin, count anders lejonstedt (1649-1725), swedish envoy in berlin for the second time since 1703, “to be all the more certain about the address“. lejonstedt accepted the letter willingly and promised to forward it. however, when dippel’s servant approached him again after the agreed time: … so the count mentioned took a nasty turn on him, gave him the opened letter back, said he hadn’t sent it away and didn’t want to have anything to do with such things, yes, he even threw insults and threats around.40 one gets the impression that the swedes had no interest in secretly poaching a chymist who was in the service of the prussian royal court to sweden. against the background of the great northern war, in which sweden was involved at the time, this is also understandable. the kingdom of prussia remained neutral in this conflict and sweden certainly did not want to provoke prussia into entering the war on the side of the enemy coalition. on the contrary, it was hoped that prussia would take the swedish side. roughly one and half year later, towards the end of 1706, a book was published by johann friedrich mayer (1650-1712) a well-known orthodox lutheran theologian. from 1701 he was general superintendent of swedish pomerania, professor of theology at the university of greifswald and pastor of st. nikolai in greifswald. he was the most important lutheran theologian in the german lands under swedish rule. after the occupation of saxony by swedish troops in the ongoing war, mayer had rushed to the swedish camp at altranstädt and conferred with king karl xii about the increasing influence of the pietists and what to do about it. in nearby leipzig he then had his book “a swedish theologian’s short report about pietists” printed without naming the author.41 this book was a fierce but not clumsy attack on the pietists. mayer personally attacked various pietists in this book, including the pietists from halle and also dippel. dippel reacted to this with his own polemic, which was called "impartial thoughts" for short.42 at the instigation of the swedish envoy, dippel was arrested around february 7th because of his book, in particular because of the harsh criticism it contained of the swedish king. according to the royal order of february 12, the imprisoned dippel was then to be released on bail of 2,000 thalers. on february 14, august count zu wittgenstein took over the bail “sub hypotheca bonorum”, whereby dippel was not allowed to travel from berlin before the matter was resolved, had to be available to the commission and had to refrain from all writing on religious matters.43 dippel was released from prison the same day. figure 5 displays the short letter dippel wrote to count august zu wittgenstein asking him to take over the bail of 2,000 thalers. alexander kraft manuscript for substantia page 15 figure 5: letter from johann conrad dippel to count august zu wittgenstein dated berlin, february 14th, 1707 (source: gsta pk, i. ha rep 9 geheimer rat allgemeine verwaltung d4c fasc 24, f. 24) a week after his release, on february 21, 1707, dippel wrote a rather unwise letter to the prussian general-fiscal3 wilhelm duhram (1658-1735). in this letter, dippel wrote that among his still confiscated correspondence was a letter that he had written to the swedish king in 1705. we have already discussed this letter. dippel would fear that he would be questioned again about this letter and would like to avoid that by explaining it. he then went on to write that after his arrival in berlin he had been put under great pressure because of his knowledge of alchemy and that he therefore wanted to leave berlin again. that’s why he wrote this letter to the swedish king. dippel then tried to explain further in his letter to duhram why he had written so disparagingly about the prussian court. however, there is nothing in it other than what is complained about at every table, at every assembly, and in every street by the subjects themselves.44 in any case, the letter to the swedish king was dug out, and based on its contents, dippel was to be arrested again. he found out about this in good time and fled from berlin at the end of february 1707 via several intermediate stops to the netherlands. the story of prussian blue continues after dippel left berlin, diesbach teamed up with the teacher and natural scientist johann leonhard frisch (1666-1743). together they produced and marketed prussian blue over the next years and both earned a lot of money from it. this emerges from a collection of letters that frisch sent from berlin to gottfried wilhelm leibniz (1646-1716) in hannover between 1706 and 1716.45 another letter preserved in the correspondence of leibniz proves that dippel also continued to produce prussian blue during his time in the netherlands. in this letter, written in french and dated august 17, 1714 from paris to leibniz in hannover, heinrich hasperg, church councilor and secretary to duke anton ulrich von braunschweig-wolfenbüttel (1633-1714), reported on “the blue color for the miniature ... that is made in berlin”: a german in holland called herr dipelius also makes it and i brought a sample here [to paris], but it’s not as nice as the color made in berlin.46 until the end of the 1710s, the discoverers of prussian blue had a kind of manufacturing monopoly, but then the first recipes began to appear underground, both incorrect and correct ones. but still only a few knew how to make prussian blue. that was over, however, with a publication in the renowned philosophical transactions of the royal society in 1724.47 now anyone who could master 3 general-fiscal was a kind of attorney general. alexander kraft manuscript for substantia page 16 the necessary chymical manipulations could make prussian blue himself. the price then collapsed rapidly. today almost 300 years have passed since the manufacturing instructions for prussian blue were published and this compound is still used as a pigment. in the meantime, however, it has also found other areas of application. it serves as an antidote for poisoning with thallium or radioactive caesium and as a sensor material for determining the concentration of certain substances, such as hydrogen peroxide. many other applications are still being tested or are being examined on a laboratory scale, such as the use of prussian blue as an active substance in batteries and electrochromic windows or its use in modern imaging processes in medical technology or even to combat tumors.48 surprisingly, several details in the composition, structure and chemical reactions of prussian blue are still open more than 300 years after the discovery of this amazing compound.49, 50 dippel’s stay in the netherlands 1707-1714 we had already heard that dippel left berlin for the netherlands in 1707. most of the newly discovered information about dippel’s time in the netherlands we owe to the rabensteiner letters, which we have already mentioned above. after arriving in the netherlands, dippel first lived in amsterdam. this was reported by kundmann who visited dippel in early 1708 in amsterdam. we can see this also from nine letters in the rabensteiner collection which were dated amsterdam between 1709 and 1711 and from the copy of another letter to a certain herr bergmann in darmstadt dated amsterdam, august 3, 1709.51 but, it is interesting to note that dippel’s letters to baron geuder were sent from warmond between october 1710 and early june 1711. warmond is a small village just north of the university town of leiden. from a brief remark by dippel, which senckenberg recorded in his diary, one can conclude that dippel had bought an estate there, near leiden.52 what brought dippel to this place? he, who, as far as is known, had never studied medicine, wanted to do a doctorate in medicine. however, it was not until april 1, 1711 that he enrolled as magister “johannes conradus dippelius hassus” in the register of the university of leiden.53 and already on april 17th he defended his theses and received his doctorate in medicine. it can therefore be assumed that he has already been working on his planned doctorate before he enrolled and perhaps wrote his soon to become famous doctoral thesis entitled "vitæ animalis morbus et medicina" in warmond. in older biographies of dippel it is usually mentioned that he lived in the netherlands in maarssen near utrecht. but no letter from maarssen is among dippel’s 22 letters to baron geuder, only the last dutch letter, written during his urgent departure on september 19, 1714, contained a crossed-out “maarssen” as a sending location. but this maybe explained by the fact that it is not a long way from maarssen to utrecht, only a few kilometers, so that information could be exchanged personally between the two friends. but from the content of several letters54 and from some notarial agreements55,56 it becomes indeed clear that dippel lived in maarssen in his later years in the netherlands. here he owned an estate called vredenhoef. this “buitenplaats” can easily be identified and it exists still today, however, the appearance of the house has probably changed a lot. it is located on the straatweg, the old street between utrecht and amsterdam. in front of the house flows the vecht, a small river that flows from utrecht to the gooimeer, a lake on the edge of the ijsselmeer. figure 6 shows the vredenhoef as it looked in 1836. it was built in the mid-17th century in the dutch classicist style; construction was probably started in 1666. it is not known who built the house. in dippel’s time, the house had a stable, a garden, plus an orchard and a vegetable garden. alexander kraft manuscript for substantia page 17 the tea house on the river was built later. from the above mentioned letters we can also conclude, that dippel had still to pay the purchase price for the estate which also included a “laboratorio”. figure 6: buitenplaats vredenhoef in maarssen in 1836 (source: lithographic print by p.j. lutgers / desguerrois & co, amsterdam in the collection of the author). dippel’s animal oil becomes famous after dippel had received his doctorate in april 1711, he now, as an m.d., printed his theses again and his vitæ animalis morbus et medicina became a well-selling book.57 therefore, it was reprinted several times and also translated into german as “die kranckheit und arzney des thierisch-sinnlichen lebens” (=maladies and remedies of the life of the flesh). of particular interest is a germanlanguage critically annotated and appendix edition from 1736.58 the editor and commentator, who knew dippel well and was a well-versed physician and chymist, remained anonymous, but perhaps it was johann samuel carl. through vitæ animalis morbus et medicina, dippel’s animal oil became widely known, although he dedicated only a very small part of this book to it. he wrote: i cannot avoid, for the benefit of the neighbor, to share a remedy which, as i have experienced myself very often, drives away all abating fevers, even if you have taken it only once, and with a quite wonderful effect, for the sick were overtaken by a pleasant sleep; and if at times they had passed about fifteen hours in sweet repose, with the face blooming and vivid in color, they arose fresh and healthy after they had slept through the attack of fever.59 the remedy would not bring sleep in healthy people, but even 30 hours of sleep in epileptics, after which they would also be cured. “medici”, who had seen this, almost no longer doubted the truth of the philosophical stone and the universal remedy, although it was nothing more than a very small remedy despised by the apothecaries, but which had been worked out with great patience. that all sounds very unbelievable: someone with fever sleeps 15 hours, an epileptic 30 hours at a time after taking the remedy and then they are immediately completely healed, while a healthy person does not fall asleep at all! alexander kraft manuscript for substantia page 18 however, according to dippel, this remedy has “a very penetrating and rather unpleasant smell” but a pleasant and savory taste ... it is namely a distilled oil from all parts of the animals, separated from its salt, which has been rectified and purified through the retort without any addition of anything else until it no longer leaves any black, burnt deposits, which is only attained after the 15th repetition. the dose was said to be 30 to 40 drops. this rather short section of his dissertation established the fame of dippel’s animal oil. in the critically annotated edition of 1736, the commentator on dippel’s animal oil warned that not a single example has been seen that it presented anything worth mentioning, let alone wonderous. it was much more frequently “shown that it was downright harmful”. this “miracle oil so splendidly highlighted” is “not worth a damn”60 and: “those who love their lives should leave the stuff out and get rid of it.”61 before that he had briefly remarked that “it is very often distilled from ox meat or ox blood”. in order to keep it colorless, it has to be distilled several times from potash (k2co3), possibly also from burnt lime (cao). the work was “mad and tedious”. so the commentator, who knew dippel and his animal oil well, hardly had a good word to say about this mixture of substances. the commentator also knew dippel’s “so highly and much praised light and fire principium”. however according to him, dippel “basically” did not “know and understood” this principle by himself, for otherwise he would never have done such chymeric things, and would have presented something far more real and useful to the world.62 dippel’s flight from the netherlands to hamburg and altona and his time there (1714-1719) in september 1714, dippel fled head over heels by ship from the netherlands to altona, which at the time was part of the danish dominions in northern germany.63 he stayed there and in the much larger neighboring free imperial city of hamburg until 1719. it is not yet known why he left the netherlands. but there were rumors in germany that he had to flee holland not only because of a few very unfortunate cures, but also because through many expensive alchemical operations which ended in vain he had accumulated great debts to a certain great lady.64 in altona, dippel was a protégé of the danish governor christian detlev graf von reventlow (16711738). not much is known about dippel’s chymical activities at that time, but it is clear that he was also working in the laboratory. christoph heinrich dornemann (1682–1753) from hamburg, for example, mentioned in a letter from may 1715 to the pietist professor johann heinrich may (1688– 1732) in giessen that dippel was very busy with laboratory work. ... i suspect that he is searching for gold, although he found a medicine lately, and our gentlemen pastors are also looking for the same with him ... .65 these were, in particular, messrs. heinson, i.e. johann theodor heinson (1663-1726), senior pastor of st. peter’s church and winckler, i.e. johann friedrich winckler (1679-1738), senior pastor of st. nikolai church, who “did their utmost to find the lapidem”. if that were to be true, these people alexander kraft manuscript for substantia page 19 interested in alchemy would have been the two most important lutheran-orthodox preachers in the free imperial city of hamburg. heavy disputes between dippel and the various local authorities in altona and the surrounding danish controlled region (e.g. glückstadt, pinneberg) began in 1717. in early 1719 dippel fell also out with his protector reventlow and in the course of the affair he was imprisoned in may 1719 and eventually sentenced to life imprisonment in september of the same year.66 he had to serve this on the danish island of bornholm. dippel imprisoned on the danish island of bornholm 1719-1726 on the island of bornholm, dippel was imprisoned in the mighty fortress of hammershus on the northwestern corner of the island. today a picturesque ruin, it was still an impressive and functional fortification in dippel’s time. but dippel was the last prisoner who was incarcerated in hammershus. after his release the decay of the building began. not much is known about dippel’s nearly seven years in hammershus, but close reading of the preface of one of his books,67 the study of some letter’s in the dippel-letter collection of count august zu wittgenstein and of some entries in senckenberg’s diary give us at least an impression of his chymical activities there. so in 1732, dippel reported to his visitor senckenberg in berleburg that in hammershus he was only able to do little or next to nothing in chymicis in his prison, and only built a furnace for simple extraction.68 in mid-1725, the last year of his imprisonment had begun, dippel was visited by christian pagencopen from hamburg, an emissary of count august zu wittgenstein. for dippel’s book eröffnete muhtmassungen und merckwürdige gedancken (= opened conjectures and remarkable thoughts) pagencopen wrote the preface signed with his initials c.p. only, but since pagencopen also wrote several preserved letters on the same subject to count august, we know that it was him who wrote the preface. in a letter dated hamburg, september 5, 172569 pagencopen reported count zu wittgenstein about his visit of dippel in his arrest on bornholm. from the preface of the book and from this letter we learn that dippel lived in a small detention room on the fifth floor of the central mantle tower of the fortress. however, he was allowed to prepare his own meals in the hall in front of his cell and also to produce medicines there himself, which he would distribute to patients who came to him frequently. dippel’s visitors were always accompanied by a senior officer and a noncommissioned officer, with the latter remaining in the hall while the other went into the small detention room together with the visitor. figure 7 shows the ruin of the mantle tower as it appears today. alexander kraft manuscript for substantia page 20 figure 7: ruin of the mantle tower of hammershus on the danish island of bornholm. dippel was imprisoned here on the top floor for about seven years. (source: photo of the author 2019) although dippel the chymist could obviously only produce some medicine during his time on bornholm the danish royal court was also interested to receive more information about dippel’s gold making attempts. this can be shown by a letter from dippel from february 1724, in which he answered questions from the governor of bornholm niels madsen west (1666-1752) about his gold making. dippel wrote: meanwhile, i can say so much in general that the productum will far exceed the cost, but whether it will turn out 10,000, 100,000, or 1,000,000 remains to be seen. regarding the cost of carrying out the experiments, dippel replied: “600 reichsthaler” and the duration: “one and a half years”. whether the gold produced is good ducat gold?: “the gold must not only be ducat gold, but far better...”.70 so in this case, too, we see dippel's typical exaggerations when he wrote about his chymical knowledge. and there is no evidence that royally sponsored goldmaking experiments with dippel’s recipes actually took place in denmark. in june 1726, dippel, sentenced to life imprisonment, was released from prison on condition that he had to leave denmark immediately and never to set foot in danish lands again. he had been in the hammershus prison for six years and ten months. dippel’s swedish period 1726-1728 dippel next went from bornholm to sweden and stayed in that country for almost two years until march 1728. ironically, after his release from prison, dippel actually wanted to return from bornholm to his native germany. but since the shipping connections via southern sweden (skåne) were better, he first traveled to ystad in sweden in order to get to germany from there. but then he followed the invitation of a swedish pietist merchant johan hoffmeister (1699–1744) from kristianstad and accompanied him to that place, where he lived for the next few months. here dippel became a center of the swedish pietist movement. it is interesting to note that the swedish king at that time was a compatriot of dippel from hesse, fredrik i (1676-1751, king of sweden from 1620), the son of the landgrave of hesse-kassel. this swedish king invited the physician dippel, meanwhile an international celebrity, to come to stockholm. after some hesitation dippel finally moved to the swedish capital and arrived there in mid-january 1727. alexander kraft manuscript for substantia page 21 not much is known about the chymical work done by dippel in sweden. about one episode he informed senckenberg. according to him, he had given count frölich in sweden an opportunity to work on the phosphorus, and he completely distilled ☉ mixed with it into a ☿ium, which the comes held very highly ... .71 this count frölich is probably one of the descendants of carl gustav frölich (1637–1714), a general in the swedish infantry, perhaps count bengt frölich (1684–1744), a swedish follower of dippel. elsewhere it was reported that various bigwigs in sweden held dippel for a great gold maker and tried to learn this art from him; but finally found themselves deceived in their opinion.72 this may have happened in stockholm, where dippel lived in the house of the wealthy elias von walcker (1660-1733). dippel must have impressed emanuel swedenborg (1688-1772) as well. swedenborg, an inventor and scientist, later also a mystic theologian, was perhaps among the guests of dippel in von walcker’s house. alfred acton (1867-1956) wrote swedenborg’s intercourse with dippel was probably and perhaps exclusively on the scientific or rather the chemical side of his learning, and among other things, on his claim to make gold not exactly, as it would seem, a claim totally to transmute metals, but to draw gold from them.73 swedenborg’s words concerning the “dippelian experiment” according to acton were: when dippel was staying in sweden, he preached his process as a sure argument for the transmutation or augmentation of gold from metals; for he promised by this art and process to extract more gold from copper than can be done by any common way.74 swedenborg also recorded this in one of his books as an “experimentum quoddam dippelianum”: according to this, one part of copper is mixed with 2 parts of saltpetre, placed in a crucible, which is closed and heated in the reverberatory fire. after cooling, the obtained mass is pulverized in a mortar and placed in a flask together with spiritus vini rectificatus. this flask is then kept in mild heat for a day, during which time the spiritus vini turns red. put this red spiritus vini in another flask. the leaching of the red color from the mass is repeated. the red spirits are combined and distilled into a recipient. a materia rubra or sal rubrum remains behind in the flask. this sal rubrum is mixed with half the amount of silver lime and placed in a crucible. after melting and cooling, you get a regulus, which after separation with aquafort gives quite a lot of gold lime.75 this recipe reminds on dorothea juliana wallich’s (1657-1725) theory of extracting the colouring soul (anima tingens) or tinging sulphur out of several materials, among them copper, and introduce this soul into silver to produce gold. she had published this in her book the mineral gluten in 1705.76 this was a so-called particular recipe, not a process description for the philosophers’ stone. so, dippel used essentially the same procedure as wallich, although details of the process may be different. interestingly, in sweden, a country with huge copper mining industry, dippel tried to impress people with a chymical recipe for extracting anima tingens from copper to transmute some silver into gold. but if we look at this recipe with the eyes of an chemist, it seems to be very dubious. if you add copper metal to a saltpetre (potassium nitrate kno3) melt, blue-green copper nitrate will be produced, accompanied by red fumes of nitrogen dioxide. copper nitrate can be dissolved in ethanol, but this is also a blue-green solution not a red one. and if we distill off the ethanol from this solution, a blue-green solid will be found, not a red salt. a red copper compound would be copper(i) oxide alexander kraft manuscript for substantia page 22 cu2o, but this should not be produced by the process described by dippel. maybe this is the reason why the swedish bigwigs felt themselves deceived by the chymist dippel. but much more important for dippel’s fate in sweden were the quarrels around his theological writings. their content and the fact that he found a substantial number of followers in sweden led the swedish clergy to work on his extradiction from this country. finally, dippel was forced to go. he left stockholm early in december 1727, and sweden in march 1728. dippel and the tincture made from phosphorus so what about the phosphorus that dippel introduced to graf frölich in sweden? from some entries in the senckenberg diary, from several other documents in the senckenberg collection and from a recipe which was found in the manuscript collection of the state and university library in hamburg it is now established knowledge that dippel wanted to produce the philosophers’ stone from phosphorus. he pursued this idea for more than three decades, from at least 1701 until his death in 1734. dippel’s first acquaintance with phosphorus as a raw material for the production of the philosophers’ stone seems to have been an alleged transmutation in 1701 in frankfurt am main. dippel must have been very impressed. he reported about this to his visitor senckenberg in berleburg in 1732: back then, the projection happened at saltzwedel’s, and he had the laboratory work done at his place ... in phosphoro, ... and that’s what it was supposed to be, ... at that time you could almost smell the operationis ex stercore et urina [operations from feces and urine] in ff. [frankfurt am main] on every street, ... he always had the laboratory workers collect the human feces in baskets.77 according to johann conrad creiling’s (1673-1752) collection of transmutation stories, this transmutation was carried out by a journeyman apothecary named godwin hermann braun from osnabrück in the apothecary shop at the swan in frankfurt in the presence of the owner nikolaus saltzwedel (1651-1726) and other distinguished persons, and “a lead ball weighing 2 lots and otherwise also lead and ☿um turned into good gold with his tincture”. a “principal piece of the tincture” was “phosphorum ... ex regno animali ...”.78 so the tincture for the frankfurt transmutation was made from phosphorus, which in turn was derived from human urine and feces. in the archived collection of senckenberg’s writings and correspondence there is also a “copia of mr. saltzwedel’s process which tinges ♄ in ☉“:79 recipe, 14 bowls of human excrement without urine, put them in the sun so that they get a thick black crust on top, take this off and put it in a flask ... whereupon is a blind helmet, put it in the sun again until you get the spiritum phosphori made from this (which will be so strong that one can light powders with it), with this spiritu extract the tr [tincture] from the crusts, when all is out put the tr in a circulating glass, and leave it well circulating in the ☉ [sun], but then pass it over per alembico, the tr left in fundo tinges ♄ in ☉, but there must be a large phosphorus addition and it must be dissolved in the tr, so that it is in digestion for 4 days, if it is not tinging yet, some phosphoro is to be added until 4 drops transform 1 quint ♄ into good ☉. nb. in may, june, and july the matter must be collected. senckenberg’s copy of a letter from dippel to him takes the same line. senckenberg had noted: alexander kraft manuscript for substantia page 23 author j. c. dippelio / you must know that i still have no other experience with the tincture than from phosphoro with which ☉ or ☽ is dissolved and also sublimated by appropriate manipulations, afterwards dissolved and abstracted in 🜈 rect. and you have an elixir tingens within a few weeks ...80 so there it is, the tincture made from phosphorus! dippel then continued: just because phosphorus requires a lot of effort and trouble and its handling is very dangerous for someone who has not learned the right laboratory techniques well and has not seen them with his own eyes, i have not yet been able to resolve to give part of it, but now i am well provided with it. a corresponding recipe is the “dippelii tinctura universalis” found in the manuscript collection from the hamburg state and university library.81 let’s take a closer look at this process description now: dippel described that at first three preliminary works have to be carried out, namely: i.) to prepare vitriolus martis (iron vitriol = iron sulphate feso4) ii.) to prepare spiritus luminosus and phosphorus in stock, and iii.) to prepare a sublimated regulus antimonis et martis resulting in flores that shine like diamonds. the regulus antimonis et martis should be an alloy of the metals antimony and iron, we also know about iron vitriol and phosphorus, but what is spiritus luminosus? a glowing or shining spirit? if we use the analogy to the early modern terms: spiritus vini = distilled wine = ethanol, spiritus salis = distilled common salt nacl = hydrochloric acid (hcl), spiritus vitrioli = distilled vitriol salt, e.g. feso4 = sulfuric acid (h2so4), spiritus nitri = distilled saltpetre (kno3) = nitric acid hno3, and continue with spiritus luminosus = distilled luminous matter, i.e. phosphorus = phosphoric acid (h3po4)? back to the recipe of dippelii tinctura universalis. figure 8 displays the reaction scheme of this process description. according to this, a.) one part of the ominous spiritus luminosus is mixed with iron vitriol and sublimated to obtain a homogeneous sublimate, then b.) purified phosphorus is dissolved in the second part of the spiritus luminosus and purified by cohobationes, whereby one would obtain a phosphorus liquidus. figure 8: reaction scheme of dippelii tinctura universalis from the hamburg state and university library. alexander kraft manuscript for substantia page 24 what could dippel mean by phosphorus liquidus, a liquid phosphorus? in his chemistry textbook einleitung in die chymie (= introduction into chymistry),82 hieronymus ludolf (1708-1764) also described the production of “liquid phosphorus”, which was said to be of great benefit. he further claimed: “this liquor shines brightly when you rub your hand with it and it doesn’t do you any harm.” of course, this can by no means be real phosphorus, because it causes serious injuries when it comes into contact with the skin. ludolf also remarked: “i haven’t been able to do it yet because of its length, but i think it’s practicable”. at this point, ludolf brought a recipe that he had not yet tried out himself. he had never seen phosphorus liquidus himself, and maybe dippel hadn’t either? the melting point of pure white phosphorus is 44.2°c. if it is contaminated, it may melt at a slightly lower temperature, so that a chymist could easily obtain liquid phosphorus, but of course not with the properties described by ludolf. ultimately, what was meant by phosphorus liquidus at this point in the recipe must remain open. in the next step c.) the phosphorus liquidus should be conjugated with the sublimate obtained under a.), which also results in another homogeneous sublimate. with this d.) “our lead” is dissolved. in addition, it should be noted that the adjective “our” before a substance in the alchemical arcane language of the time often meant that, as in this case, it was not lead, but something else that was then called “our lead” but its actual nature remained open. in step e.) you had to mix this mixture with the diamond flores. a steaming crystall, the menstruum universale would be created. this heated with gold ferment, results in the tinctura universalis. this recipe remains difficult to understand because some intermediate products cannot be identified. this includes the spiritus luminosus and phosphorus liquidus. in the senckenberg collection, too, there are several phosphorus recipes in connection with records of dippel. the process description “de phosphoro” is particularly interesting. this is much more detailed than what has just been discussed and the process is also very different. figure 9 shows the corresponding reaction scheme. figure 9: reaction scheme of de phosphoro from the senckenberg collection. according to this process, phosphorus is produced following the kunckel method from putrefied urine with the addition of sand and purified by rectification (figure 9, left column). the “menstruum universale or the fiery water and watery fire of the philosophers” is then to be produced from this alexander kraft manuscript for substantia page 25 phosphorus (figure 9, 2nd column from the left). for this purpose, “a quint of phosphoro” is gently heated in a glass flask with a helmet in an “ash oven” in such a way that the phosphorus does not over-distills and the vapors “always roll around in the flask”. over time, a “loose matter white as snowflakes” would build up on the bulb wall. this fluffy white matter can be interpreted as phosphorus pentoxide p4o10, which is formed as the phosphorus vapor circulates as a result of the reaction with the oxygen in air. the phosphorus pentoxide is then dissolved in distilled rainwater and some water is distilled from it. one then obtains the "fiery water and watery fire." that’s the recipe. the "fiery water" can be interpreted as a more or less concentrated phosphoric acid solution h3po4 in water. a gold lime was then required, the production of which was described in the section “praeparatio calcis solis” according to the right-hand column in figure 9. in the alchemical literature, gold lime was usually understood to mean very finely distributed gold, not a gold compound, but still elemental, metallic gold.83 to do this, purified gold (“poured through the antimonium”) should be dissolved in aquafort (hno3) to which some salmiac nh4cl was added. nitric acid containing chloride dissolves gold. at a certain concentration ratio, this mixture is also called aqua regia because it dissolves the king of metals, gold. an aqueous solution of venereal vitriol, i.e. cuso4, should then be added to this gold solution, “this is how a beautiful brown-red and very subtle gold limestone precipitates”. it would have to be tested experimentally whether gold is really precipitated. but gold can be precipitated very easily from an acidic solution of gold chloride if a suitable reducing agent is added. in any case, with the “fiery water” and the gold lime, the starting materials for the next process step of the compositio were now available. to do this, one should put one part gold lime and three parts “of the menstruo philosophico or fiery water” in a vial, “melt the glass shut, set it in an athanorum, and let it ... pass through the colors, coagulate and fix into a red stone.” that is probably the philosophers’ stone, the lapis philosophorum. if you compare this entire reaction sequence with other alchemical process instructions for the production of the philosophers’ stone, then the process from urine to the “fiery water” corresponds to the preliminary work for the production of the menstruum universale and the dissolution of the gold lime in the menstruum universale and the subsequent steps of going through the colors in the athanor, coagulating and fixing is the after-work. the multiplicatio and the fermentatio are also briefly mentioned in the process description. the multiplicatio is again typically alchemical, you take the result of the preliminary work, the “fiery water”, three parts and add one part of the result of the after-work, the red stone and let it go through the colors, coagulate and fix. the fermentatio refers to the 12th key of basilius valentinus. in contrast to the hamburg process description, this recipe from the senckenberg collection can be followed and understood in every single step. the question would of course be at which point in the process description the actual chemical reaction is different from the one described. this should be the dissolution of the gold lime in the “fiery water”, for gold does not dissolve in phosphoric acid. there are several other process descriptions in the senckenberg collection that use phosphorus as an important ingredient. however, we have discussed the most important of them. but there are of course other references in original sources that point to the importance of phosphorus for dippel’s chymical path to the philosophers’ stone: among the dippeliana in the archive in bad laasphe we also find a letter by amsterdam apothecary albertus seba (1665-1736) to count august zu wittgenstein from january 1717.84 from this letter we learn that “dippelius” bought 20 ounces of “phosphorus” from seba at a price of 22 guilders per alexander kraft manuscript for substantia page 26 ounce. this price would have been very cheap, wrote seba, and he only sold it so cheaply for his “old friend”. but even at that price, based on weight, phosphorus was more expensive than gold! it is somewhat surprising that dippel as an experienced chymist would have preferred to buy the very expensive phosphorus rather than produce it by himself. dippel himself mentioned phosphorus already in his doctoral thesis vitæ animalis morbus et medicina from 1711: ... the so strange fruit of the noble art of chymistry, namely the so-called phosphorus ... which can be prepared from all liquid parts of the animals by the greatest power of fire, if they have been properly putrefied beforehand. ... this phosphorus, no matter how well it is sealed in the jar and only aroused by the slightest heat, immediately bursts into flames; even if it is held under water, it still does not stop spewing flames and spreading them over the water...85 the latter is not true, because phosphorus burns in air but not under water and is therefore also stored under water. dippel’s chymical experiments in laasphe and berleburg in the two counties of wittgenstein eventually being expelled from sweden, dippel finally returned to germany via copenhagen in mid1728. on the way, dippel had repeatedly received letters from count august zu wittgenstein, who urged him to come to the county of wittgenstein. dippel then replied in a letter dated june 25, 1728 from copenhagen to the count’s representative pagencopen and asked for “100 ducats to my travel”.86 the count would “find contentment for this and for everything else on my arrival” in wittgenstein. the first stop during dippel’s return to germany was the free imperial city of hamburg. in november 1728, dippel wrote to count august zu wittgenstein again, thanking him for the 100 thalers he had sent. from hamburg he went via lauenburg, lüneburg and celle to liebenburg near goslar in the prince-bishopric of hildesheim. a letter dated september 7, 1729 states that dippel stayed there to “complete some chymical experiments on medicine and other curiosities in solitude”.87 when he was finally expelled from the prince-bishopric of hildesheim, dippel went to the counties of wittgenstein, where he arrived in december 1729. a few days after his arrival in berleburg in the county of sayn-wittgenstein-berleburg, a carriage brought dippel from berleburg to laasphe in the county of sayn-wittgenstein-hohenstein. for the first few months of 1730, dippel was a guest of count august zu wittgenstein at the wittgenstein castle near laasphe. however, around mid-april 1730 he returned to berleburg where he stayed the next four years. what has happened, that dippel left his old friend and supporter count august zu wittgenstein? we may find an answer to this in a letter that dippel sent to count august on december 24, 1731 from berleburg: hope with god that the annoyances and criante incidents between your excellence and your subjects were once resolved and brought to a good end, so i could, without hurting my conscience and without angering others, cultivate closer correspondence, and restore the old trust to your excellence.88 alexander kraft manuscript for substantia page 27 and on september 25, 1732 he wrote to count august that he “finds the wittgenstein castle too restless and annoying to advance my affairs there”.89 dippel also said to his young admirer senckenberg: count august in wittgenstein, when he was still in berlin, was much nicer than now, when he lives brutally with his children and harasses his subjects.90 to summarize, dippel rejected the count’s dealings with his subjects. during this time, the count tried to reduce the largely free peasants, who were only obliged to a little forced labor, to the status of serfdom. as a result, the count was widely hated. and that also affected the family, servants and friends of the count. those who worked for him were despised by the population of the county. in the four-year period that now followed, dippel tried to create an opportunity to work out his chymical universal recipe in a suitable laboratory. with count casimir in berleburg, where he now lived, he found no interest in it. he therefore remained in contact with count august zu wittgenstein and also resumed the old contact with his former sovereign, ernst ludwig von hesse-darmstadt (1667–1739), who was known for his passion for hunting and also as a keen alchemist. first, dippel tried to convince count august to finance a laboratory in the small village of schwarzenau, which belonged to the county of sayn-wittgenstein-hohenstein but was closer to berleburg than to laasphe. the negotiations went through august frensdorf (1693–1755), a councilor of the count. in the end, this failed because he asked the count for too much money and because he did not want to reveal too many details of his process to count august. therefore, dippel now turned to the landgrave of hesse-darmstadt. in september 1732, they met in breidenbach in hesse-darmstadt near the border with the counties of wittgenstein.91 the negotiations resulted in various draft treaties. first, johann conrad dippel offered the landgrave his "arcanum chymicum" for 100,000 thaler, to be paid from the income of the work with 5% interest. as the negotiations progressed, dippel gave up the money and now wanted frankenstein castle, where he was born, as a fief for himself and the dippel family. namely “along with all dependencies, subjects and justices”. details about the arcanum were not given in the documents, only that it should yield as much revenue ... as the whole amount when the property should be sold according to the ordinary taxa and this with easy effort, without art and dangerous work, and with the help of only 3 to 4 people. but the landgrave did not agree to this and the project was not carried out. during senckenberg’s second visit to dippel in berleburg in 1732, dippel also showed him “a ☽ regulus, which also contained some gold”.92 he “had dabbed the ☽ underneath with aquafort, there you could see the yellow ☉.”93 dippel also described the corresponding particular process to senckenberg: according to this, 2 parts of mercury with one part of silver and a certain menstruum should be placed in a closed vessel in the fire. from letters94 exchanged between dippel and august zu wittgenstein it becomes clear that this certain menstruum was “olij vitrioli” i.e. concentrated sulfuric acid h2so4. this mixture of mercury, silver and sulfuric acid had to stand in the fire for 14 days. thereafter, the vessel had to be opened and all liquid to be distilled away. now fresh sulfuric acid had to be added to the remaining material and this had to be placed in a closed vessel in the fire again and so on. this process had to be repeated 10 to 12 times until everything would be fixed. dippel thought that during these 140 to 168 days of heating the light and fire principle would move through the vessel walls into the reaction mixture. mercury and oleum vitrioli would help this principle to enter the silver and transform some of the silver into gold. according to dippel as noted by senckenberg, this alexander kraft manuscript for substantia page 28 particular sample of ☽ and ☉ is very lucrative, without much headache, to force ☿ into ☉ and ☽, the yield is more than 200,000 thalers each year, but he doesn’t know how to find a place to do it.95 so we have learned that besides his universal process based on phosphorus dippel also worked in berleburg on a particular process for the transmutation of parts of the silver used into gold. senckenberg also noted about dippel that he offered me that if he had a laboratory and i wanted to be with him for a while, i could do it … when he has set up the laboratorio, i should come to him for a few weeks and leave happy.96 dippel’s death after hesitating for a few years, the 60-year-old dippel finally went to count august at wittgenstein castle in april 1734 to carry out chymical experiments together with the count. he arrived at the castle on april 12, but count august had once again traveled to wetzlar to the german imperial chamber court. dippel began to prepare the planned chymical experiments, but since “the most important praeparata ... were locked away ...” he could not continue the work. was that the phosphorus he couldn’t get hold of during the count’s absence? in the last letter to count august dated april 13, dippel asked august zu wittgenstein to give him or his son count friedrich permission to use these praeparata.97 we do not know of a reply from the count to this letter. twelve days later, early in the morning of april 25, 1734, dippel was found dead in his bed in the living room provided for him. the count, who was still or again staying in wetzlar, was immediately informed of dippel’s death. dippel’s belongings were sealed, his living room locked and a sentry posted in front of it. figure 10: view on laasphe and wittgenstein castle. engraving by matthäus merian (1593-1650) publshed in topographia hassiae, matthäus merians erben, frankfurt am main, 1655. (source: wikimedia commons, https://commons.wikimedia.org/wiki/file:laasphe_de_merian_hassiae_144.jpg , last access 10.4.2023) figure 10 shows laasphe and wittgenstein castle high above the small town. dippel died in the castle and was buried in the town church of laasphe. a few days after dippel’s death, count august zu wittgenstein began to receive letters in which various people to whom dippel owed money were trying to get their money back. these included johannes hummel (1700-1769) from elberfeld and the “protection jew” joseph schmul from marburg. hummel had, as can be seen from the letters, also worked together chymically with dippel. in addition, johann christoph dippel from grünberg, a son https://commons.wikimedia.org/wiki/file:laasphe_de_merian_hassiae_144.jpg alexander kraft manuscript for substantia page 29 of dippel’s younger brother johann albert (1678–1717), reported to the count on behalf of dippel’s heirs. but since dippel also owed the count a lot of money himself, none of the petitioners received anything. on august 27, 1735, about 16 months after dippel’s death, count august david zu saynwittgenstein-hohenstein died at his castle above laasphe at the age of 72. an interesting note from october 1737 can also be found in senckenberg collection.98 it says about phosphorus: “but count zu wittgenstein has several pounds of the same and gives it cheaper” than the phosphorus from the “laboratorio” of godfrey in london, where it was sold at 50 shillings per ounce. since count august had already died in 1735, it must be his son and successor as regent, count friedrich zu saynwittgenstein-hohenstein (1708-1756). perhaps count august had phosphorus produced or bought in larger quantities in order to obtain the philosophers’ stone according to dippel's instructions? and now that both dippel and count august had died, did count friedrich at least try to sell the phosphorus to make some money from it? conclusions many new archival sources connected with johann conrad dippel have been found in the last 15 years. combined with a close reading of some of dippel’s books they give a new account of johann conrad dippel’s life as a chymist. this closes a gap in the research of the biography of this important german theologian, physician and chymist from the turn of the 17th and 18th centuries. we learned that dippel was a chymist with broad range of interests, spanning from recipes for medicines to transmutation processes by use of phosphorus. he also developed his own special chymical theory based on what he called the light and fire principle. this account shall serve as a starting point for the research community to explore the life of this popular figure more deeply to draw an accurate picture of this man and to refute the many wild speculations which are distributed on the internet. references. [1] m. shelley, frankenstein or the modern prometheus, lackington, hughes, harding, mavor & jones, london, 1818. [2] r. florescu, in search of frankenstein, new graphic society, boston, 1975. [3] m. müller, archiv für hessische geschichte und altertumskunde, 2009, 67:367-396. [4] w. scheele, burg frankenstein – eine zeitreise, tredition, hamburg, 2015. [5] anon., conrad dippel, the mad scientist of castle frankenstein, https://knoji.com/article/conraddippel-the-mad-scientist-of-castle-frankenstein/ (last access: 8.4.2023) [6] anon., johann conrad dippel https://www.chemeurope.com/en/encyclopedia/johann_conrad_dippel.html (last access: 8.4.2023) [7] parish register nieder-beerbach, germany, 1672-1764, f. 6. [8] s. goldschmidt, johann konrad dippel (1673–1734), seine radikalpietistische theologie und ihre entstehung, vandenhoek & ruprecht, göttingen, 2001. [9] christianus democritus [j.c. dippel], weg-weiser zum verlohrnen liecht und recht, 2 volumes, n.p., 1704. [10] w.r. newman, l.m. principe, early science and medicine, 1998, 3:32–65. [11] dippel, weg-weiser, vol. 2, p. 6-7. [12] dippel, weg-weiser, vol. 2, p. 7. [13] dippel, weg-weiser, vol. 2, p. 9. [14] dippel, weg-weiser, vol. 2, p. 11. [15] dippel, weg-weiser, vol. 2, p. 11-12. https://knoji.com/article/conrad-dippel-the-mad-scientist-of-castle-frankenstein/ https://knoji.com/article/conrad-dippel-the-mad-scientist-of-castle-frankenstein/ https://www.chemeurope.com/en/encyclopedia/johann_conrad_dippel.html alexander kraft manuscript for substantia page 30 [16] dippel, weg-weiser, vol. 2, p. 27. [17] dippel, weg-weiser, vol. 2, p. 154-5. [18] dippel, weg-weiser, vol. 2, p. 153. [19] dippel, weg-weiser, vol. 2, p. 154. [20] dippel, weg-weiser, vol. 2, p. 132-3. [21] l.m. principe, the transmutations of chymistry. wilhelm homberg and the academie royale des sciences, the university of chicago press, chicago, 2020, p. 172–231. [22] beinecke rare book & manuscript library, new haven, usa, mellon collection of alchemy and the occult, mellon ms 141, fol. 3–7. [23] getty research institute library, los angeles, usa, manly palmer hall collection of alchemical manuscripts, 1500-1825, box 18, ms 102, v. 14, p. 171-180. [24] fürstlich wittgensteinisches archiv (fwa), bad laasphe, germany, folder d40 and p90. [25] landesarchiv nordrhein-westfalen (lanrw), abteilung westfalen, münster, germany, 4.3. fürstentum nassau-siegen, msc. vii, nr. 6507. [26] j.c. kundmann, kurtze abhandlung vom verstande des menschen vor und nach dem falle, david richter, bautzen, 1716, p. 219–221. [27] about professors hoffmann and stahl see: f.p. de ceglia, i fari di halle: georg ernst stahl, friedrich hoffman e la medicina europea del primo settecento, il mulino, bologna, 2009. [28] universitätsbibliothek frankfurt am main (ub ffm), germany, kurtzes verzeichnüß vom gebrauch einiger bewährten artzeneyen, sign.: q 17/822 vol. 1 and 2. [29] v. faßhauer, accessing, editing and indexing large manuscript collections. the selected edition of j. chr. senckenberg’s journals, in: c. wartena, m. franke-maier, e. de luca (eds.), knowledge organization for digital humanities, freie universität berlin, berlin, 2018, p. 31–36. [30] universitätsbibliothek frankfurt am main, germany, observationes in me ipso factae [diaries of johann christian senckenberg] (senckenberg diary), volume 2, p. 406. [31] g.e. stahl, experimenta, observationes, animadversiones, ccc numero, chymicae et physicae, ambrosius haude, berlin, 1731, p. 280-285. [32] a. kraft, bull. hist. chem., 2008, 33:61-67. [33] a. kraft, bull. hist. chem., 2016, 41:1-2. [34] a. kraft, brandenburgisches genealogisches jahrbuch, 2017, 11:101-108. [35] senckenberg diary, vol. 2, p. 406. [36] staatsbibliothek zu berlin preußischer kulturbesitz (stabbpk), berlin, germany, j.e. berger, kerrn aller friedrichstädtischen begebenheiten, berlin ca. 1730, ms. boruss. 4° 124, fol. 16. [37] geheimes staatsarchiv preußischer kulturbesitz (gsta pk), berlin, germany, i. ha rep 9 geheimer rat allgemeine verwaltung d4c fasc 24. [38] gsta pk, fol. 11. [39] gsta pk, fol. 14-15. [40] gsta pk, fol. 13. [41] j.f. mayer, eines schwedischen theologi kurtzer bericht von pietisten, grossens erben, leipzig, 1706. [42] j.c. dippel, unparteyische gedancken über eines so genannten schwedischen theologi kurtzen bericht von pietisten nebst einer kurtzen digression von der brutalität und illegalität des religions-zwangs, laodicea, 1706. [43] gsta pk, fol. 6. [44] gsta pk, fol. 13. [45] l.h. fischer (ed.), johann leonhard frisch. briefwechsel mit gottfried wilhelm leibniz, p. stankiewicz, berlin, 1896. – it has to be noted that this publication does not contain all preserved letters from frisch to leibniz and that some of the letters are only partially printed. [46] transkriptionen des leibniz-briefwechsels 1714 für die leibniz-akademie-ausgabe (überprüft). version 1, hannover 2020. p. 307-310; https://www.gwlb.de/fileadmin/leibniz/repositorium-des-leibnizarchivs/laa-transkriptionen1714-v1.pdf (last access: 12.12.2022). [47] a. kraft, bull. hist. chem., 2009, 34:134-140. [48] y. guari, j. larionova (eds.), prussian blue nanoparticles and nanocomposites: synthesis, devices and applications, pan stanford publishing, singapore, 2019. [49] v.d. ivanov, ionics, 2020, 26:531-547. [50] a. kraft, ionics, 2021, 27:2289–2305. [51] staatsund universitätsbibliothek hamburg (subhh), germany, cod. alchim. 580, fol. 12r-13r. [52] senckenberg diary, vol. 2, p. 363. https://www.gwlb.de/fileadmin/leibniz/repositorium-des-leibniz-archivs/laa-transkriptionen1714-v1.pdf https://www.gwlb.de/fileadmin/leibniz/repositorium-des-leibniz-archivs/laa-transkriptionen1714-v1.pdf alexander kraft manuscript for substantia page 31 [53] w.n. du rieu (ed.), album studiosorum academiae lugduno batavae, martinus nijhoff, den haag, 1875, p. 820. [54] lanrw, letters no. 16-22. [55] notary johan bosch, utrecht, netherlands, deed of 24.06.1719, het utrechts archief, inventory number u146a002, file number 343. [56] notary johan kruyder, utrecht, netherlands, deed of 08/23/1723, het utrechts archief, inventory number u154a003, file number 9. [57] christianus democritus [j.c. dippel], vitæ animalis morbus et medicina, officina luchtmanniana, leiden, 1711. [58] christianus democritus [j.c. dippel], kranckheit und artzney des animalischen lebens, annotated and with an appendix by anon., johann leopold montag, regensburg, 1736. my citations from vitæ animalis morbus et medicina are all from this edition. [59] dippel 1736, p. 194-198. [60] dippel 1736, p. 199-200. [61] dippel 1736, p. 206. [62] dippel 1736, p. 53. [63] lanrw, letter no. 16. [64] archiv der franckeschen stiftungen zu halle (saale), germany, afst/h a 188b, fol. 30b [65] t. wotschke, mecklenburgische jahrbücher, 1931, 95:103–142. [66] w. rustmeier, schriften des vereins für schleswig-holsteinische kirchengeschichte r. ii, 1957, 15:91116. [67] christianus democritus [j.c. dippel], eröffnete muhtmassungen und merckwürdige gedancken über herrn jacobs von melle … commentatiunculam de simulacris aureis &c., johann georg piscator, hamburg, 1725. [68] senckenberg diary, vol. 2, p. 357. [69] fwa, d40, fol. 24-26. [70] h. kofod, bornholmske samlinger, 1964, 1:27–41. [71] senckenberg diary, vol. 2 p. 385. [72] d. fassmann, leben und thaten des allerdurchlauchtigsten und großmächtigsten königs von schweden friederich landgrafens zu heßen caßel, wolfgang deer, frankfurt am main, 1736, p. 959. [73] a. acton, emanuel swedenborg, a study of the documentary sources of his biography, covering the period of his preparation, 1688-1744, academy of the new church, bryn athyn, 1958, p. 329. [74] acton, swedenborg, p. 329. [75] e. swedenborg, regnum subterraneum sive minerale de cupro et orichalco, friedrich hekel, dresden, 1734, p. 339-340. [76] d.j. wallich, das mineralische gluten, doppelter schlangenstab, mercurius philosophorum, langer und kurtzer weg zur universal-tinctur, joh. heinichens witwe, leipzig, 1705, p. 97-116. [77] senckenberg diary, vol. 2, p. 384. [78] j.c. creiling, die edelgeborne jungfer alchymia, , tübingen, 1730, p. 137–138. [79] ub ffm, na 31 nachlass johann christian senckenberg, 183 aufzeichnungen zu chemischen prozessen, na 31, 183, fol. 71r. [80] ub ffm, na 31 nachlass johann christian senckenberg, 183 aufzeichnungen zu chemischen prozessen, na 31, 183, fol. 31. [81] subhh, cod. alchim. 763, fol. 246. [82] h. ludolf, einleitung in die chymie, joh. heinr. nonnen, erfurt, 1752. [83] c. priesner, k. figala (ed.), alchemie. lexikon einer hermetischen wissenschaft, c.h. beck, munich, 1998, p. 191. [84] fwa, p90, fol. 57. [85] dippel 1736, p. 114-115. [86] fwa, d48, fol. 38–39. [87] anon. (ed.): eröffneter weg zum frieden mit gott und allen creaturen durch publication der sämtlichen schrifften christiani democriti, volume 3, johann jacob haug, berleburg, 1747, p. 631–633. [88] fwa, p90, fol. 14. [89] fwa, p90, fol. 9–10. [90] senckenberg diary, vol. 2, p. 349. [91] w. diehl, neue beiträge zur geschichte johann konrad dippels in der theologischen periode seines lebens, in: beiträge zur hessischen kirchengeschichte, erg.-band 3, darmstadt 1908, p. 162–163, 183– 184. alexander kraft manuscript for substantia page 32 [92] senckenberg diary, vol. 2, p. 349. [93] senckenberg diary, vol. 2, p. 423. [94] fwa, d48, fol. 49 and fwa, p90, fol. 15–17. [95] senckenberg diary, vol. 2, p. 349. [96] senckenberg diary, vol. 2, p. 426, 428. [97] fwa, p90, fol. 21–22. [98] ub ffm, na 31 nachlass johann christian senckenberg, 183 aufzeichnungen zu chemischen prozessen, na 31, 183, fol. 34r. 1 enzo ferroni (1921-2007): the history of an eclectic chemist luigi dei dipartimento di chimica “ugo schiff”, università degli studi di firenze, via della lastruccia, 13, 50019 sesto fiorentino (fi), italy email: luigi.dei@unifi.it, url: https://www.unifi.it/p-doc2-0-0-a-3f2a3d2b34282a.html received: feb 17, 2023 revised: may 2, 2023 just accepted online: may 3, 2023 published: xxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: l. dei, (2023) enzo ferroni (1921-2007): the history of an eclectic chemist. substantia. just accepted. doi: 10.36253/substantia-2055 abstract. enzo ferroni (florence, 25 march 1921 – 9 april 2007) was an italian chemist, full professor in physical chemistry at the university of florence, where he served as rector from 1976 to 1979, a renowned international scientist who initiated a new branch of chemistry, that applied to cultural heritage conservation. the history of his scientific and academic life offers a particular interest in a half-century cross-section of the history of chemistry in italy and the entire world. in particular, ferroni developed the colloids, surface, and interface chemistry in italy immediately after the second world war in a country where it was almost non-existent, sensing the extraordinary potential of this branch of chemistry in the fields of basic and applied research. this paper aims to reconstruct the history of this eclectic chemist starting from his pioneering studies in italy on colloids, surfaces, and interfaces that, after the second world war, came to be widely popular within the international scientific literature following three milestones represented by the studies of the nobel laureates in chemistry, richard a. zsigmondy (1925), theodor svedberg (1926), and irving langmuir (1932). enzo ferroni’s far-sighted and visionary ideas concerning the investigation of these systems and others with biological implications by the nascent resonance spectroscopies and surface diffraction techniques were recognised and underlined as the revolutionary approach by ever more sophisticated instrumentations that were to characterise chemistry research to this day. the consecration of the extraordinary potential and peculiarities of colloids, surfaces, and interfaces would come to fruition in 1991 with the nobel laureate in physics pierre-gilles de gennes, who finally discovered that “the methods developed to study ordinary phenomena in simple systems can be generalised to more complex states of matter, especially liquid crystals, and polymers” (official motivation of the prize), recognising soft matter as a peculiar form of matter in the condensed phase. these pioneering frontiers in the newly established soft matter field can be considered ferroni’s last message in the bottle to young researchers facing the twenty-first century. the eclecticism of this chemist emerged from two other compelling aspects that are illustrated in this article: the chemistry for cultural heritage that ferroni mailto:luigi.dei@unifi.it https://www.unifi.it/p-doc2-0-0-a-3f2a3d2b34282a.html 2 conceived, pushed by the dramatic damages suffered by the works of art after the florence flood in 1966, and his strong vision about the equal dignity of basic and applied research, that led him to establish fruitful relationships with industries aimed to enhance technological fallouts, as the research by the nobel laureates in chemistry (1963) giulio natta and karl ziegler had clearly shown. keywords: history of 20th-century chemistry, colloids, surfaces and interfaces, chemistry for cultural heritage conservation, fundamental and applied research, soft matter. 1. introduction from the vantage point of the second fifth of the 21st century we have the possibility to look at the history of science of the second half of the 20th century with the eyes of the science historian, considering that all the discoveries made after the end of the second world war until the beginning of the new century can be considered as sufficiently sedimented to re-evaluate them in a historical perspective.1 the advance of science and technology in every field during such period was tremendous, and the people devoted to its progress have exponentially increased. every discipline underwent an extraordinary multiplication of specialisations; simultaneously, science and technology had the need to be increasingly more multiand inter-disciplinary. moreover, science and technology started to create bridges towards human and social sciences in a sort of total globalisation of knowledge. in this frame, many scientists in every part of the world substantially increased their cooperation and research groups in different countries developed the various topics of each discipline, creating centres of excellence able to attract young scholars interested in the progress of science and technology. in this context, italy was a noteworthy case since it emerged from twenty years of darkness characterised by the totalitarian fascist regime with all the consequences for the freedom of research and teaching. until the end of the second world war the biggest advances in science were mainly prerogative of the united states of america, germany, and united kingdom: as an example, italy had earned only two nobel prizes in physics (enrico fermi, 1938; guglielmo marconi, 1919) and one in medicine or physiology (camillo golgi, 1906), whereas three great writers received the nobel prize in literature (giosuè carducci, 1906; grazia deledda, 1926; luigi pirandello, 1934).2 chemistry had lived through a less prosperous period with respect to the glorious 19th century, where the giants amedeo avogadro3 (turin, 1776-1856), stanislao cannizzaro4 (palermo, 1826 – rome, 1910), and raffaele piria5 (scilla, 1814 – turin 1865) had dominated the world scenario.6 indeed, some important chemists worked in italy in the first half of the 20th century: among them we can include giacomo ciamician7 (trieste, 1857 – bologna, 1922), nicola parravano8 (fontana liri, 1883 – fiuggi, 1938), emanuele paternò9 (palermo, 1847 – 1935), raffaello nasini10 (siena, 1854 – rome, 1931), and mario betti (1875 – 1942),11 but nobody succeeded in gaining the same great renown as the italian school of physics: the first nobel prize in chemistry – still the only one – will arrive in 1963 with giulio natta (porto maurizio, 1903 – bergamo, 1979).2 due to the proximity of the second half of the 20th century with our times, apart from the nobel laureate giulio natta,12 the literature is quite scarce about chemists who have lived and worked in this period: as examples, we recognize interesting papers on giovanni battista bonino (genoa, 1899 – 1985)13, massimo simonetta (pella, 1920 – milan, 1986),14 adolfo quilico (milan, 1902 – 1982),8 giovanni canneri (montelupo fiorentino, 1897 – florence, 1964),7,8 lamberto malatesta (milan, 1912 – 2007),15 piero pino (trieste, 1921 – milan, 1989),16 eolo scrocco (tivoli, 1916 – rome, 2012).17 3 since the present paper aims to report and discuss the work of the academic chemist enzo ferroni (florence, 1921 – 2007), it seemed worthwhile to frame the scenario where he carried out most of his scientific activity, that is, the university of florence. after the end of the second world war, chemistry in italy presented six main branches: analytical, industrial, inorganic, organic, pharmaceutical, and physical; inside each of these broad sub-disciplines, there were some specialisations within which, during the following decades, some important centres of excellence developed. at the university of florence, inorganic chemistry took the path of coordination chemistry thanks to work initiated by luigi sacconi (santa croce sull’arno, 1911 – florence, 1992).18 as far as organic chemistry is concerned, the path set by angelo angeli (tarcento, 1864 – florence, 1931)8,19 and adolfo quilico (milan, 1902 – 1982)8,19 who moved to the politecnico di milan in 1943, was followed by giovanni speroni (florence, 1910 – 1984).8,19 analytical chemistry was led by the already mentioned giovanni canneri. in contrast, pharmaceutical chemistry had two key scientists, sergio berlingozzi (montevarchi, 1890 – fiesole, 1957) and mario torquato passerini (casellina e torri, now scandicci, 1891 – florence, 1962).8,19 industrial chemistry started to develop precisely in the period subject of the present study thanks to the work of franco piacenti (florence, 1927 – 2002).20 the chair of physical chemistry, the discipline that enzo ferroni selected for his chemistry master’s degree thesis, was held by giorgio piccardi (florence, 1895 – riccione, 1972), a significant italian scientist, though for some aspects quite controversial.21 enzo ferroni defended his chemistry master’s thesis (from now on, it will be used for this title the verb to graduate) in 1945 magnum cum laude, under the supervision of giorgio piccardi. the title of his work was “recent advances and opinions on chemical kinetics” .23 starting from this first research, enzo ferroni began a long academic career that allowed him to open many new research fields in physical chemistry that the time will reveal being characterised by the strong impact on the history of chemistry. this paper aims to reconstruct the milestones of the academic life of this scientist, individuating the five topics which demonstrate the remarkable visionary capacity of this man to open new horizons in his field of research, creating research paths that nowadays appear normal and foregone but that at the time of ferroni’s work were completely uncharted and for which it was impossible to foresee the success they would have. by initially looking at his pioneering studies on colloids, surfaces, and interfaces, the present study is devoted to following how ferroni sensed the importance of the nascent resonance spectroscopies and surface diffraction techniques, the fruitful relationship between chemistry and cultural heritage conservation, the new frontiers in soft matter, and the strategic role played by applied chemistry, technology, and industry. finally, the study aims to show that some of the most current topics in chemistry, such as supramolecular chemistry, self-assembly, nanoscopic world, nanomaterial chemistry, scientific diagnostics in cultural heritage conservation, and soft matter, were already outlined in the studies and research enzo ferroni designed and carried out. 2. the beginning: colloids, surfaces, and interfaces ferroni started his research activity at the beginning of the second half of the 20th century: indeed, his first two articles23, 24 clearly showed the direction he wanted to pursue, i.e., physical chemistry of colloids, surfaces, and interfaces. one of these systems' most peculiar physical properties is surface tension, which became the first topic on which ferroni focused his attention and desire to deepen his knowledge. ferroni intuitively knew that the works by three nobel laureates in the chemistry of the last decades, namely, richard a. zsigmondy (1925), theodor svedberg (1926), and irving langmuir (1932)2 could be fundamental milestones and the basis for a new branch of physical chemistry in italy. in particular, he read with great curiosity and interest langmuir’s papers,25-53 from which the crucial and peculiar role of the solid-liquid, solid-gas, solid-vacuum, and liquid-gas interfaces emerged, indicating that surface chemistry was fundamental in determining the physicochemical mechanisms of a vast multitude of phenomena. 4 at the beginning of his research career, ferroni was attracted by the liquid-gas interface. his attention was focused on measuring the surface tension of many liquid systems in static or dynamic conditions.54-58 these first studies were also the result of the interaction with the group of raymond defay (anderlecht, 1897 – brussels, 1987)59 and ilya prigogine (moscow, 1917 – brussels, 2003)60 at the université libre de bruxelles with whom ferroni had collaborations, even spending time at their laboratories in brussels. indeed, during these years, ferroni’s scientific activity converged with the studies of these two great scientists, as proved by the subject of some of their publications61-66 focused on surface tensions of many different liquid systems. moreover, the proof of these relationships is given by correspondence dated some years later, also denoting a friendship, from which we report, in figures 1 and 2, two letters (from raymond defay to ferroni and from ferroni to maria prokopowicz prigogine, the second wife of ilya prigogine) coming from ferroni’s archive.67,68 the research on the liquid-gas (air) interface was immediately extended to the bulk of the liquid that contained surfactants to investigate critical micellar concentration,69,70 polymerisation,71,72 electrophoresis,73 aggregation phenomena,74,75 and equilibrium constants and complex formation.76,77 following the path traced by langmuir, ferroni continued his pioneering work for building a school of colloids, interfaces, and surfaces in italy, extending his studies to monomolecular films at the liquid-gas interfaces but also starting to explore solid-gas and solid-solid interfaces. his attention was concentrated on polymorphisms at the interface,78-81 monoand multilayers of organic substances,82,83 adsorption onto solid surfaces,84 solid → gas reactions,85 and epitaxy.86,87 figure 1. letter by raymond defay, université libre de bruxelles, to enzo ferroni dated 8 november 1965. “my dear colleague, i received your letter dated 25 october, and i am surely interested in your experiments on phase transitions in adsorption films. unfortunately, i have no experience dealing with high molecular weight polymers in solution. therefore, i am not certain i will be able to elucidate your doubts, but i am happy to try and ponder on it if you state exactly the precise question. i will be quite occupied with many commitments until the end of january. after this date, i hope to have enough time for a deep and serious reflection. please accept, my dear colleague, my best regards, yours sincerely, raymond defay”. (translation by the author). 5 ferroni’s intense work resulted in a remarkable scientific impact in the physical chemistry of condensed phases following the research lines of two great schools, that of irving langmuir at general electric company laboratories, schenectady, usa, and of raymond defay and ilya prigogine at the université libre de bruxelles, and allowed him to gain the chair – full professor in physical chemistry – at the university of cagliari in 1961 presenting 85 scientific publications,88 including three articles on the journal of physical chemistry,76 the journal of the american chemical society,84 and nature. 79 in 1965, he succeeded in gaining the same chair at the university of florence, faculty of mathematical, physical, and natural sciences, where he remained until his retirement in 1996, becoming emeritus the subsequent year. during the years spent at the university of florence, he was director of the institute of physical chemistry (1965 – 1968), dean of the faculty of mathematical, physical, and natural sciences (1968 – 1971), rector (1976 – 1979), and head of the chemistry department (1983 – 1985).89 from 1961 until the end of 1965, when he returned to the university of florence, he continued his activity in cagliari90-99 cultivating his pupils enzo tiezzi (siena, 1938 – 2010) and gianfranco rovida (rome, 1939), who followed him at the university of cagliari after getting their chemistry master’s degree at the university of florence in 1963 under the supervision of the young colleague giulio g. g. t. guarini (forlì, 1932 – florence, 2015). another pupil of ferroni’s, older than rovida and tiezzi, was gabriella gabrielli (cortona, 1930 – florence, 2022), who had already published many papers with ferroni.55-57, 74-76, 79-81, to the same team, even though not his pupils, belonged silvano bordi, almost a peer of ferroni’s (florence, 1922 – 1995) and rolando guidelli (florence, 1938) who, taking inspiration from the school of large interface systems founded by ferroni, would go on to develop the physical chemistry of surfaces and interfaces in electrochemistry.89 6 figure 2. draft of a letter by enzo ferroni to maria prokopowicz prigogine, the second wife of ilya prigogine. “dear madame, i wrote you just one year ago that i was improving (fine-tuning) some research on phase transitions in adsorption films, carried out following some remarks about the “molecular polymorphism” that grabbed your attention. during this time, i have obtained several experimental results and i am going to put them in a good correlation frame to draw some concluding considerations able to explain this phenomenon clearly. i have just written to professor defay, whom i have known for a long time, asking for his comments and suggestions. i shall inform you without delay to ask for your much appreciated opinion if you would. please accept, madame, and extend my best regards to your husband, professor i. prigogine and m.me saraga. yours sincerely, enzo ferroni”. (translation by the author). the path was then traced during the two decades 1950-1970, and the consecration and consolidation of the italian school on colloids, interfaces, and surfaces founded by ferroni came in 1993 (vide infra) with the foundation of the italian centre for colloids and surfaces (consorzio interuniversitario per lo sviluppo dei sistemi a grande interfase, csgi) which is still active. enzo ferroni was its president from the foundation until his death in 2007; its director for over 25 years was piero baglioni (florence, 1952), who graduated in chemistry under the supervision of ferroni in 1977, with the dissertation “membranes selectively permeable to gases”. baglioni succeeded in continuing the legacy and of his maestro, leading the csgi to become a centre of excellence highly regarded all over the world.99 3. the advent of resonance spectroscopies and surface diffraction techniques when ferroni returned to his hometown, he found a group of young scientists, partly pupils of his, partly of other colleagues at the university of florence: the first group included the already mentioned gabrielli, guarini, rovida, and tiezzi; in the second one he found bordi and guidelli; and finally in the third giorgio taddei (florence, 1935 – 2019), mario pio marzocchi (arezzo, 1935). a few years later, giacomo martini (pistoia, 1943 – quarrata, 2012), another chemist, albeit not one of his pupils, joined ferroni’s team. as soon as he got back to the university of florence on 15 december 1965, ferroni took over the direction of the institute of physical chemistry88, 89 and, strengthened by his experience at the university of cagliari where he held the first chair in italy of physical chemistry of colloids and interfaces in the academic year 1963-1964,88 put together a group of scientists devoted to the physical chemistry of colloids, surfaces, and interfaces. he had already constituted the first seed during 1950-1961, writing some papers with gabrielli and directing his pupil guarini to investigate solid interfaces. still, on his return to florence at the end of 1965, he had his second great visionary idea, partly generated by a fortuitous case (vide infra), sowing the seed for a novel approach to the physical chemistry of large interface systems by exploiting the unique potentialities of the nascent resonance spectroscopies and surface diffraction instrumental techniques. indeed, ferroni had already perceived the importance of the spectroscopic approach when he published two papers with marzocchi100, 101 studying halogen-amine interactions by infrared spectroscopy, but he had not yet in mind, immediately after the graduation of tiezzi and rovida, what topics could represent some new research lines in the field of colloids and surfaces. the fortuitous case originated the research line dealing with nuclear magnetic resonance (nmr) and electron paramagnetic and spin resonance (epr/esr) spectroscopies, while the second idea was associated with the subject of surface diffraction techniques. tiezzi and rovida, after graduating in chemistry in 1963, became ferroni’s assistants at the university of cagliari where they remained until 1965 – tiezzi – and 1966 – rovida –, and participated with him in the 20th international iupac congress in chemistry held in moscow on 12 18 july 1965. figure 3 shows ferroni and tiezzi at the congress discussing with the russian chemist and physicist boris vladimorovič derjagin (1902 – 1994), one of the world’s most prominent scientists in the field of colloids and surfaces. 7 figure 3. photo taken during a coffee break at the international iupac congress of chemistry, moscow, 12-18 july 1965: from left to right enzo ferroni, enzo tiezzi, and boris vladimorovič derjagin. but ferroni was also always eager to hire promising young researchers besides his pupils and consequently, when back to florence, selected leo burlamacchi (viareggio, 1933), a 1960 graduate from the university of pisa, to work as a pioneer in the field of epr/esr. indeed, burlamacchi, as a graduate worked some years in the industry, and in 1965 he attended the laboratories at the national council of research, institute on microwaves in florence, founded and directed by the distinguished physicist nello carrara (florence, 1900 – 1993).102 in these laboratories, two instruments were built for epr/esr and nmr measurements. still, nobody used them since no chemists – the principal users of such apparatuses for physicochemical characterisation – were present there at that time. therefore, burlamacchi had been involved in scientific investigations using these two emerging techniques. ferroni, consulted by director carrara, immediately found a fellowship for burlamacchi, entrusting him with opening new research frontiers. he suggested creating a couple of young researchers – burlamacchi and his pupil tiezzi – to introduce epr/esr and nmr techniques to the florence research group on colloids and surfaces. the first papers103-107 showed that exploring these new frontiers of physicochemical research was possible. it is worth recalling that tiezzi taught at the university of cagliari102 when ferroni held the chair of physical chemistry there. even after ferroni’s transfer to florence in december 1965, tiezzi continued his activity at the university of cagliari. ferroni himself suggested to enzo tiezzi to spend one year in the united states to deepen his knowledge of resonance techniques: indeed, during 1966 and 1967, tiezzi worked in the laboratories of the university of washington in st. louis, department of physics under the supervision of samuel i. weissman (1912 – 2007) with a fulbright scholarship, developing the use of electron spin resonance, and then as post-doctoral research associate, at the department of botany and centre for the biology of natural systems of the same university under the supervision of barry commoner (1917 – 2012), further refining his skills in the field of magnetic resonance spectroscopies. in particular, tiezzi started to explore the possibility of using resonance spectroscopies in biology and medicine.102,108 tiezzi would always be deeply grateful to ferroni, stating several times that he considered ferroni his mentor since the academic year 1957-1958 when he attended his lectures on fundamentals of chemistry 2nd course at the university of florence.102 when tiezzi returned to florence, he was ready to carry out fundamental research using esr/epr and nmr spectroscopies collaborating with burlamacchi and, from 1967, with the young martini (see above).109-114 after the florence flood, in 1967, ferroni obtained funds to buy the epr/esr instrument from varian that was placed at the institute of physical chemistry of the university of florence in the city centre, via gino capponi, 7-9. tiezzi would become a full professor in physical chemistry at the university of siena in 1979 and one of the most distinguished scientists in the world developing, the first in italy, the concept of sustainability together with other scientists from across the globe. burlamacchi became a full professor in 1980 at the same university of cagliari that twenty years before had welcomed ferroni. 8 this research line was pursued for many years with the contribution of other people, among which the already mentioned baglioni, maurizio romanelli (florence, 1943) and maria francesca ottaviani (florence, 1951; later sandra ristori (florence, 1960) also joined the team. the research was developed in collaboration with larry kevan (1938 – 2002) at the chemistry department of the university of houston. many papers were published over several years, finally extending their scope to large interface systems, as it was in ferroni’s mind.115-139 it is worth mentioning that ferroni appeared only a few times as co-author of these studies of which he was a staunch supporter: we recognise in this behaviour both a commendable generosity and a habit of mind diametrically opposed to what one might imagine in the common sense of the university barony, and intellectual honesty, since ferroni was aware that he had no skills in resonance techniques when he suggested to burlamacchi to start his adventure with epr/esr and to tiezzi with nmr. the fortuitous case allowed ferroni to meet nello carrara and leo burlamacchi and to create the conditions for the subsequent development of resonance techniques in the florence colloids and surfaces group headed by ferroni. the second route associated with his visionary idea to apply new instrumental techniques to colloids and surfaces studies dealt with surface diffraction techniques. ferroni set the goal to understand atomic and molecular mechanisms at the basis of gas adsorptions on well-characterised surfaces, namely {hkl} metal monocrystal faces. to realise this objective ferroni encouraged his pupil rovida to spend some months in paris at trillat’s laboratories (vide infra) to ascertain whether the technique of reflection of high energy electron diffraction (rheed) under grazing incidence was able to reach the goal or not. rovida’s trials did not produce reliable results. indeed, ferroni was fascinated by the concept of understanding atomic and molecular mechanisms at the basis of gas adsorptions onto solid surfaces. when he was back at the university of florence, ferroni had the opportunity to read a brochure illustrating that, thanks to the ultra-high-vacuum instrumentation supplied by varian associates, it had become possible to build instrumentations able to collect reproducible and well-interpretable low energy electron diffraction (leed) patterns. ferroni was impressed by the brochure's content, which illustrated this innovative technique's impressive power to study all the phenomena at the solid-vacuum interface, especially to deepen the gas adsorption mechanisms onto well-characterised solid surfaces, namely well-defined crystallographic faces. the future nobel prize in chemistry (2007) gerhard ertl (stuttgart, 1936) was involved in these studies, and two years later he published a ground-breaking article that opened vast horizons for surface science studies.140 ferroni grasped the opportunity and gave rovida the brochure asking his opinion about the new leed instrumentation. the answer was positive and a new and fascinating challenge started. ferroni obtained funds to order the leed apparatus, which arrived in the autumn of 1966. still, it had to remain at the customs offices for several months due to the florence flood (vide infra) that had damaged the institute of physical chemistry of the university. finally, during the spring of 1967, the leed instrument arrived, was installed, and in a short time, the first two articles on surface studies by leed from the university of florence institute of physical chemistry were published.141, 142 once again, the path was open thanks to a scientist who constantly desired to see farther, to guide his pupils, but simultaneously leave them free to unleash their talents and abilities without undue pressure or need for complacency and flattery towards him. in the following years, the group that welcomed ermanno zanazzi, marco torrini, ugo bardi and andrea atrei gradually came to be headed by rovida and published many important papers,143-157 establishing international cooperations, among which the most meaningful was that with gabor a. somorjai (1935), university of california, berkeley.158, 159 4. florence flood (1966): chemistry and cultural heritage conservation as it is well known160 the dramatic event of the florence flood on 4 november 1966, caused a great echo across the world, mainly because of the extensive damages suffered by the exceptional concentration of cultural heritage present in the city. this echo is well condensed in the book dark water by robert clarke: “there is florence and there is firenze. firenze is the city where the citizens of the capital of tuscany live 9 and work. florence is the place where the rest of us come to look.” 160 ferroni had been back in florence for just a year and he was immediately involved with all his other colleagues in rescuing damaged instrumentations, books, documents, chemicals, laboratory glassware from the chemistry institutes (see figure 4) in the centre of the city where the arno’s water reached ca. 1 m of height. after the emergency of the first few days, it appeared clear that the damage to the works of art was vast, especially for the wall paintings that could not be removed. ferroni understood that a scientific approach was essential to help in solving the myriad of problems that conservators and cultural heritage officials encountered. during those frantic days ferroni was able to invent two different methodologies and simultaneously inaugurate a new epoch for conservation and restoration, the scientific approach and the continued and constant integration between art history, conservation, science and specifically chemistry.161 figure 4. enzo ferroni rescuing some laboratory glassware from the cellars of the chemical institutes of the university of florence some days after november 4, 1966. the first dramatic emergency came from the rapid deterioration of the fresco l’ultima cena (the last supper) by taddeo gaddi (ca. 1300 – 1366) in the refectory of santa croce basilica. after the waters receded the consequent salt efflorescence due to nitrates was rapidly causing the colour to fall off the wall. this masterpiece was literally vanishing before the anxious eyes of the experts. the only solution was to urgently detach the fresco from the wall and transfer it onto another suitable support. unfortunately, the detachment was made impossible due to the very high nitrates concentration into the water impregnating the porous structure of the wall. this high ionic force inhibited the sol → gel transition of the animal glue solutions used to impregnate both the paint surface and the canvases onto which, after the gelation of the animal glue, the painting layers would have had adhered allowing the detachment of a few microns of pictorial mortar. the situation was desperate; each day that went by, the coloured powder was found at the feet of the fresco. ferroni remembered some of his studies96, 162 where he had demonstrated that tributyl-phosphate (tbp), an organic compound almost insoluble in water (only 6 g/l at 20 °c)163 and with very low surface tension (27.79 mn/m at 20 °c),163 forms monomolecular films onto nitrates water solution 10 with an average molecular area depending on the cations, due to the formation of the different complexes at the water-air interface. he thought that wetting the wall surface with tbp would lead to monomolecular films spread onto the aqueous nitrate solution layers, which adhered to the solid particles of both the mortar and the pigments, besides filling the wall pores. in a way, he prefigured that in this manner, the whole exposed surface of the first layers of the wall would become highly hydrophobic due to tbp, forming a sort of impermeable film that would prevent the migration of the ions coming from the nitrates into the animal glue solution, which therefore would be able to gel and allow the subsequent detachment.164, 165 the various experts were very sceptical about this hypothesis, and ferroni replied as isaac newton: “hypotheses non fingo, please try!” the trial was carried out by the restorer dino dini on a small portion of a less famous fresco by jacopo ligozzi (ca. 1547 – 1627) and the result was astonishing: the glue set, and the small portion could be easily detached. the whole fresco by gaddi was then subjected to the same treatment, detached, and repositioned in the same place onto appropriate support. it is still there in good health: it was an actual rescue rather than a restoration or conservation intervention. without this most significant and brilliant idea by the chemist ferroni, we would not be able to admire this wonderful work of art now. the second critical question about wall painting damage was the worsening of the degradation by a process called sulphatisation.166 the transformation of the binding caco3, formed by the setting of lime, into gypsum (caso4.2h2o) resulted in a severe deterioration of the painted surface with formation of white patinas, crusts, powdering, and other dangerous pathologies that compromised both the reading and the stability of the pictorial surface: it was evident that the flood had visibly accelerated this phenomenon. again, ferroni activated his brilliant and eclectic mind and proposed to re-convert gypsum into caco3 by using ammonium carbonate followed by a barium hydroxide treatment. to ascertain whether this chemical approach was effective in recovering a readable and compact painting surface, ferroni remembered both his time at the cnrs laboratoire de diffraction des rayons x at bellevue in france and the correspondence167 with its director jean jacques trillat (paris, 1899 – versailles, 1987). trillat was a very distinguished scientist with expertise in colloids and interfaces. in 1956 he authored a fundamental book168 and precursor of the studies that would be developed in italy by ferroni, such as those on molecular layers of fatty substances on metals.169 reflecting on these memories, ferroni and co-workers measured the reconversion of gypsum to caco3 using ammonium carbonate and subsequent barium hydroxide treatment by x-rays diffraction (xrd) using an apparatus invented by trillat and reconstructed at the institute of physical chemistry of the university of florence.170 the results were extremely encouraging since the xrd patterns were in agreement with a total reconversion (see figure 5). the successive application on the wall painting san domenico in adorazione del crocifisso (st. dominic in adoration of the crucifix) by beato angelico (ca. 1395 – 1455) at the san marco convent in florence showed excellent results, not only in terms of reconversion but also in firmly consolidating the painting surface and the thin layers of mortar (intonaco) underneath.171 during the subsequent years and up to the present day, this technique became the legacy of wall painting conservators worldwide. it was named the ferroni-dini method after the chemist inventor and the conservator who devised and applied the procedure.172-178 11 figure 5. enzo ferroni close to a flow chart recorder during the collection of xrd to ascertain the mechanism of the frescoes' sulphatisation and the reconversion to calcium carbonate thanks to the treatment with ammonium carbonate followed by barium hydroxide, the so-called ferroni-dini method. ferroni’s passion for connecting science and art continued throughout his life, and several other studies testified to the outstanding contribution this chemist made to the world of cultural heritage conservation: autogenous lime-based grouts179-181 and oil-in-water microemulsions182-185 used for the conservation of wall paintings by masaccio (1401 – 1428) in the brancacci chapel164, 165, 186-188 in florence, the role of the deliquescent salts189, 190 for the deterioration of the wall paintings of la leggenda della vera croce (the legend of the true cross) by piero della francesca (ca. 1412 – 1492) in the san francesco basilica in arezzo,191 the chemical stability of some pigments192 or solvents193 used for cleaning pictorial surfaces, until his last intuition about a possible role of nanoscience and nanotechnology194-199 for a revolutionary approach to conservation and restoration. ferroni had been convinced ever since that the studies dealing with the physical chemistry of colloids and interfaces with potential applications for cultural heritage conservation had to be considered on par with traditional physicochemical papers. towards the end of his long career, he received a prestigious award when the journal named after the scientist that was ferroni’s inspiration, irving langmuir, decided to dedicate the cover of its 26th issue of 1999, published on 1 december to a photo illustrating the damage done by salt efflorescence in wall paintings. the image was the damaged face of christ in the last supper by taddeo gaddi, which ferroni had rescued about thirty years before. the article200 was penned, among others, by two of ferroni’s pupils, piero baglioni and the author of the present article. subsequently, many renowned international journals accepted papers on the physical chemistry of colloids and interfaces devoted to bringing a contribution to the improvement of cultural heritage conservation and sometimes dedicating again their covers201: enzo ferroni’s challenge was definitively won at the beginning of the 21st century, as testified by various papers201-208 that received critical reviews .209-220 5. new frontiers in soft matter as previously written, at the beginning of the 1990s, the physical chemistry of colloids and interfaces was well cultivated at the department of chemistry of the university of florence into which, in 1983, the institute of physical chemistry was merged. there were at least six sub-groups that germinated from the seeds sown by ferroni: the teams of monolayers and langmuir-blodgett films (gabrielli with her pupil gabriella caminati, florence, 1960), surface diffraction techniques (rovida), esr/epr (martini), solid-state reactions and solid-gas interfaces (guarini), scattering techniques (baglioni), and electrified interfaces (guidelli). moreover, in almost all the universities in italy, there were scientists actively working on these 12 topics and the discipline that forty years before was almost inexistent in italy was in excellent health. during the second part of the 1970s and the entire 1980s, ferroni pointed his attention to monomolecular films constituted of polymers.221-231 this interest had been certainly inspired by his previous relationship with the nobel laureate giulio natta167 and by the flory-huggins theory232-234 for polymer solutions. indeed, one of the articles ferroni published in these years directly involved huggins221. the results of a study on the bidimensional state conformation of poly β-benzyl-l-aspartate were compared precisely with huggins’ theory. ferroni’s interest in surface properties of polymers was also stimulated by reading the studies by de gennes: the future nobel laureate in physics (1991) considered the physical chemistry of polymers at the interface and their interactions with surfactants as one of the most advanced topics in the physics of the condensed phases.235-241 the year after winning the nobel prize, de gennes published a short survey on science entitled soft matter:242 a new era for physics, chemistry, and physical chemistry was born, and ferroni would have been pleased to have preconised, some forty years before, that this branch of science had the characteristics to play a fundamental role. in his article,242 de gennes explained the peculiarities of this soft matter, often called complex fluids, and he introduced the two main characteristics: complexity and flexibility. he then investigated the various systems that can be considered as belonging to this fourth state of the matter: polymers, surfactants, monolayers, bilayers and multilayers, cell membranes, liquid crystals, micelles, vesicles, and liposomes. this opened a staggering multitude of theoretical and applicative studies in many fields, such as biology and medicine, materials science, technology, and electronics, among others. ferroni thought that the times were ripe to launch the institution of a national centre for colloids and interfaces. on 4 may 1993, a new government was constituted with prime minister carlo azeglio ciampi (livorno, 1920 – rome, 2016), the future president of the italian republic, and the chemist and industrialist umberto colombo (livorno, 1927 – rome, 2006) was appointed as the minister for the university and scientific research. colombo immediately saw the strategic importance of ferroni’s proposal regarding the institution of a national centre on colloids and surfaces, and at the end of 1993, the consorzio interuniversitario per lo sviluppo dei sistemi a grande interfase, csgi – as was called the national centre for colloids and surfaces – was born under the supervision and control of the italian ministry for university and scientific research. ferroni was appointed president, and his pupil baglioni, director. 6. applied chemistry, technology, and industry the first mention in the chemical abstract of enzo ferroni as an author is relative to an italian patent243 deposited on 27 february 1948 aimed to formulate a thermosetting powder. the young researcher who had carried out a chemistry master’s degree thesis on theoretical considerations of chemical kinetics,22 immediately demonstrated to be interested in aspects dealing with applied chemistry, technology, and industry. indeed, this feeling and approach would continue throughout his long career and life: ferroni profoundly understood the deep meaning of iupac (international union of pure and applied chemistry), that, as its name implies, focused on the union of pure and applied chemistry. among the various aspects of his applied research, we selected four emblematic instances of his approach. first, we thought it significant to recall the ten years of correspondence between ferroni and natta from 1958 until 1968, as recently studied by laura colli.167 the interaction between them was intense and found its significant moment just one year after the awarding of the nobel prize to natta: they published a paper in cooperation that linked the two domains of study these scientists had carried out in the last years, that is polymers for natta and surface adsorbed films for ferroni.244 13 the second significant contribution was generated by the extended partnership with the italian entity snamprogetti operating in the field of fuels and energy. ferroni was convinced that the idea of snamprogetti to build a coal pipeline, apparently, a utopian mirage, could actually be pursued since large interface systems as coal-water stable dispersions would be able to generate slurries with suitable fluidity to flow into the pipeline and simultaneously burn at the end of the pipeline without separating the coal from the water. thanks to some ad hoc surfactants ferroni and co-workers developed stable suspensions of fine powdery coal in water containing up to 70% coal by weight, which was above the threshold required to be burnt without eliminating water.245, 246 these suspensions are called slurries, and they were heavily investigated247-249 discovering their viscosity behaviour as non-newtonian fluids with memory. ferroni had the idea to involve his friend and colleague, the mathematician mario primicerio (rome, 1932), in the study: the mathematical analysis succeeded in calculating the exact length (security distance) of the pipeline between two contiguous pumping stations to avoid coal sedimentation and stoppage.250, 251 another interesting connection with the industry to find applications of large interface systems has already been mentioned in section 4. dedicated to chemistry applied to cultural heritage conservation. both autogenous lime-based grouts and oil-in-water microemulsions created during the conservation workshop of the masaccio, masolino, and filippo lippi wall paintings in the brancacci chapel were developed in cooperation with the national industry syremont s.p.a. whose president at the time was a friend of ferroni’s, paolo l. parrini.179-184 finally, there was the long and fruitful cooperation with yet another industrial sector, tecnotessile of prato, founded in 1972 and still actively operating in the field of new technologies applied in the textile industry. ferroni was designated as president of this technology centre right from its inception in 1972. in 1980 he was still collaborating with the textile industry district in prato (see figure 6). figure 6. during the workshop “energy and industry, financial aspects, technological innovations: the experience in the textile sector at prato” held in prato on 28 november 1980: enzo ferroni is the fourth from the left seated at the organisers’ table. the cooperation was mainly dedicated to developing large interface systems able to improve textile production. ferroni was convinced that soft matter could offer many fruitful opportunities to the textile industry, but at that time, the textile industry was not ready to develop strong synergies with academic research. and again, in this case as well, ferroni could see ahead of him: at the beginning of the 21st century, some papers from researchers of the csgi were published, and ferroni was lucky enough to see them.252 14 256 the last of his ideas we will mention is that of uv radiation-absorbing fabrics using nanotechnology; it was again a brilliant idea, but ferroni was not able to read the paper: it was published online on 30 october 2007, six and half months after the eclectic chemist had passed away.257 7. conclusions the scientific activity of enzo ferroni, critically revisited and investigated in the present study, allowed us to individuate the main original, novel, and creative ideas developed by this scientist, who operated mainly in the second half of the last century. it showed how he succeeded in creating a new physicochemical school in italy on colloids, interfaces, and surfaces, a field that the future would reveal particularly worthy of being thoroughly investigated until the end of the 20th century when it became a sort of new state of the matter called “soft”, after the studies by the 1991 nobel laureate in physics pierre-gilles de gennes. ferroni perceived this discipline's enormous potential, studying irving langmuir's work and deepening his knowledge and skills attending the laboratories led by raymond defay and ilya prigogine at the université libre de bruxelles. his first visionary idea to develop a branch of physical chemistry, almost neglected in italy until the end of the second world war, was followed by his second extraordinary intuition of applying the new and budding resonance spectroscopies (nmr and epr/esr) to research, first in solution chemistry and successively to investigate large interface systems. his eclecticism forcefully emerged in the aftermath of the florence flood in 1966 when he understood that chemistry, and science and technology in general, could play a fundamental role first in solving the dramatic and urgent problems facing the damaged works of art and then inaugurating a new conception of conservation and restoration, with solid scientific bases and a continuous cross-exchange among different and complementary competencies to create what, in the following years, would become the field of scientific restoration and conservation of cultural heritage. all these merits were acknowledged in the obituary that appeared in the independent.258 the consecration of his visionary ideas and intuition arrived in 1991 when pierre-gilles de gennes was awarded the nobel prize in physics for having discovered that the methods developed for studying ordinary phenomena in simple systems can be generalised to more complex states of matter, especially liquid crystals, and polymers, individuating soft matter as a peculiar form of matter in the condensed phase. some new topics, such as supramolecular chemistry, soft matter, self-assembly, nanoscience and nanotechnology, nanoscopic phases, and so on, surely have their root in the colloids and surfaces that ferroni selected as his main interest for his long academic career. the paper also showed ferroni’s eclecticism, considering his vision of the relationship between fundamental or basic research and applied chemistry, technology, and connection with industry. ferroni was always convinced that all aspects of research possessed equal dignity, and the proof of this vision was the close relationship that ferroni had with the nobel laureate in chemistry giulio natta and the numerous applied studies he carried out having as partners important companies in the energy, fuels, and textiles sectors. thanks to his long and fruitful work, ferroni received numerous awards, among which we recall: the gold medal by the italian ministry of the public education (1967) as meritorious for school, culture, and art for “his generous collaboration offered for the preservation and recovery of the artistic and cultural heritage of florence damaged by the flood of 4 november 1966”; the designation of grande ufficiale dell’ordine (1977) by the president of the italian republic giovanni leone (naples, 1908 – rome, 2001); the granting of the title officier de l’ordre national du mérite (1979) by the president of the french republic valéry giscard d’estaing (coblenz, 1926 – authon, 2020); the title of emeritus in physical chemistry (1997) by the italian minister for the university and scientific research luigi berlinguer (sassari, 1932). 15 the amazing variety of interests and subsequent content of his numerous studies and papers leads to conclude that for enzo ferroni, two different statements – the first by leonardo da vinci259 and the second by primo levi260 – can be used to summarise his multifaceted personality. leonardo stated, “study science first, and then follow the practice born from that science” (“studia prima la scienza, e poi seguita la pratica nata da essa scienza”)259. levi wrote about his the following, speaking about his own chemistry, and we suggest the same is applicable to ferroni’s: “[a] solitary chemistry, unarmed and on foot, at the measure of man, which with few exceptions has been mine: but it has also been the chemistry of the founders, who did not work in teams, but alone, surrounded by the indifference of their time, generally without profit, and who confronted matter without aids, with their brains and hands, reason and imagination” (“chimica solitaria, inerme e appiedata, a misura d’uomo, che con poche eccezioni è stata la mia: ma è stata anche la chimica dei fondatori, che non lavoravano in équipe ma soli, in mezzo all’indifferenza del loro tempo, per lo più senza guadagno, e affrontavano la materia senza aiuti, col cervello e con le mani, con la ragione e la fantasia”).260 ken shulman, in his wonderful book on the brancacci chapel,164 succeeded in masterfully condensing these two quotations in an exceptional sentence: “ferroni preferred to work alone, ruminating in his office in the early morning, applying his genially elastic mind until arriving at a solution”.261 8. acknowledgements the author expresses his gratitude to drs annantonia martorano, andrea de santis, and fabio silari of the university of florence, dr eleonora todde of the university of cagliari for the kind collaboration in finding the documents in the various archives; 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conservation scientist, obituary on the independent, may 26, 2007. 259. p. a. m. d’anghiari, riv. filosof. neo-scolast. 1920, 12(3/4), p. 209 (transl. by the author). http://www.formath.it/ita/articoli/i%20numeri%20giusti%20per%20l%27industria.pdf 24 260. p. levi, il sistema periodico, einaudi, turin, 1975, p. 207; the periodic table, transl. by r. rosenthal, michael joseph, london, 1985, p. 203. 261. same as ref. 164., p. 139. substantia. an international journal of the history of chemistry 3(1): 43-62, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-208 citation: d.m. rogers (2019) range separation: the divide between local structures and field theories. substantia 3(1): 43-62. doi: 10.13128/substantia-208 copyright: © 2019 d.m. rogers. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article range separation: the divide between local structures and field theories david m. rogers university of south florida, 4202 e. fowler ave., che 205, tampa, fl 33620, us e-mail: davidrogers@usf.edu abstract. this work presents parallel histories of the development of two modern theories of condensed matter: the theory of electron structure in quantum mechanics, and the theory of liquid structure in statistical mechanics. comparison shows that key revelations in both are not only remarkably similar, but even follow along a common thread of controversy that marks progress from antiquity through to the present. this theme appears as a creative tension between two competing philosophies, that of short range structure (atomistic models) on the one hand, and long range structure (continuum or density functional models) on the other. the timeline and technical content are designed to build up a set of key relations as guideposts for using density functional theories together with atomistic simulation. keywords. electronic structure, liquid state structure, density functional theory, bayes’ theorem, vapor interface, molecular dynamics. many of the most important scientific theories were forged out of controversy – like particles vs. waves, for which democritus claimed (with his teacher, leucippus of 5th century bc) that all things, including the soul, were made of particles, while aristotle held to the greek notion that there were continuous distributions of four or five elements.1 it is telling to note that aristotle’s objection was strongly biased by his notion that the continuum theory was elegant and beautiful, and does not require any regions of vacuum. in addition, his conception of kinetic equations were first order – like brownian motion, navier-stokes, or the dirac equation, but not second order like newton’s or schrödinger’s. newton sided with democritus. in 1738, daniel bernoulli first explained thermodynamic pressure using a model of independent atomic collisions. that theory was not scheduled to be widely adopted until the caloric theory (which postulated conservation of heat) was overthrown by james joule in the 1850s. wilhelm ostwald was famously stubborn for refusing to accept the atomic nature of matter until the early 1900s, after einstein’s theory of brownian motion was confirmed by jean perrin’s experiment. the working out of gas dynamics by maxwell and boltzmann in the 1860s depended critically on switching between a physical picture of a 2-atom collision and a continuum picture of a probability distribution over 44 david m. rogers particle velocities and locations (fig. 4a). collision events drawn at random from a boltzmann distribution were useful for predicting pressures and reaction rates. whether that distribution represented a probability or an actual average over a well-enough defined physical system was left open to interpretation. five decades later, gibbs would argue with ehrenfest2 over this issue. gibbs seemed to understand the continuous phase space density as any probability distribution that met the requirements of stationarity under time evolution. an observer with no means of gathering further information would have to accept it as representing reality. ehrenfest argued that a well-defined physical system is exact, mechanical, and objective. the controversy was only resolved by the advent of the age of computation,3 since we forgot about it. three decades on, the physicist jaynes championed the (subjective) maximum entropy viewpoint,4 while mathematicians like sinai and ruelle5-8 moved to do away with the whole subjectivity business by using only exact dynamical systems as starting assumptions. maxwell described light propagation by filling the continuum with ‘idler wheels,’ and the resulting partial differential equations inspired much of 20th century mathematics. planck saw his own condition on quantized transfer of light energy as a regrettable, but necessary refinement of maxwell’s theory. planck believed so strongly in that theory that he at first rejected einstein’s 1905 concept of the photon.9 it was also five decades later, around 1955, when a field theory of the electron (quantum electrodynamics) was gaining acceptance from precise calculations of experimental details like the gyromagnetic ratio, radiation-field drag (spontaneous emission) and the lamb shift. this quantum field theory is not a completely smooth continuum, since it incorporates particles using ‘second quantization.’ it understands particles as wavelike disturbances that pop in and out of existence in an otherwise continuous field. the technical foundations of that theory are derived by ‘path-integrals’ over all possible motions of maxwell’s idler wheels. as a consequence, infinities characterize the theory,10 so that the mathematical status of many path integrals is still not settled11 except in the gaussian case,12,13 and where time-sliced limits are well-behaved.14 this article discusses some well-known historical developments in the theory of electronic and liquid structure. as its topic is physical chemistry, this history vacillates without warning between experimental facts and technical details of the mathematical models conjured to describe them. the topics, outlined in table 1, have been chosen specifically to highlight the debate between local structural and field theoretical models. note that we have also presented the two topics in an idiosyncratic way to highlight their similarities. differences between electronic and liquid structure theories are easy to find. by the nature of this type of article, we could not hope to be comprehensive. there has not been space to include many significant historical works, while it is likely several offshoots and recent developments have been unknowingly overlooked. both histories trace their roots to the herapath/maxwell/boltzmann conceptable 1. contrasting long-range (lr) and short-range (sr) ideas showing stages of debate over atoms and electrons (top sections), along with concepts from hybrid theories (lower section). sr/discrete lr/continuous (democritus) atoms elements (aristotle) (ehrenfest) microstate ensemble (gibbs) (einstein) particle wave (ostwald) (boltzmann) distribution function 1-body probability density (jaynes) (wein) n(ν) ν2dν (rayleigh-jeans) n̂(r, p) n(r), v ext(r) jellium (sommerfeld) (mott) insulator conductor (pauli) (hartree-fock) slater determinant electron density (hohenberg-kohn-sham) (bornoppenheimer) nucleii electrons correlation hole polarization response (bohm-pines) ←−−−−quasiparticle phonon−−−−→ ←−−−−cooper pair hybrid dft−−−−→ 45range separation: the divide between local structures and field theories tion of a continuous density (or probability distribution) of discrete molecules, and both remain active research areas that are even in communication on several points. we will find that, like democritus and aristotle, not only are there are strong opinions on both sides, but progress continues to be made by researchers regardless of whether they adopt discrete or continuum worldviews. electronic structure theories between the lines of the history above, we find bose’s famous 1924 z. physik paper describing the statistics of bosons, which einstein noted ‘also yields the quantum theory of the ideal gas,’ and the thomas-fermi theory of 1927-28 for a gas of electrons under a fixed applied voltage. their basic conception was to model the 6-dimensional space of particle locations, r and momenta, p with the volume element, g(p')dp' = dp' ∫ δ(|p| − p')h−3 dr3 dp3 = 4πv h−3p'2dp' (1) using p' = hν/c for photons of frequency ν provides g(ν), the number of available states for photons near frequency ν. applying bose counting statistics to n(ν) photons occupying 2g(ν) possible states for each frequency gives bose’s derivation of planck’s law. in the thomasfermi (tf) model, p' is electron momentum. applying fermi statistics to the occupancy number n = 2∫ 0 hkfg(kh) d(kh) now gives a fermi distribution for an ideal gas of electrons under a constant external potential (electrostatic voltage). in both cases the number of states is doubled – counting 2 polarizations for photons or 2 spin states for electrons. the result of the first procedure is a free energy expression for the vacuum. the result of the second is a free energy for electrons under a constant voltage. this idea of a gas with uniform properties uses a long-range field to guess at local structure. quantitatively, if the voltage at point r is ϕ(r), then the theory predicts electrons will fill states up to maximum momentum of kf = √(2mee0ϕ(r))/h, (where the kinetic energy is ef = h2k2f/2me and e0 is the electron charge) so the local density is, n(r) = k3f/3π2. (2) the resulting model is then usually found to predict long-range properties of metals relatively well. fig. 1a and b show plots of free energy vs number of electrons in an independent electron solution of the schrödinger equation for a well of positive potential.15 panel b shows a simple adaptation of that model where electrons bind in pairs. the states of the electrons in these exact solutions still represent momentum levels, and are thus qualitatively very close to those of the thomas-fermi theory. the free electron gas evolved into the famous ‘ jellium’ model of electron motion rather quickly, as can be seen by the earliest references in a discussion of that model from the late 20th century.20 the term jellium was coined by conyers herring in 1952 to describe the model of a metal used by ewald21 and others consisting of a uniform background density of positive charge. the electrons are therefore free to move about in gaslike motion. at high density, the electrons actually do act like a free gas, so it was possible to use the thom3 5 10 1 10 rs = 1 lr sr rs = 1 10 lr sr c) d) e) f) a) b) reprinted figures with permission from ref. [19] copyright 1994 by american physical society. reprinted figures with permission from [16] copyright 1930 by american physical society. reprinted figures with permission from [18] copyright 2014 by american physical society. reprinted by permission from springer: "fundamentals of dft" by h. eschrig, copyright 1996. figure 1. long-range (left) and short-range (right) theories of electronic structure. (a) and (b) show free energy vs. electron number for a potential well.15 (c) shows ‘epstein’ profile of dielectric response16,17 at a metal/vacuum interface. numbers for each curve give the surface/bulk conductivity ratio. (d) shows surfaces of constant voltage at a water/vacuum interface, (e) and (f ) show the correlation function of jellium from accurate calculations.19 46 david m. rogers as-fermi theory to qualitatively describe the electronic contribution to specific heat, cv = π2k2bt/2ef, as well as the spin susceptibility and width of the conduction band (after re-scaling the electron mass).22 these are long-range properties from the collective motion of many electrons. the predictions become poor for semi-metals and transition metals. it also rather poorly described the cohesive energy of the metal itself. those cases fail because of the importance of shortrange interactions that a free electron theory just doesn’t have.23 the contrast becomes important at interfaces, as is visible when comparing fig. 1c,d. on the left is an early model of local charge density response due to placing an external voltage at a point near a metal surface. on the right is a map of the local voltage for one surface configuration of an electrolyte solution computed using an accurate quantum density functional theory. chloride ions are green, and sodium ions are blue. treating one of the sodium ions as a test charge, the material response comes from rearrangement of waters (red and white spheres) and cl− ions within a nuanced voltage field (colored surfaces). it turns out that the electron gas in ‘real’ jellium behaves rather differently at low and high density. at low density, the electron positions are dominated by pairwise repulsion, and organize themselves into a lattice (of plane waves) with low conductivity.24 this low-density state is named the ‘wigner lattice’ after e. p. wigner, who computed energetics of an electron distribution based on the lattice symmetry of its host metal.25 at higher densities, collective motions of electrons screen out the pairwise repulsion at long range. this gives rise to a nearly ‘free,’ continuous distribution of electrons with higher conductivity more like we would picture for a metal. fig. 2a, from a well-known particle-based simulation of ceperly and alder,26 shows the wigner lattice as well as both spin-polarized and unpolarized high-density states. taking the opposing side, early applications of selfconsistent field (hartree-fock or hf) theory to molecules and oxides noticed that the long-range, collective ‘correlated’ behavior of the electrons was usually irrelevant to the short-range structure of electronic orbitals. getting the short-range orbital structures right allowed hf theory to do well describing the shapes of molecules and the cohesive energy of metal oxides,27 as well as magnetic properties.28 more recent work has shown explicitly that a model that altogether omits the longrange tail of the 1/r potential still allows accurate calculations of the lattice energy of salt crystals.29 although both theories worked well for their respective problems, the transition from insulating to conducting metals (as electron density increases) also proved to be difficult because it involved a cross-over between both shortand long-range effects. because of this mixture of size scales required, relying exclusively on a theory appropriate for either shortor long-range produces results that increasingly depend on cancellation of errors. this sort of error cancellation is illustrated by the phenomenology of ‘overdelocalization’. well known to density functional theorists, ‘overdelocalization’ is the tendency of continuum models for electron densities (having their roots in the longrange tf theory) to spread electrons out too far away from the nucleus of atoms. the result is that electron clouds appear ‘softer’ in these theories, and polarization of the charge cloud by the charge density of a far molecules contributes too much energy. on the other hand, induced-dipole induced-dipole dispersion forces are not modeled by simple density functionals, and so their stabilizing effect is not present. it has been found that the over-delocalization can be fixed by making a physical distinction between short and long-range forces. however, the resulting binding energies are not strong enough. after the correction, they need a separate addition of a dispersion energy to bring them back into agreement with more accurate calculations.30 thus, a bit of sloppiness on modeling short-range structure can compensate for the missing, collective long-range effects. hybrid theories in electronic structure when looking at properties like the cross-over between conducting and insulating behavior of electrons, it’s not surprising that successful theories strike a balance between short-range, discrete structure and long-range continuum effects. even in the venerable born-oppenheimer approximation from 1927, we see that atomic nucleii are treated as atoms (immovable point charges), while electrons are described using the wave theory. the separation in time-scales of their motion makes this work. by the time the atoms in a molecule have even slightly moved, the electrons have zipped back and forth between them many times over. correlation functions are a central physical concept in the debate between long and short range ideas. the distance-dependent correlation function, g(r), measures the relative likelihood of finding an electron at the point, r, given that one sits at the origin. one of the first attempts at accounting for electron-electron interaction was to use perturbation theory to add electron interactions back into the uniform gas model (g(r) = 1). the first order perturbation modifies this by looking at 47range separation: the divide between local structures and field theories interactions between electrons of the same spin. this interaction is termed the exchange energy, since it comes from pairs of electrons with the same spin exchanging momentum.22 after the correction, electrons with parallel spin now have smaller density at contact, g(r) = 1 − ⁹/₂(sin(kfr) − kfr cos(kfr))2/(kfr).6 the correlation function between infinite periodic structures is s(k), the long-range analogue of g(r) (in fact its fourier transform). the function s(k) is called the structure factor by crystallographers. if the system consisted only of electrons, the structure factor could be measured directly by light or electron scattering experiments. there, s(k) is the intensity scattered out at angle θ = 2 arcsin(λk/4π) when the material is placed into a weak beam of photons or electrons of wavelength λ pointed in the θ = 0 direction. this function has been computed using an accurate particle simulation technique and shown in fig. 1e,f.19 the curves are labeled by rs = (3/4πn)1/3, measured in units of bohr radii. there is a duality between short and long range perspectives inherent in g(r) and s(k) as well. longrange behavior appears at large r when g(r) approaches 1. at small r, the geometry of inter-particle interactions determines the shape of g(r). because particle dynamics is carried out in real-space, g(r) tends to be used by its practitioners to characterize short and long-range structure. analytical solutions of many models, and especially those aiding experimental measurements, are simpler in fourier space. there, s(0) is the integral of g(r). it provides information on the total fluctuations in the number of particles, and is a long-range quantity from which the compressibility, partial molar volumes, and other properties can be computed.31 short-range structures that repeat with length d show up as peaks in s(k) at correspondingly large k = 2π/d. back to the metallic/insulator problem, between 1950 and 1953 bohm and pines pioneered the idea of explicitly splitting the energy function (hamiltonian) governing electron motion into local and long-range degrees of freedom.32-34 using the intuition that longrange collective motions of electrons should look like the continuous plane-wave solutions to maxwell’s theory, they added and subtracted those terms and called them ‘plasmons’ (fig. 4d). just like photons, the plasmons are continuous waves when treated classically, but are quantized particles when understood quantum mechanically. what remained after the subtraction was a hamiltonian whose interactions were only short-ranged, but could not be treated with a continuum description. instead, the short-range part describes interactions be tween effective discrete particles which bohm and pines dubbed ‘quasiparticles’. the quasiparticles were like packs of electrons surrounded by empty space, ‘holes.’ the quasiparticles thus have larger mass and softer, screened, pair interactions (explaining why the mass has to be fixed when applying the free electron theory figure 2. comparing phase diagrams of the electron gas dissolved ions. both show an insulating phase at low density (labeled wigner crystal in (a)) and a conducting phase at high density separated by a minimum. the corresponding transition in an electron gas has not been well studied, but critical temperatures feature in the phase diagram of superconducting cuprates (where n is percent of solid impurities).36 (b) phase diagram of a z:z electrolyte like nacl where n is the cation concentration. lines show the position of the spinodal using methods appropriate for each theory, and the minimum indicates a critical point for fluctuation in ionic concentration. note the temperature axis is reversed by β = z2/dkbt and η = πnd3/6, d is the ion diameter. reprinted from ref. 35, with the permission of aip publishing. (a) ground state energy vs. density for the uniform electron gas.26 four separate phases were observed (at zero temperature). note that the density axis is reversed by the transformation 1/n = 4πrs3/3. reprinted figure with permission from ref. 26. copyright 1980 by the american physical society. 48 david m. rogers to metals). these new ‘renormalized’ electron quasiparticles could even have effective pairwise attraction. this latter effect was a central component to the bcs model of superconductivity, where the quasiparticles are known as ‘cooper pairs.’ because of its dual representation, the bohm-pines model gave good answers for both cohesive energies and conductivities – and described the crossover between insulating and metallic regimes as electron density is increased.24 for all its descriptive power, the bohm-pines approach was often lamented for its requirement for a specific set of approximations. most damningly, it required inventing a continuum of plasmons to describe the long-range interactions of a finite set of electrons. this adds infinite degrees of freedom to a system with an initially finite number. it also required the plasmons to stop and the particles to commence at some cutoff wavelength. these troubles lead us into the problem of renormalization group theory, which is beyond the scope of the present article. in fact, in 1954, just after the publication of the last article in the bohm and pines series above, lindhard provided a model for collective electronic response of a metal that involved only the metal’s correlation function (by means of its dielectric coefficient, ε).34 following a decade later in 1964-65 was hohenberg, kohn and sham’s density functional theory.37-39 both developments rephrased the description of electronic structure in terms of a continuous field of electron density. linear response (perturbation) theory says that an initially homogeneous density n0 responds to an applied field, ϕ as, ∆n(r) = n0 ∫ χ(r, r')ϕ(r'), (3) where χ(r, r') is the fourier transform of the structure factor above. their defining characteristic is the focus on continuous response of that density to a continuous external field, ρ(r) = ρ[ϕ(r')](r). the theory may be understood as a fully longranged point of view that includes short-range effects indirectly through s(k). it shows how to use integration to calculate all thermodynamic quantities from structure factor. the only problem is that it does not broach the issue of how to predict the structure factor. one wellknown method is to assume the probability of n(r) is a gaussian on function space (so the exponent depends on ∫n(k)2/χ(k)dk3, and χ(k) is just slightly different from s(k)). in that case, the inverse of the correlation function (1/χ(k)) is a self-energy term plus the inter-particle energy function. this assumption is known as the random phase approximation (rpa), named because of its historical discovery by bohm and pines following from neglecting couplings between a set of linearly independent (fourier) modes, n(k). this ends up excluding all non-gaussian fluctuations. the ‘dielectric’ ideas encapsulated in the linear response theory of eq. 3 can be combined with the free electron model of eq. 2 (t [n] proportional to n5/3), or a wavefunction calculation of the kinetic energy, t[n], to synthesize modern density functional theory (dft).20;40 it writes the electron configuration energy as, . (4) now the (long-range) correlation function of the electron, χ, is obtained from the curvature of a[ϕ]. mathematically, the unknown structure factor has been migrated into an unknown functional, exc[n]. the initials stand for exchange and correlation, its two major components. the principle advantage gained by this rephrasing is that new, accurately known (usually shortrange) terms like t[n] can be added to a[ϕ] in order to decrease the burden on exc to model ‘everything else.’ the disconnect between short and long-range energies can be shoveled into some fitting parameters. again moving forward 40 years, the relative unimportance of long-range coulomb interactions for local structuring noticed by lang and perdew29,41 lead to the suggestion that the density functional method itself should also distinguish between short and long range structural effects. implementation of this idea was perhaps first carried out by toulouse, colonna and savin in 2004.42 there, the local density approximation deriving its roots in the tf theory is applied to describe shortrange interactions, while the hf theory is used to ensure proper electron-pair repulsion (exchange) energies at long-range. the association of hf with long-range and density functional (df) with short-range apparently runs counter to our association between continuum, density-based, models for long-range interactions vs. discrete, particle-based models for short-range interactions. a major complication with our association is that it is known that the hf method describes the long-range (asymptotic) electronic interactions well, whereas the df method does not. df methods were historically used to describe the ‘entire’ energy function, and have thus been tailored to describe quasi-particles (the so-called exchange hole), rather than asymptotics. this association was put to the test shortly after by vydrov and co. 43 using an earlier df called lsda that is not strongly tailored in this way. they separately averaged the short 49range separation: the divide between local structures and field theories lr lr srsr b)a) d)c) f)e) reprinted from [49], with the permission of aip publishing. 0 20 40 reprinted from [48], with the permission of aip publishing. ref. [47], fig 2, copyright (1998) national academy of sciences. ref. [47], fig. 1, copyright (1998) national academy of sciences. reprinted from [50], with the permission of aip publishing. reprinted from [50], with the permission of aip publishing. figure 3. shortand long-range theories of solvent dipole and electrolyte structure. (a) and (b) show free energies and number occupancy distribution for spherical cavities in water.47 (c) shows the dielectric response in a spherical geometry48 and (d) shows the dielectric permittivity computed in a slab geometry.49 (e) and (f ) show the correlation function of a supercritical lennard-jones fluid near n = 0.52/σ3, t = 1.34ε/kb.50 50 david m. rogers and long-range components of hf and df and checked their ability to predict the cohesive, formation energies of small molecules. doing so, they discovered that models with no hf at long range had similar descriptive power to those that used only df at short range and only hf at long range. split-range functionals are still an evolving research topic. liquid-state theories the divide between short and long-range, discrete, and continuous distributions also plays a key role in the development of thermodynamic theories for gasses and liquids. in the 1860s, boltzmann proposed his transport equation for the motion of gas density over space and time. the model employed the famous stoßzahlansatz, which states that the initial positions of molecules before each collision is chosen ‘at random.’ (fig. 4a) in the original theory, the probability distribution over such random positions was often confused with their statistical averages44 – a point which lead to enormous confusion and controversy persisting even until 1960.45 this history very nearly parallels the development of electronic density theories. after electromagnetism and gas dynamics had been worked out at the end of the 19th century, gibbs’ treatise on statistical mechanics laid out the classical foundations of the relationship between statistics and dynamics of molecular systems. nevertheless, there were contemporary arguments with ehrenfest and others about the need for introducing statistical hypotheses into an exact dynamical theory.2 early on, it had been hoped that an exact study of the motion of the molecules themselves could predict the appropriate ‘statistical ensemble’ by finding long-time limiting distributions. however, that hope was spoiled by the notice that initial conditions must be described statistically. the idea persists even at present, though it has been tempered by the recognition that sustaining nonequilibrium situations requires an infinitely extended environment, which has to be represented in an essentially statistical way.46 the resolution, according to jaynes,4 is to understand the boltzmann transport equation as governing the 1-particle probability distribution, np(r|c), rather than the average amount of mass, n(r), at point r. it turns out that this switch in perspective from exact knowledge of all particle positions to probability distributions is one of the key ways of separating short and long-range effects. two of the oldest and most widely known uses of this method are in the dielectric continuum theory dating from before maxwell’s 1870 treatise, even to sommerfeld (fig. 4c), and the debye model of ionic screening from 1923. for both, a spatial field e(r − r0), emanating from a discrete molecule at r0, is put to a bulk thermodynamic system whose average properties are well-defined using, for example, p(r|e) for the dipole density μ(r) at point r, due to a field, e or n(r; ϕ) for the ion density at point r due to a voltage, ϕ. treating ϕ and e as weak perturbations and looping µ(r) (or n(r)) back in as additional sources gives a self-consistent equation for the response of a continuum. as was the case for electronic structure theory, the most concise description of this type of self-consistent loop is provided by a density functional equation for the helmholtz free energy (with β = 1/kbt), . (5) the curvature of a with changing applied field, e, gives the response function which is related to the conventional dielectric. consider first a case where µ contains enough information to exactly assign a dipole to every one of n molecules. an example would be a single molecule with twice as many ways to create a small dipole as a large one, g(4 d) = 2 and g(2 d) = 4 (1d = 1 debye). then g(µ) is a product over counting factors. the free energy, a, will have jump discontinuities in its slope as the field, e is varied because the solution jumps from one assignment (µ = 2 d) to another (µ = 4 d at βe ≥ (ln 2)/(2 d)). its graph is very much like fig. 1a. in a discrete function space, density functional theory equations yield solutions exhibiting a discrete nature. on the other hand, if g(µ) varies continuously with µ in some range of allowed average densities, then the solution will describe a smooth field free energy. interestingly, starting from the first situation and computing (6) leads to such a continuous version of log g(µ) ≈ s(µ) (in fact its concave hull). this concave function allows densities that are intermediate between discrete possibilities for the system’s state. such intermediate densities could only be reached physically by averaging, so that µ̄ is an average polarization over possible absolute assignments of dipoles to molecules, µ. after the theory of self-consistent response to a long-range field had been worked out, further development of liquid-state theory had to wait 40 years for developments in quantum-mechanical interpretation of 51range separation: the divide between local structures and field theories light absorption and scattering experiments. some early history is given in ref. 51 and debye’s 1936 lecture52 in which he explains how electronic and dipole orientational polarization could be clearly distinguished from measurements of the dielectric capacitance of gasses along with the great advancements made in the 1920s (which debye credits to von lau in 1912) of using x-ray and electron scattering to confirm molecular structures already adduced by chemists from symmetry and chemical formulas alone. thus, the long-range theory gave a comprehensive enough description of macroscopic electrical and density response that it could be used as a basis to experimentally determine local structure. with statistical mechanics, quantum mechanics, and molecular structure in hand, liquid-state theories developed in the 1930s-50s through testing hypotheses about the partition function against experimental results for heat capacities. one of the earliest models was the ‘free volume’ (also known as cell model) theory, developed by eyring and colleagues and independently by lennardjones and devonshire in 1937. the theory was put on a statistical mechanical basis by kirkwood in 1950,53 as essentially expressing the free energy of a fluid in terms of the free energy of a solid composed of freely moving molecules trapped, one each, in cages exactly the size of the molecular volume, plus the free energy cost for trapping all the molecules in those cages in the first place. it competed54 with the ‘significant structure’ theory of liquids (also proffered by eyring and colleagues55,56). in the significant structure theory (fig. 4f), the partition function for the fluid is described as an average of gas-like and solid-like partition functions to account for the difference in properties between highly ordered and more disordered regions (which contain vacancies). scaled particle vs integral equations also around that time, a competition emerged between the scaled particle theory57 and the ‘integral equation’ approach based on (and now lumped together with) percus and yevick’s58,59 closure of a theory created by ornstein and zernike in 1914 to calculate the effect of correlated density fluctuations on the intensity of light scattered by critically opalescent fluids.60 this connection was significant, since theories of the correlation function prior to 1958 applied the superposition approximation due to kirkwood, yvon, born, and green (ca. 1935).61,62 the scaled particle theory (spt) approach takes the viewpoint that the number, sizes and shapes of molecules in a fluid are determined by integrating the work of ‘growing’ a new solute particle in the middle of a fluid. its organizing idea is that the chemical potential of a hydrophobic solute is equal to the work of forming a nanobubble in solvent. for simple hard spheres, the work is pdv , where p = kbtn0g(d), n0 is the bulk solvent density, and g(d) (fig. 4b), the density of solvent molecules on the surface of the solute of diameter d. hence, knowing the contact density for any shape of solute molecule provides complete information on the chemical potentials of those molecules. this very local idea can be related to counting principles at very small sizes,63 and continued through to macroscopic ideas about surface tension at very large sizes – creating a way to interpolate between the two scales. on the other hand, the integral equation approach expresses the idea that long-range fluctuations in density are well described by a multivariate gaussian distribution. if the probability distribution of the density, n(r), was actually gaussian, its probability would be,64 p [n(r)] = p [n0] exp (−β/2∫∫drdr'(n(r)−n0)g(r,r')(n(r')−n0))/ z[βg], (7) where g(r, r') ≡ const · δ(r−r')−c(r−r')/β. in the rpa, −c(r)/β is energy for placing a pair of molecules at positions r and r'. 65 when they are not gaussian distributed, the correlations in instantaneous densities, n(r), provide a means of estimating c, the direct correlation function.66 this longrange idea has been used to show that g degenerates to the pairwise energy for very large separations (g(r) → u (r) as r → ∞). for simple hard spheres, it can also be related to counting principles at short separations, since there the correlations must drop to -1, expressing perfect exclusion. assuming both limits hold right up to the discrete boundary of a solute yields the mean spherical approximation (msa, fig. 4b). these two theories thus express, in pure form, the divide between short-range and long-range viewpoints on molecular structure. integral equation theories are most correct for describing continuum densities and smooth interactions. theories that, like spt, are based on occupancy probabilities of particles in well-defined local structures and geometries are most correct for describing short-range interactions that can contain large energies and discontinuous jumps. fig. 3b shows p (n|d), the probability that a randomly chosen sphere of radius d contains exactly n discrete water molecules. each curve is marked by its value of d in nanometers. the free energy for creating an empty nanobubble of size d in water is shown in its counterpart, fig. 3a. both computations are very closely related, and easiest to do from the local picture of scaled particle theory. the cavity formation free energy (fig. 3a) is, in 52 david m. rogers principle, also able to be computed from a density functional based on relating the logarithm of eq. 7 with the entropy.64 however, when the calculation is done in the usual density functional way the cavity formation free energy is surprisingly difficult to reproduce.67,68 this difficulty is related to the abrupt decrease in solvent density to zero at the cavity surface. in addition to mathematical difficulties,69 this complicates creating a physically consistent functional from bulk properties alone. from scaled particle theory, we know the free energy should scale with the logarithm of the volume for small cavities, but later switch over to scale with the surface area. the transition distance is determined by the size of discrete solvent molecules. perturbation theories slowly but surely during the same time period as integral equation theories were being developed the method of molecular dynamics emerged.70 its primary limitations of small, fixed, particle numbers, large numbers of parameters, finite sizes and short timescale simulations weigh heavy on the minds of its practitioners.71 early models of water needed several iterations before reproducing densities, vaporization enthalpies and radial distribution functions from experiment. initial radial distributions from experiment were wrong, and the models had to be corrected and then un-corrected to chase after them.72 surprisingly, early calculations took the time and effort to calculate scattering functions and frequency-dependent dielectrics to compare to experiment.73-75 by contrast, the bulk of ‘modern’ simulations report only the data that can be readily calculated without building new software. by checking data from integral equations against molecular dynamics (md) and scattering experiments it was clear by 1976 that many powerful and predictive methods had been created to describe the theory of liquids.76,77 nevertheless, there remained even then lingering questions about the applicability of integral methods to fluids where molecules contained dipole moments, and the treatment of long-range electrostatics in md. some difficulties in modeling phase transitions and interfaces were anticipated, but it was hardly expected that bulk molecular dynamics methods themselves would stall and eventually break down when simulating liquid/vapor and liquid/solid surfaces. this trouble is illustrated by the simulation com munity’s reception of the work leading to fig. 3b,c. both show the dielectric response function for water dipoles at the interface with a large spherical particle (left) or vacuum (right). the latter shows a correlation function computed from all-atom molecular dynamics by ballenegger.49 this full computation was preceded two years earlier by less well-cited theoretical work from the same author.78 as of writing, the citations counts are 140 and 19, respectively. even after its publication, the technical difficulties caused by simulating collective dipole correlations inside a finite size box cast a cloud over the interpretation that drove ballenegger back into those fine details for the following nine years.79,80 on the left (fig. 3c) is a simulation of water’s dipolar response next to a large sphere.48 the finite-size effects are less severe, and a comparison (not common in contemporary literature) is made to analytical theories that apply to infinite systems. however, those analytical theories work best at long-range, and disagree on the short-range order. the disagreement is jarring because energetic contributions of long and short-range order are on the same order of magnitude. figure 4. hybrid discrete/continuum theories. (a) boltzmann picture of scattering by one particle chosen ‘at random’ from the continuum. (b) mean spherical approximation for the hard sphere fluid of diameter σ. g(r) and c(r) are known at r << σ and r >> σ, but the central region is a guess. (c) sommerfield conception of a dipole above a continuous polarizable medium. (d) bohm-pines conception of a quasiparticle (purple, central peak) and two long-range plasmons (blue). (e) dressed ion, quasichemical, or lorenzlorentz-mossotti-clausius51 cavity models of a discrete molecule in a continuum solvent, (f ) significant / inherent structure theory of a coexisting mixture of ordered and disordered regions making up an overall homogeneous phase. 53range separation: the divide between local structures and field theories it was also beginning to be recognized that there were two complementary approaches to the theory of fluid structure. the short-range viewpoint stated that the radial distribution function should be reproduced well at small intermolecular separations (small distance in realspace as in fig. 3f ). this leads to good agreement with interaction energies and pressures so that the virial and energy routes to the equation of state work well.50 the long-range viewpoint instead emphasizes reproducing the structure factor at small wavevectors (as in fig. 3e). because of this, it favors using the compressibility route to the equation of state and leads to good agreement with fluctuation quantities.81 inherent structures water proved to be a major challenge to molecular models because of its mixture of short-range hydrogen bonding and long-range dipole order.82 one successful physical picture of water was provided by the stillingerweber ‘inherent structure’ model introduced in the early 1980s.83 it represented a cross between the ‘significant structure’ theory and the free volume theory. in it, molecules are fixed to volumes defined by their energetic basins, rather than by a rigid crystal lattice. where the free volume theory had only one reference structure, the inherent structure (like the significant structure theory) had many. one for each basin. each energetic basin looks, on an intermediate scale, like a distortion of one of the crystalline phases of ice. thermodynamic quantities can be predicted using the energies and entropies associated to each basin – by virtue of the minimum energy structure and the number of thermal configurations mapping to that minimum. hybrid theories in liquid-state structure the lennard-jones fluid presented a challenge to the integral equation and scaled particle theories above because it contains both short-range repulsion and longrange attraction. at high densities, however, it was found that the radial distribution function was almost identical to the radial distribution for hard spheres (compare fig. 3e and fig. 4b). the transition from liquid to solid was also described fairly well using the hard-sphere model. on the other hand, at low densities the distribution function could be described by perturbation from the ideal gas. these two discoveries justify the use of a perturbation theory to calculate the effect of long-range interactions at very low and very high densities.84 a comparison of molecular dynamics with integral equation plus correction theories is shown in figs. 3e,f.50 at intermediate densities, however, a liquid-to-gas phase transition occurs that can be qualitatively understood, but not explained well as a perturbation from either limit. instead, the integral equation method turns out to hold the best answer in the supercritical region.85 it is often encountered in the form of a perturbation theory from the critical point.86 it is no accident that the integral equation method works well here. supercritical fluids are characterized by long-range correlations that can take maximum advantage of that theory. for the same reason, integral equations describe the compressibility well, but do poorly on the intermolecular energy. comparing to developments in electronic structure raises the question of whether perturbation theory could fix the short-range correlations in high and low density fluids. this approach was popularized by widom’s potential distribution theory.87 its central idea is to drop a spherical void into a continuum of solvent, and then to drop a solute into its center. this divides the new molecule’s chemical potential into a structural part (due to cavity formation) and a long-range part (due to response of solvent to the molecule). originally, the former were based on a local density approximation from the hard sphere fluid and the latter from a pairwise term that amounted to a van der waals theory. around 1999, this basic idea had been combined with older notions about working with clusters of molecules to create a new ‘quasi-chemical’ theory.88 it refined the simple process of creating an empty sphere devoid of solvent into that of creating a locally well-defined cluster of solvent molecules. the free energy required for this process is still local and structural, but now the entire cluster of solute plus solvent can be regarded as one, local, chemical entity. in order to work with molecules that have ‘loose’ solvent clusters, a third step was also added. after pulling solvent molecules into a local structure and adding the long-range interactions between solute and solvent, the third step releases the solvent cluster, liberating any energy that might have been trapped by freezing them.89 the opposite of this short-range-first approach could be an inverse perturbation theory – first deciding on the long-range shape of correlation functions and second correcting them for packing interactions at short-range. this kind of correction would look like an adjustment to the solution of the poisson-boltzmann equation. such an approach may first have been presented in refs. 90;91, and followed with interesting modifications of the debye theory.92-94 even more recently, the basic idea was rigorously applied to molecular simulation models by remsing and weeks. their scheme eliminates a hard discon54 david m. rogers tinuity between short and long-range in the first step by splitting the coulomb pair potential into smooth, longrange and sharp, short-range parts. the long-range forces (from the smooth part of the potential) are used to compute a ‘starting’ density using rpa-like perturbation from a uniform fluid. although it seems a lot like the molecular density functional method,62,95,96 the density after the first step remains smooth at the origin, lacking any hard edges. it has previously been considered under the title ‘ultrasoft restricted primitive model’.97 remsing and weeks added a final step to this model to create a cavity at the origin and compared the results to md simulations. detailed molecular simulations have been used to compare the two approaches with exact simulations by brute force calculation of all the energetic contributions. focusing on the short-range structure leads to a model whose first step is to form an empty cavity in solution (blue curve in fig. 5a, labeled ‘packing’). fig. 5a shows the free energies of the next step (na+ and cl− ions) divided into ‘long-range’ and ‘inner-shell’ parts of the re-structuring.99 all points come from md. if, instead, the long-range interaction between an ion and solvent occurs first, we are lead to couple the solvent to the smooth electric field of a gaussian charge distribution. fig. 5b shows the free energy of that first step as a function of charge for a variety of gaussian (smoothing) widths. the lines show continuum predictions, and the points show md. integral equation approaches to the dipolar solvation process have also continued independently. matyushov developed a model for predicting the barrier to charge transfer reactions.100 in that work, the dipole density response to the electric field of a dipole is worked out in linear approximation. a sharp cutoff is used to set the field to zero inside the solute, resulting in a hybrid short/long range theory. the approach succeeds because the linear response approximation (stating density changes are proportional to applied field) is correct at long range, where the largest contributions to the solvation energy of a dipole originate. other authors have expanded on numerical and practical aspects of correlation functions.101-103 the theme of separating long-range, continuous vs. short-range, discrete interactions runs throughout numerous other molecular-scale models. models in this category include the ‘dressed’ ion theory, which posits that ions in solution always go in clad with strongly bound, first shell, water molecules so that their radius is larger than would be suggested from a perfect crystal (fig. 4e). these enlarged radii appear in the stokeseinstein equation to describe the effect of molecular shape on continuous water velocity fields when computing the diffusion coefficients for ions.104 they should also appear to describe how excluded volume of ions will affect the continuous charge distribution predicted by the primitive model of electrolytes. this modification is not common, and so would yield some nonstandard −8 −7 −6 −5 −4 −3 −2 −1 0 1 2 2.5 3 3.5 fr ee e ne rg y (e v ) r (å) cl− (right) is hs -1+1 lr na+ (left) total inner−shell packing long−range long−range bounds figure 5. comparing components of the sr-first (left) and lr-first (right) calculations of the free energy gained on dissolving a charged ionic species in water. (a) ion solvation free energy components for the short-range (empty cavity first) model computed from an md model of nacl in spc/e water. r is the cavity radius, ‘hs’ denotes the cavity formation cost, ‘lr’ is the full ionspc/e water interaction after a cavity is present, and ‘is’ is the free energy of removing the cavity constraint. (b) interaction free energy of spc/e water with a gaussian charge distribution, q exp(−r2/l2)/(l√π)3. points correspond to simulation data, while lines assume a constant dielectric model. adapted with permission from ref. 98, copyright 2016 american chemical society. 55range separation: the divide between local structures and field theories plots of hydration free energy as a function of ion concentration.105 solvent orientational order changes form again beyond about 1.5 micrometers due to the finite speed of light.106 the marcus theory of electron transport describes two separate, localized structural states of a charged molecule that interact with a continuously movable, long-range, gaussian, field. larger magnitude f luctuations in the solvent structure lead to broader gaussians, which in turn are the cause of more frequent arrival at favorable conditions for the electron to jump. it is common practice in quantum calculations to explicitly model all atoms and electrons of a central molecule quantum-mechanically while representing the entirety of the solvent with a continuous dielectric field.107-109 the theories above are not perfect. they show issues precisely at the point where shortand long-range forces are crossing over. at high ionic concentrations, the dressed ion theory breaks down due to competition between ion-water and ion-ion pairing. when solvent molecules are strongly bound, the use of a continuous density field cannot fully capture their influence on thermodynamic properties. even without strongly bound solvent, dielectric solvation models leave open the important question of whether electrons from the fully modeled molecule are more or less likely to ‘spill out’ into the surrounding solvent. returning back to aristotle’s objection to discrete objects, it is known that density based models don’t accurately capture the free energy of forming a empty cavity.67,68 thousands of years on, we are still vexed by the question of how to understand the interface between material objects and vacuums. the future: a middle way early eastern thought tends to place opposing ideas next to one another in an attempt to understand them as parts of a whole picture. written around the beginning of the middle ages, in 400 ad, the lankavatara sutra relates buddha’s view that this unity applies to atoms and ‘the elements’ (which refer to something like the classical greek elements). taking liberties, we can say he is discussing a process like instantaneous disappearance (annihilation) of a quantum particle in saying, “even when closely examined until atoms are reached, it is [only the destruction of ] external forms whereby the elements assume different appearances as short or long; but, in fact, nothing is destroyed in the elemental atoms. what is seen as ceased to exist is the external formation of the elements.” bohr was well-known for his view on the ‘complementarity’ principle, stating in this context that the act of removing a particle makes its number more definite, while making the amount of energy it exchanged with an external observer undefined.110 perhaps inspiring to bohr sixteen centuries later,111 the quote concludes, “i am neither for permanency nor for impermanency … there is no rising of the elements, nor their disappearance, nor their continuation, nor their differentiation; there are no such things as the elements primary and secondary; because of discrimination there evolve the dualistic indications of perceived and perceiving; when it is recognised that because of discrimination there is a duality, the discussion concerning the existence and non-existence of the external world ceases because mind-only is understood.” bohr’s complementarity could be contrasted with physicist john wheeler. he advocated, as a working hypothesis, that participants elicit yes/no answers from the universe. replies come as discrete ‘bits,’ and are ultimately the reason that discrete structures emerge whenever continuum models try to become precise.112 wheeler, in turn, could be contrasted with hugh everett, whose working hypothesis was that the universe operates by pure wave mechanics.113,114 a modern resolution of those debates invokes small random, gravitational forces to explain how quantum particles could become tied to definite locations.115 it is does not appear that there will be a resolution allowing us to do away with either continuum or discrete notions. of course, it is impossible to deduce scientific principles if we include any elements of mysticism in a theory. nevertheless, the debate on the separation between short and long-range seems to permeate history. this idea that a meaningful understanding of collective phenomena should be sought by combining physical models appropriate to atomic and macroscopic length scales was taken up even recently by laughlin, pines, and co-workers.36 they state, “the search for the existence and universality of such rules, the proof or disproof of organizing principles appropriate to the mesoscopic domain, is called the middle way.” on one account it is clearly possible to set the record straight. there are well-known ways of converting local structural theories into macroscopic predictions and as vice-versa. bayes’ theorem states that, for three pieces of information, a, b, and c, p (b|ac)p (a|c)p (a|bc) = p (b|c) . (8) if ‘c’ represents a set of fixed conditions for an experiment, ‘b’ represents the outcome of a measurement, and ‘a’ represents a detailed description of the underlying physical mechanism (for example complete atomic coordinates), then bayes’ theorem explains how 56 david m. rogers to assign a probability to atomic coordinates for any given measurement, ‘b’. of course, in a reproducible experiment, c will completely determine b, so b = b(c). thus, the probability distribution over the coordinates is a function only of the experimental conditions, p (a|bc) = p (a|c). this summarizes the process of assigning a local structural theory from exactly reproducible experiments. on the other hand, a local structural theory provides an obvious method for macroscopic prediction. given a complete description, ‘a,’ simply follow the laws of motion when interacting with a macroscopic measuring device, ‘b.’ this would properly be expressed in the language above as p (b|ac) = p (b|a), since the experimental conditions are irrelevant. bayes’ theorem then gives us a conundrum, p (b|c) = p (b|a), stating that every microscopic realization of an experiment must yield an identical macroscopic outcome. the solution to the puzzle is to realize that unless an experiment is exactly reproducible, bc is always more informative than the conditions, c, alone and p (a|bc) ≠ p (a|c). this explains why studying exactly integrable dynamical systems is such a thorny issue, and is the central conceptual hurdle passed when transitioning from classical to quantum mechanics. now identifying ‘b’ with a partial measurement that provides a coarse scale observation of some long-range properties, p (a|bc) describes a distribution over the short-range, atomistic, and discrete degrees of freedom. because of experimental uncertainty, the exact location of those atoms is evidently subjective and unknowable (since it is based on measurement of b). nevertheless, it can in many cases be known to a high degree of accuracy. density functional theory traditionally focuses on p (b|c), where ‘b’ is the average density of particles in a fluid and ‘c’ is the experiment where a bulk material is perturbed by placing an atom at the origin. however, with a minor shift in focus, p (b a'c) can also be found, representing the average density under conditions where a particle is placed at the origin and some atomic information, a' is also known. the objective of such a density functional theory would be to more accurately know the long-range structure by including some explicit information on the short-range structure. the dual problem is to predict p (a|b'c), the distribution over coordinates when we are provided with some known information on the long-range structure. in a complete generalization, we might focus instead on p (ab|a'b'c), representing the average density and particle distribution under conditions where density and particle positions are known only in part. bayes’ theorem shows us that such a generalization would just be the result of weaving the primal and dual problems together, since (given the redundancies, b' = b'(b) and a' = a'(a)), p (a|a'b'c) = p (a|b'c)/p (a'|b'c), and p (b|a'b'c) = p (b|a'c)/p (b'|a'c). the arguments above can be repeated for each of the elements in table 1 – replacing sr with a and lr with b. what emerges is a persistent pattern of logical controversy, where a problem can be apparently solved entirely from either perspective. in some areas, one or the other approach is more expedient. in every case, however, recognizing and using both sides has proved to be profitable. comparing these two perspectives, we find that the discussion concerning the existence of long and short-range theories ceases, leaving only different ways to phrase probability distributions. we have now arrived at a point in the history of molecular science where these two great foundations, short-range, discrete structures and long-range, continuum fields are at odds with one another. molecular dynamical models are fundamentally limited by the world view that all forces must be computed from discrete particle locations. computational methods treating continuum situations focus their attention on solving partial differential equations for situation-specific boundary conditions. connecting the two, or even referring back to simple analytical models, requires time and effort that is seen as scientifically unproductive. what’s worse, it reminds us that many, lucidly detailed, broadranging, and general answers were already presented in the lengthy manuscripts which set forth those older, unfashionable models. indeed, local and continuum theories are hardly on speaking terms. in molecular dynamics, the math ematics of the ewald method for using a fourier-space sum to compute long-range interactions are widely considered esoteric numerical details. much effort has been wasted debating different schemes for avoiding it by truncating and neglecting the long-range terms.116-118 on the positive side, the central issue of simulating charged particles in an infinite hall of mirrors has been addressed by a few works.119-121 much greater effort has been devoted to adding increasingly detailed parameters, such as polarizability and advanced functional forms for conformation and dispersion energies, to those atomic models. apparently, automating the parameterization process 122 is unfundable. in the case of polarization and dispersion, the goal of these atomic parameters is, somewhat paradoxically, to more accurately model the long-range interactions. the problem of coupling molecular simulations to stochastic radiation fields has, apparently, never been considered as such. instead, we can find comparisons of numerical time integration methods intended to enforce constant temperature on 57range separation: the divide between local structures and field theories computed correlation functions.123 in continuum models based on partial differential equations, actual molecular information that should go into determining boundary conditions, like surface charge and slip length (or, more accurately, boundary friction124), are replaced by ‘fitting parameters’ that are, quite often, never compared with atomic models. indeed, studies in the literature that even contain a model detailed enough to connect the two scales are few and far between. we are also at a loss for combining models of different scales with one another. of the many proposed methods for coupling quantum mechanical wavefunction calculations to continuous solvent, essentially all of them neglect explicit first-shell water structure that could be experimentally measured with neutron scattering, diffusion measurements, and ir and raman spectroscopy. jumping directly into applications is a disease infecting much of contemporary science. rather than attempting to faithfully reproduce the underlying physics, many models are compared by directly checking against experimentally measured energies – and no clear winner has emerged (nor can it). to be correct, models must be checked for consistency with experiments at neighboring length scales. similar remarks can be made for implicit solvent models coupling molecular mechanics to continuum. even marcus theory is not untouched. there is currently debate on the proper way to conceptualize its parameter that sets the ‘stiffness’ of the solvent linear response.125 in order to make progress, we must apparently work as if we had one hand tied behind our back. used correctly, simulations provide a precise tool to answer a well-posed question within a known theory, or as a method of experimentation to discover ideas. however, when used absent a general theory, simply as a tool to reproduce or predict a benchmark set of experimental data, simulation is not capable of providing any detailed insight or understanding of molecular science. acknowledgements i thank the anonymous reviewers for their comments 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separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 4(2) suppl.: 49-55, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-833 citation: m. shahid, m. taseidifar, r.m. pashley (2020) a study of the bubble column evaporator method for improved ammonium bicarbonate decomposition in aqueous solutions: desalination and other techniques. substantia 4(2) suppl.: 49-55. doi: 10.36253/substantia-833 copyright: © 2020 m. shahid, m. taseidifar, r.m. pashley. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. a study of the bubble column evaporator method for improved ammonium bicarbonate decomposition in aqueous solutions: desalination and other techniques muhammad shahid, mojtaba taseidifar, richard m. pashley* school of science, university of new south wales, northcott drive, canberra, australia *corresponding author: r.pashley@adfa.edu.au abstract. a bubble column was used to study the improved thermal decomposition of nh4hco3 in aqueous solution using a continuous flow of hot gas bubbles of optimum sizes (1-3 mm) produced via controlled bubble coalescence to maintain bubble size. the rapid transfer of heat from small, hot (dry) gas bubbles to the surrounding water, i.e. into a transient hot surface layer, was used as an effective and energy efficient method of decomposing ammonium bicarbonate in aqueous solution. it is shown that the continuous flow of (dry) hot gases, even at 275 °c, only heat the aqueous solution in the bubble column to about 57 °c, at which it was also established that nh4hco3 has a negligible decomposition rate even with long-term exposure to this solution temperature. hence, the effects observed appeared to be caused entirely by the effective collisions between the hot gas bubbles and the solute. it was also established that the use of high gas inlet temperatures can reduce the thermal energy requirement to only about 50% (i.e. about 575 kj/l) of that reported in previous studies and less than 25% of solution boiling. keywords: non-boiling decomposition, bubble coalescence, transient collisions, ammonium bicarbonate. 1. introduction 1.1. significance of solute decomposition this paper is concerned with optimising a range of applications that use water, be they desalination, sterilisation, reactions and more using a bubble column evaporator. the overarching goal of water treatment by decomposition is to remove unwanted substances or solutes from water affordably and robustly. for example, the decomposition of ammonium bicarbonate (with chemical formula nh4hco3) in aqueous solution is an important and energy-intensive process in the application of forward osmosis1 and, in the regeneration of ion-exchange resins.2 for the latter application, the ion-exchange resins comprising carboxylic acid and tertiary amine groups for desalination 50 muhammad shahid, mojtaba taseidifar, richard m. pashley can be thermally regenerated using the bce process at a lower energy cost than with conventional methods. more recently, shahid et al.3 studied that solutes, ammonium bicarbonate (nh4hco3) and potassium persulphate (k2s2o8) can be thermally decomposed in aqueous solutions using a bubble column evaporator (bce) process at sub-boiling condition (around 45 °c). fulks et al.4 and gokel5 studied, ammonium bicarbonate decomposition in solution over the temperature range 30−85 °c. complete decomposition into ammonia, carbon dioxide and water was observed above 60 °c. the main decomposition reaction is: nh4 hco3 (aq)≜nh3 (g)+co2 (g)+h2o (1) the decomposition rate of this solute can be readily measured from simple electrical-conductivity measurements. the decomposition of ammonium bicarbonate using the hot-gas bce process is examined in this study. 1.2. significance of the bubble column evaporator (bce) the bubble column evaporator (bce) offers a good illustration of the use of a gas-liquid interface to drive fundamental processes involving heat and mass transfer. bubble columns are devices in which a gas, often dry air, is pumped through a multi-porous sinter disc to form gas bubbles which are continuously replenished and come into intimate contact with the column solution. dry gas bubbles in the column solution may be used simply to mix the liquid phase homogenously to attain a uniform temperature distribution or to saturate dissolved gases in the column solution. substances can also be transferred from one phase to the other, for example when liquid reaction products are stripped from a gas: both massand heat-transfer processes can occur simultaneously.6 recently, aqueous bubble column evaporators have been used for a range of new applications. these exploit the long known, but still unexplained effect of bubble bubble coalescence inhibition that occurs systematically with many salts. the effect is both ion pair and concentration dependent. in combination with the effect are size dependent bubble rise rates and rapid watervapour uptake into the bubbles.3,7-9 these phenomena together offer a variety of applications. the most striking of these we have developed are in desalination. some of a wide range of other useful applications of the bce10 are: a new method for the precise determination of enthalpies of vaporisation (δhvap) of concentrated salt solutions;7,11 evaporative cooling;8 a new method for thermal desalination;12-14 a novel method for subboiling thermal sterilization;7,15-19 a novel method for the low-temperature thermal decomposition of different solutes in aqueous solution;3 a new approach to aqueous solute precipitation in a controlled manner.20 the efficient removal of heav y metal ions in an ionspecific, ion-flotation process is a specially noteworthy advance.21 in addition, a bubble column condenser has also been designed for the production of high-quality water as condensate.22-24 1.3. proposed mechanism of bce thermal decomposition the application of the bce process opens up a new approach to the thermal decomposition of degradable salts in aqueous solution. the hot surface layer produced transiently on the surface of hot bubbles (see figure 1) created in the bce appears to play a significant role in providing high heatand mass-transfer efficiency, since the bce is a direct-contact evaporator.25 degradable chemicals exposed to this hot layer can be efficiently decomposed. in addition, gaseous products are rapidly captured by the rising bubbles, due to the internal gas/vapour rotational flow produced within the rising bubbles. here the effectiveness of the bce as a method for solute decomposition was assessed and quantified. experiments were conducted using ammonium bicarfigure 1. schematic diagram of bce thermal decomposition using a hot-air bubble layer. (reprinted with permission from ref. 3. copyright 2015 american chemical society). 51a study of the bubble column evaporator method for improved ammonium bicarbonate decomposition in aqueous solutions: desalination and other techniques bonate at high inlet gas temperatures and a comparative study of energy cost was determined. 2. materials and methods 2.1. materials certified reagent-grade (≥ 99% purity), ammonium bicarbonate (nh4hco3) was supplied by may & baker ltd and used without further purification. aqueous solutions were prepared using deionized, ultrafiltered water (milli-q). at room temperature, the deionized water had a conductivity < 2.0 µs/cm and a natural equilibrium ph of 5.7. all concentrations are given in molality (m) units. 2.2.2. electrical conductivity measurements in standard nh4hco3 solutions ammonium bicarbonate solutions were prepared in the range: 0.5 to 2 m. electrical conductivity values of all the solutions were measured using a thermo fisher scientific (waltham, ma, usa) conductivity meter at 25 °c. 2.3. bce system for thermal decomposition a high-surface-area gas/water interface was produced continuously by pumping dry gases (laboratory grade air and nitrogen separately), through a 40−100 micron pore-size glass sinter into a 120 mm diameter open-top glass column (büchner type, pyrex® borosilicate, vwr) filled with 250 ml solution. the bce apparatus used to study improved decomposition with a high-temperature gas (air) flow is shown in figure 2. this system enables the use of inlet dry gas temperatures of more than 275 °c. the inlet air temperature was varied using a tempco air heater (300w) with a thermocouple temperature monitor and an ac variac electrical supply. the actual temperature of the dry gas flowing into the solution was measured at the centre of the sinter by a tenmars thermometer (±1.5 °c) without any solution in the column. the gases (air and nitrogen) were produced by cylinder (coregas pty ltd, australia) and a boc gas flow meter. the temperature of the column solution was also continuously monitored using a thermocouple positioned at the centre of the column solution. the air flow at temperatures of 300−600 °c, was needed to produce gas temperatures just above the glass sinter up to 275 °c, and this necessitated the use of steel and brass connectors for the downstream output from the heater and the use of fm insulation rock wool as an insulating material. for comparison, the effects of solution temperature on the decomposition of nh4hco3 solutions was studied over time using stirred samples in a tamson (beiswijk, the netherlands) heating bath at temperatures matching those of the bce tests. during these experiments, samples were regularly taken out from the column and water bath, and their electrical conductivities and ph values measured using a eutech con 700 ph 700 bench meter (eutech instruments pte ltd.). 3. results and discussion 3.1. thermal decomposition of ammonium bicarbonate solutions using a bce 3.1.1. measurement of the electrical conductivity of nh4hco3 solutions at different concentrations as the nh4hco3 salt thermally decomposed into nh3 and co2 gases, the concentration of nh4+ and hco3reduced in the aqueous solution. so the decomposition process could be monitored through the measurement of the electrical conductivity of the samples taken from the bubble column. the ph of aqueous solutions were also measured and found to be basic. as hot dry bubbles enter the column, water vaporisation occurs, and water vapour passes into the bubbles. variac ac gas heater thermometers gas in gas cylinder heat gas warm/hot gas in bubble column evaporator air flow meter figure 2. schematic diagram of the bubble column evaporator (bce) for solute decomposition. (reprinted with permission from ref. 3. copyright 2015 american chemical society). 52 muhammad shahid, mojtaba taseidifar, richard m. pashley the amount of vaporised water removed, mv (g) after time t (sec), during a typical bce process was estimated using the following relation: (2) where, rf (l/s) is the room-temperature gas flow rate, measured just prior to the heater, about 22.5 l/min in this study; tc, tf are the gas temperatures (in k) at the top of the column solution and at the flow meter; and pc, pf are the corresponding pressures at the same positions. these are the factors used to estimate the “bubble column flow rise” rate. here is the water-vapour density in g/l at the temperature of the solution at the top of the column, which was calculated from the vapour pressure of the solution using the ideal gas equation. using the measured electrical conductivity of the nh4hco3 solutions at different time intervals, the percent decomposition of nh4hco3 at time (t) in the bce process was calculated: decomposition%=[1– ]×100 (3) here [nh4hco3]t is the concentration of nh4hco3 at time (t) during the bce operation and [nh4hco3]0 is the initial concentration of nh4hco3, just before pouring the solution into the bubble columns. 3.1.2. decomposition of nh4hco3 solutions some typical decomposition results (using air and nitrogen) obtained under different solution conditions are given in figure 3. these results clearly demonstrate that the improved bce process is much more efficient for nh4hco3 decomposition than the standard method using a simple stirred heating (without bce) at the same solution temperature, here around 57 °c. the results in figure 3 obtained for quite different stirring conditions showed that the decomposition rates for simple heating (without the bce) remained the same. this shows that the continuous mixing by the bubbling process in the bce did not itself contribute to the nh4hco3 decomposition. different concentrations of nh4hco3 were also studied, as shown in table 1. it was observed that the presence of nh4hco3 at concentrations above about 0.5 m inhibited bubble coalescence to a similar degree as that at 0.17m. (this critical concentration is the same for all 1:1 salts like nacl that exhibit the fusion inhibition phenomenon9) it was also observed that fine (1−3 mm diameter) bubbles were produced in the bce process (see figure 4a). it was clear from the photos taken during the decomposition of 2 m nh4hco3 solution that, after bubbling for 10 min, the average bubble size started to increase (figure 4b). that is expected as electrolyte concentration reduces.9 finally, after almost complete decomposition of nh4hco3 at around 20 min, the bubble size became the same as in pure water. this provides explicit visual indication of the complete decomposition of ammonium bicarbonate in the aqueous solution (figure 4c). the thermal decomposition of ammonium bicarbonate solutions into ammonia and carbon dioxide gas and the resulting reduction in nh4hco3 concentration reflects the increase in bubble size. table 1. decomposition efficiency for an initial solution of 2 m nh4hco3 solution using a heated (dry) air inlet in the bce process. time (min) column solution temperature (°c) electrical conductivity (ms/cm) ph 0 room temp. 85 7.74 5 54.2 52.1 9.25 10 56.7 28.3 9.44 15 57.1 8.95 9.33 20 57.8 1.57 8.87 figure 3. percent decomposition of nh4hco3 solutions at different concentrations in the bce with an inlet gas (air and nitrogen) temperature of 275 °c and column solution temperature of 57 °c and in a stirred vessel for simple heating at around 57 °c. 53a study of the bubble column evaporator method for improved ammonium bicarbonate decomposition in aqueous solutions: desalination and other techniques 3.1.3. effect of initial bubble temperature on nh4hco3 decomposition in a bce it appears that the decomposition of nh4hco3 in aqueous solutions within a hot air bce system occurs due to the hot surface layer initially present around the stream of hot air bubbles released from the frit. we consider the likely thickness of this transient heated layer as a function of inlet air temperature. the maximum extent of the layer can be estimated for a given temperature, assuming that it is uniform, from the total heat available from the freshly released bubble. for example, for a 1mm bubble we can estimate the maximum layer thickness of water heated to, say, 80°c by the bubbles with an initial release temperature of about 150 °c (i.e. the inlet gas temperature) as follows. this bubble layer thickness varies with bubble size (v) and the temperatures of the inlet air, the steady state column temperature and the average temperature of the heated surface film surrounding the bubbles. the maximum heated layer thickness can be estimated using the thermal energy balance equation: cp∆tv=cwater∆t4πr2ρwz (4) where cp, cwater are the air and water heat capacities, in units of j/(m3×k) and j/(kg×k), respectively, and ρw is the liquid water mass density (in kg/m3). ∆t, ∆t are the transient temperature increase in the water layer and the temperature reduction within the cooling bubbles, in units of k, respectively. the volume of a layer of thickness z around a bubble is given by 4πr2ρwz, when z is much smaller than r. hence the cooling of the bubble by ∆t must determine the thickness z. for example, for bubbles cooling by 100 °c, the maximum heated water layer thickness, heated from 20 to 80 °c, is about 70 nm. so ammonium bicarbonate could be decomposed in this surface region, as illustrated in figure 5. when the inlet gas temperature is increased, the thickness of the surface hot water layer would also be increased, provided the mean temperature of the film and other assumptions are fixed. consequently, the volume of the decomposition area (in the hot bubble layer) is correspondingly increased, leading directly to improved decomposition. it is useful to estimate the thermal energy cost to produce decomposition of an ammonium bicarbonate solution. we have done this by passing 22.5 l/min of air heated to 275 °c through a bubble column for 20 mins with 1-3 mm size bubbles. different concentrations of ammonium bicarbonate solution were used. the heat capacity cp at a constant pressure of air in units of j/gk can be calculated from gas heat capacity per mole. this is fairly constant with temperature. at 275 °c this corresponds to about 1.017 j/gk respectively. for a flow rate of 22.5 l/min, this requires a total heat to raise the temperature of gas from 20 to 275 °c of about 144 kj per 250 ml of solution or 575 kj/l. by comparison, heating a litre of ammonium bicarbonate solution using different inlet gas temperatures is shown in figure 6. figure 4. photographs of the bubble sizes in nh4hco3 solutions in a bce with an inlet of (dry) air at 275 °c, at experimental times: (a) 0 min (b) 10 min; and (c) 20 min. 54 muhammad shahid, mojtaba taseidifar, richard m. pashley 4. conclusions and future work a method for sub-boiling, thermal decomposition of ammonium bicarbonate solutions was presented. this is a considerable improvement on standard methods. we have shown that a bubble column can rapidly exchange heat from hot gas bubbles to the nearby water surrounding the bubbles. this can be used as an effective and energy efficient method of decomposing ammonium bicarbonate in solution. it can be readily scaled up to treat industrial ammonium bicarbonate draw solutions used in forward osmosis desalination. an important inference is this: the bce process, in addition to those applications already mentioned, might also be used to destroy unwanted solutes. hormones and pharmaceutical compounds present in wastewater present intractable problems for city water recycling. conventional technologies do not effectively treat these contaminants. antibiotic residues from human consumption or intensive farming can contribute to the development of antibiotic-resistant bacteria. protozoa, residual pharmaceutical compounds and hormones are believed to have potential risks to humans and the environment. examples of such treatments with co2 are given in other papers in this volume. the possibilities of achieving very high temperatures within bubbles say with oxygen to carry out reactions at low cost are open. 4. nomenclature abbreviations ab ammonium bicarbonate bce bubble column evaporator symbols °c degree celsius m concentration in mol/l m concentration in mol/kg n number of moles t temperature ∆hvap enthalpy of vaporisation ∆p pressure difference between inside and outside of the bubble ∆t temperature difference between inlet gas and bubble column solution 5. acknowledgment we would like to thank the australian research council for funding this project. 6. references 1. j. r. mccutcheon, r. l. mcginnis, and m. elimelech, a novel ammonia—carbon dioxide forward (direct) osmosis desalination process, desalination, 2005, 174(1), 1-11. figure 5. relationship between the temperature of the inlet gas and the estimated thickness of the transient hot bubble surface layer around a 1 mm radius bubble in pure water, 0.5 m nacl and 5.0 m cacl2. reprinted by permission of the publisher (taylor &francis ltd, http://www.tandfonline.com) from ref. 10. figure 6. comparison of thermal energy cost using air as carrier gas; a indicates energy cost at 150 °c inlet gas temperature using 2 m ab solution; b shows at 150 °c inlet gas temperature with 1 m ab solution; c illustrates at 150 °c inlet gas temperature with 0.5 m ab solution and d explains energy cost at 275 °c using 2 m ab solution. 55a study of the bubble column evaporator method for improved ammonium bicarbonate decomposition in aqueous solutions: desalination and other techniques 2. n. p. g. n. chandrasekara and r. m. pashley, study of a new process for the efficient regeneration of ion exchange resins, desalination, 2015, 357, 131-139. 3. m. shahid, x. xue, c. fan, b.w. ninham, and r.m. pashley, study of a novel method for the thermolysis of solutes in aqueous solution using a low temperature bubble column evaporator, j. phys. chem. b, 2015, 119 (25), 8072–8079. 4. g. fulks, g. b. fisher, k. rahmoeller, m. c. wu, e. d’herde, j. tan, a review of solid materials as alternative ammonia sources for lean nox reduction with scr, 2009, sae technical paper. 5. g. w. gokel, dean’s handbook of organic chemistry. mcgraw-hill new york, 2004, 71375937. 6. p. zehner and m. kraume, bubble columns, ullmann’s encyclopedia of industrial chemistry, 2000. 7. c. fan, m. shahid, r.m. pashley, studies on bubble column evaporation in various salt solutions, j. sol. chem., 2014, 43(8), 1297-1312. 8. m. francis, r. pashley, application of a bubble column for evaporative cooling and a simple procedure for determining the latent heat of vaporization of aqueous salt solutions, j. phys. chem. b, 2009, 113(27), 9311-9315. 9. v. s. j. craig, b. w. ninham, r. m. pashley, the effect of electrolytes on bubble coalescence in water, j. phys. chem. , 1993, 97(39), 10192-10197. 10. m. shahid, c. fan, r. m. pashley, insight into the bubble column evaporator and its applications, int. rev. phys. chem. , 2016, 35(1), 143-185. 11. c. fan and r. m. pashley, precise method for determining the enthalpy of vaporisation of concentrated salt solutions using a bubble column evaporator, j. sol. chem., 2015, 44(1), 131-145. 12. m. j. francis, r. m. pashley, thermal desalination using a non-boiling bubble column, desalin. water treat., 2009, 12(1-3), 155-161. 13. m. shahid, r. m. pashley, a study of the bubble column evaporator method for thermal desalination, desalination, 2014, 351, 236-242. 14. m. taseidifar, m. shahid, r. m. pashley, a study of the bubble column evaporator method for improved thermal desalination, desalination, 2018, 432, 97-103. 15. x. xue and r.m. pashley, a study of low temperature inactivation of fecal coliforms in electrolyte solutions using hot air bubbles, desalin. water treat., 2015, 1–11. 16. m. shahid, a study of the bubble column evaporator method for improved sterilization, j. water process. eng., 2015, 8, 1–6. 17. a. g. sanchis, m. shahid, and r. m. pashley, improved virus inactivation using a hot bubble column evaporator (hbce), colloids and surfaces b: biointerfaces, 2018, 165, 293-302. 18. a. g. sanchis, r. m. pashley, b. w. ninham, virus and bacteria inactivation by co2 bubbles in solution, npj clean water, 2019, 2(1), 5. 19. m. shahid, r. m. pashley, m. rahman, use of a high density, low temperature, bubble column for thermally efficient water sterilisation, desalin. water treat., 2014, 52, 4444–4452. 20. c. fan, r. m. pashley, the controlled growth of calcium sulfate dihydrate (gypsum) in aqueous solution using the inhibition effect of a bubble column evaporator, chem. eng. sci., 2016, 142, 23-31. 21. m. taseidifar, f. makavipour, r. m. pashley, a. f. m. m. rahman, removal of heavy metal ions from water using ion flotation, environ. technol. innov., 2017, 8, 182-190. 22. p. n. govindan, g. p. thiel, r. k. mcgovern, j. h. lienhard, m. h. elsharqawy, bubble-column vapor mixture condenser. google patents. 23. g. p. narayan, j. h. lienhard, thermal design of humidification–dehumidification systems for affordable small-scale desalination, ida j. desalin. water reuse, 2012, 4(3), 24-34. 24. m. schmack, h. goen, and a. martin, a bubble column evaporator with basic flat-plate condenser for brackish and seawater desalination, environ. technol., 2015 37(1), 74–85. 25. c. p. ribeiro, p. l. c. lage, gas‐liquid direct‐contact evaporation: a review, chem. eng. technol., 2005, 28(10), 1081-1107. substantia. an international journal of the history of chemistry 4(2) suppl.: 119-121, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1146 citation: b.w. ninham (2020) postscript. substantia 4(2) suppl.: 119-121. doi: 10.36253/substantia-1146 copyright: © 2020 b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. postscript barry w. ninham department of applied mathematics, research school of physical sciences, the australian national university, canberra, australia e-mail: barry.ninham@anu.edu.au 1348 was the year of the great plague in europe. one third of the population died. a project into causes commissioned by the king of france from the best doctors of medicine of the premier sorbonne university found out why. the plague, they discovered, was due to a rare conjunction of the planets mars, jupiter and saturn. that all made sense. these planets were associated with 3 of the 4 humours of the body, the balance of which determined health. astrology was god-given in those geocentric times. to dispute such a proof was tantamount to impiety. similar dogma attends the certainty of the science of each and every era. with time the theories of one generation evolve and are dismissed by the next as naïve, comparable with the book of genesis. but not so credible! witness quantum entanglement. this we know. nonetheless current scientific theories are invariably defended as vigorously as the bible is taken literally to be god’s revealed truth by some fundamentalist believers. and so it is today.1 priests will be priests and professors will be professors. we have reported on a suite of simple new water technologies, in desalination, in sterilisation, in heavy metal pollution and harvesting, in cavitation, in a new class of environmentally friendly surfactants, on control of slimes and sludges from mining and floods. all are cheap, scalable. all are desperately needed. why were these not developed before? the answer is that all depend on science2 that does not fit into the standard dogmas of physical, colloid and surface chemistry. these theories we expect to be the enabling disciplines that underpin life sciences and chemical engineering sciences. in this, the physical sciences have signally failed. they have not done the job. the greeks told us why. of the four elements, fire, water, earth and air, we forgot about the air. our theories ignored dissolved gas in water the exemplar is the electrolyte ion pair specific bubble-bubble fusion interaction inhibition phenomenon.3 it occurs around 0.17 m, precisely the 120 barry w. ninham ionic strength of the blood. it has been known for a century, widely known for 40 years. perhaps the simplest imaginable experiment, it cannot be explained by classical physical chemistry. the standard theories also omit specific ion (hofmeister effects). all of our novel technologies depend on these things. concepts like ph and buffers, and pka and osmotic pressure, activities, zeta potentials and membrane potentials, ion pumps, electrostatic forces, molecular recognition, antibody-antigen and enzyme specificity are part of the language and intuition of biology and electrochemistry. the interpretation of such measurements that depend on a now outmoded astrology, flawed theories that omit the role of dissolved gas. “hydrophobic” interactions go away when dissolved gas is removed.4. similarly the theories omit or treat incorrectly specific ion effects. simulation suffers from the same defects. so what we think ought to be the relevant science in exploring new arenas is impotent. it is as handicapped as was that geocentric astrology of the good doctors of paris. our new technologies rely on unexplained effects associated with bubbles and dissolved gas. and as we proceeded it became clearer that we could begin to see the outline of something very new. the very effective sterilisation of water, killing of viruses and other pathogens by warm co2 in a column above 0.17 m, physiological concentration suggested more.5,6 nanobubbles of co2, oxygen and nitrogen under these conditions will also be stable and produce free radicals that drive not just enzymatic reactions,7,8 but chemical reactivity generally.9,10,11 and so it turns out. for example, the structure and function of the endothelial surface layer in physiology was revealed as a dynamic foam of co2 nanobubbles.12 it complements the lung surfactant structure and its delivery of oxygen and nitrogen via nanobubbles.13 the esl protects tissue from invasions by pathogens and acts to destroy covid viruses.14 the self-assembly of gas nanobubbles as a function of salt in bulk solution4 and at surfaces mimics the same subtleties in self-assembly as surfactants15,16 and provides the energy that drives chemical reactions.7-11 the ubiquity of stable spontaneous nanobubbles that are sources of free radicals17 adds a whole new flexibility to the rigidity and limitations of present antibody-antigen and enzyme substrate interaction ideas in immunology and biochemistry. these things if only dimly perceived, are now a little clearer there remains the hurdle of dean swift’s confederacy of dunces and their dialogue of the deaf. but if we ignore them, we can begin to see a scientific parallel for the reverend martin luther king’s promised land. we remark finally that an excellent study of the effects of shaking and bubbles on inactivation of virues and bacteria as long ago as 1948.18 references 1. b. w. ninham, the biological/physical sciences divide and the age of unreason, substantia, 2017, 1 (1) 724. 2. b. w. ninham, r. m. pashley, p. lo nostro, surface forces: changing concepts and complexity with dissolved gas, bubbles, salt and heat, curr. opin. colloid interface sci., 2016, 27, 25-32. 3. v. s. j. craig, b. w. ninham, r. m. pashley, the effect of electrolytes on bubble coalescence in water, j. phys. chem. 1993, 97 (39), 10192-10197. 4. b. w. ninham and p. lo nostro, unexpected properties of degassed solutions, j. phys. chem., 2020, 124(36), 7872-7878. 5. a. g. sanchis, r. m. pashley, b. w. ninham, water sterilisation using different hot gases in a bubble column reactor, j. environ. chem. eng., 2018, 6, 2651-2659. 6. a. g. sanchis, r. m. pashley, b. w. ninham, virus and bacteria inactivation by co2 bubbles in solution, npj clean water, 2019, v 2 number 1. 7. h.-k. kim, e. tuite, b. nordén, b. w. ninham, coion dependence of dna nuclease activity suggests hydrophobic cavitation as a potential source of activation energy, eur. phy. j., 2001, 4, 411-417. 8. b. feng, r. p. sosa, a. k. f. mårtensson, k. jiang, a. tong, k.d. dorfman, m. takahashi, p. lincoln, c. j. bustamante, f. westerlund, b. nordén, hydrophobic catalysis and a potential biological role of dna unstacking induced by environment effects, p. national acad. sci. united states of america, 2019, 116, 17169–34343. 9. m. e. karaman, b. w. ninham, r. m. pashley, effects of dissolved gas on emulsions, emulsion polymerization, and surfactant aggregation, j. phys. chem., 1996, 100 (38), 15503-15507. 10. m. alfridsson, b. w. ninham, s. wall, role of co-ion specificity and dissolved atmospheric gas in colloid interaction, langmuir, 2000, 16 (26), 10087-10091. 11. b. w. ninham, k. kurihara, o. i. vinogradova, hydrophobicity, specific ion adsorption and reactivity, colloids surf., a: physiochem. eng. aspects, 1997, 123-124, 7-12. 12. b. p. reines, b. w. ninham, structure and function of the endothelial surface layer: unraveling the nano121postscript architecture of biological surfaces, quarterly rev. biophys., 2019, 52, 1–11. 13. m. larsson, k. larsson, s. andersson, j. kakhar, t. nylander, b. w. ninham, p. wollmer, the alveolar surface structure: transformation from a liposomelike dispersion into a tetragonal clp bilayer phase, j. dispersion sci. technol., 1999, 20 (1&2), 1-12. 14. b. p. reines, b. w. ninham, pulmonary intravascular coagulopathy in covid-19 pneumonia, lancet rheumatol., 2020, 2(8), 458-459. 15. b. w. ninham, k. larsson, p. lo nostro, two sides of the coin. part 1. lipid and surfactant self-assembly revisited, colloids surf.  b: biointerfaces, 2017, 152, 326–338. 16. b. w. ninham, k. larsson, p. lo nostro, two sides of the coin. part 2. colloid and surface science meets real biointerfaces., colloids surf. b: biointerfaces, 2107, 159, 394-404. 17. n. f. bunkin, b. w. ninham, p. s. ignatiev, v. a. kozlov, a. v. shkirin and a. v. starosvetskiy, longlived nanobubbles of dissolved gas in aqueous solutions of salts and eurythocyte suspensions, j. biophotonics, 2011, 4 (3), 150–164. 18. m. h. adams, surface inactivation of bacterial viruses and of proteins, j. gen. physiol., 1948, 31(5), 417-431. sub-covid-808 citation: l. campanella (2020) even covid-19 could teach us something if we were good students! substantia 4(1) suppl. 1: 917. doi: 10.13128/substantia917 received: apr 19, 2020 revised: apr 22, 2020 just accepted online: apr 27, 2020 published: apr 27, 2020 copyright: © 2020 l. campanella. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia editorial even covid-19 could teach us something if we were good students! luigi campanella department of chemistry, sapienza university, piazzale aldo moro 5, 00185 rome, italy *corresponding author: luigi.campanella@uniroma1.it in these dramatic times most of the attention is paid to the statistics of recovered, dead and infected people. but here i would point out another aspect that can make us able to forget even for a very short moment the terrible statistics i mentioned above and open us to hope. while we are closed and locked in our homes nature seems to take a breath. some days ago, a family of ducks walking around in a desert florence and looking for something to eat inspired an incredible feeling of tenderness. this was just the latter of a series of images available on the web, at the same time disquieting, romantic and bucolic, that illustrate the amazing transformation of nature and of fauna in the time of this pandemy. these images disquiet because we never saw so many animals walking free down the streets of our cities, in places that are now empty and neglected and that just two months ago were palpitating of life. these images are romantic and bucolic as they show that despite the war bulletins of death of these weeks nature wants to speak of continuing life. however this is not the only subject on which we have to ponder. the vision of our earth from the space is deeply changed. if we start from italy, we can see the po valley finally smog-free: the yellow and red colours of the meteomaps representing different levels of pollution recorded in january and february 2020 left room to a pure atmosphere. the air pollution of this area has lead to pathologies and deaths: we must recall and think about the last conclusion of the environment european commission. there, it was stated that due to nitrogen oxides pollution in italy during the last year about 15 thousand people died! during this pandemy the concentration of these dangerous pollutants fell abruptly about 50% of the initial values. another data reported in these days indicates that in 20 days the carbon dioxide level measured in the state of new york is the same as that produced during a whole year. this occurred because of the turned off diesel engines, of the reduced industrial work, civil activities and airflights. but other pictures force us to reflect: the hares in the parks in milan, the transparency of the water in the venice lagoon that make that allow us to see swimming fish, and the dolphins in the cagliari's harbour. the question is: will we be able to learn a lesson from what covid-19 has taught us on the social, civil and scientific side about new lifestyles and more active interactions between medicine and other discplines? substantia. an international journal of the history of chemistry 4(1) suppl. 1: 917, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-917 substantia. an international journal of the history of chemistry 3(2) suppl. 5: 29-48, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-582 citation: j. h. maar, a. maar (2019) the periodic table and its iconicity: an essay. substantia 3(2) suppl. 5: 29-48. doi: 10.13128/substantia-582 copyright: © 2019 j. h. maar, a. maar. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 1 retired, chemistry department, federal university of santa catarina 2 department of philosophy, state university of londrina, paraná e-mail: juergen.maar@gmail.com, alexander.maar@web.de abstract. in this essay, we aim to provide an overview of the periodic table’s origins and history, and of the elements which conspired to make it chemistry’s most recognisable icon. we pay attention to mendeleev’s role in the development of a system for organising the elements and chemical knowledge while facilitating the teaching of chemistry. we look at how the reception of the table in different chemical communities was dependent on the local scientific, cultural and political context, but argue that its eventual universal acceptance is due to its unique ability to accommodate possessed knowledge while enabling novel predictions. furthermore, we argue that its capacity to unify apparently disconnected phenomena under a simple framework facilitates our understanding of periodicity, making the table an icon of aesthetic value, and an object of philosophical inquiry. finally, we briefly explore the table’s iconicity throughout its representations in pop art and science fiction. keywords. dmitri mendeleev, the periodic table of elements, philosophy of chemistry, science and pop art, science fiction. the periodic table was incredibly beautiful, the most beautiful thing i had ever seen. (oliver sacks) an exposition of all that matters in matter. (bruce greenhalgh) introduction the periodic table of elements is chemistry’s most universal ‘tool’, used both as a teaching method and research instrument. but it is also a sign and icon that unites all chemical knowledge. in philosophy of language, ‘iconicity’ is the name given to a certain similarity relation between the form and the meaning of a sign. the lack of similarity is arbitrariness, which means that there is nothing in the form of the sign that resembles its meaning, and simple convention associates the two. we borrow such terminology to claim that the periodic table is truly an icon, not just convention. each of the little ‘squares’ in any of the table’s representations encloses the totality of chemi30 juergen heinrich maar, alexander maar cal and physical knowledge about a given element. in this sense the table is truly iconic: it is perceived as being so closely similar to that which it represents (the totality of chemical knowledge), that form and meaning become intrinsically bounded. since its first formulation, the table has become a universally accepted icon which transits in many places of knowledge. it transits in classrooms and books as a didactic tool, it transits through research laboratories as a reference source, and it transits in annals and records of chemistry as a repository of scientific information and interpretations collected over time. considering its widespread presence, we believe the table parades a dual nature: it is the consolidation of current chemical knowledge, but also a heuristic tool used by chemists in their attempts to expand and consolidate such knowledge. surprisingly perhaps, the ‘tool’ has not changed much since its conception. in the words of scerri: the periodic table of elements is one of the most powerful icons of science: a single document that consolidates much of our knowledge of chemistry [and] despite the dramatic changes that have taken place in science in the last hundred years [relativity and quantum mechanics] there has been no revolution in the basic nature of the periodic system.1 let us next say a few things about how the table came about, from early attempts to find analogies among chemical elements, to more refined views on periodicity. analogies the practice of classifying is an important task in any science. it is a task that involves obtaining the particulars (objects) to be classified, finding non-spurious similarity relations – analogies – between the object and other entities thought to be of the same kind, and drawing empirical and logical conclusions from the way entities are organised. scientific disciplines often make great efforts to divide particulars into kinds and theorise about the nature of these kinds. if one has realist inclinations regarding scientific knowledge, one will often think of a kind as being ‘natural’, i.e. a grouping of particulars that is made possible by how nature is (and not by one’s interests or actions). if this is the case, then scientific taxonomies correspond to real natural kinds. and, as bird and tobin put it, “the existence of these real and independent kinds of things is held to justify our scientific inferences and practices.”2 a classic example is carl von linné’s (1707-1778) botanical and zoological classification in his systema naturae (1735), which became a ‘model’ of classification for other sciences as well. it inspired, for instance, johann beckmann (1739-1811) to classify technological activities in his entwurf einer allgemeinen technologie (1806). chemists too felt the need to classify elements and substances. lavoisier himself, in presenting his table of elements in 1789, classified them. each of the four groups of ‘simple substances’ presents similar or even identical qualities. if we look more closely at a table of affinities, such as that of torbern bergman (1735-1784) from 1775, we will find a classification: each group of substances presents qualitatively equal and quantitatively decreasing properties. after lavoisier, the concern of chemists in classifying became more evident, and we can cite classificatory attempts of richter (1792), döbereiner (1817, 1829), meinecke (1819), thenard (1813), ampère (1816), gmelin (1842), gibbs (1845), among many others. all these attempts are analogical in form, i.e., elements are grouped together based on how the author ‘perceives’ similarities and differences among the elements’ properties. there is an obvious challenge for objectivity here, as similarity relations of one kind will often take priority over other similarity relations, depending on the authors’ theoretical preferences. none of these attempts was a periodic classification, however. the concept of analogy was important to the prevailing naturphilosophie at the time, especially in germany. associated with romanticism, such classificatory attempts were motivated by a desire to formulate a system of thought capable of encompassing both empirical knowledge and a priori, deductive reasoning. natural philosophy has been gradually eliminated from scientific thought; thanks to the rise of empiricism. john locke, for example, argued that the prior formulation of hypotheses and the use of analogical reasoning played a minor role in science – a view consistent with that of experimental philosophy.3 with the decline of speculative philosophy, early classificatory attempts – except maybe döbereiner’s and gmelin’s – became of little philosophical relevance. furthermore, there is an element of subjectivity motivating the formulation of such classificatory systems. an author’s philosophical preferences will often play a decisive role in what counts as relevant in analogical arguments, and therefore on how the elements are classified. let us see how. for jeremias benjamin richter (1762-1807), once a student of kant, some mathematical relations are a priori hypotheses – a view he formulated based on his 31the periodic table and its iconicity: an essay studies of ponderal and stoichiometric relations. for him, any chemical classification had to consider the laws (such as the law of definite proportions, which says that the ratio by weight of the compounds consumed in a chemical reaction stays always the same) according to which substances unite to form compounds. eduard farber4 and georg lockemann5 consider richter to be the first chemist to consider mathematical aspects in his theories. johann ludwig meinecke (1781-1823) reasoned from analogy by giving priority to the notion of chemical affinity, i.e., the tendency exhibited by atoms or compounds to combine (chemically react) with certain atoms or compounds (of unlike composition) in preference to others. this is, of course, a well-established theory today, but during his time ‘affinity’ referred only to bodies who reacted intensively, perhaps ‘unavoidably’, one with the other. it was this older conception of affinity that inspired goethe to write his metaphorical novel elective affinities, in which human passions appear to be governed by the laws of chemical affinities, with the potential to undermine social institutions such as marriage. andré-marie ampère (1775-1836), criticising what he saw as an exaggerated importance given to oxygen, attempted a natural classification or order, or even in the words of jean-baptiste dumas (1800-1884), “a classification of bodies into groups based on primary properties capable of determining all secondary properties.” ampere used an experimental criterion for the classification of the elements, as he focused on “associations and products to which elements are known to be committed.”6 johann wolfgang döbereiner (1780-1849), in his “an attempt to group elementary substances according to their analogies” (1829), ascribed great importance to numbers representing the atomic weights of the elements forming the four “döbereiner triads”. döbereiner identified a pattern with the elements of the triads: if you order them according to their atomic masses, the average of the molar mass of the first and third element of the triad equals the molar mass of the second element (sulphur, selenium and tellurium, for example). on a modern periodic table, these elements are stacked vertically. his work started on the same insight that would later result in the formulation of the periodic law and classification of the elements. for leopold gmelin (1788-1853), another forerunner of the periodic table, physical and chemical relations among simple substances ( = elements) are important, but the structural basis for their classification lies in their electronegativity or positivity, as defined by jöns jacob berzelius (1779-1848) in his lehrbuch (1823). getting into the details of such early classificatory attempts falls outside the scope of this article. but we wish to highlight the motivation that guides them all: to find a form of representing observations of similarities and order among elements that could be universally accepted while containing all the relevant information known about the elements, their ‘kinds’ (grouping) and ordering. this desire for universality sometimes surpasses the limits of chemistry. john alexander newlands (18371898) formulated in 1864 his “law of octaves”, according to which the ordering of the elements accruing to increasing  atomic weight reveals a periodic pattern of similarity after each interval of seven elements. newlands’ detection of periodicity was overlooked possibly because of the analogy he drew between chemistry and the musical scale, thought to be naïve and distracting. striving for universality, newlands tried to force all known elements to fit into his octaves – but some new discoveries (heavy elements) escaped the pattern. also, james blake (1815-1893) went beyond chemistry when he attempted to classify some elements based on their pharmacological effects (1848).7 while such attempts were not well received, if one thinks of kinds as being natural, and not socially constructed, there is no reason to assume any periodicity would confine itself to conventional disciplinary boundaries. the perception of the periodic table let us now focus on the mainstream periodic tables of dimitri mendeleev (1834-1907) and lothar meyer (1830-1895). mendeleev ordered the elements according to their increasing atomic mass. he placed elements underneath other elements with similar chemical behaviour. for example, he placed sodium underneath lithium because both exhibited similar chemical behaviour: shiny and soft metals which react promptly with oxygen and violently with water. sometimes the atomic mass of an element would not be in the right order to put it in the group of elements with similar behaviour. he placed a question mark (?) next to its symbol to indicate he was uncertain the atomic mass had been measured correctly. some other times the next heaviest element would not display the properties expected of the next element in the table, and he thought important to only group together elements with similar properties. he postulated the existence of an unknown element to occupy that place, and left blanks, allowing for (temporary) holes for undiscovered elements in the table. mendeleev used dashes (-) to indi32 juergen heinrich maar, alexander maar cate the predicted mass of the element to be discovered. it was precisely this abductive reasoning that allowed for the future discovery of gallium (1875) and germanium (1882), for example, to be accommodated by the table. germanium’s fit in its group and its behavioural contrast with neighbouring elements gave mendeleev’s classification strong empirical support. as kemp puts it: “mendeleev’s periodic table permitted him to systematise crucial chemical data. but its real triumph was as an exercise in theoretical modelling, allowing the prediction of the discovery of previously unknown elements.”8 the table formulated by mendeleev is a tour de force in terms of resilience. since its first appearance 150 years ago the table has been able to accommodate the discovery of new elements (lanthanides), and groups of elements (noble gases, transuranic and transfermic elements). new theories and philosophical positions did not affect the solidity of mendeleev’s formulation, nor did the revolutionary empirical discoveries since the end of the nineteenth century: the discoveries of atomic divisibility and subatomic particles, radioactivity, artificial transmutation, and innovations generated by quantum mechanics. it is certainly this capacity to accommodate (and help predict) novelties, and withstand theoretical criticism, that gave mendeleev’s periodic table its iconi city and universal appeal. eventually, it became a definitive representation of elemental periodicity. it is interesting to note that none of the previous proposals for classifying the elements had more repercussion outside their context of creation than mendeleev’s. its high degree of empirical adequacy gave mendeleev’s systematization the status of scientific law (mendeleev’s periodic law). such status was later corroborated by what is now known as moseley’s law (1913). up until moseley’s work, the atomic number of an element was just its place in the table, and it was not associated with, or determined by, any known measurable physical property. but moseley demonstrated that the frequencies of certain characteristic x-rays emitted by atoms are approximately proportional to the square of the element’s atomic number. this discovery also supported antonius van den broek’s (1870-1926)  and niels bohr’s atomic model, according to which the atomic number is the same as the number of positive charges in the atom’s nucleus. it is precisely this degree of consilience, i.e. this ‘jumping together’ (convergence) of evidence originated from different, unrelated sources, that help explain mendeleev’s success in formulating a definitive and universal representation of elemental periodicity. the motivation for drawing a table of the elements was to find a way of representing them that could be universally accepted. representations that were only based on analogies – and did not constitute scientific laws – did not achieve this objective. the discovery of periodicity, followed by mendeleev’s insight when grouping the elements according to their similar properties while allowing for gaps, did achieve universality and, ultimately, iconicity. in part, such iconicity is derived from the table’s widespread use as a teaching tool. it is widely used by teachers to aid students with the abstractions necessary for a proper understanding of chemistry. abstractions such as the ordering of a periodic system, systematization of possessed knowledge, prediction and projections involving new discoveries, chemical properties, correction of data, and finally understanding of the macro and microcosmos in terms of atoms, molecules and substances. so, what we mean by the universality of the periodic table goes beyond geographic universality. it is endurance in time and space, and unity of meaning and form, of sign and concept. the universality of the periodic table of the elements is so pervading, that it is even capable of connecting intellectual ideas and human passions. in the words of s. alvarez: “the periodic table of elements is the agora where art, science and culture meet to dialogue about matter, light, history, language and life. it is an extraordinary tool that allows us to find the connections between humanistic culture and science.”9 the iconic table has a variety of uses: as a teaching tool; as a heuristic method for scientific practice; as an aid to classify and preserve chemical knowledge; as a theoretical foundation for the understanding of chemistry; as a research tool for other sciences, such as mineralogy; as a tool for the popularisation of chemistry; as an aesthetic component in the corpus of chemical knowledge; as a factor of integration between science and the humanities; as a pop-cultural object. meyer’s and mendeleev’s didactic purposes both mendeleev and meyer developed their periodic tables confessedly for didactic purposes – the ordering of the contents in writing their textbooks principles of chemistry (1869) and the modern theories of chemistry (1864), respectively. lothar meyer’s die modernen theorien der chemie und die bedeutung für die chemische statik (maruschke & berendt, breslau, 1864) is very 33the periodic table and its iconicity: an essay concise. from the outset, the author makes it clear that he intends to systematise and order, among all available knowledge, those he considers more fundamental (greater reliability and precision). the starting point is the berthollet essai de statique chimique (1804). meyer also accepted dalton’s atomic theory and some reductionism. as he writes: “the development followed by chemistry has brought with it the necessity of abstracting every theoretical point of view from a great deal of widely scattered detail.”10 speculations about the cause and essence of phenomena are various, and often conflicting points of view coexist. what theories that remain and which ones will be rejected is a decision that belongs only to the opinion of today’s active chemists, and only exceptionally and fragmentary in their writings [as the literature overestimates the amount of disagreement]. the struggle for the systematic ordering of chemistry’s body of knowledge seems to be long over.11 in meyer’s view, the long-lasting dispute on whether the properties of a compound depend on its nature or on the arrangement of its components seems to be solved to the satisfaction of both parties, for probably no one in the right mind would categorically reject the atomic theory. the didactic aspect to which we refer in the text of meyer is the systematisation in function of the choice of the most appropriate hypotheses for a rational exposition of the problems of chemistry. meyer keeps a hypothesis only so long as it is useful. let us now focus on the didactic purpose that led mendeleev to elaborate his classification to better order the contents of his principles of chemistry (1869/1871). when in 1867 he succeeded alexander voskresensky (1808-1880) as professor of inorganic chemistry at the university of st. petersburg, mendeleev wrote: “i began to write [the principles] when i started to lecture on inorganic chemistry at the university after voskresensky and when, having looked through all the books, i did not find anything to recommend to students.”12 this direct association between mendeleev’s table and his principles of chemistry was carefully examined by bonifaty m. kedrov (1903-1985). in another analysis, masanori kaji (1956-2016) also considered social and scientific factors as motivations for the table’s formulation. kaji identified a close relationship between the periodic law and mendeleev’s concept of ‘element’. mendeleev participated in the congress of karlsruhe in 1860, and the ideas of stanislao cannizzaro (1826-1910) exposed there exercised great influence on his chemical thought. he accepted the atomic theory (with certain exceptions, for there were exceptions to the law of constant proportions), allowing him to establish a relation between the properties of the elements and the atomic masses, the origin of the “periodic law”. following in the footsteps of cannizzaro, mendeleev distinguished between “simple bodies” (material entities) and “element” (abstract entity). he would later refer to an element as a “chemical individual”, highlighting the existence of multiple elements, consistent with his view of natural diversity (as opposed to there being a unity of matter). in his “faraday lecture” (1889), mendeleev claimed that the periodic law had been arrived at by inductive reasoning, i.e. “a direct outcome of the stock of generalisations and established facts which had accumulated by the end of the decade 1860-1870: it is an embodiment of those data in a more or less systematic expression.”13 clearly, the more data the better basis for any generalisation. and “sound generalisations – together with the relics of those which have proved to be untenable – promote scientific productivity, and ensure the luxurious growth of science under the influence of rays emanating from the centres of scientific energy [scientific societies].”14  as for those who at the time hoped the periodic law would lend support to the notion of a unity of matter (such as berthelot), mendeleev showed little sympathy: …the periodic law, based as it is on the solid and wholesome ground of experimental research, has been evolved independently of any conception as to the nature of the elements; it does not in the least originate in the idea of a unique matter; and it has no historical connection with that relic of the torments of classical thought (…) none of the advocates of a unique matter has ever tried to explain the law from the standpoint of ideas taken from a remote antiquity when it was found convenient to admit the existence of many gods – and of a unique matter.15 in this lecture, mendeleev also defended the use of conceptual structuring as an important complement to the experimental method, foreshadowing much of the 20th century preoccupation in placing “agreement between theory and experiment” at the centre of scientific thought and method. much of the iconicity of mendeleev’s table lies of course in its success in visually representing an agreement between an inductively identified regularity of nature and vast empirical chemical data. if properly used as a teaching tool, as meyer and mendeleev intended, the very same conceptual structuring would help rid the scientific world of obsolete metaphysical notions, and guide scientists towards scientific progress. 34 juergen heinrich maar, alexander maar the reception of the table about the reception of the periodic table by different scientific communities, stephen brush mentions that at the end of 19th century there were few and irregular citations of the table. it is therefore difficult to say if it was widely accepted by chemists, or if only a specialised circle of chemists showed interest in the novelty. brush mentions 236 citations of the table during the period 1871-1890: 20 from 1871 to 1875, 72 from 1875 to 1880, 61 from 1881 to 1885 and 83 from 1885 to 1890. concerning textbooks, we should not forget that usually many years elapse from the original inception of a new idea by the author and its inclusion in a textbook: 244 textbooks were published from 1871 to 1890, but only 76 of them mention the periodic table.16 first “modern” periodic tables were presented in russia and in germany, and we could suppose that in these countries such a powerful instrument would be accepted without any restrictions. history shows many drawbacks in accepting periodic classification because of singularities related to the scientific milieu of the two countries. in russia, as kaji and brooks observe, the main difficulty was just the fact that the periodic table was presented by a russian, deeply immersed in russian intellectual and scientific atmosphere.17 despite a dispute about priorities between mendeleev and lothar meyer (caused by wurtz’s criticism of a german translation of one of his books), russian chemists of german descent (friedrich beilstein, victor von richter, felix wreden) did much towards the recognition of mendeleev’s system. an early presentation of mendeleev’s first paper at the st. petersburg academy of sciences by nikolai menshutkin (1842-1907) was largely ignored. nikolai zinin (1812-1880) suggested that mendeleev should devote himself to actual chemical lab work. after months of silence, mendeleev’s ideas began to be discussed in scientific meetings by important russian chemists: markovnikov, butlerov and even zinin. the first russian textbook to include a periodic table was victor von richter’s (1841-1891) “textbook of inorganic chemistry, based on most recent theories” (1874). most later textbooks included mendeleev’s classification. in germa ny, where precursors li ke r ichter, döbereiner, gmelin, kremers, pettenkofer, among others, worked on classification before mendeleev, the adoption of a periodic table was delayed.18 karl seubert (1851-1942), meyer’s colleague in tübingen, explains this delay by a generalised lack of interest by most chemists in inorganic chemistry, especially issues like “periodic classification”: meyer’s explanations were too short and succinct, while mendeleev’s were deemed too complex and included non-chemical knowledge. rudolf fittig (1835-1910) in tübingen and eugen von gorup-besanez (1817-1878) in erlangen mention the periodic table in 1873: fittig in an encyclopaedia article, gorup-besanez in the 5th edition of his “lehrbuch der arnorganischen chemie”. g. boeck considers victor von richter’s german translation (1874) as the first german textbook to present a periodic table. brush takes the third edition of carl rammelsberg’s (1813-1899) grundriss der chemie (lüderitz, berlin, 1873; brush mentions erroneously 1874) as the first textbook outside russia to discuss periodicity.19 august michaelis’ (1847-1916) ausführliches lehrbuch der chemie (1878) and karl arnold’s (18531929) repetitorium der chemie (1885) deserve mention. most of the nineteenth-century college-level textbooks don’t include classification, the famous “schule der chemie” by adolph stoeckhardt (1809-1896), and not even the last editions from 1881 (19th) and 1919 (22nd).20 the introduction of mendeleev’s table in different scientific contexts, in central as well as in peripheral science, met some degree of opposition or reluctance. in many places, there were already prior classifications and tables, some of them with a long tradition and successful in their task in organising the content of textbooks. more pragmatic or theoretical scientific schools considered the efforts of looking for a periodic classification as useless. it is necessary to say that before mendeleev’s classification, other classifications, e. g. thenard’s “artificial” classification, or “classifications” not even taken as such, like that of berzelius, entered the scientific literature of several countries: thenard in the latin world, and berzelius in germany. and, finally, some local scientific communities produced their own classifications, like those of lewis reeve gibbes (1810-1894) in the united states (published in 1884) or of the catalan pharmacist josep antoni balcels (1777-1857) in spain (1838). in great britain, not even classifications suggested by english chemists, like william odling (1829-1921), in 1865, or john alexander newlands (1837-1898), in 1864, were taken seriously.21 there was little interest in mendeleev or lothar meyer. but the discovery of gallium (1875) by lecoq de boisbaudran (1838-1912) changed the situation. after the awarding of the royal society’s davy medal to mendeleev and meyer (1882) there was some revival of “newland’s octaves” (newland’s davy medal in 1887), but english scientists had little interest in “classifications”, although they produced very important empirical data to confirm the “periodic law” as a scientific law (the discovery of noble gases, moseley’s work). first texts to include a periodic table were those of william allen miller (1817-1870), “elements of chemistry” (6th edition, 1876) and george fownes (1815-1849), 35the periodic table and its iconicity: an essay revised by his assistant henry watts (1815-1884) in 1877. s. brush mentions thomas edward thorpe (1845-1925) as author of the first english language textbook including mendeleev’s table (1877).22 also in france mendeleev’s table remained almost unnoticed, a “non-event” in the history of french chemistry in the opinion of b. bensaude-vincent.23 but in the period of precursors of a classification we must remember contributions of thenard (1813) and ampère (1816), dumas’ numeric table (1851), as well as the exotic “telluric screw” of chancourtois (1862) – the “screw” connects chemistry and geology, another example of the universality of the periodic table. the strong influence of positivism and refusal to accept atomism by influential scientists like marcellin berthelot (1827-1907) explain why most french chemists looked for alternative classificatory systems, ignoring mendeleev (the “equivalentists”).24 berthelot agrees that mendeleev’s table may have some practical utility, but for him, it is not a “law” or a theoretical argument, as this would undermine the empirical, logic and positive bases of science,25 and could also lead to a return to mysticism. in 1885, in his les origines de l’alchimie, berthelot discusses the periodic system as an “artificial construction based on vague theoretical arguments”.26 among the exceptions are notables like charles adolphe wurtz (1817-1884), who dedicates an entire chapter of his “atomic theory” to mendeleev, edouard grimaux (1835-1900) and paul sabatier (18541941). after 1890, mendeleev’s system began to gain some sympathy: paul schutzenberger (1829-1897) published the first french textbook containing the periodic classification (traité de chimie générale, 1880). georges urbain (1872-1938) was perhaps the first to try to explain the opposition of equivalentists and atomists (1934).27 mendeleev himself was not truly an atomist, he used “equivalent weight” instead of “atomic weight”.28 in france, there was not only the opposition between positivists-rationalists but also the opposition between “natural” classifications (ampère, dumas) and “artificial” classifications (thenard). differently from what happened in great britain and in the united states, the discovery of gallium did not contribute to the acceptance of mendeleev’s ideas: lecoq insisted that his discovery was due only to his skills as a spectroscopist and had nothing to do with mendeleev’s table ‘blanks’.29 a recently unified italy presented a fertile soil for the introduction of new scientific ideas. in the case of the periodic table this is exemplified by the almost immediate acceptance of mendeleev’s system by important italian chemists, such as augusto piccini (18541905), who translated richter’s textbook into italian (1885), and giacomo ciamician (1857-1922). it was accepted that former classifications were based on less reliable properties.30 in spain, thenard’s text (traité de chimie élémentaire, 1813) and classification were largely used. thenard’s classification was also present in other french textbooks translated into spanish, like that of mateo orfila (1787-1853). there is no reference to mendeleev in the extensive text published in 1875 by rafael sáez palacios (1808-1883), but there is such reference in a book (1880) by santiago bonilla mirat (1844-1899).31 eugenio mascareñas (1853-1934) published in 1884 in barcelona “introdución al estudio de la química”, discussing mendeleev’s work and presenting his own table.32 theoretical and speculative studies on periodicity were done by ángel del campo y cerdán (1881-1944), suggesting interactions of protons with protons and with neutrons as the origin of periodicity (1927): “the properties of the elements seem to be simultaneously a periodic function of the masses of their atoms and the electric charge of their nuclei, that is, of the atomic masses and the atomic numbers.”33 as a consequence of bohr’s studies, miguel catalán sanudo (1894-1957) presented a table relating periodicity to spectra (1923).34 modern portuguese science has its beginnings with the renovation of the university of coimbra by the marquis de pombal (1699-1782) in 1772. a new reform followed in 1841, and since 1870 a strong influence of positivistic thought in scientific practice can be observed. antônio luís ferreira girão (1823-1876) did not mention mendeleev in his teoria dos átomos e os limites da ciência (published 1879), but his student agostinho de sousa published (1880) in french la loi périodique, the first reference to mendeleev in portugal. this was later repeated in the 2nd edition (1895) of a textbook by antônio joaquim ferreira da silva (1853-1923).35 in northern europe, the reception of mendeleev’s table occurred in different contexts. in sweden, berzelius’ treatise on chemistry (1818) presented a classification of the elements based on their electronegative or electropositive character. in denmark julius thomsen (1826-1909) worked out his own table (1887, 1895), in which he tried to turn more visible the relation between periodicity and atomic structure – a subject studied later by another danish scientist, niels bohr (1885-1962). lundgren suggests that in sweden the reception of mendeleev’s system was by no means dramatic: no opposition, but also no enthusiasm.36 swedish chemistry shows no difference before and after mendeleev, it was a pragmatic and practical chemistry, with a reduced theoretical component (a theoretical revival took place with svante arrhenius after 1884). according to lundgren, sweden’s only contribution to 36 juergen heinrich maar, alexander maar periodicity and the classification of the elements, lars f. nilson’s (1840-1899) discovery of scandium (1879), was seen as an analytical problem. in denmark, the situation was similar – a pragmatic, practical chemistry, some theory (thomsen).37 in kragh’s opinion, thomsen presented in 1865 one of the “many incomplete anticipations of the periodic system”, but in 1880 most danish chemists already knew mendeleev’s and meyer’s systems. odin christensen (1851-1914) wrote the first danish paper (1880) and textbook about the periodic system (elements of inorganic chemistry, 1890). the case of norway is in some sense sui generis – linked to sweden since 1814 but de facto independent since 1905, the country used its own chemical terminology and had a small but important scientific community (peter waage, kristian birkeland). mendeleev’s system had little effect on chemical practice and was introduced relatively late, with a textbook (1888) by thorstein hallanger hiortdahl (1839-1925).38 a situation which deserves a wider and detailed study, even outside chemistry, is the reception of mendeleev’s periodic system in scientific communities which used their own language and had their own scientific evolution but were not independent nations at mendeleev’s times. this is the case of czech and croatian chemical communities, politically and economically linked to austria-hungary until 1918. somewhat different is the polish chemical community, spread throughout russia, austria and germany, they did not constitute a united group of chemists. using their own languages, terminologies and nomenclatures, not only in science but also in literature, philosophy and the humanities, czech and croatian scientists saw in russia a leader, and positive reception of mendeleev’s system was an a priori decision.39 use of one’s own language in intellectual activities created and fortified emerging nationalisms in the 19th century. in the present czech republic,40 until 1918 austria’s kingdom of bohemia, nationalism forced the creation in 1869 of a polytechnic school (independent from the german polytechnic) and the separation of the old prague university (1348) into a german and a czech university (1882). a textbook authored by vojtech safarik (1829-1902) was the first to mention the periodic table in the czech language, but in strbanova’s opinion, the most important defender of mendeleev’s system in czech lands was his personal friend bohuslav brauner (1855-1935). in the face of growing russophylia and anti-german sentiment, brauner defended mendeleev’s ideas and vindicated the replacement of german scientific influence in czech lands by slavic influence. this case illustrates how nationalism and xenophobia may constitute a threat to the autonomy of science. there was some resistance to the acceptance of mendeleev’s work by safarik (a slovak), and by jaroslav formanek (1864-1936). both wanted a ‘natural’ classification of elements. ambiguous behaviour of czech intellectuals may be seen in cermak ’s germanisation of his name, gustav von tschermak (1836-1927). tschermak presents his own periodic table (1859), the first to draw attention to ‘blanks’.41 in croatia, until 1918 part of the austro-hungarian empire, the reception of the periodic table was more straightforward.42 since 1861 school textbooks were published in croatian, and since 1873 there was a university in zagreb (then called agram), but only in 1901, an academic textbook by julije domac (1853-1928) presented mendeleev’s system. a former text by pavao zulic (18311922), even in his second edition from 1877, omitted the periodic classification. the acceptance of mendeleev’s system in croatia is largely due to the czech chemist gustav janecek (1848-1929), whose text on the subject (1914) goes back to döbereiner and other precursors. not only czechs and croats, but also other nationalities lived in polyethnic austria-hungary, maintaining their language, traditions and many centuries of their own cultural activities, like hungarians. since the ausgleich from 1867, between the emperor and the hungarian government, hungarian became the official language in schools, and karoly than (1834-1908) was designated chemistry professor at budapest university. than was the author of the most popular chemistry textbook in hungary, elements of experimental chemistry (1898), in which he presented mendeleev’s classification and systematisation.43 at the same time, in serbia, a slavic country de facto independent since 1867, with a university in belgrade (1905), there was modest chemical activity. frequently repeated information about a first non-russian textbook on a periodic system written by serbian chemist sima lozanic (1846-1935) in 1874 (chemistry as viewed by modern theories) is incorrect. lozanic included mendeleev’s system only in the second edition of his book (1897).44 like serbia, bulgaria, another slavic nation de facto independent since 1876 (treaty of san stefano) had modest scientific activity. a recent essay by borislav toshev suggests that all bulgarian publications on mendeleev are hagiographic, with the only exception being professor dimitar balarev’s (1885-1964) significance of the periodic system, 1950).45 balarev himself designed a three-dimensional form of the periodic table.46 it is difficult to state precisely which latin-american country first received the periodic system. latin ameri37the periodic table and its iconicity: an essay can historiography rarely refers to science, and when it does, it pays close attention to institutional history, or biographical data. equally difficult to obtain information on latin american contributions to the periodic system. it is however easy to ascertain that from the 1940s interest in the periodic table of the elements has spiked. it’s great potential as a teaching tool was the main driving factor, as can be seen in ceccon and berner’s monograph.47 the first record of the periodic system in latin america is probably due to álvaro joaquim de oliveira (18401922), professor at the rio de janeiro polytechnic school. in his textbook apontamentos de química (1883) he critically examines the table under the influence of positivist dogmas.48 oliveira was one of the founders of the brazilian positivist society (1876), but his views and interpretation of mendeleev’s work met strong opposition from his peers,49 prompting another leading brazilian positivist, raimundo teixeira mendes (1855-1927), to publish an alternative textbook, la philosophie chimique (1898).50 there were different versions of the periodic table in use by brazilian teachers. we mention, because of its originality, a contribution presented in 1949 by alcindo flores cabral (1907-1983), professor of chemistry at the school of agriculture in pelotas. cabral’s spiral classification, elegant in its symmetry and use of colours, made use of what he called the ‘differentiating electron’.51 another formulation of the table (1950) worth mentioning was made by professor werner gustav krauledat (1908-1990), from rio de janeiro state university. in spanish speaking latin america, a very successful table was designed in 1952 (and revised in 1962) by gil chaverri rodrigues (1921-2005), a physicist and chemist from costa rica. his table follows a logical sequence derived from the sequence of atomic numbers and has done well in presenting lanthanides and actinides without disrupting the sequence of elements.52 like cabral, chaverri lectured at an agricultural school, which showed a widespread interest in periodic classifications. another successful table was that of peruvian chemist oswaldo baca mendoza (1908-1962), from cuzco university, generic laws of the chemical elements. a new periodic system (1953), inspired by the theories of his spanish teacher a. del campo y cerdán.53 julio antónio gutierrez (b. 1955) continued mendoza’s work (sistema periódico armônico and leyes genéticas de los elementos, 2004) on the ‘quantification’ of mendeleev’s table. spaniard antónio garcía-banús (1888-1955), creator of the great mural table in barcelona, immigrated in 1938 to colombia (1938) and lectured at the bogotá national university, where he got involved with the periodic system. in uruguay, a chemical institute was created at the faculty of medicine in montevideo (1908), where studies on periodicity largely focused on using the table as a teaching tool. during the decades of 1930 and 1940, there were some original ideas about the best position for the actinides in the table, and during the seventies, there were discussions about a new spiral design of the periodic system, but without a successful outcome.54 western science found its way to japan through dutch textbooks used in “dutch studies”: before the meiji period, the netherlands were the only western nation to have consistent contact with japan. the first japanese chemistry textbook, seimi kaiso, was written by utagawa yoan (1798-1846) around 1830 and included parts from lavoisier’s treatise.55 robert william atkinson (1850-1929), an english chemist, the first western chemistry teacher in japan, was interested in periodic classification but preferred lothar meyer’s table. naokishi matsui (1857-1911), a professor in tokyo, was the first to mention mendeleev in a paper (1882), and toyokichi takamatsu (1852-1931) was probably the first to mention it in a textbook. research on the subject was also done by kikunae ikeda (1864-1936) and masataka ogawa (1865-1930), the former from a theoretical point of view, and the latter in an empirical context.56 of notable interest was the difficult introduction of the periodic table in turkey. two problems contributed to making this task complicated: an absolute lack of modern chemistry texts and the use of arabic symbols for letters and numbers – arabic texts are written from right to left, which turns writing formulas, equations and reactions even more difficult. despite these difficulties, vasil naum (1856-1915) included mendeleev’s system in his book medical chemistry, with names of elements and numbers in arabic characters (the official language of the ottoman empire). in 1914, the turkish government decided to modernise its higher education system, and from 1915 to 1918 a group of german chemists lectured in constantinople, headed by fritz arndt (1885-1969) – gustav fester (1886-1975) and kurt hoesch (1882-1932) were the other members of the mission. after facilities and equipment, arndt’s priority was the production of textbooks in turkish language (arndt was fluent in turkish), and in his first medical experiments (1917) we find the second turkish periodic table, with latin characters used for the elements and their symbols, but with the text itself remaining in arabic, read from right to left.57 in the united states, we distinguish between the reception of mendeleev’s system and the reception of several other classifications, some of them proposed by american chemists, a situation similar to that observed 38 juergen heinrich maar, alexander maar in great-britain and france. in 1854, harvard professor josiah parsons cooke (1827-1894) presented before the american academy of arts and sciences in boston a lecture numeric relations between atomic weights and some ideas about classification of elements, considered by edgar fahs smith (1854-1928) as the first serious attempt in studying this subject (1914).58 gustavus hinrichs (1836-1923) published his textbook in 1874, but instead of mendeleev’s system he included his own spiral classification (worked out in 1867), not even mentioning mendeleev’s formulation.59 lewis reeves gibbes (1820-1896) published in 1886 a synoptical table of chemical elements, using an ‘inverted’ procedure with respect to mendeleev’s, arranging a great number of chemical proprieties and deriving from them a periodicity of atomic weights.60 stephen brush could not find a single american textbook discussing mendeleev’s ideas until lecoq’s discovery of gallium in 1875. in 1877, ira remsen (1846-1927), from johns hopkins university, published his principles of theoretical chemistry, the first text in the united states to mention mendeleev.61 the table as a research tool mendeleev`s periodic table contains ‘ blanks’ (though he was not the first to postulate their existence); all periodic tables presented after mendeleev’s also contained ‘blanks’. the desire to replace such blanks with new discoveries strongly motivated chemical research. the increasing number of elements discovered since 1800 (thanks to improved analytical techniques), the degree of uncertainty associated with many physical properties (such as atomic weights), the dispute on what properties to use as criteria of periodisation, and the inability to forecast how many elements remained to be discovered, all illustrate how the study of the ‘blanks’ became a powerful centraliser of experiments and discoveries. in one way or another, research activity revolved around the question: how many elements are there, and how can we best order them? let us detail two recent events in the history of chemistry related to ‘blanks’ in the periodic table: the troubled hunt for mysterious element 43 (technetium, masurium), and the controversial discovery (1923) of hafnium, element 72. it was precisely the discovery of three of the elements foreseen by mendeleev (three ‘blanks’) which promoted the acceptance of mendeleev’s system: (eka-aluminium or gallium by lecoq de boisbaudran in 1875, ekaboron or scandium by nilson in 1879, and ekasilicon or germanium by winkler in 1886). the epistemological status of these discoveries is still a matter of contention among philosophers of chemistry. mendeleev considered the existence of nine unknown elements (including gallium, scandium and germanium), as well as the need to correct the atomic weights of five elements (including beryllium, tellurium and uranium). and as put by mendeleev himself, “the confirmation of a law is possible only by deducing consequences from it, and by justifying those consequences by experimental proof.”62 but as highlighted by scerri, the number of verified predictions equals the number of predictions which turned out to be false, so not a good score for the confirmation of the law of periodicity.63 however, despite fewer than optimal numbers, mendeleev’s table had a predictive ability which was lacking in alternative formulations, such as the tables by odling, newlands, and lothar meyer, hence mendeleev’s eventual widespread acceptance. how can the periodic table guide research? a simple example: by the position of the ‘gaps’ predicted by mendeleev in the table, one can predict in which minerals these new elements should be sought. in the 10th series, group vii, from his second table (1872), mendeleev predicted the existence of two elements still unknown below manganese, that would have atomic masses 100 and 190, respectively. he named them ekamanganese and dwi-manganese; ekaand dwiare sanskrit prefixes, meaning ‘first’ and ‘second’. mendeleev was a friend of german indologist and sanskrit scholar otto von böhtlingk (1815-1904), his colleague in st. petersburg, which may explain his use of sanskrit (mendeleev did not know the language). speculations on a possible analogy between the periodicity of the elements and the phonemes of sanskrit are fantasies. elements with atomic masses 100 and 190 were really discovered: technetium (atomic number 43) and rhenium (atomic number 75). for over two centuries chemical literature accumulated innumerable cases of spurious, never confirmed discoveries, i.e. ‘discoveries’ of already known elements or of mixtures of elements.64 unguided research rarely led to new discoveries. but the discoveries mentioned above were achieved by using the positions of the missing elements in mendeleev’s table as a guide. the most striking example of such a ‘guided’ discovery is the discovery of hafnium (1923) by gyorgy de hévesy (1885-1966) and dirk coster (1889-1950). hafnium was mendeleev’s ekazirconium and was effectively obtained from zirconium silicate (zrso4) extracted from the mineral alvite. mendeleev’s prediction was in this case strengthened by bohr’s theoretical arguments, and by the discovery of the new metal by mineralogist victor goldschmidt (1888-1947) in 1925. 39the periodic table and its iconicity: an essay the association between prediction and discovery is not obvious in the case of elements 43 and 75. although walther noddack (1893-1960), ida tacke (1896-1978) and otto berg (1873-1939) published an article “die manganelemente” (1925), rhenium was actually discovered in the minerals molybdenite (mos2, today the most important source of rhenium), columbite [(fe,mn)(nb,ta)o6] and gadolinite, and in platinum minerals.65 masurium, the supposed element 43, was never obtained from natural sources (there is a recent controversy on this issue), but allegedly identified spectroscopically in molybdenite. properties of technetium and rhenium are more similar to molybdenum (element 42) than to manganese, but there are diagonal relations in the periodic table. chemists, historians and philosophers of science questioned the predictive capacity of the periodic table. lothar meyer doubted the possibility of making predictions based on classification. after the formulation (1913) by henry moseley (1887-1915) of what would be known as ‘moseley’s law’, some have questioned whether these predictions had heuristic status since mendeleev’s times, or if it was moseley’s law that was responsible for any heuristic value ascribed to the periodic system. moseley predicted the existence of only 14 rare earths, one of them still unknown (element 61), and of six elements to be discovered – six ‘blanks’, in the periodic system (elements with atomic numbers 43, 61, 72, 75, 85 and 87). the ‘criticism’, while reasonable, seems exaggerated. one can justifiably say that moseley’s law and the discoveries that followed from it added to the stock of empirical data that ultimately offers support to the prior discovery of elemental periodicity. the periodic table has also seen many uses in nonstrictly chemical research. it is employed in fields such as mineralogy, geology and geochemistry.66 the table itself benefited from the search for new minerals and still unknown elements in these minerals. before ionic rays were known, isomorphism and so-called isomorphic substitutions were important for the ‘periodisation’ in mineralogy. this can be seen in the table by vladimir vernadsky (1863-1945), of the university of moscow, considered one of the ‘fathers’ of geochemistry. the introduction of magnitudes such as atomic mass, atomic number and ionic radius allowed norwegian mineralogist victor goldschmidt (1888-1947) to establish the substitutions in mineral series, such as the feldspars (goldschmidt’s rule). periodicity and some philosophical considerations in 1869, mendeleev’s periodic table, the model of all tables to come, appeared. mendeleev’s representation is not only the prototype, so often modified, of the record of all subsequent tables, but its own theoretical basis (the periodic law) – is the basis for all later tables. mendeleev’s classification should not be regarded, however, as the crowning of precursor classifications – the russian chemist’s table is grounded, malgré lui, on philosophical assumptions. mendeleev initially did not consider philosophy important for the formation of chemists, but during his professional life, especially after the congress of karlsruhe (1860), he became himself a philosopher of chemistry. his intellectual positions are original and difficult to fit into some philosophical school. but it is generally accepted that later in life, as an old man, mendeleev would accept something like kantian epistemology: the belief that humankind, even when well-equipped with the tools of science, was unable to comprehend the “thing-in-itself ”, i.e. substances as mind-independent entities. in fact, he would say that substances can only ever be studied by “their properties or by their relations to our organs of sense and to other substances and bodies” although he clearly accepted substances’ independent existence “for there is something in its nature which is self-existent.”67 such a view was also dear to goethe, namely, that experience is, to an important extent subjective – every scientist experiences phenomena in a way that is only his/her, not being able to see through the eyes of someone else. it is according to this kantian framework that mendeleev considers himself to be a realist (although it must be said that there is a less prominent interpretation of kantian ontology which places the german philosopher closer to idealism). according to vucinich: to mendeleev being a realist meant denying the ontological unity of the universe and rejecting revolution as a source of natural and social change. it also meant recognising not only the powers of science but also its limitations. but above all, it meant adopting a philosophical outlook untrammelled by metaphysics.68 so, despite being a self-declared realist of some sort, positivists, nihilists and marxists alike all attempted, in vain, to exhibit mendeleev’s ideas were in agreement with their intellectual frameworks (and political agendas) and count him as one of their own. several of the periodical classifications presented during the nineteenth-century show relations with philosophy, relations only sometimes explicit. but it was mendeleev’s periodic system that most aroused the attention of philosophers of science, not forgetting the ‘philosophy of science’ implicit in the work of mendeleev himself – which for some is empirical, for others 40 juergen heinrich maar, alexander maar theoretical, or even empirical/theoretical). also, his table is sometimes considered just a classification based on experimental data, and sometimes a representation of a law or theory. it is necessary to separate the theoretical bases of chemical periodicity together with experimental data from the experimental data of the philosophical aspects involved in the periodic law and the resulting table. a supposed dialectical materialism that would permeate mendeleev’s science is a fiction by friedrich engels (1820-1895), for whom the periodic classification was a victory of dialectical materialism, an unconscious application of hegel’s law of transformation (though marx explicitly states that his dialectic differs and opposes that of hegel) concerning the transformation of quantity into quality. engels’s analysis of 1890 was made in the absence of mendeleev himself, who never accepted this interpretation by engels and marx, or even heraclitus’s principle of transformation as a universal principle. for mendeleev, and in accordance with leading ideas from his time, “the elements are constituents of nature, essentially unique, permanently fixed and genetically discrete, irreducible to a primary matter.”69 richard feynman (1918-1988) would later say about something seeming permanently fixed: “to our eyes, our crude eyes, nothing is changing, but if we could see it a billion times magnified, we could see that from its own point of view it is always changing: molecules are leaving the surface, molecules are coming back.”70 mendeleev, after the discussions at the karlsruhe congress, approaches the issue later raised by feynman with surprising insight, solving the problem inherent in atoms and molecules in three stages; at the macroscopic level, at the microscopic level, and in the relationship between the macroscopic and the microscopic. on the macroscopic level, it is necessary to distinguish in current chemical language between ‘body’ and ‘substance’; at the microscopic level, to distinguish between ‘atom’ and ‘molecule’; and finally, to establish a relationship between the two levels.” he expands on this: it is evident that water does not contain gaseous oxygen or oxygen in the form of ozone; it contains a substance capable of forming oxygen, ozone and water… it is necessary to distinguish the concept of a simple body from that of an element. a simple body substance, as we already know, is a substance, which taken individually, cannot be altered chemically by any means produced up until now or be formed through the transformation of any other kinds of bodies. an element, on other hand, is an abstract concept; it is the material that is contained in a simple body and that can, without any change in weight, be converted into all the bodies that can be obtained from this simple body. a similar definition of an element and the same argument for the need to distinguish clearly between an element and simple body were later presented in the first part of principles.”71 an immediate perception by the senses refers to macroscopic phenomena, it is a perception of the transformations that occur in ‘bodies’. but ‘bodies’, necessary to understand the transformations that occur, refer to the idea of ‘substance’ (= element). as gaston bachelard (1884-1962) would later say, the experiment never puts us in contact with the ‘substance’, but without the notion of ‘substance’ it is impossible to understand experiments (which refer to ‘bodies’). it proceeds at the microscopic level, differentiating atom from molecule: we call a ‘molecule’ the quantity of ‘substance’ that reacts with other molecules, and which occupies in the vapor state volume equal to two weights of hydrogen [...] ‘atoms’ are the smallest quantities of chemical masses indivisible from the elements, which form the molecules of simple and compound bodies.72 for more than 60 years our high school teachers, capturing the essence of mendeleev’s argument, taught students that ‘atom’ is the smallest part of an element that conserves its properties, and ‘molecule’ is the smallest amount of a substance that retains its properties. in a similar fashion, ‘element’ is the set of all atoms of the same atomic number (atomic weight, in the time of mendeleev): the simple substances coal, graphite and diamond are formed by atoms of the element carbon. mendeleev’s simple but ingenious innovation related macroscopic and microscopic levels: a simple body is something material endowed with physical properties and capable of chemical reactions. the term ‘simple body’ corresponds to the idea of ‘molecule’ ... the name ‘element’ should be reserved for the particles which form the simple and compound bodies, and which determine how they behave from the point of physical and chemical view.73 fritz paneth (1887-1958), one of the few chemists to philosophise, rationalised these concepts along with ontological and epistemological considerations. the word ‘element’ refers to the idea of ‘atom’. the element, the grundstoff, belongs to the transcendental world and is not observable. the simple substance, einfacher stoff, is observable because it belongs to the world of ‘primitive’ or ‘naive’ realism. the grundstoffe are, therefore, the entities that fill the ‘squares’ of the periodic table. still on this subject, american chemist benjamin harrow (1888-1970) offered much earlier (1930) a very simple, perhaps too simple, anthropomorphic explanation: 41the periodic table and its iconicity: an essay this periodic law is really more complicated than our exposition would lead the reader to believe; but for our purpose [diffusion of scientific knowledge] all complications can here be discarded. for us the important lesson that the periodic law teaches is that since there are family relationships among, since there are brothers and sisters, there must be fathers and mothers, from which we conclude that there must be a ‘something’ in the universe simpler and still more fundamental than the elements – a ‘something’ out of which the elements themselves are built. this ‘something’, recent studies have shown, is the proton and the electron, the positive and the negative particles of electricity. all atoms are made up of protons and electrons. the atoms of any element, such as gold, are practically alike, but an atom of gold is different from an atom of chlorine. on the other hand, the protons and electrons, so far as we can tell, are the same, whether they are found in an atom of gold, in an atom of chlorine, or in any atom of the 92 elements.74 harrow certainly knew moseley’s law: there is no direct evidence of this, but reference to anthropomorphic “ brothers” and “mothers” must have been inspired by the radioactive decay series. mendeleev himself explained harrow’s ‘something’ in 1869 when he referred to carbon, diamond and coal. in the following quote, we can identify paneth’s classification of grundstoff and einfacher stoff: it does not matter how the properties may change, something remains unchanged, and when these elements form compounds, this something acquires a material value and establishes the properties of the element containing compounds. with respect to this, we know only one property characteristic of each element, the atomic weight. the magnitude of the atomic weight, according to the very essence of matter, is a number unrelated to the degree of division of simple bodies but related to the material part common to the simple body and its compounds. the atomic weight does not refer to coal or diamond, but to carbon.75 finally, it may prove useful to verify if the concept of the element has remained unchanged over the years, or whether it has undergone some sort of ‘reconceptualization’. going to back to lavoisier, we can see that the french chemist introduced a pragmatic concept of element: a substance which cannot be further subdivided by any chemical means. this pragmatic, empirical and operational approach to the definition of ‘element’ can be traced back to condillac and even to locke, and it can be singled out as one of the probable causes of lavoisier’s inability in elaborating a philosophy of chemistry. the alternative to the pragmatic approach can be found in classic metaphysics: the element is a ‘substance’ (from the greek ousia = being). substantia (latin) is that which ‘grounds’ things like attributes or properties. substances, in generic philosophical terms, can therefore, be said to be the fundamental entities of reality. according to this definition, if atoms are the basic things from which all else is constructed, then atoms are (or are like) substances. there is an obvious realist interpretation of reality here, substances – the basic building blocks of reality – are real, and so are all instantiated properties.76 philosophical schools such as logical positivism or pragmatism (i.e. those which consider metaphysics a simple matter of convention) would deny the reality of substances. for the antirealist there can be no fact of the matter about the foundation of reality, so substances, atoms, elements, or any candidate to what can be ontologically basic, lose their objective status. it must also be said that one can coherently think of a substance in different terms. it can be said to be a kind of entity, like an object. and an object can perhaps be thought of as a bundle of properties, in which case ‘object’ is not basic, or simple. the same reasoning could be applied to an atom or even element. mendeleev’s views, according to martin labarca and alfio zamboni, seem to somehow combine pragmatism with a metaphysical approach to substance, what they call a dual sense.77 elements are foundational, abstract and real, but deprived of properties. ‘operational’ elements are ‘simple’ substances (like atoms) which possess properties. one could think of such a hybrid approach used by mendeleev – in contrast to other classifications – as vulnerable to challenges originating from soddy’s definition of isotope. but paneth, in the 1930s, sustained that isotopy does not modify chemical properties (hydrogen being the exception), so no revision of the chemical periodic table would be necessary. each new isotope would be a new ‘simple substance’, and not a new abstract element. paneth’s arguments convinced the iupac to substitute the atomic mass as characteristic of each element by the atomic number (1923), a property of the abstract (real) element. but with the discovery of the neutron (chadwick, 1932) some adaptations were indeed necessary: for each element, there is an upper and lower limit of the number of neutrons, and of atomic mass, to ensure the atom’s stability. an up-to-date representation of periodicity would be based not just on the atomic number, but also on the number of neutrons. labarca and zamboni propose to reconceptualise the element as: “a certain class of entity constituted by a ‘fundamental substance’ [metaphysical concept] which exhibits two representative properties, the atomic number and the limits for the atomic mass, with contingent proprieties varying 42 juergen heinrich maar, alexander maar case-by-case.”78 the primary criterion for the classification of the elements, they propose, would be the number of neutrons, whereas the second criterion would be the electronic distribution – and not the atomic number. nevertheless, even under such a reconceptualisation, the periodic system maintains most of mendeleev’s conception. the periodic table and aesthetics georges urbain (1872–1938), a chemist interested in so many arts and involved in filling the “blanks” or “voids” left by mendeleev in his table, said in one of his non-chemical works: “from an intellectual point of view, the sage and the creative artist are twin brothers.”79 it is also often the case that scientists regard the products of their work (theories, models, proofs) as holding aesthetic value. but the precise nature of the relationship between science and aesthetics is difficult to grasp, and often involves confusion of categories. as an example, one could refer to a rather cryptic quote from the engineer who turned physicist and philosopher, abraham moles (1920-1992): in the act of creation, the scientist does not differ from the artist: in principle, there is no difference between artistic creation and scientific creation, they work with different materials of the universe [ … ] creation is an act of spirituality, which, using all ‘ dimensions’ of spirituality, all its planes of freedom and phenomenological apprehension, cannot be limited to a logical universe, to a ludic universe of gratuity, but must include all aspects of spiritual freedom, [ … ] there is only one unique intellectual creation.80 it is one thing to say there can be beauty in the products of scientific investigation, or in the tools used to represent scientific knowledge (such as the periodic table), quite another to say there is beauty in the ‘act’ of creation. intermingling aesthetics with spirituality does not do moles any favours either. furthermore, in science, there is often talk of discovery, instead of creation, so where and when scientific creation occurs must be specified. several aspects of science may hold aesthetic value. it is possible that aesthetic considerations play a role in theory choice – for example, in a situation of empirical underdetermination of theories: when having to choose between empirically equivalent rivals, one could appeal to aesthetic properties of one theory to favour it over the other. or, it could be said that valuing simplicity as a heuristic guide is yet another instance of science intermingling with aesthetics. more importantly, as singled out by ivanova, “beauty is also often taken to stand in a special epistemic link to truth. many scientists argue that a beautiful theory is more likely to be true.”81 to assign an epistemic role to aesthetics is difficult. can we ever justify confidence in the truth of a theory as arising from its beauty? any aesthetic judgement is secondary to empirical adequacy, which remains to this day the main criterion theory acceptance. furthermore, it seems unlikely that beauty can ever be a predictor of scientific success. one could easily challenge the association between aesthetics and scientific progress (or truth, or empirical adequacy) and claim it to be arbitrary and misleading. one could do so by pointing out cases of ‘beautiful’ theories that turned out to be false (such as newtonian mechanics), while highlighting the success of theories which lack any aesthetic appeal. as ulianov montano points out, aesthetic values such as simplicity and unity are not [usually] instantiated by highly successful theories.82 however, if one considers not truth but understanding to be the aim of science, then it may be easier to assign an epistemic role to aesthetics. for henri poincaré (1854-1912) aesthetic values, ivanova reminds us, reduced in the case of science to simplicity and unity, work as “regulative ideals to be followed because they are linked to the ultimate aim of science, namely, gaining an understanding of the relations that hold among the phenomena.” therefore, aesthetic value gains an epistemic role because it shows how, given a certain theory, “apparently disconnected phenomena are unified under a simple framework.”83 we may now return to the case of the periodic table. while its acceptance is clearly owed to its success in predicting the discovery of a few elements, our appreciation of it as an object possessing important aesthetic value can be said to be the result of its excellent capacity to unify phenomena under a simple framework, therefore facilitating our understanding of, among other things, periodicity. it falls outside the scope of this essay to address the question of whether aesthetic judgements in chemistry or science in general, may have objective validity. we wish to highlight, however, that there is consensus among the scientific community that the periodic table exhibits aesthetic properties that are widely regarded as desirable, such as unity and simplicity. this helps explain why different representations of the table exist outside chemistry or academia. so, let us now focus on less abstract digressions, and briefly survey the periodic table’s existence outside chemistry books. it can be found in works of art around 43the periodic table and its iconicity: an essay the world, ranging from gigantic murals or monuments to postal stamps. in fact, the first homage of the periodic table on a postal stamp was issued by the spanish mail in 2007 (centenary of mendeleev’s death). created by inorganic chemist, javier garcia-martinez (alicante university), it was designed to transmit a “modern and positive image of chemistry” and “to catch the attention of stamp users and collectors alike with a colourful and highly geometric design.” garcia-martínez was inspired by dutch painter piet mondrian (1872-1944), whose abstract expressionism, geometric expression, and judicious use of colours help detail the ‘voids’ in the table.84 on the verse of the stamp, there are mural tables and printed tables in laboratories and classrooms. over the years, some representations of the periodic table acquired notoriety or made the news – like the one recently discovered at st. andrews university, printed in vienna (1885) and brought to scotland by thomas purdie (1843-1916). the oldest preserved printed table (1876) can be found in the museum of the university of st. petersburg. the historically most interesting case of mural tables is the large mural (2,2 x 2,7m) existing in an auditorium in the old building of the university of barcelona (taula de garcía-banús), painted in 1934 by commission of professor antonio garcia-banús (18881955). historians later discovered that it was a reproduction of the table conceived in 1926 by bonn professor andreas von antropoff (1878-1956), a popular table at the time,85 but abandoned in 1945 because of antropoff ’s ideological positions. some historians refer to bauhaus and de stijl influences in antropoff ’s table. recently rediscovered by philip stewart (b. 1939), the table was carefully restored in 2008 by professor claudi mans i teixidó.86 mans would say this is a unique case in the history of chemistry: a republican and socialist professor adopted a table created by a national-socialist professor, which was restored during a fully democratic government, after surviving franco’s dictatorship. j. marshall suggests antropoff ’s table was situated halfway between mendeleev’s classic short table and alfred werner’s (1866-1919) “long” table from 1905, and that the resulting practicality was responsible for the popularity of antropoff ’s table, even in the united states.87 it would probably be best if ideologies never intervened in the progress of science. but ideologies often accompanied mendeleev’s career: his prestige in tsarist russia was enormous, malgré lui a national hero of the soviet union, although he did not see himself as socialist and despite his criticism of popular demonstrations after failure of the 1905 revolution. mendeleev, in brooks’ opinion, was always loyal to the tsarist regime, although there were frequent disagreements between the scientist and lower-ranked bureaucrats.88 another classic table, very popular in the 1920s and 30s, was the one designed by american chemist henry david hubbard (1870-1943), from 1901 to 1938 secretary of the united states national bureau of standards. hubbard modified mendeleev’s table (1924), giving it a more compact form, suitable for use in class. it has been updated several times, 12 editions until 1936, 18 until 1963, sponsored by sargent & welch, buffalo, manufacturers of teaching material. hubbard’s was the most widely used periodic wall table in american schools. it was also well received in brazil during the 1930s, the so-called “hubbard’s brazilian table” from the former escola nacional de engenharia (now the polytechnic school of the federal university of rio de janeiro), a table ‘rediscovered’ by sir martyn poliakoff, of nottingham university. hubbard’s brazilian table includes dated symbols, like cb (columbium 41, instead of niobium), ma (masurium 43), il (illinium 61), ab (alabamine 85), and vi (virginium 87), among other curiosities, none of which were recognized discoveries.89 in an era of atavistic nationalism, hubbard’s table clearly illustrates the reluctance to abandon elements ‘discovered’ in the united states, even though these were not recognised by the international chemical community and would later have to be removed from the table. in past centuries chemists had different, often subjective, views on the structure of matter, which reflected on their teaching of chemistry. the same can be said of chemistry teachers and their subjective views on how best to present the periodic table. in some cases this personal exploration of the table by teachers was incredibly creative, and quoting bertomeu-sanchez (et al): the most creative books were not necessarily the great treatises written by creative academic chemists. obscure chemistry teachers, who were not necessarily active in scientific research, attempted innovative and ambitious systems of elements in order to satisfy both didactic and scientific constraints. textbook writing remained a creative activity. by creative, we do not necessarily imply innovation or great discovery. they were creative in a more modest way as they expressed original and ambitious interpretations of the foundations of chemistry.90 this idea is exemplified by one of the few brazilian contributors to represent the periodic system, alcindo flores cabral (1907-1982), professor at the school of agriculture eliseu maciel (nowadays part of the federal university of pelotas), in 1946. examining a mysterious mural at the entrance of the chemistry building in pelotas, professor eder lenardão rediscovered his table (2001).91 44 juergen heinrich maar, alexander maar in the case of a few talented chemists the necessity to write more engagingly and creatively – often inspired by episodes from their personal and professional lives – was responsible for the production not just of textbooks, but high-quality, transcendent or poetic literary pieces. two examples deserve special attention: “il sistema periodico” by primo levi (1919-1987), published in 1975, and the biographical “uncle tungsten – memories of a chemical boyhood” (2001) by neurologist oliver sacks (1933-2015). for sacks: the periodic table is incredibly beautiful, the most beautiful thing i had ever seen. i could never adequately analyze what i meant here by beautiful – simplicity? coherence? rhythm? inevitability? or perhaps it was its symmetry, the comprehensiveness of every element firmly locked into its place, with no gaps, no exceptions, everything implying everything else.92 the elements in primo levi’s “il sistema periodico” become symbols and metaphors for the various phases of the author’s life, so that a summation of elements becomes his life story or a memoir. on such metaphorical usage luigi dei (b. 1956) concluded that “we can say that the properties of the elements often reflect the properties of life itself: volatile, inert, lustrous, precious, poisonous, brittle, explosive...”93 in the chapter dedicated to iron, levi thus refers to the periodic table: that the nobility of man, acquired in a hundred centuries of trial and errors, lay in making himself the conqueror of matter, and that i had enrolled in chemistry because i wanted to remain faithful to this nobility. that conquering matter is to understand it, and understanding matter is necessary to understanding the universe and ourselves: and that therefore mendeleev’s periodic table, which just during those last weeks we were laboriously learning to unravel, was poetry, loftier and more solemn than all the poetry we had swallowed down in liceo, and come to think of it, it even rhymed! that if one looked for the bridge, the missing link…94 most of such literary pieces portray the periodic system in a positive light. this need not always be so. in the poem “the periodic table of elements”, australian poet bruce greenhalgh shows his disenchantment with the table: …that it listed more/and less/than earth, wind, fire and water, [but 118 elements are] arranged by atomic number/ in an obscure scheme/of electrons and abbreviations, [without any] reflect/on sodium/or potassium/or byzantium [in reference to yeats’s poem], no flair, no mystery, no poetry, nothing for me”, [poet and periodic table] have gone our separate ways.95 chilean poet nicanor parra (1914-2018), professor of theoretical physics in santiago, has a similar, if more ironic, take on the table. in his long poem “los profesores” (“the teachers”), he speaks of “teachers turning us mad/with questions which do not matter” – including the periodic table. one may be tempted to explain why, given the success of the table in systematizing existing knowledge and predicting new elements, a chemist would react negatively to it. one could speculate that the table, for some people, may fall victim to its own success. it would be very difficult for a chemist to attempt any different form of systematisation today, which some would see as a limitation to creativity. the table also indicates what possible new chemical discoveries may be like, which may lessen our sense of amazement when progress is indeed achieved. finally, some chemical elements, isolated or classified by the table, inspired musical compositions as well. edgar varèse (1883-1965) honoured platinum with a piece for flute solo (1936), “density 21.5” (the density of the metal), and the composer and theorist andrew stiller (b. 1946) composed in 1988 “a periodic table of the elements” for 14 wind and percussion instruments.96 this brief survey of the table’s presence in nonchemical or academic contexts goes to show that some scientific achievements, when consolidated through a universally accepted form of representation, have the tendency, or at least the potential, to become iconic – in the sense defined at the beginning of this essay. more on this in the next section. the periodic table and pop culture the periodic table is the object of this essay, so let us define less rigorously what after all is ‘popular culture’. also, the definition of “science fiction” differs from author to author; let us adopt here the definition given by darko suvin (b. 1930): “... a literary genre or verbal construct whose necessary and sufficient conditions are presence and interaction of estrangement and cognition, and whose main device is an imaginative framework alternative to the author’s empirical environment.”97 science fiction does not necessarily deal with the actual periodic table, but often invents (sometimes even foresees) fantastic and fanciful imaginary elements in an environment artificially constructed, but still plausible and credible. hans dominik (1872-1945), engineer, in his time famous as author of many science fiction stories and novels conceived in atomgewicht 500, published in 1934, artificial elements with very high atomic weights. 45the periodic table and its iconicity: an essay at the time he wrote it uranium had the highest atomic weight, 238. dominik’s scientific views are no longer valid, but the author’s utopian vision with respect to the future of nuclear chemistry is worthy of note. some lines from the book: “the most important! you know what i mean. atomic weight? two hundred and forty-two! four unities more than the atomic weight of uranium. congratulations, slawter! you were the first to obtain a substance non-existent on earth and in terrestrial conditions”98. transuranic and transfermic elements exceed this weight; the heaviest known element to date is oganesson (og, atomic number 118 first synthesised in 2002 at the  joint institute for nuclear research  in  dubna, russia, by russian and american scientists), with an atomic weight of 294. with the probable completion of the ninth series of the table, we will surpass the value 300 ... will these imaginar y elements one day become reality? suze kundu wrote in nature: “scientists and non-scientists alike have long been dreaming of elements with mighty properties. perhaps the fictional materials they have conjured up are not as far from reality as it may at first seem.”99 in face of “atomic number 500” and the ongoing study (a reality) of the periodic table, may we expect an upper limit for this “expanded” periodic table? or a lower limit? what will this limit be? sima lozanic speculated about a limit already in 1906. niels bohr (1885-1962) in 1922 expanded electronic configuration to element 118, but in 1924 he concluded theoretically that it would be difficult to surpass atomic number 137.100 beyond the “island of stability” around atomic masses 290 – 300, perhaps atomic number 128 will be the limit, or, for albert khazan (b. 1934), this figure would be 155.101 pekka pyykkö (b. 1941) and burkhard fricke, on the basis of mathematical calculations, suggest a limit of z = 172 (suggesting a noble gas)102, and for walter greiner (1935-2016) there is no limit for the periodic table. on the chemical properties of aluminium (an element already known but still unused at the time), charles dickens (1812-1870) wrote in 1856: within the course of the last two years [...] a treasure has been divined, unearthed and brought to light [...] what do you think of a metal as white as silver, as unalterable as gold, as tough as iron, which is malleable, ductile, and with the singular quality of being lighter than glass? such a metal does exist and that in considerable quantities on the surface of the globe.103 dickens’ ‘treasure’ element did become reality. another contemporary of dickens, english chemist and industrialist john carrington sellars (1840-1916), in an attempt to popularise chemistry and find connections with christianity, published in 1873 a curious and rather long poem titled chemistianity, “an oratorical verse, in poetic measure, on each known chemical element [ ... ] in the universe.”104 each of the 63 then-known elements received symbolic names. dickens’s wonder metal aluminium, for instance, was called ‘ktyon’, and about it sellars says: “aluminium, the bright star of metals,/ the principal metal in common clay/in extremely light, bright, and silver-like/it does not oxidise in exposure to air...”105 sellars described in ‘oratorical verse’ the properties of the element. according to van der krogt, sellar’s book (today very rare and collectable) was wellreceived at the time of publication.106 on the other hand, there is a perceptible trend in more recent fictional writing in which plausibly imagined chemical knowledge gives way to fantastic, farfetched chemical worlds – as can be seen in superhero comics (captain america, wolverine), or in tolkien’s fantasy books, and even in janet kuypers’ poetry: “i wracked my brain, ‘wait a minute,/i know osmium, it’s the densest metal/in the periodic table. but diburnium?”107 j. ober and t. krebs include amongst their favourite fictional elements the mithril of the hobbit, by j. r. tolkien (1892-1973), the dilithium from the universe of star trek, and the vibranium of captain america’s shield.108 mithril, made by dwarves, resembles silver, but it is lighter and stronger than steel. dilithium, a mineral found on different planets of the star trek universe, regulates the reaction between matter and antimatter. vibranium, originating from wakanda (africa) exhibits a powerful capacity to absorb, store, and release vast amounts of kinetic energy. one cannot help but wonder whether reality will meet fiction at some point, and whether we will be able to say of a new element something similar to what dickens said of aluminium. still, in the genre of popular culture, the musician, comedian and harvard professor of mathematics tom lehrer (b. 1928) authored a song containing all the elements of the periodic table. the song was based on comic opera “the pirates of penzance” (aka “the slave of duty”), by sir arthur sullivan (1842-1900). in the case of cinema, probably one of the most efficient vehicles of mass communication, there has been little interest in the periodic table and its creator, mendeleev. he has not been the subject of any movies, figuring only in documentaries such as “the mystery of matter” (2014). this is in sharp contrast to the cinema’s interest in the lives and works of many notable scientists, such as pasteur, marie curie, ehrlich, paracelsus, copernicus, and even julius robert mayer. 46 juergen heinrich maar, alexander maar final remarks on november 2nd, 2017, the 39th general conference of unesco in paris proclaimed 2019 the international year of the periodic table. this is, of course, a result of the table’s iconicity and universal appeal. such recognition does not mean that the table itself, or even the discovery of periodicity, are the most important innovations in the history of chemistry. one could think of dalton’s quantitative atomic theory, or lavoisier’s oxygen theory, as better candidates for most important breakthrough moments. yet, most are quick to recognise the table as chemistry’s most important icon. michael mingos (b. 1946), from oxford university, resumes the real possibilities of the periodic table: the periodic table is neither a biblical tablet of rules nor a monolithic rosetta stone, which provides accurate translations of chemical trends and properties. it does, however, offer a flexible two-dimensional mnemonic for recalling the important characteristics of the 118 known elements and the structure of their constituent atoms. […] it thereby provides a way of thinking for chemists which also reflects the individual’s unique history and personality.109 the table has undoubtedly been the most successful tool for the popularisation of chemistry and, by extension, scientific knowledge and practice. this cannot be explained just as a response to the discovery of periodicity. but perhaps it can be explained by the table’s success in both, accommodating and systematizing existing knowledge (theories and data) and predicting new discoveries. as is always the case in science, empirical adequacy was the primary reason for the table’s worldwide adoption as the best representation of what is known about the elements, atoms and their structure. but there were also other reasons for its positive reception in different countries. finally, we hope to have shown that it is the dual nature of the table – its capacity to enclose the totality of chemical and physical knowledge about the elements, and its usefulness as a 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2018. 97. d. suvin, positions and suppositions in science fiction, macmillan, london, 1988, p. 37. 98. h. dominik, atomgewicht 500, e-art now, 2018, p. 16. 99. s. kundu, nature: chemistry, 11, 2019, 13. 100. h. kragh, the european physical journal, 38, 2013, 411. 101. j. emsley, nature’s building blocks: an a – z guide to the elements, oxford university press, oxford/new york, 2011. 102. p. pyykkö, phys. chem. chem. phys., 13, 2011, 161. 103. c. dickens, household words, vol. xiv, bradbery & evans, london, 1856. 104. . j. sellars, quoted in c. reilly, mid-victorian poetry, 1860-1879, mansell, london, new york, 2000, p. 410. 105. p. van der krogt, personal communication; partial transcription of p. sellars, chemistianity, pp. 124-125. url = <https://elements.vanderkrogt.net/element. php?sym=al>. 106. p. van der krogt, op. cit. 107. j. kuypers, the periodic table poetry: the poetry for every element in the periodic table, scars publications & design, gurnee, 2015. 108. j. ober, t. krebs, j. chem. ed., 86, 2009, 1141. 109. m. mingos, structure and bonding, 118, 2018, editorial. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna substantia. an international journal of the history of chemistry 7(1): 67-78, 2023 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-2040 citation: adams m. h. (2023) surface inactivation of bacterial viruses and of proteins. substantia 7(1): 67-78. doi: 10.36253/substantia-2040 copyright: reproduced from surface inactivation of bacterial viruses and of proteins, published by mark h. adams on journal of general physiology, 5(31), 417-431, 1948. copyright © 2023, by mark h. adams. reproduced with permission of the publisher. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article surface inactivation of bacterial viruses and of proteins mark h. adams department of bacteriology, new york university college of medicine, new york due to the covid-19 pandemic an enourmous number of papers have appeared in the literature. here we republish, with permission, the paper written by m.h. adams in 1948 for the remarkable contribution in physiology and in other fields. a short introduction by barry w. ninham precedes the paper. missed opportunities and fashionable pursuits by barry w. ninham department of materials physics, australian national university, canberra, australia the extraordinary paper of mark h. adams: surface inactivation of bacterial viruses and of proteins appeared in a mainstream journal of physiology, in 1948.1 it was neglected and has been ever since. in retrospect this was and is a tragedy for science of the very first order.2 adams was recognised in his time as a brilliant bacteriologist who, sadly, died young (1912-1956). his peers completed a partially finished book on his work in 1959.3 it was forgotten in the rush to join the dna biological revolution. in that revolution the physical sciences, the physical chemistry of solutions, colloid and surface science have played almost no serious conceptual role at all. the biological/medical and the physico-chemical sciences have diverged almost completely, to a point where their languages are mutually incomprehensible.2 of course, characterisation and diagnostics of disease by myriad new techniques has been essential to progress in medicine and biology. but the gap remains. we are missing something. 1 adams, m. h. surface inactivation of bacterial viruses and of proteins. journal of general physiology 1948, 31 (5), 417–431. https://doi.org/10.1085/jgp.31.5.417. 2 ninham, b. w. the biological/physical sciences divide, and the age of unreason. substantia 2017, 1 (1), 7–24. https://doi.org/10.13128/substantia-6. 3 blair, j. e. bacteriophages. mark h. adams, with chapters by e. s. anderson, j. s. gots, f. jacob and e. l. wollman. interscience publishers, inc., new york, 1959. clinical chemistry 1959, 5 (6), 634. https://doi.org/10.1093/clinchem/5.6.634. http://www.fupress.com/substantia 68 mark h. adams adams paper circumscribes that something. to see why we remark that 1948 was the same year that overbeek ’s landmark thesis on colloid stability marked the basis for the dlvo theory of colloid stability.4,5 it introduced long ranged quantum mechanical, dispersion forces of interaction between particles and dominated thinking about forces until now. its limitations were spelt out by derjaguin and overbeek. many of these limitations appeared to be resolved by sophisticated further extensions that embraced many body forces via lifshitz theory, on charge regulation, on effects due to solvent structure and molecular size. direct force measurements between surfaces that confirmed theory, a challenge dating back before newton, appeared to represent a triumph.6 but there was and remained an uneasy juxtaposition with the classical theories of the physical chemistry of electrolytes and electrochemistry, and colloid science. these theories, of ph, of activities, of pkas, of conductivity, the electrical double layer, of zeta potentials that were developed before quantum mechanics, and ignored it. dispersion forces between ions and ions and surfaces are the key to specific ion (hofmeister) effects essential to biology. and hydration was unquantified. add to that the fact that undefined anthropomorphic words like hydrophilic and hydrophobic figured prominently in the conversation and we have an unquantifiable mess. that is explicit in that standard measurements like ph and zeta potentials were based on inadequate theory. it got worse when it was realised that even the apparently impressive addition of electromagnetic quantum field theory embodied in lifshitz theory was 4 verwey, e. j. w. theory of the stability of lyophobic colloids. j. phys. chem. 1947, 51 (3), 631–636. https://doi.org/10.1021/j150453a001. 5 derjaguin, b. v., & landau, l. (1941). acta physicochim. urss. journal of experimental and theoretical physics, 14, 635-649. derjaguin, b. v., & landau, l. (1941). theory of stability of highly charged lyophobic soils and adhesion of highly charged particles in solutions of electrolytes. zhunal eksperimentalnoi; theoretischekoi fisiki, 11, 801-818. derjaguin and landau publications in russian were not easily accessible in the west during the 2nd world war. landau was appallingly scathing of sam levine who nearly had the theory first. he did so because sam replaced a nonlinear coupling constant integration in calculating the double layer free energy by a linear one. it is therefore ironic that landau’s students dzyaloshinski, lifshitz and pitaevski made the same mistake in their tour de force of quantum electrodynamic forces. see also: ninham, b. w.; brevik, i.; boström, m. equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the π₀ meson, its mass and lifetime. substantia 2022. just accepted https://doi.org/10.36253/substantia-1807. 6 ninham, b. w.; lo nostro, p. molecular forces and self assembly: in colloid, nano sciences and biology; cambridge molecular science; cambridge university press: cambridge, 2010. https://doi.org/10.1017/ cbo9780511811531. flawed too, and that the ansatz of additivity of electrostatic and electrodynamic fluctuation (dispersion) forces, the one treated in nonlinear theory, the other linear, violates the laws of physics.7,8 since hardly anyone understood mathematics or physics, it did not matter. matters reached a nadir in the 1980s when the leading speaker at a nobel symposium, from a swiss drug company began his lecture with slide: nmr. no, not nuclear magnetic resonance he said. it means no more research! by which, he explained, the game was over. modern computer simulation with 70,000 effective molecular interaction parameters without water, could design any required drug or protein or enzyme with ease. a laconic biochemist asked; what happens if you raise the temperature above body temperature of 37 degrees. ha! easy. we change the parameters! such mind-blowing idiocy continues and marks the end of an era. faraday would be turning in his grave. we can forgive the medical and biology people for ignoring what ought to be the enabling discipline of physical chemistry on the reasonable grounds that they have more than enough to do than be confused by the subtleties of the physical sciences; especially if even the quantum electrodynamicists produce a flawed theory. but there is much more, and here we come to adams. the physical theories (and simulation) ignore any effects due to dissolved atmospheric gases. the ancient greeks tell us that there were 4 elements. these are: fire (temperature), water, earth, and air. take away air and hydrophobic interactions go away; emulsions become stable, chemical interactions cease, enzymes working. the simplest of experiments is bubble-bubble interactions in salt water. bubbles do not fuse above a concentration of 0.17 molar for 1:1 salts like nacl.9,10 not coincidently, that corresponds exactly to the ionic strength of 7 ninham, b. w. b. v. derjaguin and j. theo. g. overbeek. their times, and ours. substantia 2019, 3 (2), 65–72. https://doi.org/10.13128/substantia-637. 8 lo nostro, p.; ninham, b. w. after dlvo: hans lyklema and the keepers of the faith. advances in colloid and interface science 2020, 276, 102082. https://doi.org/10.1016/j.cis.2019.102082. 9 craig, v. s. j.; ninham, b. w.; pashley, r. m. the effect of electrolytes on bubble coalescence in water. j. phys. chem. 1993, 97 (39), 10192– 10197. https://doi.org/10.1021/j100141a047. 10 bunkin, n. f.; ninham, b. w.; ignatiev, p. s.; kozlov, v. a.; shkirin, a. v.; starosvetskij, a. v. long-living nanobubbles of dissolved gas in aqueous solutions of salts and erythrocyte suspensions. journal of biophotonics 2011, 4 (3), 150–164. https://doi.org/10.1002/jbio.201000093. 69surface inactivation of bacterial viruses and of proteins salts in the blood. the phenomenon occurs for a whole range of salts. but for other ion pairs, no such effect occurs. there are strict rules that govern which ion pairs “work ” and which do not. the effects occur at higher concentrations for sugars. they occur at much lower concentrations for amino acids.11 classical physical and colloid chemistry are impotent in the face of such a challenge. the answer seems to lie in the fact that in any solid or liquid impurities aggregate, in much the same way that surfactants aggregate to form micelles. there is a natural critical salt concentration for stable nanobubble formation. this shows up in conductivity measurements in salt solutions with and without dissolved gas.12 such nanobubbles inhibit bubble-bubble fusion by known depletion forces. nanobubbles that form spontaneously in enzymesubstrate interactions produce free radicals that drive catalysis. cavitation produced by ship propellers, a very major economic transport problem, disappears if a jet of air deficient water is projected onto the propeller.13 the tensile strength of water is two orders of magnitude higher when gas is removed, a fact known for more than a century, and explained immediately by griffith’s theory of. the strength of solids if gas aggregates of nanobubbles impurities occur. much more to the point stable nanobubbles of co2 produced by metabolism produce a foam that forms the endothelial surface layer lining all cells and tissues. it is extremely effective in killing viruses like covid and other pathogens.13,14,15 nanobubbles of oxygen/nitrogen are delivered by the lungs to capillaries, not molecularly and catalyse many reactions.16 11 nafi, a. w.; taseidifar, m.; pashley, r. m.; ninham, b. w. the effect of amino acids on bubble coalescence in aqueous solution. journal of molecular liquids 2023, 369, 120963. https://doi.org/10.1016/j.molliq.2022.120963. 12 ninham, b. w.; lo nostro, p. unexpected properties of degassed solutions. j. phys. chem. b 2020, 124 (36), 7872–7878. https://doi. org/10.1021/acs.jpcb.0c05001. 13 vol. 4 no. 2 suppl. 1 (2020) – about water: novel technologies for the new millennium | substantia. b.w ninham and r.m pashley eds. 14 garrido sanchis, a.; pashley, r.; ninham, b. virus and bacteria inactivation by co2 bubbles in solution. npj clean water 2019, 2 (1), 1–9. https://doi.org/10.1038/s41545-018-0027-5. 15 reines, b. p.; ninham, b. w. structure and function of the endothelial surface layer: unraveling the nanoarchitecture of biological surfaces. quarterly reviews of biophysics 2019, 52, e13. https://doi. org/10.1017/s0033583519000118. 16 ninham, b.; reines, b.; battye, m.; thomas, p. pulmonary surfactant and covid-19: a new synthesis. qrb discovery 2022, 3, e6. https:// doi.org/10.1017/qrd.2022.1. the present state of affairs as it exists in colloid science can be seen in ref. 17.17 it is seems clear that dissolved gas is a hidden variable that is essential to understanding the properties of condensed matter. the effects are dramatic. the greeks told us so. our theories have ignored dissolved gas. they compare gas-free models with real world soft matter that does contain gas. a simple example is the deviation from theory of the measured debye length in a 1:1 electrolyte above the critical concentration for nanobubble formation. it is impossible to simulate these effects. adams paper on effects on proteins of shaking test tubes containing physiological saline, or not, containing gas or not covered all this 75 years ago. a pity we missed it. there is nothing we can do about it except wonder at what might have been had he lived. there are appearing now a number of good papers that are following adams lead.18 and finally we can note that the extinction of species after various ice ages makes sense if we allow dissolved gas to do its job. during an ice age salt is precipitated out. after the ice age the melt water is salt depleted below the critical concentration for bubble-bubble (and nanobubble) fusion. all single celled creatures would die of the bends. some few souls are beginning to shake things up and surprised at what they see. barry w. ninham 17 ninham, b. w.; pashley, r. m.; nostro, p. l. surface forces: changing concepts and complexity with dissolved gas, bubbles, salt and heat. current opinion in colloid & interface science 2017, 27, 25–32. https:// doi.org/10.1016/j.cocis.2016.09.003. 18 bunkin, n. f.; shkirin, a. v.; ninham, b. w.; chirikov, s. n.; chaikov, l. l.; penkov, n. v.; kozlov, v. a.; gudkov, s. v. shaking-induced aggregation and flotation in immunoglobulin dispersions: differences between water and water–ethanol mixtures. acs omega 2020, 5 (24), 14689–14701. https://doi.org/10.1021/acsomega.0c01444. 70 mark h. adams it has been noticed previously that certain viruses can be rapidly inactivated by shaking or by bubbling gases through the virus suspensions. campbell-renton (1) studied the effect of violent mechanical shaking on bacteriophages and found them to be fairly rapidly inactivated, at rates which were charac teristic for each phage. grubb, miesse, and puetzer (2), while studying the effect of various vapors on influenza a virus, noted that bubbling air at the rate of 1 liter a minute through the virus suspension resulted in detectable reduction in infectivity in 10 minutes. in a somewhat more extensive study mclimans (3) found that both eastern and western strains of equine encephalitis virus were rapidly inactivated by shaking in buffered saline suspensions. the inac tivation also occurred when gases were bubbled through suspensions of the virus. the rate of inactivation was the same whether oxygen or helium was the gas used, indicating that the inactivation was probably a physical process, rather than the result of chemical interaction between virus and gas. he also noted that the rate of inactivation increased markedly as the ph was reduced from 7 to 5, though control suspensions at rest suffered no inactivation. the inactivation of certain physiologically active proteins such as enzymes (4) and toxins (5) on shaking is a familiar phenomenon. perhaps not quite so wellknown is the fact that this kind of inactivation can be specifically pre vented by the presence in the diluent of very small amounts of proteins. it has been demonstrated that the spreading of a protein at a gas-liquid interface results in the denaturation of the protein, since the spread protein becomes completely insoluble in water (6) presumably the role of the shaking or bub bling in the inactivation of viruses and physiologically active proteins is simply that of enormously increasing the area of the gas-liquid interface, and hence increasing the chances of the susceptible protein being spread on that surface. this paper is devoted to the kinetics of the inactivation of bacteriophage by shaking and to the effect of environmental influences on the rate of inactivation. materials and methods the group of seven coli-dysentery phages studied by demerec and fano (7) was used. the properties of this group of bacterial viruses have been summarized by de1bl-tick (8). these phages were grown on escherichia coli, strain )3, in a chemically defined medium of the following composition: nh4c1 ........................................................................... 1.0 gm. mgso4 ........................................................................... 0.1 gm. kh2po4 3.5 gm. lactic acid .................................................................... 9.0 gm. naoh ............. about 4.0 gm. or to a final ph of about 6.5 h2o ........................................................................... 1,000 ml. since t5 is not produced in the absence of calcium ion, calcium choride to a concen tration of 0.001 m was added when preparing stocks of this phage. all phage stocks used contained about 1010 plaque forming particles per ml. all phage assays were made on strain b of e. coli using the agar layer technique of gratia as modified by hershey (9). the saline buffer diluent used in the inactivation experiments contained 0.15 m naci, 0.001 m mgso4, 0.01 m buffer, and other additions as noted. most experiments were performed using phosphate buffer at ph 6.5. inorganic chemicals were reagent grade; the gelatin was eastman ash-free calfskin gelatin; the bovine serum albumin was armour’s fraction v; yeast nucleic acid was a purified specimen from eimer and amend; the thymus nucleic acid was a highly viscous hammarsten type preparation. in the bubbling experiments nitrogen was passed through a coarse grade corning sintered glass filter at the rate of 1 liter per minute producing a vigorous effervescence in the virus suspension held in the filter. the gas was saturated with water vapor and the gas stream as well as the filter and its contents was in a constant temperature bath. the shaking experiments were carried out in test tubes 15 mm. × 100 mm. with a capacity of 16 cc. these tubes as well as dilution tubes were cleaned with hot acid dichromate, well rinsed, and twice boiled with distilled water. pipettes were simi larly acid-cleaned and rinsed with hot distilled water the test tubes were closed with rubber stoppers which were boiled with sodium hydroxide, well rinsed, then twice boiled with distilled water before each use. the most meticulous cleanliness was essential in obtaining consistent results. the shaking machine had a horizontal reciprocating motion of 320 cycles per minute and the carriage traversed a distance of 7 cm. the test tubes were shaken with the long axis parallel with the direction of motion of the carriage. experimental kinetics of the inactivation reaction. — bacteriophage t7 at an initial concen tration of 6 × 109 plaqueforming particles per ml. was diluted in the saline-buffer diluent to a concentration of about 104/cc. the conditions of the experi ment were: phosphate buffer of ph 6.5, temperature 26°c., volume of phage suspension 5 71surface inactivation of bacterial viruses and of proteins cc., shaker stopped every 2 minutes for sampling. the log per cent survivors proved to be a linear function of time indicating that the rate of phage destruction was proportional to the concentration of surviving phage; or k=1/t lnp0/pt the data of this sample experiment are given in table i. the first order velocity constant for the inactivation of t7 under the stated conditions was 0.28 min-1. there was no recovery of activity on standing in buffer diluent or broth, and inactivation occurred at a significant rate only during the periods of shaking (table i). the velocity constants for the inactivation of each of the seven coil phages and of two of their mutants at ph 6.5 and 26°c. are given in table ii. from the data in table ii it may be noted that the small phages t1, t2, and t7 are inactivated more rapidly than the larger phages. phage t4r+ and its rapid lysing mutant (10) t4r are much more stable than the other phages. with both t2 and t4 phages there was no significant difference between the stabilities of wild type and rapid lysing mutant. also in mixtures of wild type and mutant forms, the proportion of the two types remained constant during the inactivation. the volume of phage suspension was varied from 4 cc. to 7 cc. per 16 cc. tube without affecting the velocity of the inactivation. however, if the tube is filled with virus suspension so that no air space is left, there is no perceptible inactivation of the phage during 40 minutes’ shaking, even when half a dozen glass beads are added to the tube. because of the possibility of inactivation of phage through adsorption to the glass walls of the tube or to the rubber stopper, both of these surfaces were coated with melted paraffin. in the paraffin-coated tube the rate of inactivation of phage was the same as in un coated tubes even though the paraffin surfaces were not wetted by the suspen sion of phage. if loss of activity were due to adsorption, the virus must adsorb equally well to glass and to paraffin. from these experiments it would appear that the shaking or agitation of the fluid suspension in contact with glass sur faces is not the cause of the inactivation of virus, but rather that the inactivation occurs at the gas-liquid interface which is present in enormous area when tubes half filled with liquid are violently shaken. the variation of velocity constant of inactivation as a function of ph is shown in the curves of fig. 1. from these curves it is evident that the rate of inactivation by shaking is minimal between ph 5 and 8 but increases rapidly outside this range. the small phage t7 is much more rapidly inactivated at all ph values than are the larger phages, and repeated assays at a given ph are less reproducible with the small table i. the inactivation of tt bacteriophage by shaking in saline-buffer diluent at 26°c. and ph 6.5 time sample count survivors per 0.1 ml. pe/pt in po/pg k 0 0 ml. 0.02 0.02 136 165 av. 753 2 0.05 225 450 1.67 0.51 0.26 4 0.05 104 208 3.6 1.28 0.32 6 0.05 68 136 5.5 1.7 0.28 8 0.05 45 90 8.3 2.1 0.27 10 0.1 52 52 14.4 2.7 0.27 15 0.1 13 13 58 4.1 0.27 35 0.1 1 1 753 6.6 (0.19) av. 0.28 table ii . the average velocity constants for the shaking inactivation of coli phages at 26°c. and ph 6.5. phage velocity constant t1 0.59 min.-1 t2r+ 0.24 t2r 0.23 t3 1.2 t4r+ 0.05 t4r 0.07 t5 0.24 t6 0.20 t7 0.48 72 mark h. adams phages, resulting in a more erratic looking curve. all phages were markedly unstable in the absence of shaking at ph 3 except t4. at ph 4 the phages were more stable than at ph 3 but in a few cases there was a 10 to 50 per cent loss in activity on standing at room temperature for 1 hour. at the higher ph values studied there was no detectable loss in activity in un shaken controls during the course of the experiments. phage t7 which is very rapidly inactivated by shaking at ph values above 7 is not detectably inacti vated in unshaken control tubes after 1 hour at ph 8.7. the effect of temperature on the velocity constants of inactivation was determined for phages t1 and t7. the averages for a number of determinations at 0°, 25°, and 38°c. are given in table iii. from these values, using the arrhenius equation, the arrhenius constant for the shaking inactivation of phages t1 and t7 appears to be about 10,000 cal./mol. this value is higher than the reported values for the heat of activa tion of denaturation of proteins by urea and by shaking (11) and far less than the values for heat denaturation of proteins. in the presence of 1 mg./ml. of gelatin all phages were stable on shaking for 1 hour at room temperature at ph 6.5. therefore, the protective effect of various concentrations of gelatin on phage t5 was determined. the results are summarized in fig. 2. it will be seen from fig. 2 that as little as 0.01 γ per ml. of added gelatin has a definite protective effect on phage t5 while 1 γ/ml. gave complete protection for 14 minutes. however, after 20 minutes of shaking with 1 γ/ml. of gelatin the phage activity began to decrease. it would appear that the duration of the protective effect of gelatin is a function of the concentration of gelatin, and that the gelatin also appears to be inactivated by shaking. if the survival time of the gelatin is taken as the time when the inactivation curve becomes parallel to the inactivation curve in the absence of gelatin, then it becomes possible to estimate the rate of disappearance of the gelatin. the disappearance of the gelatin under these conditions appears to follow the kinetics of a first order reaction with a half-life of about 2 minutes. this relationship does not hold for concentrations of gelatin figure 1. velocity constants, k minute-1, as a function of ph for the phages t2, t4, t5, and t7 at about 26°c. table iii. the average velocity constants for inactivation of t1 and t7 at 0°, 25°, and 38°c. temperature velocity constants for t1 t7 cc. 0 0.31 0.09 25 0.59 0.48 38 0.97 0.70 figure 2. the inactivation of phage t6, shaken in the presence of various amounts of gelatin. 73surface inactivation of bacterial viruses and of proteins above about 0.5 γ/ml. since as the protein concen tration becomes higher the kinetics change from those of a first order reaction to those of a zero-order reaction in which the rate of inactivation is determined by the available surface rather than by the concentration of protein in solution (11). if this supposition is correct, preshaking of the gelatin solutions before adding the phage should destroy the protective effects of the gelatin. the experiment illustrated in fig. 3 is identical with the previous experiment except that the dilutions of gelatin in saline-buffer diluent were preshaken for 15 minutes before addition of phage. then after phage addition the tubes were shaken and samples withdrawn at intervals for assay. it may be seen from fig. 3 that the protective effects of all quantities of gelatin through 0.33 γ/ml. are destroyed by shaking for 15 minutes so that the resultant inactivation curves are identical with the curve with no added protein. there is little appreciable diminution in the protective effect of 1 γ/ml. of gelatin after 15 minutes of shaking. similar experiments have been carried out using various concentrations of gelatin with t7 and t2r, with very similar results. since gum arabic is a colloidal substance with reputed protective effect against inactivation of tuberculin (12) it was tested for its effect on the shaking inactivation of phage t5. as may be seen from fig. 4 gum arabic gives a family of curves similar to those given with gelatin, except that about 100 times as much gum arabic is required to equal the effect of gelatin. it is probable that the protecting effect of the gum arabic is due to contamination with about 1 per cent of protein. this agrees with previously made quantitative estimates of the protective effect of gum arabic against the surface inactivation of tyrosinase (13). in a similar manner yeast nucleic acid and thymus nucleic acid prepared according to hammarsten were tested for possible protective effect. both of these substances had a protective effect equivalent to about 1 per cent of their weight of gelatin. since no amino acid analfigure 3. the inactivation of phage t5, shaken in the presence of various amounts of gelatin which had already been shaken for 15 minutes before addition of phage. the symbols correspond to the same gelatin concentrations as in fig. 2. the solid line is the curve for no added gelatin and the dotted line is an average curve for the tubes containing added gelatin. figure. 4. the inactivation of phage t5, shaken in the presence of various amounts of gum arabic. 74 mark h. adams yses were available for these samples of nucleic acid we cannot say whether the protective effect is due to contamination with protein or is an inherent property of nucleic acids. a commercial sample of bovine serum albumin (armour fraction v) prepared by alcohol fractionation was tested for its protective effect with the results shown in fig. 5. by a comparison of the curves of fig. 5 with the curves with gelatin in fig. 2 it may be seen that serum albumin is about one-tenth as active in protecting the virus from inactivation as is gelatin. this observation is in accord with experi ments of berger, slein, colowick, and cori (14) on the inactivation of hexo kinase in which the protective effect of serum albumin was about one-tenth that of insulin or rabbit muscle protein. it also agrees qualitatively with reported effects on the stability of diphtheria toxin diluted for the schick test. edsall and wyman (15) reported that 500 γ/ml. of human serum albumin gave in complete protection while 1 mg./ml. gave excellent protection. moloney and taylor (16) using similar test conditions reported that 12.5 γ/ml. of gelatin gave considerable protection while 25 γ/ml, of gelatin gave complete protection for 6 months. if the inactivation of bacteriophages is due to some change occurring at the surface of gas bubbles produced in the fluid by shaking, this same kind of in activation should occur when an inert gas is bubbled through a suspension of the virus. accordingly 25 ml. of bufferdiluent at ph 6.5 containing phage t2r at a concentration of 2.5×104 infectious particles per ml. were placed in a corning sintered glass filter of coarse grade. this was held in a water bath at 30°c. and nitrogen gas was bubbled through the filter at the rate of 1 liter per minute. samples were withdrawn at 5 minute intervals for an hour without interrupting the gas flow. the inactivation followed the kinetics of a first order reaction throughout this time with a velocity constant of 0.047 minute-1, as compared with 0.23 minute-1 for shaking with air at 26°c. similar results were obtained with t7 although the rate was somewhat faster with this phage. discussion the denaturation of proteins probably involves the unfolding of a highly specific globular structure into a relatively unspecific polypeptide chain. this change exposes hitherto hidden -sh and phenolic groups to the action of chemi cal reagents, and results in the loss of solubility and of the specific physiological activity of the protein. denaturation may be brought about by the action of heat, of chemicals such as urea, of detergents, of excessive concentrations of h+ or oh’ ions, and by shaking. all of these denaturing agents will also bring about a destruction of the infectious properties of viruses. that vigorous shaking will cause the precipitation of proteins from solution has been known for a long time. the precipitation of egg albumin from 1 per cent solutions on vigorous shaking follows the course of a zeroorder reaction since the high concentration of protein maintains the gas-liquid interface in a saturated condition. the rate-limiting factors are the amount of surface available, and the rate at which the surface is renewed by agitation (11) with highly diluted proteins however, one might expect the kinetics of the reaction to be first order since the number of protein molecules arriving at the surface in unit time will be proportional to the protein concentration. there is very little data on this point in the literature. shaklee and meltzer (4) in 1909 studied the effect of shaking on the stability of pepsin in hcl. from their data it can be calculated that the inactivation of pepsin follows the course of a first order reaction with a velocity constant of 0.029 minute-1at 33°c. since no charac terization of the pepsin was made it is impossible to say how much pepsin was present or even how figure 5. the inactivation of phage t5, shaken in the presence of various amounts of bovine serum albumin. 75surface inactivation of bacterial viruses and of proteins much total protein was present in the shaking experiments. however, it is significant that the addition of peptone stabilized the pepsin, there being a loss of only 25 per cent of the pepsin activity on shaking for 24 hours at 33°c. in the presence of peptone. shaklee and meltzer made certain observations that agree closely with our own observations on the inactivation of bacteriophage by shaking, namely: 1. presence of glass beads did not accelerate shaking inactivation. 2. no inactivation of shaking full bottles, with or without glass beads. 3. results in paraffined bottles were same as in nonparaffined glass bottles. 4. results in sealed glass tubes were same as in rubberstoppered bottles. 5. inactivation rate increased with increasing acidity. 6. results were the same with air, co2, or h2 as the gas phase. macfarlane and knight (17) in 1941 studied the α toxin of cl. welchii which they demonstrated to be an enzyme, lecithinase. this enzyme when highly diluted was rapidly inactivated by bubbling air or nitrogen through the enzyme solution. they did not follow the course of the inactivation over a sufficient range of activities to make it possible to decide whether the kinetics are those of a zero order or a first order reaction. it has been observed repeatedly that physiologically active proteins on high dilution often show a spontaneous loss of activity which may be prevented by carrying out the dilution procedure in the presence of other proteins. in table iv is listed a number of examples of this phenomenon culled from the literature. included are the concentration at which the activity of the protein in question is measured and at which the inactivation is observed, together with the concentration of added protein which has been found to prevent this inactivation. it should be noted that in many cases the concentration given is the lowest concen tration of protein tested for protective effect since no titration of the protecting protein was made. it may also perhaps be significant that many of the enzyme activities are assayed in a warburg or similar manometric apparatus in which a vigorous shaking of a highly diluted enzyme preparation is part of the assay procedure. from table iv it may be noted that the physiologically active proteins with which this type of instability has been observed are all proteins in which the specific activity is measured at a final protein concentration of 4 γ/ml. or less. presumably proteins which must be assayed at higher concentrations do not show this phenomenon. also it may be noted that where the protecting protein has been assayed, the amount required has varied from 1 γ/ml. of gelatin in the case of short duration experiments with bacteriophage to 25 γ/ml. of table iv. a summary of data from the literature concerning physiologically active proteins which are unstable when highly diluted, including the concentration at which the protein is usually assayed and at which its lack of stability is noted, and the concentration of protective protein employed to stabilize it. physiologically active protein concentration at which protein is markedly unstable concentration of protective protein employed reference diptheria toxin in schick test 0.02 to 0.2 γ/mi. 1 mg./ml. serum albumin 15 25 γ/ml. gelatin 16 tetanus toxin m. l. d. is 3×10-4 γ protein 10 mg./ml. peptone* 18 α toxin of cl. welchii or lecim.l.d. is 0.2 to 0.5 y 5 mg./ml. gelatin* 19 thinase γ protein 10 mg. /ml. serum albumin* 20 botulinus toxin m.l.d. is 10-4 γ pro tein 2 mg./ml. gelatin* 21 invertase 2 to 4 γ/m1. gelatin 22 tyrosinase 1 γ/ml. 10 γ/m1. gelatin 13 ascorbic acid oxidase 1 γ/ml. 6 γ/m1. gelatin 23 carbonic anhydrase 1.6 γ/mi. 33 γ /ml. peptone 24 catalase <3 γ/ml. 25 desoxyribonuclease 3 γ/ml. 100 γ/ml. gelatin* 26 hexokinase 4 γ/ml. 6 γ/m1. insulin or 14 60 γ/nil. serum albumin α glycerophosphate dehydro genase 2.5 γ/ml. 1 mg./ml. gelatin* 27 bacteriophage 104 particles/ml. 1 to 10 γ/m1. gelatin * protective effect not titrated, concentration given is lowest one tested or only one given in reference cited. 76 mark h. adams gelatin needed to stabilize schick toxin for 6 months at room temperature. serum albumin when it has been compared with other proteins such as insulin or gelatin has been much less effective as a protecting agent. it is highly significant that proteins present in solutions of less than a few γ/ml. concentration are highly unstable, and that they are protected from inactivation by the presence in so lution of other proteins at a concentration higher than a few γ/ml. it has been shown that proteins will unfold at a gas-liquid interface to form a monomolecu lar film about 10å thick and covering an area of about 10 cm.2/γ of protein (28). this protein film is insoluble in water, and once formed on a quiet surface will effectively prevent more protein molecules of the same or different type from reaching the surface. on stirring or agitation of the surface however, the protein film will be folded upon itself to form an insoluble coagulum of denatured protein, leaving a fresh interface for the unfolding of additional protein. a physiologically active protein present at a concentration of 1 γ/ml. could then be completely spread and inactivated at a total interface corresponding to 10 cm.2/ml., an area readily obtainable with very little shaking. in the presence of a second protein, the rate of inactivation of the physiologically active protein would be a function of the relative concentrations of the two proteins, of their respective diffusion constants, and of the relative ease with which they unfold once they reach the surface. a protective protein present at a concentration of 10 γ/ml. should effectively exclude from the surface a protein of similar proper ties present at a concentration of 1 γ/ml. also if a physiologically active pro tein is present at a concentration of 10 γ/ml. or higher, the available surface will be saturated with an undetectably small fraction of this protein and hence no loss in activity will be noticed unless the shaking is more violent and prolonged than in the usual assay procedures in the warburg apparatus for instance. langmuir and schaefer (29) derived an equation for the diffusion of solute molecules to the surface, assuming only that every molecule which reached the surface stayed at the surface. this is a reasonable assumption for protein molecules if every molecule which reaches the surface unfolds into a film. the equation is where n is the amount of protein reaching 1 cm.2 of surface in time t, no is the concentration of protein per cm.’ and d is the diffusion constant of the protein. for egg albumin at 20°c. and a concentration of 100 γ/m1., the surface should be saturated in 1 second, whereas at a concentration of 5 γ/ml. it would take 26 minutes to saturate the surface. bull (30) measured the rate of fall of surface tension with time in solutions containing various concentrations of egg albumin. at albumin concentrations higher than 50 γ/m1., the major portion of the surface tension drop occurred in less than a minute, while at a concentration of 5 γ/ml. there was no noticeable drop for several minutes, then the major fall in surface tension occurred between 5 and 15 minutes, the surface tension ap proaching the equilibrium value in 30 minutes. at a concentration of egg albumin of 1 γ/m1., the albumin will reach the sur face in the quantity of 10-2 γ per cm.2 of surface in 100 seconds. if the surface to volume ratio is increased by shaking or bubbling it is obvious that a large proportion of the total protein would reach the surface in a fairly short time especially since langmuir and schaefer (29) point out that in stirred solutions the amount of solute reaching the surface is proportional to time rather than to the square root of time as it is in solutions at rest. failure to realize that the concentration of protein in solution was the critical factor in determining whether or not rapid spontaneous inactivation occurred on dilution, has resulted in the publication of probably erroneous conclusions. for instance traub, hollander, and friedemann (31) concluded that broth and serum “potentiated” the lethal action of tetanus toxin. they considered the possibility that the added broth or serum prevented the inactivation of tetanus toxin but discarded this explanation, largely on the grounds that if the low titer of toxin in saline were due to inactivation it would have to occur with unreason able rapidity, and because “potentiation” occurred in the case of titrations in small animals such as mice but not in large animals such as rabbits. exami nation of their data reveals that with toxin lot 1556 the lethal dose in rabbits is 0.1 ml. of a 1/10 dilution in either broth or saline; whereas in the guinea pig the lethal dose is 0.1 ml. of a 1/2000 dilution in saline, and 0.1 ml. of a 1/128,000 dilution in serum. it seems not unreasonable to assume that culture filtrates containing tetanus toxin when diluted beyond 1/2000 in saline contain less than the critical 1 γ/ml. of protein; especially since in the titrations recorded in their paper, the potentiating effect of broth decreased to almost nothing when the broth was diluted 1/1000 in saline. the observations of traub et al. on poten tiation can be satisfactorily explained on the assumption that tetanus toxin is markedly unstable when it is diluted beyond a limiting value for total protein concentration, and that dilution in the presence of small amounts of protein prevents this loss of activity. 77surface inactivation of bacterial viruses and of proteins in the present paper we have discussed the inactivation of viruses by shaking as a process quite analogous to the surface denaturation of proteins. we do not picture the inactivation of the virus as necessarily involving an unfolding of the entire virus particle into a protein layer 10å thick. in fact seastone has shown (32) that tobacco mosaic and vaccinia viruses do not readily unfold in the way that egg albumin does, but that never the less these viruses do form surface films. we merely suggest that once the virus reaches a gas-liquid interface it is subjected to such forces that it may very rapidly be deprived of the property of infectivity. this loss of infectivity may be prevented by saturating the gas-liquid interface with another protein, thereby denying the virus acess to the surface. in this respect the phenomenon is analogous to the surface denaturation of proteins. the prevention of surface denaturation is not the only protective role which may be played by proteins. sumner (33) has demonstrated that dilute solu tions of crystalline urease are rapidly inactivated by traces by heavy metals. this type of inactivation can be prevented by the addition of proteins, as well as by gum arabic, hydrogen sulfide, amino acids, and many other substances. urease can similarly be protected by proteins against inactivation by small amounts of oxidizing agents. proteins should play a similar role in the pro tection of viruses against the inactivating effects of heavy metals and oxidizing agents. it is probably a summation of these various protective mechanisms which is responsible for the generally recognized fact that viruses are more stable when diluted in serum or broth than when diluted in salt solutions or distilled water. summary 1. the seven bacterial viruses of the t group active against e. coli, are rapidly inactivated at gas-liquid interfaces. 2. the kinetics of this inactivation whether brought about by shaking or by bubbling with nitrogen are those of a first order reaction. 3. this inactivation may be prevented by the addition of enough protein to maintain the gas-liquid interface in a saturated condition. 4. the analogy between this phenomenon and the surface denaturation of proteins is pointed out and discussed. the author wishes to acknowledge his indebtedness to miss nancy j. collins for technical assistance. addendum. — since submitting this manuscript, we have found a paper by j. steinhardt (34) on “the stability of crystalline pepsin” in which the inactivation of pepsin by shaking is noted. at a ph of 6, temperature of 25°c., and pepsin con centration of about 30 to 60 micrograms per ml., pepsin is inactivated by shaking in accordance with the kinetics of a first order reaction. the velocity constant was independent of ph over the range of 4 to 6 but was somewhat dependent on the rate of shaking. the inactivated pepsin separated from solution as an insoluble suspension. references 1. campbell-renton, m. l., j. path. and bact., 1937, 45, 237. 2. grubb, t. g., miesse, m. l., and puetzer, b., j. bact., 1947, 53, 61. 3. mclimans, w. f., j. immunol., 1947, 56, 385. 4. shaklee, a. 0., and meltzer, s. j., am. j. physiol., 1909, 25, 81. 5. glenny, a. t., pope, c. g.,waddington, h., and wallace, v., j. path. and bad., 1925, 28, 471. 6. langmuir, i., and waugh, d. f., j. gen. physiol., 1938, 21, 745. 7. demerec, m., and fano, u., genetics, 1945, 30, 119. 8. delbriick, m., biol. rev., 1946, 21, 30. 9. hershey, a. d., kalmanson, g., and bronfenbrenner, j., j. immunol., 1943, 46, 267. 10. hershey, a. d., in cold spring harbor symposia on quantitative biology, cold spring harbor, long island biological association, 1946, 11, 67. 11. bull, h. b., in cold spring harbor symposia on quantitative biology, cold spring harbor, long island biological association, 1938, 6, 140. 12. gottschall, r., and bunney, w. e., j. immunol., 1938, 34,103. 13. adams, m. h., and nelson, j. m., j. am. chem. soc., 1938, 60, 2472. 14. berger, l., slein, m. w., colowick, s. p., and cori, c. f., j. gen. physiol., 1946, 29, 379. 15. edsall, g., and wyman, l., am. j. pub. health, 1944, 34, 365. 16. moloney, p. j., and taylor, e. m., tr. roy. soc. canada, section v, 1931, 25, 149. 17. macfarlane, m. g., and knight, b. c. j. g., biochem. j., 1941, 35, 884. 18. pillemer, l., j. immunol., 1946, 53, 237. 19. adams, m. h., j. immunol., 1947, 56, 323. 20. zamecnic, p. c., brewster, l. e., and lipmann, f., j. exp. med., 1947, 85, 381. 21. abrams, a., kegeles, g., and hottle, g. a., j. biol. chem., 1946, 164, 63. 78 mark h. adams 22. saul, e. l., and nelson, j. m., j. biol. chem., 1935, 111, 95. 23. lovett-janison, p. l., and nelson, j. m., j. am. chem. soc., 1940, 62, 1409. powers, w. h., lewis, s., and dawson, c. r., j. gen. physiol., 1944, 27, 167, 181. 24. scott, d. a., and mendive, j. r., j. biol. chem., 1941, 139, 661. 25. sumner, j. b., in advances in enzymology and related subjects of biochemistry, (f. f. nord, editor), new york, interscience publishers, inc., 1941, 1, 165. 26. mccarty, m., j. gen. physiol., 1945, 29, 123. 27. racker, e., personal communication. 28. gorter, e., in chemistry of amino acids and proteins, (c. l. a. schmidt, editor), baltimore, charles c. thomas, 1938, 428. 29. langmuir, i., and schaefer, v. j., j. am. chem. soc., 1937, 59, 2400. 30. bull, h. b., physical biochemistry, new york, john wiley and sons, inc., 1943, 199. 31. traub, f. b., hollander, a., and friedemann, u., j. bact., 1946, 52, 169. 32. seastone, c. v., j. gen. physiol., 1938, 21, 621. 33. sumner, j. b., and hand, d. b., j. biol. chem., 1928, 76, 149. 34. steinhardt, j., k. danske vidensk. selsk., mat.-fys. medd., 1937, 14, no. 11. substantia an international journal of the history of chemistry vol. 7, n. 1 – 2023 firenze university press superbugged pierandrea lo nostro equivalence of electromagnetic fluctuation and nuclear (yukawa) forces: the π0 meson, its mass and lifetime barry w. ninham1, iver brevik2, mathias boström3,4 the rate constant – reaction free energy dependence for the electron transfer reactions in solutions. the way to interpret the experimental data correctly lev i. krishtalik1,† training of future chemistry teachers by a historical / steam approach starting from the visit to an historical science museum valentina domenici a new response to wray and an attempt to widen the conversation eric scerri boxing partula: 25 years after stephen t. hyde surface inactivation of bacterial viruses and of proteins mark h. adams johann beckmann (1739-1811) and modern chemical technology juergen heinrich maar kuroda chika (1884-1968) – pioneer woman chemist in twentieth century japan yona siderer review of a cultural history of chemistry. peter j. t. morris and alan rocke, eds., bloomsbury academic: london, 2022 robert h. crabtree1, arthur greenberg2, seth c. rasmussen3 substantia. an international journal of the history of chemistry 4(2): 7-13, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-865 citation: l. schwartz, a. devin, f. bouillaud, m. henry (2020) entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics. substantia 4(2): 7-13. doi: 10.13128/ substantia-865 received: feb 27, 2020 revised: may 14, 2020 just accepted online: may 27, 2020 published: sep 12, 2020 copyright: © 2020 l. schwartz, a. devin, f. bouillaud, m. henry. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 1 assistance publique des hôpitaux de paris, paris, france 2 université bordeaux, ibgc, umr 5095, 33077 bordeaux cedex, france 3 institut cochin, inserm, cnrs, université de paris, paris, france 4 laboratoire de chimie moléculaire de l’etat solide, umr 7140 uds-cnrs, université de strasbourg, france *corresponding author: dr.laurentschwartz@gmail.com abstract. in nature, every physical process involving matter is ruled by the second law of thermodynamics (the total entropy of an isolated system can never decrease over time, and is constant if and only if all processes are reversible). the living cell being a material system should comply by releasing entropy either into the body or into the outside environment. in case of pathologies, entropy cannot be fully exported outside the body and stays inside the body either in the form of intracellular biomass, of extracellular waste products. we propose hereafter, a new way of classifying diseases by looking at the kind of entropy which cannot be easily excreted outside the body. in such a classification, inflammatory diseases play with entropy through increased heat, biomass synthesis (proliferation of lymphocytes and neutrophils) and secretion of pro-inflammatory proteins (waste products from the cell’s point of view). in the case of chronic inflammation, it induces mitochondrial impairment, owing to the increased osmotic pressure associated to hyper-osmolarity leading to cancer and degenerative diseases (dds). in the special case of degenerative diseases, cellular entropy is mostly released in the form of wastes, such as amyloid plaques or lewy’s bodies, and not as proliferating cells as in cancer. consequently, despite quite different symptoms, these two diseases are proposed to be janus-like twins, meaning that a remedy active against cancer, should also be active against various forms of dds. keywords: entropy, inflammation, cancer, extracellular pressure, classification of diseases. introduction life appeared on earth over 3,6 billions years ago. life is a robust phenomenon with similar concentrations of sodium, potassium and chloride in every living cell. moreover, similar lipoproteins constitute the membranes and the nucleic acids are always built with the same bases.1 metabolism corresponds to a set of life-sustaining reactions that are doomed to generate entropy. conversion of food into energy and heat (catabohttp://www.fupress.com/substantia http://www.fupress.com/substantia mailto:dr.laurentschwartz@gmail.com 8 laurent schwartz, anne devin, frédéric bouillaud, marc henry lism) generates a large entropy flux. heat is then released in the environment. entropy can also be transduced into the building blocks of life such as proteins, membranes or nucleic acids (anabolism) with elimination of wastes. in a previous paper,1 we have shown how it is possible to classify biological molecules into food and wastes, according to their intrinsic entropy content. from such a standpoint, secretion of hormones, growth factors or any other small molecules should be considered as generation of wastes, triggering a mandatory response of the cell. it follows that any kind of “waste” should be considered as a potential signaling molecule. this new positive interpretation of “wastes” is a key step allowing deep-rooting of life processes into thermodynamics. as previously stated, in order to be a spontaneous chemical process, metabolism should always lead to a global increase of entropy. this has allowed deriving a fundamental law of life1 stating that the sum of the entropy of the biomass created added to the entropy of the wastes secreted by the cell added to the heat released should be higher than the entropies of the ingested nutrients. if one considers the cell as being the inside, to comply with the second law of thermodynamics, the excess entropy has to be exported outside the original cell. the excess entropy can be exported either in the form of radiation (heat) or in the form of matter named in biology: biomass. biomass can be exported in the form of the extracellular secretion of molecules. the secreted molecules can be simple deposits of proteins such as amyloid plaques or can be released in the blood and absorbed by other cells. some of these molecules have special signaling properties and modify the activity of the target cell. hormones are secreted by the sexual organs and are secreted, first, in the extracellular space then in the blood stream. these hormones bind to specific receptors and are taken up by target cells whose genetic activity they modulate. similarly, lactate released by glial cells is secreted by the glial cells. lactate is uptaken by the adjacent neurons, enters the kreb’s cycle and is burnt releasing entropy outside the body in the form of heat. entropy of the primary cell can also be released in the form of a daughter cell. the division of the primary cell in two different entities decreases by two the entropy of the original cell. thus entropy can be released either in the form of heat or in the form of supplementary cells and/or cellular waste. heat will be released outside the body but waste and biomass will stay outside the original cell but inside the body. taking these premises for granted, it follows that diseases are also regulated by the second law of thermodynamics. accordingly, it appears that diseases are similar across species. for example, cancer,2 but also inflammation and degenerative diseases3 have been described across species in almost every metazoan. life expectancy, physiology and metabolism are deeply linked. this was demonstrated through allometry, the study of the relationship of body size to anatomy as first outlined by d’arcy thompson.4 thus, atanasov has evidenced a linear relationship between the total metabolic energy per life span and the body mass of 95 mammals5. similarly, levine correlates the life expectancy with the rest heart rate.6 today diseases are understood by the biologist as a cascade of events resulting in organ failure or in cancer. in deep contrast with biology, physics and thermodynamics do not look for detailed mechanisms, diseases being the mere consequences of fundamental laws. the goal of this paper is to better understand diseases by classification according to the second law of thermodynamics. hereafter, by focusing on clinical symptoms such as the ones described by the physician, it is possible deducing the physical laws at stake. as of today changes in the cycle of life are understood as the staightforward consequences of biological mishaps. they can also be described by the way the affected cells release entropy. most common diseases (if not all) and conditions can be understood by the modulation of entropy secreted by the cell. entropy synthesized by the cell can either be exported outside the body in the form of heat or be secreted outside the cell in the extracellular space or stay inside the cell. from the cell’s point of view the synthesis of another cell is a way to decrease the entropy by two. 1) conditions with heat release: circadian rhythm and ovulation during the circadian rhythm, there is an oscillation of the body temperature. temperature is higher in the evening and lower in the morning.7 at night a decrease in body temperature and cell proliferation as well as the release of hormones such as steroids are observed.7 at time of ovulation, there is an increase in body temperature. the sexual hormones are released by the ovaries as cholesterol derived, entropy rich, molecules. the hormone will bind to the receptor and interact with the genome. entropy will be released mostly in the form of heat. 2) conditions with biomass synthesis: childhood growth infancy and childhood are characterized by body growth. growth starts with fecundation and suddenly 9entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics stops shortly after puberty. body growth is harmonious and is partially controlled by mechanical constraints.8 attempt of classification of diseases as of today, diseases are classified by symptoms and affected sites. we will try to classify the pathologies by the typologies of entropy. in a few rare diseases, the amount of entropy can be increased or lowered. diseases with increased entropy synthesis: drug abuse, hyperthyroidism. during hyperthyroidism there is increased heart rate, weight loss, diarrhea, ner vousness, irritability, increased perspiration and hand tremors. all these symptoms are caused by increased metabolism secondary to enhanced hormone secretion. during drug abuse like cocaine or heroin, there is increased heart rate, respiration and euphoria. diseases with decreased entropy synthesis: hypothyroidism, hibernation, abuse of sedative on the contrary, during hypothyroidism, constipation, feeling of tiredness, depression and slow heart rate are observed. abuse of sedative may result in somnolence, amnesia and possibly dementia. diseases with increased biomass synthesis and waste secretion some benign tumors secrete proteins that are excreted in the blood stream. these proteins secreted by the cell could be considered as waste-signaling products. other proteins have no peculiar biological functions. benign prostatic adenoma secretes a glycoprotein: protein specific antigen (psa) which can be measured in the blood stream and used as a diagnostic tool. when present in the blood, this psa has no known biological function. other benign tumors can secrete hormones which can be toxic. best known are the thyroid adenoma. some of these benign tumors secrete high level of t3 and t4 thyroid hormones which can, in turn, be toxic to the heart or the brain (thyreotoxicosis). sclerosis, cancer and neurodegenerative diseases also experience increased biomass synthesis and waste products secretion. they will be discussed later in the paper as they are the direct consequence of inflammation. diseases with increased waste secretion and temperature: infection and cell death hyperthermia is present in most acute infections, but also during tissue necrosis (like cardiac infarct). during infection or cell death there is an increase secretion of pro-inflammatory proteins or crp. during cardiac infarct, multiple proteins present in the myocardial cells such as troponin are released in the blood stream. diseases with increased temperature and biomass synthesis we were not able to isolate any disease displaying increased temperature, biomass synthesis and no increased waste production. diseases with increased heat, biomass and waste synthesis: this is the signature of every kind of inflammatory disease. a) acute inflammation as stated by galen about two thousand years ago, inflammation can be stated as «tumor, dolor and calor». during the inflammatory process there is increased heat, synthesis of biomass and increased waste secretion. inflammation can be caused by a different set of circumstances such as heat, cold, chemical or bacterial and viral injuries. the name of the inflammatory diseases varies upon the affected organ (table 1 and 2). to name a few, hepatitis, crohn’s disease, ulcerative colitis, meningitis or bronchitis… some inflammatory diseases are confined to one organ (for example asthma or psoriasis) but may also extend to several organs (scleroderma, rheumatoid arthritis…). inf lammatory diseases have all in common an increase in extracellular osmolarity. in every inflammatory fluid there is increased osmotic pressure (9, 10, 11 and references therein). the increased osmotic pressure results from an increased oncotic (and osmotic) pressure because of the presence of abnormal level of proteins in the extracellular fluid. this is in line with the fact that the concentration of protein in the extracellular fluid is pathognomonic with inflammation.12 increased osmotic pressure results in cy tokine and lymphokine secretion as well as the immune response.13,14 the waste products secreted during the inflammatory process are well documented. they are the c-reac10 laurent schwartz, anne devin, frédéric bouillaud, marc henry tive proteins (crp) and numerous cytokines and lymphokines which can be assessed in the blood.10 this increased secretion of lymphokine and cytokine will result in vasodilatation, increased vascular permeability and leukocyte extravasation. the activation of the immune system caused by these lymphokines and cytokines results in phagocytosis and cell death. b) chronic inflammation  and its consequence: sclerosis chronic inflammation is secondary to the persistence of the inflammatory agent. for example, hepatitis because of persistent alcohol consumption or unrelenting auto immune disease will result into cirrhosis (sclerosis of the liver). similarly, persistent bronchitis secondary to excessive smoking will result in change in the table 1. entropy release by the affected cell. heat biomass waste circadian rhythm: day night yes no no yes no yes growth no yes no glands no no hormones infection yes no pro-inflammatory cytokines cell death (infarct) yes no yes (troponin) benign tumors no yes psa/ hormones degenerative diseases no yes (inflammation) yes (amyloid plaques, loewy’s body) cancer no cell multiplication yes (tumor markers) inflammation yes immune system activation yes (crp) ageing no yes (inflammation) yes (crp) table 2. classification of diseases. organ inflamatory disease sclerosis diseases resulting from metabolic rewiring cns encephalitis meningitis multiple sclerosis lateral amyotrophic sclerosis, schizophrenia glioma, neuroblastoma, alzheimer, parkinson, huntington’s disease cv myocarditis pericarditis atherosclerosis heart failure gi crohn’s, ulcerative colitis dysfunctional colonic syndrom adenocarcinoma, squamous cell carcinoma reproductive organs salpingitis, orchitis endometriosis infertility seminoma, adenocarcinoma liver hepatitis cirrhosis heart failure, hepatocarcinoma breast mastitis adenoma, fibroma adenocarcinoma skin erysepelas, sun burn lupus, psoriasis, sclerodermia basal cell carcinoma, melanoma lung flu, bronchitis chronic bronchitis emphysema pulmonary fibrosis squamous cell carcinoma, respiratory failure joints and bone arthristis arthrosis osteopenia sarcoma muscle myositis sclerosis sarcopenia, sarcoma eye inflammation glaucoma, cataract, near sightedness macular degeneration immune system infection cytopenia, myelofibrosis lymphoma, leukaemia general inflammation ageing ageing 11entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics lung architecture with lung fibrosis and/or emphysema15 (table 2). in the confined environment of the affected organ, the intracellular pressure must be equal to the pressure in the extracellular space. the increased multiplication of the epithelial cells will increase mechanical loads on the surrounding fibroblasts. this increased pressure results in the secretion of collagen by the fibroblasts.16 chronic inflammation has another consequence: the occurrence of cancer17 and neurodegenerative diseases.18 this may be in part because of the change in tissue architecture secondary to fibrosis.19 cancer cells usually originate from the epithelium on the lumen of an organ. in the case of sclerosis, the architecture is distorted resulting in loss of polarity of the epithelial cell. numerical models demonstrate that the loss of cell polarity alone, is enough to induce an invasive, fractal, dendritic pattern such as seen in cancer. this transition shows a sequence of morphologies in the following order as a function of loss of polarity: first an apparently normal but already diseased tissue, then metaplastic followed by a dysplastic tissue, and eventually carcinoma first, in situ, then invasive carcinoma.19 c) cancer and neurodegenerative diseases because of the warburg’s effect, cancer has a defective metabolism.20,21 the glucose is mostly degraded into lactic acid which is secreted, as a waste, in the extracellular space. lactic acid is a nutrient for the surrounding benign cells (inflammatory cells, fibroblast or vascular cells).22 lactic acid is an energy rich molecule. its release by the cancer cell results in a drastic drop in energy yield1. a molecule of glucose fully burnt by a normal cell releases 36 molecule of atp. the same molecule of atp releases only 2 molecules of atp in a cancer cell. the energy yield is divided by at least 10 times resulting in a decrease in heat export outside the cancer cell1. to compensate this decrease energy yield, there is increase uptake of glucose such as seen in pet scan.1 cancer could be viewed as the consequence of increased osmotic or oncotic pressure. recently hamraz23 has demonstrated that increased osmotic pressure such as seen in inflammation is enough to induce the warbug’s effect. the addition to the cell culture medium of mannitol or other osmotic agents induce an increase in glucose uptake and an inhibition of the mitochondrial respiration. moreover, treatments aiming at restoring the normal metabolic profile inhibit tumor growth.24 degenerative diseases are also induced by inflammation. for example, alzheimer’s disease can be caused by repeated trauma over a long period.25 in alzheimer’ s disease the waste products stay in the vicinity of the neurons to form the amyloid plaques. upon examination under the microscope there is a coexistence of intense apoptosis of neurons and proliferation of the inflammatory and the glial cells (increased biomass synthesis). in cancer and in degenerative diseases there is metabolic rewiring with decreased atp synthesis.20,21,26,27 the main difference between cancer and degenerative diseases is the intracellular ph. in cancer cells the intracellular ph is alkaline.20,21 there is decrease synthesis of co2 and carbonic acid resulting in the alkalinisation of the intracellular medium. alkaline ph is responsible of unrelenting cellular growth.28 to the difference of cancer cells, the main nutrient of neurons is not glucose but lactic acid.29 accumulation of lactic acid results in an acidic ph and cell death.30 conclusion modern medicine is characterized by a hyper-specialization with the consequence of classifying the various diseases of the body into unrelated categories. for instance, the rheumatologist takes care of the bones and joints while the pulmonologist considers only the lung. such a wide diversification of medicine goes in the opposite direction of physics which eagerly looks for unification. this is a very strange situation as both medicine and physics play with systems made of matter. it follows that if the race for unification observed in physics is a wise goal, the same goal of unification should apply to medicine. in this paper, we proposed a very first step towards unification and classification of diseases. the red lead of our classification was the entropy concept, the single known concept ruling time evolution for every kind of material system. we do hope that the usefulness of the proposed classification will be demonstrated in a very near future. we are sincerely convinced that deep-rooting biology into physics, as done here, should not only be useful for healing diseases but also crucial for the survival of humanity. this is because our modern civilization is currently overwhelmed by wastes with the consequence of heavy pollution of air, water and soils. but, as explained here, wastes management should be synonymous of entropy management. accumulation of wastes, i.e. entropy that is not released in the form of heat into the intergalactic space, means accumulated disorders with only one possible outcome: death. this applies to a human body, as well as to the whole earth. time is then ripe enough to put entropy management at the very heart of any kind of living system. 12 laurent schwartz, anne devin, frédéric bouillaud, marc henry references 1. henry, m., schwartz, l. (2019). entropy export as the driving force of evolution. substantia, 29-56. 2. aktipis, c. a., boddy, a. m., jansen, g., hibner, u., hochberg, m. e., maley, c. c., wilkinson, g. s. (2015). cancer across the tree of life: cooperation and cheating in multicellularity. philosophical transactions of the royal society b: biological sciences, 370(1673), 20140219. 3. schwartz, l., lafitte, o., da veiga moreira, j. (2018). toward a reasoned classification of diseases using physico-chemical based phenotypes. frontiers in physiology, 9, 94. 4. d›arcy, w. t. (1952). on growth and form cambridge university press. 5. atanasov, a. t. (2007). the linear allometric relationship between total metabolic energy per life span and body mass of mammals. biosystems, 90(1), 224-233. 6. levine, h. j. (1997). rest heart rate and life expectancy. journal of the american college of cardiology, 30(4), 1104-1106. 7. refinetti, r., menaker, m. (1992). the circadian rhythm of body temperature. physiology and behavior, 51(3), 613-637. 8. wertz, x., schoëvaërt, d., maitournam, h., chassignet, p., schwartz, l. (2006). the effect of hormones on bone growth is mediated through mechanical stress. comptes rendus biologies, 329(2), 79-85. 9. tubiana, m., attie, e., flamant, r., gérard-marchant, r., hayat, m. (1971). prognostic factors in 454 cases of hodgkin›s disease. cancer research, 31(11), 18011810. 10. arai, k. i., lee, f., miyajima, a., miyatake, s., arai, n., yokota, t. (1990). cytokines: coordinators of immune and inflammatory responses. annual review of biochemistry, 59(1), 783-836. 11. schwartz, l., guais, a., pooya, m., abolhassani, m. (2009). is inflammation a consequence of extracellular hyperosmolarity?. journal of inflammation, 6(1), 21. 12. fleck, a. (1989). clinical and nutritional aspects of changes in acute-phase proteins during inflammation. proceedings of the nutrition society, 48(3), 347354. 13. binger, k. j., gebhardt, m., heinig, m., rintisch, c., schroeder, a., neuhofer, w.,voelkl, j. (2015). high salt reduces the activation of il-4–and il-13–stimulated macrophages. the journal of clinical investigation, 125(11), 4223-4238. 14. schwartz, l., abolhassani, m., pooya, m., steyaert, j. m., wertz, x., israël, m., chaumet-riffaud, p. (2008). hyperosmotic stress contributes to mouse colonic inflammation through the methylation of protein phosphatase 2a. american journal of physiology-gastrointestinal and liver physiology, 295(5), g934-g941. 15. schwartz, l., balosso, j., baillet, f., brun, b., amman, j. p., sasco, a. j. (2002). cancer: the role of extracellular disease. medical hypotheses, 58(4), 340-346. 16. bishop, j. e., laurent, g. j. (1995). collagen turnover and its regulation in the normal and hypertrophying heart. european heart journal, 16(suppl c), 38-44. 17. coussens, l. m., werb, z. (2002). inflammation and cancer. nature, 420(6917), 860. 18. holmes, c., cunningham, c., zotova, e., woolford, j., dean, c., kerr, s. u., perry, v. h. (2009). systemic inflammation and disease progression in alzheimer disease. neurology, 73(10), 768-774 19. fleury, v., schwartz, l. (2003). numerical investigation of the effect of loss of cellular polarity on cancer invasiveness and geometry. fractals, 11(04), 397-414. 20. schwartz, l., t supuran, c., o alfarouk, k. (2017). the warburg effect and the hallmarks of cancer. anti-cancer agents in medicinal chemistry (formerly current medicinal chemistry-anti-cancer agents), 17(2), 164-170. 21. seyfried, t. n. (2015). cancer as a mitochondrial metabolic disease. frontiers in cell and developmental biology, 3, 43. 22. warburg, o. (1956). on the origin of cancer cells. science, 123(3191), 309-314. 23. hamraz, m., abolhassani, r., andriamihaja, m., ransy, c., lenoir, v., schwartz, l., bouillaud, f. (2019). hypertonic external medium represses cellular respiration and promotes warburg/crabtree effect. the faseb journal. 24. schwartz, l., guais, a., israël, m., junod, b., steyaert, j. m., crespi, e., abolhassani, m. (2013). tumor regression with a combination of drugs interfering with the tumor metabolism: efficacy of hydroxycitrate, lipoic acid and capsaicin. investigational new drugs, 31(2), 256-264. 25. nogueira, m. l., hamraz, m., abolhassani, m., bigan, e., lafitte, o., steyaert, j. m., schwartz, l. (2018). mechanical stress increases brain amyloid β, tau, and α-synuclein concentrations in wild-type mice. alzheimer›s & dementia, 14(4), 444-453. 26. gibson, g. e., sheu, k. f., blass, j. p. (1998). abnormalities of mitochondrial enzymes in alzheimer disease. journal of neural transmission, 105(8-9), 855870. 27. kösel, s., hofhaus, g., maassen, a., vieregge, p.,graeber, m. b. (1999). role of mitochondria in 13entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics parkinson disease. biological chemistry, 380(7-8), 865-870. 28. shrode, l. d., tapper, h., grinstein, s. (1997). role of intracellular ph in proliferation, transformation, and apoptosis. journal of bioenergetics and biomembranes, 29(4), 393-399. 29. smith, d., pernet, a., hallett, w. a., bingham, e., marsden, p. k., amiel, s. a. (2003). lactate: a preferred fuel for human brain metabolism in vivo. journal of cerebral blood flow & metabolism, 23(6), 658664. 30. ruffin, v. a., salameh, a. i., boron, w. f., parker, m. d. (2014). intracellular ph regulation by acid-base transporters in mammalian neurons. frontiers in physiology, 5, 43. substantia an international journal of the history of chemistry vol. 4, n. 2 2020 firenze university press some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy, ph.d., j.d. …and all the world a dream: memory outlining the mysterious temperature-dependency of crystallization of water, a.k.a. the mpemba effect evangelina uskoković1, theo uskoković1, victoria wu1,2, vuk uskoković1,3,* the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries aleksander sztejnberg communicating science: a modern event antonio di meo sub-covid-809 1 citation: a. karpas, d. bainbridge, s. ash (2020) considerations for treating corona virus (sars-cov-2) infection with passive immunotherapy. substantia 4(1) suppl. 1: 924. doi: 10.13128/substantia-924 received: may 01, 2020 revised: may 03, 2020 just accepted online: may 04, 2020 published: may 04, 2020 copyright: © 2020 a. karpas, d. bainbridge, s. ash. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative com mons attribution license, which per mits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia feature article considerations for treating corona virus (sars-cov-2) infection with passive immunotherapy abraham karpas,1* douglas bainbridge,2 stephen ash3 1 formerly assistant director of research, department of haematology, cambridge university clinical school 2 emeritus consultant in immunology, royal london hospital 3 associate dean and emeritus professor of infectious diseases, auc school of medicine *corresponding author: karpasa@hotmail.com for many disease-causing viruses in man such as the polio viruses, measles, rubella and mumps, vaccination in childhood gives protection and confers lifelong immunity. other viruses such as influenza continuously mutate and need new vaccinations as fresh strains emerge each year. among relatively recently discovered disease-causing viruses some are not easily transmissible, like the retro-oncovirus htlv/atlv. this was found to cause adult t-cell leukaemia (atl) in japan 1 and subsequently in some people of african origin;2 and although not easily transmissible, it is present in a significant percentage of the population in some villages in south-west japan. most transmission has been found to occur shortly after birth through breastfeeding, by htlv-infected cells in the milk of infected mothers. thus testing pregnant women for htlv and stopping positive mothers from breast-feeding their newborn babies has effectively reduced the spread of the virus in japan significantly.3 in contrast, despite enormous efforts and the expenditure of vast sums over the past 35 years, the primate retro-lentiviruses hiv-1 and its minor variant hiv-2, which are responsible for the globally important disease of aids, have resisted all attempts to develop an effective vaccine. the reason: hiv is a retrovirus. through its reverse transcriptase hiv makes a dna copy of its rna genome; and this, integrating into the dna of infected cells, does not kill them but maintains an infectious state througout life.2 during the 80s and into the 90s there were no effective anti-hiv drugs, but early on we were able to establish that although both aids patients and healthy hiv-infected individuals tested positive for anti-hiv antibodies, aids patients had a far lower level of antibodies and more significantly, were devoid of antibodies that were capable of neutralising the virus. we were therefore encouraged to initiate a trial of passive immunotherapy in cambridge in 19854 and later in london. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 924, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-924 a. karpas, d. bainbridge, s. ash 2 plasma from healthy hiv-positive individuals who still had a high number of cd4+ t-cells (which we found correlated with high levels of neutralising antibody) was collected by plasmapheresis and given by infusion to patients with advanced aids. 5-6 right from the beginning, infusion of the plasma improved their well-being. subsequent double-blind controlled studies from the usa7 and france8 confirmed the long-term benefit. as far as the donors were concerned, we had only a limited number, which meant many were required to donate repeatedly at monthly or bi-monthly intervals in order to provide long-term treatment for the aids patients. plasmapheresis avoids depleting red and white blood cells, but we were concerned whether repeated donation might have other detrimental effects on the donors. in the event detailed study of their various lymphocyte populations showed no ill-effects.9 over several years passive immunotherapy for aids patients was given both at the royal london hospital by db and at ealing general hospital by sa. we learned from this experience that collection of plasma by plasmapheresis machine is readily achievable on a substantial scale, even if somewhat labourintensive. several reports have appeared of successful passive immunotherapy (pit) following a single infusion after ebola infections in africa;10 but here it was of restricted scope, because most ebola-infected individuals die of the infection, greatly limiting the supply of blood/plasma available to use in treatment. in the absence of generally effective drugs to treat corona-infected individuals, or the prospect of a vaccine in the near future, is there a place for pit in order to save life and relieve some of the enormous amount of medical and nursing time that it takes to care for the sick? the corona viruses are transient rna viruses; once an infected individual recovers he or she becomes virus-free and immune. one could expect that in sars-covid-19 also, infected individuals who recover will have developed some form of protective immunity. very little is yet known about its development, when and for how long it might last, and though it is very likely to involve virus-neutralising antibodies, to what extent it might depend on the appearance of such antibodies. however in a recent report 10 very advanced corona patients were treated with a single 200 ml dose of plasma obtained from individuals recovered from the infection. there was impressive clinical improvement.11 we have been told of a similar outcome from passive immunotherapy in germany.12 there are some ten times more individuals recovered from infection than deaths. this argues that the majority are likely to be making or to have made effective antibody responses to the virus. it would then not be unreasonable to ask those among the younger recovered individuals to donate blood. since blood can be stored for a month medical centres could collect such donations and create a bank of blood/plasma (presumed hyperimmune), to be provided firstly to the severely ill patients as a blood or plasma transfusion with a matching blood group, and thereafter to newly infected individuals developing clinical symptoms. hopefully the majority of the sick patients receiving pit would recover and those in the early phase of the disease would recover more quickly. caveats: passive immunotherapy will not necessarily help: (1) if the donated plasma contains little antibody. in plasma collected some time after recovery the donor’s antibodies could have waned too far, due to their normal half-life; and this would be particularly important if the normal immune response to sars-covid19 is in any case usually short-lived. we are just beginning to know something of the dynamics of the response 13; (2) if the donor’s antibodies are not effective in neutralising the virus. detection of antibodies to the coronavirus is critical to the epidemiology of the infection but will say little about the immunity of the individual unless the antibody test is a functional one, measuring anti-viral activity. (3) if a donor’s recovery occurs principally by mechanisms other than neutralising antibody, probably cellular responses mediated through, for example, tand nk-like lymphocyte responses. at this stage of our knowledge of covid-19 our guide to the use of pit and the choice of donors can only be empirical – if one person’s plasma does not work, try somebody else’s. this consideration argues that it is of major importance to create, and expand the availability of, reliable tests for virusneutralising activity of anti-corona antibodies. then one will be able to decide with confidence which plasmas will work and which won’t; and, thus, who can donate and when.14 references 1. y. hinuma, k. nagata, m. hanaoka, m nakai, t matsumoto, k i kinoshita, s shirakawa, i miyoshi, proc. nat. acad. sci. usa, 1981,78, 6476-6480 2. a. karpas, a. biol.rev., 2004, 79, 911-933. 3. y. hinuma, personal communication. 4. a karpas, f hill, m youle, v cullen, j gray, n byron, f hayhoe, m tenant-flowers, l howard, d gilgen, proc. nat. acad. sci. usa 1988, 85, 9234-9237 5. a karpas, i k hewlett, f hill, j gray, n byron, d gilgen, v bally, j k oates, b gazzard, j e epstein, proc. nat. acad. sci. usa, 1990, 87, 7613-7617 6. g. blick, w. f. scott, s.w. crook, s. buchanan, t. garton, u. hopkins, a. m. vadaboncoeur, j. doolittle, l. a. bulcraig, p. greiger-zanlungo, a. karpas, biotherapy, 1998, 11, 7-14 7. j. levy, t. youvan, m.l. lee, blood, 1994, 84, 2130-2135 considerations for treating corona virus (sars-cov-2) infection with passive immunotherapy 3 8. d. vittecoq, s. chevret, l. morand-joubert, f. heshmati, f. audat, m. bary, t. dusautoir, a. bismuth, j. p. viard, f. barré-sinoussi, proc. nat. acad. sci. usa, 1995, 92, 11951199 9. d. r. bainbridge, m. w. lowdell, i. m. hannet, k. w. strauss, a. karpas. phil.trans. roy. soc. lond. b, 1997, 352, 763-770. 10. f. sahrhr, r. ansumana.,t.a. massaquoi, b.r.idriss, f.r.sesay, j.m. lamin, s. baker, s. nicol, b. conton, w. johnson, o.t. abiri, o. kargbo, p. kamara, a. goba, j.b. russell, s.m. gevao. j. infection, 2017, 74, 302-309 11. k. duan, b. liu, c. li, h. zhang, t. yu, j. qu, m. zhou, l. chen, s. meng, y. hu, c. peng, m. yuan, j. huang, z. wang, j. yu, x. gao, d. wang, x. yu, l. li, j. zhang, x. wu, b. li,y. xu, w. chen, y. peng, y. hu, l. lin, x. liu, s. huang, z. zhou, l. zhang, y. wang, z. zhang, k. deng, z. xia, q. gong, w. zhang, x. zheng, y. liu, h. yang, d. zhou, d. yu, j. hou, z. shi, s. chen, z. chen, x. zhang, x.yang, proc. nat. acad. sci. usa, 2020, 117 (17), 94909496 12. z. lichtenstein, personal communication. 13. k.k.to, o.t.tsang, w.leung, a.r.tam, t.wu, d.c.lung, c.c.yip, j.cai, j.m.chan, t.s.chik, d.p.lau, c.y.choi, l.chen, w.chan, k.chan, j.d.ip, a.c.ng, r.w.poon, c.luo, v.c.cheng, j.f.chan, i.f.hung, z.chen, h.chen, k.yuen, lancet infect. dis., 2020, https://doi.org/10.1016/s1473-3099(20)30196-1 14. interestingly, a recent italian scheme by blood transfusion services in the localities of lombardy most severely affected by covid-19 proposes to screen all regular normal blood donations and test for viral neutralising antibody on the grounds that most individuals in the area will have had to face the virus. those who did not succumb will have either been unusually lucky enough to escape entirely, or will have been able to resist infection and, as asymptomatics, are probably more strongly immune than individuals recovering from the disease. by screening and selecting plasma with proven neutralising activity it is hoped to build up a bank of hyperimmune plasma for use in emergency. details of the scheme and the test methods are not known to the authors. sub-covid-807 1 citation: d. bergandi, f. galangauquérat, h. lelièvre (2020) coronavirus and the heterogenesis of ends: underpinning the ecological and health catastrophe is a political crisis. substantia 4(1) suppl. 1: 911. doi: 10.13128/substantia-911 received: apr 17, 2020 revised: apr 21, 2020 just accepted online: apr 22, 2020 published: apr 22, 2020 copyright: © 2020 d. bergandi, f. galangau-quérat, h. lelièvre. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia feature article coronavirus and the heterogenesis of ends: underpinning the ecological and health catastrophe is a political crisis donato bergandi,1* fabienne galangau-quérat,2 hervé lelièvre3 1 dept. origines et évolution, muséum national d’histoire naturelle, paris, france 2 dept. homme et environnement, muséum national d’histoire naturelle, paris, france 3 dept. histoire de la terre, muséum national d’histoire naturelle, paris, france *corresponding author: donato.bergandi@mnhn.fr abstract. the coronavirus catastrophe that we are experiencing is first of all the result of an ecological catastrophe, but its underlying fundamental cause is the political crisis that our democracies are living. the sustainable development model is a smokescreen that will lead not to making deepgoing changes to the economic paradigm but to continuing with business as usual. the betrayal of the elites, both political and economic, supported by a system that is no longer democratic, has exposed the population to this type of sanitary problem. a deep transformation of our political system is urgently needed. the people must take part in a true democracy, a direct democracy, that initiates a new democratic revolution capable of countering the sinister interests of the elites, of the caste in power. keywords. coronavirus, sustainable development, direct democracy, ecological catastrophe, health catastrophe, political crisis. 1. is development sustainable? the dystopic ecological catastrophe that we are living is preparing us for other catastrophes that are coming. everyone on the planet knows the name of this sanitary catastrophe: coronavirus and covid-19, referring to “severe acute respiratory syndrome coronavirus 2 (sars-cov-2)” and the disease it causes. unfortunately, far fewer people are aware that the proximate cause of this sanitary catastrophe is ecological. and, assuming the virus is not a military product or bioweapon, its animal source will be confirmed, sooner or later. it seems likely that this will be a bat or a pangolin. by the way, in 2017 the us military had already predicted, with a certain clairvoyance, that a respiratory disease was the “enemy to fight”. numerous international treaties, declarations and conferences have affirmed ad nauseam that the erosion of biodiversity must be stopped – essentially because humanity depends on this. the stockholm declaration (the united nations conference on the human environment) affirmed back in 1972 that, “of all things in the world, people are the most precious (§ 5).” substantia. an international journal of the history of chemistry 4(1) suppl. 1: 911, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-911 d. bergandi, f. galangau-quérat, h. lelièvre 2 the brundtland report, the report of the world commission on environment and development: our common future (1987) underlines, yet again, the instrumental value of biodiversity: “53. the diversity of species is necessary for the normal functioning of ecosystems and the biosphere as a whole. the genetic material in wild species contributes billions of dollars yearly to the world economy in the form of improved crop species, new drugs and medicines, and raw materials for industry. but utility aside, there are also moral, ethical, cultural, aesthetic, and purely scientific reasons for conserving wild beings.” and the united nations conference on environment and development (unced, 1992) adopted the rio declaration on environment and development, which affirms that: “human beings are at the centre of concerns for sustainable development” (principle 1). ten years later, at the world summit on sustainable development (wssd, 2002), it is once again stated: “24. human activities are having an increasing impact on the integrity of ecosystems that provide essential resources and services for human well-being and economic activities.” in 2012, the united nations conference on sustainable development rio+20 reaffirmed the importance of the universal declaration of human rights, in particular that: “6. we recognise that people are at the centre of sustainable development, and in this regard, we strive for a world that is just, equitable and inclusive, and we commit to work together to promote sustained and inclusive economic growth, social development and environmental protection and thereby to benefit all.”. at the un sustainable development summit (2015), transforming our world: 2030 agenda for sustainable development proposed: “9. we envisage a world … [o]ne in which development and the application of technology are climate-sensitive, respect biodiversity and are resilient. one in which humanity lives in harmony with nature and in which wildlife and other living species are protected.” given all this, it is hardly surprising to see that a large majority of major corporations declare that they support the sustainable development paradigm and its implementation! yet the dreamworld of the international treaties is going against reality, which is shown not least of all by the results up to now… meagre at best. some recent analyses consider that humanity is even creating the conditions for a “biological annihilation” (ceballos, ehrlich and dirzo 2017). already back in the 19th century george perkins marsh (1801–1882), the environmentalist, enlightened catastrophist forward-thinking in his encyclopaedic work, noting the irrational behaviour of humankind and warning of a “war against nature” (1864). in short, sustainable development is a misinterpreted humanism (ehrenfeld 1978) – anthropocentric, resourcist, and economicist (the intrusion of economics into everything else). it is a kind of smokescreen that fails to make any substantive change in the economic model while permitting the continuation of business as usual. even if formally it stigmatises the erosion of biodiversity, in reality, productivism goes unquestioned. in an oxymoronic way, between “development” and “protection”, when development takes place, it annihilates the protection of biodiversity (bergandi, 2018). sustainable development is one clear filiation of the “conservationism” of gifford pinchot (1865–1946), an american forester and politician, the first head of the united states forest service and the 28th governor of pennsylvania. pinchot along with john muir (1838-1914) and george perkins marsh are the people who started the first forms of environmentalism. in his philosophical manifesto (1910), gifford pinchot supported the development of natural resources, which are equated to capital that you need to increase and save, together with the prevention of waste. the third principle of this manifesto declared that all other interests were to be subordinated to the “public good”. for pinchot, nature was nothing more than a resource to be exploited. with john muir, pinchot started a war against the irrationalism of woodworking industrialists, but at one point the differences between their visions of the world emerged into broad daylight. after the great earthquake of san francisco in 1906, the city’s mayor wanted to bring in water, using the nearby resources of yosemite national park. john muir stood in defence of hetch hetchy valley in the national park, but in the end pinchot and the mayor won the battle, allowing the utilisation of part of the park. this definitively confirmed pinchot's dastardly pact with economic interest groups, and the separation between the two souls of the environmentalist movement. to give a more concrete idea of the divergences between the two, we can quote pinchot’s account of an episode that clearly reveals two universes of sensibility and action, at antipodes. pinchot tells us, during a journey with muir and the members of a commission whose purpose was to identify some remarkable places: “while the others drove through the woods to a ‘scenic point’ and back again, with john muir i spent an unforgettable day on the rim of the prodigious chasm, letting it soak in. i remember that at first we mistook for rocks the waves of the rapids in mud-laden colorado, a mile below us. and when we came across a tarantula he wouldn’t let me kill it. he said it had as much right there as we did” (pinchot, 1946, p. 103). but why speak about sustainable development and the environment in a paper that is supposed to be about coronavirus and the health catastrophe we're experiencing? why? because the proximate cause of this pandemic is the ecological catastrophe that we are living; because it is determined in turn by the political crisis that our democracies are undergoing – and that is the primary and fundamental cause. coronavirus and the heterogenesis of ends: underpinning the ecological and health catastrophe is a political crisis 3 2. the coronavirus pandemic reveals the political crisis and incompetence of our governments? even fewer people are conscious that the coronavirus catastrophe results, in turn, from a political crisis that at least in the democratic countries has lasted for three or four decades and has concretised itself in the “tacit” alliance of the political and economic castes “against” the (human) populations and the other species and environments that allow humanity to survive. the objective alliance of the political and economic elites is not only draining the wealth of countries, but regardless of the political programme on display, they have “married” on the basis of liberal and neoliberal programmes. for the record, the neoliberal programmes propose an extreme form of liberal objectives, policies that 1) promote the market economy, 2) oppose increased public intervention in the economy; 3) support the deregulation of markets; and 4) encourage the gradual disappearance of the public sector in favour of the private sector. these programmes started a policy of austerity, which was vehicled and imposed by the european commission along with all the multilateral organisations at many levels. among other objectives, they targeted health care systems. hospitals followed new laws (that put entrepreneurs in charge of constituting the stocks of protective materials) and were headed by the “cautious” figure of a so-called manager-director (a political figure: in general, someone not competent in the domain where the decision-maker works). the hospitals were not able to maintain stocks of protective materials in the event of a pandemic (masks, gloves, respirators, etc.). in such circumstances, the negligence and incompetence of the caste governing us was dramatically revealed. not only have they left us tragically unprepared for the onset of the virus, because of the lack of protective material that the hospitals could not constitute or reconstitute, in an effort to save money, as was demanded by the european commission. but the governments have also used only confinement as a strategy to respond to the coronavirus attack, and systematically lied, particularly the french government, denying the clear evidence and insulting our intelligence: “masks are useless”, they solemnly intoned, whereas taiwan and south korea have jugulated the disease using masks, mass testing and confinement. in contrast to oriental populations like in taiwan and south korea, the occidentals privileged more “passive” strategies like confinement, as in italy, spain and france, among others. then there’s the laissez-faire of the english and americans, who initially privileged a misunderstood darwinian principle (“survival of the fittest”), “herd immunity”, which develops when a sufficient percentage of a community become immune to an infectious disease such that it stops the disease from spreading. the result: boris johnson, prime minister of the united kingdom, caught covid-19, and the americans are now top of the class in terms of disease spread and mortality. but the reality of “facts” (thousands of dead), including the lack of protective equipment, led them to row back to confinement. the us has now surpassed even the italians, who at least faced the difficulty of a population who were older than average. in contrast, taiwan and south korea, and to a lesser degree germany, have chosen a more “active” strategy, doing mass “testing” of the population at large. not only were our governments unprepared for the pandemic’s arrival, but their cacophony of rules that changed quasi-daily showed how they have clumsily sought to hide the lack of tests, masks, gloves and other protective material. it is this lack that has largely dictated the strategies of our governments. earlier, the masks were said to be useless, except for caregivers. later, they became useful for everyone. the endless changes in policy seek to conceal that there is not enough protective equipment, including the masks and above all the tests. c’est la vie… we must change the model of civilisation. as ecocentric environmental ethics proposes (muir, 1916; leopold, 1949; taylor, 1986; callicott, 1989; callicott, 2013; bergandi, 2013; bergandi and blandin 2012), we must recognise that nature has intrinsic value; nature is not there for “our interest” or “our good”. nature is not there as a “means” to our ends; its value depends solely on the intrinsic properties of the (natural) entity, not on our evaluation of it. these are different ways of saying that nature must be respected, just as humans are respected, simply because … they are human (universal declaration of human rights). we must go beyond a hierarchicalistic worldview in which “persons are more valuable than things” (geisler, 1971). animals and even plant species must cease to be “things”, and become “persons” (hall, 2011). but sometimes history deals us unforeseen cards … sometimes, the heterogenesis of ends (vico [1744] 1948; wundt 1886) becomes an actor in human life. that is, “an intentional action can produce unintentional consequences”. in other words, “the destroyers of nature” (of the ecosystems), that is, the productivistic model of our economy and the “uninhibited” entrepreneurs who disrupt the ecosystems and “exploit” them with ever-increasing efficiency “to reap more money”, thereby create the conditions for the “passage” of the virus, adapted to secular ecosystems, in the human species – because their original environment is being destroyed (by human economic activities). a word that we will hear more frequently in coming years is “zoonosis”, that is, “an infectious disease caused by bacteria, viruses, or parasites that spread from non-human animals (usually vertebrates) to humans” (see quammen, 2012, 2014). between 60% and 75% of infectious diseases in humans originate in the bodies of other animals. d. bergandi, f. galangau-quérat, h. lelièvre 4 we must change our dietary model structured on meat (badariotti, f. et al., “eviter les prochaines crises en changeant de modèle alimentaire”, libération, 30 march 2020). we must stop eating meat, not only because a large majority of pandemic diseases originate in animals, i.e. because this is dangerous (zoonosis), but also for ethical reasons, to enlarge the “moral community” to the point of including non-human animals. eating meat will then be considered as committing an act of “cannibalism”. long ago, in 1894, henry stephens salt (1851–1939) proposed an enlargement of the moral community based on the extension of the idea of “humanity” to all other animals. we are long overdue. 3. representative democracy is not democracy representative democracy cannot be considered as being a true democracy. in athens, the source of our democracies, democracy was direct and not indirect (osborne, 2010). this means that all the people participate in the elaboration of the laws, and not only an elite of professional decision-makers. paradoxically, in representative democracy, at the very moment voting arose, the sovereignty of the voter was irrevocably denied (rousseau, [1762] 2002). in reality, our so-called democratic societies are pseudo-democracies, which act, in reality, like oligarchies. the caste in power can be predominantly political (when the decision-makers belong to the class of professional politicians) or economic (when the entrepreneurs descend into politics), or both. when the political mandate comes from the party and not from the people, we should more correctly speak of a partitocracy, and not of democracy, i.e. a party, an (political) elite that has taken power. the totalitarian states (for example, russia and china) do not find themselves in a better position. only the procedures for the selection of the elite change, but always one or another elite/caste is in power (pareto, 1935; mosca, 1896; mills, 2000). furthermore, the transnational lobbies can and must be thwarted with a system of direct democracy that increases the ecological “sense of place”, because people take greater care of the place where they live than disembodied elites that program an economic activity from the other side of the planet ever will. finally, we can speak of human sinister interests. sinister interests (or perverse interests) are interests that run counter to the interests of the community (bentham, 1815; mill, 1865). in this case, by community is meant the entire community of humans-animals-plants. but in reality, today only a small part of humanity is responsible: the politicaleconomic caste. in evaluating the consequences of its acts, when evaluating the human-nature relationship, these acts are ascribed to the whole of humanity, whereas a large part of the “criminal” activity (pollution, mass murder in the “concentration camps” around the globe that are the slaughterhouses, etc.) are the responsibility of the large corporations and the politicians (men and women) who allow them to act. so we need a direct democracy that finally allows the people to “make” history and not to suffer it. a direct democracy characterised by some new institutions and rules, for example: mandates must be “imperative”, in the sense that “delegates” cannot change the programme during the time in which they are elected; the choice of the candidate must be by “lot”, and “officials” cannot present themselves more than two (non-consecutive) times in their lifetimes; the function of the candidate at the election is a “service” and not a “profession”; their salary is the average salary of the population; blank ballots must be counted, and candidates cannot present themself another consecutive time if the blanks constitute a majority; a citizens' initiative referendum must allow the people to propose a law directly; a repealing referendum can rescind a law; a delegate may be recalled from their elective function if they fail to respect their mandate. the coronavirus catastrophe confronts us with the opportunity and the necessity to start a new civilisation, a new society structured around (a utopian) democratic revolution (bergandi, 2018, 2017). a society where the people and not some pre-selected elite are the “motor” of democracy. a society where the people are not a subject, submissive to the goodwill of an elite, but themselves actively create the conditions of development of the society. references badariotti, f. et al. 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(2017). the ecological catastrophe: the political-economic caste as the origin and cause of environmental destruction and the pre-announced democratic disaster. in: the role of integrity in the governance of the commons. edited by l. westra, g., janice, g., gottwald, f.-t. (eds.) (pp. 179–189). switzerland, cham: springer. bergandi, d. (2018). a utopian democratic revolution to overcome flawed democracy and ecological catastrophe. in: ecological integrity, law and governance. edited by l. westra, k. bosselmann, janice g., k. gwiazdon. oxon and new york: routledge,taylor & francis group. bergandi d. and p. blandin (2012). de la protection de la nature au développement durable: genèse d'un oxymore éthique et politique. revue d’histoire des sciences, 65, (1), 103-142. doi:10.3917/rhs.651.0103 bergin, t.g. & t.g. fisch (translators) (1948). the new science of giambattista vico. london: cornell university press. callicott, j.b. 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([1762] 2002). the social contract and the first and second discourses. edited and with an introduction by susan dunn; with essays by may, g., r.n. bellah, d. bromwich and c.c. o’brien. new haven/london: yale university press. salt, h.s. (1894). animals' rights considered in relation to social progress: with a bibliographical appendix. new york and london:macmillan & co. taylor, p.w. 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(1886). ethik. stuttgart: enke. doi: https://doi.org/10.36253/substantia-959 received: jun 02, 2020 revised: aug 25, 2020 just accepted online: aug 26, 2020 published: mar 01, 2021 https://doi.org/10.36253/substantia-959 substantia. an international journal of the history of chemistry 1(2): 75-93, 2017 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-28 citation: j.(h.) lyklema (2017) interfacial potentials: measuring the immeasurable? substantia 1(2): 75-93. doi: 10.13128/substantia-28 copyright: © 2017 j.(h.) lyklema. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declared that no competing interests exist. feature article interfacial potentials: measuring the immeasurable? johannes (hans) lyklema physical chemistry and soft matter, wageningen university, stippeneng 4, 6708 we wageningen, the netherlands. e-mail: hans.lyklema@wur.nl abstract. the scientific background of measuring and interpreting potentials at interfaces is discussed in a historical setting. various types of potentials have to be distinguished. some are measurable, others not. static and dynamic aspects will be covered and, as applications, the interaction between electric double layers and the slip process in electrokinetics will be considered. in several cases it is expedient to interpret results in terms of charges rather than in terms of potentials. keywords. interfacial potential, surface potential, zeta potential, colloid interaction, electrokinetic slip. 1. introduction – zum unterschied von δψ, das wenigstens prinzipiell immer messbar ist, sind absolutwerte von δφ bis heute noch nicht zugänglich1 – ... the value of the potential of a single electrode is not amenable to direct experimental determination2 – we measured the electrosurface potential electrophoretically3 – the keyword “surface potential” occurred in a recent paper on modern afm – like techniques4 – surface potentials can be evaluated by second harmonic generation and similar non-linear optical techniques5 these five statements all relate to the measuring of surface potentials, but that seems to be the sole binding element between them. for the rest these quotes differ in many respects, even regarding the definitions and even with respect to the basic tenet whether or not these potentials are experimentally accessible at all. it sounds as a cacophony. do all quotes refer to the same quantity? it is noted that between the oldest and the more recent of these quotes almost a century elapsed. one would wonder if over such a long time span the improvement of the experimental techniques and the development of better defined systems would have contributed so much to our physical insight that quantities that could not be measured long ago are now within reach of our technical achievements. or, are there certain generic laws of principle precluding that? 76 johannes (hans) lyklema the present paper intends to help solving this basic question and considers how our understanding developed historically. prior to that it is necessary to agree on the meanings of basic concepts, their terminology and definitions. in trying that, it is realized that in certain scientific circles group-specific nomenclature is used, that does not necessarily match with that of other teams. some people state that they have studied potentials whereas it appears that they are dealing with something else. one typical illustration is the notion of pair potential, routinely encountered in simulation science. this dubbing is a generally adopted habit, which everybody involved in this field appears to understand. nevertheless, it is basically incorrect because the quantity under discussion is an energy and not a potential. routinely, interaction potentials are expressed in units of kt or ev, that is in units of energy whereas potentials ought to be expressed in volts. another illustration is that of measuring socalled electrokinetic or zeta potentials (ζ), a daily routine for every colloid scientist. the procedure is straightforward: one measures, say the electrophoretic mobility, of a colloidal particle and interprets it in terms of, say the helmholtz-smoluchovski law, which immediately produces ζ in volts. this looks like a direct potential measurement. however, in reality this is not what happened; an applied electric field can lead to the displacement of free charges, not to the displacement of potentials. so, in the derivation of the helmholtz-smoluchovski equation some conversion of a charge into a potential must have taken place. not everybody is conscious of that. we shall come back to this in sec. 6. in the present paper we shall reserve the notion of “potential” to the electric potential, expressing it in volts. with this in mind, it is realized that, before dealing with the issue of measuring interfacial electric potentials, it is mandatory to agree on terms and definitions. to that end we shall heed the recommendations made over the past decennia by the international union of pure and applied chemistry (iupac). this organization is appreciated for its attempts to recommend internationally accepted rules for definitions of standards and nomenclature. the obvious reason is to “decacaphone” the literature from incorrect statements. some of its recommendations refer directly to the measurement and interpretation of interfacial potentials.2,6-10 and below we have heeded them maximally. in this way it is hoped that at least the text is understandable for a wide readership. this might be particularly useful when addressing the older literature, stemming from before the time that such recommendations were available. 2. early 20th century there are good reasons for starting the historical considerations with the first part of the 20th century. the centuries before that saw the development of rigorous theories for electric fields, some of these resulting in field vector equations like gauss’ and stokes’ theorems and general phenomenological laws derived from these, such as poisson’s law for the relation between charges and potentials and smoluchovski’s laws for electrophoretic mobilities and streaming potentials. these theories did not address the basic question what the origin is of the spontaneous charging of colloidally dispersed particles; it was just accepted that (surface) charges were apparently present and that hence the particles would be the seats of an accompanying (surface) potential. the advent of understanding these origins, together with the development of options for their measurements take us to the beginning of the 20th century, and to the central theme of the present study. what was the state of understanding electrified interfaces around ca. 1920? in that year theory of diffuse double layers was already available, thanks to the pioneering work of gouy11 and chapman.12 their model is based on the poisson-boltzmann (pb) distribution for the countercharge. underlying the pb theory are two assumptions. in the first place, ions are considered point charges, i.e. as volume-less charges. as a result, the theory is generic: dependent on the valences of the ions but not on their sizes. the second, mostly tacit, assumption is that the potential occurring in the poisson equation is the same as that in the boltzmann equation. this is not necessarily correct: the former is an average potential whereas the latter is a potential of the mean force. this distinction is rather esoteric, and considered in the domain of statistical thermodynamics. if needed we shall return to this issue later; but let it for the moment be accepted that the difference between the two types of potential are negligible when the potentials are low and when the potentials are very high.13 notwithstanding these quantitative limitations, the gouy-chapman (gc) theory was an important leap forward because it was one of the first relevant attempts to quantify some surface potential. however, with respect to our main question about the origin and measurability of the interfacial potential, gc theory does not help. the reason was that this theory was developed as an attempt to interpret electrocapillary curves, in the measurement of which the surface potential across a mercury–water interface is simply applied externally. this leaves unanswered why isolate colloidal particles can also carry a charge, let alone what their surface potentials are. 77interfacial potentials: measuring the immeasurable? apart from this central issue in the present context, let us recall another piece of wisdom of the gc model. it predicted the screening of charges to scale with the square root of the electrolyte concentration, a law observed often thereafter, but which was difficult to understand otherwise. still another feature of diffuse double layer theory was the prediction of expulsion of electrolyte by a charged diffuse double layer, a phenomenon that was independently measured and called the donnan effect.14 the basic phenomenon is the electrostatic expulsion of co-ions, which is a purely electrostatic phenomenon. however, phenomenologically it is observed as the expulsion of electroneutral electrolyte by charged surfaces, colloids and polyelectrolytes. the insight that this phenomenon found its basic origin in diffuse double layer theory grew only several decades later. what was not yet known around 1920 included (what is now known as) stern theory for non-diffuse layers15 and the debye-hückel theory16 for the activity of strong electrolytes. nowadays it is common practice to consider as a first approximation the aqueous side of double layers as consisting of two parts, an inner part, or stern layer and an outer diffuse part, or gouy layer. the inner part is the seat of ion specificity, meaning that the sizes and non-electric binding gibbs energies are different between different ionic species. the impact of stern theory is in recognizing that ions can also adsorb without electric attraction and hence spontaneously create or reduce an electric potential difference. the idea itself of a molecular condensor was familiar around 1920 though, thanks to the work of helmholtz in the 19th century. such layers were mostly called helmholtz double layers and considered as an alternative for diffuse double layers, rather than as an addendum to them. however, around 1920 this essential step in the spontaneous creation of interfacial potentials by specific adsorption in the stern, or helmholtz part of a double layer was not yet so clear. 3. freundlich with this in mind it is historically interesting to read the pertinent literature from that period. a very rich source for obtaining this information is found in the standard books by herbert freundlich (1890-1941), one of the most versatile and all-round colloid scientists of that era. he wrote a sequel of books under the main (german) title kapillarchemie, where the subtitle eine darstellung der chemie der kolloide und verwandter gebiete explained what he understood by the title and subtitle. nowadays one would call it “colloid and related science”. later, also english translations appeared under the name capillary chemistry. for the present purpose we shall now consider the second print of 1922.17 the problem that freundlich was facing was matching the interfacial electrochemistry of large flat surfaces and colloidally dispersed systems. are there common principles in the creation of electric potentials at the surfaces of dispersed particles and macroscopic amounts of surface? it is particularly interesting to read how freundlich interprets disparate measurements, some even for ill-defined systems. in chapter 6 of that book he starts with comparing measurements on nernst-type potentials for macroscopic surfaces with those obtained electrokinetically for colloids.17 at that time it was by no means clear to which extent measured potentials would be identical under identical ambient conditions. translated into modern symbols, his question was by how much ψo (the electric potential at the phase boundary) and the electrokinetic potential ζ differ. at that time for colloids no other independent experimental evidence (like titrations) was available. it was even not yet clear whether there was a difference of principle between transversal and tangential potentials jumps. of course, potentials being scalars, their absolute values are only determined by the position in the double layer, hence this question can be translated into that of the spatial variation of ψ and ζ along a surface. given the scarcity of experimental evidence, freundlich approached this problem by investigating how the addition of certain substances affected ψo and ζ. of the many reported facts involved he states that, following nernst, oxide and carbon electrodes may be considered as hydrogen or oxygen electrodes. with a bit of surprise he also refers to glass electrodes in the sense that their ”potential jumps” with respect to electrolyte solutions behave as if the glass were a swollen gel layer containing a fixed concentration of h+ and/or ohions. he reports that the ζ potential for this system, in agreement with earlier measurements, is very sensitive to the presence of low concentrations of additives. for example, h+ ions can reduce ζ without changing its negative sign, whereas alcl3 and crystal violet do invert the sign of ζ already at concentrations as low as 1-2 and 50 μm, respectively, without having any substantial influence on the nernst potential, ψo. the only effect alcl3 had on ψo was changing the spontaneous acidity of the solution, because it is a weak electrolyte. if this effect was suppressed by carrying out the experiment in an (acetate) buffer, the influence on ψo disappeared completely. freundlich had to conclude that ψo and ζ are different quantities. supposed that ζ would be measurable that would not yet mean that ψo would be measurable as well. 78 johannes (hans) lyklema his qualitative explanation for this difference is essentially the same as our present idea, namely the existence of a slip plane, or a thin slip range. his argument was that upon tangential shear of the water the forces involved are not strong enough to move the water by shearing it at the solid-liquid border. rather a thin adhering layer remains stagnant. freundlich also realized that the very fact that electrokinetic phenomena could be observed at all must mean that the double layer must have a certain thickness, supporting the existence of a diffuse part. he quoted smoluchovski who already in 1914, two years before the publication of gouy theory, arrived at the same conclusion.18 figure 1 sketches these ideas. qualitatively, the shapes of the two curves do not differ that much from our present insights. curve 1 applies to simple double layers, curve 2 for systems with overcharging (as it is nowadays called). the most striking difference with (good) recent pictures is the absence of anything quantitative. there are no ideas about the potential inside the solid, it is not clear why there is a bending point in curve 1 and whether the position of that point coincides with the minimum in curve 2. that minimum (x = d) is apparently the distance from the surface where specific adsorption takes place. however, freundlich identifies the potentials at that distance as ζ-potentials and this suggests that the plane of specific counterion adsorption is assumed to coincide with the boundary between tangentially moving and tangentially stagnant water, nowadays called the slip plane. no argument for this is given; at any rate the identity between the two is not obvious: the distance from the solid surface where bound counterions are situated is determined by short range forces and water structure, whereas the position of the slip plane is determined by the tangential motion of many water molecules. there is no a priori reason for their identity. we shall return to that in sec. 6. 3.1 application of gauss’s law one feature underlying the sketches of figure 1 that freundlich did not further elaborate, although its basic physics were perfectly well known to him, was the inference on the various surface charges that can be drawn, using gauss’s vector theorem (also known as ostrogadski’s or green’s theorem). it is a general theorem for a vector field e in a volume v, bound by a closed area a of arbitrary shape. the space (triple) integral over the divergence of e equals the surface (double) integral over the inner product e·n where n is the unit vector normal to the surface and directed outward. the mathematics becomes easy if applied to a flat interface, say for a charged sphere with radius r→∞ then e·n simply becomes the field strength e = -dψ/dx normal to the surface. e corresponds to the slope of the curves drawn in figure 1, integrated over the entire surface a. the triple integral over div·e can be written as div·(gradψ), mostly written as ∇2ψ which, according to poisson’s law equals -ρ/(εε0) where ρ is the local space charge density, ε is the local relative dielectric permittivity and εo is the dielectric permittivity of free space. this triple integral leads to the total charge in the volume v. in our specific case with no space charges in the solid interior, this charge is the surface charge σ multiplied by the area a. combining all of this leads for one-dimensional situations to the simple expression ψ σ ε ε =− d dx 0 (1) eq. (1) is generally valid: at any position in the double layer can we make a cross-section where the part on the left and the part on the right have equal, but opposite charges, given by this equation. for instance, just to the right of the x = 0 plane the slope for curve 2 is steeper than that for curve 1, which means that in the second case the surface charge is higher. phenomenologically this trend is correct: stronger screening leads to higher surface charge at given surface potential. however, curve 2 cannot be correct, because it predicts a maximum in figure 1. sketch of the potential distribution ψ(x) in a flat double layer after smoluchovski (1914) and freundlich (1922). the border between the solid (hatched) and the liquid is situated at x = 0. discussion in the text. 79interfacial potentials: measuring the immeasurable? the countercharge around the slip plane, which is physically unrealistic. moreover, it would also predict a zero charge coinciding with the slip plane for which also no physical reason can be given. far from the surface all charges are zero, which is obviously correct. although all of this must have been known around 1920, little of such argumentation is encountered in freundlich’s book. in his attempts to get hold of the charging principles he collected many data on the electrokinetic properties of a great variety of systems. regrettably, in that respect he was not very successful, mainly because he did not have sufficiently well-defined systems at his disposal. 4. lange and koenig about ten years after freundlich, lange and koenig wrote a completely different approach, in which they considered electrical potentials thermodynamically.1 not surprisingly, this approach also involved the question of the measurability of surface potentials. the paper is “deutschgründlich” written, with the excuse that they could not present it in even more detail because of lack of space. the lange–koenig paper helped the understanding of interfacial potentials in at least two respects: distinguishing between measurable and immeasurable potentials and the introduction of the notion “potentialdetermining ions”. their most significant contribution is the insight that there is in principle no way for measuring the (electric) potential difference between two adjacent, chemically different phases. let us by way of paradigm consider the potential of a solid (particle or electrode) with respect to the solution in which it is imbedded. measuring electric potential differences, say between locations a (the solution) and b (the solid), requires bringing a unit charge from a to b and determining the electric work per unit charge involved. however, when points a and b are located in chemically different condensed phases, the transport of the charge carrier also involves chemical work. for colloids the charge carriers are ions, which have finite sizes and hence they also interact non-electrostatically with their surroundings. the gibbs energy of that interaction is non-zero even if the phases are uncharged. this chemical contribution cannot unambiguously be separated from the electrical one. hence, absolute values for the potentials in condensed phases are in principle immeasurable. it is historically interesting that, in the first quote of the present paper lange and koenig take a less absolute stance; they just state that separation is as yet not possible, apparently they believed in technological solutions for all scientific problems. nowadays the insight is that the impossibility of measuring absolute potentials in condensed phases is intrinsically coupled to the impossibility of measuring thermodynamic potentials of single ionic species. in no way can the energy and entropy of, say a mole of protons be determined because no process can be envisaged to prepare and transport that mole without simultaneously also transporting the same amount of anions. otherwise stated, potential differences between different condensed phases are inoperable. lange and koenig realized that. given this impossibility, the problem was, and is, how to cope with that in practice. generally, for such issues two ways are open: avoiding it or subjecting it to penetrating theoretical analyses, two options that are not very handy in daily practice. lange and koenig came with two suggestions, the introduction of the notion of potential-determining (pd) ions and distinguishing various types of potentials, some measurable, others immeasurable. 4.1 charge-determining ions as to the former, although absolute potential differences between adjacent condensed phases of different compositions are inoperable, changes therein are often accessible, in particular when the material under study can function as an electrode in a galvanic cell. the simplest example is a cell containing the electrode under study in an electrolyte solution and a reference electrode. the cell potential ecell is in principle measurable and consists of the sum of the sought electrode-solution potential difference δψ and the reference electrodesolution potential jump δψref. with such a cell one can measure changes in the cell potential as a function of changes in the composition of the solution, like changes of the electrolyte concentration or changes in ph. if the reference electrode is insensitive to those changes, as is the case for a suitable calomel electrode, the change in cell potential comes only on the account of δψ. so, although δψ is inoperable, dδψ is relatively well accessible. it was already known to freundlich that in many systems dδψ shows nernst behavior, according to which dδψ is proportional to the log of certain electrolyte concentrations to the amount of 58 mv per decade of the concentration of that ion. in many cases that electrolyte contains the proton, h+ and this rule is the basis for applying glass electrodes for the ph measurements. the thermodynamic background of nernst’s law led to the introduction of the notion of potential determining ions by lange and koenig. 80 johannes (hans) lyklema according to lange and koenig, potential-determining ions are thought as being present in both of the adjacent phases in sufficient amount as to be thermodynamically significant. then, an electrochemical potential can be assigned to the activity of the proton in the solution and the solid and their equalization leads to the establishment of the dδψ(dph) relation. mathematically, electrochemical potentials consist of three terms, for pd ion i generally written as μoi + zi fψ + rt ln ai.we are interested in the variation upon changes in ai. in the solution this leads to zifdψ(solution) + rtdln ai and in the solid to zifdψ(solid). equating these two changes in chemical potentials, writing ψo for ψ(solid) – ψ(solution), leads to zifdψ0 = rtdlnai (2) which predicts dψo/(rt dlnai) to be constant and equal to rt/(zf) per decade of the activity of z-valent pd ions. at room temperature this amounts to 58 mv/z per factor 10 in the activity of i, i.e. the observed nernst behavior. the above derivation gives some insight into the assumptions that had to be made in order to arrive at nernst’s law. the observed applicability of this law for a given solid-liquid interface is a justification in retrospect for the applicability of the model assumptions for that particular system. as to the measurement it has to be added that measuring relative activity changes of single ionic species (dlnai) is not possible; only activity changes of neutral electrolytes or electrolyte mixtures are measurable. to overcome this problem in practice, the procedure is working in swamping electrolyte that has the anion in common with the acid that produces the protons to be measured. for example, if the activity of protons must be measured in hcl, the measurement is carried out in swamping kcl, of which the concentration is fixed so that in dlna(h+) + dlna(cl-) the second term vanishes. calibration is necessary to ensure that this situation is attained. if it is not sufficiently controlled the trend is that lower than 58 mv is found for the nernst slope. it may be added that “swamping” means “large as compared to the concentration of i”, implying that not necessarily high salt concentrations are needed. the notion of potential-determining ions has been generally accepted and used for several decades. nowadays these ions are rather dubbed “charge-determining (cd) ions”, just because of the reason that the absolute value of the potential in a chemically different phase cannot be determined, whereas charges can be very well measured. below we shall adhere to the term “chargedetermining”. the conclusion of this part is intuitively sound: nernst behavior means that upon transport of one ion from one condensed phase to the adjacent requires an energy of kt per unit charge zie and as energy = charge x potential its quotient is a unit potential kt/(zie) = 58/z mv. ions for which this is in practice measurable are charge-determining ions. 4.2 the χ-potential as to the fundamental impossibility of determining absolute values of the potential difference lange and koenig proposed to distinguish between different types of potentials, each with its own symbol: the galvani (φ), volta (ψ), real (α) and χ-potentials. ref. 1 is replete with relationships between these potentials, and with the thermodynamic and electrochemical potentials in solutions. galvani potentials are the (immeasurable) inner potentials, in our example the potentials in the heart of a colloid particle or electrode with respect to the bulk of the solution. volta potentials are measured in the solution so close to the outside of the condensed phase that the effect of the nature of that phase is not felt, but close enough to pick up any longer range effect of the electric charge on the phase. by this definition volta potentials are in principle measurable, but the information they carry is much less interesting than that of galvani potentials. real potentials refer to a specific ionic species, say i, and they are combinations of μi and the volta potential. we shall not use this quantity but note that it is identical to the electronic work function for extracting an electron from a metal (or ion from a non-metal) and take it to infinity. lange and koenig distinguished between galvani and volta potentials through the different symbols φ and ψ, respectively. hence the distinction between dφ and dψ in the first quote of this paper.1 we shall not use this distinction and only use ψ for the electric potential. where needed, we shall provide enough information on the way in which the non-electric contributions are sequestered. the last suggestion by lange and koenig, was the introduction of the notion of χ-potential, also recommended by iupac. we shall call it the interfacial potential jump. the potential jump in going from a to b we shall denote as χab. in the lange-koenig nomenclature χ = φ – ψ. the quantity χ is immeasurable but has a clear physical meaning: it accounts for the potential jump at the interface between two phases caused by the local polarization of the molecules at the interface, orientation of water dipoles at the interface, polarization of the surface layer of the solid; in short, all contributions to the potential difference between uncharged adjacent phases, that is: at the point of zero charge. the reason why the introduction of χ is so handy, even though it is immeas81interfacial potentials: measuring the immeasurable? urable, is that all contributions grouped into it are shortrange, a few molecular diameters at most, whereas electric double layers have thicknesses of the order of κ-1 which can be orders of magnitude larger. for colloids an additional argument is that surfaces are rarely perfectly flat. roughness of the order of a few molecular layers can rarely be avoided. an additional consideration for using χ is that the properties of diffuse double layers that are relevant for the daily practice of colloid science (say for the interpretation of colloid stability and electrokinetics) can to a large extent be understood by considering the diffuse part only. however, assuming that the surface charge σo has been measured, the very relevant and interesting issue is which fraction of the countercharge (-σo) finds itself in the region very close to the surface, that is: in the stern layer, and which fraction remains for the diffuse part. this is one of the most recurrent question of double layer science anyway, because the stern layer coincides with the layer determining χ. one typical illustration of employing this insight is in establishing the point of zero charge (p.z.c.) for amphoteric colloids, that is the point where the total amount of positive charge on the surface is the same as that for negative charge. this is a measurable quantity. for oxides it is a specific value of the ph, to be indicated as pho. tables of pho values can be found in the literature.19 the point is that these points are not identical to the corresponding points of zero potential. the difference between the two zero points is just χ, the elusive unknown. “elusive” is a disputable notion. nowadays χ is a popular topic of investigation because many modern techniques do shed some light on it, if not in the literary sense of optical measurements but also by molecular simulation, statistical mechanics, colloid chemical, and even thermodynamic tools. as to the last one, thermodynamics are phenomenological, hence cannot tell something about molecular organization but do teach us how to obtain surface excess entropies, which in themselves are challenging quantities. for example, for the surface of pure water the surface excess entropy, (that is: the entropy of the layer that is responsible for the χ-potential) has been obtained from the temperature dependence of the surface tension.19 in this way the difference between the surface energy and the surface tension could be quantified. on the other hand, guggenheim refused to discuss χ at all because of its immeasurability.20,21 however, if one is not from the very onset at war with model assumptions or approximating experiments, some information about the χ potential of water (χw) can, and has been, obtained. it stems from different sides, like making assumptions for single ionic activities for some untypical electrolytes, comparisons between different electrolytes or of ionic gibbs energies in different media and simulations, jokingly called “experiments”. all these “partial” or approximate analyses led to roughly the same order of magnitude of a few tens of mv positive.19 the positive sign means that water is positive with respect to water vapor: the negative sides of the superficial water molecules (the oxygens) are on the average pointing outward. recent studies of the present author seem to indicate that that is also the case for water in contact with condensed apolar media like mercury or silver iodide. the conclusion is that the immeasurability of potential jumps between condensed phases is basically upheld, but that there are interesting attempts of measuring the immeasurable. see also briefly sec. 8.2. figure 2 illustrates how lange and koenig visualized the χ-potential at the boundary between a condensed phase (left) and an aqueous solution (right). the picture is extremely simplified. as to χw the authors are thinking of a monolayer of oriented parallel water dipoles, this is a very unrealistic model because forcing all those molecules into parallel positions is entropically very improbable. in fact, the numbers for χ and ψo that the authors substitute by way of illustration are about a factor of 10 higher than we now know and the peak at x = d cannot be that sharp. the figure also contains a diffuse double layer part that in their text is not discussed; apparently they envisage that the creation of a double layer by adsorption of charge-determining ions simply comes additively, a view that is mostly adhered to till today. figure 2. sketch of the potential jump at a solid-liquid phase boundary as caused by the χ-potential. modified after ref. 1, their figure 1. discussion in the text. 82 johannes (hans) lyklema in the last pages of their longish (190 pages) paper lange and koenig discuss electrokinetic phenomena, emphasizing the complicated inf luences on the ζ-potential by various electrolytes. in their figure 75 they place the slip plane at the boundary between the stern layer and the diffuse part, subsuming the χ-potential in the potential of the solid, which is not further discussed, leaving a variety of issues about double layer potentials and charges for their successors., as we shall do in sec.6). the conclusion of this section is that essentially the impossibility of measuring the absolute value of the potential difference between adjacent condensed phases of different chemical composition is translated into the problem of evaluating the corresponding χ-potential. for many purposes working with charges rather than with potentials is preferable. 5. silver iodide, the lucky strike of the dutch school in the years before world war ii one of the major challenges in the domain of interfacial potentials and charges was finding systems for which potentials and/ or charges could be assessed, if not measured, both for macroscopic surfaces and for colloids. for macroscopic surfaces, in electrochemical cells double layer capacitances could at that time be measured with great precision for mercury electrodes, using wheatstone bridge techniques. for colloids, stability against coagulation and electrokinetic potentials could be measured for several systems with reasonable confidence. however, from mercury it is virtually impossible to make colloidal sols and for colloids it was impossible to determine the surface potential or surface charge. otherwise stated, systems for which surface potentials/charges and electrokinetic potentials/charges were both measurable did not (yet) exist. it appeared that silver iodide was an excellent candidate to fill that gap. colloidal studies with the agi system have been carried out over more than a century with a major contribution of the dutch school of kruyt, overbeek and offspring. as a model substance for both interfacial electrochemistry and colloidal studies, agi has many attractive features. the material is chemically nearly inert, its solubility in water is very low (solubility product about 10-16 at room temperature), stable sols (many years without perceptible coagulation) can be made of it and the material is very hydrophobic (contact angles for water droplets around 120°). agi sols are really hydrophobic sols; their stability is exclusively determined by the interaction of overlapping electric double layers. changes in the surface charge of dispersed agi can be measured by titration with ki or agno3: changes in ψ° obey nernst’s law, with silver and iodide ions charge-determining, i.e. changes in the surface charge σ° can be measured as a function of changes in pag or pi. this last fact means that dσ° as a function of dψ° is measurable, so that the differential capacitance c = dσ°/dψ° can be established. for mercury, the primary measurable is also the differential capacitance, hence properties of very disparate materials in different states (macroscopic surfaces versus finely dispersed) can be compared with each other, a most rewarding exercise! studying all of that does not require information on the absolute values of ψ°. hence, they can be carried out without being thwarted by its principally immeasurability. given the fact that the point of zero potential cannot be established, one usually refers the point of zero charge for which good experimental methods are available (the common intersection point in figure 5, see below). the development of all that insight took several decades and in the following sections some typical achievements in line with the present theme will be considered. for historical reasons it be noted that kruyt et al. were not the only investigators of the agi system. for example, older, but more primitive titrations have been carried out by lange and berger22 and for agbr by lottermoser and petersen.23 one of the first, but still rather primitive, titration of agi with different ag salts was conducted by de bruyn.24 5.1 interaction at constant potential or at constant charge? during the second world war colloid science got a tremendous boost by the publication of the dlvo theory for the stability of hydrophobic colloids.25,26 the abbreviation stands for deryagin, landau, verwey and overbeek. the history is well known: the russians wrote their paper in 1941 in a russian journal,25 which because of the war conditions did not make it to the west, whereas the dutch couple elaborated the theory during the war and then wrote an extensive monography on the matter.26 it was only after the war that it became clear that the two theories were identical as to the main principles stability is determined by a balance of van der waals attraction and double layer repulsion. the qualitative insight that the stability of hydrophobic colloids had its origin in the interaction between electric double layers was more or less generally accepted in 1940 but the quantifications, some of them by respectable scientists like levine and langmuir, were not successful: after all, it is not so obvious to prove that interaction between 83interfacial potentials: measuring the immeasurable? two double layers that as a whole are electroneutral are repulsive at any distance between the surfaces. in addition, it must be realized that, say around 1935, the role of attractive van de waals forces was not yet quantitatively established, so that some investigators even considered electric double layers, that, although electroneutral as a whole, could nevertheless be electrically repulsive over some part of the interaction, but attractive over another range. now we know that attractive van der waals forces are quantitatively comparable to electrostatic double layer repulsion forces. however, this part of the story, interesting for its own sake, does not belong to the present theme. let us state that at the start of the second world war the main problem was to develop a quantitative theory for the electric double layer repulsion that was strong enough to protect the particles against coagulation by van der waals attraction. needless to state that this repulsion is sensitive to the potential and charge distribution during overlap, which brings us back to the theme of this paper. a crucial proof of the pudding was to explain the observed extreme sensitivity of the stability of hydrophobic sols to the valence of the counterion (the socalled schulze-hardy rule). both dl and vo were able to do so quantitatively and the two couples arrived at the same law. as to the way of presentation, in particular the motivation of some decisions, the vo book is far more useful than the dl paper: the former gives a careful consideration of all the decisions taken, whereas in dl theory sometimes hand-waving arguments are used. for example, when v and o make a conscientious distinction between double layers at high potential and those at high charge, dl only speak of “strong double layers”. in connection with the present theme, we are now dealing with double layers resulting from free ionic charges, which may reside in the diffuse or stern part; the fact that there exists something like a χ-potential does not (yet) play a role, but may show up later. as to the elaboration of the electric interaction, dl and vo have in common that both compute the charge and potential distribution between two approaching particles at any distance d using a charging process. in this way, not the energy but the gibbs energy of interaction is obtained, which also contains the entropic contribution. the interaction gibbs energy is then found as the isothermal-reversible work to adjust the charge and potential distribution upon increasing the overlap between the two surfaces. in passing, it is a pity that this procedure seems to be forgotten when interaction between more complicated colloids has to be considered, for example upon the interaction of oppositely charged polyelectrolytes, as in the formation of complex coacervates. overlap of (diffuse) double layers implies that the two original ψ(d) curves will change. the sum of the two contributions at given distance d is not necessarily additive. for the elaboration of the differential equations describing the potential and charge distributions it is mandatory to know the boundary conditions. will ψ° remain constant or will it increase? and what will happen with the concomitant charge σ °? pondering this question, it becomes clear that the problem exceeds that of something purely mathematical: basic physical processes are involved. this becomes immediately clear when eq. (1) is considered. see figure 3b. keeping the potential fixed upon the approach of a second double layer of the same charge sign can only be realized by reducing the charge, that is: by desorption of chargedetermining ions. this is a chemical process. when the double layers are far apart the double layer forms spontaneously; its gibbs energy of formation is negative. thus, the origin of the stability has a chemical nature. case a is the other extreme. then no ion desorption takes place; upon approach the potential must shoot up and now electric work must be done to let the surfaces approach. in reality always repulsion is observed, at any d, but the mechanism can be different. otherwise stated, equal double layers always repel but not necessarily for figure 3. sketch of the difference between interaction between two diffuse double layers at constant charge (a) and at constant potential (b). in case a, ψo increases; the nature of the interaction is electric, whereas in case b, σo decreases and the interaction is of a chemical nature. dashed lines: the slopes, proportional to the charges because of eq. (1). reprinted from j. lyklema, fundamentals of interface and colloid science. chapter 3: pair interactions. 2005. elsevier, amsterdam. copyright © 2005 elsevier 84 johannes (hans) lyklema electrostatic reasons. case b could well apply to the agi system, and most of the oxides. adsorbed ag+ ions have to desorb upon approach. case a is representative for clay minerals for which the charge is more or less fixed because σo is determined by isomorphous substitution of ions inside the solid. on closer inspection, the distinction between constant potential and constant charge has a dynamic origin. the critical question is whether or not the adsorbed charge-determining ions have enough time to desorb during particle encounter. supposed we would be able to shoot the particles very rapidly onto each other, so fast that the adsorbed ions would not have enough time to escape, repulsion would still prevail, but the nature of the repulsion would be different. returning to verwey and overbeek, they realized all of this but for practical reasons had to make a choice which system to elaborate in detail. not surprisingly, they had the agi system in mind. their decision was to treat purely diffuse double layers interacting at constant potential. theory for such double layers at large separation was available.11,12 going for diffuse double layers implied ignoring ion specificity and was motivated by the fact that the challenge of explaining the very dramatic ion valence effect on sol stability was generic (as diffuse layers are) whereas the less pronounced ion specific effect (typically in the stern layer) depends on the nature of the colloidal material. (in passing, ref. 26 also contains a section on stern layers). as a consequence, the dlvo model is that of a diffuse double layer with surface potential ψ° and surface charge σ°. the choice for interaction at constant potential was also made with the agi system in mind: because of the nernst behavior: ψ° is determined by pag and as the latter remains constant upon particle interaction, so does the former. nowadays dynamic arguments support this choice: the time for particle interaction is large compared to the relaxation time of a diffuse double layer. in summary, the theory considers interaction between two (flat) double layers at fixed ψ°. in fact, the russians arrived at the same model, although they did not justify their arguments in so much detail. in order to apply the theory quantitatively a measure for the stability had to be developed. nowadays that would go in terms of turbidities, but v and o did not yet have such data at their disposal. the alternative of that time were critical coagulation concentrations (cc), that are the salt concentrations above which the sol is unstable. at that time, by trial and error a procedure was developed to determine such data with a surprisingly good reproducibility. the procedure involved making series of test tubes containing the sol to which increasing amounts of the electrolytes were added. using a smart empirical mixture of what is now called perikinetic and orthokinetic coagulation, sharp boundaries between fully coagulated and fully stable sols could be created. the virtue of this time-consuming method was that the relatively complex phenomenon of aggregation could be translated into only one single number, the critical coagulation concentration cc, a parameter wanting theoretical interpretation. 5.2 dlvo stability and the schulze-hardy rule the dlvo relation between the critical coagulation concentration cc, and the valence of the (z-z) electrolyte can for the present purpose be written as ( ) =c const tanhzy a z ·c 0 4 2 6 (3) where the constant contains known quantities (like natural constants, temperature, dielectric constants, etc.) and a is the hamaker constant, a measure of the van der waals attraction between the particles, not surprisingly in the denominator. the most crucial parameter is the surface potential, for which the dimensionless abbreviation ψ ψ = =y f rt y f rt etc,  ,  .0 0 (4) is used. for the interpretation of the role of the surface potential the dependency of tanhy on y is critical. at sufficiently high potentials the hyperbolic tangent is independent of y and equal to unity. verwey and overbeek pondered the issue. they wondered whether they should substitute y° or the dimensionless electrokinetic potential yek = fζ/rt. one argument for the latter was that for hydrophobic sols often a good correlation between zeta potentials and stability was found. however, the desired data available at that time were not yet sufficiently reproducible and it was not clear where the slip plane was located. hence they fell back on the well-known surface potential, which at the pag where the stability measurements had been carried out was several hundreds of mv negative, that is, well into the domain where the tanh function equals unity. in that case the critical coagulation concentration is independent of the surface potential and inversely proportional to the 6th power of the (counter)ion valency. in passing, as the russians considered “strong” double layers, they also arrived at the z-6 power. 85interfacial potentials: measuring the immeasurable? establishing this law was the beautiful vindication and quantification of the qualitative schulze-hardy rule and it became the justification of dlvo theory, even to the extent that the 6th power was sometimes identified as the schulze–hardy rule. verwey and overbeek tested the inverse 6th power law for critical coagulation concentrations of agi and other hydrophobic sols. they confirmed the quantitative applicability of the law for the difference between z =1 and z = 2, with as a trend a lower power for the difference between z = 2 and z = 3. this solved one of the main problems of colloid stability at that time. however, it was a pity that for the present issue the result is not useful because the potential does not play a role when it is high enough. 5.3. hofmeister series and stern layers superimposed on the 6th power law of dlvo there is a less dramatic, but certainly quite interesting and not negligible ionic specificity effect. at that time, series of data for different ions of the same valency were called lyotropic series. nowadays, the term hofmeister series is more common. for the critical coagulation concentrations of agi sols these data were well known. verwey and overbeek were familiar with the data by kruyt and klompé,27 which were also obtained during the war time. (marga klompé was a phd student of kruyt; later she became the first female dutch minister of education). in the table her results are given for monovalent nitrates. table 1. coagulation concentrations of some (1-1) electrolytes for agi sols. data by kruyt and klompé (1942). lino3 165 mm nano3 140 mm kno3 136 mm rbno3 126 mm for alkali ions, the differences in the ion specificities are relatively large, about 30% between li+ and rb+ as the counterion. other investigators of agi find somewhat different concentrations but always the same sequence. as a digression, it depends on the nature of the colloid whether the sequence is in the direction of increasing or decreasing ion radius. otherwise stated, the hofmeister sequence depends on the surface properties of the colloid. in fact, recent studies have confirmed the fact that generally such series are not properties of isolated ions but of pairs. in passing, it is an idiosyncrasy of the agi system that for hno3 cc = 137 mm, similar to that for the cations mentioned in the table: the proton behaves as an ordinary counterion, in contradistinction to most other systems. for oxides protons are even charge-determining. not knowing how to deal with ion specificity, verwey and overbeek just took the average value, 142 mm for the monovalent alkali ions. by the same token, for seven bivalent cations they obtained the average of 2.43 mm. the ratio 142/2.43 = 58.4, is close to 26 = 64. they also tested other colloidal systems, like as2s3 and au sols, and positive sols, like fe2o3 and al2o3 which gave rise to hofmeister series of anions, and grossly confirmed the z-6 dependence. so, the interpretation of stability by overlap of the diffuse layers is almost quantitatively explained. this result is still considered as the most important quantitative success of dlvo theory. around 1955, when i started my phd work with overbeek i focused on the, then still open hofmeister trend, trying to exploit the other characteristic propensity of the agi system, namely that it is possible to measure double layer charges by titration. do the titration charges also depend on the nature of the (counter) ion? in figure 4 results are presented for three of the four alkali nitrates considered in the table. the p.z.c. is located at pag = 5.6. to the left of it the surface is positively charged; there the nitrate is the (common) counterion so that no cationic specificity is observable; to the right, at sufficiently negative charge, hofmeister effects do show up upon increase of the surface charge in the direction li+ < k+ < rb+. it was a satisfying result of this research that the ion specificity found in the stability recurred in that of the double layer. at figure 4. the surface charge on agi as a function of the pag in decimolar solutions of the indicated electrolyte, that is the order of magnitude of the cc. reproduced from b.h. bijsterbosch, j. lyklema, adv. coll. interface sci. 1978, 9, 147, copyright 1978, with permission from elsevier. 86 johannes (hans) lyklema the same time it posed a problem in that the direction was unexpected: along the lines of dlvo one would not expect that sols for which the surface charge at given pag is higher would correspond to less stable sols. on mercury the same sequence was found in the surface charge but the alkali ion specificity was lower by about a factor of 10.28 in fact, had the specificity been so low on agi, it would have been impossible to measure it at all. had it been possible to measure the stability of mercury sols, the result as to the hofmeister effect for alkali ions, would be very dull. this comparison indicates that not only the sequence but also the extent of the specificity depend on the nature of the adsorbent. returning to the agi case, the seemingly contrasting hofmeister sequences between cc and σ° proves that one is dealing with the non-diffuse part of the double layer, that is: with stern layers. for agi the non-electrostatic affinity increases in the sequence li+ < k+ < rb+. rb+ ions screen the negative potentials near the surface better than li+ ions do, apparently because they adsorb stronger. consequently, at given ψ°, σ° will become more negative but at the same time more of the countercharge is compensated in the stern layer so that less charge is left for the diffuse part, which controls interaction, hence the lower cc values. the combined action of electric and specific interactions in determining double layer properties is also very well reflected in by overall σ°(pag) curves, given in figure 5. the 10-1 curve corresponds to the kno3 curve of figure 4. on the r.h.s the surface becomes more negative with increasing salt concentration because of screening of the surface charge by electrolyte. the counterion plays the more important role. a large part has an electrical origin, where, typically for pb theory, the vertical distances between the curves scale as √c. the chemical contributions become visible at higher charges and higher salt concentrations, see also figure 4. on the left hand side of the point of zero charge the surface is positively charged, this charge becomes even more positive by the addition of electrolyte for the same reason as what happens at the negative side. only at the point of zero charge there is no charge to screen, hence there is no effect of electrolyte, unless one of the ions adsorbs specifically. in fact, this is the common way of establishing the (pristine) p.z.c., that is the p.z.c. in the absence of specific adsorption. for agi the common intersection point is located at pag = 5.6 till concentrations of 1 m, where the surface is no longer pristine: a slight shift to the right is observed, indicating specific adsorption of the anion, no3in this case. so, the double layer properties of colloidal agi are well understood, without the need of measuring ψ°. it be repeated that the point of zero charge is not identical to the point of zero potential, which remains immeasurable. the difference between the pag of zero potential and that at zero charge is just the χ-potential at the agi-water interface. when comparing with mercury, the model surface for the electrochemist, it appears that the agi did become a grown-up counterpart model for which the lesser reproducibility and precision is outweighed by the propensities that double layer charges can be measured because the areas are so large and because the charge-determining ions have been identified. at this place it is interesting to note that curves like those of figures 4 and 5 have also been measured by the “mercury“ method, that is by direct measurement of the differential capacitance of agi electrodes. the trick is that the adsorption of charge-determining ions is suppressed by working at very high frequencies. the results are very close to those obtained by titration.19,29 this does not yet exhaust the analysis. it is obvious from the above that the dlvo idea of a purely diffuse double layer is untenable. at least a stern layer has to be added, to account for the fact that even the closest counterions cannot approach the layer where the surface ions are located because of their non-zero volume. that gives rise to a thin charge-free layer close to the surface, the so-called zeroth order stern layer. it has a (differential) capacitance ci that is in series with the capacitance cd of the outer, diffuse part of the double layer. the sum capacitance c is given by = + c c c 1 1 1 i d (5) figure 5. surface charge as a function of pag for silver iodide. t = 25o. electrolyte, kno3. the pag axis may also be read as a ψ° axis with 58 mv per unit of pag. 87interfacial potentials: measuring the immeasurable? the total capacitance is dominated by the lower one of the two. when, in addition to the ion size exclusion, also specific ion adsorption has to be considered, eq. (5) has to be modified the point is that figure 5 shows that the double layer is completely diffuse only over a narrow range of very low potentials. the differential capacitance of a purely diffuse double layer depends on ψ° according to a cosh function, which has a minimum at the p.z.c. for agi these capacitances are, except for a constant, the slopes of the curves in this figure. obviously such a minimum is clearly visible only in very dilute solutions around the p.z.c. this conclusion is at variance with the popular statement that one has worked with a “diffuse double layer with stern corrections”. nevertheless, as long as no specific adsorption is detectable, the relation between charge and potential for diffuse layers remains valid, except that the diffuse part does not start at the surface but at a short distance from it, corresponding to the thickness of the stern layer. figure 6 illustrates how we look nowadays at the structure of double layers. the distinct subdivision between a diffuse and a non-diffuse part is well-motivated and has many practical advantages, even if we neither know exactly how thick the stern layers are, nor how much charge they contain. all short-range effects are subsumed in it, so that beyond this layer the layer is purely diffuse, where gouy-chapman theory does apply with impunity. depending on conditions the diffuse part may contain all or only a minor part of the countercharge but even if this is only a low fraction, it nevertheless plays a dominant role in colloid stability and rheology. figure 6a is the most simple double layer with a charge-free stern layer. in this case the diffuse charge σd equals minus the surface charge, which is measurable. for a flat double layer (in practice, for κa>>1) gouy theory has derived the following useful equation,19 relating the surface charge to the diffuse potential ψd (yd = fψd/ (rt)): σ εε=− rt sinh zy 8 2 d d 0 (6) in the inverse situation, when the charge has been measured, the potential follows from its inverse: σ εε = −−y z sinh rt 2 8 d d 1 0 (7) this equation is often used in electrokinetics, where the charges on moving particles are measured but where these charges are by force of habit converted into ζ-potentials, (sec. 6). figure 6b is characteristic for situations where ion specificity is observed, as in the agi case of figure 4. the specifically adsorbed charge is called σi and the potential at their locus of adsorption is denoted ψi. sometimes the planes where the specifically adsorbed ions reside and the plane from whereon the layer is diffuse are called the “inner and outer helmholtz layer” (ihp and ohp, respectively). as to our present theme, ψi is immeasurable. eq. (6) remains valid, of course, but only for the diffuse part. beyond that, its application becomes problematic because from the charge balance σ° + σi +σd = 0 the diffuse charge σd cannot be computed (unless additional data are available, see sec 5.4). in this connection, eq. (6) is often used under conditions where it is not (a) gouy-stern double layer without specific adsorption. finite counterion size. (b) gouy-stern double layer with specific adsorption. (c) gouy-stern double layer with superequivalent adsorption. figure 6. actual view of gouy-stern double layers. taken from ref. 19 with permission. copyright © 1995 academic press. published by elsevier. discussion in the text. 88 johannes (hans) lyklema allowed. perpetrators are psychologically lured by the scientific magic and apparent rigor, and by the suggestion that unknown potentials can seemingly, but erroneously be identified. with three unknown potentials and two unknown charges there are six ways of going wrong and only one of them is correct. turning to figure 6c, this is a sketch of the potential distribution in cases where the double layer contains more countercharge in the stern layer than needed to compensate the surface charge. this phenomenon is commonly called overcharging. several theories have been proposed to explain it. for the agi case, and probably much more generally, overcharging occurs for counterions of higher valency if they hydrolyse in the adsorbed state. the hydrolyzed complexes have a strong chemical affinity to the surface. that this is the right mechanism can be proven by systematically investigating the ph dependence of the charge inversion.30 so, it is a chemical, rather than electrical phenomenon. 5.4 dlvo theory revisited it is obvious from the previous sections that the premises of dlvo theory, notwithstanding its successes, have to be reconsidered. the main correction is that only part of the counterlayer is diffuse and that the potential of the diffuse layer is not ψ° but ψd. the latter potential is quite a bit lower than the former and depends on the nature of the counterion. let us consider these points systematically. is ψd measurable? there is no argument against measurability of the nature as we invoked when explaining why ψ° is immeasurable, because the location of the potential ψd is in the same solution as the reference. on the other hand, ψd is a model parameter; it is based on a number of assumptions. the most relevant is that of having replaced some gradual functions by step distributions, say the extent to which the dielectric permittivity changes with distance. so, in practice quantification is rather a matter of doing independent experiments that give information on the charge of the diffuse part of the double layer only and then subtracting that from the total (titration) charge to find how much is left for the inner layer. electrophoresis is one of these (a double layer with only a stern layer as the counterlayer will not move in an electric field), to which we shall come back in sec. 6. electrokinetic potentials are difficult to measure for systems on the verge of instability, but the order of magnitude is at least a factor of ten lower than the ca. 400 mv assumed for ψ° in dlvo theory. this means that in (3) it is no longer allowed to replace the hyperbolic tangent by its high potential limit (unity), rather tanhy must rather be replaced by the first term of its series expansion, tanhy ≈ y. consequently for the coagulation concentration we obtain instead of (3), ψ( ) =c const a z 'c d 4 2 2 (8) so, for low diffuse double layer potentials ψd can be obtained from stability measurements. the inference is that the interpretation of the schulze-hardy rule is more complicated than expected by dlvo. an exact z-6 power would require ψd to scale as z-4. more pertinent to the present theme is the finding that ψd depends on the nature of the counterion in the stern layer, hence the hofmeister effect is automatically incorporated. it is a small step to consider again charges instead of potentials, by moving further and use (6) to compute σd, subtract that from σ° (from titration) to find the stern charge σi. in many situations the charge in the diffuse part is only a minor fraction of the total. in those cases one does not have to estimate σd very accurately but still find for σi an acceptably correct value. applying the frumkin-fowler-guggenheim adsorption isotherm equation (a modified langmuir isotherm) it is even possible to estimate the specific ionic gibbs energy of adsorption of the alkali cations on silver iodide.31 the ranges are 2.3 3.6 kt, 2.5 4 kt and 2.9 4.2 kt for li+, k+ and rb+, respectively. (the uncertainty margins are mainly caused by the uncertainties in the assessment of ψi). that is about as a far as we can get with classical means for a well-studied model system. similar exercises have also been carried out for other systems, like oxides. the general message is that for a proper handling of interfacial potentials measuring absolute values for the surface potentials are not needed and that there are advantages in considering charges instead. introduction of a stern layer has also an important advantage when considering the interaction dynamics. recall that, according to dlvo theory, interaction at constant (surface) potential required discharging of the particles upon encounter. for negatively charged agi sols that would mean desorption of adsorbed iions and transporting them through the narrowing gap between the approaching surfaces toward the open space further away. this does not look like a simple and fast process. on the other hand, if there are two stern layers between the surfaces, discharging can be rapidly realized by the formation of ion pairs between surface charges and the close-by counterions. this, somewhat extended, review of the agi work illustrates how far one can get nowadays with the simple gouy-stern picture without worrying about the immeas89interfacial potentials: measuring the immeasurable? urability of ψ°. it is questionable whether more advanced models would work better because of the inherent imperfections of solids such as the reproducibility of the interface, and the homogeneity of the surface charge distribution. 6. electrokinetic potentials. having dealt in some detail with the (im)measurability of various static potentials it is appropriate to also consider the domain of electrokinetic, or zeta (ζ) potentials. the main reason for that decision is their outstanding practical relevance for colloid stability and hence for much industrial process control. as over the years the instrumentation has become quite sophisticated, measuring them is nowadays more or less routine, but instead now the interpretation is the issue. in particular the question is how electrokinetic potentials match into the static pictures of figure 6? anticipating the discussion, we shall show that in many practical cases identifying the slip plane with the (ohp) plane where the diffuse part of the double layer starts appears to be a very acceptable approximation. this identification has no scientific background, but it adds to the accessibility of ψd. electrokinetic potentials are very different from static potentials. they do not relate to equilibrium situations but to stationary state processes, involving tangential shear parallel to the surface. it leads to slip between a thin liquid layer, close to the surface, that remains stagnant and a mobile layer in which charge transport takes place. the shearing motion creates a potential difference between the tangentially mobile and the tangentially stagnant parts of the liquid. phenomenologically it looks as if the fluidity of the liquid decreases rapidly with distance from the (solid) surface, but for lack of simple theory about this, the fluidity profile is usually replaced by a step function with a slip plane, where the fluidity increases jump wise from zero to its bulk value. the double layer potential at the slip plane is identified as ζ. of the many electrokinetic phenomena we shall emphasize electrophoresis, perhaps the most familiar illustration, and indeed suitable to discuss how ζ-potentials fit into the picture. for a more extended review see ref. 32. many equations have been derived for converting electrophoretic mobilities into ζ-potentials, depending on the nature, size and shapes of the particles and their conductivities. here, we shall consider two limiting cases: spherical, non-conducting particles for high and low κa. the equation for converting the electrophoretic mobility u into a zeta potential depends on κa where κ is the reciprocal debye length and a the radius of the (spherical) particle. for the κa >> 1 limit the helmholtz-smoluchovski relation is ε εζ η =u 0 (κa >> 1) (9) whereas for κa << 1 the hückel-onsager equation applies, which reads ε εζ η =u 2 3 0 (κa << 1) (10) equation (9) is characteristic for dilute sols of small particles whereas (10) rather represents macroscopically flat surfaces, where the flow takes mainly place parallel to the surface. equations also exist for intermediate κa cases. we shall not worry here about these and neither about surface roughness problems, although these are very relevant for daily practice. equations (9) and (10) are straightforward: a mobility is measured and the ζ-potential follows directly, by force of habit. this procedure looks as a direct measurement of a potential. however, as stated in sec. 1, things are not as they like. rather a charge is measured, which is converted into a potential. for example, in the derivation of (10) this step involves the writing of the total charge q as 4πaεoεζ. this is a decent equation of electrostatics where ζ stands for the potential at the surface of a charged sphere with radius a. however, electrostatics does not consider something like a slip plane or stagnant layer; hence the border between the moving particle and the stationary fluid is taken to be identical to the borderline between the solid and liquid, demanding that ζ and ψ° coincide. a colloid scientist would therefore rather say that a is the particle radius, inclusive the stagnant layer. a similar argument can be presented for the derivation of (9). in this case the poisson equation is used, which relates the space charge density to the second derivative of the potential, similar as in the derivation of (1). for all electrokinetic phenomena the question is what determines the existence of a slip plane. by what factors is it determined? it is imaginable that some of the fluid molecules, in close or immediate contact with the surface could remain somewhat adhered to that surface, and it could also be imagined that upon increasing distance from the surface the fluidity would gradually increase with increasing distance. as stated, the basic electrokinetic assumption is that for practical purposes the gradual transition from stagnant to mobile may be 90 johannes (hans) lyklema replaced by a step function. such a step function was also assumed for the double layer potential to introduce ψd. given the very different origins for assuming a step function in the potential and in the fluidity there is no a priori reason for assuming the outer helmholtz plane and the slip plane to be identical. or, for that matter, assuming ψd and ζ to be identical. nevertheless, experience has shown that often the two are so close that they are experimentally indistinguishable. perhaps the most cogent argument for identifying the ohp and the slip plane is in the very meaning of the slip plane: it separates the electrokinetically active charges from those inactive. the former category coincides with the diffuse parts of the double layer, the latter with the stern part, just as is the case for the ohp. ions in the stern layer are not electrokinetically active (a particle with a stern layer around it will not move in an electric field), although the ions there are not immobile (they do contribute to the surface conductivity). so, the ohp and the slip plane have in common that for both the outer side is the diffuse part of the double layer. hence, for both can we apply equations (6) and (7) to relate charge and potential of the diffuse part. in order to better understand the slip process, in figure 7 for some amphoteric model systems the electrokinetic and surface charge are plotted. these are all experimental data, the only difference with more classical measurements is that charges are plotted instead of potentials. this makes the role of the position of the slip plane better visible. the skewed straight line (σek = σ°) would apply if the thickness of the stagnant layer would be zero (slip plane coincides with solid-liquid boundary), or if the diffuse layer is so extended that no measurable amounts of charge are detectable between the surface and the slip plane. this limit is always reached for very low surface charge, say about 1 μc cm-2. but when the surface charge becomes a bit higher, the electrokinetic charge always falls far below that of the surface charge, meaning that a relatively large fraction of the countercharge resides within the stagnant layer. electrokinetic charges are not very high. about 2.5 μc cm-2 appears the maximum that can be reached, independent of the nature of the surface. this charge can be compared with the surface charge which can become 10 times as high, especially for oxide surfaces. so, only a minor fraction of the counterlayer is electrokinetically active. the same may be stated about the fraction of the countercharge that is accounted for by the diffuse parts of the double layer. also in this respect there is a definite analogy between the diffuse part and the electrokinetically active double layer part. a second striking point is that the inf luence of indifferent electrolyte is not as strong as when the data would have been presented in terms of potentials. for iron oxide the 10-2 and 10-3 curves even coincide. it would be interesting if more data of this kind would become available to generalize this observation. given the present query about the nature of the slip process this figure contains some interesting pieces of information. consider first the situation with the iron oxide (feooh), which is typical in that it is rather symmetrical with respect to the point of zero charge. this important observation means that the stagnant layer is the same to the right (surface negative) as to the left (surface positive) of the point of zero charge; it does not depend on the sign of the charge. stagnant layers must also be present around the zero point of charge, even though there we cannot electrokinetically measure them. we conclude that the formation of macroscopically stagnant layers is a hydrodynamic phenomenon; it does not have an electrical origin and the double layer is there only to measure and quantify its existence. for rutile (tio2) the situation is less symmetrical but here the presence of a stagnant layer on the uncharged surface is beyond discussion. stagnant layers are not very different between hydrophilic and hydrophobic surfaces: compare the hydrophobic agi with the hydrophilic oxides. this observation means that attraction between water in the first adjacent rows and the surface does not lead to thicker stagnant layers. neither is there a thin empty layer between the agi surface and the first adjacent bulk water along which the liquid could slide away (of course, sliding might occur if the interfacial layer would contain microscopic air bubbles). figure 7. comparison between electrokinetic (σd) and surface charges (σ°) for a number of amphoteric model colloids. taken from ref. 32 with permission. copyright © 1995 academic press. published by elsevier. 91interfacial potentials: measuring the immeasurable? the collected inference on the slip process is that stagnancy results from the mutual repulsion between adjacent fluid molecules. this repulsion gives rise to a layer-like ordering in the fluid: the density distribution exhibits a few maxima and minima, petering out rapidly with distance. as this mutual stacking of the water molecules holds for all liquids in contact with solid surfaces the phenomenon is general. one must therefore expect that also for non-aqueous systems such a process with slip occurs. the general conclusion is that the observations made are sufficiently relevant to look for additional information on well-defined systems 7. potential danger? in may 2014 a conference on electrokinetic phenomena took place in gent (belgium). at that occasion a problem surfaced with the measurement of electrokinetic potentials. as this issue has its ramifications it deserves paying attention. the problem had to do with the sophistication of instrumentation that went so far that the very truth was huddled in uncertainties about the software. at the beginning of electrokinetic investigations, say about a century ago, measuring electrophoretic mobilities was very laborious. stable sols had to be made, thin homogeneous glass tubes blown, arrangements made to view the motion of individual particles ultramicroscopically, and exhausting velocity measurements carried out on different levels inside the capillary. inconvenient as such measurements were, they had at least the advantage that the individual behaviour of the particles could be directly observed. with time novel techniques were developed and marketed; in the first place those based on laser-doppler techniques. more recently very powerful instrumentation was developed on the basis of modern techniques that could, hand-waivingly summarized as electroacoustics.32 very sophisticated instruments based on these principles are now commercially available. they allow fast electrokinetic and rheological studies of concentrated systems in a variety of media. industrial labs are willing to pay prices of the order of 105 € apiece. the challenge is that the road from primary data to the desired end product is long and replete with problems. the ways in which these problems are solved depend on the different providers and is so deeply hidden in the software that the average user will not notice them. during the conference mentioned above, a discussion developed when measurements of the electrolyte concentration dependency of silica sols in alcohol, measured by two electroacoustic apparatus of differing provenance, did give different results for the zeta potentials.33 (the difference was smaller if electrokinetic charges were considered instead of potentials). the roots of this difference must be attributed to differences in the software and in the assumptions made in developing it. at the time of the meeting representatives of both industries were present but they were not available to explain how their software worked on grounds of propriety arguments. although the dispute did not assume faustian dimensions it is mandatory to remain alert on the possibility that such issues may develop more easily than with less sophisticated apparatus. anticipating and dealing with them involves also an ethical aspect. 8. still other potentials or should we say “still other ways to measure (interfacial) potentials”? more recently, increasingly sophisticated techniques have been developed for “measuring” surface potentials and more will become available. do these attribute really new insights or do they just reflect a repetition of techniques already considered? we shall briefly discuss two of those developments, anticipated in two of the quotes with which we started this discussion.4,5 8.1 surface potentials from afm and related techniques to this category belong the several techniques by which properties of a surface are measured by probing it with a probe, measuring the force of interaction as a function of distance and position. when the force that the probe experiences as a function of distance obeys classical laws of colloid interaction (say, an exponential decay with distance) extrapolation to zero distance yields a “surface potential”. however, this is not our (immeasurable) ψ° but ψd because the exponential decay only applies to the interaction of diffuse double layers. so, the immeasurability is not affected although measuring ψd has its virtues. 8.2 surface potentials from non-linear optics this is a new development with a physical basis, which offers promised additional information on measuring interfacial potentials. the techniques involve modern developments of surface spectroscopy and go under acronyms like shg (second harmonic generation), and 92 johannes (hans) lyklema sfg (sum frequency generation).34-36 for our present purpose the challenging new element is that molecules can be studied that are located under non-centrosymmetry conditions, implying that in a two-phase system molecules at the interface are selectively measurable, in fact through their molecular susceptibilities. charges at the interface lead to an additional dipole contribution, which is measurable and can be analyzed to produce an interfacial potential. which potential? it is obvious that, as far as our present theme concerns, the added value refers to the stern part of the double layer, not to the diffuse part. this is immediately seen in figure 6, where the high field strengths (slopes of the curves) are almost exclusively in the stern part. in fact, the habit of dividing the counterlayer in a diffuse and a non-diffuse part tacitly presumed ideality, and hence centrosymmetry, of all ions in the diffuse part. more arguments can be given, such as the fact that the charges in the stern part (figure 7) are too low for dielectric saturation. all of that is a happy coincidence because the stern part is much less understood than the, relatively dull, diffuse part. in practice, so far only very few elaborations have been given leading to values of a potential, be it ψ° or ψi or still something else. these elaborations are somewhat suspicious because they contain hyperbolic functions, typical for the diffuse part only. the conclusion is that here is a field awaiting systematic elaboration from a team containing physicists and colloid scientists. 9. conclusions the issue of surface potential measurement is considered in a historical context. the absolute value of the potential difference between two condensed phases is and remains principally immeasurable. changes in it as a function of the composition of one of the phases are sometimes accessible, with nernst’s law as a typical illustration. immeasurability does not mean that no theories can be made for them. many of these attempts belong to the domain of model approaches to assess interfacial potential jumps χ. avoiding these immeasurabilities, a variety of other interfacial potentials have been introduced. these are discussed with a critical evaluation of the steps and assumptions to be made in order to assess them. several interfacial systems are more transparently analyzed if interpreted in terms of charges rather than of potential. it is recommended to change the notion of “potential-determining ions” into “charge-determining ions”. references 1. e. lange, f.o. koenig, elektrochemie der phasengrenzen, in handbuchder experimentalphysik, (eds. w. wien and f. harms), akademische verlagsgesellschaft mbh, dresden, 1933, part vii, 265. 2. s. trasatti, pure appl.chem. 1986, 58, 955. (iupac recommendation on the absolute electrode potential). 3. undisclosed author of a paper that the present author was asked to review. 4. h. yamada, t. fukuma, k. umeda, k. kobayashi, k. matsushige, appl. surf. sci. 2002, 188, 391. 5. one of the main themes of a workshop “surface potentials facts, findings and fantasies”, organized in lausanne (switzerland) by s. roke, sept. 2015. 6. d. h. everett, pure appl. chem. 1972, 31, 579 definitions, terminology and symbols in colloid and surface chemistry. part i. (iupac report). 7. r. parsons, pure appl. chem. 1974, 37, 501. manual of symbols and terminology for physico-chemical quantities and units. app iii electrochemical nomenclature. (iupac report). 8. i. mills, t. cvits, k. homann, n. kallay, k. kuchitsu, quantities, units and symbols in physical chemistry, (iupac report), blackwell, oxford, 1988. 9. j. lyklema, pure appl. chem. 1991, 63, 895. (iupac recommendation on the measurement and interpretation of interfacial electrochemical data in aqueous disperse systems). 10. a.v. delgado, f. gonzález-caballero, r.j. hunter, l.k. koopal, j. lyklema, j. coll. interface sci. 2007, 309, 194. (iupac report on the measurement and interpretation of electrokinetic phenomena). 11. g. gouy, comptes rendus 1909, 149, 654; j. phys.(4) 1910, 9, 457; ann.phys. (9) 1917, 7, 129 12. d.l. chapman, phil. mag. 1913, 25, 475. 13. h.b.g. casimir, tweede symposium over sterke elektrolyten en de elektrischedubbellaag, dutch chem. soc., 1944, 6. 14. f.g. donnan, a.b. harris, j. chem. soc. 1911, 99, 1554; f.g. donnan, z. elektrochem. 1911, 17, 572; f.g. donnan, chem. rev. 1924, 1, 73. 15. o. stern, z. elektrochem. 1924, 30, 508. 16. p. debye. e. hückel, physik. z. 1923, 24, 49, 185 and 305, 1924, 25, 97. 17. h. freundlich, kapillarchemie: eine darstellung der chemie der kolloide und verwandter gebiete. akad. verlagsgesellschaft, leipzig, 1922. 18. m. von smoluchovski in graetz, handbuch der elektrizität und des magnetismus. vol ii, 1914, p. 393. 19. j. lyklema, fundamentals of interface and colloid science. vol. ii solid-liquid interfaces; chapter 3, electric 93interfacial potentials: measuring the immeasurable? double layers. academic press. london, 1995. 20. e.a. guggenheim, j. phys. chem. 1929, 33, 847. 21. e.a. guggenheim, thermodynamics. 4th ed, north holland publ. com. amsterdam, 1959, ch. 9. 22. e. lange, r. berger, z. elektrochem. 1930, 36, 171. 23. a. lottermoser, w. petersen, z. phys. chem. 1928, 133, 69. 24. h. de bruyn, rec. trav. chim. 1942, 61, 21. 25. b.v. derjaguin, l.v. landau, acta physicochim. urss, 1941, 14, 637. 26. e.j.w. verwey, j. th. g. overbeek, theory of the stability of lyophobic colloids. the interaction of sol particles having an electric double layer, elsevier, amsterdam, (also available as a dover reprint), 1948. 27. h.r. kruyt, m.a.m. klompé, kolloid beihefte 1942, 54, 484. 28. d.c. grahame, j. electrochem. soc. 1951, 98, 343. 29. j.h.a. pieper, d.a. de vooys, j. electroanal. chem. 1974, 53, 243. 30. j. lyklema, t. golub, croat. chem. acta 2007, 80, 303. 31. j. lyklema, adv. coll. interface sci. 2013, 100-102, 1. 32. as ref. 19, but now chapter 4, electrokinetics. 33. r.j. kortschot, j. lyklema, a.p. philipse, b.h. erné, j. coll. interface sci. 2014, 423, 65. 34. k.b. eisenthal, chem. rev. 2006, 106, 1462. 35. e.c.y. yan, y. liu, k.b. eisenthal, j. phys. chem.b 1998, 102, 6331. 36. s. roke, chem. phys. chem. 2009, 10, 1380. substantia. an international journal of the history of chemistry 5(1): 157-158, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1184 citation: kragh h. (2021) review of what is a chemical element? by eric scerri and elena ghibaudi. substantia 5(1): 157-158. doi: 10.36253/substantia-1184 copyright: © 2021 kragh h.. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. book reviews review of what is a chemical element? by eric scerri and elena ghibaudi, eds. oxford: oxford university press, 2020 helge kragh niels bohr institute, university of copenhagen, denmark e-mail: helge.kragh@nbi.ku.dk whereas philosophy of physics and philosophy of biology have for long been well-established academic sub-disciplines, philosophy of chemistry in its modern sense is of more recent origin. the field essentially originated in the late 1980s, not least through the pioneering works and organizational efforts of eric scerri. since then philosophy of chemistry has flourished and attracted much attention not only from historians and philosophers of science but also from some practicing chemists. as indicated by its title, the present work edited by scerri and elena ghibaudi focuses on the nature and meaning of a chemical element, obviously a concept at the very heart of the chemical sciences. the book contains 14 chapters written by specialists in the philosophy and foundation of chemistry, with all of the chapters expertly discussing aspects of what constitutes an element and how the concept has developed through history. some of the chapters are historically oriented, examining the development from lavoisier over dalton to mendeleev and further on. this is the topic of a penetrating essay by bernadette bensaudevincent, whereas nathan brooks focuses on mendeleev’s ideas prior to his 1869 formulation of the periodic system. contrary to the common conception, brooks argues that mendeleev was not opposed to the idea of elements made up of subatomic units. other contributions are primarily of a conceptual and philosophical nature, and others again relate to the history of ideas, such as do the contributions of farzad mahootian and klaus ruthenberg. while mahootian discusses the influence of immanuel kant and ernst cassirer, ruthenberg calls attention to the non-atomistic ideas of františek wald, wilhelm ostwald and gaston bachelard. the latter, a french philosopher, introduced the notion of “metachemistry,” which to him had quite different connotations than metaphysics. incidentally, the term is also occasionally used by historians of science to characterize speculative trends in late-nineteenth-century chemistry, such as the views of william crookes. a common theme in many of the chapters is the current official definition of an element as given by iupac, which defines the concept in a somehttp://www.fupress.com/substantia http://www.fupress.com/substantia 158 helge kragh what ambiguous dual form. on the one hand there is the abstract meaning of a species of atoms as given by the number of protons in the nucleus (the atomic number); and on the other hand there is an operational meaning stated in terms of the macroscopic concept of a pure substance. the two meanings are meant to coexist, but do they? as sarah nijmans and other authors point out, the iupac definition is problematic for both historical and philosophical reasons. while most of the authors are highly critical to the iupac formulation, mahootian suggests that its two parts are not contradictory but rather stand in a complementary relationship. he argues that niels bohr’s famous but vague principle of complementarity can and should be extended from the realm of quantum physics to elucidate also problems in the philosophy of chemistry. iupac’s definition of an element reflects to some extent the important ideas of fritz paneth, the austrian radiochemist who in influential works between 1916 and 1962 analyzed in depth the concept of an element. several of the contributions deal with paneth’s ideas and their later impact, a topic discussed in some detail by scerri, hijmans and joseph earley, among others. one of the essays, written by ghibaudi, alberto regis and ezio roletto, includes a discussion of the chemical element from an educational perspective, albeit in a rather abstract way which may not be directly relevant to teachers of chemistry. in an interesting chapter on “the existence of elements and the elements of existence” robin hendry focuses on the chemical element from an ontological point of view and with an emphasis on the artificially produced elements at the end of the periodic table. some of these so-called superheavy elements of atomic numbers z > 103 have been detected only in the form of extremely short-lived atomic nuclei, whereas atoms with their shells of electrons have escaped detection. nonetheless, they are recognized as proper elements no less real than oxygen and iron. to hendry, this not only raise questions regarding criteria of existence, it also relates to the problem of the existence of composite bodies in general or what in philosophical circles is known as the “special composition question.” as stated by the editors of what is a chemical element? the aim of the book is “to provide an update to the current state of the debate on elements” (p. 2). the book is more than just an update, though, as it offers a series of wide-ranging and in part innovative scholarly analyses of the subject. the attentive reader will not find a final answer to what an element is, but he or she will better appreciate the complexity and many facets of the question. the book is written by specialists in the philosophy of chemistry and mainly addressed to other specialists, and for this reason it is less relevant to the average chemical reader with an interest in the foundational problems of chemistry. for better or for worse, it illustrates how philosophy of chemistry has come of age as an independent branch of academic philosophy of science. with the independence follows almost inevitably a specialized academic language and a scholarly style that makes the new research area uninviting or even slightly incomprehensible to outsiders. in my opinion, the primary audience of what is a chemical element? will primarily be philosophers of science and secondarily historians of chemistry. substantia an international journal of the history of chemistry vol. 5, n. 1 2021 firenze university press giving credit where it’s due – the complicated practice of scientific authorship seth c. rasmussen history of research on antisense oligonucleotide analogs jack s. cohen chemistry, cyclophosphamide, cancer chemotherapy, and serendipity: sixty years on gerald zon thermodynamics of life marc henry darwin and inequality enrico bonatti loren eiseley’s substitution bart kahr new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors yona siderer capillary electrophores is and its basic principles in historical retrospect 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis ernst kenndler1,*, marek minárik2,3 the eminent russian – german chemist –friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries aleksander sztejnberg review of what is a chemical element? by eric scerri and elena ghibaudi, eds. oxford: oxford university press, 2020 helge kragh 1 citation: l. corbetta, l. m. fabbri, d. cavalieri, p. bonanni, a. mantovani, b. thompson, f. luo (2021) stand on the same side against covid – 19: scientific evidence on vaccine for covid-19. substantia 4(1) suppl. 1: 1233. doi: 10.36253/substantia-1233 received: feb 04, 2021 revised: mar 09, 2021 just accepted online: mar 09, 2021 published: mar 09, 2021 copyright: © 2021 l. corbetta, l. m. fabbri, d. cavalieri, p. bonanni, a. mantovani, b. thompson, f. luo. this is an open access, peer-reviewed article published by firenze university press (www.substantia.net) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia webinar stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 this document is the direct transcription of a webinar organized by prof. l. corbetta of the university of florence on december 10th, 2020. scientific coordination: lorenzo corbetta associate professor of respiratory diseases university of florence scientific and website director of the european association for bronchology and interventional pulmonology (eabip) organizing secretary: consorzio futuro in ricerca via saragat 1 – corpo b – 1° piano | 44122 – ferrara cfr@unife.it translation coordination and editing: giorgia biagini, md info@covid19expertpanel.network webinar’s partecipants: prof. lorenzo corbetta university of florence prof. leonardo m. fabbri – university of modena and reggio emilia prof. duccio cavalieri university of florence prof. paolo bonanni university of florence prof. alberto mantovani humanitas university of milan prof. bruce thompson swinburne university of technology prof. fengming luo west china hospital, sichuan university corresponding author: lorenzo.corbetta@unifi.it substantia. an international journal of the history of chemistry 4(1) suppl. 1: 1233, 2020 issn 2532-3997 (online) | doi: 10.36253/substantia-1233 http://www.fupress.com/substantia l. corbetta et al. 2 “stand on the same side” videoconferences https://www.covid19expertpanel.network “implementing a science-based lockdown exit strategy is essential to sustain containment of covid-19. china’s experience will be watched closely, as other countries start considering—and, in some cases, implementing—their own exit strategies” the lancet, volume 395, issue 10232, 18–24 april 2020, pages 1305-1314 this phrase expresses the purpose of this program called “stand on the same side against covid-19” that takes advantage of the new and rapid digital technologies to put together several experts worldwide. it’s a global space were many countries hit by sars-cov-2 can share only scientific information in order to face the pandemic. december, 10th 2020 “stand on the same side against covid – 19: scientific evidence on vaccine for covid-19” lorenzo corbetta: good afternoon, welcome to the first webinar on the educational project for medical practitioners called stand on the same side against covid19. the proposal of this programme is to take advantage of the new rapid digital technologies to put together several experts worldwide. it's a shared space where many countries hit by sars-cov-2 can share only scientific information in order to face the pandemic. today, we will focus on scientific evidence on vaccines for covid-19. i would like to express my deepest thanks and gratitude to the panel of experts who accepted the invitation to speak today. first of all, i would like to introduce my cochairman and mentor, professor fabbri. please, professor fabbri. leonardo m. fabbri: thank you, thank you all. i think that this is a very interesting and informative initiative that goes on for several months and thanks to lorenzo corbetta for organising it. without further ado, i'd like to ask him to introduce the first speaker. lorenzo corbetta: thank you. please join me in welcoming our first speaker, professor paolo bonanni, who is a professor of public health at the university of florence, and his topic will be the point on the vaccines. paolo bonanni: okay, thanks a lot professor fabbri and professor corbetta. it's a pleasure to be invited again to this very important webinar, and i will try to give you some highlights on the current status of covid-19 vaccines. of course, it's a big topic and it's difficult to give you all the data that is coming from the research in this moment, but i will try to make a summary. of course, it might be different, but i will try my best. so, we are waiting to have a solution to this big, big issue of the pandemic at the world level, and we are all waiting of course for a covid-19 vaccine or more covid-19 vaccines. what should we ask of a covid-19 vaccine? first of all, safety and efficacy, effectiveness. we will see the effectiveness in the coming months when vaccines will be applied in a large scale mass vaccination programme. the second question is how many doses do we need? up to now, we have vaccines that will be used mainly with two doses, but there might be some vaccines that could require only one dose. available since? we know that in the uk for instance they started very recently, and in other countries, they also started with the different vaccines, but we should have vaccines available in all countries from the beginning of next year. then, also, a big problem is the logistical needs and the cold chain requirements for the vaccines that are coming first. so, what do we know today? so, what are the known concepts about vaccines and immunity? of course, there will be the presentation of professor mantovani after mine that will highlight these issues, but anyway. coronaviruses sars and mers induce an antibody response, and we don’t know how long it lives. so, is it a short-lived or long-lived antibody response? studies on mice suggest that t lymphocytes have an important role in protection. so, even if antibodies are no longer present, there might be a role for t lymphocytes. there is a possibility and there is a risk of antibodydependent disease enhancement, which is possible, but up to now all vaccines have been studied for this potential threat and none of them was shown to have this kind of problem, although we will have to monitor this situation in the future. the other known is that infected subjects may remain positive for many weeks. probably not knowing that we would experience such a dramatic pandemic in 2017, the coalition for epidemic preparedness innovation, also called cepi, was created with the aim to prompt the development and stocking of vaccines against diseases that may cause dreadful epidemics. so, in a way, the big leaders in the world already forecasted that there might be such a dramatic situation like we are experiencing today. so, with an investment initially of $2 billion for this purpose. i would like to go back to this paper that i already presented in a previous presentation, but i think that this still remains a paper that gives us a good light on what are the expected issues to be solved while developing a vaccine. so, what are the main challenges for the development of a sars-cov-2 vaccine? first, define what is protective immunity. so, can we find a correlate of protection? up to now, no, but we should strive to find one if possible. the duration of immunity, of course, is never known at the beginning of vaccine development, but we have to monitor and to study this duration. https://www.covid19expertpanel.network/ stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 3 then, we have variable endpoints for the concept of efficacy. are we speaking of protection from infection? or reduction of viral replication or reduction of number of diseases? these are different concepts. of course, in the first phases we have verified the ability of vaccines to avoid the diseases but we should also study if they can avoid transmission of infection from vaccinees to the other population. then the role of neutralising antibodies and t cells. the difficult understanding of the real incidence of infection, how many people are symptomatic or asymptomatic, and this makes things more complicated for us in public health. then, the creation of independent labs with identical validated serological tests to confront different candidates and different clinical trials. every vaccine producer is developing vaccines according to their own tests, their own protocols, but we should try to have a common denominator, a common lab that could also make comparisons among the different vaccines. then there is the big issue of also from the ethical point of view of human challenge trials. are they useful and ethically acceptable or not? then also we have to monitor, as i said before, the immune enhancement risk, but i don’t want to go into more depth on this. so, when we decided to start this enterprise and to study these new vaccines, i showed this slide already in july, but i have added some concepts. so, we must pay attention to vaccine safety, we cannot run the risk of approving a vaccine which has not undergone all possible scrutiny of safety, because we could endanger the perception of all vaccines for the population. but, today, i would add that as a matter of fact, the preclinical development and the regulatory evaluation phases of submitted dossiers were accelerated, but the clinical trials involved the same numbers of volunteers and study phases as for all other traditional vaccines. so, we sped it up, but not the phases that are crucial for evaluation of safety and efficacy. we sped up the preclinical development, we are speeding up the regulatory verification of the data, but not the data themselves. so, this should make us confident that what we have available today has undergone the same evaluations as for traditional vaccines. the target for our vaccines is the spike protein which binds to the ace2 receptor as we all know. and as of the day before yesterday, so december 8th, the coronavirus vaccine tracker tells us that we have thirteen vaccines in large scale efficacy trials. we have overall 58 candidates in clinical trials, and 86 candidates in the preclinical phase of development. as we know, the dna and rna vaccines are the ones that are closer to approval and especially the rna, messenger rna vaccines which include vaccines that have an mrna encoding for the spike protein encased in a lipid coat so that they can enter the cell. and the two candidates that are closer or have already started to be administered are the ones from pfizer and biontech and the one from moderna. so, regarding the pfizer biontech, the proposed indication is for an active immunisation for the prevention of covid-19 caused by sars-cov-2 in individuals of sixteen years and older, with two doses at least 21 days apart. the primary efficacy endpoints are the incidence of covid19 in participants without serological or virological evidence of past sars-cov-2 disease. the first primary endpoint, but also a secondary endpoint, also in those who already had an infection, with evidence of past sars-cov-2 infection. yesterday, there was an announcement from pfizer that said that the second generation vaccine should be developed soon over summer. the aim is to make the cold chain requirements less stringent because you know that this vaccine has to be stored at minus 75 or minus 80 celsius. these are the results that were published in july with the preliminary result in phase one, in 45 healthy adults, where they gave the two doses one month apart, and the conclusions of this preliminary report were that neutralising antibodies were detected in all participants, which is good news also in terms of possibility to prevent infection, and not only the disease. also an acceptable safety profile. regarding the moderna vaccine, these are the studies of safety and immunogenicity of this vaccine in older adults, and the conclusions of this study published in the new england journal of medicine are that in this small study involving older adults, adverse events associated with this vaccine were mainly mild or moderate. l. corbetta et al. 4 the 100 microgram dose induced a higher binding and neutralising antibody titres than the 25 micrograms, so this supported the 100 micrograms continuation of studies. regarding the phase three of these two vaccines based on mrna technology, both of them are double blind randomised efficacy trials, with inclusion of 30,000 participants for moderna and 45,000 for pfizer. the two doses are given four weeks apart for the moderna vaccine instead of three weeks apart for the pfizer vaccine. the participants are constantly monitored to evaluate if they developed covid-19 symptoms and if they tested pcr positive. also, the possible safety signals are carefully monitored. there is a predetermined number of cases that should occur before the study can go to an evaluation which is, for a 60% theoretical efficacy, this was 151 cases for the moderna vaccine and 164 for the pfizer vaccine. so, these are the results that were made available very recently for the pfizer vaccine, which shows that in all participants we have a 95% vaccine efficacy in preventing confirmed covid-19 occurring at least seven days after the second dose of the vaccine. so, there was a striking difference in the occurrence of covid-19 in the placebo compared to the study group which received the mrna vaccine in this study. the safety was studied in approximately 38,000 participants over 16 years, and there was no major signal of safety concern. of course, there was no signal of vaccine enhanced disease but we have to evaluate further this aspect when the vaccine will be distributed and administered to a large population of subjects. what is the news from the european medicine agency, the ema? on december 1st they announced that they were starting rolling the review for one vaccine that is the covid-19 adenoviral vaccine based from janssen. there is not yet a deadline here, but for the two vaccines that are based on mrna, you see here that they received the application for conditional marketing authorisation both for moderna and for the biontech vaccine. they foresee to conclude their assessment by 12th january, at least, at the latest for the moderna vaccine and by 29th december (ema has recommended granting a conditional marketing authorisation for the vaccine comirnaty, developed by biontech and pfizer, to prevent coronavirus disease 2019 (covid-19) in people from 16 years of age https://www.ema.europa.eu/en/news/ema-recommendsfirst-covid-19-vaccine-authorisation-eu) for the pfizer biontech vaccine at the latest. so, this is the status in europe, and especially in the uk. so, the vaccine appears to be safe, these are the evaluations of the uk public health. the vaccine appears to be safe and well tolerated, and there were no clinically concerning safety observations. so, the community advises that the vaccine should be used in the first phase of the programme according to a priority of groups. of course, healthcare workers, elderly people, and people with chronic diseases that are discussed further in this slide. so, the joint committee on vaccination and immunisation, so the body that, in the uk, gives advice on the use of vaccines, they advised that at the start of the vaccination, there will be no definitive reply according to the ability of the vaccines to prevent transmission. regarding the two vaccines that will be the first probably to be used in the uk, they say that for organisational ease, since the pfizer vaccine should be given at least 21 days apart and the astrazeneca vaccine 28 days apart, they will probably go for the 28 days for both vaccines to make the organisational issues and the administration of a second dose easier from the logistical point of view. of course, there is also the issue, if you have to complete a vaccine course and you started with the vaccine but the same vaccine is not available for the second dose, and they advise is, if possible, you should complete the vaccination with the same vaccine, but if not possible, all vaccines are producing s proteins, you should complete the vaccination with the available vaccine irrespective of this problem if there is nothing else to do. regarding other vaccines, i mentioned the dna vaccines, this is still the data from the preclinical studies on rhesus macaques for the dna vaccine that was produced by the beth israel deaconess medical center at the harvard medical school in boston with the collaboration of janssen. here, they show that vaccinated animals had developed humoral and cellular immune response including neutralising antibodies with titres comparable to those found in convalescent humans and macaque serum. and that the viral load was decreased both in the lower but also in the upper respiratory tract. regarding the adenoviral vaccines, we know that regarding the vaccine from astrazeneca, the vaccine induces a robust humoral and cell-mediated immune response in mice, and in vaccinated macaques virus-specific neutralising antibodies are detected. after challenge, there was a significant reduction of viral load in the lower respiratory tract in vaccinated primates, while no difference was found in the viral load in the higher respiratory tract. we must say that the viral load that they gave for this challenge was a very high dose, so we don’t know if this resembles or not the natural infection as it occurs in nature. however, the vaccine was very efficacious in preventing pulmonary damage with this high challenge dose, and no signal of immune-enhanced disease was revealed and detected. so, we know that also for this vaccine there is a big phase three trial over 30,000 participants. there was a stop in this vaccine, and this should be seen as a signal of attention to the possible association of side effects to the vaccine, and when the adverse events following the vaccine were ruled out as to causality, the phase three trial started again with no problem. astrazeneca announced recently on november 23rd that they had a higher efficacy when they gave the first dose with a half dose compared to the two full doses, and this was reported recently, 2 days ago, in the lancet with a study where they showed that for those who received the two full doses, the efficacy against clinically significant disease was 62%, while in those which were younger, however, who received half a dose with the first dose and a full dose for the second dose, the efficacy was 90%. (https://www.thelancet.com/action/showpdf?pii=s01406736%2820%2932661-1) so, now there should be some extra study to evaluate and to understand why there was such a difference. we have also the https://www.ema.europa.eu/en/news/ema-recommends-first-covid-19-vaccine-authorisation-eu https://www.ema.europa.eu/en/news/ema-recommends-first-covid-19-vaccine-authorisation-eu https://www.thelancet.com/action/showpdf?pii=s0140-6736%2820%2932661-1 https://www.thelancet.com/action/showpdf?pii=s0140-6736%2820%2932661-1 stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 5 adenoviral vaccine by johnson and johnson, which is involving 60,000 participants in phase three trials. this is also the one which is under evaluation. the interesting thing for this vaccine is that also this was stopped, but the interesting thing is that this might require one dose only instead of two. this has to be evaluated, but this would make vaccination courses much easier if it is confirmed that only one dose is needed. then we have the adenoviral vaccine from china, from cansino, 40,000 participants, a very interesting vaccine too. concerning the inactivated viral vaccine, we have two candidates, sinovac phase three and sinopharm phase three. this is the data from sinovac, the preclinical data where they showed that they induced a high level of neutralising antibodies. sorry, i couldn't translate this, it's in italian. anyway, the neutralising antibodies for this vaccine seem to be very high and very constant in all vaccines https://jamanetwork.com/journals/jama/fullarticle/2769612 then we have the vaccine from sinovac and the conclusion of this preliminary communication is that they authors report a good tolerability profile in the absence of serious vaccine-related side effects, and more than 97% of participants seroconverted in terms of neutralising antibodies. i will go quickly to the last part of my presentation. we also have a potential protein-based vaccine in subunits or virus-like particles, but we are lagging a little bit behind with these vaccines. we also have other approaches like the pathogen-specific artificial antigenpresenting cells, that could be sensitised and stimulated with viral structural proteins. but also, pathogen-specific autologous antigen-presenting cells that could be taken by plasmapheresis, charged with the s proteins, and reloaded in the same subjects, an individualised approach to vaccination. the last slide, again, we speak of the issue of human challenge trials. so, in the uk, they say 'dozens to be deliberately infected with coronavirus in the human challenge trials', is this feasible, is this useful, and is this ethically acceptable? the questions are open for discussion. the uk also highlighted the problem with the logistics, especially with the pfizer vaccine which requires minus 75 or minus 80 degrees, so this is a challenge for the logistics. we have to vaccinate many people at the same time, when you open the box containing the vaccine, that must be used within a few hours from opening it. i would like to finish with two or three slides, but the last two are very quick. these are my conclusions, in a way. what are the prominent problems and opportunities in the development and availability of covid-19 vaccines? the development process of safe and effective vaccines against covid-19 has been sped up. the urgency to contrast the pandemic never impacted on our first aim when we develop a vaccine. in latin, it's primum non nocere, for those who do not know latin, it means first, do no harm. we needed to be extremely stringent on safety and we are all, not the damage the credibility of sars-cov-2, but also all other traditional vaccines. strategies of use of covid-19 vaccines will depend on the expected effect of each product. a vaccine against disease only will be targeted to healthcare workers, the elderly and subjects of any age with chronic diseases, but a vaccine able to prevent also the infection could also be used in those responsible for the spread of infection, maybe in schoolchildren, young adults and adolescents, and might be crucial in obtaining the community protection. i prefer community protection compared to herd immunity effect. just to finish, also in the usa, they highlighted how in the first phase when few courses are available, we must prioritise adults aged 65+, adults with high-risk medical conditions and health care workers, and only after we can go to the other groups of the population. this is the final. so, when there are limited doses available, highly targeted administration is required to achieve coverage in priority populations. then, when a larger number of doses are available, we should enlarge this to the other populations, non-healthcare critical workers, people in congregate settings and all other older adults. finally, when many doses are available, all the other population that could impact on infection transmission at the population level. with this, this is my email for those who want to write to me for further discussion. i thank you very much for your attention. leonardo m. fabbri: thank you professor bonanni, i'm pleased to introduce now the second speaker, professor alberto mantovani, who is emeritus professor of pathology and scientific director at humanitas milano institution. the title of his presentation is immunity and vaccines, scientific and sharing challenges. thank you. alberto mantovani: so, good afternoon, and i would like to thank leo and lorenzo for the pleasure to be with you and professor paolo bonanni for a fantastic talk. we have really touched only one selected aspect of vaccines. so, this is the virus and this is a picture of the virus prepared by three of my grandchildren, and when we were confronted with the virus, we were brought back to our culture in the western world, greek culture, and i know that we don’t know, that was my feeling. together, i am going to share with you some of the progress that we have made in the understanding of the interaction of the virus with the immune system. i'll also draw your attention to this website of the national academy of science of italy, accademia dei lincei, where guido forni and i have updated our understanding of vaccines. naturally, we are going to release the december report. so, here is an attempt to summarise the natural history of covid-19. https://jamanetwork.com/journals/jama/fullarticle/2769612 l. corbetta et al. 6 the virus, in terms of vaccine, we should not forget that there may be the possibility after introduction of the virus of the appearance of escaping variants. so, we should be prepared for that. and interaction with the host, and the end result of the interaction with the host is dictated by viral load. we had summertime of course, ageing, there is a general paradigm related to the tone, inflammatory tone in relation to ageing, inflammageing, lifestyle, obesity for instance, and genetics. i would like to comment on genetics because we have contributed to the field, we did i think one of probably the first genetic analyses of the italian population, and then we were part of a european effort. i want to emphasise that in this european effort, we found that chromosome genes located on chromosome three, and these genes include chemokine receptors, and i’ve long been interested in chemokines and my laboratory was one of the groups that discovered chemokines. chemokine receptors are there, inflammation. in the same in this manhattan plot, you can also see blood group. i'm aware of work in the uk that again points to this, to chromosome three and this region of chromosome three. so, downstream of the interaction and genetics of course, there is innate immunity, the directors of the immunological orchestra, t cells and b cells in production of antibodies and plasma therapy. i would like to emphasise that, again, what paolo already said, we don’t have standards, we don’t have standards for measuring antibodies. we don’t have standards for measuring neutralising antibodies or standards to measure t cell activity as we i should emphasise that in three controlled trials, plasma, hyperimmune plasma therapy has failed. there may be good reasons, a long time in the natural history of the disease, and in addition, hyperimmune plasma contains many things and i will get back to that. of course, downstream is uncontrolled cytokine release syndrome, macrophage activation, involvement of the microvascular bed in the lungs, and uncontrolled inflammation, including a new disease, multi-inflammatory syndrome see for children, as a late consequence of infection. so, this is an early study that we did, starting in april. (https://doi.org/10.1101/2020.05.24.20111245) we are monitoring a population of 4,000 people in our community and this is the bergamo region with high prevalence of seral positivity. interestingly enough, and we were discussing this before the meeting and it's hard to dissect whether this is some hint, the lower disease burden in this region now may in part reflect previous exposure, as well as better behaviour, having been so dramatically affected by the first wave. therapy: well, the only therapy proven to change mortality is glucocorticoids. dexamethasone in the early study done by hornby et al., published in the lancet, nhs uk, and this has now been confirmed in larger studies and my research according in our own institution was part of this. so, this is pretty solid. let me voice a concern i have. based on what i hear, and what i hear in my hospital. i keep hearing of patients admitted to the hospital and treated with glucocorticoids at the early stages of the disease. we should emphasise that the evidence in this study, in the hornby study, shows benefit of glucocorticoids in a welldefined window, when there is need of oxygen, let's simplify things a little bit. outside of that window, if anything, there is a hint, and there was a recent opinion written by tony fauci published in jama, and again he was concerned about inappropriate usage of glucocorticoids by practitioners outside of the window of efficacy of these agents. the virus interaction-, let me go back to the first interaction of the virus, it interacts with innate immunity, the cellular arm of innate immunity, macrophages, myeloid cells and the humoral arm of innate immunity complement, and i will get back to that in a moment. early on, some of us hypothesised that there should be, based on previous evidence on sars, a mechanism whereby the virus blocks this pathway of resistance. these are two studies, done under the leadership of nih with contributions from several hospitals in northern italy. jean laurent casanova at nih and gigi notarangelo again, at nih. so, there are in-borne errors of the pathway leading to the https://doi.org/10.1101/2020.05.24.20111245 stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 7 production of type one interferon, so hidden immunodeficiency accounts for severe diseases in a fraction of the patients. in addition, in other patients, there are autoantibodies directed against and blocking the same interferondependent pathway of resistance to viruses. i should say that in part it has also been shown that autoantibodies, for instance, similar to the antiphospholipid syndrome autoantibodies appear in patients, and are likely to play a role in thrombosis, which is a major problem in these patients. so, i would summarize that this may be one of the reasons why hyperimmune plasma therapy didn't work. so, the emerging picture is that covid-19 actually displays that interception between autoimmunity as i mentioned, genetic predisposition, chromosome three, immunodeficiency up here, and uncontrolled inflammation, and i want to discuss some work that we have done on uncontrolled inflammation. so, we have long been interested in pathways of innate immunity, including the humoral arm of innate immunity and many years ago we cloned a molecule, cloned a mouse gene and human cdnh genomic. it's a distant relative of c reactive protein, and it has functions, there is genetic evidence that it is important for resistance against selected microbes in humans including fungi, and it behaves as a functional ancestor of antibodies. so, we have been dissecting innate immunity in the patients, in our hospital, and we have been collaborating with alessandro rambaldi at giovanni xxiii hospital in bergamo. this is an analysis, and among the genes that popped up in this analysis, ptx3 was prominent. (https://doi.org/10.1038/s41590-020-00832-x) then, we looked at bronchoalveolar lavage fluids, we looked at adaptations, we looked in silico at patients in israel and the united states. the take home message is that in peripheral blood, as well as in lungs, myelomonocytic cells are a major source of this protein. and in autopsy examples, the molecule is there, it's there in the lungs, and it's there for instance in vascular cells surrounding a clot. so, we then measured with a high-cost sophisticated technology. these are the results of our cohort, 96 patients and as you can see, it turns out-, and the endpoint here is a hard endpoint, death at 28 days, and it turns out to be an independent, and i will accelerate a bit, an independent risk factor for death. apparently, better than anything else, and the same results were obtained in an independent cohort in bergamo. i'm aware of a third study with identical results to those that are shown here. so, this is the take home message. we need biomarkers. we need to dissect the diversity of the disease, and tailor therapy to patients based on genetics, autoimmunity and degree of inflammation with biomarkers predicting outcome. this is our contribution stemming from our own work, ptx3. in terms of mechanism, we assume that this molecule-, we have evidence actually that it is involved in microbe recognition, regulation of compliment activation and regulation of inflammation, and this is again the kaplan-meier work. i should mention that the main people here were brunetta, folci and bottazzi in my lab. so, vaccines. i will not repeat what paolo said, absolutely, so clearly. it has been depicted as a race and it is a race, but it's a peculiar race because it's not so important to get there first, but it's important to get well at the end of the race. this is where the race is actually a marathon, and we should not forget that the data that we have seen referred to two months after the second administration of the vaccine. paolo has already gone through the various platforms that are used to generate vaccines and we have a review coming out with (mw 41.39) and i, and again i direct you to the website of the accademia dei lincei where you can find references and a summary. this is the adeno in the paper that again paolo already beautifully commented on. so, this is a painting from a painter called ligabue. this painting conveys a message, and the message i think is from polio. we may live in a polio-free world, a couple of months, three months ago, africa was declared free of wild type polio and this amazing result was obtained thanks to two vaccines which have been used in a complementary way. in addition to living in a polio-free world, we need a third vaccine, i will not be led by the point. so, i feel that it is very important that we have an array of vaccines available, and i'm very worried about clinical trials now based on the conditional approval and emergency approval. i am worried and this may be a point of discussion. how are we going to have people enrolled in clinical trials with at least two vaccines, possibly three vaccines approved, conditional and emergency? finally, there is an aspect of vaccines or at least of selected vaccines that we should not forget, and that's pathogen agnostic protection. we have known for a long time that usage of selected vaccines is associated again with protections against pathogens which are antigenically unrelated to the target of the vaccine itself. a major mechanism of pathogen agnostic protection is the general fitness of the first line of the immune system, of innate immunity, and this is an essay that mihai netea and i wrote recently and published in new england, because i did some of the early work and mihai did all this, underlying molecular mechanisms. (https://doi.org/10.1056/nejmcibr2011679) so, selected vaccines increase the baseline tone. we call it trained innate immunity of myelomonocytic cells at the level of precursors, and mature cells. this is mediated by epigenetic remodelling and trained innate immunity involves microbial killing, production of cytokines, and triggering of adaptive immune responses. and i feel that we should ask the question whether the upcoming covid-19 vaccines do elicit trained innate immunity. in addition, there are a number of prospective trials designed to try and take advantage of trained innate immunity, of immunological fitness if you pass me the word as a strategy to decrease the risk of covid-19. finally, general message, we wrote this paper before covid-19, rino rappuoli, angela santoni and myself. both angela and myself-, i have been part, she is part of the global alliance for vaccines and immunisation, and which is making a tremendous effort to share vaccines with the poorest countries in the world, including covid-19. i feel that this general tenet that vaccines are an achievement of civilisation, a human https://doi.org/10.1038/s41590-020-00832-x https://doi.org/10.1056/nejmcibr2011679 l. corbetta et al. 8 right, and i feel that we should not forget that one newborn, one kid out of five does not have access to fundamental vaccines on health, let alone covid-19. and we know it now based on covid-19 that vaccines represent a health insurance, a safety belt for humanity. once more, leo, lorenzo, thank you for having me on board today. leonardo m. fabbri: thank you alberto. we will have a discussion at the end, we will have some minutes at the end to discuss all the presentations. now, i introduce professor duccio cavalieri, professor of general macrobiology of my university, the university of florence, with a presentation on sars-cov-2 gene stability and its implications. duccio cavalieri: it's totally expected that new variants of the virus have developed since its first appearance in wuhan. all viruses mutate as they make new copies of themselves to spread and thrive. there are many thousands of different versions, or variants, of covid circulating. according to evolutionary theory most of these differences are likely neutral. a few can even be harmful to the virus's survival, thus leading to their disappearance. but some can make it more infectious or threatening. what i'll discuss today is the current knowledge on how the variation in the virus indeed plays a role in the dynamics of the infection. i will also try to show convincing evidence that understanding the genetic background of how the virus varies is a crucial point to develop effective strategies for its containment. the first slide below, shows how the first set of sequences from wuhan were basically identical, and how they basically clustered differently from the first isolate of the virus. this is the first paper published in nature. it's impressive that this paper basically was received on the 20th january and published, accepted on the 29th, and published on the 3rd february. what this paper describes is basically entering the “heart of darkness”. i would say, taking the name from conrad’s book, describing the trip into the study of genetic variation of sars-cov2 is the discovery of the “heart of darkness” of the pandemic. in the following slide you can find the metagenomic analysis of the viral sequences from the lungs of one of the patients. the majority of the viral sequences were sars-cov-2. the description of how we are entering the unknown, the heart of darkness of the human viriome, is given by the discovery of the first evidence that saccharomyces cerevisiae killer virus m1, an rna virus previously described only in yeast, is found within the lungs of this patient. but besides this, again what was impressive is that the first sequences of bat cov, of sars-cov-2 had really a very low level of divergence. these were basically claiming that we were looking at the early stages of the virus evolution. the other interesting part was that the nearest neighbour was bat sars-cov-2 ratg13, a virus came in from bats that had 88, 89% homology to the virus. this is one of, again, the first papers in which two of wuhan's patients' viruses were sequenced, and this paper that uses a specific technology for the purification of the rna only, and the sequencing of the viral rna, proposes that actually sars-cov-2 is derived from four recombination break points for recombination events in the groups of the beta coronaviruses, that is creating the emergence of this novelty that is finally infecting humans. now, the history of coronavirus research in terms of sequences has seen maybe for the first time the joining of forces from several groups and the fact that everybody working in the field has made the sequences available. this is gisaid website, from which i derived this information. the last update unfortunately is the 22nd june 2020. at that time, more than 4,000 genomes had been sequenced by the scientific community. gisaid had the largest sars-cov-2 genome collection, but the problem is that it doesn't provide the general metadata information since august 2020. so, this is an effort that has seen an explosion at the beginning of the pandemic but now, for some reason that i don’t know, is not keeping up the pace. we need to support as much as possible these initiatives. what's really important from these datasets is that it's becoming increasingly clear that the virus is novel and it's novel because its variation that is less than other coronaviruses of the same family, it can basically be used to track down, with a small subset of mutation, the origins of the virus. what we know is the vast majority of the sequences available come from males. there are a few more males than females with more than 40 years of age. some patients have missing gender information but this is really a minority, and the other thing that we can notice is that the country that is contributing the most is the usa, then belgium, china, unfortunately italy has sequenced only approximately 93 genomes on gisaid and maybe 120 genomes, but indeed it's not in the top ten nations for the number of genetic sequences uploaded to public databases. i really think that this trend must be overturned to ensure a precise and correct tracing of sarsstand on the same side against covid – 19: scientific evidence on vaccine for covid-19 9 cov-2 infections because italy, in particularly lombardy, plays a major role in the understanding. it has basically probably an understanding of the generation of one of the most important mutations that led the success of the current form of the virus that is spreading through the world. this is data from my group, we have a paper submitted currently on a meta-analysis of the existing sequences. the 93 italian strains on gisaid clearly showed, came from two different clades, so there were two clades of these strains, and these two clades have moved both to spain and to france. so, we have been the seed of the infection that arrived probably from germany and then disseminated initially to spain and to france. and then the italian strain moved to the usa, actually this is a fantastic paper applying phylogenetic theory, phylogenetic network analysis to the sars-cov-2 genome. i have to advise that this paper was initially heavily criticised because the extension of the theory of the darwinian evolution to viruses is actually criticised. i mean, it's not clear if the algorithms that we use to calculate the evolutionary constraints in bacteria, yeast or humans can be applied to viruses, but according to this theory, it was quite impressive to notice that in one month, the virus moved from wuhan to shanghai, from shanghai to munich, from munich to milan, and then from milan to mexico. we could follow and track the movement of the virus by means of this technology. then, again, it was even more impressive q paper where the authors are using this network analysis to follow the movement of the virus into the usa, and they show there have been two separate events of arrival of the virus in the usa. (https://doi.org/10.1126/science.abc8169) the first event directly from hubei to seattle, was not successful. the second event, that traced the virus that actually arrived via milan, indeed was extremely successful, because the majority of the infections on the east coast are seeded by this entry. another important problem is the dating of the mutation. this is one of the papers that dates the emergence of the virus in hubei in china, and it dates back basically to october, november, the first development of the virus in china, but some of the phylogenomic analyses are currently telling us that the virus in china was already present probably at day one, the day of the beginning, in two forms. there was a type one and type two clade of the virus. this paper published in nature (https://doi.org/10.1038/s41586020-2355-0) shows that basically these two clades might have potentially different clinical outcomes. independently from the clinical outcomes, (that in my opinion the data presented here do not really support), what's really impressive is that in one form of the virus, type one, the number of mutations, in particular of synonymous substitutions is very low. it seems that selection is neutral for this variant. on the second form of the virus, there is a significant amount of non-synonymous substitution in the virus and the rate between synonymous and non-synonymous substitutions clearly indicates the evidence of selection. this is telling us that the second form of the virus is indeed under selection, and why is this interesting? because https://doi.org/10.1126/science.abc8169 https://doi.org/10.1038/s41586-020-2355-0 https://doi.org/10.1038/s41586-020-2355-0 l. corbetta et al. 10 the number of sequences is small, thus strengthening the indication of natural selection in action. with the increasing of the number of sequences that are taken into account, (already from 7,666 viral genomes), there are 198 recurrent mutations that are emerging independently (homoplasy). 80% of the mutations are inducing non-synonymous changes, so they have an effect, very likely they are derived from the second form of the chinese virus. we have four sites that have the same mutation in more than fifteen patients and these are the four sites. now, starting from this paper, let's try to see how the analysis on the four sites progressed. the next slide describes another interesting publication that was published on molecular phylogenetics and evolution. the authors were suggesting that the origin of the sarscov-2 was not china, but was actually india, and maybe bangladesh, but what's interesting besides looking at where the virus comes from, is that the authors do a proper evolutionary analysis trying to track down the origins of selection in the mutations that appear in more than ten sequences in the subset. and they discovered two extremely interesting things. first, there are eight sites that show positive selection. one is a site that changes an amino acid in a very important gene, it's the rna polymerase. and sars-cov-2 is supposed to be so stable because of the particular proofreading capability and fidelity of its rna polymerase. it's more stable than influenza, it's more stable than hiv and several other viruses, probably for these characteristics. but if you knock off the proofreading ability of the rna polymerase, then you might give rise to a more evolvable form of the strain. the second mutation is a mutation in the spike protein, it's the gs614 mutation, that actually is the mutation that has been taking over in italy. it is the most represented mutation in italy. now, this is a paper from the group of davide zella, it’s the university of trieste, so it's a very good group of geneticists working in italy. what they show, they actually claim that the emerging mutation in the polymerase could be one of the most problematic ones for the emerging of the virus, because it could favour an increased variation in those strains that carry this mutation. they also follow the spread of this mutation following the lockdown in several countries in the world, but what's most interesting is that from the beginning, from the early days of infection, ( as shown in the first paper published on the sequencing of the first two sars-cov-2 strains in italy), you find both the original chinese form of the strain that has the d614 mutation, and what i would call the european variant, the gs614 mutation. now, why is this relevant to the discussion today? because from the beginning, a few papers suggested that the spike mutation, gs614 was associated with a higher transmissibility of the virus. these are actually the dynamics of the two alleles. in yellow, you see the d614 allele, in blue, you see the gs614 allele, this is march. (https://doi.org/10.1016/j.cell.2020.06.043) this is then through march the progressing of the infection, and you see that the blue variant, the g614 variant is taking over the other variant. now, the authors claim that this confers a higher transmissibility. there has been a lot of debate on this subject, and in my opinion, one of the most interesting contributions came from the group of sara p. otto. sara p. otto is a well-established evolutionary biologist. i had the honour of meeting her when i was in harvard many years ago. sara published in my opinion one of the most interesting papers on the evolution of sars-cov-2, it's on the evolution epidemiology of sars-cov-2. what sara shows is that based on genomic sampling over time, the substitution rate you can estimate for sars-cov-2 is 0.00084% per site per year, this is two to sixfold lower than the rate of influenza and is 50 times less than the original sars virus. so, this was the original sequence, the chinese sequence. sara also built a mathematical model predicting the development of the infection, and before the summer, sara predicts that in the countries that went under lockdown there is going to be a second wave of infection probably in october, so the timing was correct because this is exactly what happened. then, sara predicts that the virus, will increase the transmission rate, with a reduction of the asymptomatic fraction, an increase in the duration of the incubation phase and slowly reduce the virulence. but what sara also shows is that the search for an adaptive mutation in sars-cov-2 is indeed hampered by the fact that the sampling is not done properly, so the sampling is not statistically correct because the number of sequences that we have from different countries are different. as we see, italy has a very small number of sequences, china and the us have a lot, so this imbalance in sampling could lead to a false statement on the selection that occurs on the different forms of the spike protein. this is clearly said by sara in this paper. (https://doi.org/10.1016/j.cub.2020.06.031) so, the non-neutral sampling process could indeed lead to the fact that you could find differences in sequences that are not really associated with the difference in aggressivity of the viral infection, but they are due to a bias in the statistical sampling. yet, what sara could become realistic with the increase in sequences, the field has progressed enormously in these months and maybe otto’s models could lead to increased precision in the predictions. i think that rarely we have seen such an explosion of publications and research in a specific field like what we have seen in the past 12 months. a recent publication in nature genetics proposes a fantastic computational tool that models the interactions and the effect of the mutation in the virus, on, let's say, the receptor. this modeling tool indicates which mutation sites could be the most relevant, and predicts if a mutation in the spike could https://doi.org/10.1016/j.cell.2020.06.043 https://doi.org/10.1016/j.cub.2020.06.031 stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 11 reduce the affinity of neutralizing antibodies. and now comes in my opinion one of the papers that i consider to be the first strong evidence of the fact that the spike mutation, d614g alters sars-cov-2 fitness, because this mutation shows first on cell lines and then on lung tissue, that this mutation increases the replication of the virus in cell cultures, increases the level of spike protein within the infected cells, increases the infection ability in the upper human airways, so here in red you see the gene mutation in the spike and most importantly you see here in this graph the gs614 mutation and the d614 form of the original form of the virus, this mutation affects, in particular, reduces the susceptibility of sars-cov-2 to neutralizing antibodies. in august and september 2020, a sars-cov-2 variant linked to infection transmitted from humans to farmed mink and/or subsequently transmitted to humans, was identified in north jutland, denmark and called “cluster 5” variant due to a combination of mutations that may result in reduced virus, decreasing immune protection following natural infection or vaccination. minks were suppressed and this variant does not appear to have spread widely. experts' concerns since december 2020 focus on a small number of additional new variants of coronavirus that are apparently dominating the scene in the first months of 2021, that could be much more contagious or elusive than earlier versions: • a uk variant that has become dominant in much of britain and has spread to more than 50 other countries • a south africa variant that has also been found in at least 20 other countries, including the uk • a variant from brazil all three have undergone changes to their spike protein the part of the virus which attaches to human cells, in addition to other parts of the virus. as a result, these variants seem to be better at infecting cells and spreading. the uk variant, called sars-cov-2 voc 202012/01 (variant of concern, year 2020, month 12, variant 01),contains 23 nucleotide substitutions and is not phylogenetically related to the sars-cov-2 virus circulating in the united kingdom at the time the variant was detected. this variant is rapidly expanding in the rest of europe, has a total of 17 coding mutations (in each one changing or missing an amino acid), in four different proteins of the virus. eight mutations are in the spike protein, the one against which the vaccines of biontech, modern and astra zeneca were developed (18). three of these have potential effects on the ability to infect and cause severe symptoms. the n501y variant could increase affinity with the ace receptor by facilitating the entry of the virus into our cells. deletion 69-70 del was described in the context of the ability to evade the human immune response by altering the maturation of the spike, ie in that site cut by one of our enzymes, with a crucial role in promoting infection. nothing can be said about any other effect at the moment, but it is definitely important to know that another prediction of the models is that the lethality of the virus should slowly decrease by increasing the fraction of paucisymptomatic carriers. since october, the uk variant has become dominant across much of britain and has spread to more than 50 other countries. recent research from public health england indicates that the english variant may be between 30% and 50% more contagious than previous ones. so we can certainly say that it is more diffusible than the others, this data also shows how sequencing the virus can allow us to understand which variants are taking over and associate them with a phenotype, even simply by measuring their statistical distribution. the south africa variant, the so called 501y.v2 variant, emerged in october, and it has more potentially important changes in the spike protein than the uk variant. while sars-cov-2 voc 202012/01 from the uk also has the n501y mutation, phylogenetic analysis has shown that 501y.v2 from south africa are different virus variants, since it carries two more that scientists think may interfere more with vaccine effectiveness. the n501y mutations in the spike protein of coronavirus is 50 percent more transmissible than previous variants, genomic sequencing data highlighted that the 501.v2 variant rapidly displaced other lineages circulating in south africa. the brazil variant emerged in july and has three key mutations in the spike protein that make it similar to the south africa one. one of them e284k could make spike hard to be recognized by the antibodies induced by the current version of the vaccines. the current vaccines were designed around the wuhan variant, but the ability to generate a number of different antibodies against different epitopes strongly suggests they should still work against the above mentioned variants, although perhaps not quite as well. in the worst case scenario, the vaccines could be redesigned in a matter or weeks or months, to target the new version of the spike. what i mean here, i am confident that the vaccines that we have developed will work on the short term, and that we will be able to modify them to capture the virus evolution. thus it's really important that we follow up very carefully the evolution of the virus to make sure that we will develop future vaccines that will work on the future forms of the virus. i want to conclude with the fact that i do think that we have to really consider what's the best vaccination strategy because one of the ways to take into account the high variability of the spike is maybe to introduce other antigens besides spike in the generation of the vaccine. regarding differences in mortality rate, there is currently no evidence to suggest that any of them cause more serious illness, and on the contrary evolutionary theory would predict that slowly the virus should decrease its lethality. leonardo m. fabbi: thank you professor cavalieri. even now we have no time for discussion, questions will be at the l. corbetta et al. 12 end to respect the schedule. it is now my pleasure to introduce the next speaker, professor bruce thompson, he is professor at alfred health, and now is dean of health science of swinburne university of technology. the title of his presentation is different approaches, different outcomes. professor thompson. bruce thompson: thank you so much for the invitation to speak tonight, and i'm speaking on the other side of the globe with the wonders of modern technology. here it's about ten past midnight, so if i'm sounding a little tired then just bear with me. i've actually talked a little about this, it has got not a lot of straight science in it. this is really what's happened in australia, and we've had a very different experience of covid than other areas of the globe. i really just wanted to talk a little bit about the australian response to this particular virus, and in particular start talking a little bit about some of the issues that we've had actually in the hospitals where we've actually had significant healthcare worker transmission of virus. not necessarily from the patient to the workers, but the workers to each other. so, we'll talk a little bit about some of the things that we've done to actually start preventing this because it's started to become a very real issue. it's almost where covid meets occupational health and safety. i'd just like to acknowledge a couple of people who've passed me some slides. in my current role as the president of the thoracic society of australia and new zealand, i had a lot to deal with our federal deputy chief medical officer, dr nick coatsworth, and also professor lou irving from the royal melbourne hospital. i'd also like to acknowledge brigitte borg from the alfred hospital who passed me a couple of slides about the laboratory experience. so, this is the australian curve. it looks quite different to other countries around the globe, it's very different to the us experience. as you can see, we had a first wave that peaked just before april, the end of march, and then we had some isolated cases, and then we had a significant peak starting at the beginning of july. unfortunately, that peak was actually due to our state that i live in, victoria, where actually we had pretty well the majority of the cases in the second wave. that's another story in itself on potentially how that actually occurred, but i'll start talking a little bit about what we did to basically lead to where we are at the moment. so, this is some data of where we are in australia, here, right now, as i collected the data this morning. if we actually look in this particular column here, overall australia had the best part of 28,000 cases which is really nothing compared to what we're hearing around the globe and if you look at the us which is actually having in excess of 200 cases a day, we really have a very, very different experience. indeed, this column here is actually the number of new cases across the whole country, and we've only had six new cases. we actually only have 48 active cases in this country at the moment. if we actually look at the days since last case, in victoria, we're actually very proud to say we actually haven't had a new case for 40 days. so, that's quite significant compared to actually us leading the number of cases that we had in the second wave by a huge amount, we're now actually in a situation where we actually haven't had a new case for 40 days. this is the number of days since the last death, and in some cases in other states you can just see it's actually the best part of the year, and in victoria it's actually nine days. that last case that actually happened nine days ago was an historical case from about 30 or 40 days ago. so, as a society what did we do? we locked down extremely hard and very, very quickly. our international state borders were closed, and indeed if you actually did have to cross the state border for whatever reason you had to be in quarantine for two weeks. our international borders are closed only for people who are-, you're only allowed into australia if you're an australian who wishes to return home for a very good reason. once you've done that in australia you have to quarantine for fourteen days, and that quarantine actually has security. so, you're actually locked stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 13 into a hotel room for fourteen days and then you obviously have to be tested and proven to be negative. masks were mandatory across the whole of the community, and even though we've been, in victoria, 40 days without a case, masks are still mandatory in areas such as public transport, shopping centres and malls and what have you. so, in victoria it's, sort of, about a third of the way of that second wave. we had, what we called, stage four lockdown. you're not allowed to travel more than five kilometres from your own house. the only reason you're allowed outside of the house was due to go to the supermarket, a medical appointment, pharmacy and you are only allowed to exercise for one day, so they closed down the state. they closed down all retail, restaurants, no public gatherings, no sporting events. our chief medical officer of the state, basically, at the point, actually has control of the actual legal system, and that's what we did. so, i actually haven't gone to work, been on my campus at my university since march, i now work from home. with the healthcare workers, what they did and what they are still doing and they are just now unravelling this, they basically divided up the whole of the hospitals in to three working groups. so, if someone became infected in that group, they would basically remove that whole team. and that would seem to have been highly effective. then, finally, the government really did step in because, basically, you think of closing down the whole of the workforce, people still need to earn and income and the government provided a baseline income for all people who were unable to work due to to the lockdowns that we experienced. so, if we look at healthcare infections, up until the time of eighteenth of september, that's the latest data that we had, 9.1% of all the cases that we actually had were due to healthcare workers. so, it was a significant component of the total number of cases that we had were actually due to healthcare infections. so, if we look at the period of the first wave, 530 healthcare workers were infected and that's about 11%, so it's still roughly the same ratio and there was about 32 outbreaks of healthcare workers across the state. but if we look at the actual second wave, clearly there are a lot more healthcare workers who are infected, which makes sense because there was such a strong response that we had, and that was actually 8.4% of all infections during this period was due to healthcare worker infections and there were 88 outbreaks. so, one thing i just briefly want to talk a little bit about is ppe. and this became a real issue for my role in the thoracic society of australia and new zealand and also within the federal government. there was significant anxiety amongst the healthcare workers about adequate ppe. so, and i call myself actually having ppe ptsd, because i actually had a significant number of physicians write to me personally with letters of demand that we need to actually increase the amount of ppe available. and part of it was thought to be around the use of n95 masks because, basically, there was a strong view at that time that the transmission of this virus was purely by aerosol transmission as the predominant cause, and that is still yet in debate. and so, however, we only have a finite resource, it's expensive and also it needs to be fit tested and it's not necessarily straight forward. but senior physicians who were working on the front line had significant levels of anxiety and this, sort of, led to us having to actually change our policies across the nation, more in line with the precautionary principle. and this is a slide that i got from our deputy chief medical officer about this, because we were basically forced to go down this pathway. however, the precautionary principle, as we know, doesn't necessarily eliminate all risk, it basically potentially reduces and you actually have this trade off between over-regulation and then, basically, the actual under regulation and uncertainty of the risk. also, the precautionary, if it's applied, the more infections that we avoid, the more often that it turned out that we might have actually acted too excessively, and we actually went in too hard. and don't forget, we have a number of physicians who were given no choice but to work in to, what would seem to be, a high-risk environment. l. corbetta et al. 14 and then on top of that, if you look at the precautionary principle, there's actually ignoring the costs of associated with doing this, and it's basically, 'hang the expense, let's just do this.' the other thing that we learned, and again being significantly involved in this, is the various levels of government. australia actually has three levels of government, and it has basically, local government for your community, state level government and then the federal government. and then we also have various jurisdictions in terms of the infection control expert group which is a government run organisation, various jurisdictional quality and safety federal and state committees as well. and they, actually, didn't agree with each other. now, half the problem is we had such an affective response, with actually now having really almost eliminated the virus out of this country, and we're now still arguing about why we let this thing break out so much. i'm sure other people in this audience are thinking, you know, 'you do not have a problem,' and we really don't compare to other areas around the globe. so, the other thing is, hospitals are actually the responsibility of state government. federal government cannot actually intervene and tell them what the actual state hospitals can do. and, again, that led to a timed confusion and also irregularities in terms of having a consistent response to the actual infection. so, this particular hospital, where i've had a little bit to do with as well, the royal melbourne hospital in victoria, had really pretty well every case of covid for a while because, don't forget, victoria in the second wave had the majority of these cases. and so there was significant learnings that we can get from this. it's a number of campuses, it's a 550 acute bed hospital in it's main campus. it's a pretty old hospital, it's actually not really designed under modern guidelines however, i am talking to many people from europe at the moment who are probably thinking it's a relatively new hospital compared to some others. but it also has significant resident aged care facilitates as well and it has about 10,000 staff. and, as you can see, there's actually many open wards that had to open up for these patients and the ventilation is not necessarily all that great. so, what was actually happening is we started getting a number of reports that healthcare workers were contracting the virus and, on top of that, the nation that we are, we have many who people who have family and colleagues who are overseas and we started to hear significant issues of healthcare infections and, indeed, fellow colleagues actually dying of this virus overseas, and that actually led to significant anxiety. and it was originally thought that the healthcare infection from covid in the first wave, was potentially the inadequate or the unavailability of ppe, potentially large numbers of covid positive patients that they were exposed to. we had worker fatigue of people working long hours and also there was limited testing, and our contact tracing just frankly wasn't good enough to start off with, paper based and it took an inordinate amount of time up to, sort of, seven to eight days before we got results. so, in the first wave, we had ten positive patients in a single negative pressure room and that was, sort of, described as what we call a 'hot ward,' in march, they established a staff screening clinic and a separate community clinic as well, and this was ultimately to keep everybody away from each other. but it was also, what they were particularly interested in, is if they had to lay off staff if they actually became symptomatic or indeed contracted the virus. so, in the first four weeks in the first wave, they had over 1100 symptomatic staff, which eleven of those were positive and would seem to be, even though they thought it might have actually been contracting the virus from the patients they cared for, it was actually community acquisition rather than the workplace infection and they published this in one of our local journals. so, even though there was significant anxiety of people contracting the virus from patients they cared for, in reality, it was actually community acquisition as opposed to a workplace infection. so, this particular figure here, we've got a number of lines drawn on this one. this is the victorian prevalence and this is on the y axis on this side, is basically 0.1% of the victorians were contracting the virus. but if we look at the catchment area of royal melbourne hospital, you can see actually the prevalence is higher in that particular catchment area and it's probably due to the socioeconomic group that this particular hospital lies in, and also the ethnic backgrounds from this particular group as well. however, if you look at the actual prevalence of virus amongst the healthcare workers at royal melbourne hospital, you can see it's actually a magnitude higher than the actual prevalence of the community being about 1.2% of the actual staff contracting the virus compared stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 15 to 0.1% of the community contracting the virus. so, this is obviously a very significant concern. so, with the second wave, we're looking between the 1st of july and the 31st of august. 262 healthcare infections were actually-, this particular hospital we're talking about, the majority were actually the nursing staff which makes sense, they're the ones spending the most time with the actual patients, and there's also significant support staff in terms of allied health and other groups of people and only 8% of the medical staff actually acquired the virus. in the main though, it was actually a relatively mild illness for all the staff of varying ages. 89% of the healthcare workers that contracted the virus, it was a relatively mild illness, would even go as far as significant influenza, is was just a relatively mild experience. however, 11% and in fact fifteen patients were actually admitted, thirteen patients, this is hospital in the home, a programme that we run in this country in particular, but two of those were admitted to intensive care. one was actually intubated although, no one died. and here's a ct scan of a 30 year old healthcare worker who was in icu for 35 days, now four weeks post discharge and you can see there's significant ards associated with his. so, even though you could argue, sort of, for 90% of the people who contracted this virus it was a relatively mild illness, clearly for 10% of healthcare workers it was definitely not the case and of significant concern. however, as we talked about before, this virus as we know, it contributes mostly to an elderly population, and what we had is significant numbers of people contracting the virus in aged care facilities, and these actually were admitted in to acute care hospitals and this became a significant problem. so, over a one week period in early august, an intake of covid positive elderly patients from residential aged care, but they were sitting in open wards. two weeks later though, there was a rapid increase of inpatient infections, up to 60 happened within a couple of weeks. and this also led to 101 healthcare worker infections. so this was becoming a significant problem, trying to manage these patients and actually endangering the staff and putting them in a relatively unsafe environment. so one of the potential reasons we end up having a lot of patients sitting in very small area and very large viral load. we had open wards, which seemed to be a significant problem with confused patients, they were calling out and actually not aware of their environment with high and significant nursing care. potentially poor ventilation in some areas, and then a breakdown in infection control. so, not so much the use of n95 masks or not having them, it was really a breakdown in infection control relative to removal of ppe in inappropriate ways, and also potentially people walking in to, sort of, tea rooms and other public areas still with ppe on, which is not necessarily a great thing. we had a large number of staff who potentially came in to contact with positive people with covid and so, therefore, we had to actually isolate those large numbers of staff so, therefore, the staff sitting behind had significant staff fatigue and then also staff working across multiple sites which is potentially a problem. and then finally, community acquisition of virus from people who-, because healthcare workers tend to share accommodation with each other for the various reasons. so, some of the things that were done. for starters, actually close the open wards and start transferring people to single rooms and actually start reducing the actual critical burden. upgrading the levels of ppe to n95 and face shields which was above government guidelines. putting spotters and senior staff who are basically ensuring people were not getting a breakdown of their ppe. extra cleaning, (tc 01:30:00) rapid testing of staff, looking at prevalence testing of all staff and l. corbetta et al. 16 then service support of infected and furloughed staff, and at one point in time this particular had 680 staff who were actually laid off from work which was a potential issue. but this figure i actually found quite interesting and again, as i said, i had significant concern and anxiety of staff about adequate ppe and if you look at it in terms of hierarchy of risk, ppe is probably the actual least effective and really what we need to try and do is eliminate and isolate a virus to try and reduce harm. so, if we start looking at our laboratories, as we know this spirometry and other types of respiratory functions tests are aerosol generating procedures and there was significant concern about continuing testing. now my background is as a respiratory scientist and laboratory-based and i could not believe, as one of my roles as the president of the thoracic society of australia and new zealand, that they closed down all respiratory function laboratories across the country on the 25th of march. and that was, basically, close down all services unless it was totally, clinically essential that the tests were done. however, it was the appropriate thing to do because, again, we had significant concern of basically transmission of virus inappropriately. so, it's interesting with biofilters which we try and protect, actually, transmission of viruses and bacteria between each other via the actual spirometer or the lung function equipment, but this is more an environment issue that we don't want to have people contacting the virus from patients coughing and what have you. so, and then there was a significant amount of work about ventilation of laboratories and the european respiratory society is about to come out with a document on that particular topic. i don't think i need to talk about the way we accessed our ppe and what have you, but clearly, there's been a significant amount of work in the policy space about this area. so, what have we learned? we've learned a lot about managing this particular condition, especially in the hospitals and aged care facilities. aerosol transmission is likely to be a significant issue in managing these people and we need to start thinking about this as an occupational health and safety issue, more than just straight contracting the virus off the patients. so, even though there are people sat thinking that this might be similar to an influenza, i think we'll all agree on this webinar, this is a very, very different infection and the way we have to manage it. so, thank you so much again for the invitation to speak, and i look forward to any questions that might appear later. thank you. leonardo m. fabbri: thank you. thank you very much, professor thompson. we have the same problem in europe with the elderly residents, it's a global problem. thank you for the recommendation. we can move directly to professor fengming luo, who is a professor/chief physician/doctoral supervisor at west china hospital, sichuan university who had a very, very big experience in the city of wuhan. he will speak about how to prevent future sars. please. fengming luo: okay, thank you, i want to talk about how to fight covid-19 in china, and i want to talk about our experience and the situation in china now and the future in china. the west china hospital on january 18th, we made a protocol for patients with a fever, all patients with travel history to wuhan should be screened for covid-19. we also prepared a special ward and more beds in case of more patients. we also prepared icu for severe patients in our hospital. and on january 25th, all staff should be recalled from vacation and be ready for treating covid-19 patients. we also prepared ppe and other things for a medical team to wuhan and our hospital at the same time. we also established a headquarter for our hospital to fight covid-19. so, the medical team from west china to wuhan, we had three teams. in total we have more, almost 200 doctors and nurses and rts to wuhan. we worked in different hospitals and took care of severe patients and returned to chengdu in march and april. across the country, the highest level response to the epidemic situation in most provinces, that means all people should stay home and wear masks in public areas. in my experiences of organising an emergency medical team to help other places, we should have doctors and nurses from department of pulmonary critical care medicine, department of infection diseases also from icu. we should bring ppe, ventilators and medicines to the city so where we support. now we made a working flow chart and protocols for treatment of the patients and also to protect ourselves. as to the ppe, we made the protocol to put on the ppe and then take off the ppe and if you perform a high-risk procedure, they should put on the positive ventilator. after these protection measures, all the doctors and nurses returned from wuhan tested negative for covid-19. in fact, i think that the aerosol transmission is in some situations, but if you protect yourself with suitable ppe, i think it will decrease the risk of infection. to prevent the spread of disease in wuhan, we locked down wuhan on january 23rd. that means, 'don't go to wuhan and don't leave wuhan,' and published the data of our patients, and also performed the early protection, early detection, and early diagnosis and early isolation. wearing a mask is required in public places. help from other cities. we sent 42,600 doctors and nurses to wuhan and they brought ppe, ventilators, high flow and medicines and test reagents to wuhan. we also sent three ecmo to wuhan from west china hospital. 42,600 doctors and nurses returned from wuhan with negative tests of covid-19. we also have fangcang shelter hospitals, all the mild symptoms of all the people should isolate in the fangcang shelter hospital, and the doctors and nurses take care of them and if the disease progressed and we sent them to the hospital immediately. (https://doi.org/10.1016/s0140-6736(20)30744-3) also, wearing masks in a public area, advise the people to wash hands and you can see here, lockdown wuhan, and after two weeks lockdown the number of diseases reaches a peak, and four weeks later under basic control. https://doi.org/10.1016/s0140-6736(20)30744-3 stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 17 and the strategy for the treatment of covid-19, all patients with covid-19 under the monitor of healthcare staff in healthcare facility in order to identify the rapid progress of covid-19 in the early stage. we gave sufficient respiratory support at an early stage to reduce tissue and organ hypoxia. we gave regular oxygen therapy, high flow, non-invasive ventilation, and also mechanical ventilation and also ecmo for the patient. this is an indicator for ecmo. and sometimes we perform a bronchoscopy for the patient with ecmo and perform the lavage and you can see here after the lavage, the right lower lung becomes very clear and the saturation of oxygen improved. (https://doi.org/10.1159/000507898) and we also used the prone or lateral position, high flow intervention, the oxygen saturation index improved. and also rox index improved and the borg score improved at the same time. sometimes we used the high dosage of steroids when the patient's symptoms progressed very fast and the ct scan worsened in two or three days, we maybe used the high dosage of steroids to deal with the inflammation. and discharge standard is that normal body temperature and symptoms improved and lesions on ct improved, and the nucleic acid is negative twice. and after discharge from the hospital, quarantine at the designated place for two weeks. we reopened wuhan on april 4th and after that there are several new cases in helong jiang province, jilin province, also wuhan, and beijing, and xinjiang, dalian, and also quingdao. right now, we have several new cases in chengdu so we took some measure to prevent the spread of the disease. and right now, sometimes there are new cases in several cities during winter. but almost normal life, the stores, restaurants, schools remain open and a mask is required in public transportation, a mask is required in a crowded room but sometimes it is not necessary to put on a mask. and we always advise people to wash their hands and test covid-19 if close contact with a patient. to the hospitals, all patients who enter a hospital should measure temperature and they should test for covid-19 and the same as to the family members. we also have a quick response code which records your travel history. and it's very strict measures to prevent the spread of covid-19 in most hospitals. if there are new cases in a city, all the local people may be tested for covid-19. for example, we test more than 10 million people within five days in quingdao when there are new cases. isolating people with positive results and all the costs of the patient were paid by the government. and if there were people from abroad over the pandemic, we will pick up the people from the aeroplane and send them to a specific hotel in a single room for each person, and we perform the first test and also isolation for fourteen days, and then perform the second test. after that, we have a self-quarantine for another seven days. because we have some patients affected by the cargoes from abroad so we test the seafood and other cargoes for covid-19 from abroad. all workers dealing with these things should be screened regularly. i think chinese model is good for china because there are many people in the country and there almost six cities whose population are more than 10 million in china. if the situation in wuhan had happened in two or more big cities, https://doi.org/10.1159/000507898 l. corbetta et al. 18 i think the healthcare system would maybe break down. so, we should take strict measures to prevent the spread of covid-19 in china. in the future, i think the vaccine is very important. we have five types of vaccine in china under development and two vaccines almost finished their stage three clinical trial. in fact, i took a shot, one month ago for covid-19 vaccine and i think i will take another shot tomorrow. in our hospital, we have one recombined protein vaccine developed, finished stage one and under the stage two clinical trial and will begin stage three clinical trial soon. in fact, in china right now, we have a vaccine so people with high risk, for example pulmonologists, staff of emergency room, and the staff in custom and airport can take this vaccine. also, in the next stage, people with risk to progress in to severe if they are infected with covid-19. for example, older people, people with chronic diseases should maybe have the vaccine. to prevent the transmission the measure for prevention depends on the situation of the pandemic. we maybe lock down a specific area when there are new cases. preventing transmission from pandemic areas, we should test covid19 for the people and also at the same time, the cargo, to prevent the transmission. in summary, i think lockdown for preventing the spread of the disease in wuhan is very important. early diagnosis, early treatment and early isolation is very important to prevent the spread of the disease. track people who have contact with patients with new technology, especially with the cell phone signal. i think the vaccine may be helpful to end this pandemic. i think only protect yourself and then our healthcare staff can help more people. thanks for your attention. leonardo m. fabbri: thank you very much for this very informative and interesting presentation. now, the general discussion is opened. we have twelve minutes but if we need it, we can stay some minutes longer. if i may ask the two initial speakers the first question, paulo and alberto. the fragile population is elderly and multimorbid, and certainly treated with multiple drugs. my question is, is there any evidence that any of the treatments that they may be on, may influence the effects of adverse events of the vaccine? i know it's a difficult question but from a theoretical, alberto, and practical, paolo, point of view, do you think that the trials should take these variables in to account? alberto mantovani: paolo, shall i start with immunology, and then we move to the real stuff, you are the real stuff. i mean, there are data on the immune response of the vaccines, and there is a paper that came out, i would say, four weeks ago, five weeks ago, and they had been presented at a meeting from the oxford group, on the response of elderly people. to be honest, i was surprised. i mean, paolo knows better than i do, that with influenza we have geriatric vaccines to elicit some kind of immune response so more antigen inoculant and i was surprised to see the data suggests that even people like me or you have as good a response as duccio, which doesn't make sense. okay, anyway, so that's the background. but, anyway at face value, i would accept that it's a good response. i didn't see a major difference in response between males and females which is, again, something with other vaccines that does occur. and that's more or less it. concerning drugs, i'm very concerned about inappropriate use of drugs. i mean, in the first wave, patients were given a lot antivirals. absolutely useless. you get toxicity because of that i keep hearing people taking that drug and it's inappropriate. the data suggests that it may have, of course, cardiac toxicity, central nervous system toxicity, and no reason why. and now i'm worried about glucocorticoids, i mean glucocorticoids being given outside of the-, i mean, you and lorenzo are the real experts. i mean, but in early covid, if they get early covid i don't want to get glucocorticoids early. leonardo m. fabbri: you're right. you're right. alberto mantovani: i'm an immunologist, i assume i understand something, and early on i wouldn't-, and the evidence is not there for that. so, those are inappropriate uses, concerning the multi-treatment of elderly people, i am not aware of data i'm afraid. leonardo m. fabbri: thank you. paolo? paolo bonanni: yes, of course. alberto has already replied to the question. i don't think we have the data now, at this point in time, to understand the difference in the antibody and the immediate response after a vaccine in people with chronic comorbidities. of course, i agree that if you give any vaccine to someone who is under a heavy immunosuppressive treatment, the vaccine usually doesn't work as it works in normal people without any treatment. but this is too early to understand now. i think we have to vaccinate all risk groups and we will have a lot of material to understand this in the next months. we cannot know everything since the beginning. so, it's the same when people ask me, 'how long will the protection last?' and i have to say, 'i don't know,' we have to follow up the vaccines and see if the protection is there for one year, two years and three years. so we would like to know everything since the beginning but, in this case, even more we have to follow up to see what happens and we will have dozens of thousands of people on which we could evaluate this in different studies in the coming months and the coming years. leonardo m. fabbri: you will have a lot of work in the next month. there are two questions from the audience. one is from a doctor: is corona, as i said, being used in china already? it's a question for professor fengming, yes. fengming luo: we have a vaccine for emergency use, we have the vaccine for some doctors with high risk for infection, for example, the department of pulmonary and critical care stand on the same side against covid – 19: scientific evidence on vaccine for covid-19 19 staff and also emergency room staff, also staff who work in the airport. these kinds of people can be injected with the vaccine right now based on their waiting. leonardo m. fabbri: when will you begin with the vaccination? to the doctors-, fengming luo: vaccinations, probably one or two months ago. leonardo m. fabbri: two months ago, okay. so, you have more experience than us. there is another question from dr mohamed amin to professor bonanni. it is very difficult. based on representation, which vaccine will have the best chance to succeed? paolo bonanni: probably i would say that a vaccine which is highly effective, a vaccine which also prevents infection in addition to disease but we want a vaccine which is able to prevent the vast majority of diseases and possibly, to add to that, an effect on infection and a vaccine which is practical. because, the other problem is the logistics and the cold chain. that's the reason why, i think, that the pfizer biontech vaccine is an excellent vaccine according to what we know today. the problem is, the difficulty is in the logistics, and it's not by chance that they already announced that they are preparing a second-generation vaccine for the coming months, because they realised that having to deal with minus 80 for transportation and to have to distribute the vaccine very quickly a few hours after you open the box is something that is okay for the first phases of application, but it cannot be done on a vast scale for a mass vaccination programme. leonardo m. fabbri: any other questions from the panel? from the faculty? alberto mantovani: can i comment on the last point? and then a question to paolo. or to everybody, i mean, not to paolo but to everybody. we should not forget that biontech-, we all talk about pfizer, but it is actually the biontech vaccine and that was developed by christoph huber and, i mean, that strategy was designed for cancer and for selected tumours such as melanoma, so small numbers and very restricted. so, i think there is this original sin, it comes from cancer research and for a very specific tumour and experimental therapy. my general comment, i'm very worried about how are we going to get results? i mean, the vaccine is in marathon, paolo, correct me, and we are getting results after the first five kilometres so how are we going to get the long term results with many vaccines? and we heard about china, we have russia the same and here were are going to have at least two, probably three vaccines available. i mean, in my hospital, how can i have-, it's an issue that we are discussing. how can i have physicians and nurses involved in a trial while we have available the emergency or the-, how are we going to solve that, you see? paolo bonanni: no, it's a challenge and i think there is no solution evident for us for this challenge. and also, the mixing of vaccines that will be given in the next months. so, if you have three, four, five, six vaccines available and we will give all of them, we will have issues in understanding the real effect of each vaccine. we should follow all groups of people vaccinated with a certain product, but we are also mixing populations so also the herd immunity effect might change the real picture. because, if a vaccine has a permanent effect, and another one which does not have that effect, but the people who got the second vaccine are living together with the ones who got the first vaccine, we are mixing up a lot of data and it's absolutely not easy. we should think of how to organise these kind of follow up studies, but i must admit it's very hard. and another thing i wanted to stress, i didn't stress this in my presentation, we have to be able to make a very complete and timely surveillance on adverse events following vaccinations, because this might be an incredible tract to the credibility of vaccination. so, there must be task forces on the territory able to take the notifications of adverse events following vaccination, and be able to verify the causality between the vaccine administration and adverse events. otherwise, i'm afraid we will be in trouble with millions of doses given at the same time and events occur statistically because they are there, but if we mix them and verify them after vaccination there might be people, and be sure that there will be people that will say, 'this is due to the vaccine and not by chance,' so, we must be very careful on this. fengming luo: maybe you can test the antibody before you take the vaccine? or it will cost a lot. paolo bonanni: yes, that's possible also to verify the genetics of antibodies but we must plan very, very well done studies and it's not easy with all these vaccines that will be used at the same time. leonardo m. fabbri: one question for bruce thompson, i mean, having such a low prevalence, what is the country's strategy for the vaccination? bruce thompson: this is a really interesting question and in fact, plenty of people in the media and other areas are, sort of, saying, 'well we're not in, necessarily, a type of rush,' because our borders are closed, they're going to remain being closed, especially when there's a main tourist from europe, asia, and the us. so, they're not going to open in a hurry. so, we've got time to wait, to actually start seeing which is going to be the most likely effective virus, and so, it was almost a comment, 'well let's see someone else take their lead first and see how it goes,' ultimately, what we're going to be doing is rolling out the pfizer vaccine, looks like it's going to happen in late march and the cold chain issue that we'd talked about before is a real issue for us, we're obviously, a very warm country as well and a very sparse country so, actually, transport and what have you is very difficult and also to roll out virus in such a sparsely l. corbetta et al. 20 large nation is actually very difficult. so, we're lucky in that we basically don't have any cases really, and it's a matter of now just sitting back and looking at the most effective way of rolling out the virus. but, as i said, we'll be starting to use the pfizer vaccine in march. leonardo maria fabbri: thank you very much. there is a question from bruno horta from brazil saying, 'brazil is facing varying infection cases nowadays. how comfortable should we be with vaccines facing 4,000 genomes of this virus?' that's a good question for alberto and paolo, i believe, and also duccio. alberto mantovani: i mean, there is an issue of reinfection. i think that a conservative of summarising the evidence is that it is a relatively rare event. very few documented cases there but of course, it's a relatively short follow-up. the second point concerns the stability of the virus, the spike protein which, as was illustrated by paulo, is the target of the vaccines in the pipeline, it is relatively stable. duccio discussed the 614 mutations, it doesn't affect recognition by the response elicited by vaccines, fortunately enough. of course, we may have variants coming up and they may be selected, i mean, duccio discussed about the evolution, they may be selected by deployment of the vaccines. i guess that is a possibility and we will see, we should be ready. leonardo maria fabbri: thank you. paolo, do you want to comment? paolo bonanni: no, i totally agree with alberto so no further comment. i think that a vaccine should be able to prevent for the coming months and probably, and hopefully, years, the coronavirus we know today, but we have to follow up and to verify that this is true also for the coming months and years. leonardo maria fabbri: well, thank you all. i give the lead to lorenzo to close the meeting. it was very interesting, thank you very much for devoting your time to this interesting event and instruptive event that will be posted on the website. lorenzo. lorenzo corbetta: thank you very much. we had thousands, maybe 5,000, 6,000 participants from china as usual, and hundreds, 500 of participants from the rest of the world. so, i thank you all for your very informative presentations and i hope to see you again and to have you in the next webinars because now it is a very, very hot topic the vaccine, and maybe in some months we will have many, many more information. thank you all, and see you soon. 1 citation: a. hocquet (2020) open science in times of coronavirus: introducing the concept of "real-time" publication. substantia 4(1) suppl. 1: 937. doi: 10.13128/substantia-937 received: may 11, 2020 revised: may 21, 2020 just accepted online: may 22, 2020 published: may 22, 2020 copyright: this article is republished from the conversation under a creative common licence. read the original article. copyright © 2020 by alexander hocquet. translated and republished with permission of the author alexander hocquet. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia feature article open science in times of coronavirus: introducing the concept of "real-time" publication alexandre hocquet archives poincaré, université de lorraine, & cnrs, nancy, france email: alexandre.hocquet@univ-lorraine.fr keywords. open science, pubpeer, peer-review, post-publication peer-review who doesn't have an opinion about hydroxychloroquine? the recent developments of the latest research in marseilles on the potential of this antimalarial drug to reduce the viral load of sars-cov-2 have been heating up.1 obviously, the current pandemic is a sudden and unprecedented health crisis. unexpectedness and scale are turning the outbreak into widespread panic: science is summoned to find solutions as soon as possible. in a sense, the worldwide situation is a way of asking how fast can science go. the famed publication from didier raoult's group2 allows us to highlight an evolution in peer review practices, and this trend allows us to question what it means to be "open" in science. drug development studies take years, even decades. the publication process that follows usually takes months or even years. it is increasingly difficult for scientific journals to find reviewers and to get the reviewers comments in time. the task of reviewing is burdensome. it usually is anonymous and voluntary, yet it is a liability since the reviewers’ comments are supposed to certify the validity of the publication. the volume of manuscripts submitted has been increasing exponentially. finding adequate reviewers and getting comments reported back in time has become a dauntless task for many journal editors.3 yet, in times of urgent crisis, with means and relations, a preliminary study can be done in a fortnight and published very quickly. after having submitted a manuscript to a journal on march 18, raoult's famous paper got its reviews back for publication... on march 20! in exceptional circumstances, exceptional publication times are key. the two reviewers therefore analyzed the publication and delivered their comments in less than two days. indeed, science seems to be able to speed up its process when emergency calls. what's new is that the critique of science can itself go very fast. in times of global panic, publications that deal with potential treatments for coronavirus are actually read, and even scrutinized by an attentive and numerous readership. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 937, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-937 https://theconversation.com/ https://theconversation.com/science-ouverte-en-temps-de-coronavirus-publication-en-temps-reel-136397 https://theconversation.com/science-ouverte-en-temps-de-coronavirus-publication-en-temps-reel-136397 http://www.fupress.com/substantia alexandre hocquet 2 among them are colleagues, competitors, doctors, pharmacists, microbiologists, statisticians, bio informaticians, mere curious readers, some enthusiastic, others malicious. a myriad of potential reviewers from a diversity of backgrounds, in sharp contrast with the officially appointed reviewers, who are seldom thematically far away from the authors. for scientific journals, peer review has been playing the role of certification (does the article deserve to be published?) but it also takes the role of evaluation (is the article good enough for such or such journal?).4 consequently, an article is considered cutting-edge science or not depending primarily on the prestige of the journal in which it appears, to the detriment of the evaluation of its content itself. journals prestige is key in defining a tiered system of publication. "publish or perish" has become "impact or perish".5 in contrast, pubpeer is a grassroots web platform launched in 2012, whose purpose is to potentially open a discussion forum about any scientific article. it was designed by its creators as the online version of a journal club (a sort of lab meeting where publications are critiqued) and was imagined out of the frustration that stems from the virtual impossibility to critique articles within the journals themselves. pubpeer is a form of post-publication peerreview. it is radical in the sense that anyone can comment, and can even comment anonymously. this "anyone can edit" principle is similar to wikipedia's principles, where a contribution can indeed be criticized or reverted by anyone, the difference being that in pubpeer, articles are commented but not edited. not unlike in wikipedia, the most affected articles are those that shine under the media spotlight.6 comments from people from different backgrounds entail multifaceted critique. in the pubpeer thread dedicated to raoult's article in our example,7 one can find a flurry of comments about such themes as the publication process, the compliance with the state of the art, medical ethics, statistical methodology, statistical processing... among many others. what's new is that it includes reanalyses, i.e. analyses that the commentator has inferred from the data provided by the authors, rather that from the publication text. reanalyses are carried out with the aim to design new calculations, new graphs, new interpretations, in order to put the "results and discussions" of the paper to the test.8 they can actually achieve this goal only if the data is provided by the authors, which is still far from systematic. the publication is thus becoming a sort of "live" paper, instead of being set in stone, just as a wikipedia article follows, by definition, a never-ending dynamics. in this regard, pubpeer looks like a social network. critics, reanalyses, and potential answers from the authors to their critics are discussed, debated. the article review itself is becoming a live process. in times of crisis, it may even turn into a bursting of interactions. the publication from didier raoult's group has been dissected in less time than it took to publish it: a hundred or so comments on pubpeer between mid and late march made the article look like a "real-time" publication. pubpeer is criticized among scientists for its anonymity and (sometimes rightly) for its denunciatory atmosphere... just as anonymity in wikipedia is criticized.9 in both cases, anonymity is seen by the community as a condition to enhance participation (since it allows to escape from the pressure of hierarchy or competition). on the other hand, it is viewed as cowardice by people who fear that anonymity may lead to the promotion of abuse. as michel dubois and catherine guaspare point out, the tension lies in what constitutes a "peer".10 how can a platform warrant potential commentators to feel free enough to contribute in a hierarchical and competitive scientific world, while at the same time protecting from malicious attacks? as in wikipedia, pubpeer possesses rules to ensure that attention is focused on content rather than on individuals, but as in wikipedia, malicious attacks do exist. amusingly enough, the exact same tensions and debates emerged when referees were becoming anonymous in mid-xixth century.11 another criticism of pubpeer (and wikipedia) is the pervasive obsession of contributors about technical details (such as image editing) rather than the substance of the articles.12 pubpeer founders respond that no faking of data is benign enough to be delegitimized as irrelevant.13 what happens on pubpeer is also performative: contributors play the role of moral entrepreneurs by defining through commentary what is acceptable or deviant.14 in a way, the thematic diversity of comments about didier raoult's publication does pubpeer justice to its "journal club" credentials. commentators from a wide range of backgrounds suddenly take an interest in hydroxychloroquine. what is key here is a situation of global emergency combined with the inclusiveness of access to critique. the situation allows for the emergence of a globalized, real-time journal club. it would be naive to see pubpeer as the enchanted world of "self-correcting" science progressing through disputatio. conversely, it would be equally naive to think that the publication system as it exists readily lends itself to constructive criticism. the vast majority of journal articles cannot be commented upon. the function of a publication is more about recording antecedence than to engage in debate, which the conservative structure of scientific journals discourages.15 as a matter of fact, pubpeer receives bad press in the quarters of scientific institutions. those institutions entice researchers into publishing their papers in "open access" and to make their data available, yet they criticize those open initiatives that they fail to control.16 everybody wants open science, but the scientific community finds it difficult to realize that encouraging open data (in the name of transparency requirements) results in the possible reuse of these data, and thus, among other things, in the availability open science in times of coronavirus: introducing the concept of "real-time" publication 3 of those data for post-publication critique, a critique that has been almost non-existent until now. some scientific journals are trying to change peer reviewing rules. several ideas are devised to separate evaluation from certification: reviews can be made before or after publication, they can be confidential or transparent, they can be spontaneous or invited, anonymous or identified. some new editorial practices transform a "version of record" into a record of versions, according to bianca kramer's phrasing.17 unfortunately, the most prestigious journals, those that make or break careers, are often maintaining the statu quo. the scientific landscape of journals is diverse, though. the situation of journals in the humanities, for example, is far from this depiction. pubpeer is actually most active in the field of life sciences where the likes of cell and nature concentrate the criticism from the scientific community. in this sense, the pubpeer platform not only undermines the conservatism of scientific journals. by questioning the peer review process, it questions the very utility of the concept of publication and scientific journals. even without going as far as extreme cases of retraction, the risk for the publication is to be contested in its role as a reference document, and the scientific journal its role as a gatekeeper contested too. alternative viewpoints about openness put inclusiveness at the centre of their concerns. it poses problems (such as the question of legitimacy) while trying to solve others, but it has the merit of raising awareness that some ways of being open are more complex and challenge more things than we imagine... like wikipedia does.18 acknowledgments the author wishes to thank jean claude guédon, marianne noël, konrad hinsen, christelle rabier and christophe pouzat for their insightful comments. references (1) evelyn, k. trump stops hyping hydroxychloroquine after study shows no benefit. the guardian. april 22, 2020. (2) gautret, p.; lagier, j.-c.; parola, p.; hoang, v. t.; meddeb, l.; mailhe, m.; doudier, b.; courjon, j.; giordanengo, v.; vieira, v. e.; dupont, h. t.; honoré, s.; colson, p.; chabrière, e.; la scola, b.; rolain, j.-m.; brouqui, p.; raoult, d. hydroxychloroquine and azithromycin as a treatment of covid-19: results of an open-label non-randomized clinical trial. international journal of antimicrobial agents 2020, 105949. https://doi.org/10.1016/j.ijantimicag.2020.105949. (3) halffman, w.; horbach, s. p. j. m. what are innovations in peer review and editorial assessment for? genome biology 2020, 21 (1), 87. https://doi.org/10.1186/s13059-020-02004-4. (4) guédon, j.-c. future of scholarly publishing and scholarly communication: report of the expert group to the european commission; 2019. (5) gaming the metrics: misconduct and manipulation in academic research; biagioli, m., lippman, a., eds.; the mit press, 2020. https://doi.org/10.7551/mitpress/11087.001.0001. (6) hocquet, a. wikipédia en tant que forum: une analyse de réseaux sociaux pour l’ethnographie de la production d’articles. in wikipédia, objet scientifique non identifié; barbe, l., merzeau, l., schafer, v., eds.; sciences humaines et sociales; presses universitaires de paris ouest: nanterre, 2015; pp 165–176. (7) pubpeer forum. hydroxychloroquine and azithromycin as a treatment of covid-19: preliminary results of an open-label non-randomized clinical trial, 2020. (8) hulme, o. j.; wagenmakers, e.-j.; damkier, p.; madelung, c. f.; siebner, h. r.; helweg-larsen, j.; gronau, q.; benfield, t. l.; madsen, k. h. a bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with covid-19. medrxiv 2020, 2020.03.31.20048777. https://doi.org/10.1101/2020.03.31.20048777. (9) larousserie, d. pubpeer, le site par qui le scandale de «l’inconduite scientifique» arrive. le monde.fr. october 23, 2018. (10) dubois, m.; guaspare, c. « is someone out to get me?» : la biologie moléculaire à l’épreuve du postpublication peer review. zilsel 2019, n° 6 (2), 164–192. (11) csiszar, a. peer review: troubled from the start. nature news 2016, 532 (7599), 306. https://doi.org/10.1038/532306a. (12) blatt, m. r. vigilante science. plant physiology 2015, 169 (2), 907–909. https://doi.org/10.1104/pp.15.01443. (13) pubpeer blog. vigilant scientists, 2015. (14) larregue, j.; saint-martin, a. troubles dans l’ethos scientifique. zilsel 2019, n° 6 (2), 149–163. (15) ross-hellauer, t. what is open peer review? a systematic review. f1000res 2017, 6, 588. https://doi.org/10.12688/f1000research.11369.2. (16) larousserie, d. le plan du cnrs pour lutter contre les tricheurs. le monde.fr. november 20, 2018. (17) sondervan, j. open science and open media studies — questions on a culture in transition by jeroen sondervan. open media studies. (18) hocquet, a. enseigner wikipédia par les anecdotes. the conversation. march 13, 2017. https://doi.org/10.1016/j.ijantimicag.2020.105949 https://doi.org/10.1186/s13059-020-02004-4 https://doi.org/10.7551/mitpress/11087.001.0001 https://doi.org/10.1101/2020.03.31.20048777 https://doi.org/10.1038/532306a https://doi.org/10.1104/pp.15.01443 https://doi.org/10.12688/f1000research.11369.2 substantia. an international journal of the history of chemistry 5(2): 121-128, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1201 citation: chetan (2021) disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india. substantia 5(2): 121-128. doi: 10.36253/substantia-1201 received: jan 27, 2021 revised: may 05, 2021 just accepted online: may 06, 2021 published: sep 10, 2021 copyright: © 2021 chetan. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan department of english, bharati college, university of delhi, india e-mail: chetansain@gmail.com abstract. the article focuses on the use of different kinds of disinfectants used for sanitization and cleaning of public and private places for curbing the spread of diseases from one place to another. multiple methods were employed for disinfection; some of which are easily accessible to the common people while others were particularly used in infirmaries and hospitals at the time of treatment. the article also shows that disinfectants were supplement to medicine and they were used to limit the contagion to a space whereas medicines were not accessible for the treatment of patients. historically, the eighteenth and nineteenth centuries witnessed an unprecedented development in the field of chemistry which led to the discoveries of different types of antiseptic solutions and disinfectants apparently endorsed by the germ theory. keywords: disinfection, sanitization, detoxification, public health, medicine, chemical compound, metal. amidst the rising number of covid19 cases across the globe, the health ministries and disease control agencies of different countries have been periodically issuing guidelines and protocols for people to safeguard themselves from the contagion. these guidelines give people psychological satisfaction that if they bring change in their lifestyle and live disciplined public life, then they would soon resume their daily choruses. medical researchers and health experts have revealed that people are required to be more conscious towards their personal hygiene and use disinfectants/sanitizers frequently in their homes and offices. in this context, the world health organization (who) and the us environmental protection agency (epa) have recommended a list of disinfectants, such as hydrogen peroxide, hypocholorus acid, sodium hypochlorite, sodium chlorite, calcium hypochlorite (bleaching powder)1 detergent powder and soap, to disinfect places. the indian ministry of health and family welfare also issued a brochure titled “covid19: guidelines on disinfection of common places including offices”2 to explain people what kinds of disinfectants to be used for cleaning indoor and outdoor spaces. the brochure also incorporated the list of cleaning agents (chemical compositions), details of hand hygiene and use of mask to encourage people for adopting clean ways of living. http://www.fupress.com/substantia http://www.fupress.com/substantia 122 chetan this article is a chronological study of disinfectants with an objective to trace and analyse how these sanitization methods were employed by administrative authorities and medical institutions in europe and india during the eighteenth and nineteenth centuries for confining diseases to specific locations. the article also gives an insight into four broad categories of disinfectants that were used in both civil and military firmaments against diseases and to provide clean and hygienic environment to patients in hospitals. it also studies the reasons for the recurring breakout of epidemics in slums of european cities in the nineteenth century despite persistent advocacy for disinfectants. the article also analyses the problem of frequent emergence of diseases in colonies and how they pressurized the colonial administration for pro-active steps to curb contagions. germ theory while people associated with different fields of science had been conducting experiments and analysing data to approve their theories of the existence of diseases causing agents in the air, it was in the nineteenth century that the ‘germ theory’ got recognition owing to the efforts of scientists and physicians like ignaz philip semmelweis, louis pasteur, robert koch and joseph lister. in this list, ignaz philip semmelweis, the hungary born physician and scientist, deserves special mention for his astonishing contribution in finding the causes for the death of labouring women in obstetrical and midwifery wards.3 in 1844, semmelweis took master’s degree in midwifery and applied for the position of assistant to the clinic of obstetrics in vienna general hospital. while working in the midwifery section of the hospital, semmelweis observed that “the disease from which prof. kolletschka (his friend) had died was identical with that from which i had seen so many lying-in women die.”4 his pathological discovery produced astonishing results as “the mortality of parturient women in the first clinic (where the entry of physicians and students working in mortuary and post mortem restricted) fell from 12% to 3% in the course of two months.”5 this plunge in mortality rate semmelweis attributed to following a simple practice of hand hygiene before entering the obstetrics wards but his inference was discarded by his colleagues and other physicians. although semmelweis’s discovery of pathological agent that cause puerperal fever in lying-in women was received with indifference, louis pasteur, robert koch and joseph lister consistently worked in this field and transformed the perception of people towards pathology and diseases with their revolutionary ideas and findings. sterilization of surgical instruments and cleaning the space with disinfectants considerably reduced in-hospitalization and post-operative deaths apparent from an article by a physician george f. elliott on ‘germ theory’6 wherein he credited professor lister for his experiment with carbolic acid (phenol) in surgical theatre. not only this, prof. elliott argued that the rooms where patients were taken post-surgery ought to be free from germs and therefore disinfected by means like fumigation, chemical solutions and spraying of germs killing deodorants. with the progress in healthcare procedures and medicines, the use of disinfectants was voraciously advocated by physicians, microbiologists, biologists and pharmacists to clean laboratories, dormitories, infirmaries, clinics, and areas ravaged by diseases.7 hence, disinfectants were used as supplementary chemical compounds that would help in killing germs and curbing the spread of diseases like cholera, smallpox and plague. types of disinfectants in the eighteenth and nineteenth centuries, disinfection was carried out in four distinctive ways – a) use of physical agents, b) use of chemical compositions, c) use of biological agents, and d) deodorants. physical agents were profoundly used for disinfection in the ancient time and remained the prime and easily accessible for the common people in the latter centuries. some of the common physical agents were i) boiled water –boiled water was the most common disinfecting agent in the ancient time. the greek philosopher aristotle suggested soldiers and army heads to boil water before drinking while fighting in areas unknown to them. he believed, “everything that may abide by fire had to be put into the fire and the rest had to be immersed in boiling water. he understood the need to avoid disease and instructed alexander the great that his armies boil drinking water and bury dung.”8 not only this, objects and clothes of medical professionals were disinfected by placing them in boiled water for a specific time period and then let them dry in the sunlight. the prevalence of this practice could be assessed from the fact that “in 1797, viborg recommended heating up to 64-65°c objects which had been in contact with the ‘contagious poison’ responsible for equine glanders”9 with the increasing level of contamination of rivers water, it became necessary to employ water filtration techniques for clean water in the 123disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india nineteenth century britain. on the one hand, the industrial waste was released in the rivers and on the other hand, water closets were connected with the main sewers. for instance – after the uplifting of ban on connecting the household water closets to the main sewer in 1815, the city of london faced the problem of clean water because household discharge was directly released in the thames. thereafter, the pressure was built on the local administration to supply clean drinking water to people particularly in wake of frequent outbreaks of cholera in sullied, congested pockets of cities in the first half of the nineteenth century. the local authorities took steps in this direction and provided clean drinking water for which investments were made in filters and water treatment technologies. those areas of the city where pipe water could not be reached, people were encouraged to boil water before drinking. in india, the practice of boiling water for drinking was quite old and diligently followed in many communities. health conscious people continued this ancient practice in the eighteen and nineteenth centuries for which they heat water under the sun and then filter it with gravel and charcoal. boiled water was a necessary component of medicine and dietary chart especially to those who fall sick from critical ailments. in the city of puri (princely state of keonjhar), victims of leprosy were given herbal medicine with boiled water and emphasis was laid on incorporating boiled water in diet. the dietary prescription with their stress on vegetarianism, demonstrate a significant level of hinduization. the stress on warm and boiled water seems particularly striking perhaps ref lects interaction with the colonial medical system.10 ii) fire – in the middle ages, people were scared of dead bodies afflicted from diseases. incineration of corpses, both human and animals, was perceived as the only way to avert contagion from spreading to others. the belongings of people died from diseases were immolated with the body and the premises where the death occurred sanitized and left unoccupied for nearly three months. additionally, the family members and the ones who came in contact with the person died of disease (like plague) were forced to burn their clothes else severe punishment was given on failing to comply with the social and cultural norms. another example of burning clothes came from the eighteenth century when families of those who died from tuberculosis were mandatorily placed everything in fire. iii) fumigation – sanitization of a place where a person died of contagion was a compulsory practice for which fumigation through herbs was aggressively promoted in the eighteenth century. burning of odoriferous herbs was a widely accepted practice to chase away insects in the streets and to disinfect clothes and objects of those suffered from mild diseases. the popularity of fumigation for sanitization could be understood from the advisory of english physician daniel layard issued in 1752 during the epidemic of cattle plague (‘contagious distemper’) – “the fumigation of stables using the following mixture: wet gunpowder, pitch, tar, brim-stone, tobacco, frankincense, juniper and bay-berries, [...] should be burnt, and the smoke confined in these stables, more than once”11 sulphur and mercury were two chemicals frequently used for fumigation of spaces and to detoxify objects that could not be immersed in boiled water. in india, susruta wrote in his book susruta tantra that the fumes of sulphur should be released in rooms used for surgical purposes to purify them from all kinds of impurities. disinfection through chemical compounds although there are several literary and non-literary records from the ancient times12 to testify the use of chemicals for detoxification and purification of spaces and objects, the pre-modern era (around renaissance movement) witnessed extensive research and application of chemicals like sulphur, mercury, sodium, calcium and others for sanitization purposes. in the last phase of the middle ages, europe became the centre of knowledge with endorsement to the classification of data and emphasis on empirical approach. practical chemistry received extensive attention along with the documentation and translation of books in many european languages. georg pawer, a german thinker, studied chemistry, physics and medicine in the 16th century and spent his entire life in understanding of mining and metal production. similarly, john pettus, an english scientist, had deep interest in metallurgy and mining that made him the member of society of mines royal and battery works in 1651. the impact of these developments could also be seen on chemical disinfectants and their uses i) sulphur sulphur and its derivatives were the main disinfectants used for sanitization of not only places but also objects used for the treatment of patients. 124 chetan owing to its awful smell and lethal impact on small plants and insects, sulphur dioxide was produced through chemical reaction or by burning the metal in fire. the fumes of sulphur dioxide easily spread in streets, houses and closed spaces. in the last quarter of eighteenth century, fumes of sulphur dioxide were used to disinfect spaces in england where the cattle plague wreaked havoc. the fear of infection was so deeply rooted in the minds of people that many european countries in the nineteenth century passed “rules not to take correspondences or letters from asian countries like india until they were sanitized in ships before unloading and then dispatched to the addresses after twenty four hours.”13 parcels shipped from the disease ridden colonies were first placed in a room and fumes of sulphur dioxide were released and then left them unattended for some-time before starting their deliveries. ii) mercury from the ancient time till the late nineteenth century, chemists and metallurgists observed corrosive properties of mercury that encouraged people to use the metal in medicines for treatments of diseases in both humans and animals. compounds of mercury were abundantly used for treatments of diseases like leprosy, syphilis, tuberculosis and other kinds of contagious diseases. robert koch, the nineteenth century german physician and microbiologist, demonstrated with his experiments that due to corrosive effect of mercury, it can sublimate the multiplication of microorganisms. although mercury was used in india prior to the british intervention in indigenous cures, the metal was aggressively endorsed by the british indian government for the treatment of syphilis in european soldiers. in the article “sexually transmitted diseases and the raj,” r. basu roy writes the mainstay of the treatment of syphilis in the 19th century was mercury. in india, mercurial preparations had been in use for years for the treatment of many non-venereal complaints, and its side effects were well known. in the case of syphilis, the army authorities did not like oral treatment with mercury compounds because of gastrointestinal side effects and the difficulty of securing compliance… in 1903 the expert adviser to the army at the time proposed repeated injections of “mercurial cream”, also known as “grey oil”, a suspension of metallic mercury in oil and fat which had been devised by lange in vienna in 1887 the metal was applied to the skin of patients.14 iii) copper – unlike mercury and sulphur, this metal was primarily used for manufacturing utensils and objects. people were familiar with corrosive property of copper apparent from its hostility to the growth of algae and fungi. in india, copper utensils were extensively used to store drinking water. in the eighteenth and nineteenth centuries, cholera ravaged several parts of india. hakims and veds recommended to their patients and their family members to store drinking water in copper utensils because the metal was known for its anti-microbial properties. iv) potassium permanganate (condy’s fluid) – crystals of potassium permanganate were dissolved in water to prepare a solution called condy’s fluid in which saucer and utensils of patients were dipped for some-time before placing them in running clean water. the solution was used to soak in the clothes of sick people and to spray on furniture kept in the rooms of patients. besides, the solution was used to disinfect rooms, halls, galleries and compounds of hospitals and even kept in hospital toilets to sanitize the hands of doctors. henry bollmann condy, an englishman chemist and industrialist, prepared condy’s fluid in 1857 to be used externally as well as internally. condy recommended not to use this fluid with carbolic acid because of their opposite properties. the fluid was purchased in abundance by cargo companies in the nineteenth century for the purification of ships. the british government released advisories for the cargo shipping companies to disinfect their coolie ships coming from cities like calcutta and bombay in the wake of frequent outbreaks of epidemics like cholera and plague. consequently, the manufacturers exploited the growing concerns of epidemics in britain and advertised their disinfectant products in newspapers advertisements that appeared in the kingston newspaper – the gleaner – during 1860s and 1870s proclaimed that condy’s fluid was strong enough to be used ‘to purify bilge water in ship’s well to parity with the interior or hold of a ship.15 v) carbolic acid (phenol) – carbolic acid gained popularity for its qualities of disinfection and antiseptic to treat wounds and other kinds of injuries. joseph lister, the british surgeon, acknowledged louis pasteur’s contribution of microbes and introduced carbolic acid as an antiseptic solution for sterilizing of surgical instruments. lister widely used carbolic acid to minimize post-surgical infections. owing to its highly inflammable qualities, carbolic acid was given to people in crystalline solid form. crystals were dissolved in water to prepare a solution 125disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india used for washing clothes, furniture, utensils, and to clean hands of attendants, sick and children. during the bombay epidemic 1896-97, the british indian government made steam disinfection mandatory near the quarantine centre and people coming to these centres were bound to take bath. besides, they were given douche of 2 per-cent solution of carbolic acid. clothes of patients and suspected people were immersed in 1-1000 solution of perchloride of mercury for ten minutes.”16 the pure form of carbolic acid was used for surgical purposes and its lotion was applied on ordinary sores and ulcers. the significance of carbolic acid at the breakout of cholera could be assessed from the report – ‘cholera: its nature, detection and prevention’ published in public health reports in 1910. the report highlights multiple uses of the acid including in the room with the patient, there should be a tub or other large vessel containing five per cent solution of carbolic acid crystals for the immediate reception of soiled linen… the stools and vomit of the patient should be disinfected at once by adding an equal volume of five per cent carbolic acid solution, five per cent formaldehyde solution, or milk of lime.17 vi) chlorine gas – carl wilhelm scheele discovered chlorine in 1774 and studied its properties that resulted in its massive industrial use like bleaching agent in paper and textile mills. considering the exclusive quality to disinfect, chlorine was used to clean portable water and to disinfect sewages but it did not find much use in hospitals and infirmaries since it caused irritation in eyes and lungs. chlorine gas was obtained through several methods but the one most often used was adding water to chloride of lime (bleaching powder) in small quantities. for the purpose of disinfecting rooms occupied by sick people, chlorine gas was obtained in large quantities using several chemical agents. vii) different kinds of acids – due to corrosive properties of different types of acids on some metals and stones, the use of such chemical liquids was aggressively adopted in the ancient times. among them, wine, alcohol, ink, lemon, sodium tartrate, sulphuric acid and vinegar were commonly used as medicines and disinfectants. for instance – vinegar was given to people having complaints of abdominal pain and wounds. lemon was advised to people for the treatment of many skin problems excluding leprosy and other deadly contagions. disinfection through biological agents this is one of the oldest techniques of disinfection in which decomposable and disintegrable matter is buried in soil to suppress the foul odour. human bodies, carcasses of animals and excreta are buried deep to expedite enzymatic degradation and to cut off oxygen supply that was assumed to activate chemical reaction and release unpleasant smell in the atmosphere. this practice apparently discards the concept of disinfection through fire owing to the acceptance of some unscientific explanations. for instance in many cultures, it was believed that bodies of people died from contagious diseases ought to be buried instead of burning them in woods as the smoke emerged out of pyre had pathogens that spread rapidly in the air. these pathogens reach to human beings through air and cause infection. disinfection through deodorants this kind of practice for disinfection was perceived essential to counter the spreading of diseases that might be caused by unattended carcasses of animals that release unpleasant odour. deodorants have the capability to subsume filthy smell with fragrance but lose their potentiality to remain effective disinfectants. some examples of deodorants were brown paper, tar fumes, acetic acid, ammonia, roasted coffee and pastilles. disinfectants, slums and personal hygiene in britain these methods of cleanliness and decontamination had profound impact on exterminating diseases and to reduce the circumference of epidemics to certain pockets or cities. however, it is equally important to take into account that the use of chemical agents for sanitization in the nineteenth century worked well in major metropolitan cities of europe like london, manchester, bristol, paris and others. since these cities witnessed the mushrooming of dark and filthy slums infested with pathogens at the time of industrial revolution, the disinfectant solutions emerged as potent tools for the government authorities to curtail the spreading of diseases and to safeguard the premises of upper class people. in the article “the public’s view of public health in mid-victorian britain,” the authors argued the sanitary reforms in the 1830s, 40s, 50s and 60s bounded authorities for providing better hygienic conditions to the city dwellers and induced perceptual change among them for living healthy life. for example – in the cholera epidemic 126 chetan of 1848-49, people did not resist against cleanliness drive as they had objected to in the cholera outbreak of 1831-32. in 1848-49, people “allowed cholera victims to be removed to houses of recovery or special hospitals. these institutions were operated, on official anticontagionist lines, not to isolate victims as such, but to remove them from the poisonous conditions which had produced their disease.”18 with regard to personal hygiene and home cleanliness in the slum, it was found that “certain families were clean and wholesome while their immediate neighbors were filthy and verminous.”19 this aspect of personal and social hygiene opens up the seamy side of institutional and governmental negligence. instead of putting onus on individuals for their inability to adopt clean ways of living owing to poverty, it criticized utilitarian approach for affixing people’s habits with their birth. to highlight the administrative failure in providing better facilities, examples of local governments and their indifference towards improving the constantly increasing slums ought to be cited. for instance – during the outbreak of cholera in 1831-32, liverpool was one of the worst overcrowded cities with extremely poor amenities and a large section of the population living in slums. more than half a million people migrated to liverpool from ireland in the first half of the nineteenth century that put a lot of pressure on the city’s infrastructure. since the population density was very high in slums and basic amenities like disposal of waste and supply water were almost absent, cholera spread at a rapid pace in which 1523 people died out of 4977 cases in the city.20 one of the main reasons for such pitiable conditions of industrial towns was the corruption and strong class biasness apparent from the sanitary works undertaken in the nineteenth century. while chadwick’s sanitary report (1842) recommended providing, better amenities to people living in filthy slums where atmospheric impurities accelerated diseases, the local governments worked on “piped water, glazed sewers, street widening, drainage and paving were to be found first in the areas where rate payers, local councillors traded or lived.”21 disinfectants, indigenous medicines and colonial india british colonies offered more complex conditions with limited access to medicine and sanitization products. britishers were dependent on natives for various kinds of menial works including cleaning of toilets, disposable of sewages, fetching water from wells and domestic choruses. in the absence of modern disinfectants, british administrators and soldiers were vulnerable to native diseases even in their cantonments. j. r. martin, presidency surgeon of bengal and later president of the eic’s medical board, argued that the natives lack habits of personal hygiene owing to their deep rooted belief in religion. on the one hand, martin admired the efforts of william bentinck for his utilitarian approach to introduce social and cultural reforms in india; on the other hand, he vehemently criticized the bengalis for their poor hygiene habits and wrote the natives have yet to learn that the sweet sensations connected with cleanly habits, and pure air, are some of the most precious gifts of civilization. neither did they seem to be impressed by the importance of pure water. everywhere one finds the tanks in an impure and neglected condition.22 the concerns of surgeon martin did not vanish even after lapsing of several decades and investments in healthcare with the opening of hospitals and dispensaries. e carrick freeman captures the fear of british people and challenges they have to face in india owing to the primitive habits of natives, the face of the country, wherever the population is at all dense, as little may be regarded as little better than one huge latrine. the purifying and germicidal agencies which tend to counteract the evils of this state of affairs are the intense heat and light of the sun, extreme dryness of the air in many parts and length, volume, and rapid flow of the great rivers.23 in this regard, sir william moore, surgeon general with the bombay government, prepared a comprehensive manual titled a manual of family medicine and hygiene for india, published in 1889 to educate british men and women in domestic (indigenous) medicine and their preparations. he also elaborately discussed the management of room occupied by sick, application of local disinfectants, preparing medicines from indigenous items in emergency and instructions on protecting oneself during epidemic. on the non-availability of modern medicines and sanitary products, surgeon moore prepared a list of medicines with their hindustani names that could be easily purchased from local bazars – english names hindustani names alum phitkarree camphor kafoor sulphur ghundak potash, nitrate of, salt petre shora source a manual of family medicine and hygiene for india. the manual comprehensively explained the need to 127disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india dispose discharge of sick like vomit, urine, and bowels during epidemic outbreak, disinfection of rooms with proper ventilation and charcoal; disinfecting clothes, utensils and furniture with chemical compounds like carbolic acid or condy’s fluid (if available) or with boiled water to kill germs. moore also emphasized on personal hygiene especially in tropical climate. the complexity could also be understood from the fact that on january 18, 1924, e. h. hankin24 wrote a letter highlighting the major challenges for british troops and officers owing to the lack of awareness for sanitization among indians. based on his personal experiences, hankin pointed to the autocratic and hierarchical system as obstacle in providing safe environment during cholera outbreak. hankin discovered that filters used for cleaning drinking water could not kill germs that cause cholera. hence, military officers, administrators, soldiers, engineers and others, who came alone or with their families to colonies to serve the british empire, had to be trained in indigenous items that could be used as alternatives of western products. although the british administered indian cities witnessed infrastructure development, they were still far behind to their counterpart cities in england especially in terms of decongestion plans, sanitary works, drinking water supply and drainage system. owing to the poor infrastructure in the indian cities, british families were taking necessary precautions to stop the incursion of diseases in their residences for which they exclusively invested in disinfectants. dining tables, cutlery and crockery were cleaned with dish bar and detergents. in case any family member was ill, tableware were not only cleaned with dish bar but also shown to steam heat or immersed in boiling water. these conditions provided favourable environment to druggists and chemists to exploit the demand of english medicines and chemicals compounds in india. consequently, british pharmacies selling western medicine started to sprout in major indian cities to meet the requirements of british officers who gave preference to modern methods of treatments over indigenous techniques of cure and prevention. on tracing the history of pharmacies in india, it is found that the first chemist shop named bathgate was opened in 1811 at lal bazar in calcutta followed by opening of a pharmaceutical company in 1812 by the two british surgeons john robinson and james williamson who primarily dealt in apothecary and surgical instruments. assessing the drug list of pharmaceutical company thomson and taylor, it is found they dealt in more than “three thousand items which included surgical instruments, chemical, physical and pharmaceutical apparatus, dental goods, electrical apparatus, microscopes, bacteriological goods, spectacles, photographic goods, medicine chests, foods and dietary preparations, aerated waters, proprietary preparations, toilet and nursery requisites, patent medicines, wines and spirits, and hospital requisites.”25 these items were promoted through catalogues that were circulated with newspapers. medical journals like chemist and druggist regularly published advertisements of those products that might see huge sales in the indian market considering the country’s climate and paucity of resources. products used for sanitization had good demand in the market owing to perpetual fear of contamination and frequent outbreaks of epidemics. conclusion disinfectants remain integral to the activities of people knowingly or unknowingly inherited from their ancestors. as and when new compounds hit the market, people resist to their adoption but gradually homogenize them in their lives considering their benefits. analysing the history of disinfectants, it is not wrong to say that these compounds and techniques of disinfection in the past were primarily targeted at controlling diseases from spreading to others but their utility has changed in the contemporary times as precautionary items to protect people and to maintain personal hygiene. families, in metro cities, use disinfectants on daily basis to clean floors, toilets and bathrooms that ensure healthy and illness free lives. demand of disinfecting products spirals with the rapid circulation of information and the onslaught of seasonal diseases. in the present times, it becomes imperative to depend on chemical disinfectants for protection against pathogens. references and notes 1. united states, environmental protection agency, 2020 list n: disinfectants for use against sarscov-2, 2020 retrieved from website: https://www. epa.gov/pesticide-registration/list-n-disinfectantsuse-against-sars-cov-2 2. ministry of health and family welfare, india, covid-19: guidelines of disinfection of common public places including offices, 2020 retrieved from: https://www.mohfw.gov.in/pdf/guidelinesondisinfectionofcommonpublicplacesincludingoffices.pdf 3. semmelwies tried to prove that the mortality rate in obstetrics clinics could be drastically cut down if the physicians and students examining lying-in women 128 chetan should wash their hands thoroughly with chlorine water. 4. richard cold newton, a brief study of the contribution of ignaz philip semmelwies to modern medicine. william wood company, new york, 1910, p 12. retrieved from https://archive.org/stream/ b28978250/b28978250_djvu.txt 5. ibid. p 12. retrieved from https://archive.org/stream/ b28978250/b28978250_djvu.txt 6. george f. elliot, “the germ theory.” the british medical journal, 1870, 1: 489. retrieved from https:// www.jstor.org/stable/25218933 7. it is important to mention here that the process of disinfection in the mid-nineteenth century was not mere an exercise to suppress foul smells coming from certain gases produced by living matter called miasmas. in the initial years of 1860s, joseph lister popularized the use of antiseptic in surgical practices that drastically reduced the death of patients from sepsis. lister’s techniques were widely adopted in britain and abroad. these kinds of new medical practices endorsed the germ theory which received unprecedented acceptance in the public and private domains. 8. seymour s. block, (ed.) disinfection, sterilization and preservation. philadelphia: lippincott williams & wilkins, 2001, p 3. 9. j. blancou, “history of disinfection from early times until the end of the 18th century.” rev. sci. tech. off. int. epiz., 1995, 14:1, p 35. retrieved from https://www.oie.int/doc/ged/d8963.pdf 10. biswamoy pati and mark harrison, (ed.) the social history of health and medicine in india. delhi: routledge, 2009, p 306. 11. michael bennett, war against smallpox: edward jenner and the global spread of vaccination. cambridge: cambridge university press, 2020, p 26. 12. in the odyssey, homer mentions the demand of protagonist to burn sulphur in the house to detoxify and purify the space after its return from the soil of rival. 13. “disinfection of mail.” vadophil: quarterly news bulletin. vadodra: 131-132, 2012, p 12. retrieved from http://www.vadophil.org/ 14. r. basu roy, “sexually transmitted diseases and the raj.” sexually transmitted infections. 1998, 74:1, p 21. retrieved from https://sti.bmj.com/content/74/1/20 15. nilanjana deb, “(re)moving bodies: people, ships and other commodities in the coolie trade from calcutta.” in commodities and culture in the colonial world. ed. supriya chaudhuri, josephine mcdonagh, brian h. murray & rajeswari sundar rajan. new york: routledge, 2018, p 326. 16. sir james macnabb campbell,  report of the bombay plague committee – appointed by the government resolution no 1201/7201 on the plague in bombay for the period extended from the 1 july 1897 to the 30 april 1898. (bombay: times of india steam press, 1898, p 197. retrieved from https://archive.org/ details/b24974535 17. a. j. mclaughlin. “cholera: its nature, detection and prevention” public health reports. 1910, 25:44, p 1577 18. michael sigsworth and michael worboys, “the public’s view of public health in mid-victorian britain.” urban history, 1994, 21:2, p 242. doi:  https://doi. org/10.1017/s0963926800011044 19. ibid p 246. d oi: https://doi.org/10.1017/ s0963926800011044 20. srabani sen, “indian cholera: a myth.” indian journal of history of science, 2012, 47:3, p 367. retrieved from https://insa.nic.in/writereaddata/uploadedfiles/ijhs/vol47_3_2_ssen.pdf 21. michael sigsworth and michael worboys, “the public’s view of public health in mid-victorian britain.” urban history., 1994, 21:2 p 241. doi:  https://doi. org/10.1017/s0963926800011044 22. j. r. martin, notes on the medical topography of calcutta, calcutta, 1837, p 43 23. e carrick freeman, the sanitation of british troops in india. london: redman limited, 1901, p 8 24. e. h. hankin was british bacteriologist and naturalist who studied malaria, cholera and other diseases. hankin worked under the guidance of robert koch in berlin and then with louis pasteur in paris. in 1892, hankin was offered the position of chemical examiner, bacteriologist and government analyst by the united provinces and the central provinces. retrieved from https://www.jstor.org/stable/43430692 25. stuart anderson, “travelers, patent medicines, and pharmacopeias: american pharmacy and british india, 1857 to 1931.” pharmacy in history. 2016, 58:3-4, p 66. https://www.jstor.org/stable/10.26506/ pharmhist.58.3-4.0063 substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 4(2) suppl.: 57-67, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1030 citation: a. garrido sanchis, b.w. ninham (2020) very high efficiency of e. coli inactivation by body temperature co2 bubbles: in pursuit of mechanism. substantia 4(2) suppl.: 57-67. doi: 10.36253/substantia-1030 copyright: © 2020 a. garrido sanchis, b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. very high efficiency of e. coli inactivation by body temperature co2 bubbles: in pursuit of mechanism adrian garrido sanchis2,*, barry w. ninham1 1 department of applied mathematics, research school of physical sciences, the australian national university, canberra, australia 2 school of sciences, university of new south wales, canberra, australia *corresponding author: a.garridosanchis@adfa.edu.au abstract. a co2 bubble column (cbc) has been developed as a body-temperature lab-scale water sterilization process for the inactivation of pathogens. both co2 and combustion gas bubbles inactivated escherichia coli c-3000 (atcc15597) with extraordinary efficiency in solutions with low alkalinity. the mechanisms of inactivation were not known. to characterise the phenomena a new first-order kinetic equation that correlates e. coli inactivation rates with a total alkalinity of the solutions has been developed as a first step towards understanding. this leads us to propose a new mechanism of inactivation. keywords: e. coli, water reuse, carbon dioxide, combustion gas, alkalinity. 1. introduction water-borne pathogens remain one of the leading risks to public health worldwide. the world health organisation (who) estimated that over 30 million cases of diseases and millions of deaths could be caused by pathogen-infected water sources, globally, each year.1 the inactivation of microorganisms like bacteria and viruses in aqueous solutions is a perpetual challenge. for example, pathogenic bacteria present in water used in food or pharmaceutical manufacture can cause product contamination. in a bigger scenario wastewater from agricultural or industrial uses or water obtained from environmental flows, contains pathogenic microorganisms that need to be inactivated before the water is used for industrial or agricultural purposes or drinking water. this is an existential problem for humanity. present methods for inactivating viruses, bacteria, and other microorganisms include heat, irradiation (e.g. ultraviolet treatment), treatment with chemicals (e.g. ozone), high-pressure treatment, and filtration (e.g. membrane filtration). many of these methods, especially, heat treatment, are energy-intensive. more energy-efficient treatment technologies are desperately needed. 58 adrian garrido sanchis, barry w. ninham high density and high-pressure co2, known as dense phase carbon dioxide (dpcd), is being used as a non-thermal disinfection alternative.2,3 our process is different. we have previously studied co2 sterilization effects at atmospheric pressure in a bubble column on e. coli and viruses. the process has been implemented commercially. we found that for both pathogenic groups the sterilization effects increase with the temperature.4 it is of much interest that inactivation becomes optimal above 38 degrees, body range temperature. carbon dioxide, being a greenhouse gas, is assigned some responsibility for global warming. but it is also literally vital for plant growth. recently it has been shown likely to be nature’s way of controlling viral infection in the human body, following from these co2 antiviral properties a recent study has identified the use of body temperate humidified co2 as a possible early therapy to mitigate infection in covid-19 patients.5, 6 many alternatives to reduce co2 emissions have been proposed, apart from planting trees and controlling bushfires. geological sequestration in depleted gas and oil reservoirs, ocean storage, seaweed production, co2 mineralization are just a few. sterilisation by co2 has been widely used throughout history. after sodium chloride, natron, sodium bicarbonate is probably the first industrial-scale chemical used by mankind. natron, in ancient egypt, was essential for mummification. the still and little understood peculiar hydration properties of the bicarbonate ion in contact with air affects both tissue dehydration and sterilization against bacterial degradation. the magic of the bicarbonate ion has remained, with the still unexplained problem of roman and other cement formation. the foundation of physical chemistry can arguably be marked by berthollot’s observation that reactions are temperature dependent: he saw soda-lime, sodium carbonate rocks instead of the calcium carbonate on the banks of the nile river during napoleon’s scientific expedition to egypt in 1792. the normal precipitation of calcium carbonate from a sodium chloride calcium carbonate solution is reversed at high temperatures of the drying nile flood in summer. the astute chef and detergent companies know that wet sodium bicarbonate is extremely effective in cleaning. it cuts peptide bonds of proteins bound to saucepans or dishes. but why? 1.1. nature of the present studies the work here presented studies the e. coli inactivation effect of co2 at different alkalinity levels at 38 °c (human body temperature range) and atmospheric pressure. alkalinity is defined as the ability of water to resist changes in ph when acids or bases are added to the solution or the capacity of water to neutralize acids. the co2carbonate system describes which of the four forms of total inorganic carbon (molecular aqueous co2, carbonate ion, co3-2, bicarbonate ion, hco3-, or carbonic acid, h2co3) is the dominant species as a function of ph.7,8 we have analysed our results within the boundaries of the accepted theory of physical chemistry of solutions. this allowed the development of a new first-order kinetics equation that correlates e. coli inactivation rates with total alkalinity when bubbling co2 or combustion gases in a bubble column at atmospheric pressure and body temperature. but while it fits the data it does not account for why the process is efficient. we are then led to such an explanation outside the confines of classical theory. 2. materials and methods 2.1. coliform bacteria escherichia coli is a gram-negative bacterium with a straight cylindrical rod shape of 1.0-2.0 µm size.9 e. coli are harmless, can be found in the intestines of healthy humans and animals but some are pathogenic to the host. as a result of fecal contamination, it can be found in water and soil. its presence in water is used as an indicator to monitor water quality.10 the strain e. coli c-3000 (atcc15597) is a biosafety level-1 organism11 which was selected as a representative model for bacterial contamination in water.12,13 spinks at al.14 demonstrated that pathogenic bacteria are inactivated in a temperature range of 55 to 65 °c. other studies found that e. coli presents the first signs of thermal inactivation at temperatures over 55 °c, with high inactivation rates at 60 °c.15 an overnight e. coli c-3000 (atcc 15597) culture was grown in 10 ml broth (see section 2.3 for more details) without agar at 37 °c for 18–20 hours in a labtech digital incubator, model lib-030m, while shaken at 110 rpm by a psu-10i orbital shaker. 2.2. experimental solutions solutions with different alkalinity levels (see table 1) were prepared and sterilized by autoclaving in an aesculap 420 at 15 psi and 121–124 °c, for 15 minutes.16 a standard secondary-treated synthetic sewage medium (organisation for economic co-operation and 59very high efficiency of e. coli inactivation by body temperature co2 bubbles development (oecd) medium) was prepared according to water-quality guidelines and standards.17,18 the official journal of the european community for secondary-treated water quality has the following requirements for discharges from urban wastewater-treatment plants: 125 mg/l of cod; 2 mg/l of total phosphorus; and 15 mg/l of total nitrogen.19 this solution was designed to meet the european standards by using the following ingredients in a liter of boiled tap water or milli-q water (depending on the experiment): 120 mg of peptone; 90 mg of meat extract (replaced here by bovril® according to recommendations in biology of wastewater treatment20); 30 mg of urea; 13 mg of dipotassium hydrogen phosphate; 7 mg of sodium chloride; 2 mg of calcium chloride dehydrate; and 2 mg of magnesium sulfate heptahydrate. two nacl solutions with concentrations of 0.001 m and 0.17 m nacl (nacl ≥ 99% purity, obtained from sigma-aldrich) in milli-q water, a 0.01 m cacl2 solution (cacl2.≥ 99% purity, obtained from sigma-aldrich) in milli-q water and tap water. these concentrations were chosen to coincide roughly with the physiological concentration of humans and to typical environmental conditions faced by the bacterium. to ensure the full elimination of chlorine from tap water it was previously boiled for 30 minutes, therefore e. coli (c3000) was not affected by the disinfecting action of chlorine. 2.3. e. coli growth media the plate count method21 is commonly used for the detection of e. coli in, both wastewater and marine water. the degree of contamination in water is assessed based on the ability of bacteria to propagate forming colonies in a layer of agar.22 for each bacterial-growth experiment, two broths were prepared (a and b). broth a was prepared with 1 g of yeast extract, 6 g of nacl, 13 g of tryptone, and 1,000 ml of milli-q water. this medium was aseptically distributed into two vessels containing 1.41% agar and no agar, respectively; the agar used in the experiments was molecular-biology grade from sigma-aldrich. the medium was heated to boiling to dissolve the agar and sterilized by autoclaving for 15 minutes in an aesculap 420 at 15 psi and 121–124 °c. broth b was used to improve the viability of the bacteria. it was prepared by adding 0.010 g of thiamine and 1 g of glucose to 50 ml of milli-q water and filtered through a 0.22 µm filter for its sterilization. once cooled to 50 °c, it was added aseptically to broth a in a proportion of 1:19. the resulting 1.34% agar medium was poured into 100mm × 15mm petri dishes and dried above a bunsen burner to maintain local environmental sterility until the agar was not too dry nor too moist.23 2.4. co2 bubble column (cbc) process the cbc process used two different gases: co2 and combustion gases. a flow of 24 l/min of co2 was pumped through the electrical heater that maintained the gas temperature just above the sinter surface at 38°c for the co2 experiments. when using combustion gases, the exhaust pipe of an lpg gas generator (greenpower 2.5 kw) was attached to an isolated metal pipe with a valve that provided an exhaust-gas flow rate of 27 l/min through the bubble column reaching a temperature of 58 °c just above the sinter surface. the base of the bubble column evaporator was fitted with a glass sinter (type 2) of 135 mm diameter and pore size 40–100 µm. once the experimental solutions (0.17 m nacl, 0.01 m cacl2, 0.001 m nacl, secondary treated synthetic sewage made with milli-q water and tap water) were poured into the column, the temperature of the solution was measured with a thermocouple in the center of the column. hot bubbles of both gases passed through the sinter into the 300 ml solution, inactivating e. coli. the sterilization effects of other gases like air, argon, and nitrogen on e. coli have been discussed24, they are not significant compared with co2 bubbles, especially at low temperatures. 2.5. experimental setup and procedure the cbc treated 0.17 m nacl, 0.01 m cacl2, 0.001 m nacl, secondary treated synthetic sewage made with milli-q water, and tap water containing e. coli c-3000 (atcc15597) at inlet co2 temperature of 38 °c, and combustion exhaust gas from an lpg generator at 60 °c. the plate count method25,26,27 was used to assess the viability of e. coli. samples were collected from 10–15 mm above the central area of the bubble column. each sample of 0.1 ml was spotted in triplicate. alkalinity measures the acid-neutralizing ability of dissolved substances in water and is equivalent to the amount of strong acid required to lower the ph of the solution from an initial value to about 4.2. the total alkalinity of each solution, in mg/l caco3, was determined by the amount of 0.02 m hcl added in a titration until a ph electrode (thermofisher scientific) measured an end ph of 4.2. the initial ph of the sample of each of the 6 solutions was less than 8.3 therefore the alkalin60 adrian garrido sanchis, barry w. ninham ity was calculated with the carbonate ion concentration multiplied by a factor of two since each [co3-2] ion neutralised two protons28, see table 1. 2.6. data analysis the linear decay model was used to study the inactivation of e. coli over time in cbc.24,29,30 the evaluation of viable e. coli in the samples was performed using the plate count agar (pca) method.23,26,31 plate counts numbers indicate the number of e. coli colonies that grow on the surface of a solid and translucid agar media in a petry dish. the mean and standard deviation of each triplicated sample was obtained using bacteria survival factor, log10(cfu/ cfu0), where cfu0 is the initial number of colony-forming units (cfu) per sample and cfu is the number of e. coli colonies per sample after a set exposure time to the co2 bubbles.32 when analysing the data we assumed that the inactivation of e. coli by co2 in different alkaline solutions follows first-order kinetics. we proposed a model that uses the decimal reduction time (d-value) to measure how the alkalinity of a given solution can influence e. coli inactivation. the d-value is defined as the time, in minutes, needed to inactivate 90% (i.e. 1-log ) loss of e. coli. d-values were calculated using a linear exponential decay model. log(cfut)=log(cfu0)– [1] [2] here, is the number of e. coli colonies at time t, = the initial number of e. coli colonies, d= the decimal reduction time, -(1/d) = the slope of the curve. 3. results and discussion 3.1. cbc process inactivating e. coli at 38 °c and one atmosphere zhong et. al.33 observed that when bubbling co2 in different electrolyte solutions, their ph dropped until it reached a steady value in less than 10 minutes; this value was different for each solution. similar behavior was observed when co2 gas at 38 °c and combustion gases were bubbled for 10 minutes through six different solutions (0.17 m nacl, 0.01 m cacl2, 0.001 m nacl, secondary treated synthetic sewage made with milli-q water and tap water) in the bubble column (see table 1). the absorption of co2 into different solutions increases when co2 gas is bubbled through the sintering area in a bubble column; many bubbles are produced with a large co2-liquid contact surface that is continually produced. when co2 dissolves in water 99% stays as the dissolved molecular gas and less than 1% as carbonic acid (h2co3 (equations 1 and 2) which reduces the ph of the solution (see table 1). carbonic acid dissociates into bicarbonate ion (hco3-) and carbonate ion (co32-) (see equations 3 and 4).34 co2(g)→co2(aq) [3] co2(aq)+h2o(l)⇆h2co3(aq) [4] h2co3(aq)⇆h++hco3-(aq) [5] hco3-(aq)⇆h++co32-(aq) [6] this is the reason why the ph of every solution dropped (see table 1) and was different from that of the other solutions.34 when a 24 l/min flow of co2 passes through a single glass tube immersed in a beaker containing e. coli in 300 ml of 0.17 m nacl the big bubbles of 1-3 cm diameter do not inactivate the pathogens.4 however, when the same flow of co2 gas at the same temperature in the same solution is bubbled through a sintering area in a bubble column e. coli inactivation occurs. the bubble column produces many small co2 bubbles (1-3 mm diameter). the consequent co2 dissolution rate increases due to the large co2-liquid contact surface that is constantly produced. mass transfer from the co2 to the liquid depends highly on the interfacial area (α).4 this increases the amount of co2 dissolved in the solution and produces a similar sterilization effect to what can be achieved by raising the pressure in dense phase carbon dioxide (dpcd) processes. the overwhelming advantage of the bubble column delivery is that only atmospheric pressure is required. a possible mechanism previously described4, could explain in part why e. coli (doesn’t work for viruses) can be inactivated by bubbling co2 at body temperature in a bubble column. it is that the ph decreases when co2 dissolves in a solution and this acidification of the solution increases the binding of bicarbonate ion to bacterial membrane phospholipid head groups. the resulting change in the head group area and membrane structure to an open mesh phase then allows free diffusion of co2 through the bacterial membranes. the co2 inside the cell produces an intracellular ph decrease that exceeds the cell’s buffering capacity, resulting in cell inactiva61very high efficiency of e. coli inactivation by body temperature co2 bubbles tion.35,36 orij et al. observed that saccharomyces cerevisiae cell division rate is controlled by intracellular ph changes and low intracellular ph could reduce the cell division.37 this idea has a degree of plausibility and may well contribute to bacterial inactivation. however, it does not explain the inactivation of viruses. when co2 was bubbled at 38 °c through 0.17m nacl and 0.001 m nacl solutions (made with milli-q water) in the bubble column evaporator, for both solutions, 0.6-log of e. coli inactivation was observed after 10 minutes due to the high co2 surface area in the solution (see fig. 1). this occurred even though the two solutions had very different bubble densities. when using secondary-treated synthetic sewage and 0.01 m cacl2 (both made with milli-q water), a 0.2-log and 0.3 log reduction of e. coli was achieved respectively after 10 minutes (fig. 1a and table 1). however, when the same experiment was conducted with boiled tap water and with secondarytreated synthetic sewage (made with boiled tap water), no inactivation was observed after 11 minutes (fig. 1a). when combustion gas from a generator (with 12.5–14% of co2)38 at 60°c was used in the bubble column experiments an e. coli inactivation rate of 2.6-log in 0.17 m nacl solutions (made with milli-q water) was observed after 10 minutes.24 however, when using secondary-treated synthetic sewage (made with boiled tap water) no inactivation was detected after the same period (fig. 1b). this is consistent with the hypothesis that reduced ph buffering capacity aids inactivation. within the combustion gas, other products than co2, h2o, and n2 could be present due to minor components and impurities in the fuel and different fuel/air ratios. these gases are carbon monoxide (co), hydrogen (h2), sulfur oxide (so2), and mono-nitrogen oxides (nox) such as no and no2.38 even with the presence of these gases, no inactivation was observed. the tap water used in this work had a total alkalinity of 87.4 mg caco3/l (table 1), and an initial ph of 8 and therefore can act as a buffer solution. after bubbling co2 the ph was reduced to 4.9 for the pure tap water and 5.4 for the secondary-treated synthetic sewage, with an alkalinity of 94.5 mg caco3/l (table 1). this ph is too high to allow the penetration of the co2 through the membranes, with a consequent lack of e. coli inactivation when using the cbc process in solutions with high alkalinity. milli-q-water-based solutions had a reduced buffer capacity of only 6 mg caco3/l (table 1), reaching low ph values of 4 for nacl and cacl2 based solutions. for milli-q-water based secondary-treated synthetic sewage the ph reached 4.4 and the total alkalinity value was 27.7 mg caco3/l (table 1); this solution contains different salts that can slightly increase its alkalinity, with a consequent reduction in inactivation. 3.2. effect of alkalinity on e. coli inactivation when bubbling co2 and combustion gases decimal reduction times (d-values) (table 1), calculated from inactivation values, have been used to understand the effect of alkalinity on e. coli inactivation. to do this, we compared e. coli inactivation performance of the cbc when using body temperature co2 with that of combustion gases for six solutions (0.17 m nacl, 0.01 m cacl2, 0.001 m nacl, secondary treated synthetic sewage made with milli-q water and tap water) with different alkalinity values, see fig. 2. the correlation between the log of the d-values and the corresponding total alkalinity is shown in fig. 2 and table 1. a d-value is a time needed to inactivate 90% (i.e. 1-log) of the e. coli. to measure the impact of alkalinity on e. coli inactivation when bubbling co2 we have proposed figure 1. (a) comparison of e. coli inactivation with co2 at 38 °c in a bubble column in 6 different solutions; (b) e. coli inactivation with combustion gas at 60 °c in a bubble column in 2 different solutions. 62 adrian garrido sanchis, barry w. ninham the new al-value. th e al-value gives the total alkalinity required to change the d-value by a factor of 10 and refl ects the alkalinity impact on e. coli inactivation. th e smaller the al-value, the greater the sensitivity to low alkalinity. figure 2 compares the impact of alkalinity on e. coli inactivation between co2 and combustion gases. above and to the right of the lines e. coli will be inactivated by at least 1-log. from the al-values obtained with co2 (al=40.5) and combustion gases (al=35), it can be seen that the inactivation for both gases showed a similar alkalinitydependent behavior (fig. 2). a reduced al-value of 35 to 40.5 mg/l of caco3 suggests that when bubbling both gases inactivation rates of e. coli will highly depend on the alkalinity of the solution, see table 1 and figure 1. for a lka linit y va lues in the range, 5–95 mg caco3/l, combustion gases presented higher e. coli inactivation rates than when using pure co2, with d-values of 16.3 min at 6 mg caco3/l for pure co2 and 4.6 min at 6 mg caco3/l for combustion gases. at higher alkalinity values both gases needed longer times to achieve 1 log e. coli inactivation, combustion gases required 1,666 min at 95.4 mg caco3/l, pure co2 needed 3,333 min at 95.4 mg caco3/l (fig. 2 and table 1). for both gases, e. coli inactivation can be increased by reducing the alkalinity of the solution. solutions with a low buff er capacity, low alkalinity, aft er bubbling co2, or combustion gases in the bubble column for 10 minutes signifi cantly reduced their ph as observed in our experiments (table 1). this reduced ph could affect microbial cell inactivation, since cell membranes stop protons from penetration but also make them more permeable to other substances, like co2, due to the chemical modifi cation on the phospholipid bilayer of the membranes.35,36 when co2 penetrates inside of the bacteria dissolves in the intracellular fl uid producing carbonic acid (h2co3) what triggers an intracellular ph decrease that exceeds the cell’s buff ering capacity, resulting in cell inactivation.35,36 3.3. development of an inactivation model based on alkalinity based on the evidence (see figure 3) that e. coli inactivation in diff erent alkaline solutions when bubbling 38 table 1. initial and fi nal ph values aft er bubbling co2 and combustion gas in 6 diff erent solutions, amount of 0.02 m hcl to reduce the ph of the solutions to 4.2, alkalinity in mg/l of caco3 and d-values. solution ph initial ph fi nal ml of hcl 0.02 m to reach ph 4.2 ml of hcl 0.02 m to reach fi nal ph total alkalinity (mg/l of caco3) (to reach a ph of 4.2) equivalent (mg/l of caco3) (to reach fi nal ph) d-value (min) log10 (d-value, min) co2 gas at 38°c 0.001m nacl in milli-q water 5.78 4 0.9 1.3 6 8.7 16.3 1.21 0.17m nacl in milli-q water 5.86 4 0.9 1.3 6 8.7 16.6 1.22 0.01m cacl2 in milli-q water 5.94 4 1 1.5 6.7 10 34.1 1.53 tap water 8 4.9 13.1 12 87.4 80.1 2,000 3.30 secondary-treated synthetic sewage made with tap water 7.63 5.4 14.3 10.5 95.4 70.1 3,333 3.52 secondary-treated synthetic sewage made with milli-q water 6.83 4.4 4 2.6 26.7 17.3 54.9 1.74 combustion gas at 60 °c secondary-treated synthetic sewage made with tap water 7.63 6.5 14.3 5.4 95.4 36 1,666 3.22 0.17m nacl in milli-q water 5.86 4 0.9 1.3 6 8.7 4.6 0.66 figure 2. minimum co2 bubbling times at diff erent alkalinity values to achieve 1-log bacteria inactivation in 6 diff erent alkaline solutions. above and to the right of the lines the pathogens will be sterilized by 1-log. 63very high efficiency of e. coli inactivation by body temperature co2 bubbles °c co2 and combustion gases follows first-order kinetics we proposed a new e. coli inactivation equation that considers the alkalinity of different solutions. 3.4 disinfection kinetics model the disinfection efficiency of bubbling co2 or combustion gases at low temperatures through a solution with e. coli depends on the total alkalinity of the solution. a new model that includes alkalinity based on the chick-watson first-order equation has been developed in this work. e. coli inactivation follows the first-order kinetics, thus the model results in the following equation: =–k cfu [7] where the e. coli population (cfu) varies with processing time (t) at a constant rate (k). the new model based on the decimal reduction time (d-value) and the new al-value explains how the alkalinity of a given solution can influence e. coli inactivation when co2 or combustion gases, that contain co2, are bubbled through at atmospheric pressure. the d-value is defined as the time, in minutes, needed to inactivate 90% (i.e. 1-log) of e. coli. d-values were calculated using a linear exponential decay model. logs(t)=log [8] where s(t) is the survival fraction after a time (min), is the number of e. coli colonies at time t, = the initial number of e. coli colonies, d= the decimal reduction time, -(1/d) = the slope of the curve (see figure 3). for this work, we have defined a new parameter, the al-value, that is the reduction in alkalinity needed to reduce the d-value by 1-log when bubbling co2 in a bubble column at body temperature (38°c) and atmospheric pressure. it measures the impact of alkalinity on e. coli inactivation. thus: logd1= (a1–a2)+logd2 [9] al= [10] where, a1 first alkalinity of the interval, a2 second alkalinity of the interval, and d1 and d2 are the d-values at a1 and a2. equation 5 is obtained from fig. 3, where a is alkalinity. logd=0.0253a+1.0087 [11] from quations 2 and 5. [12] where, cfut is the number of e. coli at time t, cfu0= the initial number, a= is the alkalinity of the solution in mg/l of caco3 (see figure 3). 4. possible mechanisms of sterilisation 4.1. negotiating the quagmire: nanobubbles we began this and previous works4,24 with the remarkable discovery that co2 bubbles at body temperatures are extremely efficient sterilising agents for both bacteria and viruses. the technology is being implemented at industrial scales. potential applications are legion. the use of recycled water in cities has been prohibited in large part because viruses could not be easily removed from drinking water. a recent discovery in physiology has revealed the structure and function of the ubiquitous endothelial surface layer (els), unknown for 150 years.39 it is a micron thick foam of carbon dioxide nanobubbles. co2 is being produced by metabolism. and passes through a molecular frit that is the polymeric glycocalyx to form nanobubbles. this mimics our bubble column apparatus and vice versa. the esl foam repels red cells and protects organs from invasion by bacteria, neutrophils, low-density lipoproteins, and a legion of figure 3. minimum co2 and combustion gas bubbling times at different alkalinity values to achieve 1-log bacteria inactivation in 6 different alkaline solutions. above and to the right of the lines the pathogens will be sterilized by 1-log. 64 adrian garrido sanchis, barry w. ninham other invaders, good and bad. viruses like covid-19 have to run the gauntlet of this layer of nanobubbles on their way out to the adjoining bloodstream and exit with co2 nanobubbles via the lungs. the issue of co2 sterilisation takes on a wider import as nature’s gift to protect us from the disease. the question of what factors combine to account for the mechanism of sterilisation then takes on a decided imperative. the results of the experiments we have been able to subsume in the single first-order kinetic equation of section 3.3. we now have to see if we can extract any sense and hints at mechanism from this. in attempting to do so we have negotiated our way through a swamp of misinformation. by this, we mean the classical foundations of physical chemistry that inform our intuition suffer from serious sins of omission and of commission. 40 these are due to the omission of specific ion (hofmeister) effects, of dissolved gas: and the organization and reactivity of nanobubbles. their universal presence has been a hidden variable that controls reactivity in solution. they are the energy source via free radicals that drive in polymerization41, and enzymatic reactions.42,43 their presence has been revealed and studied extensively by laser spectroscopy over many years.44-46 nanobubbles even appear on mechanical shaking and contain highly reactive hydrogen peroxide and of course on sonication.47-49 4.2. available evidence with these complications of classical theory in mind we marshall what further evidence we can that could illuminate the issue of mechanism. other gases: argon, air, and nitrogen have no deleterious on pathogens at low temperatures. at very high temperatures they do explore in a succeeding paper.24 our problem is peculiar to co2. 4.3. sodium bicarbonate. the astute chef and detergent companies know that the removal of food proteins adhering to utensils is not easily accomplished. it is by using reasonably warm concentrated sodium bicarbonate solution. this involves active nanobubbles nucleated at the surface that cut peptide bonds. it is also aided by berthelot’s 1795 observations on the nile of precipitation of sodium carbonate rather than calcium carbonate. the ion exchange at and above 50 degrees removes calcium and weakens adhesive bonds. this occurs with the destruction of proteins and their adhesion in the protective coats of both bacteria and viruses. with bacteria the lipids of the exterior membranes of both gram-positive and gram-negative types fall apart above 50-60 degrees because of the same change in head group hydration with temperature – apart from the obvious change in hydrocarbon chain packing. 4.4. ph changes with salt and salt concentration we have already remarked on apparently peculiar specific differences in ph with different salts with bubbling co2 through the solution. this artifact occurs for solutions with co2 and those without. they are because the classical theory of ph and buffers assumes that electrostatic forces alone are operating. specific hofmeister effects arise when the theory is corrected to include dispersion force acting ions, anion cations, and buffer ions. further complications of buffers show up explicitly in42. but also listed below of course all classical measurements ignore dissolved gas that also affects matters like the interpretation of surface potentials (ph). reversal of the hofmeister series for ph is seen with buffers nominally at the same ph, e.g., phosphate vs cacodylate, nominally ph 7.50-52 these are serious complications around which we have to tread carefully. see e.g. for an explicit illustration of obstacles to interpretation caused by the use of classical theory.53 this reports studies of growth rates of staphylococcus aureus and pseudomonas aeruginosa as a function of salt concentration for a large range of anions spanning the hofmeister series. the variations are enormous and not explainable in the usual framework of colloid science.53 4.5. finally a mechanism of sterilisation so armed for pitfalls of theory, we can tread carefully towards an understanding of what is going on. essentially this: nanobubbles are formed through the turbulent passage of co2 through the bubble column frit. they are stabilised by the adsorption of ions and proteins from the bubble column solution. the nanobubbles will have a dynamic highly reactive surface containing bicarbonate and carbonate ions in amounts depending on alkalinity that determines the proportion of each. carboxylates form due to surface reactions with solutions depending on solution constituents. if in high enough concentration these will react with peptides of bacterial (and viral) coats, resulting in destruction. this is consistent with the astute chef and detergent companies cleaning recipe. 65very high efficiency of e. coli inactivation by body temperature co2 bubbles 5. conclusions pure co2 gas or combustion gases can be used in the bubble column to effectively inactivate e. coli c-3000 (atcc15597) in the water at atmospheric pressure and ambient temperatures. the efficiency of the process appears to depend on the alkalinity of the solution. co2 bubbles will have a dynamic highly reactive surface containing bicarbonate and carbonate ions in amounts depending on the alkalinity of the solution that determines the proportion of each. carboxylates form due to surface reactions with solutions on solution constituents. if in high enough concentration, especially in low alkalinity solutions, this will react with peptides of bacterial (and viral) coats, resulting in their inactivation. we have developed a new first-order kinetics equation that predicts e. coli inactivation rates from solutions with different alkalinity when bubbling co2 or combustion gases in a bubble column at atmospheric pressure. 6. addendum since this work was written we discovered an excellent paper from 1948 dealing with the surface inactivation of bacterial viruses and of proteins by mark h.adams.54 it explores the effects of shaking with different gases but not co2 on viruses and proteins. it even compares with the effect of bubbling through a frit. this and references contained therein go back to the beginnings of genuine molecular biophysics and predate the molecular biology dna revolution. it would be remiss of us not to refer the reader to the beginnings of quantification of the physical effects of gas and nanobubbles, long-forgotten and missing from contemporary physical chemistry. 7. contributions adrian garrido 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presence of weak organic acids, ind eng chem res, 2019, 58(11), 4667-4673. 29. a. garrido, r.m. pashley, b.w. ninham, low temperature ms2 (atcc15597-b1) virus inactivation using a hot bubble column evaporator (hbce), colloids surf b, 2016, 151, 1-10. 30. a.g. sanchis, m. shahid, r.m. pashley, improved virus inactivation using a hot bubble column evaporator (hbce), colloids surf b, 2018, 165, 293-302. 31. m.r.j. clokie a.m. kropinski, enumeration of bacteriophages by double agar overlay plaque assay, in bacteriophages, u.o. leicester, editor. 2009: humana press. 32. k. seo, lee, j. e., lim, m. y., ko, g., effect of temperature, ph, and nacl on the inactivation kinetics of murine norovirus, j food prot, 2012, 75(3), 53340. 33. h. zhong, k. fujii, y. nakano, f. jin, effect of co2 bubbling into aqueous solutions used for electrochemical reduction of co2 for energy conversion and storage, j phys chem c, 2015, 119(1), 55-61. 34. w. knoche, chemical reactions of co2 in water, in biophysics 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b.w. ninham, a. lo nostro, g. pesavento, l. fratoni, p. baglioni, specific ion effects on the growth rates of staphylococcus aureus and pseudomonas aeruginosa, phys biol, 2005, 2(1), 1-7. 54. m.h. adams, surface inactivation of bacterial viruses and of proteins, j gen physiol, 1948, 31(5), 417-431. substantia. an international journal of the history of chemistry 5(1): 135-156, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1097 citation: sztejnberg a. (2021) the eminent russian german chemist friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries. substantia 5(1): 135-156. doi: 10.36253/substantia-1097 received: sep 12, 2020 revised: nov 30, 2020 just accepted online: dec 01, 2020 published: mar 01, 2021 copyright: © 2021 sztejnberg a. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries aleksander sztejnberg university of opole, oleska 48, 45-052 opole, poland e-mail: a.sztejnberg@uni.opole.pl abstract. friedrich konrad beilstein (1838-1906) was one of the most prominent chemists of the second half of the nineteenth century. his life and scientific achievements were described in the literature published between the 19th and 21st centuries in different countries. the purpose of this paper is to familiarize readers with the important events in the life of beilstein and his research activities, in particular with selected results of his experimental studies. the names of authors of biographical notes or biographies about beilstein, published in 1890-2018, and literature on his correspondence are given. in addition, a list of his publications is included. keyword: f. k. beilstein, organic chemistry, beilstein test, handbuch der organischen chemie, russia, germany – xix century. 1. the important events in beilstein’s life friedrich konrad beilstein (fyodor fyodorovich beil’shtein, фëдор фëдорович бейльштейн) was called a man of high rank in the profession1 as well as a man of extraordinary erudition and excellent language skills.2 one hundred and fourteen years have passed since his death, but in that time little has appeared in the literature about this outstanding man. he went down in the history of chemistry as one of the creators of synthesis in organic chemistry, as well as a person who for a long period of his life systematized organic compounds. beilstein was born into a family of german emigrants in st. petersburg on february 5 [according to the julian calendar (old style); feb. 17, by the gregorian calendar (new style), adopted in russia on february 1, 1918] 1838, and he was the son of karl friedrich beilstein (1809-1865), and katharina margarete (née rutsch) (1818-1883). his grandfather moved to russia in his youth from the city of darmstad.3 at the age of 14, after study at petrischule,4 the excellent german school of the russian capital, he continued his education (september, 1853-1855) at heidelberg, where his interest in chemistry was inspired and directed by robert bunsen (1811-1899).5 in 1855, he transferred to munich, where he http://www.fupress.com/substantia http://www.fupress.com/substantia 136 aleksander sztejnberg listened to lectures of justus von liebig (1803-1873) as well as he studied mathematics and physics. in munich, under philipp von jolly (1809-1884) he completed his first experimental investigation ueber die diffusion von flüssigkeiten (concerning the diffusion of liquids).6 in april 1856, he returned to heidelberg, where he worked under bunsen until march 1857. then he went to göttingen where, under friedrich wöhler (1800-1882), he established murexide as the ammonium salt of purpuric acid.7 in february 1858, at the age of 20, he submitted his thesis ueber das murexid to the philosophical faculty of the university of göttingen and obtained his doctor’s degree in philosophy.8 in october 1858 he went to paris where he worked in the laboratory of charlesadolphe wurtz (1817-1884) in the école de médecine until september 1859. then he moved to breslau (now, wrocław, poland), where he became the laboratory assistant of carl jacob löwig (1803-1890). in 1860, he was invited by wöhler to return to göttingen, where he spent six years actively engaged in organic chemistry experimental research.9 in the same year, he attended the first ever international congress of chemists held in karlsruhe (germany) on 3-5 september. in november, as a private docent at the university of göttingen, he began to lecture. in 1865, he was appointed extraordinary professor. from this year, together with hans hübner (1837-1884) and rudolph fittig (1835-1910), he continued editing zeitschrift für chemie (1865-1871), founded by august kekulé (18291896).10 in 1866, at the age of 28, beilstein was invited to succeed dmitri ivanovich mendeleev (1834-1907) at the imperial technological institute of st. petersburg, where he subsequently taught for 30 years. his duties included lecturing on general chemistry (inorganic, organic and theoretical), laboratory management and conducting laboratory classes on analytical chemistry. he performed these duties until 1891, when after 25 years of work and approval as an honorary professor, he still worked as a professor until 1896. in that year, professor mikhail dmitrievich lvov (1849-1899) became his successor.11 since 1867, in parallel with his professorship at the imperial technological institute, he lectured in chemistry at the nikolaev engineering academy and was a chemist in the council of trade and manufactures (ctm).12 in 1868, he was one of the founding members of the russkoye khimicheskoye obshchestvo (russian chemical society) at the saint petersburg imperial university. for his scientific work, in particular for his experimental studies, in 1874 he was elevated to the to the degree of doctor of chemistry imperial moscow university.13 beilstein was appointed official delegate of ctm to almost all international expositions, starting from paris in 1867. after visiting an exhibition in vienna, together with alexander kirillovich krupsky (1845-1911), they wrote a book in russian called factory chemical industry of western european countries at the vienna universal exhibition of 1873. it was published in 1874.14 a year earlier, beilstein’s book entitled die chemische grossindustrie auf der weltaustellung zu wien im jahre 1873 was published in leipzig.15 “beilstein’s international prestige was to a certain extent contributed by his personal qualities: great erudition, interest in social life and excellent knowledge of languages, which allowed him to take an active part in the work of various international congresses, exhibitions, in celebrations of anniversaries. in addition to russian and german, french and english, beilstein was fluent in italian and swedish.” 16 beilstein’s participation in the scientific celebrations abroad beilstein repeatedly was a representative of the imperial saint petersburg academy of sciences on anniversaries, e.g. university of halle (1894). in 1900, he visited berlin to participate in the conference devoted to the 200th anniversary of royal prussian academy of sciences.17 figure 1 is a photography made during this celebration.18 benjamin harrow (1888-1970) inserted this photo on the one of first pages of his book entitled eminent chemists of our time. he also wrote that it “showing several eminent chemists was taken at one of the international scientific gatherings.” 19 photograph was published by harrow thanks to the kindness of the dutch chemist ernst julius cohen (18691944).20 from the left to right are standing: the german chemist albert ladenburg (1842-1911),21 the danish chemist and historian of chemistry sophus mads jørgensen (1837-1914),22 the finnish chemist and historian of chemistry evard immanuel hjelt (1855-1921),23 the german chemist hans heinrich landolt (1831-1910),24 the german chemist clemens alexander winkler (18381904),25 who discovered germanium in 1886, and the british chemist and historian of chemistry thomas edward thorpe (1845-1925).26 to the left of beilstein, who sat second from the left, was the dutch chemist jacobus henricus van’t hoff (18521911),27 a nobel laureate in chemistry in 1901, and on the right ‒ the scottish chemist william ramsay (18521916),28 who discovered of inert gaseous elements in air (neon, argon, krypton, and xenon) and was awarded the nobel prize in chemistry in 1904, the russian chemist d. i. mendeleev,29-30 who discovered the periodic law in 137the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries 1871, the german chemist adolf von baeyer (1835-1917),31 who received the nobel prize in chemistry in 1905, and the italian chemist alfonso cossa (1833-1902).32 death of beilstein beilstein died of a heart attack on october 5 (old style); oct. 18 (new style) 1906. his funeral took place on october 9 at the volkov cemetery in st. petersburg.33 in 1945, the russian-american chemist vladimir nikolayevich ipatieff (1867-1952) wrote in his memoirs: “when i entered the auditorium for a meeting of phys.chem. society, it has already begun, and the chairman asked everyone to stand up to honor the memory of the deceased. when i asked who died, i was told that beilstein died on that day... this event struck me very much, especially since f. f. [fyodor fyodorovich] was not yet old, full of energy and did not stop working.(…) belstein was a bachelor, but he adopted one girl, who was the heir to his entire fortune. f. f.’s funeral was organized very solemnly, and a huge number of chemists and other scientists took part in them.” 34 obituaries have been published in several chemical journals. the russian chemist nikolay nikolayevich beketov (1827-1911) published his text in zhurnal russkogo fiziko-khimicheskogo obshchestva35, and the president of the french chemical society, the chemist armand gautier (1837-1920) in bulletin de la société chimique de paris.36 the german chemist paul jacobson (1859-1923) wrote about beilstein in the chemiker-zeitung in 1906.37 the german chemist otto nikolaus witt (1853-1915) and e. i. hjelt published their obituaries in berichte der deutschen chemischen gesellschaft.38-39 witt’s obituary also appeared in english in the journal of the chemical society, transactions in 1911.40 otto lutz published his obituary in angewandte chemie.41 one of his statements about beilstein was also quoted by lyudmila anatolyevna shmulevich and the russian historian of chemistry yusuf suleymanovich musabekov (1910-1970). they wrote: “chemistry again suffered a sensitive loss ... died a man who did a lot for the progress of science, a man who, thanks to his peculiar talent, combined with extraordinary hard work, was able to create a work that has no equal and is intended to facilitate the work of chemists and encourage them to be creative.” 42 2. beilstein’s works the list of works published by him includes over one hundred and eighty articles and books that appeared in print for forty-three years from 1856 to 1899. the majority of these are the articles presenting the results of his experimental works, published in the zhurnal russkogo fiziko-khimicheskogo obshchestva in russia, as well as in german and french journals. among them are his original papers devoted to the problems of the of isomerism of the organic compounds, various analytical chemistry issues, and chemistry and technology of the petroleum can be found. a large number of the results of the experimental research carried out by him were published in german in the justus liebigs annalen der chemie, zeitschrift für chemie and berichte der deutschen chemischen gesellschaft. a few his articles were published in french in the comptes rendus hebdomadaires des séances de l’académie des sciences and bulletin de la societe chimique de paris. in the period from 1856 to 1882, he published, mainly from organic chemistry, the results of 152 studies. in the next, almost 25-year period from 1882 to 1906, the number of his publications was 27. a large part of all beilstein’s works was done between 1867 and 1884 jointly with few his collaborators, such as alfons pavlovich kuhlberg (1867-1873), apollon apollonovich kurbatow (1874-1883), ludwig julievich jawein (1879-1884) and others.43 his first works in the field of organic chemistry was published in 1859 and concerned on the conversion of acetal to acetaldehyde.44 in subsequent years, aromatic compounds were the main area of his research interests. in 1863, he and julius wilbrand (1839-1906) obtained para-nitrobenzoic acid by oxidation of nitrotoluene.45 beilstein’s research interests also focused around analytical chemistry. he devised a sensitive test, “the beautifully simple procedure now constantly employed in all figure 1. beilstein with the group of the prominent chemists (public domain, from reference 18). 138 aleksander sztejnberg laboratories under the name of the beilstein test for halogens in organic compounds.” 46 in 1872, he published it in zhurnal russkogo khimicheskogo obshchestva47 and in berichte der deutschen chemischen gesellschaft.48 the procedure for the beilstein test was also quoted by an american chemist eduard farber (1892-1969) in an article published in isis. beilstein called the test “not new in principle”, since it was based on “the known [the swedish chemist jöns jacob] berzelius [(1779-1848)] reaction showing the presence of cl, br, i in mineral substances by means of copper oxide (...).” 49 beilstein proposed the following variation: “a little quantity of copper oxide is brought into the ear formed in a platinum wire and fastened there by short heating to a glow. this copper oxide is then dipped into the substance, or a little of the solid material is sprinkled on, and then the wire is brought into a moderately strong flame near its lower and inner rim. at first the carbon burns and the flame is bright, right afterward the characteristic green or blue color of the flame appears.” 50 in 1867, beilstein’s book under the title rukovodstvo k kachestvennomu khimicheskomu analizu (manual of qualitative chemical analysis) was published in russia.51 in the same year, this book was published in germany under the title anleitung zur qualitativen chemischen analyse.52 the second, revised german edition was published in leipzig in 1870,53 the seventh in 1892,54 and the last, ninth in 1909. the dutch edition of beilstein “rukovodstvo” appeared in 1868.55 this book has also been published in english by william collins, sons, & company in glasgow in 1873. the book ’s translator was william ramsay.56 in the united states this book was published in 1876 under the title an introduction to qualitative chemical analysis, translated from the third german edition of beilstein “anleitung” by i. j. osbun.57 the french edition of this book was published in 1882.58 he was also the author of a book entitled lessons in qualitative chemical analysis (1883) published in saint louis in usa.59 it was translated from the fifth german edition of his anleitung zur qualitativen chemischen analyse (1877) by charles o. curtman (1829-1896), professor of chemistry in the missouri medical college. the second edition of this book was published in 1886.60 in 1868, he published his rukovodstvo k kolichestvennomu analizu (manual of quantitative analysis).61 twenty-two years later, his book written jointly with jawein under the title rukovodstvo k kachestvennomu i kolichestvennomu khimicheskomu analizu (manual of quantitative and qualitative chemical analysis) was published in st. petersburg.62 this was the sixth, extended edition of beilstein “rukovodstvo” (1867).63 the seventh edition of this book was released in 1896.64 beilstein is one of the first researchers in the field of chemistry and technology of russian oil. in the first half of the 1880s, he together with the engineer a. a. kurbatow (1851-1903) began a systematic study of the composition of the caucasian petroleum. their two important papers on this topic were published in german in berichte der deutschen chemischen gesellschaft 65-66. in 1883, their russian article issledovaniye kavkazskoy nefti was also published in zhurnal russkogo fiziko-khmicheskogo obshchestva.67 these researchers also showed the difference between russian and american oil.68 from 1881, he continued his scientific activity of other nature. instead of previous laboratory and experimental work, he began to devote almost all his energy to systematizing organic compounds.69 the world’s first multi-volume handbuch der organischen chemie by beilstein the problem of classif ying organic compounds according to their properties, methods of preparation, etc., beilstein found very interesting during his stay in germany. at the time, he considered writing a handbook to organic chemistry. for almost 17 years of his life, he collected information about organic compounds described in world literature.the fruit of his gigantic and independent work was the first two-volume edition entitled handbuch der organischen chemie, which was published in 1881 and 1883 in the publishing house of leopold voss in leipzig.70 thanks to his perseverance, it became possible to document and systematize the 15,000 organic compounds71 known at the time in these two volumes, which comprised a total of 2,201 pages.72 after a few years, there was a need to expand and improve this work. beilstein himself edited the next two editions of his handbuch. the second edition (three volumes, 4,080 pages)73 was published in 1886-1890,74-76 and is available in the internet archive. the next, third, four-volume edition, which required seven years of his work, comprised of 6,844 pages77 and contained almost 74,000 organic compounds.78 it was published in 18931899.79 all volumes of this edition are also available on the internet.80-83 the american chemist and chemical bibliographer henry carrington bolton (1843-1903) was full of admiration for beilstein’s work. he characterized his “handbuch” as follows: “a stupendous monument of industrious, intelligent compilation.” 84 pavel ivanovich walden (1863-1957), ordinary academician of the imperial saint petersburg academy of sciences, wrote in his ocherk istorii khimii v rossii (essay on the history of chemistry in russia) that “its significance and fame will survive 139the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries many generations of chemists. this is a labor that has been a prototype for other branches of chemical science and a lasting monument to energy, knowledge and diligence of its author.”85 supplementary volumes for the third edition of the handbuch der organischen chemie were published by the deutsche chemische gesellschaft in 1901-1906. these were exclusively the work of paul jacobson and his collaborators.86-90 the fourth edition, including five supplements, was published from 1918-1998, covering the chemical literature through 1979. beilstein realized from as soon as he completed the first edition that a major revision of the classification would be needed. however, he himself never felt that he had the time to complete such a reorganization of the entire work. the “beilstein system,” the basis for the organization of the fourth edition, was developed by p. jacobson, bernhard prager (1867-1934), and dora stern beginning in 1906. this classification was not subsequently changed; indeed, the stability of the beilstein system from its origins in 1906 through the final volumes of the fifth supplement to the fourth edition in 1998 was a foundation of great usefulness of the work. the primary challenge necessitating the constant need to publish more and more supplementary volumes was the massive quantity of new research published in organic chemistry, whether it addressed novel compounds or provided additional significant information about previously known compounds. from 1933, friedrich richter (1896-1961) was the director of the beilstein editorial office and on august 1, 1951, he was appointed president of the institute in frankfurt am main91 under the name beilstein-institut für literatur der organischen chemie (beilstein-institut for literature of organic chemistry), which acted as a non-profit foundation.92 he was followed by hansgünther boit (1916-1985) in december 1961. until 2011, the editor of beilstein handbook was reiner luckenbach (1941-2011), who succeeded boit in 197893. in 1999, the name of the institute was modified to beilstein-institut zur förderung der chemischen wissenschaften (beilstein institute for the advancement of chemical sciences).94 in the same year, the institut “revised and updated its constitution (...), redefining its role in the era of electronic publishing and online information systems.”95 richter wrote several articles about beilstein’s handbuch der organischen chemie. his first paper was published in agnewandte chemie in 1925.96 his book with retrospectives on the handbuch appeared thirty-two years later.97 his other article under the title beilsteins handbuch – 75 jahre organisch‐chemischer dokumentation was also published in angavandte chemie in 1958.98 on the hundredth anniversary of beilstein’s birth, in 1938, richter published an article in journal of chemical education. he wrote in it: “the history of science knows no standstills and famous textbooks mark its course like milestones. when (1881-83), scarcely thirty years after gmelin’s death, friedrich konrad beilstein (1838-1906) put out the first parts of his “handbuch der organischen chemie,” he could not have foretold that this modest attempt, as he called it, would make his name immortal. from the two small volumes of the first edition it could not have been foreseen that eventually forty volumes would not suffice to house the total treasure trove of organic chemistry.”99 it should be emphasized here that the german chemist leopold gmelin (1788-1853) became very wellknown through his handbuch der chemie, whose provided a model for the kind of reference work that beilstein compiled. after gmelin’s death, subsequent editions of the handbuch der chemie had focused on inorganic compounds only, leading to its retitling as gmelins handbuch der anorganischen chemie, an inorganic counterpart to beilsteins handbuch that was also edited by the deutsche chemische gesellschaft beginning in the 1920s. in 1981, luckenbach and josef sunkel wrote an article titled das wissenschaftliche handbuch. 100 jahre beilstein, which was published in naturwissenschaften.100 these authors about beilstein “handbuch” wrote: “the beilstein’s handbook, which in its 4th edition up to the end of 1980 reaches 225 volumes …, covers all organic compounds described in the science literature. together with “gmelin’s handbook of inorganic chemistry”…, which describes inorganic compounds, they cover almost the entire area of chemistry.”101 in 1990, the fourth edition of the beilstein handbook of organic chemistry consisted of over 350 printed volumes containing over 275,000 pages of text,102 and in 1998, reached a total of 503 volumes and over 440,000 pages.103 the british historian evan hepler-smith wrote on beilstein’s handbuch and his role in the development of systematic organic nomenclature in his article published in ambix in 2015.104 3. biographical notes or biographies about friedrich konrad beilstein published in 1890-2018 in 1890, p. alekseyev described beilstein’s life and works in vengerov’s dictionary under the title kritikobiograficheskiy slovar’ russkikh pisateley i uchenykh (ot 140 aleksander sztejnberg nachala russkoy obrazovannosti do nashikh dney).105 a biographical note about him was published in brokgauz – yefron, entsiklopedicheskiy slovar’ in 1891.106 seven years later, information about him and his publications appeared in poggendorff ’s handwörterbuch.107 in 1915, walden108-109 published his biographical note in materialy dlya biograficheskogo slovarya deystvitel’nykh chlenov imperatorskoy akademii nauk.110 the russian historian of chemistry maks abramovich blokh (1882-1941) presented beilstein’s biographical note in his book published in 1931.111 richter published two articles about him in german chemical journals in 1938.112-113 in the same year, professor of organic chemistry at the massachusetts institute of technology (mit) (u.s.a.) ernest h. huntress (1899-1970) published his article about beilstein’s life and works in the journal of chemical education in 1938. the american chemist henry monmouth smith (1868-1950) wrote beilstein’s brief biographie in his book published in new york in 1949,115 and the british chemist and historian of chemistry james riddick partington (1886-1965) wrote about him in his history of chemistry published in 1964.116 musabekov and shmulevich wrote about beilstein in their article in 1969.117 his biographical note, written by the german chemist and historian of chemistry otto krätz (b. 1937), was published in chemie in unserer zeit.118 the first in the world beilstein’s full-length biography was written by shmulevich and musabekov in 1971. in this book, the first chapter is devoted to the life of the scientist. in the second chapter of this monograph, the authors discussed the experimental research carried out by beilstein. the third chapter describes his work on the handbuch der organischen chemie. the structure of the book also includes extensive systematic bibliography and a list of selected literature published until 1969 about beilstein and his “handbuch.”119 a beilstein’s biographical note, written by the russian chemist feliks kazimirovich velichko (b. 1931), was published in 1972.120 luckenbach wrote about him in chemie in unserer zeit in 1981.121 in 2004, in göttingen, in the third edition of the publication devoted to the 300th anniversary of saint petersburg appeared an article entitled friedrich konrad beilstein: chemiker zweier nationen (friedrich konrad beilstein: chemist from two nations).122 its author is the chemist and historian of natural sciences elena evgenievna roussanova, candidate of chemical sciences, from st. petersburg. she works at the institut für geschichte der naturwissenschaften, mathematik und technik (institute for the history of science, mathemtics and technology) at the university of hamburg and at the sächsische akademie der wissenschaften zu leipzig (saxon academy of sciences and humanities in leipzig). two years later, she wrote about beilstein in an article published in the collection of papers of the international conference devoted to the 145th anniversary of the structure theory of organic compounds of a. m. butlerov and 100th anniversary of the memory to f. f. beilstein.123 the american historian of science michael d. gordin, professor of modern and contemporary history at princeton university, wrote about beilstein’s life and work in his article published in chemical heritage in 2003,124 and also in the chapter entitled beilstein unbound: the pedagogical unraveling of a man and his handbuch in a book edited by david kaiser, professor of the history of science at mit, which was published in mit press in 2005.125 beilstein is also discussed fairly extensively in another gordin’s book that was published by the university of chicago press in 2015.126 in 2006, a books about beilstein, written by roussanova appeared on the 100th anniversary of his death.127 one year later, together with olga shcherbinina, she wrote an article entitled fridrikh konrad beyl’shteyn (1838-1906) k 100 letiyu co dnya smerti russko-nemetskogo khimika (friedrich konrad beilstein (1838-1906) on the 100th anniversary of the death of a russiangerman chemist).128 in the same year, rosussanova wrote an article about beilstein’s election to the imperial saint petersburg academy of sciences entitled f. k. beilsteins wahl in die petersburger akademie der wissenschaften.129 roussanova’s article entitled friedrich konrad beilstein und sein beitrag zur kommunikation zwischen deutschland und russland auf dem gebiet der chemie (friedrich konrad beilstein and his contribution to communication between germany and russia in the field of chemistry) was published in 2011.130 one year later, david e. lewis, professor of chemistry at the university of wisconsin-eau claire (u.s.a.), briefly described beilstein’s life and selected results of his chemical works in the book entitled early russian organic chemists and their legacy in its chapters friedrich konrad (fyodor fyodorovich) beilstein and beilstein’s legacy.131 a beilstein’s biographical note, written by r. klaus müller, was published in 2014.132 roussanova’s article under the title sankt-peterburgskiy khimik fridrikh konrad beyl’shteyn (st. petersburg chemist friedrich konrad beilstein) was published in st. petersburg in 2015 in a book edited by the german historian dittmar dahlmann (b. 1949) and the russian historian galina ivanovna smagina.133 in 2018, roussanova wrote about beilstein’s life and works in the first part of her book, entitled deutsch-russische beziehungen in der che141the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries mie des 19. jahrhunderts (german-russian relations in chemistry in the 19th century).134 in the same year, the academician of the russian academy of sciences, chemist yuri alexandrovich zolotov wrote about him in his book ocherki istorii analiticheskoy khimii (essays on the history of analytical chemistry).135 4. literature on beilstein’s correspondence ernest h. huntress, in an article published in the journal of chemical education in 1938, provided an english translation of one of beilstein’s unpublished letter to his friend august kekulé (1829-1896), which nicely exemplifies the 22-year-old beilstein’s rather biting sense of humor.136 otto krätz is the editor of the collection of correspondence between beilstein and emil erlenmeyer (1825-1909), with whom he maintained close relations.137 roussanova’s article entitled aspekte der deutsch-russischen wissenschaftsbeziehungen in der chemie in der zweiten hälfte des 19. jahrhunderts in briefen des chemikers friedrich konrad beilstein (aspects of germanrussian scientific relations in chemistry in the second half of the 19th century in letters from the chemist friedrich konrad beilstein) was published in 2005.138 one year later, she wrote an article about new sources of beilstein’s scientific correspondence.139 her book, published in 2007, is an edited collection of beilstein’s correspondence, an invaluable resource for those interested in his life, work, and professional and personal relationships with contemporaneous chemists. besides the already mentioned kekulé and erlenmeyer, he was also in a close relationship with jacob volhard (1834-1910), as evidenced by his extensive correspondence.140 the russian chemist and historian of chemistry georgiy vladimirovich bykov (1914-1982) was the editor of the book entitled pis’ma russkikh khimikov k butlerovu (letters of the russian chemists to butlerow), in which he included letters written, among other, by beilstein.141 together with l. m. bekassowa he also wrote an article under the title beiträge zur geschichte der chemie der 60-er jahre des xix. jahrhunderts. f. beilstein’s briefe an a. m. butlerow (contributions to the history of chemistry of the sixties of the xix. century. f. beilstein’s letters to a. m. butlerov), which appeared in italy in 1966.142 at the beginning of the 1880s, beilstein also corresponded with the italian chemist stanislao cannizzaro (1826-1910).143-144 in 1906, sir henry e. roscoe published in his autobiography an english translation of the congratulatory letter he received from his friend beilstein on the occasion of his graduation jubilee on april 22, 1904. a fragment of this letter is as follows: highly honoured colleague, dear friend and fellow-student, to-day, when so many of your colleagues, scholars, and friends are tendering you their congratulations, you may not be unmindful of the voice of one who is far away, but who has been privileged to follow the development and outcome of your career for fully fifty years. only a few remain from that happy time, but for that very reason their voices may have the greater weight. it was in the winter semester of 1853-54 that i came to heidelberg to listen, in the class-rooms in the old cloisters, to the teaching of our revered master, bunsen, at the end of which semester you took your degree. this occurred soon after the beginning of that brilliant period of the academic activity of that immortal man which attracted the enthusiastic youth of the whole world. … in april 1856, when i returned to heidelberg from munich, where i had listened to liebig and worked with jolly, you and i were colleagues in the new laboratory, then just finished, and where later on you were a frequent and welcome guest. in june 1856, we—the senior pupils in bunsen’s laboratory—were photographed together. in this picture, which lies before me, i see the forms of many dear old friends who are now no more. yes, most of them —[johann friedrich] bahr [((1815-1875)], [ludwig] carius [(1829-1875)], kekulé, lothar meyer [(1830-1895)], [leopold von] pebal (1826-1887)]—have gone. besides we two, our excellent and honoured comrade landolt is the only one remaining.145 the german chemist richard anschütz (1852-1937), professor of chemistry at the university of bonn in the first volume of his biographical book on kekulé, introduced the reader to beilstein’s stay in heidelberg in the second half of the 1850s. he also posted a group photo of young chemists, which beilstein wrote about in a letter sent to roscoe.146-147 memories of beilstein’s stay in heidelberg were deeply rooted in his memory, as he also wrote about this photograph in a letter to anschütz dated 3/16 june 1906, four months before his death. in it he wrote the correct year the photo was taken, compared to the letter he had sent to roscoe two years earlier. he wrote, among other things: “during my entire year in heidelberg, i dined with kekulé daily. we all dined at the ‘darmstadt hof ’ (near the end of the main street) and our society consisted of chemists, with the exception of the economist adolf wagner [1835-1917]. when i left at easter 1857 we had ourselves photographed together. you probably saw this picture: in front, in the first row: kekulé, pebal, carius, bahr, landolt, behind them: a. wagner, [angelo] pavesi [(1830-1896)], [agostino] frapolli [(1824-1903)], lothar mayer, roscoe and others, at the end me.”148-149 142 aleksander sztejnberg 5. conclusion friedrich konrad beilstein was a great chemist of the second half of the xix century. in the years 18801896, he was elected as a member of two academies of sciences and several scientific associations. he became a corresponding member of the imperial saint petersburg academy of sciences on december 3, 1883, and he was elected an ordinary academician in chemistry and technology on december 13, 1886.150 he became member of the academy of sciences in göttingen in 1884, the royal prussian academy of sciences in 1888, and academy of science in uppsala in 1899.151 beilstein was elected as a member of the royal scientific society in göttingen in 1880. in 1883, he became an honorary member of the london chemical society, and two years later ‒ deutsche chemische gesellschaft (german chemical society). he was elected as an honorary member of the société de médecine de paris (paris society of medicine) (1879), the imperial technical society (1888), philadelphia medical society (1893), the manchester literary and philosophical society (1895) and the imperial technological institute in st. petersburg (1896). in 1876, at the proposal of ordinary academicians nikolai nikolaevich zinin (1812-1880) 152 and aleksandr mikhailovich butlerov (1828-1886),153 the imperial saint petersburg academy of sciences awarded him the lomonosov prize. beilstein’s death did not go unnoticed. in the years 1890-2018, books and articles with his biographical notes or biographies were published in russia, germany, great britain and u.s.a. occasional exhibitions were also organized. on october 26, 2006, the göttingen branch of the german chemical society organized an exhibition on the 100th anniversary of beilstein’s death at the bereichsbibliothek chemie niedersächsische staatsund universitätsbibliothek göttingen. on march 30, 2007, the exhibition was held in the fundamental library of the technological institute in st. petersburg, where beilstein worked from 1866 to 1896.154 since 2005, the beilstein-institut zur förderung der chemischen wissenschaften has published the beilstein journal of organic chemistry “to provide unrestricted access to high-quality scientific information in the field of organic chemistry.”155 the name of beilstein is associated with his handbuch and research in organic synthesis. the results of his experimental studies have been published in scientific journals in germany, france and russia. the imperial technological institute where he worked for thirty years was completed by about 1,000 technologists chemists, who, through their work, have made a great contribution to the development of chemical science.156 shmulevich and musabekov, the authors of beilstein’s biography, wrote about the immortality of his name as follow: “the greatest popularity comes to a scientist when his own name becomes widely known: his name, for example, is called a unit of measurement – and write it without a capital letter – or any edition. in other words, the name is transferred to an inanimate object. this happened with a native of russia, st. petersburg academician fyodor beilstein, so famous among chemists all over the world. when the word “beilstein” is spoken, the chemist’s imagination is not a man with a thick beard and a handsome, typically learned appearance, but a multivolume handbook, where you can quickly find the information you need about any of the myriad organic compounds.”157 this outstanding russian-german chemist took forever a well-defined place in the history of chemistry. his name and the name of gmelin158 are associated with the gmelin-beilstein-denkmünze (gmelin–beilstein memorial medal) award. it is awarded biennially by the gesellschaft deutscher chemiker (german chemical society) since 1954, to domestic and foreign “individuals have produced outstanding contributions to the history of chemistry, chemical literature or chemical information.”159 the prize-winning gmelin-beilstein-denkmünze receives a silver medal, certificate and accompanying prize of € 7,500.160 references 1. h. c. bolton, science, new series. 1899, 10(259), p. 869. http://doi.org/10.1126/science.10.259.865 2. l. a. shmulevich, yu. s. musabekov, fedor fedorovich beil’shtein (1834 – 1906), izdatel’stvo “nauka”, moskva, 1971, p. 65 (in russian). 3. see ref. 2 (shmulevich, musabekov), p. 7. 4. e. roussanova, o. shcherbinina, fridrikh konrad beyl’shteyn (1838-1906) k 100 letiyu co dnya smerti russko-nemetskogo khimika. sankt-peterburg. 2007, p. 48. 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d. kaiser), mit press, cambridge, ma, 2005, pp. 11-39. 126. m. d. gordin, scientific babel: how science was done before and after global english, university of chicago press, chicago, 2015. 127. e. roussanova, „deshalb ist mir um meinen ruhm nicht bange …︁”. zum 100. todestag des deutsch-russischen chemikers friedrich konrad beilstein (1838– 1906). begleitheft zur ausstellung in der bereichsbibliothek chemie (bbn) der niedersächsischen staats und universitätsbibliothek göttngen vom 26. oktober bis 27. november 2006 und in der bibliothek des departements chemie der universität hamburg vom 8. bis 22. dezember 2006, books on demand gmbh, hamburg, norderstedt, 2006. 128. see ref. 4 (roussanova, shcherbinina) for details. 129. e. roussanova, mitteillungen fachgruppe geschichte der chemie (frankfurt/main), gesellschaft deutscher chemiker. 2007, 19, 107-132. retrieved from https:// www.gdch.de/fileadmin/downloads/netzwerk_und_ strukturen/fachgruppen/geschichte_der_chemie/ mitteilungen_band_19/2007-19-09.pdf 130. e. roussanova in naturwissenschaft als kommunikationsraum. internationale tagung, leipzig, 29.9.147the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries 1.10.2010, (eds.: o. riha, m. fischer), shaker verlag gmbh, aachen, 2011, pp. 75-96. 131. d. e. lewis, early russian organic chemists and their legacy, springer, heidelberg, new york, dordrecht, london, 2012. 132. k. müller in important figures of analytical chemistry from germany in brief biographies. from the middle ages to the twentieth century, (d. t. burns, r. k. müller, r. salzer, g. werner), springer, cham, heidelberg, new york, dordrecht, london, 2014, pp. 69-70. http://dx.doi.org/10.1007/978-3-319-12151-2 133. e. roussanova in nemtsy v rossii. nemetskiy mir sankt-peterburga (germans in russia. german world of st. petersburg), (eds.: d. dahlmann; g. i. smagina), rostok, sankt-peterburg, 2015, pp. 272-300. (in russian). 134. e. roussanova, deutsch-russische beziehungen in der chemie des 19. jahrhunderts. erster teil. biobibliographen, shaker verlag gmbh, aachen, 2018, pp. 146172. 135. yu. a. zolotov, ocherki istorii analiticheskoy khimii (essays on the history of analytical chemistry), tehnosfera, moskva, 2018 (in russian). 136. see ref. 5 (huntress), pp. 303-305. 137.o. krätz (ed.), beilstein – erlenmeyer. briefe zur geschichte der chemischen dokumentation und des chemischen zeitschriftenwesens, w. fritsch verlag, münchen, 1972. 138. e. roussanova in deutsche im zarenreich und russen in deutschland: naturforscher, gelehrte, ärzte und wissenschaftler im 18. und 19. jahrhundert. vorträge des symposiums vom 26. und 27. august 2004 am karl-sudhoff-institut für geschichte der medizin und der naturwissenschaften, (eds.: i. kästner, r. pfrepper), medizinische fakultät der universität leipzig. band 12., shaker verlag gmbh, aachen, 2005, pp. 227-272. 139. e. roussanova, friedrich konrad beilstein (18381906): scientific correspondence of f. k. beilstein: new sources. “organic chemistry since butlerov and beilstein until present“: international conference devoted to the 145th anniversary of the structure theory of organic compounds of a. m. butlerov and 100th anniversary of the memory to f. f. beilstein, st. petersburg, 26.-29.6. 2006, pp. 822-829. 140. e. roussanova, friedrich konrad beilstein—chemiker zweier nationen: sein leben und werk sowie einige aspekte der deutsch-russischen wissenschaftsbeziehungen in der zweiten häalfte des 19. jahrhunderts im spiegel seines brieflichen nachlasses. band ii. briefe und dokumente. (friedrich konrad beilstein — chemist of two nations: his life and work as well as some aspects of the german-russian scientific relationship in the second half of the 19th century in the mirror of his letters. volume ii. letters and documents). books on demand gmbh, hamburg, norderstedt, 2007. 141. g. v. bykov (ed.), pis’ma russkikh khimikov k a. m. butlerovu (letters of russian chemists to a. m. butlerov), nauchnoye nasledstvo, t. 4, izdatel’stvo akademii nauk sssr, moskva, 1961, pp. 33-51. 142. g. w. bykow, l. m. bekassowa, physis. rivista internazionale di storia della scienza, 1966, 8, 267-285. 143. see ref. 129 (roussanova), p. 117. 144. d. marotta (ed.), stanislao cannizzaro. scritti vari e lettere inedite nel centenario della nascita (various writings and unpublished letters on the centenary of his birth), associazione italiana di chimica generale ed applicata, tip. leonardo da vinci, roma, 1926, pp. 325-326. 145. h. e. roscoe, the life & experiences of sir henry enfield roscoe, d.c.l., ll.d., f.r.s. written by himself, macmillan and co., limited, london, new york, 1906, pp. 414-415. retrieved from https:// archive.org/details/lifeexperienceso00roscrich/page/ n7/mode/2up 146. r. anschütz, august kekulé. band i., leben und werken, verlag chemie, g.m.b.h., berlin, 1929, p. 64. retrieved from https://archive.org/details/ b29931654_0001/page/n3/mode/2up 147. ficheiro: ak bunsen-heidelberg 1857.jpg. n.d. retrieved from https://pt.m.wikipedia.org/wiki/ ficheiro:ak_bunsen-heidelberg_1857.jpg 148. see ref. 4 (roussanova, shcherbinina), pp. 9, 49. 149. see ref. 135 (roussanova) for details. 150. beil’shtein fedor fedorovich (fridrikh konrad) (friedrich konrad beilstein), 2017, (in russian). retrieved from arkhivy rossiyskoy akademii nauk website: http://isaran.ru/?q=ru/person&guid=f51dd9010609-c7e0-eeb5-2a70e3104401&str= 151. see ref. 10 (walden), p. 27. 152. a. sztejnberg, rev. cenic cienc. quím. 2019, 50(1), 90–102. retrieved from https://ojs3.cnic.cu/index. php/revquim/article/view/297 153. b. halton, chem. n. z. 2018, 82(1), 46-52. retrieved from https://nzic.org.nz/app/uploads/2018/07/cinzjan-2018-min.pdf 154. see ref. 78 (roussanova), pp. 257-261. 155. beilstein journal of organic chemistry. 2020. (second paragraph). retrieved from beilstein-institut website: https://www.beilstein-institut.de/en/publications/organic-chemistry/ 156. fedor fedorovich beil’shtein (05.02.1838 – 05.10.1906). 2015. retrieved from web-muzey 148 aleksander sztejnberg sankt-peterburgskogo gosudarstvennogo tekhnologicheskogo instituta website: https://museum-spbti. wixsite.com/museum/belstein 157. quoted in ref. 2 (shmulevich, musabekov), p. 5. 158. p. stumm, leopold gmelin (1788-1853). leben und werk eines heidelberger chemikers, centaurus verlag & media ug, freiburg, 2012. 159. j. gregor, gmelin-beilstein medal will be awarded to guillermo restrepo. max-planck-institut für mathematik in den naturwissenschaften (mpimis). 2020. retrieved from https://nachrichten.idw-online.de/2020/02/27/gmelin-beilstein-medal-will-be-awarded-to-guillermorestrepo/ 160. j. herr, gmelin-beilstein-denkmünze. 2020. retrieved from the gesellschaft deutscher chemiker website: https://www.gdch.de/gdch/preise-und-auszeichnungen/gdch-preise/gmelin-beilstein-denkmuenze.html a list of beilstein’s publications 1856 —ueber die diffusion von flüssigkeiten. justus liebigs ann. chem. 99(2), 165-197. https://doi.org/10.1002/ jlac.18560990203 1858 —ueber das murexid. justus liebigs ann. chem. 107(2), 176-191. https://doi.org/10.1002/jlac.18581070206; inaugural-dissertation zur erlangung der philosophischen doctor würde, von fr. c. beilstein aus russland, göttingen. —with a. geuther. ueber das natriumamid. justus liebigs ann. chem. 108(1), 88-102. https://doi. org/10.1002/jlac.18581080119 1859 —ueber die einwirkung verschiedener aetherarten auf aether‐natron und über die aethylkohlensäure. justus liebigs ann. chem. 112(1), 121-125. https:// doi.org/10.1002/jlac.18591120113; action des différents éthers sur l’alcoolate de soude et sur l’acide éthylcarbonique. comptes rendus hebdomadaires des séances de l’academie des sciences. 48, 960963. retrieved from https://gallica.bnf.fr/ark:/12148/ bpt6k30054/f956 —ueber die umwandlung des acetals zu aldehyd. justus liebigs ann. chem. 112(2), 239-240. https://doi. org/10.1002/jlac.18591120218; sur la transformation de l’acétal en aldéhyde. comptes rendus hebdomadaires des séances de l’academie des sciences. 48, 1121-1122. retrieved from https://gallica.bnf.fr/ ark:/12148/bpt6k30054/f1117.item —sur l’action du perchlorure de phosphore sur l’acétal. bull. soc. chim. 45-47. retrieved from https://books. google.mw/books?id=4ii5aaaacaaj&pg=pa5 —sur l’isomérie des combinaisons organiques. comptes rendus hebdomadaires des séances de l’academie des sciences. 49, 134-135. retrie ved f rom https://gallica.bnf.f r/ark:/12148/ bpt6k3006f/f136 —ueber die identität des aethylidenchlorürs und des chlorürs des gechlorten aethyls. justus liebigs ann. chem. 1860, 113(1), 110-112. https://doi. org/10.1002/jlac.18601130117 1860 —ueber die identität des chlorbenzols mit dem gechlorten chlorbenzyl (bichlortoluol). justus liebigs ann. chem. 116(3), 336-356. https://doi.org/10.1002/ jlac.18601160307 —notiz über die einwirkung des phosphorsuperchlorides auf cyanursäure. justus liebigs ann. chem. 116(3), 357-358. https://doi.org/10.1002/jlac.18601160308 —with f. seelheim. ueber das saligenin. justus liebigs ann. chem. 117(1), 83-91. https://doi.org/10.1002/ jlac.18611170104 1861 —ueber die einwirkung des jodphosphors auf glycerinsäure. justus liebigs ann. chem. 120(2), 226-236. https://doi.org/10.1002/jlac.18611200210 —note sur le bromure d’éthyle bromé. bull. soc. chim. 121-122. retrieved from https://gallica.bnf.fr/ ark:/12148/bpt6k298485n/f124 1862 —ueber die umwandlung der glycerinsäure in acrylsäure. justus liebigs ann. chem. 122(3), 366-374. https://doi.org/10.1002/jlac.18621220310 —with a. geuther. notiz über das dicyandiamid. justus liebigs ann. chem. 123(2), 241-245. https://doi. org/10.1002/jlac.18621230213 149the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries —with r. rieth. ueber ein einfaches verfahren zur darstellung des zinkäthyls. justus liebigs ann. chem. 123(2), 245-248. https://doi.org/10.1002/ jlac.18621230214 —with r. rieth. ueber neue synthetische bildungsweisen des amylens und des propylens. justus liebigs ann. chem. 124(1), 242-248. https://doi.org/10.1002/ jlac.18621240109 1863 —with r. rieth. ueber die zersetzung der aldehyde und acetone durch zinkäthyl. justus liebigs ann. chem. 126(2), 241-247. https://doi.org/10.1002/ jlac.18631260212 —with r. rieth. ueber die darstellung des zinkäthyls. justus liebigs ann. chem. 126(2), 248-250. https:// doi.org/10.1002/jlac.18631260213 —with r. rieth. notiz über die darstellung des jodäthyls. justus liebigs ann. chem. 126(2), 250-251. https://doi.org/10.1002/jlac.18631260214 —with p. christofle. note sur la coloration de la flamme de l’hydrogène par le phosphore et ses composés. comptes rendus hebdomadaires des séances de l’academie des sciences. 56, 399-401. retrieved from https://gallica.bnf.fr/ark:/12148/bpt6k3013s/f399 —with w. kellner. ueber trinitrocressol und chrysanissäure. justus liebigs ann. chem. 128(2), 164-177. https://doi.org/10.1002/jlac.18631280205 —with a. reinecke. ueber die reduction der salicyligen säure zu saligenin. justus liebigs ann. chem. 128(2), 179-180. https://doi.org/10.1002/ jlac.18631280207 —with a. wilbrand. ueber eine neue reihe isomerer verbindungen der benzoëgruppe. — nitrodracylsäure und deren derivate. justus liebigs ann. chem. 128(3), 257-273. https://doi.org/10.1002/ jlac.18631280302; vorläufige notiz über nitrodracylsäure. justus liebigs ann. chem. 126(2), 255-256. https://doi.org/10.1002/jlac.18631260217 1864 —über die reduction der nitrokörper durch zinn und salzsäure. justus liebigs ann. chem. 130(2), 242245. https://doi.org/10.1002/jlac.18641300215 —with p. alexeyeff. préparation facile du zinc-éthyle. synthèse du propylène. comptes rendus hebdomadaires des séances de l’academie des sciences. 58, 171-173. retrieved from https://gallica.bnf.fr/ ark:/12148/bpt6k3015d/f173.item —with e. reichenbach. untersuchungen über isomerie in der benzoëreihe. zweite abhandlung. justus liebigs ann. chem. 132(2), 137-155. https://doi. org/10.1002/jlac.18641320202 —with e. reichenbach. untersuchungen über isomerie in der benzoëreihe: ueber die natur der sogenannten salylsäure. dritte abhandlung. justus liebigs ann. chem. 132(3), 309-321. https://doi.org/10.1002/ jlac.18641320309 1865 —ueber das xylol. justus liebigs ann. chem. 133(1), 32-47. https://doi.org/10.1002/jlac.18651330103 —ueber amidozimmtsäure und carbostyryl. zeitschrift für chemie, 1, 1-3. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/ page/n6/mode/2up —ueber die isomeren chlorbenzoësäuren. zeitschrift für chemie, 1, 141-144. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/ page/n146/mode/2up —ueber einige derivate der brenzschleimsäure. zeitschrift für chemie, 1, 144-147. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/ page/n150/mode/2up —ueber eine neue bildungsweise der toluylsäure und terephtalsäure. zeitschrift für chemie, 1, 212-214. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/page/n220/mode/2up —beschreibendes und theoretisches handbuch der chemie. von w. odling. deutsch von dr. a. oppenheim. erlangen 1865, f. enke. i band. (book review). zeitschrift für chemie, 1, 254-256. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/ page/n264/mode/2up —ueber das cumel des steinkohlentheers. zeitschrift für chemie, 1, 277-280. retrieved from https://archive. org/details/zeitschriftfrch06unkngoog/page/n286/ mode/2up —with p. geitner. ueber amidodracylsäure und amidobenzoësäure. zeitschrift für chemie, 1, 505-506. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/page/n514/mode/2up —einleitung in das studium der organischen chemie von a. butlerow. 385s. kasan 1864-1865. (book review). zeitschrift für chemie, 1, 727-730. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/ page/n736/mode/2up —with f. schlun. untersuchungen über isomerie in der benzoëreihe. vierte abhandlung. ueber die isomeren chlorbenzoësäuren. justus liebigs ann. 150 aleksander sztejnberg chem. 133(2), 239-252. https://doi.org/10.1002/ jlac.18651330218 —with a. reinecke. ueber cyanverbindungen der aromatischen aldehyde. justus liebigs ann. chem. 136(2), 169-176. https://doi.org/10.1002/ jlac.18651360213; zeitschrift für chemie, 1, 464-466. retrieved from https://archive.org/details/zeitschriftfrch06unkngoog/page/n474/mode/2up —with h. schmelz. ueber einige derivate der brenzschleimsäure. justus liebigs ann. chem. suppl. 3, 275-286. retrieved from https://babel.hathitrust.org/cgi/pt?id=uva. x002457967&view=1up&seq=283 —ueber amidozimmtsäure und carbostyryl. zeitschrift für chemie, 1, 1-3. retrieved from https://archive. org/details/zeitschriftfrch06unkngoog/page/n6/ mode/2up 1866 —with h. yssel de schepper. untersuchungen über die kohlenwasserstoffe des steinkohlentheers. zweite abhandlung. ueber die umwandlung des xylols in toluylsäure und terephtalsäure. justus liebigs ann. chem. 137(3), 301-311. https://doi.org/10.1002/ jlac.18661370306 —with a. kögler. untersuchungen über die kohlenwasserstoff des steinkohlentheers. dritte abhandlung. ueber das cumol des steinkohlentheers. justus liebigs ann. chem. 137(3), 317-327. https://doi. org/10.1002/jlac.18661370308 —with p. geitner. untersuchungen über isomerie in der benzoëreihe. fünfte abhandlung. ueber amidobenzoësäure und amidodracylsäure. justus liebigs ann. chem. 139(1), 1-16. https://doi.org/10.1002/ jlac.18661390102 —with p. geitner. untersuchungen über isomerie in der benzoëreihe. sechste abhandlung. ueber das verhalten der homologen des benzols gegen chlor. justus liebigs ann. chem. 139(3), 331-342. https://doi. org/10.1002/jlac.18661390308 —ueber die nichtidentität des chlortoluols mit dem chlorbenzyl. zeitschrift für chemie, 2, 17-19. retrieved from https://archive.org/details/bub_gb_ mgy4aaaamaaj/page/n23/mode/2up —ueber isomere chlortoluole. zeitschrift für chemie, 2, 307-308. retrieved from https://archive.org/details/bub_gb_mgy4aaaamaaj/ page/n313/mode/2up —with g. hirzel. ueber die oxydationsproducte des steinkohlentheer-cumols (trimethyl-b enzol). zeitschrift für chemie, 2, 503-504. retrieved from https://archive.org/details/bub_gb_ mgy4aaaamaaj/page/n511/mode/2up 1867 —rukovodstvo k kachestvennomu khimicheskomu analizu (manual of qualitative chemical analysis). tipografiya tovarishchestva obshchestvennaya pol’za, sankt-peterburg. —anleitung zur qualitativen chemischen analyse. verlag von quandt & händel, leipzig. —über das verhalten des toluols gegen brom. bulletin de l’académie impériale des sciences de st-pétersbourg, ser. 3. 1867, 11, 301-302. retrieved from https://babel.hathitrust.org/cgi/pt?id=osu.3243506 5017626&view=1up&seq=163; justus liebigs ann. chem. 143(3), 369-372. https://doi.org/10.1002/ jlac.18671430320 —with u. kreusler. über para-nitrotoluylsäure und deren derivative. bulletin de l’académie impériale des sciences de st-pétersbourg, ser. 3., 11, 412-428. retrieved from https://babel.hathitrust.org/cgi/pt?id= osu.32435065017626&view=1up&seq=218 —with u. kreusler. untersuchungen über isomerie in der benzoëreihe: siebente abhandlung. ueber para‐ nitrotoluylsäure und deren derivate. justus liebigs ann. chem. 144(2), 163-184. https://doi.org/10.1002/ jlac.18671440207 —ueber benzylbromid und bromtoluol. zeitschrift für chemie. 3, 281-282. retrieved from https://archive.org/details/zeitschriftfrch16unkngoog/ page/n288/mode/2up —with a. kuhlberg. ueber substituirte alkohole und aldehyde. zeitschrift für chemie. 3, 467-469. retrieved from https://archive.org/details/zeitschriftfrch16unkngoog/page/n474/mode/2up —with a. kuhlberg. ueber substitutionsproducte des toluols. zeitschrift für chemie. 3, 513-514. retrieved from https://archive.org/details/zeitschriftfrch16unkngoog/page/n520/mode/2up —rukovodstvo k kachestvennomu khimicheskomu analizu. tipografiya tovarishchestva obshchestvennaya pol’za, sankt-peterburg. 1868 —inleiding tot de qualitatieve chemische analyse (h. ijssel de scheppe, trans.). bij g. brouwer, te deventer. —rukovodstvo k kolichestvennomu analizu (manual of quantitative analysis). tipografiya tovarishchestva obshchestvennaya pol’za, st. petersburg. 151the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries —with a. kuhlberg. ueber einige derivative des toluols. zeitschrift für chemie. 4, 25-27. retrieved from https://archive.org/details/zeitschriftfrch13unkngoog/ page/n32/mode/2up —with a. kuhlberg. ueber isomere tetraund pentachlortoluole. zeitschrift für chemie. 4, 276278. retrieved from https://archive.org/details/zeitschriftfrch13unkngoog/page/n284/mode/2up —with a. kuhlberg. ueber hexachlortoluole. zeitschrift für chemie. 4, 561-563. retrieved from https:// archive.org/details/zeitschriftfrch13unkngoog/page/ n566/mode/2up —with a. kuhlberg. ueber para-dichlorund trichlorbenzoesäure. zeitschrift für chemie. 4, 661-664. retrieved from https://archive.org/details/zeitschriftfrch13unkngoog/page/n666/mode/2up —ueber die oxydationsproducte des theer-cumols. zeitschrift für chemie. 4, 672. retrieved from https://archive.org/details/zeitschriftfrch13unkngoog/ page/n678/mode/2up 1869 —with a. kuhlberg. ueber substituirte alkohole und aldehyde. justus liebigs ann. chem. 147(3), 339355. https://doi.org/10.1002/jlac.18681470306 —with a. kuhlberg. untersuchungen über isomerie in der benzoëreihe. neunte abhandlung. ueber die gechlorten derivate des toluols. justus liebigs ann. chem. 150(3), 286-314. https://doi.org/10.1002/ jlac.18691500303 —with a. kuhlberg. untersuchungen über isomerie in der benzoëreihe. zehnte abhandlung. ueber di‐ und trichlorbenzoësäure. justus liebigs ann. chem. 152(2), 224-246. https://doi.org/10.1002/ jlac.18691520212; zh. russ. khim. o-va. 1, 155-172. —with a. kuhlberg. ueber heptachlortoluole. zeitschrift für chemie. 5, 75-77. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/ page/n82/mode/2up —ueber die identität von dichlorbenzoesäure und paradichlorbenzoesäure. zeitschrift für chemie. 5, 180181. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/page/n188/mode/2up —with a. kuhlberg. ueber perchlorbenzol und seine bildung aus toluol und xylol. zeitschrift für chemie. 5, 183. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/page/n190/mode/2up —with a. kuhlberg. ueber eine reihe isomerer toluol-derivative. zeitschrift für chemie. 5, 280-281. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/page/n288/mode/2up —supplementband zu gmelin handbuch der chemie. seite 1-516, bearbeitet von a. husemann; seite 5171272, bearbeitet von k. kraut, 2 abthl. heidelberg 1867-68. k. winter. (book review). zeitschrift für chemie. 5, 287-288. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/ page/n294/mode/2up —with a. kuhlberg. ueber aethyl-phenol. zeitschrift für chemie. 5, 461-463. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/page/n468/mode/2up —with a. kuhlberg. ueber isomere nitrotoluole und toluidine. zeitschrift für chemie. 5, 521-524. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/page/n528/mode/2up —with a. kuhlberg. ueber isomere nitroäthylbenzole und xylidine. zeitschrift für chemie. 5, 524-525. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/page/n532/mode/2up —with a. kuhlberg. ueber dichlorund trichlorbenzoesäure. zeitschrift für chemie. 5, 526-529. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/page/n534/mode/2up —with a. kuhlberg. benzolderivative aus toluol. zeitschrift für chemie. 5, 529-529. retrieved from https://archive.org/details/zeitschriftfrch07unkngoog/ page/n536/mode/2up —with a. kuhlberg. issledovaniya ob izomerakh v benzoynom ryadu. x. o dvui trikhlorbenzoynykh kislotakh (research on isomers in the benzoic series. x. about diand trichlorobenzoic acids). zh. russ. khim. o-va, 1, 155-172. 1870 —with a. kuhlberg. untersuchungen über isomerie in der benzoëreihe. elfte abhandlung. die isomeren formen des nitrotoluols. justus liebigs ann. chem. 155(1), 1-29. https://doi.org/10.1002/ jlac.18701550102; zh. russ. khim. o-va. 2, 131-151. —with a. kuhlberg. untersuchungen über isomerie in der benzoëreihe. zwölfte abhandlung. ueber die isomeren toluidine. justus liebigs ann. chem. 156(1), 66-84. https://doi.org/10.1002/ jlac.18701560110; zh. russ. khim. o-va. 2, 229-242. —with a. kuhlberg. untersuchungen über isomerie in der benzoëreihe. dreizehnte abhandlung. ueber einige derivate des aethylbenzols. justus liebigs ann. chem. 156(2), 206-215. https://doi.org/10.1002/ jlac.18701560213 152 aleksander sztejnberg —with a. kuhlberg. ueber isomere nitrotoluole und toluidine. zeitschrift für chemie. 6, 102-103. retrieved from https://archive.org/details/zeitschriftfrch11unkngoog/page/n110/mode/2up —j. wiesner, die technisch verwendeten gummiarten, harze und balsame. erlangen, f. enke. 1869. 205 s. (book review). zeitschrift für chemie. 6, 192. retrieved from https://archive.org/details/zeitschriftfrch11unkngoog/page/n200/mode/2up —with a. kuhlberg. zur kenntniss des ortho-nitrotoluols. zeitschrift für chemie. 6, 298-299. retrieved from https://archive.org/details/zeitschriftfrch11unkngoog/page/n306/mode/2up —with a. kuhlberg. ueber ortho-nitrotoluols. zeitschrift für chemie. 6, 417-418. retrieved from https://archive.org/details/zeitschriftfrch11unkngoog/page/n424/mode/2up —ueber die gewinnung des jods ans rückständen. zeitschrift für chemie. 6, 528-529. retrieved from https://archive.org/details/zeitschriftfrch11unkngoog/page/n536/mode/2up; izvlecheniye yoda iz ostatkov (on the extraction of iodine from the residues). zh. russ. khim. o-va, 2, 186-205. —fortsetzung zu gmelin’s handb. der chemie. bearbeitet und herausgegeben von k. kraut. register zu gmelin’s handb. der chemie. bd.4-8 und suppl. von k. kraut. heidelberg, k. winter. (book review). zeitschrift für chemie. 6, 672. retrieved from https://archive.org/details/zeitschriftfrch11unkngoog/ page/n680/mode/2up —with a. kuhlberg. o izomernykh nitrotoluolakh (about isomeric nitrotoluenes). zh. russ. khim. o-va, 2, 131-152. —with a. kuhlberg. ob izomernykh toluidinakh (about isomeric toluidines). zh. russ. khim. o-va, 2, 229-242. —with a. kuhlberg. o nektorykh proizvodnykh etilbenzola (on some derivatives of ethylbenzene). zh. russ. khim. o-va, 2, 268-274. 1871 —with a. kuhlberg. untersuchungen über isomerie in der benzoëreihe. vierzehnte abhandlung. ueber die bestimmung des chemischen ortes in einigen toluolderivaten. justus liebigs ann. chem. 158(3), 335353. https://doi.org/10.1002/jlac.18711580310 —with a. kuhlberg. ueber nitrirtes ortho-toluidin. zeitschrift für chemie. 7, 99-100. retrieved from https://archive.org/details/zeitschriftfrch31unkngoog/ page/n106/mode/2up —with a. kuhlberg. isomere toluylen-diamine. zeitschrift für chemie. 7, 134-135. retrieved from https://archive.org/details/zeitschriftfrch31unkngoog/ page/n142/mode/2up —with a. kuhlberg. ueber meta-nitrozimmtsäure und meta-nitrobenzoesäure. zeitschrift für chemie. 7, 616-618. retrieved from https://archive.org/details/zeitschriftfrch31unkngoog/page/n624/mode/2up —with a. kuhlberg. ob opredelenii khimicheskogo mesta v nekotorykh proizvodnykh toluola (determination of the chemical site in some toluene derivatives). zh. russ. khim. o-va, 3, 128-141. 1872 —with a. kuhlberg. untersuchungen über isomerie in der benzoëreihe. vierzehnte abhandlung. ueber zimmtsäure und metanitrobenzoësäure. justus liebigs ann. chem. 163(1), 121-143. https://doi. org/10.1002/jlac.18721630107 —ueber den nachweis von chlor, brom und jod in organischen substanzen. ber. dtsch. chem. ges. 5(2), 620621. https://doi.org/10.1002/cber.18720050209 —ob otkrytii khlora, broma i yoda v organicheskikh soyedineniyakh (on the discovery of chlorine, bromine and iodine in organic compounds). zh. russ. khim. o-va, 4, 308, 358-359. —with a. kuhlberg. o korichnoy i meta-nitrobenzoynoy kislotakh (about cinnamic and meta-nitrobenzoic acids). zh. russ. khim. o-va, 4, 79-95. 1873 —a manual of qualitative chemical analysis, (w. ramsay, trans.), william collins, sons, & company, london, glasgow. —die chemische grossindustrie auf der weltaustellung zu wien im jahre 1873, verlag von quandt und händel, leipzig. —with a. kuhlberg. ueber die nitroderivate des naphtalins. justus liebigs ann. chem. 169(1-2), 81-100. https://doi.org/10.1002/jlac.18731690105 —with a. kupffer. ueber cymole. justus liebigs ann. chem. 170(3), 282-290. https://doi.org/10.1002/ jlac.18731700303 —with a. kupffer. ueber cuminsäure. justus liebigs ann. chem. 170(3), 301-304. https://doi.org/10.1002/ jlac.18731700306 —with a. kuhlberg. ueber trinitro‐naphtaline. ber. dtsch. chem. ges. 6(1), 647-649. https://doi. org/10.1002/cber.187300601202 —with a. kupffer. mittheilungen. i. ueber cymole. 153the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries ber. dtsch. chem. ges. 6(2), 1181-1184. https://doi. org/10.1002/cber.18730060299 —ueber die metall‐derivate des cyanamids. ber. dtsch. chem. ges. 6(2), 1185-1185. https://doi.org/10.1002/ cber.187300602100 —die chemische grossindustrie auf der weltaustellung zu wien im jahre 1873. verlag von quandt & händel, leipzig. retrieved from https://opacplus.bsbmuenchen.de/title/bv013564871 —with a. kuhlberg. o nitroproizvodnykh naftalina (about nitroderivatives of naphthalene). zh. russ. fiz.-khim. o-va, 5, 256-270. —with a. kupffer. o tsimole (about cymol). zh. russ. fiz.-khim. o-va, 5, 428-434. —with a. kupffer. o polynnom masle (about wormwood oil). zh. russ. fiz.-khim. o-va, 5, 435-444. —with a. kupffer. o kuminovoy kislote (about cumic acid). zh. russ. fiz.-khim. o-va, 5, 444-447. 1874 —with a. k. krupskiy. fabrichnaya khimicheskaya promyshlennost’ zapadno-yevropeyskikh stran na vsemirnoy vystavke v vene 1873 goda. sankt-peterburg. —with a. kurbatow. ueber den zusammenhang substituirter benzole und phenole. ber. dtsch. chem. ges. 7(2), 1395-1399. https://doi.org/10.1002/ cber.187400702141 —with a. kurbatow. ueber gechlortes phenylsenföl und dessen derivate. ber. dtsch. chem. ges. 7(2), 14891491. https://doi.org/10.1002/cber.187400702168 —with a. kurbatow. ueber isomere dichlorbenzole. ber. dtsch. chem. ges. 7(2), 1759-1762. https://doi. org/10.1002/cber.187400702249 1875 —with a. kurbatow. o sootnoshenii ryadov zameshchennykh benzolov i fenolov (on the ratio of the series of substituted benzenes and phenols). zh. russ. khim. o-va. 7, 10-32. —with a. kurbatow. ueber den zusammenhang substituirter benzole und phenole. justus liebigs ann. chem. 176(1), 27-54. https://doi.org/10.1002/ jlac.18751760104 —untersuchungen über isomerie in der benzoëreihe. fünfzehnte abhandlung. ueber dichlorbenzoësäuren. justus liebigs ann. chem. 179(3), 283-295. https://doi.org/10.1002/jlac.18751790303 —ueber dichlorbenzoësäure. ber. dtsch. chem. ges. 8(1), 813-815. https://doi.org/10.1002/cber.187500801268 —notiz über chlorsalicylsäure. ber. dtsch. chem. ges. 8(1), 816-816. https://doi.org/10.1002/ cber.187500801269 —ueber dichlorbenzoësäure. ber. dtsch. chem. ges. 8(2), 924-925. https://doi.org/10.1002/cber.18750080208 —with a. kurbatow. ueber m‐chlornitrobenzol. ber. dtsch. chem. ges. 8(2), 1417-1418. https://doi. org/10.1002/cber.187500802150 —with a. kurbatow. ueber di‐ und trichloranilin. ber. dtsch. chem. ges. 8(2), 1655-1656. https://doi. org/10.1002/cber.187500802226 1876 —an introduction to qualitative chemical analysis (i. j. osbun,trans.), van nostrand, new york. —with a. kurbatow. ueber tetrachlorbenzol. ber. dtsch. chem. ges. 9(1), 579-580. https://doi.org/10.1002/ cber.187600901179 —with a. kurbatow. ueber chlornitraniline. ber. dtsch. chem. ges. 9(1), 633-635. https://doi.org/10.1002/ cber.187600901194 —with a. kurbatow. ueber die substitution im benzol. justus liebigs ann. chem. 182(1-2), 94-112. https:// doi.org/10.1002/jlac.18761820108 1877 —with a. kurbatow. o produktakh zameshcheniya benzola (about benzene substitution products). zh. russ. fiz.-khim. o-va. 9, 99-114. —with a. kurbatow. ueber die chlorderivate des benzols. ber. dtsch. chem. ges. 10(1), 270-274. https://doi. org/10.1002/cber.18770100180 —with a. kurbatow. ueber das verhalten einiger nitrokörper gegen schwefelwasserstoff. ber. dtsch. chem. ges. 10(2), 1992-1994. https://doi.org/10.1002/ cber.187701002184 —with a. kurbatow. ueber dichloraniline. ber. dtsch. chem. ges. 10(2), 2089-2091. https://doi.org/10.1002/ cber.187701002218 1878 —with a. kurbatow. 1. ueber die chlorderivate des benzols. justus liebigs ann. chem. 192(1-2), 228-240. https://doi.org/10.1002/jlac.18781920125; o khlorzameshchennykh produktakh benzola (on chloroderivatives of benzol). zh. russ. fiz.-khim. o-va. 10, 326-336. 154 aleksander sztejnberg —ueber die scheidung des zinks vom nickel. ber. dtsch. chem. ges. 11(2), 1715-1718. https://doi. org/10.1002/cber.187801102130 —with a. kurbatow. ueber chloraniline. b er. dtsch. chem. ges. 11(2), 1860-1863. https://doi. org/10.1002/cber.187801102170 —with a. kurbatow. ueber chlornitroaniline. ber. dtsch. chem. ges. 11(2), 1978-1980. https://doi. org/10.1002/cber.187801102200 —with a. kurbatow. ueber das verhalten einiger nitrokörper gegen schwefelwasserstoff. ber. dtsch. chem. ges. 11(2), 2056-2057. https://doi. org/10.1002/cber.187801102228 —ueber perchlorphenolchlorid c6cl5 (ho).cl2, ber. dtsch. chem. ges. 11(2), 2182-2183. https://doi. org/10.1002/cber.187801102264 —ob otdelenii tsinka ot nikelya (separation of zinc from nickel). zh. russ. fiz.-khim. o-va, 10, 400-404. 1879 —with a. kurbatow. ueber chlor‐ und chlornitraniline. justus liebigs ann. chem. 196(2), 214-238. https:// doi.org/10.1002/jlac.18791960204 —with a. kurbatow. ueber das verhalten einiger nitrokörper zu schwefelwasserstoff. justus liebigs ann. chem. 197(1), 75-85. https://doi.org/10.1002/ jlac.18791970107 —with l. jawein. ueber die quantitative bestimmung des zinks. ber. dtsch. chem. ges. 12(1), 446-448. https:// doi.org/10.1002/cber.187901201124 —with l. jawein. behandlung der bunsen’schen elemente. ber. dtsch. chem. ges. 12(1), 448-448. https:// doi.org/10.1002/cber.187901201125 —with l. jawein. ueber die quantitative bestimmung des cadmiums. ber. dtsch. chem. ges. 12(1), 759-762. https://doi.org/10.1002/cber.187901201212 —with l. jawein. ueber die directe trennung des mangans vom eisen. ber. dtsch. chem. ges. 12(2), 15281531. https://doi.org/10.1002/cber.18790120280 —with a. kurbatow. o khloranilinakh i khlornitroanilinakh (about chloranilines and chloronitroanilines). zh. russ. fiz.-khim. o-va, 11, 325-344. —with a. kurbatow. ob otnoshenii nekotorykh nitrotel k sernistomu vodorodu (on the relation of some nitrobodies to hydrogen sulphide). zh. russ. fiz.khim. o-va, 11, 368-377. 1880 —with a. kurbatow. ueber die constitution einiger naphtalinderivate. justus liebigs ann. chem. 202(2), 213-229. https://doi.org/10.1002/jlac.18802020205 —with a. kurbatow. ueber dinitronaphtalin. ber. dtsch. chem. ges. 13(1), 353-354. https://doi.org/10.1002/ cber.188001301104 —with a. kurbatow. ueber dinitrobenzoësäure. ber. dtsch. chem. ges. 13(1), 355-355. https://doi. org/10.1002/cber.188001301105 —with l. jawein. ueber die werthbestimmung von zink und zinkstaub. ber. dtsch. chem. ges. 13(1), 947950. https://doi.org/10.1002/cber.188001301265 —ueber dinitroparatoluidin. b er. dtsch. chem. ges. 13(1), 242-244. https://doi.org/10.1002/ cber.18800130166 —with a. kurbatow. ueber die natur des kaukasischen petroleums. ber. dtsch. chem. ges. 13(2), 1818-1821. https://doi.org/10.1002/cber.188001302143 —with a. kurbatow. ueber die kohlenwasserstoffe des amerikanischen petroleums. ber. dtsch. chem. ges. 13(2), 2028-2029. https://doi.org/10.1002/ cber.188001302182 1881 —with a. kurbatow. ii. ueber kaukasisches petroleum. ber. dtsch. chem. ges. 14(2), 1620-1622. https://doi. org/10.1002/cber.18810140211 —with l. jawein. zh. ob opredelenii i otdelenii nekotorykh metallov (on the determination and separation of certain metals). russ. fiz.-khim. o-va, 13, 9-18. —with a. kurbatow. o stroyenii nekotorykh proizvodnykh naftalina (on the structure of some derivatives of naphthalene). zh. russ. fiz.-khim. o-va, 13, 136149. 1882 —manuel d’analyse chimique qualitative (a. buisine, p. buisine, trans.), elie masson, lille. —ueber petersburger rhabarber. ber. dtsch. chem. ges. 15(1), 901-902. https://doi.org/10.1002/ cber.188201501194 —with e. wiegand. ueber einige reaktionen des aethylenbromids. ber. dtsch. chem. ges. 15(1), 1368-1370. https://doi.org/10.1002/cber.18201501292 —with e. wiegand. ueber propylenbromid. ber. dtsch. chem. ges. 1882, 15(2), 1496-1498. https://doi. org/10.1002/cber.18820150209 —with e. wiegand. ueber die darstellung von propylen. ber. dtsch. chem. ges. 15(2), 1498-1499. https://doi. org/10.1002/cber.18820150210 155the eminent russian – german chemist friedrich konrad beilstein (1838-1906) in the literature between 19th and 21st centuries —with e. wiegand. ueber isodibrombernsteinsäure. ber. dtsch. chem. ges. 15(2), 1499-1500. https://doi. org/10.1002/cber.18820150211 —with e. wiegand. ueber angelikaöl. ber. dtsch. chem. ges. 15(2), 1741-1742. https://doi.org/10.1002/ cber.18820150265 —with e. wiegand. ueber einige ätherische oele. ber. dtsch. chem. ges. 15(2), 2854-2855. https://doi. org/10.1002/cber.188201502272 1883 —handbuch der organischen chemie. zwei bände (2 vols.). verlag von leopold voss, hamburg und leipzig, 1881-1883. —lessons in qualitative chemical analysis. (c.o. curtman,trans.), st. louis stationery & book co., saint louis (mo.). —with e. wiegand. ueber kaukasischen ozokerit. ber. dtsch. chem. ges. 16(2), 1547-1551. https://doi. org/10.1002/cber.18830160209 —with e. wiegand. ueber alkylsulfaminsäuren. ber. dtsch. chem. ges. 16(1), 1264-1268. https://doi. org/10.1002/cber.188301601281 —ueber petroleumprüfung. z. f. analyt. chem. 22, 309316. retrieved from https://books.google.pl/books?id=6 epmaaaamaaj&printsec=frontcover&hl=pl&source —with a. kurbatow. issledovaniye kavkazskoy nefti (study of the caucasian oil). zh. russ. fiz.-khim. o-va, 15, 5-32. 1884 —with e. wiegand. ueber eine neue bildungsweise der brenztraubensäure. ber. dtsch. chem. ges. 17(1), 840842. https://doi.org/10.1002/cber.188401701225 —with e. wiegand. ueber angelikasäure und tiglinsäure. ber. dtsch. chem. ges. 17(2), 2261-2263. https:// doi.org/10.1002/cber.188401702136 —obituary. hans (julius anton edward) hübner. ber. dtsch. chem. ges. 17(2), a763-a776. https://doi. org/10.1002/cber.188401702326 —with l. jawein. ob opredelenii dostoinstva tsinka i tsinkovoy pyli (about defining dignity zinc and zinc dust). zh. russ. fiz.-khim. o-va. 16, 363-366. 1885 —with e. wiegand. ueber einige ungesättigte verbindungen der fettreihe, ber. dtsch. chem. ges. 18(1), 481-483. https://doi.org/10.1002/cber.188501801103 1890 —handbuch der organischen chemie. zweite auflage. drei bände (3 vols. i bd., 1886; ii bd., 1888; iii bd., 1890). verlag von leopold voss, leipzig, 1886-1890. —with l. jawein, rukovodstvo k kachestvennomu i kolichestvennomu khimicheskomu analizu (manual of quantitative and qualitative chemical analysis). st. petersburg. —with o. von blaese. untersuchungen über die basicität der antimonsäure. bulletin de l’académie impériale des sciences de st-pétersbourg, 33, 97-116. retrieved from https://www.biodiversitylibrary.org/ item/105810#page/105/mode/1up —with o. von blaese. über die quantitative bestimmung des antimons. bulletin de l’académie impériale des sciences de st-pétersbourg, 33, 201-207. retrieved from https://www.biodiversitylibrary.org/ item/105810#page/213/mode/1up —with o. von blaese. über die bestimmung des natrons neben kali. bulletin de l’académie impériale des sciences de st-pétersbourg, 33, 209-211. retrieved from https://www.biodiversitylibrary.org/ item/105810#page/221/mode/1up —with th. grosset. über die analyse der schwefelsauren thonerde. bulletin de l’académie impériale des sciences de st-pétersbourg, 33, 147-153. retrieved from https://www.biodiversitylibrary.org/ item/105810#page/155/mode/1up 1892 —with r. luther. über die verfahren zur trennung des eisenoxyds von der thonerde. bulletin de l’académie impériale des sciences de st-pétersbourg, 34, 155164. retrieved from https://www.biodiversitylibrary. org/item/106464#page/160/mode/1up 1894 —o rabotakh chlenov russkogo fiziko-khimicheskogo obshchestva po aromaticheskomu ryadu. rech’ (on the works of members of the russian physicochemical society on the aromatic series. speech). zh. russ. fiz.-khim. o-va, 26, 39-56. 1896 —with r. rinne. über die bestimmung des glicerins und die analyse des wachses. bulletin de l’académie impériale des sciences de st-pétersbourg, sér. 5., 5(4), 156 aleksander sztejnberg 283-293. retrieved from https://www.biodiversitylibrary.org/item/93790#page/377/mode/1up —pamyati avgusta kekule (in memory of august kekulé). zh. russ. fiz.-khim. o-va, 28, 703-705. 1899 —handbuch der organischen chemie. dritte auflage. vier bände (4 vols., i bd., 1893; ii bd. 1896; iii bd.1897; iv bd. 1899. verlag von leopold voss, hamburg, leipzig, 1893-1899. substantia an international journal of the history of chemistry vol. 5, n. 1 2021 firenze university press giving credit where it’s due – the complicated practice of scientific authorship seth c. rasmussen history of research on antisense oligonucleotide analogs jack s. cohen chemistry, cyclophosphamide, cancer chemotherapy, and serendipity: sixty years on gerald zon thermodynamics of life marc henry darwin and inequality enrico bonatti loren eiseley’s substitution bart kahr new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors yona siderer capillary electrophores is and its basic principles in historical retrospect 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis ernst kenndler1,*, marek minárik2,3 the eminent russian – german chemist –friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries aleksander sztejnberg review of what is a chemical element? by eric scerri and elena ghibaudi, eds. oxford: oxford university press, 2020 helge kragh substantia. an international journal of the history of chemistry 5(2): 41-54, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1187 citation: siderer y. (2021) translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects. substantia 5(2): 41-54. doi: 10.36253/substantia-1187 received: nov 04, 2020 revised: apr 29, 2021 just accepted online: may 04, 2021 published: sep 10, 2021 copyright: © 2021 siderer y. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research articles translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer edelstein center for history and philosophy of science, technology and medicine, the hebrew university of jerusalem e-mail: sideryon@netvision.net.il abstract. this research studies two translations of henry enfield roscoe’s chemistry book of 1872 into japanese (1873) and hebrew (1929). roscoe’s original chapter on candle burning is presented, in which he manifested his attitude to chemical experiments. the japanese and hebrew historical backgrounds of the translations, as well as their cultural and linguistic aspects are discussed. roscoe’s relations with japanese scholars are presented. the study moves between events in three countries, england, japan and israel. the importance and complexity of translation of science and its later results are discussed. keywords: translation of chemistry, henry e. roscoe, japanese language, hebrew language, candle burning. translation of science transferring knowledge from one culture and language into another target language that does not yet have a suitable vocabulary for the subject studied is an intensive human endeavor; creating new, appropriate vocabulary in order to look at the behavior of nature is the topic of this research. inventing language in a new scientific discipline depends on contemporary knowledge in that field. within the process of translation, the subject matter changes some of its features to suit the culture, the beliefs and understanding of the target people and their language. as bensaude-vincent stated in her article “the language of chemistry”: language plays a key role in shaping the identity of a scientific discipline (bensaude-vincent 2003).1 the new thought and new terminology serve to augment the discussion and practices of the scholars and people using the target language. later, the new terms go on to infiltrate and fertilize the daily language of the people. according to montgomery, in rendering technical knowledge mobile between peoples and through the centuries, translation has been a crucial force behind both the creation and the continual refertilization of science (montgomery 2000).2 http://www.fupress.com/substantia http://www.fupress.com/substantia 42 yona siderer following are translations into japanese and hebrew of roscoe’s science primers chemistry for school. roscoe’s explanation about the candle burning experiment highlights the historical and cultural background of the translations, the chemical terminology of the languages and what translation of science may lead to. roscoe’s life and his early chemistry books henry enfield roscoe (1833-1915) was an english chemist who spent a few years in the laboratory of robert bunsen in heidelberg before returning to england in 1857. the same year he moved to manchester, organized and revived the chemistry department of owens college, which was incorporated into victoria university in 1880. his main fields of research were vanadium and photochemistry. after retirement from victoria university in 1887 he moved to london and became a member of parliament, devoting time to several scientific committees. he was elected president of the chemical society in 1881 and was a founder-member and first president of the society of chemical industry in 1881 (roscoe 1906). the early chemistry books by roscoe were lessons in elementary chemistry  (roscoe 1866) and lessons in elementary chemistry: inorganic and organic (roscoe 1868). roscoe’s book chemistry in the science primers series was published in london by macmillan addresses the following topics: fire; air; water; earth; non-metallic elements; metals; results (roscoe 1872). science primers chemistry (1872) was a part of a series that included physics, geology, logic, botany etc.3 it was also published in the united states of america by d. appleton and company, new york 1872. editions of the book are still being republished. those books have been translated into more than nine languages. the book lessons in elementary chemistry  was translated into russian, italian, hungarian, polish, swedish, modern greek, japanese and urdu.4 translations of science primers chemistry appeared in german, icelandic,5 polish, italian, japanese, bengali, turkish, malayan, tamil3 and chinese.6 as osawa stated, it is a proof to the excellence of the small book (osawa 1978).7 a short, original english text of roscoe (roscoe 1872) and its japanese (kogaku 1873) and hebrew (oirbach 1929) translations are presented and studied in the following chapters. a copy of roscoe’s book in japanese was given to the current author by kida akiyoshi in kyoto in 2014; this led to the following research. the experiment of the burning candle is the first experiment presented and explained by roscoe and his translators. in addition to the observation of the chemical phenomena, roscoe explained what a chemical experiment is and its importance. roscoe: science primers chemistry the first chapter discusses the chemistry of air, water, earth and starts with fire. original texts from roscoe’s book: 2. what happens when a candle or a taper burns? the wax as well as the wick of the taper gradually disappears as the taper burns, and at last all is gone – wick, wax, and all. what has become of the wax? it has disappeared. is it lost? so far as our eyes are concerned certainly it is lost, but so is the ship which sails away on the sea, and yet we know that the ship still exists though we do not see it; and so the lump of sugar appears to be lost when we put it into a cup of hot tea, and yet we know that the sugar is not really lost, because the tea is made sweet. now we must look for the wax of our taper in another way; we must put a question to nature for her to answer, and we shall always find that our question, if properly asked, is always clearly and certainly answered. we must figure 1. candle burning experiment.9 43translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects make an experiment, and if this is properly made we shall never fail in the end to get the information we want.8 […] and if you quickly press a sheet of white paper on to the flame so as not to burn the paper, you will see that it becomes stained with a black ring of soot or carbon. 3. besides carbonic acid gas there is another substance formed when the candle burns, viz. water.10 in the experiment described above the taper in the bottle was burnt, the fire was stopped, and (some of) the material disappeared from sight. the question roscoe asked is what happened to the material of the candle, did it disappear completely? he addressed the question to nature and the answer he gave after performing more experiments is that the carbon of the wax was turned into colorless carbonic acid and water. in a further experiment adding lime to the bottle in which the candle burnt it changed color to turbid white by forming calcium carbonate. the calcium of the lime (calcium hydroxide) reacted with the carbonic acid gas to produce calcium carbonate. roscoe didactically stresses the aim of the experiment and its result: we want to know what happens when a candle burns. we have learnt – 1. that a candle soon goes out if it be burnt in a bottle of air. 2. that a colorless invisible gas called carbonic acid is formed in the bottle after the candle has burnt. 3. that the carbonic acid gas comes from the carbon or soot contained in the wax. 4. that the water is also formed when the candle burns.11 the experiment gave answers to the question, thus roscoe emphasized that chemistry is an experimental science [bold letters are in the original book]. however, roscoe’s statement that we shall always get the right answer if we ask the proper question is open to debate. the english text can be seen on-line in the web.12 the japanese translation of roscoe’s text the japanese translation of roscoe’s chemistry book was published by the ministry of education 文部 省 mombusho in 1873, translated by ichikawa seizaburou 市川盛三郎, titled kogaku kagakusho hyoumoku 小 學化學書標目 chemistry book for elementary school. the author of this article possesses a hand bound volume 1 of 1873. its title page is presented in fig. 2. there are many holes made by worms during one hundred and forty eight years since it was wood block printed, but still, in spite of the holes and the brownish background of the pages, it is clearly readable. the full translation was published in 1874 (osawa 1978, yamaguchi 2017). japanese book can be seen on-line in the web.13 the experiment of candle burning in its japanese translation is presented in fig. 3. the figure of candle burning is the first of 36 figures, shown and discussed by roscoe in his book. the japanese translation of the english text is written in kanji, chinese characters that convey meaning, and also in katakana, the phonetic square japanese script. this style is different from current use of kanji and hiragana, the phonetic cursive syllabaries. (b. frellesvig).14 the old writing style and some old characters will be discussed below. the pronunciation of the text in romaji, adapted to today’s writing and reading is presented in note.15 the japanese text follows the english description in the paragraph on candle burning and running an experiment. according to sato shin it cannot be considered a good text by today’s standards.16 this is understood as we know that understanding chemistry and the language of chemistry have developed since 1873, examples follow. the hebrew translation by pesach oirbach, himia, chemistry figure 4 presents oirbach’s hebrew translation of roscoe’s arguments on the disappearance of things and figure 2. front page of roscoe’s book 十八百七十三年 ロスコ ウ 小學化學書標目 1873 roscoe kogaku kagakusho hyoumoku chemistry book for elementary school. 44 yona siderer the explanation about setting an experiment. the full hebrew text of experiment 1 on candle burning is presented in note 17.17 the hebrew content follows faithfully the english original. it is written with somewhat elevated language, adding explanatory details that are discussed below. in the following section, history, culture and linguistic aspects of the texts and the significance of its translations are presented and discussed. historical, cultural, and linguistic aspects of the translations historical background in 1873 japan and in 1929 palestine-israel, processes of the nation’s revival evolved. the japanese people shortly after meiji restoration of 1868, which moved the tokugawa feudal rule and put the emperor back to its seat, strived to reform and to unite the country. the jews since late nineteenth century, started returning and renewing life in their ancient, biblical motherland. these processes of nation building formed the need for updated scientific knowledge including chemistry. hence, the motives to translate roscoe’s chemistry teaching book in both countries. the japanese translation of roscoe’s book by 1873 the ministry of education of the new regime in japan published the japanese translation of roscoe’s science primers chemistry book under the title chemistry book for elementary school. how come the ministry of education decided to translate roscoe’s book, rather than a book by any other author? three potential reasons are presented in notes.18, 19, 20 however the iwakura mission is figure 3. candle burning experiment in japanese, 1873. figure 4. candle burning experiment in hebrew, 1929. 45translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects the only one of those three that might have had roscoe’s science primers chemistry book. thus, griffis holding roscoe’s book elements in chemistry, inorganic and organic, kume kunitake diary emphasis on chemistry education during the travel of the iwakura mission, specifically during the visit in manchester, at roscoe’s laboratory in owens college, and ichikawa’s-ritter’s copy, might have inf luenced the ministry of education to order the translation of roscoe’s latest book. cultural aspects of the translations looking at the differences between the original english text and its japanese and hebrew translations, how faithful are they to the original text, are there any changes and what might be the reasons for these changes? in order to explain the disappearance of the candle wax during burning, roscoe presented two cases for the disappearance of items out of our sight and yet we are aware of their existence. those cases serve to emphasize the fact that although the burning candle in the bottle has disappeared, its material is present in other forms. in the first case, a ship is going away and we do not see her any longer; nevertheless, we are sure of its existence. the japanese translation tells about a ship, fune, 舟, that cannot be seen, without any additional information. the hebrew translation broadens the description, telling about a ship with masts and sails, sailing beyond the horizon. this description is more figurative, adding more features to the original text. the second case tells about material that disappears and actually changes its state. roscoe told of a lump of sugar that enters into a cup of hot tea. the sugar disappeared, yet we are aware of its effect since the hot tea became sweet. this example tells about an english custom in which a lump of sugar is introduced into the tea. the japanese translation of hot tea changed it into water, mizu, 水, not even hot water that has a different character yu 湯. the water becomes sweet therefore we are aware of the sugar dissolving effect. since the japanese do not sweeten their tea, in order to make the description closer to the japanese experience, the english tea description is replaced by water. the hebrew translator went even further: instead of hot tea the description is of a piece of sugar put into coffee. the reason for this change is not clear. was coffee more popular than tea in israel in 1929? there is no evidence for that. it can be said in general that the hebrew translation uses a more elevated linguistic style than the english does, new hebrew terms are used, and in an elaborate style. oirbach wrote improved examples and a somewhat more detailed story. the vocabulary is widened, the style is new and the existing culture affects the terminology chosen for the translation. there is a large time gap between the japanese translation of 1873 and the hebrew translation of 1929: understanding chemistry had progressed in the world between those almost sixty years. moreover, the main difference is related to the translators. the japanese translator had very little to rely on. earlier chemistry translation in japan were the seven volumes of seimi kaiso, introduction to chemistry, by udagawa youan published during 1836-1847 (udagawa 1836-1847, tanaka 1975, siderer 2017). udagawa youan studied more than twenty books in dutch on chemistry before he composed seimi kaiso (dōke 1973, azuma 2015, siderer 2021). perhaps udagawa youan’s seimi kaisou books on chemistry might have been good sources for chemistry vocabulary if the translator ichikawa seizaburou had access to them. in distinction, the hebrew translator pesach oirbach was born in kishinev, moldova, in 1877 and died in tel-aviv, 1945. he was a teacher, school principle, an author, researcher of nature and wrote books for teaching natural sciences. he immigrated to palestine-israel in 1908 (wikipedia, 21.4.2021 oirbach’s biograph).21 oirbach had the advice from engineer m. vinik (1886-1966) and other experts on the officially chosen and invented terms by a large group of scholars. moreover, members of the hebrew language committee in mandatory palestine-israel had earlier studied chemistry in the countries they immigrated from, and they had already learnt chemistry in russia and germany (simchoni 1949, leibovitch 1951, shapiro 1959). so when they came to coin hebrew chemistry terms their scientific basis was much better than that of the japanese translator ichikawa. it enabled the hebrew translator oirbach to choose terms and to present a more elaborate translation. nevertheless, we see in the next section that not all the terms oirbach used has survived, and they were replaced by other, more appropriate terms. an example can be seen in yizhak klugai, a professor of the technion, israel institute of technology, who translated general chemistry by linus pauling in 1965. japanese chemistry language and terminology the f irst english-japanese chemistr y dictionary was published in 1891 by tokyo chemical society that later became the chemical society of japan. it has english alphabetic order of the terms and the japanese 46 yona siderer term opposite it. some of the terms in the text above were modified during several changes of rules for writing kanji. during the years there were several committees that considered, omitted, added and modified kanji writings and kanji usage (gottlieb 1995). the text under study itself has very few periods to mark the end of a sentence. also, several of the syllables in the text like ha, sa, su, ki, ku are nowadays pronounced ba, za, zu, gi, gu respectively and are written with inverted commas (”) at the right top of the character, not present in the old text, (e.g. は＞ば、き＞ぎ、く＞ぐ）. following are examples of few of the words written in kanji in the text and their modernized character (denshi jisho, 2017): – 燈 (tou), lamp, an old kanji is replaced today by 灯 (tou) meaning lamp, and also in a combination: instead of 燈心 (toushin) it is now written 灯心 (toushin), meaning (lamp)/wick. – 蠟燭 (rousoku) in the text, now an obsolete term, was changed into its variant 蝋燭 (rousoku), meaning wax, candle. the old term 蠟 (rou) having 25 brush strokes was modified to 蝋 (rou), having 14 strokes only. – 氣體 (kitai) meaning vapor, gas, nature, atmosphere, was modified to 気体 (kitai). 気 (ki) stands for spirit, mind, air, atmosphere, mood. 体 (tai) means body, substance, object, reality. in this case both characters were modified: 氣 > 気, 體 > 体. – 大氣 (taiki); 大 (tai) large, simplified letter 気 (ki) air, atmosphere. 大気 (taiki) atmosphere. in the text, talking about the atmosphere in the bottle. – 石灰水 (sekkaisui), limewater, the term is formed by combination of three characters: 石 (seki) stone, 灰 (hai) ashes, 水 (sui, mizu) water. – 造化 (zouka) creation/nature/the universe. 造 (zou) create, 化 (ka) change, take the form of, -ization. it is a word that is used in shinto faith: 造化 の三神.9 other chemistry related terms:22 – 燭 (akari) light, candlepower. also written 灯 (hi) – 炎上 (enjou) blazing/destruction – 壓 (atsu) pressure. its variant 圧 has 5 strokes instead of 17 in the old term. – 環 (wa, kan) ring/circle – 玻璃 (hari) glass / quartz (buddhist term) – 盃 (sakazuki) glass, cup – 実地試験 (jichchi shiken) practical experiment, 実 地 (jichchi) practice. the language of chemistry is a specific topic in language planning. chemistry and other sciences as well have to adapt to international rules for naming. the japanese text of the chemistry book of the nineteenth century is written in a combination of kanji characters and katakana phonetic syllabaries. current chemistry is written using kanji, hiragana replace katakana; katakana is used for foreign names. the chemical elements and compounds have their japanese names but chemical formulas and equations are written according the western conventions. the japanese names of the elements have either a japanese word, e.g. iron, 鉄 (tetsu), or are written by katakana following foreign words, e.g. manganese, マンガン mangan, or use a combination of kanji character and katakana, e.g. iodine, ヨウ素 (youso). history of writing chemistry book in hebrew after the hebrew people were exiled from their biblical land of israel the hebrew language was not a daily spoken language. however, for many hundreds of years it was kept for reading the bible, in prayers, and in writing and reciting religious services. since the eighteenth century, when jewish people started returning to and living in the land of israel then under ottoman (turkish) rule, that was followed by the league of nations  british mandate for palestine (1920-1947), there arose a gradual need to define, revive, restore and renew the spoken and written hebrew language. in 1890 the committee of the language was established in order to plan the language. in 1953, after the 1948 independence of the state of israel, the committee became the academy for the hebrew language (iair g. or 2016). the editorial preface by the publisher of the hebrew translation of roscoe’s book presented his motivation in the beginning of the book: textbooks for the studying youngsters and for everyone who seeks knowledge, this is a need that is felt every day in the life of the hebrew school in the land of israel and outside of it....chemistry book is the first in this series of books.…”daat” [knowledge] books are meant not only for the younger ones needs, but also for the people, mainly those young ones who devote their days to labor and the evenings for studying (torah). (oirbach 1929, pp. 3-4).23 a study by noach shapiro (1900-1964) surveyed the historical development of the hebrew terminology for chemistry. it shows the long various periods in which scholars of the hebrew language paid attention to nature and gave names to physical materials. shapiro pointed at biblical names of six metals that remained unchanged in modern time, those are gold, silver, copper, iron, tin and lead; he added names of different forms of gold and silver. shapiro emphasized that chemistry teachers among 47translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects jewish immigrants to the land of israel in the 1920s felt the absence and need for hebrew vocabulary and teaching books (shapiro 1959, shapiro1 1964). leibovitch explained the discussion, dispute and agreement between the members of vaad halashon committee and the committee for chemistry terms of the chemistry teachers organization concerning the construction of the names of chemical compounds (leibowitch y. 1951).24 interestingly, those metals of the ancient world have their names in chines-japanese kanji, since they were also known in ancient asia. those are: gold 金, silver 銀, copper 銅, iron 鉄, tin すず (金属 metal, old time’s name) and lead 鉛 sugahara 1990). hebrew terms were also changed, as is shown in table 1. names of the elements in hebrew carry biblical names in hebrew, e.g. iron, ברזל barzel, or foreign name in hebrew, like neon, ניאוןneon, or modified foreign names to adapt to the hebrew sound, e.g., manganese, מנגן mangan. the style of the language of oirbach’s himia looking at titles of the scanned page on fig. 4: title ַמה the fire (haesh) and the following subtitle ָהֵאש .1 ב. ֵחֶלב? ֶשל נֵר ְּכֶשּדֹּוֵלק -what is presented when a can ִמְתַחּזֶה dle of tallow is burning? (ma mitchaze keshedolek ner shel chelev?) those two lines and the last sentence in that paragraph are written with what is called nikud, punctuation, small marks that serve as vowels to facilitate and clarify the reading. most of the rest of the text is written without those. currently the nikud is used mainly for writing children books, poetry, and to help reading words that might have more than one meaning when it is differently pronounced and punctuated. in the text, the words בָקֶפה in the coffee (bakafe) and הָקֶפה the coffee (hakafe) are also punctuated, to make their reading clear.25 (incidentally, an interesting panel discussion for the japanese term for “coffee” is described in: okayama dutch learning group, 2016).26 hebrew terms in oirbach’s translation were those accepted by the committee for chemistry terms near vaad halashon, language committee. the list has some eighty one terms. fifty two of the terms are in use today, by chemists and by the general public. twenty nine terms are not in use today, replaced by other words. a few examples of terms not in use today and their recent alternatives are listed in table 1 and discussed below. this author does not remember using the word retort or abik while working in the chemical laboratory, even though one finds them in the hebrew dictionary, meaning a tool for distillation; the foreign name kolba was used. the concise hebrew dictionary by a. ben shoshan hamilon ha’ ivri hamerukaz, (hamilon ha’ivri hamerukaz, 1972) divides the literary sources of the vocabulary presented into five categories: the bible, talmud and ancient scrolls from judea desert, meditable 1. oirbach’s himia terms translated from english and german27 and recent hebrew terms. english german hebrew term in himia hebrew reading hebrew term today hebrew reading retort retorte אביק abik אביק lunar caustic höllenstein even-hatofet אבן-התופת כסף חנקתי kesef chankati agno3 alkali lauge בורית borit 1.אלקלי 2. בסיס 1. alkali 2. basis galena(lead sulphide) bleiglanz ברק עופרת brak oferet עופרת גופריתית oferet gofritit pbs marsh-gas sumpfgas gaz bitza גז ביצה מתאן methan ch4 fire damp grubengas גז מחפורת gaz machporet גז מיכרות: מתאן, פחמן דן-חמצני, פחמן חמצני, חמצן, חנקן gaz michrot: mines gas: ch4, co2, co, o2, n2 prussian blue berlinerblau kohel berlini כהל ברליני כחול פרוסי kachol prussi feiii4[feii(cn)6]3.  magnesium magnesium מגנון magnon מגנזיום magnezium ferrycyanide gellbes blutaugensalz מלחת malachat פריציאניד ferricianid gold leaf blattgold רדי זהב01, עלי זהב radey zahav, aley zahav עלה זהב aley zahav 48 yona siderer eval literature, new literature since the haskalah (age of enlightenment) including press and spoken language and terms from foreign languages.28 the word “borit” comes from the talmudic literature, a name of a wild plant that contains saponin, which dissolves in water to produce emulsion with oil, like soap. borit is also a synonym for soap, sabon. hebrew uses the foreign word gas, pronouncing “gaz”, but gives the chemical names of methane and other gases for “gaz bitza” and “gaz machporet”. prussian blue is translated today to “kachol prussi”, meaning prussian blue. magnesium and ferrycyanide are pronounced similar to their foreign names, not using oirbach’s term. “aleh zahav” meaning golden leave remained in use today. roscoe’s influence on chemistry studies in japan how much was roscoe involved in the education of japanese chemists? after meiji restoration, 1868, the japanese authorities invited foreign teachers to teach chemistry. the ministers felt the need to start modern technology and modern industry for the benefit of the people and the country’s prosperity. moreover, they sent students to study abroad, supported by the ministry of education. a few students were sent to owens college, manchester. other students were sent to university college, london. the connection of japanese scholars with roscoe did not end with the 1873-1874 translation of science primers chemistry. in his autobiography roscoe mentioned his japanese chemistry student sugiura shigetake 18771879, and y. kiraga 1878-1879 and wrote with appreciation his recollections of his japanese students.29 the japanese who studied abroad were influenced by what they saw, by the cultures they were exposed to and what they learned in foreign countries. after their return to japan some of them were appointed as school teachers, others had government and prefectural administration positions and a few others became professors in the new universities. they introduced what they have absorbed into the scientific thought, teaching and administration of their own country. roscoe had an inf luence on japanese researchers and chemistry education since 1872 and later. the translated chemistry books were edited and republished in later editions. osawa lists eleven books related to roscoe between the years 1874-1889. there were several translators and reviewers, and different books titles. kaji mentioned ira ramsen’s popular book the elements of chemistry: a textbook for beginners. originally published in 1887, it included a classification of elements based on valency but made no mention of the periodic law. kaji listed its japanese translations.30, 31, 32 further promotion from the west to japanese chemical education western chemistry education in japan was achieved from two directions. the japanese students who studied abroad and returned to japan after spending some months or years in european countries or in america. after returning to japan they could get positions in industry, in governmental and prefectural administration, or as teachers in schools and in the developing universities. gradually they developed the japanese chemical and technological terminology. there is a list of more than one hundred and fifty japanese who studied chemistry abroad during meiji era 幕末明治海外渡航者総覧 bakumatsu meiji kaigai tokō-sha sōran (published 1992). the list includes their birth year, the countries they went to, the year(s) of their return to japan, the positons they held after returning.33 another source of studying chemistry came from the foreign chemistry teachers in japan and the translation of their courses by their japanese students. discussed above are griffis and gratama. other teachers like william robert atkinson, a british chemist who taught at tokyo kaisei school during the meiji period,34 and the american teacher d. penhallow teaching in hokkaido, included in their curriculum to their japanese students local japanese materials and what is available in the japanese environment for teaching natural sciences, including chemistry and botany. penhallow later wrote about his experience in japan.35 david wright in his thorough study on translating science, the transmission of western science into late imperial china 1840-1900, looks at various aspects of translation (wright 2020). wright explains the subtitle transmission. his study concentrates on china, but the more general view he developed can apply to japan, even though the methods and approach for translation science were different between china and japan. in china, in the official translation offices, the translation was carried out by collaboration between chinese translators and a western scholar, whereas the japanese translated mainly by themselves. wright looks at translation model of transmission that “includes the political, social, economic and historical matrices within which the translation is conducted, affecting not only the nature of the process but also its velocity and acceleration.”36 we have looked in this study into aspects of culture, linguistic, 49translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects history and politics. after meiji restoration, there was a change from the reluctance of the edo era feudal rule to the spread of western knowledge among the common people, and there evolved the recognition of the new regime in the need for modern knowledge in order to modernize japan. that recognition caused the support for translation and publishing a basic chemistry teaching book by the ministry of education in 1873, as a part of the general new rules for basic education. highlights of world recognition in chemistry in japan and israel for early twentieth century international collaboration on nomenclature see japan’s engagement with international chemistry (1900-1930) (kikuchi 2017). a japanese-english chemistry dictionary presents the current rules for japanese chemistry nomenclature (gewehr 2007). the japanese society for the history of chemistry (kagakushi gakkai) published a comprehensive encyclopedic dictionary on the history of chemistry that is now available to the japanese readers (encyclopedic dictionary 2017). both japan and israel developed prosperous chemical industries. there have been nobel laureates from both countries in recent years, their history deserves another study. in 2016, the superheavy synthetic element 113, discovered by kyushu university professor kosuke morita, head of a team of scientists, was officially given the name nihonium, after the japanese name of their country nihon or nippon. nihonium is the first element to be discovered in an asian country. it might be said that the translation of chemistry from the west into japanese in the nineteenth century, and all the educational, theoretical, experimental, technological and industrial chemistry that followed, culminated into these japanese achievements. summing up the practice of chemistry and chemistry teaching were involved in carrying knowledge across continents from the eighteenth to the twentieth century. the chapters above presented the transformation of the original english book in chemistry (1872) from england to america, then to asia in 1873, to finland in northern europe, and to the middle east in 1929. within the translations new terminology for the specific discipline chemistry was required and invented. later authors of chemistry texts used the old terms, changed them, or rejected and replaced them with more appropriate terms. those translations were the building blocks for increasing the number of people that have access to chemistry and its theory, to deepen modern knowledge in the respective countries, supporting modern approach to chemical manufacturing industry. what conclusions the reader can draw from this comparison as a whole? this comparison reflects the dynamics of language movement between people and thru time. this is true for languages in general, and in this study for the case of the science of chemistry in japan and israel. acknowledgements i thank prof. akiyoshi kida, kyoto university, for giving me the copy of kogaku kagaku hyōmoku. prof. shin sato is deeply acknowledged for his continuous help in translating the japanese text. i thank mr. masao uchida for his suggestions during the beginning of this work. dr. neomy soffer is heartily thanked for reviewing and making editorial suggestions. notes 1. bensaude-vincent 2003, 174. 2. montgomery 2000, 270. 3. roscoe’s autobiography 1906, 151. 4. roscoe autobiography 1906, 150. 5. icelandic efnafrædi 1879, cited by morris 2015, 174. 6. chinese translation of roscoe’s science primers chemistry 1886. received with thanks from chang h. 2017. 7. osawa 1978. the book size is 18x12 cm, including 16 drawings of experiments in 35 folded pages. mr. roscoe’s chemistry 羅斯珂氏化学 was co-translated by sugiura shigetake 杉浦重剛 and miyazaki michimasa 宮崎道正, one of the first three graduates of tokyo university department of chemistry (kikuchi, correspondence of 23 april 2017). this is probably a translation of roscoe’s 1866 book elements of chemistry (osawa 1978). 8. roscoe 1872, 2. 9. roscoe 1872, 3. 10. roscoe 1872, 4. 11. roscoe 1872, 5. 12. roscoe’s science primers chemistry book is available on line at: https://archive.org/details/bub_ gb_8rsnaaaayaaj/page/n3/mode/2up 50 yona siderer 13. the chemistry book in japanese is available on line at: https://archive.wul.waseda.ac.jp/kosho/ni04/ ni04_03127/ni04_03127_0001/ni04_03127_0001.html 14. frellesvig 2011, 14 sec.1.1.2.5 manyōgana; pp. 158162 sec. 6.1.2, kana (hiragana, katakana, hentaigana). the hiragana and katakana developed as reduced shapes of man’yōgana. kanji letters as they are read phonetically, not logographically. there are two sets of fifty kana letters: hiragana stands for the cursive set, katakana are the square shaped letters set. mixed writing of kanji and kana started in the middle of heian period (794-1185). 15. professor shin sato is acknowledged for providing the following romaji transcription for reading the text of the candle burning experiment in fig. 3. 小学化学書巻一 shougaku (ora l ly: sho-ga ku) kagakusho kan ichi p.1 roscoe shi sen ichikawa morisaburo yaku [skipped] the japanese description of the candle burning, experiment 1: dai ichi shi hosokuchibin no seijou naru mono wo tori, rousoku sono naka ni moyasu ni (sono naka de moyasu to) kaen shidai ni otoro e shimai ni mattaku shoumetsu suru ni itaru wa hito no mazu miru tokoro nari. kore ni oite sono shikaru tokoro no ri wo akiraka ni sezuba aru bekarazu. sore wo nasu ni wa binchuu taiki no jousei, rousoku imada moezaru mae to sude ni moyuru no nochi to onaji ki ka inakaya wo kensuru ni arazareba fuka nari. sonohou wa toumei no sekkaisui wo tori, rousoku no moezaru bin to sude ni moetaru bin to wo narabete hakari na p.4 gara kore wo sosogi irete ai kurabureba ni binchuu tadachi ni taiki no jou no koto naru wo miru beshi. sunawachi koubin wa sekkaisui toumei ni shite sara ni henka sezu to iedomo otsubin wa tachimachi hakudaku wo shouzu. kore hakua wo shouzuru ni yorite shikaru nari. kono hakua wa tansan to sekkai to yori naru mono ni shite, tansan wa taiki no gotoku iro wa naku shite miru bekarazaru kitai nari to iedomo sekkaisui wo shiroku suru sei aru nite kore wo shiru nari. ima, sono binchuu ni tansan no son suru ri wa rousoku chuu no tanso mo ete kore wo shozuru nari. rousoku nai ni tanbun wo fukumu koto wa sono ichibu moezu shite kemuri to nari masaru nite shiru beku, mata sumiyaka ni hakushi wo motte honoo ue yori ooi asseba sono tanso kuroki wa to narite tsuku wo miru nari. dai san kai rousoku moyuru wa tansan no hoka sara ni mizu wo shouzuru koto. 16. sato s. comments in correspondence of 1 april 2017. 17. the full text of experiment 1 on candle burning is presented in hebrew: צואר בעל זכוכית של נקי בבקבוק דולק נר נכניס – א’ נסיון עד והולכת פוחתת השלהבת את נראה קלה שעה כעבור צר. מדוע לדעת החפץ את בנו יעורר מיד זה דבר ותכבה. שתדעך הבק בתוך עתה הנמצא האוויר את נבדוק זו לתכלית הנר. ־כבה הנר דלק טרם מתחלה, שהיה כזה עודנו אם דעת למע]ן[ בוק, בשני צלולים* סיד מי מעט ניצוק – נבדוק? וכיצד בבקבוק. ־בקבוקים, שאחד מהם יהיה מלא אויר אשר נר לא דלק בו, והש בבקבוק ההבדל: את נכיר מיד וכבה. בו דלק שהנר זה יהא ני הראשון יהי המים צלולים ובשני – עכורים. מכאן ראיה, כי ע”י עכירות לנו תסביר – זה שנוי מהו באויר. שינוי חל הנר בעירת עשוי וזה קירטון, ידי על אלא נעכרו לא המים הסיד(. )מי המים חסר גז היא הפחמנית החומצה ומחומצה-פחמנית. חי מסיד מי עוכר שהוא אלא כאויר, ממש העין, מן וסמוי ושקוף זך צבע, והיה נהפך החלב מן שחלק נמצא דולק. נר ומכבה צלולים סיד שנשרף בחלב הכבוש הפחם או הַּפְחָמן כלומר, לחומצה-פחמנית, עשן בדמות לנו נראה זה מפחם חלק העין. מן סמוי בגז נתגלגל כי נראה, הנר בשלהבת לבן ניר פסת לרגע שקע אם פיח: או יוטל פיח של ועגול שחור כתם כעין אלא באש יאוכל לא הניר בו. ופיח זה אינו אלא פחם שלא הספיק להשרף. ג. ִמְלַּבד ֻחְמָצה-ַּפְחָמנִית מוִׄׄליָדה ַהְבִּעיָרה עוׄד חוֶׄמר ַאֵחר ָמיִם. 18. potential source for the awareness of the japanese ministry of education was the copy of the book ordered to japan by william elliot griffis (18431928), an american graduate (1869) of rutgers university at new brunswick, who was invited to teach chemistry to youngsters in remote fukui in japan and started teaching there in may 1871. in a letter of 15th july 1871 to his sister margaret in philadelphia he wrote: “… send one copy of roscoe’s chemistry, latest american edition, by mail, it costs $1.50…” (yamashita 1965). uchida mentioned griffis reading to his students in fukui from a copy that used to belong to kusakabe taro, who studied in rutgers and died there. when griffis came to japan shortly thereafter, he brought with him kusakabe’s personal effect. it is possible that after reading to his students in fukui from kusakabe copy on 12th july, griffis 51translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects wrote the request cited above. after moving to tokyo in january 1872 griffis was involved in preparation of curriculum for a new university and in 1872-74, he taught chemistry and physics at kaisei gakkō (the forerunner of tokyo imperial university). the three chemistry books that are noted by griffis in the library of fukui are: 1. h.l. roscoe, lessons in elements of chemistry: inorganic and organic (new york, 1868). 2. w.a. miller, elements of chemistry: theoretical and practical, 4th edition (london, 1867). 3. j.e. bowman, an introduction in practical chemistry, including analysis, 5th edition (london, 1866) (cited by uchida p. 247, and by edward r. beauchamp p. 33, both in edward r. beauchamp and akira iriye eds. in foreign employees in nineteen century japan, 1st edition 1990. after returning to america griffis published and lectured about japan. his book the mikado’s empire, 1895 edition, had a new edition in 2007 and printed on-line in 2015. 19. the iwakura mission diary, the mission’s accumulated oral and written information. the statesman iwakura tomomi  (1825–1883)  headed the iwakura mission (december 1871-1873) that was sent to america and europe in order to introduce the new japanese regime; to renegotiate the commerce treaties of 1859; and to observe and study western systems of law, commerce, transportation, education and others ways of life in the countries they visited. in his diary (nikki) of the iwakura mission its historian kume kunitake observed chemistry studies and industry in several places. he wrote and emphasized the need of the japanese to learn the fundamentals of chemistry (in liverpool, kume true account 2002, vol. ii p. 143). while in manchester during 4th-9th october 1872 the iwakura mission visited the chemistry laboratory in owens college (kume true account 2002 vol. ii chapter 29 pp. 190-191, japanese pocket edition 2009 p. 182). it is possible that the mission’s visitors have collected roscoe’s science primers chemistry book during the visit and sent it to japan. the book first edition was already mentioned in a letter by huxley dated 11th april 1872 (roscoe 1906, p. 148). 20. ichikawa seizaburou assistance to hermann ritter. the translator ichikawa seizaburou (alas morisaburou), later changed his name to hiraoka morisaburou (1852-1882), studied at university college london between 1866 june 1868 when he had to return to japan due to the fall of the bakufu regime. he became a teacher of higher education for the ministry of education and an assistant of the german chemist hermann ritter (1827~1874). ritter taught chemistry and physics in osaka and tokyo in english, and succeeded the dutch chemist koenraad wolter gratama (1831-1888). gratama stayed in japan for five years from 1866 to 1871 and taught chemistry in osaka chemistry school, seimikyoku, which was built in 1869. osaka chemistry school was closed in meiji 3, 1871 and moved to kyoto. ichikawa saw roscoe’s earlier chemistry book that was used by ritter. ichikawa moved to tokyo on may 1873 and about that time he made the translation that was published in 1873 and 1874 (osawa 1978). ichikawa went again to england and was in manchester owens college studying physics during 1877-8 and 1878-9 and published physics book under the name hiraoka morisaburou. 21. oirbach assisted the renowned poet, translator and editor chaim nachman bialik (1873-1934) when he came to kishinev to write a report, and later famous poems, about the kishinev pogrom that took place there in 1903. thanks to dr. ruhama albag and agnon house for the information concerning the acquaintance between oirbach and bialik. 22. 金箔 kinpaku golden leaf. in kanazawa city– kinpaku production survives to-date. 23. oirbach, 1929, pp. 3-4. 24. leibowitz 1951 vol. 18 (ח”י) p. 104-105. 25. adding punctuation in order to distinguish between hakafa ַהָקָפה hakafe meaning ‘the coffee’ and הָקֶפה meaning ‘surrounding’. 26. the suitable characters for the word “coffee” were searched by the scholar udagawa youan (1798-1846), when he introduced the word コーヒー ko-hiand 咖啡 written by ateji, phonetic pronunciation of the kanji, not its meaning. he wrote 27 kanji combinations and 6 katakana combinations before he chose the combination that satisfied him: コーヒーの当て字 各比伊, 歌兮, 迦兮, 可喜, 哥非乙, 哥兮, 骨喜, 架 非, 咖啡, 黒炒豆, 可非, 膏喜, 茶豆湯, 架菲, 豆の湯, 和蘭豆, 加非, 雁喰豆, 過 稀, 可否, 香湯, 滑否, 滑韭, 骨非, 茶豆, 架啡, 煎 豆湯 コォヒー・コーシー・コーヒィ・カウヒイ・コヲ ヒ豆・コッヒイ 27. oirbach english and german in word list. the hebrew terms in this list were mostly accepted by vaad halashon based on the suggestion of m. vinik (1886-1966). pp. 111-114. 52 yona siderer המרוכז .28 העברי hamilon ha’ivri hamerukaz. page המילון facing inside front cover 1972. 29. roscoe, 1906, pp. 113-115. sugiura shigetake 杉 浦 重剛 (1855-1924), in britain (1877-1879), and y. kiraga (1878-1879.) roscoe wrote: “…since that time i have had several letters from my japanese friends and pupils, some of which are interesting:” a letter from y. kiraga 1878-1879, at the technical institute, asakusa, tokio, japan, october 1st 1886. kiraga (formerly known as sadam takamatsu) apologized for not writing since he returned to japan and happily announced his appointment as a chair of technical chemistry in the established technical institute by the ministry of public instruction, devoting himself to the chemistry of dyeing. kiraga sent to roscoe a copy of his “maiden work” on guidance of dyeing for the dyers. 30. osawa, table 2, pp. 857 (75), 1978. 31. osawa, vol. 29, no. 10, p. 72-79, (854-861), 1978 32. kaji 2015, p. 287; notes p. 300 no. 13, lists several translations of roscoe and ira remsen’s books. p. 301 no. 15. ira remsen, the elements of chemistry: a textbook for beginners, london: macmillan, 1887. 33. after returning from studies abroad, japanese chemists various field of research include: academic research on fertilizer, agricultural chemistry, applied chemistry, beer brewing, biochemistry, cement making, chemical education, chemistry of sake brewing, common salt production, components of oriental drugs, copper engravinglithograph, dyeing, electrochemistry, gunpowder production, industrial gas, industrial pharmaceutical production, inorganic chemistry, internal medicine, isolation of glutamate – ajinomoto (the element of taste), manufacturing of window glass, meat-making, metallurgy, minting, paint manufacturing, paper making engineering, physical chemistry, plant physiology, oil and sugar manufacturing, organic chemistry, wine brewing, and more. 34. william robert atkinson, a british chemist. atkinson stayed in japan during september 9, 1874 september 8, 1878 and february 3, 1879 july 4, 1881. he taught agricultural studies at tokyo kaisei school and faculty of science, university of tokyo. he concentrated on natural produce of japan, e.g. studying the brewing method of sake (japanese liquor) and the dye that is used for dyeing cloths, indigo blue dye, that he called “japan blue”. 35. david p. penhallow japan, mcgill university magazine 3 (april 1904), pp. 88-103. 36. wright, 2000, chapter 12. the translation of western science. p. 403. 37. kikuchi 2017 p.17. references azuma, toru “chemical materials related to udagawa youan held in waseda university library”. in kagakushi, 早稲田大学図書館宇田川榕菴化学関係 資料 waseda daigaku toshikan shozou udagawa youan kagaku kenkkei shiryou vol. 42, 2015, pp. 21-30. r. beauchamp, william and akira iriye eds. elliot griffis: the tokyo years, 1872-1874, in foreign employees in nineteen century japan, 1st edition 1990, pp. 33-48. bensaude-vincent, bernadette: “language in chemistry in the history of science”, vol. 5 the modern physical and mathematical sciences, pp. 174-190. (editor mary jo nye), cambridge university press 2003, pp. 174-190. denshi jisho, japanese-english english-japanese on-line dictionary: http://jisho.org/search 2017. dōke, tatsumasa, “yoan udagawa – a pioneer scientist of early 19th century feudalistic japan”. in japanese studies in the history of science, 1973, no. 12 pp. 99-120. frellesvig, bjarke a history of japanese language, cambridge university press 2011. gewehr, markus, editor: japanese-english chemical dictionary, wiley-vch verlag gmbh & co. kgaa weinheim, 2007. encyclopedic dictionary of the history of chemistry, (edited by the japanese society for the history of chemistry), published by kagaku-dojin publishing co., inc. kyoto 2017. 化学史事典 化学史会編 kagakushi jitten kagakushi kaihen (j). google. roscoe 1872, p.3 copied from https://archive.org/ details/b28118145 gottlieb, nanette: kanji politics. kegan paul international, london and new york, 1995. kaji, masanori: “chemical classification and the response to the periodic law of elements in japan in the nineteenth and early twentieth century”. in early responses to the periodic system, (editors masanori kaji, helge kragh, gábor palló), oxford university press, 2015, pp. 283-304. kikuchi, yoshiyuki: “japan’s engagement with international chemistry (1900-1930)”, book of abstract, 11th international conference on the history of chemistry, trondheim, 2017. kogaku kagakusho hyoumoku 小學化學書標目 “chemistry book for elementary school”, published by the ministry of education 1873. japanese translation from roscoe’s science primers chemistry by ichikawa morisaburo 市川盛三郎, (1873 and 1874) kume, kunitake. the iwakura embassy 1871-1873, a true account of the ambassador extraordinary and pleni53translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects potentiary’s journey of observation through the united states of america and europe, compiled by kume kunitake, (editors–in-chief of the english translation graham healy and chushichi tsuzuki), the japan documents, 2002 vol. ii chapter 29 pp. 190-191. leibowitz yeshayahu on “chemistry terms”, leshonenu 1951. 1591 י”ח, כרך ”לשוננו” הכימיה”, ”מונחי על ליבוביץ’, in)י. hebrew). montgomery l. scott: science in translation, movements of knowledge through cultures and time, the university of chicago press, chicago and london, 2000. okayama dutch learning group 岡山蘭学の群像 udagawa youan, de vinci of edo era, the man who coined the character(s) for [coffee]. 「珈琲」の文字 を作った男 江戸のダ•ウィンチ 宇田川榕菴 koffee no moji wo tsukutta otoko edo no da uinchi. panel speaker shimoyama yoshimasa p. 166, the sanyo broadcasting foundation, 2016. p. 91 (j). morris, j. t. peter: the matter factory, a history of chemistry laboratory, reaktion books, london, 2015. oirbach, p. translator: himia, kupat hasefer publisher, tel aviv 1929. translated from roscoe’s science primers chemistry of 1872. מדע ספרי ”דעת” אוירבך. פ. .לנוער ולעם חימיה הוצאת ”קופת הספר” תל-אביב, תרפ”ט or, g. iair creating a style for a generation: the beliefs and ideologies of hebrew language planners, ov z.a.p. tel aviv publishers (in hebrew) 2016. סגנון בוראים בארץ העברית הלשון מתכנני של והאידיאולוגיות האמונות לדור, (ישראל, הוצאת אוב-ז.ע.פ. –תל אביב (2016 osawa, masumi: 大沢眞澄 明治初期の初等化学教育 meiji shoki no shotou kagaku kyouiku elementary chemistry education in the early meiji era. in 科学 の実験 kagakushi no jikken experiments in science, 1978. pauling, linus general chemistry second edition 1953 was translated into hebrew by yitzhak klugai, 1965 בשני כללית כימיה בע”מ לאור מוציאים איחוד יחדיו, הוצאת .in two volumes by yahdav, ihud publishers חלקים, roscoe, henry enfield: lessons in elementary chemistry, london, macmillan and co., 1866. roscoe, henry enfield: lessons in elementary chemistry, inorganic and organic, london, macmillan and co.,1868. roscoe, h. e.: science primers chemistry. london macmillan and co.,1872. roscoe h. e.: the life & experiences of sir henry enfield roscoe, d.c.l., ll.d., f.r.s. written by himself. london: macmillan and co. limited, new york: the macmillan company, london, 1906. google: roscoe 1872, p.3 copied from https://archive.org/ details/b28118145 shapira, noach: “development of the chemical terminology in hebrew”, in leshonennu: journal for the study of the hebrew language and cognate subjects vol. 42, pp. 95-106,”בעברית הכימית הטרמינולוגיה התפתחות “ לה, הסמוכים והתחומים העברית הלשון לחקר כתב-עת לשוננו: .כרך כ”ד, עמ’ 601-59 1959 siderer, y. “udagawa youan’s (1798–1846) translation of light and heat reactions in his book kouso seimika.” in foundations of chemistry, 2017  19(3), 223-240, doi 10.1007/s10698-017-9287-2. siderer y. “udagawa youan (1798-1846) pioneer of chemistry studies in japan from western sources and his successors”, in substantia an international journal of the history of chemistry, published by the university of firenze, italy. vol. 5 no.1, 2021. pp. 99-117. doi: 10.36253/substantia-963. simchoni s., a suggestion of hebrew chemistry terminology, in leshonenu 1949 vol. 16, p. 47. ,שמחוני ש. עמ’ ט”ז, כרך לשוננו, בעברית”, כימית טרמינולוגיה ”הצעת 45-74 sugahara kunika, chapter 4: 舎密から化学へ from seimi to kagaku in on the history of the discussion on elements names in meiji. (editors era sadaaki shito and ichiro yabe). kindai nihon, sono kagaku to gijutsu: genten eno shotai, kogaku shuppan, 1990. title: science and technology in modern japan: an introduction to the original texts.1990. uchida takane, oki hisaya, sakan fujio, isa kimio, and nakata ryuji 1990, “william elliot griffis’ lecture notes on chemistry” in foreign employees in nineteenth-century japan , (eds. edward r. beauchamp and akira iriye, boulder, san francisco and london), westview press, 1990, pp. 247-258. tanaka minoru, seimi kaiso ni okeru yoan no kagaku n i n s h i k i 舎 密 開 宗 に お け る 榕 菴 の 化 学 認 識 in udagawa youan seimi kaiso fukkoku togendai koyaku•chuu 宇田川榕菴舎密開宗復刻と現代語 訳・注 udagawa youan seimi kaiso, republishing, (its) recent language and explanatory notes” (editor tanaka minoru) 1975 pp. 99-114. tokyo, publisher noma shouichi 発行者: 野間省一 tokyo. udagawa youan, seimi kaiso, introduction to chemistry in seven volumes, 宇田川榕菴舎密開宗 published 1836-1847 published in edo: suharaya ihachi, in japanese. wikipedia biography of pesach oirbach, in hebrew 21.4.2021: https://he.wikipedia.org/wiki/%d7%a4%d 7%a1%d7%97_%d7%90%d7%95%d7%99%d7%a8 %d7%91%d7%9a wright, david, translating science, the transmission of western chemistry into late imperial china, 18401900, brill, leiden•boston•koln, 2000. 54 yona siderer yamaguchi, tatsuaki 山口達明 2017 early meiji era studies on organic chemistry 明治初期の有化学教科 書：丹波敬三, 下山順一郎, 柴田承桂纂譯『有機 化學』 organic chemistry in kagakushi, vol. 44, no. 2 p. 102 (46). abstracts book of the annual general meeting of the japanese society for the history of chemistry, 2017. yamashita eiichi. griffis’ fukui letters, william elliot griffis pioneer educator, author of the mikado’s empire ed. 1965, several publishers, in 2009 and 2013. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 4(2): 139-149, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-879 citation: a. sztejnberg (2020) the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries. substantia 4(2): 139-149. doi: 10.13128/substantia-879 received: mar 13, 2020 revised: apr 25, 2020 just accepted online: may 11, 2020 published: sep 12, 2020 copyright: © 2020 a. sztejnberg. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21st centuries aleksander sztejnberg professor emeritus, university of opole, oleska 48, 45-052 opole, poland e-mail: a.sztejnberg@uni.opole.pl abstract. claude-louis berthollet (1748-1822) was one of the greatest french chemists of the eighteenth and the first 20 years of the nineteenth century. his life and scientific achievements were described in the literature published between the 19th and 21st centuries in different countries. the purpose of this article is to familiarize readers with the important events in the life of berthollet and his research activities, in particular some of his experimental research results, as well as his selected publications. in addition, the names of authors of biographies or biographical notes about berthollet, published in 1823-2018 are presented. keywords: c.-l. berthollet, composition of ammonia, natron lakes of egypt, the society of arcueil, france (xviii-xix century). la chimie fut toujours l’occupation principale de sa vie; et il aima et protégea tous ceux qui la cultivèrent (chemistry was always the principal occupation of his life; and he loved and protected all who cultivated it) jacques-alphonse mahul (1795-1871) 1 1. the important events in berthollet’s life claude-louis berthollet (1748-1822) (fig. 1) was born in talloire (upper savoy) on december, 9, 1748, and he was the son of louis berthollet, a notary and castellan, and philiberte donier. he first studied at a nearby college in annecy and then at a college in chambery. to continue with his education, he began medicine studies at the university of turin. he graduated from the turin university in 1770. after two years he continued his education in paris, where he became a naturalized french citizen. he attended the courses of lectures on chemistry given by augustin roux (1726-1776), jean-baptiste-michel bucquet (1746-1780), and http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia mailto:a.sztejnberg@uni.opole.pl 140 aleksander sztejnberg pierre-joseph macquer (1718-1784). then he worked as physician-in-ordinary at the household of louis philipe i (1725-1785), duke of orléans. he was assigned to the service of charlotte-jeanne béraud de la haye de riou (1738-1806) known as madame de montesson, the second wife of the duke of orléans. berthollet continued his medical practice for several years. in 1778 he began the process of obtaining a medical degree from the paris faculty of medicine. in 1779, he successfully defended his doctorate thesis de lacté animalium médicamentose. in the same year he married marguerite-marie baur. their only son, amédée-barthélemy, was born in 1780.2 since 1784, he, as a well-known chemist, was administrator at the gobelins manufactory in paris. he worked in it as a dyeing director.4 in 1792, he was appointed as one of the mint’s commissioners, into the processes of which he introduced significant improvement. two years later, he was named member of the commision of agriculture and the arts.5 on november 9, 1794, berthollet was chosen as professor of chemistry at the normal school in paris. his chemistry course included 12 oral lectures delivered from january 26 to may 11, 1795, and an additional lecture delivered on june 10, 1801, in which he described the progress of chemistry since 1795. the lectures were included in the seven volumes (i-vi and ix), published in paris in a new edition in the years 1800-1801, under the title séances, des écoles normales, recueillies par des sténographes, et revues par les professeurs. they were published in 2006.6 the french historian of science bernadette bensaude vincent, who was one of the authors of the edition of berthollet’s lectures wrote about them as follows: “the structure of berthollet’s course (…) reveals both an interest in the theoretically arcane and a concern for practical aspects of the social practice of chemistry. in his first programmatic lecture berthollet advocated the view of technological applications and improvements deduced from theoretical understanding. he intended to provide the broad deductive framework on which basis future teachers would have to develop more particular aspects according to their audience.”7 berthollet, napoleon and the egyptian campaign berthollet was a friend and confident of napoleon bonaparte (1769-1821), and he was one of the scientists who went with napoleon to the egyptian campaign, which began with the landing at night at marabout on july 1, 1798, after a 40-day journey. another person who accompanied napoleon’s army in this campaign was the mathematician gaspard monge (1746-1818), a good friend of berthollet. “a staff of over a hundred savants, mechanics, engineers, architects, authors, and interpreters, among others, monge, the mathematician, and berthollet the chemist, accompanied the general to make a scientific conquest of the east, to prepare the way for the projected colonization, and to open up the indispensable waterways”.8 in one of the letters received by the german naturalist alexander von humboldt (1769-1859) on april 30, 1798, the astronomer and mathematician johann karl burckhardt (1773-1825) informed him about the preparations for the egyptian campaign and berthollet’s participation in it. “berthollet, bonaparte’s physician, is director in chief of the scientific department of the expedition, in which are included the following antiquarians:” dominique-vivant denon (1747-1825), edme-françois jomard (1777-1862), françois pouqueville (17701838)], and françois-michel de rozière (1775-1842). “on the 30th floréal (may 19, 1798) the fleet weighed anchor from toulon, and bonaparte’s campaign in egypt was openly declared”.9 in egypt napoleon, the commander in chief, formed l’institut d’égypte (the institute of egypt) on the 3d fruĉtidor, 6th year (20th august, 1798) in cairo. the institute was divided into four scientific sections which figure 1. claude-louis berthollet (1748-1822) (public domain, from reference 3). 141the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21st centuries were named “mathematics”, “natural philosophy”, “literature and the fine arts”, and “political economy”. berthollet belonged to the section “natural philosophy” which was composed of ten members. there were among them, nicolas-jacques conté (1755-1805), inventor of the graphite pencil and the conté crayon, the chemist hippolyte-victor collet-descotils (descostils) (1773-1815), the mineralogist déodat de gratet de dolomieu (17501801), whose name is given to the dolomites in the italian alps and the mineral dolomite, and the naturalist étienne geoffroy saint-hilaire (1772-1844).10 one of berthollet’s assignments in egypt was “finding fuels for bread ovens, substitutes for hops in the brewing of beer, and raw materials for the manufacture of gunpowder.”11 on january 23, 1799, he and the mathematician joseph fourier (1769-1830) were the main civilian members who took part in the five-day expedition under the command of general antoine françois andréossy (1761-1828) to explore the valley of the natron lakes.12 they were six lakes below sea level, situated on the borders of the north-western desert, some 45 miles [72 km] to the north-west of cairo. the natron lakes were bordered by a thick crust of natron3 (a mineral form of sodium carbonate decahydrate).14 the aim of this visit was to prospect the possibility of exploiting the deposits of soda, a product of economic importance in the nitre refining for the gunpowder production. in addition, the observation of the efflorescence of soda was a significant point in berthollet’s construction of his system of chemical affinities. one of the most important essays provided to l’institut d’égypte by him in 1800, contained conclusions from the study of the nature of some phenomena presented by the natron lakes.15 bonaparte’s egyptian campaign ended when napoleon abandonment of his command leaving behind his troops on august 21, 1799. he decided to return to france suddenly and secretly. bonaparte chose only monge and berthollet among the scientists to accompany him on a dangerous journey back. his army remained two more years in egypt before returning to france. the austrian historian august fournier (1850-1920), professor of history at the university of vienna, in the biography of napoleon, wrote: “on the night of august 21st, napoleon set sail, accompanied only by a few devoted followers, berthier, lannes, marmont, murat, andréossy, bessières, duroc, monge, berthollet, bourienne, and a few hundred soldiers of the guard.”16 the supreme command of napoleon’s army in egypt was entrusted in writing to general jean-baptiste kléber (1753-1800). berthollet’s career in the years 1799-1814 was staggering. after the egyptian campaign on december 1799, he became a senator in the french senate under the napoleon bonaparte as a first consul. on 14th june 1804, napoleon made him grand officer of the legion of honour and count. on may 14, 1806 he became titulaire de la sénatorerie de montpellier (holder of the senatorie of montpellier). berthollet received a greatcroix of the order of the reunion on april 3, 1813, and after the restoration, louis xviii created him a peer of france on june 4, 1814. on april 23, 1820, the académie des sciences, belles-lettres et arts de savoie (academy of sciences, belles-lettres and arts of savoy) elected berthollet its member in recognition of his merits. disease and premature death of berthollet’s son amédée berthollet lived only 31 years. hugh colquhoun in his article on the life and writings of claude-louis berthollet briefly described his suicide in 1811. this event to the last degree embittered the life of his father. “the promising son of berthollet, in whom his happiness was wrapped up, was unhappily subject to the fearful malady of despondency, which at length grew upon him to such a degree that neither the rank and fame of his father, nor the affection of his aged mother, nor the respect of friends, nor the honours which science seemed to hold out to his young years, could prevent it from gaining a gloomy mastery over his soul. he grew weary of his existence, and at length his life became wholly unsupportable. retiring to a small room, he locked the door, closed up every chink and crevice which might admit the air, carried writing materials to a table, on which he placed a second watch, and then seated himself before it. he now marked precisely the hour, and lighted a brazier of charcoal beside him. he continued to note down the series of sensations he then experienced in succession, detailing the approach and the rapid progress of delirium, until, as time went on, the writing became confused and illegible, and the young victim dropped dead upon the floor!”17 berthollet and the society of arcueil berthollet and the mathematician pierre-simon laplace (1749-1827) were a founding members of the society of arcueil.18 the name of this society comes from the village in which they lived as neighbors. a very complete laboratory was created there in berthollet’s house, suitable for carried out experiments in physics and chemistry. on june 7, 1809, the members of the society of arcueil were the physicists jean-baptiste biot (1774-1862) and étienne-louis malus (1775142 aleksander sztejnberg 1812), the naturalist alexander von humboldt, the chemists joseph-louis gay-lussac (1778-1856), louisjacques thénard (1777-1857) and h.-v. collet-descotils, the swiss botanist augustin pyramus de candolle (1778−1841), berthollet and his son, amédée.19 in 1813, malus, collet-descotils and amédée berthollet were not on the list of members of the society. however, the names of new members appeared. there were among them the physicist dominique-françois arago (17861853), the mathematician siméon denis poisson (1781840), the chemists pierre-louis dulong (1785-1838), invited by berthollet in 181120, jacques-étienne bérard (1789-1869) and jean-antoine chaptal (1756-1832).21 this society has published three volumes of very valuable memoirs. the first volume appeared in 1807.22 the second volume was published in 180923 and the third in 1813.24 the activities of the society have been partially discontinued for political reasons in 1816.25 death of berthollet the article, written by hugh colquhoun, appeared three years after berthollet’s death. he wrote about berthollet’s disease and the last several months of his life as follow: “his end was worthy of the manner in which he had lived. a fever, apparently slight, left behind it a number of boils, which were soon followed by a gangrenous ulcer of uncommon size. under these he suffered for several months with the greatest constancy and fortitude. his complaint was of that desperate nature which medicine cannot cure. he himself, as a physician, knew the extent of his danger, felt the inevitable progress of the malady, and steadfastly but calmly regarded the slow advance of death. during all this time, his mental suffering, and the loss of his son, engrossed him more than his bodily pain. at length, after a tedious period of suffering, in which his equanimity had never once been shaken, berthollet died on the 6th of november, 1822, at the advanced age of 74 years. he has left the faithful partner of his joys and griefs, to mourn his loss in desolate, childless widowhood.”26 etienne pariset in éloge de m. le comte berhollet described berthollet’s meeting with his friend jeanantoine chaptal the day before berthollet’s death. berthollet felt his death approaching. “mr. chaptal, alone with him, sought to reassure him on his situation. “i give you thanks,” berthollet answers tenderly hollet taking his hand; but your goodness is deceiving. herself trying to abuse me. i feel death approach, and i feel it with joy. why should i fear it? i have never done any harm, and at the last hour i carry off the consoling idea that the friendship which has attached us to each other for more than forty years, and of which you have given so much proof to me and mine, has never been troubled for a moment. that it is given to few men to render of themselves a such a testimony! this one is enough for me: i do not want others.”27 at the funeral of berthollet, joseph-louis gay-lussac and louis-jacques thénard spoke at his grave alternately. jean-antoine chaptal honored his memory on the tribune of the chamber of peerst, the upper house of the french parliament.28 2. berthollet’s works berthollet’s published works are extremely numerous and have a very diverse character. the list includes 88 papers.29 the earlier ones were mainly published in various volumes of mémoires de l’académie royale des sciences. he published many papers in the annales de chimie, and the journal de physique, de chimie, d’histoire naturelle et des arts. his papers can also be found in various volumes of the mémoires de physique et de chimie, de la société d’arcueil. in 1787, berthollet jointly wrote méthode de nomenclature chimique with louis-bernard guyton de morveau (1737-1816), antoine-laurent lavoisier (1743-1794) and antoine-françois de fourcroy (1755-1809).30 berthollet’s research interests also focused around chemistry and technology of dyes. in the years 17981799, he published two articles in la décade egyptienne, journal littéraire et d’économie politique about the use of safflower31 and henna32 in egypt. he was the author of a two-volume book entitled essai de statique chimique (1803) published in paris.33,34 this book has also been published in italian35,36 and english a year later.37,38 the german edition was published in 1811.39,40 in this work he was the first to define the new notions of chemical equilibrium and mass action. the rules he proposed was one of the first and important contributions to the study of predicting chemical reactions. amédée berthollet (1780-1811), the most persistent and succesful young man, collaborated with his father in preparing a second edition of the éléments de l’art de la teinture. these books have been revised, corrected, increased and was published in the year xiii (1804) under names c. l. and a. b. berthollet.41,42 “the names of the father and son stand together on the title-page as joint authors, and the natural affection which must ever subsist between two persons connected by so intimate a degree of relationship was in their case strengthened and exalted by a community of feeling, and by kindred pursuits.”43 143the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21st centuries 3. berthollet’s greatest discoveries the year 1785 marks an important event in the career of berthollet. it was then he formally renounced the phlogiston theory and supported lavoisier’s theory of combustion. in the same year, he discovered that after heating ammonium nitrate to about 150°c, it decomposes into water and diminished nitrous air (laughing gas, nitrous oxide). the following reaction took place: nh4no3(aq) = n2o(g) + 2h2o(l).44 one of berthollet’s greatest discovery was the determination of the composition of the alkaline gas (volatile alkali), which the swedish chemist torbern bergman (1735-1784) gave the name ammonia in 1782. berthollet’s paper in this topic appeared in the journal de physique, de chimie, d’histoire naturelle, et des arts on may 1785. in addition, he read his paper analyse de l’alkali volatil before the academy on june 11, 1785.45 in 1786 he sent a letter to an english natural philosopher henry cavendish (1731-1810) regarding the analysis of alkaline gas (ammonia). he wrote, among others: “i have used a method that is more direct and more exact: 1.7 cubic inches of alkaline gas when decomposed yielded 3.3. cubic inches of a gas… i exploded four measures of this gas with an excess of vital air [oxygen] in the eudiometer of mr. volta, and this experiment showed that this gas contains 2.9 of inflammable gas of water [hydrogen] and 1.1 of mephitic air [nitrogen].”46 amédée berthollet repeated the ammonia analysis previously carried out by his father. his results were reported to the institut de france on march, 24, 1808. he found that “1 litre de gaz ammoniac fournit, par sa décomposition, 2litres, 046 d’un mélange de gaz dans lequel il entre 1 litre, 545 d’ hydrogène et o litre, 501 d’azote [the decomposition of 1 liter of ammonia gas yielded 2.046 liters of a mixture that contained 1.545 liter of hydrogen and 0.501 liter of nitrogen]”. from these he calculated that “d’ammoniaque contiennent 18,87 d’ hydrogène et 81,13 d’azote [ammonia contains 18.87 per cent hydrogen and 81.13 per cent nitrogen].”47 the corresponding modern values are 17.76 and 82.24 per cent. berthollet also determined the composition of prussic acid (hydrogen cyanide) in 178748, and sulphuretted hydrogen (hydrogen sulfide) in 1789.49 a year earlier, he the first prepared in a pure state potassium chlorate (berthollet salt – potassium chlorate) by passing chlorine into hot aqueous potash (potassium hydroxide). the reaction is expressed by the following equation: 6koh(aq) + 3cl2(g) = 5 kcl(aq) + kclo3(aq) + 3h2o(l)50 this discovery was of great importance to obtain a more powerful kind of gunpowder replacing nitre. in 1788, he also determined the usefulness of chlorine and potassium hypochlorite as bleaching agents.51 berthollet’s greatest theoretical discovery was his innovative theory of the chemical affinities.52 this was a theory that intended to replace the theory of the elective affinities and that gave support to the law of the variable proportions of combination in opposition to joseph-louis proust’s (1754-1826) law of the fixed proportions of combination. in the second volume of the english edition of his essai de statique chimique53, he “definitely challenged proust’s opinion that invariable proportions and constant attributes characterise all the true compounds of art or of nature, and that the chemist is no more able to control these proportions and attributes than he is able to control the affinities which the elements possess for one another. (…) berthollet maintained that the elements can combine in variable proportions, constancy of composition being secured only when some constituent crystallises out, or distils out from the mixture of interacting substances.”54 berthollet held a lengthy controversy with proust about the law of fixed (definite) proportions.55 at the end of the first decade of the nineteenth century, the discussion between them ended in favor of proust. the law of definite proportions was recognized by most chemists. at the begining of the 20th century, it turned out that the proust’s law is not universally true, because solid compounds with slight variations in chemical composition were discovered. in memory of berthollet they were called “berthollide compounds” or “non-stoichiometric compounds”.56 4. biographies or biographical notes about claude-louis berthollet published in 1823-2018 in the nineteenth century, some authors wrote biographical notes or biographies of berthollet. there was among them jacques-alphonse mahul, who wrote his biographical note in 182357, and hugh colquhoun, who published his article about him in annals of philosophy.58 in 1823, the biographical memoir of count claudelouis berthollet was also published in the the edinburgh philosophical journal by an anonymous author.59 the physician and historian of medicine giovanni giacomo bonino (1791-1858), wrote berthollet’s biographical note in his book entitled biografia medica piemontese in 1825.60 the naturalist george cuvier (1769-1832) wrote about him in his éloge historique de m. le comte berthollet.61 berthollet’s life and activities was also described by historian of chemistry thomas thomson 144 aleksander sztejnberg (1773-1852) in his book entitled history of chemistry.62 jomard wrote his biography in the book entitled notice sur la vie et les ouvrages de cl. l. berthollet.63 the perpetual secretary of the royal academy of medicine etienne pariset (1770-1847) wrote about him in his éloge de m. le comte berthollet.64 a berthollet’s biographical note written by cecilia lucy brightwell (1811-1875) was published in 1859.65 ferdinand hoefer (1811-1878) described his life in histoire de la chimie.66 at the beginning of the second decade of the 20th century, berthollet’s life and work was described by ethel roberts.67 the chemist james cambell brown (18431910), professor at the university of liverpool, published a biographical note about him in 1920.68 doctor of medicine and pharmacy pierre lemay (1893-1962) and historian of chemistry ralph edward oesper (1886-1977) briefly described the life and discoveries made by berthollet in their article published in journal of chemical education.69 the chemist and historian of chemistry james riddick partington (1886-1965) wrote berthollet’s biographical note in his book published in 1962.70 berthollet’s fulllength biography was written by michelle sadoun-goupil (1934-1993) in 1977. in this book, the first eleven chapters are devoted to the life of the scientist. the second part of this monograph is devoted to the work of berthollet. the structure of the book also includes notes, very extensive systematic bibliography and complete index of names and persons. in addition, this work is enriched by list and summary of the content of berthollet’s correspondence with many scientists.71 another author nicole fleury-heusghem wrote about berthollet in her article published in bulletin de la sabix.72 his biographical note was published at the vestnik rossiyskoy akademii nauk in 200373 , as well as by jaime wisniak in 2008.74 in 2018, valentin matyukhin also wrote about him on the 270th anniversary of his birth.75 5. conclusion claude-louis berthollet was one of the greatest french chemists of his time. he was elected a member of l’académie royale des sciences (the royal academy of sciences) in paris on april 21, 1780.76 la société hollandaise des sciences à haarlem (the dutch society of science in haarlem) elected him a foreign member in 1786.77 on december 17, 1787, he was elected a national member of l’académie royale des sciences de turin (the royal academy of sciences of turin).78 on april 30, 1789, he became a fellow of the royal society of london.79 on april 30, 1790, he was elected an honorary member of the literary and philosophical society of manchester.80 berthollet’s death did not go unnoticed. in the nineteenth century, books and articles with his biographical notes or biographies were published in france, great britain, and italy. in the twentieth and twenty-first centuries, his life and discoveries were described by authors of books and articles from great britain, united states, france, russia, israel and lithuania. for cecilia lucy brightwell, berthollet was an outstanding chemist. in her book, she wrote: “among the illustrious men renowned for their devotedness to the cause of science, and its application to the practical purposes of civil and social advantage, m. berthollet holds a high and honourable place. his name has long been known in every part of europe, and will ever rank among those of the distinguished chemists of the nineteenth century”.81 berthollet, while he was still alive, was considered by his colleagues a great chemist. the mathematician joseph fourier, spoke about him in a letter sent in january/february 1795, to his teacher claude-louis bonard (1757-1819)82, a professor of mathematics at the école centrale in auxerre, with “notes on the école normale and the persons attached to that estabilishment”. he also listed some of the personality traits characteristic for him: ”berthollet is the greatest chemist we have, either in france or aboard: he is not old and has a rather ordinary appearance. he only speaks with the most extreme difficulty, hesitates and repeats himself ten times in one sentence, and seems to find difficulties in the least important details of an experiment. his course is only understood by those who study much or understand already, and it is for this reason that he displeased the great majority. his course is a collection of useful dissertations, very wise and very learned; he has much difficulty in making himself understood”.83 hugh colquhoun wrote about his friend as follows: “there are some men whose characters combine those estimable qualities which render them the delight of their friends, with those splendid talents which destine them to form an era in that branch of study to which they devote themselves, – men, whose memories should live from age to age endeared to the cultivators of science, a generous incitement to their ardour as students, and a bright example to their conduct as philosophers. such a friend, and such a man of genius, (…) nor needs there much of prophecy to pronounce that such also shall long be the hallowed memory of claude-louis berthollet”.84 in the months of february and march 1819, the swedish chemist jöns jacob berzelius (1779-1848) stayed in berthollet’s country-house in arcueil. he carried out many experiments there in berthollet’s laboratory.85 in the years 1810-1822, correspondence was exchanged 145the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21st centuries between them. it consisted of 42 letters, including 21 from berzelius and the same from berthollet. berzelius sent the last letter to him on november 18, 1822, twelve days after his death.86 after berthollet, not only his papers and letters survived. in addition, several of his lithographic portraits were produced by french lithographers in various years of the nineteenth century. his portraits were made by julien-léopold boilly (1796-1874)87, ambrosie tardieu (1788-1841)88, ephraïm conquy (1808-1843)89, alphonse boilly (1801-1867)90 and françois-séraphin delpech (1778-1825).91 pierre lemay in his article presented a portrait of berthollet when he received the honorary title of peer of france.92 noteworthy is the fact that the oil painting painted by théobald chartran (1849-1907) in 1886-1889, depicting berthollet in the lavoisier laboratory, is a decoration of the peristyle at the sorbonne university in paris.93 in addition to lithographic portraits and oil painting, the bust of berthollet was commissioned by the state to the french sculptor raymond gayrard (18071855). the plaster bust was modeled, after berthollet’s death. then it was carved in marble. its height is 59.0 cm, width 40.0 cm and depth is 25.0 cm. there is an inscription on the plinth: c. l. berthollet / sc. 1748-1822. the sculptor’s name as well as date appear on the right: gayrard st / mdcccxxiii.94 on august 25, 1844, a monument was erected by subscription in honor of berthollet in annecy, not far from talloires, the village where he was born. four years earlier, king charles albert of savoy (1798-1849) agreed to build the monument and was one of the subscribers. the clay model of the statue was made free by french sculptor baron carlo marochetti (1805-1867). its founder was louis claude ferdinand soyer (1785-1854). in 1863, the berthollet statue made of bronze was transported to the open space in a public garden and placed on a new pedestal ornamented with basreliefs erected by architecte henri poreaux (1818-1893). on four basreliefs we can see berthollet introduce itself to the physician théodore tronchin (1709-1781) in paris; berthollet receives the duke of orléans in his laboratory; berthollet and bonaparte in front of the pyramids in egypt; berthollet sits at the bedside of sick monge in saint-jean-d’acre. in 1944, by order of the occupation authorities, the statue was intended to be melted, but it survived and took its place again on october 12 of that year.95 upon the front of the statue was the following inscription, in french, “claude-louis berthollet, / his fellow citizens and admirers. / mdcccxliii [1843]. / born in talloires, the ix [9] december mdccxlviii [1748]. / died at arcueil, near paris, the vi [6] november mdcccxxii [1822]).” inscriptions, in french, on the opposite side of the pedestal inform the reader about the education of berthollet, his work, and honors, for example “professor of chemistry in the l’école normale / and in the l’école polytechnique, / member of the academy of sciences of the institute. / he created with lavoisier the chemical nomenclature.”96 berthollet was a very talented chemist and went down in history as the author of numerous chemical discoveries. one of the asteroids (12750 berthollet) discovered by the belgian astronomer eric walter elst (b. 1936) on february 18, 1993, was named in his honour.97 it is also worth emphasizing that the genus of south american plants bertholletia, to which is assigned the species the brazil nut (bertholletia excelsa humb. & bonpl.) in the family lecythidaceae98, was estabilished in 180899, and named after berthollet. “the genus bertholletia was so named by humboldt and bonpland in honour of berthollet, of which the grandest species – bertholletia excelsa – is the juvia or brazil-nut tree, one of the largest trees of the primeval forests in the central parts of brazil, bordering the amazon, in its colossal fruit are contained those hard three-cornered nuts, similar in flavour to the cocoa-nut, which abound in all the fruit markets of europe, and pass among the ignorant as palm-nuts.”100 references 1. a. j. mahul, berthollet (claude-louis), chimiste. annuaire nérologique, ou complémentannuel et continuation de toutes les biographies, ou dictionnaires historiques; [iiie année, 1822]. ponthieu, paris, 1823, p. 19. retrieved from https://archive.org/ details/annuairencrologi1822mahu/page/14 2. p. lemay, r. e. oesper, j. chem. educ. 1946, 23(4), 158-164. https://doi.org/10.1021/ed023p158 3. berthollet claude louis, public domain. retrieved from wikimedia website: https://upload.wikimedia. org/wikipedia/commons/f/fd/berthollet_claude_ louis.jpg 4. m. sadoun-goupil, rev. hist. sc. 1972, 25(3), 221252. retrieved from https://www.persee.fr/doc/ rhs_0151-4105_1972_num_25_3_3291 5. h. colquhoun, ann. phil. new series. 1825, 9(1), 1-18; 9(2), 81-96; 9(3), 161-185. retrieved from https://archive.org/details/annalsphilosoph08braygoog/ page/n7 6. b. bensaude-vincent, p. bret, p. grapi in l’école normale de l’an iii. vol. 3. leçons de physique, de chimie, https://archive.org/details/annuairencrologi1822mahu/page/14 https://archive.org/details/annuairencrologi1822mahu/page/14 https://doi.org/10.1021/ed023p158 https://upload.wikimedia.org/wikipedia/commons/f/fd/berthollet_claude_louis.jpg https://upload.wikimedia.org/wikipedia/commons/f/fd/berthollet_claude_louis.jpg https://upload.wikimedia.org/wikipedia/commons/f/fd/berthollet_claude_louis.jpg https://www.persee.fr/doc/rhs_0151-4105_1972_num_25_3_3291 https://www.persee.fr/doc/rhs_0151-4105_1972_num_25_3_3291 https://archive.org/details/annalsphilosoph08braygoog/page/n7 https://archive.org/details/annalsphilosoph08braygoog/page/n7 https://archive.org/details/annalsphilosoph08braygoog/page/n7 146 aleksander sztejnberg et d’histoire naturelle. haüy, berthollet, daubenton, (ed.: e. guyon), éditions ens rue d’ulm, paris, 2006, pp.239-366. http://dx.doi.org/10.4000/books. editionsulm.1341. 7. b. bensaude vincent in compound histories: materials, governance and production, 1760-1840, (eds.: l. l. roberts, s.werrett), brill, boston, 2018, p. 263. retrieved from https://brill.com/view/book/ edcoll/9789004325562/b9789004325562_012.xml 8. a. fournier, napoleon i. a biography. 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(j. lassell, c. lassell, trans.), longmans, green, and co., london, 1873, p. 231. retrieved from https:// archive.org/details/lifeofalexanderv01bruhrich/page/ n9 10. memoirs relative to egypt, written in that country during the campaigns of general bonaparte, in the years 1798 and 1799, by the learned and scientific men who accompanied the french expedition, printed by t. gillet, london, 1800, pp. 1-2. retrieved from https://archive.org/details/memoirsrelativet00inst/page/n4 11. s. w. weller, bull.hist.chem. 1999, 24, p. 64. retrieved from http://acshist.scs.illinois.edu/bulletin_ open_access/bull99-2-num24.php 12. andreossi in memoirs relative to egypt, printed by t. gillet, london, 1800, pp. 253-303. retrieved from https://archive.org/details/memoirsrelativet00inst/ page/n261/mode/2up 13. p. fournier, c. viel, j. fournier, l’actualité chimique, 1998, 219, 37-46. retrieved from https://www. lactualitechimique.org/chimie-et-chimistes-dans-lexpedition-d-egypte-1798-1801 14. m. a. hamdan and f. a. hassan in the geology of egypt, (eds.: z. hamimi, a. el-barkooky, j. m. frías, h. fritz, y. a. el-rahman), springer nature switzerland ag, cham, 2020, p. 482. http://dx.doi. org/10.1007/978-3-030-15265-9 15. berthollet in memoirs relative to egypt, printed by t. gillet, london, 1800, pp. 304-312. retrieved from https://archive.org/details/memoirsrelativet00inst/ page/304 16. quoted in ref. 8 (fournier), p. 176. 17. quoted in ref. 5 (colquhoun), p. 178. 18. m. crosland, the society of arcueil. a view of french science at the time of napoleon i, heinemann, london, 1967. 19. mémoires de physique et de chimie, de la société d’arcueil. tome second, 1809, p. 499. retrieved from https://gallica.bnf.fr/ark:/12148/bpt6k1050356z/ f9.image 20. j. wisniak, educación química, 2001, 12 (4), p. 220. http://dx.doi.org/10.22201/fq.18708404e.2001.4.66330 21. mémoires de physique et de chimie, de la société d’arcueil. tome troisiéme, 1813, p. 5 retrieved from https://gallica.bnf.fr/ark:/12148/bpt6k1049772z/ f9.image 22. mémoires de physique et de chimie, de la société d’arcueil. tome premier, 1807. retrieved from https://gallica.bnf.fr/ark:/12148/bpt6k10503544 23. see ref. 19 for details. 24. see ref. 21 for details. 25. j. lequeux, françois arago. a 19th century french humanist and pioneer in astrophysics, springer international publishing switzerland, cham, heidelberg, new yor, dordrecht, london, 2016, p. 6. 26. quoted in ref. 5 (colquhoun), p. 179. 27. e. pariset, histoire des membres de l’académie royale de médecine; ou, recueil des éloges lus dans les séances publiques de l’académie royale de médecine, tome premier, chez j.-b. baillière, paris, 1845, pp. 206-207. retrieved from https://archive.org/details/histoiredesmembr01unse/page/n5 28. see ref. 1 (mahul), p. 19. 29. jomard, notice sur la vie et les ouvrages de cl. l. berthollet, 1844, pp.55-63. retrieved from bayerische staatsbibliothek digital website: https://reader.digitale-sammlungen.de/de/fs1/object/display/ bsb10061708_00005.html 30. de morveau, lavoisier, bertholet, de fourcroy, méthode de nomenclature chimique. on y a joint un nouveau système de caractères chimiques, adaptés à cette nomenclature, par m.m. hassenfratz & adet, cuchet, paris, 1787. retrieved from https://archive. org/details/b2803806x/page/n7 31. berthollet, la décade egyptienne, journal littéraire et d’économie politique (premier volume), 1798, 129131. retrieved from https://gallica.bnf.fr/ark:/12148/ bpt6k106598h/f129.image 32. descostils, berhollet, la décade egyptienne, journal littéraire et d’économie politique (second volume), 1799, 264-266. retrieved from https://gallica.bnf.fr/ ark:/12148/bpt6k106599w/f264.image 33. c. l. berthollet, essai de statique chimique. (premiere partie), chez firmin didot, a paris, 1803. retrieved from https://archive.org/details/essaidestatiquec01bert/page/n6 34. c. l. berthollet, essai de statique chimique (seconde partie), chez firmin didot, a paris, 1803. http://dx.doi.org/10.4000/books.editionsulm.1341 http://dx.doi.org/10.4000/books.editionsulm.1341 https://brill.com/view/book/edcoll/9789004325562/b9789004325562_012.xml https://brill.com/view/book/edcoll/9789004325562/b9789004325562_012.xml https://archive.org/details/napoleonibiogra01four/page/n10 https://archive.org/details/napoleonibiogra01four/page/n10 https://archive.org/details/lifeofalexanderv01bruhrich/page/n9 https://archive.org/details/lifeofalexanderv01bruhrich/page/n9 https://archive.org/details/lifeofalexanderv01bruhrich/page/n9 https://archive.org/details/memoirsrelativet00inst/page/n4 https://archive.org/details/memoirsrelativet00inst/page/n4 http://acshist.scs.illinois.edu/bulletin_open_access/bull99-2-num24.php http://acshist.scs.illinois.edu/bulletin_open_access/bull99-2-num24.php https://archive.org/details/memoirsrelativet00inst/page/n261/mode/2up https://archive.org/details/memoirsrelativet00inst/page/n261/mode/2up https://www.lactualitechimique.org/chimie-et-chimistes-dans-l-expedition-d-egypte-1798-1801 https://www.lactualitechimique.org/chimie-et-chimistes-dans-l-expedition-d-egypte-1798-1801 https://www.lactualitechimique.org/chimie-et-chimistes-dans-l-expedition-d-egypte-1798-1801 http://dx.doi.org/10.1007/978-3-030-15265-9 http://dx.doi.org/10.1007/978-3-030-15265-9 https://archive.org/details/memoirsrelativet00inst/page/304 https://archive.org/details/memoirsrelativet00inst/page/304 https://gallica.bnf.fr/ark:/12148/bpt6k1050356z/f9.image http://dx.doi.org/10.22201/fq.18708404e.2001.4.66330 https://gallica.bnf.fr/ark:/12148/bpt6k1049772z/f9.image https://gallica.bnf.fr/ark:/12148/bpt6k10503544 https://gallica.bnf.fr/ark:/12148/bpt6k10503544 https://archive.org/details/histoiredesmembr01unse/page/n5 https://archive.org/details/histoiredesmembr01unse/page/n5 https://reader.digitale-sammlungen.de/de/fs1/object/display/bsb10061708_00005.html https://reader.digitale-sammlungen.de/de/fs1/object/display/bsb10061708_00005.html https://reader.digitale-sammlungen.de/de/fs1/object/display/bsb10061708_00005.html https://archive.org/details/b2803806x/page/n7 https://archive.org/details/b2803806x/page/n7 https://gallica.bnf.fr/ark:/12148/bpt6k106598h/f129.image https://gallica.bnf.fr/ark:/12148/bpt6k106599w/f264.image https://gallica.bnf.fr/ark:/12148/bpt6k106599w/f264.image https://archive.org/details/essaidestatiquec01bert/page/n6 https://archive.org/details/essaidestatiquec01bert/page/n6 147the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21st centuries retrieved from https://archive.org/details/essaidestatiquec02bert/page/n6 35. c. l. berthollet, saggio di statica chimica (v. dandolo, traduzione), parte prima, presso luigi noseda, como, 1804. retrived from https://babel.hathitrust. org/cgi/pt?id=uc1.b4253976&view=1up&seq=11 36. c. l. berthollet, saggio di statica chimica (v. dandolo, traduzione), parte seconda, presso luigi noseda, como, 1804. retrived from https://babel.hathitrust. org/cgi/pt?id=uc1.b4253977&view=1up&seq=11 37. c. l. berthollet, an essay of chemical statics; with copious explanatory notes, and an appendix on vegetable and animal substances. (vol. i.). (b. lambert, trans.), printed for j. mawman, london, 1804. retrieved from https://archive.org/details/ b21727326_0001/page/n6 38. c. l. berthollet, an essay of chemical statics; with copious explanatory notes, and an appendix on vegetable and animal substances. (vol. ii.). (b. lambert, trans.), printed for j. mawman, london, 1804. retrieved from https://archive.org/details/ b21727326_0002/page/n6 39. c. l. berthollet, claude louis berthollet’s versuch einer chemischen statik, das ist einer theorie der chemischen naturkräfte (g. w. bartoldy, trans.). duncker und humblot, berlin, 1811. retrieved from https:// archive.org/details/b2934024x_0001/page/n5 40. c. l. berthollet, claude louis berthollet’s versuch einer chemischen statik, das ist einer theorie der chemischen naturkräfte (zweiter theil). (g. w. bartoldy, trans.), duncker und humblot, berlin, 1811. retrieved from https://archive.org/details/ b2934024x_0002/page/n3 41. c. l. berthollet, a. b. berthollet, éléments de l’art de la teinture, avec une description du blanchîment par l’acide muriatique oxigéné (seconde édition). (tome premier), chez firmin didot, paris, 1804. retrived from https://gallica.bnf.fr/ark:/12148/bpt6k86237z/f3.image 42. c. l. berthollet, a. b. berthollet, éléments de l’art de la teinture, avec une description du blanchîment par l’acide muriatique oxigéné (seconde édition). (tome second), chez firmin didot, paris, 1804. retrived from https://archive.org/details/lmentsdelar02bert/page/n6/mode/2up 43. quoted in ref. 5 (colquhoun), p. 177. 44. t. m. lowry, historical introduction to chemistry, macmillan and co. limited, london, 1915, p. 79. retrieved from https://archive.org/details/historicalintrod00lowrrich/page/n8 45. berthollet, histoire de l’académie royale des sciences. avec les mémoires de mathématique & de physique, pour la même année, tirés des registres de cette académie, année mdcclxxxv, 1785, pp. 316326. retrieved from https://gallica.bnf.fr/ark:/12148/ bpt6k35847/f490.image 46. quoted in ref. 2 (lemay, oesper), p. 159. 47. a. b. berthollet, mémoires de physique et de chimie, de la société d’arcueil (tome second). 1809, pp. 285-286. retrieved from https://gallica.bnf.fr/ ark:/12148/bpt6k1050356z/f276.image 48. see ref. 44 (lowry), p. 243. 49. see ref. 44 (lowry), p. 177. 50. see ref. 44 (lowry), p. 227. 51. see ref. 44 (lowry), p. 228. 52. c. l. berthollet, researches into the laws of chemical affinity, (m. farrell, trans.), printed for john murray, london, 1804. retrieved from https://archive.org/ details/b30795102/mode/2up 53. see ref. 35 (berthollet), pp. 315-316. 54. quoted in ref. 44 (lowry), p. 299. 55. p. j. hartog, nature, 1894, 50 (1285), 149-150. https:// www.nature.com/articles/050149b0retrieved from https://archive.org/details/paper-doi-10_1038_050149b0/ mode/2up 56. j. daintith (ed.), a dictionary of chemistry (6th ed.), oxford university press, oxford, 2008, p. 65. 57. see ref. 1 (mahul), pp. 14-20. 58. see ref. 5 (colquhoun) for details. 59. art. i. biographical memoir of count claude louis berthollet in dr brewster, professor jameson (eds.), the edinburgh philosophical journal, 1823, 9, pp. 1-7. retrieved from https://archive.org/details/in.ernet. dli.2015.21021/page/n7 60. g. g. bonino, biografia medica piemontese. (volume secondo), dalla tipografia bianco, torino, 1825, pp. 552-570. retrieved from https://archive.org/details/ biografiamedicap02boni/page/552/mode/2up 61. g. cuvier, mémoires de l’académie des sciences, 8, 1829, pp. clxxix-ccxi. retrieved from https:// f r.wikis ource.org/wiki/page:m%c3%a9moires_ de_l%e2%80%99acad%c3%a9mie_des_sciences,_ tome_8.djvu/184 62. t. thomson, the history of chemistry. vol. ii. henry colburn and richard bentley, london, 1831, pp. 141-165. retrieved from https://archive.org/details/ ost-chemistry-historyofchemist02thomuoft/page/n6 63. see ref. 29 (jomard) for details. 64. see ref. 27 (pariset), pp. 164-208. 65. c. l. brightwell, heroes of the laboratory and the workshop, george routledge and sons, london, new york, 1859, pp. 9-16. retrieved from https:// archive.org/details/hero esof lab orato00brigrich/ page/n7 https://archive.org/details/essaidestatiquec02bert/page/n6 https://archive.org/details/essaidestatiquec02bert/page/n6 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pharm.1932.9967 93. lavoisier et berthollet, n.d. retrieved from larousse encyclopédie website: https://www.larousse.fr/encyhttps://archive.org/details/histoiredelachim02hoefuoft/page/n8 https://archive.org/details/histoiredelachim02hoefuoft/page/n8 https://archive.org/details/famouschemists00robe/page/n6/mode/2up https://archive.org/details/famouschemists00robe/page/n6/mode/2up https://archive.org/details/famouschemists00robe/page/n6/mode/2up https://archive.org/details/historyofchemist00browuoft/page/n7 https://archive.org/details/historyofchemist00browuoft/page/n7 http://journals.openedition.org/sabix/239 http://journals.openedition.org/sabix/239 http://www.ras.ru/fstorage/fileinfo.aspx?catalogid=47d09280-7d70-4722-94eb-5f8f93148fda&id=fd752629-94b3-4248-8045-ef62b908804d http://www.ras.ru/fstorage/fileinfo.aspx?catalogid=47d09280-7d70-4722-94eb-5f8f93148fda&id=fd752629-94b3-4248-8045-ef62b908804d 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http://www.bildarchivaustria.at/pages/imagedetail.aspx?p_ibildid=3539501 http://www.bildarchivaustria.at/pages/imagedetail.aspx?p_ibildid=3539501 http://www.bildarchivaustria.at/pages/imagedetail.aspx?p_ibildid=3539513 http://www.bildarchivaustria.at/pages/imagedetail.aspx?p_ibildid=3539513 http://www.bildarchivaustria.at/pages/imagedetail.aspx?p_ibildid=3539525 http://www.bildarchivaustria.at/pages/imagedetail.aspx?p_ibildid=3539525 http://dx.doi.org/10.3406/pharm.1932.9967 http://dx.doi.org/10.3406/pharm.1932.9967 https://www.larousse.fr/encyclopedie/images/lavoisier_et_berthollet/1314142 149the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21st centuries clopedie/images/lavoisier_et_berthollet/1314142 94. buste (ronde-bosse): claude-louis berthollet, n.d. retrieved from la région auvergne-rhône-alps website: https://patrimoine.auvergnerhonealpes.fr/ dossier/buste-ronde-bosse-claude-louis-berthollet/ fb8907ab-97e6-4371-9262-5dfade69c89c 95. d. perchet, monument à claude louis berthollet – annecy, 2011. retrieved from https://e-monumen. net/patrimoine-monumental/monument-a-claudelouis-berthollet-annecy/ 96. see ref. 29 (jomard), p. vii. 97. l. d. schmadel, dictionary of minor planet names. sixth edition. volume 2. springer verlag, berlin, heidelberg, 2012, p. 826. 98. s. a. mori, g. t. prance, advances in economic botany, 1990, 8, 130-150. retrieved from https://www. jstor.org/stable/43927571 99. a. humboldt, a. bonpland, voyage de humbold et bonpland. sixieme partie. botanique (tome premier), f. schoell, paris, 1808, pp. 122-127. retrieved from https://www.biodiversitylibrary.org/ item/9696#page/143/mode/1up 100. k. bruhns, j. löwenberg, r, avé-lallemant, a. dove, life of alexander von humboldt. compiled in commemoration of the centenary of his birth (volume ii.). (j. lassell, c. lassell, trans.), longmans, green, and co., london, 1873, p. 32. retrieved from https:// archive.org/details/lifeofalexanderv02bruhrich/page/n8 https://www.larousse.fr/encyclopedie/images/lavoisier_et_berthollet/1314142 https://patrimoine.auvergnerhonealpes.fr/dossier/buste-ronde-bosse-claude-louis-berthollet/fb8907ab-97e6-4371-9262-5dfade69c89c https://patrimoine.auvergnerhonealpes.fr/dossier/buste-ronde-bosse-claude-louis-berthollet/fb8907ab-97e6-4371-9262-5dfade69c89c https://patrimoine.auvergnerhonealpes.fr/dossier/buste-ronde-bosse-claude-louis-berthollet/fb8907ab-97e6-4371-9262-5dfade69c89c https://e-monumen.net/patrimoine-monumental/monument-a-claude-louis-berthollet-annecy/ https://e-monumen.net/patrimoine-monumental/monument-a-claude-louis-berthollet-annecy/ https://e-monumen.net/patrimoine-monumental/monument-a-claude-louis-berthollet-annecy/ https://www.jstor.org/stable/43927571 https://www.jstor.org/stable/43927571 https://www.biodiversitylibrary.org/item/9696#page/143/mode/1up https://www.biodiversitylibrary.org/item/9696#page/143/mode/1up https://archive.org/details/lifeofalexanderv02bruhrich/page/n8 https://archive.org/details/lifeofalexanderv02bruhrich/page/n8 substantia an international journal of the history of chemistry vol. 4, n. 2 2020 firenze university press some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy, ph.d., j.d. …and all the world a dream: memory outlining the mysterious temperature-dependency of crystallization of water, a.k.a. the mpemba effect evangelina uskoković1, theo uskoković1, victoria wu1,2, vuk uskoković1,3,* the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries aleksander sztejnberg communicating science: a modern event antonio di meo dear prof 1 dalton’s long journey from meteorology to the chemical atomic theory pier remigio salvi dipartimento di chimica “ugo schiff”, università di firenze, via della lastruccia 3, 50019 sesto fiorentino (fi), italy email: piero.salvi@unifi.it received: apr 24, 2023 revised: jun 17, 2023 just accepted online: jun 23, 2023 published: xxxx this article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the version of record. please cite this article as: p. r. salvi (2023) dalton’s long journey from meteorology to the chemical atomic theory. substantia. just accepted. doi: 10.36253/substantia-2126 keywords: meteorological studies; theory of mixed gases; law of partial pressures; gas solubilities in water; chemical atomic theory; relative atomic weights. abstract the purpose of this paper is to review dalton’s contributions to science in various fields of research in relation to the first intimation of the chemical atomic theory. early “germs” of his physical ideas may be found in the initial meteorological studies where water vapour is viewed as an “elastic fluid sui generis” diffused in the atmosphere and not as a species chemically combined with the other atmospheric gases. the next object of dalton’s attention was atmosphere itself. he discarded affinity between atmospheric gases as a possible cause of homogeneity and, making recourse to newtonian principles, considered the repulsive forces among particles. experiments on the “nitrous air test” and on the diffusion and solubility of gases were instrumental to arrive at the chemical atomic theory. the slow, laborious, and persevering work of dalton to get the first table of atomic weights is a fascinating piece of science which may be fully appreciated by referring to his laboratory notebook. 1 – introduction there has been in the years continuing interest on the genesis of the dalton’s chemical atomic theory [1-20]. according to thomson1 dalton told him in a meeting that occurred in august 1804 1 see ref. [1], p. 289. 2 that he had come to the theory by speculating on the analyses of methane (“carburetted hydrogen gas”) and ethylene (“olefiant gas”) which indicate that for a given weight of carbon methane contained twice as much hydrogen as ethylene. this narrative cannot be trusted [4] given that the reported data were acquired in the summer of 1804, almost one year after the appearance, september 1803, of the first table of atomic weights in dalton’s notebook [4]. a second proposal2 was advanced by william henry, dalton’s closest friend, and his son, william charles, dalton’s pupil. in conversation with them twenty-seven years after the event, dalton stated he took inspiration for the atomic hypothesis thinking about the importance of richter’s table of equivalents. this is an equally doubtful assertion since (i) it is generally accepted [4,8-10] that dalton was not aware of richter’s work in 1803 and (ii) in the table of atomic weights no entry refers to acids and bases, the subject of richter’s studies [8]. the young henry himself expressed uncertainty about the validity of this recollection3. a third account, coming from a dalton lecture held at the royal institution in 1810, was provided by roscoe and harden [4], responsible for the precious discovery and publication of dalton’s laboratory notebooks4. they point to the fact that the theory arose from considerations on the physical properties of gases rather than from experiments on multiple proportions. unfortunately, this version comes from beliefs about atomic sizes and weights that dalton proposed in 1804 or 1805 [5,9], rather than 1803 as claimed [4]. all this considered, it has been acutely remarked that a great scientist is not necessarily a good historian [5]. successively, two positions emerged [5,8,9]. shortly, the first [5] focuses the attention on the experiments performed by dalton in 1803 relative to the reaction of nitric oxide with oxygen while the second [8,9] strongly advocates that the theory was first conceived to explain the differences in water solubility of various gases and that only in a second time dalton realized the importance of application to chemical processes. more recently, other studies appeared [10-17]. in one of them [10] the initial dalton’s recognition of the novelty and significance of the theory from the chemical point of view is on the contrary stressed. in another study of particular interest, the nitric oxide/oxygen crucial experiment has been reproduced [12] and dalton’s pioneering observation of oxygen combination with one or two volumes of nitric oxide has been confirmed. dalton also tested the nitrous oxide/oxygen reaction by eudiometry [13]. finally, the influence of london atomists, such as william and bryan higgins, on dalton has been hypothesized and the concept of atomic sizes reexamined [14-16]. on the other hand, it may be worthwhile to review the evolution of dalton’s scientific studies from meteorology [21] to the physics of atmosphere [22,23] and to the first papers on the atomic theory [24,25] through a detailed analysis of his contributions to these fields, as it is proposed in this work. in summary, the paper is organized as follows. in the next section meteorological observations such as pressure measurements of water vapour, are presented and the conclusion is reached, in disagreement with the leading view at his times, that steam is an “elastic fluid” not chemically combined with the other atmospheric components [21]. then at the end of the 18th century dalton became interested in the nature of the atmosphere. to explain the atmospheric homogeneity, the theory of mixed gases was elaborated, and the enunciation was made of the law of partial pressures. this is the subject of section 3 [22,23]. gas diffusion and solubility were two experiments in agreement with the theory [26-28]. the two papers introducing the chemical atomic theory are reviewed in section 4 [24,25]. in the first [24], by applying the “nitrous air test” to oxygen detection 2 see ref. [2], p. 63, 84-85. 3 see ref. [2], p. 86. 4 dalton’s laboratory notebooks were destroyed during the second world war in a bombing over manchester. 3 in the atmosphere, dalton discovered the law of multiple proportions. in the second [25], the solubility of a series of gases in water was investigated and discussed as a purely physical process. the big difficulty, not amenable to the physical origin, was that the solubility varies considerably from one gas to another. dalton’s concern about this effect brought him to meditate about chemical atomism and eventually to present the first table of atomic weights. in section 5 the main ideas developed on this issue and the criteria on which the table is based, are described with the fundamental help of his laboratory notebook [4]. the conclusions section includes a few comments on the outgrowth of the atomic theory. it is hoped that our approach, though of limited historical viewpoint, will not be without interest for scholars curious about the birth of modern chemistry. 2 – meteorological studies dalton kept a constant interest in meteorology all along his life. in 1793 he published his first book, meteorological observations and essays, the second edition appearing in 1834 [21]. the book, divided into two parts with appendixes, deals with various aspects of meteorology ranging from descriptive information on instruments such as barometers and thermometers, to data collection about atmospheric pressure and temperature and to reports on thunderstorms, winds, snow, and the like. attention was also devoted to aurora borealis as a phenomenon related to the occurrence of magnetic matter in the atmosphere. later, faraday reported on “atmospheric magnetism” after his discovery of paramagnetic oxygen [29]. the second part of the book accounts for a few atmospheric processes; the sixth essay is concerned with evaporation, rain, and dew and shows “germs” of his physical ideas about vapour. dalton states in the opening lines of the essay the two opposing views on vapour “whether the vapour of water is ever chemically combined with all or any of the elastic fluids constituting the atmosphere [i.e., the view of lavoisier and french chemists], or it always exists therein as a fluid sui generis, diffused among the rest”5 and reports on pressure measurements of saturated water vapour at several temperatures in the range 80 – 212of (≈ 26 – 100oc). the results were interpreted in agreement with the second hypothesis although he acknowledged that the observed behaviour with temperature could have also suggested the first choice, “the fact that a quantity of common air of a given temperature, confined with water of the same temperature, will only imbibe [dissolve] a certain portion of the water, and that the portion increases with the temperature, seems characteristic of chemical affinity; but when the fact is properly examined, it will, i think, appear, that there is no necessity of inferring from it such affinity” 6. 5 ref. [21], p. 125. 6 ref. [20], p. 128. 4 there are comments on vapour saturation and condensation that are still valid. suppose, he says, to reduce the pressure of 1 atm on vapour in equilibrium with water at 100oc, to a smaller value, 1/10 atm. the new equilibrium temperature is t(oc) < 100oc, associated not only with the saturation pressure of 1/10 atm but also with the maximum vapour density at that temperature, called “extreme density” by dalton. then vapour, if mixed with dry air at t(oc), will not condense until the pressure reaches 1/10 atm and the vapour density 1/10 that at normal ebullition (neglecting the weak dependence on temperature). dalton concludes that “there is no need to suppose a chemical attraction in the case”. the independence of the saturated vapour pressure on dry air addition is the second point of interest of the essay. the general, though not universal, view about water evaporation was in the opposite sense, i.e., it was argued that the water vapour is chemically combined with air and that only at the boiling temperature, 212of, and above the vapour takes the form of an elastic fluid, called steam [5]. the only contrary opinion was from wallerius, which was able to evaporate water into a vacuum [18]. however, affinity remained a necessary factor for evaporation under open air, it was replied, since the pressure of the saturated vapour is much lower than one atmosphere at ordinary temperatures and then not sufficient to cause the escape from the liquid. in the appendix to the sixth essay, dalton reports on pressure measurements at several temperatures on water placed into the vacuum of a barometer, confirming the values taken in the presence of air. thus, vapour does not combine with air but rather “the vapour of water (and probably of most other liquids) exists at all times in the atmosphere, and is capable of bearing any known degree of cold without a total condensation and the vapour so existing is one and the same thing with steam, or vapour of the temperature of 212of or upwards. the idea, therefore, that vapour cannot exist in the open atmosphere under the temperature of 212of unless chemically combined therewith, i consider as erroneous; it has taken its rise from a supposition, that air pressing upon vapour condenses vapour equally with vapour pressing upon vapour, a supposition we have no right to assume”7. dalton concludes that “the condensation of vapour exposed to common air does not in any manner depend upon the pressure of the air”. it is fair to say that this statement is substantially, but not entirely, correct. in fact, as it may be seen in various physical chemistry textbooks [30-32] and educational papers [33], the pressure of saturated vapour in the presence of air increases with respect to that in a vacuum, the effect being related to the collisional pressing of nitrogen and oxygen molecules on the liquid inducing an additional transfer of water molecules in the gas phase [30,31]. the difference between pressures with and without air is significant only for added air at extremely high pressure while under the external pressure of 1 atm the two values are practically the same [33]. summarizing, water vapour is viewed as an independent elastic fluid and evaporation is explained in mechanical terms without invoking a chemical combination of water with atmospheric gases. maximum vapour pressure is associated with any given temperature, and water evaporates until this value is reached and no further. 3 – theory of mixed gases 7 ref. [21], p. 188. 5 the preliminary account of the theory was published in october 1801 [22] while the final expanded version is contained in the first of four experimental essays, read the same month, and printed one year later [23]. dalton recalls that it was “ascertained” in the past that atmosphere behaves as “a homogeneous fluid [all its particles are of the same kind]” and that “the elastic force of air was accurately as its density, in a given temperature [i.e., at constant temperature the air pressure is proportional to density, as required by the boyle law]”. being dalton strongly influenced by newtonian mechanics he was eager to explain the result on the basis of the newton’s mathematical principles of natural philosophy [34]. to this purpose, he takes inspiration from proposition 23, book 2 of the principles “if the density of a fluid composed of particles that are repelled from one another is as the compression, the centrifugal forces [or forces of repulsion] of the particles are inversely proportional to the distances between their centres. and conversely, particles that are repelled from one another by forces that are inversely proportional to the distances between the centres constitute an elastic fluid whose density is proportional to the compression”8. as to the nature of the elastic fluid, newton added cautiously at the end of the scholium accompanying the proposition “whether elastic fluids consist of particles that repel one another is, however, a question of physics. we have mathematically demonstrated a property of fluids consisting of particles of this sort so as to provide natural philosophers with the means with which to treat that question”9 on the authority of lavoisier, an elastic fluid was thought to be a combination of matter, or material principle, with caloric [18]. dalton conceived [4] the “ultimate atoms of bodies” as “those particles which in the gaseous state are surrounded by heat; or they are the centres or nuclei of the several small elastic globular particles”10. since the caloric around the particles was postulated to be selfrepelling [36], a plausible argument is provided for the supposed repulsion, putting apart the prudent warning from newton. dalton recalls that “the atmosphere is not a homogeneous fluid; it is constituted of several elastic fluids”, in sharp contrast with a basic principle of aristotelian physics. but for an atmosphere of this kind, the newtonian proposition is still valid? the question led him to discuss two critical points: (a) whether particles of different fluids repel each other as it happens for particles of the same fluid, and (b) why from their mixing a homogeneous fluid is formed. dalton answers by taking advantage of the static model of fluid particles, of newtonian origin [18], i.e., particles in fixed positions each with respect to any other. in this model, the pressure is due only to the repulsion between particles [19]. on expanding at a given temperature the interparticle distance increases, the repulsion weakens, and the pressure upon any particle lowers. on increasing the temperature at constant volume, the repulsion between particles increases [36] and the pressure goes up. according to dalton, when two fluids a and b are mixed four types of “affections [interactions]” may be guessed 8 ref. [34], p. 697. the proof of the direct theorem in an updated version may be found elsewhere [35]. 9 ref. [34], p. 699. 10 ref. [4], p. 27. 6 “1. the particles of one elastic fluid may repel those of another with the same force as they repel those of their own kind. 2. the particles of one may repel those of another with forces greater or less than that exerted upon those of their own kind. 3. the particles of one may possess no repulsive (or attractive) power or be perfectly inelastic with regard to the particles of another; and consequently, the mutual action of such fluids, or the action of the particles of one fluid on those of the other, will be subject to the laws of inelastic bodies. 4. the particles of one may have a chemical affinity, or attraction, for those of another.”11 dalton considers the four cases and concludes that only the third is consistent with atmospheric homogeneity. suppose, he says, that m “measures [volumes]” of a and n “measures” of b are enclosed in two boxes having a common wall, under atmospheric pressure at a given temperature. removing the wall, the total volume will be in the first three cases (n + m). as to cases 1 and 2, if the two fluids have different “specific gravities”, the lightest would rise to the upper part of the vessel, due to the weaker gravitational attraction. the two fluids will separate in layers, forming what it may be called in our terms a two-phase fluid system. the pressure on any particle would be equal to one atmosphere. no two elastic fluids behave in this way [23]. on the contrary, since in the third case the repulsion between a and b particles is absent “the two fluids, whatever their specific gravities may be, will immediately or in a short time, intimately diffused through each other, in such a manner that the density of each, considered abstractedly, will be uniform throughout; namely (calling the density of the compound, unity) that of a will be m/(n+m) and that of b = n/(n+m) …………. the pressure upon any one particle in this case will not be as the density of the compound, as before, but as the density of the particles of its own kind: that is, the pressure upon a particle of a will be equal [m/(n+m)]∙30 inches of mercury; that upon a particle of b = [n/(n+m)]∙30 inches; those pressures arising solely from particles of their own kind”12 the fourth case implies that after mixing “a union of particles ensues”. the product may be solid, liquid, or gaseous. for instance, “when muriatic acid gas [hcl] and ammoniacal gas [nh3] are mixed together in due proportion, a solid substance, muriate of ammonia [nh4cl] is formed, and the gases wholly disappear”. when a gas is formed, the most probable effect is the volume reduction together with an increase of specific gravity and temperature, for instance “when nitrous gas [no] and oxygenous gas [o2] are mixed in due proportion, the two unite and form a new elastic compound of greater specific gravity and consequently of less bulk, nitric acid gas [no2]”. no evidence of chemical affinity has been reported mixing o2 with n2 and therefore “this hypothesis fails equally with the other two”. as a result of these considerations the structures of single atmospheric gases and their mixture are illustrated in fig. 1, where “in the compound atmosphere the same arrangement is made of each kind of particles as in the simple; but the particles of different kinds do not arrange at regular distances from each other; because it is supposed they do not repel each other”. a law is stated, which is now known as dalton’s law of partial pressures: 11 ref. [23], p. 536. 12 ref. [22], p. 242-243. 7 “when two elastic fluids, denoted by a and b, are mixed together, there is no mutual repulsion amongst their particles; that is, the particles of a do not repel those of b, as they do one another. consequently, the pressure of whole weight upon any one particle arises solely from those of its own kind”13. on this basis dalton makes remarkably advanced considerations. the four components of the atmosphere considered by dalton (nitrogen, oxygen, water vapour and carbon dioxide) press on the surface of earth independently of each other so that the disappearance of any one of them does not affect the density and the pressure exerted by the others. therefore, the definition of atmosphere by lavoisier as “a compound of all the fluids which are susceptible of vaporous or permanently elastic state in the usual temperature [liquids, like water, undergoing evaporation or gases at ordinary temperatures], and under the common pressure”14 can be accepted only if the last five words are omitted. second, even if all atmospheric fluids were eliminated, except aqueous vapour, little effect would result on the water evaporation, the only important factor being the pressure of saturated vapour at the given temperature. this was a strong argument against the prevailing idea that water was in liquid form at room temperature because of the atmospheric pressure on its surface. fig. 1 – dalton original plate [23] of simple (“aqueous vapour, oxygenous, azotic, carbonic acid gases”, upper) and mixed (“compound”, lower) atmospheres. a – studies on gas diffusion and solubility in water under pressure 13 ref. [23], p. 536. 14 a. lavoisier, traité de chimie, 1789, i, p. 31. 8 two experiments support the theory of mixed gases [37,38]. in the first [37] (read january 28𝑡ℎ, 1803, published in 1805) the gas diffusion is investigated: two gases are enclosed in two phials connected by a narrow vertical tube with the heavier in the lower phial. such a simple set-up was kept “in the state of rest” as much as possible and the capillary tube, ten inches long, was “not instrumental in propagating an intermixture from a momentary commotion at the commencement of each experiment”. although priestley had already shown that elastic fluids of different specific gravities do not separate in layers, with the heaviest in the lowest place [39], he nevertheless hypothesized that “if two kinds of air, of very different specific gravities, were put into the same vessel, with very great care, without the least agitation that might mix or blend them together, they might continue separate, as with the same care wine and water may be made to do”15. dalton was aware that the outcome of his experiment, “which seems at first view but a trivial one, is of considerable importance; as from it we may obtain a striking trait, either of the agreement or disagreement of elastic and inelastic fluids in their mutual action on each other”, i.e., may corroborate or not the theory of mixed gases. obviously, in the long run, all pairs of gases mix uniformly, co2 (“carbonic acid gas”, lower phial) with air, h2, n2 and no (“nitrous gas”) and h2 (upper phial) with air and o2, thus establishing “the remarkable fact that a lighter elastic fluid cannot rest upon a heavier”. the second experiment is concerned with gas dissolved in water under pressure. the study reports on what is now known as henry’s law [38]. it is in our opinion worth outlining the experimental apparatus, as an example of the chemical expertise of dalton’s times. as shown in fig. 2, the two legs (a and b) of a syphon tube, a being a small, graduated bottle and b an ordinary glass tube open to the atmosphere, are filled with mercury up to the complete replenishment of a and rise at the corresponding level in b. a given quantity of water and a volume of gas may be poured into the bottle through the stopcock a when the stopcock b situated between the two legs is opened to allow mercury to run out. then, with a closed the level of mercury in both legs is adjusted to the same height so that the gas is under atmospheric pressure. let us suppose now to add mercury in b to form a column 76 cm higher than the a level. the gas inside the bottle is compressed to two atmospheres and its volume is found to be half that previously occupied. the bottle is vigorously agitated, the absorption of gas takes place and the level of mercury in the bottle rises. to reestablish the pressure difference between a and b it is necessary to add mercury in b: in these conditions, the gas pressure is again two atmospheres and the volume of gas absorbed by water is exactly equal to the mercury added in the last step. with this apparatus henry determined the solubility of gases such as “carbonic acid”, “sulphuretted hydrogen [𝐻2𝑆]”, “nitrous oxide [𝑁2𝑂]”, “oxygenous and azotic gases” in water up to three atmospheres. the most significant result was that “under equal circumstances of temperature water takes up in all cases the same volume of condensed gas as of gas under ordinary pressure”. to exemplify, if a given quantity of water absorbs 10 ml of a gas at p = 1 atm, it will absorb 10 ml of the same gas at p = 2 atm. but the volume absorbed at p = 2 atm, if expanded to p = 1 atm, would be double that absorbed at p = 1 atm, or in more general terms “water takes up of gas condensed by one, two, or more additional atmospheres, a quantity which, ordinarily compressed, would be equal to twice, thrice, etc. the volume absorbed under the common pressure of the atmosphere”16 15 cited in ref. [37], p. 260. 16 ref. [38], p. 42. 9 then, the weight of the gas dissolved at p = 2 atm will be double that at 1 atm and the law takes the more familiar enunciation that the absorbed gas weight is proportional to the incumbent gas pressure [19]. dalton realized that this behaviour could not be explained in terms of chemical combination of dissolved gas with water, given that the gas is kept in water only due to the gas pressure. this point is clearly attested by henry in the appendix [40] of the paper with the following words “the theory which mr. dalton has suggested to me on this subject, and which appears to be confirmed by my experiments, is, that the absorption of gases by water is purely a mechanical effect, and that its amount is exactly proportional to the density of the gas, considered abstractedly from any other gas with which it may accidentally be mixed”17. fig. 2 – solubility of gases in water: henry’s experimental apparatus for measurements under pressure from ref. [38]. the larger vessel a was used with “less condensible gases”. 17 ref. [40], p. 274. 10 b – theory of mixed gases: historical perspective and limits after having reviewed the theory of mixed gases, we feel appropriate to refer shortly to the underlying topic, i.e., forces acting between “ultimate particles”, and specifically on the theory proposed by the mathematician and astronomer roger boscovich [41]. then, we will make a few general comments on the dalton theory. let us start by saying that in the 18th century matter was considered to consist of discrete particles or “corpuscles” supposed to be stationary, namely motionless and not colliding [35]. the concept of potential energy was unknown, and the physical world was described in terms of mechanical forces between particles [35]. of great interest for the originality of the model was the boscovich theory of oscillatory force. at the planetary and interstellar scale, the gravitational force of attraction, depending on distance as 1 𝑟2 , dominates. as 𝑟 recedes, the force is increasingly negative and particles accelerate when approaching each other but at sufficiently short distances, to account for the fact that matter cannot disappear into itself, particles must slow down and then, as 𝑟 decreases, a repulsive force is supposed to emerge leading first to the inversion of the force from negative to positive and for 𝑟 → 0 to a repulsion force arbitrarily high. if these two forces were the only ones in action, a single homogeneous solid would result at equilibrium, i.e., at the inversion point. boscovich assumed that between the two extremes, 𝑟 = 0 and 𝑟 → ∞, additional inversion points occur so that the force oscillates alternatively, depending on the experimental conditions [42]. for instance, the caloric fluid, capable of flowing in and out of all matter, was known to be self-repulsive and then responsible for the repulsion force suggested by the boyle law. the point at which the gravitational and caloric forces are equal constitutes a second inversion point which determines the static equilibrium in gases. in summary, starting from exceedingly small distances the force oscillates from highly repulsive to attractive (in solids) to repulsive (in gases) and again to attractive at exceptionally large distances. going to the second point, it has been wisely noted [18] that the subject of mixed gases can be correctly treated only after admitting that the particles are in motion and not rigidly located at fixed positions. in the absence of the kinetic theory of gases18 and not resorting to the thermodynamic notion of entropic increase to justify why elastic fluids of whatever density occupy all the available volume, dalton ascribed to the supposed repulsion between particles the tendency of gases to expand in the whole space. now we know that gaseous particles weakly attract each other, as it was established by the van der waals equation for non-ideal gas, but only seventy years later. thus, a gas must be rather regarded as composed of particles in motion exerting weak attraction forces on each other. all these considerations give evidence of the extraordinary degree of ingenuity of dalton who, though lacking essential theoretical instruments, arrived at the law of partial pressures by taking only advantage of a bold ad hoc hypothesis, “every gas is a vacuum to every other gas”, as expressed concisely and brilliantly by henry [44]. 4 – stepping into the chemical atomic theory as already noted in the introduction, the narratives concerning the origin of dalton’s atomic theory go back to dalton himself [1,2,4]. in later years they were critically reviewed, and alternative 18 it should be however recalled that the concept of particle motion was at the centre of the bernoulli equation obtained in 1738 [43], 𝑝𝑉 = (1 3⁄ ) 𝑛𝑚𝑣2 , where 𝑝 is the pressure defined as the force 𝑓, due to the collisions in unit time on the container wall, over its area 𝐴, 𝑛 the number of particles, each of mass 𝑚 and mean velocity 𝑣. 11 explanations were proposed [5,8-10,12,13]. in this section, we approach the atomic theory taking into consideration the two basic papers [24,25] upon which the theory is founded with the essential support of the dalton laboratory notebook [4]. a – experimental enquiry into the proportion of the several gases or elastic fluids, constituting the atmosphere [24] the essay under heading was read at the meeting of the literary and philosophical society of manchester on november 12𝑡ℎ, 1802; the publication was delayed until november 1805. starting from the consideration, based on the theory of mixed gases, that the pressure of a fluid is the same as a single component or in a mixed state, depending only on density and temperature, dalton determines (i) the pressure of each “simple atmosphere” in the “compound atmosphere” and then the volume percent of each gas, (ii) the weight percent in a given volume and (iii) the dependence of these properties upon the height above the earth’s surface. the gases under examination are “azotic, oxygenous, aqueous vapour, and carbonic acid”, which were detected in any atmospheric region by means of the analytical methods known at his time. beginning with (i), the reactions for oxygen detection were carried out over water and “if it should appear that by extracting the oxygenous gas from any mass of the atmospheric air, the whole was diminished 1 5 in bulk, still being subject to a pressure of 30 inches of mercury [one atmosphere]; then it ought to be inferred that the oxygenous atmosphere presses the earth with a force of 6 inches of mercury”19. the reagents were “nitrous gas [𝑁𝑂]”, “liquid sulphuret of potash and lime [water solutions of 𝐾2𝑆 and 𝐶𝑎𝑆, the reaction being 2𝐻𝑆 − + 𝑂2 → 2𝑆 + 2𝑂𝐻 −]”, “hydrogen gas [2𝐻2 + 𝑂2 → 2𝐻2𝑂]” and “burning phosphorous [𝑃4 + 5𝑂2 → 2𝑃2𝑂5]”. dalton reports volumetric estimates of air reduction only for the first and third reaction, specifying that when all these reactions are conducted “skilfully” no difference between results occurs. for instance, by firing 60 “measures” of hydrogen with 100 of common air, the final volume is again 100 with complete oxygen disappearance. from these data he found that the oxygen volume is 21 “measures” and then the oxygen pressure 6.3 inches. we may suppose that the calculation was done along the following lines (in present-day notation) (𝑎) 𝑉𝐴 + 𝑉𝑂2 = 100 (𝑏) 𝑉𝐻2,𝑟 + 𝑉𝐻2,𝑢𝑛𝑟 = 60 (𝑐) 𝑉𝐻2,𝑟 𝑉𝑂2 = 1.85 (𝑑) 𝑉𝐴 + 𝑉𝐻2,𝑢𝑛𝑟 = 100 where 𝑉𝐴 is the volume of all gases in common air except oxygen and 𝑉𝐻2,𝑟, 𝑉𝐻2,𝑢𝑛𝑟 the reacted and unreacted parts of the total hydrogen volume. the ratio (𝑐) is the value measured by dalton [24], 1.85, (the theoretical value 2 was unknown). solving for 𝑉𝑂2 he obtained 𝑉𝑂2 = 21. the “nitrous air test” greater attention must be deserved to the oxygen detection with 𝑁𝑂. after the discovery by hales pouring nitric acid on walton pyrites [45] the reaction was studied in detail by priestley in 1772 [46]. since then, many chemical investigators (including dalton) used this reaction to estimate the purity or “goodness” of air. priestley found that combining any kind of metals then known (except zinc) 19 ref. [24], p. 246. 12 with “spirit of nitre [nitric acid]” an “air”, that he called “nitrous air”, evolved forming deep “red fumes” in the presence of common air. in actual terms the reaction is 2𝑁𝑂 + 𝑂2 → 2𝑁𝑂2 “nitrous air” “red fumes” and since 𝑁𝑂2 is easily dissolved in water (while 𝑁𝑂 is not) it follows that, if correctly chosen volumes of 𝑁𝑂 and 𝑂2 are mixed over water, all gases disappear. starting with common air priestley always found a large amount of residual gas, which turned out to be the smallest when two volumes of common air were mixed with one of 𝑁𝑂. in this case, the residue was about 1.8 volumes and the remarkably high contraction of 1.2 volumes corresponded to the volume of added 𝑁𝑂 plus 20%. the degree of volume reduction was then ~ 1 3 . he noted with satisfaction that this contraction “is peculiar to common air or air fit for respiration; and …. very nearly, if not exactly, in proportion to its fitness for this purpose; so that by this means the goodness of air may be distinguished much more accurately than it can be done by putting mice or other animals, to breathe in it ….. a most agreeable discovery to me”20. on the contrary, no reaction with 𝑁𝑂 was observed for air “unfit for respiration” such as fixed air (𝐶𝑂2) or inflammable air (𝐻2) so that their “goodness” is zero. intermediate degrees of reduction between zero (no reaction) to ~ 1 3 (reaction of 1 volume of 𝑁𝑂 and 2 volumes of common air) represent intermediate degrees of “goodness”. priestley proudly stated that “we are in possession of a prodigiously large scale [i.e., 0 − 1 3 ] by which we may distinguish very small degrees of difference in the goodness of air”. going now back to the dalton paper, he found that the reacting volumes were strongly dependent on the experimental conditions. in fact, after preparing “nitrous gas” adding the water solution of nitric acid to copper or mercury (point 1), he says in the successive points “2. if 100 measures of common air be put to 36 of pure nitrous gas in a tube 3 10 of an inch wide and 5 inches long, after a few minutes the whole will be reduced to 79 or 80 measures and exhibit no signs of either oxygenous or nitrous gas. 3. if 100 measures of common air be admitted to 72 of nitrous gas in a wide vessel over water, such as to form a thin stratum of air, and an immediate momentary agitation be used, there will, as before, be found 79 or 80 measures of pure azotic gas for a residuum. 4. if, in the last experiment, less than 72 measures of nitrous gas be used, there will be a residuum containing oxygenous gas; if more, then some residuary nitrous gas will be found”21 20ref. [46], p. 114, bold letters, our addition. 21ref. [24], p. 249. 13 these data indicate that a given volume of oxygen (making part of the common air) reacts with another of 𝑁𝑂 or its double. this implies the law of multiple proportions. the conclusion is expressed by dalton with the following significant words “these facts clearly point out the theory of the process: the elements of oxygen may combine with a certain portion of nitrous gas, or with twice that portion, but with no intermediate quantity. in the former case nitric acid [2𝑁𝑂 + 𝑂2 → 2𝑁𝑂2] is the result; in the latter nitrous acid [4𝑁𝑂 + 𝑂2 → 2𝑁2𝑂3]: but as both these may be formed at the same time, one part of the oxygen going to one of nitrous gas, and another to two, the quantity of nitrous gas absorbed should be variable; from 36 to 72 per cent for common air…. in fact, all the gradation in quantity of nitrous gas from 36 to 72 may actually be observed with atmospheric air of the same purity; the wider the tube or vessel the mixture is made in, the quicker the combination is effected, and the more exposed to water, the greater is the quantity of nitrous acid and the less of nitric that is formed”22. there has been much debate among science historians about when dalton obtained the results of points 2 and 3. these, if presented at the reading date, november 12𝑡ℎ, 1802, would mean that the law of multiple proportions was discovered long before the proposal of the atomic theory (which is, as it is well known [4], september 6𝑡ℎ, 1803). the dalton notebook [4], from november 1802, the date of the earliest records on his laboratory activity, until the end of 1803, supports the idea that both the experimental results and the discussion were made at a time later than november 1802. for instance, dalton writes, march 21𝑠𝑡 , 1803, “nitrous gas – 1.7 or 2.7 may be combined with oxygen, it is presumed”23. second, on april 1𝑠𝑡 , 1803, several experiments are listed on “nitrous gas” and common air in relation to the higher absorption of the reactant when the mixture is rapidly formed but the record ends with the doubtful question “query, is not nitrous air decomposed by the rapid mixture?”. at that date, six months after november 1802, dalton had not reached the well-defined conclusions expressed in the paper [4]. the discrepancy between presentation and publication has been explained [4] by the fact that dalton, as secretary of the manchester literary and philosophical society since 1800, had many opportunities to revise the work according to his latest findings. further, the numbers quoted in points 2 and 3 of the paper were written in the notebook at an undetermined date between october 10𝑡ℎ and november 13𝑡ℎ, 1803, more than one month after the first appearance of the atomic weight table [4]. however, dalton in some experiments before september 1803 had noticed a simple ratio for the volumes of “nitrous gas” reacting with a given volume of oxygen. the notebook reports, august 4𝑡ℎ, 1803, that “it appears, too, that a very rapid mixture of equal parts com. air and nitrous gas, gives 112 or 120 residuum. consequently, that oxygen joins to nit. gas sometimes 1.7 to 1 and at other times 3.4 to 1 [the theoretical ratios, unknown to dalton, for the formation of nitric and nitrous acid, are 2: 1 and 4: 1, respectively]”24. this extract paved the way for the proposal [5] that dalton, 22ref. [24], p. 250. 23 ref. [4], p. 34. the two ratios, 1.7: 1 and 2.7: 1, are narrow tube and wide vessel values, respectively. 24 ref. [4], p. 38. a possible justification of the second ratio, 3.4: 1, may be derived as follows. the three equations to be considered are (a) 𝑉𝐴 + 𝑉𝑂2 = 100; (b) 𝑉𝑁𝑂,𝑟 + 𝑉𝑁𝑂,𝑢𝑛𝑟 = 100; (c) 𝑉𝐴 + 𝑉𝑁𝑂,𝑢𝑛𝑟 = 112, where 𝐴 denotes, as usual, all atmospheric gases except oxygen and 𝑉𝑁𝑂,𝑟 and 𝑉𝑁𝑂,𝑢𝑛𝑟 are the reacting and excess volumes of 𝑁𝑂. taking from previous experiments as a reasonable approximation of the oxygen volume 𝑉𝑂2 = 20 we have 𝑉𝑁𝑂,𝑢𝑛𝑟 = 32; 𝑉𝑁𝑂,𝑟 = 68 and then 𝑉𝑁𝑂,𝑟 𝑉𝑂2 = 3.4. the same calculation with 120 residuum gives 𝑉𝑁𝑂,𝑟 𝑉𝑂2 = 3. 14 pondering about the significance of the 2: 1 ratio of the reacted “nitrous gas” under different conditions, made the bold generalization, going from the particular 𝑁𝑂 reaction to the law of multiple proportions and then to the chemical atomic theory, which would have appeared within one month. in other words, here the suggestion is that the atomic theory was derived from the law of multiple proportions [5]. this view has been subject in the following years to a strong criticism emphasizing the experimental difficulties to replicate these ratios even when the reaction was carried out with the updated instrumentation available to researchers more than one century later [7,8]. for instance, it has been pointed out that, out of many reaction trials personally performed, few of them gave a ratio reasonably approximating 3.4: 1, the most difficult to replicate [8]. but, in contrast, a successful reconstruction of the experiment has been recently reported, where the narrow tube value, 1.7: 1, has been confirmed and the 3.4: 1 ratio justified observing that gas-phase and dissolved oxygen in the wide water vessel are involved when 𝑁𝑂 is in excess with respect to 𝑂2 [12]. it has been added [12] that if the reaction is complete, i.e., in the presence of a sufficient amount of water, all excess 𝑁𝑂 is consumed and any 𝑁𝑂/𝑂2 ratio greater than 2: 1 may be obtained; then dalton carried out the reaction optimizing the experimental conditions to achieve the desired result, as it is evident comparing the notebook entries of march 12th and august 4th. thus, the plausible conclusion was that dalton discovered the first example of the law of multiple proportions having already in mind the implications of the atomic theory [12]. for completeness, it remains to report on the other points discussed in the paper. the pressures of water vapour and “carbonic acid” [𝐶𝑂2] in the atmosphere were determined by means of the analytical methods known at that time. dalton took advantage of the pressure diagram of saturated water vapour with temperature, already determined by himself and reported in meteorological observations and essays. it was enough to measure the dewpoint temperature of the vapour: the pressure of this vapour in the atmosphere coincides with that of the saturated vapour at dewpoint temperature25. then, dalton analyzed the amount of 𝐶𝑂2 by adding “lime-water” [saturated water solution of 𝐶𝑎(𝑂𝐻)2] to precipitate atmospheric 𝐶𝑂2 contained in a bottle with a capacity of “102400 grains of rain water [≈ 7𝐿]”. he found that “102400 grains measures of common air contain 70 of carbonic acid”. going to point (ii) of the paper, dalton, using densities from lavoisier and kirwan (𝑁2 and 𝐶𝑂2), davy (𝑂2) and himself (𝐻2𝑂 vapour), arrived at the gravimetric percent composition of the air from volumetric data. pressure (in “inches of mercury”) and percent of each component resulted to be: “azotic gas” 23.36, 75.55%; “oxygenous gas” 6.18, 23.32%; “aqueous vapour” 0.44, 1.03%; “carbonic acid gas” 0.02, 0.10%. as to point (iii), it was found that at higher altitudes the atmospheric oxygen decreases with respect to the other gases but only slightly. from this dalton concluded that “at any ordinary heights the difference in the proportions will be scarcely if at all perceptible”. b – on the absorption of gases by water and other liquids [25] 25 dalton had already given the definition of dewpoint in the following terms [47]:“whatever quantity of aqueous vapour may exist in the atmosphere at any time, a certain temperature may be found, below which a portion of that vapour would unavoidably fall or be deposited in the form of rain or dew, but above which no such diminution could take place, chemical agency apart. this point may be called the extreme temperature [i.e., dewpoint] of vapour of that density. whenever any body colder than the extreme temperature of the existing vapour is situated in the atmosphere, dew is deposited upon it”. 15 this paper was read in front of a selected audience of nine members and friends at the meeting of the literary and philosophical society of manchester held on october 21𝑠𝑡 , 1803 and printed on the manchester memoirs of the society in november 1805, following the paper of the previous subsection. the experiments on gas solubilities in water were prompted by henry’s studies in this field and represent a big part of dalton’s work in the last months of 1802, from january to march 1803 and in august of the same year [4]. both men interpreted the results as being due to a mechanical, rather than to a chemical effect, arising only from the pressure of the absorbed gas and independent of the presence of any other gas [40]. fifteen experiments, numbered as “articles” in the paper, are presented, the most significant being undoubtedly the second: “if a quantity of water thus freed from air be agitated in any kind of gas, not chemically uniting with water, it will absorb its bulk of the gas [co2, h2s, n2o], or otherwise a part of it equal to some one of the following fractions, namely, 1 8 [c2h4], 1 27 [o2, no, ch4], 1 64 [h2, n2, co], &c. these being the cubes of the reciprocals of the natural numbers 1, 2, 3, &c. or 1 13 , 1 23 , 1 33 , 1 43 , &c. the same gas always being absorbed in the same proportion ……………: – it must be understood that the quantity of gas is to be measured at the pressure and temperature with which the impregnation [saturation] is effected.”26 it has been noted [8] that dalton often indulged in the search of simple mathematical relations even in the presence of experimental values affected by a large error such as those relative to solubility measurements of the period january – march 1803 [4]. the difficulties encountered in data acquisition are evident in this long paragraph of the paper: “in my experiments with the less absorbable gases, or those of the 2d, 3d, and 4th classes, i used a phial holding 2700 grains of water, having a very accurately ground-stopper; in those with the more absorbable of the first class, i used an eudiometer tube properly graduated and of aperture so as to be covered with the end of a finger……… [which] was applied to the end and the water within agitated; then removing the finger for a moment under water, an additional quantity of water entered, and the agitation was repeated till no more water would enter, when the quantity and quality of the residuary gas was examined. in fact, water could never be made to take its bulk of any gas by this procedure; but if it took 9 10 , or any other part, and the residuary gas was 9 10 pure, then it was inferred that water would take its bulk of that gas. the principle was the same in using the phial; only a small quantity of the gas was admitted, and the agitation was longer”27. but by march 6𝑡ℎ, 1803, he trusted data on hydrogen, nitrogen and oxygen [4] since “it now appears more than probable that in all cases hydrogen and azotic gases in water have their particles 4 times the distance that they have incumbent = 1 64 or 1.5625 per cent, and oxygen gas 3 times = 1 27 density = 3.7 [per cent]”. to our opinion, much of the credit for the better-defined relation of solubilities to inverse cubes of natural numbers belongs to the more reliable henry data [39], as dalton fairly acknowledges with these words: “by the reciprocal communication [between dalton and henry] 26 ref. [25], p. 271. 27 ref. [25], p. 280. 16 since, we have been enabled to bring the results of our experiments to a near agreement; as the quantity he has given in his appendix to that paper nearly accord with those i have stated in the second article”. on october 21st, 1803, dalton had sound data for the three gases (and for “carbonic acid” and “nitrous oxide [𝑁2𝑂]” [4,8]). the data relative to “carburetted hydrogen” and (probably) “olefiant gas” were obtained at a later date [4,8,18]. dalton explains the solubility of gases in water in “mechanical” terms saying that “all gases that enter into water and other liquids by means of pressure, and are wholly disengaged again by the removal of that pressure, are mechanically mixed with liquids, and not chemically combined w ith it”28. as already outlined in the past section, the gaseous particles were thought to form an array of hard-packed spheres repelling each other both in water and out of it; further, the gas was retained in water only by the pressure of particles of the same kind and “water has no other influence in this respect than a mere vacuum”. dalton asks in the notebook [4]: “is it not two atmospheres pressing one against the other?” of which one is the “atmosphere” of the gas pressing on water and the other the hypothetical “atmosphere” of the dissolved gas. the two “atmospheres” have different densities and the ratio is given by the reciprocal of cubes of natural numbers. for instance, oxygen in water is less dense than out by 1 33 = 1 27 ; the same ratio for nitrogen is 1 43 = 1 64 . thus, the distance between adjacent dissolved particles is a multiple of the distance in the atmosphere, “in oxygenous gas, &c. the distance is just three times as great within as without; and in azotic, &c. it is four times.”29. some drawings are attached to the paper, to make more explicit dalton’s physical theory of gas absorption. in “view of a square pile of shot”, fig. 3, squares of packed spheres (white, water particles) are pressed by the upper sphere (black, a gas particle) and the pressure is distributed among the water particles, first on 4, then from 4 to 9, from 9 to 16, etc., until the next lower particle of absorbed gas is reached. since in fig. 3 the ratio of the distance between gas particles and between water particles is supposed to be 10: 1 the final pressure is distributed among 100 water particles and “[since] in the same stratum each square of 100 [has] its incumbent particle of gas, the water below this stratum is uniformly pressed by the gas, and consequently has not its equilibrium disturbed by that pressure”30. 28 ref. [25], p. 283. 29 ref. [25], p. 281. 30 ref. [25], p. 284. 17 fig. 3 – a particle of gas (black sphere) pressing particles of water (white spheres), from ref. [25]. in “profile view of air in water”, fig. 4, right, the oxygen dissolved in water is considered. its pressure amounts to 1 27 of the incumbent pressure and, as dalton points out, this pressure is exerted on the container walls and on the gas above the water, not on water. at equilibrium, atmospheric oxygen presses the dissolved portion by the same pressure, 1 27 , and the remaining, 26 27 , is the pressure of the gas on the water’s surface. there is repulsion between the two strata of oxygen just adjacent to this surface, though much smaller, 1 27 , than between particles in the atmosphere. being the repulsion inversely proportional to the distance, this means that the two strata must be apart 27 times the distance of particles in the atmosphere. applying the same line of reasoning to 𝑁2 and 𝐻2, the distance between the two strata increases to 64 times, as seen in fig. 4, left. fig. 4 – the gas profile along the vertical axis, from ref. [25]: left, 𝑁2 and 𝐻2; right, 𝑂2, 𝑁𝑂 and 𝐶𝐻4. in the concluding paragraph of the paper, the big difficulty arises in the application of the hard spheres model to the solubility data of gases. the model cannot explain the intriguing result of his (and henry’s) experiments: why different gases dissolve differently in water? it has been suggested [8] that dalton answered this question by invoking the correlation between solubility and density data. 18 on september 19𝑡ℎ, 1803, the specific gravities of several gases (with respect to air) are reported in the laboratory notebook, including those of the first and last group of the table, i.e., hydrogen (0.077), nitrogen (0.966), “carbonic acid [𝐶𝑂2]” (1.500), “nitrous oxide [𝑁2𝑂]” (1.610). taking into consideration only the gases on which solubility data were known at the reading date, the indication is clear: elementary and low-density gases are scarcely soluble in water while compound and highdensity gases are appreciably soluble. given this premise, to the question “why does water not admit its bulk of every kind of gas alike?” dalton was enabled to answer with great ingenuity (bolds are our additions) “the circumstance depends on the weight and number of the ultimate particles of the several gases: those whose particles are lightest and single being least absorbable and the others more according as they increase in weight and complexity”31. dalton had in mind weight and complexity of the “ultimate particles”, thus initiating the transition from a physical to a chemical atomic theory. the correlation of solubility with density led to a research project described in these terms “an enquiry into the relative weights of the ultimate particles of bodies is a subject, as far as i know, entirely new: i have lately been prosecuting this enquiry with remarkable success.” thus, the paper ends with the result of this enquiry, a long table (see fig. 5) containing “the relative weights of the ultimate particles of gaseous and other bodies”. how this table was obtained by dalton and on which criteria was based in order to get to the particles’ weights is the subject of the next section. fig. 5 – the table of relative weights of “ultimate particles” of elements and compounds from ref. [25]. 5 – dalton’s chemical atomism 31 ref. [25], p. 286. in the footnote, dalton adds: “subsequent experience renders this conjecture less probable”. 19 in his laboratory notebook, september 6𝑡ℎ, 1803, dalton wrote notes bound to become a milestone in the history of chemistry [4]. the earliest set of “characters [chemical symbols]” was drawn to represent the “ultimate particles” of the elements and to give an unequivocal description of their combination in a compound. in agreement with his idea of atoms, dalton’s “characters” are circles with a distinguishable inner part; the initial choice for hydrogen and oxygen (open and dotted circle, respectively) were interchanged in later tables. the original page 244, taken from ref. [4], is shown in fig. 6. page 248, shown in fig. 7, contains the first table of (relative) atomic weights, two years before that of fig. 5. the numerical values could have been easily established from the relative gas densities if dalton had been willing to accept what is now known as the avogadro’s principle. for instance, from the densities reported in the notebook32, the oxygen and nitrogen weights would have been found to be 14.6 and 12.5, respectively, that of hydrogen. but this hypothesis was rejected since the very first conception of the atomic theory with the following words 32 see ref. [4], p. 41. 20 “though it is probable that the specific gravities of different elastic fluids have some relation to that of the ultimate particles, yet it is certain that they are not the same thing; for the ult. part. of water or steam are certainly of greater specific gravity than those of oxygen, yet the last gas is heavier than steam”33. it is plain, dalton says, that, if the “ultimate particle” of water is composed by those of oxygen and hydrogen, it must be heavier than that of oxygen. then, being experimentally observed that the water vapour is less dense than oxygen, this necessarily means that in equal volumes fewer particles of water vapour are contained than of oxygen. this was not a unique example since from the same table (see footnote 32) it is seen that ammonia, formed by nitrogen and hydrogen, is less dense than nitrogen, and carbon oxide, formed by oxygen and carbon, is equally less dense than oxygen. it would be difficult to avoid the conclusion that different numbers of particles were in the same volume of several gases [48]. fig. 7 – the first table of the relative weights of elements and compounds from the original in ref. [4]. it is written on page 248: “ ult. at. hydrogen 1 33 ref. [4], p. 27. the rebuttal of avogadro’s hypothesis was justified by dalton also on a different basis in a new system of chemical philosophy, p. 71: “it is evident the number of ultimate particles or molecules in a given weight or volume of one gas is not the same as in another: for, if equal measures of azotic and oxygenous gases were mixed, and could be instantly united chemically, they would form nearly two measures of nitrous gas, having the same weight as the two original measures; but the number of ultimate particle could at most be one half of that before the union. no two elastic fluids, probably, therefore, have the same number of particles, either in the same volume or the same weight”. the apparently impeccable argument of dalton runs as follows: starting from 𝑛 “ultimate particles” of nitrogen and 𝑛 of oxygen in equal volumes 𝑉, “nitrous gas” is obtained in the volume 2𝑉. since the particles of “nitrous gas” cannot be more than 𝑛, this means that 𝑛 2 particles of “nitrous gas” are in the volume 𝑉. 21 ------ oxygen 5.66 ------ azot 4 ------ carbon (charcoal) 4.5 ------ water 6.66 ------ ammonia 5 ------ nitrous gas 9.66 ------ nitrous oxide 13.66 ------ nitric acid 15.32 ------ sulphur 17 ------ sulphureous acid 22.66 ------ sulphuric acid 28.32 ------ carbonic acid 15.8 ------ oxide of carbone 10.2” ____________________________________________________________ excluding the information from physical data, dalton made use of chemical data for the derivation of atomic weights. in simple words, the question was: being known from the lavoisier analysis that the oxygen weight content of water is 85% (and hydrogen 15%), is it possible to determine the weight of an oxygen atom (with respect to hydrogen)? the entries of fig. 7 contain the dalton answer not only for oxygen (5.66) but also for three other elements (nitrogen, carbon, and sulphur, 4, 4.5 and 17, respectively), however without any detailed explanation of the computational procedure to arrive at these values. it has been said [8,18] that all calculations, implicitly or explicitly, are based on the following principles: (i) matter is constituted of extremely minute particles (atoms), (ii) atoms are indivisible and cannot be created or destroyed, (iii) atoms of a given element are identical and have the same invariable weight, (iv) atoms of different elements have different weights, (v) the particle of a compound is formed by a fixed number of atoms of its component elements (law of definite proportions) and its weight is the sum of the weights of the constituent atoms, (vi) if more than one compound of two elements is known, the numbers of atoms of either element in the compound particle are in the ratio of whole (small) numbers (law of multiple proportions). given a binary compound of 𝐴 and 𝐵 composed of particles with 𝑛 atoms of 𝐴 and 𝑚 of 𝐵, i.e., 𝐴𝑛 𝐵𝑚, and the weight percent, (%)𝐴 and (%)𝐵 , in the compound, the atomic weight of 𝐵 with respect to 𝐴, 𝑝𝐵 𝑝𝐴 , results 𝑝𝐵 𝑝𝐴 = 𝑛 𝑚 ∙ (%)𝐵 (%)𝐴 . to determine 𝑝𝐵 𝑝𝐴 , it is then necessary to know not only the percent composition of each element in the compound but also the number of 𝐴 and 𝐵 atoms entering the particle. if this latter information is missing but it happens that only one compound of 𝐴 and 𝐵 is formed, dalton adopted the “rule of greatest simplicity”; he reasonably assumed that the compound is 𝐴𝐵, 𝑛 = 𝑚 = 1, unless there is some reason to the contrary. the water particle was taken to be 𝑂𝐻 and therefore 𝑝𝑂 𝑝𝐻 = 0.85 0.15 = 5.66. being not known any other compound of nitrogen and hydrogen in addition to ammonia, which in an old austin analysis was reported to be composed by about 80% nitrogen and 20% hydrogen, dalton found 𝑝𝑁 𝑝𝐻 = 0.80 0.20 = 4 with the ammonia particle expressed as 𝑁𝐻. the atomic weight of carbon, 𝑝𝐶 𝑝𝐻 = 4.5, was determined from the lavoisier analysis of the “carbonic acid” gas, 72% oxygen and 28% carbon. since two gases, “carbonic acid” and “oxide of carbone”, are composed by the same elements, carbon and oxygen, the specification of the “ultimate particles” requires an additional proviso. the extended version of the “rule of greatest simplicity” dictates that in this case one particle is 𝐶𝑂 and the other 𝐶𝑂2 or 𝐶2𝑂 34. dalton correctly opted for 𝐶𝑂2, as to 34dalton in later years justified this rule starting from the newtonian proposition 23 [49] with the following speculation about the atomic architecture of the 𝐴𝐵𝑛 particles: “when an element 𝐴 has affinity for another, 𝐵, i see no mechanical 22 “carbonic acid”, and for 𝐶𝑂 in the case of “oxide of carbone”, using probably as a clue the relative gas densities (see footnote 32). with this assignment he calculated 𝑝𝐶 𝑝𝐻 = ( 𝑝𝐶 𝑝𝑂 ∙ 2 1 ) ∙ 𝑝𝑂 𝑝𝐻 = ( 0.28 0.72 ∙ 2) ∙ 5.66 = 4.4 (in the table of fig. 7 the entry 4.5 is either a miscalculation or a “rounded off” value [4]). in the same table the reported weights of the “ultimate atoms” of the two gases are 15.8 (𝐶𝑂2) and 10.2 (𝐶𝑂). as to the atom of sulphur, two sets of data were available for the “sulphuric acid” gas, one from chenevix (61.5% sulphur; 38.5% oxygen) and the other from thenard (56% sulphur; 44% oxygen). as for the pair 𝐶𝑂/𝐶𝑂2 , the particles of “sulphureous acid” and “sulphuric acid”, not breaking with the “rule of greatest simplicity”, were taken to be (incorrectly) 𝑆𝑂 and 𝑆𝑂2. “sulphuric acid” was assumed to be 𝑆𝑂2, the choice being presumably based again on the densities of the two gases (see footnote 32). the atomic weight of sulfur was calculated from the expression 𝑝𝑆 𝑝𝐻 = 𝑝𝑆 𝑝𝑂 ∙ 𝑝𝑂 𝑝𝐻 , which gives 18.1 and 14.4 depending on the set of data, averaged to 17. the weights of 𝑆𝑂 and 𝑆𝑂2 are 22.66 and 28.32 (see fig. 7)35. the last three entries of the table refer to “nitrous gas”, “nitrous oxide” and “nitric acid”. according to the “rule of greatest simplicity” and given the relative gas densities (see footnote 32) they were formulated as 𝑁𝑂, 𝑁2𝑂 and 𝑁𝑂2. the assignment is correct for the first two gases. as to the third, since dalton accepted the composition proposed by lavoisier for nitric acid [18], the weight was calculated 4 + 2 ∙ 5.66 = 15.32, corresponding to 𝑁𝑂2. in addition, since the atomic weight of an element does not vary from a compound to another, as a second point of interest in these gases dalton observes that “from the composition of water [oh] and ammonia [nh] we may deduce ult. at. azot 1 to oxygen 1.42 [i.e., 𝑝𝑂 𝑝𝑁 = 𝑝𝑂 𝑝𝐻 ∙ 𝑝𝐻 𝑝𝑁 = 5.66 4 = 1.42]” so that the “ult. atom of nit. gas [𝑁𝑂] should therefore weigh 2.42 azot [i.e., 𝑝𝑁𝑂 = 2.42𝑝𝑁]” 36. the law of equivalent proportions says that the ratio 𝑟 of the weight of oxygen to that of nitrogen in the three oxides is either equal to 1.42 or a simple multiple or fraction of 1.42 (see table i). this means that also the law of equivalent (or reciprocal) proportions is implied by the theory [18]. in occasion of the first lecture, december 22𝑛𝑑 , 1803, of a series of 20 at the royal institution in london dalton received the experimental results of davy on the three compounds, reported by dalton in table i [4]. reason why it should not take as many atoms of 𝐵 as are presented to it, and can possibly come into contact with it (which may probably be 12 in general), except so far as the repulsion of the atoms of 𝐵 among themselves are more than a match for the attraction of an atom of 𝐴. now this repulsion begins with 2 atoms of 𝐵 to one of 𝐴, in which case the two atoms of 𝐵 are diametrically opposed; it increases with 3 atoms of 𝐵 to 1 of 𝐴, in which case the atoms of 𝐵 are only 120° asunder; with 4 atoms of 𝐵 it is still greater, as the distance is then only 90°; and so on in proportion to the number of atoms. it is evident then from these positions that, as far as powers of attraction and repulsion are concerned (and we know of no other in chemistry) ……. binary compounds must first be formed in the ordinary course of things, then ternary and so on, till the repulsion of the atoms of 𝐵 ……. refuse to admit any more”. 35it should be again stressed that the relative atomic weights could have been determined from the weight percent and the avogadro principle. in fact, being in this hypothesis 𝑚 𝑝𝐵 𝑝𝐴 = (%)𝐵 ∙ (𝑛𝑝𝐴+𝑚𝑝𝐵) 𝑝𝐴 = (%)𝐵 ∙ 𝜌(𝐴𝑛𝐵𝑚) 𝜌(𝐴) , the weight of 𝐵 in 𝐴𝑛 𝐵𝑚 results to be an integral multiple of 𝑝𝐵 𝑝𝐴 . thus, analyzing a sufficiently large group of compounds of 𝐵 and determining their densities 𝜌(𝐴𝑛 𝐵𝑚 ) (together with 𝜌(𝐴), the 𝐴 density) at equal temperature and pressure, the smallest of these multiples corresponds very probably to 𝑚 = 1 and therefore identifies 𝑝𝐵 𝑝𝐴 . this proposal, which is substantially the cannizzaro rule, was unfortunately advanced only sixty years later. 36 ref. [4], p. 28. 23 table i – the composition of the three nitrogen oxides according to theoretical (dalton) and experimental (davy) results. the particle weight is expressed in units of the nitrogen weight (see ref. [4]); r is the ratio 𝑂(%) 𝑁(%) . _____________________________________________________________________________ dalton results davy experimental results weight n(%) o(%) r n(%) o(%) r n2o 2+1.42 58.5 41.5 0.71 0.5 63.3 36.7 0.58 0.46 no 1+1.42 41.3 58.7 1.42 1 44.05 55.95 1.27 1 no2 1+2∙1.42 26.0 74.0 2.84 2 29.5 70.5 2.39 1.88 ______________________________________________________________________________ within approximately one month from september 6𝑡ℎ dalton (i) tested the theory regarding the dependence of the gaseous solubilities on the particle weight and (ii) presented a set of chemical formulae for an appreciable number of compounds. on september 19𝑡ℎ , 1803, eleven gases were arranged in order of increasing weight and divided into three groups [4] (see fig. 8). hydrogen and nitrogen, having the least particle weights, are the least soluble gases in water. on the opposite, “nitrous oxide [𝑁2𝑂]”, “sulphurated hyd. gas [𝐻2𝑆]” and “carbonic acid gas” with the highest particle weight are the most soluble gases. in the middle six gases of intermediate weights have intermediate solubilities. once compared with the second “article” of the paper [18], the order results being nearly the same, except for 𝐶𝑂. 24 fig. 8 – the three groups of gaseous solubilities ordered according to the weight of the compound atom. the “carbonated hyd. gas” is ethylene, elsewhere called “olefiant gas”, while the “carb. aqueous vapour” was later shown by dalton to be a mixture of 𝐶𝑂 and 𝐻2. the table of fig. 8 was probably prepared to establish the correlation between solubilities and diameters of gaseous particles [8]. dalton calculated this parameter (with respect to the diameter of a reference particle, in this case that of liquid water, see footnote 32) assuming that the gas is an ordered array of spherical particles. the attempt was obviously unsuccessful, and the negative result may have caused the appearance of the already cited footnote in the paper of 1805 [25] about the lower probability of the atomic “conjecture”. on october 12𝑡ℎ , 1803, a classified list of “ultimate atoms” of compounds appears in the notebook, reproduced in fig. 9. the advantages of the dalton approach to identify the compound are apparent, (i) each atom has its own symbol, (ii) the compound particle is represented by means of the symbols of the constituting elements and (iii) the number of times each atom is present in the compound particle is indicated by the symbol repetition. in fig. 9 the phosphorus symbol is added to those of nitrogen, sulphur, hydrogen, and oxygen (the latter two are exchanged with respect to fig. 6). dalton distinguishes binary, ternary, etc. “ultimate atoms”, some of which have been already considered in the table of fig. 7. among binary particles, “carbonated hydrogen gas [i.e., “olefiant gas”, ethylene]” is formulated as 𝐶𝐻, “phosphorous acid” as 𝑃𝑂 and “phosphorated hydrogen [posphine]” as 𝑃𝐻. “ether” is constituted by ternary particles 𝐶2𝑂. in analogy with “sulphuric acid”, the formula of “phosphoric acid” is 𝑃𝑂2 37. tetraand penta-atomic particles are viewed as secondorder compounds. thus, alcohol is 𝐶𝐻 + 𝑂𝐻, the combination of the hydrocarbon particle 𝐶𝐻 with water 𝑂𝐻. sugar is 𝐶𝑂 + 𝑂𝐻, “gaseous oxide of carbon [𝐶𝑂]” and water 𝑂𝐻. in “nitrous acid [𝑁2𝑂3]” the complicated ratio 2: 3 is expressed as the combination of two particles, 𝑁𝑂 + 𝑁𝑂2 [18]. 37 the atomic weight of phosphorus, 𝑝𝑃 𝑝𝐻 = 7.2, appears in the notes of september 19𝑡ℎ , 1803 [4] and is calculated considering the lavoisier data about “phosphoric acid [𝑃𝑂2]”, 39.4% phosphorus and 60.6% oxygen, and assuming 5.5 as the atomic weight of oxygen. 25 fig. 9 – the constitution of some biand polyatomic particles according to the dalton theory. the notes contained in the dalton’s notebook between september and october 1803 are the essence of the chemical atomic theory. the theoretical principles remained unchanged in all later publications [5,18]. comparing now with the table of fig. 5, the gases present in fig. 7 and 9 appear in this table with compositions confirmed except in two cases. the “ether” particle is represented as 𝐶2𝐻 in fig. 5, not 𝐶2𝑂, with weight 2 ∙ 4.3 + 1 = 9.6 and the particle of alcohol as 𝐶2𝑂𝐻 (not 𝐶𝑂𝐻2) with weight 2 ∙ 4.3 + 5.5 + 1 = 15.1. but a new piece of information appears in fig. 5 and comes from the “carburetted hydrogen from stagn. water [methane]” formulated as 𝐶𝐻2 with weight 4.32 + 2 = 6.3. as already noted, the relation between methane and ethylene (“olefiant gas”) was established almost one year after the proposal about the atomic theory. dalton describes in his notebook, august 24𝑡ℎ , 1804, the reaction of ethylene and methane with oxygen with volumetric details [4] 26 “olefiant gas [ethylene] meas. acid. oxy. dimin. 100 200 300 200 stagnant [methane] 100 100 200 200”38 which may be interpreted in modern terms as 𝐶2𝐻4 + 3𝑂2 → 2𝐶𝑂2 + 2𝐻2𝑂 𝐶𝐻4 + 2𝑂2 → 𝐶𝑂2 + 2𝐻2𝑂 fixing the same number of carbon atoms for both compounds, i.e., the same volume of “carbonic acid” gas precipitated by “water lime”, for instance 100 “measures”, a little reflection on the volumetric data shows that the volumes of the reacting and products gases (in the same order given by dalton) are in the ratio 50: 100: 150: 100 for ethylene and 100: 100: 200: 200 for methane. thus, the final volumes in the fourth place are 1: 2 and therefore the ratio of the hydrogen atoms in the particles of the two gases is 1: 2. this means that the particle of “carburetted hydrogen from stagn. water” contains a number of hydrogen atoms double that in “olefiant gas”. the former was formulated as 𝐶𝐻2 and the latter as 𝐶𝐻, a conclusion which stands as the first successful experimental verification of the atomic theory after one year of silence [8]. it was a result particularly impressive for dalton to the point that he informed thomson, who visited him august 27𝑡ℎ, 1804, about the atomic theory referring specifically to these gases. this narrative, centered on the chemical development of the theory one year later with respect to the intimation, has been questioned and it was argued, on the contrary, that dalton actively tested the implications of the incipient theory from the start and was eager to communicate his merits [10]. for instance, it has been noted [10] that the law of multiple proportions was already in operation in the table of fig. 7 and considered as the rule by means of which the atom-to-atom association in the compound formation may occur. examples are the weights of the “ultimate atoms” of the oxides of nitrogen, carbon and sulfur [10]. as to the diffusion of the theory, dalton included the atomic theory as a small part of the subject matter in the lectures held at the royal institution on natural philosophy in the period december 1803 – january 1804, as evidenced by reported annotations [10]. in this occasion dalton was introduced to davy and not only was informed about nitrogen oxides but also, had the opportunity to present to davy the atomic theory. finally, on his return to manchester dalton gave on february lectures whose content is unfortunately not known but whose titles suggest that atomic theory was part of them [10]. 6 – conclusions in this paper, the attention is directed to the history of dalton scientific interests from the studies in meteorology to the first intimation of the chemical atomic theory. the distinctive traits of his personality were great perseverance, self-reliance, and a laborious mind. he promoted vigorously the theory of mixed gases explaining atmospheric homogeneity in terms of repulsive forces acting among 38 ref. [4], p. 63. 27 particles of the same kind rather than of affinity or chemical combination. differing specific gravities of the particles would have caused the atmospheric gases to settle down in layers. to avoid this difficulty dalton opted for the theory of mixed gases which would ultimately lead to the formulation of the atomic theory. but he had a peculiar aversion to the idea of a direct relation between specific gravities and particle weights. the statement was reiterated over the years saying that it is a “confused idea …… that the particles of elastic fluids are all of the same size”39. dalton’s contributions to the atomic theory have been discussed at length [9,47]. there is no need to say that the idea dates back to the greek (and earlier) philosophies and that interest in the atomic theory revived in the xvii century [7,17,19]. the following magnificent, perhaps unsurpassed, passage of newton’s opticks, transcribed by dalton’s own hand in the notebook [4,48], is proof that atomistic ideas were diffused among the xviii century scientists “all these things being consider'd, it seems probable to me, that god in the beginning form'd matter in solid, massy, hard, impenetrable particles, of such sizes and figures, and with such other properties, and in such proportion to space, as most conduced to the end for which he form'd them; and that these primitive particles being solids, are incomparably harder than any porous bodies compounded of them; even so very hard, as never to wear or break in pieces; no ordinary power being able to divide what god himself made one in the first creation. while the particles continue entire, they may compose bodies of one and the same nature and texture in all ages: but should they wear away, or break in pieces, the nature of things depending on them, would be changed. water and earth, composed of old worn particles and fragments of particles, would not be of the same nature and texture now, with water and earth composed of entire particles in the beginning. and therefore, that nature may be lasting, the changes of corporeal things are to be placed only in the various separations and new associations and motions of these permanent particles; compound bodies being apt to break, not in the midst of solid particles, but where those particles are laid together, and only touch in a few points.” thus, the striking advance of dalton’s theory may be synthesized in three points, (i) the emphasis on a single atomic property, the weight of the atom, singled out of the several properties of the “ultimate particles” envisioned by newton, weight (“massy”), hardness (“hard”), size, shape (“figures”) [8], (ii) the calculation procedure for deriving atomic weights or, in other words, the rule of greatest simplicity [9,10], (iii) the symbolic representation of atoms and their combinations [4]. acknowledgements i gratefully thank prof. vincenzo schettino and prof. fabrizio mani, university of florence, for their careful reading of the manuscript and helpful suggestions. 39 a new system of chemical philosophy, part 1, p. 188. 28 references [1] – t. thomson, history of chemistry, 1831, london. [2] – w.c. henry, memoirs of the life and scientific researches of john dalton, 1854, london. [3] – g. wilson, religio chimici, macmillan, london, 1862. [4] – h.e. roscoe, a. harden, a new view of the origin of dalton’s atomic theory – a contribution to chemical history, macmillan, london, 1896. [5] – a.n. meldrum, manchester mem., 55, 1910-1911, nos. 1, 2, 3, 4, 5, 6. [6] – j. larmor, the wilde lecture. on the physidal aspect of the atomic theory, manchester mem., 52, 1908, no. 10. [7] – j.r. partington, the origin of the atomic theory, annals of science, 4, 1939, 245-282. [8] – l.k. nash, the origin of dalton’s chemical atomic theory, isis, 47, 1956, 101-116. [9] – a.w. thackray, the origin of dalton’s chemical atomic theory: daltonian doubts resolved, isis, 57, 1966, 35-55. [10] – a.j. rocke, in search of el dorado: john dalton and the origins of the atomic theory, soc. res., 72, 2005, 125-158. [11] – h.j. pratt, a letter signed: the very beginnings of dalton’s atomic theory, ambix, 57, 2010, 301-310. [12] – m.c. usselman, d.g. leaist, k.d. watson, dalton’s disputed nitric oxide experiments and the origins of his atomic theory, chemphyschem, 9, 2008, 106-110. [13] – p. grapì, the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combinatioon, substantia, 4, 2020, 51-61. [14] – m.i. grossman, john dalton and the london atomists: william and bryan higgins, william austin, and new daltonian doubts about the origin of the atomic theory, notes rec., 68, 2014, 339-356. [15] – m.i. grossman, john dalton and the origin of the atomic theory: reassessing the influence of bryan higgins, british journal for the history of science, 50, 2017, 657-676. [16] – m.i. grossman, john dalton’s “aha” moment: the origin of the chemical atomic theory, ambix, 68, 2021, 49-71. [17] – k.r. zwier, john dalton’s puzzles: from meteorology to chemistry, studies in history and philosophy of science, 42, 2011, 58-66. [18] – j.r. partington, a history of chemistry, vol. 3, macmillan, 1962, london. [19] – a.j. ihde, the development of modern chemistry, dover, 1984, new york. [20] – s. califano, storia della chimica, bollati boringhieri, 2010, torino. [21] – j. dalton, meteorological observations and essays, london, 1793. [22] – j. dalton, new theory of the constitution of mixed aeriform fluids, and particularly of the atmosphere, nicholson j., v, 1801, 241-244. [23] – j. dalton, on the constitution of mixed gases: and particularly of the atmosphere, manchester mem., v, ii, 1802, 538-550; read october 2, 1801. [24] – j. dalton, experimental enquiry into the proportion of the several gases or elastic fluids, constituting the atmosphere, manchester mem., 1, 1805, 244-258; read november 12, 1802. [25] – j. dalton, on the absorption of gases by water and other liquids, manchester mem., 1, 1805, 271-287; read october 21, 1803. 29 [26] – j. dalton, on the tendency of elastic fluids to diffusion through each other, manchester mem., 1, 1805, 259-270. [27] – w. henry, experiments on the quantity of gases absorbed by water, at different temperatures, and under different pressures, phil. trans., 93, 1803, 29-42. [28] – w. henry, appendix to experiments on the quantity of gases absorbed by water, at different temperatures, and under different pressures, phil. trans., 93, 1803, 274-276. [29] – m. faraday, experimental researches in electricity. twenty-sixth series, phil. trans., 147, 1851, 29-84. [30] – p. atkins, j. de paula, chimica fisica; oxford university press, oxford, uk, 2002; p. 136 (it. ed.). [31] – k. denbigh, the principles of chemical equilibrium, cambridge university press, cambridge, cambridge, 1977, p. 208 (it. ed.). [32] – l.m. raff, principles of physical chemistry; prentice-hall, upper saddle river, nj, 2001; p. 278. [33] – j. andrade-gamboa, d.o. martire, e.r. donati, one-component pressure temperature phase diagrams in the presence of air, j. chem. ed., 87, 2010, 932-936. [34] – i. newton, the principia – mathematical principles of natural philosophy, [i.b. cohen and a. whitman translation], university of california press, 1999, berkeley. [35] – j.n. israelachvili, intermolecular and surface forces, academic press, amsterdam, 2011. [36] – s.c. brown, the caloric theory of heat, am. j. phys., 18, 1950, 367-372. [37] – j. dalton, on the tendency of elastic fluids to diffusion through each other, manchester mem., 1, 1805, 259-270. [38] – w. henry, experiments on the quantity of gases absorbed by water, at different temperatures, and under different pressures, phil. trans., 93, 1803, 29-42. [39] – j. priestley, experiments and observations on different kinds of air, 3, 1777, 301-305. [40] – w. henry, appendix to experiments on the quantity of gases absorbed by water, at different temperatures, and under different pressures, phil. trans., 93, 1803, 274-276. [41] – r.j. boscovich, theoria philosophiae naturalis redacta ad unicam legem virium in natura existentium, quoted after the latin-english edition: a theory of natural philosophy, edited by james mark child, the open court, new york, 1922 [42] – l. guzzardi, ruggero boscovich and “the forces existing in nature”, science in context, 30, 2017, 385-422. [43] – d. bernoulli, hydrodynamica, strasbourg, 1738, p. 200, fig. 56. [44] – w. henry, illustrations of mr. dalton’s theory of the constitution of mixed gases. in a letter from mr. wm. henry, of manchester to mr. dalton. communicated by the writer, nicholson j., 8, 1804, 297-301. [45] – s. hales, statical essays, london, 1733. [46] – j. priestley, experiments and observations on different kinds of air, 1, 1774, 108-128. [47] – j. dalton, experiments and observations to determine whether the quantity of rain and dew is equal to the quantity of water carried off by the rivers and raised by evaporation; with an enquiry into the origin of springs, manchester mem., 1802, v, ii, 346-372; read march 1, 1799. [48] – l.k. nash, the atomic-molecular theory, harvard case histories in experimental science, 1, 1957, 215-321. [49] – j. dalton, observations on dr. bostock’s review of the atomic principles of chemistry, 30 nicholson’s j., 29, 1811, 143-151. firenze university press www.fupress.com/substantia preface it is a great honour for me to write these few lines of preface to the special issues of substantia dedicated to the 150th anniversary of the periodic table by dmitrij mendeleev. in 2019 there are other important anniversaries besides that of the periodic table. one of these is the centenary of primo levi’s birth. i believe these two anniversaries are strictly related, in fact the periodic table by levi has been considered by the royal institution of great britain as the “best book of science ever written”. it would be sufficient to recall an impressive excerpt from “iron”, a tale of the the periodic table, to acknowledge the uniqueness of this literary work: “we began studying physics together, and sandro was surprised when i tried to explain to him some of the ideas that at that time i was confusedly cultivating. that the nobility of man, acquired in a hundred centuries of trial and error, lay in making himself the conqueror of matter, and that i had enrolled in chemistry because i wanted to remain faithful to this nobility. that conquering matter is to understand it, and understanding matter is necessary to understand the universe and ourselves: and that therefore mendeleev’s periodic table […] was poetry …”. when we designed the project related to these special issues, we had in mind levi’s work and in particular his wonderful tales that belong to the periodic table. i like to recall this homage to a chemist-writer-witness to introduce the six topics that are associated to the special volumes of substantia. as president of the university of florence which is the owner of the publisher firenze university press, i am truly grateful to the editors – marc henry, vincenzo balzani, seth rasmussen, luigi campanella, mary virginia orna with marco fontani, and brigitte van tiggelen with annette lykknes and luis moreno-martinez – for accepting the invitation made by the editor-in-chief pierandrea lo nostro and for the extraordinary work for the preparation of these special issues. of course the choice of the six subjects was not accidental: we tried to identify some features of the chemistry realm, related for several reasons to the periodic table. they are strikingly associated to the great challenges for our future: these are water, sustainability, energy, open chemistry, the history and the educational perspectives of the periodic table. during its long path of progress and civilisation mankind has strongly modified nature to make our planet more comfortable, but at present we must be very careful with some dramatic changes that are occurring in our earth. science and technology, and chemistry primarily, can help mankind to solve most of the environmental and energy problems that emerge, to 8 scientific board build a radically different approach from that that has prevailed in the last two centuries. it is a fantastic challenge, since for the first time we can consider nature not as a system to simply exploit, but a perfect ally for improving life conditions in the whole planet. chemistry has already engaged and won a similar challenge when, understanding the pollution problems generated by a chaotic and rapid development, succeeded in setting up a new branch, green chemistry, that turned upside down several research topics. now is the time to develop sustainable chemistry: the occurring events demand that chemists propose new routes and innovative approaches. in the last two centuries we have transformed immense amounts of matter from nature into waste without thinking that we were using non renewable energy sources. we have been acting as our natural resources were unlimited, but knowing that they are instead limited. now we are realizing that it is not possible to continue along this road. our planet and our atmosphere are made of finite materials and their consumption during the last two centuries has been impressive. some elements that are crucial for current and future industrial countries are known to be present on earth crust in very small amounts and their recycling from waste cannot be a choice anymore, but it is rather an obligation. climate is another big problem associated to the terrific changes occurring in some equilibria, both as a consequence of the violent industrial development and energy consumption. we need, and we will always need more and more, an immense amount of energy. the only solution to secure wellness to future generations is the conversion to renewable energy sources. in this view, food and water, due to the strong increment in the demographic indices, could become the true emergencies for billions of individuals. looking at the picture i tried to draw in this short preface it becomes more clear why we selected those topics for our special issues. i am optimistic, and i have the strong confidence that chemistry, that studies matter and its transformations, will give mankind the picklock to overcome those challenges. we will definitely need insightful minds, creativity, knowledge and wisdom. luigi dei president of the university of florence firenze university press www.fupress.com/substantia substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press firenze university press www.fupress.com/substantia preface it is a great honour for me to write these few lines of preface to the special issues of substantia dedicated to the 150th anniversary of the periodic table by dmitrij mendeleev. in 2019 there are other important anniversaries besides that of the periodic table. one of these is the centenary of primo levi’s birth. i believe these two anniversaries are strictly related, in fact the periodic table by levi has been considered by the royal institution of great britain as the “best book of science ever written”. it would be sufficient to recall an impressive excerpt from “iron”, a tale of the the periodic table, to acknowledge the uniqueness of this literary work: “we began studying physics together, and sandro was surprised when i tried to explain to him some of the ideas that at that time i was confusedly cultivating. that the nobility of man, acquired in a hundred centuries of trial and error, lay in making himself the conqueror of matter, and that i had enrolled in chemistry because i wanted to remain faithful to this nobility. that conquering matter is to understand it, and understanding matter is necessary to understand the universe and ourselves: and that therefore mendeleev’s periodic table […] was poetry …”. when we designed the project related to these special issues, we had in mind levi’s work and in particular his wonderful tales that belong to the periodic table. i like to recall this homage to a chemist-writer-witness to introduce the six topics that are associated to the special volumes of substantia. as president of the university of florence which is the owner of the publisher firenze university press, i am truly grateful to the editors – marc henry, vincenzo balzani, seth rasmussen, luigi campanella, mary virginia orna with marco fontani, and brigitte van tiggelen with annette lykknes and luis moreno-martinez – for accepting the invitation made by the editor-in-chief pierandrea lo nostro and for the extraordinary work for the preparation of these special issues. of course the choice of the six subjects was not accidental: we tried to identify some features of the chemistry realm, related for several reasons to the periodic table. they are strikingly associated to the great challenges for our future: these are water, sustainability, energy, open chemistry, the history and the educational perspectives of the periodic table. during its long path of progress and civilisation mankind has strongly modified nature to make our planet more comfortable, but at present we must be very careful with some dramatic changes that are occurring in our earth. science and technology, and chemistry primarily, can help mankind to solve most of the environmental and energy problems that emerge, to 8 scientific board build a radically different approach from that that has prevailed in the last two centuries. it is a fantastic challenge, since for the first time we can consider nature not as a system to simply exploit, but a perfect ally for improving life conditions in the whole planet. chemistry has already engaged and won a similar challenge when, understanding the pollution problems generated by a chaotic and rapid development, succeeded in setting up a new branch, green chemistry, that turned upside down several research topics. now is the time to develop sustainable chemistry: the occurring events demand that chemists propose new routes and innovative approaches. in the last two centuries we have transformed immense amounts of matter from nature into waste without thinking that we were using non renewable energy sources. we have been acting as our natural resources were unlimited, but knowing that they are instead limited. now we are realizing that it is not possible to continue along this road. our planet and our atmosphere are made of finite materials and their consumption during the last two centuries has been impressive. some elements that are crucial for current and future industrial countries are known to be present on earth crust in very small amounts and their recycling from waste cannot be a choice anymore, but it is rather an obligation. climate is another big problem associated to the terrific changes occurring in some equilibria, both as a consequence of the violent industrial development and energy consumption. we need, and we will always need more and more, an immense amount of energy. the only solution to secure wellness to future generations is the conversion to renewable energy sources. in this view, food and water, due to the strong increment in the demographic indices, could become the true emergencies for billions of individuals. looking at the picture i tried to draw in this short preface it becomes more clear why we selected those topics for our special issues. i am optimistic, and i have the strong confidence that chemistry, that studies matter and its transformations, will give mankind the picklock to overcome those challenges. we will definitely need insightful minds, creativity, knowledge and wisdom. luigi dei president of the university of florence firenze university press www.fupress.com/substantia substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press citation: l. campanella, m. anastasio (2020) a possible scientific answer to covid-19 among open science, big data, old and new expertise and knowledge: the position paper of chemistry. substantia 4(1) suppl. 1: 890. doi: 10.13128/substantia-890 received: mar 27, 2020 revised: mar 30, 2020 just accepted online: apr 01, 2020 published: apr 01, 2020 copyright: © 2020 l. campanella, m. anastasio. this is an open access, peerreviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative com mons attribution license, which per mits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia editorial a possible scientific answer to covid-19 among open science, big data, old and new expertise and knowledge: the position paper of chemistry luigi campanella*, maurizio anastasio department of chemistry, sapienza university, piazzale aldo moro 5, 00185 rome, italy *corresponding author: luigi.campanella@uniroma1.it "the single biggest threat to man's continued dominance is the virus” this statement was made by joshua lederberg in 1958 in the occasion of his nobel lecture. this claim cannot be forgotten in this period while we are looking for a reason of hope and this hope, after ensuring adequate sanitary services and responsible behavior of citizens, can come only from science. medical sciences represent undoubtedly the queen disciplines, but many other disciplines can play a very important role. at this particular moment the basic core of knowledge is provided by the group of biosciences such as medicine, virology, biology, biotechnology. it is fundamental to have an intradisciplinary group that speaks the same language at the start of any research activity. after the working group started it is absolutely necessary that the same group acquires interdisciplinary features because a scientific problem has to be regarded from different competences and cultures. this is the only approach to increase the likelihood of finding an acceptable and positive solution. that said, it is clear that the solution must emerge from cultural and speculative differences. in other words, generally speaking, the successful team must be as heterogeneous as possible. analyzing from a general point of view the various disciplines that participate in the study. perhaps chemistry can guarantee a specific attitude in criticism, a forma mentis, with its epistemological characteristics that are highly dependent on conceptual, theoretical and experimental diversity. for these reasons, chemistry can support and act as a “glue” in the group of disciplines that have made up the fundamental historical group to combat covid-19. chemists have the full right to be part of the group of researchers for these types of works. somebody may think that such a heterogeneous group, could have difficulties in language and culture for the benefit of the work, but this interaction, between heterogeneous competences clearly fits into a holistic vision of the health problems, related to hygienic, environmental, alimentary, social conditions. speaking of the coronavirus, it is probably the best way to face such integral approach if chemistry is taken into consideration. in fact chemistry can contribute by looking at aspects and problems never considered before and which can only be highlighted through a sensitivity that is characteristic of this discipline. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 890, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-890 luigi campanella, maurizio anastasio this is the profound value and meaning of working in diversity. a fundamental issue is related to particulate matter. a sound scientific literature describes the role of particulate matter (pm) as an efficient carrier to transport and to diffuse a great lot of chemical and biological contaminants, including viruses. particulate matter plays a negative role if it shows binding capacity to retain bioparticles. the latter would remain in the air for hours or days in active and vital conditions. waiting for better times when different styles of life will be adopted in order to improve environmental conditions, for their physical and chemical characteristics they can be considered co-indexes and co-markers of the possible spread of viruses. this hypothesis could be easily checked by advanced instrumental analysis by taking samples of air in certain areas and analysing them for its chemical pollutants and virus content, or better still, investigating as per regarding possible chemical or physical bonds between the two components. other than viruses it does not seem easily understood why real regulations about pm consider only the weight and the size of the particulate without any scientific interest toward its nature, to correlate to hygiene and safety limits. during several international congresses chemists have presented proposals focused on the determination of pm toxicity levels together with its weight; for instance immobilizing pm particles on specific collecting filters the abiological component could be able to give information about the toxicity level of the collected pm. another point refers to the fact that starting from the way by which a virus is multiplied in hosting human cells a question comes up: why in some cases viruses cause the death of cells and therefore of organisms while in other cases none or modest damages are observed? a possible answer may be a genetic or epigenetic difference between living beings as well as a difference of antinflammatory and antioxidant patrimony that varies from person to person. these patrimony differences can be determined through many chemical or biochemical methods. another important aspect of chemistry concerns scientific data, their meaning, but above all how they are obtained and how they must be communicated. chemistry is a predominantly an inductive science, then the scientific method is synonymous with an experimental method. for this reason, it is essential that communication and data sharing must proceed successfully, but this latter condition presupposes easy accessibility to magazines, journals and research results. this is why the chemical community has always defended “open science criteria”. having examined, even if shortly, the set of almost unique and original characteristics of the chemical sciences, we can imply that chemistry is entitled to join and contribute with the other disciplines side by side, by making available its own techniques and significant contents, particularly in this dramatic moment. the working group, for which we propose a a rational composition, has an absolute need to receive certain answers from chemistry through its two main features, that is analysis and synthesis. we have seen how chemistry, or better chemical sciences, can collaborate closely with those disciplines and subjects already mentioned above whose presence and activities in the group are absolutely necessary and we all agree on this. but beyond the technical and scientific contributions that chemistry can provide, it is necessary to re-emphasize one of its unique characteristics that perhaps could act as a catalyst in the team's work: chemistry works positively if and only if it can cultivate, by working alone or in a team, the concept of diversity and scientific doubt. sub-covid-806 1 citation: v. balzani (2020) a providential last warning. substantia 4(1) suppl. 1: 907. doi: 10.13128/sub stantia-907 received: apr 11, 2020 revised: apr 14, 2020 just accepted online: apr 15, 2020 published: apr 15, 2020 copyright: © 2020 v. balzani. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia editorial a providential last warning vincenzo balzani university of bologna, italy *corresponding author: vincenzo.balzani@unibo.it rather than being afraid of the coronavirus, today we must be afraid that once the health emergency is over we will return to the situation we were in before. in a famous photograph, taken by nasa astronaut william anders on december 24, 1968 during the apollo 8 mission, you can admire the extraordinary spectacular rising of the earth seen from the moon. contemplating the scene he was photographing, anders said, "we came all this way to explore the moon, and the most important thing is that we discovered the earth". from this and other similar photos of the earth taken from afar you can see what our situation is: we are travelling through the infinity of the universe on a spaceship. a spaceship that can never "land" anywhere, can never dock at any port to load resources or unload waste. the resources on which the nearly eight billion passengers can count are the materials that make up the spaceship and the sunlight. in the past few months a dangerous and highly contagious virus, covid-19, has been circulating on the spaceship earth. waiting to fight it with a vaccine, we defend ourselves with the obnoxious weapon of social distancing. according to scientists, the virus passed from wild animals to humans because of one or more of the following mistakes in our relationship with nature: exaggerated use of resources, environmental degradation, climate change, increasing consumption of animal products, exaggerated anthropization of the soil, loss of biodiversity and the search for wild food by the poorest populations. viruses are somehow "refugees" of the environmental destruction caused by our aggressiveness. they were fine in the forests and in the bodies of some animals, we gave them the opportunity to multiply. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 907, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-907 vincenzo balzani 2 many of the western rich countries' citizens are worried about the health crisis, but they never seem to have noticed the ecological and social crisis. they are terrified by some tens of thousands of deaths caused by the virus in the world, but perhaps they do not know that about one million people die every year in china, 650,000 in the european union and 80,000 in italy alone because of air pollution. scientists have been warning for many years that we are not guarding the planet, and sociologists warn that the enormous economic and social inequalities are becoming unsustainable. the current development model, consumerism, based on disposable goods, established a culture of waste that leads to environmental degradation and extends right into people's lives. in the laudato si' encyclical, a few years ago pope francis wrote: "we are faced not with two separate crises, one environmental and the other social, but rather with one complex crisis which is both social and environmental." that needs to be approached with a unified view of ecological and economic problems. and in the blessing urbi et orbi imparted on march 27, 2020, in the ghostly deserted st. peter's square the pope added: "we carried on regardless, thinking we would stay healthy in a world that was sick." we are living one of the worst periods in our history, gripped by a crisis that has three intertwined aspects: ecological, social and health. but we must not lose heart: history itself teaches us that every crisis offers the opportunity for a better situation. since the spaceship earth is the only place where we can live, we cannot miss this opportunity. we must see in covid-19 a providential last warning. rather than being afraid of the virus, today we must be afraid that once the health emergency is over we will return to the unsustainable situation we were in before. we must all ensure that this does not happen. for a change to take place in the right direction, we must first make politicians and economists understand that unlimited growth is impossible. we cannot expect planet earth to adapt to our megalomania; we must adapt to its reality. the only goal that we may perhaps achieve, not without difficulty, is that of sustainability: that is, to live on a planet that is livable even for future generations. for this to happen, we must make a wiser use of the limited resources of the spaceship earth and exploit as much as possible the abundant energy that comes from the sun. we must decrease the extraction of materials from the earth (92 billion tons per year, equal to 35 kg per day for each of the current inhabitants of the planet) and abandon the use of fossil fuels to reduce air pollution and even more co2 emissions (37 billion tons per year), the greenhouse gas that causes climate change. we'll have to replace the combustion engines with electric motors powered by sun's energy. the scarcity of resources will no longer allow us to own the "machines" we use (for example, a car); we will have to be happy with shared "machines". we will have to deeply understand what we need and what we do not need. if we had thought about it before, for example, we would not have spent 14 billion in f-35s warplanes (that luckily we will never use), but we would have invested that money in health and education. more in general, we will have to replace the verb consume with the verb save. in order to reduce consumption, scientific studies show that it is not so important "acting on things", that is increasing the efficiency of the production processes and the machines we use. rather, it is necessary to "act on people", that is, to urge them to practice lifestyles inspired by sobriety. there is still a lot of work to do, but we are well aware of the way to achieve ecological sustainability. on the other hand, we are a long way from attaining social sustainability, that requires, first and foremost, a redistribution of wealth. there can be no social sustainability in a world where the 2.000 richest people own more than 4.6 billion people and not even in a country like italy, where the richest 1% own as much as 70% of the population. there can be no social sustainability if, as pope francis wrote in his encyclical laudato si', "we fail to see that some are mired in desperate and degrading poverty, with no way out, while others have not the faintest idea of what to do with their possessions, vainly showing off their supposed superiority and leaving behind them so much waste which, if it were the case everywhere, would destroy the planet." we must ensure that the covid-19 pandemic, from which we are emerging with difficulty, brings the problem of sustainability to the forefront. it will be necessary to carefully use the planet's resources and the sun's energy and also develop science and technology in the appropriate directions. but it will be even more important to exploit our precious sources of spiritual energy: wisdom, creativity, responsibility, collaboration, friendship, sobriety and solidarity. when we have done all this, we will remember this pandemic as a salutary lesson from nature. substantia. an international journal of the history of chemistry 3(2) suppl. 2: 45-54, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-699 citation: j. michl (2019) singlet fission: toward more efficient solar cells. substantia 3(2) suppl. 2: 45-54. doi: 10.13128/substantia-699 copyright: © 2019 j. michl. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. singlet fission: toward more efficient solar cells josef michl department of chemistry, university of colorado, boulder, co 80309-0215 and institute of organic chemistry and biochemistry, czech academy of sciences, 16610 prague 6, czech republic e-mail: michlj@colorado.edu abstract. a survey is provided of the current status of singlet fission as a tool for bypassing the shockley-queisser limit on the efficiency of single-junction solar cells. keywords. solar cells, shockley-queisser limit, singlet fission, photophysics, solid state packing. introduction the human mind is remarkable in many ways. one of them is its ability to disregard reality in order to induce pleasant feelings. i know for sure that my wife of 50 years, who recently unexpectedly passed away, will never return. yet, several times a day, i catch myself expecting her to open the door and smile at me. twice a year, i tell my students that there will be a final examination at the end of the semester. they ignore this repugnant thought blissfully, since the distant future is of no concern. a few days before the exam, when disaster is at the door, they start coming and asking what they are expected to know. i doubt that as a student i was any better. no wonder that much of the general public and numerous influential politicians deny that the incipient climate change has anything to do with human activities, least of all with the burning of fossil fuels, although in sober moments they must surely realize that thousands of climate scientists actually know their business. after all, the most serious consequences of climate change are not yet at the door, unlike many immediate and apparently more important issues of the day that are. i suspect that the tendency to deny inconvenient reality and cherish immediate gain at the expense of distant troubles are in our genes and must have offered evolutionary advantages in some distant past. they surely do not offer long-term advantages now and our generation will be cursed by all that follow. past generations did not know what effects a drastic rapid increase in the concentration of carbon dioxide in the atmosphere will have. we do and yet on the whole we act as if it did not matter. 46 josef michl given the nature of the human mind, it seems to me that the best gift that science and engineering could presently offer to mankind is to make sustainable energy economically preferable. this is not an easy task. however, if solar, wind, and other forms of energy generation that do not contribute to climate change were cheaper than the burning of fossil fuels, hardly anybody would burn fossil fuels and the already inevitable damage would be limited. solar cells and the shockley-queisser limit the largest potentially available source of safe renewable energy is solar radiation, and an increase of the efficiency or reduction of the cost of solar cells would go a long way toward reducing the currently huge release of greenhouse effect gases. many scientists and engineers are working on this task all over the world and great strides have been made in recent decades. in many parts of the world, the goal appears to be realistic, although well recognized and very formidable technical obstacles stand in the way, such as the need for large-scale energy storage and for transportation fuels. unfortunately, the energy efficiency of inexpensive solar cells is limited to about 1/3 (the shockley-queisser limit1). these cells contain only a single junction (interface) at which negative and positive charges separate to proceed to their respective electrodes, the primary cause of the limitation is the broadband nature of solar radiation, whose photon energies range from the infrared to the ultraviolet. no matter how small or large we choose the bandgap of a solar cell material, which determines the maximum voltage produced, there always are some solar photons with less energy than the bandgap that are not absorbed and utilized, and others that have more energy than the bandgap. the latter are absorbed but their excess energy is almost immediately converted into vibrational energy and ultimately wasted as heat. the current produced by a solar cell is limited by the number of photons absorbed and the voltage is limited by the size of the bandgap. a smaller bandgap permits the collection of a bigger fraction of the incident photons and hence leads to a larger current at the cost of generating a smaller voltage. a larger bandgap will produce a higher voltage but will cause a smaller fraction of the photons to be absorbed and therefore will generate a smaller current. the power generated is the product of the current and the voltage, and the best compromise is to choose a bandgap of about 1.1 electronvolt (ev), which provides a theoretical efficiency of about 1/3 (figure 1), a limit that has been approached but not quite reached by modern silicon cells. little further improvement of the efficiency of single junction cells is possible. all this has been known for over half a century, ever since shockley and queisser, his postdoc at the time, published their pivotal paper.1 once i asked prof. queisser about the correct pronunciation of his name (it is german, kwi-ser) and he told me about the hard time they had when they tried to get the article accepted for publication. the reviewers did not see anything wrong in the derivations, but they felt that the results were of no theoretical or practical interest and publishing them would waste precious journal pages. half a century later, this may well be one of the most quoted paper ever published in the journal. i mention this story to remind myself and others not to get discouraged when our papers are not immediately accepted for publication and proposals for funding. beyond the shockley-queisser limit overcoming the shockley-queisser limit at low cost is a stimulating challenge. true, the use of cells containing multiple junctions with different bandgaps already has led to efficiencies approaching 1/2. however, since the currents f lowing through each junction need to be matched, the fabrication is very demanding and so expensive that such cells are suitable only for special figure 1. maximum theoretical efficiency of a single-junction solar cell, assuming 1 sun illumination, full absorption of incident solar light above 1.1 ev, detailed balance, 200% triplet yield in the singlet fission layer, and production of an electron-hole pair from each triplet. bottom curve (blue): ordinary; top curve (red): top layer, singlet fission and bottom layer, ordinary. reproduced by permission from hanna and nozik.2 47singlet fission: toward more efficient solar cells uses, for instance on space vehicles. they are valuable, but using them does not have much chance to be cheaper than burning coal. several other schemes have been proposed for going beyond the shockley-queisser limit, promise to be inexpensive, and are the subject of intense research. one of them is multiple exciton generation (meg), which relies on solids in which each high-energy electronic excitation can be converted into two or more lower energy electronic excitations faster than it is converted into vibrational excitation and thus ultimately into heat. then, each absorbed low-energy photon is used to produce a single electron-hole pair as in ordinary solar cells, while absorbed high-energy photons act as if they were two or more low-energy photons. as a result, a smaller fraction of their high energy is converted into heat and efficiency rises. materials known to behave in this manner are of two types: (i) semiconductor nanoparticles and (ii) organic molecular solids. the most obvious difference between the photophysics in the two is the absence of a clear distinction between singlet an triplet excitations in semiconductors and its presence in organic molecular solids. the latter are the subject of the present article. the conversion of a singlet exciton into two triplet excitons, known as singlet fission (figure 2),3,4,5,6 was first observed over half a century ago.7 since the two triplets are coupled into an overall singlet when they are first born, the process is spin-allowed. it can be very fast and can outcompete all other decay modes, providing an up to 200% triplet yield. the fundamental nature of the phenomenon was elucidated in half a dozen years after the initial discovery and thereafter interest in it died off. it revived early in this century when hanna and nozik pointed out that a combination of a top layer of singlet fission capable material followed by a bottom layer of an ordinary solar cell material would increase the maximum theoretical efficiency of a solar cell to almost 1/2 (figure 1).2 no current matching would be required and the cost would remain low. a similar suggestion in this direction was made even earlier by dexter but did not elicit much attention until very recently. by now, singlet fission has been shown in two laboratories to provide an external quantum efficiency over 100%.9,10,11,12,13 singlet fission solar cells why, then, if the theory is understood and the principle proven in the laboratory, are singlet fission solar panels not commercially available after a decade of intense effort in many laboratories? the problem has to do with finding a practical singlet fission material and with moving charges out of it into a useful electrical circuit. a truly practical material must produce two triplets upon absorption of nearly every photon of sufficient energy. this will occur if singlet fission outcompetes all other modes of excited state decay, which is only possible when the process is exothermic or only slightly endothermic. it should not be too exothermic, since that would incur a loss of efficiency by converting electronic excitation energy into vibrational and subsequently into heat. for the maximum efficiency to approach 1/2, the singlet excitation energy should be about 2.2 ev and the triplet excitation energy, about 1.1 ev. the two triplets must separate easily, must be long-lived, and must move readily through the material in order to reach an interface where the negative and positive charges are to separate. during their travel to this junction, the triplets should not encounter any of the separated charges, because these quench triplet excitation efficiently to generate the ground state and heat.3 there is another reason for insisting that singlet fission must occur very fast, even if there are no competing decay processes other than the relatively slow fluorescence, which occurs on a nanosecond time scale. ordinarily, singlet excitation moves through a molecular solid much faster than triplet excitation. although singlet excitation is much shorter lived, nanoseconds instead of microseconds, it still may reach the interface where excitation separates into charges before singlet fission has had a chance to occur, especially if the initial excitation occurred very close to or right at the interface. if this happens, only one electron-hole pair will result and efficiency suffers. the requirement of approximate thermoneutrality of the singlet fission process imposes a demanding condition on the energies of the lowest excited singlet and triplet levels in the solid, δe(s1) and δe(t1), respectively:figure 2. schematic representation of singlet fission. 48 josef michl δe(s1) ≥ 2 δe(t1) (1) only a handful of compounds, mostly tetracene, pentacene, and their derivatives, are known to meet the condition and to perform singlet fission with full efficiency. unfortunately, structures of this type are notorious for their inability to withstand the combination of light and air. yet, a practical singlet fission material must continue to function after a long time of exposure to sunlight under ambient conditions. it is possible to protect it from the atmosphere with a suitable coating, but the more perfect the insulation against traces of oxygen, the higher the cost. in addition to meeting the conditions imposed by the requirements of singlet fission, the material must meet many others that are common to all solar cell materials: for instance, it should have a high absorption coefficient for all visible and ultraviolet photons with energies above the absorption threshold, and its redox properties must be appropriate for the intended separation of charges at the junction. assuming that all these potential pitfalls are avoided, all the necessary conditions met, and the charges generated at the junction are successfully brought to electrodes, the question remains, how do we identify an optimal practically useful singlet fission material? the search can be subdivided into two tasks: (i) what molecular structure do we choose? (ii) how do we pack the molecules in the solid? before addressing these issues, the singlet fission mechanism needs to be described in more detail. singlet fission mechanism the process is rather complex and provides many opportunities for decay to the ground state, all of which need to be bypassed if triplet yield is to be 200%. in figure 3, the desirable path is indicated by narrow blue arrows and the decay paths by stubby red arrows. the introductory event is the absorption of a photon, which generates a singlet exciton. this contains a single excitation, which is however typically shared among half a dozen or perhaps a dozen adjacent molecules in the solid. note that in contrast, a triplet exciton would be usually localized on a single molecule. singlet fission consists of two main events. first, the singlet exciton is converted into a singlet biexciton, a molecular pair in which each partner is in its triplet state and the two triplets are coupled into an overall singlet. second, the spin state of the biexciton transforms from singlet to a mixture with quintet and triplet, and the two triplet excitations separate as two free and independent triplet excitons whose spins usually remain coherent (“entangled”) for tens of nanoseconds. we shall consider the two main events separately. (i) formation of a biexciton the singlet exciton may meet one of several fates. it can undergo singlet fission to produce two triplet excitations as desired, but it can also undergo intersystem crossing to produce a single triplet, it can form an excimer, it can form a charge-transfer state, in which one molecule has transferred an electron to a neighbor, and it can perform a photochemical reaction. if all of these processes are too slow, it will ultimately fluoresce. the formation of a biexciton typically occurs without any intermediates and its rate can be approximately divided into a dominant “superexchange” contribution mediated by virtual singlet charge-transfer configurations and a usually negligible “direct” contribution provided by the two-electron part of the interaction hamiltonian. in rare cases, the relative energy of the chargetransfer configurations is so low that they describe real states that correspond to minima in the potential energy surface of the first excited singlet s1. they then have a finite lifetime and are actually observable. they still have an opportunity to generate a triplet biexciton and sometimes they do,14 but mostly they take one of two other undesirable options. one is internal conversion to the singlet ground state by back electron transfer, with a complete loss of all the excitation energy as heat. the other option is intersystem crossing to the nearly isoenergetic triplet charge-transfer state. in that instance only half of the original excitation energy is lost, and one triplet exciton is generated. it may be difficult to tell whether the origin of observed triplets is singlet fission or this type of intersystem crossing.15 in certain solids limited molecular motion is relatively facile.the crystal structure may permit two of the molecules that share the initial singlet excitation to approach each other and form a stabilized stacked pair, known as an excimer. its wave function typically contains comparable amounts of the initial locally excited configurations and charge-transfer configurations, whose energy has been lowered by the approach of the two partners. the excimer is often considerably stabilized relative to the original exciton and its conversion to a biexciton is usually too endothermic to compete with radiative and non-radiative decay to the ground state. it is likely that the formation of charge-transfer states, which also can compete with singlet fission from the singlet exciton, is merely a more extreme version of 49singlet fission: toward more efficient solar cells the process of excimer formation. if the approach of the two molecules stabilizes the charge-transfer configurations so much that they dominate in the excimer wave function, even a small dissymmetry that favors electron transfer from one partner to the other over electron transfer in the opposite direction will collapse the wave function in the more favorable direction and form a radical ion pair, known in solution as an exciplex, and in the solid as a charge-transfer state. the facility of the collapse is due to the very small value of the interaction element between the two charge-transfer configurations, which only contains contributions from the two-electron part of the hamiltonian. once again, the exciplex is usually stabilized too much relative to the original exciton to permit its conversion to a biexciton. as noted above, such states usually decay to the singlet ground state by back electron transfer, or to a triplet exciton by intersystem crossing to the nearly isoenergetic triplet chargetransfer state. (ii) formation of free triplet excitons once the singlet biexciton is formed, the path to its dissociation into two independent triplet excitons figure 3. a: symbolic representation of states available to molecules a and b. b: the general mechanism of singlet fission. the possible electronic configurations of partners a and b are listed in black and the actually occupied configuration is shown in red. frames located above each other indicate the sets of configurations that need to be mixed to form a state. black frames indicate real states and red frames show states that usually are only virtual. thin blue arrows indicate the path for singlet fission and fat red arrows indicate undesirable decay channels. see text. 50 josef michl may appear to be smooth. in reality it is anything but smooth, and the yield of free triplet excitons is often disappointingly low. although the calculated biexciton binding energies are usually quite small and the dissociation should be fast, the decay of the biexciton to two ground state molecules, or possibly to one ground state and one triplet molecule, tends to compete successfully. unfortunately, relatively little is known about the mechanisms involved. first of all, we need to note that the conversion of a singlet exciton into a singlet biexciton is reversible.16 the reverse process is known as triplet-triplet annihilation. an exact reversal yields the singlet exciton back and delayed fluorescence may be observed. two free triplet excitons can still be formed, but it will take longer and this is not helpful. conversion of the singlet biexciton into the singlet ground state of both molecules might be expected to be slow because of the large energy gap, but often it is fast and competitive with the desired dissociation into two free triplet excitons. the mechanism that makes it so is not understood, and conceivably the process goes through the intermediacy of the quintet or triplet states of the biexciton. if it goes solely through the singlet manifold, it might possibly be related to events that occur during photochemical pericyclic reactions, specifically photocycloadditions.17,18 in these reactions, the ground state of the starting material correlates with a doubly excited state of the product and vice versa. this correlation produces a conical intersection (“pericyclic funnel”) half-way along the reaction path, through which the excited molecule or molecular pair returns to the ground state surface and then partitions between starting material and photocycloadduct. since the doubly excited state has a singlet biexciton (double triplet) character, it is conceivable that the decay of the biexciton formed in the first step of singlet fission involves an approach toward the same conical intersection. the lowest energy point of the intersection would not have to be reached before decay to the ground state potential energy surface becomes rapid. at this point, however, this is pure speculation. if the biexciton has time to modify its spin function, the reverse process might produce a triplet excited molecular state. formation of the lowest triplet state would be strongly exoergic and probably quite slow, but if the excitation energy of one of the next higher molecular triplet states lies only a little below the energy of the biexciton, it might be formed fast. subsequent internal conversion would afford the lowest triplet and this decay process would then represent the conversion of the singlet biexciton to one triplet exciton, a significant loss. although such a process has apparently not yet been observed with certainty, in order to minimize its likelihood it is desirable although probably not essential to complement the condition expressed in equation (1) with the condition δet2 > 2 δet. in principle, the biexciton might also convert to a molecular quintet excited state, but this will hardly ever be energetically possible. after all, even the lowest molecular quintet state is a doubly excited state and the condition δeq > 2 δet is fulfilled more or less automatically. why should the wave function of the singlet biexciton change its spin part into triplet or quintet so easily when it is an eigenfunction of the electrostatic hamiltonian and only some very minor additional terms in the full hamiltonian can be responsible? the relatively facile intersystem crossing is enabled by the nearly exact degeneracy of the singlet, triplet, and quintet states of the biexciton. then, even the very weak magnetic dipole magnetic dipole interactions, familiar from electron paramagnetic resonance spectroscopy of triplets (zerofield or d, e tensor), are able to induce intersystem crossing. the levels can also be mixed by zeeman terms due to an external magnetic field and indeed, the sensitivity of singlet fission to external magnetic fields was one of its early recognized hallmarks.19 according to theory, the initial conversion should be from the singlet biexciton to the quintet biexciton, which has already been observed,20,21and then to triplet.3,19 these pathways, and the paths from the three spin states of the biexciton to free excitons and to the ground state, are currently under intense scrutiny. the separation into two independent triplet excitons that are spatially separated seems to occur by a hop of excitation in one of the triplet partners in the biexciton to a neighboring ground-state molecule, similar to the hopping motion of triplet excitons through the solid.22 molecular structure some of the structural requirements on the molecules to be used in singlet fission materials are dictated by common knowledge. the need for high absorption coefficients and absorption onset near 2.2 ev is generally satisfied by the use of extended π-electron systems. the redox properties can normally be controlled by a choice of substituents. the need for slow intersystem crossing is usually met by avoiding heavy atoms and low-lying nπ* states. suppression of fast internal conversion calls for structural rigidity and absence of structural elements with low-frequency vibrations. inspiration for light fastness is provided by industrial dyes. 51singlet fission: toward more efficient solar cells the condition that is the most difficult to meet is the location of the lowest triplet level (t1) approximately half-way between the ground (s0) and first excited (s1) singlet levels.23 in most ordinary molecules, t1 and s1 result from the same promotion from the highest occupied molecular orbital (homo) to the lowest unoccupied molecular orbital (lumo) and are separated by approximately twice the exchange integral between these two orbitals. this integral is very small for nπ* excitations and excitations with strong charge-transfer character, in which the homo and the lumo avoid each other in space. it is also small in most non-alternant hydrocarbons and in contrast, tends to be large for alternant hydrocarbons (no odd-membered cycles). thus, large alternant hydrocarbons tend to be good choices. tetracene and pentacene were recognized as suitable a long time ago, and a derivative of a large alternant hydrocarbon, terrylene, has also been recently shown to perform well.23 a more general group of compounds that was recognized early on as providing suitable candidates are biradicaloids, compounds that are part way between perfect biradicals and ordinary molecules. in the former, the s0-t1 gap is typically much smaller than half the s0-s1 gap, and in the latter, much bigger. in between, there is a range of biradicaloid structures where the two are comparable. considerations of this type led to a set of guidelines for the choice of two partially overlapping sets of chromophores that meet the energy criterion, large alternant hydrocarbons and biradicaloids.22 theoretical requirements for the use of biradicaloids have subsequently been elaborated24,25,26,27 and several biradicaloid structures have been identified as suitable candidates computationally.22,27,28,29,30 so far, only one of these proposals has been tested. the compound in question is 1,3-diphenylisobenzofuran, which was indeed found to be highly efficient.31 however, the triplet yield was up to 200% in only one of its two very similar known crystal modifications, and was a mere ~15% in the other.32 packing in the solid phase the above observation leads us to the second variable in singlet fission materials, and that is the packing of the selected molecule in the solid phase. there is ample evidence that it plays a critical role in determining the suitability of a compound as singlet fission material.34 we leave aside the difficult question of methods for enforcing a particular packing, whether by crystal engineering or synthesis of non-conjugated covalent dimers, and focus on the need to know what packing to aim for. this was not clear in the past, but recently theory has provided some advice. this is available in the form of a publicly available computer program simple,34 which finds the local maxima of the rate constant for the formation of a singlet biexciton from a singlet exciton by singlet fission as a function of all physically possible geometrical arrangements of a pair of rigid π-electron chromophores (six degrees of freedom). geometries in which the molecules interpenetrate are excluded. the output consists of the best geometries, drawn in the order of decreasing relative rate constant, and an example35 is provided in figure 4. the calculation is based on the fermi golden rule, according to which the rate is proportional to the square of the electronic matrix element for singlet exciton into biexciton conversion and the density of states at the energy of the biexciton. it involves the evaluation of the electronic matrix element at billions of geometries but is still quite fast, because it uses a series of physically motivated and tested34,36 approximations. the relative rate constants are evaluated using marcus theory, and the program has been used without problems for molecules as large as cibalackrot, with 36 atoms in the conjugated π-electron system of each member of the pair.36 a simplified version of the theory was used to develop pictorial rules for evaluating the suitability of a pair geometry, which require only the knowledge of the approximate shapes of the frontier orbitals of the molecule, homo and lumo.37,38 figure 4. multi-view projections of the nine best pairs of the c2 rotamer of 1,3-diphenylisobenzofuran optimized for the rate of singlet fission. the computed rate constants for biexciton formation relative to the rate computed for the structure actually found in the crystal, in the order 1-9, are 4306, 2944, 2261, 896, 892, 806, 717, 546, and 536. 52 josef michl inspection of the results for several chromophore choices suggests that two dominant factors determine the relative rate of singlet fission at the optimized geometries. they are, first, the size of the squared electronic matrix element, and second, the energy balance of the process. the former enters directly into the fermi golden rule and the latter, along with the reorganization energy, enters the marcus equation. the energy balance is not determined solely by molecular properties. it depends strongly on the size of the davydov splitting, the separation of the two levels into which an exciton pair is split by intermolecular interactions. after vibrational equlibration, the exciton level that is energetically lower will carry the bulk of the initial population. if it is stabilized excessively, it will not have enough energy to produce a biexciton, even if in the isolated molecule the t1 level was positioned ideally half-way between the s0 and s1 levels. instead, the exciton will decay to the ground state, radiatively or radiationlessly. the magnitude of the dav ydov splitting can be approximated as four times the electrostatic interaction between the s0-s1 transition charge densities on the two molecules, which in turn can be roughly estimated from the interaction of their transition dipoles. it vanishes when the dipoles are perpendicular to each other and this goes a long way toward an explanation of the twists seen in the optimal pair structures shown in figure 4. these geometries reflect a compromise between the tendency of the electronic matrix element to favor strong overlap of the two molecules and the proclivity of the dipole-dipole interaction to minimize their interaction and vanish at orthogonally twisted geometries. intramolecular singlet fission this survey would not be complete if we did not mention singlet fission in which the two generated triplet excitons reside in different parts of the same molecule, known as intramolecular singlet fission. when the interaction between the two covalently connected chromophores is strong, especially when the bridging unit or units are capable of π conjugation, it becomes difficult and ultimately even impossible to distinguish the now intramolecular singlet biexciton state from other intramolecular singlet excited states and the use of the term singlet fission could then be questioned. it would be unusual to refer to the internal conversion of the optically allowed bu state of 1,3-butadiene into its “double triplet” ag state as singlet fission, although their wave functions suggest it. it is not obvious just where to draw the line. a case of particular interest are conjugated polymers, but only a few recent references can be provided here.39,40,41,42,43 in such polymers, the two triplet excitations can move quite far apart on the same chain, and also jump to separate chains. it is then certainly appropriate to talk about singlet fission. as long as the two excitons stay on the same chain and only undergo a onedimensional diffusion, they have a high probability of re-encountering each other, and it is then important that they do not mutually annihilate. as discussed above, such a reverse of singlet fission would often provide ample opportunities for ultimate decay to the ground state with a release of heat. summary in conclusion, it is fair to say that singlet fission is now known to be a much more complicated process than it appeared to be before the recent spurt of activity in the field, and that there are many ways in which it can go astray. it is possible that a practical material for singlet-fission solar cells will be recognized tomorrow, but it is also possible that it will take many years. i believe that the ultimate goal, making sustainable energy less expensive than the burning of fossil fuels, is important enough to make it worth turning over every stone on the beach. it should also be recognized that by their very nature, scientific discoveries build on each other in unpredictable ways. the fundamental understanding of the photophysics of organic molecular systems that is generated in the studies of singlet fission may end up being the largest gain from the enterprise, and may turn out to be valuable in very unexpected contexts. for example, perhaps the initial spin coherence (“entanglement”) of the two triplet excitons generated by singlet fission might be utilized in quantum information science? after all, when bunsen and kirchhof discovered that the sodium d line is a doublet, their discovery must have appeared to have no practical consequences. they could not have foreseen that they have launched a process that will lead to the concepts of electron spin, nuclear spin, magnetic resonance spectroscopy, and a century and a half later, imaging of brain tumors! acknowledgement i am grateful to dr. eric buchanan for efficient help with graphics. our work on singlet fission was supported in boulder by the u.s. department of energy, office 53singlet fission: toward more efficient solar cells of basic energy sciences, division of chemical sciences, biosciences, and geosciences, under award number desc0007004, and in prague by the institute of organic chemistry and 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j. michl, j. am. chem. soc. 2017, 139, 15572. 38. e. a. buchanan, z. havlas, j. michl, bull. chem. soc. jpn., doi 10.1246/bcsj.20190229. 39. e. busby, j. xia, q. wu, j. z. low, r. song, j. r. miller, x.-y. zhu, l. m. campos, m. y. sfeir, nat. mater. 2015, 14, 426. 54 josef michl 40. s. n. sanders, e. kumarasamy, a. b. pun, m. l. steigerwald, m. y. sfeir, l. m. campos, chemistry 2016, 1, 505. 41. j. hu, k. xu, l. shen, q. wu, j.-y. wang, j. pei, j. xia, m. y. sfeir, nat. comm. 2018, 9, 2999. 42. e. lafalce, u. huynh, e. olejnik, t. p. basel, e. ehrnfreund, z. v. vardeny, x. jiang, j. photonics energy 2018, 8, 032217. 43. a. j. musser, m. al-hashimi, m. heeney, j. clark, j. chem. phys. 2019, 151, 044902. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press doi: https://doi.org/10.36253/substantia-964 received: jun 09, 2020 revised: aug 09, 2020 just accepted online: aug 11, 2020 published: mar 01, 2021 https://doi.org/10.36253/substantia-964 substantia. an international journal of the history of chemistry 5(1): 119-133, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1018 citation: kenndler e., minárik m. (2021) capillary electrophoresis and its basic principles in historical retrospect part 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis. substantia 5(1) : 119-133. doi: 10.36253/ substantia-1018 received: jul 10, 2020 revised: aug 30, 2020 just accepted online: aug 31, 2020 published: mar 01, 2021 copyright: © 2021 kenndler e., minárik m. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles capillary electrophoresis and its basic principles in historical retrospect part 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis ernst kenndler1,*, marek minárik2,3 1 institute for analytical chemistry, faculty of chemistry, university of vienna, währigerstrasse 38, a 1090, vienna, austria 2 elphogene, s.r.o., cz 161 00, prague, czech republic 3 institute for analytical chemistry, faculty of science, charles university, cz 128 00, prague, czech republic * corresponding author. e-mail: ernst.kenndler@univie.ac.at abstract. here we set forth the first from a series of reports devoted to the history of capillary electrophoresis. in this opening part, we go more than two centuries back in time and revisit original discoveries of electrolysis, electrophoresis and electroosmosis. we emphasize the essential role of a brilliant invention of 1799 by alessandro volta, the voltaic pile, basically the first battery delivering a constant-flow electricity, which has made all the scientific advances in the subsequent years and decades possible. we describe the experiments of william nicholson and anthony carlisle revealing electrolytic decomposition of river water followed by enlightened investigations by nicolas gautherot, ferdinand frédéric reuss and robert porrett that each independently and unaware of the works of the other uncovered the phenomena of electrophoresis and electroosmosis. we give not only a technical description and a chronological overview of the inventive experiments, but offer also some formidable details as well as circumstances surrounding some of the initial inventors and their observations. we conclude this time period, for which we coin the term “1st epoch of electrophoresis”, with the same year 1914 as the astonishingly coincident period of the european history between the french revolution in 1789 and the begin of the first world war, termed the “long 19th century” by the british historian eric hobsbawm. we accentuate the surprising fact that over this entire cycle of 125 years no attempts were taken to utilize the findings and newly acquired knowledge to perform an electric driven separation of compounds from a mixture. in the field of electrophoresis and electroosmosis, it is rather the epoch of pure than of applied science. keywords: capillary electrophoresis, history, discovery, electroosmosis, electrolysis. preface electrophoresis is the motion of electrically charged particles, which are dispersed in a liquid, and which drift relative to the fluid under the influhttp://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 120 ernst kenndler, marek minárik ence of a spatially uniform electric field.1 capillary electrophoresis is the version of electrophoresis in which the liquid is inserted into a narrow open tube.2 the liquid dispersion can be a solution of ions, an emulsion or a sol of colloids or – in rarer cases – a suspension of coarse granular particles, a noteworthy differentiation, which is often ignored (colloids do not form solutions; please pay heed to footnote3). notwithstanding that nowadays electrophoresis is nearly exclusively used as a separation method, the term electrophoresis classifies the electrically driven movement of charged particles of any size in liquids in a general meaning. electroosmosis (also named electro-endosmosis in the past), can be seen as the reverse phenomenon compared to electrophoresis. hence, electroosmosis is the motion of a liquid around an electrically charged surface in response to an applied electric field.4 the electrically 1 we do not always use the iupac recommendations (ref. [1] iupac, compendium of chemical terminology gold book, online version https://goldbook.iupac.org/ ed., 2014 [2] t. a. maryutina, e. y. savonina, p. s. fedotov, r. m. smith, h. siren, d. b. hibbert, in iupac recommendations, pure appl. chem. ; 90(1): 181–231, 2018.) because in some (rare) cases they are incomplete, ambiguous or out-of-date.) 2 it is a matter of fact that no general definition exists for the inner diameter (i.d.) a narrow tube must possess to be considered as a capillary. in separation methods capillaries are open tubes with i.ds. of about 100 to 300 µm in capillary gas chromatography (gc), at the time of the replacement of the packed gc columns (which had i.ds. of 2 to 5 mm) by capillaries, so-called wide bore capillary columns with i.ds. of 540 µm were commercially offered. in modern instrumentation of capillary electrophoresis, the open tubes have i.ds. ranging from 25 to 100 µm, but also those with 5 µm i.d. are applied in zone electrophoresis and of 300 µm in isotachophoresis. the dimensions mentioned serve only as orientation for the reader. 3 we use the following terminology for these liquid systems in the present paper: the generic term for the different types of the particle-solvent systems is dispersion. in a dispersion the particles are distributed in a continuous medium (in electrophoresis the continuous medium is usually a liquid). depending on the size of the particles, the following kinds of dispersions can be differentiated: (i) solutions, (ii) emulsions and sols, and (iii) suspensions. ad (i) small particles of molecular size (with typical radii in the range of several 10-10 m) e.g. stemming from electrolytes (either from solids like salts or from liquids like some pure low molecular weight saturated carboxylic acids) form a homogeneous mixture with the liquid, which is termed solution. ad (ii) a colloid, synonymously termed colloidal system or colloidal dispersion, consists of a heterogeneous mixture of two phases, where the dispersed particles which are also named colloids are larger than small ions; their sizes range between about 10-9 and 10-6 m. solid colloidal particles dispersed in liquids form sols, liquid colloidal particles form emulsions. note that a colloidal system consists – in contrast to solutions of two different phases, which are separated by an interface. ad (iii) particles which are larger than colloids form suspensions as heterogeneous dispersions in the liquid. other than solutions and colloids, the particles sediment during long-standing periods. a special case are gels in which liquids are dispersed in solids. 4 other electrokinetic phenomena are the streaming potential and the streaming current, the sedimentation or centrifugation potential gradicharged surface could be an inner wall of a capillary, a membrane, a porous plug or an immobilized set of particles. electroosmosis plays an important role in practical capillary electrophoresis, because its flow velocity adds to the velocity of the charged particles. review papers on capillary electrophoretic methods (e.g. refs. [4-8] and others) usually mention only briefly the historical background on which the electrically induced migration of ions or colloidal particles is based. although we assume that in the majority of cases in practice the basic principles are known, we wish to lay out an investigatory tale of the development of the technique from a more general perspective including some noteworthy historic facts such as that – contrary to the widely accepted perception – electrophoresis in open narrow glass tubes with a few hundred micrometers inner diameter (today widely recognized as capillary electrophoresis) is not an invention from the 1960s. in fact, it was first systematically carried out nearly a century prior, viz. in the years 1860 and 1861 by t. jürgensen[9] and by g. quincke,[10] albeit not for separation purposes. thus, we here put forward a retrospect of the history of (capillary) electrophoresis from a broader perspective. in our opinion, this long period can be subdivided into three distinctive epochs: in the 1st epoch of electrophoresis (whereby electrophoresis was not named as such over the entire period5) the focus of the research was directed to the basic physical and chemical principles, hypothesis, theories and laws of the electrically-induced migration of charged particles in liquids, and of the electroosmotic movement of liquids. the decisive characteristic of this 1st epoch is a lack of intent to use electrophoresis as a separation method. this epoch commenced by the discoveries of electrolysis, electrophoresis and electroosmosis. it was rendered possible by an invention of a tool that enabled these discoveries, viz. a source of constant-flow electricent, the colloid vibration potential, and the electrokinetic sonic amplitude. they do not play a role in the present topic. readers are referred for details to ref. [3] j. lyklema, fundamentals of interface and colloid science. vol. ii: solid-liquid interfaces, vol. 2, academic press, london, san diego, 1995. 5 as typical examples we mention that f. kohlrausch, who was one of the leading scientist in the area of ion migration, entitled his paper from 1893 “über die geschwindigkeit elektrolytischer ionen” (on the velocity of electrolytic ions), ref. [11] f. kohlrausch, ann. phys. chem. 1893, 50, 385-408., and that from 1897 which served as base for the understanding of the different electrophoretic separation methods “ueber concentrations-verschiebungen durch electrolyse im inneren von lösungen und lösungsgemischen” (on concentration shifts due to electro lysis inside solutions and mixtures of solutions”), ref. [12] f. kohlrausch, ann. phys. chem. 1897, neue folge band 62, 209-239. both papers deal with ion migration, not with electrolytic processes. 121capillary electrophoresis and its basic principles in historical retrospect ity by alessandro volta in 1799, the voltaic pile, which transformed chemical into electric energy. however, we let this 1st epoch begin even earlier, that is to say by the initiation of voltá s ideas of a new kind of electricity which contrasted the misinterpretation of the wellknown frog experiments by luigi galvani in the 1780s. during the 125 years following galvani ś experiments and the invention of voltá s pile electrophoresis was applied solely to study the physical and chemical properties of pure compounds. surprisingly, although all principles that govern the migration of ions and of dispersed colloidal particles in free solutions6 were already progressively known, no attempts were made to apply them to separate constituents of mixtures. this 1st epoch lasted until the midst of 1910 with the first intentional use of electrophoresis to perform separations in free solutions and it is the time period covered by the first series of our historical expeditions. due to his reading of the political works of the prominent british historian eric j. e. hobsbawm,7 one of the present authors (e.k.) ascertained the remarkable coincidence of the duration of this 1st epoch with an era referred to as the “long 19th century” in political sciences, specifically the time between the french revolution in 1789 and the begin of the first world war in 1914. the term long 19th century was introduced as a kind of a 6 we are fully aware of the fact that only ions can be dissolved and exist then in free solution, but colloidal particles are forming emulsions or sols, not solutions. however, we further use for the sake of convenience the attribution free solution also to colloidal particles. 7 eric john ernest hobsbawm [1917 (alexandria, egypt) 2012 (london)] was a british historian with marxist orientation. the family of his father, named obstbaum (verbatim in english translation “fruit tree”), had migrated from austria to great britain and modified the name to hobsbawm. the father got a position in the sultanate egypt, which was a british protectorate at that time. his mother came from a wealthy viennese family. after the first world war, the family went back to vienna, where they lost their assets due to the gigantic inflation at that time. after the death of his parents (the father died in 1929, the mother in 1931) relatives took hobsbawm to berlin, where he came in contact with the german communist party. in 1933, the family went to london. for the following years hobsbawm received a stipend for cambridge, where he became member of communist party of great britain, what he remained livelong. in 1947, hobsbawm became lecturer at an evening school at london university, the birkbeck college. during this time, he published jazz-critiques in new statesman under the pseudonym francis newton. after publication of his tetralogy between 1962 and 1987 (ref. [13] e. j. e. hobsbawm, the age of revolution: europe: 1789–1848. ref. [14] e. j. e. hobsbawm, the age of capital: 1848–1875. ref. [15] e. j. e. hobsbawm, the age of empire: 1875–1914. ref. [16] e. j. e. hobsbawm, the age of extremes: the short twentieth century, 1914–1991) about the history of the 19th and the 20th century he became known worldwide. for the time period between 1789 and 1914, described in the first three volumes of his tetralogy, the term the long 19th century was coined, that described in the fourth volume over the years between 1914 and 1991 was termed the short 20th century. not until 1971 he was appointed professor in london, where he died at the age of 95. clamp for the first three volumes of hobsbawn’s tetralogy on the history of the 19th and of the 20th century. [13-15] due to this astonishing temporal co-occurrence we have adopted the term long 19th century for the 1st epoch of electrophoresis, which is the topic of the first series of our retrospect. the 2nd epoch of the history of (capillary) electrophoresis we let begin with its first intended utilization as separation method in the midst of 1910, and this period lasted till the 1990s. for the 2nd epoch of electrophoresis we adopt the name, the “short 20th century”, from the fourth volume of eric hobsbawn’s tetralogy entitled the age of extremes: the short twentieth century, 1914–1991.[16] in this book, the short 20th century was defined as the time period between the begin of the first world war in 1914 and the collapse of the ussr in 1991. during this time various electrophoretic methods were developed for the separation of ionic and colloidal particles. a notable highlight was the spectacular separation of serum globulins by arne tiselius in 1937 (awarded the nobel prize in 1948) by using the moving boundary method in free solution (which is one of the variants of electrophoresis). nota bene that the separation followed the principles of the “beharrliche funktion”, the regulating function, derived by friedrich kohlrausch already in the previous 1st epoch (viz. in 1897).[12] it is to mention that during the first part of this 2nd epoch most of the electrophoretic separations were not carried out in free solutions, they applied supporting or separating materials like paper, gels, etc. in contrast, our main interest is directed on electrophoresis in the capillary format in free solution, which was introduced in the 1960s. this method obeys the laws of the traditional electrophoresis in free solution, those which were derived during the long 19th century, and were refined at the begin of the short 20th century (e.g. by the concept of the chemical activity). in the 1960s several variants of capillary electrophoretic techniques were established, mainly by the pioneering work of frans everaerts and his coworkers in eindhoven with isotachophoresis (see e.g. ref. [17]), and by stellan hjertén in uppsala with zone electrophoresis (see e.g. ref. [18]). these methods, (interestingly both were suggested by nobel laureates, a. j. p. martin and arne tiselius, respectively) were performed in open narrowbore tubes with inner diameters down to ca. 200 µm. at this time, isotachophoresis (persistently called displacement electrophoresis by hjertén), became the dominant variant, while capillary electrophoresis itself played only a niche role compared to well-established chromatography and gel-based electrophoresis. 122 ernst kenndler, marek minárik the 2nd epoch was concluded in the late 1980s with the advent of a new capillary material – amorphous quartz, named fused silica – which has led to a sudden increase of interest in the separation methods community. the favorable mechanical, optical and surface properties of this material, which has extensively been exploited in gas chromatography, facilitating an enormous separation capability and a highly sensitive detection of extremely low quantities of analytes, prompted the commercial availability of a number of different user-friendly instruments. consequently, capillary electrophoresis, especially the zone electrophoresis version, became a member of a family of the high performance separation methods the short 20th century, lasting only 75 years from midst 1910s to about 1990, was followed by that we are consequently terming the 3rd epoch of electrophoresis, which brought an outstandingly large number of innovative experimental and instrumental approaches as well as novel applications. coupling to mass spectrometry has brought a new dynamic to capillary zone electrophoresis. perhaps the outmost notable achievement was a transfer of the classic size-based separation of dna fragments from slab-gel electrophoresis into capillary electrophoresis mainly enabled by the introduction of linear entangled polymers as replaceable sieving matrices. this progress enabled, to mention only one wellknown example, the execution of the human genome project, which started 1990 and completed officially 2003 with the determination of the entire dna sequence of the euchromatic human genome. in the present 3rd epoch, capillary electrophoresis is an indispensable tool in nearly all scientific disciplines, in life sciences for instance in genomics, proteomics and metabolomics. since current research is the topic of this 3rd epoch, we will not include it in our historical retrospect. this time is rather the theme of a topical, not of a historical review. following this brief overview, we will now return back to the dawn of the discoveries of the electric phenomena in the early decades of the long 19th century, to the period between the late 1780s and the midst 1810s. at the turn to the long 19th century until the end of the 18th century the sources of electricity were electrostatic generators or electrostatic machines. these devices transformed mechanical work into electrical energy by a process of generation of charge by friction and induction. one such a device was invented in the 1760s by the swedish physicist johan carl wilcke (wilke in his papers written in german language)[19-21] and re-invented and improved by alessandro volta in 1775 who named it elettroforo perpetuo. it was a simple generator of static electricity by induction, which became very popular as electrophore or electrophorus.8 a drawing of an electrophore is shown in figure 1. it consists of two plates.9 the bottom plate, the cake or sole, is a dielectric, i.e. an electrically non-conductive material. a detailed instruction for the preparation of an electrophorus in a book from 1814[23] recommends a resinous “cake” of about half an inch thickness, formed by melting equal parts of resin, shellac and venice turpentine10 together. the upper part (the “cover”) is a metal plate with an insulated handle, comparable with the plate of a capacitor. electricity is generated by electrostatic induction (see footnote 11). the generated electricity could be stored e.g. at a special cylindrical capacitor, the leyden jar. though this 8 we have chosen this device, because it demonstrates the principle of the generation of static energy in a very simple form. in addition, we accentuate that the term electrophore points to the little known fact that a word combined from greek ήλεκτρον (‘elektron’), and ϕέρω (‘phero’), freely translated as “the bearer of electricity”, was in use already in the 18th century. it was not a new term when it was introduced at the begin of the 2nd epoch of electrophoresis for the method under discussion in the present paper. 9 an early description of this popular device is given e.g. in chapter iv, p. 380.389, from ref. [22] t. cavallo, a complete treatise of electricity in theory and practice with original experiments, edward and charles dilly, london, 1777 or later in 1814 on p. 121-122 of ref. [23] g. j. singer, elements of electricity and electro-chemistry, london, 1814. in this book, a large number of practical experiments are describes. a further description is given in the section ”l´électrophore” in chapitre ix. des electricités dissimulées. in vol. 1, pp. 571-575, of jean-baptiste biot´s textbook of experimental physics from 1821 (1st ed. in 1817, (ref. [24] j.-b. biot, précis élémentaire de physique expérimentale. tome i, vol. 1, 2nd ed., deterville paris, 1821.) 10 venice turpentine is a highly viscous oleoresin, a mixture of bicyclic diterpenoid compounds, mainly with carboxylic and alcoholic functional groups. it is collected from the exudate of the european larch in tyrol, austria. it must not be confused with oil of turpentine, which is a mixture of liquid monoterpenes. 11 for the generation of electricity, the upper surface of the earthed bottom resin plate becomes negatively charged by rubbing, e.g. by a piece of dry fur (cat´s skin is the best, according to ref. [23]), or a piece of wool. then, the metal plate is placed on the “cake”, and becomes positively charged by induction at the surface directed towards the cake, and negatively at the opposite surface of the metal. the plate is taken off from the cake, then the upper, opposite surface is touched with a finger, causing the transfer of the negative charge to ground. at the metal plate only the positive charge formed by induction remains. it can then be, for example, transferred to a leyden jar. this operation can be repeated many times without the need to rub the resin again, and was therefore termed by volta elettroforo perpetuo (perpetual electrophorus). 123capillary electrophoresis and its basic principles in historical retrospect capacitor was able to deliver large electric potentials,12,13 it’s capacity to store static electric energy was low, which required frequent recharging for use over longer period of time. the capacity could be increased by connecting several jars in parallel, forming a leyden battery in this way.14 however, the need for recharging remained and, further to its disadvantage, the discharge current did not remain constant. a new aspect for the generation of electricity was unintentionally opened up by luigi galvani ś false conclusions of his experimental results. galvani,15 professor of anatomy in bologna, investigated since early 1780s the effect of electricity on animals. galvani ś findings, which he misinterpreted, were the prelude for the invention of a revolutionary new source of electricity by alessandro 12 in the literature, voltage has normally been used to describe the electric potential difference. according to iupac “…this term is discouraged, and the term applied potential or (electric) potential should be used instead for non-periodic signals…” (pac, 1985, 57, 1491 (recommended terms, symbols, and definitions for electroanalytical chemistry (recommendations 1985)), p. 1505). in order to avoid confusion, we prefer to use the term (electric) potential difference if appropriate. 13 with replica of historical leyden jars potential differences of several ten thousand volt were obtained. 14 we consider n capacitors, i, connected in parallel, and use the symbols u for potential, q for charge, and c for capacity. then utot = ui ; qtot = σqi ; ctot = σci. this connection in parallel is applied to increase the capacity of the leyden battery. upon discharging of the capacitor, the discharge current, i, decreases exponentially with time, t, according to i(t)=-i0 e-t/t; t is the time constant of the discharge process. 15 luigi aloisio galvani [(1737) bologna, papal states, at present italy 1798], (in latin aloysius galvanus) was an anatomist, physician, physicist, physiologist and biologist. volta. the story began with an observation of one of galvani ś students, who touched with the tip of a scalpel a lumbar nerve of a dead skinned frog which was placed nearby an electrostatic machine. this accidental contact caused a convulsive twitching of the frog ś legs as if alive. galvani, who assumed a context of this contraction with electricity, commenced in 1789 a series of experiments by which he noticed that the muscles of the frog ś legs were contracted even in the absence of an electrostatic machine. they also twitched when they were connected by contacts made of two different metals (e.g. of copper and iron).16 galvani postulated that the source of this contraction was a new kind of electricity, which he termed animal electricity. he believed that this new energy was intrinsic to the body of the dead frog, and hypothesized that the frog ś brain produced electricity, and its body acted as a kind of electric condenser. he further assumed that the nerves are the conductors which transmit the electricity to the muscles. galvani published his findings in 1791 in “de viribus electricitatis in motu musculari commentaries” (“commentary on the effects of electricity on muscular motion”),[28] which attracted extraordinary attention by his scientific colleagues, amongst them also by alessandro volta.17 the voltaic pile volta was highly experienced in the field of static electricity, and was initially convinced by the existence of the animal electricity, but since summer 1892 he began to doubt galvani ś hypothesis of animal electricity. volta, in contrast, supposed, that the source was the contact electricity originating from the metallic wires in connection with the interposed body fluid of the frog as a conducting medium. he executed experiments with different metals and was able to measure even very low quantities of electricity when the metals were brought into mutual contact.18 [31] 16 very detailed descriptions of galvani´s observations are given e.g. in ref. [26] e. du bois-reymond, untersuchungen über thierische elektricität, vol. 1, g. reimer, berlin 1848., and in ref. [27] o. e. j. seyffer, geschichtliche darstellung des galvanismus, j.g. cotta, stuttgart und tübingen, 1848. 17 alessandro giuseppe antonio anastasio volta, [1745 (como, at present northern italy) 1827], since 1810 count volta; since 1774 professor of physics at the royal school in como, and professor in natural philosophy, and chair in experimental physics at the university of pavia since 1819. 18 the measurement of very low quantities of electricity was possible by a device which combined a condenser – which volta constructed and built – with an electrometer created by tiberius cavallo (described in his book, ref. [22] t. cavallo, a complete treatise of electricity in theory and practice with original experiments, edward and charles dilly, lonfigure 1. drawing of an electrophore or electrophorus (volta termed it elettroforo perpetuo), a device for the generation of static electricity by induction. for explanation, see footnote 11. taken from ref. [25]. 124 ernst kenndler, marek minárik he also found that the quantity of the generated electricity was higher when the two metals were separated by a third, non-metallic conductor, for example by a 2nd class conductor like a piece of paper soaked with salt solution. [32, 33] thus, volta argued that the nerves in galvani ś experiments were stimulated by the electricity delivered by the communicating metals,[34] not by animal tissues, and believed in what he coined metallic electricity instead of galvani ś animal electricity. the debate between the two scientists ultimately led to the refusal of galvani ś idea of an animal electricity (which was, with voltá s generous agreement, further named galvanic electricity, and its topic galvanism; for details, see e.g. ref. [35]). the seminal result of voltá s investigations of his metallic electricity was the creation of an electric element, which transformed chemical into electric energy.19 in contrast to the leyden jar, voltá s device enabled the generation of a continuous and constant-flow electricity. in 1800 volta described the battery, a stack of assembled electrochemical elements later named voltaic pile, in a detailed paper titled “on the electricity excited by the mere contact of conducting substances of different kinds”.[37] he sent the description of the pile as a letter dated march 20, 1800 to the president of the royal society, sir joseph banks. the letter was read june 26, 1800 befor the royal society in london.[38] following we include the verbatim reproduction of the first two paragraphs from voltá s letter to banks with its exemplary clear description of the battery, and illustrate this explanation in figure 2. …in prosecuting his experiments on the electricity produced by the mere contact of different metals, or of other conducting bodies, the learned professor was gradually led to the construction of an apparatus, which in its effects seems to bear a great resemblance to the leyden phial, or rather to an electric battery weakly charged; but has moreover the singular property of acting without intermission, or rather of re-charging itself continually and spontaneously without any sensible diminution or perceptible intervals in its operations. the object of the don, 1777. volta´s device was presented for the royal society in london, read march 14, 1782, entitled “del modo di render sensibilissima la piu debole elettricità sia naturale, sia artificiale” (ref. [29] a. volta, phil. trans. roy. soc. (london) 1782, 72, 237-280. (“of the method of rendering very sensible the weakest natural or artificial electricity”) and ref. [30] a. volta, phil. trans. roy. soc. london. part i 1782, 72, 453 (vii-xxviii). this sensitive device was also essential for volta´s research on his pile. 19 sir humphry davy, [1778 (penzance, cornwall, england) 1829], teacher and mentor of michael faraday, said volta’s work was “an alarm bell to experimenters all over europe” (see e.g. ref. [36] c. russell, in chemistry world, vol. 1 august 2003, royal society of chemistry, 2003.). present paper is to describe this apparatus, with the variety of constructions it admits of, and to relate the principal effects it is capable of producing on our senses. it consists of a long series of an alternate succession of three conducting substances, either copper, tin and water; or, what is much preferable, silver, zinc, and a solution of any neutral or alkaline salt. the mode of combining these substances consists in placing horizontally, first, a plate or disk of silver (half-a-crown, for instance,) next a plate of zinc of the same dimensions; and, lastly, a similar piece of a spongy matter, such as pasteboard or leather, fully impregnated with the saline solution. this set of threefold layers is to be repeated thirty or forty times, forming thus what the author calls his columnar machine. it is to be observed, that the metals must always be in the same order, that is, if the silver is the lowermost in the first pair of metallic plates, it is to be so in all the successive ones, but that the effects will be the same if this order be inverted in all the pairs. as the fluid, either water or the saline solution, and not the spongy layer impregnated with it, is the substance that contributes to the effect, it follows that as soon as these layers are dry, no effect will be produced.” as depicted in figure 2 any number of elements can be combined in order to increase the total electric potential of the pile. in his letter volta described that each element consists of a pair of discs made from three materials, viz. from two different metals and a layer of a matter wetted with water or saline solution; the elements can be stapled about each other.20 at the uppermost and the lowermost disc, respectively, metal wires are attached, and each of these elements contributes additively to the electric potential of the pile by its individual potential which depends on the kind of the metals.21 effects of 20 in each single volta element in figure 2 zinc is oxidized to zn2+, and releases 2 electrons. for the electrochemical reduction at the silver electrode several reactions are possible. if the silver plate is covered by a layer of silver oxide or silver salt (as it is when e.g. used half-a-crown coins are applied, as mentioned in volta´s letter), ag+ can be directly reduced. in absence of silver ions, e.g. when the plate is polished, oxygen from air or hydrogen ions from the impregnation solution can be reduced. 21 in the voltaic pile the elements (also named cells) are connected in series, i.e. the plus pole of the one element is connected with the minus pole of the adjacent element. all elements are flown through by the same current, which has the disadvantage that it is determined by the element with the lowest current. in the worst case the potential fails if one element is defective. the total electric potential difference of the series of elements of the battery is equal to the sum of the potentials differences of its single elements. the potential difference of an element made for instance from zinc and copper is about 1.1 volt. thus, in a staple of say 10 elements the applied potential is about 11 volt between the two extreme discs. when the elements are connected in parallel (which is not the case in the voltaic pile), i.e. when the plus pole of the one element is connected with the plus pole of the adjacent one, and the minus pole with the minus pole, the load capacity of the battery (in a.h, ampere hours) is the sum of the load capacities of the single elements. the total electric 125capillary electrophoresis and its basic principles in historical retrospect electricity on solutions could be investigated by immersing the wires̀ tips of the pile into the liquid, where they act as the electric poles.22 at last, we want to contrast volta’s story of his triumphant scientific successes – among many other honors he was made a count in 1810 by napoleon after the conquest of italy – with a largely unknown and rather tragic-comic story, which is a matter of the metallic electricity volta discovered. as early as in may 1793 john ribison, [1739-1805], a british professor of natural philosophy at the edinburgh university (he was physicist and mathematician) reported a peculiar experiment in a letter[39] sent to alexander fowler, the editor of “experiments and observations relative to the influence lately discovered by m. galvani, and commonly called animal electricity”,[40] (translated into german in ref. [41]). the experiment was carried out by ribisoǹ s son, who brought a piece of silver and a piece of zinc in contact with his tongue and felt a strong stimulus, similar to a taste. ribison repeated this experiment and obtained the same result. he was aware about some curious discoverpotential difference of the battery is equal to the electric potential difference of the single elements in case of their connection in parallel. 22 in the contemporary literature, the terms electrode and electrolyze were unknown; they were proposed about three decades later by m. faraday. the term pole was used in analogy to the poles of a magnet. ies which had been made in italy some time ago, but he had no further knowledge of what was going on in the recent years. we describe here only some of the experiments which he reported in the letter. in one particular experiment he felt the same irritation at the tongue as already mentioned above when he placed a piece of zinc, in contact with a piece of silver at any other part of the mouth, the nose, the ear, the urethra or the anus. also he applied a piece of zinc onto a wound of a toe, and a piece of silver to the tongue, and each time when he brought the metals in contact he felt a painful irritation at the wound where zinc was placed. next, ribison applied a rod of zinc and one of silver to the roof of the mouth. upon connecting the ends of the rods, he felt a painful, convulsive pruritus, together with a bright refulgence in the eyes. finally, robison made a number of pieces of zinc of the size of a shilling-coin and formed a roll with an equal number of silver shillings. he observed under certain conditions an intensified irritation at the tongue, which was increased when the tongue touched all pieces of the metals at the side of the roll, effects which sourced from contact electricity. ribisoń s report ended with his regret that he was not able to continue his experiments due to his indisposition. one might speculate that under more favorable circumstances he possibly invented an electric battery even few years prior to volta. the decomposition of water by electricity: the discovery of electrolysis volta sent his above mentioned letter in two separate parts to sir joseph banks in london. after receipt of the first part of this letter, banks has shown its first pages to antony carlisle.23 it was already known that electricity can be sensed as electric “shocks”, e.g. when electrostatic batteries were getting in touch with wetted hands or with the tongue. based on the description in the letter, carlisle assembled a pile, and – together with his friend william nicholson24 – repeated on april, 30 several experiments which were described in voltá s letter (a 23 anthony carlisle [1768 (stillington, england) – 1840], an english surgeon, was professor of anatomy of the royal society from 1808 to 1824. as a matter of curio we mention that carlisle is probably the anonymous author of the gothic novel the horrors of oakendale abbey, published in 1797 and previously attributed to “mrs. carver”. 24 william nicholson [1753 (london) – 1815], an english chemist, founded the journal of natural philosophy, chemistry and the arts in 1797 (known as nicholson’s journal). it was the first english monthly scientific journal. figure 2. drawing of volta´s piles combined from 8, 16 and 32 elements, respectively, consisting of pairs of zinc (z) and silver (a) discs. in these piles, the elements or cells are formed by a pair made from two discs of different metals which are in direct contact, in this figure of silver, a, and zinc, z, communicating with the next pair by an interposed spongy matter (e.g. a piece of cloth, leather, or pasteboard) moistened with a salt solution. the elements are stapled one upon the other, here with a silver disc as the lowermost, and a zinc disc as the uppermost one. taken from ref. [37]. 126 ernst kenndler, marek minárik graphical interpretation of their experiments is shown in figure 3). nicholson subsequently reported[42] this pile gave us the shock as before described, and a very acute sensation wherever the skin was broken. our first research was directed to ascertain that the shock we felt was really an electrical phenomenon. for this purpose the pile was placed upon bennett’s gold leaf electrometer, and a wire was then made to communicate from the top of the pile to the metallic stand or foot of the instrument. … in all these experiments it was observed, that the action of the instrument was freely transmitted through the usual conductors of electricity, but stopped by glass and other nonconductors. very early in this course, the contacts being made sure by placing a drop of water upon the upper plate, mr. carlisle observed a disengagement of gas round the touching wire. this gas, though very minute in quantity, evidently seemed to me to have the smell afforded by hydrogen when the wire of communication was steel. being interested whether or not this release occurs also when the wires were placed separated from each other, in a series of experiments carlisle and nicholson filled river water into a glass tube, and plunged the two wires in a distance of several centimeters from each other into the water. upon closing the electric circuit, an effect which surprised the experimenters was observed, viz. that at one of the wires a fine stream of bubbles of oxygen, at the other wire bubbles of hydrogen evolved.25 after testing wires made of several different metals, the most distinct result was obtained with platinum or gold. it was obvious that the evolved gases must originate from the water, but the question raised how the gaseous hydrogen or oxygen could be invisibly transported through the liquid water to the opposite pole when they were formed – as initially assumed – at one and the same pole and from the same individual water molecule (for more details of this anecdote the readers are recommended to ref. [36]). since it was evident that the two gases are products of the disintegration of water, carlisle and nicholson 25 it has to be mentioned that the decomposition of water by electricity, albeit not by an electrochemical reaction, was already carried out prior to the invention of the voltaic pile, viz. by electric machines. george pearson reported in 1797 the experiments made by the dutch chemists adriaan paets van troostwyk and j. r. diemann, assisted by john cuthbertson (see ref. [43] g. pearson, phil. trans. roy. soc. (london) 1797, lxxxvii, 142-157.; and ref. [44] g. pearson, journ. nat. philos chem. & arts 1797, 1, 241-246. ). cuthbertson was a highly qualified maker of scientific instruments and fellow of the philosophical society of holland and utrecht. in the cumbersome and laborious experiments electric sparks generated by a leyden battery were induced in succession in liquid water, which was decomposed into gaseous oxygen and hydrogen in measures of one to two. after collecting a sufficiently large quantity of the liberated gases, a spark was sent through them, causing their inflammation and the reconversion into liquid water. observed for the first time an electrochemical decomposition, which was later – as proposed by michael faraday – termed electrolysis. nicholson published the results26 prior to the publication of voltá s letter[37] – in a paper entitled “account of the new electrical or galvanic appa26 the first public report about these experiments appeared in the “morning chronicle”, a london newspaper, on may 30, 1800. the authors found this information in otto ernst julius seyffer´s “geschichtliche darstellung des galvanismus”, (“historical presentation of the galvanism”), published in 1848, ref. [27] o. e. j. seyffer, geschichtliche darstellung des galvanismus, j.g. cotta, stuttgart und tübingen, 1848. the book contains about 640 pages and describes in detail the history of the galvanism, from its first observation by j.g. sulzer as soon as in in 1760 in berlin, and galvani in 1790, till 1845, with addition of some sources till 1847. it describes the contributions of about 600 authors (including the source of their publications), it circumstantiates detailed experimental set-ups, procedures and results in many contributions, it describes the reception of the results, controversial discussions between the authors, and puts them into the historical context. this is, in the opinion of the authors, an enormous achievement of seyffer, considering the difficulty to get access at that time to the large number of different german, english, french, italian and russian journals. figure 3. an illustration of an experiment of electrolysis by william nicholson and anthony carlisle on may 2, 1800, by decomposing water by electricity of a voltaic pile. taken from ref. [45], “la pile de volta”, chapter iii, p. 629, fig. 324. 127capillary electrophoresis and its basic principles in historical retrospect ratus of sig. alex. volta, and experiments performed with the same” in 1801 (in the july 1800 issue) in journal of natural philosophy, chemistry, and the arts.[42] it is to be stated that the observations which were made by nicholson and carlisle in april and may 1800 introduced electrochemistry as a new scientific discipline. the spectacular invention of volta (and the effect of electricity on the decomposition of water) was rapidly communicated by the scientist across europe, and provoked an eminent impulse for research in this novel discipline. although the fact of the decomposition of water at the poles was corroborated by the formation of the gas bubbles, the transport of the electricity27 through the solution remained completely unintelligible. in the course of the various experiments which were executed by numerous researchers in europe other phenomena that could occur between the two poles of voltá s pile were discovered. the observation of these phenomena was facilitated because they could directly be followed visually. it was the migration of dispersed coarse granular particles, and – under certain conditions – the electrically induced movement of the liquid. the former phenomenon is now known as electrophoresis, the latter as electroosmosis.28 the discovery of electrophoresis and electroosmosis by n. gautherot, f.f. von reuss and r. porrett until the midst of the 19th century, robert porrett29 was accounted as the discoverer of electroosmosis. this attribution was based on a paper which he published in 1816, entitled “curious galvanic experiments”[46] (in 1820 in german).[47] in one of the described experiments, porrett divided a glass jar by a bladder, obtaining two separated chambers in this way. when he filled one chamber 27 at that time and later the flow of the electric current was named the transport of electricity. however, transported are the charges, either by the electrons in 1st class conductors like metals, or by ions or other charged particles in 2nd class conductors, e.g. in electrolyte solutions or in melted salts. for historical reasons, we temporarily also use the term transport of electricity. 28 it is pointed out that the terms electrode, electrolysis, electrophoresis, electroosmosis, to name a few, were not known at that time. the first use of the term electro-endosmosis or electroosmosis was initiated in the 1830s, the term electrophoresis one century later. we use these terms (ahistorical) in the present paper when it serves for its better readability. 29 robert porrett jr. [1783 (london) – 1868] was chief administrator of the armory of london tower by profession. he was member of the society of antiquaries and fellow of the chemical society. interested in chemistry and physics, he obtained thiocyanic acid from prussian blue (berlin, parisian, paris or turnbull’s blue, iron(ii,iii) hexacyanoferrate(ii,iii)) upon reaction with potassium sulfide. and examined, amongst others, the chemistry of compounds containing iron and cyanide. with water the other chamber remained dry even when left for several hours as the water did not penetrate the bladder. next, porrett put a few drops of water into the empty chamber, just covering its bottom. then he used a voltaic pile connecting the positive pole to the waterfilled chamber and the negative pole to the chamber with wet. porrett then observed that water was transferred from the water full chamber through the bladder divider into the nearly empty chamber, resulting, within half an hour after completion of the electric circuit, in equal water levels in both chambers. this transport process further continued, raising the level in the negative chamber ¾ of an inch above the level of the positive chamber. without having an explanation for this phenomenon porrett named it electro-filtration. with our hindsight it is evident that the water transport observed by porrett was by electroosmosis due to the electric double layer formed in the pores of the bladder. the discovery of electroosmosis has been attributed to porrett until the midst of the 19th century, when otto ernst julius seyffer referred to two experiments by ferdinand frédéric reuss (ferdinand friedrich von reuß)30 published about one decade prior to porrett, but which up to that moment were nearly unnoticed so far by the majority of the scientific community. in his book from 1848 seyffer identified reuss as the discoverer of electrokinetic phenomena.[27] as reminded by seyffer, reuss described the execution of two experiments in publications which appeared in a russian journal in 1809 (in french)[48] and in 1821 (in latin).[49] the first publication was entitled “sur un nouvel effet de l’ électricité galvanique”, the paper from 1821 “electricitatis voltanae potestatem hydragogam tanquam novam vim motricem, a se detectam, denuo proposuit ejusque in naturae operibus partes investigare tentavit” (reuss was well-known for his chemistry lectures at the university held in latin). in the first experiment reuss packed quartz sand between two platinum wires (a and b in fig. 4, top drawing) positioned as electric poles at the bottom of a v-shaped quartz tube. the tube was filled with degassed water, and the platinum wires were connected to a voltaic pile. after closing the electric circuit, reuss observed the already known decomposition of water under formation of gaseous oxygen and hydrogen at the poles. 30 ferdinand friedrich von reuß [1788-1852] was born in tübingen, germany, where he studied medicine. he finished his studies in göttingen as dr. med. et chir. and became college lecturer for general medical chemistry in 1801. he became known for his investigations of the horse lymph, which was probably the cause for the assignment to a professorship at the imperial university moscow in 1808. in addition, he was professor for chemistry and pharmacography at the imperial medico-chirurgical academy from 1817 to 1839. 128 ernst kenndler, marek minárik even mor importantly, he also observed a slow rise of the water level at the side of the tube with the negative pole b, and an according decrease of the level at the positive pole a. disconnection of the wires led to a reversal of the flow due to gravity, reconnection reproduced the initial effect of the rise of the water level. after fourteen hours, the tube at positive pole a was empty, while that at pole b was completely filled with water. after four days the experiment was concluded, the wires were disconnected and the initial state with the equal water levels was reconstituted within a few minutes. the results of this experiment unequivocally confirmed the occurrence of electroosmosis (here with a flow of the liquid towards the negative pole31), a phenomenon reuss termed motus stoechiagogus. in his second experiment reuss filled a block of moist clay into a container (a in figure 5) and inserted two glass tubes. the bottoms of the tubes were covered 31 in this experiment of reuss, the electroosmotic flow of the liquid towards the negative pole has its cause in the negatively charged surface of the quartz sand which he inserted into the tube. the sand consists of silica, polymerized silicic acid, which possesses residual silanol groups at its surface. this groups have weak acidic property and dissociate in the presence of water into negatively charged silanolate groups (≡si-o). these groups are the sources of the fixed negative charges at the surface of the quartz sand, which is the one side of the so-called electrochemical double layer. in electroosmosis positive ions dissolved in the liquid phase compensate the negative charges, but due to their thermal energy they are not rigidly attached at the solid surface, and always at least a fraction of the cations is freely movable. if a tangential electric field is applied, the free cations are attracted towards the cathode due to electric forces dragging a layer of water into the same direction, which represents the first water layer flowing by electroosmosis. due to viscosity forces, the flow impulse is transferred to each adjacent water layer into the bulk of the liquid, and within shortest time the entire liquid is flowing by electroosmosis. in the present case of quartz, water is driven by by thin layers of carefully washed sand (indicated by shaded zones in the figure), and the tubes were filled by 3 cm with water. platinum wires were inserted into the centers of the tubes through their open ends (plugged with corks), and were connected to a voltaic pile. after completion of the current, the clay first began swelling and softened to mud at the bottom of the tube with the positive pole; in the following the penetration of the sand layer by clay particles was observed under formation of a pointed mound at position a in the figure. muddy liquid was separating from the mound and formed a mud layer at the surface of the sand. this process occurred only in the tube with the positive pole, but no effect was noticed in the other tube. upon continuation of the experiment for four days, electroosmosis of water from the positive to the negative pole was observed, most probably caused by the same source as in the first experiment, viz. by the negatively charged quartz sand (see footnote 31). the question now arises whether electrophoresis or electroosmosis was causing the transport of the clay particles through the sand layer into the tube with the positive pole. reuss attributed the penetration of the clay to electroosmosis. since commonly the clay particles (like quartz the cations of the interfacial double layer towards the negative pole. it is interesting that electroosmosis was originally discovered by crystallized silica as described above, because the same material, in its amorphous form, named fused silica, is the universal choice for the common narrow open tubes used in contemporary capillary electrophoresis. in this separation method, the electroosmotic flow is a fundamental component of the separation set-up utilizing the migration of the analytes. figure 4. v-shaped quartz tube device used by reuss in his first experiment on electroosmosis. the dimension of the tube was “3 lignes de diamètre et de 7 pouces de lorgueur”, i.e. 3x2.26 mm in diameter and 7x2.706 cm in length. the stippled portion is quartz powder. a and b are the wires of the + and the – pole, respectively. reproduced from reuss, ref. [48]. figure 5. b and c are two water-filled tubes (of circ. 3 cm i. d., placed at a distance of about 14 cm), plunged in a clay base, a, the arrangement used by reuss in his second experiment on electroosmosis. the stippled portions in b and c are sand layers. the wires of the + and the – poles are immersed into the water. reproduced from reuss, ref. [48]. for details, see text. 129capillary electrophoresis and its basic principles in historical retrospect sand) are negatively charged,32 electroosmotic flow caused by the porous clay of block a in figure 3, bottom, would be directed towards the negative pole. by reason that the clay particles migrated towards the positive pole electrophoresis, not electroosmosis, was probably the cause of their migration. thus, the first observation of electrophoresis had to be attributed to reuss, and not to porrett. but by midst 19th century only few scientists drew attention to reusś work, amongst others gustav heinrich wiedemann and georg hermann quincke, reputed scientists in the field. in a paper from 1861 entitled “ueber die fortführung materieller theilchen durch strömende electricität” (“on the transport of material particles by flowing electricity”. quincke asserted that[10] … reuss in moskau beobachtete zuerst, im jahre 1807 daß ein galvanischer strom flüssigkeiten in der richtung des positiven stromes mit sich fortführte, wenn die flüssigkeit an einer stelle durch eine poröse scheidewand unterbrochen war. seine beobachtungen scheinen jedoch bis in die neuste zeit hinein wenig bekannt geworden zu seyn, so daß oft porret, der 1816 ganz ähnliche versuche beschrieben hat, als der entdecker dieser später auch wohl mit dem namen „elektrische endosmose“ bezeichneten erscheinungen angesehen wird…33 in this comment quincke referred to an unpublished lecture entitled “indicium de novo hucusque nondum cognito effectu electricitatis galvanicae” (“notice of a new, hitherto unknown effect of galvanic electricity”) which reuss held in november 1807 before the physical-medical society, instituted at the moscow imperial university of letters.[51] it should nevertheless be pointed out, that although the first observation of electroosmosis should be attributed to the 1807 work of reuss,34 porrett wrote his 1816 paper without any knowledge of its existence. 32 in his textbook from 1909, w. ostwald summarized the charge of colloidal particles as follows: “ … so erweisen sich bei reinem wasser als dispersionsmittel … als negativ: …die meisten dispersen festen stoffe wie ..., stärke, quarz, feldspat, ton, kaolin,…“; ref. [50] w. ostwald, grundriss der kolloidchemie, theodor steinkopff, dresden, 1909., p. 233 (“thus, with pure water as the dispersant … are negative: … most of the disperse solids, such as … starch, quartz, feldspar, clay, kaolin, …”). 33 “… reuss in moscow observed, in 1807, as first that a galvanic current transports liquids in the direction of the positive current, given that the liquid is divided at one position by a porous membrane. his observations, however, seem to have become little known until very recently, so that often porret, who in 1816 described very similar experiments, is regarded as the discoverer of these phenomena, later also termed electric endosmosis.” 34 a fact deserves to be mentioned which is nearly always ignored in the context of reuss` investigations about electrokinetic phenomena. it is his collaboration with the russian scientist pjotr ivanovich strakhov [1757-1813], who held the chair at the newly-created institute for experimental physics at the moscow university since 1791. strakhov was well-known – in addition to his research in other fields – for his observations of electrical conductivity of water and earth. interestingly, the history about the discovery of electroosmosis and electrophoresis does not end here. the complete story has been reported recently in a carefully researched and informative essay by christian biscombe. [52] the author referred to yet another nearly disregarded report by nicolas gautherot, which found only a passing mention by humphry davy in his bakerian lecture,35 read november 20, 1806 (ref. [53], p. 20). gautherot was born in 1753 in is-sur-tille (côte-d’or), france, in a poor family. he became a well-known composer and musician by profession (in 1799 he published a book entitled “théorie des sons”[54]), and an amateur chemist by interest. fascinated by the newly discovered galvanic electricity (he was member of the société galvanique, founded in 1802), he had carried out some experiments around 1800. one of his very few reports was read by him at march 17, 1801 (26 ventôse an 9) at the classe des sciences de l’institut des sciences, lettres et arts, entitled “mémoire sur le galvanisme”[55] and published in 1801, only one year after voltá s publication of his pile. we find the relevant part of gautherot́ s experiments on pages 205 and 206 of ref. [55], which reads … voyant que les plaques métalliques sont fortement oxidées lorsque la pile ou la batterie galvanique a été pendant quelque tems soumise aux expériences, j’ai voulu voir d’une manière plus particulière l’influence de l’attouchement des métaux pour la décomposition de l’eau. pour cet effet, j’ai placé sur les deux côtés opposés d’une plaque carrée de zinc deux petites bandes de carton pour supporter une plaque d’argent de même dimension que celle de zinc. j’ai place une goutte d’eau entre ces plaques, de sorte qu’elle touchait aux deux métaux. en examinant de tems en tems ces plaques, je ne me suis point apperçu, même au bout de soixante-douze heures, d’aucun effet d’oxidation; tandis qu’un autre appareil disposé de même, avec cette seule différence qu’il y avait une légère communication métallique entre les deux plaques, l’oxidation commencait déjà à être sensible au bout seulement de huit minutes. ici, l’oxide de zinc, quoi que d’une pesanteur spécifique supérieure à celle de l’eau, abandonne le zinc qui est à la partie inférieure, pour adhérer à l’argent en y dessinant le contenu de la goutte d’eau. si l’on a laissé écouler assez de tems pour que l’oxide de zinc soit plus abondant, une partie seulement adhère à l’argent, et le reste parait former dans l’eau des espèces de grumeaux gélatineux.”36 35 in a single sentence davy mentioned that “m. gautherot has stated, that in a single galvanic circle of zinc, silver, and water, in an active state, the oxide of zinc formed is attracted by the silver;” 36 “… seeing that the metal plates are strongly oxidized when the battery or the galvanic battery has been subjected to experiments for some time, i wanted to see in a more particular way the influence of the touching of the metals on the decomposition of the water. for this purpose, i placed two small strips of cardboard on two opposite sides of a square plate of zinc to support a silver plate of the same size as that of zinc. i placed a drop of water between these plates, so that it touched the two metals. in examining these plates at times, i did not perceive, even at the end of seven130 ernst kenndler, marek minárik we interpret and comment this experiment as follows.37 at first, gautherot horizontally arranged a zinc and a silver plate of equal size, the former below the latter, both separated by a small dry strip of cardboard as non-conducting spacer. note that, in contrast to a voltaic element, the cardboard was neither wetted nor impregnated. gautherot placed a drop of water between the plates such that the drop touched both metals. note also that the two plates were not electrically interconnected at this stage of the experiment (notwithstanding that the impure water gautherot had available was certainly conductive). gautherot registered that even after seventy-two hours no indications of an oxidation could be seen. this is what one expects because no electric circuit was closed. in contrast to his first one, in a second experiment gautherot interconnected the two plates with a metallic conductor. hence, upon closing the circuit by the metallic connection, gautherot observed oxidation at the bottom zinc plate within eight minutes and assumed that zinc oxide had been formed.38 that was the so far expected result of electrolysis. however, at the same time gautherot observed the detachment of particles of this newly formed material from the zinc surface and – despite their higher specific weight compared to water – their movement upwards through the water drop and their adherence at the upper silver plate. later on, only a part of the particles stuck at the silver surface, the rest remained in the water, dispersed as “gelatinous” clots. this material was probably the well-known typical voluminous and jellylike precipitate of zinc hydroxide. we might assume from this experiment that the positively charged zinc hydroxide particles39 which were ty-two hours, any effect of oxidation; while at another apparatus arranged likewise, with the only difference that there was a slight metallic contact between the two plates, the oxidation already began to be sensible after only eight minutes. here, the oxide of zinc, although of a specific gravity greater than that of water, abandons the zinc from the bottom part, and adheres to the silver by drawing the content of the drop of water. if enough time has elapsed for the oxide of zinc to be more abundant, only a part adheres to silver, and the rest appears to form gelatinous lumps in water.” 37 please note that the authors use a terminology in the present interpretation and comments which was not known at gautherot´s time. 38 it was probably sparingly soluble zinc hydroxide formed by the zinc ions due to anodic oxidation which were released into the solution. the solubility product of zn(oh)2 is 3.10-17 mol3.l-3. the measured concentration of dissolved free zn2+ ions in water at ph between 6 and 7 and ambient temperature is a few hundred µg.ml-1 (it is lower than that calculated from the solubility product), see ref. [56] g. dietrich, hartinger handbuch abwasserund recyclingtechnik, 3rd ed., karl hanser verlag, münchen, wien, 2017.. 39 this is in accordance with the summary of wolfgang ostwald in his standard text book about one century later, which we have cited in the context of clay in reuss´ experiments: “so erweisen sich bei reinem wasser als dispersionsmittel… als positiv: alle metallhydroxyde” (ref. [50] w. formed by anodic oxidation indeed migrated in the electric field towards the cathode. if we accept this as a fact (even though the description of the experimental conditions is somewhat vague), gautherot indeed was first who observed electrophoresis, prior to von reuß and porrett. about two years later, on november 29, 1803 nicolas gautherot died, as reported by urbain rené thomas le bouvier desmortiers,[57] caused by a shock from an electric battery (see ref. [58]). summary here we present the first of a series of papers on the history of observations and method development in the field of (capillary) electrophoresis. in this contribution we take a journey at the outset of what we coin as the “1st epoch of electrophoresis”, which we outline as a period of 125 years between the 1780s and the 1910s. due to the striking coincidence with the same period of european political history we deliberately choose to borrow the term “long 19th century” from the british historian eric hobsbawm (see footnote 7), who coined it for the time from the french revolution in 1789 till the beginning of the first world war in 1914. it is astounding that in the course of this epoch nearly all fundamental concepts, models, hypotheses, theories and laws concerning the electrically induced motion of charged particles (in electrophoresis) and of the transport of the liquid medium (in electroosmosis) were formulated, derived and became well-known. but it is the singular and even more astonishing characteristic of this epoch that no approach has been undertaken to utilize all this knowledge for the separation of constituents of a mixture. it has to be recalled that electrophoresis by itself is a drift of charged particles – dispersed in a liquid – under the influence of an electric potential difference. the only specific of capillary electrophoresis is that the motion takes place within an open narrow tube, but it is still obeying the general laws of electrophoresis. it is further to note that capillary electrophoresis as we know it from the midst of the 20th century, was first performed as early as in the 1860s, albeit not for separation purposes. as the basic principles of electrophoresis, though it was not named as such, came into the focus of research at about 1800, we find it appropriate to include here the history of the general physical and chemical principles on which it is based. in the years from 1800 to 1816 three electricallyostwald, grundriss der kolloidchemie, 1909., p. 233 (“thus, with pure water as the dispersant … all metal hydroxides turn out to be positive”). 131capillary electrophoresis and its basic principles in historical retrospect induced phenomena were observed upon the application of an electric potential difference to a liquid containing charged or chargeable particles: electrolysis at the electrodes, electrophoresis in the liquid dispersion of the charged particles, and its converse phenomenon, electroosmosis (an electrically-induced transport of the liquid relative to charged surfaces). all these discoveries relied on a source of a constant-flow electricity, not on the static electricity known at the time. this new source was provided by the voltaic pile, which transformed chemical into electrical energy upon a contact between two different metals with a moistened layer of spongy material in between. it was invented by alessandro volta, prompted by galvani ś incorrect theory of an animal electricity published in 1791. we find it thus justified that with this context the history of electrophoresis, and that of capillary electrophoresis commenced. the discovery of electrolysis is attributed to william nicholson and anthony carlisle, who in 1800, while trying to copy voltá s pile, observed formation of gas bubbles as a result of the decomposition of river water by galvanic electricity. the history of the discoveries of electrophoresis and electroosmosis is far more intricate. chronologically, electrophoresis was first observed in 1801 by an amateur chemist, nicolas gautherot, who observed motion of small particles (probably zinc oxide or hydroxide) formed at a zinc plate towards a silver plate upon connecting the two by a metal conductor. to his misfortune, however, his experiments were almost completely ignored by the scientific community, he was never cited as discoverer of electrophoresis (mentioned only briefly by davy ś bakerian lecture in 1806) and died as a result of electric shock from a battery. in 1807 ferdinand frédéric reuss (ferdinand friedrich von reuß) reported unexpected generation of flow of water within a v-shaped tube covering its bottom part with quartz sand. after closing the circuit, the water level at the one side of the tube raised, whereas that at the other side decreased accordingly. upon inverting the polarity, the reversed effect of the water levels occurred. thus, reuss unequivocally discovered the phenomenon of electroosmosis. in a second experiment, he placed a quartz sand layer above wetted clay in two water-filled tubes, each with wires dipped into the water as poles. upon connecting the poles to a voltaic pile he observed movement of clay particles through the sand. during these experiments reuss inadvertently, yet undoubtedly, observed both electroosmosis and electrophoresis. chronologically, robert porrett was the tritagonist in the cast of the play about the priority of the discovery of these electrically-induced phenomena. in 1816 porrett, not aware of any of the previous discoveries, observed a transport of water from one chamber of a divided jar to another chamber through a bladder divider upon connecting the chambers to the poles of a voltaic pile. upon publishing his observation in annals of philosophy, he gained attraction in the scientific community and up until the middle of the 19th century has been regarded as the discoverer of electroosmosis, in contradiction to the historical facts. it is to note that just as reuss had no knowledge of gautherot̀ s prior experiment observing electrophoresis, neither porrett was aware of reuss' priority in discovering electroosmosis. the above experiments revealing the phenomena of electrolysis, electrophoresis and electroosmosis were merely observatory and offered no formulations of hypotheses on their underlying causes. it is thus expectable that the scientific interest that followed in the subsequent years and decades was directed towards their principles and origins. after the discovery of electrolysis the research on the motion of ions40 was immediately intensified. attempts at theories about their inseparable connection, which may have led to an understanding of ion migration, and were undertaken between 1800 and the 1830s, will therefore be the subject of part 2 of the first series of our historical reviews. references [1] iupac, compendium of chemical terminology gold book, online version https://goldbook.iupac.org/ ed., 2014. 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[58] c. blondel, in luigi galvani international workshop (ed.: b. s. i. h. o. science), universita di bologna, bologna, 1999, pp. 187-209. substantia an international journal of the history of chemistry vol. 5, n. 1 2021 firenze university press giving credit where it’s due – the complicated practice of scientific authorship seth c. rasmussen history of research on antisense oligonucleotide analogs jack s. cohen chemistry, cyclophosphamide, cancer chemotherapy, and serendipity: sixty years on gerald zon thermodynamics of life marc henry darwin and inequality enrico bonatti loren eiseley’s substitution bart kahr new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors yona siderer capillary electrophores is and its basic principles in historical retrospect 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis ernst kenndler1,*, marek minárik2,3 the eminent russian – german chemist –friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries aleksander sztejnberg review of what is a chemical element? by eric scerri and elena ghibaudi, eds. oxford: oxford university press, 2020 helge kragh substantia. an international journal of the history of chemistry 3(2) suppl. 3: 9-11, 2019 firenze university press www.fupress.com/substantia citation: m. henry (2019) water and the periodic table. substantia 3(2) suppl. 3: 9-11. doi: 10.13128/substantia-701 copyright: © 2019 m. henry. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-701 editorial water and the periodic table marc henry université de strasbourg e-mail: henry@unistra.fr once upon a time, there was a russian guy named dmitri mendeleev (1834-1907), who became doctor of science in 1865 at saint petersburg state university for his dissertation «on the combinations of water with alcohol», a most important mixture in eastern european countries. after becoming a teacher in this university (1867), he planned to prepare a book for his teaching and after a dream, he has envisioned the complete arrangement of the elements as a 2d-table based on the “magic” integer 8. on 6 march 1869, he made a formal presentation to the russian chemical society, describing elements according to both atomic weight and valence. the role of the magic number 8 was elucidated between 1923 and 1930 through the development of quantum mechanics and new magic electron count numbers were discovered: 2 (he), 10 (ne), 18 (ar), 36 (kr), 54 (xe), 86 (rn) and 118 (uuo). in october 1957, a most important paper was published showing that the three most abundant elements in the universe was in that order: h, he and o.1 as helium is an inert and unreactive gas, it directly follows that the most abundant molecule in the universe should be a combination of hydrogen, a monovalent atom, with oxygen, a divalent atom, i.e. a substance having a h2o stoichiometry and with a magic count of 10 electrons. but, in order to get a better understanding of our universe, ordering chemical elements in a table is just the very first step and the next step is to consider relative chemical abundance, leading to the order: h > he > o > ne > n > c > si > mg > fe > s > ar > al > ca > na > ni > p > cl > cr > mn > k > ti > co. hence, after water, we get the (h, o, n, c) quadruplet for building organic molecules followed by (o, n, c, si, mg, fe) sextuplet for building meteorites. with water, organic matter and meteorites, everything is in place in the universe for the apparition of life. obviously, as water is by far the most abundant molecule in any living cell (more than 99%), a good understanding of its physical and chemical properties becomes mandatory. first, by looking at the ratio between boyle temperature (temperature at which attractive and repulsive forces are in balance in gas) and molecular weight, the most cohesive molecules are found to be h2o > hf > nh3 > h2 1 e. m. burbidge, g. r. burbidge, w. a. fowler, f. hoyle, «  synthesis of the elements in stars », rev. mod. phys., 26 (1957) 547. 10 marc henry > hcl > h3c-nh2.2 so, after being the mots abundant molecule of the universe, water is also the most cohesive one. considering the two couples of conjugated thermodynamic variables (volume v, pressure p) and (entropy s, temperature t), liquid water is further characterized by many critical temperatures at a pressure close to 0,1 mpa: t = -42°c: lowest limit temperature for super-cooled liquid water. t = -13°c: isochoric heat capacity maximum, i.e. minimum cv = <(δt)2> fluctuations. t = 0°c: crystallization of hexagonal ice with a lower density than the liquid. t = 4°c: liquid water density maximum, i. e. αp = <(δs)·(δv)> = <(δp)·(δt)> = γv = 0. t = 37°c: isobaric heat capacity minimum, i.e. minimum cp = <(δs)2> fluctuations. t = 46°c: isothermal compressibility minimum, i. e. minimum κt = <(δv)2> fluctuations. t = 64°c: adiabatic compressibility minimum, i. e. maximum κs = <(δp)2> fluctuations. t = 100°c: liquid water vaporization with very high latent heat of vaporization. t = 280°c: highest limit temperature for superheated liquid water. that water should be the cradle of life is thus easily understandable. so, it should be no surprise that water is also the most studied substance in science, literature and arts. being involved in water science and research since about 40 years, i have asked to 5 scientists having a worldwide reputation to put the focus on domains where water is doomed to play major role for the next century. i will begin by dr. josé teixeira, a prominent scientist, expert in water physics. he will give us an overview of a highly debated issue concerning the existence of a second critical point in deeply super-cooled liquid water. accordingly, if such a critical point really exist in the socalled “no man’s land” (160 k ≤ t ≤ 232 k) not accessible to experiments owing to hexagonal ice nucleation, a direct consequence would be a theoretical justification for the occurrence of so many temperature minima and maxima for liquid water (see above). as a complementary reading on this crucial subject, see reference 2. if you have never heard about aquaphotomics, you should read carefully the paper by e. b. van de kraats, j. s. munćan and r. n. tsenkova. this novel field shifts the paradigm of seeing water in a system as a passive, inert molecule to one which can build various structures with various functionalities, giving water an active role in biological and aqueous systems. i sincerely think that 2 m. henry, inference : int rev. sci., 4, n°3, march 2019; available online. it is one of the most promising techniques for characterizing watery systems in the very near future. as we all know, human beings are currently facing a most prominent danger owing to large climate changes on earth. after reading the contribution of ernst zürcher, you will probably understand why by firing forests for producing more food, we are putting all living beings on earth, including ourselves, in great danger. you should be aware that the current water cycle on earth is incomplete and time is ripe for revisiting it at the light of our current knowledge. as a complementary reading to this special issue, i would suggest considering gerald pollack’s wonderful book about ez-water.3 since about 12 000 years, humanity is living near a river or a lake for agricultural as well as industrial reasons. the consequence for our very near future will be that the tiny amount of fresh liquid water on earth will become more and more polluted. the discovery of the fact that rivers are able to undergo a self-purification process is thus of the utmost importance for future generations. more on this most fascinating subject in the contribution of w. schwenk and c. sutter. as a complementary reading concerning the importance of seawater, i would strongly recommend an amazing book devoted to rené quinton’s life and works, the so-called “french darwin” at the dawn of the xxth century.4 finally, our future is also deeply darkened by our inability to heal cancer and neurodegenerative diseases. i think that the main reason for such a failure despite billions and euros and dollars spent, is that we have not yet recognized the role played by water in a cell and that we ignore the basic physical laws responsible for life apparition on earth. with the contribution of l. schwartz, one of the best expert in the world in oncology, a new paradigm is proposed based on entropy and water. a possible scenario presenting how water and earth and sun have plotted several billions years ago for making life appear on this planet is discussed. both authors of this contribution are fully convinced that by grounding biology into physics, new ideas for healing people will automatically emerge in the next few years. another subject that could have been developed in this special issue and that will take more and more importance over the next years, is related to the interaction of water with very low frequency electromagnetic fields. the scientific demonstration by experiments and theory that molecules are able to leave an electromag3 pollack, g. h. (2013) : «  the fourth phase of water beyond solid, liquid and vapor », ebner and sons, seattle, usa. 4 dray, j.-f., quattrocchi-woisson, d., saint-geours, y. «  sur les traces de rené quinton (1866-1925): sa vie, son œuvre, sa postérité en france et en espagne », agami-editions, paris (2019). https://inference-review.com/article/water-and-its-mysteries 11water and the periodic table netic signature in water was a real breakthrough,5 as well as the confirmation by independent groups of this amazing phenomenon.6 however, as we have not yet enough hindsight on such a very hot topic, i have make the choice to not include it in this special issue. now, going back to mendeleev and to the celebration of the 150th anniversary of the periodic table, i would like stressing that water is probably the only substance on earth able to carry the whole periodic table from our immediate environment into our body either as ionic species (minerals), nanobubbles (gases) or micelles (organic molecules). consequently, a third step was needed in order to perpetuate mendeleev’s ideas by considering how water could interact with each element of the periodic table according to its oxidation state and electronegativity. this was the job of my phd thesis7 explaining how i was introduced in water chemistry and science some forty years ago. a prolongation of this work was that, in order to understand the crucial role played by water in many fields of science, a good understanding of quantum field theory was manadatory.8 accordingly, it is only by moving towards quantum field theory, that one could realize that vacuum is a more important stuff than matter. accordingly, it is worth recalling that atoms were for greek philosophers such as leucippus and democritus immaterial entities, in perfect harmony with quantum physics that see them either as waves packets (schrödinger’s viewpoint) or transcendental matrices (heisenberg’s viewpoint). mendeleev was also on the same line of thought as the hydrogen atom hardly exists by itself. the fact that it is nevertheless potentially found in all atoms as the sole building block needed for producing the whole periodic table is then quite remarkable. if a single entity, hydrogen, is able to generate the whole material world, filled with so many different substances with quite different physical or chemical properties, a mandatory conclusion is that a hydrogen atom should be more a fruitful concept, a productive thought, than a material thing. if such is really the case, hydrogen and thus water should 5 l. montagnier & al. (2017), «  water bridging dynamics of polymerase chain reaction in the gauge theory paradigm of quantum fields  », water mdpi, 9, 339. doi:10.3390/w9050339. 6 b. ting qang & al. (2019), «  rate limiting factors for dna transduction induced by weak electromagnetic field  », electromagnetic biology and medicine, 38:1, 55-65, doi: 10.1080/15368378.2018.1558064. 7 j.-p. jolivet, m. henry, j. livage (2000), «  metal oxide chemistry and synthesis  : from solution to solid state  », john wiley & sons, chichester, new-york. based on a french version published in 1994. 8 m. henry, « the topological and quantum structure of zoemorphic water », in aqua incognita: why ice floats on water and galileo 400 years on, p. lo nostro & b. w. ninham eds, connor court pub., ballarat (2014), chap ix, pp. 197-239. see also my book in french, «  l’eau et la physique quantique », dangles, escalquens (2016). also have something to do with consciousness, a fascinating line of research that have started this year9 and will be continued in this journal.10 so stay tuned to the substantia journal, as so many good things are coming very soon. 9 j.-p. gerbaulet, m. henry (2019), «the ‘consciousnessbrain’ relationship», substantia 3(1): 113-118. doi: 10.13128/substantia-161. 10 m. henry, j.-p. gerbaulet (2019) « a scientific rationale for consciousness », substantia 3(2): 37-54. doi: 10.13128/substantia-508. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 4(2): 5-6, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-1005 editorial some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss department of chemistry and institute for soft matter synthesis and metrology, georgetown university, washington, dc, usa e-mail: weissr@georgetown.edu we are human beings, imbued with the ability to make decisions and think deductively and inductively. however, our ability to do so is related asymmetrically to external factors such as wealth and physical strength; some are imbued with more power than others and use that extra power as a tool to influence how fair and equitable are defined or, in extreme cases, to oppress the weaker. as a consequence, individuals and groups sometimes behave in ways that are destructive both physically and emotionally to others. thus, it is not surprising that throughout our recorded history there have been actions affecting masses of people that we consider (at least in retrospect) to be based on illogical and uncivilized criteria. after all, we are human beings. perhaps what separates us most dramatically from other animals on earth is our ability to reason and recognize when we have erred. we can apologize and we can change our behavior in dramatic ways over short periods of time. the fact that we can does not mean that we do when we should. after all, we are human beings. the currently highlighted examples of racism, sexism, religious intolerance, etc. in the united states are not new. they have been a part of our ‘culture’ throughout history. they have occurred in various forms to greater or lesser degrees in every corner of our world during many millennia. the impetus for many wars can be traced to the subjective criteria for how we perceive other members of our species. after all, we are human beings. without accepting and respecting the different ways by which we view others, we, as a species, are inexorably tied in the future to prejudice of thought, and eventually, to actions against others. so, what can we do? if we have not eradicated racism, sexism, and religious intolerance in our long history on this planet, is it reasonable to expect that we will be able to do so now? is there a vaccine that can protect us against hatred and intolerance? i think not; this type of ailment is not like polio or covid-19. after all, we are human beings. however, we can recognize that the society that forms our ideas about others includes, almost always, embedded prejudices in our brains that cannot be erased completely. fortunately, because we can reason, we should be able to work, over time, to minimize our prejudices. recognizing our shortcomings gives human beings the ability to adapt in ways that separate us from other animals. although there is no recipe for using our powers to ensure rational decisions, we are capable of changing how our brains process information and translate that information into more constructive actions. if we do so with the welfare of others in mind, it should be possible to reduce over time the damage our species is capable of inflicting on others, as well as on our envihttp://www.fupress.com/substantia mailto:weissr@georgetown.edu 6 richard g. weiss ronment. the real question is whether we will use, more judiciously, the examples of the past to improve the lives of all in the future. if history is our guide, the answer is, “yes, we can but, no, we won’t.” however, there is hope. after all, we are human beings. closer to our professional home, what is the role of science in addressing racism, sexism, and religious intolerance? do we consider who is the author of data or just the validity of the data? do we weigh the quality of the data without considering its source? do we, as scientists, bring total objectivity to our profession? recent examples in the literature indicate that, no matter how much we profess otherwise, scientists are just another slice of humanity, in which (hopefully no more than) a small fraction operates on their prejudices under the false guise of objective, scientific judgments. however, there is hope. after all, scientists are human beings too. richard g. weiss an aspiring scientist and flawed human being substantia an international journal of the history of chemistry vol. 4, n. 2 2020 firenze university press some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy, ph.d., j.d. …and all the world a dream: memory outlining the mysterious temperature-dependency of crystallization of water, a.k.a. the mpemba effect evangelina uskoković1, theo uskoković1, victoria wu1,2, vuk uskoković1,3,* the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries aleksander sztejnberg communicating science: a modern event antonio di meo sub-covid-810 1 citation: d. quammen (2020) from spillover to pandemic. substantia 4(1) suppl. 1: 930. doi: 10.13128/substantia-930 received: may 07, 2020 revised: may 09, 2020 just accepted online: may 11, 2020 published: may 11, 2020 copyright: excerpted from spillover: animal infections and the next human pandemic by david quammen. copyright © 2012, 2013 by david quammen. used with permission of the publisher, w. w. norton & company, inc. all rights reserved. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia feature article from spillover to pandemic david quammen e-mail: dq@davidquammen.com the excerpt below, published in 2012 in the american edition of my book spillover, came after 500 pages in which i described the phenomenon of zoonotic diseases (those caused by viruses and other pathogens passed from nonhuman animals to humans), the importance of those diseases amid the problems of global human health, the work of the scientists who study such diseases, and the danger that a virus newly emerged from an animal host could cause a terrible pandemic. immediately preceding this section, i had recounted my visit with dr. robert webster, one of the world’s leading influenza researchers, who worried that a highly pathogenic form of avian influenza, known as h5n1, might evolve the capacity to transmit human-to-human. “and then god help us,” he said. another senior authority, as you’ll see below, warned me especially about the coronaviruses. and now here we are. some people have flattered me by saying that my book has been prescient or prophetic; but if the book has been prophetic, it’s not because i was prescient. i was merely reporting a collated version of what some very smart and wise scientists, including dr. webster, had told me in answer to questions such as: “if there is a next big one, a global disease catastrophe, what will it look like?” those scientists also cautioned me that precise prediction was impossible with events as contingent on circumstance as viral spillover. and so, near the middle of this excerpt, i wrote: “if we can’t predict a forthcoming influenza pandemic or any other newly emergent virus, we can at least be vigilant; we can be well-prepared and quick to respond; we can be ingenious and scientifically sophisticated in the forms of our response.” and we could have been. the work of the scientists offered us that possibility. but alas, because of failed vision in our political leaders, we weren’t. this whole subject, like an airborne virus, is at large on the breezes of discourse. most people aren’t familiar with the word “zoonotic,” but they have heard of sars, they have heard of west nile virus, they have heard of bird flu. they know someone who has suffered through lyme disease and someone else who has died of aids. they have heard of ebola, and they know that it’s a terrifying thing (though they may confuse it with e. coli, the bacterium that can kill you if you eat the wrong spinach). they are concerned. they are vaguely aware. but they don’t have the time or the interest to consider a lot of scientific detail. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 930, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-930 d. quammen 2 i can say from experience that some people, if they hear you’re writing a book about such things—about scary emerging diseases, about killer viruses, about pandemics— want you to cut to the chase. so they ask: “are we all gonna die?” i have made it my little policy to say yes. yes, we are all gonna die. yes. we are all gonna pay taxes and we are all gonna die. most of us, though, will probably die of something more mundane than a new virus lately emerged from a duck or a chimpanzee or a bat. the dangers presented by zoonoses are real and severe but the degree of uncertainties is also high. there’s not a hope in hell, as robert webster pungently told me, of predicting the nature and timing of the next influenza pandemic. too many factors vary randomly, or almost randomly, in that system. prediction, in general, so far as all these diseases are concerned, is a tenuous proposition, more likely to yield false confidence than actionable intelligence. i have asked not just webster but also many other eminent disease scientists, including some of the world’s experts on ebola, on sars, on bat-borne viruses generally, on the hivs, and on viral evolution, the same two-part question: (1) will a new disease emerge, in the near future, sufficiently virulent and transmissible to cause a pandemic on the scale of aids or the 1918 flu, killing tens of millions of people? and (2) if so, what does it look like and whence does it come? their answers to the first part have ranged from maybe to probably. their answers to the second have focused on rna viruses, especially those for which the reservoir host is some kind of primate. none of them has disputed the premise, by the way, that if there is a next big one it will be zoonotic. in the scientific literature, you find roughly the same kind of cautious, informed speculation. a highly regarded infectious-disease epidemiologist named donald s. burke, presently dean of the graduate school of public health at the university of pittsburgh, gave a lecture (later published) back in 1997 in which he listed the criteria that might implicate certain kinds of viruses as likeliest candidates to cause a new pandemic. “the first criterion is the most obvious: recent pandemics in human history,” burke told his audience. that would point to the orthomyxoviruses (including the influenzas) and the retroviruses (including the hivs), among others. “the second criterion is proven ability to cause major epidemics in non-human animal populations.” this would again spotlight the orthomyxoviruses, but also the family of paramyxoviruses, such as hendra and nipah, and the coronaviruses, such as that virus later known as sarscov. burke’s third criterion was “intrinsic evolvability,” meaning readiness to mutate and to recombine (or reassort), which “confers on a virus the potential to emerge into and to cause pandemics in human populations.” as examples he returned to retroviruses, orthomyxoviruses, and coronaviruses. “some of these viruses,” he warned, citing coronaviruses in particular, “should be considered as serious threats to human health. these are viruses with high evolvability and proven ability to cause epidemics in animal populations.” it’s interesting in retrospect to note that he had augured the sars epidemic six years before it occurred. much more recently, burke told me: “i made a lucky guess.” he laughed a self-deprecating hoot and then added that “prediction is too strong a word” for what he had been doing. donald burke can be trusted on this as much as anyone alive. but the difficulty of predicting precisely doesn’t oblige us to remain blind, unprepared, and fatalistic about emerging and re-emerging zoonotic diseases. no. the practical alternative to soothsaying, as burke put it, is “improving the scientific basis to improve readiness.” by “the scientific basis” he meant the understanding of which virus groups to watch, the field capabilities to detect spillovers in remote places before they become regional outbreaks, the organizational capacities to control outbreaks before they become pandemics, plus the laboratory tools and skills to recognize known viruses speedily, to characterize new viruses almost as fast, and to create vaccines and therapies without much delay. if we can’t predict a forthcoming influenza pandemic or any other newly emergent virus, we can at least be vigilant; we can be well-prepared and quick to respond; we can be ingenious and scientifically sophisticated in the forms of our response. we should appreciate that these recent outbreaks of new zoonotic diseases, as well as the recurrence and spread of old ones, are part of a larger pattern, and that humanity is responsible for generating that pattern. we should recognize that they reflect things that we’re doing, not just things that are happening to us. we should understand that, although some of the human-caused factors may seem virtually inexorable, others are within our control. the experts have alerted us to these factors and it’s easy enough to make a list. we have increased our population to the level of 7 billion and beyond. we are well on our way toward 9 billion before our growth trend is likely to flatten. we live at high densities in many cities. we have penetrated, and we continue to penetrate, the last great forests and other wild ecosystems of the planet, disrupting the physical structures and the ecological communities of such places. we cut our way through the congo. we cut our way through the amazon. we shake the trees, figuratively and literally, and things fall out. we kill and butcher and eat many of the wild animals found there. we settle in those places, creating villages, work camps, towns, extractive industries, new cities. we bring in our domesticated animals, replacing the wild herbivores with livestock. we multiply our livestock as we’ve multiplied ourselves, operating huge factory-scale operations involving thousands of cattle, pigs, chickens, ducks, sheep, and goats, not to mention hundreds of bamboo rats and palm civets, all from spillover to pandemic 3 confined en masse within pens and corrals, under conditions that allow those domestics and semidomestics to acquire infectious pathogens from external sources (such as bats roosting over the pig pens), to share those infections with one another, and to provide abundant opportunities for the pathogens to evolve new forms, some of which are capable of infecting a human as well as a cow or a duck. we treat many of those stock animals with prophylactic doses of antibiotics and other drugs, intended not to cure them but to foster their weight gain and maintain their health just sufficiently for profitable sale and slaughter, and in doing that we encourage the evolution of resistant bacteria. we export and import livestock across great distances and at high speeds. we export and import other live animals, especially primates, for medical research. we export and import wild animals as exotic pets. we export and import animal skins, contraband bushmeat, and plants, some of which carry secret microbial passengers. we travel, moving between cities and continents even more quickly than our transported livestock. we stay in hotels where strangers sneeze and vomit. we eat in restaurants where the cook may have butchered a porcupine before working on our scallops. we visit monkey temples in asia, live markets in india, picturesque villages in south america, dusty archeological sites in new mexico, dairy towns in the netherlands, bat caves in east africa, racetracks in australia—breathing the air, feeding the animals, touching things, shaking hands with the friendly locals—and then we jump on our planes and fly home. we get bitten by mosquitoes and ticks. we alter the global climate with our carbon emissions, which may in turn alter the latitudinal ranges within which those mosquitoes and ticks live. we provide an irresistible opportunity for enterprising microbes by the ubiquity and abundance of our human bodies. everything i’ve just mentioned is encompassed within this rubric: the ecology and evolutionary biology of zoonotic diseases. ecological circumstance provides opportunity for spillover. evolution seizes opportunity, explores possibilities, and helps convert spillovers to pandemics. substantia. an international journal of the history of chemistry 5(2): 153-164, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1231 citation: sztejnberg a. (2021) albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death). substantia 5(2): 153-164. doi: 10.36253/substantia-1231 received: mar 02, 2021 revised: apr 19, 2021 just accepted online: apr 19, 2021 published: sep 10, 2021 copyright: © 2021 sztejnberg a. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg university of opole, opole, poland e-mail: a.sztejnberg@uni.opole.pl abstract. albert ladenburg (1842-1911) was an outstanding german chemist and historian of chemistry of the second half of the 19th century. he ascertained the formula of ozone as o3 and proposed a triangular prism structure for the molecule of benzene. he studied the structure of aromatic hydrocarbons and organic compounds of silicon and tin, and devoted his work to explaining the structure of alkaloids and their synthesis. the purpose of this paper is to familiarize readers with the important events in the life of ladenburg and his writing and research activities, in particular some of his experimental results, as well as his selected publications. keywords:a. ladenburg, organic chemistry, ladenburg’s prism formula for benzene, coniine, germany – xix century. in the minds of all chemists now living, and of all those who, in the future, trace the development of the science of our time, the name of ladenburg is, and always will be, closely associated with the chemistry of those interesting and wonderful products of nature’s laboratory, the vegetable alkaloids. frederic stanley kipping (1863-1949).1 1. the important events in the ladenburg’s life albert ladenburg was called a great man with highets achievements, “who his life worthily devoted to the advancement of knowledge”,2 and “an indefatigable worker and investigator”.3 one hundred and ten years have passed since his death, but in that time little has appeared in the literature about this eminent man. he went down in the history of chemistry as a researcher of the structure of aromatic hydrocarbons and organic compounds of silicon and tin. one of his achievements as an experimenter was the synthesis of alkaloids and the elucidation of their structure.4 albert ladenburg was born into a renowned jewish family in mannheim on july 2, 1842, as the second son of dr. leopold ladenburg (1809-1889), a http://www.fupress.com/substantia http://www.fupress.com/substantia 154 aleksander sztejnberg lawyer, and his wife delphine, née picard (1814-1882).56 his grandfather wolf haium ladenburg (1766-1851) founded the private banking house ladenburg in mannheim in 1785.7-8 at the age of 15, after study at a realgymnasium at mannheim, he continued his education (1857-1860) at the polytechnische schule in karlsruhe. in 1860, at eighteen years of age, he went to heidelberg, where his interest in chemistry was inspired and directed by robert bunsen (1811-1899). in the bunsen’s laboratory he met, among others, carl graebe (1841-1927), and hermann wichelhaus (1842-1927), who remained his close friends. here he also met the british chemist henry roscoe (1833-1915), who often visited bunsen. he also attended lectures on mathematics at the university and studied physics under gustav kirchhoff (1824-1887).9 on june 2, 1863, he “took the ph.d. degree at heidelberg university, summa cum laude in chemistry, physics, and mathematics.”10 during this time, he met emil erlenmeyer (1825-1909), which led to a lifelong friendship between them. then he worked in a small private laboratory of georg ludwig carius (1829-1875), außerordentlicher professor at the university. in the spring of 1865 he went to ghent, where he spent a semester to work in the university laboratory of august kekulé (1829-1896).11 figure 1 is a photograph taken in ghent.12-15 from left to right, standing: august mayer (1844-?), wilhelm körner (1839-1925), kekulé’s private assistant and secretary, esch, semmel, behrend, and ladenburg. seated, from left to right: théodore swarts (1839-1911), kekulé, and carl glaser (1841-1935), kekulé’s private assistant.16 in 1866, after his stay in ghent, he went briefly to london, where he visited the british chemist edward frankland (1825-1899), after which he moved to paris.17 following the advice of kékulé,18 he asked marcellin berthelot (1827-1907) for permission to become one of his students. his “request was granted forthwith, but when he proceeded to inquire where he should work, he was shown a large, empty room, devoid of all fittings, of which he would be the sole occupant.”19 however, he did not use bertholet’s offer and started work under charles adolphe wurtz (1817-1884) in his laboratory at the faculté de médecine de paris. he met there, among other, charles friedel (1832-1899), joseph caventou (1795-1877), alfred joseph naquet (1834-1916), and armand gautier (1837-1920). in the years 1866-1867, he worked for 18 months with friedel. he carried out with him series of researches in the laboratory in the école nationale supérieure des mines de paris. after obtaining his habilitation, on january 8, 1868, he became privatdozent at the university of heidelberg. the british chemist and historian of chemistry thomas edward thorpe (1845-1925) wrote about his stay in heidelberg at that time as follows: “at heidelberg, as in many other centres of chemical instruction, there was a small chemical society, composed of the extraordinary professors, the privat-docenten, and assistants, together with the senior or more active students in the various laboratories who were elected into it by favour of the teachers. in my time it numbered amongst its members erlenmeyer, ladenburg, [august friedrich] horstmann [(1842-1929)], [ernst] ludwig [(1842-1915)], [emil] cohen [(1842-1905)] (the mineralogist), rose, and [adolph] emmerling [(1842-1906)]. its president was bunsen, and the occasions on which he took the chair were the red-letter days of the session.”20 in the fall of 1868, ladenburg attended the naturforscherversammlung (meeting of naturalists) in frankfurt am main. there, he met kekulé and the russian chemist aleksandr mikhaylovich butlerov (1828-1886), whom he “knew already from heidelberg” and with whom he “had entered into closer relations at a dinner given by erlenmeyer.”21-22 on march 30, 1870, he was appointed extraordinary professor at the university of heidelberg, and on october 25, 1872 he went to kiel 23 as full professor of chemistry and director of the new chemistry laboratory at the university. he became the successor of karl himly (1811-1885),24 and he worked there for seventeen years. he “was presumably the first nonbaptized chemist who figure 1. ladenburg with august kekulé and the group of his assistants and students at the ghent university (public domain, from reference 12). 155albert ladenburg (1842-1911) received a full professorship in chemistry at a german university.”25-26 in the academic year 1884/1885 he was the rector of this university.27 on september 19, 1875, he married margarethe pringsheim (1855-1909),28 the daughter of the nathanael pringsheim (1823-1894), professor of botany at the university of berlin.29-31 the spouses had three sons: erich (1878-1908), rudolf (1882-1952) and kurt (1884-1901).32 on october 1, 1889 he went to breslau in silesia in the kingdom of prussia (now, wrocław, poland), where he started working as a professor of chemistry at the königliche universität zu breslau (royal university of breslau). he, as the successor of carl jacob löwig (18031890), became the director of the chemische institut (institute of chemistry).33 in 1901, the ladenburg’s youngest son, kurt, died prematurely at the age of 17. seven years later, his eldest son erich, a physicist34 who made a scientific career at the royal university of breslau, died tragically. he drowned in a sailboat accident on lake müggel.35-36 his third son, rudolf, became a german-american atomic physicist.37 in 1905, he has had to undergo amputation of the right leg.38 the german chemist walter herz (18751930), professor of physical chemistry at the university of breslau, wrote about it as follow: “ladenburg not only lost his right foot as a result, but also the whole right leg up to the middle of the thigh. his friends fearfully wondered whether this new, large wound would now heal and whether the now 63-year-old man would still be able to learn to walk with an artificial leg. the healing progressed slowly, but in the autumn of 1905 ladenburg was ready to return to his office thanks to the loving care of his wife. everyone who saw him was surprised at how well he had recovered from this severe blow.”39 nevertheless, he continued the duties of his chair until october 1, 1909, when he resigned from teaching due to illness. towards the end of his life, he wrote a autobiography, which his son rudolf published under the title lebenserinnerungen in breslau in 1912.40 it is worth emphasizing that this book does not contain “a single mention of antisemitism or even prejudice”.41 ladenburg was not “practicing” jew and was “fully assimilated” german. he “was in fact an atheist; for reasons that he does not explain, he finally underwent baptism in 1891.”42 according to a document written by him two years earlier, dated november 16, 1889, and stored in the archives of the university of wrocław, he called his confession evangelisch reformierte (evangelical reformed).43 ladenburg died on august 15, 1911 in breslau. herz in his obituary wrote: “when i went to the laboratory early on august 15, i first sent a telegram congratulations on the [rudolf ] ladenburg wedding at a post office. when i arrived at the laboratory, i had barely started my work when the telephone notification arrived that ladenburg had gone to sleep on the night of august 14th to 15th (at 1:00 am). he did not live to see his son’s wedding.”44 he was buried on august 18th. at his funeral, der geistliche der reformierten hofgemeinde (the clergyman of the reformed court community) pastor renner, the mineralogist carl hintze (1851-1916), and the lord mayor dr. georg bender (1848-1924) spoke at his grave alternately.45 two of his obituaries were published in 1911 by anonymous authors in the chemical news,46 and american chemical journal.47 two year later, on october 23, 1913, the english chemist frederic stanley kipping (1863-1949) delivered a lecture in memory of ladenburg at a meeting of the royal society.48 2. ladenburg’s participation in the scientific celebrations in august 1877, he attended celebrations of the 400th anniversary of the university in uppsala (sweden) as a representative of the university of kiel.49 twenty-three years later in 1900, he visited berlin to participate in the conference devoted to the 200th anniversary of the königlich preußischen akademie der wissenschaften (royal prussian academy of sciences). figure 2 is a photography made during this celebration.50 the american biochemists benjamin harrow (1888-1970) inserted this photo on the one of first pages of his book entitled eminent chemists of our time. he also wrote that it “showing several eminent chemists was taken at one of the international scientific gatherings.”51 figure 2. ladenburg with the group of the prominent chemists (public domain, from reference 50). 156 aleksander sztejnberg photograph was published by harrow thanks to the kindness of the dutch chemist ernst julius cohen (18691944).52 ladenburg is first from the left in the second row; to his left are the danish chemist sophus mads jørgensen (1837-1914), the finnish chemist and historian of chemistry edvard hjelt (1855-1921), the german chemist hans heinrich landolt (1831-1910), the german chemist clemens alexander winkler (1838-1904), who discovered germanium in 1886, and t. e. thorpe. seated from the left to right in the front row are the dutch chemist jacobus henricus van’t hoff (1852-1911), who won the nobel prize in chemistry in 1901, the russian – german chemist friedrich konrad beilstein (1838-1906),53 the scottish chemist william ramsay (1852-1916), who found neon, argon, krypton, and xenon in air and was awarded the nobel prize in chemistry in 1904, the russian chemist d. i. mendeleev, who discovered the periodic law in 1871, the german chemist adolf von baeyer (1835-1917), who received the nobel prize in chemistry in 1905, and the italian chemist alfonso cossa (1833-1902). harrow in the further part of his book described certain incident, which happened during banquet given by the organizers in this occasion and involving ladenburg. “in 1900 the prussian academy celebrated its two hundredth anniversary, and the university of petrograd sent mendeléeff as its delegate. at the banquet van’t hoff presided over one of the side tables, with ladenburg (the breslau representative) to the right, and mendeléeff to the left over him. mendeleéff was an inveterate smoker, and simply chafed because he could not smoke alternately. ladenburg tells us that immediately after the soup mendeléeff began to pump those around him as to whether he could be allowed to smoke. they answered him that was out of the question. but he repeated his question after the first, and after the second courses. then dear old van’t hoff, who hated to see anyone suffer so, stepped in with the risky suggestion that he also would join in a smoke. and the two went to it, to the great relief of mendeléeff, who from then on proved an enjoyable companion. but the sad side of the incident was that van’t hoff, who had begun to show incipient signs of tuberculosis, had been expressly forbidden smoking.”54 3. ladenburg’s works the list of works published by ladenburg includes 276 papers and books published over forty-seven years from 1865 to 1912.55 the majority of these are the articles presenting the results of his experimental works, published in berichte der deutschen chemischen gesellschaft as well as in other german, french and british journals. among them are his original articles devoted to the problems of the isomerism of benzene derivatives,56 the researches on organic compounds of tin,57-59 the studies of ozone,60-66 as well as accurately determination of the atomic weight of iodine.67-68 a large number of the results of the experimental research carried out by him were published in justus liebigs annalen der chemie, zeitschrift für angewandte chemie and journal für praktische chemie. a few his articles were published in french in comptes rendus hebdomadaires des séances de l’académie des sciences and annales de chimie et de physique. one of his articles entitled contribution to the characterisation of racemic compounds was published in the journal of the chemical society, transactions in 1899.69 his first paper in the field of organic chemistry entitled eine neue methode der elementaranalyse (a new method of elemental analysis) was published in 1865. there he described the results of several experiments, for instance, with naphthalene and with diethyl ether.70 at the end of an article (p. 24), written in february 1865 in heidelberg, he wrote thanks to carius for making it possible to carry out experiments in his laboratory: “finally, i would like to express my thanks to professor carius, in whose laboratory the experiments described have been carried out, for his assistance, which he has given me very generously.”71 in the kekulé’s laboratory, he carried out two studies on benzene derivatives, the results of which were published in 1866, one on synthèse de l’acide anisique et de l’un de ses homologues (synthesis of anisic acid and one of its homologues) and the other in collaboration with fitz called sur quelques dérivés de l’acide paroxybenzoïque (on some derivatives of paroxybenzoic acid).72-73 in the same year, from the wurtz’s laboratory, he published with carl leverkus (1804-1889) a paper entitled sur la constitution de l’anethol (on the constitution of anethol).74 in the years 1866-1867, he and friedel published several papers with the results of studies of the structure of aromatic hydrocarbons,75-76 and organic silicon compounds such as mixed silico-acetic anhydride,77 silicochloroform,78 and silicon chloroitydrosulphide.79 one of the studies was devoted to revealing the analogy between carbon and silicon.80 the experimental work of ladenburg and friedl was continued also in the years 1868-1870. the fruits of this collaboration were a three papers ueber das intermediäre anhydrid von kieselsäure und essigsäure (about the intermediate anhydride of silicic acid and acetic acid),81 einige derivate des radicals silicoallyl (some 157albert ladenburg (1842-1911) silicoallyl radical derivatives),82 and sur l’acide silicopropionique (on silicopropionic acid).83 ladenburg’s research interests also focused around synthesis of alkaloids. in 1879, he carried out the artificial production of atropine (c17h23no3),84 and in 1894, he and m. scholtz synthesized piperic acid (c12h10o4) and piperine (c17h19no3), which was the main alkaloid of black pepper.85 in 1880, he also isolated hyoscyamine (c17h23no3),86 and hyoscine (c17h21no4) also called scopolamine.87 in 1886, he for the first time synthesized in the laboratory an optically active compound identical with the alkaloid coniine (c8h17n) found in the hemlock plant.88 kipping wrote about this achievement of ladenburg as follows: “the synthesis of dl-coniine, followed by the resolution of the synthetic alkaloid into its optically active components, the culminating point of these researches, was perhaps the greatest of ladenburg’s successes.”89 at a time when the kekulé formula for benzene was the subject of much controversy,90-91 ladenburg 152 years ago, in 1869, proposed a triangular prism structure for the molecule of this compound,92-93 that was symmetrical, but didn’t contain double bonds, and turned out to be erroneous.94 in 1876, he summarized his views on the structure of the benzene molecule in his book entitled die theorie der aromatischen verbindungen (the theory of aromatic compounds).95 thirty-five years later, an anonymous author wrote: “his prism formula for benzene, although now practically universally rejected, has been of great use in the development of chemistry in that, as early as 1868, it showed the necessity of taking into account steric considerations in the formulation of the constitution of chemical compounds.”96 experimental studies carried out in the 1970s confirmed that ladenburg prism can be obtained in the laboratory. in 1973, a pure sample of “the simple molecule c6h6, known as prismane [tetracyclo[2.2.0.02,6.03,5] hexane], in which six carbon-hydrogen units are disposed at the corners of a triangular prism”, was synthetized by the american organic chemists thomas j. katz, and nancy acton from the department of chemistry at columbia university.97 the chemical literature review results indicate an interest in ladenburg’s works, for instance, information about some of his articles appeared in the gazzetta chimica italiana in 1872.98 his experimental studies and their results were introduced to readers, among others by ed. willm and maurice hanriot (1854-1933) in 1889,99 h. e. roscoe and carl schorlemmer (18341892) in the years 1888-1890,100-102 julius wilhelm brühl (1850-1911), e. hjelt, and ossian aschan (1860-1939) in 1900,103 amé picket (1857-1937) in 1904,104 as well as hans meyer (1871-1942) in 1916,105 and 1922.106 in the 1960s, the results of selected ladenburg studies in the field of organosilicon chemistry were discussed by richard müller from institute for silicone and fluorocarbon chemistry in radebeul/dresden (germany).107 at the beginning of the 21st century, these results were presented by dietmar seyferth from department of chemistry at massachutets institute of technology (u.s.a.).108 4. other works of ladenburg in chemistry ladenburg, at the age of 27, became famous for his book on the history of chemistry. it was published first in german and later in three other languages. in 1869, the first edition of his vorträge über die entwicklungsgeschichte der chemie in den letztem hundert jahren (lectures on the history of the development of chemistry over the last hundred years) was published in braunschweig.109 one year later, the german chemist hermann kolbe (1818-1884) praised this book in his article published in the journal für praktische chemie.110-111 he wrote as follow: “far from wanting to give a truthful, strictly scientific development of the chemical theories (which task young ladenburg ... has recently undertaken with seriousness and diligence...).”112 the fourth german edition of this book appeared thirty-eight years later under the title vorträge über die entwicklungsgeschichte der chemie von lavoisier bis zur gegenwart (lectures on the history of chemistry from lavoisier to the present day). he dedicated the book from this edition to his wife.113 in 1900, the first english edition of ladenburg’s book was published with the title lectures on the history of the development of chemistry since the time of lavoisier.114 the revised editions of this book appeared in 1911.115 the translator was the chemist leonard dobbin (1858-1952), lecturer on chemical theory and assistant in chemistry at the university of edinburgh. in the preface to the english edition of this book written in september 1899 in grassendale, southbourne-on-sea, ladenburg wrote: “thirty years after the appearance of the first edition of this book, an english translation of it is now being prepared. i regard this as a favourable indication of the permanent value of the book, since it is evident that the standpoint then adopted is intelligible at the present day and is still unsuperseded. moreover, it may be concluded that the exposition of the subject is not marred by national prejudices. … the english edition is a faithful translation, and, so far as i am able to judge, it is written in a good style. for these features my best thanks are due to the translator.”116 158 aleksander sztejnberg the first french edition of ladenburg’s histoire du développement de la chimie depuis lavoisier jusqu’ à nos jours (lectures of the development of chemistry from lavoisier to the present day) was published in 1909,117 and the second, in 1911.118 the translator was arthur corvisy (1855-1930), associate professor of physical sciences at the lycée gay-lussac and professeur suppléant at the school of medicine and pharmacy. in 1917, the first russian edition of his lektsii po istorii razvitiya khimii ot lavuaz’ye do nashego vremeni (lectures on the history of the development of chemistry from lavoisier to our time) was published in odessa. the translator of the fourth german edition of this book was evgeny semonovich elchaninov (1879-1922), privat-docent of the novorossiysk university.119 in the years 1882-1895, ladenburg worked intensively on his handwörterbuch der chemie (concise dictionary of chemistry), which was published in thirteen volumes in breslau.120-121 the general register created on the basis of the registers of individual 13 volumes of this book was published in 1896. among the co-authors are the names of 50 chemists who participated in the creation of this great work in different years during of thirteen years.122 one of kekulé’s works was published by ladenburg in 1904 in the ostwalds klassiker der exakten wissenschaften series.123 in the years 1907-1910, three papers written by french chemists louis pasteur (1822-1895),124 wurtz,125 and berthelot and léon péan de saint-gilles (1832-1863)126 were translated from french into german by ladenburg and his wife and published in the same series. 5. conclusion albert ladenburg was one of the prominent chemist of the second half of the xix century. in the years 1880-1910, he was elected a member of three academies of sciences. he became a member of the nationale akademie der wissenschaften leopoldina in 1880.127 he was elected a corresponding member of the british association for the advancement of science in 1887,128 and the académie des sciences de paris on december 13, 1909.129 on january 6, 1910, he became a corresponding member of the königlich preußischen akademie der wissenschaften.130 he was a corresponding member of the philadelphia college of pharmacy.131 on april 26, 1892, he became an honorary member of the manchester literary and philosophical society,132 and on august 4, 1884, he was appointed doctor honoris causa of medicine at the university of bern. on february 2, 1888 he became an honorary and foreign member of the chemical society of london.133 in the years 1901-1911, he was a foreign corresponding member of the académie nationale de médecine in paris.134 in 1899, the pharmaceutical society of great britain awarded him the hanbury gold medal for his work on alkaloids and their derivatives.135 it is awarded every five years, in memory of the british botanist and pharmacologist daniel hanbury (1825-1875). “the medal was formally received by baron [wilhelm] von mirbach [(18711918)], representing the german embassy, and a letter was read from dr. ladenburg expressing his thanks for the honour done him, and regretting that he had been unable to be present to receive the medal personally.”136 in 1905, he was awarded the davy medal “for his researches in organic chemistry, especially in connexion with the synthesis of natural alkaloids.”137-138 it is named after the english chemist humphry davy (1788-1829) and is awared annually since 1877 to an outstanding researcher in the field of chemistry by the royal society of london.139 two years later, in 1907, he nominated berthelot and mendeleev for the nobel prize in chemistry.140 however, the award went to the german biochemist eduard buchner (1860-1917) “for his biochemical researches and his discovery of cell-free fermentation.”141 later, in 19091911, he worked at the university of breslau.142 after ladenburg, not only his papers and books survived. in addition, several of his portraits were produced. one of them was included by the german chemist richard anschütz (1852-1937), professor of chemistry at the university of bonn, in his biographical book on kekulé.143 three other photo appeared in the articles written by herz,144 kipping,145 and colin archibald russell (19282013).146 the photographer adèle perlmutter (1845-1941) from vienna photographed him in 1869,147 and in the years 1870-1880 his portrait was taken by a photographer emil bühler in mannheim.148 another two of his portraits can be found in the österreichische nationalbibliotek collection,149 and in a book written by the american chemist henry monmouth smith (1868-1950).150 in 1911, the 100th anniversary of the royal university of breslau was celebrated. on this occasion, a book entitled festschrift zur feier des hundertjährigen bestehens der universität breslau, zweiter teil, geschichte der fächer, institute und ämter der universität breslau 1811 – 1911 was published, in which one of the chapters written by ladenburg and buchner was devoted to the history of the institute of chemistry at the university. the authors also presented short biographical notes of chemists who obtained their habilitation there.151 the great achievements of ladenburg in the field of alkaloids synthesis were noticed by english pharmacists. on october, 1899, william martindale (1840-1902), 159albert ladenburg (1842-1911) president of the pharmaceutical society of great britain said about it: “dr. ladenburg was best known to english pharmacists by his synthetic work in the production of homatropine.[152] by splitting up atropine he obtained tropic acid and tropine as derivatives; the latter he combined with amygdalic acid to form a compound which is easily converted into oxy-toluyl-tropeine or homatropine, an artificial alkaloid which, with its salts, has proved of the greatest service to ophthalmic surgery.”153 walter herz wrote about ladenburg’s great achievements in chemistry as follow: “like only a few, ladenburg has been granted forty years of great success in developing his science. his contributions to the constitution of benzene, his investigations into the heterocyclic compounds, his successes in the synthesis of alkaloids will always be regarded as classic examples of great chemical achievements. his uncommon scientific versatility was evident in his work on racemy, his excellent treatises on ozone and iodine, and his critical-historical perspective in his valuable history of chemistry.”154 it is worth emphasizing that ladenburg was put “in the first rank of chemists as a theorist.”155 moreover, he was not only an experienced experimental chemist, but also an excellent pianist. his acquaintance with the great german pianists and composers such as clara schumann (1819-1896) and johannes brahms (1833-1897) began at his young age.156 in a letter written to schumann in ischl, a city in austria in june 1895, brahms informed her about the meeting with ladenburg: “... professor ladenburg from breslau spent the whitsun holidays here with his wife, we were very cozy together and talked a lot about you.”157 this outstanding german chemist and historian of chemistry took forever a firm place in the history of chemistry. his name is associated with the beginning of intensive research in the field of organic synthesis. the results of his original experimental studies have been published in scientific journals in germany, france and great britain. his vorträge über die entwicklungsgeschichte der chemie has been published many times, not only in germany but also in great britain, france and russia. his multi-volume dictionary handwörterbuch der chemie has served many generations of chemists around the world. his name is given to “a distilling flask with bulbed neck”, the so-called ladenburg flask.158 for example, one of its varieties is a flask with three-bulb.159 references 1. f. s. kipping, j. chem. soc.,trans. 1913, 103, p. 1871. https://doi.org/10.1039/ct9130301871 2. quoted in ref. 1 (kipping), p. 1871. 3. the hanbury medal. the british medical journal, 1899, 2(2024), p. 1030. retrieved from https://www. jstor.org/stable/20262133 4. a. a. baker, jr. ladenburg, albert , 2020. retrived from encyclopedia.com. website: https://www.encyclopedia.com/science/dictionaries-thesauruses-pictures-and-press-releases/ladenburg-albert 5. l. ladenburg, stammtafel der familie ladenburg, druck von j. ph. walther, mannheim, 1882. p. 10. retrieved from http://dl.ub.uni-freiburg.de/diglit/ ladenburg1882 6. h.-e. lessing, mannheimer geschichtsblätter, 2008, 15, p. 7. retrieved from https://verlag-regionalkultur.de/media/pdf/1a/94/e1/bib-35-559.pdf 7. see ref. 5 (ladenburg), pp. 1, 10. 8. wolf hayum ladenburg, 2015. retrieved from http://altneu.han-solo.net/osfia/tng_wordpress/getperson.php?personid=i20472 9. see ref. 1 (kipping), p. 1872. 10. quoted in ref. 1 (kipping), p. 1873. 11. r. anschütz, august kekulé. leben und werken, band i., verlag chemie, g.m.b.h., berlin, 1929, p. 272. retrieved from https://archive.org/details/ b29931654_0001/page/n3/mode/2up 12. kekule und mitarbeiter in gent (belgien), 1866. public domain. retrieved from wikimedia commons webiste: https://commons.wikimedia.org/ wiki/file:august_kekule_gent_ca1866.jpg 13. see ref. 11 (anschütz), p. 272. 14. j. gillis, de brug. tijdschrift van de rijksuniversiteit te gent, 1958, 2(2), p. 68. 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(kipping), p. 1872. 146. c.a. russell, br. j..hist. sci. 1988, 21(3), p. 276. retrieved from https://www.jstor.org/stable/4026830 147. ladenburg, albert, n.d. retrieved from digiporta digitales porträrchiv website: http://www.digiporta. net/index.php?id=991281888 148. ladenburg, albert, n.d. retrieved from digiporta digitales porträrchiv website: http://www.digiporta. net/index.php?id=268632181 149. ladenburg, albert, österreichische nationalbibliotek, n.d. retrieved from https://digital.onb.ac.at/rep/ osd/?1104b2e1 150. h. m. smith, torchbearers of chemistry. portraits and bibliography of scientists who have contributed to the making of modern chemistry, academic press inc., publishers, new york, 1949, p. 142. 151. a. ladenburg, e. buchner in festschrift zur feier des hundertjährigen bestehens der universität breslau, zweiter teil, geschichte der fächer, institute und ämter der universität breslau 1811 – 1911, (ed.: g. kaufmann), ferdinand hirt, königliche universitäts und verlagsbuchhandlung, breslau, 1911, pp. 451457. retrieved from https://www.bibliotekacyfrowa. pl/dlibra/publication/104025/edition/96447/content 152. a. ladenburg, ber. dtsch. chem.ges. 1880, 13(1), p. 1086. https://doi.org/10.1002/cber.188001301300 153. quoted in ref. 3 (the hanbury medal), p. 1030. 154. quoted in ref. 39 (herz), p. 3636. 155. anon., nature, 1911, 87, p. 282. https://doi. org/10.1038/087282a0 156. see ref. 39 (herz), p. 3598. 157. b. litzmann, clara schumann, johannes brahms, band 2: briefe aus den jahren 1872-1896, erste auflage, dearbooks, bremen, 2013, p. 587. 158. ladenburg flask. merriam-webster.com dictionary, n.d. retrieved from merriam-webster website: https://www.merriam-webster.com/dictionary/ladenburg%20flask 159. flask, distillation, ladenburg’s, n.d. retrieved from national museum of american history website: https://americanhistory.si.edu/collections/search/ object/nmah_897 substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas 1 citation: v. domenici (2020) distance education in chemistry during the epidemic covid-19. substantia 4(1) suppl. 1: 961. doi: 10.13128/substantia-961 received: jun 09, 2020 revised: jun 18, 2020 just accepted online: jun 25, 2020 published: jun 25, 2020 copyright: © 2020 v. domenici. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia feature article distance education in chemistry during the epidemic covid-19 valentina domenici dept. of chemistry and industrial chemistry, university of pisa, italy. dissemination of chemical culture interdivisional group of the italian chemical society email: valentina.domenici@unipi.it website: http://smslab.dcci.unipi.it/ & http://smslab.dcci.unipi.it/didattica-distanza.html abstract. during the epidemic covid-19, in most of the countries schools of all grades and univesities had to face a long period of closure without interrupting the educational mission. distance education, which has been introduced first in uk in the nineteen century as “correspondence learning” and then in usa and australia, with the institution of “open universities” (i.e. mooc and e-learning platforms), became the only way to guarantee the continuity in teaching during the pandemic covid19. the present contribution is a short overview of the literature about limits and advantages of distance education of chemistry, in particular at high school and university levels, with a focus on the experiences and peculiarities of the distance education in the period of the covid-19 emergency. keywords. distance learning, distance teaching, distance education, chemistry, didactics, interactive teaching approaches, e-learning, m-learning, open learning. a short history of distance education distance learning and distance education have quite a long history, starting from the “correspondence courses”,1,2 born during the nineteenth century, and intended for students who were not able to attend the schools, mainly due to the vast distances of the country. the first correspondence education and distance training courses were developed in uk, usa and australia.1,2 the next step of the history of distance education is related to the new idea of “open university”, developed to get a wider access of students to high school studies and university courses. in the middle of the twentieth century, first in uk, several institutions designed new types of open courses in different disciplines with the main purpose to create a learning alternative to the traditional face-to-face education, specifically intended for those who had no possibilities to attend schools for social or economic reasons. open university programs allowed a sensibly increase of the number of students as never before: up to hundreds of thousands of students for each institution every year. the possibility to raise the number of students having free access to higher education is in line with the concept of “mass education”, which characterizes the teaching systems since the beginning of the twentieth century.3 substantia. an international journal of the history of chemistry 4(1) suppl. 1: 961, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-961 http://www/ http://www/ http://www.fupress.com/substantia http://smslab.dcci.unipi.it/ http://smslab.dcci.unipi.it/didattica-distanza.html distance education in chemistry during the epidemic covid-19 2 more recently, the idea of open courses was introduced both in the european and anglo-saxon countries in connection with the “lifelong learning” concept3,4 as a constitutive part of the educational policies.5 the basic idea is that citizens learn during their whole life, not only in formal contexts (i.e. at school, at the university or during professional training courses), but also in non-formal environments3,4 (i.e. visiting a museum, taking part of cultural, social or sport activities, letting informed on the web, and so on). nowadays, internet and social media are considered central in life-long learning as well as in distance education.4 the development of internet and related technologies, in fact, opened up to many different programs and tools, usually referred as e-learning and mlearning, if they imply the use of mobile devices, such as smartphones and tablets.6 since 2012, the idea of “open university” has evolved thanks to the new digital technologies into the so-called “massive online open courses” (mooc)7,8 which were firstly conceived by several universities in usa, such as the mit opencourseware (mit ocw), a project of online courses organized by the massachusetts institute of technology (mit). since then, several mooc programs have been provided in many universities and academies all over the world covering almost all disciplines and educational fields. one of the consequences of mooc was the possibility to have an unlimited number of students and to allow the attending of specific courses to adults, workers and people who, for several reasons, would not have had this chance, otherwise. open science courses and science moocs9 were developed too, mainly using to two modalities: synchronous and asynchronous approaches. the first mode implies the presence of students at the same time of the online course, either through videoconferences, livestreaming, forum or other interactive tools. the second mode of delivery of the online course, on the contrary, does not require the presence of students at the same time, and it is characterized by higher flexibility. in principle, students can listen or watch pre-recorded video-lessons, or perform online quiz without a definite time schedule, answer to questions by e-mail messages and so on. as reported in several works,6,7 the two modes can also be used together; moreover, these typical online activities can also be combined with face-to-face teaching modalities: in such cases, the educational approach is referred as “blended learning”.10 these new ways of teaching, in particular the blended learning and the online learning modes, were object of several studies aiming to investigate their effectiveness with respect to more traditional ones, as reported in ref. 6 and therein. these studies mainly focused on the effect of online learning and blended learning in terms of specific learning outcomes, student engagement, learning perception and metacognitive objectives and they substantially showed that these distance education modalities are at least as effective as face-to-face ones. however, as discussed in the following parts, additional work is needed to investigate their effectiveness in specific disciplines, such as chemistry. another important aspect of distance education is related to its accessibility. in principle, as also stated in the unesco declaration,8 distance education and online learning should follow several criteria in order to enhance, and not limit, the access to education. as reported in ref. 11: “students in distance learning courses represent a variety of racial and ethnic backgrounds, ages, native languages, and learning styles. in addition, increasing numbers of students with disabilities participate in regular precollege and postsecondary courses. their disabilities include blindness, low vision, hearing impairments, mobility impairments, learning disabilities, and health impairments.” the free access to all students and the equality of accessibility are probably the major tasks of distance education in the next future. distance education in chemistry: methods, tools and effectiveness not surprisingly, distance learning in chemistry has been introduced several decades ago, as well as computer simulations and digital software have been largely used in many research fields of chemistry since the seventies of the previous century.12 the first critical overview12 about distance learning in chemical education was published in 1999, showing how chemistry teachers took advantage from computing quite soon. for instance, online activities related to the creation of virtual workgroups or the sharing of multimedia, such as digital video and molecular 3d animations, were largely introduced both at the high school and university levels, in combination with face-to-face and hands-on activities.13 the new technological teaching modes demonstrated to be quite effective in chemical education concerning the level of interactivity and participation of students to the classroom activities. on the other hand, the main limitations of distance learning in chemistry seem to be related to the need of a specific teaching training and of a radical change of educational models.12 moreover, from these studies,12-19 it is evident that distance education in chemistry implies the availability of new and ad-hoc educational materials and, more important, a completely free access to digital tools and internet and/or mobile devices.12,13 it’s worth noticing that in the case of distance education at the university level, in several countries, online courses in chemistry16 and distance education were encouraged based on economic reasons.13 the need to organize chemical laboratories for an increasing number of students, especially in the case of firstdistance education in chemistry during the epidemic covid-19 year undergraduate students, stimulated the development of virtual laboratories and e-learning programs to reduce their cost and to allow students to attend the classes online, for instance in case the students could not access to the university campus. as observed in the previous paragraph, the countries characterized by large geographical distances, such as usa and australia, were the first developing specific digital tools and virtual environments for distance education in chemistry. examples of virtual laboratories of general chemistry and organic chemistry are reported in the literature,13,15,18,19 giving rise to interesting findings. in particular, some of these studies18,19 can be considered very useful in terms of organization of the materials, description and availability of free digital tools, assessment schemes and on-line resources. unfortunately, so far, few studies exist concerning the effectiveness of virtual laboratories in chemistry compared with hands-on laboratories. chemical education during the pandemic covid-19 the situation related to the pandemic covid-19 caused the closure of schools and universities in many countries, for different periods depending on the specific seriousness and risks perceived in different countries and to political choices. as reported in a note by unesco20, at the beginning of march 2020: “school closures in thirteen countries to contain the spread of covid-19 are disrupting the education of 290.5 million students globally, a figure without precedent”. distance learning and distance education appeared to the most the only way to assure the continuity of education and learning of students at all school and university grades. however, based on former considerations, several countries were certainly more prepared than others to face up this emergency. concerning chemical education, distance education for high school and university students was characterized mainly by synchronous video-lessons provided by chemical teachers who had to organize and prepare the educational materials by themselves, in most of the cases without the help and assistance of the school and university systems. most of these activities were performed on elearning platforms (i.e. the moodle platform) or websites designed for videoconferences (i.e. google meet, microsoft teams, zoom, skype and so on); they were often suggested by the schools and universities, with a certain variability of access modality. obviously, in some countries, the availability of digital tools, devices and virtual programs, as well as the previous experiences and teachers’ training programs on distance education in chemistry were of great help during the pandemic covid-19. it is quite significant that most of the interactive tools and software concerning virtual laboratories and chemical molecular simulations are in english. a great number of free resources were already available in several web-sites; many distance learning and online teaching resources were provided, for instance, by the chemical education division of the american chemical society.21,22 the same association launched a special issue of the journal of chemical education, aiming to share best practices in chemical education about distance learning and distance teaching during the emergency.23 other national chemical societies, such as the royal society of chemistry in uk and the italian chemical society in italy,24 started sharing chemical laboratory experiences and free on-line resources to be used for distance teaching. an interesting consequence of the emergency related to the unusual educational situation is the exponential increase of shared teaching experiences among teachers’ groups and associations. this also happened in chemical education: many chemical teachers started recording and sharing their own video-lessons, videos about hands-on and laboratory experiences, performed at home, by using common and everyday-life materials.25,26 in a way, thanks to the web and to the social networks, the unusual situation contributed to create a “virtual community of teachers in chemical education”. on the other hand, the long period of school and university closure, in particular in some countries as in italy, revealed all the limitations of teaching modalities based on distance education only. this is particular evident for those educational activities which imply a manual training, such as chemical and instrumental laboratories. an additional issue is related to the absence of empathy and psychological implications of distance education, which were clearly get worse due to the dramatic contest and general level of diffuse anxiety related to the covid-19 emergency. to conclude, the complete substitution of distance education to traditional education can be justified due to the global emergency caused by the epidemic covid-19, however, as already put in evidence in the previous reflections, a “blended learning” approach should be preferred in the next future. figure 1. a chemistry distance lesson during the covid-19 pandemic in italy. resource: wikicommon.25 3 distance education in chemistry during the epidemic covid-19 references 1. https://en.wikipedia.org/wiki/distance_education last accessed on june 8th, 2020. 2. f. lee, history and technology 2008, 24, 239. 3. v. domenici, insegnare e apprendere chimica, mondadori università, firenze, 2018, (third part). isbn: 978-88-6184-600-5. 4. j. k. gilbert, a. s. alfonso, lifelong learning: approaches to increasing the understanding of chemistry by everybody. in “chemistry education. best practices, opportunities and trends”, j. garcia-martinez and e. serranotorregrosa (editors), wiley-vch, weinheim, 2015. 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https://axial.acs.org/2020/03/27/resources-teach-chemistry-online/?utm_source=pubs_content_marketing&utm_medium=sem&utm_campaign=0420_fmt_pubs_0320_fmt_ed_online_learning&ref=pubs_content_marketing&gclid=cj0kcqjwopl2brdxarisaemm9y_qreeprqxfxb6azsli5ikq8h9sjlgrqws9fxjox_enfhrnw39oqdeaaggeealw_wcb https://axial.acs.org/2020/03/27/resources-teach-chemistry-online/?utm_source=pubs_content_marketing&utm_medium=sem&utm_campaign=0420_fmt_pubs_0320_fmt_ed_online_learning&ref=pubs_content_marketing&gclid=cj0kcqjwopl2brdxarisaemm9y_qreeprqxfxb6azsli5ikq8h9sjlgrqws9fxjox_enfhrnw39oqdeaaggeealw_wcb https://axial.acs.org/2020/03/27/resources-teach-chemistry-online/?utm_source=pubs_content_marketing&utm_medium=sem&utm_campaign=0420_fmt_pubs_0320_fmt_ed_online_learning&ref=pubs_content_marketing&gclid=cj0kcqjwopl2brdxarisaemm9y_qreeprqxfxb6azsli5ikq8h9sjlgrqws9fxjox_enfhrnw39oqdeaaggeealw_wcb 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https://commons.wikimedia.org/wiki/file:a_chemistry_distance_lesson_during_the_covid-19_pandemic_in_italy_(cropped_squared).jpg https://commons.wikimedia.org/wiki/file:a_chemistry_distance_lesson_during_the_covid-19_pandemic_in_italy_(cropped_squared).jpg https://commons.wikimedia.org/wiki/file:a_chemistry_distance_lesson_during_the_covid-19_pandemic_in_italy_(cropped_squared).jpg http://smslab.dcci.unipi.it/didattica-distanza.html substantia. an international journal of the history of chemistry 3(2) suppl. 6: 9-11, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-741 citation: l. campanella, l. teodori (2019) where does chemistry go? from mendeelev table of elements to the big data era. substantia 3(2) suppl. 6: 9-11. doi: 10.13128/substantia-741 copyright: © 2019 l. campanella, l. teodori. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. editorial where does chemistry go? from mendeelev table of elements to the big data era luigi campanella1, laura teodori2,* 1 department of chemistry “sapienza” university of rome, p.zzale aldo moro, 5, 00185, rome, italy 2 laboratory of diagnostics and metrology, fsn-tefis-dim, enea-frascati, via enrico fermi, 44, 00044 rome, italy *e-mail: laura.teodori@enea.it who is each of us if not a combination of experiences, information, readings, imaginations? every life is an encyclopedia, a library, an inventory of objects, a sample of styles, where everything can be continually re-mixed and rearranged in all possible ways “ (from italo calvino, american lessons, six memos for the next millennium, 1988) one hundred and fifty years ago the russian chemist  dmitri ivanovich mendeleev  published the first “periodic system of the elements” originated to display the periodic trends of the chemical elements known at that time and possibly to predict unknown elements supposed to fill the empty spaces, by predicting their properties.  his prevision turned out to be essentially correct. he had about sixty elements in his  periodic table  of 1869.   other naturally occurring elements were discovered or isolated in the following years, and various further elements have also been produced synthetically. in his honor element 101, discovered in 1905, was named  “mendelevium”. the modern periodic table, of 118 elements now, constitutes an important framework for exploring chemical reactions; it provides the basis for the discovery or the synthesis of further new elements and for the development of new theoretical models. although other chemists at the time of mendeleev attempted to organize the known chemical elements in a system, the extraordinary and visionary intuition of mendeleev was to use the trends in his periodic table to predict the properties of  missing elements. the philosophy behind the mendeleev conceptions about systemizing the extant knowledge of chemistry and possibility to predict the missing information, thanks to the network support, can be considered a pioneering approach of the new science called “systems chemistry” and the harbinger of the modern “predictive chemistry”. indeed, systems chemistry  is defined as “the science which study the networks of interacting molecules, to create new functions from an ensemble of molecular components at different hierarchical levels with emergent properties” 1. as in any systems science, systems chemistry too benefits of the massive outburst of big data. 10 luigi campanella, laura teodori big data indicate data sets large and/or complex enough, that traditional processing and analysis are not sufficient. now as then, in the mendeleev’s age, the need for rationalizing and systemizing data is compelling. indeed, in the case of big data, one must deal with a large amount of data with the need of dimension reduction, as in the process of zipping them, to compress large quantity of data into smaller equivalent sets. statistical/ computational intelligence tools such as principal component analysis, fuzzy logic, neuro-computing, evolutionary computations etc. are developed to reduce the size of big data sets and extract valuable information. in this regard, we see the today-approach towards datadriven chemistry as an evolution of the mendeleev philosophy, rather than a revolution. dmitri mendeleev was actually the first to envision the possibility to systemize chemical knowledges in a frame were much space would be available to the unknown elements which would fit within a “systemic” view of the system, and he was, therefore a real pioneer of the modern predictive data science able to extract knowledge or insights from large data sets. the figure of dmitri mendeleev has inspired much fascination and his story about the idea that he said to have had it envisioned in a dream is amazing: he dreamed all the elements falling into the right place. however, we think that his philosophical thoughts had not influenced and not reported enough by the historians of science. as confirmation of this idea is the fact that mendeleev never got the nobel prize although candidate several times: in 1901, 1905 and 1906, but he lost because, according to the committee, his work was already too old and well known: paradoxically, the mendeleev’s table was victim of its own success. in 1906 the nobel award went instead to henry moisson for the discovery of fluorine, an element that was right were the table predicted to be. the following year mendeleev died, and so his table of the elements could not boast a nobel. however, we think that with the advent of systems chemistry, mendeleev’s philosophy of logic systematization and prediction of missing elements is taking a rematch. being the focus of systems chemistry research on the overall network of interacting molecules and on their emergent properties, the way in which specific interactions between the components propagate through the system may predict these emergent properties. the term “systems chemistry” was first used in 2005 by von kierowski2. he stated that: “combining kinetic, structural, and computational  studies on complex dynamic feedback systems may lead to the field of systems chemistry”. the approach is exemplified by the analysis of a simple organic self‐replicating system that has the potential to express both homochiral autocatalysis and heterochiral cross‐catalysis. von kiedrowski claimed that this new approach could pave the way to a new field he named “systems chemistry”, that is to say, the design of prespecified dynamic behavior. later on, this proposal moved away from its reductionist approach to the study of multiple variables simultaneously 3,4,5. several topics related to systems chemistry bring also philosopher and existential questions such as: what made possible on the prebiotic earth the “transmutation” of a complex mixture of molecules into living chemical systems?; why the biochemical building blocks of life were selected and how some of these biomolecules developed to have specific chirality? the latter poses fundamental questions about the origin of chiral asymmetry in biological molecules which still remains without answer6,7. systems chemistry attempts to address these issues by creating synthetic systems models with properties that could reflect aspects of prebiotic biogenesis. another topic at the core of systems chemistry is the quest for de novo life.  however, systems chemistry encompasses much more than these issues and put forward a plethora of new opportunities for the discovery of dynamic figures in all areas in chemistry. in 2005 in venice during a conference an early consensus definition of systems chemistry was established as below8: • a conjunction of supramolecular and prebiotic chemistry with theoretical biology and complex systems research addressing problems relating to the origins and synthesis of life. • the bottom-up pendant of systems biology towards synthetic biology. • searching for a deeper understanding of structural and dynamic prerequisites leading to chemical selfreplication and self-reproduction. • the quest for the coupling of autocatalytic systems, the integration of metabolic, genetic, and membrane-forming subsystems into protocellular entities. • the quest for the roots of darwinian evolvability in chemical systems. • the quest for chiral symmetry breaking and asymmetric autocatalysis in such systems. since then, systems chemistry has had a big boost due to the advent of data science tools. data science is defined as a  multi-disciplinary  science that uses scientific methods, processes, algorithms and systems to extract  knowledge  and insights from structured and unstructured  data9. it has been presented as the fourth pillar of science (being theory, experimentation and simulation the other three). with the advent 11where does chemistry go? from mendeelev table of elements to the big data era of “omics” in life sciences (genomics, proteomics, transcriptomics, metabolomics etc.) and the advent of modern high-throughput techniques of analytical chemistry and molecular biology we are able to produce a huge amount of data. thus, the way we undertake research is presently changed and the data drive science is considered the fourth paradigm (see figure). the increasing rate of data generation in all scientific disciplines is providing incredible opportunities for data-driven research, transforming our current processes. the exploitation of so-called ‘big data’ will enable us to undertake research projects never possible before but also stimulate us to reevaluate our previous data. the 2002 was identified as a turning point in data and a landmark year when digital took over from analog. indeed, it was observed that in 2009, more data worldwide were produced than all the preceding years put together. the advent of the big data age changed irreversibly the paradigm of science. thousand year ago, science was empirical, based on, or confirmed by observation rather than theory or logic speculations. a few hundred years ago science was based on theoretical models. a few decades ago, when computer modeling simulation was introduced to understand complex phenomena, the paradigm of science changed again. today we are witnessing the coming of the fourth paradigm of science which unifies theory, experiments, simulation, computation, creating big data sets and entering the era of “data science” or “systems sciences”, originating the fourth paradigm of science which is data-driven discovery. the possibility of collecting big data has surpassed, by far, the present capability of analyzing them. at this purpose more and more dedicated, open-source “highperformance computing platforms”  are being developed. open-access data repositories, where multiple  databases or  files  or experimental results are  loaded by scientists, are the backbone of these platforms and stimulate a collaborative attitude among scientists. unfortunately, data science approach represents still a rather unexplored field among the community of chemical scientists, thus, limiting many opportunities for advancing chemical sciences. conversely, many advances are being put in place in the systems biology area and learning from biological complexity can be a way of stimulating new chemistry. biological systems display an incredibly large amount of amazing capabilities that can be a rich source of models for new areas of chemistry to design nonbiological systems. it is a big challenge for the chemistry of the 21st century, perhaps it is the challenge. references 1. j.w. sadownik, otto, s., systems chemistry, encyclopedia of astrobiology, springer-verlag berlin heidelberg, 2014. 2. m. kindermann, i. stahl, m. reimold, w.m. pankau, g. von kiedrowski, angewandte chemie, 2005, 44, 6750-5. 3. r.f. ludlow, s. otto, chemical society reviews, 2008, 37, 101-8. 4. j.r. nitschke, nature, 2009, 462, 736-8. 5. j.j. peyralans, s. otto, current opinion in chemical biology, 2009, 13, 705-13. 6. a. ricardo, j.w. szostak, scientific american, 2009, 301, 54-61. 7. k. ruiz-mirazo, c. briones, a. de la escosura, chemical reviews, 2014, 114, 285-366. 8. j. stankiewicz, henning eckardt, l., angew. chem. int. ed., 2006, 45, 342–344. 9. v. dhar, communications of the acm, 2013, 56, 64–73. 10. a. agrawal, choudhary, a., apl materials 2016, 4. figure. the four paradigms of science: empirical, theoretical, computational, and data-driven. image from agrawal and choudhary 10. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 6 2019 firenze university press where does chemistry go? from mendeelev table of elements to the big data era luigi campanella1, laura teodori2,* visualizing solubilization by a realistic particle model in chemistry education antonella di vincenzo, michele a. floriano* chemistry as building block for a new knowledge and participation stefano cinti tissue engineering between click chemistry and green chemistry alessandra costaa#, bogdan walkowiakb, luigi campanellac, bhuvanesh guptad, maria cristina albertinie* and laura teodori a, f* chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity. sara tortorella,1,2,* alberto zanelli,2,3 valentina domenici2,4 substantia. an international journal of the history of chemistry 4(2) suppl.: 89-94, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-841 citation: m. ziaee, m. taseidifar, r.m. pashley, b.w. ninham (2020) efficient dewatering of slimes and sludges with a bubble column evaporator. substantia 4(2) suppl.: 89-94. doi: 10.36253/ substantia-841 copyright: © 2020 m. ziaee, m. taseidifar, r.m. pashley, b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. efficient dewatering of slimes and sludges with a bubble column evaporator mohammad ziaee1, mojtaba taseidifar1, richard m. pashley1,*, barry w. ninham2 1 school of science, unsw canberra, northcott drive, canberra, australia 2 department of applied mathematics, research school of physical sciences and engineering, australian national university, canberra, australia *corresponding author: r.pashley@adfa.edu.au abstract. the recalcitrant nightmare of de-watering slime/sludge is a major issue, for both industry and the environment. a simple process is developed that solves the problem. it uses a bubble column evaporator (bce) with heated dry air. the model slime to illustrate the de-watering process was a concentrated dispersion of spherical 5 micron silica particles in pure water. typical slime samples were de-watered in the range 20-35% colloid/water (w/w) using dry inlet gases pre-heated to temperatures of 150 °c and 250 °c. the bce process was run at sub-boiling temperatures, with the column solution in the range, 43 and 74 °c, with those two inlet temperatures operating for de-watering the slime. a significant bonus is that the pure water vapour produced can be condensed and used as a source of high-quality water for reuse. the bce process offers simplicity, resilience to slime feed quality, and a pure water biproduct. it also offers a continuous and controlled low-maintenance process. these are clear advantages in de-watering a wide variety of industrial slimes and sludges. in addition, the process involves the passage of a continuous flow of hot dry gases. this causes the dispersion to remain sufficiently fluid to allow easy transportation. however, once the hot gas flow ceased, the dispersion immediately solidified. the success of the bubble column process for dewatering and validation of the mechanism is even more enhanced if helium is used instead of air. it appears that hot helium atoms can disrupt water hydrogen-bonding in the liquid surrounding the hot bubbles and this enhances water vapour collection efficiency. the bubble method appears to offer more than significant advantages over other methods, such as hydrocyclone methods, which are often used to de-water mining wastes. keywords: slime and sludge de-watering, bubble column evaporator, silica spheres, helium gas. 1. introduction – slime and sludge de-watering the words sludge or slime are used to mean a high water-content colloidal dispersion that stubbornly resists de-watering. de-watering is a process in which water is separated from the solids, to thicken up the waste for disposal or end-user purposes. this is a problem that poses major eco90 mohammad ziaee, mojtaba taseidifar, richard m. pashley, barry w. ninham nomic, environmental and safety challenges for a range of sludge types in industries like clay production, phosphate mining, diamond mining, sewage sludges, sand washing, and sludges from paper mills, gold mining, and different metallic ores. as an example, phosphate mining produces clay tailing slurries or sludges which are usually less than 10% solid content. this must be dewatered to a value of at least 40% by an economically acceptable process. often the solid content has an average particle size equal to or less than 50 microns. this is generally characteristic of suspensions of siliceous and clay solids, and for other minerals, depending on the industrial process.1,2 different techniques to dewater sludges are employed in different industries. they include coagulation, f locculation, grinding, heating, applying high voltages and using hydrocyclones. however, each of these techniques has its own drawbacks and they often fail to provide desirable solid content levels. for instance, flocculation and coagulation methods need considerable amounts of chemical agents which might cause environmental, economic and safety concerns.2,3 conventional methods, for example ponding, also suffer from disadvantages. it is time consuming and requires large acreages of land to effectively de-water large volumes of slurries. this also increases land maintenance and remediation costs, also causes environmental and health issues.2 hydrocyclones are frequently used in different industries for de-watering of solid-liquid suspensions. generally, large hydrocyclones are used for separation of particles (larger than 25 µm) from slimes, while smaller hydrocyclones with diameters less than 10mm are usually used to separate fine particles smaller than 10 µm. the controllability and efficiency of the hydrocyclone method are limited and this method needs to be augmented by further processes like centrifugation to optimise dewatering.4 hydrocyclones, in general, are comprised of an inlet, a main body and two outlets. in order to increase the recovery of solids, the feed pressure needs to be increased. other conditions such as relationship between cutsize, bypass and water recovery determine the performance. thus, depending on the waste type, they need to be optimised in order to obtain maximum efficiency in de-watering.5,6 also, for further improvement of the hydrocyclone process, a centrifuge can also be incorporated. this uses centrifugal forces made by spinning a bowl or basket to separate the sludge solids from the liquid.7 in this work a novel method of de-watering slime using a bubble column evaporator (bce) is developed and evaluated. this can be used for many different sludge thickening applications. the bce exploits the high interfacial area between gas bubbles and water and acts as a natural semi-permeable membrane. this process uses hot bubbles to allow water vapour to escape but not the solid particles. so far, a wide range of useful applications of the bce process have been developed by our research group. the list includes: a new method for the precise measurement of enthalpies of vaporisation (δhvap) of concentrated salt solutions;8,9 evaporative cooling;10 a new method for thermal desalination11-13 a novel method for sub-boiling thermal sterilization;9,14-18 a novel method for the low-temperature thermal decomposition of some solutes in aqueous solution;19 and a new approach to aqueous solute precipitation in a controlled manner.20 in addition, a bubble column condenser has also been designed for the production of highquality water as condensate.21-23 figure 1 depicts the various applications of the bce technique we have developed. the green arrows refer to the previous applications developed by the bce method, while the red arrow refer to the latest application of this method. 2. materials and methods for each experiment 50 g of 5 µm spherical silica powder supplied by us research nanomaterials company was used. milli-q water was added to pure 50 g of silica powder to reach 250 g of water-silica mixture. then, the mixtures were stirred to produce uniform dispersions. the measured turbidity of silica mixtures (20% figure 1. different applications for the bce process. 91efficient dewatering of slimes and sludges with a bubble column evaporator weight), was about 40,000 ntu measured by hach 2100an turbidimeter. the concentration of solid particles (slime thickness) in the mixtures were calculated using the following formula: solid concentration % = × 100 (1) the bce process is illustrated schematically in figure 2. in this work, four experiments were undertaken for de-watering the prepared slime samples using two different gases (dry air, helium) at two different outlet gas temperatures (150 °c, 250 °c). in each experiment, 250 ml of the prepared slime sample was poured into a 120 mm diameter open-top glass column (büchner type, pyrex® borosilicate, vwr) with a sinter porosity of number 2. the outlet gas temperature was varied using a tempco air heater (300w) with a thermocouple temperature monitor and an ac variac electrical supply. a tenmars thermometer (tm-84n, taiwan) with the accuracy of ± 1.5 °c was applied on the surface of the sinter to measure the temperature of hot gas introduced to the empty column. the air gas was produced from an air pump (hiblow hp40, philippines) and a boc gas flow meter was used to measure flow rates. the temperature of the column solution was also continuously monitored using a thermocouple positioned at the centre of the aqueous mixtures. due to our requirement of a slime gas temperature up to 250 °c, the temperature of the gas heater might reach above 700 °c. that necessitates the use of a steel heater and brass connectors for the downstream, and the use of rockwool as an insulating material. the effectiveness of the bce process was quantified experimentally based on the weight loss of the slime using the following equation: water loss % = × 100 (2) where w1, w2, and wd are the initial weight of slime, final weight of slime, and the weight of dry solid compounds, respectively 3. results and discussion 3.1. results for air in the first experiment, 250 g of a silica-water mixture with a concentration of 20% was poured to the column using hot dry air at a temperature of 150 °c. after 45 minutes using hot air with a flow rate of 34 (l/min) for production of hot bubbles in the aqueous mixture, the residual mixture was weighed and the new solid concentration (slime thickness) was calculated using equation (1). the results are presented in table 1. it shows that the final solid concentration (slime thickness) is 30.5%. also, the density of the dispersion was increased in this process from 1.05 g/ml to 1.16 g/ml and the operating temperature of the bce slime remained at about 48-49 °c. in the second experiment applying dry air at the temperature of 250 °c with a flow rate of 34 l/min over 45minutes, the silica concentration increased from 20 to 34.7%. the temperature of the slime mixture remained in the range of 65-66 °c. the density increased from an initial value of 1.05 to 1.25 g/ml. an example of the bubbling process is shown in the photograph in figure 3. 3.2. results for helium when helium gas was used for producing bubbles, the helium flow rates were measured using two methods: by weighing the helium cylinder and from calculations based on the helium cylinder pressure differential. the first method gave a flow rate of about 13.9 l/min and the calculations based on the helium cylinder pressure differential led to a flow rate of 10.4 l/min. therefore, an average value of 12 l/min was used for comparison with the 34 l/min dry air flow. according to the previous studies, helium is a more effective gas in bubbling because of its natural production of smaller bubbles, even in pure water.13 in these experiments helium flowed into the bce column containing 20% silica dispersion at an inlet temperature of 150 °c, flow rate of 12 l/min. after 45 min with the column solution equilibrating at about 41 °c, the silica concentration was increased to 28% and the figure 2. schematic diagram of bce system for slimes de-watering. 92 mohammad ziaee, mojtaba taseidifar, richard m. pashley, barry w. ninham solution density increased from 1.05 g/ml to 1.19 g/ml. when the helium inlet gas temperature was increased to 250 °c at 12 l/min, after 45 min with the column solution equilibrating at about 63°c, the silica concentration (slime thickness) was increased to 32.5% and the solution density increased from 1.05 g/ml to 1.23 g/ml. table 1 summarises the de-watering results of 20% silica slimes using bce process with air and helium gases. at these high silica content levels, the dispersion remained sufficiently fluid for reasonable transport but on stopping the hot inlet gas flow the dispersion immediately solidified. the values reported in table 1 are the mean values calculated based on the data obtained after three runs for each single experiment. besides undertaking experiments using silica-water slime, four experiments have been carried out using both air and helium (at 150 °c and 250 °c) with an industrial slime which had a similar compound composition. the results achieved were very close to the results obtained for de-watering the model silica slime. figure 4 shows a scanning electron microscopy (sem) image of the precipitated silica particles used in this study. this shows that they are of spherical appearance and very fine. fine particles (e.g., silica spheres) can stabilise foams even in the absence of surfactants or polymers.25 aqueous foams stabilised solely by particles, but these are usually partially hydrophobic and so have an amphiphilic nature.25 the studies reported here were based on the use of hydrophilic silica particles dispersed in pure water. these micron sized particles would generally act to destabilise foams via water film rupture and hence even with continuous air and helium gas flow no significant level of transient foaming was observed. the relative water loss under different conditions is calculated based on equation (2) and summarised in figure 5. regarding the figure, using helium gas is much more effective than dry air since this level of de-watering was achieved at about one third of the volumetric flow rate compared with air. in order to compare the efficiency of using different gases for slime de-watering the following equation 3 was used: (3) figure 3. photograph of the bce process applied to 20% silica slimes using hot air. table 1. de-watering of initial 20% silica slime (density of 1.05 g/ ml) using bce process with different gases (air and helium). gas flow rate (l/min) gas temperature (°c) slime temperature (°c) slime thickness (%) slime density (g/ml) bce with air 34 150 48-49 30.5 1.16 34 250 65-66 34.7 1.25 bce with he 12 150 41 28.0 1.19 12 250 63 32.5 1.23 figure 4. sem of micro-silica spheres produced by precipitation. 93efficient dewatering of slimes and sludges with a bubble column evaporator where e, cp, f are efficiency of gas carrier, heat capacity of gas at the constant pressure, and gas flow rate, respectively. also, numbers refer to gas carrier 1 and 2. the water loss factor for each gas carrier can be calculated from equation (2) and the cp value for air and helium gases are 29.31 and 20.77 (j mole-1 k-1), respectively. the ehelium/eair ratio regarding operational temperatures at 150 °c and 250 °c, gas flow rates, and water loss are 3.25 and 3.62 respectively. this means that to reach an equal level of slime de-watering, helium almost needs less than 1/3 of the energy which air needs. 4. conclusions the bce system was found to be very effective for slime de-watering. this is major step forward. its effectiveness was found to depend on the gas temperature. heated dry air gas at 250 °c was found to be significantly more effective than applying hot dry air at 150 °c to concentrate the slime. it was found that helium gas is more effective than air. we conjecture that this might be due to the very small size of a helium atom with a diameter of 62 pm. helium atoms can break the hydrogen bonding among water molecules adjacent to the gas-liquid interface and allow easier transfer of water molecules into the rising helium bubbles. (the length of hydrogen bonding among water molecules in the liquid phase is about 1.97 å). the bce method using hot, dry carrier gases offers a promising technique to de-water a wide variety of slimes and slurries produced in different industries. it is simple and robust. this process might offer a novel competitive dewatering process and could be readily scaled up. it offers a robust process which can replace existing techniques such as flocculation, hydrocyclones, and ponding. the bce technique applied to de-watering also has the very significant additional advantage of producing high quality water from condensation of the sub-boiling water vapour. 5. references 1. n.c. lockhart, electro-osmotic dewatering of fine tailings from mineral processing, int. j. miner. process., 1983, 10(2), 131-140. 2. t.j. laros, flocculating agent combinations for mineral slime filtration systems, 1990, envirotech corp, united states patent, patent no: 4,931,190. 3. p. pirkonen, b. ekberg, chapter nine  –  ultrasonic, prog. filtr. sep., 2015, 399-421. 4. s. pasquier, j.j. cilliers, sub-micron particle dewatering using hydrocyclones, chem. eng. j., 2000, 80(1), 283-288. 5. j.j. cilliers, l. diaz-anadon, f.s. wee, temperature, classification and dewatering in 10 mm hydrocyclones, miner. eng., 2004, 17(5), 591-597. 6. d. vega-garcia, p.r. brito-parada, j.j. cilliers, optimising small hydrocyclone design using 3d printing and cfd simulations, chem. eng. j., 2018, 350, 653-659. 7. g. chen, p. lock yue, a.s. mujumdar, sludge dewatering and drying, drying technol., 2002, 20(4-5), 883-916. 8. c. fan, r.m. pashley, precise method for determining the enthalpy of vaporisation of concentrated salt solutions using a bubble column evaporator. j. sol. chem., 2015. 44(1), 131-145. 9. c. fan, m. shahid, r.m. pashley, studies on bubble column evaporation in various salt solutions, j. sol. chem., 2014, 43(8), 1297-1312. 10. m. francis, r.m. pashley, application of a bubble column for evaporative cooling 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for improved sterilization, j. water process. eng., 2015, 8, 1–6. 16. a.g. sanchis, m. shahid, r.m. pashley, improved virus inactivation using a hot bubble column evaporator (hbce), colloids surf. b: biointerfaces, 2018, 165, 293-302. 17. a.g. sanchis, r.m. pashley, b. ninham, virus and bacteria inactivation by co2 bubbles in solution, npj clean water, 2019, 2, 5. 18. m. shahid, r.m. pashley, m. rahman, use of a high density, low temperature, bubble column for thermally efficient water sterilisation, desalination and water treat., 2014, 52, 4444–4452. 19. m. shahid, x. xue, c. fan, b.w. ninham, r.m. pashley, study of a novel method for the thermolysis of solutes in aqueous solution using a low temperature bubble column evaporator, j. phys. chem. b, 2015, 119 (25), 8072–8079. 20. c. fan, r.m. pashley, the controlled growth of calcium sulfate dihydrate (gypsum) in aqueous solution using the inhibition effect of a bubble column evaporator, chem. eng. sci., 2016, 142, 23-31. 21. p.n. govindan, g.p. thiel, r.k. mcgovern, j.h. lienhard, m.h. elsharqawy, bubble-column vapor mixture condenser, 2013, united states patents, patent no: us 8.523,985 b2. 22. g.p. narayan, j.h. lienhard, thermal design of humidification– dehumidification systems for affordable small-scale desalination, ida j. desalination water reuse, 2012. 4(3), 24-34. 23. m. schmack, h. goen, a. martin, a bubble column evaporator with basic flat-plate condenser for brackish and seawater desalination, environ. technol., 2015, 37(1), 74–85. 24. m. shahid, c. fan, r.m. pashley, insight into the bubble column evaporator and its applications, int. rev. phys. chem., 2016, 35(1), 143185. 25. a. stocco,  e. rio, b. p. binks, d. langevin, aqueous foams stabilized solely by particles, soft matter, 2011, 7(4), 1260-1267. substantia. an international journal of the history of chemistry 4(2): 151-154, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-923 citation: a. di meo (2020) communicating science: a modern event. substantia 4(2): 151-154. doi: 10.13128/ substantia-923 received: nov 23, 2019 revised: apr 26, 2020 just accepted online: apr 28, 2020 published: sep 12, 2020 copyright: © 2020 a. di meo. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article communicating science: a modern event antonio di meo sapienza university, rome, italy e-mail: dimeoantonio17@gmail.com abstract. science is by its very nature an intersubjective, public, collaborative and democratic (at least in principle) enterprise. the modern scholar of nature, in fact, cannot but communicate first of all to his/her colleagues the results of his/her research, since, in the final analysis, science is a socially shared and socially validated corpus of knowledge. the results of research must therefore be made public but non only among the specialists. the modern way of communicating science has triggered a progressively accelerating circulation of documents (rather than researchers), reversing a more than secular trend in which scholars reached the places where knowledge was deposited and archived. the modern databases, that host books, newspaper and periodicals like actual libraries and are accessible online, represent the last expression of this inverted mobility between documents and consultants. keywords: communication, modern science, ethics of research, progress, academies, scientific press, scientific entertainment. the emphasis that is generally put in modern science on the problem of communication has a very profound raison d’ être: compared to many other forms of knowledge, science is by its very nature an intersubjective, public, collaborative and democratic (at least in principle) enterprise. the modern scholar of nature, in fact, cannot but communicate first of all to his colleagues the results of his research, since, in the final analysis, science is a socially shared and socially validated corpus of knowledge. only the work which is actually understood by other scientists and used hic et nunc counts for the progress of science. the results of research must therefore be made public. whatever scientists think or say individually, their findings cannot be considered as belonging to scientific knowledge until they have been reported and recorded on a permanent basis. this imperative has been (and is) often motivated as a moral obligation; as a service rendered to humanity in general, but it has a foundation in the very structure of the functioning of modern science, which has been born and developed since the late renaissance in opposition to an elitist tradition of knowledge and its transmission. within this tradition, the language – often allegorical, metaphorical and analogical – served rather to conceal the contents of knowledge reached from the public of the uninitiated than to reveal them, in order to delimit its acquisition to restricted and selected cirhttp://www.fupress.com/substantia http://www.fupress.com/substantia mailto:dimeoantonio17@gmail.com 152 antonio di meo cles of interlocutors, to the ‘elected’, precisely. the very idea of progress, which, as is well known, is strongly linked to the beginnings and developments of modern science, since it implies a transgenerational relationship, refers to the possibility of communicating over time that only appropriate language can allow, which must use concrete means capable of making such transmission possible. but this implies in advance that the very idea of translating and transmitting one’s own thought in written form and accessible to most people is considered positive and valued. after the first phase of the correspondence in terms of private contacts, even coordinated as in the case of marin mersenne and its “cenacolo” of the so called academia parisiensis at the beginning of seventeenth century, from the sixteenth century the scientific communication developed through networks of intellectual and curious individuals. these collectives were initially unformal, like the gresham college, the bureau d’adresses, l’académie de montmor and so on, but they were soon (1657-1666) replaced by real scientific academies as the accademia dei lincei, the académie royale des sciences, the royal society of london and all the other ones that were progressively constituted between ‘700 and today in europe, north america and the rest of the world. these new institutions – either spontaneous or under the patronage of erudite men – proliferated in the modern era, not only in the scientific fields, but also in the literary and artistic ones. besides the statutes that regulated the internal life and the admissions, some academies established their own press where papers discussed in specific sessions or sent by single scientists could be periodically printed. academic proceedings were not the only way of publication; there were also books and an increasing number of journals and magazines, confirming that press played a fundamental role in the development of science and cultural dissemination. obviously, the transmission of memory in a longterm perspective needs a supporting material which is able to guarantee the circulation of knowledge from past to future. in this case the support must ensure almost unlimited reproducibility of the document, in order to make the necessary material available cheaply and easily for all those engaged in research activities or curious about the outcomes. the modern way of communicating science, therefore, has triggered a progressively accelerating circulation of documents (rather than researchers), reversing a more than secular trend in which scholars reached the places where knowledge was deposited and archived. the modern databases, that host books, newspaper and periodicals like actual libraries and are accessible online, represent the last expression of this inverted mobility between documents and consultants. but, more important, they allow a relevant shortening of the time needed for sharing knowledge. since the birth of the first academies, scientific communication has been substantially institutional, anticipating the production of knowledges, that remained a personal and private activity, secondary to that one by which researchers got the means for their subsistence till the end of 19th century. but writing in itself is not enough: the style must be clear and able to make the contents of the work comprehensible. to many “moderns”, writing in an obscure way was equivalent not to write at all! the use of a written language which is understandable by the largest number of people is fundamental to allow the comprehension of a text. this need had been satisfied for many centuries by the use of latin language. for this reason, intellectuals and thinkers faced a contradiction between the universal comprehension of science versus the more democratic access to it by the use of local and national idioms which are more easily understood by citizens. the modern science greatly contributed (albeit differently from the humanistic disciplines) to the crisis of latin as universal language. this crisis originated from social, political and religious causes, which are deeply intertwined; thus, it is very difficult to analyse them separately. the success of national languages can be ascribed to the increasing interest in science by common citizens from the emerging social classes. knowledge was no longer a privilege of erudite people and nobility: science was considered “useful” and lots of people looked at it as a mean of social growth. for example, in the introduction to the italian edition of the “cours de chymie” by nicolas lèmery (1675), it was possible to read that barbers and apothecaries would have considered this treatise so useful as to consult it with the same frequency as the priests read their breviaries. in this context it is also worth mentioning galileo galilei’s works, that represent one of the most excellent expression of the italian language of 17th century, able to maintain its virtuosity till today. between the end of 17th century and the beginning of the 18th century an ever-widening “public sphere” of science and technology was established outside academies, and scientific experimentation became a common practice in the institutions dedicated to teaching. these labs became usual rendezvous for people with different backgrounds and culture, and hosted discussions about the nature of philosophy, new techniques and discoveries. 153communicating science: a modern event a particularly rich audience meet in anomalous places like coffee rooms, hotels, guest houses, especially in england in the period ’700-’800. science became a very popular subject for public initiatives: international speakers started moving across european countries showing instruments, experiments and practical demonstrations during their conferences. successively the first international exhibitions were established; here science, technology and industry were celebrated all together as the three main aspects of the same reality and recognized as the key actors for the economic development and the improvement of the social life quality. an explicative, albeit overlooked episode of the capillary penetration of science into society is the diffusion of agricultural education in rural areas (agriculture represented the main economic activity until the end of 20th century). the nobility, especially in france, germany and england, was totally fascinated by this new tendency, producing a lot of informative printed material and giving life to a true propaganda in favour of science applied to agriculture, as shown in many literary works of that time. science became also a source of playful and ‘wonderful’ entertainment: initially restricted to the aristocratic and bourgeois elites, it progressively propagates to all social classes. this was the origin of the physique amusante, a definition given by the french chemist jeansébastien-eugène julia de fontenelle (1790-1842) in his divulgation work manuel de physique amusante, which was published in paris in 1826. this book is an example of a particular literary genre with the explicit popular aim of entertaining and amusing. however, in this kind of works there was a tendency to illustrate a certain law or principle behind some surprising phenomenon rather than demonstrating or explaining the causes, making these presentations engaging for the general public. between the 18th and 19th centuries in the most enlightened courts, as well as in noble houses, real scientific, educational or entertainment evenings took place, and the protagonist of the event was the most varied scientific instrumentation: electrostatic, mechanical, magnetic and electromagnetic, or even chemical and pneumatic. during these soirees the so-called ‘electrifying physicists’ showed thrilling experiments with the ‘electric fire’ (or ‘electric virtue’), which was considered by the new natural philosophers – as well as by actors, barkers and charlatans – the fluid responsible for the most varied phenomena, and capable of great and wonderful games, especially since it was discovered “that ladies generally electrify more easily than men and young women better than the old ones”. this ‘fire’ was also considered by some doctors (professional and not) as a vital fluid, and a possible source of new and extraordinary therapeutic methods, like a sort of universal panacea. electrical phenomena were particularly suitable for the theatricalisation of science, a very popular trend since the beginning of 18th century, especially in great britain. but scientific divulgation, even in an ‘entertaining’ or accessible way, did not involve only minor characters: the greatest disseminator of newton’s ideas in france was voltaire with his philosophical pamphlets, or jean d’alembert in the pages of the encyclopédie. the salon of emilie du chatelet (1706-1749), a scientist and philosopher in the circle of voltaire, at the castle of cirey, was a center of divulgation of newtonianism in the european continent. regarding chemistry, denis diderot (1713-1784) was brilliant propagandist, together with paul-henry thiry d’holbach (1723-1789), who, in the mid-eighteenth century, translated into french (i.e. the language of science of the time) the works of the physician and chemist georg ernst stahl (1660-1734), the founder of the phlogiston theory. very few works are capable of explaining to a wide audience the theory of chemical affinity: excellent examples are the first chapters of wolfgang goethe’s elective affinities (1809) (17491832) or, nowadays, primo levi’s periodic system (19191987). the broadening of the ‘audience’ interested in science reached both young gentlemen and – exceptionally – women: in particular works explicitly dedicated to women were composed, usually in the form of a salon or gallant dialogues, which gave life to a specific literary genre. some examples of these writings ‘for ladies’ were the entretiens sur la pluralité des mondes (1686) by bernard le bovier de fontenelle (1657-1757) who had numerous translations into italian (1711, 1744, 1765, 1831, etc.), followed in italy by the works il newtonianismo per le dame, ovvero dialoghi sopra la luce, i colori, e l’attrazione (1737) by the venetian polygraph francesco algarotti (1712-1774) and la chimica per le donne (1796) by the jacobin giuseppe compagnoni (1754-1833). many newly formed institutions, such as the royal institution (1799) in london, directed by the chemist humphry davy (1778-1829) and then by the physicist and chemist michel faraday (1791-1867), organized popular conferences on scientific subjects in the nineteenth century. these symposia became very popular, exciting events, just as concerts and theatrical performances (the christmas lectures, inaugurated by faraday in 1826, were dedicated to young people). the current return of the amusante way of science spectacularization for the general public, through websites, television and radio broadcasts, magazines, science festivals, interactive science centers, ‘science cafes’, 154 antonio di meo ‘scientific theatre’, and so on, have very prestigious precedents, in an era of great enthusiasm for a new form of knowledge which has proved to be the foundation of our current civilization. references: herbert butterfield, le origini della scienza moderna, bologna, il mulino, 1998. paolo rossi, i filosofi e le macchine: 1400-1700, milano, feltrinelli, 1962. id., la scienza e la filosofia dei moderni: aspetti della rivoluzione scientifica, torino, bollati boringhieri, 1989 id., la nascita della scienza moderna in europa, roma, laterza, 1997. aa. vv., storia della scienza, treccani, istituto della enciclopedia italiana, roma, 2001-2008, volumi v, vi, vii. substantia an international journal of the history of chemistry vol. 4, n. 2 2020 firenze university press some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy, ph.d., j.d. …and all the world a dream: memory outlining the mysterious temperature-dependency of crystallization of water, a.k.a. the mpemba effect evangelina uskoković1, theo uskoković1, victoria wu1,2, vuk uskoković1,3,* the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries aleksander sztejnberg communicating science: a modern event antonio di meo 1 citation: l. campanella, m. anastasio (2020) the concept of organization and the strategic position of chemistry in a generic research and development project focused on sars-cov-2. substantia 4(1) suppl. 1: 941. doi: 10.13128/substantia-941 received: may 20, 2020 revised: jun 26, 2020 just accepted online: jun 29, 2020 published: jun 29, 2020 copyright: © 2020 l. campanella, m. anastasio. this is an open access, peerreviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative com mons attribution license, which per mits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia feature article the concept of organization and the strategic position of chemistry in a generic research and development project focused on sars-cov-2 luigi campanella,* maurizio anastasio department of chemistry, sapienza university, piazzale aldo moro 5, 00185 rome, italy *corresponding author: luigi.campanella@uniroma1.it abstract. the tragic events related to the spread and pathologies caused by sars-cov-2 prompted the authors, whose working interests have always focused on academic and industrial scientific research, to provide their contribution in the planning of a generic applied research project. the article focuses on the synergy between the management organization of a research group and the strategic position that chemistry should occupy among other scientific disciplines in the case of scientific technological projects. keywords. covid19, scientific research, sars-cov-2 1. introduction the period we are living in is so dense with information about virulence, spread and pathologies caused by sars-cov-2 that it dramatically affects not only our physiology, but also the psychology in our daily life, making tomorrow highly uncertain.1a, 1b this continuous hammering can trigger an anxious phenomenon in the mind that can reflect in the vision of life, increasing the fear of contracting the virus compared to the probability of being infected. in the world, however, several applied research groups2 are currently working to develop a vaccine3 that would save lives and, from a psychological point of view, would probably largely reduce fears and anxieties of contracting the infection. having said this, with this article the authors offer their personal contribution to a generic applied research project, focused on sars-cov-2, by developing two different but synergistic aspects, i.e. the main organizational aspects of a research team and the position that chemistry must occupy if it operates together with other scientific disciplines in the same scientific-technological project. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 941, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-941 http://www/ http://www/ http://www.fupress.com/substantia l. campanella, m. anastasio 2 the key points are: i. the concept of organisation: this section outlines the fundamental principles that must be accepted and adopted by research groups, that would benefit from the methodological support to optimise and/or improve their research activities, both basic and applied. ii. the position of chemistry: in this second section the central position of chemistry among the scientific disciplines is explained, particularly in the case of an important research topic such as sars-cov-2. in the following paragraphs these two important issues are discussed in depth. 2. the organization of research and the position of chemistry 2.1 general the first article that we published in substantia on the covid-19 issue offered a brief presentation on the relevance of chemistry in a multidisciplinary research team, giving a genearal introductory and preparatory overlook.4 this second contribution describes the organizational aspects of a research team and the position that chemistry must assume in those multidisciplinary projects that have a technological-scientific character. the two topics are very different in terms of contents and goals to be achieved, but, in order to increase the probability of success of the project, they must coexist in a strictly synergistic way. 2.2 the concept of organization in r&d activities organization is defined: "the set of processes and structures with which people interact and manage them, in a coordinated manner, through a series of rules, to achieve a common and shareable goal".5a, 5b the organization represents therefore the best management condition to start any activity, ensuring a regular progress for the entire duration of the project. the organization is based on three main functions: the mission, the project, and the strategies. all the other functions necessarily depend on them, and in particular the layout of the laboratory structure and the team of researchers. a necessary and sufficient condition for the achievement of the objectives is that all functions are strategically aligned with each other and that each person, finally, must be able to interact within a multidisciplinary perspective. all these assumptions lead to the conclusion that: “the organizational system, defined above, and the corresponding project activity are joined up into a single strategic relationship”. 2.3 the position of chemistry in multidisciplinary projects the position and the role of chemistry is strictly dependent on the nature of the project, so they must be evaluated case by case according to the specific features of the project. after defining the general project, therefore we can propose an active presence of chemistry and give it a central position. this central position draws its origin from some peculiar characteristics of this science and from the set of laws that make chemistry unique, such as: the great analytical-instrumental variability to which has been added for some time computational chemistry for the key role it plays in the development of antiviral drugs.6 the peculiar epistemological characteristics; its laws, few and fundamental; the innovative contents applied to the study of complex systems. 3. general conclusions in this last paragraph we report the conclusions we reached in developing this general project focused on sars-cov-2. let us look at them briefly. the organization, intended as the set of functions with which people interact in a coordinated way, represents the optimal management condition to start and successfully complete any project. the position of chemistry, within the described project, must absolutely be central with respect to all the other disciplines, because of its interdisciplinary characteristic that allows a dialogue with almost all the other scientific disciplines and because of its unique epistemological properties. the characteristics of the project also define the functional, technical and scientific capabilities of the staff. the concept of organization and the strategic position of chemistry in a generic research and development project focused on sars-cov-2 3 references 1a) https://www.coronavirus.gov 1b) https://www.nih.gov/coronavirus 2) a list of the main companies currently involved in developing a coronavirus vaccine https://www.etoro.com/it/blog/market-insights/5companies-developing-a-coronavirus-vaccine-which-onewill-be-the-first-to-market/ 3) can we really develop a safe, effective coronavirus vaccine? we don’t know for sure, but if we can, it probably won’t be easy, cheap or fast this was the answer of william a. haseltine, one of the foremost biotechnology experts; april 6 2020. https://blogs.scientificamerican.com/observations/can-wereally-develop-a-safe-effective-coronavirus-vaccine/ 4) l. campanella, m. anastasio (2020) a possible scientific answer to covid-19among open science, big data, old and new expertise and knowledge: the position paper of chemistry. substantia 4(1) suppl. 1: 890. doi: 10.13128/substantia-890 5a) http://www.ctq.it/blog/organizzazione-aziendale/ 5b)https://www.organizzazioneaziendale.net/organizzazio ne-aziendale 6) j. kirchmair, s. distinto, k.r. liedl, p. markt, j.m. rollinger, d. schuster, g.m. spitzer, g. wolber development of anti-viral agents using molecular modeling and virtual screening technique; https://www.ncbi.nlm.nih.gov/pubmed/21303343 https://www.nih.gov/coronavirus https://www.etoro.com/it/blog/market-insights/5-companies-developing-a-coronavirus-vaccine-which-one-will-be-the-first-to-market/ https://www.etoro.com/it/blog/market-insights/5-companies-developing-a-coronavirus-vaccine-which-one-will-be-the-first-to-market/ https://www.etoro.com/it/blog/market-insights/5-companies-developing-a-coronavirus-vaccine-which-one-will-be-the-first-to-market/ https://blogs.scientificamerican.com/observations/can-we-really-develop-a-safe-effective-coronavirus-vaccine/ https://blogs.scientificamerican.com/observations/can-we-really-develop-a-safe-effective-coronavirus-vaccine/ https://doi.org/10.13128/substantia-890 http://www.ctq.it/blog/organizzazione-aziendale/ https://www.organizzazioneaziendale.net/organizzazione-aziendale https://www.organizzazioneaziendale.net/organizzazione-aziendale https://www.ncbi.nlm.nih.gov/pubmed/21303343 firenze university press www.fupress.com/substantia preface it is a great honour for me to write these few lines of preface to the special issues of substantia dedicated to the 150th anniversary of the periodic table by dmitrij mendeleev. in 2019 there are other important anniversaries besides that of the periodic table. one of these is the centenary of primo levi’s birth. i believe these two anniversaries are strictly related, in fact the periodic table by levi has been considered by the royal institution of great britain as the “best book of science ever written”. it would be sufficient to recall an impressive excerpt from “iron”, a tale of the the periodic table, to acknowledge the uniqueness of this literary work: “we began studying physics together, and sandro was surprised when i tried to explain to him some of the ideas that at that time i was confusedly cultivating. that the nobility of man, acquired in a hundred centuries of trial and error, lay in making himself the conqueror of matter, and that i had enrolled in chemistry because i wanted to remain faithful to this nobility. that conquering matter is to understand it, and understanding matter is necessary to understand the universe and ourselves: and that therefore mendeleev’s periodic table […] was poetry …”. when we designed the project related to these special issues, we had in mind levi’s work and in particular his wonderful tales that belong to the periodic table. i like to recall this homage to a chemist-writer-witness to introduce the six topics that are associated to the special volumes of substantia. as president of the university of florence which is the owner of the publisher firenze university press, i am truly grateful to the editors – marc henry, vincenzo balzani, seth rasmussen, luigi campanella, mary virginia orna with marco fontani, and brigitte van tiggelen with annette lykknes and luis moreno-martinez – for accepting the invitation made by the editor-in-chief pierandrea lo nostro and for the extraordinary work for the preparation of these special issues. of course the choice of the six subjects was not accidental: we tried to identify some features of the chemistry realm, related for several reasons to the periodic table. they are strikingly associated to the great challenges for our future: these are water, sustainability, energy, open chemistry, the history and the educational perspectives of the periodic table. during its long path of progress and civilisation mankind has strongly modified nature to make our planet more comfortable, but at present we must be very careful with some dramatic changes that are occurring in our earth. science and technology, and chemistry primarily, can help mankind to solve most of the environmental and energy problems that emerge, to build a radically different approach from that that has prevailed in the last two centuries. it is a fantastic challenge, since for the first time we can consider nature not as a system to simply exploit, but a perfect ally for improving life conditions in the whole planet. chemistry has already engaged and won a similar challenge when, understanding the pollution problems generated by a chaotic and rapid development, succeeded in setting up a new branch, green chemistry, that turned upside down several research topics. now is the time to develop sustainable chemistry: the occurring events demand that chemists propose new routes and innovative approaches. in the last two centuries we have transformed immense amounts of matter from nature into waste without thinking that we were using non renewable energy sources. we have been acting as our natural resources were unlimited, but knowing that they are instead limited. now we are realizing that it is not possible to continue along this road. our planet and our atmosphere are made of finite materials and their consumption during the last two centuries has been impressive. some elements that are crucial for current and future industrial countries are known to be present on earth crust in very small amounts and their recycling from waste cannot be a choice anymore, but it is rather an obligation. climate is another big problem associated to the terrific changes occurring in some equilibria, both as a consequence of the violent industrial development and energy consumption. we need, and we will always need more and more, an immense amount of energy. the only solution to secure wellness to future generations is the conversion to renewable energy sources. in this view, food and water, due to the strong increment in the demographic indices, could become the true emergencies for billions of individuals. looking at the picture i tried to draw in this short preface it becomes more clear why we selected those topics for our special issues. i am optimistic, and i have the strong confidence that chemistry, that studies matter and its transformations, will give mankind the picklock to overcome those challenges. we will definitely need insightful minds, creativity, knowledge and wisdom. luigi dei president of the university of florence firenze university press www.fupress.com/substantia substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 5(1) suppl.: 5-17, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1273 citation: s. dominici, g.d. rosenberg (2021, eds.) nicolaus steno and earth science in early modern italy. substantia 5(1) suppl.: 5-17. doi: 10.36253/substantia-1273 copyright: © 2021 s. dominici, g.d. rosenberg. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. introduction: nicolaus steno and earth science in early modern italy stefano dominici1, gary d. rosenberg2 1 museo di storia naturale, università degli studi di firenze, e-mail: stefano.dominici@ unifi.it 2 milwaukee public museum & earth sciences department, indiana university--purdue university, indianapolis, e-mail: grosenbe@iupui.edu asked to what end one should choose to live, anaxagoras replied “to study the heaven and the order of the whole cosmos” (aristotle).1 philosophy is written in this grand book – i mean the universe – which stands continually open to our gaze, but it cannot be understood unless one first learns to comprehend the language and interpret the characters in which it is written. it is written in the language of mathematics, and its characters are triangles, circles, and other geometrical figures, without which it is humanly impossible to understand a single word of it; without these, one is wandering around in a dark labyrinth. (galileo galilei, 1623).2 why would it not be permitted to hope for great things, if anatomy was transformed so that experimental knowledge would rely only on well established facts, and reason accepted only what has been demonstrated; in other words, if anatomy used the language of mathematics? (nicolaus steno, 1667)3 galileo’s telescope did not prove the validity of copernicus’ conceptual scheme. but it did provide an immensely effective weapon for the battle. it was not proof, but it was propaganda. (thomas kuhn, 1957)4 facts contain ideological components, older views which have vanished from sight or were perhaps never formulated in an explicit manner. (paul feyerebend, 1975)5 1 aristotles, ethica eudemia, in h. diels, w. kranz, die fragmente der vorsokratiker, zürich, 1951, 59 a 30. 2 g. galilei, il saggiatore, nel quale con bilancia esquisita e giusta si ponderano le cose contenute nella libra astronomica e filosofica di lotario sarsi sigensano, rome, mascardi, 1623. quote taken from translation in s. drake, discoveries and opinions of galileo, new york, doubleday & company, 1957, pp. 237-8. 3 n. stensen, canis carchariae dissectum caput, florence, stella, 1667 (canis carchariae in following notes). english translation in t. kardel, p. maquet, nicolaus steno, biography and original papers of a 17th century scientist, 1st edition, heidelberg, springer, 2013, 594 p. 4 t. kuhn, the copernican revolution; planetary astronomy in the development of western thought. cambridge, harvard university press, 1957, 297 p. 5 p. feyerabend, against method: outline of an anarchistic theory of knowledge. london, new left books, 1975, 339 p. 6 stefano dominici, gary d. rosenberg introduction a group of scientists interested in history of science and fascinated by the figure of nicolaus steno (16381686) gathered in florence for the 350th anniversary of the publication of his de solido intra solidum naturaliter contento prodromus dissertationis. a public conference held at palazzo fenzi on 16 october 2019 and a geological fieldtrip on the following day were occasions to discuss different points of view on the last published work of the danish natural philosopher, dedicated to “solids naturally enclosed in other solids” (de solido intra solidum naturaliter contento, or de solido in short). the title of the gathering, “galilean foundation for a solid earth”, emphasized the philosophical context that steno found in florence, where in 1666-1668 he established tight human and philosophical bonds with renowned italian disciples of galileo galilei and members of the accademia del cimento. the word “philosophical” then had a different emphasis than it has today. born and educated in copenhagen for a medical degree, student in the hotbed of radical thinkers that was amsterdam and public debater on human anatomy in leiden and paris, steno was already famous when he moved to tuscany at the age of 28, in 1666. there he found a new type of “anatomical theatre” to carry out the first ideal dissection of the earth and, based on his new and original observations, he wrote a book that is considered a cornerstone of modern geoscience,6 marking the passage from the late renaissance understanding of nature, to a modern, geometric approach to the study of strata, mountains, minerals and fossils. during the renaissance and early modern period geological objects such as fossils and minerals mattered in the first place for their practical properties, essentially for medical purposes, or out of simple curiosity. as such they belonged to the field of natural history and were studied and collected mainly by physicians and apothecaries. natural history (from latin historia, and greek ἱστορία, meaning research, knowledge) was a knowledge production tool concerned with the description and classification of natural things, not simply with the record of their past states, as the modern usage of the word “history” implies.7 in de solido the same objects became 6 the consequences of steno’s works in the subsequent development of disciplines such as geology and paleontology still need to be freed from anachronistic and teleological tales of “founding fathers” that “fix principles”. 7 the very name of “museum of natural history”, given in 1775 in florence to the institution that housed the 2019 conference, testifies that more than a century after de solido natural history was still concerned with organising the products of nature, irrespective of the chronological order of their origins (in a sense, “history” here is a “fossil” word). the instrumental to a reasoning that belonged to philosophy of nature, also called “physics”, a vast field concerned with the study of overarching laws of nature. the works of francis bacon (1561-1626) in england, galileo galilei (1564-1642) in italy and rené descartes (15691640) in france had radically transformed the point of view of natural philosophers, bringing observation and mathematics to the forefront. as a student of medicine in copenhagen, steno came to study fossils and minerals as a natural historian. both his anatomical and geological writings, however, clearly show that in florence he developed mathematics as a tool of the philosopher merging the two fields of knowledge. since he shared this approach with the many disciples of galileo connected with the medici court, the question remains why he decided to move and live in florence during these crucial years of his life. during galileo’s lifetime, natural philosophy was undergoing a transformation from being based on the textual analysis of classical philosophers, eminently aristotle (384-322 bc), to become an empirical science based on observation and measurements, aided by technological advancement and qualified by mathematics.8 the passage from placing authority on words (of ancient philosophers) to placing it on numbers (collected by the new philosophers) was a slow process taking place simultaneously in several european courts.9 if mathematics were already used by ancient and medieval natural philosophers to directly represent physical phenomena, modern scholarship recognizes that “no other episode in the history of western science has been as consequential as the rise of the mathematical approach to the natural world”.10 galileo had shown that to be a natural philosopher meant to be a mathematician and that, if physical phenomena could not always be translatmodern concept of history as a unidirectional and irreversible process developed starting from the end of the eighteenth century, at the height of the enlightment, with the influential works of nicolas de condorcet (1743-1794) and thomas malthus (1766-1834). 8 until then applied mathematics were generally considerd of a lower status, because “rather than giving true causal explanations of physical phenomena, rooted in the real natures of the things involved, they just coordinated quantities”: p. dear, “the mathematical principles of natural philosophy: toward a heuristic narrative for the scientific revolution”, configurations, 1998, 6, pp. 173-193. during this transition, “perspective painting, ballistics and fortification, cartography and navigation prepared the ground for galileo, descartes and newton”: d. wootton, the invention of science: a new history of the scientific revolution, harper collins, new york, 2015, 784 p. 9 p. dear, “totius in verba: rhetoric and authority in the early royal society”, isis, 1985, 76, pp. 144-161. 10 g. gorham, b. hill, e. slowik, “introduction”, in the language of nature: reassessing the mathematization of natural philosophy in the seventeenth century (eds. g. gorham, b. hill, e. slowik, k. waters), minneapolis, university of minnesota press, 2016, pp. 1-3. 7introduction: nicolaus steno and earth science in early modern italy ed into simple mathematical laws, this was simply a sign of the complexity of the mathematical order of nature.11 the new natural philosopher had therefore to find new mathematical approaches, a mission that galileo had handed down to the younger generation. de solido appeared more than a century before a science of geology became a distinct field of knowledge.12 three hundred and fifty years after that complex historical transition began, participants at the 2019 florence conference recognised the necessity to contextualise steno’s observations in tuscany and to explore what factors drove his new interests and what philosophical approach he adopted. galileo galilei more than a sudden event, the “scientific revolution” is generally considered a period spanning 1543 and 1704. in 1543 vesalius published his anatomical atlas, de humani corporis fabrica, and copernicus sent his letter, known as de revolutionibus orbium coelestium, to the pope. the publications marked achievements in observational and mathematical science, the former scientifically depicting human anatomy and the latter proposing to replace the aristotelian, geocentric model of the cosmos with the heliocentric model. in 1704 isaac newton (1642-1726) published his opticks.13 based on the residual strength of classical models, this period can be divided into the scientific renaissance (roughly 11 c. r. palmerino, “reading the book of nature: the ontological and epistemological underpinnings of galileo’s mathematical realism”, in ref. 10, pp. 36-50. regarding the famous passage from galileo’s assayer (ref. 2), palmerino observes that “the chief function of galileo’s use of the metaphor of the book of nature is precisely that of contrasting the exact and ‘obligatory’ character of mathematical language to the imprecise and arbitrary character of verbal language”. on this contrast see also d. sepkoski, “nominalism and constructivism in seventeenth-century mathematical philosophy”, historia mathematica, 2005, 32, pp. 33-59: “early modern natural philosophers did not separate mathematical and scientific pursuits from more general questions in philosophy, so understanding the philosophical basis of their beliefs gives important insight into the development of contemporary mathematical natural philosophy.” 12 m. j. s. rudwick, bursting the limits of time: the reconstruction of geohistory in the age of revolution. chicago, university of chicago press, 2005, 708 p. the work of steno was not connected to the emergence of modern geology. 13 the use of the word “modern” has changed in time and the concept of “scientific revolution” was introduced only in the twentieth century. for an overview see a. cunningham, p. williams, “de-centring the ‘big picture’: the origins of modern science and the modern origins of science”, the british journal for the history of science, 1993, 26, pp. 407432, and l. a. orthia, “what’s wrong with talking about the scientific revolution? applying lessons from history of science to applied fields of science studies”, minerva, 2016, 54, pp. 353-373. see also p. dear, and d. wootton, ref. 6. the sixteenth century) and the true scientific revolution (approximately seventeenth century).14 whatever the interval, the innovative approach to the study of the cosmos by galileo galilei (1564-1642) represents a discontinuity with the method of predecessors. since the very late 1650s galileo’s new philosophy came to be qualified as “experimental” because it was based on observational evidences collected through designed experiments15 which allowed reading “the book of nature” by the use of mathematics, particularly geometry. this took place in addition or in opposition to the approach inherited from renaissance philosophers who relied on the analysis of authoritative textual resources.16 as a young man, in pisa and florence, galileo practiced mathematics, a discipline in which he stood high, suggesting mathematics was more autoritative in the study of physics than the texts of aristotle and aristotelians. in padua, where he taught geometry, mechanics and astronomy, he started an instrument business, a new science of motion and the study of the skies, offering anti-aristotelian explanations of celestial phenomena and regarding heliocentrism as preferable.17 in 1609 he built his first “telescope” to make distant objects appear much closer. the telescope allowed for crucial observations described in nuncius sidereus (“the starry messanger”), of 1610,18 and to convince his skeptics of the validity of his assertions about the moon and other heavenly bodies. in the words of a twentieth-century scholar: “galileo’s telescope changed the terms of the riddle that the 14 p. dear, revolutionizing the sciences. european knowledge and its ambitions, 1500-1700. princeton, new jersey, princeton university press, 2001, 200 p. according to other historians the turning point was the discovery of a supernova by thyco brahe (1546-1601), proving that the skies are not fixed: “ptolemaic astronomy was unaffected by copernicus; it went into crisis with the new star of 1572” (d. wootton, ref. 8). 15 experimental natural philosophy, involving “the collection and ordering of observations and experimental reports with a view to the development of explanations of natural phenomena based on these”, is sometimes portrayed as an opposition to speculative natural philosophy (“the development of explanations of natural phenomena without prior recourse to systematic observation and experiment”): p. r. anstey, “experimental versus speculative natural philosophy”, in the science of nature in the seventeenth century: patterns of change in early modern natural philosophy (eds. p.r. anstey, j.a. schuster), dordrecht, springer, 2005, pp. 215-242. against this dichotomy, and reification of philosophy in general, see d. levitin, “early modern experimental philosophy. a non-anglocentric overview”, in experiment, speculation and religion in early modern philosophy (eds. a. vanzo, p. r. anstey), new york, routledge, 2019, pp. 229-291. 16 p. dear, refs. 6-7. for a general background on the historiography of mathematization see also g. gorham, b. hill, e. slowik, ref. 10. 17 j. l. heilbron, galileo. new york, oxford university press, 2010, 508 p. this is an excellent biography of galileo and a source also for other subjects dealt with in the present paper. 18 m. gargano, “della porta, colonna, and fontana: the role of neapolitan scientists at the beginning of the telescope era”, journal of astronomical history and heritage, 2019, 22, pp. 45-59. 8 stefano dominici, gary d. rosenberg heavens presented to astronomers, and it made the riddle vastly easier to solve, for in galileo’s hands the telescope disclosed abundant evidence for copernicanism.”19 galileo himself was aware of his role in society as a philosopher of nature: “beginning with the publication of his starry messenger in 1610, galileo took care – through the letters he wrote, the works he published, and the attention he paid to the preservation of his papers – to portray himself as the instigator of a new way of studying nature”.20 by 1623, when he published his il saggiatore (the assayer), he could safely claim that “philosophy is written in this grand book – i mean the universe – which stands continually open to our gaze, but it cannot be understood unless one first learns to comprehend the language and interpret the characters in which it is written. it is written in the language of mathematics, and its characters are triangles, circles, and other geometrical figures, without which it is humanly impossible to understand a single word of it; without these, one is wandering around in a dark labyrinth.”21 accademia dei lincei in 1611 galileo joined the accademia dei lincei (“academy of the lynxes”) in rome, which had been congregating there since 1603 around the figure of the young natural philosopher federico cesi (1585-1630). the lincei, and galileo with them, promoted knowledge about new discoveries, starting with astronomy,22 but also including plants, animals and minerals. thanks to refined dutch instruments, in 1625 the lincei published a study on insects including the first printed illustration made with the aid of a microscope, also introduced in 19 t. kuhn, ref. 4, p. 219. the telescope brought about the immediate and irreversible collapse of ptolemaic astronomy: d. wootton, ref. 8. 20 r. raphael, reading galileo. scribal technologies and the two new sciences, baltimore, johns hopkins university press, 2017, p. 190. in the last part of the twentieth century epistemologists and historians of science fought over the nature of the “scientific method”, positioning galileo at centerstage: “hardly any other icon of modern science has become as much a victim of his interpreters as galileo,” wrote klaus fischer (“die wissenschaftstheorie galileis – oder: contra feyerabend”, journal for general philosophy of science/zeitschrift für allgemeine wissenschaftstheorie, 1992, 23, p. 165-197). fischer opposed the opinion held by paul feyerabend (against method, see ref. 5). 21 s. drake, discoveries and opinions of galileo, new york, doubleday & company, 1957, pp. 237-8. 22 a. c. scott, federico cesi and his field studies on the origin of fossils between 1610 and 1630. endeavour, 2001, 25, pp. 93-103. d. freedberg, the eye of the lynx. galileo, his friends, and the beginnings of modern natural history. university of chicago press, 2002, 513 p. on the debates following the 1604 supernova see also p. j. boner, change and continuity in early modern cosmology. springer, dordrecht, 2011, 181 p. the accademia by galileo.23 this group included italians and foreign members, and formed an interface between learned men pursuing scholarship, like the austere cesi, and those with more practical interests like the german johann faber (1574-1629), in contact with physicians, apothecaries and surgeons.24 their plan for the diffusion of knowledge culminated in 1623-1627 with the publication of the rerum medicarum novae hispaniae thesaurus (“history of mexican plants, animals and minerals”, also known as the “mexican treasure”), a study made possible thanks to the network established by cesi with naples and spain.25 an important “lynx” and correspondent to galileo was the neapolitan fabio colonna (1567-1640), who carried out experiments on the nature of fossils and proposed their organic origin in an appendix at the end of his ekphrasis (fig. 1), and in the essay de glossopetris, both of 1616. colonna was the first to place fossils in a biological context,26 a field in which he was well-versed.27 he also understood the promotional importance of illustrating plants, animals and fossils, a task brilliantly achieved through the new technique of etching.28 in the end his interpretation of fossils relied more on morphological similarities with modern animals, than on experimental evidence, and his published texts were tightly connected with the erudite tradition inherited from late renaissance and earlier naturalists.29 this confirmed that experimentalism of early galile23 several other publications illustratated with images of magnified objects (order of magnification being within the range of twenty to one hundred times) followed in rome and elsewhere in europe, until the much better-known images in robert hooke’s micrographia of 1665: d. freedberg, ref. 22, p. 222. 24 s. de renzi, “medical competence, anatomy and the polity in seventeenth‐century rome”, renaissance studies, 2007, 21, pp. 551-567. “the sixteenth-century expansion of higher education, the rediscovery and publication of ancient medical and philosophical texts, and the subsequent debates between ‘lower’ and ‘learned’ practitioners over who was the true inheritor of ancient traditions all led to the emergence of an institutional debate about the nature of, and relationship between, various natural philosophical disciplines, and a concomitant emphasis that natural knowledge should be derived from experience rather than apriorist reasoning. […] since the learned physicians accused the practitioners of being base empirics, the latter sought to turn the accusation into a positive by elevating the status of experiential knowledge”: d. levitin, ref. 15, pp. 234-235. 25 mexican treasure. library of congress, washington d.c., world digital library, https://www.wdl.org/en/item/19340/ (accessed 5 march 2021). see d. freedberg, ref. 22. 26 m. j. s. rudwick, the meaning of fossils. episodes in the history of paleontology, chicago, university of chicago press, 2nd edition, 1976 [1972], pp. 1-48. 27 a. ottaviani, “fra diluvio noaico e fuochi sotterranei. note sulla fortuna sei-settecentesca di fabio colonna”, giornale critico della filosofia italiana, 2020, 13, pp. 260-271. 28 rudwick, ref. 26; freedberg, ref. 22. 29 a. ottaviani, “la natura senza inventario: aspetti della ricerca naturalistica del linceo fabio colonna”, physis, 1997, 34, pp. 31-70. 9introduction: nicolaus steno and earth science in early modern italy ans went hand in hand with the humanistic textual approach transmitted by the scholastic tradition. the experience of the lincei as devised by cesi, who kept contacts with galileo until cesi’s death in 1630, ended with the definitive edition of the mexican treasure in 1651. a second academy, directly connected with galileo’s teaching, was founded 15 years after his death. this was called accademia del cimento, or “academy of experiment”. the accademia del cimento after the publication of galileo’s “dialogue concerning the two chief world systems” in 1632, followed in 1633 by his public recantation of copernicanism – imposed after trial and condemnation by the roman catholic inquisition – galileo spent his last years in florence, host of the grand duke ferdinand ii of medici (1610-1670). here he was visited and assisted by two of his disciples, the mathematicians evangelista torricelli (1608-1647) and vincenzo viviani (1622-1703).30 after galileo’s and torricelli’s deaths, viviani was among the most active to transmit to posterity galileo’s teachings, mainly by promoting a galilean agenda through his participation in the accademia del cimento. this new accademia congregated in florence beginning in 1657 around prince leopold of medici, brother of grand duke ferdinand ii. from its inception to about 1660, members pursued research on the physical world through experiments and observations, led by skilled mathematicians like viviani himself and the sicilian giovanni alfonso borelli (1608-1679) and animated by the activity and publications of founding member francesco redi (1626–1697) and others, such as carlo dati (1619-1676). this activity took place in continuity with that of other leading savants in contact with the medici court, such as marcello malpighi (1628-1694). in 1656 malpighi had been appointed professor of theoretical medicine at the university of pisa, continuing his career in bologna where in the early 1660s he pioneered the use of the microscope in the study of the human body.31 in those same years he undertook a close collaboration on mechanical anatomy and physics (or “iatromachanics”) with borelli, perhaps the most gifted mathematician of the cimento.32 malpighi, prince leopold and other academicians kept contact with learned societies that were flourishing at that time across europe, so that the italians were an integral part of that community of natural philosophers and humanists called the “republic of letters”.33 lorenzo magalotti (1637-1712), secretar y since 1660, compiled a collection of the cimento experiments and published it in 1667 with the title saggi di natura30 j. l. heilbron, galileo. new york, oxford university press, 2010, 508 p. 31 according to d. wootton, “between 1661 and 1691 more was discovered in biology than in any other generation since the death of aristotle”. this interest for a new type of observation, fuelled by expectation of economic gains, motivating investors like the medici, gradually waned: “in the seventeenth century, descartes had promised that sound natural philosophy would lead to a new medicine that would enormously extend life expectancy; by the end of the century even french cartesian doctors had reconciled themselves to traditional medicine:” d. wootton, bad medicine: doctors doing harm since hippocrates, oxford university press, 2007, 336 p. 32 m. malpighi, the correspondance of marcello malpighi (ed.: h. b. adelmann), cornell university press, ithaca-london, 1975, 1, pp. 318319. see also l. boschiero, “introduction”, in borelli’s on the movement of animals. on the force of percussion (tr.: p. maquet), brill, leiden, 1989, p. i-xxi. 33 r. rappaport, when geologists were historians, cornell university press, ithaca and london, 1997, 308 p. figure 1. engraving of fossils from malta, interpreted as shark teeth (“melitenses linguae, charchariae dentes et lamiae”) in fabio colonna’s de purpura, aliisque testaceis rarioribus, appendix to his ekphrasis of 1616. some fossils are portrayed within the encasing rock. creative commons, public domain. 10 stefano dominici, gary d. rosenberg li esperienze (fig. 2).34 probably to avoid controversies among members of the academy, magalotti intentionally excluded debates about theory, giving the appearance of a non-speculative approach, at the same time boosting the idea that galileo had started and transmitted a new method to the academy, one to produce atheoretical, fac34 l. magalotti, saggi di naturali esperienze fatte nell’accademia del cimento sotto la protezione del serenissimo principe leopoldo di toscana e descritte dal segretario dell’accademia, florence, giuseppe cocchini all’insegna della stella, 1667, 286 p. translated “experiments in natural philosophy” in the fundamental study by w. e. k. middleton, the experimenters: a study of the accademia del cimento, baltimore, johns hopkins university press, 1971, 415 p. see also l. boschiero, experiment and natural philosophy in seventeenth-century tuscany. the history of the accademia del cimento, springer, dordrecht, 2007, 251 p., and m. beretta, m. feingold, p. findlen, l. boschiero, “regress and rhetoric at the tuscan court”, metascience, 2010, 19, pp. 187-210. tual knowledge of nature by experiments. complex relations, different temperaments and rivalry between academicians have in part hindered the reconstruction of the philosophical debate taking place in florence in 16571667. it is nevertheless clear that those debates testify to a fervent activity of research and of the ability of prince leopold to establish an environment where different approaches to natural philosophy could coexist.35 europe and the new philosophy galileo’s writings influenced the work of three natural philosophers of the scientific revolution in france. the first was marin mersenne (1588-1648), who translated in french and promoted galileo’s discourse one year after its publication and repeated some of the “experiences” of the italian.36 the second was rené descartes (1569-1640), who was marginally interested in galilean writings and seemed more critical,37 but nevertheless succinctly recognised in 1638 that galileo’s teaching was revolutionary because it abandoned “the errors of the schools and [brought] mathematics to bear on problems in physics”.38 as did galileo, descartes rejected aristotelian physics, and replaced it with a physics grounded in a mechanistic conception of nature, one that could be approached with mathematics. according to the french philosopher, the universe is made of void and of particles that can freely move by inertia, eventually colliding one with another. the fortune of cartesian atomistic cosmology, circulating in the 1630s and published posthumously in paris in 1664 with the title traité du monde et de la lumière,39 reached behind the evident flaws of the laws of inertial motion proposed by its author, and continued to inspire through the seventeenth century many aspects of natural philosophy. in astronomy it offered explanation to planetary motion, necessary for a self-consistent copernican system. johannes kepler (1571-1630) had devised a mechanistic solar system 35 p. findlen, in m. beretta, m. feingold, p. findlen, l. boschiero, ref. 34, p. 204. 36 r. raphael, “galileo’s discorsi and mersenne’s nouvelles pensées: mersenne as a reader of galilean ‘experience,’ ” nuncius, 2008, 23, pp. 7-36. c. r. palmerino, “experiments, mathematics, physical causes: how mersenne came to doubt the validity of galileo’s law of free fall,” perspectives on science, 2010, 18, pp. 50-76. 37 w. r. shea, “descartes as critic of galileo”, new perspectives on galileo (eds. r. e. butts, j. c. pitt), dordrecht, reidel, 1978, pp. 139-159; r. ariew, “descartes as critic of galileo’s scientific methodology”, synthese, 1986, 67, pp. 77-90; r. raphael, ref. 19. 38 letter to m. mersenne of 11 october 1638, in r. ariew, ref. 37, p. 81. 39 r. descartes, traité du monde et de la lumière, paris, girard, 1664 [1633], 260 p. figure 2. frontispiece of saggi di naturali esperienze by lorenzo magalotti and including the description of the experiments carried out in 1657-1660 at the accademia del cimento, in florence. the book expressed part of the philosophical approach of disciples of galileo at the medici court. it was published in 1667, a few months after steno’s arrival there. creative commons, public domain. 11introduction: nicolaus steno and earth science in early modern italy governed by forces that move the planets around the sun. in the light of the concept of inertial motion introduced by descartes, kepler’s system was amended by borelli in 1666,40 and separately, but simultaneously, by robert hooke (1635-1703) in england.41 finally, philosophy of knowledge, or epistemology, was at the core of descartes’ discours de la méthode (1637), a brief but influential book about method in science.42 the third key figure of the new philosophy in france was pierre gassendi (1592-1655), an experimenter who also followed in the footsteps of galileo.43 differently from descartes, who in his principia philosophiae of 1644 had proclaimed that there cannot be indivisible atoms, gassendi proposed that primordial atoms may combine with one another to form larger and structured particles called “molecules”. the french scenario developed until an institution similar to the accademia del cimento started in paris, the académie royal des sciences. this was formally founded in 1666, preceded by the work of informal academies that had been gathering there since 1661.44 the gassendian approach was embraced in england by robert boyle (1627-1691), who brought the atomic and mechanical philosophies within the compass of experiment with the publication in 1661 of nova experimenta physico mechanica.45 one year earlier, boyle had been one of the founding members of the royal society of london, the british analogue of the florentine institution which, on matters concerning experimental philosophy, inherited the teachings of francis bacon and of the oxford school.46 boyle adopted a “vitalistic corpuscularianism” and the experiments proposed by the iatrochemist daniel sennert (1572-1637) and the alchemical atomist jan baptist van helmont (1580-1644).47 the 40 g. a. borelli, theoricae mediceorum planetarum ex causis physicis deductae, florence, s.m.d., 1666, 184 p. 41 t. kuhn, ref. 4, p. 237-260. 42 d. garber, descartes embodied. reading cartesian philosophy through cartesian science, cambridge university press, 2000, 337 p. 43 r. raphael, ref. 20. 44 n. dew, orientalism in louis xiv’s france, oxford university press, oxford, 2009, 301 p. 45 m. p. banchetti robino, the chemical philosophy of robert boyle. mechanicism, chymical atoms, and emergence, new york, oxford university press, 2020, 196 p. 46 r. jr frank, harvey and the oxford physiologists: scientific ideas and social interaction, berkeley, university of california press, 1980, 368 p.; m. c. w. hunter, establishing the new science: the experience of the early royal society, woodbridge, boydell, 1989, 382 p.; d. levitin, ref. 15. for bacon see also d. jalobeanu, “ “the marriage of physics with mathematics”. francis bacon on measurement, mathematics, and the construction of a mathematical physics”, in ref. 10, pp. 51-80. 47 m. p. banchetti robino, the chemical philosophy of robert boyle. mechanicism, chymical atoms, and emergence, new york, oxford university press, 196 p. new practice of studying the inner nature of matter and its transformations was then called “chymistry”. in the dutch republic, perfected microscopes were opening a window into the minutest parts of nature such as insects, showing “the wonders of god in the humblest creatures”. new observations were influential during the 1660s, driving the transformation of museums “from collections of curiosities to cabinets of naturalia.”48 in conclusion, during the years of activity of the accademia del cimento (1657-1667), when steno received his formal education and made some of his most influential discoveries, an impressive series of paneuropean events was shaping natural philosophy in an unprecedented way. the new “experimental philosophy”, as it was also called then in england,49 did not however break abruptly with the traditional approach, but remained in many ways connected with the humanistic tradition of reading ancient texts and interpreting them in the light of the new approaches to the study of nature.50 a particular case related to the quintessential book, the bible. if the works of aristotle or other classics were rediscovered during the late middle ages and the renaissance, biblical exegesis had been practised at the highest levels without interruption for two thousand years and taught in european universities for centuries. theology, and biblical scolarship with it, at least in part adapted to the new philosophy of nature by a process of inclusion, so that the learned anglican bishop edward stillingfleet (1635-1699) could write in 1662 that “the best way to cure the world of atheism is true philosophy, or a search into the natures of things; which the more deep and profound it is, the more impossible will it be found to explicate all the phenomena of nature by mere matter and motion.”51 the early modern period was however also a time when skepticism towards its literal interpretation grew.52 textual criticism came to be 48 e. jorink, reading the book of nature in the dutch golden age, 1575– 1715, brill, leiden, 2010, 472 p. 49 a. e. shapiro, “newton’s “experimental philosophy”,” early science and medicine, 2004, 9, pp. 185-217. 50 d. levitin, ref. 15. 51 e. stillingfleet, origines sacrae: or a rational account of the grounds of the christian faith, as to the truth and divine authority of the scriptures, and the matters therein contained, london, mortlock, 1662, p. 408. see also s. hutton, “science, philosophy, and atheism. edward stillingfleet’s defence of religion”, in skepticism and irreligion in the seventeenth and eighteenth centuries (eds. r. h. popkin , a. j. vanderjagt), amsterdam, brill, pp. 102-120. 52 for the role of these freethinkers in their cultural environments see r. h. popkin, a. j. vanderjagt, skepticism and irreligion in the seventeenth and eighteenth centuries, amsterdam, brill, 374 p.; a. hessayon, n. keene, scripture and scolarship in early modern england, ashgate, aldershot, hampshire, 2006, 255 p.; e. jorink, “ “horrible and blasphemous”: isaac la peyrère, isaac vossius and the emergence of radical 12 stefano dominici, gary d. rosenberg openly discussed across different christian confessions, such as in the work of the protestants isaac la peyrère (1596-1676) and isaac vossius (1616-1689), the anglican francis lodwick (1616-1694) and the catholic richard simon (1638-1712). the most influential critic was the jewish philosopher baruch spinoza (1632-1677), who adopted a form of natural religion in his ethica, ordine geometrico demonstrata (“ethics, demonstrated in geometrical order”), written between 1661 and 1675, a book that fuelled debate.53 notwithstanding the first burst of textual criticism of modernity, from peyrère’s “praeadamites” of 1655 to spinoza’s “ethics” of 1675, most seventeenth-century natural philosophers did not doubt that the first book of the bible, the book of genesis, was a reliable historical account of the distant past. its understanding needed interpretation, the reason why a science of biblical chronology became a necessity, from the early works of 1642-1655 of john lightfoot (16021675) and james ussher (1581-1656), to that of isaac newton in the early eighteenth century.54 nicolaus steno at the age of 21 in 1659, while a student of anatomy at the copenhagen medical school, steno kept a private journal in which he collected excerpts from, and wrote comments on, the books he and his teacher ole borch (1626-1690) read.55 titled “chaos”, this journal indicates that steno’s readings went beyond strictly medical matters needed in his university curriculum. he evidently aimed at an “understanding of the whole cosmos”, to use aristotles’ words,56 and not simply at becoming a court physician, or the danish royal anatomist he later became.57 many of the excerpts relate to philosophical and methodological subjects. regarding galileo, steno excerpted a passage from sidereus nuncius as it applied biblical criticism in the dutch republic,” in nature and scripture in the abrahamic religions: up to 1700 (eds. j. m. van der meer, s. mandelbrote), brill, leiden, 2016, pp. 429-450. 53 r. rappaport in ref. 33, p. 76. criticism towards historicity of the biblical narrative was discussed only privately, and in small circles: see an eloquent example in w. poole, “the genesis narrative in the circle of robert hooke and francis lodwick”, in scripture and scolarship in early modern england (eds. a. hessayon, n. keene), ashgate, aldershot, hampshire, 2006, pp. 41-56. 54 m. j. s. rudwick, earth’s deep history. chicago university press, chicago, 2014, pp. 9-30. 55 a. ziggelaar, “niels stensen’s chaos-manuscript copenhagen, 1659. complete edition with introduction, notes and commentary”, acta hist. sci. nat. med., 1997, 44, p. 301-302. 56 aristotle, ref. 1. 57 g. scherz, “biography of nicolaus steno”, in ref. 2 (kardel, maquet), pp. 6-346. to a test for telescopes.58 an interest in telescopes was coupled with a possibly greater fascination with microscopes, which, similarly to galileo’s telescope, posed the problem of sensory perception, whether the instruments revealed natural phenomena or artifacts of the technology. steno wrote passages in his journal on the use of microscopes that related to different topics such as optic aberration, refraction, and geometric shapes seen in tiny crystals that appear round to the naked eye.59 regarding corpuscularism, he extensively excerpted the writings of pierre gassendi and ole borch, and used the word corpuscula (“tiny particles”) 43 times in his journal, seeking to explain through atomistic theory disparate phenomena such as light, magnetism, colour, senses, changes in state, and the chemical behaviour of different solids and fluids.60 this research reached its climax in 1666-1668, when corpuscular theory had became an integral part of the florentine writings,61 the word corpuscula being meanwhile substituted by particulas (repeated 36 times in the 78 pages of de solido). sennert’s institutionum medicinae libri v was a book that in 1659 he read with enthusiasm and excerpted only on medical matters, but where he would have learned about an influential look on atomism in chemistry. descartes had brought method to centerstage. steno widely read and excerpted the french philosopher, declaring in 1659 that he was willing to work “more accurately and orderly following descartes’ method.”62 in the first year of his stay in florence he publicly praised descartes’ lesson in the use of mathematics as a means to true knowledge: “whoever thinks that its true understanding can be sought without mathematical assistance must also think that there is matter without extension, and body without figure.”63 in florence he 58 a. ziggelaar, in ref. 55, pp. 301-302. 59 the journal of 1659 contains five passages on microscopes: a. ziggelaar, in ref. 55, p. 290, 292, 296, 395, 396. 60 a. ziggelaar, in ref. 55. “clavis chymiae verae desideratur,” steno wrote, meaning “the key of true chemistry is wanted”: p. 127). 61 a. clericuzio, “meccanicismo ed empirismo nell’opera di steensen”, in scienza, filosofia e religione nell’opera di niels steensen (eds.: m. a. vitoria, f. j. insa gómez), pagnini, firenze, p. 123-138. 62 a. ziggelaar, in ref. 55, p. 123. 63 n. stensen, elementorum myologiae specimen, seu musculi descriptio geometrica, in t. kardel, p. maquet, ref. 3, p. 547, and references therein. see also s. olden-jørgensen, “nicholas steno and rené descartes: a cartesian perspective on steno’s scientific development,” in the revolution in geology from the renaissance to the enlightenment (ed. g. d. rosenberg), geol. soc. am. mem., 2009, 203, 149-157. olden-jørgensen sees all of steno’s works as “operated within a securely cartesian world” (p. 155). application of the cartesian method of doubt led steno to experiment with new hypotheses in anatomy and new methods of dissection: v. grigoropoulou, “steno’s critique of descartes and louis de la forge’s response,” in steno and the philosophers (eds. r. andrault, m. lærke), brill, leiden, 2018, p. 113-137. a critical view on steno’s cartesianism, and his debts to pierre gassendi and francis bacon, is found in a. clericuzio, ref. 61. 13introduction: nicolaus steno and earth science in early modern italy interacted with some of the most learned mathematicians of his time, including perhaps the two most notable galileans vivani and borelli. this he did in coincidence with the publication of the ultimate work on the activities of the accademia del cimento, the saggi di naturali esperienze (fig. 2).64 scholars are of the opinion that steno was influenced by the florentine method, particularly in de solido, by the deliberate adoption of “experience” as advocated in the saggi as historia. through the narration of experiments, historia was a form of empirism that focused on experience and challenged the scholastic approach of aristotelian speculations about philosophical causes.65 at the same time steno distanced himself from the inductivist attitude expressed in the saggi66 by remaining a natural philosopher, interested in causal investigation.67 a science for the earth the main subject matter of de solido, earth materials, such as strata, minerals and fossils, served as an attempt to establish a general method in the study of nature and a scale-independent means to disclose chronology of events in earth’s history. the interest in fossilia, or res metallica (meaning anything dug up from the earth), had been emerging during the late renaissance within the wider realm of natural history. natural history was the job of keepers of museums, whether private such as that of ferrante imperato (1525-1615), or attached to public institutions, such as that of the vatican metallotheca in rome, kept by michele mercati (1541-1593), and that of the gallery of the university of pisa, first organised by andrea cesalpino (152464 l. magalotti, ref. 26. 65 j. bek-thomsen, from flesh to fossils – nicolaus steno’s anatomy of the earth, in a history of geology and medicine (eds.: c. j. duffin, r. t. j. moody, c. gardner-thorpe). geological society of london, special publications, 2013, 375, 17 p.; j. bek-thomsen, steno’s historia: methods and practices at the court of ferdinando ii, in ref. 13 (andrault, lærke), p. 233-258. 66 p. findlen, controlling the experiment: rhetoric, court patronage and the experimental method of francesco redi, history of science, 1993, 31, p. 35–64; l. boschiero, experiment and natural philosophy in seventeenth-century tuscany. the history of the accademia del cimento, springer, dordrecht, 2007, 251 p. borelli, who contributed his thoughts to the saggi, was particularly concerned to present the work of the accademia as the accumulation of knowledge through rigorous experimenting, free of any theorising (boschiero, p. 185). inductivism is the view that science proceeds via generalization from facts recorded in basic sentences: j. preston, feyerabend, philosophy, science and society. cambridge, polity press, 234 p. 67 “steno was not writing as an anatomist or court physician but as a natural philosopher:” j. bek-thomsen, ref. 15b, p. 251. 1603).68 in the late 1650s and early 1660s, a number of phenomena relating to fossilia were attracting the attention of natural philosophers, as they had a few years earlier attracted fabio colonna in rome (fig. 1). steno’s elder competitors in this field were athanasius kircher (1602-1680) in italy, pierre borel (1620-1671) in france, ole borch in denmark and robert boyle (1627-1691) in england. in florence, the young dane proposed the first coherent and modern solution to explain the origin of fossils together with that of the strata that enclosed them. anticipated by the publication of canis carchariae dissectum caput, hastely written and published in 1667 (fig. 3), his theory was briefly, but completely exposed in de solido, published in 1669.69 both essays had immediate feedback in europe. the early modern period had become a time of travels in the explicit search of historical evidences of natural events. noteworthy european travellers who interacted with steno and who published essays on fossils (although the relationship among their travels and the study of fossils is not always clear), were his teacher in copenhagen thomas bartholin (1616-1680)70 and the early fellows of the royal society of london, john ray (1627-1705), martin lister (1638-1712) and robert hooke.71 philosophy of nature in the widest sense was at stake, not simply the explanation for the existence of “figured stones” or sports of nature. common destinations for such travels were montpellier, sicily and malta, where fossils are dug up in abundance to the present day. agostino scilla (1624-1700), another contemporaneous contributor to the debate on the origin of fossils,72 could study them in his homeland, sicily, a richly fossiliferous region. steno, after travelling to montpellier, 68 l. tongiorgi tomasi, giardino dei semplici. l’orto botanico di pisa dal xvi al xx secolo (eds.: f. garbi, l. tongiorgi tomasi, a. tosi), pacini, ospedaletto, 1986, pp. 161-170; m. j. s. rudwick, ref. 26; p. findlen, possessing nature: museums, collecting and scientific culture in early modern italy university of california press, berkeley, 1994, 449 p. 69 t. yamada, hooke–steno relations reconsidered: reassessing the roles of ole borch and robert boyle, in g. d. rosenberg, ref. 7, p. 107-126. m. romano, “ ‘the vain speculation disillusioned by the sense’: the italian painter agostino scilla (1629–1700), called ‘the discoloured’, and the correct interpretation of fossils as ‘lithified organisms’ that once lived in the sea,” historical biology: an international journal of paleobiology, 2014, 26, p. 631-651. 70 g. scherz, niels stensen eine biographie, 1987, translated in ref. 2 (kardel, maquet), p. 7-346. a. ottaviani, “officiosissimam salutem nomine meo nunciabis cl. viro mario schipano parentis amico veteri, quem laetus humanis adhuc interesse accepi, utinam diu”: memorie di viaggio e viaggio nella memoria nel tour italiano di thomas bartholin. schede umanistiche: rivista semestrale dell’archivio umanistico rinascimentale bolognese, 2, 2004, pp. 89-110. 71 m. j. s. rudwick, ref. 54, p. 49-100. 72 although never mentioning him, scilla had surely heard about steno’s works through john ray and giovanni alfonso borelli: see p. findlen, ref. 68. 14 stefano dominici, gary d. rosenberg had found in tuscany the perfect place to immediately set out to work and study the natural setting where fossils were found, finally merging history of the earth with animal anatomy and corpuscular theory.73 by the time steno’s two “geological” works were translated and published by the royal society of london, in 1671, his primary interest in natural philosophy was waning, gradually substituted by the study of theology, seen as superior to the first as a way to truth (he became priest in 1675). nevertheless, by combining the laws of physics and geometry with historical process and biblical scolarship, he had inaugurated a fruitful period in the study of the earth. this fluorished 73 a. clericuzio, ref. 61. in the publication of a series of other theories, particularly among philosophers of the royal society, each one proposing his own take on merging natural history with the reports of human witnesses, centered in the book of genesis and the tale of the universal deluge. the sheer number of theories of the earth published in 1669-1695, from those by john ray, martin lister and robert hooke, to those of thomas burnet (1635-1715) and john woodward (1665-1728), together with the fantasies of their constructs, gained their authors the title of “world makers”.74 by the time steno died, in 1686 the focus of many learned men around him had gradually changed, no longer emphasizing mathematics as the language of the universe, but speculating on earth’s history so as to merge physics with the biblical narrative. “theory of the earth”, or geotheory, became a genre, cultivated through the eighteenth century throughout europe and culminated in the work of louis buffon (1704-1788), with his world-famous les époques de la nature (1778). when jean-baptiste lamarck (1744-1829) in france published his own geotheory in 1802 with the title hydrogélogie, the genre had gone out of fashion among savants. younger researchers had learned to start off from scratch once again. this they did by avoiding speculations and concentrating on the reconstruction of historical facts through the analysis of stratal relationships and the punctiform record of fossil occurrences of their own region. the leading figures of this new science, performed with hammer in hand in field activities and by study of museum collections, were georges cuvier (1769-1832) and alexandre brongniart (1770-1847) in france, giambattista brocchi (1772-1726) in italy, and george bellas greenough (1778-1855) and william buckland (1784-1856) in england. what they were doing was being called “geology” for the first time.75 the thematic volume for participants to the 2019 gathering, the museum of natural history of the university of florence, hosting some of steno’s geological specimens, and the region of tuscany itself, formed the perfect location to discuss the phenomena that steno had observed from 1666-1668, the motivations for his research, the methodology of his discovery and, generally stated, the european scientific context which informed his inquiry. some of the talks given in that meeting are included within this volume, kindly hosted by substantia, international journal of the history of chemistry published by the florence university 74 m. j. s. rudwick, ref. 26, p. 49-100; r. rappaport, ref. 33. 75 m. s. j. rudwick, ref. 54. figure 3. portrait of a shark’s head by anton eisenhoit (1553-1603), originally engraved around 1590 for michele mercati’s metallotheca vaticana (published postumously in 1717) and used by steno in 1666 to illustrate his canis carchariae dissectum caput. photograph by saulo bambi, reproduced with permission from metallotheca vaticana, courtesy of the botanical library of the florence university. 15introduction: nicolaus steno and earth science in early modern italy press. in addition some of the invited speakers who were unable to attend, also contributed a paper to this publication. the collection is about earth science in the early modern period, when the study of minerals, rocks, and the fossilized remains of living things did not yet form a distinct path to knowledge about earth history, but was an integral part of the wider “philosophy of nature”. participants to the thematic volume came from different parts of the world and from different backgrounds. some are historians of science, others are physicians and geologists, with an experience in either medicine, mineralogy, paleontology or geochronology. each understood from a particular point of view what observation, the experimental method, and use of geometry meant to early modern natural philosophers active in italy, whether interested in the study of muscles, fossils, crystals or sedimentary strata. their papers in this volume contribute to understanding nicolaus steno’s natural philosophy in the context of 17th century europe. they reveal steno and his contemporaries’ interest in structure, origins, processes, and history of earth materials and fossil remains in a way that constitutes a glimpse into early attempts to understand natural history as we now understand it, even as many early conceptions of that story retained remnants of biblical and aristotelian ideas. stated a bit differently, the ideas in this volume bear on understanding the beginnings of the science of natural history, or evolution, as it is understood today. nicolaus steno was a galilean in the company of other galileans, natural philosophers who largely shunned traditional scholastic speculations and valued instead observation and use of mathematics to describe nature and reveal its mysteries. the identification and description of scientific detail of the objects of nature – rocks, stones, fossils, animals, and plants – which is a recurrent theme in the volume – are pre requisites for understanding their evolution. alessandro ottaviani’s tour de force study of primary sources details the status of theories in the 17th century for the origin of stones and fossils (which then were anything dug up from the earth). fabio colonna did, however, predate steno in recognizing that fossils are the remains of once-living things, but he invoked an aristotelian model of material causes (water and earth) and efficient causes (heat and cold) for the origin of stones. other natural philosophers, such as federico cesi, and francesco stelluti had advocated origin of fossils by various aristotelian vegetal or plastic forces. and cesi went further and adopted the idea of the continuum of divine creation, the great chain of being, a classification scheme in which angels occupied a position closest to divinity followed successively by humans, animals, plants, and finally stones, any one of which could undergo degeneration, moving it farther away from divinity. nuno castel-branco examines the rapidly changing and vigorously debated epistemological role of mathematics in the 17th century as it applied to early modern medicine and particularly to steno’s accomplishments in anatomy. he shows how steno used mathematics to reveal the structure of muscle and to show that glandular activity involved “humours,” that is fluids, in a way that advanced the scientific understanding of the structure of the human body beyond the cartesian model which oversimplified it as a machine. this approach by numbers in the study of the animal body, is argued, preceded steno’s first arrival in italy. troels kardel relates that steno used mathematics to describe anatomical structures at microscopic scales not easily studied given the state of the instrumentation at the time, and so to leave him to hypothesize the existence of various anatomical transformations, among them, as kardel has previously reported, and which he reinforces here, steno’s geometrical model whereby muscles contract by fiber shortening, not by a change in volume induced by animal spirits as was commonly speculated in the 17th century. kardel emphasizes that steno’s mathematically inspired insight led him to propose time-related changes in organic and inorganic materials – even some that were too fast and others too slow to be observed by any individual. yet many, including steno’s model of fiber shortening, were confirmed centuries later. in short, steno used the predictive potential of geometric modeling to position himself on the verge of understanding time-related physiological changes in the human body. steno’s embrace of galilean methodology also facilitated his ascertainment of the founding principles of modern stratigraphy (what we now call original horizontality, superposition, and lateral continuity of sedimentary strata), paleontology (fossils are the remains of once-living things), and crystallography (constancy of interfacial angles in crystals, and anisotropic variations in crystal growth from accretion rather than by vegetative growth from within) – long before they became formal sciences. steno was of course neither always the first nor the only one to transition to modernity, but his steadfast galilean natural philosophy elevated him to prominence. silvio menchetti states that steno was the first to formulate constancy of interfacial angles of crystals, specifically for quartz and implicitly for hematite, but that he did not generalize his observations sufficiently to constitute expression of the universal law of interfacial 16 stefano dominici, gary d. rosenberg angles. menchetti believes that distinction belongs to later and more comprehensive studies by romé de l’isle (1736-1790). however, menchetti asserts that steno’s discussion of crystal growth provides a more secure claim to his fame. that is, although steno carefully considered aristotelian causes in formation of crystals: material, formal, efficient, and final, he nevertheless concluded that crystals do not grow vegetatively from within, but by accretion of deposits from external fluids. furthermore, steno correctly theorized that crystal faces grow anisotropically (at various rates, accounting for different sizes and shapes of similar faces in different specimens, while maintaining constancy of interfacial angles). stefano dominici’s study indicates that steno also studied fossil and modern shells and bones given to him by giovanni alfonso borelli of the accademia del cimento and that he knew about tuscan fossiliferous localities from reading of late renaissance authors. dominici proposes that steno had planned geological fieldwork in tuscany and that his geological works aimed also at attesting the veridicity of the biblical narrative. in that view, steno’s observations on fossils and strata did not start after the dissection of a shark’s head, as it is generally assumed. for steno the processes of transport and accumulation of sediments were consistent with the separation of the aristotelian elements, earth and water, on the third day of creation according to scriptures. similarly, his recognition that “glossopetrae” were not simulacra of shark teeth molded by aristotelian vital forces within the earth but were actually the dental remains of sharks that once lived in the waters of the deluge, the second universal sea of scriptures. steno regarded the flood as scientifically consistent with the “freedom and powers” of the “first mover,” the divinity. steno’s description of the structure of tuscan sedimentary strata involved relative age dating (organizing events in sequence), but he also tackled duration of that history (what is now called “absolute time”), albeit consistent with the 5,000-year age of the earth as described in scriptures. alan cutler’s paper finds the beginnings of the modern rock cycle in steno’s study of tuscan strata. although neither steno nor any of his contemporaries understood igneous or metamorphic processes, steno nevertheless understood the role of erosion, transport, and deposition in the production of rocks that we now classify as sedimentary. thus, steno began the generative classification of rocks, or classification of rocks by method of origin, in this case the derivation of rock from pre-existing earth materials and thus the cyclicity of the earth processes that we now accept today. cutler points out that such generative classifications are unique to geology. specifically, steno explicitly stated that structural characteristics of rocks and fossils reveal their place and mode of origin. although steno accepted that these cyclic processes started after the “malediction of earth” due to the curse of adam, cutler presents evidence that steno was onto not only a modern understanding of relative time (e.g., his principles of molding and sufficient similarity as well as superposition, original horizontality and lateral continuity), but also a clear understanding that the duration of earth processes varies from instantaneous to prolonged (now known as “deep time”). in steno’s case the biblical narrative of 5,000 years since the creation framed his conception of deep time. cutler’s point is that steno nevertheless understood time as a scale-independent concept in a way that is critical to modern geoscience and distinctive of it, in this example that the rock cycle has no set time frame. all of this is integral to our modern understanding of earth history: short-term and inconspicuous processes, instantaneous catastrophic events, and slow changes which take place over eons all play a role in earth history. desmond moser finds a fundamental analogy in steno’s prodromus between microstructural surfaces in crystals and surfaces of sedimentary strata and that steno’s recognition of it was “implicit in the prodromus but not always recognized.” his interpretation gives a coherence to steno’s diagrams in the prodromus of crystals, some showing surfaces constituting zonation, and sedimentary strata showing layering. moser tabulates steno’s references to chemical as well as structural microand megascopic layerings in various materials that steno recognized were useful in establishing timeseries (historical) sequences of formation – relative geochronology that is scale invariant in respect of both space and time. moser asserts that steno’s presentation amounts to a “revolutionary perception of scale invariance among the processes of solid formation in nature.” further, steno’s “observational acuity” combined with the “provenance of his [galilean] philosophy” facilitated his recognition of geologic history which continues to be fundamental and evident to the present day in both relative (sequential) and absolute (durational) geochronologies at scales ranging from microcrystalline to regional geographic and on to planetary levels. moser quotes steno in saying, “…these representations respond to a sign as if the macrocosmos laid hidden in the microcosmos,” manifestation of a long philosophical history in which the human body has been regarded as a model for “the animate earth.” the result is a collection of papers on the cultural environment that steno found in italy and on his previous experiences, how he innovated the discourse on 17introduction: nicolaus steno and earth science in early modern italy minerals and fossils, and the geometric, scale-independent approach that stemmed from his published works, one that continues to be taught at universities around the world. the historical interval embraced by the different contributions spans from the early seventeenth century in rome, at the accademia dei lincei, includes an extensive discussion of steno’s science while in florence, and ends at our time on mars, where steno’s geometric, visual approach to reconstruct historical processes proves to be basic for planetary science. in short, the papers in this volume establish that nicolaus steno had a more foundational insight into the modern concept of natural history than heretofore recognized. substantia. an international journal of the history of chemistry 1(1): 43-48, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-10 citation: d. xie, d.e. dunstan (2017) modelling polymers as compressible elastic spheres in couette flow. substantia 1(1): 43-48. doi: 10.13128/substantia-10 copyright: © 2017 d. xie, d.e. dunstan.this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the authors declare no competing interests. research article modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* department of chemical and biomolecular engineering, university of melbourne, vic 3010, australia. e-mail: davided@unimelb.edu.au abstract. a model of polymer chains as compressible elastic spheres in flow is presented. the spherical polymer blobs are assumed to compress in simple couette flow in accord with recent rheo-optic measurements on semi-dilute solutions. the experimentally determined decrease in radius with increasing shear rate is predicted by the model. furthermore, the model predicts power law exponents for the viscosity-shear rate within the range of measured values for polymer chains. keywords. semi-dilute polymer solutions, couette flow, compression, modelling, power law. introduction the rheology of polymers is of both fundamental interest and considerable practical importance.1-4 predicting the flow behaviour of polymeric solutions from the fundamental physics of the individual chains has long been the quest of soft condensed matter.5,6 the combination of statistical mechanics and fluid mechanics has been used to predict polymer rheology.7,8 kuhn was the first to develop a model of chains in flow.9 he modelled the chains as beads on a spring in which the beads account for the hydrodynamic forces and the spring embodies the elastic nature of the chain. he also developed the first statistical mechanical model that enabled the calculation of the effective spring constant from the chain properties.9 kuhn’s 1933 kolloid z. paper also showed that the chains experience both extensional and compressive hydrodynamic forces as they tumble in flow in so called jeffery orbits.10 interestingly, since kuhn’s original paper, the compressive forces have been ignored and only extension is assumed to occur. the dumbbell model presented by kuhn enables the hydrodynamic forces to be evaluated and the steady state condition of the forces to be equated as a function of the angle around the vorticity axis. since kuhn’s pioneering work, an essential assumption of polymer dynamics is that the single molecule response to applied stress may be used to interpret the observed macroscopic material behaviour.2,4,6 the elegant models of single polymer chains which assume that the chain can be described as 44 donglin xie and dave e. dunstan a random walk on a periodic lattice have been successful in predicting a number of the key properties of polymers.5,6 furthermore, the inclusion of excluded volume to the ideal chain has enabled prediction of the solution size of polymers.3,11,12 the entropy of the chain is derived in terms of the end-to-end vector of the random chains.2 this model forms the basis of rubber elasticity and is used to incorporate elasticity in models of flow where chain deformation results in entropy reduction and elasticity.13 the theory of rubber elasticity (based on the same physical assumptions) predicts the elastic behaviour of rubbers over a wide strain range.13 importantly, the “rubber theory” predicts both the compressive and extensional behaviour of rubbers. this agreement between the theory and experiment, albeit at effectively “infinite” molecular weight and high polymer concentration with excluded volume interactions neglected, gives confidence that the fundamental tenets of the theory are correct. however, due to their complexity there exist very few simulations of polymer solutions and melts in the semi-dilute and concentrated regimes.8,14-16 a general assumption used in models of polymers in flow is that the chains extend in response to the hydrodynamic forces.14-16 recent experimental evidence shows that synthetic polymer chains compress in couette flow at semi-dilute concentrations.17-19 recent studies on semidilute dna solutions shows that extension and tumbling occurs.20,21 it appears that the general assumption of chain extension in flow may not be valid for concentrations above critical overlap in couette flow.18,19,22,23 furthermore, recent brownian dynamics simulations for dilute solutions predict chain compression by neglecting excluded volume effects and including hydrodynamic interactions.24,25 while these simulations have been done for dilute chains, the neglect of excluded volume effects is consistent with concentrated solution behaviour. the inclusion of hydrodynamic interactions in concentrated solution where they are screened is not however consistent with the physics of concentrated solutions. many of the models and experiments presented in the literature are for purely extensional flows.2,26 recent simulations on the blood borne protein von willebrand factor (vwf) show that in couette flow the vwf chain tumbles when exposed to high shear rates to extend and then refold. when exposed to relatively low extensional shear rates, the vwf unfolds and extends.27-29 in light of recent experimental evidence showing chain compression in couette flow, a new model is presented where the chains compress in response to the hydrodynamic forces. we also note that coil compression is an elastic event which leads to reduced friction in the system and is therefore consistent with the shear thinning and visco-elasticity observed for polymer solutions in simple flow. purely extensional flow results in an increasing extensional viscosity with shear rate.30 results the shear rate dependence of the end-to-end distance, r, has been measured for polymethyl methacrylate (pmma) using fluorescence resonance energy transfer (fret) tagged chains in laminar couette flow.22 the conformation of poly-4-butoxy-carbonyl-methylurethane (4-bcmu) in flow has been measured using absorption spectroscopy where the change in segment length with shear is used to determine the change in polymer size.18 the results of the previous studies are re-plotted on a log-log scale in figure 1 below. both polymers show a decrease in the end-to-end distance with increasing shear rate. reversibility was observed upon cessation of shear for all shear rates measured.18,22 the results presented in figure 1 are from two different rheo-optical experiments for two different polymeric systems. the data for pmma was collected using time resolved fret measurements on end tagged pmma as a molecular tracer in a matrix of untagged pmma figure 1. measured end-to-end distance plotted as log r versus log shear rate. ata for 800kd 4-bcmu.18 has the fitted equation: log(r) = – 0.0046log(γ ∙ ) + 1.7 with the coefficient of determination: r2 = 0.23. data for 49kd fret tagged pmma in couette flow22 shows the fitted equation: log(r) = – 0.0072log(γ ∙ ) + 0.69 with r2 = 0.88. the lines of best fit yield an inverse 0.07±0.02 power of the radius with shear rate for the pmma and 0.0042±0.002 for the 4-bcmu. the error bars are approximately the size of the symbols. the error associated with each point is: ~5% in the shear rate due to the radius/gap ratio of the couette cell. for the 4-bcmu the un-sheared size of the chain is 49±1nm and for pmma the size is 4±0.1nm. 45modelling polymers as compressible elastic spheres in couette flow at ~2c*. the data for 4-bcmu is taken from reference 1 where the segment lengths of the 4-bcmu are measured to decrease with increasing shear rate at a polymer concentration of ~1.6c*.18 calculation of the average segment length and conversion to an end-to end distance using the equation r = an1/2 yields the results presented in figure 1 for 4-bcmu. here n is the number of segments and a the segment length as taken from literature values.18 both data sets show a decreasing radius with shear rate with a power law behaviour. theory the polymers are modelled as space filling, spherical elastic objects at semi-dilute concentration. the spheres are compressible and may change their volume through deformation. the flow is defined as simple couette flow where the spherical blobs are exposed to a uniform velocity gradient at low reynolds number, re = vr/η for neutral buoyancy spheres. in view of recent experimental evidence showing that polymer chains compress in couette flow (see figure 1), we assume that the translational hydrodynamic forces on the sphere act to compress the chain in accord with the experimental evidence.17,22,31 the semi-dilute concentration is such that the spherical blobs are in contact with each other and compress in flow. we postulate that the reason compression rather than extension dominates the flow response of these polymers is due to the crowding of the single chain by the neighbouring chains in semi-dilute solution. the tumbling motion of the chains results in a time average compressive hydrodynamic force on the sphere in semidilute solutions. for the semi-dilute solutions, the blobs experience both rotational and compressive forces in flow. the rotational force (torque) acts to make the compressive hydrodynamic forces on the sphere uniform. as such the hydrodynamic translational force acts isotropically inward on the blob and is opposed by the elastic force. the force acting on each half space in the couette flow acts in the opposite direction and is simply one half of the stokes’ drag on the sphere. goldman, cox and brenner32,33 determined the hydrodynamic force on a sphere in couette flow at low reynolds number as: fy s* = fy s /6πηru (1) here f is the force with the subscript y defining the direction of the translational motion in the unperturbed shear rate s, r is the sphere radius, u the fluid velocity and h the solvent viscosity. equation 1 defines the force on the sphere at distances from the walls greater than the radius as: fhyd =6πηru (2) the torque on the sphere, faxen’s law, was also determined as:33 tx s* =tx s / 8πηr3ω (3) where t is the torque on the sphere, with the superscript s defining the undisturbed shear rate, the subscript x is the vorticity axis and ω is the rotational velocity. the local forces may then be equated under steady state flow. the elastic and hydrodynamic forces on sphere then act to change the radius in flow. the forces are used in the following treatment as at each point in the system the hydrodynamic and elastic forces oppose each other. in order for the system to reach steady state, the figure 2. schematic showing the polymer represented as a sphere in couette flow. at semi-dilute concentrations each sphere is in “contact with the surrounding spheres. the shaded area shows the region which experiences a compressive force from the flow. the upper half experiences a compressive force from left to right while the bottom right hand part of the image experiences a similar compressive force from the flow from right to left. each surface experiences a compressive force equal to one half the stokes’ drag on a sphere. the total compressive force is then equal to fcompressive = fhyd = 6πηru where η is the solution viscosity, r the sphere radius and u the velocity difference across the sphere in the direction shown. the sphere also experiences a torque around the vorticity axis. this rotational motion causes a tumbling which yields an averaged symmetric compression on the blobs in flow. at each point across the surface the hydrodynamic force is equal to the elastic force under steady shear. local fluctuations will occur with the system reaching an average reduced size of the coil with increasing shear rate and commensurate hydrodynamic force. the arrows pointing inward on the blob represent the local hydrodynamic compressive force. 46 donglin xie and dave e. dunstan completely isotropic forces throughout the solution are equivalent. obviously, the forces will fluctuate around the steady state average as the blobs rotate around the vorticity axis in the shear field. in steady state flow the hydrodynamic and elastic forces are then equated: fel = fhyd (4) where the magnitude of the elastic force for the blob is taken from the theory of rubber elasticity and has a similar form as that reported previously:13,34 fel = e× area= 3nkbt r (5) where e is the young’s modulus of the blob, kb is boltzmann’s constant, t the absolute temperature and r the sphere radius. the elastic force so described embodies the entropic nature of the chain. here we define n as the number of chain interactions (usually assumed to be entanglements) where n may be assumed to be constant for finite deformation. the theory of rubber elasticity defines n as the number of cross links in the gel.13 note that the theory of rubber elasticity introduces an r0 term into equation 5 to allow for compression and the finite size of the chain in the quiescent state.13 neumann has previously suggested that the inability to account for r0 in the hookean force law used in models of polymers in flow arbitrarily restricts the chain to extension.35,36 indeed the neglect of the r0 term results in a hookean response of the chains that is not physically correct in that the radius is zero at zero force and infinite at infinite extension. the formalism introduced by neumann has the correct limiting behaviour for the force law in both extension and compression. compression of the chains to point size would require an infinite force as would large stretching. at each localised point, we assume that the elastic force acting normal to the surface of the blob as shown in figure 2 opposes the hydrodynamic force. the hydrodynamic force on the spherical blob is developed from equation 2 above using the assumption that the velocity in couette flow u defines the shear rate as: !γ =u / 2r (6) then fhyd =6πη!γr 2 (7) here the viscosity of the polymer solution is η, !γ the shear rate experienced by the chain and r the average end-to-end vector of the chain as defined above. it is assumed that the end-to-end distance is equivalent to the radius of the sphere that experiences the hydrodynamic force. the hydrodynamic force varies as r2 in accord with the original derivation of the hydrodynamic drag on a dumbbell derived by kuhn.9 to first order the viscosity of the solution, is approximated by a modified version of einstein’s equation: η ~η0φ (8) where the η0 is the effective solvent viscosity and ϕ the volume fraction of the chains. we assume that the effective solvent viscosity composed of solvent and the surrounding polymers. the polymer chains in flow act as compressible objects where the (incompressible solvent) may exchange freely throughout the system. the solution viscosity will depend on the polymer volume fraction and the shear rate. we assume that η0 is also proportional to the volume fraction ϕ so that: η ~φm (9) de gennes and later rubinstein and colby have derived the volume fraction dependence for the viscosity of semi-dilute solutions using scaling arguments and determined that m = 2. furthermore, experimental data confirms the scaling arguments for polyethylene oxide in the semi-dilute concentration range.2,37 by assuming φ ~ r3 by substitution into equation 5 we obtain the following: η ~ r3m (10) equating the hydrodynamic and elastic forces on the spherical object in flow; 3nkbt r =6πr3m!γr2 (11) yields: nkbt ~ !γr 3 m+1( ) (12) so that r ~ nkbt !γ −1/3 m+1( ) (13) the generally accepted power law model is of the form: η ~ !γ n (14) values of n reported for polymeric systems range between p ~ -0.2 to -1.0.38-40 interpretation of the data 47modelling polymers as compressible elastic spheres in couette flow presented by stratton indicates that for monodisperse polystyrene, p = -0.82.40 the value of p = -2/3 predicted by the model is well within the range of accepted values for shear thinning polymers.38 the viscosity-shear rate in model developed has the power law form: η ~ !γ−m/ m+1( ) (15) the dependence of the radius with shear rate for m = 2 is then: r ~ kbt !γ −1/9 (16) and η ~ !γ−2/3 (17) thus the model predicts values for the power law model in accord with those determined experimentally for polymer solutions and hard sphere suspensions.39,40 discussion the measured dependence of the decrease in the radius with increasing shear rate (power law of -0.09±0.02) is in close agreement with the model prediction of -1/9 (-0.11) (equation 16) when m = 2 is used for the volume fraction power law of the viscosity for the pmma data. furthermore, the model predicts a power law for the shear thinning viscosity of -2/3 (-0.67) that is within the range observed for polymer solutions which have been found to lie within the range of -1.0 to -0.2.38-40 using the approximation that the viscosity follows a volume fraction squared behavior allows the model to fit both the power law behavior of the radius and viscosity with shear rate for pmma. expansion of the einstein equation involves the addition of higher order terms in the volume fraction as attributed to batchelor.33 any correction to the viscosity-volume fraction dependence would presumably require higher order terms (m > 2) that would yield lower values of the predicted power law at higher concentrations. indeed, scaling arguments predict that the viscosity follows a 14/3 power of the volume fraction at concentrations above the entanglement concentration.37 the measured viscosity-molecular weight behavior for a range of polymers is consistent with the volume fraction dependence used in equation 7.41 furthermore, de gennes and later rubinstein and colby have modeled the viscosity-polymer volume fraction dependence described in equation 9 using scaling arguments to show that m = 2 in the semi-dilute concentration range.2,37 this relationship between the volume fraction of the polymer and the effective solvent viscosity enables the macroscopic viscosity-shear rate power law to be predicted (equation 15). the predicted and measured decrease in radius with shear rate for the pmma are in excellent agreement when the second order dependence of the viscosity on volume fraction (m = 2) is used. fitting the bcmu data requires that m is approximately 1 (m = 1.0015). this suggests a power law for the viscosity of ~-1/2. equation 7 yields an unbounded radius (and viscosity) as the shear rate tends to zero so that a modified form of the above equations must be used at low shear rates. the form of the equations at low shear rates will be similar to the cross equation for shear thinning.39 the recently measured shear induced phase separation observed in semidilute polymer solutions may be explained by chain compression in flow where the solutions appear to be more heterogeneous as reflected in the scattering measurements. the observed compression in flow lays the foundation for an explanation of the observed shear induced phase changes observed for polymer solutions.42,43 furthermore, it is noted that the model predicts a value of p = -1/2 and a radius dependence of the shear rate with a power of -1/6 for dilute solutions where it is assumed that the viscosity is proportional to the volume fraction. a review of the literature on the power law behavior observed for polymer solutions of differing volume fraction would be appropriate in validating the current model. the power law of the viscosity with volume fraction is used as an adjustable parameter in the model and suggests possible reasons for the different power law behavior reported in the literature for the same polymer systems. conclusions the model for polymers in flow is presented where the chains behave as elastically deformable spheres that compress in simple shear flow at semi-dilute concentrations. equating the elastic and hydrodynamic forces on the blob enables the power law observed for shear thinning and the reduction in end-to-end distance with shear rate to be predicted over the range of shear thinning. physically the model is consistent with the observed rheology of polymer solutions in couette flow which is attributed here to compression of the chains in flow rather than the previously assumed extension. development of the model using the assumption that the chains compress enables a simple analytical prediction of polymer visco-elastic behavior including the power law for shear thinning. 48 donglin xie and dave e. dunstan authors’ contributions dx undertook data analysis and contributed to writing the paper. dd contributed to writing the paper and developed the model. acknowledgements we would like to thank elisabeth hill, yalin wei, ming chen and nikko chan for their experimental work in undertaking the rheo-optical measurements. references 1. l.h. sperling, introduction to physical polymer science, wiley interscience, new jersey, 1992. 2. p.g. de gennes, scaling concepts in polymer physics, cornell university press, ithaca, 1979. 3. w.w. graessley, polymeric liquids & networks: structure and properties. new york, garland science, 2004. 4. m. doi, s.f. edwards, the theory of polymer dynamics, clarendon press, oxford, 1986. 5. p.j. flory, principles of polymer chemistry. ithaca, cornell university press, 1953. 6. p. flory, statistical mechanics of chain molecules, hanser publications, new york, 1988. 7. j.d. ferry, viscoelastic properties of polymers. new york, john wiley, 1980. 8. r.b. bird; c.f. curtiss; r.c. armstrong, o. hassager, dynamics of polymeric liquids, volume ii, kinetic theory, wiley-interscience, new york, 1987. 9. w. kuhn, kolloid z. 1933, 62, 269. 10. g.b. jeffery, proc. roy. soc. london series a 1922, 102, 161. 11. g. cheng, w.w. graessley, y.b. melnichenko, phys. rev. lett. 2009, 102, 157801. 12. m. daoud, j.p. cotton, b. farnoux, g. jannink, g. sarma, h. benoit, r. duplessix, c. picot, p.g. de gennes, macromolecules 1975, 8, 804. 13. l.r.g. treloar, the physics of rubber elasticity, oxford university press, oxford, 1975. 14. g. marrucci, j.j. hermans, macromolecules 1980, 13, 380. 15. g. marrucci, n. grizzuti, j. nonnewton fluid mech. 1986, 21, 319. 16. r.b. bird, j.r. deaguiar, j. nonnewton fluid mech. 1983, 13, 149. 17. s. gason, d.e. dunstan, t.a. smith, d.y.c. chan, l. r. white, d. v. boger, j. phys. chem. b. 1997, 101, 7732. 18. d.e. dunstan, e.k. hill, y. wei, macromolecules, 2004, 37, 1663. 19. n. y. chan, m. chen, d.e. dunstan, eur. phys. j. e, 2009, 30, 37. 20. p. leduc, c. haber, g. bao, d. wirtz, nature 1999, 399, 564. 21. r.e. teixeira, h. . babcock, e.s.g. shaqfeh, s. chu, macromolecules 2004, 38, 581. 22. n.y. chan, m. chen, x.-t. hao, t.a. smith, d.e. dunstan, j. 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university press, 2003. 38. d. song, r.k. gupta, r.p. chhabra, ind. eng. chem. res. 2011, 50, 13105. 39. h.a. barnes, j.f. hutton, k. walters, an introduction to rheology, elsevier, amsterdam, 1989. 40. r.a. stratton, j. coll. interface sci. 1966, 22, 517. 41. r.a. l. jones, soft condensed matter, new york, oxford university press, 2002. 42. m. minale, k.f. wissbrun, d.f. massouda, j. rheol. 2003, 47, 1. 43. b. hammouda, a.i. nakatani, d.a. waldow, c.c. han, macromolecules 1992, 25, 2903. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments substantia. an international journal of the history of chemistry 5(2): 55-77, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1181 citation: travis a. s. (2021) first steps: synthetic ammonia in the united states. substantia 5(2): 55-77. doi: 10.36253/substantia-1181 received: jan 06, 2021 revised: apr 27, 2021 just accepted online: apr 28, 2021 published: sep 10, 2021 copyright: © 2021 travis a. s. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research articles first steps: synthetic ammonia in the united states anthony s. travis sidney m. edelstein center for the history and philosophy of science, technology and medicine, safra campus, the hebrew university of jerusalem, jerusalem, israel e-mail: tony.travis282@gmail.com abstract. the synthetic ammonia industry, originally based on fritz haber’s 1909 invention of a catalytic high-pressure method as scaled up by carl bosch at basf, grew globally in the years following world war i, based on the processes of brunner, mond & co. (britain), luigi casale (italy), georges claude (france), and giacomo fauser (italy). the ammonia was mainly converted into ammonium sulphate fertilizer. there was less impetus in the united states for taking up these developments, because america relied on ammonia from its by-product coking ovens and coal gas works, sodium nitrate (chilean nitrate) from south america, and calcium cyanamide as manufactured by the american cyanamid company. even when a synthetic ammonia industry started up in the united states, it was on a smaller scale than in europe. however there emerged just before the wall street crash two major producers of synthetic ammonia, allied chemical and du pont. this article presents a historical reconstruction of the early synthetic ammonia industry in the united states focusing on the 1920s, paying particular attention to du pont’s success, which relied on the ammonia process of casale. standard accounts suggest that du pont acquired casale technology as the result of a straightforward business acquisition. however, the situation, as shown here, was far more complex. du pont had to engage in aggressive litigation in order to acquire rights to the casale process in 1927. keywords: synthetic ammonia, casale process, niagara ammonia company, allied chemical, du pont. introduction the 1920s were the take off years for science-based chemical industry in the united states. this is nowhere better illustrated than in the realm of coal-based synthetic organic chemistry, in which american firms drew on german technology to master and even excel in the production of colorants and, later, novel products, such as pharmaceuticals, derived from the dye intermediates.1 the need to catch up with germany, and to invent new products for new needs, such as the automobile industry, stimulated unprecedented research and development. the growth and diversification of the us chemical industry was tremendous, and included development of novel polymers, and expansion at firms engaged in electrochemical technologies. some http://www.fupress.com/substantia http://www.fupress.com/substantia 56 anthony s. travis of the most significant developments drew on catalyzed, high-pressure industrial chemistry, following introduction of the haber-bosch synthetic ammonia process by basf in 1913.2 in this area of chemical technology, however, the united states was a late starter. relative to the synthetic dye industry, the parallels, particularly with imitation of german dye technology, are more difficult to discern. this article will explore the several reasons, as well as the early development of the us synthetic ammonia industry. the extraordinary success of the haber-bosch synthetic ammonia process in contributing to germany’s industrial effort in the production of munitions during world war i was widely acknowledged.3 after the cessation of hostilities, basf was not prepared to license the process, preferring instead to use it as a bargaining tool in attempts to gain access to various international tie-ups and also to control the global market in nitrogen fertilizer. this pretention to world leadership, however, spawned imitators, and rivalry. here we recount two related but distinct stories— insofar as they concern similar technologies and their transfers across the atlantic from europe—in the development of the large-scale american synthetic ammonia industry. one concerns the allied chemical & dye corporation, whose process originated with one of its predecessor firms, and was similar in operating conditions to the haber-bosch process. the other describes the du pont corporation’s entry into synthetic ammonia, based on the acquisition of the processes of georges claude (france) and luigi casale (italy) that were worked at around four times the pressure of the haber-bosch process. it was the casale process that enabled du pont to become an american technology and market leader in high-pressure chemistry. for this reason i focus mainly on du pont’s entry into what was also a completely new venture, based on a novel technology that relied on sophisticated engineering expertise, and that was decidedly removed from synthetic dyes. the background involves the transfer in 1927 of casale technology from an ambitious but struggling start-up to du pont, which planned a major scale up of ammonia manufacture, mainly for the fertilizer market, particularly of ammonium sulphate. at the outset, it should be pointed out that massive transatlantic technology transfer from europe, whether of dyes or of high-pressure chemistry, by whatever means, was part of a pattern that impacted on the entire american chemical industry during the 1920s. much of this encounter has been well analysed, including the mergers and acquisitions, and the partnerships with europan firms, that led to the rapid growth of major corporations. shortages of vital chemicals as a result of the cutting off of imports from germany during world war i provided the impetus for diversification, and for the foundation of start-ups that mastered many features of synthetic organic chemistry, often using information gleaned from sequestered german patents. in some cases, the war enabled the survival and expansion of struggling firms. in others, firms denied access to intermediates made in europe drew on processes that under peacetime conditions were not economically viable. what is absent in many cases from the historical record are accounts of the complexities of how this industrial transformation was achieved at a more detailed level. this account is an attempt to compensate for the lacunae in one specific sector, though it serves as an outstanding indicator of what was achieved overall by 1930. its contemporary relevance to the historian resides in the oft neglected focus on the technologies involved; they are often overlooked in accounts that are more focused on business history. as is frequently the case in the pursuit of industrial history, archival sources are limited, often long ago lost in fires and explosions or discarded following mergers and acquisitions. fortunately there is adequate material to guide us at the hagley museum and library, in wilmington, delaware, in examining an important part of the early history of synthetic ammonia in america. we are aided by the few articles on developments in the united states published between 1930 and the early 1950s, particularly since records of technical progress at du pont are mainly absent.4 while the fragments of history may not make a whole, they can certainly aid our understanding of how the synthetic ammonia industry evolved in america. among the handful of novel, successful ammonia processes developed in europe around 1920, the most widely adopted, and successful, was that of the italian chemist and entrepreneur luigi casale, who requires a brief introduction. luigi casale luigi casale (1882-1927) studied chemistry at the royal polytechnic of turin (reale politecnico di torino), where he graduated in 1908. his teacher was arturo miolati (1869-1956). during 1909-1912, casale worked under michel fileti at the turin institute of chemistry, where he received his postgraduate degree in 1910.5 publicity surrounding the successful outcome of fritz haber’s work at karlsruhe on a high-pressure synthetic ammonia method no doubt stimulated casale’s interest 57first steps: synthetic ammonia in the united states in physical chemistry and gas reactions at high pressures. during 1912-1913, casale undertook research in physical chemistry under walther nernst, in berlin, and kept in touch with the latest developments in the thermodynamics of gas reactions, as well as their commercial utility. after returning to italy, casale undertook research in organic chemistry, as assistant of miolati, during 1913-1915, while retaining an interest in synthetic ammonia. during world war i, after studies on war gases, casale worked at industrial concerns, including the electrochemical firm idros (società idros; it derived its name from idrogeno and ossigeno), founded on 19 february 1916, to supply hydrogen to the italian navy for dirigible and other aerial balloons, and oxygen for oxyacetylene welding. idros was located in terni, umbria, close to italy’s main steelworks company. hydroelectricity provided an inexpensive source of power for idros. around 1917, while at idros, casale began to study the synthesis of ammonia from its elements. by 1920, assisted by the american physicist and inventor rené leprestre (1876-1941), casale had invented a high-pressure ammonia process. the main inventive concepts included application of far higher pressures (at up to 850 atmospheres) than used in the haber-bosch process (around 200 atmospheres) and a converter made of ordinary steel that survived the huge stresses. as with the haberbosch process, unreacted gases were recirculated to the converter through a closed loop. the yield of ammonia was around fifteen to eighteen per cent, compared with five to eight per cent for the haber-bosch process. the use of ordinary steel in casale’s converter was made possible by the forced cooling action on the inner casing of the converter shell of the mixed reactant gases, hydrogen and nitrogen, that were introduced under pressure (figure 1). as a result of the very high pressure, the converter required a less active iron catalyst than needed for the german process. surrounding the inner catalyst chamber was a concentric heat exchanger, providing heat for the incoming gases. overheating in the region of the catalyst was prevented by allowing some ammonia to remain in the recirculated gases, thereby slowing the reaction down. the process, for a given output, used smaller equipment than employed in the haber-bosch process. this also applied to the french process of georges claude, of air liquide, which was worked at 1,000 atmospheres. moreover the energy requirements in the casale and claude processes were not much greater than required in units that were operated at considerably lower pressures. a major difference with claude’s high-pressure process was that the latter, as a result of its design, which involved passage of reactant gases through a series of converters (without recirculation), required special steels in order to withstand the severe operating conditions. one important advantage of the two eponymous very high-pressure processes of casale and claude was that they gave directly anhydrous ammonia, in contrast figure 1. casale ammonia converter (reactor), 1920s. key: 1, gas (nitrogen-hydrogen) inlet; 2, 2’, concentric annular spaces, divided by corrugated partition; 3, electrical heater; 4, catalyst space; 5, ammonia and unreacted nitrogen-hydrogen outlet. redrawn from a. miolati, synthetic ammonia and the casale process. amplified edition of a lecture delivered the 27th february 1927 at the institute of chemistry of the polytechnic school of prague (transl. g. impallomeni, 2009). “l’universale” tipografia poliglotta/ammonia casale sa, rome, 1927, p. 24. 58 anthony s. travis to processes carried out under haber-bosch conditions which required expensive refrigeration equipment to achieve an anhydrous product. casale erected a pilot plant in an old iron works belonging to the terni steelworks company (from 1922 società per l’industria e l’elettricià terni). in april 1921, he founded ammonia casale sa, in lugano, switzerland, which soon licensed the technology to entrepreneurs, companies, and state organisations in japan and europe. though patents were filed in the united states, there was little interest in casale’s and other synthetic ammonia processes. america was well supplied with nitrogen products, through entrenched businesses and processes. here we need to understand the background to the nitrogen fertilizer market in the united states. nitrogen products in the united states three products enabled self-sufficiency in nitrogen compounds for use as fertilizers, and contributed to a healthy export trade in ammonium sulphate. the sulphate was the main nitrogen fertilizer, produced from the ammonia from by-product coking ovens that were rapidly replacing the beehive ovens from which valuable products were lost. in 1925, the united states ammonium sulphate capacity from many of the 10,000 by-product coking ovens was “well over 600,000 tons.”6 imported chilean nitrate was widely used as fertilizer, notably in citrus growing regions. the third important source of fertilizer nitrogen was calcium cyanamide, as manufactured by the american cyanamid company on the canadian side of the niagara falls from 1910. during 1924-1925 the import of chilean nitrate into the united states grew considerably, including through the involvement of the increasingly diversified du pont company. from the nitrate, du pont manufactured nitric acid, which was essential in production of explosives, dyes, and other products. there was a new route to nitric acid, much used in europe: catalytic oxidation of ammonia (the ostwald process). conversion of ammonia derived from cyanamide and from coking ovens into nitric acid using this process had been achieved just prior to world war i by, respectively, american cyanamid, at warners, new jersey, and the solvay process company, at syracuse, new york. however the earlier method of making the acid starting with chilean nitrate was generally favoured for both economic and technical reasons until the late 1920s. this is one reason why du pont had a not inconsiderable interest in the chilean nitrate industry. ammonia for refrigeration in contrast to the situation in postwar europe and japan—where the synthetic ammonia industry was often backed by government self-sufficiency programmes related to both fertilizers and explosives—the early interest in synthetic ammonia in the united states was in supplying the more restricted refrigeration market. ammonia was used as an industrial refrigerant well before world war i, notably by armour & company of chicago that was involved in meat packing and storage. the coal gas manufacturers were sources of aqua ammonia (ammonia water) used to produce the anhydrous ammonia for industrial refrigeration. anhydrous ammonia was shipped in cylinders. from around 1890, the harrisburg pipe & pipe bending company manufactured the cylinders from hand-welded steel pipes. after 1910, following the lowering of an import tariff, seemless highpressure gas cylinders made by mannesmann in germany were imported into the united states. harrisburg responded by producing a quenched and drawn heat cylinder of lighter weight, which could be handled by one man, instead of two as previously. in 1923, the production of anhydrous ammonia used in industrial refrigeration came to 23,966,000 pounds, valued at $6,415,000.7 domestic refrigerators that relied mainly on sulphur dioxide for cooling were introduced later in the 1920s.8 armour had pioneered large scale long-distance transportation of otherwise perishable foodstuffs in refrigerated railroad cars. this was far more important than in europe, where transportation involved much shorter distances, and in generally cooler climates. brewers were among the other important consumers of ammonia for refrigeration. the leading distributor in the east was the national ammonia company, of st louis, formed in 1889 at the initiative of edward mallinckrodt, of the mallinckrodt chemical works, by merger of five large producers of ammonia (subsequently other companies in the ammonia business were acquired). by the early 1900s there were factories in both st louis and philadelphia, and branches in canada and australia, offering both anhydrous and aqua ammonia. on the west coast, the pacific ammonia & chemical company, managed by robert p. greer, monopolised the market in anhydrous and aqua ammonia. pacific ammonia, founded in san francisco in the 1890s, moved its manufacturing base to seattle in 1908-1909. by 1920, it was represented by agencies in japan, china, the philippines, the hawaiian islands, and british columbia. in 1922, pacific ammonia became associated with national ammonia; the two stockholders in pacific ammonia, with almost equal holdings, were 59first steps: synthetic ammonia in the united states national ammonia and robert greer. national ammonia retained its strong interest in distributing ammonia to the refrigeration market, but did not compete with producers and distributors of nitrogen fertilizers. the fnrl and its 3-ton per day ammonia unit despite the range of commercial nitrogen products available in the united states, interest in high-pressure ammonia processes and general nitrogen fixation was certainly not lacking. from march 1919, the role of synthetic nitrogen compounds as fertilizers and in production of nitro compounds for munitions were investigated at the state sponsored fixed nitrogen research laboratory (fnrl) in washington dc, under the aegis of the u.s. army’s nitrate division. during 1919, american military officers visited the basf ammonia facility at oppau, in the french zone of occupation. though they were not always welcome, they made useful observations, and, probably surreptitiously, procured samples of catalysts, that ended up on the test benches of the fnrl.9 in just over half a decade, its staff resolved most of the chemical and technical problems related to the ammonia synthesis. thus, alfred t. larson developed a catalyst similar to that used in the haber-bosch process, no doubt based on analysis of samples obtained from oppau, and patents for german recipes. this contributed to the success of the fnrl in producing synthetic ammonia, at around 200 atmospheres pressure, drawing on pure hydrogen obtained by electrolysis of water in cells provided by the electrolabs company of pittsburgh.10 from 1924, the results of the fnrl were made freely available to chemical firms and entrepreneurs; many of its chemists subsequently contributed to the us synthetic nitrogen industry.11 larson, for example, joined du pont. the fnrl’s 3-ton per day (tpd) synthetic ammonia unit became a model for a handful of american firms, all working on a small scale. the most expensive input was hydrogen, for which operators of the fnrl process relied mainly on by-product hydrogen from electrochemical processes in locations where abundant hydroelectric power was available. first to adopt the fnrl process, in 1924, was the pacific nitrogen corporation, at the seattle works of pacific ammonia (then associated with national ammonia). the entire installation was erected under the supervision of fnrl staff. in this case, dedicated cells produced the hydrogen, which was far more costly than by-product hydrogen. next, during 1924-1925, was the mathieson alkali works, at niagara falls, followed in 1926 by the roessler & hasslacher chemical company, also at niagara falls (table 1).12 these firms manufactured ammonia for the refrigeration market or for use in production of other chemicals. thus, roessler & hasslacher relied on inhouse by-product hydrogen from electrolytic production of sodium, and used the ammonia to manufacture sodamide (sodium amide), for its sodium cyanide process. the small scale of working with fnrl type units, as compared with manufacture in europe and japan, did not permit economic production of nitrogen fertilizers. at best, the fnrl had aided in the creation of a minor branch of chemical industry. however, nitrogen fertilizers based on synthetic ammonia required large-scale operations and economies of scale. this was achieved in europe by merging the two cultures of engineering and chemistry. ammonia casale sa was a front runner in this endeavour. casale in america here we turn to the story of the introduction into the united states of the casale ammonia process. luigi casale not only promoted and, unlike basf, licensed his process but also served as a contractor, supplying italian made converters, compressors, and associated equipment to clients. at first there were no rivals: claude’s process faced difficulties with converters; and the italian process of giacomo fauser, under montecatini, was confined to italy. the first licensee of ammonia casale sa was noguchi shitagau (founder of the nitchitsu corporation) in japan, who met with great success and within a short time was ordering additional converters. casale converters were put to work in belgium, france, switzerland, spain, and elsewhere.13 figures of nitrogen consumption in the united states clearly suggested to luigi casale that here was an untapped and potentially vast market for synthetic ammonia, including for use in refrigeration. in 1923, following the filing of certain key patents on his inventions, casale set about the creation of a new enterprise, niagara ammonia company, inc., established in new york city. this american branch of ammonia casale sa would not only engage in licensing arrangements and the supply of equipment, but would also undertake manufacture on american soil, using converters and compressors imported from italy. casale’s niagara ammonia would not only be a showpiece for americans to admire, but its product, usefully, would not be subject to import tariffs on ammonia. ammonia casale sa also established in new york the ammonia corporation (figure 2). it retained ownership of the casale patents in the united states.14 also involved, as an assignee jointly with luigi casale of cer60 anthony s. travis tain of casale’s patents, was rené leprestre, who was based, in part at least, in new york. the ammonia corporation assigned patent rights and provided funding to niagara ammonia; they were to share any licensing compensation. reports of successful operation of the casale process must have gone a long way towards convincing american investors, especially those with interests in electrical power, to back casale. as a result, the principal external backer was the electric bond & share company, a major utilities trust originally founded by general electric in 1905.15 around four-fifths of both preferred and common stock in niagara ammonia were held by the ammonia corporation, while around one-fifth of the stock was held by electric bond & share, represented by the banker and entrepreneur henry j. pierce (1859-1947).16 the electric bond stock was held in the name of nominee frank l. smiley (1871-1948) a dealer in utilities stocks. ammonia was in some ways an unusual investment for electric bond & share, which was mainly involved in power stations and electrical infrastructure, including interurban and street railways. however, the chemical industry was a major, and rapidly growing, consumer of electricity, and synthetic ammonia, which relied on electrically powered machinery, no doubt offered a novel area for diversification. (the interest in synthetic ammonia at electric bond & share, later ebasco, continued until well after world war ii.) other investors included the new york stockbroking houses a. iselin & company, which had close connections with europe, and h. t. carey & company. there was also david barker rushmore, an engineer formerly at general electric, and an enthusiast for hydroelectric power generation. in 1923, rushmore published the second edition of a book, co-authored with eric a. lof, on power stations.17 in the same year, lof drew up a report on atmospheric nitrogen fixation. the iselin firm held the stock certificates of ammonia casale sa investments in the united states. to all intents and purposes, the aspirations of the ammonia corporation were based on a business plan table 1. synthetic ammonia facilities, united states, 1927. name location and process rated daily capacity, tons of ammonia daily operating rate, tons of ammonia yearly nitrogen equivalent in tons (based on 350-day operation) atmospheric nitrogen corp. syracuse, ny (solvay/allied), general chemical 30 30 7,750 lazote, inc. (du pont) charleston w. va. (belle), claude 25 15 4,350 mathieson alkali works niagara falls, ny. 3 tpd in 1925, american 10 10 2,900 niagara ammonia company (to du pont, 1927; ceased operating july 1927) niagara falls, ny, casale 13 (17) 8 1,250 (approximately six months) roessler & hasslacher chemical co. (to du pont 1930) niagara falls, ny, american 3 (increased to 9 tons, 1928) 3 865 pacific nitrogen corp. (to du pont 1927) seattle, washington, american 3 3 865 great western electrochemical co. pittsburg, california, american 1 1 290 commercial solvents corp. peoria, ill. southwest of chicago, american 15 0 converted to methanol, shortly after inauguration in 1927. sources: f. a. ernst, fixation of atmospheric nitrogen, chapman & hall, ltd., london, 1928, p. 121. f. a. ernst, f. c. reed, w. l. edwards, “a direct synthetic ammonia plant,” industrial and engineering chemistry, august 1925, 17(8), 775-788. editorial, industrial and engineering chemistry, august 1925, 17(8), 772. f. a. ernst, m. s. sherman, “the world’s inorganic nitrogen industry,” industrial and engineering chemistry, february 1927, 19(2), 196-204, on 199. notes: american = based on the fixed nitrogen research laboratory (fnrl) method. the original source of hydrogen at syracuse was water gas, until may 1927, when in house by-product hydrogen became available. niagara ammonia company used its electrolytic cells for generating hydrogen, as well as purchasing by-product hydrogen from the adjacent hooker electrochemical plant. pacific nitrogen used electrolytic hydrogen from its dedicated cells; mathieson and great western used byproduct electrolytic hydrogen. commercial solvents used by-product hydrogen from fermentation. 61first steps: synthetic ammonia in the united states aimed at marketing the ammonia casale brand in north america, underpinned by proven success, and patent protection. in terms of rated converter capacity, of around 7-8 tpd, the casale process certainly offered far more than the processes based on the fixed nitrogen research laboratory’s 3-tpd unit, which in 1923 had not yet been introduced on an industrial scale, and the then problematic claude process. the only viable rival was the general chemical process, of allied chemical, which was confined to solvay operations at syracuse (see next section). the ammonia corporation, it must have seemed, stood to benefit from growth in demand for nitrogen products, including, the founders probably anticipated, the fertilizer market, that would bring in substantial royalties following the signing of licensing agreements. this differed from arrangements elsewhere, in which sole licenses for given countries or geographical regions were sold to chemical manufacturers, without, it appears, direct investment from ammonia casale. the general chemical process the first attempt to introduce a catalytic high-pressure synthetic ammonia process in the united states was made by the general chemical company (a consolidation of twelve companies established in 1899), just prior to the outbreak of war in europe. much interest had been generated after the demonstration by basf of haber’s method at the eighth international congress of applied chemistry, held in new york in 1912. this was followed by careful scouring of the available literafigure 2. stock certificate, the ammonia corporation, preferred stock, assigned to a. iselin & co., 30 july 1923. iselin held the stock certificates of ammonia casale sa holdings in the ammonia corporation and the hydro-electric chemical company. from: the ammonia corporation, a preferred stock. records of e.i. du pont de nemours & co. absorbed companies. manuscripts and archives department, hagley museum and library, wilmington, delaware, accession 500, series ii, part 1, box 67. author’s photograph. reproduced with permission. 62 anthony s. travis ture and patent applications concerning the process. at general chemical, frederick w. de jahn and colleagues developed a process similar to that of basf, and discovered an iron catalyst incorporating sodamide. the company put together a small pilot plant during 1915-1916. subsequent government supported wartime experimental work based on the process was not successful. however, by 1919 these studies enabled general chemical chemists to overcome several technical problems, including a suitable steel for the converter shell, and devise an improved catalyst.18 in late 1919, general chemical and the solvay process company brought together their interests in synthetic ammonia through the atmospheric nitrogen company, in order to set up an ammonia unit at solvay’s syracuse works. the development of the general chemical process benefitted greatly from the free exchange of technical information between solvay process and the british firm brunner, mond & company, in accord with arrangements dictated by the belgian licensor of the solvay ammonia-soda process, solvay et cie. this included details of the catalyst used in the haber-bosch process, samples of which were taken by brunner, mond investigators during their visits to oppau in 1919.19 in 1920, general chemical, solvay process, and five other firms, including national aniline & chemical (a merger of four firms dating from 1917), were absorbed into a new behemoth, allied chemical & dye corporation. this was one of the first major interwar mergers in the chemical industry, preceding those that led to i.g. farben (1925), and britain’s ici (1926). it was in many ways a response to concerns arising from the fact that du pont and basf had begun discussions on the opening of a haber-bosch facility in the united states, much to the chagrin of general chemical and solvay process, who were anticipating collaboration with basf in a similar venture. in the end, du pont failed in its dealings with basf, and for a while lost interest in synthetic ammonia.20 on 8 august 1921, atmospheric nitrogen started up what became known as the general chemical synthetic ammonia process at syracuse. the initial rated output was 9-tpd. the source of hydrogen was water gas, obtained by the reaction between steam and red hot coke, the latter available from semet-solvay coking ovens. this followed the success of basf and brunner, mond with water gas processes. nitrogen was initially obtained by air liquefaction. in september 1921, william henry nichols, chairman of allied chemical, “caused a deal of surprise” when he announced this considerable achievement at a luncheon during the american chemical society’s 62nd meeting, held at columbia university.21 in 1922, however, the german observer bruno waeser suggested that the process was facing technical difficulties.22 moreover, the syracuse anhydrous ammonia was not at first well suited to refrigeration due to the presence of impurities, as a result of which distillation equipment had to be introduced. some ammonia was probably used to produce sodamide for the allied chemical synthetic indigo process, and for manufacture of sodium cyanide. its potential for use in the solvay ammonia-soda process was also significant. published figures of the rated annual output of syracuse ammonia indicate growth from 3,000 tons in 1921 to 7,750 tons in the mid-1920s.23 this increase took place following the decision of the head of allied chemical, orlando weber, to invest heavily in synthetic ammonia and inorganic products at the expense of dyes and other organic chemicals.24 allied chemical’s ammonia process was not made available for licensing. by 1925, allied chemical had embarked on construction of a large synthetic ammonia facility, using the modified general chemical process, at the new hopewell, virginia, factory of solvay process. it opened in late 1928, and relied for hydrogen on water gas made from coke brought in from allied’s remote coking ovens. the first product made at hopewell was anhydrous ammonia, soon followed by the fertilizers ammonium sulphate and sodium nitrate. for the first time in the united states, economies of scale enabled synthetic ammonia to compete in the agricultural fertilizer market with chilean nitrate, coking oven and gas works by-products, and calcium cyanamide. according to historian of the us chemical industry williams haynes the syracuse ammonia unit continued in service, as had been the case earlier, as a pilot facility for process development, while markets for synthetic ammonia were being investigated.25 however, with downsizing, following construction at hopewell, there was an alternative source of hydrogen at syracuse. from may 1927, the new solvay electrolytic plant there supplied by-product hydrogen for the synthetic ammonia unit, in addition to chlorine for dye manufacture at the nearby factory of national aniline (part of allied chemical), and caustic soda for local manufacturers of artificial silk (viscose). for development purposes, there were advantages in employing electrolytic hydrogen. it was pure, unlike that from the water gas process (which required extensive purification to prevent poisoning of catalyst). also, reliance on electrolytic hydrogen permitted intermittent, small-scale, operation, unlike the cokebased processes. these factors were also important in 63first steps: synthetic ammonia in the united states deciding the source of hydrogen at the fnrl, and also at casale’s american factory. the syracuse experimental unit continued to operate until well into the 1930s.26 ammonia casale sa in america the function of the niagara ammonia company, as its name might suggest, was to operate the casale process at niagara falls, the hub of the us electrochemicals industry. in this connection there was also an associated casale enterprise, again with the close involvement of electric bond & share, the hydro-electric chemical company, founded in maine in july 1923 (figure 3). hydro-electric’s holding company was the chemical investment corporation, also established in 1923 (table 2).27 the president of hydro-electric chemical was henry j. pierce, again representing electric bond & share. among the investors (and later a director) was the new york lawyer josiah turner newcomb, the special council for electric bond & share. a director, and holder of a single share, was rené leprestre. the interests of electric bond & share and ammonia casale in america were now closely intertwined. together they embarked on an ambitious venture aimed at dominating certain novel and emerging sectors of the us chemical industry, based on electrochemicals and high-pressure technology. colonel frederick pope the president of both the ammonia corporation and niagara ammonia was the harvard educated chemical engineering consultant and entrepreneur colonel frederick pope (1877-1961), a resident of new york.28 before 1914, following stints in mining operations, including in south africa, pope had studied aromatic nitro compounds, those used to make modern explosives and synthetic dyes. during world war i, it was later claimed, he opened the first new american synthetic dye figure 3. stock certificate, hydro-electric chemical company, preferred stock, in the name of the casale ammonia company (often used in english language documents for ammonia casale sa), 1 august 1923. from: hydro-electric chemical company, stock certificate book, 1923-28. records of e.i. du pont de nemours & co. absorbed companies. hagley museum and library, wilmington, delaware, accession 500, series ii, part 1, box 848. author’s photograph. reproduced with permission. 64 anthony s. travis factory, prior to specialising in gas warfare in the united states and france. in 1918, before the cessation of hostilities, he took from england to the united states details of the technology for producing mustard gas by the levinstein process, which was taken up at edgewood arsenal. in 1919, he was among the technical experts who visited german chemical factories, in his case twice, to follow up developments in organic chemical and dye manufacture and the production of toxic chemicals. pope’s brief published account does not indicate the sites that he visited, though they probably included the synthetic ammonia facility of basf at oppau.29 his chemical warfare service colleague theodore sill visited oppau, which he described as a wonder of modern technology. what pope saw or heard about oppau must have aroused in him an interest in the potential for highpressure industrial chemistry.30 above all, it was colonel pope’s status as an experienced entrepreneur, with an extensive network of contacts, that recommended him to the american casale enterprise. hydrogen for niagara ammonia as with all synthetic ammonia processes, the main operational cost was associated with production of hydrogen, at first obtained by electrolysis in locations where abundant hydroelectric power was available. on the united states side of the niagara falls firms such as hooker electrochemicals manufactured chlorine, alkali and chlorinated organic compounds, as well as making available by-product hydrogen, from its electrolysis process. in 1918, hooker first supplied hydrogen to a joint enterprise, hydrofats., inc., for hardening vegetable oils.31 hydrofats, located on hooker’s land next to the latter’s niagara falls factory, ceased operating in 1922. in the following year, the former hydrofats site was leased by hooker to niagara ammonia, whose directors included willard e. hooker, youngest son of the founder of hooker (elon huntington hooker, 1905). in november 1923, a contract with electrolabs for purchase of a hundred and sixteen of its 5,000 amp cells, including their installation, at a cost of $40,356, was approved, as was a contract with the general electric company for “motor generators, exciters, switchboards, etc., being the complete apparatus to furnish direct current at the proper voltage to the cells, for the sum of $45,308:00.” niagara ammonia director a. e. bonn, previously at american cyanamid, reported that the electrolabs cells at the fnrl “had been entirely satisfactory.” (bonn, through bonn & company, was an investor in the american casale enterprises.) also, it was reported that the two-month old casale ammonia plant in japan was so successful that an order had been placed for two additional converters, each with a rated daily capacity of 7 ½ tons of ammonia. hydroelectricity from the niagara lockport & ontario power co. (which was independent of electric bond & share) drove all machinery at niagara ammonia, including compressors and circulation pumps, and provided power for the electrolysers. niagara lockport also supplied electricity to the syracuse factory of solvay process. the source of nitrogen for the ammonia process was based on another of luigi casale’s inventions, the removal of atmospheric oxygen from air by its reaction with hydrogen, the so-called burning of air.32 table 2. ammonia casale sa investments in the united states, 1923-1927. holding corporation affiliate place and year of foundation date of transfer of stock to du pont fate the ammonia corporation new york, 1923 may-june 1927 bankrupt, february 1928 niagara ammonia co., inc. new york, 1923 may-june 1927 bankrupt, february 1928 chemical investment corporation 1923 1927 hydro-electric chemical company maine, 1923 october 1927 (to lazote december 1927) notes: the ammonia corporation: in 1923, ammonia casale sa held 2,000 shares of preferred stock, and 3,050 shares of common stock, in the ammonia corporation. niagara ammonia co., inc.: the second largest stockholder was frank l. smiley, nominee for electric bond & share company, whose holdings were transferred to du pont in may 1927. hydro-electric chemical company: the authorised capital was $750,000, with 20,000 shares non par. ammonia casale sa held 2,125 of preferred stock, and 7,840 of common stock. the chemical investment corporation, the holding company for hydro-electric chemical, held 5,000 preferred stock, out of a total of 7,500 (later increased to 9,000), and 10,191 common stock. a major stockholder in the hydroelectric chemical company was bonn & co., whose holdings were transferred to lazote in 1929. 65first steps: synthetic ammonia in the united states to protect the considerable investment in highpressure chemistry, that would soon reach well over half a million dollars, the board of niagara ammonia discussed acquisition of a license for a german synthetic ammonia process from the chemical foundation, inc., which held sequestered german patents on a number of nitrogen processes as well as on synthetic organic chemicals.33 this would be of value to niagara ammonia should the casale patents in the united states come under threat through litigation arising from patent disputes. the precaution was justified. this was still the start-up period, based on a relatively new industrial technology, with unknown risks, at least in the united states: “it was the consensus of opinion that approval to the taking out of that license [from the chemical foundation] should be be given only as a measure of defense, since the casale patents under which this company would operate, have not as yet been the subject of judicial determination and there are certain claims which might give rise to litigation and the consequent expense and loss... approval was deemed wise as a matter of business precaution.” the drawing up of a contract with the chemical foundation was “unanimously approved.”34 in december 1923, frederick pope, in his role as president of niagara ammonia, reported that progress in construction work at the niagara falls site was satisfactory. the first consignment of machinery had arrived from italy. bonn advised that there might be some delay in receiving a second seaborne shipment of machinery from italy, and that there “is a substantial amount of machinery on the third boat.”35 the machinery included casale converters, probably manufactured at the terni steelworks. an alternative source was the italian works of armstrong sa, a subsidiary of the british engineering firm armstrong whitworth, at pozzuoli, in southern italy, that manufactured casale converters for installation at the nera montoro synthetic ammonia factory, located near terni.36 also from italy were the special high-pressure compressors, manufactured by the firm of pignone, of florence, and circulation pumps. in 1922, pignone introduced the first commercial multistage compressor suited to the synthesis of ammonia under casale’s operating conditions. during may 1924, niagara ammonia first received by-product hydrogen from hooker.37 though niagara ammonia intended to generate its own supply of hydrogen from the in-house electrolysers, the availability of hydrogen from hooker was a useful reserve supply. on july 30, pope reported that this was the first occasion when he could report actual production, “the plant having operated off and on during the month of july, making about 72,000 pounds of ammonia, which at 15ȼ a pound, amounts to $10,800.” the monthly bill for hydrogen was approximately $5,000. the payroll was about $4,000, and cost of supplies $600. pope believed that “the plant profit, excluding overhead and sales expenses, could be about $1,000.”38 however, niagara ammonia was forced to delay sale of its anhydrous ammonia until quality issues had been dealt with. pope drew attention to the fact that for use as refrigerant the anhydrous ammonia was unacceptable to an important potential customer, and distributor, armour & company, “as it contained more than the allowable percentage of water and foreign gases.” this difficulty could be overcome by the installation of a distilling apparatus, costing between ten and fifteen thousand dollars. the decision to install suitable distillation equipment was based on a report from d. t. kiley of armour & company, whose chief chemist, j. r. powell, visited the niagara ammonia factory. kiley’s report revealed the difficulties involved in producing ammonia for the refrigeration market, and not just at niagara ammonia. our chief chemist, mr powell, has returned from niagara falls and i am enclosing to you a copy of his report. you will see that it is going to be necessary for you to put in another still. the syracuse people [allied chemical/ solvay process] had the same trouble and their ammonia was condemned by the trade until after they had installed an extra still to put out an anhydrous ammonia that was equal to that made by other manufacturers. i know that you will go into this at once, as you personally know that should we send out any ammonia that was not fully equal to that made at syracuse, the niagara ammonia would get a ‘black eye’ that would take a long while to get over and our competitors would take advantage of it. you may rest assured that the first ammonia we put out will be watched closely and they will all be buying cylinders and testing the ammonia and if it isn’t ‘up to snuff ’, you can bet the consumers are going to know about it through them. powell found contamination of the anhydrous product with moisture and foreign gas that was three or four times greater than required of an ammonia suited to the exacting requirements of the refrigeration market. an italian representative of ammonia casale had been on hand during powell’s visit and “seemed thoroughly convinced that the source of the water was the accidental introduction of small amounts of oxygen with the gases before they entered the system.”39 colonel pope observed that henry pierce, as a member of the niagara ammonia board, “has been of great service to the company while abroad, in urging dr. casale to come to the united states the middle 66 anthony s. travis of august, and in following the delivery of the italian machinery for the third unit of our plant.” if the three units were identical, this indicates, on the basis of published reports of rated capacities, that each one was of around 7-tpd capacity. on the same occasion, funds were approved for completion and “tuning up” of the first unit.40 not long after, luigi casale visited the united states to deal with his business interests there. according to casale’s professor, arturo miolati, casale attended an event with fritz haber in new york, which must have been around the time of the benjamin franklin centenary celebrations, held in philadelphia during september 17-19, where haber was a speaker.41 changes and challenges at niagara ammonia the departure of fredrick pope on 14 november 1924, colonel frederick pope tendered his resignation, as president, of niagara ammonia, and apparently of other casale interests, and was replaced by henry pierce. on the same occasion, anticipating substantial investment in scaling up, or at least in making improvements, it was resolved that the “president be authorized to borrow from the ammonia corporation the sum of $150,000, in such amounts as might be required, upon this company’s notes, at the rate of 6% per annum.”42 by early 1925, willard hooker had been appointed a vice president of niagara ammonia.43 pope perhaps foresaw difficulties, including the great expense of generating hydrogen from electrolysers at the niagara falls operation.44 that may have suited europe and japan, where strong political and strategic commitments and local and state support were significant factors in the adoption of hydroelectric power. in the united states, electricity, though widely available, was expensive. very few additional electrolysers were installed at niagara ammonia. the actual output of synthetic ammonia never exceeded 8-tpd, which was considerably less than the combined rated capacities of the converters. lured away by new challenges, pope’s experience at niagara falls, and of the new synthetic ammonia technology of luigi casale, was timely and put to good use. pope became involved in the nitrogen engineering corporation (nec), founded in 1926, which offered an ammonia converter based on a process that was far better adapted to large scale production than the so-called “american” process of the fnrl. the co-inventors of the nec process, louis c. jones and major charles o. brown, had previously been employed by allied chemical. pope also became associated with the chemical construction company (chemico), an engineering firm based in charlotte, north carolina, that in 1929 acquired nec, and held patents on novel catalytic processes, including the selden vanadium catalyst for sulphuric acid, and that had developed a process for oxidation of ammonia to give nitric acid. in 1930, chemico was acquired by the american cyanamid company. cyanamid’s chemical construction corporation (still referred to as chemico), offered design and construction services for high-pressure plant, and other equipment. around 1930, pope was involved in introduction of the nec process in the soviet union, perhaps after convincing the russians that it was better suited to their conditions than the casale process (which was introduced at one site in russia in 1928). in june 1932, at a time when the soviet union was anxious to gain diplomatic recognition from the united states, the russians managed to gain his assistance.45 however, pope’s relationship with the russians was not smooth. he ceased dealing with them in 1934.46 later, he was closely associated with attempts to introduce american cyanamid’s (chemico) chemical technologies in china, mexico, egypt, and elsewhere. the hydro-electric chemical company and the liljenroth process, and royalties on ammonia in 1924, an interest in production of mixed nitrogen-phosphorus fertilizers, and at the same time a new source of hydrogen, led hydro-electric to back the electrothermal phosphoric acid-hydrogen method of frans georg liljenroth, of stockholm, sweden. phosphorus, produced by reduction of phosphate rock in an electrically heated furnace, was reacted with steam to afford phosphoric acid and hydrogen. the phosphorus-hydrogen company had been established in new york to promote the process in the united states, and during 1925 began experimental work at the niagara ammonia factory. chemist thomas edward warren, who worked at niagara falls on the swedish process in 1925, recalled that the intention was to move away from ammonia for use in refrigeration towards synthetic fertilizers, in particular ammonium phosphate, and phosphoric acid, as well as generating hydrogen from the liljenroth process for use in the ammonia process.47 however, the liljenroth process was not taken up in practice. hydro-electric, like niagara ammonia, also promoted the casale process. one item in its correspondence file is of interest for revealing the royalty rates, and also the difficulty in finding licensees. during 1925, the royalty on the casale process was fixed at 5 dollars per 67first steps: synthetic ammonia in the united states ton. on 9 december 1925, the board of hydro-electric discussed a reduced royalty, to be “granted by this company at any time within two years from and after the date of this meeting, the royalty rate to be fixed ... at not less than 0.4ȼ per pound of nh3.” board member charles hardy voted against this proposal because he considered that it was not good for business to reduce the royalty rate from 5 dollars per ton until the latter “had been refused by some of the prospective licensees” (of which there were few, if any).48 the discussion on royalty rates had been stimulated by the abrupt 50 per cent fall in the price of anhydrous ammonia late in 1925. the price of aqua ammonia also fell, though less sharply. this encouraged widespread oxidation of ammonia into nitric acid, and the use of the acid in manufacture of sulphuric acid, in particular using processes developed by du pont and chemico.49 however, this hardly helped niagara ammonia and other companies that relied on sales of synthetic ammonia for the industrial refrigeration market. they had a hard time matching the price of ammonia from the other sources.50 by 1926, the ammonia suppply industry in general was suffering from severe competition and a glut. the niagara ammonia company, operating at less than half capacity, faced an uncertain future, and not just as a result of an increasingly difficult trading environment. in march 1926, at a meeting of the directors of niagara ammonia, it was revealed that the company was in debt to the tune of $600,000, for one loan, and $25,000, for a second loan, to the ammonia corporation. the repayment dates for both loans were extended from april 1st to may 20th.51 on may 17th, the redemption date was extended until july 20th.52 these and other heavy debts owed to the ammonia corporation would remain on the books. this state of affairs arose from the precariousness of niagara ammonia’s situation in 1926. it was facing heavy losses, apart from those arising out of substantial cuts in the price of anhydrous ammonia. for various reasons, the daily output target could not be met. though there were plans to enter into the nitrogen fertilizer business at niagara ammonia, the facility was too small to compete with the major producers of nitrogen products for agriculture. as with the operators of fnrl units, the scale of working with electrolytic hydrogen was both limiting and expensive. by 1926, the main investors had sunk well over half a million dollars into the venture and had seen no return. debts were mounting up, and, with the reduced price of ammonia, a turn to profitability did not seem likely. investors must have been wary of injecting additional funds into an enterprise that was confronting several challenges, including from a new, and powerful, player in the industry. du pont ammonia du pont’s interest in synthetic ammonia was revived early in 1923, following somewhat exaggerated claims concerning the claude process made by a representative of air liquide to du pont’s norwegian born and german trained fin sparre, director of the development department, and head of much of the corporation’s diversification programme. sparre had previously been against embarking on manufacture of synthetic ammonia, though he expressed a strong interest in oxidation of ammonia to nitric acid. what impressed him now was the high yield achieved at pressures far greater than used in the process of allied chemical, possibly sufficient to make the latter obsolete, and the potential of catalyzed high-pressure technology.53 samuel k. varnes of du pont, writing in 1947, observed that when in october 1923 a du pont commission travelled to monterau, france, to investigate claude’s pilot plant they were somewhat disappointed.54 claude advised du pont that his process was not yet fully developed. the first steel converters were incapable of withstanding the severe operating conditions. by 1924, major improvements had been made, with the introduction of special alloys for the converters. as a result, in the summer of 1924, du pont acquired exclusive us rights to the claude process from air liquide.55 to formulate a nationwide marketing programme, du pont also acquired national ammonia, the major us distributor of ammonia for refrigeration purposes. du pont now prepared to repeat its success with organic chemicals in the area of nitrogen products. du pont’s stated original intention was to enter the market for ammonia as refrigerant, distributed through national ammonia, and later move into oxidation of ammonia, to nitric acid, and production of nitrogen fertilizers. national ammonia would thereby begin to play a new role in the nitrogen distribution business. on 21 may 1925, jointly with air liquide, du pont incorporated in west virginia the firm lazote, inc. air liquide provided 25 per cent of the capital in this partnership. fin sparre was appointed president of lazote. construction work began on an ammonia factory at belle, east kanawha county. soon after, du pont announced that georges claude had on 30 june 1925 received letters patent 1544373, assigned to lazote, “covering broadly a method of conducting the synthetic operation wherein the pressure-sustaining wall is cooled by the incoming gases which are preheated by heat exchange with outgoing gases from the zone of reaction.” tellingly, “lazote, inc., is prepared to enforce its rights under this patent and prevent infringement thereof.”56 68 anthony s. travis a catalyst testing laboratory, under the supervision of chemical director roger williams, and modelled after that of the fnrl, was installed at du pont’s wilmington experimental station. alfred larson, as noted previously at the fnrl, conducted further investigations at wilmington. the belle facility, where hydrogen was produced from water gas, and nitrogen from producer gas (blow-run gas, or blow gas), both made from coke, opened on 1 april 1926. du pont announced that it was represented by its distributor, the national ammonia company.57 the claude process did not come up to expectations.58 there were problems with the high-pressure, or hyper-, compressors (“hypers”), water gas and gas purification equipment, liquefaction plant, and converters.59 the rated capacity, of 20-tpd, was difficult to achieve. aware of the difficulties, and dangers, including explosions and casualties, du pont began to take an interest in the casale process, no doubt in part because, having invested in hypercompressors, it wished to continue working with pressures way beyond those used in other synthetic ammonia processes (all of which du pont intended to outperform). apart from these considerations, casale’s process was still the only independent, well-tried process suited to large scale production available for licensing in the united states in 1926 (the german mont cenis and the nitrogen engineering corporation processes were new, and the italian fauser process was in the hands of montecatini, which had only just started to consider licensing arrangements). while access to casale’s process could have been obtained through a licensing agreement with the ammonia corporation, du pont chose another way, acquisition of the casale ammonia patents in the united states. challenging the casale patents the way to capture the superior casale technology was to engage in litigation based on a patent suit, in which it would be argued that the casale patents infringed certain of claude ammonia patents. this would bring about the downfall of existing interests in the casale process in the united states and open the way for du pont’s acquisition of casale technology. in 1926, lazote commenced proceedings against the ammonia corporation and niagara ammonia, in buffalo, new york state, for patent infringement. because the claims in the united states for both processes were construed as broad, the wording of certain of the casale patents were open to attack. this mainly concerned the very high pressure, considerably greater than that of the haberbosch process, which was a feature common to both the casale and claude processes. du pont, through lazote, pushed for an injunction against niagara ammonia’s operations, in addition to claiming damages.60 niagara ammonia, totally reliant on casale technology, prepared to be tested in litigation. the company, facing difficulties, financial as well as operational, and unable to achieve its intended output of ammonia, was a weak contestant. though no account of the proceedings appear to have survived, it is apparent that the indictment offensive engineered by du pont’s high powered patent lawyers was sufficient to topple the defence. matters were brought to a head during the last week of may 1927. the outcome was an out of court settlement, at a closed-door meeting, in the favour of du pont.61 in view of the parlous state of affairs at niagara ammonia, what du pont offered may even have appealed to some of those associated with the casale enterprises. the arrangement enabled du pont to aquire all rights to the casale patents in the united states. du pont, by injection of capital, also took over control of niagara ammonia, the ammonia corporation, and electro-chemical. a du pont press release from the publicity bureau revealed only the acquisition of patent rights from the ammonia corporation.62 a boardroom reshuffle at niagara ammonia took place on 27 may 1927, at a meeting held in new york, followed on the same day by decisions on certain manufacturing operations at niagara falls. pierce, the president, and the other niagara ammonia directors resigned. du pont senior people were installed in their places, with f. s. macgregor as president, and w. s. gregg as vice president.63 as for the ammonia corporation, pierce and his co-directors were summarily ousted, and replaced by du pont men, with macgregor as president.64 the changes were soon known in the trade. in may 1927, herbert humphrey of britain’s ici ammonia facility at billingham was on a fact finding mission in the united states, and was informed of the fate of ammonia casale interests.65 by 6 june 1927, the day the transfer of patent rights was announced in the oil, drug and paint reporter, du pont was in possession of all stock in niagara ammonia.66 this included electric bond & share’s former substantial interest, as held in the name of frank smiley. arrangements began for the transfer of ammonia casale stock in hydro-electric to du pont.67 macgregor, niagara ammonia’s new president, replaced pierce as president of hydro-electric. on the occasion of the may 27 shakeout, macgregor recommended sale of the electrolytic plant, including the electrolabs cells. latterly (and perhaps for some time) the plant had relied on hydrogen purchased from hook69first steps: synthetic ammonia in the united states er.68 (the electrolabs cells remained in place, unused, until moved to seattle in 1928; see later.) undoubtedly, the high cost of hydrogen was a major contributor to the losses at niagara ammonia. the niagara ammonia factory ceased operating in july 1927.69 du pont made further share transfers and continued to reshuffle the boards. on 3 october 1927, ammonia casale’s stock of 2,125 shares in hydro-electric were transferred to du pont, and, in turn, on 22 december 1927 they were transferred from du pont to lazote (table 3). du pont people elected to the board of hydroelectric were jasper e. crane (member of the executive committee responsible for international affairs, and vice president of du pont from 1929), and engineer frederick a. wardenburg.70 on 30 december 1927, du pont transferred its stockholdings in the hydro-electric chemical company, the phosphorus-hydrogen company, and the chemical investment corporation, to lazote. crane was appointed chairman of the board of directors of lazote inc., and wardenburg, until then vice president, was appointed president, replacing fin sparre. on 26 january 1928, at a meeting held in the du pont building, wilmington, presided over by macgregor, the voluntary petition in bankruptcy of the niagara ammonia company was sanctioned.71 on the same day, the directors of the ammonia corporation met at its offices in new york. of the seven directors present, six agreed that because the corporation was unable to pay its debts (as a result of the failure of niagara ammonia) it was necessary to declare the corporation bankrupt.72 macgregor, as president of both niagara ammonia and the ammonia corporation, filed voluntary petitions in bankruptcy. the new york times reported that the liabilities of niagara ammonia were $947,748, and assets $107,899. the principal creditor was the ammonia corporation, with liabilities of $839,249, and assets of $498,467. the corporation was indebted to lazote for the sum of $821,714. the principal listed assets of the corporation were rights to “foreign” patents, namely those relating to the casale synthetic ammonia process, valued at $350,000 (this sum probably included the phosphorus-hydrogen company’s patents). these valuable patents were now in the hands of lazote. plant, stock and fixtures of niagara ammonia were valued at $97,579, which in the newspaper report were assigned to the ammonia corporation, as creditor.73 it had been an expensive business all round, but now, at least, lazote was firmly in control of the casale ammonia process, and the useful italian-made high-pressure converters and equipment of niagara ammonia. the ammonia corporation and niagara ammonia, together ammonia casale’s sole overseas venture, were laid to rest. du pont immediately introduced the casale ammonia process at the belle lazote facility. as a first step, the converters and machinery from the defunct niagara ammonia factory were shipped to belle. over the winter table 3. holdings in common stock, hydro-electric chemical company, probably late 1927. bonn & co., inc. 980 (assigned 1923) jasper e. crane 1 luigi casale 1 (deceased february 1927) chemical investment corporation, wilmington, 10,191 (assigned 1923) lazote, inc., 7,840 (originally assigned to ammonia casale, 1923) charles j. hardy 490 (assigned 1923) ernest iselin 1 g. a. henrie 1 josiah t. newcomb 50 (assigned 1923) henry j. pierce 200 + 200 (assigned 1923) walter u. reisinger 1 samuel k. varnes 1 david barker rushmore 40 (assigned 1923) roger williams 1 m. l. farrell 1 f. a. wardenburg 1 total 20,000 source: undated typewritten list, “stockholders – hydro-electric chemical company.” added, in hand, holders of preferred stock were listed as bonn & co. (250 shares), lazote, inc. (2,125 shares, from ammonia casale sa, also referred to as casale ammonia co.), chemical investment corporation (5,000), and charles j. hardy (120). hydro-electric chemical co., stock certificate book, 1923-28. records of e. i. du pont de nemours & co. absorbed companies. hagley museum and library, wilmington, delaware, accession 500, box 848. the authorised capital of hydro-electric was $750,000, with 20,000 shares non par. casale ammonia co. (ammonia casale sa) in 1923 held 2,125 preferred, and 7,840 common stock in hydroelectric. the 2,125 preferred shares were transferred to du pont on 3 october 1927, and then to lazote on 22 december 1927. the chemical investment corporation, the holding company for hydro-electric, held 5,000 preferred stock, out of a total of 7,500 (later increased to 9,000), and 10,191 common stock. the bonn & co. holdings were transferred to lazote on 28 february 1929. apart from ammonia casale, chemical investment corporation, and bonn & co., early investors were charles j. hardy, henry j. pierce, and david b. rushmore. hydro-electric directors in 1924: henry j. pierce (president), clement r. ford, a. e. bonn, rené leprestre, ernest iselin, charles j. hardy, george s. baker (resigned september 1925; m. l. farrell became director in his place), george h. howard, frank mccommon. hydro-electric directors in may 1925: henry j. pierce (president), clement r. ford, r. l. farrell, ernest iselin, j. w. mooney, luigi casale, george h. howard, frank mccommon, frank e. southard. southard, of augusta, maine, was a lawyer representing utility interests, probably including electric bond & share. hydroelectric chemical co. directors & stockholders minutes, 1924-26. records of e. i. du pont de nemours & co. absorbed companies. hagley museum and library, wilmington, delaware, accession 500, box 847. 70 anthony s. travis of 1927-1928, du pont authorised three-fold expansion in output of synthetic ammonia, based on the introduction of the casale process. new casale-type converters were ordered for installation in a designated building.74 by this time, casale converters of 20-ton daily rated capacity were in general use. hydro-electric was retained as a du pont subsidiary, probably in the hope that the phosphorus-hydrogen process, or other electrochemical processes might become viable. lazote’s arrangements with casale interests presumably included access to a new feature, the ejector, a static piece of equipment which did away with the need for a gas circulation pump, as developed by luigi casale at terni. this was an important consideration since reciprocating pumps and compressors working under the high pressure conditions required frequent attention, and there were always concerns over contamination of gas mixtures with lubricating oils. diversification at belle the success with ammonia encouraged roger williams to develop a high-pressure methanol process, using the same converters as employed in the ammonia synthesis. methanol production was expanded greatly from around 1928. it was used in the production of formaldehyde (for bakelite), antifreeze, and other large volume products. significantly, by 1928 american inventors had developed four of the eight synthetic ammonia processes in use (general chemical/allied chemical, du pont, fnrl, and nec). however, it was du pont’s entry into high-pressure chemistry that stimulated the development of more general high-pressure chemical production. technology transfer from europe to du pont in the area of ammonia production included a contribution from britain’s ici. at the end of the 1920s, ici and du pont drew up an agreement for exchange of knowhow. ici (into which brunner, mond had been merged in 1926) had an interest in allied chemical, through solvay process, and the agreement was strongly opposed by orlando weber. in november 1928, ici severed its ties with allied chemical. soon after, du pont representatives inspected the ici billingham ammonia factory. while much was learned, it was perhaps not readily applicable to the high-pressure processes at belle. probably of great interest were the water gas process for manufacture of hydrogen, which closely followed german technology, as copied from basf, oxidation of ammonia to nitric acid, control instruments, and perhaps ici’s then early work on steam reforming of hydrocarbons for manufacture of hydrogen. in 1929, following the increased reliance on casale technology, du pont bought out air liquide’s holdings in lazote, a strategy that was adopted in other cases of joint ventures with european companies.75 du pont’s ammonia interests became the du pont ammonia corporation. by september 1929, expansion at belle brought the rated daily capacity of ammonia to over 220 tons. in around 1930, the daily capacity at belle was 100 tpd of ammonia by the casale process, and 125-tpd by the claude process.76 reminiscences of managers and staff at belle show that for a few years the claude and casale processes were confined to separate production areas; and the main early increase in production was due to the introduction of casale technology.77 the du pont synthetic ammonia process, through innovations adopted from the casale process, had become the modified process of du pont.78 contemporary accounts, including by du pont personnel, speak of the excellence of du pont’s ammonia process. the process, it was noted, “has decidedly new and advantageous features and represents a radical departure from the original claude process.”79 jasper crane, writing in 1933, stated that the “best features” of the french and italian processes “were adapted to … american conditions.”80 one author even referred to the “modified casale process operated by du pont.”81 in 1931, the assets of the du pont ammonia corporation were transferred to the new ammonia department, with wardenburg as general manager. national ammonia remained a separate du pont company, working closely with the ammonia department.82 further expansion at belle during the early 1930s brought the annual rated capacity of synthetic ammonia to around 145,000 tons. ammonia was converted into ammonium sulphate fertilizer, nitric acid, and other industrial products. a sales development division investigated new uses for the ammonia. the location of the belle facility, in the lower kanawha valley, well inland, and protected, was used to emphasise the strategic value of the site for purposes of producing nitrogen products important to the national defence. contrary to the early expectations at du pont, its very high-pressure process did not make the allied chemical (general chemical) and similar processes carried out below 300 atmospheres obsolete. by the mid-1930s, allied chemical was responsible for 60%, and du pont for 40%, of synthetic ammonia produced in the united states. they collaborated in control of the fertilizer market, partly through allied chemical’s barrett division, as distributor of ammonium sulphate. one important outcome of the availability of inexpensive synthetic ammonia was that during the 1930s 71first steps: synthetic ammonia in the united states it almost completely replaced chilean nitrate as the source of the world supply of nitric acid. anhydrous ammonia, from all sources, continued to be largely used as a refrigerant, though consumption relative to synthetic ammonia for fertilizer use was not great. national ammonia remained du pont’s distributor of anhydrous ammonia. du pont innovations the wilmington-based du pont was, for long periods of its history in the 20th century, the most innovative chemical company in north america. during and after world war i it became one of the leaders in aromatic organic chemistry, enabling massive expansion during the 1920s in the manufacture of synthetic dyestuffs and modern explosives. in dyes and other sectors du pont relied on its capabilities as a prolific dealmaker, particularly for access to new technologies. this is reflected in the long list of strategic acquisitions made by the corporation as held at the hagley museum and library. how, and under what circumstances, those acquisitions were made, and for what reasons, varied according to the perceived needs of the corporation. in the case of ammonia, as this article has demonstrated, it was the failure of the expensive claude technology, but the commitment to high-pressure chemistry, that was the stimulus for acquisition of the casale technology that operated over a similar pressure range. niagara ammonia, the ammonia corporation, and the hydroelectric chemical company, are just three entries in the portfolio that direct historians to folders on absorbed companies. these casale enterprises contributed to the great success with catalytic high-pressure chemistry achieved by 1930. the lessons taken from this small but highly instructive episode relate to the balance of power between weak firms or start-ups with a useful technology and large corporations desperate to gain access to that technology. by delving deeply into the archival records, much about how and why has been revealed, directly and indirectly, concerning du pont’s motives and actions for entering into a new area of the nitrogen industry. above all, the fine detail of these acquisitions reveals far more than the overlapping stories of one struggling start-up and the initial failure of a major corporation when embarking on a completely new area of diversification. it concerns what was genuinely an important, and eventually highly successful, phase in du pont’s interwar entry into a new sector of heavy chemical industry. this provided a novel context for innovation, and, i argue, probably the key to one of the most profound transformations at du pont, ensuring that the corporation remained relevant in commercialization of new discoveries for decades to come. though synthetic ammonia was certainly low in the list of du pont innovations, and at first hardly met the criteria for investment, it had a tremendous impact on the long term standing of a technology giant. early on, research and development for new products based on high-pressure processes enabled du pont to alleviate the difficulties confronted by the loss-making ammonia department.83 this helped to propel the corporation to first place as the leading innovative chemical firm in the united states, drawing on catalytic high-pressure technologies for industrial production of a proliferation of new of products, notably nylon, followed by other polymers, and later even broader diversification.84 from 1930, there was also, from a different direction, the first chlorofluorocarbon (cfc) cooling refrigerant, freon, commercialized by du pont, following research at general electric. it was adopted for air conditioning, and later household refrigeration; in several uses it replaced sulphur dioxide and ammonia.85 du pont’s expertise in ammonia technology, drawing on its acquisition of the casale process, contributed to american preparedness for war after the government decided to construct ammonia factories for munitions production. du pont built the first government-owned contractor-operated facility, completed in 1941, at the morgantown ordnance works, monongalia county, west virginia, with a capacity of 180,000 tons of nitrogen per year. du pont, pacific nitrogen, and roessler & hasslacher co. for sake of completeness, it is worth including a brief account of du pont’s two other acquisitions in early synthetic ammonia businesses, one on the west coast and the other on the east coast. the west coast venture, which we have already met, was the pacific nitrogen corporation, of pacific ammonia, the affilitate of national ammonia, in seattle, washington. pacific nitrogen, was incorporated in 1924. its entire stock was acquired by du pont in 1927. pacific nitrogen used the fnrl process to produce both anhydrous ammonia and ammonia liquor. in may and june 1928, the seattle plant produced 2.98 tons of ammonia every 24-hour hours, in accord with the daily capacity of its single fnrl unit.86 in april 1928, pacific nitrogen was authorised to receive the electrolytic cells of niagara ammonia: “app[ropriation]n $35,000.00 – purchase and installation of 170 electrolytic cells owned 72 anthony s. travis by lazote, inc., and at present at the plant of the niagara ammonia company, niagara falls, new york” (capitals in the original).87 their installation in seattle was completed in july 1928. caustic potash for charging the cells was due to arrive on july 22nd, “and it is anticipated that the cell installation will be ready for trial operation the latter part of august.” on 31 december 1930, the du pont ammonia corporation, as owner of the stock of pacific nitrogen, arranged to take over its assets and property.88 the pacific nitrogen factory, the last in the united states to use dedicated electrolysis cells for hydrogen in manufacture of ammonia, was closed down in the early 1930s.89 the east coast synthetic ammonia business was that of roessler & hasslacher co., of niagara falls, where production based on a modified fnrl process, also at a rated capacity of 3-tpd, began in 1926. for synthetic ammonia, it relied on in-house by-product hydrogen from electrolytic manufacture of sodium, and, from 1928, by-product hydrogen piped to the factory from hooker electrochemical.90 in 1928 the ammonia capacity of the facility was raised to nine tons daily. uses included in the manufacture of sodium cyanide, as well as for general sale. in 1930, du pont acquired roessler & hasslacher co.; in 1932 it became the r&h division of du pont (and later the electrochemicals division). conclusion late in 1927, the leading american journal of industrial chemistry, industrial and engineering chemistry, reported that “a belated start in the fixation of atmospheric nitrogen seems to have been overcome by the development of our own processes—so satisfactory as to more than hold their own in world competition.”91 the turning point in the establishment of a competitive american synthetic ammonia industry would be achieved from late 1928. until then, production in the united states was on a small scale, and mainly for the refrigeration market. this, however, demanded purer ammonia than was at first available, as we have seen at allied chemical and niagara ammonia. significantly, allied chemical’s syracuse facility, the first to operate with any degree of success, served mainly as an experimental facility. the same was true elsewhere, including at du pont, even if not intended. du pont, suffering from problems with the claude process, had to look elsewhere. during 1926-1927, du pont resorted to patent litigation against a weaker rival, the group of financially troubled casale-related firms, to gain access to the latter’s process patents. du pont, after having acquired its intended trophy, as well as casale equipment, quickly dismembered and bankrupted niagara ammonia and the ammonia corporation, and embarked on nitrogen fertilizer and nitric acid production, both starting with synthetic ammonia. from late 1928, five years after success in europe and japan, and partly through changing economic conditions, the us synthetic ammonia industry began to stand its ground in production for the fertilizer market. du pont and allied chemical were the main producers; their competitive advantages arose from the large scales of production. however, not long before the wall street crash the exuberance of the late 1920s was already being tested by the threat of global overproduction and overinvestment in nitrogen fertilizers. during 1929-1932, cutbacks were substantial. however, when recovery and renewed diversification began, there was an atmosphere of free and uninhibited innovation and extraordinary growth in the american chemical industry, especially at du pont. synthetic nitrogen fertilizers and catalytic high-pressure processes, including for methanol, higher alcohols, and the spinoffs from research into synthetic gasoline, were at the forefront, stimulated by the examples of rivals in europe. the new triumph of american high-pressure chemistry enabled innovations that became bargaining tools in dealing with foreign manufacturers. the export of du pont and nec ammonia technologies and know how brought in considerable revenue. a decade on, in the mid-1940s, the us synthetic ammonia industry, following massive expansion for munitions purposes during world war ii, had become a world leader, and was still growing. within the larger context of the growth and expansion of the american chemical industry, the ammonia sector represented one of the main areas in which diversification relied on the adoption of european technologies and acquisition of firms that offered novel product lines.92 in this, du pont moved from the manufacture of dyes and intermediates, through inhouse research, and then into high pressures and synthetic nitrogen and related products. however, the delayed entry into the latter was in part due to the already high investment in imported nitrates that were necessary for production of nitric acid used in synthetic dye and explosives production. once success had been achieved in synthetic ammonia at du pont, following acquisition of niagara ammonia, and the casale patents, the conversion of ammonia by oxidation into nitric acid was a logical next step, as was invention of a synthetic methanol process, and conversion of ammonia into urea. this was the prelude to du pont’s rise to first place among innovative american firms, particularly in the mid-1930s, with manufacture of 73first steps: synthetic ammonia in the united states nylon, which relied on synthetic ammonia. allied chemical may have been less innovative, but, significantly, sacrificed synthetic organic chemistry in order to enhance its role in ammonia production, with, from the late 1920s, an emphasis on nitrogen fertilizer production. in nitrogen products, there were strong parallels elsewhere, most particularly at the american cyanamid company which during world war i had converted its calcium cyanamide, based on a german process, and originally produced as a fertilizer, into ammonia for the manufacture of explosives, and of urea for du pont. the ammonia was oxidised in german-made plant, imported just before the war. american cyanamid, however, moved into synthetic dyes later than du pont, with the acquisition in 1927 of the calco chemical company, itself a merger of firms engaged in dyes and pigments.93 in 1930, american cyanamid entered into synthetic ammonia and methanol through acquisition of the chemical construction company (chemico) that had acquired the nitrogen engineering corporation and its synthetic ammonia process. chemico’s synthetic ammonia process, like that of du pont, was soon after licensed to several european firms. from the 1930s, transatlantic technology transfer of high pressure and many other chemical processes, including for nitric acid, was just as likely to be from america to europe (and elsewhere) as it was from europe to america. acknowledgements the two reviewers are thanked for their extremely constructive criticisms. special thanks to the staff at hagley museum and library, wilmington, delaware; the othmer library, science history institute, philadelphia, pennsylvania; and the sidney m. edelstein library, the national library of israel, jerusalem, israel. references and notes 1. k. steen, the american synthetic organic chemicals industry: war and politics, 1910-1930. the university of north carolina press, chapel hill, 2014. 2. d. a. hounshell, j. k. smith jr, science and corporate strategy. du pont r and d, 1902-1980. cambridge university press, cambridge, 1988, pp. 183-189. 3. a. s. travis, nitrogen capture: the growth of an international industry (1900-1940). springer, cham, 2018. 4. hounshell and smith, science and corporate strategy, pp. 183-189; p. a. ndiaye, nylon and the bomb: dupont and the march of modern america (transl. elborg forster) the johns hopkins university press, baltimore, 2007, pp. 74-81. that little had appeared on developments in the claude process is indicated in w. h. shearon, h. l. thompson, ammonia at 1000 atmospheres, chem. ind. eng., 1952, 44(2), 254-264, on 260. 5. g. bruni, luigi casale, giornale di chimica industrial ed appplicata, 1927, 9(2), 90. 6. j. b. lipman, fertilizer prospects for 1926: the use of concentrated fertilizer materials in potato fertilization, american potato journal, 1926, 3(1), 3-9, on 4. 7. o. wilson, gases in commerce and industry, ind. eng. chem., 1926, 18(12), 1273-1276, on 1276. 8. on dangers associated with early refrigeration, see j. rees, ‘i did not know… any danger was attached.’ safety consciouseness in the early ice and refrigeration industries, technology and culture, 2005, 46(3), 541-560. see also h. peavitt, refrigerator: the story of cool in the kitchen. reaktion books/science museum, london, 2017. 9. m. j. clarke, the federal government and the fixed nitrogen industry 1915-1926. phd dissertation, oregon state university, 1976. 10. following the 1921 suspension of the nitrate division, administration was transferred to the department of agriculture. in 1926, the fnrl was absorbed into the laboratories of the bureau of soils. 11. clarke, the federal government, pp. 158-160. 12. synthetic ammonia, ind. eng. chem., 1925, 17(8), 772. 13. travis, nitrogen capture, pp. 227-245, 330-334. 14. luigi casale us patent 1348428 of 12 july 1921 (burning of air; process for generating from air and hydrogen, either nitrogen and hydrogen mixtures or nitrogen; filed 7 july 1920); and 1408987 of 7 march 1922 (catalytic apparatus for the synthesis of ammonia; filed 7 october 1920). see also patents 1447123 (“self making of ammonia”), 27 february 1923; 1478549 (catalytic apparatus for the synthesis of ammonia) and 1478550, both of 25 december 1923. on 28 july 1925, casale was granted patent 1547362, for electrolysis of water (filed 19 july 1922). 15. for the electric bond & share company, see t. p. hughes, networks of power: electrification in western society, 1880-1930. johns hopkins university press, baltimore, 1983, pp. 392-401. in 1925, the electric bond & share company was absorbed into the electric bond & share securities corporation, as holding company for general electric. 16. previously, pierce had been president of the wood products company (1885-1905), before taking up an 74 anthony s. travis interest in railroads. henry j. pierce dies; utilities official, new york times, 10 august 1947, p. 10. 17. d. b. rushmore, e. a. lof, hydro-electric power stations. john wiley & sons, new york, 1923 (first edition 1917). 18. clarke, the federal government, pp. 77-107, 122123. 19. no. 77, nitrogen prod. synth amm. haber proc. catalysts. analysis of samples received from germany between february and august 1919. h. e. jones, brunner, mond & co., northwich, february-august 1919; and no. 78, nitrogen prod. synth amm. haber proc. catalysts and catalysers. examination of oppau catalysts from vanadium. h. e. jones, brunner, mond & co., northwich, may 1920. solvay process company archives, microfilm reel 2, the sidney m. edelstein library, national library of israel, jerusalem. 20. k. bertrams, the making of international alliances. in solvay: history of a multinational family firm (eds.: k. bertrams, n. coupain, e. homburg) cambridge university press, cambridge, 2013, pp. 193228, on 199-202. 21. american chemical society favors selective embargo, oil, paint and drug reporter, 12 september 1921, p. 23. 22. b. waeser, the atmospheric nitrogen industry: with special consideration of the production of ammonia and nitric acid (transl. e. fyleman) p. blakiston’s son & co., philadelphia, 1926, p. 287. this was a translation of b. waeser, die luftstickstoff-industrie mit besonderer berücksichtigung der gewinnung von ammoniak und salpetersäure. springer-verlag, berlin, 1922. e. fyleman, was chief chemist at the crowley & partners engineering consultancy in london that represented the casale ammonia process in the united kingdom. 23. w. haynes, american chemical industry: a history, vol. ii. the world war i period: 1912-1922. d. van nostrand, new york, 1945, p. 122; f. a. ernst, fixation of atmospheric nitrogen. chapman & hall, ltd., london, 1928, pp. 131-132. 24. steen, american synthetic organic chemicals, p. 254. 25. for a number of years it served “as an experimental plant to explore markets and develop technical information and operating experience” that was put to use at hopewell. williams haynes, american chemical industry: a history. vol. vi. the chemical companies. d. van nostrand, new york, 1949, p. 394. 26. r. e. welch, solvay process among state’s mightiest plants, syracuse journal, 28 july 1934, p. 8. 27. hydro-electric chemical co. and frederick pope were among holders of preferred stock in the ammonia corporation. the ammonia corporation, a preferred stock, box 66; and the ammonia corporation, directors & stockholders minutes 1926-28, box 67. records of e. i. du pont de nemours & co. absorbed companies. hagley museum and library, wilmington, delaware (hereafter: hagley), accession 500, series ii, part 1 (hereafter: ammonia corporation); and hagley, hydro-electric chemical co. stock certificates, 1923-28, accession 500, series ii, part 1, box 848 (hereafter: hydro-electric stock). see also list of stockholders, in h. j. pierce to hydro-electric chemical co., new york, 1 august 1923. hagley, hydro-electric chemical co. directors & stockholders minutes, 1924-26, accession 500, series ii, part 1, box 847 (hereafter: hydro-electric). 28. frederick pope, engineer dead. set up synthetic ammonia plants here and abroad, new york times, 13 august 1961, p. 88. 29. f. pope, condition of chemical plants in germany, ind. eng. chem., 1919, 11(6), 512. 30. t. w. sill, the dyestuff plants and their war activities, ind. eng. chem., 1919, 11(6), 509-512. 31. r. thomas, salt & water, power and people. a short history of the hooker electrochemical company. hooker electrochemical company, niagara falls, 1955, p. 47. 32. two proposals for sale of oxygen from the electrolabs cells were considered: one for sale to the international oxygen company; the other for the formation of a joint marketing company with electrolabs. 33. steen, american synthetic organic chemicals. 34. regular monthly meeting of the directors of the niagara ammonia company, 14 november 1923, niagara ammonia co., inc. directors & stockholders minutes, 1923-26. hagley, accession 500, series ii, part 1, box 1366 (hereafter: niagara ammonia). see also haynes, the world war i period, pp. 503, 504. 35. regular monthly meeting of the directors, 21 december 1923, niagara ammonia. 36. l. cerruti, la fissazione dell’azoto, ovvero l’ambiguità della scienza, 5-6. http://www.minerva.unito.it/ storia/chimicaclassica/azoto/azoto4.htm (accessed 20 december 2020) 37. haynes, chemical companies, p. 394. 38. minutes of meeting of board of directors, 30 july 1924, niagara ammonia. 39. minutes of the board of directors, 30 july 1924. with attachments: d. t. kiley, armour co., chicago, ill, to a. e. bonn, niagara ammonia, 30 july 1924; and j. r. powell to kiley, 24 july 1924, niagara ammonia. 40. minutes of the board of directors, 30 july 1924, niagara ammonia. 75first steps: synthetic ammonia in the united states 41. a. miolati, synthetic ammonia and the casale process. amplified edition of a lecture delivered the 27th february 1927 at the institute of chemistry of the polytechnic school of prague (transl. g. impallomeni, 2009) “l’universale” tipografia poliglotta/ammonia casale sa, rome, 1927, p. 34. 42. meeting of the board of directors, 14 november 1924. it was resolved, as at that date, that the offices be moved from 280 madison avenue to 65 broadway, niagara ammonia. 43. stockholders were: hooker electro-chemical co., common stock, 250; the ammonia corporation, a preferred, 3,983 1/3, common, 889 1/6; and frank l. smiley, a preferred, 1,016 2/3, common, 260 5/6. total a preferred stock 5,000; total common stock 1,400. annual stockholders meeting, 2 february 1925, niagara ammonia. 44. pope was also a broker, and later sold (what probably included his own) holdings in the ammonia corporation. note of sale of 350 preferred (at $100) and 652 2/3 common (at $25) stock from pope & company, 60 broadway, new york, to tucker, anthony & co., 120 broadway, new york, 22 september 1925, ammonia corporation, box 67. 45. frederick pope, envoy needed in russia, new york herald, 14 november 1932. 46. a. c. sutton, western technology and soviet economic development, 1930-1945. hoover institution, stanford, 1971, pp. 99-100. the american chemical engineer alcan hirsch ostensibly demonstrated more enthusiasm for the soviet system. travis, nitrogen capture, pp. 316, 322-324. 47. phosphorus-hydrogen company to hydro-electric chemical co., 21 april 1924, hydro-electric. see also, thomas edward warren, the dissociation pressures of the orthophosphates of ammonia, research paper, mcgill university, 1926. oai identifier:  oai:digitool.library.mcgill.ca:141772 (accessed 20 december 2020) 48. meeting of the board of directors, 9 december 1925, hydro-electric. 49. a. m. fairlie, sulfuric acid manufacture. reinhold publishing corporation, new york, 1936, pp. 150151. 50. why synthetic ammonia prices are lower, chemicals, 1926, 26(25), 12-13. 51. meeting of the board of directors, 2 rector street, new york, 15 march 1926, niagara ammonia. the ammonia corporation was in turn indebted to the irving bank-columbia trust company (formed, in 1923, when the columbia trust company of new york merged with the irving national bank). 52. meeting of the board of directors, 17 may 1926, niagara ammonia. 53. on fin sparre, see hounshell and smith, science and corporate strategy, pp. 35-36, 37. 54. s. k. varnes, pioneering in high pressure. in sentimental history: the du pont belle works. a 75 year history (ed.: charles j. denham) du pont, charleston, 2001, pp. 11-16, on 12 (from an account written in 1947). 55. claude’s first ammonia patent in the united states was no 1332460 of 2 march 1920. in 1921, he received a us patent for obtaining hydrogen from a gas mixture, and another for an apparatus suited to high pressure, high temperature exothermic reactions; in 1922, two patents for producing hydrogen and one for separating constituents in a gas mixture; in 1923, one patent for high pressure apparatus for production of ammonia, and one patent for a thermally insulated apparatus. three of claude’s six us patents filed in 1924 covered the use of ammonia in production of ammonium chloride and sodium carbonate, which was relevant to the solvay alkali process. 56. claude patent for a method for direct synthesis of ammonia, ind. eng. chem., 1925, 17(9), 985. claude’s us ammonia patents were assigned to lazote. 57. glancing back over 1926, the du pont magazine, 1927, 21(3), 1. 58. varnes, pioneering in high pressure, p. 14. 59. hounshell and smith, science and corporate strategy, pp. 183-189. 60. w. haynes, american chemical industry: a history, vol. iv. the merger era. d. van nostrand, new york, 1948, p. 88. meantime, national ammonia co. and armour & co. in 1926 had taken out licenses for ammonia processes from the chemical foundation. 61. haynes, the merger era, p. 88. 62. du pont obtains american rights on casale process, chem. met. eng., 1927, 34(6), 388. 63. board of directors. meeting no. 29 (special meeting), 27 may 1927, niagara ammonia. 64. following the death of luigi casale earlier in the year (on 18 february), his place was taken by gregg, as vice president. board of directors. meeting no. 38 (special meeting), 27 may 1927, ammonia corporation, box 66. 65. herbert alfred humphrey, preliminary report on visit to united states of america. 9 april to 28 may 1927. papers of herbert alfred humphrey, imperial college archives and corporate records unit, london, item m6, pp. 94-97. 66. du pont gets the u.s. rights to casale patents, oil, paint and drug reporter, 6 june 1927, p. 21. e.i. du 76 anthony s. travis pont de nemours & co. held 1,116 2/3 of a preferred stock, and 310 5/6 of common stock; the ammonia corporation held 3,883 1/3 a preferred stock, and 839 1/5 of common stock (out of a total of 5,000 a preferred stock, and 1,150 common stock). minutes of special meeting of stockholders, 6 june 1927, niagara ammonia. 67. hydro-electric chemical co., stock certificates, transfer documents, 10 june 1927. including affidavits of guiseppe albisetti, member of the council of administration, ammonia casale sa, and luigi calissano, manager of ammonia casale sa, before the consulate of the united states of america, milan, italy. hydro-electric stock. 68. ernst, fixation of atmospheric nitrogen, pp. 121-123; b. waeser, die luftstickstoff-industrie, mit berücksichtigung der chilenischen industrie und des kokereistickstoffs. springer-verlag, berlin, 1932, pp. 163-164. 69. haynes, the chemical companies, p. 213. 70. du pont, wilmington, to ernest iselin, a. iselin & company, 30 december 1927, hydro-electric. 71. du pont, wilmington, letters regarding meeting to be held on 26 january 1928 to consider voluntary petition in bankruptcy of niagara ammonia company, inc., 19 january 1928, niagara ammonia. ammonia corporation, board of directors, meeting no. 41 (special meeting), 26 january 1928; board of directors, meeting no. 42 (special meeting), 10 march 1928, ammonia corporation, box 66. 72. board of directors, meeting no. 41 (special meeting), 26 january 1928, ammonia corporation, box 66. 73. niagara ammonia bankrupt. ammonia corporation creditor, also is insolvent, new york times, 16 february 1928, p. 37. 74. denham, sentimental history, p. 144. 75. independently, air liquide eventually modified its claude process, with, in the case of the mississippi chemical corporation of yazoo city, missouri, two converters in series, and recirculation of unreacted gases. h. l. thompson, p. guillaumeron, n. c. updegraff, ammonia synthesis at 1000 atmospheres: the present-day claude process, chem. eng. prog., 1952, 48(9), 468-476. see also w. h. shearon, h. l. thompson, ammonia at 1000 atmospheres, p. 260 76. b. waeser, die luftstickstoff-industrie (1932), pp. 163164; c. stewart, a glance at 25 years. in denham, sentimental history, pp. 16-18 (from an account written in may 1950). 77. denham, sentimental history. 78. r. norris shreve, the chemical process industries. mcgraw-hill book company, new york, 1945, pp. 402-404. 79. the pressure synthesis of the du pont ammonia corp., ind. eng. chem., 1930, 22(5), 433-437, on 433. 80. jasper e. crane, of du pont, to george w. norris, senator, nebraska, 8 may 1933, in h. tongue, the design and construction of high pressure chemical plant. chapman & hall, london, 1934, pp. 377-378. 81. g. w. taylor, nitrogen production facilities in relation to present and future demand. in agronomy: a series of monographs. vol iii. fertilizer technology and resources in the united states (ed.: k. d. jakob) academic press, new york, 1953, pp. 15-61, on 43. 82. du pont ammonia corp. dissolved, chem. eng. news, 1931, 9(17), 28. 83. hounshell and smith, science and corporate strategy, pp. 186-189. 84. p. h. spitz, petrochemicals: the rise of an industry. john wiley & sons, new york, 1988, pp. 274-279. 85. s. b. mcgrayne, prometheans in the lab: chemistry and the making of the modern world. mcgraw-hill, new york, 2001, pp. 79-105, esp. 96-101. 86. sales of anhydrous ammonia were made to the distributors pacific ammonia & chemical, the main purchaser, and national ammonia co., inc.; and of liquor to hercules california, du pont washington, and fleischmann, of sumner, washington, totalling 276,633 pounds of ammonia. walter dannenbaum, vice president, to board of directors, pacific nitrogen corporation, 13 july 1928. pacific nitrogen corporation. reports of walter dannenbaum 1926-29. hagley, accession 500, box 1471. 87. pacific nitrogen corporation. board of trustees, minutes of special meeting, 24 april 1928. present: f. a. wardenburg, in the chair; jasper e. crane; walter dannenbaum, vice president; h. dannenbaum; walter u. reisinger, treasurer. pacific nitrogen corporation, minutes, 1924-31. stockholders and board of trustees. hagley, accession 500, box 1468 (hereafter pacific nitrogen). 88. pacific nitrogen corporation. board of trustees. minutes of special meeting, 31 december 1930, pacific nitrogen. 89. haynes, the merger era, p. 88. 90. ernst, fixation of atmospheric nitrogen, p. 94; haynes, the chemical companies, p. 213. 91. significant trends in nitrogen fixation, ind. eng. chem., 1927, 19(12), 1307. 92. a. d. chandler, jr., t. hikino, d. mowery, the evolution of corporate capability and corporate strategy and structure within the world’s largest chemical firms: the twentieth century in perspective. in chemicals and long-term economic growth: insights 77first steps: synthetic ammonia in the united states from the chemical industry (eds.: a. arora, r. landau, n. rosenberg) john wiley & sons, new york, 1998, pp. 415-457, 417-421. 93. a. s. travis, dyes made in america, 1915-1980. the calco chemical company, american cyanamid and the raritan river. sidney m. edelstein center/hexagon press, jerusalem, 2004. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 5(1): 91-97, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-973 citation: rasmussen s. c. (2021) new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry. substantia 5(1): 91-97. doi: 10.13128/substantia-973 received: jun 22, 2020 revised: aug 18, 2020 just accepted online: aug 23, 2020 published: mar 01, 2021 copyright: © 2021 rasmussen s. c. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry seth c. rasmussen department of chemistry and biochemistry, north dakota state university, ndsu dept. 2735, p.o. box 6050, fargo, nd 58108-6050, usa e-mail: seth.rasmussen@ndsu.edu abstract. in 2000, the nobel prize in chemistry was awarded to hideki shirakawa, alan g. macdiarmid, and alan j. heeger “for the discovery and development of electrically conductive polymers.” while this award was in reference to their collaborative efforts on conducting polyacetylene in the mid-to-late 1970s, the narrative leading up to these efforts began in 1967 with the production of polyacetylene plastic films via what has been called a “fortuitous error.” at the heart of this discovery were shirakawa and a visiting korean scientist, hyung chick pyun. the current report provides background on pyun and, for the first time, presents his version of the events leading to the discovery of polyacetylene films in order to provide new insight into this important historical event. keywords: polyacetylene, plastic films, nobel prize 2000, polymerization conditions, ziegler-natta catalysis. introduction in 2000, the nobel prize in chemistry was awarded to hideki shirakawa, alan g. macdiarmid, and alan j. heeger (figure 1) “ for the discovery and development of electrically conductive polymers,” which was in reference to collaborative efforts by these investigators on conducting poly acetylene in the mid-to-late 1970s.1-9 the narrative leading up to these collaborative efforts, however, began in 1967 with what shirakawa has referred to as a “fortuitous error,” an event that resulted in the very first production of polyacetylene in the form of plastic films.10-13 according to meriam-webster, a legend is defined as “a story coming down from the past; especially: one popularly regarded as historical although not verifiable”. the story behind the critical discovery that polyacetylene could be synthesized as lustrous, silvery films has achieved such legendary status, with it having been told and retold by many different people over the years, with the story rarely told the same way twice.10-29 what is generally agreed upon is that this discovery was made in october of 1967,10-15 approximately a year and a half after shirakawa had joined the group of sakuji ikeda (1920-1984) at the tokyo institute of technology (tokyo tech).14 according to shirakawa,10-15 another researcher under his supervision was preparing a sample of polyacetylene, but mistakenly used a http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia 92 seth c. rasmussen thousand-fold excess of catalyst. the result of this error then caused the formation of “ragged pieces of a film”14 on the surface of the catalyst solution, rather than the typical black powder normally produced within the solution.30-41 although interest in the electronic properties of polyacetylene date back to the 1958 report of giulio natta (1903-1979),32 studies prior to the discovery of polyacetylene films were limited to power samples, typically as pressed pellets. at the same time, however, there are a number of variable aspects given in the many retellings of this event, including the identity and nature of the researcher who made the critical error. while the researcher’s gender is generally viewed as male, he has been described by various sources as a “student”,16,19-21 “shirakawa’s student”,16 “foreign student”,19 “graduate student”,16,18,21 “korean graduate student”,21 “visiting korean researcher”,20 “korean visitor”,22 or “visiting scientist”.14 another variable point is the specific reason for the error itself. while most agree that it was the result of miscommunication, the nature of the miscommunication differs even within the accounts of the three nobel laurates. for example, shirakawa states14 “i might have missed the “m” for “mmol” in my experimental instructions, or the visitor might have misread it,” while macdiarmid gives a different account,19 stating “i asked him how he [shirakawa] had made this silvery film of polyacetylene and he replied that this occurred because of a misunderstanding between the japanese language and that of a foreign student”. although somewhat similar to that of macdiarmid, heeger gives still yet another version,22 stating “he [shirakawa] had a korean visitor who misunderstood what he said in japanese.” it is only in the acknowledgment of his nobel lecture that shirakawa finally reveals the name of the researcher at the center of this event to be dr. hyung chick pyun (figure 2).10-13,15 pyun was never included as a co-author on any of the papers on the synthesis of the polyacetylene films, although the initial 1971 report included an acknowledgment to “h. c. pyun”.42 other than that, very little is known about pyun and it is only recently that some biographical data has been reported.28 the goal here is to provide background on pyun and, for the first time, present his version of the events leading to the discovery of polyacetylene films in order to provide new insight into this event. hyung chick pyun hyung chick pyun (byun hyung jik; byeonhyeongjik) was born december 23, 1926 in bongsan county of hwanghae province, now within north korea.43 his family moved to seoul in 1936,44 where he was educated at kyungdong high school.43 in april of 1945, he entered the sixth high school in japan (which become part of okayama university in 1949), before returning to seoul in october 1945 to enter kyungsung university’s preparatory school.44 kyungsung university became part of seoul national university in 1946, were pyun completed a b.s. in chemical engineering in 1951.43 with the onset of the korean war (1950-1953), he began working for the science research institute of the ministry of national defense in december of 1950, while also completing his university studies.43,44 he continued there figure 1. hideki shirakawa (b. 1936), alan g. macdiarmid (1927-2007), and alan j. heeger (b. 1936) [reproduced from ref. 20 with permission of the royal society of chemistry]. 93new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry until 1960, when he moved to the newly established korea atomic energy research institute (kaeri).43 beginning in february of 1961, he spent a year at the university of kansas,43,44 where he worked with william e. mcewen (1922-2002).28 he then published his first papers in 1964,45,46 the first of which was based on his work with mcewen.45 in 1967, he received support from the international atomic energy agency (iaea) to carry out research in japan.43,47 thus, from may 1967 to the following march, he worked in tokyo on a joint project between sakuji ikeda (1920-1984)28 at tokyo tech and yoneho tabata (b. 1928) of the nuclear engineering department at the university of tokyo.44,47,48 although it has been reported that pyun had acquired his doctorate before working in ikeda’s laboratory,24 this is incorrect and he received his ph.d. in nuclear engineering from seoul national university in 1970, based on work he had published in 1964.43,49 although he expressed a desire to pursue polyacetylene research after his return from japan, he was discouraged to do so by his superiors. as such, the only publication that appears related to his time in tokyo was a 1969 report on the comparison of gamma irradiation vs. ziegler-natta catalyzed methods for the copolymerization of phenylacetylene and styrene.50 however, his work turned primarily to polymeric materials and composites after that point, which seemed to be the focus of this research for the rest of his career. pyun retired from kaeri in 199143 and died on march 8, 2018 after an extended illness.44 pyun’s account while previous efforts to obtain pyun’s version of the events had been unsuccessful,24 the collaborative approach utilized here included a native researcher with access to korean-language resources less available to western historians. thus, it was confirmed that pyun was still alive as of late 2017, although quite ill and had been in the hospital since the fall of 2016. while we were unable to talk to pyun directly, his son dr. joongmoo byun was quite helpful and provided us with a written account his father had prepared prior to his failing health. this document, roughly entitled “what is a nobel prize?” in english, was last revised in 2013 and detailed his memories and views on the discovery of polyacetylene films (see supporting information for the original korean document and a working english translation).47 a previous version of this account had also appeared in a kaeri publication in 2002.48 according to pyun, he arrived at tokyo tech in 1967 to begin work on a collaborative project between sakuji ikeda and yoneho tabata (university of tokyo), with the goal of studying the copolymerization of ethylene and tetrafluoroethylene (tfe) via the ir analysis of isotopically labeled species. the needed deuterated ethylene was to be prepared in ikeda’s laboratory, which would then be copolymerized with tfe at the university of tokyo. pyun had successfully completed the work in ikeda’s lab, but his work at the university of tokyo was postponed as tabata was visiting the united states and his return was delayed. during the month wait, pyun became interested in the polyacetylene studies carried out by others in ikeda’s lab and felt that its properties could be improved if larger polymer particles were generated.47,48 he proposed that this could be accomplished by decreasing the stir speed during polymerization and began investigating this. pyun stated that:47 one day…the stirring motor stopped during the experiment because the stirring speed had been excessively reduced. i was very embarrassed at first, but after a closer look, i found it surprisingly to see a silver film on the surface of the reaction solution. it was nothing more than a polyacetylene film... i realized that the scientists who were studying this field had not synthesized the acetylene in the film state because the polymerization reaction had proceeded with stirring. that is, if it is not stirred, it is allowed to polymerize in the film state. stirring thereby was hindering film formation. pyun stated that he repeated the film production more than 10 times and thought that ikeda would be very pleased, so he went to his office and gave a verbal report of his results. however, according to pyun,47,48 ikeda became upset and reminded him of the joint project with prof. tabata, who had now returned from the us. the following day, pyun was then sent to tokyo figure 2. hideki shirakawa and hyung chick pyun (1926-2018) at tokyo tech in 1967 [courtesy of joongmoo byun]. 94 seth c. rasmussen university to finish his project there. weeks later, pyun returned to ikeda’s lab in order to collect a deuterated ethylene sample, at which point shirakawa asked him to demonstrate how to make the film. according to pyun,47,48 he showed shirakawa his method in detail, after which shirakawa was able to reproduce his results. meanwhile, the research in tabata’s lab was proceeding smoothly, but due to the initial delay, pyun was short on time and decided to apply for an extension to the iaea. this required a recommendation letter from ikeda, however, which he refused to give, thus denying any extension.47 pyun then returned to korea in march of 1968. discussion in his written account,47 pyun highlighted a number of issues he had with the accepted version of the accidental discovery. this included statements that described him as only a graduate student, that said he that did not know japanese well, and that said he did not follow directions, specifically that he had used a thousand times too much catalyst. the first two of these were indeed incorrect, as has been previously pointed out by select historical studies of these events.24,26,28 as given above, although he did not yet have his ph.d. during his time in ikeda’s lab, the research that became his dissertation had already been completed and pyun was already 17 years into his professional career at the time. in a similar vein, the issue of language had already been disproven by hargittai,24 who had confirmed with shirakawa that pyun had grown up in korea during the years that the country was under japanese occupation and thus spoke fluent japanese. to be fair, however, shirakawa had never described him as a student, nor had he ever said that pyun’s japanese was a limitation and both of these points had been introduced by others during the many retellings of these events. the final point, however, is more problematic. according to pyun, he did not make any errors in the experimental conditions, did not use excess catalyst, and had purposely reduced the stirring rate, which resulted in the formation of the polyacetylene films.47,48 as such, he felt that he had been unfairly denied the credit for the discovery, which in his view was not an accident. the view that this innovation was solely the result of reduced stir rate, however, is not consistent with the wealth of evidence to the contrary. the production of linear, conjugated polyacetylene dates back to the 1955 work of giulio natta (1903-1979), who had used very similar conditions to that of ikeda’s group.30-32 more critically, natta’s original polymerizations were performed both with and without stirring, but always giving a crystalline powder, not a film. furthermore, the critical requirement of catalyst concentration for film formation was independently confirmed by multiple groups after shirakawa and ikeda finally reported the detailed experimental procedure in 1974.28,51 finally, in 1987, herbert naarmann at basf, along with coworkers from the university of montpellier, published a paper that probed in great detail the effect of polymerization conditions on the properties of the resulting polyacetylene.52 this study too was done without stirring and concluded that the film density was directly related to the catalyst concentration, with true films only formed via the application of high catalyst concentrations. as such, there is no experimental or literature support for pyun’s belief that he did not use a thousand-fold excess of catalyst in the original experiments. at the same time, it should be pointed out that his insistence that the reaction not be stirred does play a role in this process. as the film is formed at the gas-solvent interface, an unstirred solution provides a calm, undisturbed surface optimal for the production of smooth, uniform films, and it is perhaps not coincidence that pyun did not observe film formation until the stirrer failed. while there has never been any doubt that pyun was the first one to prepare polyacetylene films, the addition of his version to the previously available accounts now allows some additional insight into these events. from pyun’s own accounts, he began performing acetylene polymerizations, but seemingly with limited knowledge of the existing polyacetylene literature at the time,28 or even the wealth of such work carried out at tokyo tech.33-41 furthermore, based on ikeda’s reaction when pyun reported his results and pyun’s own insistence that shirakawa did not supervise his polymerizations, it appears that he did not have permission to carry out these experiments. after pyun had been expelled from the lab, shirakawa was then tasked with figuring out what pyun had done, but could not reproduce his results. while it is not currently possible to confirm this, it appears that pyun’s notebook did not indicate the atypical catalyst concentration and it was only after witnessing pyun perform the experiment that the unusual amount of catalyst came to light, after which shirakawa was then able to reproduce the results. shirakawa was then the one that studied the process in detail, after which he able to provide an accurate account of how the polyacetylene films were being produced, as well as detailed studies of the polymer structure, film morphology, and resulting electronic and optical properties. while it is very unfortunate that pyun felt he was denied fair credit, this new insight does allow us to finally 95new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry understand pyun’s role in these events. his actions did result in the first formation of polyacetylene films, but the lack of understanding of what he did makes it difficult to give him sole credit for discovery as he desired. still, many researchers would have probably made him a coauthor on the first paper reporting the film formation, rather than just an acknowledgement.42 of course, the specific criteria for determining authorship can vary by both discipline and research group, and deciding what merits authorship is not always a straightforward process.53-55 furthermore, it is important to remember that while shirakawa is always the focus when discussing this work, he was only a research associate at the time and would not have been the one to determine authorship. rather, it was ikeda who was the principle investigator and the decision concerning authorship would have ultimately been his to make. finally, some may feel that shirakawa’s version of the discovery was an attempt to distort the facts or cover up what happened. here it is essential to separate the legend from verifiable statements, recognizing that while many have attributed comments to him, the truth is shirakawa has actually said very little on the subject and what has been said is somewhat vague. unfortunately, this has led others to fill in the details based on their own preconceptions, thus leading to the multiple and erroneous versions of this important event. associated content supporting information: pyun’s original account in korean, as well as a working english translation. acknowledgment i would like to thank joongmoo byun for providing significant material on his father, as well as choon h. do, whose collaboration made this project possible. references 1. press release. nobelprize.org. nobel media ab 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japan 1967, 70, 1880-1886. 42. h. shirakawa, s. ikeda, infrared spectra of poly(acetylene). polym. j. 1971, 2, 231-244. 43. byun hyung jik, the chosun ilbo (chosun. com), http://focus.chosun.com/people/people-01. jsp?id=20494 (accessed october 6, 2017). 44. j. byun, personal communication with the son of pyun, 2018. 45. h. c. pyun, pre-equilibrium in the schmidt reaction of benzhydrols. j. korean chem. soc. 1964, 8, 25-29. 46. h. c. pyun, j. r. kim, isotopic exchange 5-bromouracil-br82. j. korean chem. soc. 1964, 8, 39-42. 47. h. j. byun, what is a nobel prize? 2013. 97new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry 48. h. j. byun, i can’t doubt the facts… kaeri magazine 2002, 10, 7-8. 49. h. c. pyun, pre-equilibrium in the schmidt reaction of benzhydrols. ph.d. dissertation, seoul national university, 1970. 50. h. c. pyun, j. kim, w.-m. lee, copolymerization of phenyl acetylene with stryrene. j. korean chem. soc. 1969, 13, 387-393. 51. t. ito, h. shirakawa, s. ikeda, simultaneous polymerization and formation of polyactylene film on the surface of concentrated soluble ziegler-type catalyst solution. j. polym. sci. polym. chem. ed. 1974, 12, 11-20. 52. a. munardi, r. aznar, n. theophilou, j. sledz, f. schue, h. naarnann, morphology of polyacetylene produced in the presence of the soluble catalyst ti(onbu)4-n-buli. eur. polym. j. 1987, 23, 11-14. 53. w. p. hoen, h. c. walvoort, j. p. m. overbeke, what are the factors determining authorship and the order of the author names? jama 1998, 280, 217-218. 54. s. p. dibartola, k. w. hinchcliff, deciding on authorship: giving credit where it is due (and only where it is due). j. vet. intern. med. 2006, 20, 803-804. 55. v. venkatraman, conventions of scientific authorship. science magazine, april 16, 2010. http://www. sciencemag.org/careers/2010/04/conventions-scientific-authorship (accessed august 13, 2020). substantia an international journal of the history of chemistry vol. 5, n. 1 2021 firenze university press giving credit where it’s due – the complicated practice of scientific authorship seth c. rasmussen history of research on antisense oligonucleotide analogs jack s. cohen chemistry, cyclophosphamide, cancer chemotherapy, and serendipity: sixty years on gerald zon thermodynamics of life marc henry darwin and inequality enrico bonatti loren eiseley’s substitution bart kahr new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors yona siderer capillary electrophores is and its basic principles in historical retrospect 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis ernst kenndler1,*, marek minárik2,3 the eminent russian – german chemist –friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries aleksander sztejnberg review of what is a chemical element? by eric scerri and elena ghibaudi, eds. oxford: oxford university press, 2020 helge kragh substantia. an international journal of the history of chemistry 3(1) suppl.: 49-52, 2019 firenze university press www.fupress.com/substantia citation: r. santi (2019) do monetary systems rediscover precious metals in the era of ‘bitcoins’?. substantia 3(1) suppl.: 49-52. doi: 10.13128/substantia-605 copyright: © 2019 r. santi. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-605 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi headmaster of the professional technical institute margaritone vasari, arezzo e-mail: skyrup@inwind.it keywords. monetary systems, bitcoins, precious metals. current monetary systems are based on a fiduciary currency. in fact, the international exchange of goods and their valuation is currently in us dollars, despite the unlikely decline of that currency in the times to come. actually, the question is often asked whether it is possible (when and how) that another system of payment instruments shall replaces the dollar. since its historical memory, “la moneta” has met two needs: value reserve and transport values in time and space. like a trunk, like a railroad car, like a cart carries, the coins bring the value from one place to another. in a patriarchal economy of floats and trunks, few carriages were needed. gold, as well as its favourite lieutenants, silver and copper, also indestructible, transferred values in time and space sufficiently. gold, like other metals, therefore had an intrinsic value, free from the dangers of a regulated and representative currency, from one day to the next, it could have reduced its purchasing power and could have inflated itself; or be treasured, provoking deflation. as described by mr. gresham, the coin that always confirms its value, drives away the one that is not able to do it. gold, as well as silver and copper, took the place of the ‘pecunia’ (from sheep, livestock) and of the ‘salis’ (salt, salary), thanks to their uniformity of value in time and space. consequently, inflation also occurred in metallic money systems too. the roman emperors, from nero up to the 3rd century, they had entrusted themselves to the augustan system, articulated on four minted metals: gold, silver, orichalcum (copper and zinc alloy, like our brass) and copper. the deception consisted in the reduction of the precious metal contained in the coins: in those of gold and silver it passed from 99% in the augustan age, to 50% of the times of caracalla. the situation became unsustainable during the chrisis of the third century and the economic system always collapsed in the time of diocletian. the military demanded continuous increases in salary, the imperial bureaucracy absorbed most of the resources, and taxation was becoming too high in the countryside. in 301 a.d., the emperor issued an edict which established the prices of the principal goods. for that reason everything stopped, nobody sold 50 roberto santi goods in exchange for money. the monetary circulation disappeared and it was unnecessary to mint more coins. thus, one wagon that made one trip a day, was equivalent to seven wagons with one trip per week. the edict was, as it was to be expected, a complete failure. shortly, after costantine he tried again and, unlike diocletian, did not pretend to stabilize the prices of products by decree. costantine fixed the parity of the circulating currency with fine gold, instead: in 310 a.d., he introduced a new gold coin, the “solidus aureus”, beaten to 1/72 of lbs (= 4.54 g) unchanged. the ‘solidus’ (that comes with the modern italian term “soldo”, that means ‘money’) guaranteed, the weight and the title in gold for decades, restoring trust to long-distance value relationships between the various part of the vast empire and over time. the fall of the empire would not have happened for monetary reasons thanks to the safety of gold and coins.1 roman monetary affairs of the 3rd century certainly happened also in previous civilizations, and they would be repeated again in the following centuries. instead, what happened at the dawn of modernity, at the beginning of the eighteenth century changed the history of money systems and the lives of men. since the earliest times of which we have witnessed until the industrial revolution, especially in england in the eighteenth century, the lifestyle, habits, rhythms and ‘traditio’ (cultural heritage) had not undergone sudden changes in any of the great human civilizations on earth. during the centuries, without traumas, economics and exchanges, cultures and ways of thinking, had seen grandparents, fathers and sons “live in the same meanings” with techniques and productions that did not register sudden changes. the massive inflation under emperor diocletian2, but also wars, invasions, famines and the black plague of 1247 in europe had never been able to settle deep gaps among generations. until the first half of 1700 the world changed without rapid jumps and heavy falls. the industrial and monetary revolution, first of all, in england in the eighteenth century, on the contrary, speeded up the changes in the economy and lifestyles in a short time. originating from three factors, namely technical improvements, capital accumulation and the introduction of paper money, the changes that have occurred in the last three centuries are only comparable, probably, to what happened at the end of the last ice age, before the beginning of the ancient history. steam trains, 1 in fact, the fall of imperial rome in the west occurred in the fifth century for military reasons and political feuds within the roman senate, while constantinople with the new monetary system (the greek byzantium) remained standing up for centuries. 2 it drove silver completely out of circulation. assembly line, taylorism in industrial production, coal, electricity, petroleum, chemistry, plastics, steel, industrial automation, optical fibers, nuclear applications, nanotechnology, spacecraft, and so on, represent the evolution, amazing and fast, of the production techniques of modern time. in modernity, it could be glimpsed a second factor, the accumulation of capital, whose beginning we can date at the beginning of the seventeenth century, thanks to the return of sir francis drake’s f lagship golden hind. in “the year of grace” 1580, golden hind landed in the thames estuary with the cargo of gold stolen by drake from the spaniards by boarding the galleon nuestra señora de la concepción. the expedition had been financed by queen elizabeth of england herself, who personally climbed on the newly moored golden hint to meet and greet sir francis. the loot, equal to 6 tons of gold, was used to pay the entire substantial foreign debt of the british. there were still £ 40,0003 left over, invested in the levant company in the a.d. 1600, then company of the east indies, and imperial british army until 1874. the ‘english centuries’ began from that moment, time and space of the british global hegemony in history. an essentially maritime domain, based on military projection, with a first-rate and technological background and, as a third factor, due to modern monetary changes, thanks to the monetary projection based on the pound with a golden background. the introduction of paper money by the british empire in 1694 represents, in fact, an epochal turning point for the history of economics and an instrument of incomparable domination. therefore, it was industrial and technical revolution, accumulation of capital and, finally, paper money. until 1694, in england and elsewhere, the only officially circulating currency was the coined coins. and, as in ancient times or those of augustus and constantine, metal coins have always had an ingrained value. since 1694 a bill was issued, the pound sterling, subsequently produced in series from the early 1700s as gold-based paper money: it corresponded to a fixed exchange with gold deposited at the bank of england. for that reason, it was called “gold standard”, but gold did not circulate “physically” any more: in the hands of men from that time the paper was circulating and no longer metal. the paper can be printed without limits, while any metal must be extracted from the mines. the english ‘golden system’ will remain the foundation of the british empire until 1914. the issuing banks after 1694 became almost all private (they are still today) and the public coinage and metal will remain 3 it is estimated that every pound brought home by drake has been transformed, in almost three centuries, into 100 thousand pounds thanks to the compound interest of 3.25%. 51do monetary systems rediscover precious metals in the era of ‘bitcoins’? residual. no one would have been able to verify the carats of gold coinage any more, or the weight of gold kept in deposits. the printing of banknotes allowed to increase of the resources of the state budgets based on the confidence that the banknote received. alexander the great in persepolis and the inca treasure of pizzarro had recorded the dispersion of immense quantities of gold and precious. now the gold that the rand miners had brought to light was concentrated and buried again in the central bank’s warehouses. but the loss of value of “paper money” can sometimes be faster than the “metallic one”. the vladimir ilič lenin’s (1870-1924) hope, after the end of the british ‘gold standard’ in 1914, was that inflation would cause the collapse of capitalims: “governments confiscate with secret hands, promote the ‘rentiers’, they depress trade”. this is the premise for the “revolution in the capitalist countries”. indeed, the post-war economic crisis will have more complex connotations linked primarily to def lation more than inf lation. def lation is not only a problem of the twentieth century. certainly, the deflation was the origin of the crisis of 1929, illustrated by j. maynard keynes (1883-1946). lord keynes proved how excess production capacity compared to aggregate demand was the primary cause of deflationary phenomena, provoke even more damage than the german inflation of the weimar republic. the british attempt to restore the gold standard, which lasted until 1931, will produce heavier effects than any loss of purchasing power of the currency. the same gold has been, during the history of civilizations, a sovereign whose defects have remained hidden by utility. as difficult to reproduce, sometimes monopoly of caves, disputed, the gold and the silver can’t in fact transport all the wealth produced by man in times and spaces. the claim of the british empire, also at its own epilogue in 1930, to repropose the pound at the gold base at the centre of international trade. as keynes writes, what matters is not the exchange rate between gold and pound that does not involve an increase in production, but the impulse of consumption and aggregate demand: if the products remain unsold and the warehouses are full of stocks, it is useless produce again, while the money saved will not be invested in new plants and machinery. to increase the circulation of money, with the pound tied to a fixed parity with gold, it would have been necessary to discover new mines. it does not happen with the fast pace and lilts of modern technological progress. since 1946 the dollar standard replaced the pound as international reference currency. carriages, wagons and trunks were now called dollars in the new system. reserve money and world transactions, like the pound sterling until then, flanked the gold with a fixed parity of $ 35 per ounce of gold. the proposal of the ‘bancor’ proposed by keynes in 1943 as part of a project, not implemented, of union for international compensation (international clearing union) was discarded in the new american imperial vision. the “novus ordo saeculorum”, motto taken from virgil’s eclogue iv, even printed in us notes, has a clear meaning. other quotes from virgil, the american “founding fathers” had, moreover, reported in the ‘great seal’ usa, such as that readable on the back of the same dollar bill: “quid non, mortalia pectora cogis, / auri sacra fames”4. keynesian commodity money was therefore discarged. in july 1944 at bretton woods, new hampshire location where the dollar standard was approved, us currency was chosen like international currency paper. this exchange system was established by a state under a monopoly regime. it lasted less than the english currency in the gold exchange and it was abandoned in 1971. without any link with gold, after 1971, the dollar is still today the most internationally recognized payment instrument, despite the fact that at the end of the 1999 the so-called derivatives circulating in the world amounted to 30,000 billion dollars, equal to 285% of world gdp; and, only ten years later, at the end of 2009, they had reached the rating of 690,000 billion dollars, that is 1057% of world gdp. the path of history, of scientific discoveries, of technologies, up to the eighteenth century, initially very slow and then, faster and faster, accompanied by the invention of banknotes, fiduciary money and credit, has determined in the monetary systems the replacement first physically and, subsequently, also of purely theoretical reference of precious metals and of gold in particular. finally, to the present day, we have passed from paper banknotes to credit plastic card, to reach crypto currencies, a pure technological sign far away from concrete goods and services provided. just the ‘digital currency’. an operation in crypto currency has its own specific id code, its name and surname and its history. if romeo buys a meal with coin a (e.g./ id: 834567), the transaction puts in the archive the passage of currency ‘a’ from romeo’s wallet to juliet’s in exchange for an asset. the link between a bitcoin platform and the cripto currencies, established in 2009, manages transactions and exchanges of information and data in the finance and payment areas. the proof of the passage of the new property is created thanks to a digital signature 4 on the american banknote there is also another quote: ‘annuit coepitis’ (god is in favor of the enterprise) taken from the trojan prayer to jupiter «audacibus annue coepitis» (almighty jupiter, consents to the audacious undertakings, aeneid, ix, 625) 52 roberto santi of the transaction. in order to use bitcoin currency as an exchange currency, simply install an application on your computer or mobile phone. the currency of ethereum, for example, takes its name from a “virtual currency” called “ether” which itself represents the possibility of producing the shops in cryptocurrency “ether” by it we can “pay” for the realization of contracts. ether is basically and concretely a ‘token’ with an attached digital signature, whose trust is at the base of the ether or bitcoin system. messages are encrypted and access keys are available only to those who are part of the network. the control system, called blockchain, allows all participants to confirm or not a transaction. bitcoins are virtual but produce the same effects of traditional banknotes. therefore they do not represent anything in the physical world, but they have value for the mere fact that people agree to exchange them with goods or services, in order to have an ever greater number on their account, convinced that other people do the same. the new global computer technologies, based by search engines, artificial intelligences in the service of finance, have magnified the global speculations. the “quick earnings” (‘subiti guadagni’) are also mentioned by dante alighieri (1265-1321) with reference to the black guelphs in the 13th century florence. a finance whose wealth expands without control and without limits by the individual nations and the central banks themselves; without the limits that the golden base had, even with its defects, and which had guaranteed the ancient empires. the triumph of the representative credit currency is today at its peak in the world of transnational finance and the introduction of the bitcoins. modern finance and its many products, hedge funds, the protagonists of speculation, have passed the stage of printing banknotes without a gold standard as in 1694. the new phase registers the use and the loan of money that do not even exist. it has not been printed by any central bank. this is the moment of virtual money. will it last? will be there any surprises? in 1930 irving fisher (1867-1947), in his work “monetary illusion”, proposed one currency based on a basket of goods. a real currency in which gold could combine real products to guarantee the circulation of money. the keynesian idea of ‘bancor’ could also have foreseen a basket of coins similarly to what was represented today by the imf’s5 special drawing rights, whose values were based on a basket of national currencies. will we go, with a delay of over 70 years, in this direction? will gold and silver remain the prerogative of the production of prestigious jewels of the great goldsmiths in arezzo and elsewhere, or will they remain deposited in the vaults of the central banks? a wagon in a dead track, a trunk in the attic or in a vault are no longer currency, but a store of value. gold is to be returned to goldsmiths only? or will the monetary systems rediscover the gold and other precious metals to ensure a circulation without ‘volatility’, not subject to speculation and ‘ quick earnings’? 5 international monetary funds. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe substantia. an international journal of the history of chemistry 3(2) suppl. 4: 9-12, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-737 citation: b. van tiggelen, a. lykknes, l. moreno-martinez (2019) the periodic system, a history of shaping and sharing. substantia 3(2) suppl. 4: 9-12. doi: 10.13128/substantia-737 copyright: © 2019 b. van tiggelen, a. lykknes, l. moreno-martinez. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. editorial the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 1 science history institute, paris 2 department of teacher education, norwegian university of science and technology, norway 3 “lópez piñero” institute for science studies, university of valència, spain *email: bvantiggelen@sciencehistory.org by now, everyone knows that 2019 has been dedicated to the international year of the periodic table of the chemical elements (iypt) by unesco. at the very least, this is true for the chemical community and science teachers and popularizers at large. on many occasions during this year, historical accounts have been provided by specialists and profane alike. the year 2019 was chosen precisely because it corresponds to the 150th anniversary of the first publication of a classification of the then known elements by dmitrii ivanovitch mendeleev (transcribed from the russian as dmítriy ivánovich mendeléyev), a classification he ended up calling a periodic system when publishing it. he devised the system while he was working on a textbook of chemistry – the famous principles of chemistry (two volumes, 1868–1870) –, but immediately recognized the importance of what he had just sketched and published a separate one-sheet comprising the first “periodic table” with the title an attempt at a system of elements based on their atomic weights and chemical similarities on march 6, 1869 (or 17 february in the julian calendar as written on the sheet ).1 two features of what we have just outlined call for our attention. first, mendeleev spoke and wrote about a periodic system (and later a periodic law) and not about a periodic table. indeed mendeleev’s system is often referred to as a classification of the elements, and in many cases the periodic system was indeed first received as a classification by many of mendeleev’s contemporaries and successors. this is however not how mendeleev viewed it. second, the system emerged in a teaching context, even though mendeleev published it separately from his textbook and continued publishing on it as 1 mendeleev rushed the publication of that separate sheet all the while he asked his colleague nikolai alexandrovich menshutkin to read his paper to the russian chemical society on 18 march 1869 (6 march julian calendar). it was published as a few months after as “sootnoshenie svoistv s atom s atomnym vesom elementov” (“the relations between the properties of the elements and their atomic weights”). zhurnal russkogo khmicheskogo obshchestva (journal of the russian chemical society). 1 (1869) 2/360-77. 10 brigitte van tiggelen, annette lykknes, luis moreno-martinez a research topic in itself, in parallel with the successive editions of his principles of chemistry.2 to this day, the pedagogical use of the periodic system is still preeminent, as it is hard to imagine a lecture hall or a textbook in chemistry (or science) that would not feature a representation of the periodic system. let us first deal with the issue of nomenclature. this special issue uses the periodic system rather than table, which is a deliberate choice. there are thousands of periodic tables, according to mark leach who keeps a comprehensive database of periodic tables. his website provides a large variety of representations of the periodic system, most of them in two dimensions.3 they come in many shapes, inner organizations and colors, and have evolved alongside new understandings of matter and the inner structure of atoms over the course of 2 van spronsen, j. w. (1969). the periodic system of chemical elements: a history of the first hundred years (elsevier, amsterdam, london and new york, ny; scerri, e. r. (2007). the periodic table: its story and its significance (oxford university press, oxford) and gordin, m. d. (2004). a well-ordered thing: dmitrii mendeleev and the shadow of the periodic table (basic books, new york, ny). 3 https://w w w.meta-synthesis.com/webb o ok/35_pt/pt_database. php?button=all 150 years. mendeleev himself designed and published several versions, demonstrating that what lied at the core of his thought was not the periodic table, even though it was presented in that form, but a system from which he inferred his periodic law. this is very clear from the title of his march 1869 publication mentioned and illustrated above. he perceived it as a natural law, which could be used to deduce the existence of elements and foresee their properties, not just describe existing knowledge. his trust in this law was such that it enabled him to predict correctly three elements that were discovered within less than 20 years of his initial statement. but his conviction also led him to failed predictions and errors of appreciation in the wake of new discoveries such as the noble gases or the phenomenon of radioactivity. to mendeleev, if the system derived from the periodic law did not have space for an element, then this element could simply not exist. this is how he reacted when the news about the discovery of argon was announced before accepting a whole new group, the noble gases.4 while the distinction between table, system, classification or law might seem more of theoretical interest than anything else, these different conceptions of periodicity in relation to classifying chemical elements will be discussed in some of the contributions to this issue. that such distinctions are relevant and important will be demonstrated in the contributions dedicated to the response to the periodic system. indeed, the appropriation process of the iconic tool that the periodic system is for chemistry, and its different shapes since its initial publication, do explicitly refer to a spectrum of conceptual objects, ranging from a mere classification to a system to a law of nature, including tables and charts that adorn textbooks or classrooms. depending on which object is used or referred to, the reception is different and belongs to a different context of use. this leads us to the second point. as mentioned earlier the teaching context was crucial from the start. it is within the context of teaching that the system emerged as a new tool, and it is also in this context that the appropriation process really took place. for a long time, historical accounts of the development of this seminal idea and the scientific icon have been limited to the traditional succession of chapters devoted to the questions of forerunners, co-discoverers (including the delicate question of priority), successful predictions, rearrangements according to atomic numbers instead of the atomic weights, and alongside atomic, subatomic and quantum interpretations. the discovery of new elements is often discussed as well, as is the question of the bounda4 see for instance: giunta, c. (2001). argon and the periodic system: the piece that would not fit. foundations of chemistry. 3. 105-128. figure. 1. the hand-written copy of the “attempt” that would be published under the title “attempt at a system of elements based on their atomic weights and chemical similarity” in both russian and french, and kept at the mendeleev museum and archives, saint petersburg state university, saint petersburg, russia. 11the periodic system, a history of shaping and sharing ries between chemistry and physics. for instance, both van spronsen and scerri mentioned above use that organisation in their table of contents. such traditional narratives, consciously or not, stress mendeleev’s genius, as if he were a prophet, able to devise a classification/ system while atoms were still not accepted entities for chemists. as a result, the success of the periodic system often appears as a natural consequence of it being “correct”. when taking a closer look though, it appears that in many countries and institutions, periodic tables appeared rather late – which is hard to grasp given the position the system holds in today’s chemistry. the question of “being correct” has a different meaning in teaching; teachers adopt what is helpful and efficient. thus explaining the dissemination of the periodic system/ table/classification in chemical education is crucial to understand its success and how it has become the icon we all recognize today. a few years ago, a collective work edited by masanori kaji, helge kragh and gabor pallo was devoted to the first responses to the periodic system demonstrating the diversity of appropriation processes across the world, by offering case studies for several countries, some of which had not been studied before.5 this built on a contribution by stephen brush which was influential even though limited to the mention of the periodic system or the mere inclusion of a table in textbooks, and had already pointed at some delay for the acceptance of mendeleev’s and meyer’s initial ideas.6 in this special issue, we have deliberately left aside the questions of priority, the discussion about predictions, and adaptations or rearrangements of the system to focus on the process of how the periodic system became a shared universal tool for chemistry and science. we envision this process as dynamic, and active, and we claim that this process was exactly so right from the very beginning when mendeleev, meyer and others published and discussed the periodic system and the periodic law. in fact, the periodic system published by mendeleev in march 1869 is not the one we use today, as it was shaped in the following ten years by a succession of additions, changes and improvements that were the result of ongoing discussions with the community and constant interactions with teaching practice, as much as the outcome of a few men’s solitary train of thoughts. the process continued all over the last 150 years. in the same way, when the periodic system eventually was 5 kaji, m., kragh, h. and palló, g., eds. (2015). early responses to the periodic system (oxford university press, oxford). 6 brush, s. (1996). the reception of mendeleev’s periodic law in america and britain. isis, 87(4). 595–628. adopted as a teaching device, this came most of the time as a result of a process of appropriation during which teachers, chemists and students shaped their own understanding and sometimes invented their own version. this is precisely why there are (and will be) so many periodic tables around: for a concept to become universal it has to be plastic enough to accommodate personal appropriation. interestingly history becomes a part of how this tool is incorporated and legitimized in the textbooks and teaching practice. even in science texts that leave very little place to the historical development of the chemical sciences, the discovery of the periodic system (or, quite often the periodic table) is mentioned as well as its discoverer(s). in a weird way this mention often smoothens or ignores the appropriation process, in a manner that negates the historical evidence and defaces the nature of science. the history of shaping and sharing of the periodic system is approached in this special issue in three acts. the first three contributions illustrate how the periodic system emerges and is shaped through the context of teaching chemistry. the contribution “julius lothar (von) meyer (1830-1895) and the periodic system” by gisela boeck provides insight into the development of lothar meyer’s thought on a periodic system of the elements while he was devising the successive editions of his chemistry textbook from 1864 onwards. the wide variety of responses to the periodic system in portugal analyzed by isabel malaquias and joão a. b. p. oliveira in the ”shaping the periodic classification in portugal through (text)books and charts” provides a good example of how reception is linked to the different contexts of use. “the st andrews periodic table wallchart and its use in teaching” by alan aitken and m. pilar gil shows how a precious wall chart acquired in 1888 was used, getting us one step closer to the fine grain process of appropriation of the periodic system which is often hard to track. the following two contributions analyze the way the history of the periodic system is presented in textbooks and how this kind of history shapes not only the central place of the periodic system in the teaching but also conveys something about the way chemistry developed. in “the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks”, luis moreno martinez and annette lykknes underline how the brief historical presentation of the periodic system in many textbooks affects the underlying teaching of the nature of chemistry and its history. gebrekidan mebrahtu tesfamariam and mengesha ayene make the same assessment for ethiopian chemistry textbooks for the sec12 brigitte van tiggelen, annette lykknes, luis moreno-martinez ondary schools as they pose the question “are history aspects related to the periodic table considered in ethiopian secondary school chemistry textbooks?”. the periodic system is alive and well, and its versatility and continuing evolution represents a challenge to the present and future sharing of this universal tool of chemistry, a challenge which lies at the core of the last three contributions. the attempts and so far limited success at standardization by the international union of pure and applied chemistry are described in “order from confusion: international chemical standardization and the elements, 1947-1990” by ann robinson. this variety has its advantages. for instance, alfio zambon shows in his contribution “periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication” how a specific design, the periodicity tree he has devised, opens the way to a more chemical approach to the teaching of the periodic system. along the same line, in “compounds bring back chemistry to the system of chemical elements”, guillermo restrepo reconstructs the 1869 system on the basis of computer analysis of chemical knowledge, and the use of contemporary databases yield other systems or groupings of elements classification according to their similarities. these provide a less physically laden approach to the periodic system that is nowadays usually explained in quantum mechanical, or even relativistic terms, ignoring the chemistry behind the making of the periodic system 150 years ago. the result of a history of shaping and sharing, the periodic system will continue to evolve and its plasticity will no doubt continue to serve as one of its core values. as professor emeritus pekka pyykkö (university of helsinki) expressed it during several talks along the iypt: “it is a human right to make your own periodic table. don’t let anyone take that right from you”.7 7 these views were expressed a.o. during p. pyykkö’s lecture at the mendeleev-150 conference in saint petersburg, russia, and confirmed to the authors through a private communication, october 14, 2019. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo 1 citation: l. corbetta, s. li, j. li, s. guo, p. bonanni, f. herth, j. flandes, m. munavvar, l. qiang, n. wang (2020) stand on the same side preventing a second wave of covid-19's outbreak. substantia 4(1) suppl. 1: 950. doi: 10.13128/substantia-950 received: may 19, 2020 revised: may 22, 2020 just accepted online: may 29, 2020 published: may 29, 2020 copyright: © 2020 l. corbetta, s. li, j. li, s. guo, p. bonanni, f. herth, j. flandes, m. munavvar, l. qiang, n. wang. this is an open access, peerreviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative com mons attribution license, which per mits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia webinar stand on the same side – preventing a second wave of covid-19’s outbreak this document is the direct transcription of a webinar organized by prof. l. corbetta of the university of florence on april 19th, 2020. scientific coordination: lorenzo corbetta associate professor of respiratory diseases university of florence scientific and website director of the european association for bronchology and interventional pulmonology (eabip) organizing secretary: consorzio futuro in ricerca via saragat 1 – corpo b – 1° piano | 44122 – ferrara cfr@unife.it translation coordination and editing: giorgia biagini, md info@covid19expertpanel.network webinar’s partecipants: prof. shiyue li first affiliated hospital of guangzhou medical university prof. jing li first affiliated hospital of guangzhou medical university prof. shuliang guo chongqing medical university prof. paolo bonanni university of florence prof. felix jf herth university of heidelberg prof. javier flandes – university autonoma madrid prof. lorenzo corbetta university of florence prof. mohammed munavvar university of manchester prof. li qiang shanghai oriental hospital affiliated to tongji university dr. na wang shanghai oriental hospital affiliated to tongji university corresponding author: lorenzo.corbetta@unifi.it substantia. an international journal of the history of chemistry 4(1) suppl. 1: 950, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-950 http://www/ http://www/ http://www.fupress.com/substantia l. corbetta et al. 2 “stand on the same side” videoconferences https://www.covid19expertpanel.network “implementing a science-based lockdown exit strategy is essential to sustain containment of covid-19. china’s experience will be watched closely, as other countries start considering—and, in some cases, implementing—their own exit strategies” the lancet, volume 395, issue 10232, 18–24 april 2020, pages 1305-1314 this phrase expresses the purpose of this program called “stand on the same side against covid-19” that takes advantage of the new and rapid digital technologies to put together several experts worldwide. it’s a global space were many countries hit by sars -cov-2 can share only scientific information in order to face the pandemic. apr, 29th 2020, china-europe videoconference “stand on the same side against covid-19 preventing a second wave of covid-19’s outbreak” shiyue li: hi, everyone. welcome to the webinar. this meeting is the second china/europe seminar on fighting covid-19. last meeting was about one month ago. before this webinar, many thanks to dr. corbetta for organising this meeting. today, the topic for this webinar is preventing a second wave covid-19 outbreak. we have doctors from europe and china to join together to exchange our opinions on this topic. so, i have just a brief opening speech and then i'd like to invite dr corbetta to give some words. please, professor corbetta. lorenzo corbetta: okay, professor. hello, everyone. professor jing li, if you want to introduce the speakers, please. jing li: okay. it's my honour to introduce all the speakers one by one. today, we have seven outstanding speakers, talking about various topics on when the second wave of covid-19 outbreak will be. there is german speaker, uk speaker, italian speakers, chinese speakers. i'm happy to introduce the first one that is from china, professor guo shuliang. professor guo is the head of department of respiratory and critical care medicine at the first affiliated hospital of chongqing medical university. he's also the leader of the international group of the committee into the intervention of respiratory diseases. he is also vice president of the respiratory endoscope society of the world endoscope physicians association. his topic today will be a strategy in the community, in hospitals, with the second wave of outbreak in china. shuliang guo: okay. thank you for your introduction, professor li. hello, everyone. it's my great pleasure to introduce a strategy in communities and hospitals to prevent a second wave of outbreak in chongqing, china. china has had great success in fighting against the covid19 until now. we began to restore normal economic and social order. however, some experts expressed their concern on a second wave of outbreak. even in china, there is a highprobability event. so, after the first wave, is there going to be a second wave? the answer is probably. in the spanish flu pandemic in 1918, there were multiple waves and here shows the second wave of sars, and the second wave of covid19 in singapore recently. so, china has a potential risk of a second wave epidemic because china is far from herd immunity and they're under a great pressure of imported infections and emerging asymptomatic transmissions. the recent epidemic rebound, here, you can see in heilongjiang province due to the dramatic increase of imported cases and the recent local chain and cross provincial spread in harbin due to dining, gathering and cross infection in hospital intensifying these concerns. so, how to prevent a second wave of outbreaks. we introduce some strategies for communities and hospitals in chongqing.  the first one is the riskand the region-specific resumption and reopening. we resume and reopen based on the risk rating. the risks are ranked as low, medium, high risk regions. for example, the low-risk regions means administrative regions with no confirmed cases and without new confirmed cases in the past consecutive fourteen days. here, on march 20th, all districts in chongqing were declared no risk and the emergency response had adjusted to the third level. so, in different risk regions, there are different strategies. for example, in low-risk regions, the main strategy is to prevent imported cases. in medium-risk regions, the principal strategy is to prevent imported cases and domestic rebound and re-infections meanwhile. we focus on the strategy at city and community level here. we demand staying alert constantly and we resume and re-open gradually and dynamically.  for example, the graduating class begins schooling first, the class is divided into smaller ones, we prefer remote teaching and large entertainment are still closed.  we also want to control by taking temperature at ports and stations. also, we scan the health coding before entry, as shown here. if the code is blue, you can pass, but if it is yellow or red, it's not permitted entry.  we continue to wear masks, keep a one-metre distance and avoid gathering.  we expand pcr and detection, and this testing, to find out asymptomatic persons. all of the three groups that https://www.covid19expertpanel.network/ stand on the same side preventing a second wave of covid-19's outbreak 3 should be tested including their close contacts, people from hubei and wuhan to chongqing, and the person inbound to chongqing within fourteen days. this people will be isolated for fourteen days in different designated hospitals or home.  so, at a hospital level, we have careful entry control. we scan a health code, like here shows, and we check temperature and face recognition. we do pre-check triage and fever clinic control. the patient will be admitted only after the pcr (polymerase chain reaction) and the ct (computer tomography) scan examination. besides above, the anti-epidemic agencies, measures and isolation wards remain unchanged. we strengthen internet medical services to reduce patient gathering. for all hospitalized patients and high-risk operations, pcr testing should be done firstly. we continue personnel training and remain vigilant. we protect medical workers with ppe (personal protective equipment) in high-risk departments during diagnosis and treatment. we do escort testing. emergency isolation sections have been set up in each ward and we do strictly terminal disinfection.  to deal with a second outbreak, the government in chongqing strengthen the construction and storage of the epidemic emergency system. the government are now building four new public health emergency hospitals with a capacity of 5,000 beds in chongqing. here, we can see they're located in the central, in the west, in the north east and the south east district. that covers the whole of chongqing city. china is accelerating the research and development of vaccines and specific drugs. as director of cdc (center of diseases control) in china, gao fu, mentioned the china vaccine may be available for emergency use in september. so, all of the strategies and measures worked well.  here, from february 25th, there were no confirmed cases, and all the asymptomatic cases are imported with zero to five cases per day. however, globally, more than 200,000 people have died of covid-19 and the american cdc director warned that the second wave could be even more devastating. so, we must join hands, do more efforts, stand on the same side, to fight against covid-19 and to prevent a second wave. so, thanks for your attention. thanks. jing li: thank you very much, professor guo for his intensive introduction. he introduced different waves of the covid-19 outbreak in several cities in china, and also raised some risks of the second outbreak, and introduced some strategy, including some vaccines, very nice. now, we move to the second one. the second speaker will be professor paolo bonanni. he is the professor of hygiene, university of florence, and director of the specialisation school in hygiene and preventive medicine, university of florence. he's going to give us a talk on control strategies outside the hospital to prevent a second spike of covid-19. let's welcome professor bonanni. paolo bonanni: thanks a lot for the second invitation to this second webinar. the situation has changed, obviously, since the last webinar, because of course the epidemic has progressed. in italy and in europe, we are lagging behind china regarding the number of cases, because you showed that you had no longer cases in some provinces since february 25th, when we were starting. so, the phase two is just starting now in europe and in italy, and i would like to highlight some points of discussion regarding the control strategies outside the hospital to prevent a second spike. the first slide i want to show is a little bit crowded-, i apologise for this, but this is the official data from italy from two days ago. i want to draw your attention to the number of cases here. we have almost 200,000 cases. we surpassed that amount in the last two days. but, of course, this number is an underestimate, because i would like to remind you that in italy, for a long time, only cases who were strongly symptomatic and who accessed the hospital were for sure tested for pcr. so, probably, the real number will be much higher than these figures. you see this, also, from the number of deaths that we've had, that puts us with a case fatality rate which is much higher than in other countries. this is not, probably, due to different characteristics of the virus or differences in italy compared to cases in other countries, but the problem is that we are underestimating the denominator of these numbers. the other important thing is that many healthcare workers were infected. you see here that around 10% of the overall cases were healthcare workers. the other important part is the case fatality rate, which despite this being probably overestimated, all the same you can see here that people from 60 to 69 have a case fatality rate, provisional fatality rate, of almost 10%, much higher in the elderly population. but this is putting a special focus, because there was a discussion in the country saying that we shouldn't prevent people from 60 to 69 years going back to work in the first phase two weeks, because there might be a danger for them if they get infected. my contribution to today's webinar is mainly of questions rather than answers, because we ask ourselves a lot of questions in this preparation for the phase two. so, we are starting our phase two on may 4th and there was a lot of discussion in the country, because many people who are waiting to go back to work were a little bit deluded by the progressive opening that the italian government decided to do. so, we are opening little by little, and some elements of consideration for the progressive reopening of work activities. of course, in all the companies and fabrics, people will be tested for temperature. if they are over 37.5 degrees, they will not be let in the industry or the office. but the questions i want to raise are the following ones. what is the real number of infected subjects still unknown? and what is the proportion of the overall population which is still spreading the virus? so, of course, we have a question mark on the number of asymptomatic subjects that are going around, without being l. corbetta et al. 4 aware of being a person who can infect other people. then, how long an infected subject carries the virus in saliva, this clinically healed subjects who still test pcr-positive three weeks later. so, three weeks after they were considered healed from a clinical point of view. so, it's difficult to understand how long the spread of the virus can be sustained by people who are clinically okay. the other problem is, is the virus shed in faeces? we know yes, but how long? this is also a problem for the management of toilets in the companies and offices. are face masks always needed outdoors and in the workplace? which masks should be worn, and should that be compulsory? also, here, there is a lot of discussion. probably, in some companies, they are trying to avoid the permanent masking of people who work there if they can keep a distance of more than two metres. but, the other question is, how frequent is aerosol production from an infected subject? is this substantially contributing to virus spread or not? again, we are going towards summer and, of course, there is a lot of air conditioning foreseen for the next months. the question is, is air conditioning dangerous? should its maintenance be different from normal times? my last question here is, can serological tests be useful to manage re-admission at work or not? i tried to make some consideration on what i asked ourselves. so, we need to test people twice, and they need to be negative to pcr with at least 24 hours of distance between the first and second test, for re-admission in the community. because, otherwise, we are risking them to spread the virus. if pcr is not performed and people are not confirmed cases, but only suspected covid-19 cases, i suggested to the people who ask me, for the reopening of work facilities, to leave the subject at home for two or three weeks more if this is possible. if this is not possible, they should compulsorily wear the masks anywhere and at all times outside their home when they go to work. we need to provide the careful sanitisation of toilets, handles, taps, and we should have different toilets for internal and external workers in workplaces. we should keep 1.8 metres between workers whenever possible. if not, surgical masks should be worn when the distance is less. we need to exchange air. so, window opening whenever possible. air conditioning does not seem, from the evidence we have, to contribute to virus spread. so, normal maintenance for them. the only suggestion is to keep humidity at a higher level, because this probably makes the possible drop that's containing the virus be bigger and fall down. so, the spread is mainly through big droplets and, in this sense, hand hygiene is crucial and to be very much stressed. some considerations and suggestions  need to test twice negative to pcr (24-hour interval) for re-admission in community.  if pcr not performed by suspected covid-19 case, leave subject at home for 2-3 weeks after healing is possible if not, compulsory wearing of surgical mask at any time.  careful sanitization of toilets, handles, taps, different toilets for internal and extenal workers.  keep 1.8 meters between workers whenever possible. surgical masks must be worn if distance less.  exchange air (window opening) whenever possible. air conditioning does not seem to contribute to virus spread, normal maintenance, humidity not too low.  spread mainly thorough big droplet, hand hygiene crucial.  serological tests: different types (rapid strip; elisa; chemiluminescence), different sensitivity and specificity; unclear role of igg in virus clearance.  are antibodies long lasting? protective? how long? still to be proven. regarding serological tests, we have a lot of adaptations. so, there are different types. rapid strips, elisa, chemiluminescence. they have different sensitivity and specificity, and we don't know yet the role of igg in virus clearance. so, i think that we must go on testing these tests-, let me say it like this, but we don't have definitive answers on the role of the serological testing. also, because, how long are antibodies lasting? are they protective and if they are protective, how long? all of this needs to be proven. i just want to highlight an interesting paper from china that should be published in the next month, showing that in restaurant in guangzhou, there was a way to show that in a restaurant, before the closing, people who are under the air conditioning machine spread the virus to the closer tables, but not to the tables here, e and f. so, air conditioning is probably not contributing to the distribution of the virus through the machine, but creating an air flow might bring the droplets from the table of infected subjects to the nearby tables. so, this is also interesting for the management of restaurants and bars in the near future. this is an example of something we're doing with companies here in italy. the original article can be found here: https://wwwnc.cdc.gov/eid/article/26/7/20-0764_article this is an example of management of face masks in an italian mechanical company. so, they wrote guidelines for their workers, saying that, for distribution criteria, for activities with an interpersonal distance of less than two metres, they should stop work, evaluate with a responsible for the work management, if there can be another way to work with a distance of more than two metres. but, if there is no possibility to work without this distance, they should ask for an ffp2 mask if this work is short-lasting. but, if this is needed for a long time, they should ask for a surgical mask. the disposal of masks is in dedicated bins as special waste, and bins should also be located near changing rooms and infirmaries. masks are also supplied by the company, for people who travel from home to workplace and back, and the preference for mask-wearing at any time during work. so, if there are some people who want to wear this mask for all the entire duration of work, they can be provided with these masks. so, i want to close my presentation. we still have to learn much also on effective containment in the phase of lockdown release. https://wwwnc.cdc.gov/eid/article/26/7/20-0764_article stand on the same side preventing a second wave of covid-19's outbreak 5 an example of management of face masks in an italian mechanical company use of face masks in accordance with who recommendations: distribution criteria  for activities with interpersonal distance < 2 meters the following criteria apply:  stop work to evaluate with the responsible of work management  identify hazard identify phases which require a distance < 2 m  control hazards & verify barriers identify together with the responsible alternative ways of performing tasks which allow a distance > 2 m  if not possible (i,e, 3-4 times per turn, few minutes) ask for a ffp2 mask  if continuously < 2 m for the entire turn (i.e. mounting the same component closely), ask for a surgical mask disposal  masks must be disposed of in dedicated bins as "special waste (cer 180103*)"  bins should also be located near to changing rooms and infirmaries masks are also supplied by the company for  travel home/workplace and back  preference for mask wearing at any time during work we do hope that this can be done successfully and with limited need of new selective closures of activities and communities in the next phase. but we must be very careful and we must be able to close the places where new contagion occurs, if this should be the case in the next few weeks. thank you very much for your attention. jing li: thank you very much, professor bonanni, for your very interesting talk on the prevention of the outbreak outside hospital. you have very important three points and i want to have a summary. you mentioned the unknown proportion of the population that it’s still spreading the virus on the probability of the second outbreak, and you introduced some elements of the consideration for the progressive reopening of work activities. the third, i would like to thank you again, you mentioned a very interesting paper from china for the restaurant management. also, you mentioned the face mask selection on certain situations. thank you very much. now, we come to the next speaker, professor felix jf herth. professor herth of thorax university in heidelberg in germany. he also is the head of department of internal medicine pulmonology and critical care. also, the chief of the european committee for bronchology and interventional pulmonology. he's going to give us the talk with a topic of role of hospital reorganisation and testing capabilities to achieve the best outcome. now, professor herth, please. felix herth: yes. thanks a lot for giving me the opportunity to share with you what we did in germany in the past and how germany is handling the covid situation. to be honest, i can tell you what we did, i have no idea what we have to do next, because nobody knows if a second wave is coming and when. just to give you a brief update, this is the actual situation in germany. we have about 160,000 cases and we lost about 6,000 patients. lorenzo asked me to show our real data. this is our reproduction rate. diapo since fourteen days, we are now below one. so, that means that only one patient is infecting one other. yesterday, we have had a little peak: we have to upgrade to 1.00. before, we have been 0.94. so, actually, the situation in germany is quite stable regarding the infection rate. as you see here, we have had a couple of patients on the icu (intensive care unit) like everybody else in the world. but many patients reached a level of entering an icu with a mortality of 30%. so, that means, in the severe population, dealing with covid, we have to compare the mortality rate to the other parts of the world. i've just put here a couple of other european countries on the table. germany was actually quite successful to keep the mortality of covid-19 really on the lower limits. we had a range of 2%. austria has the same results published, but all other countries are really above us. so, the question is-, maybe this is the reason why lorenzo asked me to participate today, the question was why germany did it a little bit, or it seems, did it a little bit better than the rest of the world. now, here are my explanations for that. https://ourworldindata.org/coronavirus this is the timeline of how we shut it down. the first patient in germany we have at the end of january, and at least in march 13th, the decision was made for angela merkel to shut down germany. we closed schools, we closed universities, nobody was able to enter germany anymore. so, this has been a timeline of shutting down. what was decided on march 13th for the hospitals, we postponed all elective procedures, the outpatient clinics have been closed, and only 50% of the beds from the hospitals are occupied by normal patients. so, the reserve of https://ourworldindata.org/coronavirus l. corbetta et al. 6 covid patients have been 50% of the whole hospital capacities in germany. from march 13th, we didn't allow any visitors in the hospital and any patient who entered the hospital have had to answer a couple of questions. if they have contact with covid patients, if they're coming from a risk area, and we measured all patients' fever from the beginning. in the case the patient developed fever, they were directly transferred to covid unions that have been received this way. a couple of additional reasons why germany is quite successful at the moment to handle covid-19 is the handling of its hospital beds. again, this is a comparison. japan and south korea, they even have more hospital beds for people in their country, but when you compare it to the other european areas and also to the united states, we have three times more hospital beds than the uk has. so, the capacity for the hospital is bigger than in other areas. also, not looking at hospital beds, looking to the icu beds, we have more icu beds per inhabitants compared to other areas in the world. so, therefore, the hospital capacity is quite high, so we were able to handle the patients maybe in a better situation than perhaps the colleagues in north italy, or in france, where they really reached the limits of what the hospitals can offer. https://www.destatis.de/ i put the data up, measured at march 2020, when the peak really came. in germany, we really have the opportunity to do a lot of pcr tests. so, actually, we're doing about 300,000 pcr tests per week in germany. so, that might be that we're detecting more patients at an earlier stage. this is one explanation from me why we have had, from the beginning, a low mortality rate, that we have a huge capacity for pcr tests which allow us to even offer tests to patients with mild symptoms. this is also one of the major reasons why we still are lucky with the mortality rate. a couple of days after the shutdown, we opened so-called drive-in testing. so, patients were able to come to bigger areas. they just opened the window of their car, we did the swab, they got a qr code and we sent the test result from the patient data to the qr code of the patient. but the contact between patient and medical-healthcare providers have been very limited. see, this is one of the pictures from our drive-in testing. so, we offered a lot of testing, even not inside the hospitals what we also did, we established so-called corona taxis. we are knowing that the patient has a positive swab and, often, quite mild symptoms, but we're knowing that seven is the critical day, so all patients would be sent home. home quarantine have been visited by a doctor at the five and six. we measured, at that time, the situation. we looked at a patient and in the case the patient developed symptoms, we directly hospitalised them. so, the corona taxis, which have been mentioned here in the new york times, have been quite successful to identify mild patients who are on their way to getting a severe illness at an earlier stage, so we brought them into the hospital system and we started the treatment with various medication. so, last slide. this has been the first wave of germany. you see, this is our timeline, this is the actual data. so, it looks like we survived the first wave-, actually, we're doing similar things we just heard from paolo. we're giving a lot of recommendations and a lot of information to the population, and we're hoping that the second wave, if a second wave appears, would be a little bit smaller and hopefully the germans can handle their patients in the way we handled the first wave here in germany. thanks for your attention. jing li: thank you. thank you very much for this explanation of the germany strategy on the prevention and treatment of covid-19. you introduce the prevalence of covid-19 and even the icu and administration. very impressive. also, the mortality rate is very low in germany in a tight line. also, you have some very successful strategies for the patients administration in the hospital and also the icu bed capacities. it's highest among the european countries. also, the testing's available in every way. yes, very https://www.destatis.de/ stand on the same side preventing a second wave of covid-19's outbreak 7 impressive. thank you very much. then we go to the next speakers, professor javier flandes. he's the director of the bronchoscopy and interventional pulmonology unit and section head of pulmonary medicine. university hospital foundacion jimenez diaz in madrid, spain. president of the spanish association for bronchoscopy and interventional pulmonology. also, he is the governor of spain american college of chest physicians, association for bronchology and interventional pulmonology. he's going to give us the topic on how to manage people under investigation and probably covid-19. javier flandes: okay. good morning. thank you for inviting me to do this webinar. my topic is about the management of patients with suspected covid-19. in the initial part of my lesson, i want to show the management of the programme to any potential suspicious cases. this is the situation during the lockdown period, which started here in spain in march and has been extended to the 9th may in spain. madrid is the region with the highest rate of infections in all the country. i want to show you, the differences inbetween countries. sorry, i don't put germany. that's a pity, because germany is very successful in their position. but it's very similar, the curve that we have, in italy. in spain, and also the united states with a different plateau. it is very different from the chinese curve, and also we can discuss with dr guo this point of view. we can see the new cases per day in the time. this is data from spain. it's very bad. it's worse than other countries. but we are very similar to italy, as dr paolo bonanni showed us. we have, now, at this moment, a total-, in the blue line, you can see the infected patients. more than 200,000 patients. in the grey line, you can see the patients who are recovering. more than 100,000. in the black line, deceased people. about 23,000. the data is very similar to italy. but i have this data from spain about the mortality rate of coronavirus by age group. people older than 80, the mortality is about 2021%, all these people will die. we count a cut of-, in people older than 70 years old, they have a high possibility to die with this disease. unfortunately, we have a special situation is the infection of the healthcare workers, and spain is the country with the highest number of healthcare workers infected. we have now, at this moment, more than 40,000. in italy, i hear now, from my friend, the number is 20,000. it's twice. the nurses are 60% of all the affected healthcare workers. but, apparently, this result is because we started our country with all the indispensable safety issues. we are overflowing facilities and we are not prepared for this pandemic. focusing on the main topic of the lesson, one question comes out. do all patients need to be tested? well, today, the agreement is, we need to sample all the patients with suspected infection with moderate or severe symptoms. and also, of course, all the patients are witnessing that is the rule. these are their symptoms. but, in the case of the patients without any risk factors, without co-morbidities, they don't need to be hospitalised. patients have to take an active role in their treatment and follow carefully an indication of healthcare authorities. we must perform pcr test, regardless of when the symptoms have started and, of course, at least twice. when the pcr test is negative, we need to consider testing from another respiratory-tract site. but, in this moment, we can question the role of the bronchoscopy. the bronchoscopy has four indications. but, when it's possible, we need to avoid the bronchoscopy procedures and i think it's a paradox because, apparently, madrid is the place where we perform more bronchoscopies in the world to the covid patients. only in my institution, we perform more than 500 bronchoscopies in the icu for covid patients. but in some situations, it's mandatory. definitely, in the journal of thoracic disease there's the indication of the bronchoscopy procedures in five steps. emergent, urgent, acute, subacute and elective. this group permit to organise in their timing for a schedule. but i think, and i prefer the suggestion, the presentation, the stratification made by the american association for bronchology and ip. in patients with suspected or confirmed covid infection, they separate in three groups. emergent bronchoscopy, people with severe or moderate symptomatic tracheal or bronchial stenosis, airway obstruction, massive haemoptysis or a stent that's migrated. urgent bronchoscopy, oncology indication, whole lung lavage and also foreign body aspiration. stratification bronchoscopy procedures emergent bronchoscopy urgent bronchoscopy non urgent bronchoscopy severe or moderate symptomatic tracheal or bronchial stenosis lung mass suspicious for cancer mild tracheal or bronchial stenosis symptomatic central airway obstruction (endotracheal or endobronchial mass or mucus plug) mediastinal or hilar adenopathy suspicious for cancer clearance of mucus massive hemophysis whole long lavage high suspicion of sarcoidosis with no immediate need to start therapy migrated stent foreign object aspiration chronic interstitial lung disease mild to moderate hemoptysis detection of chronic infection (mai) suspected pulmonary infection in immunocompromised patients chronic cough tracheobronchomalacia evaluation bronchial thermoplasty bronchoscopic lung volume reduction l. corbetta et al. 8 most of the procedures are performed in the icu units with patient under medical ventilation. this is our situation in our hospital. we perform about 95% of the bronchoscopy in the icu and only 5% in the bronchoscopy suite, at this moment, in the last six weeks. for the diagnostic purposes, we've had three indications. first, when an alternative diagnosis is suspected. second, in case of an infection. three, in neoplastic scenarios. generally lavage should be avoided in severe patients because it could it can be worse. weeks ago, this article appeared in respirology (colt h, april 11, 2020) is summarizing the recommendations for different medical associations about bronchoscopies, in this period of pandemia. i think we can consult the protect measures for the patients and the doctors, but in general, it's more about the personal protective equipment that we use. answering the question of where to place the covid patients, we can see symptomatic positive patients, so they would be hospitalised of course, in isolation rooms. also, patients with a negative swab but high-clinical suspicions should be admitted like covid, also in the same area. the treatment, you have no definite treatment. also, supportive depends on the state of the infection, but there is no definitive therapy. finally, about the antiviral therapy, if there are different therapeutic treatments, it depends on the hospitals. or it depends, also, on the countries. but the only drug that we say is the antivirus. we must use it as soon as possible, in the early stages of this disease. that's all i have. thank you very much. jing li: thank you for your talk. very interesting cover from the pre-runs to the indication the testings and the decision to certain kinds of patients in the hospitals and pcr testings. also, your indications for the therapeutic and diagnosing, safety considerations of bronchoscopy in covid-19 patients. also, you mentioned some treatment and support of antivirus for covid-19 patients. very interesting talk. then, we go to the next one. now, for professor lorenzo corbetta. lorenzo corbetta is an associate professor of respiratory disease in the university of florence. he is also a director of the educational programme in interventional pulmonology. also, he is the scientific and website director the european association for bronchology and interventional pulmonology. he is the national regent of the association of bronchology and interventional pulmonology. he's going to give us a talk on the risks and benefits of aerosol-producing procedures in the area of covid-19. lorenzo corbetta: thank you very much, professor li jing. good morning to everyone and good evening to our chinese and asiatic colleagues. this is florence, now the squares are completely empty under the lockdown. after 4th of may, we will unlock, but only the manufacturing companies, but not the museums, churches and shops. they will be closed. so, the landscape will remain the same for the next month. much of the information i will show comes from the statements of the main associations, mainly british thoracic society, american academy, who, chinese statementthat was their first one. the most recent is the statement from the society for advanced bronchoscopy and they are all posted in our website on the european association of bronchology and interventional pulmonology (eabip) where there are other updated articles. the last one is also in italian, the aipo position paper. but my presentation will follow the true story of our colleague, mp from overseas, 50 years old, interventional pulmonologist like many of us, with no co-morbidities and he tells his story in a social network. for some reason, he went to work last tuesday morning as https://eabip.org/ stand on the same side preventing a second wave of covid-19's outbreak 9 usual, he did what is considered a high-risk bronchoscopic procedure on a patient with lung cancer. this is considered a high-risk procedure, because the procedures generate aerosol. but, we have to do it, because unfortunately cancer doesn't seem to care about a pandemic. it's very dangerous, this procedure, because it generates small particles, smaller than ten microns. the aerosol that reaches down lungs with the covid-19 produces pneumonia and more. not only bronchoscopy but also tracheotomy and aspiration, lung aspiration are very risky. but, our colleague did the right thing because we know that we have to reduce the number of bronchoscopy, but as flandes showed before, there are some emergent, urgent and acute diseases that require a bronchoscopy in few time and what is recommended by the society for advanced bronchoscopy is within two weeks. so, he did a bronchoscopy for a patient that can't wait. and he told in his story that his hospital provided all the proper protection. what are the proper protection, appropriate protection? they are recommended by the who since 19th march, that is a complete protection, like you can see in this picture of one of my colleagues. and in every aerosol generating procedures performed on covid-19 patients, not only but also suspected, we must wear respirator n95 or ffp2 better, ffp3, gown, gloves, eye protection and apron. and better, especially in some procedures, like bronchoscopy, powered air purifying respirators. because they protect better and they are more comfortable because avoids breathing resistance, suffocation and moisture. powered air purifying respirators (papr) a papr is a battery-powered blower that provides positive airflow through a filter, cartridge, or canister to a hood of face piece. advantages of using a papr kit during covid-19 pandemic:  most of the papr kits use hepa filters which give a greater level of respiratory protection than n95 masks.  extremely useful for doctors who are performing prolonged surgical procedures and health care workers posted in covid19 isolation areas as it avoids breathing resistance/suffocation and moisture build up associated with using n95 mask along with goggles/face shield.  provides head and neck protection. approved for people with facial hair and it does not require fit testing because of a full hood. but our patient, when arrived at home that evening didn't feel right and he had a fever and short of breath. so, he called the infectious disease colleague, who recommended to go to the er. he said goodbye to his wife and his daughter and this is a very sad situation because, in this situation, there are no visitors allowed and sometimes it's the last time that you can say goodbye to your family. this is very, very sad so, so being he a doctor, he cried all the way to the er in his car. in er, the shortness of breath got worse and he had a nasal swab for covid-19, that was negative, he had a ct scan and was moved to the icu because of the concern for possible quick decompensation that, in covid, is very frequent. the infectious disease colleague considered some strange l. corbetta et al. 10 infectious disease being swab negative, like, for example, malaria, brucellosis, leptospirosis and others, putting him in treatment with the doxycycline. he did another swab and that was negative again. but despite two negative tests, he remained in isolation as we know there are many false negative tests and the clinical situation was very suspected for covid. the question is, is it covid? what other test do we have to do? we know that the swab is the primary and preferred method for diagnosis and we know that a bronchoscopy should have an extremely limited role in diagnosis of covid-19 and only be considered in intubated patients and only for upper respiratory symptoms where negative and if other diagnosis considered that would significantly change clinical management. but we know also, that it's more sensitive because this study demonstrated 93% of positivity versus 63% of the nasal or pharyngeal swabs 32%. in this study, sars-cov-2 was detected in specimens from multiple sites of 205 patients with covid-19, with lower respiratory tract samples most often testing positive for the virus (93%). the original article can be found here: https://jamanetwork.com/journals/jama/fullarticle/2762997 and another study, demonstrated that endotracheal aspiration from the deep lung had demonstrated an higher viral load in every phase of the disease and persisted more than nasal swab. the link to the original article is: https://www.atsjournals.org/doi/10.1164/rccm.2020030572le. for this reason, the guidelines said that, as flandes showed before, although bronchoscopy has to be limited, it has potential diagnostic indications but the recommendations are very generic. additional testing patient with suspected covid-19 is very, very generic after negative nasal swabs. this slide is in italian but you can understand that in our hospital, we perform bal for the diagnosis of covid only after two negative swabs and indeterminate ct scan. if you have typical ct scan, also after two negative swabs, we consider the patient as positive. and our patient, our colleague, fortunately he was feeling better after three days but because there is still a very rare possibility of having covid-19, he had to be quarantined for two weeks. he asked himself, do i have covid-19? he doesn't know and we don't know, he maybe close to 50/50 and also, the antibody testing doesn't resolve the problem, doesn't answer it. and the problem is that he had no symptoms before the fever and he was at work with colleagues and patients. so, this is the story, now our colleague is better, this is the story of a colleague like us that performed bronchoscopies every day. so, we have to consider this and the recommendation for performing bronchoscopy procedures during covid-19 are now, for the moment, that bronchoscopy is not considered as a diagnostic modality for covid because the primary preferred method is the nasopharyngeal, oropharyngeal swab and sputum analysis. and we have to evaluate the need for bronchoscopy in every bronchoscopy that we perform. better to perform bronchoscopy procedures under general anaesthesia and not awake or under conscious sedation in order to limit the dissemination of aerosols. for this, some tricks recommended by the chinese thoracic society are to ensure that the patient wears a cap that also covers the eyes. place a suction catheter in the patient's oral cavity, cover the patient's mouth with a surgical mask and if the patient is ventilated, use the access port to limit the production of circulation. precautions provided by the chinese thoracic society for bronchoscopy to avoid aerosol spreading during bronchoscopy:  ensure the patient wears a cap that also covers the eyes, place a suction catheter in the patient's oral cavity and cover the patient's mouth with a surgical mask.  use the access port in the patient's mask/the mount during noninvasive/invasive mechanical ventilation. see also: https://www.ers-education.org/publications/europeanrespiratory-review.aspx it's mandatory to use a disposable bronchoscope, especially in an icu care setting and also to use a sampler that's easier to use. again, perform the bronchoscopy possibly in negative pressure isolation rooms, minimize the staff for bronchoscopic procedures and avoid training fellows, at least in this period. and personal protective equipment should be used and it's very important donning and doffing protocols, especially doffing protocols. standard disinfection for all equipment and be careful during the rigid bronchoscopy and better to wear a powered air purifying respirator kit and be wise in choosing any bronchoscopy procedure. thank you very much for your attention and i hope to see you soon for the next webinars 19th may and 29th may, focused on diagnosis and treatment of covid-19. thank you very much. jing li: thank you professor corbetta for your very interesting story and come up to the introduction of the guideline for the bronchoscopy in covid patients and also https://jamanetwork.com/journals/jama/fullarticle/2762997 https://www.atsjournals.org/doi/10.1164/rccm.202003-0572le https://www.atsjournals.org/doi/10.1164/rccm.202003-0572le https://www.ers-education.org/publications/european-respiratory-review.aspx https://www.ers-education.org/publications/european-respiratory-review.aspx stand on the same side preventing a second wave of covid-19's outbreak 11 your emphasis, the indication and also the strategy and safety procedure to perform bronchoscopy, thank you very much. and then, we come to the next speaker, professor mohammed munavvar. professor mohammed munavvar is a consultant, chest physician, an interventional pulmonologist and works in the lancashire teaching hospital. and he's also the honorary senior lecturer in university of manchester and also he's the president of british thoracic society, president of the european association of bronchology and interventional pulmonology. he's going to give us a talk with the topic of how the thoracic societies could lead the political position. now professor munavvar, please. mohammed munavvar: wonderful, thank you so much dr li jing, dr shiyue li and the organising committee for inviting me to speak here today, it's an absolute delight, a pleasure, an honour to be here and interacting with so many friends and colleagues from around the world including lorenzo, javier, felix. the title of my talk was slightly amended a couple of days ago by lorenzo, so i'm showing you the up to date title and in my ten minutes that's been allocated, i'm going to give you a very brief introduction. spend some time with regard to education, statement and guidelines, focus more on research and therapeutic trials and spend a minute concluding my presentation. that's the plan. first of all, i do not have any conflict of interest with regard to this talk, my primary job is with the lancashire teaching hospitals in preston in the uk although i work with a number of other organisations, including bts, eabip. so, in the uk we've been hit very hard by covid, as we've seen, colleagues in italy, spain, france, us and many other countries. as of yesterday, we've had 161,000 positive cases and very sadly we've lost more than 20,000 patients in the uk. the total number of cases has been going up although we are now seeing, fortunately, a slight flattening of the curve, thanks to the lockdown and various other measures. as javier mentioned, unfortunately, there have been a high percentage of infection amongst healthcare workers, one particular study from the health service journal showed that more than 100 healthcare workers unfortunately passed away as a consequence of covid. our thoughts and prayers are indeed with each and every family that's been affected, not just the healthcare workers but around the country. so, moving to the next part of my talk on education, statement and guidelines, when this whole saga of covid started, there was a great deal of confusion as to how we deal with this new disease. what do we do in specific situations related to covid? and at british thoracic society, our main ethos is to work on high quality educational reviews, guidelines which can then be disseminated widely throughout the world, free of cost. and a whole machine of people, a whole team of people sprung into action and have produced, in a matter of about twenty days, what would have taken several months to create. that is a whole lot of statements and guidelines, trying to review literature and producing consensus statements and this is not just respiratory. we will see everything from oxygen use to lorenzo and javier spoke about bronchoscopy procedures, guidelines. plural procedures, critical care, pulmonary rehabilitation, also venous thromboembolism in these patients, acute kidney injury in these patients, so unique problems that have arisen during this devastating pandemic. so, all of this is available to you on the british thoracic society website, free of cost and besides all these collaborative work, we have also worked with nice, national institute of clinical excellence, nhse, royal college of physicians and a host of other organisations to produce collaborative documents, guidelines to assist people at the frontline to be able to provide the bets possible care for these patients. there's a whole team and i'm enormously grateful to every member of bts who has contributed, including the bts board, the council, the specialist advisory groups, some renowned professors like wei shen lim in nottingham, the team behind bts and the headquarters. all of them have worked 24/7 and remember that many of these respiratory physicians and the bts, also are working day-to-day in the covid wards, they are at the frontline providing care to these patients. a very simple statement which was produced, which is unique, i wish to highlight, and this is the brainchild of our chair of bts, professor john bennett from glenfield hospital, leicester and this is called spaces. this is totally unique, where a simple concept, sharing patient assessments cuts exposure to staff. javier highlighted the 20% incidence of infection of our healthcare workers and this very simple principle that john initiated, where any healthcare worker, irrespective of their grade, attending to a patient suspected or proven covid would then check everything that there needs to be checked rather than duplicating assessments and also, looking at possibility of remote consultations, phones, ipads, two way radios, intercoms etc. so, this is, i think made an enormous difference and has been disseminated throughout the world. education and guidance is at the top of what we do at bts and you will see, only a couple of days ago, our deputy chief executive, sally welham, informed me that over 200,000 documents have been downloaded from the bts website, over 100,000 page views of covid-19 guidance and a lot more. so, please do visit our website and make use of the documents that people have put together with so much effort. okay, so moving to the second major part of my talk, third rather, is i'm going to focus on research and therapeutic trials. if you type in covid-19 studies on the database, on the who database you will see that there are about 915 studies and increasing every day, going on throughout the world, scientific studies. and if you type in on pubmed reference, there are more than 7,000 manuscripts that have already been written. however, there needs to be a coordinated effort to get robust evidence, systematic studies with systematic literature. the uk government pumped in millions of pounds, inviting applications for grants a couple of months ago, and as a consequence, a number of studies have been started in the uk, more than twenty major studies. simple ones like principle, which is in primary care, the use of l. corbetta et al. 12 hydroxychloroquine to reduce hospitalisation and eventually expedite recovery, to vaccine development. you might have heard, vaccine development is the flavour of the month and last week, a couple of volunteers have already been injected with a new trial coronavirus vaccine at oxford. we await the results with excitement, although unfortunately that's going to take quite a few months before we see any result. a number of other areas are also being tested, such as plasma transfusions in covid and a huge number of other studies which are taking place, besides vaccine development, therapeutic trials, prophylaxis among healthcare workers, a very adaptive platform of remap cap trial in intensive care. recovery, which i hope will be a landmarkstudy and i'll come to that in a minute. therapy development, antibody testing, population surveillance, behaviour and policy research, virology, transmission and mathematical modelling and a lot more. i just want to spend a few minutes describing the recovery trial, this is a randomised evaluation of covid-19 therapy, initiated from oxford, this is the chief investigator, professor peter horby, we must congratulate this team for coming up with this idea. and this is, again, a very adaptive trial because they started off looking at people, patients who were eighteen years of age who are admitted to hospital, proven or suspected sarscov-2 infection and divided them and separated them, randomised them in a two is to one is to one is to one fashion. no additional treatment, just standard supportive therapy. lopinavir-ritonavir, which is, as we know an anti hiv drug. low dose dexamethasone steroid. hydroxychloroquine. subsequently azithromycin was added. the idea, the outcome was primary outcome of 28 days of all-cause death, secondary outcome of duration of hospitalisation, need for ventilation and need for renal replacement therapy. as the recruitment has progressed, i was pleased to hear that more than 7,500 patients have been recruited. under normal circumstances in any other study, this would be a huge number and would be called a success, yes it is a success, but because, if you look at the fact that we have multiple arms in this study, we need (tc 01.20.00) many more thousand patients and these studies taking place in multiple centres across the uk. congratulations to every single site who are actively recruiting, including ours, there's a lot more to do, many more thousand patients need to be recruited before we can draw meaningful conclusions. recently, a second randomisation has been added to the study wherein, if the patient becomes hypoxic or deteriorates with regard to inflammatory markers, despite the first randomisation and treatment, the assumption is that you might be heading towards a cytokine storm and therefore an anti-il6 inhibitor, such as tocilizumab has been introduced. again, as a randomised fashion, randomisation with control, for each of these arms. the outcomes will be mortality at 38 days and need for ventilation. as i mentioned earlier, that is going to be a massive trial and i think will hopefully be a game changer in the field of covid treatment. i just want to briefly mention my own hospital's involvement. there's a very dynamic research team, clinical research facility who have been working round the clock with a number of studies, and this number is going up every day. more than 400 patients have been recruited. a number of local studies also being planned including immunity levels and antibody testing among healthcare workers, recovery trial is certainly up and running in our hospital at the preston lancashire teaching hospital. i'm very grateful to each and every person at lancashire teaching hospital research department who are involved with this. so, in conclusion, what is the future plan with covid? we spoke about another wave, pandemic, flattening of the curve, further low incidence with waves, are we looking at number of waves? or are we moving to an endemic phase? we have all got to be vigilant and do not take the foot off the pedal. we will also have to restructure, adapt, reorganise services, both in the hospital and primary care. we'll have to progressively, we've already started this, progressively move to digital healthcare, telehealth, minimise face to face consultation, everybody coming to the hospital or any interaction will need to be tested, screened, isolated prior to any intervention as lorenzo and javier have eluded to. maybe we need novel, quicker methods for assessment, including non-invasive methods, speedy, accurate tests, effective tests, even therapy will need to be planned on a remote basis. virtual pulmonary rehabilitation has been started. but research is going to be pivotal to our success in the war against this condition. vaccines, without a doubt, but what about prophylaxis for these patients? what about effective therapy? i've mentioned one trial but there may be similar trials around the world that will help. but more than ever before, we need to have a truly collaborative approach across borders, across countries and continents and fight in a collective, consistent fashion because the reality is, nobody is safe until everyone is safe, with regards to this condition. we need to make the dream come true to overcome covid. many thanks indeed for your very kind attention. take care, stay safe, stay well, god bless you, hope to meet you again. jing li: thank you professor munavvar, very sophisticated talk on the introduce the strategy of the treatment and prevention and future challenge that we face. also you introduced a very nice clinical trial and research carrying on now in the uk, very, very nice talk. yes, maybe we need to discuss the topic later and very impressed with your statement that no one is safe until everyone is safe. yes, very nice. okay, now we move on to the next one, professor li qiang, he's the director of respiratory department and chief physician. professor, doctoral supervisor and he's also director of world association for bronchology and interventional pulmonology and he's a member of chinese thoracic society and also the deputy director of interventional pulmonology group of chinese thoracic society and also the standing committee of committee of minimally invasive therapy in oncology, okay? and he's going to give us the talk with the topic of application of mesenchymal stem cells in the treatment of severe covid19 patients. now, please professor li. stand on the same side preventing a second wave of covid-19's outbreak 13 qiang li: okay, thank you the professor li jing and many of the old friends, the professor herth and professor corbetta and professor guo and professor shiyue how are you? today, i would introduce my recent research for the use of stem cell, it's the element that would treat the covid-19. now, i want to invite my colleague, dr wang na to introduce that. na wang: right, it is my great honour to have this opportunity, give us all the lecture about the mesenchymalstemcell therapy for covid-19 pneumonia and first i would like to introduce our hospital first. the shanghai east hospital is located in the lujiazui pudong new area, which is very developed nowadays and we have two major campus, one is lujiazui and the other one is world expo in campus of our hospital and we are very welcoming for all of our friends including all of the professors today, coming to our hospital and sharing, and exchange different thoughts and experience based on both pulmonology as well as critical care medicine. so, today we're going to take about viral sepsis and ards secondary covid-19 cases and also we would like to talk about the current situation of mesenchymal stem cell therapy in terms of the covid-19 disease. and also, we would like to share some of our own experience in the treatment of mesenchymal stem cell. first i would like to share two of the studies which was run by professor bin cao from china, these two articles were published in march, they shared the data about the risk factors and also some epidemic characteristics, based on the large patient population. the data showed that around 15.7% patients would develop to severe cases and among them, the mortality was over 50% among the patients. and also, several risk factors associated with ards, including elder age, over 65 and higher fevers, and also on the risk of factors (inaudible 01.29.54) associated with that score and the higher level of d-dimer. so, and also, this is another article shared (tc 01.30.00) about the complication of covid-19 as we saw that sepsis is one of the most common complications and the second one would be the respiratory failure and ards. and followed by heart failure and septic shock, also including coagulopathy. this slide shows the time course about the covid-19 disease's evolution. we saw that, on average, day nine and ten, people can develop sepsis and after one or two days, the ards would come out. so, we found, the data showed that the ards always happened after the sepsis onset, so we think about them. maybe this ards was secondary to the sepsis, and also, as shown in the lower chart, among the known survivors, we saw that after the sepsis and ards onset, there were several secondary organ dysfunctions including kidney and cardiac injury, secondary infection, as well as even death. and in terms of the current management strategies, we have several medications talked about a lot, including remidesivir, hydrochloroquine or arbidols but actually, on all these medications are showed a limited get us support in the treatment aspect. and also, for the corticosteroids, which is recommended in our chinese guidelines with a low dosage within the short term usage to suppress the inflammatory reaction, and there were several traditional medicine. and beside the medications we have several respiratory support, including oxygen therapy, high flow and nppv and mechanical ventilation and ecmo. but actually, there were no very promising treatments, so we were thinking about, how can we modulate the viral sepsis to prevent the disease progress of covid-19? we came up with an idea about the mesenchymal stem cell therapy so, i would like to talk about it. current teams in china, we have four teams, the biggest, which is led by professor wang fusheng from pla medical center. and the second is led by professor zhou qi from harbin medical university and also, zhao chunhau professor from shanghai university. and the fourth one is our team, headed by professor liu shongmin and li qiang. this is a review article about mesenchymal stem cell, talking about how it works in the covid-19 treatment. msc could release cytokines and have some immunomodulatory effect, it can suppress the inflammation reaction and stimulate the recovery process at the same time. as a result, it could protect the alveoli epithelial cells, reclaim the pulmonary microenvironment and can prevent the pulmonary fibrosis as well as cure the lung dysfunction. this is a recently published article from zhao chunhau's team on the agent and the disease. they talk about the transplantation of ace2-negative mesenchymal stem cell. they enrolled ten patients in total and three of them were assigned to the control group and the seven of them were assigned in the treatment group and the result showed that, this is the mass cytometry profile about them, plus more cell properties. we can see that, let's say, the right figure, this is we're seeing in normal people. different part of the cells were marked as different colour and labelled as different numbers. this is from the normal people, and the left two figures were covid-19 infected patients. before the treatment of stem cells, we found that several clusters of cells, such as cd4 and cd8 t cell and k cell and endocentric cells, which were marked as purple, blue and brown, were overreacted in our blood. then after the stem cell therapy, all these overreacted immune cells subsided and the other part of the normal cells increased after the treatment. as we can see, the different colours shown in the left figure. and for the immune cytokine levels, we saw that for the some anti-inflammatory cytokines, including il-10, vegf and ip-10, which were increased after the stem cell treatment and for tnf alpha, which is known as the pro inflammatory cytokine, was decreased after the treatment. now, we think about, how is the safety and efficiency of mesenchymal stem cell therapy in the treatment of severe covid-19 patients? so, we came at this idea and started all the preparation process in early february, including study design, cooperation, irb approvement, sort of, like this. but actually, due to the limited patient population in shanghai, we actually have less than 300 patients in total in shanghai, we don't think that's sufficient for us to recruit in this study, so we decided to move to wuhan and are recruiting patients there. so, we left shanghai and headed to wuhan or march 5th. i l. corbetta et al. 14 would like to show you several photos of our team and this is professor li and this is professor li, this is our whole team, we have eight physicians together, including pulmonary department and radiology department as well as pharmacology department. but initially, after we arrived at wuhan, there were several issues that we've met, first, most of the critical patients, they have already lived through the acute inflammatory and the cytokine storm stage and most of the patients are already in the recovery process of the disease. and also, a lot of patients present as different severity of pulmonary fibrosis which present as dyspnea and decreased exercise capacity, clinically. here are some ct scan features shown up on our patients, we can see there was a predominant pulmonary fibrosis, noticed in the recovery process. then we were thinking that, how can the mesenchymal stem cell help with the recovery process? this is also a review article that showed that msc may have many therapeutic effects on the fibrosis, based on the different mechanism, including immunomodulation and decreased inflammatory reaction and anti-apoptosis and scarring effect. on the other hand, it can stimulate angiogenesis and chemotaxis, which are pretty critical in the tissue recovery progress. so, we made our protocols, we decided to give the umbilical cord mesenchymal stem cell on day zero, day five and day ten, for three times in total, with a dosage of one times six power of ten per kilogram and through the iv line within one to two hours. before the infusion of the cells, we used a promethazine for prophylaxis of the allergic reaction and the follow up date will be day fifteen, 30, 60 and 90. and we would like to observe several parameters including the pef ration, inflammation status, ct chest or ct evolution and also symptom improvements which was measured by the mmrc score and the fatigue score. for the safety aspect, we collected if there were any adverse effect onset, how's the liver enzyme level, as well as a creanine level as for the kidney function and the d gamma level for coagulation function. we start our first case enrolled on march 5th, in the first week we have ten patients in total from wuhan sixth hospital and from the second week we have 36 patients in total from wuhan taikang tongji hospital. and after almost 30 days, on march 30th, we moved back to shanghai. here are several photos during our study process, this is the moment we were enrolling our applicants based on the criteria of selection and execution. and this is the moment professor li and the faculty of the hospital, they were talking about the protocols as irb discussions with the hospital. and this is the moment before we go into the critical care unit and the quarantine ward to give the patients the stem cells. this is our stem cell, and this is the moment we were rounding with the patients. so, for the baseline characteristics of our patients, we have nine patients assigned in the control group and eleven patients had only one infusion of stem cells, and ten patients had two times and sixteen patients have three times together. and for the parameters including gender, age, allergic history, surgery history as well as medication history, there were no differences noticed among these groups. next we, about the results, first we analyzed the safety about the msc treatment, there was no significant differences between the control and experimental group, along with the time course, including d-dimer, creanine level, ast and alt level which means that there was no significant change in the liver, kidney function as well as the coagulation. and as for the inflammation status, we compared the crp level between these two groups and also, we didn't notice any differences. next, we collected the mmrc score and the fatigue score according to different symptoms and signs of our patients, we can see that, along with the time course, all these q scores were decreased but no differences was noticed between these two groups. we also compared the pf ratio to assess the oxygenation function of our patients, the data showed that, compared with the control group, the pf ratio was significantly improved seven days after the treatment of msc. the p value was less than 0.05. we also compared the lymphocytes and the neutrophil levels before and after the stem cell treatment and also, we didn't find any significant differences between these two groups. as for the ct scan features, we used a ct score calculation which was published earlier for the assessment of covid-19 severity, compared with the control group, the ct score was significantly improved seven days after the treatment and p value was less than 0.05. here i would like to show you several of the ct scans, this is one of our patients in our team, we've had the ct follow up on march 13th, 22nd and 27th, we saw that there's significant improvement on pulmonary fibrosis. so, for our conclusions, we firstly found that msc therapy had a greater safety, including liver function, renal function and the coagulation change and we found that msc (mesenchymal stem cells) therapy might have the therapeutic effect for severe covid-19 patients, based on the improvement of pf (pao2/fio2) ratio as well as the ct (computed tomography) scan evolution. but there were also several limitations of our study, first, most of our patients were under the recovery process in pulmonary fibrosis, the change of the inflammation stage was a lack of our study. and second, we just had a very short term follow up, as long as less than 30 days. we still need the more long term data to have a better conclusion of our msc therapy. so, the highlight of our speech today, there are several studies that show msc might have the potential role in the modulation of inflammation during the acute stage of covid-19. there were several academic clinical trials running in china and though our study mainly focused on the anti-fibrous effect of msc in covid-19. and there were very limited data that showed the relative promising results of msc, in terms of the inhibition of inflammation, improvement on both clinical symptoms and the ct features but we do need a long term follow up and analysis to have a comprehensive conclusion of msc therapy. so, this is pretty much our lecture today. thank you for all your listening. jing li: thank you very much for your very clear introduction of your clinical trial as i can say, of the application of the mesenchymal stem cells in the treatment stand on the same side preventing a second wave of covid-19's outbreak 15 of severe covid-19 patients and the design and the location of the patients, and the observation of efficacy and the safety of this kind of treatment. we look forward for your further, comprehensive results. now, we've finished with all the talks and then we come to the discussion and i would like to invite professor corbetta and to join me to chair the discussion. lorenzo corbetta: yes, thank you, unfortunately we have no time, because our connection lasts until 2:30pm. we have a lot of questions but we can answer all of one or two questions. the other will be posted on the website, we and answer in the next video conferences. one question that is repeated, i share with you, is if the temperature and the hot season will change the viral answer of the covid. if you have experience in china where you had these changes of climate? shiyue li or professor guo? shuliang guo: i will try. i will try. this is a question for america this morning, for california, and in my opinion, there is no proven evidence to support the temperature effect on the covid and these worries. in a research from hong kong university, they are comparing the temperatures, different temperature and humidity effect on the various symptoms. they found when the temperature reach to 68 degrees, the virus will be active less for than five minutes. however, when the temperature is between 22 to 25 degrees, with humidity of 40% to 60%, the virus will survive longer than 14 days. but this is research involved with sars but not sars-cov-2 and another research from hong kong university is they're using temperature up to 70 degrees and the virus has been killed quickly. we need more evidence, maybe after this summer we can get some answers and we need more laboratory simulation to make sure. and for clinical practice, as we know, the patient, the confirmed patient in the southern hemisphere is smaller than those in the northern hemisphere, for example, the patients in australia, indonesia and new zealand is reported as only around 10,000 per country so maybe a large indicator shows the higher temperature has slowed down the transmission of the virus. however, this data should be due to the, maybe, the poor testing conditions. so, we need more data to make clear, okay, thank you. lorenzo corbetta: okay, we have hundreds of questions and i ask you to answer to them in the next time, the next days i can send you and we will post on the website so we can give the answer to our connections. so, i invite you, all of you, and the other people to the next video conference on diagnostic tools for the screening and diagnosis of covid that will be happening on 19th may and the other on treatment for intensive care and pharmacology treatment and clinical management on 29th may. i thank all of you and i hope to see you soon in the next video conferences, thank you very much. l. corbetta et al. 16 1 citation: f. bagnoli, d. lorini, p. lió (2020) modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios. substantia 4(1) suppl. 1: 914. doi: 10.13128/substantia-914 received: apr 21, 2020 revised: jun 05, 2020 just accepted online: jun 11, 2020 published: jun 11, 2020 copyright: © 2020 f. bagnoli, d. lorini, p. lió. this is an open access, peerreviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative com mons attribution license, which per mits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia research article modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios. franco bagnoli,1,2* daniele lorini,1 pietro lió3 1 dept. of physics and astrophysics, and center for the study of complex dynamics, university of florence, sesto fiorentino, italy 2 infn, florence section 3 dept. of computer science and technology, university of cambridge, uk *corresponding author: franco.bagnoli@unifi.it abstract. the covid19 pandemic is distinct from spanish flu of 1918 from many aspects among which the contrast between the overabundance of worldwide exchange of information (infomedia) and the actual scarce knowledge of the pathogen and the infection mechanism. another important distinction is that the epidemics threaten society components, social groups, communities and jobs in very different ways and different death tolls. with this in mind, we start with simple models of pandemics and we drive the reader to more complex models that take into accounts social compartments and communities. the discrete-state models are built by adding elements, first in a mean-field approximation, then adding age classes and differential contact rates, and finally inserting the social group dimension. the novel element we insert is the effect of restrictions in contacts and travels, filtered by the risk perception, according with the growth of the number of infected or recovered people. assimilating risk perception with cognitive behavior, we obtain several coarsegrain scenarios, that can be used for instance to calibrate the level of restrictions so not to exceed the capacity of the health system, and to speed the post-emergency recovery. keywords. epidemic modelling, infection dynamics, risk perception, agent-based models 1. introduction the covid-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (sars-cov-2). (1) the virus is most contagious during the first three days after symptom onset, although spread may be possible before symptoms appear and in later stages of the disease (2). time from exposure to onset of symptoms is generally between two and fourteen days, with an average of five days (3). the infectivity of the virus is quite high, one person generally infects two to three others (4). at present there is no vaccine available. the infection’s outcome strongly depends on age. toddlers and teenagers get easily infected but are almost 100% spared from the effects: they are asymptomatic; youngsters (up to 39 years old), could mistype it as common influenza. people in their forties, could find it an ultra-tough influenza. older people may get pneumonia and could progress to multi organ failure (5) (6), especially in case of co-morbidity (7). figure 1 shows a representative death toll substantia. an international journal of the history of chemistry 4(1) suppl. 1: 914, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-914 http://www/ http://www/ http://www.fupress.com/substantia f. bagnoli, d. lorini, p. lió 2 distribution by age. due to the media coverage we may expect that the risk perception for the infection to follow closely this distribution. there is also a substantial ethnic difference, not related to biological factors. for example, african americans are dying in larger numbers than white people, particularly in many big usa cities as a result of differential access to medical care (for example mechanical ventilators). at the time of writing, it looks that the mortality is larger in those cities (and continents, such as africa) with an overloaded health system or with very low density of icus (intensive care units) as a result of decades of budget cuts or chronic lack of funding. many developed countries have population distribution largely skewed towards middle and older ages. from one side, older ages are correlated to higher probability of needing intensive cares, from the other middle and older ages need more frequently hospitalization in case of infection. the combined effects of these two factors, coupled to the limited number of hospital beds per capita results in severe limitations in handling the sudden spike in the number of covid-19 hospitalization. the infection initial growth curves for several countries at the date of 12 april 2020 are shown in fig. 2. the curves are influenced by the social (contacts) and cognitive behaviors of the groups. for example, elderly people often live together in halls and special structures and may be exposed to higher probability of contagion, unless special precautions are observed. on the other hand, as we shall see in the following, individual behavior (protective habits, avoidance of contacts) can deeply influence the evolution of the disease. the limited bed per capita capacity and the need for specialized nurses and doctors are significant drivers of the need to flatten the curve (to keep the speed at which new cases occur and thus the number of people sick at one point in time lower). one study in china found 5% were admitted to intensive care units, 2.3% needed mechanical support of ventilation, and 1.4% died (8). around 20–30% of the people in hospital with pneumonia from covid19 needed icu care for respiratory support (9). the extensive sampling of vo (10) shows that about 43% of infected people are asymptomatic and 17% needed icu recovery. it is noteworthy that the incubation period for covid-19 is typically five to six days but may range from two to 14 days. a fraction of 97.5% of people who develop symptoms will do so within 11.5 days of infection. this and the large number of asymptomatic infected make the counts of infected people extremely difficult. the occurrence of the intergenerational caring and the need pf protecting middle-age and elder people has urged the adoption of lockdown practices, thus causing an immediate arrest of the economy and industrial activities. the crucial point for the human species to return to the past lifestyle and avoid millions of deaths is to flatten the curve of infection. worldwide measures of restriction of contacts, which can take the form of compulsory or voluntary quarantine have been taken by national governs. the main criticism has focused on the rapid decay of national and world economies. another important factor is the self-restraint and selfquarantine, induced by the perception of risk of contracting the infection and/or of infecting others. it is noteworthy for instance that the first chinese patients in the spallanzani hospital in rome (the 30th of january 2020) always wore their masks (also before showing any symptoms) and did not infect any other participant of their journey through italy. similarly, in spite of the huge return to their families in the south of italy of people escaping from the forecasted quarantine in the north italy (around the 21st of february 2020), very few cases appeared in the south, possibly due to a self-imposed quarantine, or at least to a careful obedience to imposed restrictions. finally, the spreading of the virus in lombardy is mainly due to the concentration of ill people in hospitals without the proper isolation, a fact that corresponds also to a huge infection rate and mortality among the local medical personnel. figure 1. case fatality rates by age group in china. data through 11 february 2020. figure 2. number of confirmed cases aligned to the 1000th case (11). modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 3 models are needed to forecast the progression of the disease and the effects of countermeasures. most models are based on continuous dynamics, i.e., mean-field, as described in the section 2, with parameters adapted so to fit average data. however, such models cannot reproduce the sawtooth patterns seen in experimental data (see fig. 3), and in general do not include the explicit dependence of restriction measures with the progression of the disease. in many cases indeed the patterns in fig. 3 show a weekly oscillation, which however cannot be ascribed to insufficient data collection during weekends, since the oscillation are not so regular, they span several days and not just the weekend, and the subsequent peak (due to delayed report of data) are not evident. one possibility could be that data not collected/transmitted during weekends are incrementally passed to subsequent days till friday, but it is improbable that this habit be so widespread in the world. another possible factor is that there is a weekly contact pace, for instance due to work contacts, that diminishes during weekends and increases the infection rate during workdays. in general, the simplest infection model says that the infection can stop only if the average number of new infections per each infectivity individual should be less than one. given the bare infectivity probability 𝜏 (for the all duration of the infectivity period) and the average number of contacts ⟨𝑘⟩, in the absence of immune people, we have to reduce the product 𝜏⟨𝑘⟩ (better, 𝜏⟨𝑘2⟩/⟨𝑘⟩, which is generally similar to 𝜏⟨𝑘⟩ for uncorrelated networks (13)) to less than one. this can be done either using protective means (like masks, washing hands) which have the effect of reducing 𝜏, or isolation, i.e. reducing ⟨𝑘⟩. in any case, the pre-pandemic high connectivity of humans (implying both the number of contacts and the mobility) constituted an important factor for the spreading of any disease. it can be shown that for scale-free networks (that show a diverging second moment of the connectivity) the epidemic threshold (the critical value of 𝜏) is zero, i.e., no epidemics can be stopped without restrictions to contacts (13). the effects of the risk perception on the mitigation of an epidemics has been introduced in ref. (14), and studied in refs. (13) (15) (16) (see also ref.(17)) and it has been shown that for networks with finite connectivity (and finite second moment of it), there is always a value of the perception able to stop the epidemics though self-restrictions, but for scale free networks, additional precautions has to be taken by hubs, i.e., people with high connectivity like physicians. however, the other important ingredient is that the risk perception has to be really given by the actual community of real contacts. what happens is that the information contact network can be quite different from the real one (18), and clearly in this case one can either underestimate the risk, as in lombardy, or overestimate it, which is harmless unless the over-restrictions then lead to breakage of the norms. finally, data from china, italy and france are best fit by a power-law (19), which is not consistent with the standard mean-field models. this ingredient can be inserted as a phenomenological factor in such models (20). in this work we present some models incorporating the risk perception and/or the dependence of restriction measures on the number of cases, the presence of several age classes and 0 1000 2000 3000 4000 5000 6000 7000 0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 italy -5000 0 5000 10000 15000 20000 25000 30000 35000 40000 45000 0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 usa 0 1000 2000 3000 4000 5000 6000 7000 8000 0 7 14 21 28 35 42 49 56 63 70 77 84 91 germany 0 1000 2000 3000 4000 5000 6000 7000 8000 0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 france 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 0 7 14 21 28 35 42 49 56 63 70 77 84 91 98 spain 0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000 0 7 14 21 28 35 42 49 56 63 70 77 84 91 uk 0 1000 2000 3000 4000 5000 6000 0 7 14 21 28 35 42 49 56 63 70 77 turkey 0 2000 4000 6000 8000 10000 12000 14000 0 7 14 21 28 35 42 49 56 63 70 77 russia 0 500 1000 1500 2000 2500 3000 3500 4000 0 7 14 21 28 35 42 49 china 0 5000 10000 15000 20000 25000 0 7 14 21 28 35 42 49 56 63 70 77 84 brazil 0 100 200 300 400 500 600 700 800 900 0 7 14 21 28 35 42 49 56 63 70 77 84 91 sweden 0 100 200 300 400 500 600 700 800 900 0 7 14 21 28 35 42 49 56 south korea figure 3. patterns of daily confirmed cases in different countries/regions starting from the 100thcase (12). data retrieved the 29th may 2020. the horizontal scale is in unit of 7 days to put into evidence the weekly oscillations. notice that in many cases there in an evident effects of data collection, for instance in chine there is a jump to 16,000 cases in one day (out of scale), and in russia there is twice an evident one-day shift of data so that the data jumps to zero are followed by a peak due to the shift. this occurs also in france while in germany there is a possible anticipation (due to ill-registration) of data. in other countries (italy, spain) this shift also occurs, but without the subsequent peaks. however, in many cases there are many variations that cannot be ascribed to data shifts, since they occur over many days. there is often an evident weekly pattern, although not always so regular to be ascribed to data collection. modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 4 finally the geographic distribution. this model cannot be used to fit existing data, due to the great number of parameters (and the lack of an extensive investigation on them) but may be useful for visualizing some possible scenarios. 2. modelling epidemics most of “classical” epidemics models are based on differential equations, but this approach has several “hidden” assumptions, so let us start from the very basics. in principle, the most accurate model is that in which each individual in a real population is represented by an “agent” in the computer simulation. clearly, we have to simplify drastically the representation of a person. first of all, we can assume that the state 𝑋𝑖 of an individual 𝑖 can assume a certain number of values, say susceptible (s), infected (i) and, if the disease confers immunity, recovery/refractory (r), i. e., the sir model. other common models include also an exposed/asymptomatic (e) state (seir model) and can distinguish between actual recovered people and dead ones (the seird model). given these states, we have to specify the unit of time for which there can be a transition among states; it is quite natural to assume a time unit of one day, since the reports are issued on a daily base. we should then define the probability of the transition from one state to another, which can depend on the state of other people (as in the case of an infection), or on the previous state of the individual. for accurately modelling the infection phase, one could add intermediate steps, like 𝐼1, 𝐼2,… so that one can avoid the appearance of improbable recovering after a too short period. for what concerns the infection phase, we should consider the network of contacts of individual 𝑖, which can be conveniently defined by a matrix 𝐴𝑖𝑗, which gives the probability of a daily contact between individual 𝑖 and 𝑗. actually, the matrix needs not to be symmetric, since it expresses the modulation of infectivity of individual 𝑖 from individual 𝑗, and this depends on the precaution adopted. the matrix 𝐴𝑖𝑗 can replicate the fact that intimate (family) connections are stronger, followed by those among the own community, etc., and can also reflect the job or the age class of individual 𝑖, so that for instance a teacher or a physician (but also an adolescent) may have more (and more intense) contacts than a retired elder individual. so, the simplest sir model for one individual 𝑖 can be expressed as in fig. 4, where [⋅] = 1 if ⋅ is true and zero otherwise, 𝛼 is the “bare” infection probability and is the recovery probability. a healthy 𝑋𝑖 = 𝑆 individual has a 1 − 𝛼 probability to remain in its state following a contact with an infectious person (recovered ones do not convey any more the disease) and 𝛼 probability to be infected. if infected, he/she has 1 − chance of remaining in the infected state and of healing. this model can be extended by adding more states, like asymptomatic exposed e, mild symptoms m, people in therapy t, dead individuals d, etc. one can also add age classes, so that susceptibles, for instance, can be in state 𝑆𝑘, where 𝑘 identifies the class, and can pass to state 𝐼𝑘 with probability proportional to 𝛼𝑘, etc. clearly, this model requires many parameters and is not susceptible by analytic treatment. so, before computers, scholars imposed a “mean-field” or “chemical” assumption, implying homogeneity and isotropy. with these assumptions, one can introduce the probability s of staying in state s (susceptible), 𝐼 of staying in state i (infective) and 𝑅 of staying in state r (refractory), i.e., for a population of 𝑁 individuals, 𝑆 = 1 𝑁 ∑[x𝑖 = s] 𝑖 . indicating by 𝐾 the average connectivity 𝐾 = 1 𝑁 ∑𝐴𝑖𝑗 𝑖𝑗 , one gets the following discrete-time equations (for the sir model) s(𝑡 + 1) = (1 −𝛼𝐾𝐼(𝑡))𝑆(𝑡); 𝐼(𝑡 + 1) = (1 − )𝐼(𝑡)+ 𝛼𝐾𝑆(𝑡)𝐼(𝑡); 𝑅(𝑡 +1) = 𝑅(𝑡)+ 𝐼(𝑡); and 𝑆 +𝑅 + 𝐼 = 1. finally, assuming continuous time, one can convert the previous equations into differential ones. 3. our model the models are based on discrete states of individuals. in the first version (fig. 5) we have 7 states, which correspond in principle to observable quantities: figure 4. simple agent-based sir model modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 5 s: susceptible; e: exposed (infectious but yet asymptomatic); a: asymptomatic (otherwise like e); m: mild symptoms; t: therapy (intensive); d: dead; r: recovered (heal); where 𝛼, 𝜖, 𝜇, 𝜏, 𝜉, 𝜌, 𝛾 and 𝛿 are the transition probabilities on a daily base, and 𝐾 is the average number of contacts per agent. in order to simplify a bit the model, and also due to the difficulties of detecting asymptomatic people, we can include them into the exposed, and fusing together the probabilities 𝜏 and 𝜉, getting the model-b of fig. 5, so that we have 𝜖 : probability of going from e to r (healing from asymptomatic state); 𝜇 : probability of passing from e to m (inverse of the incubation time); 𝜏 : probability of passing from m to t (aggravation); 𝛿 : probability of passing from t to d (death); 𝛾 : probability of going from t to r (healing with therapies); 𝜌 : probability of recovery from mild symptoms. 3.1 estimation of the range of probabilities we have to estimate the daily probabilities, knowing that the average time ⟨𝑡⟩ is related to the probability 𝑝 by ⟨𝑡⟩ = 1/𝑝. obviously ϵ is not known, but we have that 𝛼 = 1 − 𝜇𝜏. in the following, we shall extend the model to different classes of people, either based of their age or on their profession. the probability of infection (transition 𝐸 → 𝐴) is given both by the fraction of infected (𝐸 and/or 𝑀, according with the class of people considered) and by the number of contacts per day (that can depend on the age class) 𝐾. given that 𝛼 is the probability of infection by one contact, indicating with 𝑋 the probability that a neighbor is infected, we have on average 𝐾𝑋 infected neighbors and therefore the probability of not becoming infected is (1 − 𝛼)𝐾𝑋 and that of becoming infected is 1 − (1 − 𝛼)𝐾𝑋 ≃ 𝛼𝐾𝑋 if 𝛼 is small. if 𝐾 and 𝑋 are constant, the average time ⟨𝑡⟩ to contract the infection is ⟨𝑡⟩ = 1(𝛼𝐾𝑋) and therefore 𝛼 = 1(𝜏𝐾𝑋). an infected individual surrounded by healthy people can infect in average 𝑛 ≃ 𝛼𝐾 people per day (𝑛 ≃ (1 − 𝑋)𝛼𝐾), so if the infectivity period (the quarantine) is 𝑄 ≃ 14 days is, roughly, 𝑛 ≃ 𝛼𝐾𝑄. if 𝑛 is about 2.5 and taking for 𝐾 a value of about 𝐾 ≃ 10, we have 𝛼 = ≃ 0.2. if we now combine the two formulas, assuming that 𝜏 ≃ 2, we have that the fraction of infected individuals (among those exposed) should be 𝑋 ≃ 1(2𝑛) or approximately the 20%. since the probability of remaining in state e is 1 – (𝜖 + 𝜇), assuming that the incubation time is about 𝑤 = 7 days, we have 𝜖 + 𝜇 = 1. the probability ϵ should be about the inverse of children’s recovery time, say 𝜖 ≃ 1/10. the incubation period is about 5 days, but this is not related to 1/𝜇, since this parameter is rather the probability of showing symptoms. all probabilities are obviously positive and less or equal to one, and + 𝜇 ≤ 1 𝛾 + 𝛿 ≤ 1 (1) 4. mean-field equations in the following we shall indicate with the same symbol (italic) the fraction of agents in a given state or, in for the stochastic version, the probability of finding an agent in such state. the discrete-time equations, essentially equivalent to the euler scheme for solving differential equations with 𝛥𝑡 = 1, are 𝐸(𝑡 + 1) = (1− −𝜇)𝐸(𝑡) +𝑆(𝑡)𝐾(𝐸(𝑡),𝑀(𝑡))𝑋(𝑡); 𝑀(𝑡 + 1) = (1 −𝜌 − 𝜏)𝑀(𝑡) +𝜇𝐸(𝑡); 𝑇(𝑡 +1) = (1− 𝛿 −𝛾)𝑇(𝑡)+ 𝜏𝑀(𝑡); 𝑅(𝑡 +1) = 𝑅(𝑡) + 𝐸(𝑡) +𝜌𝑀(𝑡) +𝛾𝑇(𝑡); 𝐷(𝑡 +1) = 𝐷(𝑡) +𝛿𝑇(𝑡); 𝑆(𝑡) = 1 −(𝐸(𝑡) +𝑀(𝑡) + 𝑇(𝑡) + 𝑅(𝑡) + 𝐷(𝑡)). (2) the system is linear except for a quadratic nonlinearity in the first equation. the quantity 𝐾(𝐸,𝑀) denotes the average number of contacts of an agent. in the following, we shall let 𝐾 decrease according to the restriction strategies and perception of the risk, i.e., on the fraction of infected or recovered people. the quantity 𝑋 denotes the probability of meeting infected people who can spread the disease, so either 𝑋 = 𝐸 or 𝑋 = 𝐸 + 𝑀, according with the prevention measures applied to segregate manifestly infectious people. all simulations start with a small fraction 𝐸(0) = 𝐸0 = 10−6 of infected people. simulations show, as expected, the classic sir behavior, with the number of susceptible people going to zero, people figure 5. (left) model-a, 7 states. (right) model-b, 6 states modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 6 in therapy showing a peak and the deaths reaching a certain final fraction of the population (fig 6). in the following we monitor the final fraction of deaths 𝐷∞ = 0.125 and the maximal fraction of people in therapy 𝑀𝑀𝐴𝑋 = 0.09, for the simulation of fig. 6. these values applied to the world population would imply over 900 million deaths and 675 million hospitalized. applied to the italian population they would mean 7.5 million dead and 5.4 million hospitalized. 5. effects of restrictions and/or risk perception now let’s insert the effect of the restriction measures and/or the perception of the risk, modelled through the decrease of the connectivity k with the number of infected people e, or of people in therapy 𝑀. we assume that the connectivity k is given by the sum of a fixed component k0 (family) and a variable term 𝐾𝑉, as 𝐾(𝑌) = 𝐾0 + 𝐾𝑉 exp(−𝑐𝑌) (3) with a new parameter 𝑐. we assume that the connectivity decreases with the number showing mild symptoms (𝑌 = 𝑀(𝑡)), but with the increasing of sampling, it might depend on the number of detected asymptomatic (𝑌 = 𝐸(𝑡)). by increasing c to 10, we observe a decrease in connectivity in correspondence with the peaks of people in therapy (fig. 7-right), with a final fraction of deaths 𝐷∞ = 0.124 (almost unchanged), but a maximal fraction of people in therapy mmax = 0.07, for the simulation of fig. 7. by further increasing 𝑐 (i.e., with much stronger restriction measures) and letting 𝐾𝑉 depend on 𝐸 (implying extended sampling of asymptomatic people), we get a smaller number of 𝑀𝑀𝐴𝑋 = 0.02, at the cost of a longer emergence phase (the timescale is roughly six times in fig. 8 with respect to fig. 6). the fraction of deaths has not changed much (𝐷∞ = 0.12) but now not all susceptible people got infected 𝑆∞ > 0 (fig. 8). this is not the same as herd immunity, since the susceptible people can be re-infected once that 𝐾 has grown again. another interesting effect of the risk perception is that the curve of infected people, which in the seird model shows an exponential growth and decrease (fig. 9-left), with risk perception starts showing a different behavior (fig. 9-right). 6. age classes different age classes have both different susceptibility, different contact patterns and, moreover, different probabilities of showing symptoms. we start defining three age classes: young (0-25 y), middle age (25-65 y) and elders (> 65). from the census 2019 in italy, we get that the respective percentages are 23%, 54% and 23% (21). all parameters now carry an index k, k = 1,2,3 for young, middle age and elder, resp. 𝐸𝑘(𝑡 +1) = (1 − 𝑘 − 𝜇𝑘)𝐸𝑘(𝑡) + 𝑆𝑘(𝑡)𝑋(𝑡); 𝑀𝑘(𝑡 + 1) = (1 − 𝜌𝑘 − 𝜏𝑘)𝑀𝑘(𝑡) +𝜇𝑘𝐸𝑘(𝑡); 𝑇𝑘(𝑡 +1) = (1 − 𝛿𝑘 − 𝛾𝑘)𝑇𝑘(𝑡) + 𝜏𝑘𝑀𝑘(𝑡); (4) 𝑅𝑘(𝑡 +1) = 𝑅𝑘(𝑡) + 𝑘𝐸𝑘(𝑡) +𝜌𝑘𝑀𝑘(𝑡)+ 𝛾𝑘𝑇𝑘(𝑡); 𝐷𝑘(𝑡 +1) = 𝐷𝑘(𝑡) +𝛿𝑘𝑇𝑘(𝑡); 𝑆𝑘(𝑡) = 1 − (𝑅𝑘(𝑡) +𝑀𝑘(𝑡) +𝑇𝑘(𝑡) +𝑅𝑘(𝑡) +𝐷𝑘(𝑡)), the equations are coupled by the fraction of infected people 𝑋(𝑡) 𝑋(𝑡) = ∑𝐾𝑘(𝑡)𝐸𝑘(𝑡) 𝑘 . for beginning, we used the set of parameters of table 1 table 1. set of parameters of the age-class model of eq. (4). parameter young middle age elders α 0.02 0.02 0.02 ϵ 0.1 0.01 0.001 μ 0.0 0.01 0.1 τ 0.0 0.01 0.1 δ 0.0 0.001 0.01 γ 0.0 0.001 0.02 ρ 0.01 0.01 0.01 kv 20 20 4 k0 2 2 1 c c0 c0 c0 as expected, with a small value of c0 = 1, little changes for the total values (although not all susceptibles now get infected), but the distribution for the different age classes are obviously different (and the most of infected came from middle age), fig. 10. however, even for limited risk perception, the number of deaths seems to follow a curve similar to a power-law, as in real data (19). the final fraction of deaths is d∞≃ 0.067 and the maximum fraction of people in therapy is mmax≃ 0.08. for larger values of c0 (100), as in the previous case the epidemics lasts longer, but the numbers mmax≃ 0.017 and d∞≃ 0.059 lower, and the fraction of susceptibles who do not get infected increases, see fig. 11. 0 100 200 300 400 500 time 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 s m t r d x figure 6. simple seir model, 𝐾 = 22, 𝛼 = 0.02, 𝜖 = 0.1, 𝜇 = 0.1, 𝜏 = 𝛿 = 𝛾 = 𝜌 = 0.01. here and in the following figures, time is in days (iterations). modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 7 figure 8. seir model with risk perception, 𝑐 = 100, other parameters as in fig 7. left: time plot of observables eq. (2), right: time plot of connectivity 𝐾(𝑡), eq. (3) figure 9. plots in a log-lin scale. (left) fraction of m people without risk perception (𝑐 = 0); (right) fraction of m people with extreme risk perception 𝑐 = 1000, other parameters as in fig 7 figure 10. 𝑐0 = 1, other parameters as in table 1. (top left) total fractions; (top right) infected for different age classes; (bottom left) people in therapy; (bottom right) deaths on a log-log scale. modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 8 7. social groups model the main goal of restriction measures is that of stopping the epidemics before it reaches all the country. in order to model it, we need to introduce a spatial model. let us denote by aij the probability of contact between individuals i and j. the contact needs not to be symmetric, since the transmission of the disease depends on the precautions taken. we consider a hierarchical network (22), of the type of fig. 12-left. it is defined by a block matrix 𝐼 of the type of fig. 11-right. the index matrix 𝐼 defines the parameters of the matrix 𝐴: 𝐴𝑖𝑗 = 1 with a certain probability 𝑝(𝐼𝑖𝑗) such that the average number of contacts of an individual in community 𝑛 is 𝐾(𝑛). the index matrix 𝐼 is defined by the size 𝐿 of the blocks, in the example of fig. 12 they are 𝐿(1) = 2,𝐿(2) = 3,𝐿(3) = 2 (the size of the smallest community is 2, the following one is composed by 3 smaller communities, and the whole system is composed by 2 intermediate communities). one can think of families, cities and country. the number of connections may change from individual to individual, when chosen with the realization of the stochastic choice of connections with probability 𝑝(𝑛), as in fig. 12-left, but for simulations it is faster to keep 𝐾𝑛 fixed and choose this number of individual at random among the given community. the random choice is repeated in each time step (annealed version) or may be kept fixed (quenched version). the annealed version assures that there is no isolated community, a case that may happen in the quenched version for low connectivity. in the following we use the annealed version. the matrix 𝐴 is generated according to 𝐼 and 𝑝’s at each time step (annealed), and actually in simulations we do not have any matrix, just the probability of connections that are translated into the number of contacts in each community, randomly chosen. the equations are the same, but now the connection 𝐾 is split into that of the different communities, and also the infection rate α depends on the community 𝑛, so we have now figure 11. 𝑐0 = 100, other parameters as in table 1. (top left) total fractions; (top right) infected for different age classes; (bottom left) people in therapy; (bottom right) deaths on a log-log scale. figure 12. (left) index of a hierarchical network with three-community sizes 𝐿 = {2,3,2}. (right) a realization of a network with 𝐿 = {6,4,4} and connection probability 𝑝 = {1,0.04,0.002}. modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 9 a real agent-based model (for the moment without age structure). let us consider for the moment a simple model with four states: s, e, r and d (serd) and three parameters: 𝛼(𝑛) , infection probability from infected people in community 𝑛,𝜌, recovery rate and 𝛿, death rate. the transition probabilities of an individual 𝑖 are 𝑆𝑖 → { 𝐸𝑖 with probability ∑ ∑ 𝛼 (𝑛)[𝑄𝑗(𝑚)∈𝐿(𝑛) = 𝐸𝑖]; 𝐾(𝑛) 𝑚=1𝑛 𝑆𝑖 otherwise; 𝐸𝑖 → { 𝑅𝑖 with probability 𝜌; 𝑆𝑖 with probability 𝛿; 𝐸𝑖 otherwise; (5) 𝑅𝑖 → 𝑅𝑖; 𝐷𝑖 → 𝐷𝑖; where 𝑗(𝑚) indicates and individual at random in community 𝑚, 𝑄𝑗(𝑚)∈𝐿(𝑛) is its state and again [⋅] is one if ⋅ is true and zero otherwise. let us consider for instance the case 𝐿 = {4,10,20} (800 individuals), 𝐾 = {4,2,1} and 𝛼 = {0.8,0.01,0.001}, see fig. 13 and 14-left. as expected, we see a quick propagation inside a first-level community, followed by sporadic breakdown in other communities, fig. 13. the infection curve starts to assume the saw-tooth appearance of those coming from actual data, fig. 3 and all curved show sudden jumps, fig. 14-left. if we allow the contacts among communities only during workdays (increasing the inter-community infectivity 𝛼 = {0.8,0.05,0.003}), we get a more marked pattern, fig. 14right. 8. improvements and perspectives the models here presented constitute just the first approximations to the problem. first of all, we are developing the spatial model with age classes, and implementing a more real network structure, with quenched and annealed parts, representing the connections that are stable (family, school, some kind of work) and those that are variable (casual contacts, commerce, travels). in this way one can simulate with more efficacy the effects of restrictions and the perspective of reopening. clearly, these improvements come figure 13. a snapshot of the status of the network. bottom line denotes susceptible individuals (blue marks infected or recovered or died), middle lines are infected (light green marks), top line represents deaths (red marks). figure 14. (left) saw-tooth behavior of infection curve. (right) more pronounced behavior with infection limited to workdays. modeling social groups, policies and cognitive behavior in covid-19 epidemic phases. basic scenarios 10 at the cost of increasing the number of parameters, which are quite difficult to estimate from field data (often missing and quite sparse). 9. conclusions we have presented some basic simulation scenarios for an infectious disease inspired by the observed characteristics of covid-19. we started with the “classical” mean-field approach based on time-discrete equations, introducing the risk perception effects by means of the restrictions of contacts, and age classes, showing that in this case the overall growth of deaths (and of other quantities) is no more an exponential, but shows a power-law like behavior. we then introduced an agent-based model, limited to the standard infection case (without age classes and risk perception) showing that the network of contacts organized in communities is a crucial ingredient for reproducing the observed saw-tooth behavior and sudden outbreaks. further work is ongoing for developing a unified model, with the goals of furnishing a tool for interpreting the observed scenarios, without any presumption of fitting observed data and forecasting the outcome of the pandemic. references 1. who, world health organization. naming the coronavirus disease (covid-19) and the virus that causes it. [online] 2020. https://www.who.int/emergencies/diseases/novelcoronavirus-2019/technical-guidance/naming-thecoronavirus-disease-(covid-2019)-and-the-virus-thatcauses-it. 2. cdc, center for disease control and prevention. how covid-19 spreads. [online] apr. 2, 2020. https://www.cdc.gov/coronavirus/2019-ncov/preventgetting-sick/how-covid-spreads.html. 3. hui, david s., et al. the continuing 2019-ncov epidemic threat of novel coronaviruses to global health — the latest 2019 novel coronavirus outbreak in wuhan, china. 2020, vol. 91, pp. 264-266. 4. politi, daniel. who investigating reports of coronavirus patients testing positive again after recovery by daniel politi. slate. [online] 4 11, 2020. https://slate.com/news-and-politics/2020/04/who-reportscoronavirus-testing-positive-recovery.html. 5. heymann, davide l., shindo, nahoko, et al. (who scientific and technical advisory group for infectious hazards). covid-19: what is next for public health? 2020, vol. 395, pp. 542-545. 6. cascella, marco, et al. features, evaluation and treatment coronavirus (covid-19). 2020. 7. palmier, luigi et al. (covid-19 surveillance group). characteristics of covid-19 patients dying in italy. s.l. : istituto superiore di sanità, italy, 2020. https://www.epicentro.iss.it/en/coronavirus/bollettino/report -covid-2019_2_april_2020.pdf. 8. guan, wei-jie guan et al. clinical characteristics of coronavirus disease 2019 in china. 2020. 9. center for disease control and prevention. interim clinical guidance for management of patients with confirmed coronavirus disease (covid-19). centers for disease control and prevention. 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[online] 4 12, 2020. https://data.europa.eu/euodp/it/data/dataset/covid-19coronavirus-data. 13. bagnoli, franco, lió, pietro and sguanci, luca. risk perception in epidemic modeling. 2007, vol. 76, p. 061904. 14. capasso, v. and serio, g. a generalization of the karmak-mckendrick deterministic epidemic model. mathematical biosciences. 1978, vol. 42, pp. 43-61. 15. pastor-satorras, romualdo, et al. epidemic processes in complex networks. 2015, vol. 87, p. 925. 16. d'onofrio, a. and manfredi, p. information-related changes in contact patterns may trigger oscillations in the endemic prevalence of infectious diseases. j. theor. biol. 2009, vol. 256, pp. 473–478. 17. manfredi, p. and d'onofrio, a. (editors). modeling the interplay between human behavior and the spread of infectious diseases. new york : springer, 2013. isbn 9781-4614-5473-1. 18. massaro, emanuele and bagnoli, franco. epidemic spreading and risk perception in multiplex networks: a selforganized percolation method. 2014, vol. 90, p. 052817. 19. dong, e., du, h. and gardner, l. an interactive webbased dashboard to track covid-19 in real time. 2020, vol. 3099, pp. 19-20. 20. fanelli, duccio and piazza, francesco. analysis and forecast of covid-19 spreading in china, italy and france. 2020, p. 109761. 21. istat. popolazione per età, sesso e stato civile 2019. tuttitalia. [online] 1 1, 2019. https://www.tuttitalia.it/statistiche/popolazione-eta-sessostato-civile-2019/. 22. girvan, michelle and newman, mark e.j. community structure in social and biological networks. 2002, vol. 99, pp. 7821–7826. substantia. an international journal of the history of chemistry 3(2) suppl. 4: 115-124, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-739 citation: g. restrepo (2019) compounds bring back chemistry to the system of chemical elements. substantia 3(2) suppl. 4: 115-124. doi: 10.13128/substantia-739 copyright: © 2019 g. restrepo. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. compounds bring back chemistry to the system of chemical elements guillermo restrepo max planck institute for mathematics in the sciences, leipzig, germany e-mail: guillermo.restrepo@mis.mpg.de abstract. the periodic system of chemical elements was historically devised by assessing order and similarity relationships among the elements from their compounds, that is, using the accumulated results of chemical practice and knowledge. however, the current approach to the system is based on an ontology of isolated atoms where similarities, especially, are addressed through resemblances of electronic configurations. here we show how the historical approach can be combined with computational tools for data analysis to build up the system based on the compounds reported by chemists. the approach produces well-known similarities of chemical elements when applied to binary compounds. the results come from the analysis of 4,700 binary compounds of 94 chemical elements, whose resemblances are quantified based on the elements they form compounds with and the proportions of those combinations. it is found that similarities do not always correspond to columns of the conventional periodic table and that besides robust similarities such as those of alkali metals, halogens and lanthanoids, there are other mixed similarities involving transition metals and actinoids, some of which were already known for a long time. these similarities are described. finally, the advantages and disadvantages of the electronic and the compound approach to the system are discussed. it is concluded that the current data availability and computational facilities make possible to think of a periodic system closer to the chemical milieu of compounds, bringing chemistry back to the system. keywords. compound, substance, periodic system, chemical space, similarity. introduction while some of the formulators of the periodic system1 were after numerical relationships among atomic weights,2 julius lothar meyer (1830 –1895) and dmitri ivanovich mendeleev (1834-1907) were especially interested in systematizing chemical knowledge.3 they sought to highlight relationships 1 according to van spronsen (reference 1), there were at least six formulators: alexandre-emile béguyer de chancourtois, john alexander reina newlands, julius lothar meyer, william odling, gustavus detlef hinrichs and dmitri ivanovich mendeleev. 2 this is especially visible in newlands’ and odling’s approaches. see references 2 and 3, respectively. 3 the importance of textbook writing in the process of formulating the periodic system for meyer and mendeleev has been stressed by gordin (reference 4) among other historians. 116 guillermo restrepo among chemical elements. the two relations supporting their sketches were similarity and order,[5] which built up a system for chemical elements; where “system” is understood in the ample sense of a set of related objects,[6] in this case chemical elements.4 the providers of order and similarity were in fact chemical compounds. atomic weights, which constituted the order criterion; were determined by finding the smallest common weight of large numbers of compounds containing the reference element in question. [7] similarity was based on resemblance in the composition of substances. as mendeleev stated it in 1905: “if co2 and so2 are two gases which closely resemble each other both in their physical and chemical properties, the reason of this must be looked for not in an analogy of sulphur and carbon but in that identity of the type of combination, r x4, which both oxides assume’’.[8] he concludes: “the elements, which are most chemically analogous, are characterized by the fact of their giving compounds of similar form rxn”.[8] gathering together chemical compounds constitutes a chemical space, which spans all energetically stable atomic ensembles.5 by chemical space we designate all material species chemists experiment with, ranging from substances that can be stored in “bottles” such as liquids, solids or gases, to atomic clusters held together by van der waals interactions. throughout history, chemists have explored such a space by synthesis or extraction of new compounds. as chemists report their findings of new substances in the scientific literature, a suitable proxy for knowing how fast the exploration of the space has been carried out is the rate of reports of new chemical substances. we recently demonstrated that the chemical space has been historically explored in an exponential fashion with an annual growth rate of 4.4%,[10] indicating that about every 16 years chemists have doubled the number of substances since 1800, which was the starting point of the study reported in reference 10. this magnitude can be better expressed by the fact that the new substances reported in 2015 amount to the total of those reported between 1800 and 1950, i.e. the production of 2015 is equivalent in magnitude to the production of 150 years of new substances.6 4 interestingly, little emphasis has been made on the periodic system as an actual system. what we stress in reference 5 is that order and similarity are the structure keepers of all possible periodic systems. 5 as later discussed, by atomic ensembles we mean substances, which may be transient ones. moreover, in most extreme cases the ensembles do not necessarily require the presence of chemical bonds. more on the chemical space is found in reference 9. 6 the idea of assessing chemistry growth through the frequency of reports of new substances was initiated by schummer (reference 11). quantitative studies of scientific growth began with solla price (referthis rapid growth poses a challenge to the periodic system and raises different questions: what was the chemical space in the 1860s when the system was formulated? what is the current chemical space and how does it affect the periodic system? we recently explored the space in the 1860s and found that several of the classes of similar elements known at that time could actually be obtained by analyzing the resemblance of the elements through their compounds through our approach, confirming the fact that mendeleev and meyer had indeed mapped the chemical space of their time.[13] in the current paper we analyze the question of the relationship between the current space and the periodic system and the implications for teaching the system. classifying through the chemical space a classification of the chemical elements based upon the known chemical space up to 2011 was reported in 2012[14] through the analysis of 4,700 binary compounds,7 which accounted for 94 chemical elements (figure 1).8 by binary compounds we mean substances made of two elements, e.g. water, ammonia and methane, but not sulfuric acid and fullerene, for instance. following the mendeleevian approach to similarity of chemical elements, which states that two elements are similar if they form compounds with common elements in similar proportions, leal et al.[14] formalized the notion as follows: for a given set of compounds the elements and proportions of combination of each element x are gathered in the neighborhood of the element x, called nx. for example, if only becl2, mgcl2, bebr2 and mgbr2 are the substances considered, the neighborhoods are: nbe={cl2/1, br2/1} = nmg and ncl = {be1/2, mg1/2} = nbr, which shows the similarity between be and mg and between cl and br, respectively.9 with the neighborhoods for each of the 94 elements, the similarity of every couple of elements was calculated ence 12), who analyzed the growth of scientific literature in different disciplines. chemistry was found to be the most rapid growing discipline in terms of published abstracts. 7 these compounds are a representative sample of the space by 2011, as 4,700 > √12,060,017, where 12,060,017 is the number of known substances by 2011. details of the annual production of new compounds are reported in reference 10. 8 the elements analyzed are: h, li, be, b, c, n, o, f, na, mg, al, si, p, s, cl, k, ca, sc, ti, v, cr, mn, fe, co, ni, cu, zn, ga, ge, as, se, br, kr, rb, sr, y, zr, nb, mo, tc, ru, rh, pd, ag, cd, in, sn, sb, te, i, xe, cs, ba, la, ce, pr, nd, pm, sm, eu, gd, tb, dy, ho, er, tm, yb, lu, hf, ta, w, re, os, ir, pt, au, hg, tl, pb, bi, po, at, ra, ac, th, pa, u, np, pu, am, cm, bk, cf, and es. 9 in general, for a compound xayb, the neighborhood of x is given by {xa/b, yb/a}. 117compounds bring back chemistry to the system of chemical elements as the commonalities of their neighborhoods. in general, the more common neighbors two elements have, the more similar they are (see appendix 1 for details). this is exemplified with the following compounds:15 hf, b2h6, b5h9, b10h14, from which the neighborhoods of the elements involved are: nf= {h1/1}, nh= {f1/1, b2/6, b5/9, b10/14}, nb = {h6/2, h9/5, h14/10}. thus, according to these compounds, hydrogen is more similar to boron than to fluorine, for there are more commonalities with the former than with the latter. once the similarities for all pairs of elements are calculated, clusters of similar elements are built up, for example through hierarchical cluster analysis. this technique looks for the most similar pair of elements and group them together in a first cluster. the new cluster is then included as a new object, where the similarities of the two members of the cluster regarding all the other elements are averaged.10 in this setting, the most similar couple of elements is found, which may be made either of two elements, or of the cluster of the first merg10 merging elements into a cluster and calculating the similarity of the cluster regarding the other elements is equivalent to finding the distance from an object to a set. there are different ways to find such a distance and the selected here of averaging the similarity of the elements of the cluster is called group average methodology. other approaches are, for instance, the complete linkage, where the similarity of the cluster to the other elements is based on the similarity of the most dissimilar of the elements of the cluster. further details on these and other grouping methodologies are found in reference 15. ing and a third element. a new cluster is then formed and the process iterates until all elements have been merged.11 the outcome of the classification through hierarchical cluster analysis is a nested system of similarity classes that establishes the hierarchy of classes from which the classificatory technique takes its name. in the next section, we discuss the results of applying this methodology to the 4,700 binary compounds. similarity landscapes: from classification to system the hierarchy of similarity classes for the 94 chemical elements studied in leal et al.14 can be depicted either as a classification tree, as in reference 14, or as a similarity landscape as in reference 15. in the current section, we present a simplified version of the similarity landscape (figure 1). hydrogen is the most dissimilar element, which indicates that other elements combine very differently than hydrogen does. other dissimilar elements are carbon, oxygen, sulfur, boron, phosphorus, and nitrogen (top of figure 1). there are well-known classes of similar elements, e.g. alkali metals and halogens, with opposite chemis11 particular details of the clustering process are found in reference 15. figure 1. most relevant similarity classes for 94 chemical elements obtained by analyzing binary compounds. elements are spread on the plane trying to keep their positions as those depicted in the current middle-form periodic table while at the same time spatially indicating nearness in .behavior, expanding on the traditional grid. sets and subsets group elements by similarities. pairs of similar elements are denoted by subsets of two elements. whenever a subset belongs to a larger subset, this indicates a hierarchical similarity. for example, rb and cs are similar elements, which in turn hold a more relaxed similarity regarding k. 118 guillermo restrepo fi gu re 2 a. m en de le ev ’s pe ri od ic t ab le s by 1 87 1. a ) fo ld in g ta bl e in h is te xt bo ok , d . i . m en de le ev , o sn ov y kh im ii (th e pr in ci pl es o f c he m is tr y) , o bs hc he st ve nn ai a po l’z a: s t. pe te rs bu rg , pa rt i i, 18 71 .16 119compounds bring back chemistry to the system of chemical elements tries and ways of combining with other elements. this was noted and detailed by mendeleev in the table published in his second volume (1871) of principles of chemistry[16] (figure 2a), where it is explicitely written that alkali metals combine with oxygen in a 2:1 ratio (r2o using mendeleev’s notation). in contrast, halogens do it in a 2:7 fashion (r2o7). this table, among several other commonalities, shows that alkali metals form hydroxides of the form xoh, being x an alkali metal. one of the commonalities for halogens in this table is that they form compounds rh, where r is a halogen. the table was then simplified to the second table of mendeleev’s 1871 paper on the periodic system17 (figure 2b), where only the general formulae for oxides and hydrides remain, but the particular details of the table in figure 2a are omitted.12 in our work on the periodic system of 1869 using the known chemical space at that time, we found additional commonalities for alkali metals, e.g. xaso4, x2co3, x2so4, xno3, xcl, and xi.13 for halogens, we found rc2h3o. finding alkali metals and halogens as classes of similar elements with the sample of compounds analyzed in reference 14, which include not only oxides and 12 as suggested by brigitte van tiggelen during the revision of the current paper, this is an early evidence of how the simplification of the table through its dissemination started to leave aside valuable chemical information. hydrides, indicates that the commonalities of the members of these families extend to most of their combinations with other elements, not only to those with oxygen and hydrogen. delving into the details of each of these classes, alkali metals can be divided into two sub-clusters, one of light metals: lithium and sodium and a second of heavier ones: potassium, rubidium, and strontium. halogens follow a nested similarity structure, chlorine and bromine being the most akin halogens, with some resemblance to iodine. fluorine is the most dissimilar halogen. the explanation of the strong dissimilarity of fluorine is based upon its small atomic size. this is part of the socalled singularity principle, which states that the chemistry of the second period elements is often different from the latter members of their respective groups.[18] such principle is generally evident in the lack of similarities of carbon, oxygen and the other elements mentioned above and shown at the top of figure 1. alkali-earth metals appear together with group 12 metals. this cluster of eight elements was recognized by mendeleev as early as 1871 and is characterized by a 1:1 ratio of each element in the cluster with oxygen (ro and r2o2 in mendeleev’s 1871 periodic table (figure 2)). as for alkali metals and halogens, this similarity class indicates that its elements combine in a similar fashion not only with oxygen but also with other elements (more details to be found in reference 14). in the study of the figure 2b. mendeleev’s periodic tables by 1871. b) as in his table ii in his publication, d. mendeleev, die periodische gesetzmässigkeit der chemischen elemente, ann. chem. pharm. 1871, 8 (supplementband).17 120 guillermo restrepo system of 1869 using the known chemical space, other resulting commonalities were rf2, rcl2 and rs.[13] another cluster of similar elements is the couple of selenium and tellurium, which constitutes the only case of similarity among chalcogens.13 all other chalcogens constitute single classes. likewise, arsenic and antimony are the only cluster including pnictogens.14 this lack of vertical similarity for groups of the periodic table indicates differences among elements members of each group. although it is true that most chalcogens have rh2, ro3, and r2o6 combinations as stated by mendeleev (figure 2),[16,17] the sample of substances used in leal et al.[14] shows that there are other combinations disturbing this similarity put forward in 1871.15 on the other hand, the already discussed singularity principle makes oxygen behave differently in comparison with the other chalcogens, combining with other elements in a rather different way as its homologues do. the same argument applies for pnictogens, with nitrogen behaving differently, but still with rh3 and r2o5 combinations, as noted by mendeleev (figure 2).[16,17] other clusters of similar elements are the trio of vanadium, niobium and tantalum, today labeled as group 5 and recognized by mendeleev as a set of elements having relations rh3 and r2o5.[16,17] interestingly, the quartet of ferrous metals: iron, cobalt, nickel, and palladium, which are members of the group viii for mendeleev[16,17] and the old iupac group numbering, or viiib in the cas numbering, forms a cluster.[15] this cluster indicates that these elements have indeed commonalities in terms of the compounds they form, for example ro4 and r2o8.[16-17] in the current group numbering of the periodic table, group viii corresponds to groups 8 to 10, which include nine elements. the results of leal et al.[14] actually show that resemblances among these elements are not only restricted to iron, cobalt, and nickel: the trio ruthenium, osmium, and platinum is another case.16 by considering larger clusters, it is found that ruthenium, osmium, and platinum also have certain resemblance with molybdenum and tungsten. interestingly, the pair of similar elements rhodium and iridium, traditionally considered as part of platinum metals,17 do not appear closely related to the other plati13 group 16 of the conventional periodic table. 14 group 15 of the conventional periodic table. 15 in reference 13 we found that another commonality for chalcogens is xnh5, being x a chalcogen. 16 according to rayner-canham, ruthenium and osmium become similar as each forms compounds where the +8 oxidation state is favored. the commonality of these two elements with platinum stems mainly from compounds where the +4 oxidation state of the metal is present. details in reference 19. 17 by platinum metals is understood: ruthenium, osmium, rhodium, iridium, palladium, and platinum. num homologues as usually stated but loosely connected to some lanthanoids and actinoids. titanium, zirconium and hafnium, forming group 4 of the current periodic system, constitute a cluster of similar elements, which holds similarity ties with the actinoids thorium and uranium. these transition metalactinoid resemblances were noted by seaborg as early as 1945[20] and are based on similarity of combination with other elements where the +4 oxidation state of the metal is the commonality.18 the resemblance of transition metals zirconium and hafnium was explained by goldschmidt through the lanthanoid contraction, which is currently understood as the spatial shrinking of lanthanoid atoms as a consequence of the filling of 4f shells that contracts 5p and 6s shells. this contraction makes that zr4+ and hf4+ have roughly the same ionic radii when six-coordinated.[22-24] as we remarked in our previous work[15], even if the zirconium and hafnium resemblance is known, in some theoretical communities, it is considered an exception caused by “anomalous cancellation of relativistic effects” for elements of the 5thand 6th-rows of the system.[24,25] in the study by leal et al. mentioned earlier,[14] it was found that out of the 17 possible pairs of 5thand 6th-row elements that belong to a group, there are five other pairs sharing similarities: niobium and tantalum; molybdenum and tungsten; technetium and rhenium; ruthenium and osmium; and, finally, rhodium and indium. the first two couples here listed were discussed by huheey and huheey on the basis of the very close radii for 5thand 6th-row species.[23] this resemblance was also discussed in terms of similar oxidation states.[26] our work uncovered a cluster of elements belonging in group 13, but which excludes boron. here, gallium and indium are the most similar elements, which then have resemblance relations with aluminum and finally with thallium. interestingly, this quartet turns out to be similar to gold and to a lesser extent to the couple of coinage metals cooper and silver. so far, we have discussed clusters that are only a few elements in length, but there are also larger clusters corresponding to elements that are very similar in terms of the compositions they form. these are the lanthanoids and actinoids. it was found that lanthanoids are more similar among themselves than actinoids. this is caused by a dominant +3 oxidation state, which has been explained on electronic grounds.[15] remarkably, rare earths constitute a large cluster of similar elements that groups together scandium and 18 schwarz recently discussed the similarity of early actinoids with some transition metals of the 6th-row of the periodic system (details in reference 21). 121compounds bring back chemistry to the system of chemical elements yttrium and is relevant to an ongoing iupac discussion about the elements that should be recommended as belonging to group 3 of the periodic system.[27] part of the question is whether scandium and yttrium should be grouped together with lanthanum or with lutetium. the results here discussed show that lanthanum should be placed in group 3 as the element holds similarities with 11 lanthanoids and scandium and yttrium. in contrast, lutetium is more akin to lanthanoids and not so much to scandium and yttrium.[14,15] in contrast with the strong similarities among lanthanoids, actinoids are tied by a more diverse repertoire of combinations because of a more ample set of available oxidation states that vary from +2 to +6. this has been explained on quantum chemical grounds and is known as the actinoid contraction, which is more irregular than the lanthanoid contraction.[21,26] resemblances between transition metals and f-elements are not specific to lanthanoids. actinoids also keep some of these similarity ties, for example with zirconium, hafnium, technetium and rhenium. in particular, uranium is similar to titanium, zirconium and hafnium (group 4) and also to thorium. similarities of these sorts have been reported by rayner-canham and studied by schwarz and rich.[18,28] an actinoid worth mentioning is plutonium, which holds similarities with other actinoids19 along with lanthanoids terbium and praseodymium. it has been argued that plutonium particularities stem from its peculiar electronic properties resulting from the changing roles of the 5f orbitals, which, for example make it equilibrate four oxidation states in solution, something not reported for any other chemical element.[31] mendeleev retrieved – and much more we have underlined the central role of compounds as providers of order and similarity relationships for the elements in mendeleev’s approach to the periodic system. using this argument, we analyzed the results of chemical similarity of chemical elements through a sample of their known binary compounds in the early years of the 21st century. the results show that several of the well-known similarities of chemical elements are recovered through this method based on the composition of compounds. regarding the similarities obtained, and contrary to the general message of current textbooks,[30] resemblances are not always vertical on the periodic table. besides 19 curium, berkelium, einstenium, americium, californium, and actinium. the well-known vertical similarities of the alkali metals, halogens, aluminum-group and copper-group, horizontal resemblances were detected such as those of 4th-row platinum metals, lanthanoids, actinoids. to which mixed similarities can be added, e.g. lanthanoids and scandium and yttrium (rare earths); and actinoids with some transition metals. interestingly, mendeleev had noted as early as 1869 that “in certain parts of the system the similarity between members of the horizontal rows will have to be considered, but in other parts, the similarity between members of the vertical columns.”[31] hence, chemically speaking, similar elements are close to each other on the table but vertical proximity is not the only and most relevant similarity scheme. the results here discussed agree with the classification of elements presented in specialized chemical books such as the classic chemistry of the elements,[32] where the classification is the basis for the distribution of the material presented in the book. it is worth noting that the same pedagogical aim rooted on a chemical system was sought for by meyer and mendeleev when writing their respective chemistry textbooks.[4] this presentation of chemical knowledge is therefore expected from books rooted in chemical information, which contrasts with the current simplistic approaches of introductory chemistry textbooks, based on electronic resemblance of free atoms. we have also shown how quantum chemistry concepts can be used to make sense of the similarity results obtained through compounds. it has been claimed that the motivation for developing a periodic system was to make sense of the large amount of information about compounds and their reactions that had been gathered by mid 19th century.[4,13] however, the exponential growth of chemical substances made it difficult for 19th century chemists to assess similarities through all known compounds, even if efforts of gathering chemical information in a systematic fashion had begun during that time as evidenced in the different editions of the famous gmelins handbuch der anorganischen chemie and beilsteins handbuch der organischen chemie, which by 1869 included more than 11 thousand substances.[13] these handbooks plus the patent chemistry database are now available in digital form in reaxys™, a large electronic database that is updated on regular basis from material published in more than 15,000 scientific journals and patents. another database gathering chemical information is scifinder™. therefore, the method here presented can be computationally applied to those databases in order to shed light on the similarity structure of the chemical space at a particular historical period of the available chemical space. 19th century approaches to similarity, the growth of 122 guillermo restrepo the chemical space, combined with the emerging atomistic ontology at the end of the century and the advent of quantum mechanics at the beginning of the 20th century, led to analyze and assess similarities among chemical elements through resemblances on the energetic distributions of valence shell electrons.[33] this is the root of the current over-emphasized textbook introduction to the periodic system through electronic configurations of free atoms.[34] however, as some authors have remarked,[34,35] these configurations are rather dissimilar to those of the bounded atoms present in compounds, which are the actual relevant species for chemistry. electronic and compounds: two approaches to a system of the chemical elements the approach discussed in the current paper therefore constitutes an alternative way to introducing the periodic system to students, with more chemical “flavor” than what has become the traditional electronic approach.[15] “compound” is the fundamental concept of chemistry that is part of the bulk level by nelson for describing chemistry.[38] by bulk level, we mean the approach to chemical education based on compounds and chemical reactions, often performed at chemistry laboratories with bulk matter or material that  consists of large numbers of atoms, molecules, or ions. we have indeed currently two options to approach the study of the periodic system and its teaching. the first approach, the electronic approach, now largely in use in chemical education and practice, requires possible molecular ensembles as input to calculate properties. however, current quantum chemical approaches are not able to systematically treat chemical species with the same levels of theoretical accuracy to end up with properties that can be compared leading to classifications of elements. this poses an interesting and worthwhile challenge to quantum chemistry which is computationally difficult, for the number of compounds populating the chemical space is extremely large:20 even the simplest quantum chemical methods would require too much time to finally end up with values for various material properties. to make matters worse, in teaching, the electronic approach cannot be introduced as here described because the periodic system is normally presented in the first year of chemistry studies, where quantum chemistry concepts are still to be developed and taught. one 20 up to march 2019, for example reaxys reported 31,134,633 chemical species. could, however, approximate the approach using quantum chemical results of isolated atoms in their ground state energy, which brings back the problem of a “fantasy chemistry”21 far from the chemistry of bonded atoms forming compounds with electronic configurations different from those of isolated atoms. the second approach to the study of the system and its teaching is the compound approach, discussed in this paper, which requires managing the rapidly growing chemical space, currently recorded in electronic databases. here, obtaining similarity classes of chemical elements requires formulas of the compounds reported and the application of classification algorithms, whose complexity, in general, does not depend on the size of the compounds nor on their number of elements. it is, in this sense, independent from both size and electronic theories, which is its advantage compared to the electronic approach. in teaching, the compound approach would require knowledge on how to operate on the chemical space, which, as noted by schummer,[37] requires data analysis techniques to make sense of the information stored in databases. one can hope that sooner or later, chemical databases will include the possibility of running data analysis studies on the cloud in such a way that clicking on “give me the system of elements” button, one can retrieve the shape of the system constructed with the available chemical knowledge.22 future perspectives: mapping similarities and creating chemical systems for now, a more realistic approach to the systems from the compounds is through random samples of the space, easy to handle in personal computers.23 another option is to run projects with enough computational facilities, able to store the complete chemical space at a given time and to process its information. this approach is currently followed in our research group, whose ini21 expression taken from peter schuster at the mathematics in chemistry meeting (leipzig 2016), when objecting classification results of chemical elements not meeting well-known similarities. 22 actually, the technicalities of the “button” should read “give me the system of elements according to the available chemical space for period p (a range of years) using the merging methods a, b, ...” a very recent instance of how data analysis techniques applied to chemical information are making their path in current chemistry is the publication of the first chemistry book written entirely by a machine (reference 38). it contains a survey on lithium-ion batteries based on 150 papers published between 2016 and 2018. 23 a similar approach was followed by schummer when analyzing the growth of chemical compounds at the end of the 1990s. details in reference 10. 123compounds bring back chemistry to the system of chemical elements tial results have analyzed the temporal evolution of the growth of the chemical space since 1800 up to 2015. a third option to apply the compound approach is through classification of the compounds of the space in such a manner that one can select representative compounds of the classes to run similarity studies. this approach requires further research on the chemical space and on its mathematics. further work to develop appropriate tools in this direction is currently carried out in our research group. even if we are advocating for a more data-driven approach to the system of elements through their compounds, it is not free of subtleties. it brings to the surface another fundamental question of chemistry. what is a chemical compound? strikingly, as noted by several authors,[39,40] even its fundamental role in the edifice of chemistry, there is no consensus on what this concept is. at first glance, it looks like the compound approach to chemical similarity here discussed cannot stand the test of time, for it relies on compounds, which are especially scarce for the heavy elements. moreover, for these elements the few compounds that are obtained are synthesized in a one-atom-at-a-time fashion, which is different from the bulk process of the traditional chemistry. [15,41] this sparks not only a clash of chemical traditions, but also the mixture of two different ontological levels for types of compounds. by contrast, the computational methods that operate on chemical databases overcome these problems, for it is actually based, beyond compounds, on their mathematical generality, i.e. their composition and stoichiometry, not on their mode of existence or acquisition. both composition and stoichiometry can be extracted from either bulk or atomic aggregate compounds; it does not matter whether the substances have been synthetized through wet-lab techniques, or in a one-atom-at-a-time fashion, or even estimated through quantum chemical approaches.[42] we have shown that a sample of the current chemical space is the natural source of information about similarity among chemical elements. these similarities, when combined with the traditional order of elements by atomic number, provide what we see as the current structure of the periodic system. this methodology is nothing else than mendeleev’s methodology applied to the current chemical space, now assisted by computational tools of data analysis. applying the same pedagogical motivation that was the hallmark of mendeleev has produced results that ought to be introduced in contemporary chemistry classrooms together with the electronic understanding of elements in order to bring chemistry back into the periodic system. appendices appendix 1: similarity calculation if nx and ny are the neighborhoods of elements x and y, respectively; the similarity s(x, y) between x and y is calculated as s(x, y) = |nx ∩ ny|/|nx ∪ ny|, where |x| represents the number of elements in the set x. thus, 0 ≤ s(x, y) ≤ 1 and values close to one indicate similar elements, whereas those close to zero, very dissimilar elements. acknowledgments the author is indebted to andrés bernal, michael gordin, wilmer leal, eugenio j. llanos, geoff raynercanham, eric scerri, joachim schummer, w. h. eugen schwarz, and josé luis villaveces for their valuable discussions and ideas. thomas endler is thanked for designing the graphical abstract. references 1. j. w. van spronsen, the periodic system of chemical elements: a history of the first hundred years, elsevier, 1969. 2. j. a. r. newlands, chem. news 1864, 10, 59. 3. w. odling, quart. j. sci. 1864, 1, 642. 4. m. d. gordin in nature engaged: science in practice from the renaissance to the present, ed. m. biagioli, palgrave macmillan us; new york, 2012, chapter 3, pp. 59-82. 5. w. leal, g. restrepo, proc. r. soc. a 2019, 475: 20180581. 6. l. bertalanffy, general system theory, george braziller, 1968. 7. e. r. scerri, the periodic table, its story and its significance, oxford university press, 2007. 8. d. mendeleev in mendeleev on the periodic law: selected writings, 1869-1905, ed. w. b. jensen, dover; new york, 2002; paper 13, pp. 253-314. 9. g. m. keserű, t. soós, c. o. kappe, chem. soc. rev. 2014, 43, 5387. 10. e. j. llanos, w. leal, d. h. luu, j. jost, 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general chemistry, mcgraw-hill, 2008. 31. d. mendeleev in mendeleev on the periodic law: selected writings, 1869-1905, ed. w. b. jensen, dover; new york, 2002; paper 2, pp. 18-37. 32. n. n. greenwood, a. earnshaw, chemistry of the elements; 2nd ed., elsevier, 2005. 33. g. restrepo in what is a chemical element? a collection of essays by chemists, philosophers, historians and educators, eds: e. scerri and e. ghibaudi, oxford university press: new york, 2019 (forthcoming). 34. c. k. jørgensen, angew. chem. int. ed. 1973, 12, 12. 35. s-g. wang, w. h. e. schwarz, angew. chem. int. ed. 2009, 48, 3404. 36. p. g. nelson, chem. educ. res. pract. 2002, 3, 215. 37. j. schummer, educación química, 1999, 10, 92. 38. b. writer, lithium-ion batteries, springer, 2019. 39. j. schummer, hyle int. j. phil. chem. 1998, 4, 129. 40. j. van brakel in handbook of the philosophy of science, volume 6: philosophy of chemistry, eds: r. f. hendry, p. needham, a. i. woody, elsevier; amsterdam, 2012; pp. 190-229. 41. m. schädel, angew. chem. int. ed. 2006, 45, 368. 42. p. pyykkö, phys. chem. chem. phys. 2011, 13, 161. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 4 2019 firenze university press the periodic system, a history of shaping and sharing brigitte van tiggelen1, annette lykknes2, luis moreno-martinez3 julius lothar (von) meyer (1830-1895) and the periodic system gisela boeck shaping the periodic classification in portugal through (text)books and charts isabel malaquias1,*, joão a. b. p. oliveira2 the st andrews periodic table wallchart and its use in teaching r. alan aitken1, m. pilar gil2,* the periodic system and the nature of science: the history of the periodic system in spanish and norwegian secondary school textbooks luis moreno-martínez1, annette lykknes2 are history aspects related to the periodic table considered in ethiopian secondary school chemistrytextbooks? gebrekidan mebrahtu order from confusion: international chemical standardization and the elements, 1947-1990 ann e. robinson periodicity trees as a secondary criterion of periodic classification: its implications for science teaching and communication alfio zambon compounds bring back chemistry to the system of chemical elements guillermo restrepo 1 citation: l. corbetta, l. m. fabbri, d. halpin, a. a. cruz, s. zanconato (2021) stand on the same side against covid-19: ics-containing products in treatment covid-19 patients with asthma and copd. substantia 4(1) suppl. 1: 1233. doi: 10.36253/substantia-1234 received: feb 04, 2021 revised: mar 22, 2021 just accepted online: mar 22, 2021 published: mar 22, 2021 copyright: © 2021 l. corbetta, l. m. fabbri, d. halpin, a. a. cruz, s. zanconato. this is an open access, peer-reviewed article published by firenze university press (www.substantia.net) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia webinar stand on the same side against covid – 19: ics-containing products in treatment covid19 patients with asthma and copd this document is the direct transcription of a webinar organized by prof. l. corbetta of the university of florence on december 17th, 2020. scientific coordination: lorenzo corbetta associate professor of respiratory diseases university of florence scientific and website director of the european association for bronchology and interventional pulmonology (eabip) organizing secretary: consorzio futuro in ricerca via saragat 1 – corpo b – 1° piano | 44122 – ferrara cfr@unife.it translation coordination and editing: giorgia biagini, md info@covid19expertpanel.network webinar’s partecipants: prof. lorenzo corbetta university of florence prof. leonardo m. fabbri – university of modena and reggio emilia prof. david halpin university of exeter (uk) prof. alvaro a. cruz federal university of bahia (brazil) prof. stefania zanconato padova university hospital corresponding author: lorenzo.corbetta@unifi.it substantia. an international journal of the history of chemistry 4(1) suppl. 1: 1234, 2020 issn 2532-3997 (online) | doi: 10.36253/substantia-1234 http://www.fupress.com/substantia l. corbetta et al. 2 “stand on the same side” videoconferences https://www.covid19expertpanel.network “implementing a science-based lockdown exit strategy is essential to sustain containment of covid-19. china’s experience will be watched closely, as other countries start considering—and, in some cases, implementing—their own exit strategies” the lancet, volume 395, issue 10232, 18–24 april 2020, pages 1305-1314 this phrase expresses the purpose of this program called “stand on the same side against covid-19” that takes advantage of the new and rapid digital technologies to put together several experts worldwide. it’s a global space were many countries hit by sars-cov-2 can share only scientific information in order to face the pandemic. december, 17th 2020, international videoconference “stand on the same side against covid – 19: ics-containing products in treatment covid-19 patients with asthma and copd” lorenzo corbetta: good afternoon everybody, welcome to the sixth webinar of the project, 'stand on the same side against covid-19'. today is ics containing products in treatment for covid-19 patients with copd and asthma. i'm pleased to welcome again leonardo fabbri, the chairman and the co-chairman and professor cruz from brazil, and the other new speakers participating to the project, professor david halpin, and professor stefania zanconato. i give now the word to professor fabbri to introduce the next speakers, and i welcome again everybody. leonardo fabbri: yes. thank you very much, lorenzo, for your invaluable energy in organising these meetings, very pleased to join. thank you very much david for the very nice presentation. i think we have a couple of minutes for discussion, if there are any questions from the panel or from the participants, you can also send messages. you know today with the talking about copd, there is an interesting controversy on the role of smoking, the protective effect of smoking that brings some crazy people to say, 'treat covid with smoking, or with nicotine as an anti-inflammatory agent.' david halpin: yes, so i think i would support the who's view that actually the evidence is inconclusive at the moment. so, there's no conclusive evidence that smoking is protective, and equally there's no evidence that it's harmful. there are again some potential effects on ace2 expression, but i think if we've got a neutral view on whether it protects or worsens covid, we know smoking is bad for people. so, they should not start smoking just to try and protect against sars-cov2. leonardo fabbri: yes, there are people that i've seen are claiming that the burning of deaths due to smoking overcounts largely the risk of any protective effect. david halpin: the protective effect, yes, absolutely. yes, i'm sure that that would be true. leonardo fabbri: thank you, any other questions? alvaro a. cruz: david, very nice presentation, thank you. do you have any information or evidence on those limits, or the benefits, of inhaled corticosteroids? whether, let's say, in severe asthma where we need a much higher dose, would it still be beneficial, or could it be harmful? david halpin: i mean, i don't have any evidence. the data that i've shown you is all the evidence that i can find in terms of mechanistic studies looking at effects. i think we have clinical evidence about the differences, so, you know, the uk data that i showed you about risks of inhaled steroids, and showing in asthmatics that there was a dose response that those patients on higher dose seem to be at greater harm. but, you know, quite clearly that is confounded by the indication for the inhaled steroid in the first place. so, i don't think we have any data on whether there is a maximum dose benefit for inhaled steroids. my overall view is that i think that inhaled steroids are, probably, of neutral benefit. so, there are reasons why they may potentially be putting at risk, there are potential mechanisms that may help you protect, but overall it's neutral. so, i don't think there's any role in pushing the dose higher and higher to get that beneficial effect, because it may potentially have a greater effect on suppressing the innate immunity, and make you more at risk. leonardo fabbri: final questions, if there are others? lorenzo corbetta: may i? one question we have an alert in italy. there is a reported reduction in the use of treatments for asthma, copd especially ics. have you noticed it in england, and what is the reason? david halpin: no, i think it hasn't happened, so the evidence that i have, and there's some quite nice data from a group called propeller health, who you all know is involved in remote monitoring, so they're involved in developing smart inhalers that monitor usage and feedback to patients. they also collect anonym data, and there was quite a marked upswing in compliance with medication early in the epidemic, so people, and in my experience my patients, they're frightened of developing the disease, they want to be as healthy as possible. so, they've been taking their https://www.covid19expertpanel.network/ stand on the same side against covid – 19: ics-containing products in treatment covid-19 patients with asthma and copd 3 medication much more regularly and, you know, according to what's recommended rather than forgetting to take it. i think there was an issue, as i mentioned that actually there was shortage of some inhalers because of the use outside respiratory disease so i think some patients did run into problems with access to medication but in my experience, if anything they've been taking more of it more regularly, rather than reducing it. leonardo fabbri: yes, while there is no evidence that asthmatics patients with copd are at an increased risk of contracting covid-19. how solid is the evidence that the presence of severe asthma and copd is actually worsening the problem or is it increasing the mortality of the patient affected by copd. david halpin: so, i know the data for copd better than for asthma. there is now, i think evidence that if you have copd in europe or in north america, you're probably lightly more likely to end up in hospital with covid but only a little bit more, so say an odds ratio of something like 1.2 whereas we know that age and other conditions have a much bigger impact so the odds ratio being over 75 is about five fold greater, so a much bigger effect than just having copd. the best data that i know on outcomes is, again, uk data where we've got good linkage with primary care coding of co-morbidities and good icu mortality data showing that in multi-variant models, neither asthma nor copd are associated with increased icu admission, nor increased mortality, so they're often with other co-morbidities or age that may put you at greater risk but in themselves, they don't appear to put you at greater risk and that's really a bit of a paradox, because we'd all think that people with impaired respiratory, particularly copd where you've got a lot of permanent damage, you would do much worse if you ended up in icu but that doesn't seem to be the case which is bizarre and interesting. leonardo fabbri: thank you. lorenzo corbetta: okay, i'm now pleased to introduce you alvaro cruz, from brazil. another expert on guidelines, he works a lot with gina and gold and also with the management of asthma copd during the outbreak in brazil. alvaro a. cruz: hello my colleagues, i'm very pleased to be here with you all, however virtually, to share observations on the management of copd during the outbreak in brazil. i thank dr corbetta for the invitation to be part of this symposium, chaired by professor fabbri, one of the major global leaders in the field of respiratory health of our times. and the panel of highly distinguished speaker, let me share my screen now. well, these pictures, taken from the same position illustrate the enormous inequalities we face in brazil. the dark side, challenging healthcare professionals, researchers and policy-makers. at the beginning of the covid pandemic, i was very worried of its consequences towards the underprivileged but i'm glad to report to you, we have free universal coverage by our national public health system which has responded well to covid in general in spite of the absurd negationists' statements and behaviours of some political leaders and their followers. regarding my conflict of interest, i must tell you, although i'm a member of the governing bodies of many organisations including the board of directors of gina, i am not officially representing any of them. my presentation reflects solely my observations which i will present and my opinion. well, i am going to try and cover these our topics that i mention are the problems. asthma, copd and covid in brazil. covid-19 mortality, asthma and copd. asthma in copd exacerbation in times of covid-19 and finally, why asthma and copd exacerbations are reduced. while these are the official statistics of the ministry of health on december 16th, over 7,000,000 cases and 180,000 deaths, a second wave is clearly starting, as you see, both in terms of number of cases and the deaths. mostly on the number of cases and in my position of front line physician, i see this as even higher, this is my perception. still not appearing in the statistics, mostly of death. this is the picture of the prevalence of asthma in brazil, of high prevalence. what we see here is a report of data generated by who survey of 5,000 adults which demonstrates the prevalence of asthma in adults in brazil is 12%. the same as what we have reported in the past. this is the prevalence of asthma, diagnosed. the figures for symptoms of asthma in the last year are around 23%, both for adults and adolescents, highlighting the likelihood of a lot of under-diagnoses. this is the prevalence of copd in five latin american cities from l. corbetta et al. 4 the platino study which shows that in sao paolo, we have a nearly 15% adjusted prevalence, one of the highest in latin america and fortunately, the proportion of smokers in brazil is not among the highest and in fact it's declining. well now, let's look at the mortality of covid in the state of sao paolo looking at over 40,000 cases or deaths. the gender distribution is a little bit skewed towards males. the age distribution, as expected of the deaths almost 80% above 60 years of age and the co-morbidities, 80% at least one comorbidity, 60% had quite cardiovascular disease. 43% diabetes. and we have here the lung disease, 8.3% have any lung disease, 3.1% have asthma. its difficult to understand why they have split here copd is in this group of any lung disease. as i have just shown to you these prevalences are much lower than the prevalence of copd and asthma in the population so we need to understand what is happening here. now, i looked at the ministry of health's databases around copd of hospitalisation in the brazilian public health system comparing 2019 and 2020 from april to september and what we see here at your right, the total numbers 60,000 hospitalisations in 2019. 28,000 in 2020. it's less than half and this trend is exactly the same in every one of the five regions of the country. now, doing the same for asthma, hospitalisations in the public health system 2019 in dark blue then 2020 in red from april to september, six months period of time. 45,000 hospitalisations last year. 19,000 hospitalisations this year and the same trend in every one of the give regions. well, we should thank god that the much feared storm did not hit hard patients with asthma and copd. on the contrary, it seems to have spare them. what i presented is just database, retrospective information, now i wish to make some comments on some prospective observations. this is a report of data from our asthma cohort from proar and a comparison between this cohort and the ubiopred european cohort of adults which shows remarkable similarities in spite of so many differences we have. we have a special group with mild or with moderate to severe asthma followed up for several years, then despite of the disruption of the entire health system and our clinics, we haven't heard of many deaths so we followed some 1,000 people with moderate to severe asthma and we just heard of three deaths so far. this is another observation from our group, it's a pragmatic cluster randomised parallel group trial of the effectiveness of collaborative care for asthma in primary healthcare funded by nihr. in this study, while we were looking at an intervention to build capacity of primary healthcare workers while looking at usual care. well, we couldn't perform the study because there was no way we could build capacity in this chaos, we are living it so we just monitor these people with a systematic questionnaires by telemonitoring every three months and we were expecting to recruit 600 patients. we recruited only 200. now what i present here are the results of the follow-up of these 200 subjects, many of them have not completed one year of follow-up so we have here the number of severe asthma exacerbations in this study, we call attack study. the year before the initial group of this study was an episode of severe asthmatic exacerbation so this is what they had before, so an average of four sever asthmatic exacerbations defined by emergency room visit plus a prescription of oral corticosteroid. in dark blue, the group in which we do the intervention but we didn't complete it and the red, the group in which there was no intervention, they would befall in usual care and what we see is that in the year after, using annualised rates, the average number of severe exacerbation went from four to 0.5, a major reduction in exacerbation. stand on the same side against covid – 19: ics-containing products in treatment covid-19 patients with asthma and copd 5 well, let's see what can be behind this. well, i put a lot of questions marks in everything i propose here which is speculation or hypothesis so these are the possible explanations for the reduction in asthmatic exacerbations in brazil in 2020. also these observations i just comment to you on our cohorts. some are related to asthma or its treatment as well illustrated by david. atopy reduces the risk of covid? some have proposed this. i see as prevents of sars-cov-2 infection. i see it attenuate covid-19, is it possible? related to patients' behaviour. was there better adherence to treatment? there is some ecological data from pharmacies in brazil to indicate that people use more corticosteroids or at least they bought more. fear of attending emergency rooms due to covid-19? we have reduced the rates of what we call 'severe exacerbations' in our studies or even reduced the number of people hospitalised due to asthma. and then related to the health system. reduced priority to asthma? reduced availability of beds? but also some related to public response to covid-19. social distancing? use of masks? reduced travelling? closing of schools? home office practices? these are all conditions or behaviours that might have resulted in mass acute respiratory infections which we know well are the major cause of exacerbations in asthma and copd. well, looking at the copd possibilities, it's about the same, related to patients' behaviour, better adherence to treatment, fear of attending emergency rooms due to covid-19, all question marks. reduced priority to copd in the health system, reduced availability of beds and all the others relating to behaviours that could have resulted in less acute respiratory infections. well, in summary, asthma and copd during the covid epidemic in brazil, covid has affected over 7,000,000 brazilians in a country with a 12% prevalence of asthma and 15% prevalence of copd in those over 40 years. there was a thought that could have a potential of a lot of problems, hopefully it didn't happen. although covid as killed over 180,000 people, the proportion of asthma and copd among those dying of covid is smaller than their respective prevalences. asthma, copd exacerbations and hospitalisations have been remarkably reduced in times of covid-19. and finally, it is likely the reduction in asthma and copd exacerbations is related to a reduced frequency of acute respiratory viral infections due to social distancing measures. i think it's time to seize the attention given to respiratory health globally to raise priority to asthma and copd. no longer separate from infections, respiratory conditions but as a whole respiratory disease, or even better, respiratory health. we have compelling evidence from major reduction in exacerbations of chronic respiratory disease due to behaviour changes. i think this warrants major, immediate investment in research to figure out what can be applied to protect subjects with asthma and copd after covid? thank you very much. lorenzo corbetta: thank you alvaro for your very elegant presentation and if there are some questions from the panel? david? david halpin: thank you alvaro, that was really interesting. have you got any data on copd or asthma, probably copd mortality during this time? because in the uk, we've seen, again or saw back in the spring quite a marked reduction in hospitalisation but there was something like a 20% increase in mortality from copd compared to previous years so it did look as though the explanation was people were frightened to come into hospital and were staying at home when they really should have come to hospital and one of the messages has been 'if you need to come to hospital, you should come to hospital, you shouldn't be afraid of covid'. have you got any similar data from brazil? alvaro a. cruz: david, the database for mortality in brazil takes much longer to be built because there are many checks, so we don't have this available. for asthma, we thought of this but in our study, the one that i showed in primary healthcare, we've been calling these people and we have no evidence that they are heavily more taxed and stay at home because they have an action plan with oral corticosteroids and they are not using it, so it seems that they are really protected somehow. l. corbetta et al. 6 david halpin: i mean i think all the things you talked about the masks, the working from home, the avoiding travelling all of those things are reducing viral infections aren't they? which has to be a good thing but it did look in the uk certainly that the copd patients were perhaps taking it just a step too far and not coming to hospital when they should have done. lorenzo corbetta: okay, if there are no more questions, now pleased to introduce professor leonardo m. fabbri, everybody knows leo fabbri, an expert in asthma, copd and with the presentation on the “position of the guidelines”. leonardo fabbri: thank you again for the invitation, title i've been assigned is very simple, the position of asthma and copd guidelines, i have to admit that gina and gold have no guidelines, have strategy documents and i highlighted the data. leonardo fabbri: first i will discuss the gina but before doing that i'd like to tell you and inform those of you who are not aware that on the 16th and 17th of november there was an international conference organized by gina and gold in philadelphia and the two days devoted one to copd and one to gina-, you may have access with the link below i leave this for you so that you can check that and you have the agenda that you can read now but if you click on the agenda once you are in you have registered that you are in and you can play all the presentations they're very informative and very nice but then in saying that, they're just an advertisement for gold and gina that are very good and very active in the field of copd and asthma. so, gina already last march released a document and posted in several websites including the gina website the global initiative for asthma and making the following recommendation first to avoid useless, invasive, potentially dangerous measurements like spirometry and in general follow infection control procedures in far as so generating procedures where needed. these regard particularly carefulness required for nebulization, oxygen therapy including nasal prongs, sputum induction, manual ventilation, non-invasive ventilation, and intubation, and you can also have a link for this-, all the other ideal strategies are the same for covid in general. the document was then updated with the recommendation that people with asthma should continue all their inhale medication including inhale corticosteroid as prescribed by the doctor, in acute asthma exactly the same including the inhaled bronchodilator with cautions for the potential dangers of using inhalation therapy and oral steroids is recommended and is required. sometimes people with severe asthma may require a longterm minimum dose of corticosteroids on top of their inhaled medication and all treatment should be continued. the patient should not interrupt the regular treatment when they take the oral steroids, and even if the evidence is very limited the recommendation is that even biologic therapies should be continued in this patient-, nebulizer avoided if possible or all confined, pmdi via spacer while the patient is treated for a severe attack their maintenance in asthma should be continued at home or in the hospital. patients with allergic rhinitis should continue their nasal corticosteroids and again spirometry should be used only if strictly necessary, which in regular management of copd and asthma is not really required. as david halpin showed you convincingly, ics should be written and corticosteroids should be used only in conjunction with exacerbations that is abuse of oral corticosteroids. we know that particularly associated with excessive use of prn short-acting bronchodilator, the patient should be instructed, not only of the use of the medication but also in the plan and again avoid nebulization. the document also makes a recommendation for the so-called by gina people, 'aco asthma copd', the gold people call it 'asthma and copd' not aco, but basically the message is in this table continue to treat the patient as recommended for a patient who has not had covid-19, so if asthma, it is asthma, if it is overlapped with the asthma, if it is only copd without asthma take the copd. let me remind you, as i highlighted in the beginning because there are controversies in the original national guidelines, that the gina is an evidence-based document that is prepared by gold by expert true evidence, true evidence taken from the literature. some of the recommendations are off-label because in some countries the drugs are not registered so there is no use of 'off-label' in the gina. stand on the same side against covid – 19: ics-containing products in treatment covid-19 patients with asthma and copd 7 for new therapies, the recommendation are usually based on at least two or one solid randomized clinical trials providing evidence and for existing medication with evidence and new regiments the same applies for the rules and when you-, the most important part of this recommendation is when assessing and treating patients you should refer to your own professional judgement and take into account local and national guidance. gold, now above the document and the teaching slide labelled 20 and 21 are available in the gold website and the release of the document was anticipated by a very nice article published in the american journal of critical care medicine by david halpin and other members of the scientific committee of gold. the main question of the management of copd is whether copd are at increased risk of becoming infected with sars, the answer is no, although the data is limited, ics long-acting bronchodilators, roflumilast, macrolides should be continued when required likewise systemic steroids with antibiotics during exacerbation. a particular, careful, clinical approach should be taken to make the differential diagnosis between an exacerbation of copd and covid, usually they are different but they may also present with very similar characteristics. patients who develop moderate to severe covid-19, including hospitalisation should be treated with evolving pharmacotherapy and-, now the slide is still updated on the document but there are some controversies on the cost benefits of remdesivir, those are matters for the severe patient and anticoagulation also when you have a suspicion of coagulation unless the patient is lying in bed for a long time. the acute respiratory failure should include appropriate oxygen supplementation and noninvasive ventilation, you have to look at the specific recommendation but again, protecting lung ventilation in patients with ards. in a patient that's developed mild copd, they should be just treated with the symptomatic drug as normal, whereas the patients who develop moderate and worse copd should be monitored more frequently than normal with particular attention to the need of oxygen therapy. you know, there is a common experience that you have a patient coming in with some dyspnoea symptoms more relevant than the saturation but you should be watching very carefully the patient admitted to the hospital because they may develop respiratory failure within hours. these are the slides that are included in the 20 and 21 gold document, protective strategies are the same for everybody including considering, shielding and sheltering in place of the patient, no spirometry, make sure not only that the drugs are properly taken but that they are also made available according to the treatment plan and no pharmacologic therapy if possible should be continued, including the influenza vaccination-, and this year there is a recommendation from the document also of pneumococco vaccination. if the patient's contract or are suspected of contracting copd you should go through the usual pcr diagnostic approach, swab oral saliva and use recommendation and pharmacotherapy and nonpharmacotherapy protective therapy and the covid-19 therapy. this is the most instructive and carefully designed, simple approach to the different covid-19 affecting copd patients. on the left you have the copd non-infected that you follow the usual ways if it is milder you have most importantly, you have to be watching the signs or symptoms that predict the development of respiratory failure, here our report has listed. and if by contrast, the patient developed more dyspnoea particularly and hypoxaemia then you have to increase the diagnostic approach and if there is respiratory failure you should treat the patients with the usual approach for respiratory failure with all the valuables that are included. the convalescent covid patient should be carefully followed up and the gold document includes also a copd follow-up checklist, that should be monitored. i think that any unit is now following a strict protocol to monitor these patients that may develop, there is no evidence yet, it may be a matter of discussion, of developing of fibrosis as immediately as we said but if we look at the experience with the ards it's not so common the developing of non-reversible hydrolysis after an acute event. this is the end of my presentation, i am happy to answer any questions. lorenzo corbetta: thank you, thank you leo for a very nice presentation. are there some questions from the circle team? i have one, in the last figures that you showed i can't see any difference between copd patients and healthy patients, are there some differences? and suggestions that you can give us? leonardo fabbri: well usually, it may present with cough and dyspnoea but most of the cases of covid-19 present with dyspnoea and fever and also as you know, taste and smell abnormality, gastroenteric systems, it's more systemic. i mean the copd exacerbation is an increase of dyspnoea, 100%, the cough is producing sputum, 20-30%, rarely a fever and so i think that in the prototype they actually are not so difficult to distinguish but equally during the pandemic like now, i think that my colleagues in the clinic, they almost avoid imaging because they say that the characteristic feature of covid-19 are almost invaluably present symptoms that i mentioned to you and in fact, they don't even do chest x-ray or most l. corbetta et al. 8 importantly ct-scan because they now have the ultrasound that helps them to avoid going to the imaging department, particularly for ct-scan i have to say, chest x-rays are much easier to be done. david halpin: it is important, i think you're absolutely right leo and what we've said in gold certainly is, to answer lorenzo's point is that actually, the management of a copd patient should be no different to the management of any other patient but i think one of the things that have become clear with covid is the high risk of venous thromboembolism, so i think if a patient is quite significantly hypoxemic then a ct looking for pulmonary embolism is an important investigation for those patients. so, having a high suspicion for thromboembolic disease applies to all patients but rather than just managing the lungs we need to think-, as your very aware-, about the pulmonary circulation as well. leonardo fabbri: yes, you're right, almost all the patients at least in my country that are admitted to the hospital and are predicted to stay for more than two or three days in bed are treated with low molecular weight heparin prophylaxis that doesn't mean that you don't have to make the, you know, proper diagnosis of potential pulmonary embolism because we know that in copd is increased but not that much, i mean it's not a common feature whereas in covid-19 not only may be frequent but may even be more complicated than that because one question i didn't have the time to ask you, david, during your presentation is that the two tissues that are actually targets of the covid-19 are the epithelium first but the endothelium second and if you look, there is a couple of papers, two or three papers of pathology that shows that it's not only embolism it's also vasculitis that makes the picture more severe, you made a very good point. alvaro a. cruz: leo, i think it's pretty clear that covid spares the airways, it enters through the airways but it hits the lungs and the vessels but spares the airways. do you have any explanation about this or any further information on how things work in terms of the information in the airways? leonardo fabbri: yes, another very interesting question. there is a case report of covid-19 deaths or of an asthmatic who died of covid-19 and he had all the characteristic features in the airways of asthma whereas he had all the characteristic features of covid in the lungs. so, the second point is that-, i'll send you the reference when this meeting is over. there is an interesting review article on covid-19 as a systemic disease and just highlighting that the endothelium is probably the most relevant and that simultaneous abnormalities are present particularly in the liver, in the kidney, in the brain and so that why the airways are spared i think that goes together to the fact that people with asthma have not increased the risk of getting covid-19 probably, you know, either for the defence mechanism that david highlighted or the protective effect of treatment might be preserved, protected maybe, but there is no evidence. lorenzo corbetta: okay, thank you. we can move to the next speaker. i'm now pleased to introduce stefania zanconato who is the head of pneumology and paediatric allergology unit, the department of women's and child health of the university of padova. thank you stefania for accepting to participate. stefania zanconato: okay, hello. thank you for the invitation to this webinar i will talk from the paediatricians side. so, i'll start just with what we know about covid-19 and children. this recent data from the who is on the distribution of confirmed cases by age. as you can see, only two percent of all cases were reported in children under four years of age, and five percent in children under fourteen years of age. so, covid-19 is reported much less frequently in children than in adults. this data from different countries, this is the initial data from china, in 2135 children with covid19 and as we can see most of the cases, most of these children are mild or asymptomatic disease, mild or moderate disease. (https://doi.org/10.1542/peds.2020-0702) so, symptoms were less severe than in adults, and young children, especially infants, were more vulnerable to severe sars cov-2 infection. this data from different european countries, you see from 82 health care institutions, in 582 children with a median age of five years and as we can see 48 of these children required the icu admissions and fifteen percent of these children that went to an icu were under one month of age, and 52% had previous medical conditions. so, the risk factors for icu admission in the paediatric age are very young age, under one month of age, male sex, preexisting medical conditions and lower respiratory tract infection signs at presentation. this data from different countries, the data more or less reports similar results. (https://doi.org/10.1016/s2352-4642(20)30177-2) children were one, two percent of all the diagnosed cases, 4-24% were asymptomatic and death rates were up to 0.7%. in our paediatric hospital since february we admitted 61 children, at least until the day before yesterday. 61 children with sars cov-2 infections. 44 were under one year of age, 38% had previous medical conditions and none had chronic respiratory diseases and none needed icu admission. so, children are more often asymptomatic, have less comorbidities, so why do children have milder presentation? there are different hypotheses. one is that ace2 receptors are less mature in the airways of children. that in children there are different, you know, children usually have many viral diseases and so sars covhttps://doi.org/10.1542/peds.2020-0702 https://doi.org/10.1016/s2352-4642(20)30177-2 stand on the same side against covid – 19: ics-containing products in treatment covid-19 patients with asthma and copd 9 2 has to compete with other viruses in the airways of children. then, probably in children there is no generalised cytokine storm and the children have more often a t2 skewed immunity that seems to be protective. so, what do we know? we know that covid-19 is reported much less frequently in children than in adults, the children have a much milder disease than adults but unfortunately there is increasing evidence of a multisystem inflammatory syndrome post covid-19, about a month after the covid infection and sars cov-2 infections. it is a kawasaki-like disease with persistent fever, elevated inflammatory markers, multi-organ involvement, cardiogenic shock. right now we have two of these children admitted in our hospital, one of them required icu admission. but we cannot forget as pediatricians the other effects of the coronavirus epidemic in children. the higher rate of psychiatric morbidities, education loss, the unhealthy lifestyle changes, we know they don't exercise, they spend a lot of time in front of a cellular phone and they eat junk food and finally, the increased child neglect. but what do we know about asthma and covid-19 in children? at the beginning of the pandemic, you know, the cdc stated that, 'asthma is a prognostic factor for covid19 outcome such as morbidity and mortality' but right now we know that initial concerns about children and young people with asthma being particularly affected by covid19 has not been realised. on the opposite, it looks like children and adolescents with allergy and/or asthma seem to be protected from sars cov2 infection or from covid disease. but this is a study that evaluated the expression of the sars cov-2 receptor, the ace2 receptor, the upper airways of 318 children were part of a quarter of children and they had the nasal brush and we can see here on the left the ace2 expression was decreasing the nasal epithelium of children with allergic sensitisation. why? in asthmatic children there was a progressive lower level of ace2 according to the degree of ige sensitisation among children with asthma. so, paradoxically, asthma may be protective, as the ace2 receptor may be underrepresented in the lungs of atopic children. (https://doi.org/10.1016/j.jaci.2020.04.009) this data from a couple of areas from north italy is where we can see 30% of the paediatric population is allergic and 11% of the paediatric population has asthma, and we see that out of 2000 people that were diagnosed with covid-19, only 40 were children and out of these 40 children only two were allergic and one had asthma. so, children with allergy and asthma are rare in the covid-19 population and this suggests that allergy could be a protective factor. this data from 182 hospitalised children from china, 42 had allergic diseases, 98% had no severe disease and what we can see there was no difference in allergic prevalence within children with pneumonia and with no pneumonia and there was no difference between allergic and non-allergic covid-19 children in disease incidence, clinical features, laboratory and immunological findings. (https://doi.org/10.1016/j.arbres.2020.07.003) this data from spain where 29 asthmatic children with covid-19 were compared, or maybe with sars cov-2 infection were compared with 183 asthmatic children with no infections and all these children had mild symptoms of sars cov-2 infections, and there were no difference in lung function and asthma control between the asthmatic children with sars cov-2 infections and those who did not have infection. so, in asthmatic children covid-19 symptoms were mild, and allergic asthmatic children are not more vulnerable to suffer from covid-19. this data from london, when there was the lockdown and the schools closed we see the dramatic decrease in emergency department attendance of children with asthma or wheeze and even though the pollution measured by pm10 levels did not change. so, in closing schools, children may have reduced exposure to viral infections, we have already talked about this and pollution on the school run and have undertaken less formal exercise. these are some of our data where we evaluated 92 asthmatic children with the same prescription for asthma in the same month of spring 2019 and spring 2020 during the lockdown, and we see that there was a better asthma control with a lower gina score in the year 2020 compared to the year 2019 and we had less acute exacerbations, so better control of asthma and finally, this data from philadelphia that i think would be applied from many different countries. what happened during the pandemic was a dramatic decrease in the in-person, outpatient care for asthma with an increase in telephone and video telemedicine. in the same time there was an important decrease in rhinovirus infection that we know is one of the main triggers of asthma exacerbation in children and a decrease in (mw 01.20.59) in the systemic steroid prescription. https://doi.org/10.1016/j.jaci.2020.04.009 https://doi.org/10.1016/j.arbres.2020.07.003 l. corbetta et al. 10 so, the care of children with asthma changed i think all over the world during this pandemic and with more video telemedicine, less asthma in-person care, less systemic steroids, less rhinovirus and less exacerbation. finally this is the last data. this data from 99 paediatric centres all over the world, and they report similar results. the virtual clinics were launched in most centres, better than expected control was reported in 20%. adherence, as we already heard in the previous talks, appeared to increase and there were only fifteen confirmed cases of covid-19 that were reported, so similar to that of general paediatric cohort. so, children with asthma were not disproportionately affected by covid-19 and clinical services have rapidly responded to the pandemic. obviously only ongoing epidemiological studies will tell us the long-term risk of covid-19 on children with asthma. these are the commendations released by the eaaci on asthma and covid-19, or allergy and covid-19. they say that paediatric allergists are dealing with a patient population that is at low risk for covid-19. that like in adults, there is no scientific evidence that allergy and asthma treatment increases susceptibility or severity of covid-19 disease, and asthma control with appropriate medications should be a major goal in all asthmatic patients, children and adults. what about children with severe asthma? as we know, there are not so many studies focusing on severe allergic phenotypes and particularly obviously in children. what we know is that in case of an active sars cov-2 infection, biological treatment needs to be stopped until recovery. what about asthma treatment-, which treatment they have to follow, children and adolescents? you all know that since 2019 that gina no longer recommends saba-only for treatment for step one. so, adolescents and adults, step one the first choice recommended, the first therapy, the first choice is the low dose ics-formoterol that can also be used as step two as an alternative to daily low dose of inhaled corticosteroids. in children, on the other end, step one, a low dose of ics is recommended whenever short acting beta agonist is taken while step two, the first choice, daily low dose inhaled corticosteroids. what else can the paediatrician do? the paediatrician can help his children particularly, his adolescents. try to help these children comply with treatment. we know that adolescents are very bad patients and also we know that children don’t use their drugs, their asthma drugs in the correct way. so, paediatricians need to monitor and correct inhaler techniques at every opportunity. just a couple of words on what happened when the children went back to school? these are just some emails parents sent to us, “dear doctor, my child does not want to wear the face mask, she can't breathe.” “dear doctor, my child does not want to wear the face mask, she can’t breathe……..” “dear doctor, i am very worried for my child who has asthma. is he at risk for covid-19?” “dear doctor, today my child has been sent home from school because she was coughing, what can i do?” and we really were overwhelmed with these phone calls and emails. what about face masks in children? the who states that, 'face masks of breathable material, worn properly, will not lead to health problems.' so, even in children you see, for most children masks won't make it harder to breathe. so, children over two years of age have to wear a face mask. this includes children with many medical conditions. what about nebulisers? we already heard what gina tells us and we know that the main route of sars cov-2 transmission is direct contact, indirect contact. the main respiratory transmission is through droplets, while the transmission of aerosol-producing generated procedure is not clearly stated. so, at present there are limited data on whether nebuliser administration may be considered an aerosol generating procedure or may represent a transmission risk and we know that many children, particularly with the acute exacerbation, use nebulised treatment. we know we have also different advice. we already heard that gina advises against the use of nebulised treatment where possible. cdc does not advise against the use of stand on the same side against covid – 19: ics-containing products in treatment covid-19 patients with asthma and copd 11 nebulised treatment but states that there is an unknown-, we don't know what the exposure is for health care personnel that has still to use the ppe. nice recommends to continue use of nebulised treatment and eaaci states that, 'in patients infected by sars cov-2, nebulisation increases the risk of virus deposition in the lower airways and should be replaced by spacers.' so, this is my last slide. what can paediatricians do? paediatricians, what else can they do? where possible-, obviously because if we find ourselves in front of a two-year old child screaming and crying, we do the best we can, but where possible we have to try to switch from nebulisation to mdi, obviously with a valved holding chamber in children. these are my conclusions. lorenzo corbetta: thank you very much stefania. very, very interesting presentation. some questions from the panel? leonardo fabbri: may i? first, thank you very much for the very clear lecture and nice to see you again after some time in padova. the question is a naïve question. every newspaper says that the children kill their grandfather, grandparents, because they bring infection home. is that evidence-based? stefania zanconato: yes, let’s say most of the children are infected in the family actually, not in their social environments. so, while we do not know how infection children are, while we know that children have the mild disease, that children are not often infected, we still don’t know how contagious the children are. while most of the children, even now in our hospital, are children that came from family where there was an infection so they did not get infected at school but in the families. leonardo fabbri: thank you. lorenzo corbetta: other questions? david? no? david halpin: there is a question on the chat. so, we do talk about this in the goal document and i think that there is evidence both for reactivation and for reinfection. it's rare, but it happens and it seems to be generally in people that have immunosuppression either because of medication or because of immune deficiencies. so, i think it is something we should be aware of but it doesn't seem very common. in terms of new mutations, i mean, there's been a lot of publicity in the uk this week about a new variant that's been identified in the south east of england and around london which seems to have a greater propensity to spread, it probably doesn't cause any worse disease but it seems to be transmitted more easily, and earlier in the year there seemed to be a different variant that emerged in spain. so, this is what you would expect with a virus, that there is mutation and new variants arising. as i understand it, and has been stated in the uk, this won't influence the efficacy of the vaccine but it does change slightly the dynamics of transmission. lorenzo corbetta: yes, i completely agree. in our last webinar we had a biologist, duccio cavalieri, that confirmed that there is a new mutation that increased infections but not the pathogenic and the response to the vaccination. stefania zanconato: that is important. lorenzo corbetta: yes. okay, leo, do you want to say something to conclude? leonardo fabbri: thank you. i think we had a very interesting webinar, we learned from each other. i hope lorenzo you continue with your organization. the last was on vaccine, today we had very nice lectures on the ics with the user, we heard about the children, we learned about the children and alvaro as usual gave us a sparkling clear picture of brazil, we are very concerned about brazil but i think that in terms of percentages, we are now more similar, you know, and we hope that-, i think that the uk already started vaccination, they said in the press today that we should have the first before the end of the year on the 28th or 29th of december, and i don't know when in brazil and i hope that these will rescue us from future disaster. let me take the opportunity not only to thank you all for your enthusiastic participation but also wish you all and your families a merry christmas and happy new year. enjoy, bye bye. stefania zanconato: happy new year, yes. bye bye. lorenzo corbetta: goodbye and thanks again. substantia. an international journal of the history of chemistry 3(1) suppl.: 61-66, 2019 firenze university press www.fupress.com/substantia citation: a. serpe (2019) hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods. substantia 3(1) suppl.: 61-66. doi: 10.13128/substantia-607 copyright: © 2019 a. serpe. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-607 hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe department of civil and environmental engineering and architecture (dicaar) and instm unit, via marengo 2, i09123 cagliari, italy e-mail: serpe@unica.it. phone n.: +39 0706755543. abstract. precious metals (pms) are valuable components of hi-tech goods such as electrical and electronic equipment, catalysts, advanced materials. these relatively recent applications and the growth of their market due to the fast technological development, heavily contribute to the high rate of element consumption and hi-tech waste accumulation of the modern consumer society. looking at these wastes with new eyes, encouraged by the recent world-wide regulations aimed to the sustainable waste management and raw materials preservation, we can appreciate the value contained in and turn them in secondary resources of raw materials. in this context, a sustainable approach in pms recovery from hi-tech waste, built on green chemistry principles and addressed to find a ready technological transfer, is described here. keywords. green processes, circular economy, secondary sorces, noble metals recovery, waste electrical and electronic equipments. overview one of the main aspects related to the modern consumer society is the fast technology development and the inevitable production of high and increasing amount of waste it entails. the assets, especially the hi-tech ones, play an essential role in our daily life and their life cycle gradually decreases. electronic equipment, automotive devices and advanced materials, often contain significant quantities of valuable and even toxic materials which would be destined to landfill, thus generating a serious environmental issue, if not valorized in a different way, e.g. through reuse or recycling. european and several other countries regulations on waste electrical and electronic equipment (weee),1,2 end-of-life vehicles (eolv)3 and batteries & accumulators,4 the fastest growing and pollution generating waste streams in the world, ban the uncontrolled disposal of these goods at the end of their life encouraging the implementation of a virtuous circular economy model where the recovered materials, obtained as output of waste valorization processes, are the input raw materials for new productions.5–7 sustainable recovery processes are also urged in order to prevent pollution and further waste generation. 62 angela serpe in this context, pms play a key role. indeed, they are widely used in hi-tech goods because of their physical and physicochemical properties. high electrical and thermal conductivity and high resistance to the oxidation (they belong to the noble metals family characterized by high reduction potentials), coupled with their malleability and ductility, make these materials particularly appealing for industrial application mainly as conductors in long lasting high technologies. besides that, they have limited natural availability and high economic value. for these reasons, and due to the relatively high pms concentration in hi-tech scraps (where often they are present in concentration even higher than in their ores),8,9,10 their recovery may represent the driving force for the profitability of more comprehensive materials recovery processes. currently the main methods used industrially to recover valued metals from the main hi-tech wastes have been mostly inherited from the well-known processes conventionally applied on ores and jewelry ashes and are mainly based on pyrometallurgy and hydrometallurgy.11,12 the former, which operates by smelting and refining, generates high financial and environmental costs, while the latter, less energy-intensive, more tunable and predictable but often based on the use of toxic and aggressive substances (e.g. cyanides, strong oxidizing acids), can heavily affect the environment, biodiversity and human health, if not strictly controlled for reactants and wastewaters production. a wide research effort is hence required to find new ways for recovering and recycling materials from hi-tech scraps able to combine effectiveness to environmental sustainability. a multidisciplinary environmental science approach is needed to face this challenge. the last two decades have seen environmental scientists with different background (e.g. chemists, engineers, biologists) and complementary skills, at work for turning this issue into a market, scientific and environmental opportunity. some interesting results, both in terms of effectiveness and environmental sustainability, have been obtained in the last two decades by deplano’s group of coordination chemists, for gold, palladium and platinum recovery from hi-tech wastes by using safe leaching agents and mild condition processes.13 here we describe the results obtained for two different families of hi-tech waste, following a new greener approach, exploiting the interaction between the complexing and oxidizing species in the reaction environment which promotes an effective nms leaching. the case of weee the weee family contains all the devices that work with electric current or electromagnetic fields, such as: personal computers, mobile phones, tvs, printers, refrigerators, washing machines, photovoltaic panels, lamps and other small and large appliances. this type of waste contains a variety of different materials that stimulate interest on recycling profitability. at the same time, they make recovery processes a really complex issue. in particular they can contain plastics, glass, copper, aluminum, iron, as well as noble materials, especially metals (e.g. gold, silver, palladium), and other critical elements such as “rare earths”, often beside toxic substances such as mercury, cadmium and lead, extremely hazardous for the environment and for human health. to understand the greatness of the weee phenomenon, it is worth mentioning that world production of weee in 2016 was around 45 million tons (+8% by 2014). according to the onu, this trend is expected to grow further to 52.2 million tons (+17%) by 2021, the fastest increasing rate in the world’s solid urban waste.14 but there is still much to do for turning them into value, recovering materials in an environmentally friendly manner differently from currently used industrial methods. conventional methods often give a not satisfactory (in terms of recovery rates) and costly (both in terms of economic and environmental impact) answer to this need. an interesting promising contribution in the field of nms recovery from weee in particular small appliances, printed circuit boards (pcbs), printer cartridges and smartcards comes from the smart use of coordination chemistry in finding sustainable reactants able to combine oxidizing and complexing properties in a single molecule. it is well-known, indeed, that the presence of a complexing agent is necessary to lower the reduction potential and make feasible the oxidation of metals with highly positive reduction potential such as gold, palladium and platinum (as in the case of cyanides and aqua regia).11 molecules coupling complexing and oxidizing moieties show enhanced reactivity with respect of the “free” reagents, as demonstrated in the 1990s by the mcauliffe’s group in a pioneering study on the reactivity of r3d·i2 (r = alkyl; d= as, p) charge-transfer (ct) complexes towards crude inactivated metal powders.15 on these basis, with the view to find safer and more effective leaching agents able to overcome the sustainability issues put by conventional methods, deplano’s group started an extensive study on the use of sulfurdonor/dihalogen ct complexes. in particular, dihalogen/interhalogen adducts of cyclic and acyclic dithiooxamides (dto), soft chelating ligands bearing two vicinal thionic groups able to favor the square planar geometry preferred by d8 metal ions, demonstrated to be a powerful class of non-cytotoxic and easily handled lixiviants towards gold,13,16,17,18 palladium,13,19 copper,13 silver,13,21 63hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods and platinum,22 under very mild conditions, mainly providing complexes of general formula [m(dto)2]n+ and/ or [m(dto)i2](n-2) (m = nm; n = charge of the metal cation) as shown in table 1. among them, the bis-diiodine adduct of the n,n’dimethyl-perhydrodiazepine-2,3-dithione (me2dazdt·2i2) behaved as the most effective in the one-pot gold dissolution at room temperature and pressure in common organic solvents, and it was employed fully satisfactorily for the sustainable gold recovery phase in weee treatments as patented by the group in the last decade for the lab scale.23,24 figure 1 summarizes the patented threestep sustainable process for the treatment of a test specimen consisting in a thin metal powder (diameter=0.4mm) obtained by small appliances and pcbs comminution and deprived by aluminum, ferrous metals and vitreous-plastic materials, consisting in the selective dissolution and recovery of i) base metals; ii) copper; iii) gold. the described process is based on the use of safe reagents. it is selective and easy to be implemented and managed consisting in just few steps which require mild operative conditions. moreover, it is effective in the recovery of noble metals, which are obtained almost quantitatively in form of elemental metal by chemical (cementation) or electrochemical (electrowinning) reduction. from the other side, me2dazdt·2i2, though recyclable at the end of the process, is a reagent not yet available on the market and which works in organic solvent. in order to promote green chemistry processes able to meet green engineering principles as well for a faster technology transfer on industrial scale,11,25,26 several changes in the process were studied and implemented as improvements. in particular: – 1st step: a refluxing citric acid solution was used in place of hcl, in order to promote the use of weaker natural acids and increase selectivity; – 2nd step: an alkaline i-/io3mixture, able to combine oxidizing with coordinative capability, was used, in the presence of ammonia, as a more reliable alternative to h2o2, avoiding effervescence phenomena and promoting in one time the copper leaching and the separation of silver from the solution in form of agi precipitate; – 3rd step: a i2/iwater solution was used as leaching agent for gold in turn of the me2dazdt·2i2 solution in organic solvent. although the demonstrated lower reactivity of the i2/imixture, the lower cost of the reagents, their availability on the market and, remarkably, the easy recyclability of i2, make this process really promising for a sustainable application on a large scale. satisfactory results (almost quantitative yields in nms recovery) were obtained on the cited test specimen through this new process design, pursuing a virtuous cycle able to limit the wastewater production.27 remarkably, this process demonstrated to be applicable satisfactorily also on coarser materials like shredded pcbs, where a heterogeneous size distribution and the presence of composite materials are present.28 these last results demonstrate the robustness of the approach which seems appealing also from a costs/benefits ratio point of view(1) and open the way for further larger scale experimentations. 1 the mechanical comminution and separation pre-treatments of the incoming material represent one of the heaviest costs of the whole recovery process table 1. summary of the reactions between cyclic dithioxamides/i2 leaching agents and au, pd, pt, ag, cu powders under mild conditions: room temperature, 2:1 molar ratio; acetone (or thf or ch3cn). leaching agent metal main product ref. au [au(me2dazdt)i2]i3 13,16,17 ag -a 13 pd [pd(me2dazdt)2]i6 13,19 pt -b 13 me2dazdt·2i2 cu [cu(me2dazdt)2]i3 13 au [au(me2pipdt)i2]i3 13 ag [ag(me2pipdt)i]2 13,20 pd [pd(me2pipdt)2]i6 13 pt [pt(me2pipdt)2]i6c 22 [hme2pipdt]i3 cu [cu(me2pipdt)2]i3 13 aunidentified product; bunreacted metal; cobtained under solvent reflux. figure 1. schematic representation of the deplano’s group cu and au recovery method from comminuted weee, based on the use of me2dazdt·2i2 as gold leaching agent.22,24 64 angela serpe the case of three way catalysts (twcs) twcs are exhaust emission control devices applied to the exhaust of vehicles in order to significantly reduce the polluting emissions (essentially of co, unburnt hydrocarbons and nox), favoring oxidation and/or reduction reactions with formation of non-harmful compounds. thanks to modern regulations that impose strict limits on vehicles emissions, from the 1st january 1993 the use of twc is mandatory for all cars in all european countries. every year, between 6 and 7 million of eolv, corresponding to 7 and 8 million tonnes of waste, are generated in the european union which should be managed correctly. well-known procedures for managing eolv, reuse of still working parts and processes for the enhancement of bulky materials such as iron, aluminum, glass, etc., have being implemented. differently, it is still an issue to enhance materials from electronic apparatus, batteries, car fluff (complex mixture of non-ferrous materials including plastics, foam, textiles, rubber and glass residue from car demanufacturing) and catalytic converters. among them, in the specific field of noble metals reclamation, catalytic converters represent a rare opportunity. indeed, they typically consists in a metal case containing the substrate (ceramic or metallic, with a “honeycomb” structure) coated by the wash-coat(2) which supports from 5 to 8g (for petrol and diesel engines, respectively) of highly dispersed catalytically active phase formed by a mix of metal platinum, palladium and rhodium. these metals are able to promote the oxidation of carbon monoxide to carbon dioxide and that of unburnt hydrocarbons to carbon dioxide and water (pd and pt), and the reduction of nitrogen oxides to nitrogen (rh).29 notably, pd-only technology has been introduced in catalytic converters in the last years.30 it is estimated that the car industry alone, which puts about 40 million new cars on the market every year, represents a potential annual resource of $1 billion of pd recovery.29 currently significant but still low (∼30%) noble metals recycling from spent car converters29 is done by non-selective unattractive methods involving unselective pyrometallurgical chlorination30 or dissolution with strong oxidizing acids30 in the crucial metal-dissolution step.31,32 based on the promising results described above on the use of dithioxamide/i2 adducts with crude metal palladium, a joint project by deplano’s group, from university of cagliari, and graziani’s group, from university of trieste, allowed to check the effectiveness of me2dazdt·2i2 on model twcs consisting in a pd(2.8%)2 high specific surface layer 40-50 mm thick, of g-alumina or ceo2– zro2/al2o3 in current technologies ceo2–zro2/al2o3 material underwent simulated aging (1050°c, 200h) for assessing its potential in pd recovery from spent car converters.33,19 almost quantitative pddissolution and recovery rates were achieved through the selective metal leaching by refluxing a methyl ethyl ketone (mek) solution of the molecular adduct in the presence of the cited test specimen in form of powder for 168 hours, has been patented and summarized as follows (figure 2). the main recovered product was the [pd(me2dazdt)2] i6 complex. pd metal was quantitatively obtained by both chemical and thermal degradation of the molecular compound. differently, pd metal recovery attempts by chemical or electrochemical reduction were unsuccessful as expected because of the dithiolenic nature of the dicationic compound.(3) nevertheless, [pd(me2dazdt)2] i6 complex demonstrated to be successfully applicable in his molecular form as valuable homogeneous catalyst for c-c coupling reactions34 and as precursor of effective photo-catalysts for h2 production.35 as a cheaper alternative, we recently studied the use of safe fully organic triiodides (organic cations: tetrabut hylammonium, tba+; tetraphenilphosphonium, ph4p+; 3,5-bis(phenylamino)-1,2-dithiolylium, (phhn)2dtl+) as pd leaching agents in organic solvents. the presence of an organic cation in the triiodide salt showed to dramatically improve its pd-leaching properties with respect to those of the fully inorganic ki3 salt, hampering the formation of pdi2 coating passivation (typically present in these cases and limiting the leaching reaction to go ahead) by promoting the formation of stable and soluble ionic couples of gen3 in this class of complexes, the reduction event involves the whole molecule without achieving dissociation into metal and ligand components. figure 2. schematic representation of the deplano’s group pd recovery method from model aged twcs based on the use of me2dazdt·2i2 as palladium leaching agent.33 65hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods eral formula org2[pd2i6].36 although the recovery rates achieved using the cited triiodide salts were found slightly lower than those found by me2dazdt·2i2 solutions in analogous experimental conditions (98%, 83%, 73% for (phhn)2dtli3, ph4pi3 and tbai3, respectively, vs almost quantitative for me2dazdt·2i2), these reactants seem really appealing for practical application due to their low cost and environmental impact, mild reaction conditions, market availability (or easy synthetic procedures), as well as for the easy metal pd and reagents recyclability. conclusions and perspectives the present work highlights how coordination chemistry, which is traditionally involved in the recovery/refining processes of nms, can give a relevant contribution in designing molecular-level methods able to combine effectiveness with low environmental impact, as promoted by green chemistry principles and required by new legislation. on these basis multidisciplinarity seems the key approach to grew up molecular to industrial scale processes meeting both green chemistry and engineering requirements in order to balance sustainability with economic development. here, a new promising sustainable approach based on the combined coordinative and oxidizing capability of safe, easy to handle and working in mild conditions charge-transfer compounds towards nms, has been presented. a further effort is required to the environmental sciences community for implementing these methods on a larger scale in order to promote the conversion of trash into resource making the “circular economy” model feasible. acknowledgements the author thankfully acknowledges tca for the kind invitation to present this work at the “i metalli preziosi nella storia della scienza e della tecnologia” symposium in the occasion of the goldsmith fair 2018 in arezzo.37 it is worth to mention that the work described here has been carried out by valuable research groups in around 30 years of research activity. the author thankfully acknowledges professor paola deplano for designing and coordinating the research activity at university of cagliari and for mentoring the author and the other co-workers on this topic for the future developments. the author also acknowledges professors mauro graziani and paolo fornasiero and their co-workers, university of trieste, for their relevant contribution in studying the twcs applications and the photo-catalytic behavior of the pd-complex in h2 production, as well as professor massimo vanzi and co-workers, university of cagliari, for weee characterization and professor luciano marchiò, university of parma, for x-ray characterization and theoretical calculations on ligands and complexes. sardegna ricerche, university of cagliari, 3r metals ltd and the companies supporting the project “#recovery #green #metal”, are greatly acknowledged for financing and supporting the research on metal recovery from hi-tech waste and the technology transfer of the research results. references 1 basel convention home page, http://www.basel.int/, (accessed 1 december 2017). 2 directive 2012/19/eu of the european parliament and of the council of 4 july 2012 on waste electrical and electronic equipment (weee), official journal of the european communities. 3 directive 2000/53/ec of the european parliament and of the council of 18 september2000 on end-of-life vehicles, official journal of the european communities, 2000. 4 directive 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green chemistry, 2015, 17, 2208–2216. 28 a. rigoldi, e. f. trogu, g. c. marcheselli, n. picone, m. colledani and a. serpe, in sardinia 2017, 2017. 29 l. bloxham, a. cowley, l. han and e. shao, 2018, 1–48. 30 s. bernal, g. blanco, j. j. calvino, j. m. gatica, j. a. p. omil and j. m. pintado, topics in catalysis, 2004, 28, 31–45. 31 c. a. nogueira, a. p. paiva, p. c. oliveira, m. c. costa and a. m. r. da costa, journal of hazardous materials, 2014, 278, 82–90. 32 h. dong, j. zhao, j. chen, y. wu and b. li, international journal of mineral processing, 2015, 145, 108– 113. 33 p. deplano, a. serpe, m. l. mercuri, e. f. trogu, p. fornasiero and m. graziani, 2005, ep1743044b1. 34 k. a. jantan, c. y. kwok, k. w. chan, l. marchiò, a. j. p. white, p. deplano, a. serpe and j. d. e. t. wilton-ely, green chemistry, 2017, 19, 5846–5853. 35 v. gombac, t. montini, a. falqui, d. loche, m. prato, a. genovese, m. l. mercuri, a. serpe, p. fornasiero and p. deplano, green chemistry, 2016, 18, 2745–2752. 36 m. cuscusa, a. rigoldi, f. artizzu, r. cammi, p. fornasiero, p. deplano, l. marchiò and a. serpe, acs sustainable chemistry and engineering, 2017, 5, 4359–4370. 37 precious metals in the history of science and tecchnology, https://eventotcametallipreziosi.it/ substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe substantia. an international journal of the history of chemistry 3(2) suppl. 6: 25-27, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-742 citation: s. cinti (2019) chemistry as building block for a new knowledge and participation. substantia 3(2) suppl. 6: 25-27. doi: 10.13128/substantia-742 copyright: © 2019 s. cinti. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. chemistry as building block for a new knowledge and participation stefano cinti department of pharmacy, university of naples federico ii, via d. montesano 49, 80131 naples, italy dissemination of chemical culture interdivisional group of the italian chemical society e-mail: stefano.cinti@unina.it abstract. chemistry has been identified as the central science: it connects the life sciences with the applied ones. in addition, the degree of branching around chemistry also influences social sciences and intersects in areas such as socio-economics and ethics. the knowledge of scientific concepts for non-specialized audiences, through communication and outreach activities, should be considered as a potent social heritage for humankind. an increase in awareness regarding the benefits based on science and trust would advantage the entire society. herein, the relevance of a novel way to communicate scientific achievements is described: themes like circular economy and sustainable development are tackled to understand the role of chemistry in developing an ex-novo culture of knowledge. keywords. dissemination, knowledge, participation. the perception around chemistry is usually felt as though one is observing a black box. however, even if the content of this black box should not be negatively conceived, this black box called chemistry is often associated with threats and complexities. of course, who perceives the black box as above written is not the only “guilty”. the role of chemistry as the central science should not only be delivered by specialists, like those who have attended chemistry classes1, in places such as a high-school or a university, but also through different platforms which are more informal such as blogs, radio, magazines. it is a consequence that everything is heard, seen, smelt, tasted, and touched, involves chemistry. the comprehension of chemistry at some basic level is necessary to understand the world around us. however, with respect to the negative perception of chemistry, a major issue is usually represented by the difficulty of non-scientists to recognize the chemistry in everyday life: food digestion, use of soaps and detergents, pharmaceutical drugs, cooking, etc. which only represents a small section portion of daily chemistry. however, the voyage along the comprehension of chemistry and chemistry-related affairs has deeper roots2 dating back to the greek theory of matter (plato and democritus, in particular) and the study of alchemy. which in turn led to the initial steps for empirical understanding. during the lat26 stefano cinti ter part of the 19th and 20th centuries, following the birth of mendeleev’s periodic table of the elements and the firsts atomic theories, chemistry has been associated with enormous possibilities towards life enhancements through its industrial growth.3 in particular, the large scale and mass production processes of petroleum refinement has delivered feedstocks for fuels, solvents, lubricants, synthetic fibers, plastics, fertilizers, etc. for many other productions. although the rising of the chemistry within the industry, together with its implementation especially in the 21st century, has led to undiscussed advantages in terms of wellness and possibilities, and two key, but opposing, perspectives should be considered. on the one hand, the positive view is that it reflects the knowledge and products given by chemistry, with major efforts in the advances in well-being over the past centuries with the introduction of smart materials, new vaccines and drugs for incurable diseases, sensors for early diagnosis, and more. on the other, chemistry has inadvertently, but not solely, contributed to a variety of emerging global problems. in this current period, termed t́he anthropocene age ,́ obvious consequences due to human activities has burdened the environment in numerous ways, such as increase in pollution, influencing climate change and over-consumption of natural resources.4 unfortunately, it seems that the latter perspective is the most popular and negative connotations are often associated with the word “chemistry” as a consequence of its history. so much so, that it has led to non-chemists experiencing “chemophobia”5. however, the forgetfulness of the benefits derived from chemistry should be carefully considered. from a chemist point of view, this trend needs to be inverted. chemistry should be considered as a partner instead of an enemy; the black box should be converted in a transparent and open box. and to do this, the role of both chemists and non-chemists is of fundamental importance to establish the role of chemistry as an added resource for a new knowledge. task for chemists the role of specialists needs to be directed towards better comprehension of the matter by identifying and implementing novel solutions to moderate potential crises. in particular, given the current state of the global environment, more sustainable processes for “greener” developments should be prioritized. the central role of chemistry represents the basis for the green development in numerous ways. by adopting new designs and methodologies, many strategies can be focused on providing more greener routes including generation and storage of sustainable forms of energy (solar energy, fuel cells, carbon capture), development of environmentally neutral synthetic methodologies for obtaining safer chemical products, solvents and (bio)catalysts, ensuring the recycle of limited resources and natural products, and the development of accurate analytical methodologies that can allow for real-time and in-process monitoring of hazardous by-products. to this regard, anastas and warner introduced the 12 principles of green chemistry in their book “green chemistry, theory and practice” in 1998.6 although the principles were outlined with the aim for greener chemical practices, the vision of sustainability within the chemical industries are often perceived as an increase of the costs of production. where, by following or adhering to these principles, it is projected to be associated with costs > us$ 50 billion by 2020 within the chemical industry.7 along with its centrality, the ethics of chemistry and chemical practices are reflected in different systems including the biosphere, human/animal health, politics and economics. to this regard, it represents the added point towards the growing of responsibility as the code of conduct proposed by the organization for prevention of chemical warfare (opcw): a “hippocratic oath” for chemists need to be observed and actively driven forward by the major chemistry bodies and rigorously practiced.8 however, the ethical engagement of chemists needs to be applied even far from the laboratory bench. a broad communication of scientif ic achievements represents a crucial tool for making chemistry less distant, less remote and less arcane to lay audience. when chemists write articles on their findings, these are published in specialized journals, and the use of (necessary) jargon make the approach to nonspecialists less effective. the majority of chemists do not actively work on communicating their research in ways that are friendly to non-specialists: from a career point of view, both in research and industry, there are no reasons for most research to be broadly communicated, and it is often perceived as a loss of time.9 in addition, scientists doing public speaking are often considered to have lost their way as to what is really important. of course, chemistry is a complex and broad field, that cannot be communicated in its entirety, and great efforts are always requested to make the communication charming. to eradicate the “chemophobia” feeling, the role of chemists should be focused on the adoption of brand-new communication strategies. nowadays, contemporary platforms such as social media, blogs and videos, open up to a plethora of possibilities for reducing the gap between scientific achievements and society. 27chemistry as building block for a new knowledge and participation task for non-chemists one of the great challenges for chemists in the 21st century is convincing the general public about the importance of chemistry and transforming the common image of factories pumping out pollution into an concept that shows progress and sustainability at its core. the perfect strategy for communicating the beauty of chemistry, and science in general, has no value if the receiver is not ethically able to participate and understand the information. however, interfacing with specialists through the different existing platforms only represents a step towards the establishment of a new concept of knowledge based on the scientific evidence, rationality and sustainability. for instance, 2019 has been the 150th anniversary and international year of the periodic table of the elements, and great efforts have been devoted to highlight the presence and the role of each element in everyday life. chemical societies, magazines, roundtables, and radio stations have emphasized many aspects of the periodic table, including its history, global trends and perspectives on science for sustainable development, and the social and economic impacts of this field.10 following the same concept, by understanding the role of chemistry and its related processes, the end-users display a major responsibility in decisionmaking for future (but also current) action regarding tremendous issues that are affecting society. in the current society of consumption, the management of waste represents the latest environmental emergency. in large, it is connected with the manufacturing, exploitation and disposal of products, where approximately 30% of all discarded plastic is not managed or recycled. this does not fit well with a society like ours that largely rely on scarce resources. in this scenario, the urgent need for a shift to a circular model of economy needs competences of chemists for introducing novel ideas of manufacture,11 the participation of citizens and the close relationship between the parties, i.e. chemists and non-chemists. shifting from linear to circular and a regenerative approach represents a turning point for changing the people ś choices of consumption. novel acquired knowledge for reprocessing of goods and materials are expected to impact social, economic, and environmental fields by generating new, energy efficient, and reducing resource consumption and waste production. simple actions like the cleaning and repurposing of glass bottles represents a quick and fast way to reuse and recycle glass, for example. moreover, waste such as organic and/ or inorganic can represent the starting point for industries and energy production systems. these actions represent only few examples that are required from a consciously involved citizen: the decrease of water pollution, the reduction of co2 emission, and improvements of environment, climate and human health, are just a consequence of a responsible behavior. conclusion nowadays, the word “chemistry” is still associated to something negative. although, many chemical disasters will not ever be forgotten, chemistry should also be synonymous with progress. the role of chemistry as the central science, and chemists too, represents a current key for a novel sustainable development for preventing the continuous decline of resources. the other key is represented by the citizens, that are asked to ethically collaborate with specialists, through actions in the field of circular economy and recycling. to do so, chemists and non-chemists need to be connected through engagement activities, such as education, where comprehension and awareness of the masses are strictly dependent on these features. acknowledgments the author thanks emily nguyen (icn2, barcelona) for proofreading the manuscript. references 1. i. eilks, eurasia j. math. sci. technol. educ. 2015, 11, 149-158. 2. j. m. rampling, ambix 2017, 64, 295-300. 3. s. a. matlin, g. mehta, h. hopf, a. krief, nat. chem. 2015, 7, 941-943. 4. r. monatersky, nature 2015, 519, 144-147. 5. p. lazlo, the public image of chemistry, world scientific, 2007. 6. p. t. anastas, j. c. warner, green chemistry: theory and practice, oxford university press, 1998. 7. world investment report 2014 overview (unctad, 2014); http://go.nature.com/pcxhai 8. opcw, report of the workshop on guidelines for the practice of chemistry under the norms of the chemical weapons convention, 2015. 9. m. r. hartings, d. fahy, nat. chem. 2011, 3, 674677. 10. m. poliakoff, a. d. makin, s. l. tang, e. poliakoff, nat. chem. 2019, 11, 391-393. 11. w. r. stahel, nature 2016, 531, 435-438. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 6 2019 firenze university press where does chemistry go? from mendeelev table of elements to the big data era luigi campanella1, laura teodori2,* visualizing solubilization by a realistic particle model in chemistry education antonella di vincenzo, michele a. floriano* chemistry as building block for a new knowledge and participation stefano cinti tissue engineering between click chemistry and green chemistry alessandra costaa#, bogdan walkowiakb, luigi campanellac, bhuvanesh guptad, maria cristina albertinie* and laura teodori a, f* chemistry beyond the book: open learning and activities in non-formal environments to inspire passion and curiosity. sara tortorella,1,2,* alberto zanelli,2,3 valentina domenici2,4 substantia. an international journal of the history of chemistry 3(2): 5-10, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-630 editorial chemical industry and sustainability vittorio maglia federchimica, milan, italy e-mail: v.maglia@federchimica.it a discussion on chemical industry and sustainability implies, first of all, a consideration of the relationship between enterprise and sustainable development. in this regard, the 2030 united nations agenda gives a clear recommendation to consider altogether the three dimensions of sustainable development: the economic, the social and the environmental aspects. this is the guideline of the present analysis.1 most of the data reported throughout this document are referred to the italian chemical industry; however the same considerations can be made for other european countries. the starting point is an indication given a few years ago, in 2009, by the high level group on the competitiveness of the european chemical industry, an initiative of the european commission joined by representatives of the member states, industry experts, academics, environmental groups and trade unions. the title page of the final report begins with a strong statement: «european chemical industry, enabler of a sustainable future». 2 in a nutshell, the report illustrates that the most important challenges that humanity has to face such as food needs for a growing population, new needs related to ageing, climate changes and the most efficient use of resources “require new solutions, many of which can be implemented only thanks to new materials and substances”, i.e., with a decisive contribution of the chemical research combined with the ability of the industry to convert scientific discoveries into technologies and products. these considerations are valid also for many of the un goals:3 “zero hunger”, “good health and well-being”, “clean water and sanitation”, “affordable and clean energy”, “responsible consumption and production”, “climate action”, in addition to the two objectives that directly concern the industry, “decent work and economic growth” and “industry, innovation and infrastructure”. in order to properly represent the sustainability of the chemical industry (as for any other sector or company) it is necessary to adopt the “concept of the three pillars”: true sustainability, as already underlined in the 1987 brundtland report, is based on the equilibrium of three type of sustainability: economic, social and environmental. the following paragraphs will describe the facts that identify the chemical industry as an important actor of sustainability. after a brief reference to the results at the european level, the data will be further analyzed for italy, as it represents a valid example for other industrialized countries. economic sustainability at the european level, economic sustainability of the chemical industry is well reflected by the very high trade balance, which is at the same time an indicator of 6 vittorio maglia strong specialization and of high level of competitiveness. although china is now the main chemical producer, europe is still the biggest chemical exporter in the world. the economic sustainability of the chemical industry is connected to its main feature: “a science and an industry come along with the same adjective”, i.e. chemical industry is a science-based industry. this is not a trivial statement. actually this fact historically implied the birth of genuine industrial research within chemical companies, through a continuous and intense interaction between the scientific and the industrial world, well represented in italy first by two eminent scientists: fauser and natta with montecatini.5 it is interesting to look closely to the famous picture taken during the 1911 solvay physics council because it well represents this feature: together with ernest solvay (the third from the left), there are 11 nobel prizes, from albert einstein to marie curie, from max planck to lord rutheford, and great experts of different disciplines (e.g. henry poincaré). it is interesting to underline also the fact that solvay was strongly interested not only in chemistry. in a “knowledge society” this feature is more and more recurrent, but the need of the chemical industry to anticipate trends and changes pervades many aspects of the enterprise life. in particular, this aspect determines the centrality of innovation, with a structured research activity involving a high percentage of companies (42% compared to a manufacturing average of 18%) and which sees more then 1200 companies in germany and almost 700 in italy: not only large chemical industries have r&d activities in europe. for european chemical companies, research-based innovation, complex systems and technologies and capital intensity determine high productivity (the added value per employee is 70% above average in europe) with the result that the high qualification and productivity of the employees allow on one hand a higher remuneration and on the other hand a greater defense from emerging competitors. in the european chemical industry these aspects are associated and closely interact with an international vocation; the european large trade surplus is a clear example. for italy, istat (the italian central statistics institute) shows that chemical industry can boast the highest percentage of exporting companies, after phar7chemical industry and sustainability maceutical industry: 56% against the manufacturing average of 23%. productive investments abroad are common in the global market, and it is worth to note that they do not lead to delocalization, as they allows either to tackle markets with on-site productions or to maintain commodity production abroad by focusing european activities on specialties and research. a fundamental contribution to participation in the global market is given by foreign capital companies that not only maintain a high share of production in the europe member states, but have also undergone a significant rise in exports. in this aspect italy shows a very interesting fact: the foreign companies have an even greater increase than the average of chemical companies of % of turnover in the last 10 years. in italy, as well as in other countries, despite the heavy constraints of external conditions, such as the cost of energy, the role of these companies is a virtuous model, and experience shows that the acquisition of local companies has lead to a better development. all these considerations converge into economic sustainability: the case of italy is interesting for the strong effect of the 2007 economy crisis on the manufacturing industry and its outcome on the gdp. in fact chemistry related export has not only grown much more than the average in italy, but also more than almost all the major chemical european producers. this aspect avoided a possible structural crisis of this sector due to the heavy drop in the internal demand. at the european level and even more in italy, this gratifying result is largely due to innovation and to the growing specialization in the most dynamic and more fitted sectors of the typical medium size company, i.e. those of fine chemicals and specialties. at the european level the share of trade surplus connected to these sectors is more and more important. in italy, the specific positive trade balance has more than tripled in 10 years and now reaches values that make this sector one of the new champions of the “made in italy”. it is very interesting to analyze the results produced by isco, an indicator that istat has been proposing in the last couple of years and that summarizes competitiveness through productivity, represented by the ratio between added value and labor cost, profitability, diffusion of innovation, percentage of exports on turnover and exports performance. the approach is not to verify the present level of competitiveness, but the possibility to stay competitive in the long term, in fact to stay sustainable. it may be surprising that the chemical industry appears among the first three sectors and consequently has a better position than those that are traditionally regarded as the flagship of italian industry. if this is right for italy, it is certainly valid for most of the major european countries. ultimately, if competitiveness is considered a decisive factor in economic sustainability, the chemical industry shows excellent results. social sustainability an outstanding issue of sustainability is its social issue, which can take various forms if referred to an industry. first of all, it means offering highly qualified job opportunities to the new generations. this aspect is well represented by the percentage of graduates among the employees and in particular among new hires: in europe this percentage is close to 40% (in 8 vittorio maglia italy it is close to 30%) and much higher than the average. the focus on human resources also determines the stability of employment relations and the commitment of companies to continuous training. for example, in italy the quality of employment relations results in a 95% share of employees having a permanent contract. furthermore, chemical industry tackles continuous change through education, a topic which sees chemical industry in the top position in italy as in other european countries: actually in italy 42% of the employees is annually involved in training courses. the italian case is extremely interesting for an important aspect of social sustainability, i.e. industrial relations. in fact, the centrality of human resources and social responsibility in recent decades has led to industrial relations based on social dialogue that in turn allowed to develop significant innovations. for those that are more concerned about social sustainability, it is important to recall the two sectoral funds for supplementary pensions and health insurance (fonchim and faschim): in both cases, the sector has been the forerunner precisely because of its sensitivity to the issues of social responsibility and the quality of relations between the social parts.6,7 another way to get the meaning and relevance of social sustainability deals with safety, i.e. accidents and occupational diseases: in italy inail (the national institute  for insurance against accidents at work) data show how the stereotyped image given by the mass media does not fit with chemical industry. for sure chemical industry is under very stringent regulation and takes advantage from innovations in plants and processes, but above all this result is related to organizational aspects. it is not by chance that there is a very evident inverse relationship between hours of training on health, safety and environment and number of injuries: in italy a +55% growth of the former from 2005 corresponds to a 52% decrease in the latter. environmental sustainability the relation between chemistry and environment is strictly linked to the role played by chemistry as a science and to its final purpose of transforming matter, which results into emissions, water effluents, energy consumption and waste. the commonly used indicators focus on the improvement and not on the level of variables, as all the industrial activities have an environmental impact. thanks to the responsible care program, a project joined by the most important enterprises involved in the environmental issue and present in all european countries, it is possible to report on the efforts, but also show of some measurable results.8 9chemical industry and sustainability in the last thirty years the main variables have shown very significant decreases. to make an example, greenhouse gas emissions due to the chemical industry decreased by 61% from 1990 (both in europe and in italy) and the sector has already reached the levels of efficiency expected in 2030 by international agreements. another feature that casts a different light on the chemical industry is an international study conducted by mckinsey: a ton of co₂ emitted during chemical productions avoids 2.6 tons of greenhouse gases from industrial customers or end because of the use of substances, materials and chemical products. an example is energy savings in buildings. conclusions and policy issues in italy, a few years ago, fondazione symbola chaired by an environmental oriented organization elaborated the internal quality product (iqp) in order to identify indicators on sustainable development. for this purpose a wide set of indicators of the three pillars of sustainability was used. although they were obtained in 2012, the data are still valid, as referred to structural assets and can be used not only for italy but also for the european chemical industry. the chemical and pharmaceutical industry holds the first place for sustainability development, with a conspicuous gap from other sectors. a first conclusion that can be drawn is that chemical industry, in a medium-to-long term perspective, is particularly suited to a european country like italy, as it offers good opportunities to the youngest. a reflection is needed: sustainability deals with a context dominated by globalization and its consequences on competitiveness. already in 1990 michael porter in his book “the competitive advantage on nations” stated that «in the global market, competition is not only between companies but also between nations».9 at that time, this was already acknowledged as the consequence of a process driven not only by the globalization of the market, but also by the availability at “zero time” of technologies, information and capital in the emerging areas. the consequence is that the competitiveness of a company depends more and more on what the “coun10 vittorio maglia trywide competitive conditions” transmits to it, because for most of the other factors the conditions are similar or almost so. if it was already true at that time, it is easy to get how central this aspect is now. chemical industry provides precise indications which appear to be more and more valid for the whole industry. because of its characteristics the countrywide competitive conditions influences many critical aspects of chemical competitiveness: the relationship with the environment determines a key system of rules and a role of the public administration in its application and control, infrastructural system in terms of availability and charges, cost of energy, relations with the territory, education and university system. the single company has a very little influence over all these elements, which are very relevant instead, in term of cost and certainty. the european commission has recently carried out a careful analysis of the costs of regulation in the chemical industry, and the results are very explanatory of what we just stated: they represent, on average, 12.1% of the added value and 30.1% of the gross operating surplus, even more for smes because the regulations mainly act as fixed costs. it seems clear that a given regulation or a different application of it in different areas or countries has a very high impact on competitiveness, and this fact is of great importance also for sustainability. in fact, it is based not on three, but rather on four pillars, the forth represented by institutions: on one hand because they have a direct role on many of the objectives indicated by the united nations, but on the other hand and above all because it is entrusted to them the very difficult task of ensuring that the three pillars support each other. as many aspects of the competitiveness of the companies depend on external factors, on which they have little or no influence, the intermediate bodies (such as industrial associations) take on great importance, with the aim not only to protect interests and to involve their representatives on themes such as sustainability (for example with voluntary initiatives, training actions and with management models that include social responsibility), but also to proactively collaborate with the institutions above all in the definition of the rules and in their application. in conclusion, chemical industry shows a clear indication of the role of institutions and intermediate bodies on the goals of sustainable development in a logic of collaboration arising from the awareness that the proposed objectives are mandatory but also very demanding. references 1. ht t p s : / / w w w. c o e . i nt / e n / w e b / p r o g r a m m e s / u n 2030-agenda, last accessed on 07/07/2019. 2. https://chemistrycan.com/app/uploads/2017/10/sdreport2017.pdf, last accessed on 07/07/2019. 3. https://www.un.org/sustainabledevelopment/sustainable-development-goals/, last accessed on 07/07/2019. 4. g. brundtland. report of the world commission on environment and development: our common future. 1987. united nations general assembly document a/42/427. 5. f. fauri. the “economic miracle” and italy’s chemical industry, 1950—1965: a missed opportunity. enterprise & society, 2000, 1, 279-314. 6. https://www.fonchim.it/homepage, last accessed on 08/07/2019. 7. http://www.faschim.it/, last accessed on 08/07/2019. 8. https://www.icca-chem.org/responsible-care/, last accessed on 08/07/2019. 9. m.e. porter “the competitive advantage of nations”, harvard business review, cambridge, ma, 1990. http://www.lapres.net/porter.pdf, last access on 10/07/2019. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 2(2): 119-123, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-65 citation: m. calamia, m. gherardelli (2018) exact time: the first scientific application of radiocommunications. substantia 2(2): 119-123. doi: 10.13128/substantia-65 copyright: © 2018 m. calamia, m. gherardelli. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article exact time: the first scientific application of radiocommunications mario calamia, monica gherardelli dipartimento di ingegneria dell’informazione, università degli studi di firenze (italy) e-mail: mario.calamia@unifi.it; monica.gherardelli@unifi.it abstract. marconi’s first experiment of signal transmission by means of hertzian waves was carried out in 1895. in the following years, wireless telegraphy progressed steadily and worldwide efforts were made to exploit the potential offered by new technologies. in those years guido alfani, a young florentine piarist teacher of promise in seismology, joined the ximeniano observatory in florence where he found the ideal environment for his experiments and his insights. he understood the importance of having the exact time in seismology, to temporally characterize the telluric movements and therefore accurately characterize them. in 1910 when the paris radio station located at the tour eiffel began regular broadcasts of exact time, he laid down the issue of its reception. as far as pendulums and chronometers were concerned, no doubt his expertise as seismologist was significant, while problems arose when it came to the radio station, due to the novelty of such situation. for this reason he arranged contacts and managed to set the first italian radio station to be used in a weather station. thus, on the night of march 16-17, 1912, he received for the first time the time signal for a particular scientific application. he wrote to marconi and in 1912 marconi expressed words of great appreciation and encouragement for such work. father guido alfani’s radio station is certainly the first one applied in seismology and among the first radios made in italy. it is an extremely important application which demonstrated that the new technique could provide solutions in different situations. keywords. exact time, radiocommunications, osservatorio ximeniano. introduction the second half of the nineteenth century has been a period where science met with great ferment. important pages on discoveries or great scientific activities have been written and often people are left wondering on how it was possible to collect such amazing results in such a short and precise time span. to keep to the topic of our contribution, we will point out that in the second half of the nineteenth century seismology became a science thanks to some great scientists. among them, father giuseppe mercalli (the mercalli intensity scale used nowadays to classify earthquakes goes back to those years, namely 1880-90) and all over the world efforts were made to compare both results and experiences. 120 mario calamia, monica gherardelli since the second half of the eighteenth century the osservatorio ximeniano has been working in florence as a research institution founded by the jesuit father leonardo ximenes and later on run by the piarists. in 1872 father filippo cecchi was appointed director of the osservatorio ximeniano; he was a skilful meteorologist who has left important contributions in weather forecasting. furthermore, he was not at all indifferent to the great deal of progress made by seismology and nowadays his works are considered of greatest value. he conceived the first “three-component seismograph” and many other tools, which can still be seen in the exhibition room dedicated to his studies in the osservatorio ximeniano. finally, the very last years of the nineteenth century could witness for other important scientific developments, thanks to the arrival to the osservatorio ximeniano of a young florentine teacher of mathematics and physics. father guido alfani, who belonged to the piarist order, was skillful and self-assertive, which helped when he became director of the osservatorio ximeniano in 1905.1 in the wake of father filippo cecchi, father guido alfani became soon an important reference in seismology, he conceived new seismographic instruments, he kept on improving already existent seismograms, while studying deeply any electrodynamics tools. his contributions to the seismology framework have been of primary importance. father guido alfani and the service of exact time the main focus of this paper is not only the father alfani’s experiences, but through his experiences we would like to pay homage to many scientists who could understand the importance of interdependency in the scientific fields. as to seismology, the activities carried out by father alfani have been presented in many excellent papers, which have already highlighted the importance of his contribution to that area. therefore it is not our intention to focus on such aspect. we would like to focus on the work of father alfani from a different perspective: he was a mathematician with strong interests in seismology and even though he was not a radio engineer, his insights enabled him to understand that what he found in a different scientific field could be of great help to seismology. he sensed that knowing the exact time was a fundamental issue in earthquake studies. therefore, he directed his efforts towards “fixing and keeping” the exact time by means of spyglasses, so as to measure culmination in star transit, as well as by means of pendulums to keep the correct measure of time. let’s read once again his words: in modern seismic stations, the accuracy of time is not only one of the important element, but even the most important one. for such reasons, there will never be too much care to get such accuracy and keep it unchanged and exact. as a matter of fact, this observatory has been working mainly on seismology, therefore i had great care to define the exact time and make it flawless. therefore, i have arranged a very special equipment to guarantee results.2 …omissis…. until 1912 (this was the year i could realize the very first set of equipment related to a radiotelegraphy station dedicated to radio time signals) the exact time reckoning has been carried out on a regular basis, nearly every evening, and at least every two days by means of star culmination measured at meridian circle.2 the “very special equipment” is in fact the first radio station he realized in italy. in 1910 the bureau central in paris, namely the french observatory located at the tour eiffel, began to transmit the exact time signal and it was at that point father alfani realized that such transmittance could serve perfectly the purpose of supplementing the star culmination method. he needed a suitable receiver, he integrated his training, he searched for information and he was able to set up a radiotelegraphy station and in the night between the 16th and 17th of march, he received for the first time the exact time from paris. it was a crucial step forward in seismology. no longer depending on star observation at a specific time, but relying on a regular time signal, as the one transmitted from paris, that was an absolutely exceptional result. father guido alfani was the first to achieve such reception and he dedicated the discovery to guglielmo marconi, thus writing: “i would like to dedicate to guglielmo marconi these pages on the first radiotelegraphy station working in an italian observatory”.3 the first radio station was nothing else than a starting point for father alfani and other seismologists who followed in his footsteps. the course of events related to those years is well described in the quoted passage dedicated to guglielmo marconi. main components of his radio equipment were the receiver itself and the aerial (the antenna). as to the receiver, he resorted to the expertise and helpfulness of ducretet & roger company and he used “elec121exact time: the first scientific application of radiocommunications trolytic diodes” because “they are much more constant than crystal sets”. he had to deal with some drawbacks he promptly pointed out to the company, thus quickly managing to have reliable components. he kept on working on the improvement of the receiving system; thus in 1923 he exploited the coherer as radio detector in his receiver, only to change in favor of vacuum tubes, once their checkout had turned out to be trustworthy. yet, it is the work on the antenna, which took up almost his time. he sensed that the shape of the antenna and the location where to place it were very important factors in defining the quality of the received signal and without such signal there was not too much to detect. when describing the types of “aerials” he realized at the ximeniano observatory (figure 1 and 2) he wrote: one of such aerials is really great; it is dipole and has its point of support in the dome of the florence duomo. it is made of two wires in phosphor bronze and it is about 300 meters long and 110 meters high. there is an iron pole (15 meters long) which has in its upper end some pulleys to be used to rise or drop the aerial’s bays by means of steel cables.2 however, not everything goes so easy as it might appear: the country is going to war (1915-1918) and therefore the government imposes restrictions such as the interruption of the broadcasting station services and the removal of the antennas at the observatory. there is a very interesting exchange of letters describing the heated argument between father alfani and the government authorities. his aim is to stand up for his activities with the radiotelegraphy station described as a support to his seismology studies and not at all meant to be part of a spy ring. as a scientist he cannot accept nor justify any stop to the progress of science; therefore he builds and adopts quad antennas for his receiver device: once overcome the problems of tuning them with the receiver’s interface, the reception capacity of such antennas turns out to be greater and allows him to work. figure 3 shows quad antennas, two with rhombic shape and one with round shape. this is not just a storytelling retrieved from books, which is of great value in itself, but it has been a work of reconstruction based on collected parts which have been brought into use again, thus allowing the recovery of a priceless heritage, along the last ten years. in the storerooms at the ximeniano obser vatory many items were found and they were supposed to be components of the radiotelegraphy station built by father alfani: only a picture could witness that in the booklet already mentioned and entitled the time service.2 one of the authors of this paper, prof. mario calamia, was informed about the possible and yet partial recovery of that equipment: the task seemed to be not easy due also to the lack of students to be involved. eventually in 2006 a solution was within reach thanks to giovanni manneschi, an engineer and arezzo “ceia figure 1. the ximeniano observatory seen from south and showing the antenna of the radiotelegraphy station.3 figure 2. drawing of the second (upper) and third (lower) radio equipment related to the aerial.3 122 mario calamia, monica gherardelli s.p.a” executive, but also very keen on radio engineering. since then a very methodical work has begun to recover, restore and put that laboratory (figure 3) back on its feet. it took about six/seven years to finish the work, but nowadays more than 95% of father alfani’s laboratory is on exhibit at the ximeniano observatory.4 it is made of 44 parts ranging from the radiotelegraphy station built in 1912 and already depicted in figure 4 to several other equipments dating back to 1940 and perfectly operative. the radiotelegraphy station has been restored by using the original ducretet & roger thermionic diode, which was found by chance in the observatory’s store-rooms. actually the station has been tuned again so as to receive the national broadcast “rai” in amplitude modulation. another noteworthy article is the radio receiver dating back to 1923 and shown in figure 5, with its original coherer. conclusions our goal has been focused on informing about events which may seem of minor importance, but which had a great social and scientific impact. this generally happens when science manages activities in some facilities. the ximeniano observatory has been one of such facilities and yet its renown is mainly related to meteorology and seismology. it has a very relevant map projection department and it is also well-known for father eugenio barsanti’s work on the internal combustion engine whose first version he invented. on the other hand, the observatory played a leading role in radio engineering during the first half of the 20th century, but this aspect has been a bit underestimated. the research carried out by father alfani had the merit of improving radio engineering as well, though his name became notorious for meteorology and seismology studies. he understood that the main shortcoming in seismology was the inability to correlate the different telluric phenomena detected along far-off areas. this could be solved if every observatory was able to benefit from the exact time service and he had the insight that this was possible when he heard of paris radio station’s regular broadcast of time signal. he did not purchase a receiver, which was not possible, but he improved his learning on radio engineering, so as to define the requirements which could make the reception more and more accurate. what he wrote in his short, and yet regularly dated and published notes, shows clearly his cleverness. guglielmo marconi, invited to florence, met full of admiration father alfani at the observatory. in fact, father alfani had used radio broadcast not only in telecommunication engineering, but also in a scientific field of great social impact. figure 3. the radiotelegraphy station of father alfani at the ximeniano observatory.2 figure 4. radio receiver built in 1912, the model of it is in the booklet father alfani dedicated to marconi during his visit held in 1912.4 the diode, head-phones and the capacitor are original. figure 5. radio receiver built in 1923 according to the model of marconi’s receiver dating back to 1895.4 a part from the battery box, all the other components like the coherer (right lower part, near to the antenna) are original. 123exact time: the first scientific application of radiocommunications finally, we would like to stress that he was never particular about his studies, experiments and outcomes. as a scientist, he was persuaded that the more the observatories adopted the proposed solution, the greater would be the usefulness of that research. his words are revealing: the first radiotelegraphic reception occured in the night of the 19th march 1912 , based on paris time signals. shortly afterwards, other colleagues joined and followed my example. i went personally to set up new equipments. one of the first radio station i installed was at the montecassini observatory on the 26th july 1913.2 references 1. d. barsanti, padre guido alfani (1876-1940), osservatorio ximeniano dei pp. scolopi, firenze, 1992. 2. g. alfani, il servizio dell’ora, pubblicazione 136, osservatorio ximeniano dei pp. scolopi, firenze, 1928. 3. g. alfani, la stazione radiotelegrafica, pubblicazione 115, osservatorio ximeniano dei pp. scolopi, firenze, 1912. 4. m. calamia, g. manneschi, kernes: la rivista del restauro, n. 83 (eds: nardini), firenze, july-september 2011. substantia. an international journal of the history of chemistry 3(2) suppl. 1: 9-11, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-691 citation: s. c. rasmussen (2019) sustainability and energy. knowledge of the past is critical for our future. substantia 3(2) suppl. 1: 9-11. doi: 10.13128/substantia-691 copyright: © 2019 s. c. rasmussen. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. editorial sustainability and energy knowledge of the past is critical for our future seth c. rasmussen department of chemistry and biochemistry, north dakota state university, fargo, nd 58108 usa email: seth.rasmussen@ndsu.edu sustainability and energy – two fundamental topics that are key to the past, and future, of humanity. of these two, however, energy has long been the primary focus and the contribution of sustainability has been a secondary concern. our preoccupation with energy via chemical means can be traced back to the initial taming of fire, dating to at least 500,000 bce1. by 300,000 bce, mankind was beginning to use fire to cook their food and, by 100,000 bce, the use of fire as a source of heat and light had become well-established, permanently changing the future of humanity2. throughout these time periods, mankind was dependent on carbon as the singular source of fuel for energy production via combustion. as the carbon sources consisted of wood and other plant matter, this earliest energy technology could at least be viewed as renewable. as such, it could be considered sustainable, providing that the consumption of wood and plant matter did not outpace the regrowth of new trees and plants to take their place. of course, as civilizations developed and population centers grew, the desire for more effective fuels grew. by the first millennium bce, coal had emerged as a more concentrated fuel for combustion, with theophrastus (c. 371–287 bce) referring to the use of coal as fuel in his geological treatise on stones3. during the 18th century it was found that coal could also be used to produce a combustible gaseous product, known as coal gas, via its destructive distillation. this gas went on to become the initial fuel for gas lighting. methane, originally known as either firedamp or marsh gas, was also first studied in the 18th century and was later determined to be the primary component of coal gas4. in the modern day, methane from natural deposits is 1 s. c. rasmussen in chemical technology in antiquity (ed.: s. c. rasmussen), acs symposium series 1211, american chemical society, washington, d.c., 2015, p. 7. 2r. shahack-grossa, f. bernab, p. karkanasc, c. lemorinid, a. gophere, r. barkaie, j. archaeol. sci. 2014, 44, 12. 3 e. r. caley, j. f. c. richards. theophrastus on stones. introduction, greek text, english translation, and commentary. the ohio state university, columbus, oh, 1956, p.48. 4 s. c. rasmussen. acetylene and its polymers. 150+ years of history. springer briefs in molecular science: history of chemistry, springer, heidelberg, 2018, pp. 5-6. 10 seth c. rasmussen10 seth c. rasmussen more commonly known as natural gas, which can also contain some higher alkanes and small amounts of other gaseous impurities. the discovery of other hydrocarbon gases such as ethylene and acetylene then followed in the 19th century, although coal gas still remained the primary gaseous fuel for applications such as lighting until the large-scale production of acetylene from calcium carbide at the end of the 19th century5. during this same time period, another commonly used fuel was whale oil, particularly for use as a lamp oil for lighting. the demand for whale oil was high during the 18th century and reached its peak in the 19th century. it was only with the development of the petroleum industry that the use of whale oils declined considerably as it was replaced by cheaper and more effective fuels. although descriptions of the distillation of crude oil by islamic philosophers date back to the 9th century6, the modern history of petroleum began with the development of kerosene by abraham gesner (1797-1864) in 18467. even though kerosene was first produced from coal, it was soon found that it could be produced more easily from petroleum. other products were also isolated during the fractional distillation of kerosene from petroleum, but these initially found little use. it wasn’t until the invention of the automobile in the late 19th century that one of these products, gasoline or petrol, was recognized as a valuable fuel. by 1916, the production of gasoline grew to surpass that of kerosene and petroleum fuels rapidly became the primary source of energy throughout the industrialized world. while we were able to view the early use of wood for combustion as sustainable, at least under specific limiting factors, the same cannot be said for these later carbon fuels. coal, natural gas, and petroleum are all fossil fuels resulting from the anaerobic decomposition of organic matter. while initially abundant, the natural deposits of these materials are thought to have taken millions of years to accumulate and cannot be replenished within a reasonable timeframe. whale oil, too, is anything but sustainable and the hunting of whales for this fuel is said to have nearly brought about their extinction. beyond carbon, the ability to obtain energy from other elements on the periodic table was not really an option until the beginning of the 19th century. it was in 1800 that energy via non-combustion methods was pri5 s. c. rasmussen. acetylene and its polymers. 150+ years of history. springer briefs in molecular science: history of chemistry, springer, heidelberg, 2018, pp. 30-35. 6 r. j. forbes. studies in early petroleum history, e. j. brill, leiden, 1958, pp. 149-150. 7 a. gesner. a practical treatise on coal, petroleum, and other distilled oils. bailliere brothers, new york, 1861, pp. 8-9 marily introduced with the discovery of the voltaic pile (i.e. the first battery) by alessandro volta (1745-1827)8. electricity via static generation had been previously known since the roman era, but could only be stored in an early form of capacitor and could not be released or applied in a controlled fashion. it was volta’s invention of the battery that really began the electric age. although volta’s initial battery utilized combinations such as copper and zinc, a variety of other metal combinations were also found to successfully generate current and modern battery technology now exhibits a plethora of chemical combinations. other electrochemical variants of the classical battery followed, most notably the fuel cell introduced by william grove (1811-1896) in 18399. it was also in the 19th century that interest began to turn to the potential of electrical energy from light, beginning with the first report of photovoltaic effects by edmond becquerel (1820-1891) in 1839. of course, mankind had always relied on the sun for both heat and light, but the possibility of harvesting electricity from sunlight ushered in the development of solar cells in the pursuit of solar energy. although initial progress was slow, the first practical silicon solar cells were developed in 1954 by bell labs10, which only further increased interest in this nascent technology. since then, great advances have been made in the development of silicon solar cells, as well as the introduction of a wide variety of other solar cell devices, including the recent focus on solar cells from semiconducting organic materials in the last couple of decades. of course, another powerful source of energy in the form of uranium (specifically uranium-235) resulted as a consequence of the manhattan project during world war ii. the first nuclear reactor was constructed in november 1942 by a group led by enrico fermi (19011954), with a self-sustaining nuclear reaction successfully demonstrated in december of the same year11. this was followed with the construction of an experimental breeder reactor in idaho, which generated the first electricity from nuclear energy on december 20, 1951. the first commercial plant to generate electricity by nuclear energy was located in shippingport, pennsylvania and reached its full design power in 1957, after which the us nuclear power industry grew rapidly in the 1960s. as can be seen from the discussion above, mankind’s love-affair with energy is long and varied. this is 8 a. volta, philos. trans. r. soc. london 1800, 90, 403. 9 a. e. becquerel, c. r. acad. sci. 1839, 9, 145. 10 j. perlin. the silicon solar cell turns 50 (nrel report no. br-52033947). national renewable energy lab., golden, co, 2004. 11 u.s department of energy (doe/ne-0088). the history of nuclear energy. office of nuclear energy, science and technology, washington dc. 11sustainability and energy 11sustainability and energy – knowledge of the past is critical for our future especially true as the current discussion has been limited to those fuels and technologies based on chemical processes. as such, physical/mechanical energy technologies such as hydroelectric power and wind energy could also be added to those previously discussed. still, considering the varied sources of energy at our disposal, the industrialized world still relies primarily on fossil fuels to meet its energy needs. this is especially concerning due to the finite nature of these fuels, as well as the toll our historic dependence on combustion technologies has inflicted upon the environment. while a hot-button topic within the general public, the vast majority of actively publishing climate scientists – ca. 97%12 – agree that global warming and climate change are the result of such human activities13. furthermore, if something is not done to change our energy habits, things will only get worse. in fact, it is believed that even if we completely stopped emitting greenhouse gases today, global warming would continue for at least several more decades, if not centuries. still, it is believed that it is not be too late to avoid or limit some of the worst effects of climate change. due to these various factors, it is clear that future energy technologies must be both sustainable in practice and shift away from our current emphasis on combustion. at the same time, there are various factors that actively inhibit such paradigm shifts, be it economic, political, limits in current technology, or simple inertia. it is only with a clear knowledge of the past that we can completely understand how mankind came to the current cross-roads. at the same time, such knowledge can also highlight factors that prohibited the development of alternate technologies that might have served us better in the long run. thus, to better serve the future, it is worthwhile to review the past in greater detail. it is with this viewpoint that i am proud to present the following special issue on sustainability and energy that highlights the histories of various energy technologies, particularly those that might provide potential paths forward to a better future. the fact that this issue is part of substantia’s celebration of the international year of the periodic table is also very fitting, as the various energy technologies discussed above have not been limited to any one element or periodic block, but have originated in chemistry based upon elements from across the periodic table. 12 j. cook, d. nuccitelli, s. a. green, m. richardson, b. winkler, r. painting, r. way, p. jacobs, a. skuce. environ. res. lett. 2013, 8, 024024. 13 n. oreskes. science 2004, 306, 1686. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press 1 citation: l. corbetta, l. m. fabbri, d. cavalieri, p. bonanni, m. munavvar, a. cruz, a. rendon, l. de paoli (2020) stand on the same side against covid19 – the future strategies against an unknown enemy. substantia 4(1) suppl. 1: 1059. doi: 10.13128/substantia-1059 received: aug 13, 2020 revised: sep 04, 2020 just accepted online: sep 07, 2020 published: sep 07, 2020 copyright: © 2020 l. corbetta, l. m. fabbri, d. cavalieri, p. bonanni, m. munavvar, a. cruz, a. rendon, l. de paoli. this is an open access, peerreviewed article published by firenze university press (www.substantia.net) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia webinar stand on the same side against covid-19 – the future strategies against an unknown enemy this document is the direct transcription of a webinar organized by prof. l. corbetta of the university of florence on july 7th, 2020. scientific coordination: lorenzo corbetta associate professor of respiratory diseases university of florence scientific and website director of the european association for bronchology and interventional pulmonology (eabip) organizing secretary: consorzio futuro in ricerca via saragat 1 – corpo b – 1° piano | 44122 – ferrara cfr@unife.it translation coordination and editing: giorgia biagini, md info@covid19expertpanel.network webinar’s partecipants: prof. lorenzo corbetta university of florence, italy prof. leonardo m. fabbri – university of modena and reggio emilia, italy prof. duccio cavalieri university of florence, italy prof. paolo bonanni university of florence, italy prof. mohammed munavvar lancashire teaching hospitals, uk prof. alvaro cruz federal university of bahia, brazil prof. adrian rendon universidad autónoma de nuevo león, mexico prof. laura de paoli world health organization corresponding author: lorenzo.corbetta@unifi.it substantia. an international journal of the history of chemistry 4(1) suppl. 1: 1059, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-1059 http://www.fupress.com/substantia l. corbetta et al. 2 “stand on the same side” videoconferences https://www.covid19expertpanel.network “implementing a science-based lockdown exit strategy is essential to sustain containment of covid-19. china’s experience will be watched closely, as other countries start considering—and, in some cases, implementing—their own exit strategies” the lancet, volume 395, issue 10232, 18–24 april 2020, pages 1305-1314 this phrase expresses the purpose of this program called “stand on the same side against covid-19” that takes advantage of the new and rapid digital technologies to put together several experts worldwide. it’s a global space were many countries hit by sars-cov-2 can share only scientific information in order to face the pandemic. july, 7th 2020, china-europe videoconference “stand on the same side against covid-19 – the future strategies against an unknown enemy” lorenzo corbetta: good morning, good afternoon or good evening, depending on where you are. my name is lorenzo corbetta. i am a professor of respiratory diseases in the university of florence and director of the educational programme in interventional pulmonology. this is the fourth webinar on the educational project called stand on the same side against covid-19, and now with the title 'the future strategies against an unknown enemy.' our aim today is to update you on the evolution of the pandemia and on evolution of the virus that we have called 'unknown enemy,' but maybe during the webinar we'll find out something more about it thanks to the presentation of professor duccio cavalieri, professor of microbiology in the university of florence. then we will talk about the development of a vaccine for covid-19 with professor bonanni, director of specialisation in hygiene and preventive medicine of the university of florence, and about clinical recommendations and clinical trials in progress with professor mohammed munavvar, who is the current president of the british thoracic society and president of the european association of bronchology and interventional pulmonology. furthermore, we have important guests from countries that are now still in full outbreak, the professor rendon, president of the mexican pulmonology society, who is already attending the latest webinar with us, and another old friend from brazil, professor cruz, professor of allergology and pneumology at the federal university of bahia. last but not least, we have the pleasure to have with us dr laura de paoli, who represents a very influential body, the who, world health organisation, and she have been working for several international organizations to provide medical assistance worldwide, recently in africa. now it's my pleasure to introduce my mentor, professor leonardo fabbri, who is a professor of respiratory and internal medicine in the university of modena & reggio emilia, who will chair with me the webinar. please, professor fabbri. leonardo fabbri: thank you lorenzo, and thank you for organizing these very interesting seminars. i'd like to thank the speakers for supporting this initiative. without further ado, i give it back to you to introduce the first one. lorenzo corbetta: okay. i introduce professor duccio cavalieri, professor of general microbiology of the department of biology of the university of florence, with the title, 'evolution of a viral spillover.' please, professor cavalieri. duccio cavalieri: thank you. so, i had the task here to try to make sense of where this virus came from and what are its dynamics. i've been trained in harvard for six years in evolutionary biology and that's why my interest spreads through several kingdoms of microbes, from bacteria to yeasts and viruses. i have been studying specifically a yeast virus. it's called killer virus. it has some similarities with sarscov-2, but kills yeasts not humans. so, in genomics the evolution of the genome it's a process that is basically constant, and since the times of darwin we know that change is brought up by mutations that occur hypothetically randomly along the genome. the same maybe holds true for covid19. covid-19 is not a complete novelty. we have had here in this life two previous emergencies, mers-cov with a 3.4 case fatality rate, 2,494 cases, 858 deaths, sars, 8,000 cases, 774 deaths, and now covid-19, 11.6 million cases, 537,000 dead, where the numbers below are italy. 242 cases, 34,869 deaths. this data is as of yesterday. a relevant point is that coronaviruses have passed through human evolution several times in the past. probably we have met at least 40 different coronaviruses, and four of which have been associated to common cold. one actually at the end of the 19th century which started in russia was probably a coronavirus. two of them came from mice, two of them came from bats. bats are a perfect incubator for coronaviruses because they rarely develop the disease. they harbour the virus and they harbour large communities of viruses. https://www.covid19expertpanel.network/ stand on the same side against covid-19 – the future strategies against an unknown enemy . 3 today there are at least 61 different bat coronaviruses that can infect man and have been described in detail. jumping species is a crucial mechanism for coronavirus evolution and survival. the virus is alive only in the host, and so bats provide the reservoir and evolution place. interestingly, mutation rate in sars-cov is apparently low with respect to flu and hiv, but recombination between different coronavirus infecting the same host is indeed frequent. some bat species can carry up to twelve different coronaviruses simultaneously. this work has been made by a researcher from wuhan, zhengli, the 'bat woman,' and the work from the ralph baric laboratory in university of north carolina chapel hill. interestingly, since the time of sars, this review came out in 2007 and it's a summary of the conclusion of the sars episode. the last author, kwok yung yuen, said: 'the presence of a large reservoir of sars-cov-like viruses in horseshoe bats together with the culture of eating exotic mammals in southern china is a time bomb.' his words come from this review. 'the possibility of re-emergence of sars and other novel viruses from animals or labs, and therefore the need for preparedness, should not be ignored.' i think we probably have not read this review carefully enough, because recently, as we all know, this is exactly what happened. this is the first paper that describes in detail the composition of the rna viruses in the lungs, this is bal, in the lungs of a patient, one of the first patients in wuhan. as you see, the vast majority of the patient that was suffering from this disease, covid-19, was actually sars-cov-2. from the first regional work published by the group of zheng-li shi, we see that the author already suggests as the origin of this bat and puts at the basic of this, at 97% identity with the sars-cov-2, the coronavirus that we've come to know so well, ratg13. remember this name because this probably is the missing link, is the virus screen in the bat that differs from the one that infects the humans, but could be the backbone. it's the nearest neighbor to what we are seeing here. the differences between the bat virus and the human virus are substantial. so, indeed the potential origin and the nearest neighbor are bat viruses, but the differences are substantial. this is the paper from the andersen group that suggests the natural origin of this virus and shows that this virus has unique traits, as we all know. the spike region is unique with respect to the other sars and mers. the sequence of the spike with the binding sites to ace2 is so diverse that in the early days for the whole month of january, february, the scientific community was doubting that actual ace2 was the target for the binding. but then we know now that this is a degenerated site that is more efficient of the one from sars for binding to ace2. the second trait that we should all remember is relevant for the infectivity of the strain is the presence of a furin-like cleavage site that is absent in coronaviruses of the same clade. these two traits, in particular the second trait, have never been described in another coronavirus before, are unique to this virus that is attacking the humans, and probably this second trait that has been seen before in viruses like hiv-, the second trait, this furin splicing site, is, kind of, interesting because it's probably within the ability of this virus to escape the immune system. now there are more than, today, 7,000 genomes of this virus sequenced, okay? the data i report here and which i'll talk during my presentation do a summary of what is known around 4,256 of those for which we have an almost complete assembly. we have a sequence of at least 85% of the sequence of the virus. amongst these, we have 350 italian genomes that are currently being published by the group of researchers from the sacco hospital in milan and their collaborators. immediately from the beginning, probably we have been exposed to two different strains of sars-cov-2. i know the definition of 'strain' within virus infection is quite peculiar because there is not a real boundary. as i have seen, 97% is the boundary between the nearest neighbour from the bat and what happens in humans, but these are the sequences extracted from the first 5,000 genomes. we see that there are two clades, one clade in which is predominant the shanghai signature, and one clade in which is predominant the wuhan signature. what does it mean? this means that even if the virus mutates slowly, evolution occurs, and this is not something surprising. in fact, this paper that is accepted in nature should come out in the next days. this preview of an accelerated article preview shows exactly this fact. you can discriminate, based on specific mutations, the two different clades. it's interesting this because there are several mutations, 80% of which are non-synonymous mutations. what it means that the virus mutates, mutations are not evenly distributed along the sequence. there are some regions that are enriched in nonsynonymous mutations, so in mutations that lead to an amino acid change. the fact that they lead to an amino acid change means that the protein is changed. the big challenge is showing that there is a change in functions, and this we don't know, but you have to know at the moment that 198 recurrent mutations describe homoplastic sites. four sites are mutated in more than fifteen patients of those that have been sequenced, and one site is mutated in over 40 patients. why is this interesting? how can we use this information? we can use this information to track the flow of the virus. this is a paper published on pnas. all of these papers have been heavily criticized. that's the way science goes. the applicability of network theory of evolution to the evolution of virus sequences is not trivial because you do not have the models of evolutionary theory that we have for yeast or for bacteria, but the applications of the nearest proxies suggest that we can track the virus that started from wuhan, arrived in shanghai, moved to munich, arrived from munich to milan, and from milan to mexico city in 30 days for a precise set of mutations. this approach allows, let's say, to estimate the success rate of the entry of coronavirus into a country. this is the american example. this is a paper published by the group of lemey, and they analysed the sequences and asked how many times the virus arrived in washington state. they found a first aborted entry that was not successful around january 15, and the second successful entry on l. corbetta et al. 4 february 15. the interesting thing of the model they built is that they could see that the first arrivals were not successful. the two arrivals that brought the virus into the us were one from hubei to seattle on february 13, and the second that brought the virus that probably expanded in milan to new york city on february 20th. so, this allows us to follow the routes, and what we know now is that these two viruses were slightly different. these are not enormous differences, but were slightly different, and what we know now is that the exact two same differences that had been discovered in china were present in milan, were present in lodi and in bergamo. this is the paper of the first published publication from an italian group. it's the group of stefanelli paola, you recognise the name, maria rita gismondo, giovanni rezza. they described the presence of two specific strains. now here's the caveat of this story. some of these papers, some of the research groups, are making claims that are currently hard to support. this paper here from montefiori and korber, it's a very interesting one but suggests that the spike mutation that we have seen being present in at least 25 of the genomes sequenced leads to a less transform to discriminate two forms of the virus, one that can be transmitted more efficiently and one that can be transmitted less efficiently. now, the big issue with these assumptions is the sampling error. the paper i'm reporting you here just came out on current biology from the group of sarah otto, an excellent evolutionary biologist. (https://www.cell.com/current-biology/fulltext/s09609822(20)30847-2) what sarah shows is that based on the genomic sampling over time, the substitution rate can be estimated. we can estimate one mutation per week during the movement of the virus in the world. we can see that the substitution rate is much less the one from influenza, and we can make assumptions on which will be the dynamics of the mutation using evolutionary theory. according to the models that sarah otto has developed, the mutation should increase transmission, reduce symptomatic fraction, increase the duration of the incubation phase, reduce virulence, and the models predicted that the lockdown period, the whole experience, will probably lead to the emergence of a second wave of the virus in mutated form in the fall, september, october. this model is supported mathematically in quite an interesting and convincing way, and this model draws a few fine lines about the searching for that mutation of sars-cov-2 and basically puts an important caveat. currently, the lack of a neutral sampling strategy, so the fact that we have sequenced not really at random, but we have sequenced in areas where we were having hotspots of the virus is leading to a potential sampling error that makes it very hard to say whether one variant is associated to an increased rate of transmission or to an increased pathogenesis. but very likely the virus is dynamically changing. this paper here shows very interestingly that we have not identified a single recurrent mutation convincingly associated with increased viral transmission, and we have to keep in mind that mutations could even make the virus worse. so, my suggestion to the audience is that when we look at the virus and its evolution, we should keep in mind what dobzhansky said. 'nothing in biology makes sense unless observed using evolution as a lens.' so, selection acts on the whole genome, on the genes of the virus, of the host, and of the other microbes that are carried by the host, but why there is no evidence currently of the outcome of sars-cov-2 adaptation? the analysis in the study of the rate of change of this virus is important to adjust and potentially drive the strategies for its containment and to make conclusions supported by evidence. thank you. lorenzo corbetta: thank you very much, duccio, for your very nice presentation. we will have many questions for you at the end of the other presentations, and for the audience, they could post the questions in the chat and we will respond later. now i introduce professor paolo bonanni with a presentation on perspectives for the development of a vaccine for covid-19. paolo bonanni: so, thank you lorenzo for the invitation to join you in this very interesting webinar. my task is to give a perspective for the development of a vaccine for covid-19, and you know that a lot is moving around this topic. i would suggest our colleagues to read this paper if they did not already read it. the authors are colleagues from the us, including anthony fauci, and in this paper we have some interesting perspective regarding the challenges for the development of a vaccine against covid-19. first one is define what is protected immunity. so, we would need to have a correlate of protection which we don't still have. another point is how long the immunity could last, so the duration of immunity. the second point is we have variable endpoints for the evaluation of a vaccine. are we speaking of protection from infection or of reduction of viral replication or reduction of the severity of the disease? these are different endpoints that should be considered separately. then the role of neutralising antibodies and t cells. we have difficulties in understanding the real incidents of infection because we don't know exactly what the percentage of asymptomatic subjects is, compared to the symptomatic ones. we have a challenge in the potential creation of independent labs with identical validated serological tests to confront different candidates and different clinical trials. we https://www.cell.com/current-biology/fulltext/s0960-9822(20)30847-2 https://www.cell.com/current-biology/fulltext/s0960-9822(20)30847-2 stand on the same side against covid-19 – the future strategies against an unknown enemy . 5 should be able to compare the very many vaccines that are in development today to see what the comparative ability of each candidate is. then an ethical point, the human challenge trials, are they useful first of all, and are they ethically acceptable? the last point is the immune enhancement risk. we must remember that vaccines against respiratory virus may induce an excessive immune response that in case of infection, instead of preventing the disease, could worsen its course, attacking the patient tissue. so, a candidate vaccine must undergo severe safety evaluations. this is a mechanism of antibody mediated immune enhancement with an increase of growing inflammatory cycle times, but also the mechanisms of antibody-dependent enhancement where no neutralising antibodies could increase the potential for the virus to enter the target cells. for sure our target is the s protein, the spike protein of the coronavirus, where there are these three identical binding domains, all of which must bind to the host cell. here we can see that when the virus needs to enter the cell there is this opening up of the spike with the receptor binding domain which can bind to the ace2 receptor. if you look at the different vaccine trackers in the web you can find sometimes different numbers on the same day because it's very difficult to keep up with the many research groups that are working on this topic. here you can see, this is from who, 129 pre-clinical studies, fifteen in phase one, nine in phase two, two in phase three, but none approved today. if you look at another tracked which is from the london school of hygiene and tropical medicine you'll find different numbers. this is also very recent from yesterday, but what is amazing is the number of projects that are in the pre-clinical phase, but some of them then are progressing to the phase one, two or three before they get approved and licensed. so, what are the possible approaches to a vaccine against covid-19? one of the most advanced approaches is based on dna and rna-based vaccines. (https://www.nejm.org/doi/full/10.1056/nejmp2005630) why an rna vaccine? an rna vaccine is probably very much scalable in a big way. how do they work? the mrna, which is the coding for the spike protein, is encased into a live lipid code, then it's introduced into the cell, it goes into the cytoplasm and produces the spike proteins that are then released for the contact with the immune system. but there are also the dna vaccines, which are introduced by an electroporation system and they must enter the nucleus and integrate into the nucleus and then produce mrna to produce the spike proteins. so, what is the advantage of mrna vaccines? the use of mrna vaccines has several beneficial features over subunit, killed and live attenuated virus, as well as over dna-based vaccines because safety is important and mrna is a non-infectious, non-integrating platform. there is no potential risk for infection or insertional mutagenesis. then the efficacy, because various modifications make mrna more stable and highly translatable. there is an efficient in vivo delivery that can be achieved by formulating mrna into carrier molecules, allowing rapid uptake and expression into the cytoplasm. the production also, i already mentioned this. mrna vaccines have the potential for rapid, inexpensive and scalable manufacturing, mainly owing to the high yields of in vitro transcription reactions. we have two sub-types of mrna vaccines. the first one is the simple mrna, you introduce the mrna which produces the spike proteins, but we have also some self-amplifying mrnas. in this case not only the mrna which is encoding for the spike proteins is introduced, but also some non-structural proteins that allow the self-amplification of mrna, and so a higher production of spike proteins. there is already a vaccine with this characteristic developed by a college in london. then the most advanced rna-based vaccines are these two. of course i cannot mention all of them, but the most advanced are the ones from moderna. this vaccine uses messenger mrna to produce viral proteins. the american company is eyeing phase three trials in july and hopes to have vaccine doses ready for early 2021. then there is another vaccine of some biotechs together with pfizer, which have also been announced on july 1st that all the volunteers for phase 1/2 trial produced antibodies against sars-cov-2 with some moderate side effects. so, this warrants further studies that are going on at this time. so, this is the plan of the phase one study for moderna, and here you see it's foreseen to end in september 2021. the other one from pfizer, they had several studies with many participants. you can see here 7,600 participants in this https://www.nejm.org/doi/full/10.1056/nejmp2005630 l. corbetta et al. 6 phase 1/2 randomised observer blind dose-finding study. then again this is a dose escalation study, so it foresees to verify what is the right dosage of this vaccine. let's turn to the dna vaccines. dna vaccines are also important because dna is easy to manipulate, it can allow rapid design and construction of potential vaccines. another advantage of dna vaccines is that they are extremely stable, and so they could reduce the need for a cold chain and increase the production shelf life, which is important, for instance, for developing countries where the cold chain could not be assured in some instances. there are some pre-clinical data of some of these vaccines. they are studied in rhesus macaques, 35 of them. they induced an important humoral and cellular immune response, including neutralising antibody titers comparable to those found in convalescent human and macaques infected with sars-cov-2. following vaccination, the animals were challenged and it was possible to demonstrate that the level of viral presence had a very important reduction in median viral loads in bronchoalveolar lavage and nasal mucosa. there are other dna vaccines, one is from inovio. there is also an oral vaccine based on the dna technology where there are billions of colony-forming units of bifidobacterium longum, which has been engineered to deliver plasmics containing synthetic dna, encoding spike proteins from sars-cov-2. another type of vaccine that is under development now is the one based on viral dna vector. this is a variation of the design of the expression plasmid, which are used to construct a dna expression system that can amplify the level of rna and protein expression as occurs in a live virus infection. the most popular ones are those based on adenoviruses, but anyway, there are around 25 groups that say that they are working on viral vector vaccines. the virus is like measles or adenoviruses that can be genetically engineered so that they can produce coronavirus proteins in the body. then we can have replicating viral vectors such as with measles or also the vesicular dermatitis virus that was used recently to produce the first ebola vaccine which was licensed, but also nonreplicating viral vectors such as adenoviruses. in this case, booster shots can be needed to induce long-lasting immunity. so, the adenoviral vector is particularly useful if you want to get a cd8+ cytotoxic t lymphocyte response, because in this way the antigens that are carried by the adenoviral vectors can be presented to t cells via mhc class 1 molecules and this causes a robust ctl response. so, in this way they can also, the intracellular virus could be killed. we have two important adenoviral-based vaccines presently underway, the ad5 coronavirus produced by cansino, a chinese company, but also the vaccine based on the chimp adenovirus 5 developed by the university of oxford. here you can see that the pre-clinical studies of the vaccine developed by the university of oxford showed to be able, under challenge, to reduce the possibility to have pneumonia in the macaques that were immunised compared to those who were control group. the other important data is that the nasal fluid, the ability of the vaccine to reduce the viral load is not as much important as is the bronchoalveolar fluid. so, there might be some doubts that this vaccine is able to avoid the disease but not the transmission of infection. so, we have here again phase 1/2 studies with different numbers, but also the vaccine from cansino, from the chinese company is very well studied. we have this phase two clinical trial to stand on the same side against covid-19 – the future strategies against an unknown enemy . 7 evaluate the safety and immunogenity of the recombinant novel coronavirus vaccine, and also this trial which is a dose escalating phase one clinical trial. we have the first result of this study where they showed that giving a low dose, a medium dose or a high dose, they had 75 to 83% participants declaring they had the side effects, but they were not bad side effects, so there was no serious adverse event noted within 28 days post-vaccination. they also studied the elisa antibodies and neutralising antibodies which increased significantly at day fourteen and peaked at 28 days post-vaccination. so, they are going on and should be one of the first groups to get a vaccine close to the license route. so, they also have another study here. then we turn to the other approach, which is the one of inactivated vaccines, and a vaccine which is advanced is the one from sinovac, a private chinese company. in june, the company announced its phase 1/2 trial on 743 volunteers, and they found no severe adverse events and produced an immune response. so, they are launching a phase three trial in brazil in this month, in july. then there is also the wuhan institute of biological products, the other vaccine. in june they are moving to a phase three trial, so they are in advanced phase. again, we have data from the sinovac vaccine on pre-clinical data showing that it's a good response and the possibility to work with this vaccine licensed are rather high at this moment. one of the last things i wanted to report is that some groups are also studying the possibility to use the mmr vaccine, the measles, mumps and rubella vaccine, for its potential to give cross-reactivity and cross-protection also for the covid-19. we have the first subunit vaccine available today in clinical trials. this is very recent news that a first subunit vaccine underwent the first phase one study. here it's a vaccine which has two different adjuvants. they are as03 adjuvant, which was used also for the h1n1 pandemic vaccine in 2009, and also the ctg, the repeat of the cytosine and guanosine sequences that are a good adjuvant also for this kind vaccine. then we also have the pathogen-specific artificial antigenpresenting cells, where genetically modified artificial antigen-presenting cells can express conserved domains of the viral structural proteins delivered by lentivirus vector, which are supposed to evoke the naïve t cells in the human body and lead to differentiation and proliferation. we also have autologous antigen-presenting cells that are charged with the antigen and re-infused in the nurses and doctors that will undergo this first study in china. final considerations. i have rushed to show you what is going on on the vaccine studies, but we have to remember that usually a vaccine takes fifteen years to be developed, and so this is the timeline we would get a vaccine if we had a normal development. we would have a vaccine in may 2036. we are rushing, so one caveat is that we cannot run the risk of approving a vaccine which has not undergone all possible scrutiny of safety because we could endanger not only the covid vaccine but also all vaccines that we are using today with exceptional results. with this i thank you for your attention and this is my address for any questions you want to address. thank you very much. lorenzo corbetta: thank you very much paolo. we will have many questions for you, and now we carry on with professor muhammed munavvar, consultant chest physician of the hospitals of preston (uk). his presentation will be an update on the current experience and plans for the future from the thoracic society's perspective. thank you mohammed. mohammed munavvar: thank you very much. it is indeed a pleasure and privilege to be here, to be able to speak and update you. i had given a similar presentation in the first event of your excellent series of webinars. what i am going to do basically is cover this topic with a very brief introduction, then an update about thoracic society-related statements and guidelines, a brief overview of clinical trials in the uk, some of which you will already read about, and then conclude this presentation. first of all, i don't have any conflict of interest. i work for lancashire teaching hospitals, british thoracic society and eabip, as you have already mentioned. the global incidence, just checked about an hour ago, as mentioned already with the first speaker, it has crossed unfortunately more than 11 million cases and more than half a million people have died. so, this unprecedented global pandemic has left a trail of devastation, despair and deep distress to a whole lot of people around the world, and it does not respect royalty or indeed position, as we have seen in the last few months. the uk data, again checked yesterday, was nearly 300,000 cases and unfortunately more than 44,000 people have passed away. the only good news is that although there was a peak in april, latter part of april and early may, we are starting to see a decline in the numbers and also in the number of deaths. so, what have we done as british thoracic society during this period? we have produced a great deal of guidance in relation to covid and i'm going to take you through some of this guidance in the next few minutes of my presentation. we have set up a separate section in the british thoracic society. i don't know whether any of you had had the opportunity to visit, but it's something that we can share free downloads of a variety of information on covid for the respiratory community. now we have started to move to this section, where we are trying to focus on how to resume services, and i'll touch upon this as well in the next few minutes. a whole lot more than 25 different statements have been produced at a record pace in the last three to four months, where they would have normally taken three to four years to put together all this guidance. a team of people have worked round the clock to produce guidance on various aspects of pulmonology, but also other l. corbetta et al. 8 conditions such as venous thromboembolism, oxygen therapy, etc. so, essentially every aspect of respiratory medicine, how should the pulmonologist or how should we non-pulmonologists manage is what we are focused on. as i said, now we have not surprisingly found that a whole lot, thousands and thousands of patients who do not have covid, who have non-covid-related respiratory problems have suffered a great deal as a consequence of the pandemic because their care has been severely affected because appointments have been delayed, elective care has been affected, even semi-emergency care has sometimes been affected. so, we put together some documents on how to plan the resumption of these services, particularly lung function tests, how to do it safely step-by-step, because there have been very few lung function tests carried out during this period. sleep physiology and sleep medicine, a crucial part because of its wide-ranging implications for the patient and the wider public. procedures related-, how to resume procedures which i'll come to in a minute. specific guidance has also been produced with regard to pulmonary rehabilitation and long-term ventilation services. and this is part three and then we're going to stretch to all the other respiratory services. we have also focused on guidance for healthcare professionals because i presume it's happening in your countries as well, where patients who are over 70 but also patients with respiratory illnesses and a variety of other illnesses, have been shielding during the lockdown period. the other big tsunami that is going to hit us, or has already started to move towards us, is the large workload of postcovid pneumonia patients. how do we systematically ensure that these patients are cared for in the weeks and months after they recover, fortunately, from covid pneumonia. this has been divided into two sections, those who have had severe pneumonia and needed admission to an intensive care unit, or high-dependency unit and those who have had mild to moderate pneumonia. patients in the severe category are given details of a helpline, this varies around the country and they are given a call or face-to-face consultation about four to six weeks following discharge from hospital. these patients then-, we have to do a systematic workup, look at-, consider new diagnoses of pe, liaise with localised cu team, post-covid holistic assessment to pick up any new problems that developed as a consequence of covid pneumonia. and twelve weeks after discharge, they have a thorough assessment, including full lung function test, where necessary a ct scan, other lung function tests, functional assessment such as a six minute walk test, consider an echocardiogram and where appropriate even repeat the ctpa required. and then we pick up a percentage, we think we'll pick up cases of interstitial lung disease, they'll go to the specialist interstitial lung disease and some may end up requiring attention from the pulmonary vascular disease specialist. in the milder category, we could relax a little bit more and have a more-, a less proactive approach but where necessary, on demand we can provide service but also twelve weeks post-discharge we will carry out an assessment initially to see how they are and then if necessary proceed to a more detailed systematic assessment as has happened in this category. all these documents are available in the british thoracic society website and are free to download and as you can see here from march to april to may, more than 100,000 people have-, 100,000 times it has been downloaded, each of these documents, to cover all these aspects. change in practice is also required, i'm just giving you an example from being an interventional pulmonologist like lorenzo, giving an example of what is happening in the bronchoscopy suite but this applies to every procedure in the hospital, every visit to the hospital. so, the moment we receive a referral, we do an assessment remotely and then ask the patient to isolate. ideally for fourteen days but of course in the lung cancer field or cancer field, that is not possible, every minute is crucial so, we ask them to isolate but continue with the diagnostic part. we are undergoing a pet-ct scan, a ct scan, have a covid swab 24-48 hours in advance. what is becoming more widespread, is the availability of igg antibody tests and then at that point we check and sometimes we need a repeat ct scan if they have not had a pet-ct scan. on the day, they will have a questionnaire done, potentially in the future they can have a point of care lateral flow assay, to check for antibody test, or even point of care swab to make it safe for those patients to undergo whatever procedure they need to. we cannot keep postponing procedures, so far we've postponed some of the elective procedures. and at the same time, we want to ensure that our staff are safe. how do we do that? we want to make sure by this pathway, that it's a green area, not a red area but a green area by admission and recovery. we want to ensure that everybody's wearing full ppe. maybe we have to adapt the area, the environment as well with regard to negative pressure rooms or the whole room. the suite needs to be changed, the layout needs to be changed to have a separate dining area, separate exit or doffing area etc. majority of procedures we try to do under general anaesthesia, as has been demonstrated by myself here with an eg tube. that is the closed circuit but sometimes and this applies also in the intensive care unit, where you have a sheet along with an eg tube and a t-piece but sometimes you have to carry out this procedure under local anaesthesia and sedation and a number of different devices have been put together imaginatively. and one such is the slotted surgical mask or face mask, make a little incision and through that you introduce the bronchoscope while oxygenating the patient through the nasal cavity. a number of other boxes are available for this purpose as well. moving on to the next major section that i want to spend a few minutes on, it is about research and therapeutic trials and when the pandemic hit us, the uk got involved in a number of studies. if you look worldwide and if you type into the us clinicaltrials.gov, there are more than 2,000 studies underway currently in the covid world and there have in fact been more than 27,000 publications. what happened in the uk very early on, it was decided that the government will pump in a great deal of money through the national institute of health research into a variety of trials, everything from vaccines to epidemiology, to policy development and research and so on. and a previous speaker very nicely covered the vaccines and some of the couple of vaccines which are being developed here. a number of clinical trials were initiated, multi-centre clinical trials, so that we get proper randomised stand on the same side against covid-19 – the future strategies against an unknown enemy . 9 trials, with meaningful conclusions and one in particular i will touch upon in a minute. the trials are plasma transfusions, trials of vaccines and a variety of other areas as well. the recovery trial is the biggest trial that was conducted in the uk, the randomised control trial and this was engineered from oxford, a team, on a national basis. almost every hospital in the uk was involved in this trial. initially the trial design looked like this. you had five arms, two is to one, is to one, is to one, is to one, no additional treatment or hiv-, anti-hiv drug lopinavir/ritonavir, dexamethasone low dose, hydroxychloroquine, or azithromycin. later on what was added was convalescent plasma or no additional treatment, another randomisation. in the second week, if the patients continued to deteriorate despite the initial intervention, then they were randomised to tocilizumab or no additional treatment when the cytokine storm was considered to be important. so, what happened? that trial was started in-, end of march early april and first week of june, on the 5th of june, the data from more than 1,500 patients, 1,542 patients, in comparison with usual care in double that number. hydroxychloroquine, it was found that there was no significant difference in the primary end point of 28-day mortality, between the hydroxychloroquine arm and the usual care. there was also no evidence of beneficial effects on hospital day duration or other outcomes. this indicated that there was no meaningful mortality benefit with hydroxychloroquine and therefore hydroxychloroquine arm was removed from the randomisation. and on the 16th june 2020, there was groundbreaking results from this trial and as you would have all seen, a total of more than 2,000 patients were randomised to receive dexamethasone 6mg, once daily for ten days and were compared with double that number of patients who were in usual care. and what it showed is that dexamethasone reduced deaths by one third in ventilated patients. for the first time, there was a medication that has proven beyond doubt to bring about mortality benefit in ventilated patients one third and in patients requiring oxygen, outside of the critical care unit, one fifth mortality benefit. based on these results therefore, it was concluded that one death could be prevented by treatment of around eight ventilated patients with dexamethasone and around one death could be prevented in 25 patients requiring oxygen alone. next came the results on the 29th june, remember dexamethasone was the 16th june. on the 29th june it was shown that lopinavir/ritonavir, the anti-hiv drugs, did not bring about any clinical benefit. again, more than 5,400 patients and comparing it, more than 3,000 patients and it showed there was no mortality benefit and there was no evidence of beneficial effects on the risk of progression to mechanical ventilation or length of stay. so, anti-hiv drugs also have been removed from the recovery trial recently. that is a quick overview of what has been happening and i'd like to conclude by making the following points. future, as far as covid is concerned, one of the biggest things that has happened, is training and teaching has been severely affected by covid because students, trainees, fellows, are not allowed into the covid ward. we need to think outside the box and think of ways and means to provide the training, continue to provide the training and we are trying to evaluate a few different techniques, such as the use of 360 degree camera, the hololens and augmented reality and so on. the pandemic curve has indeed flattened and started a downward trend in many countries around the world. however, we can expect further low incidents with waves. it could also become endemic, therefore we need to remain vigilant, there is no room for complacency. primary and secondary care services need to restructure and work collaboratively. i've spoken about post-covid follow up and need to resume services. we cannot continue to ignore all those other patients who have non-covid related conditions. we have seen a tremendous expansion of digital healthcare, telehealth, minimising face-to-face consults and this is here to stay and we've just got to expand on it and do it properly. every patient who comes through for interaction in the hospital, will need to be isolated, tested, screened, prior to any interaction, any procedure in the hospital. we need to find novel methods, innovative approaches to ensure that this is speedy, accurate and effective. we're also looking at therapy remotely, example virtual pulmonary rehabilitation. we've already looked about and talked about the importance of research into therapy, vaccines and prophylaxis and this needs to be a collaborative, collective and consistent approach across the world. as i said in my first talk, nobody should think that they can be safe without making everybody else safe. thank you very much indeed for your attention. leonardo fabbri: thank you very much dr mohammed munavvar. and it's now my pleasure to introduce the next speaker, professor alvaro cruz from the university of salvador, bahia. alvaro is a professor of medicine, has contributed tremendously to the science and education in the field of asthma and allergic disease. today he will address the topic of controlling the covid-19 outbreak in brazil. is it possible? alvaro, privileged to have you with us. alvaro cruz: thank you very much to you. i'm honoured to be part of this most relevant discussion with such distinguished chairs and speakers. i'm especially pleased by the title of the programme, 'standing on the same side'. this is exactly why i chose this title. 'controlling covid-19 outbreak in brazil. is it possible'? we are facing this combat regretfully completely divided. this is a dark side of brazil that many of you know unfortunately. we have a minority living in good conditions and a lot in underprivileged neighbourhoods. this is the major split of inequalities in brazil. the leaders should have been taking care of for a long time and trying to reduce this. now we have another problem. this is my conflict of interest disclosure. my major links are with proar foundation, federal university of bahia, the national research council in europe that is developed to supervise me in brazil. i divided this talk, brief talk, in four topics, the dimension of the brazilian covid-19 tragedy, the dangers of national division in fighting covid-19, the strong response from the public health system and respiratory health as a global priority. you see the division of the brazilian tragedy, the national trend in cumulative deaths to covid19. over 60,000 deaths, 602 the last day, mortality of 4%. l. corbetta et al. 10 over 1,600,000 cases. and here you see the distribution of cases from the big cities at the seashore, towards the countryside in every state. and you see some white areas not affected by cases, it's because the population is scarcely distributed. now, some information from the city of sao paulo, the first one that was affected. the first case was somebody coming from italy, as you know sao paolo has strong links with italy. and what you see in this upper panel here, is an estimate of adherence to social distancing by anonymised geolocation monitoring sao paolo. you can see the numbers but they are all around 50%. so, it's social distancing that was in place that was happening in sao paolo, was never beyond 60%, it got up to 59% in the beginning and now it's around 47%. i guess this is not enough, it's part of the reason that things are not well in brazil. some information which is important for coronary physicians, comorbidities amongst subjects dying with covid in sao paolo. this is an estimate by may 23rd, over 6,000 cases, 10% of them had lung disease, some sort of lung disease, and 3.4% had asthma. asthma was not a lung disease but this problem of reporting comorbidity, especially the respiratory comorbidity, is a problem all over the world. an underscore of the fact that many chronic lung disease such as asthma and copd are under-diagnosed, under-recognised. now, some good news. despite all of the problems we have and i will show you some of the background of the problems but now some good news. the numbers of deaths per day in brazil in your upper left, apparently it's reaching a plateau and perhaps a trend to decline. the same you'll see here in the number of deaths per day in the state of sao paolo, a plateau and in the city of salvador in the left lower graph where i live, there also seems to be a trend, or plateau or even decline. and the same happens in the city of sao paolo. there is certainly a plateau and perhaps a trend to decline. this is an interesting paper published recently from the us, that studied the association between mobility patterns and covid-19 transmission in the usa, using a mathematical modelling study, in which they calculate the daily mobility information derived from aggregated and anonymised mobile phone data, as it was done in sao paolo. and what they have shown, is that the mobility patterns dropped by 35 to 63%, relative to the normal conditions, very similar to sao paolo as i mentioned. mobility patterns are strongly correlated with decreased covid-19 case growth rates for the most affected counties in the usa. they observe now, that individuals apparently anticipated public health directives where social distancing was adopted despite a mixed political message. again a similarity with our situation in brazil. now, i wish to share with you some facts. i will try to abstain from making judgements. the dangers of national division in fighting covid-19. we'll see here some of the president's-, jair bolsonaro's recent statements and action. he has said in a national tv broadcast, that covid-19 is just a bit of flu, that the priority should be for economic activity, this has been always behind his statements and he attempted to fight states and municipalities when they tried to promote social distancing. there was no real lockdown in brazil in any major area and he said there was no need for social distancing because this would be bad for the economy. then due to this, the first minister of health was fired, who was doing a very good job at the time. then, he often took part in demonstrations with no mask, as you see in the picture. he ordered massive production of hydroxychloroquine in brazil and due to this reason, the second of minister of health resigned because he didn't agree with using this bribery with no scientific basis. and the ministry of health has been led by a general so far. another quote from president bolsonaro, when he was asked about increasing numbers of deaths, he said, 'and so what, i make no miracles,' and he has attributed the responsibility to the governors and mayors. then he said, 'those from the right take chloroquine. the lefties take tubaina which is a popular soft drink,' making a joke about the political divides on medical matters, that has been unbelievable. but a strong response has been set up in brazil. we have universal public health coverage from the constitution of 1988, it's far from ideal but it's there. it's one of the largest countries in the world in terms of population and you see as universal public health, by law everybody is covered. there was an emergency cash transfer to the undeserved and informal workers from the federal government, which was a law passed in agreement with the congress. there was support to employers and workers to avoid massive unemployment. there were various aids from municipalities and states, direct involvement of many governors and mayors with the policy to combat covid. there were shelters for subjects with covid-19 and the war hospitals and icu beds with ventilators built. some other examples of a good response throughout brazil, sao paolo university hospital complex offered 1,000 beds exclusively to covid-19, including 300 icu beds. there was a network developed in my university in collaboration with the fiocruz, foundation through the ministry of health, and a centre for big data called cidacs, to analyse date and publish trends, daily updated from more than 5000 municipalities in all states of the country. we set up a tele-coronavirus hotline, in bahia my state to help guide people on whether they should go to the health service. the state of bahia and the city of salvador are building covid war hospitals and shelters. there was the sos favela in rio trying to watch what happens in other certain populations. these are only a few of many good initiatives. another thing that is worth mentioning, is the rapid generation of knowledge and i bring two examples here. a report from minimally invasive autopsies of covid showing and confirming that it's stand on the same side against covid-19 – the future strategies against an unknown enemy . 11 a systemic disease with major events in the lungs and involvement of various organs and tissues. the pulmonary changes are the result of severe epithelial injury, with microthrombotic vascular phenomena. you see here, in patients with diffused alveolar damage in fatal covid-19, fibrinous microthrombotic in small sized pulmonary arterioles observed in eight out of ten patients. my colleagues, i wish to bring you to this broader scenario of respiratory disease. as you see here, copd is responsible for 5.72% of the deaths globally. lower respiratory infection, 5%. lung cancer, tuberculosis, asthma, interstitial lung disease, the major respiratory disease were responsible, the cause of 16.92% of all deaths in 2017. it's going to be much more this year. the dimension of the brazilian covid-19 tragedy is 63,000 deaths already. there is national division which leads to major weak flanks in many fronts, regretfully. a strong response from the public health system has prevailed however in states and municipalities and respiratory disease are the leading cause of deaths globally. some thoughts to share with you. health specific hospital beds and ventilators are not enough to solve the problem. social distancing has to be taken seriously from the beginning of the fight. collaboration is key to planning strategically and preparedness. capacity for research, surveillance and manufacturing essential products is crucial. who is vital for global health security co-ordination and response. respiratory infections are a major threat to mankind. cannons and bombs are useless to fight it but science, solidarity and sharing knowledge, work. political leaders must engage with health authorities, not fight them and health is the most precious asset one has. health problems respect no border and everyone must be cared for to protect all. and top priority has to be given to protect respiratory health, hopefully in a cleaner and greener role. thank you very much. leonardo fabbri: thank you very much professor cruz for your nice presentation. we now move to the next presentation by professor adrian rendon from nuevo leon. professor rendon is also president of the mexican pulmonary society and today he will address the issue of the coexistence of two pandemics, tb and covid-19. professor rendon. luis adrian rendon: thank you. okay. i live in a country, that is endemic for tuberculosis and now it's suffering the severe attack of covid. so, i may speak a little bit about the coexistence of these two pandemics. i'm a member of the green light committee from the world health organization, actually for paho, the branch for the americas. here, in these two maps, you can see the global distribution of covid. here, the darker the worse and the tb distribution. i put these two maps together because it seems that covid territories respect tuberculosis territories but we will see later that this is not true, actually the opposite. the who report, averages about 10 million new cases of tuberculosis, incident cases and for covid just in seven months we have overpassed that number with 11.5 million. about deaths, tuberculosis is in the top ten cause of death, tuberculosis is the number one infection, leading counts of deaths from an infection, with 1.5 million cases a year. but in just seven months, covid is reaching more than half a million and if it was a race, maybe covid is going to win this race if things are going on as we are seeing. early this year before tb day, the who launched this information note, before tb day because there was some concern and they were pointing out two main questions. number one, are people with tb likely to be at increased risk of covid infection, illness and death. the main concern at that time was that the tb patients would suffer in their treatment because of the pandemic. we didn't know too much about the coexistence of the two infections, actually we don't know yet about that. and the second question was, 'can we maintain and support the essential services for tb as prevention, diagnosis and treatment.' for prevention, it was clear that we have to limit the transmission of tb to covid patients and covid patients to tb because they may have similar clinical presentation, they can share some symptoms and they are often in the same places. if we were doing well with the respiratory protection measures, we shouldn't be worried, but we know that all around the world we were suffering from tb outbreaks among healthcare workers. so, bilateral transmission is a real risk. for diagnosis, we have the proposal that all the tb patients and covid patients at the moment with suspect cases, should have available the two tests, the one for tb and the one for covid. but on the field, those two problems work independently and there is a real concern about biosafety. nobody wants to test for tb if they are not sure the patient is not a covid case. for treatment and care, most of the tb programmes have very specialised staff, including the physicians, immunologists, nurses and whatever was needed and they were supposed to be a group that could help in the covid pandemic, sharing their expertise. but what happened in real life, is that expertise was transferred to covid programmes, leaving alone the tb programmes. what about the coexistence of tb and covid. l. corbetta et al. 12 what do we know now, we don't know too much. now, i'm using this map to point out the endemic regions for tuberculosis. the red dots are covid and you can see that covid is anywhere. it seems that there are more covid on the industrialized countries but we can see the numbers, we can see that this is different because of the magnification in the map. actually you can see here, we just listened to the case of brazil, i can tell you about the case in mexico. mexico, brazil and peru, are the three countries in latin america with more tb cases and they are also the three countries with more covid cases. so, they don't respect each other, they are together. i'm going to present this case briefly. the coexistence of cases with tb and covid, there are not too many. these cases, are cases in my institution. it was a young physician, a female who presented with a classical, clinical picture of pleural tuberculosis that was confirmed by culture. the patient was put on regular treatment, standard treatment. she returned to work and when she was in the hospital they performed screening for covid on all the healthcare workers and she resulted positive. she was on six months of tb therapy, she has no symptoms and the chest x-ray taken at that time didn't show any findings suggestive of covid. currently the patient is doing well, she's continuing the tb treatment and she didn't receive any covid treatment. this is the first cohort report, of the coexistence of the two diseases, tuberculosis and covid. they collected patients from russia, from europe and from brazil and they put together 49 cases. the median age was 48 years old, most of them were male, half of them were migrants, bcg has been applied in 63% of those cases. a minority was hiv positive and most of the cases were pulmonary tuberculosis. for the covid presentation, 90% of the patients were symptomatic and 48% had covid pneumonia. regarding the time for the diagnostic, tb was diagnosed first in half of the patients, covid first in almost 30% of the patients and the diagnosis was simultaneous in the same week in 88%. the second paper is a kind of continuation of the previous one. they put together the 49 patients they already had, plus twenty more from italy. they had a total number of 69 patients and they look at mortality in this group and mortality was 11%. the risk factors they found, were the same we already know for covid, the elderly population with comorbidities. they found less mortality in migrants and we can guess that one of the considered reasons was the younger population. this is a new paper that we are participating in, it was just submitted. this is a global study that includes all the continents in the world and we are looking at the impact of covid on tb services. we are comparing the study of statistics, the tb statistics from february to may 2019, to the same period 2020. i wasn't allowed to present the results but i wanted to give you some numbers from my institution. what is the possible impact of covid on tb services? this is a short list, a summary list of those. shortage of supplies because of lack of mobilization and for the patients that are not going to the clinics, so we are suffering from inadequate follow-up with the patients. there is also a lack of services for tb, the small periphery clinics have been closed. there is a lack of tb experts because they are working with covid, so that counts as poor quality of tb care. also, the money is moving to covid, the tb programmes were not prepared for it. we may guess what is the role on the severity of the two diseases when they are together. if one has got tb and they've got covid, it's going to be a more severe case and the opposite is also true? in the case i just presented to you, it didn't happen, it was a priority here for a permanent tb infection and the covid was an asymptomatic case. and what about the drug interactions. we don't know how to treat covid yet but we're using many drugs, often labelled, and the mdr patients, xdr patients, using a lot drugs that can have very dangerous interactions with those drugs that we shouldn't' be using as we are. all of these issues lead to less tb diagnosis, delay in tb diagnosis, so we are expecting to have more tb cases there in the community but we're not aware of them. all of this is happening in my country, in mexico. i've seen that and i can tell you that we are suffering from all of this and maybe in some countries like brazil, they have the same situation. here i'm going to show you some numbers that i have from mexico and from my state, nuevo leon, which is very close to the border with the united states. this is last year, this is the current year, the period january to may. on this year, tb suspects, we have more than 60,000 and in the same period we have about half. we've decreased the number of tb suspects that we're studying and the same happened in my state. what about the tb cases diagnosed in my state. this is last year, this is current year. over january and february, we were having an increasing number of tb cases, we were doing well but then the lockdown started in march and you can see that after that the number of diagnoses decreased a lot. and the worst scenario happened in my hospital. our tb clinic was closed with the lockdown because of safety reasons, you had more than two months, actually three now, because we haven't diagnosed any tb cases. stand on the same side against covid-19 – the future strategies against an unknown enemy . 13 those cases are there but we haven't diagnosed them. the who was expecting to reach the milestone for 2025 through the strategy, end tb elimination. this is the curve that they expect, this is what really was happening until 2019, this is for incidents and this is for deaths. when the pandemic hit this program, we can say that the expected is very difficult to reach for incidents and for deaths and maybe we should expect a resurgence of tb. we must be prepared to have many more tb cases, many more viral-resistant cases and also many more tb deaths and we need a damage control plan to deal with that. covid is supposed to stay, it's very probably going to stay. tb wasn't really there. tb is going to stay and actually is going to be a stronger pandemic. thank you very much for your attention. lorenzo corbetta: thank you very much, it is very interesting this correlation between tb and covid and maybe professor laura de paoli will talk about it in her presentation. i introduce laura de paoli who is the platform co-ordinator of who europe and she will talk about the resurgences after covid-19 in europe. please laura. laura de paoli: thank you very much indeed and good morning and good afternoon to everybody. thank you for inviting me here lorenzo, we've known each other for a long time. okay, so this is a situation report of resurgences in euro countries. so, my name is laura de paoli, i'm the coordinator of the covid-19 platform at who euro at the moment in copenhagen, at the moment i'm working from home. so, just a few words on the who structure. so, we all know that the headquarters are in geneva, where there is the making of policy, protocols and there are experts on a number of businesses. and, then we have the regions. the regions are coordinating entities and also support of countries. also, they do have experts there as well. so, there are six regions, afro, which is mainly the african continent, but countries can actually choose where they belong. so, we have sudan, for instance, which is an african country, also northern african countries, but sudan is not really a northern african country, which are actually they are affiliated to emro, which is eastern mediterranean region. so, there are social, cultural, political and religious regions for belonging to a region rather than another one. so, for instance, sudan belongs to emro because emro is a collection of islamic countries and sudan is mainly an islamic country. euro, which is the region i am working for, for instance, contains countries which don't belong to the european continent, but they are central asian countries, we'll see after. then, there is paho, i think, and my colleagues from america, south america can tell me if i'm wrong, so it's pan-american health organisation which is affiliated to who and i believe paho comprehends the whole of american countries. and, then we have searo, which is south-east asian region and wirro which is western pacific. so, a very quick overview of the countries which belong to who euro, which is 50 different countries and as you can see, i actually highlighted them in red, one is azerbaijan, kazakhstan, kyrgyzstan, tajikistan, turkmenistan, uzbekistan, which are not really considered normally, geographically, european countries. now, a very quick overview of the sit rep of which i'll give you a bit of a wrap up. we have over 200,000 deaths now in the euro region. since a few weeks, the number of new cases is no longer decreasing but has reached a plateau and is fluctuating at a relatively stable rate. and, we see small increases week by week, or small decreases. at this rate, we are seeing over half a million new cases per month, a very significant number of cases and this is happening at a crucial moment where countries are about one or two months from having lifted their lockdown measures. the picture is very mixed. in western europe, we still see countries where there is a stable decrease of cases, but in the balkan region, eastern europe, the caucasus and central asia, we see very significant increasing trends and in some cases, community transmission, which is the blanket transmission, which was not seen in early months. in central asia, numbers have been kept low in the early months and then with the lifting of l. corbetta et al. 14 containment measures, we see the health system of those countries struggling, with hospitals overwhelmed by the increasing number of patients. we see localized outbreaks which are explosive and have the potential to see new community transmission. what we also see, in some countries, is very prompt action and reintroduction of localized widespread measures to control those outbreaks. and, these outbreaks in school settings as we see in countries, such as asia. you know, the countries we see localized outbreaks, in specific sectors of society, for instance, food processing factories. lately, we saw an outbreak in a slaughterhouse in westphalia, west germany, where the cold surfaces promoted the stability of the virus and the outbreak. other important factors are who is working in those factories, are they migrant groups, do they live in overcrowded settings, which is a facilitating situation for spreading the virus? other outbreaks have happened in coal mines as in poland, where there are specific environmental factors, there's lack of ventilation that facilitates the transmission of the virus in confined settings. these localized outbreaks must be kept under control, otherwise they can easily spread out to community transmission. who, obviously, recommendation includes the three ts, testing, tracing, and obviously, treating. and, localized isolation, it's important to know that isolation is not only for individuals who test positive or are suspect, but also of the very place where the outbreak has taken place. for instance, the factories and the mines. over the summer months, we will be able to take action while the situation is under control, in a number of european countries. the situation will become far more encompassing in autumn as the influenza virus will start circulating in the region and the complexity of managing two respiratory viruses at the same time, with similar symptoms, will be a major public health issue, that will require a multi-sector approach with agencies at community level. there is a specific importance in this situation of recommending influenza vaccination at a political level. about the influenza vaccine, we will see a shortage of vaccines, unfortunately, due to the very situation we find ourselves in with the pandemic. there is not a specific who recommendation for pneumococcus vaccination or bcg vaccination, which has been suggested in many instances by different sources over these past few months. about bcg vaccination, we have seen observational studies in mice and humans suggesting a protection against covid-19. but we need hard evidence in the form of a randomized control trial which has been now carried out over the last few months and now we are waiting for results which should be coming by the end of october, at the latest, the end of the year. now, i would like to show you the, how do you get out here. share, and then share again. i would like to show you very quickly because i know, that's it. can you see the situation report? can you see the coronavirus disease? so, this is the sit rep that who geneva publishes every night after 9:00pm, more or less. and it's a daily report, they close gates around 10.30 in the morning, so this is the one of yesterday, the sit rep of yesterday until 10.30. so, here we have a map that shows where the most cases have happened yesterday. so, happened in the last seven days, so this is united states, brazil, unfortunately, india and then we have russia and also saudi arabia, iran and iraq, also and then egypt and south africa, in africa, you can see that africa is actually not terribly touched by the virus. here, we have a graph that shows the new cases per day and here we have the western pacific, where china, japan, south korea are, we can see they are the very first to spike up and then there are still cases but they're under control, now lately there have been, maybe a few more cases. now, there is south east asia, now this is india probably carrying out the line towards the up, but again, we don't see the spike that we saw here in europe, this is europe and we see in america, it's quite a linear arithmetic line. then, we see europe here in orange, so we see the exponential curve here and then the plateau and then now, a bit of descent. and, now we have reached a second plateau, with as i said, some countries in western europe have a downwards curve at the moment, but in the eastern european countries, balkans and central asia, we have cases going up, we'll see it in a second. then, we have eastern mediterranean which is receding but again, it's not exponential. we see america which is definitely exponential right now. and, africa, again, i worked in africa until a couple of months ago and we could see that the cases just didn't have at all that spiky tend that we saw in europe. so, is it the heat, is it the bcg vaccination, or most african countries have a policy whereby children from zero to six months of age are vaccinated with a bcg vaccine to avoid military tb in infants. so, now we go down through the countries. again, we have south africa, which is very high for an african country. we have many cases, 8,773 new cases yesterday, so it's a very high number. and, then we have nigeria with 190, now south africa is about 50 million people, inhabitants, nigeria, i think 190 plus million people and you can see that the number of cases are not very high. some people say, do they find them all, are they able to identify them to diagnose them, now, being covid, i'm sure you will agree with me, particularly in africa, where i worked for many, many years, it's actually a city disease. it expands particularly in capitals or where there is a lot of incoming people, particularly from europe, or from other countries where the incidence and the prevalence is higher. so, and then we have the americas, with the united states as well all know, 57,000, the new cases of yesterday, brazil, 37,900, so brazil is also still going up and then chile, mexico and columbia are quite high, considering, well mexico is a very populated country, but the other countries are not as populated. then, easter mediterranean, iran, still very high, iran was one of the first countries to be hit in the eastern mediterranean region. then, we have pakistan, one of the countries that should belong to south east asia, but is with eastern mediterranean for the reasons that i spoke about before and saudi arabia, they have seen a very high number of new cases. egypt as well and iraq as well, we saw it before. and, then we come to europe, so the russian federation is by far the one with highest number of new cases and also the highest number, in europe, of total cases, but keeping the number of the total number of deaths, not very high compared, for instance, to the uk, where we have a much lower number stand on the same side against covid-19 – the future strategies against an unknown enemy . 15 of total cases, but a much higher number of total deaths. now, these are official numbers, so we can believe them or not, but these are the official numbers that we do have. and, then we have spain, we have italy, which is on the coming down, fortunately. the uk has reached a plateau and it's now on the descending curve. it took it a while and it's due to the political choices really, the policies that weren't put in the place, the policies of lockdown, use of mask etcetera, were put in place much earlier in continental europe and particularly western europe and they weren't put in place, or they were put in place very loosely in the uk. turkey is still very high. germany, after seeing a resurgence a few weeks ago due to what i was talking about, this resurgence in positive cases, over 600 positive cases in westphalia in this factory, meat processing factory, where they went up to 700 and 800, now it's on the coming down again. then, i just wanted to show you in eastern europe, with israel as well, with quite a high number of new cases, considering the number of inhabitants and that's due to the resurgence we were talking about. and, then, i just wanted to show you what we were talking about. eastern europe, for the number, when we compare the total numbers, for instance, of ukraine, which is 49,000, with the number yesterday of new cases, 1,366, there is a disproportion. we can see it's a very high number of new cases, so that's why we see europe being on a plateau again, which is not really going down, because in eastern europe, as we said, balkan and central asian countries, we see the curve going up still and it's the same for kazakhstan, again a disproportion between the total cases and yesterday’s new cases, which is very high. so, the recommendations, immediate action in testing and contact tracing and isolation when we find ourselves facing localized outbreaks and time is of upmost importance. strengthening of influenza vaccination policy, influenza vaccination noting particularly for at risk groups and bcg vaccination or second dose is not yet recommended, awaiting results of randomized control trials. thank you. lorenzo corbetta: thank you very much laura. we have concluded the presentation so we can open the discussion, if somebody of the faculty has some questions, please. mohammed munavvar: well, lorenzo, if i may start. this is a question to the last speaker, laura de paoli, if you don't mind. very interesting data that you presented, with regard to the african scenario, or generally even otherwise, one of the things that is missing in the data is the denominator, which is the number of tests which were carried out in each place. because, what would be very useful, is a percentage of positive tests and secondly, also to get to know, another surrogate marker, is the number of excess deaths in that particular area compared to, say, last year. i just wondered whether you want to comment on those two points. laura de paoli: no, unfortunately we should have that, we don't have that in the sit rep of covid, we should have more studies about there, to be honest with you, i have actually come across anything. the problem is, when we do our meeting, we have people presenting, but of course, being in europe now, i'm only seeing people presenting about europe. and, basically, what they're presenting, the platform is formed by who, un agencies, they're all un agencies operating in europe and they are cross movement. so, we have people presenting on their work, what they do in the country, but we don't tend to have very scientific presentations, unfortunately and this is something i'm actually trying to work on, trying to invite people from academia to present more scientific work. it's basically, a forum formed by managers and so, we don't have enough scientific leverage on that and i wish we had more. i am not able to answer the question, unfortunately. duccio cavalieri: i have another question on a similar trend. if you look at the crude epidemiological models, that have been proposed for sars-cov-2, africa is not the only exception, there are several countries where the models do not behave as they should, i mean, as they hypothesized to and i have been collaborating with mohammed there, and the group from university for years on innate immunity activation. so, i was wondering whether anyone has overlayed the data on vaccination in general and the rate of sars-cov-2 cases, because i find the bcg hypothesis fascinating, but not sufficient to explain the differences also between the different african countries. and, the other question, several data just published by harvard and other universities that show the crucial role of uv and transmission of the virus on microparticles that could be limited thanks to uv radiation, why it could be enhanced in conditions where there's a lot of fog and i'm thinking about several areas where the numbers were very high. so, let's say, i know you don't have an answer, but it's more for a discussion point, i have looked into the mathematics of the epidemiological models and they basically ignore, like, with the theory of the black box, to put numbers that control for the environmental factors and for the variability of the virus. so, in basically all the models, the virus is like a black box, you know, it's given as constant and in my opinion, delving into those variables could be maybe possible by looking into details on the data that we derive from africa or other countries where things are unclear. but, as i said, it's true that we would need more samples, more stops, more analysis of the action presence of the virus throughout the world. but, it was an excellent presentation. laura de paoli: you're welcome, thank you. yes, it is for sure, it's a multifactorial situations, so we have the heat, also, well correct me if i'm wrong, i'm not actually a specialist, but we know that at 70 degrees, the virus is denatured, so maybe, now, i was in central african republic and there was, not a constant temperature, but for a good part of the day, we were over 40 degrees centigrade, so that must have a degree of importance. for instance, in south africa, we have cold winters, i lived in south africa for a long time and i know that in cape town it gets as cold as in europe over the winter. so, for sure, climate plays a role, i agree with you, mostly likely as you said, the micro-particles with the fog, pollution, in africa we don't have that. and also with vaccination, because also at some stage, also the polio vaccination, anti-polio vaccination was put on the table of discussion as a possible l. corbetta et al. 16 protection factor, because they switch the innate immunity on, basically, there is a modulation of t cells. so, it is probably multi-factorial, the thing is that just as well, in africa, we don't have as many cases as we had in europe, for instance, because in africa, like in central africa, we didn't have any icu beds, we had only a few ventilators, they belonged to some ngos that worked in surgical units, so they needed the ventilators for the operations. we have very few oxygen concentrators, so fortunately, there is this situation of non increased exponential line in the number of cases, otherwise all of africa will be wiped out, or a number of african people will be wiped out. we all know that the trend of an epidemic is towards a benign, it goes towards a benign outcome, the bell curve show that, but still we could have an extremely high mortality, if we had the conditions, whatever they are, that we had in europe and the states, for instance. we should find out about bcg very soon, because by the end of the year we should have the results of the brace study and i'm really hoping that there is something good coming out of that. and, there is no harm in vaccinating people, i don't know why who didn't put, okay, we have a policy of non-recommendation of bcg vaccination against covid-19, but as it has been shown, the bcg vaccination operates such a good protection against a number of bacteria and viruses, or in general, also, inflammatory diseases of the respiratory system that why not have it, you know, like everybody. i had it, so i felt quite secure, a bit safer. i actually feel quite safe because i had it. lorenzo corbetta: professor fabbri, have you any questions? leonardo fabbri: not really. i was intrigued by the presentation on tuberculosis and covid-19 and obviously, it's a very relevant epidemiological and clinical issue, but it's also a stimulating immunologic open question, because one of the predictive factors of worse outcome in covid is lymphopenia, whereas in tuberculosis, you have specific expansion of lymphocytes, particularly lymphocytes and i wondered whether in some cases, there might be actually a sort of protective effect of tuberculosis with respect to covid, but it's just an immunologic question. i wondered whether professor rendon may make comment to that. luis adrian rendon: we may argue and we may verse against and in favor of theories, because talking about bcg, bcg is supplied to all newborns in latin american, in many countries in asia and in africa and with all that, everything starts in china, bcg is supplied there, in india, bcg is supplied, they've had many cases. in latin america, bcg is supplied and we are so far in a whirlwind pandemic, so if we have any kind of potential, we would expect less cases. let's say that bcg doesn't protect against infection, but protects against severe forms of covid, we are having a daily pandemic in latin america, so you may guess against bcg, just because of the numbers. but, for instance, in my case, the case i present, there was a young physician, with bcg who has a primary tb infection and then got covid with no symptoms. was that because of the bcg primary infection, i mean the bcg vaccination or because of the tb primary infection that protected her from severe forms, we don't know, we are just arguing about that. but, anyway, if we think that bcg is good, well bcg is already played in most of these countries, so the people are already protected, they need that protection, we may argue about getting a second shot from bcg, nobody knows about that and i wondered if these studies that are being performed right now are going to give us that answer. because, it's going to be very difficult to control many ambient factors for that. and, my main worry about latin tuberculosis, that is highly prevalent in countries like mine, is when people got covid a severe form and get dexamethasone or another kind of immunosuppressive therapy, they are in danger to have a reactivation of latin tb. we should worry about that and we should be aware of that, it's going to be a great problem. lorenzo corbetta: thank you. i have one question from china, we have 2,000 people connected with us from china now and the question is about the vaccine for professor bonanni. they say, we all care when the vaccine will launch, could the speaker estimate the launch month? they are waiting for the vaccine. we are all waiting for the vaccine. paola bonanni: this is an extremely difficult question, because we are all waiting for the vaccine to be available but we really do not know when it will be and which vaccine, because you have seen from my presentation that there are several candidates, some people who are developing the vaccine are also claiming that we might have a vaccine available in the next few months, maybe, some say that it might be the end of the year. but, i'm not sure on which data this is relying, because you have seen that most of the phase one, two and we need phase three studies of course, before launching a vaccine, there are at present one, two and a couple of studies in phase three. the others are in phase two, all companies and biotechs are rushing to get the vaccine, but actually, i would like to stress once more what i reported in my final slide. we must be very careful, because if we fail on safety on this vaccine, it might be an enormous danger for the credibility of all vaccines, because we have to consider that we have the problem of immune enhancement and that problem does not seem to be very heavy up to now for the studies we have seen up to date, but it's still a problem to solve and to exclude. and, the other thing is that we are squeezing research, pre-clinical research, clinical research, which usually lasts for seven, ten, twelve years into one year and we must be aware that we shouldn't be so anxious of having a vaccine if we are not sure that the vaccine is totally safe. i'm telling this, i am a vaccine lover, i define myself, because i'm working almost exclusively on vaccines and i love vaccines, they have improved the health of mankind in a way that is not comparable to any other measure or therapeutical preventative, but i am also conscious that we must preserve the reputation of vaccines. so, we need to be really very sure that if the vaccine is put on the market it is for sure, first of all, safe and of course it should be also effective. but, i don't want to give false messages, saying, oh we will have it in stand on the same side against covid-19 – the future strategies against an unknown enemy . 17 december, or january, i don't know actually but i hope that when we start, we have a good vaccine. lorenzo corbetta: we will have another video conference in september for updating. i have, maybe the last question, for duccio cavalieri the question is, are there countries who exhibited only one strain of the virus and does this explain the different incidence found in africa? duccio cavalieri: no one knows. i mean, i don't have an answer for this question and it is true that the variance of the virus is something expected, there's nothing unexpected on the fact that the virus evolves. in virology, the definition of mutation has an interesting meaning, because there is genetic mutation and then there is a mutation sensed as usually a change in the virus phenotype, okay. there are indeed changes in the virus phenotypes, so far the two viruses described in china have a different phenotype. it's hard to say whether one is better and one is worse, apparently both viruses have been travelling and they have been all apparently, the most of them have been travelling via munich, or germany. so, germany has been one of the hubs, because it's a commercial hub. so, the other reason why in africa, potentially, there has been less of an explosion, it could be that the travelling of the virus has been less efficient, because maybe transport means have been less efficient and so, i think that mapping the evolution of these viruses is important for one reason. the theory behind the assessment of evolution of viral infection is quite complex and not necessarily seen from only one perspective. the naïve point of view says that the virus should attenuate, okay, which is what we usually expect, but the point is that viruses that can jump very rapidly from one host to another, so viruses that have a high rate of diffusion can escape this general theory, because they can basically get to the second host, when basically, irrespective of the fact that the first host is dead or alive. for sure, one of the tendencies will be to expand the phase where the individual has the virus, can transmit the virus, but the disease does not manifest, so the symptoms are not there and this is what the model that i showed is telling us, okay. i think, in general, that the summer would be a bottle neck and this is because this is the lesson we've learned from the spanish flu, if you read through the history of viruses, summers have always been a bottle neck. and, i think, the reason why they are a bottle neck is exactly related to the main factor, the transmission, how easy and how fast, what is the transmission rate. that number, 3.5 is not the same throughout the entire year, sometimes it's probably five, sometimes it's 3.5 and it could be two. and, from that number depends the attenuation, because when that number goes down, in theory, the virus should decrease it's pathogenicity, it should become less aggressive, because it has to survive within the same host for longer. but, this is all to see, we have to see what will really happen. but, i don't know how many viruses go through africa and this points out the fact that we should expand enormously the potential of sequencing the virus, rather than simply detecting the presence by means of real time pcr. currently, i work in a laboratory that has the last level of sequencing facilities, we are hoping to sequence the strains from tuscany. sequencing has almost the same cost of doing the real time pcr test. we could boil down to maybe twice as much, but the amount of information that you get is significantly higher, so i hope that what is happening to us will lead to a technological leap that will allow us to change completely the way we look at viruses and we understand their movements. lorenzo corbetta: thank you, very clear. we have to conclude if the chairman wants to say something, leonardo? leonardo fabbri: thank you lorenzo, thank you once again for organizing this initiative, i think we had a fantastic overview, very informative and very clear presentations. i'd like to thank all the speakers for putting so much work on these and i wish all of them to keep going with enthusiasm, but at the same time to protect themselves in their local situation. thank you very much, once again for the privilege to co-chair with you this session, lorenzo, thank you. lorenzo corbetta: thank you all, thank you for your presentations and see you all soon in another video conference with some updates on your studies. thank you very much and thank you to all the attendees. thank you, bye. substantia. an international journal of the history of chemistry 4(2) suppl.: 95-107, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1031 citation: a. wan nafi, m. taseidifar, r.m. pashley, b.w. ninham (2020) controlled growth of strontium sulfate particles in aqueous solution: inhibition effects of a bubble column evaporator. substantia 4(2) suppl.: 95-107. doi: 10.36253/substantia-1031 copyright: © 2020 a. wan nafi, m. taseidifar, r.m. pashley, b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. controlled growth of strontium sulfate particles in aqueous solution: inhibition effects of a bubble column evaporator atikah wan nafi1, mojtaba taseidifar1, richard m. pashley1,*, barry w. ninham2 1 school of science, unsw canberra, northcott drive, canberra, australia 2 department of applied mathematics, research school of physical sciences, the australian national university, canberra, australia *corresponding author: r.pashley@adfa.edu.au abstract. in the oil industry, strontium sulfate (srso4) scale deposits have long plagued oilfield and gas production operations. this remains an unsolved problem. we here show how the bubble column evaporator (bce) can be used to control aqueous precipitation from salt solutions. mixtures of strontium nitrate and sodium sulfate in the bce system were used to precipitate strontium sulfate at different degrees of supersaturation. the effectiveness of the bce system was compared to standard mechanical stirring. the precipitation of strontium sulfate in both processes was monitored through turbidimeter, particle counting, dynamic light scattering (dls) and scanning electron microscopy (sem). the results show that the bce system has a significant inhibition effect and so can be used to control precipitation growth rate, even from supersaturated solutions. this remarkable effect also provides new insights into mechanisms of crystallisation, of bubble interactions and mineral flotation. keywords: strontium sulfate, aqueous precipitation, nanobubbles, supersaturation, bubble column evaporator, particle growth rates, crystallisation, bubble interactions, mineral flotation. 1. introduction coatings of partially soluble salts pose significant problems. the growth of deposits on the surface of industrial equipment like boilers, heat exchangers, wastewater treatment plants and in oil and gas drilling operations is always an issue. the scales generally contain sparingly soluble carbonates and sulfates of calcium, barium and strontium. the formation of scale deposits from mixing of two incompatible solutions, such as seawater and natural brines, presents a serious problem in industry, e.g. in the operation of oil fields, desalination plants and geothermal wells. calcium carbonate and calcium sulfate scales are typical. strontium sulfate (srso4) scale is not so common. however, srso4 deposits have long plagued oilfield and gas production 96 atikah wan nafi, mojtaba taseidifar, richard m. pashley, barry w. ninham operations. its removal by fast, spontaneous precipitation remains an unsolved problem in the oil industry, despite significant research efforts.1-8 formation of sulfate scales reduces the diameters of pipes. this causes operational difficulties which may lead to additional capital cost and operating costs.9-12 further, severe plugging of equipment causes loss of production, increases the cost of oil extraction and causes many safety issues. according to howarth et al.13 wastewater facilities in the oil industry were simply not designed to handle the amount of strontium which can also include radioactive wastes. and indeed, the failure of equipment caused by strontium scale can result in safety issues due to its radioactivity.14,15 to try to mitigate these detrimental effects, research has focused on several treatment options. these are demineralization systems, thermal evaporation, condensation, and reverse osmosis. however, all these treatment processes suffer from difficulties in operation.16,17 for instance, the addition of reagents in chemical precipitation methods can result in separation problems, in which the acidic conditions produce toxic gases as by products. so, these processes have to be carefully monitored. srso4 scales are categorised as insoluble scales since they are not easily dissolved, and they are also relatively difficult to treat. the addition of acid to treat srso4 scales to reduce clogging and buildup of scale poses environmental issues. it also leads to the risk of interruption the whole operation.18-20 the reverse osmosis membrane technique offers another common treatment method. however, exposure to high salt level concentrations present in feed water can readily block the pores of the membrane sheets and so fouls the expensive membranes. these have to be regularly cleaned or replaced.21-23 this leads to low efficiency of the process, high maintenance costs and a decrease in the quality of water produced. to protect the membrane and maintain the efficiency of the process, regular feedwater pre-treatment is essential. this again increases costs, besides complicating the process.24,25 currently, there are no reports on efficient water treatment which affordably and simply inhibits srso4 particle growth. prior to disposal, wastewater treatment typically aims to maximize the concentration of contaminant using low cost energy, for example, from industrialwaste vent gases, solar heat or wind turbines. these energy sources could be used with the bce system, which concentrates wastewater and at the same time inhibits the growth of precipitate particles, as has recently been reported24,25 in work that precedes ours. it was discovered that precipitation inhibition naturally occurs in the bubble column evaporator process for supersaturated solutions of calcium sulfate. in this process, a continuous, high density, flow of rising bubbles apparently disrupts the growth of nano-particles, even in supersaturated solutions. comparison with standard mixing methods indicates that the bce process offers a cost effective and simple method to create precipitation inhibition.26 there, precipitated particles of caso4.2h2o were maintained at a steady size of <100 nm within a bce, whilst stirred solutions, at the same supersaturation rate (of about 32 times the solubility product) formed particles with sizes increasing rapidly above 1 mm.26 apart from scale deposit problems in the oil industry, srso4 is a multifunctional inorganic material used in various chemical applications, such as in electronics, ceramics, pigments, cosmetics, paper making and as a compound used for thermo-stimulated luminescence.27,28 this study is aimed at the determination of suitable treatments to prevent scale formation, and in order to do this it is important to understand in depth the precipitation reaction of srso4 in the first place. studies on the production of fine particles, through precipitation, have received vast attention with a view to controlled production of fine particles. nanoparticle materials can be obtained by several methods; such as, precipitation, hydrolysis, electrolysis etc. compared with other methods, the precipitation reaction has potential advantages of homogeneity, high productivity and controllability of the process.29,30 however, the stirred tanks often used in the precipitation process can produce particles with a broad size distribution due to inhomogeneous mixing combined with rapid and spontaneous reaction of the mixed components.31,32 the formation of particles of small size is often followed by agglomeration, which hinders the ability to produce fine particles. few studies on simple, effective, additive-free methods for controlled precipitation have been reported. this paper is one such new method. some unresolved fundamental issues on mechanisms of crystallisation come up in the course of this research that will leave for later discussion in the appendix. one of such experimental studies reports the effect of a magnetic field in combination of temperature on the precipitation of insoluble salts of alkaline earth metals, such as carbonates of calcium, strontium and barium, which were precipitated from supersaturated conditions. the structure of caco3 crystals were studied by a combination of x-ray diffraction, optical microscopy and fluorescence. all show that the application of a magnetic field with about 0.4 t, leads to inhibition of particle precipitation.33 it was discovered that insoluble salts, especially caco3, when the solution underwent magnetic treatment for about 15 min before mixing caused a sup97controlled growth of strontium sulfate particles in aqueous solution: inhibition eff ects of a bubble column evaporator pression of particle nucleation and increased the crystal size, with a reduction in crystal number density. precipitation of supersaturated salt solutions can be retarded through a combination of high magnetic fi elds and high temperature of 60 °c.34 in comparison with our experiments, the magnetic field generated in the magnetic stirring system used was likely to be too low to have any signifi cant eff ect. in addition, it was observed that in the stirring system using a magnetic bar, the particles precipitated readily and in a shorter time and with a higher growth rate. th e bce process, used in this work, exhibits an excellent ability to control the srso4 precipitation. th e process employs vigorous mixing to form a uniform solute concentration. from this a more controlled precipitation process was achieved than from a standard mixing method. th is study shows that the bce method can be used to successfully inhibit precipitation of srso4 from supersaturated solutions and reduce the rate of particle growth. th e inhibition phenomenon is clearly of much wider application than for srso4. based on these experimental results, the bce process could also be used for reducing precipitation of srso4 and other nanoparticles scales that have potential applications especially in the oil and gas industry and in industrial water treatment plants. 2. materials and methods 2.1. materials th e salts sr(no3)2 and na2so4 used in these experiments were analytical reagents with purity level ≥ 99%, purchased from sigmaaldrich. double-distilled water, milli-q water and purified bottled drinking water, ‘woolworths select mountain spring’, were used to prepare the salt solutions and to produce a low particle count comparison. at room temperature, the milliq water had a conductivity of less than 3.0 µs cm-1 and ph of 7.06. all concentrations are given in molarity (m) units at room temperature. 2.2. precipitation processes figure 1 shows a schematic diagram of the bce system, in which bubbles are sparged into the mixed salt solutions containing sr(no3)2 and na2so4 and also a standard stirring system to compare the precipitation process for srso4 at 25 °c. th e air gas is pumped from an air pump (hiblow hp40, philippines) that passes through a silica gel column to dehumidify. a fl ow meter is used to control the fl ow rate of the inlet air which was placed aft er the desiccator. normal air was used in the bce, which was pre-fi ltered using a whatman large high effi ciency particulate air (hepa) fi lter capsule to fi lter inlet air. th e inlet air passes continuously through the bce set up, which was operated within a fi ltered air, laminar fl ow cabinet. th e hepa capsule can retain 99% of particles below 0.3 mm. th e air fl ow was passed through the gas heater to provide the required temperature. th e heater temperature was controlled by a digital variac power supply and maintained using a thermometer (control company 4000 traceable). th en the controlled hot gas fl ow was pumped into the bubble column containing the mixed salt solution. to start the precipitation process, the concentration of salt solutions was set at a suitable supersaturation level. th e bubbles produced in the columns were fairly uniform within the size range of about 2-4 mm. for comparison with the bce experiment, a standard stirring experiment using the same salt solutions at the same temperature were operated using diff erent cylindrical magnetic bars with lengths of 2 to 5.5 cm at diff erent stirring rates of 0, 120, 240 and 480 revolutions per min (rpm). th e liquid samples from the bce system and standard stirring systems were taken directly using syringes and fi ltered through whatman millipore 0.22 µm at diff erent times for further characterisation and by analysis of the removed dry particles. 2.3. analytical methods th e induction and precipitation growth of srso4 particles over time were monitored by turbidity measurement (hach 2100an turbidimeter). th e solution figure 1. schematic diagram of the bubble column evaporator (bce) system and a photograph of a bubble column (a) and standard stirring process (b) for mixing 0.00152 m2 sr (no3) 2 and na2so4. 98 atikah wan nafi, mojtaba taseidifar, richard m. pashley, barry w. ninham turbidity at 0.2 ntu was taken as the onset of precipitation. this is a useful indicator because the clear water and solutions without obvious precipitates normally gave turbidity values less than 0.2 ntu. a spectrex laser particle counter (model pc-2300) was used to determine the purity of the solutions. the particle counter with detection size range 0.5–100 µm was able to detect the presence of contaminant particles that may affect the precipitation process. the presence of these particles in the solution prepared using distilled water, bottled water and milli-q water when filtered by the whatman millipore 0.22 µm was tested before each precipitation experiment. in addition, a malvern zetasizer (model zs) with detection size range 0.3 nm–10 µm was used to monitor the growth of the precipitated particles. 1 ml samples were collected into polystyrene cells using a syringe for dynamic light scattering measurement using the malvern zetasizer. solution samples were filtered before the dls analysis when precipitation became visible. then the filtered samples were kept in the open air to dry completely before examination with a fei quanta qemscan scanning electron microscope (sem), to study particle morphology. 3. results and discussion 3.1. srso4 precipitation the precipitation process typically starts when the concentration of a compound in solution is greater than its solubility, i.e. from a supersaturated solution. in the case of the reactive precipitation of srso4, as in this work, the reaction is given, by convention, as sr2+(aq)+so42-(aq)⇄srso4(s) (1) the precipitate of srso4 is produced when the product of the concentrations of sr2+ and so42ions is greater than the solubility product. the precipitation of srso4 and its morphology was determined using sem to determine the formation of srso4 precipitated from a stirred solution and from a bce. the supersaturation degree (denoted s) of a srso4 salt solution is defined as: s= (2) where ksp, the solubility product, equals [sr2+]eq x [so42-]eq which is the equilibrium product at the solubility limit, assuming ideal conditions. all ion activity coefficients are assumed equal to 1 and hence the activities of all the ions are equal to their concentration. because of the dilute concentrations involved, this assumption is reasonable. besides the main factor of supersaturation level, other factors can affect the precipitation process: impurities, temperature, contact time, ph, agitation intensity and overall ionic strength.35-39 in this study, the main factors were the degree of supersaturation, purity of background solution and the bce process as it affects precipitation compared with simple solution stirring. several studies have discussed the effect of turbulence on morphology, scale deposition and minimal inhibitor concentration.40, 41 however, there is no consistent finding on the effect of turbulence on scale deposition. barium sulfate precipitation was conducted under turbulent conditions and compared with lamina precipitates inside oilfield pipes. the results show that there is no difference in sulfate precipitation kinetics without inhibitors (polymeric based additives) in both conditions.42, 43 the present work using the bce and standard stirring system was conducted inside a laminar flow cabinet. the results obtained might be developed for application to the srso4 precipitation problem in the oil and gas industries. particle counts obtained using the spectrex counter were used to determine the purity of water samples. it was found that the particle count of all types of water samples inside the laminar cabinet are more stable compared to samples exposed to ambient air. these results also showed that the purity of water was ranked as: milli-q > bottled water > tap water > distilled water, as expected because the laboratory water distillation system used collected and stored the initially clean distilled water in a vessel which was exposed to atmospheric air. based on spectrex laser particle counter test results reported in table 1, the normal distilled water contained the highest number of particles, which is more than 227 counts per ml of particles less than 3 µm in size. this value for the salt solutions which are prepared inside laminar flow cabinet using milli-q water was increased to 87 counts per ml despite the particle count initially being only 2 counts per ml. these results suggest that, it is almost impossible to achieve a blank solution with zero particles. the lowest consistent particle count was obtained for the salt solution samples prepared using milli-q water inside a laminar flow cabinet, and this sample was used as blank solution in this work. in previous work, it was reported that with careful filtration, the particles can be reduced to less than 1000 counts per ml, however it is impossible to achieve zero particles.44 in addition, it is difficult to prepare systems completely free of fine particles and nucleation sites because 99controlled growth of strontium sulfate particles in aqueous solution: inhibition effects of a bubble column evaporator of impurities in supersaturated solutions, which are difficult to remove and act as nucleation catalysts. also, the walls of the retaining vessel, can catalyse nucleation. the presence of some impurities can even cause inhibition of crystal growth or nucleation and so affect the rate of sulfate precipitation.45-47 by filtering the solutions prior to making up the supersaturated solutions, in a laminar flow cabinet, it was possible to reduce particle densities below 50 per ml. this was the typical background level of particles used in this study. the supersaturation degree of each solution in the table 1 was calculated based on the solubility product values at 25 °c obtained from the crc handbook.48 the salt solutions of srso4 with different types of water source and degree of supersaturation were tested using a standard stirring system at 25 °c with a 3.5 cm length cylindrical stir bar (of 1 cm diameter) at a rate of 120 rpm. the induction time at which turbidity reached 0.2 ntu was recorded. figure 2 shows that with increase in degree of supersaturation, the onset precipitation time drops down noticeably. the induction time is also affected by the presence of foreign particles. solutions with the same degree of supersaturation but prepared using distilled water, precipitate in less time compared to salt solutions prepared using milli-q water. it was found that srso4 solutions in milli-q water with lower than 2 degrees of supersaturation had the longest induction time. by comparison, reported results show that the time of the appearance of nuclei (induction time) in water vapour is 103 years when the supersaturation degree is at 3.44 3.2. effects of stirring rates the induction time for the salt precipitation in a standard stirring system is also affected by different lengths of magnetic stir bar used. as shown in figure 3, srso4 solutions at similar solution conditions (0.00152 m2) were stirred at 120 rpm at 25 °c with different lengths of stirring rod. this change in length affected the induction time. it was found that longer magnetic stir bar length reduces the induction time for precipitation. however, comparison from figure 3 showed something quite unexpected: the induction time starts fluctuating when magnetic stirring bar lengths of 3.5 cm and 5.5 cm were used. under the same conditions the bce system for the precipitation of solutions provides a longer induction time of 380 min. the solution in the bce system has a stable induction time compared to a standard stirring system or even quiescent conditions. different types of impellers show significantly different results in the precipitation process, in which parameters like different length change, line speed and the shear speed within the solution during stirring. all affect the precipitation process.49 table 1. purity of srso4 solution based on particle counts and supersaturation degree. solution types prepared using distilled water (particle counts per ml) prepared using milli q water (particle counts per ml) solution filtered by 0.22µm membrane (particle counts per ml) supersaturation degree (s) distilled water 227 milli q water 2 0.0008 m sr(no3)2 + 0.0008 m na2so4 608 87 7 1.86 0.001 m sr(no3)2 + 0.001 m na2so4 629 96 19 2.91 0.0013 m sr(no3)2 + 0.0013 m na2so4 662 112 30 4.91 0.0015 m sr(no3)2 + 0.0015 m na2so4 668 126 34 6.54 0.002 m sr(no3)2 + 0.002 m na2so4 686 138 45 11.63 0.0025 m sr(no3)2 + 0.0025 m na2so4 698 156 49 18.17 0.005 m sr(no3)2 + 0.005 m na2so4 704 198 91 72.67 0 100 200 300 400 500 0 2 4 6 8 10 12 in du ct io n tim e (m in ) supersaturation degree distill ed water milli q water figure 2. the induction time of srso4 precipitation in the solutions with different level of purity and supersaturation degrees by simple stirring (120 rpm) at 25 °c. 100 atikah wan nafi, mojtaba taseidifar, richard m. pashley, barry w. ninham 3.3. comparison of srso4 precipitation using the bce and a standard stirring system figure 4 shows the precipitation results for 0.00152 m2 srso4 solutions in a standard stirring system with different speed of stirring and in the bce system. in these experiments, particle growth by the precipitation process was monitored using turbidity measurements. the turbidity in a standard stirring system of 120 rpm shows similar behaviour to a salt solution without stirring. both slowly reach onset precipitation (turbidity > 0.2). on the other hand, the salt solution that was placed in the same stirring system at 480 rpm significantly increased precipitation after 60 min. by comparison, the turbidity in the bce system remained constant below 0.2 ntu for more than 350 min, even though the salt solution used in the bce was at the same level of saturation. an increase in temperature will increase the solution solubility of srso4.50-52 initially, it was expected that continuous water evaporation within the bce will slowly increase the supersaturation level hence causing precipitation. however, based on the results given in figures 3 and 4, the bce system shows a clear inhibition effect on particle growth. the rising bubbles in the bce show complex behaviour due to coalescence and noncoalescence and bubble shape and trajectory that rise with rotational oscillation effects in the salt solution.53, 54 this behaviour appears to disturb the processes involved in particle growth, even in supersaturated solutions. low turbidity values do not indicate definitively the absence of particles in the sample, since the turbidimeter involves a light extinction method which may not be able to detect very small particles.55, 56 hence, the average size of srso4 precipitated particles in the bce and standard stirring processes were monitored using a malvern zetasizer, as shown in figure 5. precipitated srso4 particles were detected by a malvern zetasizer even at the initial point of mixing of the two solutions, with particles of around 0.3 µm, while the turbidity of the solution was found to be below 0.2 ntu. it was shown in a previous study that once particles become large, i.e. more than about 5 μm during the precipitation process, their presence can be correlated with an increase in solution turbidity.57 as a possible explanation, the salt solutions of sr(no3)2 and na2so4 mixed at the beginning of the test might was not be fully homogenous, allowing local precipitation of srso4 through a spontaneous heterogeneous process.58 numerous studies have been concerned with spontaneous precipitation processes, but no satisfactory explanation has yet been accepted.59-63 the results given in figures 4 and 5 show that increases in solution turbidity is correlated with an increase in particle size. the average size of srso4 particles was persistent with the sem analysis given in figure 7, in which the image of the particle changes from agglomerates to microrod/pod. the precipitation process in a stirring system led to broad size particle distribution, probably due to rapid reaction.64 in comparison with srso4 precipitation in the bce system, the turbidity of solution remained below 0.2 ntu until 380 min and the average size of particle remained constantly below 1 µm. it can be seen from figure 5 (a) that the bce system successfully inhibits particle growth, compared to a standard stirring system. the results suggest that the bce system for precipitation has the potential to be used as a method of controlled particle growth for the production of fine particles. 0 100 200 300 400 500 0 1 2 3 4 5 in du ct io n tim e (m in ) stir bar length (cm) stirri ng at io nic pro duct of 0.0015 m bce at i onic produc t o f 0.0 015 m bce at i onic produc t o f 0.0 02 m figure 3. the induction time of srso4 precipitation by simple stirring (120 rpm) with different stir bar length and using a bce at 25 °c. 0 0,2 0,4 0,6 0,8 1 1,2 1,4 0 100 200 300 400 t ur bi di ty ( n t u ) time (min) precipitation without stirring stirring precipitation (120 rpm) stirring precipitation (480 rpm) bce precipitation figure 4. srso4 precipitation at ionic product of 0.00152 m2 (supersaturation degree: 6.54) in a standard stirring process and a bce monitored by turbidity measurements. 101controlled growth of strontium sulfate particles in aqueous solution: inhibition effects of a bubble column evaporator the uniformity of srso4 particles over time was based on the change in the polydispersity index (pdi) using the malvern zetasizer, as given in figure 5(b). a pdi value close to 0 indicates the formation of a narrow range of particle sizes. for values that are close to 1, it correlates with a random distribution of sizes. the precipitates of srso4 in the standard stirring system were expected to experience rapid growth and so a broader size distribution. after 45 mins, the pdi was around 0.5 for the standard stirring system, whereas srso4 particles precipitated by the bce system showed a gradual increase in the pdi value. it is clear that the bce offers significant improvement in uniformity of particle growth and a controlled size distribution. figure 6 and figure 7 show images of the particles of srso4 formed in the precipitation process in the bce system and standard stirring system, respectively. the images were captured from the initial mixing point and at 60 min of the bce precipitation and at 0, 60 and 75 min of the standard stirring system. as can be seen, sem images of the precipitates formed in the standard stirring system (figure 7) show mixtures of microrods and flower-like shapes, with sizes ranging from 1.2 µm to 9.7 µm. according to these results, with the same solution conditions as given in figure 5 and figure 6, the bce system shows controlled and uniform particle growth compared to the standard stirring system. the pattern of the srso4 particles observed, consisting of microrods and flower-like shaped particles were similar to previous studies on calcium sulphate.26 the formation of srso4 particle growth follows a “two-step formation mechanism”, in which primary microcrystals are involved in the formation of monopods, followed by the continuous growth nucleation of monopods that leads to secondary microstructure growth, through the spontaneous aggregation of pods docking on planar structures.65 the latter are formed due to their similar crystallographic orientation.58 the dls measurements carried out for monitoring the particle size, gave further support to the inhibition effects in the bce system, as shown in figure 8, where 0 1000 2000 3000 4000 5000 10 110 210 310 410 a ve ra ge s iz e of d ia m et er ( nm ) time (min) bce precipitation stirring precipitation (240 rpm) 0,1 0,2 0,3 0,4 0,5 0,6 0,7 0,8 0,9 1 0 50 100 150 200 250 300 350 400 po ly di sp er si ty in de x time (min) bce precipitation stirring precipitation (240 rpm) figure 5. (a): srso4 precipitation at ionic product of 0.00152 m2 (supersaturation degree: 6.54) in bce and 240 rpm stirring system by average size at around 25 °c; (b): srso4 precipitation at ionic product of 0.00152 m2 (supersaturation degree: 6.54) in bce and 240 rpm stirring system studied by polydispersity index (pdi) measurements at around 25 °c. (b) (a) figure 6. sem image of srso4 precipitated particles at an ionic product of 0.00152 m2 in a bce at 0 min (left), 60 min (right). 102 atikah wan nafi , mojtaba taseidifar, richard m. pashley, barry w. ninham the peak size at 180 min remained close to the initial peak. it was found that through a continuous process, the bce was clearly able to produce fi ne particles in a specifi c size range due to the inhibition eff ect apparently inherent to the bce process. it might be thought that the eff ect of electrolytes on bubble coalescence inhibition53,54 might also be related to the inhibition of precipitated particle growth. however, if there is a link it is unclear from the results presented here simply because the initial mixed salts were at concentrations signifi cantly below those where bubble coalescence eff ects have previously been observed. of course, only soluble mixed electrolytes have been studied for bubble coalescence eff ects but it would be a reasonable to assume that mixing srcl2 with na2so4 should be similar to mixing cacl2 with li2so4, both of which salts have been separately studied for their eff ects on bubble coalescence inhibition. for example, cacl2 has a transition concentration (i.e. corresponding to 50% coalescence) at about 0.04 m and li2so4 has a transition concentration at about 0.025 m.54 both these concentrations are well above even the highest concentrations (of 0.005 m) used in the present study and so would not be expected to signifi cantly aff ect bubble coalescence in 0 min by bce 60 min by bce 180 min by bce figure 7. sem image of srso4 precipitated particles at an ionic product of 0.00152 m2 in a standard stirring system at 0 min (a), 60 min (b) and 75 min (c). 103controlled growth of strontium sulfate particles in aqueous solution: inhibition eff ects of a bubble column evaporator the column, even though at higher concentration these mixed electrolytes would be expected to aff ect bubble coalescence.66 in this study the precipitation levels seen in the bce process, even for supersaturated solutions, were very low and so no attempt was made to measure the particle yield, which would be very low. it might be possible, however, to continuously remove the fi ne particles using, for example, a membrane nano-fi ltration system to increase the product yield. th is study of the comparison between the bce process and a standard stirring system, for srso4 precipitates, was found to be similar to that reported earlier26 for caso4.2h2o precipitates. both studies suggest that the bce system, due to its inhibition of particle growth, can play an important role in precipitation control, especially in particle-growth-control applications and in industrial water treatment. in addition, the technique could be used in the production of fi ne particles for industrial applications in ceramics, catalysis, cosmetics, pharmaceuticals and in food products.67 4. conclusions a standard stirring system and a bce system were compared for the precipitation of srso4 particles from supersaturated solutions of sr(no3)2 and na2so4. th e precipitation of srso4 in both systems was monitored by turbidity measurements, spectrex particle counting and a dls malvern zetasizer, with particle morphologies observed using sem. it was found that the bce system, compared to the standard stirring system, had an inhibitory eff ect on the precipitation induction time and the precipitate growth rate; which allows for the production of particles over a wide size range, from nanometer to micrometer. th e results obtained were found to be similar to those observed earlier with caso4.2h2o precipitation, which leads to the proposition that this might be a general property of bubble column evaporators. th e bce system potentially off ers useful applications in various industrial processes, such as in the treatment of wastewater and other industries that are required to produce fi ne particles in a controlled manner. particle size distribution is a key parameter in quality control. th is has been highlighted in various industries, especially from material-research and processing, fresco and paper restoration. our study opens up insights into curious phenomena by adding a new hidden and neglected variable, the role of dissolved gas in reactivity. how this plays out in detail we outline in the appendix. 5. acknowledgements th is research was supported by funding from breakthrough technologies and a unsw scholarship for awn. 6. references 1. z. amjad, j. albright, strontium sulfate inhibition by biopolymers and synthetic polymers,  mater. performance, 2015, 54(12), 54-58. 2. y.d. yeboah, m.r. saeed, a.k. lee, kinetics of strontium sulfate precipitation from aqueous electrolyte solutions, j. cryst. growth, 1994, 135(1-2), 323-330. 3. f.h. butt, f. rahman, u. baduruthamal, evaluation of shmp and advanced scale inhibitors for control of caso4, srso4, and caco3 scales in ro desalination, desalination, 1997, 109(3), 323-332. 4. h.m. ezuber, prediction of strontium sulfate scale formation in oilfi eld environment,  j. astm int., 2007, 4(6), 1-11. 5. c.c. patton, applied water technology, 1986. 6. a.j. essel, b.l. carlberg, strontium sulfate scale control by inhibitor squeeze treatment in the fateh fi eld, j. pet. technol., 1982, 34(06), 1-302. 7. j.c. lindlof, k.g. stoff er, a case study of seawater injection incompatibility,  j. pet. technol.,  1983, 35(07), 1-256. 8. m. nassivera, a. essel, fateh fi eld sea water injection-water treatment, corrosion, and scale control, in  middle east technical conference and exhibition, society of petroleum engineers, 1979. 9. m.s.h. bader, sulfate removal technologies for oil fi elds seawater injection operations,  j. pet. sci. eng., 2007, 55(1-2), 93-110. 10. z. dai, a.t. kan, f. zhang, f. yan, g. ruan, n. bhandari, m.b. tomson, a th ermodynamic model figure 8. size distribution of srso4 precipitates at ionic product of 0.00152 m2 in a bce at 0 min, 60 min and 180 min. 104 atikah wan nafi, mojtaba taseidifar, richard m. pashley, barry w. ninham for the solution density and mineral solubility predictions up to 250 °c, 1,500 bars for na-k-mg-caba-sr-cl-co3-hco3-so4-co2 aq systems. in  spe international oilfield scale conference and exhibition. society of petroleum engineers. 11. f. yan, f. zhang, n. bhandari, l. wang, z. dai, z. zhang, m. tomson, adsorption and precipitation of scale inhibitors on shale formations,  j. pet. sci. eng., 2015, 136, 32-40. 12. c. yan, a.t. kan, w. wang, f. yan, l. wang, m.b. tomson, sorption study of al-o (oh) nanoparticle-crosslinked polymeric scale inhibitors and their improved squeeze performance in porous media. spe journal, 2014, 19(04), 687-694. 13. r.w. howarth, a. ingraffea, t. engelder, natural gas: should fracking stop?, nature, 2011, 477(7364), 271. 14. j. s. al-thuwaini, b. j. burr, encapsulated scale inhibitor treatment, in  middle east oil show and conference. society of petroleum engineers, 1997. 15. a.b.b. merdhah, a.a.m. yassin, calcium and strontium sulfate scale formation due to incompatible water, p. int. graduate eng. sci. 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sulfate in nacl solutions up to 6 m and 90 c with or without inhibitors,  j. colloid interface sci., 1995, 174(2), 327-335. 57. w. he, j. nan, study on the impact of particle size distribution on turbidity in water,  desalination and water treat., 2012, 41(1-3), 26-34. 58. i. x. malollari, p. g. klepetsanis, p. g. koutsoukos, precipitation of strontium sulfate in aqueous solutions at 25 °c, j. cryst. growth, 1995, 155(3-4), 240-246. 59. a. e. nielsen, homogeneous nucleation in barium sulfate precipitation,  acta chemica scandinavica, 1961, 15(2), 441. 60. a. e. austin, j. f. miller, n. a. richard, j. f. kircher, precipitation of calcium sulfate from sea water at high temperatures, desalination, 1975, 16(3), 331-344. 61. z. amjad, environment treatment & control mp, 1989. 62. f. h. butt, f. rahman, u. baduruthamal, evaluation of shmp and advanced scale inhibitors for control of caso4, srso4, and caco3 scales in ro desalination, desalination, 1997, 109(3), 323-332. 63. g. r. campbell, g.h. nancollas, crystallization and dissolution of strontium sulfate in aqueous solution, j. phy. chem., 1969, 73(6), 1735-1740. 64. m. kawase, k. miura, fine particle synthesis by continuous precipitation using a tubular reactor,  adv. powder technol., 2007, 18(6), 725-738. 65. j. sun, r. sun, z. xia, h. du, facile room temperature morphology-controlled synthesis of srso4 microcrystals,  cryst. eng. comm., 2012,  14(3), 11111116. 66. c. l. henry, c. n. dalton, l. scruton, v.s.j craig, ion-specific coalescence of bubbles in mixed electrolyte solutions, j. phys. chem., 2007, (111), 1015-1023. 67. j. toth, a. kardos-fodor, s. halász-péterfi, the formation of fine particles by salting-out precipitation,  chem. eng. process.: process intensification, 2005, 44(2), 193-200. 68. b. w. ninham, r. m. pashley, p. lo nostro, surface forces: changing concepts and complexity with dissolved gas, bubbles, salt and heat, curr. opin. colloid interface sci., 2016, 27, 25-32. 106 atikah wan nafi, mojtaba taseidifar, richard m. pashley, barry w. ninham 69. m. taseidifar, j. anthony, r.m. pashley, prevention of cavitation in propellers, in press: substantia: an international journal of the history of chemistry, 2020. 70. h. k. kim, e. tuite, b. norden, b.w. ninham, coiondependence of dna nuclease activity suggests hydrophobic cavitation as a potential source of activation energy eur. phys. j. e, 2001, 4, 411–417. 71. s. v. gudkov, g. a. lyakhov, v.i. pustovoy, i.a. shcherbakov, influence of mechanical effects on the hydrogen peroxide concentration in aqueous solutions, phys wave phenom, 2019, 27(2), 141-144. 72. b. w. ninham, p. lo nostro, unexpected properties of degassed solutions, j. phy. chem. b, 2020, 124(36), 7872-7878. 73. a. e. voinescu, d. touraud, a. lecker, a. pfitzner, w. kunz, b. w. ninham, mineralization of caco3 in the presence of egg white lysozyme, langmuir, 2007, 23, 12269-12274. 74. b. p. reines, b.w. ninham, structure and function of the endothelial surface layer: unraveling the nanoarchitecture of biological surfaces, quarterly rev. biophys., 2019, 52, 1–11. 75. a. g. sanchis, r. m. pashley, b. w. ninham, virus and bacteria inactivation by co2 bubbles in solution, npj clean water, 2019, (2) number 1. 76. a. g. sanchis, l. jin, evaluation of the new energyefficient hot bubble pilot plant (hbpp) for water sterilization from the livestock farming industry, water resour. ind., 2020, 24, 100135. appendix factors controlling precipitation the “reaction” eq. (1) for the formation of particles is impeccably correct. sr2+(aq)+so42-(aq)⇄srso4(s) however, the reactants have no respect for equations on pieces of paper and something more inscrutable lies beneath it. we note first that the entire field of physical chemistry is undergoing revision due to sins of omission and commission at this time.68 the problem of hofmeister effects with all its consequences is on the way to resolution. but the more important issue is the omission in classical theory of the effects of dissolved gas. the omission is monumental in its consequences, a fact still only dimly perceived. we showed the effects of cavitation on a propeller which is explored in detail in a paper in this substantia journal issue.69 the reactions that produce propeller corrosion is due to the collapse of nanobubbles, that are accompanied by free radical production. the same free radicals are also produced by spontaneous cavitation in the active sites of an enzyme and are due to cooperative harnessing of all the weak van der waals and other molecular forces to produce a chemical energy available to do the job.70 nanobubbles containing reactive hydrogen peroxide are produced even by shaking, without any need for heavy sonication.70,71 in this paper both stirring at different speeds and turbulence accompanying the bce process would therefore be expected to produce nanobubbles of different sizes and stability. these should also produce sites for the selective adsorption of both anions and cations and enhanced reactivity. we have already discussed another related fundamental work that studies the effects of magnetic fields and temperature on the precipitation of alkaline earth metal salts.33 the magnetic field seems too small an inf luence here. but who knows? permanent magnets placed outside steel pipes prevent scaling. this works but no one knows why. the effects of temperature are also large and specific in ref [33] and that too can be put into the nanobubble causality camp. water is generally agreed to lose its hydrogen bonding between 80-90 °c. so, our elusive nanobubbles will be different at higher temperatures, as will specific ion adsorption and reactivity. of all the different methods used to produce monodisperse nano or micro particles, the work ref [29] is closest. in our study we used a mixture of 0.005m sr(no3)2 + 0.005 m na2so4 and precipitated out particles of strontium sulphate. in ref [29] the precipitated particles were mg(oh)2. the initial solution contained soluble salts of magnesium in a background of sodium hydroxide. the counterions of the magnesium source salts affect the size and the specific surface area of crystallites with a trend that follows a hofmeister series of anions: (sulfate < chloride < nitrate < perchlorate). it was also shown that depending on the concentration of background salt the precipitated particles could vary in size from a micron to zero radius. the two experiments are difficult to compare. with mg(oh)2 the background of indifferent anions are at high concentrations 0.2, 0.4, 1, and 2 m. the solutions were vigorously stirred as for our case. the same controlled variability in particle size can be achieved with sugars in solution. 107controlled growth of strontium sulfate particles in aqueous solution: inhibition effects of a bubble column evaporator the concentrations are well above the ‘critical concentration’ for bubble-bubble fusion inhibition.53,54,66 so, it might be thought reasonable to assign the phenomena of size variability to ‘water structure’. by contrast, the situation for strontium sulfate here the concentrations were typically low at about 0.005 m and hence water structure cannot possibly be an issue. this throws us firmly back into the wide-open arena of nanobubbles. our reference [72] brings the case into strong contention as a crucial, long-neglected hidden variable. finally, we remark on two matters that mineralization of calcium carbonate in the presence of proteins is probably the most used chemical reaction in nature by weight, being responsible for shells of all invertebrates.73 this mineralization is of much interest too because of alarms about climate change. ref [73] is exceptionally important as it produced amorphous calcium carbonate for the first time. ref [74] opens up a new arena too in medicine and biology. carbon dioxide foam of nanobubbles is the key component of a crucial new organ in the body, the endothelial surface layer. it plays a key role in protection against viruses and cab and is being used industrially for sterilisation of water. see editorial and ref [75, 76]. substantia. an international journal of the history of chemistry 5(2): 79-84, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1028 citation: ginak e. (2021) the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist. substantia 5(2): 79-84. doi: 10.36253/ substantia-1028 received: jul 23, 2020 revised: jun 17, 2021 just accepted online: jun 17, 2021 published: sep 10, 2021 copyright: © 2021 ginak e. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research articles the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak d.i. mendeleyev institute for metrology (vniim), st. petersburg, russia e-mail: ginak@vniim.ru abstract. this article is timed to the celebration of the international year of the periodic table of chemical elements, declared by the un and unesco in connection with the 150th anniversary of the discovery by d. i. mendeleev of the periodic law of chemical elements (1869). the article highlights the metrological activity of d. i. mendeleev and tells about how in the scientific metrological center, he created the main chamber of weights and measures. now the d.i. mendeleyev institute for metrology (vniim) preserves the memory of the life and activities of the great russian scientist and encyclopedist. based on the research carried out in the archives of st. petersburg and the funds of metrological museum, the article for the first time details the history of the formation of the mendeleev memorial complex on the territory of vniim. the contribution of the institute metrologists to the creation of such famous sights of st. petersburg as the monument to d. i. mendeleev (sculptor i. ya. ginzburg, 1932) and the mural (mosaic) «d. i. mendeleev periodic system of elements» (1935) on the occasion of the 100th anniversary of the scientist is shown. all peripteries, related to the installation of the monument table are described: a selection of options for the arrangement of elements, decoration, manufacturer and manufacturing techniques, coordination with various organizations, solving financing issues. keywords: d. i. mendeleev, d.i. mendeleyev institute for metrology (vniim), metrological museum, monument to d. i. mendeleev, mural (mosaic) d. i. mendeleev’s periodic system of elements. figure 1. general view of the historic buildings of vniim, st. petersburg, russia, moskovsky pr., 19. photo from the collection of the metrology museum hosted by the d.i. mendeleyev institute for metrology, november 2010. http://www.fupress.com/substantia http://www.fupress.com/substantia 80 elena ginak the year 2019 was notable for the two memorable dates associated with the name of d.i. mendeleev, a great russian scientist and encyclopedic mind of his time: february 8th marked by the 185th anniversary of the scientist’s birth, and february 17th, the 150th anniversary of the periodic law that he discovered. to honor these anniversaries, the united nations general assembly, in liaison with unesco, proclaimed 2019 the international year of the periodic table of chemical elements, and the global scientific community widely celebrated these events. the year started with the opening ceremony at the unesco quarters in paris on january 29, 2019 and the closing ceremony took place on december 5, 2019, in japan. in russia, most of the anniversary events were held in st. petersburg, the city that played the most important role in the life and work of d.i. mendeleev. it was in this city indeed that he studied at the chief pedagog ica l inst itute (гла вный педа гог и ческ ий институт) (1855), discovered the famous periodic law of chemical elements (1869), and gave lectures for 40 years in the city’s largest higher educational establishments, such as institute of railway engineers, technological institute, st. petersburg university (1861–1890). then he founded and headed the first scientific metrological establishment of the country – main chamber of weights and measures (1892–1907) – which is still functioning today under the name of all-russian scientific research institute for metrology and is known to the world as the d.i. mendeleev institute for metrology (vniim). the scientist’s name was appended to that of the institute in 1945. the memory of the founder of scientific metrology has been held sacred at vniim for more than a century.1 the d.i. mendeleev institute for metrolog y was instrumental in organizing and holding main mendeleev-related events during the international conference mendeleev-150 and xxi mendeleev congress on general and applied chemistry. during the visits to vniim, russian and foreign guests got acquainted with the institute’s activities and with the unique heritage connected to mendeleev. the historical site and architectural objects located on its premises feature the century-old buildings where d.i. mendeleev lived and worked, the sculptural and painted portraits of the scientist, and the metrology museum. of particular interest is the mosaic panel displaying mendeleev’s periodic system, produced on the initiative of metrologists in 1935 to be appended on the wall of the building adjacent to vniim (at that time this building belonged to the artillery school, now housing the suvorov military school). the story behind the panel and a number of other monuments to d.i. mendeleev on the vniim’s territory is associated with the 100th anniversary of the scientist’s birth celebrated in 1934 and is the topic of the present contribution. figure 2. d. i. mendeleev was the author and the main architect of the metrological reform in russia (1892-1907). on his initiative, the depot of measures and weights was transformed into a scientific metrological center – the main chamber of measures and weights (vniim since 1934). photo from the collection of the metrology museum hosted by the d.i. mendeleyev institute for metrology, 1904. figure 3. employees of the main chamber of measures and weights, who worked with d. i. mendeleev, posing in the first exhibit of the museum. among them: mikhail mladentsev (former mcwm scientific secretary, sitting first from the left), alexey skvortsov (former personal secretary of d. i. mendeleev, standing second from left), alexander n. dobrokhotov (standing third from left), victor mueller (standing fifth from left) and etc. photo from the collection of the metrology museum hosted by the d.i. mendeleyev institute for metrology, 1934. 81the «d.i. mendeleev’s periodic system of the elements» mural in saint petersburg honoring the memory of the founder – creation of the mendeleev museum and the monument to mendeleev in the main chamber of weights and measures back in 1925, in order to preserve the memory of d.i. mendeleev and his work, his colleagues and students founded mendeleev group at the main chamber of weights and measures (mcwm). it consisted of the mcwm president dmitry p. konovalov (chairman), mikhail n. mladentsev, alexander n. dobrokhotov, victor a. mueller, alexey.v. skvortsov, as well as the scientist’s son, ivan d. mendeleev. they formed the mendeleev fund of the main chamber museum, which was opened to visitors on december 16, 1928, on the day of the annual grand meeting of vniim staff. the first exhibit, located in the scientist’s office, showcased not only d.i. mendeleev’s contribution to the development of metrology science, but also the main stages of his life and work.2 in 1930, the mcwm began preparations for the celebration for the 100th anniversary of mendeleev’s birth. to organize the celebration an all-union commission was created. among its members there were the director of the all-union research institute of metrology and standardization (vims; former mcwm, today the d.i. mendeleev institute for metrology, vniim), the academician m.a. shatelen, the heads of republican chambers of weights and measures, as well as mikhail n. mladentsev, who headed the mendeleev museum at the main chamber of weights and measures vniim from 1928 to 1941. on may 6, 1930, the commission heard the report of m.a. shatelen on the main activities planned by metrologists to prepare the celebration. the main proposal was to “ install a bronze monument to d.i. mendeleev in the main chamber courtyard in front of the house where scientist lived”. previously, negotiations were held with the sculptor ilya ya. gintzburg who “agreed to donate his beautiful work – a statue of d.i. mendeleev sitting in his chair” and offered to cast and to install the monument, free of charge. according to d.i. mendeleev’s son and his widow, and to people who knew him well and worked closely with him, “the statue bears a great resemblance to mendeleev”. ilya ya. gintzburg made a statuette depicting a scientist sitting in an armchair with a book in 1890, then d. mendeleev posed for the sculpture for three months (from march to april). i. gintzburg took this work as a basis when creating a bronze monument to mendeleev in the in the main chamber courtyard. (the author’s copy of this figurine, made by ilya gintzburg of plaster, is still kept in the collection of the metrological museum). other proposals included publication of his works, making a film and a book on d.i. mendeleev’s metrological activity, drawing (and printing) his portrait, etc.3 the commission decided to accept all those proposals submitted by m.a. shatelen.4 they were accepted by the decision of the 9th all-union conference of verification specialists and sent to the chairman of the council of labor and defense (sto) standardization committee on december 9, 1930. as a result, the resolution of the sto all-union committee for standardization presidium dated december 20, 1930, decided to erect a monument dedicated to d.i. mendeleev and to fund the corresponding work.5 ilya ya. ginzburg redeemed his promises given to the commission: he provided a model of the monument and supervised its casting and installation, all free of charge. the allocated funds were spent on materials – granite and bronze. it can be seen that the d.i. mendeleev monument was created within a relatively short period of time. its inauguration coincided with the 25th anniversary of figure 4. inauguration of the monument to d. i. mendeleev in the square of the main chamber of measures and weights. photo of february 2, 1932 photo from the collection of the metrology museum hosted by the d.i. mendeleyev institute for metrology. note. the figure (bronze, granite) is 1.86 m, the pedestal of red unpolished granite is 1 m. the monument is under protection of the state and it was included in the list of historical and cultural heritage objects of federal importance by the decree of the government of the russian federation no. 527 dated july 10, 2001). the monument is also registered with the state budgetary institution of culture “state city museum of sculpture” (since 1993) and included in the museum fund of the russian federation (preservation order dated september 18, 2019, order of the state inspectorate for the preservation of monuments no. 07-19-439/18). в 1934 г. all-union scientific research institute of metrology and standardization (vims) was renamed into the all-union scientific research institute of metrology (vniim). 82 elena ginak the scientist’s death – february 2, 1932. the monument was placed in the mcwm courtyard on the very spot of the garden house favored by the scientist for taking a rest while living in the «red house». d.i. mendeleev is portrayed sitting on a chair with an open book in his hand surrounded by heavy volumes, manuscripts, and books, one bearing of them the inscription «временник главной палаты мер и весов» (chronicles of the main chamber of weights and measures), which was the first metrological journal published in russia on the initiative and under the leadership of d.i. mendeleev. at the opening ceremony, academician m.a. shatelen said: «i hope, this monument is a precursor. probably, our state will build a worthy monument to honor mendeleev’s 100th anniversary. but this small, one might say, homely monument, will be a place of pilgrimage for us, so to speak. mendeleev is the founding father of our metrology. if we use extensive achievements of metrology, if we can legitimately consider our institute, vims (all-union scientific research institute of metrology and standardization), to be one of the leading institutions of this kind on a global scale, we undoubtedly owe that to dmitri ivanovich».6 celebrating mendeleev through the periodic system on september 22, 1933, to prepare for the 100th anniversary of d.i. mendeleev an organizing committee was created at vims for the “ceremonial honoring the memory of d.i. mendeleev”. it consisted of the institute’s staff: academician a.a. baykov (chairman), a.n. dobrokhotov, s.z. snarsky (director), profs. l.v. zalutsky, m.f. malikov, a.k. kolosov, v.e. murashkinsky, a.t. gorbov, i.d. mendeleev (son), and m.n. mladentsev (scientific secretary). the committee was tasked with developing, approving, and supervising the list of events dedicated to the scientist’s anniversary and the perpetuation of his memory, estimating the costs, liaising with other scientific institutions that wished to participate in the commemorative events.7 among the proposals received were among others: to rename the mezshdunarodniy (international) avenue into mendeleev avenue, to organize conferences, lecture courses, to republish d.i. mendeleev works, to restore d.i. mendeleev’s estate in the village of boblovo. the most interesting of the proposals received was to install a mosaic panel featuring mendeleev’s periodic system of elements on the wall of the artillery school (today the suvorov military school) adjacent to vniim. the making of the monument was discussed at the organizing committee meetings of 1933– 1934, including the issues related to expenses, contracting, styling and manufacturing, as well as obtaining the necessary permits. negotiations were conducted with the lomonosov porcelain factory, state ceramic research institute and russian academy of arts. initially, it was planned to order the table to be made of ceramic tiles at the lomonosov porcelain factory art laboratory; however, during the negotiations held by alexander k. kolosov, it turned out that the monument would be ready only by the spring of 1934 (i.e. by the anniversary, but not by february 8). yet still the most difficult was to decide which table should be used as a basis. on december 27, 1933, the organizing committee discussed the proposal of a.i. gorbov and m.n. mladentsev, who were entrusted with drawing up a draft of the table. they supported picturing the table as it was printed in the 8th (1906) edition of d.i. mendeleev’s foundations of chemistry.8 some of the committee members, including ivan dmitrievich mendeleev, believed that “the table would serve both as a monument, and a study guide, which would make it improper to depict the table in 1934 as it was in 1906, because great changes have taken place since then”.9 the discussion did not lead to a final decision, and vims director s.z. snarskiy was charged with convening an ad-hoc meeting with academicians n.s. kurnakov, a.b. favorskiy, v.e. tischenko, v.ya. kurbatov, s.p. vukolov, i.ya. gintzburg, the representatives of the lensovet development authority and vims public organizations to study drafts of the table.10 thus, by january of 1934, two main issues which of the proposed tables should be chosen and who should be commissioned to manufacture it remained unresolved. on january 15, 1934, given the newly discovered disagreements, an extended organizing committee meeting was held to discuss the drafts of the table. after an extensive debate, the committee decided to opt for the periodic table proposed by ivan mendeleev. the table published in the 8th edition of d.i. mendeleev’s foundations of chemistry was agreed upon as a basis, with addition of the elements discovered from 1906 to 1934. protocol resolution no. 11 states: • to recognize, that all additions to the table made after d.i. mendeleev’s death must be depicted in a different color, • to recognize as desirable the addition of atomic weights to the table, if no technical or esthetic considerations interfere with doing so, • to ask the vims architect to prepare, according to instructions of a.k. kolosov and i.d. mendeleev, a draft of one or more symbols of the table in full size 83the «d.i. mendeleev’s periodic system of the elements» mural in saint petersburg in two versions: with the elements only and with both the elements and their atomic weights.11 in january 1934, on behalf of the vims director s.z. snarskiy, letters requesting installation of the table were sent to the head of the artillery school and the lensovet development authority, and the corresponding permits were obtained.12 however, the issue of contractor still had not been decided upon. even the option of making a temporary table using oil paints was contemplated, but that was declined because of the unfavorable climate conditions in the city. only on june 5, 1934, an agreement was concluded between vims, represented by its director, s.z. snarskiy, and the all-russian academy of arts, represented by the head of mosaic department, vladimir a. frolov, on manufacturing of the table. the agreement states, that “the institute instructs, and the academy takes on execution of the memorial plate to professor d.i. mendeleev with unpolished mosaics (letters and digits) on faux stone cement background with marble chips and with the same frame to place it on the side wall of the building adjacent to the institute”.13 the memorial plate was manufactured by the academy using its materials; 12 barrels of portland cement required for the project were provided by the institute; the work was delivered in form of separate completed square stones of reinforced concrete without notching in two stages; the delivery of the finished parts was carried out by the academy at its own expense. all work on installation of the tablet was carried out by the academy; the institute constructed the necessary scaffolding and provided 2 workers and cement mortar to fix the square stones on the wall. the institute would pay the academy 21 000 rubles for the work. the deadline was october 15, 1934.14 all parts of the “memorial plate”, as it was initially called, were manufactured and delivered on october 16, 1934, according to the acceptance certificate.15 architectural design of the wall was developed by architect d.l. krichevskiy. inauguration of the mosaic panel with mendeleev’s figure 5. “periodic system of the elements» published in the book by d.i. mendeleev “fundamentals of chemistry”. st. petersburg. 1906. figure 6. mosaic panel «d.i. mendeleev’s periodic system of the elements». photo taken by e.ginak, 2019. 84 elena ginak periodic system of elements took place on november 10, 1935. (the height of the monument is 9 m; the total area is 69 sq.m). life of a monument «d.i. mendeleev’s periodic system of the elements» in 1983, during the preparation for the celebration of 150th anniversary of d.i. mendeleev, vniim pointed out that the periodic system mural needed some repairs. there were proposals to amend the state of the table and to add the elements discovered after 1934. to this end, vniim applied to the authoritative commission (it included well-known historians of chemistry: professors alexander a. makarenya and igor s. dmiriev) asking it to check the accuracy of the table symbols and structure. finally, it was decided to act according to protocol no. 11 dated january 15, 1934 and restore the monument to its original state. in 2013–2017, a comprehensive reconstruction and restoration of the military school buildings was conducted. vniim sent a request to the state inspectorate for the preservation of monuments to provide for the preservation and restoration of the unique mosaic on the wall. the metrological museum provided to the restorers the necessary information from archives on the history of the periodic system mural and on its particular features. a number of obvious repairs were carried out: cleaning, washing, reinforcement, etc. there are no plans now to introduce any changes to the 1935 panel. order no. 556-r dated 15.12.2017 of the state inspectorate for preservation of monuments lists the “barracks” building and the table on its wall in the register of cultural heritage objects of regional importance “complex of buildings of the imperial orphanage (konstantinovsky military school)”. conclusion thus, thanks to the efforts of the staff of the main chamber of weights and measures (vniim), a unique memorial complex was created  in 1932-1935 in the center of st. petersburg, dedicated to mendeleev and his famous discovery. it invariably  attracts the attention of st. petersburgers, russian and foreign guests of the city. acknowledgement the author thanks the editors of the journal “standards reference samples”, where the article by e.b. ginak was first published in russian: https://www.rmjournal. ru/jour/article/view/218. references 1. aleksandrov, v.s., ginak, e.b. participation of the d.i. mendeleev institute for metrology in celebrations of the 175th anniversary of d.i. mendeleev. izmeritelnaya tekhnika (measuring technique). 2009. no. 6. pp.70-72. 2. ginak, e.b. metrological museum: history, collections, exhibitions, projects. mir izmereniy (world of measurements). 2017. no. 2. p. 60. 3. archive of the metrology museum hosted by the d.i. mendeleyev institute for metrology (mm archive). оп.2. д. 64. лл. 11, 11об. 4. mm archivе. оп.2. д. 64. л. 12. 5. mm archivе. оп.2. д. 64. л.1. 6. mm archive. оп. 2. д. 58. л. 33. + https://www. vniim.ru/news_107.html 7. mm archive. оп. 2. д. 54. л. 200. 8. mm archive. оп.2. д. 54. л. 57 об. 9. mm archive. оп.2. д. 54. л. 54 10. mm archive. оп.2. д. 54. л. 56 11. mm archive. оп. 2. д. 54. л. 54-54 об. 12. mm archive. оп. 2. д. 54. лл. 183, 183 об. 13. scientific archive of the russian academy of arts (st. petersburg). ф. 7. оп. 2. д. 245. л. 14. 14. scientific archive of the russian academy of arts (st. petersburg). ф. 7. оп. 2. д. 245. л. 14 об. 15. scientific archive of the russian academy of arts (st. petersburg). ф. 7. оп. 2. д. 245. л.22. figure 6. monument to d.i. mendeleev and mosaic mural « d. i. mendeleev periodic system of elements», st peterbsurg. photo taken by e.ginak, 2019. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural near the mendeleev institute for metrology in saint petersburg: how metrologists celebrated the 100th anniversary of the scientist elena ginak the revolution in science in america, 1900-1950 jack s. cohen capillary electrophoresis and its basic principles in historical retrospect. part 2. electrophoresis of ions: the period from its discovery in 1800 till faraday’s lines of electric force in the 1840s. ernst kenndler disinfectants: use of different types of sanitization techniques in 18th and 19th centuries britain and india chetan a brief history of oil refining rafael larraz albert ladenburg (1842-1911) – the distinguished german chemist and historian of chemistry of the second half of the xix century (to the 110th anniversary of his death) aleksander sztejnberg review of “ethics of chemistry: from poison gas to climate engineering” by joachim schummer & tom børsen, eds. world scientific publishing, singapore, 2021 apostolos k. gerontas substantia. an international journal of the history of chemistry 3(2): 19-25, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-632 citation: f. real-fernández, g. pacini, f. nuti, g. conciarelli, c. de felice, j. hayek, p. rovero, a.m. papini (2019) is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome?. substantia 3(2): 19-25. doi: 10.13128/substantia-632 copyright: © 2019 f. real-fernández, g. pacini, f. nuti, g. conciarelli, c. de felice, j. hayek, p. rovero, a.m. papini. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* 1 interdepartmental laboratory of peptide and protein chemistry and biology, department of chemistry “ugo schiff ”, university of florence, sesto fiorentino, italy 2 interdepartmental laboratory of peptide and protein chemistry and biology, department of neurosciences, psychology, drug research and child health section of pharmaceutical sciences and nutraceutics, university of florence, sesto fiorentino, italy 3 neonatal intensive care unit, university hospital, azienda ospedaliera universitaria senese, siena, italy 4 child neuropsychiatry unit, university hospital, azienda ospedaliera universitaria senese, siena, italy *e-mail: annamaria.papini@unifi.it abstract. antibodies against myelin oligodendrocyte glycoprotein (mog) are associated to several disorders, and their occurrence in patients presenting an acquired demyelinating disease affects a higher proportion of paediatric subjects, as compared to adults. despite heterogeneity in clinical presentation, few connexions have been reported between the progressive neurodevelopmental disorder affecting child’s brain development and cognitive ability, i.e. rett syndrome (rtt), and a demyelination process. in order to identify the possible target of humoral autoimmune response in rtt patients, we set-up a home-made solid-phase elisa, using the recombinant extracellular portion of human mog(1-117) as an antigen. the screening to evaluate anti-mog antibodies in rtt patient sera, compared to other relative non-rtt pervasive developmental disorders (non-rtt pdd), including mainly autism, and a healthy control group gave uncertain results. in fact, student t-test and mann-whitney unpaired t test showed that differences in both igg and igm antibody titres between the different patient populations, were not statistically significant. we can conclude that the absence of anti-mog antibody recognition in rtt has possibly to be ascribed to a different relevant protein folding and/or to the lack of a relevant aberrant post-translational modification, such as n-glucosylation, that we previously demonstrated, for the first time, fundamental to recognize antibodies in rtt. keywords. myelin oligodendrocyte glycoprotein, rett syndrome, antibody detection, elisa. introduction a precise myelination is crucial for optimal transmission of nerve impulses and in providing trophic support to axons. in the central nervous 20 f. real-fernández et al. system (cns) oligodendrocytes shape the myelin sheath surrounding axons.1 intermittent uncovered short portions of the axon, called myelin-sheath gaps or the nodes of ranvier, are fundamental for optimal myelin functioning.2,3 perturbations of the nodes of ranvier and myelin can be due to several causes including autoimmune responses as in multiple sclerosis,4 guillain-barré syndrome,5 or in other immune-mediated neurological diseases.6 demyelination process can be unleashed either because of an attack directly on the myelin sheath and/ or a disruption or death of oligodendrocytes. this clear difference in triggering the same end-stage of demyelination may not be obvious and sometimes damage to both may occur. the aetiology of myelin loss includes immune-mediated, viral, metabolic, toxic, and/or genetic causes. moreover, brain damages that may occur during neonatal hypoxia or subsequent to traumatic injury may also result in successive demyelination.3,7 in this context, the involvement of cns myelin proteins is fundamental for oligodendrocyte growth and myelination.8-11 myelin proteins include myelin proteolipid protein (plp), the related dm20, myelin-associated oligodendrocyte basic protein (mobp), myelinassociated glycoprotein (mag), 2’,3’-cyclic-nucleotide 3’-phosphodiesterase (cnp), and particularly the myelin basic protein (mbp) and myelin oligodendrocyte glycoprotein (mog). proteins as mbp and mog, located in the external part of myelin, have been proposed as antigens in several immune-mediated disorders. mog localization on the outermost surface of myelin sheath and the plasma membrane of oligodendrocytes12 convert this protein into a partial exposed target (figure 1). despite the specific function of mog has still to be clarified, its role as important surface marker of oligodendrocyte maturation, regulator of microtubule stability and mediator of interactions between myelin and the immune system have been described.13,14 more controversial are the results obtained to identify and clarify the role of anti-mog antibodies, which are still a matter of discussion,15-17 particularly on their putative pathogenic involvement in autoimmune response in multiple sclerosis15,18-20. interesting data about the diagnostic/prognostic role of anti-mog antibodies in multiple sclerosis patient sera were published,21 followed by contradictory studies that could not confirm these results. in fact, the same group of authors described other contrasting data in a conflicting array.22-25 a recent review reports that methods to detect anti-mog antibodies have improved substantially with cell-based assays.26 however, a strong debate is still ongoing.27 anyway, from the molecular point of view definition of the peptide epitope (conformational and/or linear) involved in antibody recognition is a challenge. in fact, a maximum of 8-10 amino acids are involved in in vivo antibody binding.28 mog has a unique site of n-glycosylation at position 31 and the mog(35-55) peptide has been the only mog fragment able to induce neurological impairment in mice comparable with those observed in experimental autoimmune encephalomyelitis induced by mbp or plp.29 to assess the presence of a b-cell intramolecular epitope spreading mechanism, we tested synthetic peptides mapping mog(1-117), including mog(35-55). an intense igg antibody response against both the recombinant protein and the immunizing peptide mog(35-55) was observed, while no response was observed against the other synthetic fragments. furthermore, as the properly refolded recombinant probe is able to bind antibodies with greater efficiency compared with mog(35-55), we hypothesized the presence of both linear and conformational epitopes on mog(35-55) sequence.30 the arguments discussed in the current literature regarding anti-mog antibodies in multiple sclerosis can be extended to other inflammatory demyelinating diseases of the cns. in particular, anti-mog antibodyassociated disorders account for a higher proportion of paediatric patients than adults who present an acquired demyelinating disease.31 previously, we hypothesized the coexistence of a perturbation of the immune system in rett syndrome figure 1. homology model of the extracellular domain of human myelin oligodendrocyte glycoprotein (mog), with the β-turn inside the fragment mog(35-55) evidenced. 21is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? (rtt) patients.32 rtt is a neurodevelopmental genetic disorder presenting neurological regression after development during infancy. a derangement of microglia immune responsiveness might be likely to occur in these paediatric patients, as neuroinflammation is a powerful modulator of the cns immune system. we observed that rtt patients showed a consistent and highly significant increased titer of igm antibodies relative to both healthy controls and non-rtt pervasive developmental disorders (non-rtt pdd) patient groups by using a diagnostic synthetic glycopeptide antigen of multiple sclerosis (figure 2).32-34 moreover, despite heterogeneity in clinical presentation, few connexions between rtt and demyelination process have been reported. in fact, sharma et al. focused on the role of methyl cpg binding protein 2 (mecp2), one of the genes associated with rtt, and its involvement in regulation of myelin gene expression.35 additionally, a case report with similarities in rtt symptoms and anti-mog antibody encephalitis has been described.36 convergence of these diseases could lead to a better understanding in demyelination process due to immune-mediated mechanisms. with all these considerations in mind, the main goal of our work was to identify the target of the humoral autoimmune response in rtt patients, recognised by the synthetic n-glucosylated β-turn peptide structure,32 evaluating the possible cross-reaction with anti-mog antibodies. moreover, we focused on a better understanding of antibody response in rett syndrome compared to other relative non-rtt pdd, including mainly autism, apparently connected (as they share some behavioural traits), but dramatically different for their severity, life-span expectancy, and immune system derangement. to this aim, a homemade sp-elisa, based on the extracellular portion hmog(1–117) expressed in escherichia coli and properly refolded, was employed to test rtt patient population, other relative non-rtt pdd, and healthy control groups. materials and methods patients in this study, a group of 110 children was enrolled. this population consisted of three clearly distinguishable groups: the rtt syndrome group (28) versus nonrtt pervasive developmental disorders (non-rtt pdd) group (48), classification based on the clinical features and the presence of mutated rtt-related genes and healthy, age-matched controls (34). these patients were hospitalized for 1 week every 6 months, in the child neuropsychiatric unit, “azienda ospedaliera universitaria senese”, siena (italy), during the course of the study. criteria for inclusion in the study were clinical diagnosis of rtt syndrome coupled with positive identification for the presence/absence of mutated mecp2, cdkl5, or foxg1 genes. the age-matched non-rtt pdd group consisted of 48 patients, as diagnosed following well-established criteria. blood samplings in the patient group were performed during the routine followup study at hospital admission, while the samples from the control group were carried out during routine health checks, sports, or blood donations, obtained during the periodic clinical checks. the healthy control subjects were age-matched. patients were selected randomly and not previously tested for immune reactivity by elisa. parents, tutors, or guardians of all the participants provided their written informed consent for the minors to participate in this study. the study design, methods, and consent procedure were approved by the institutional review board of azienda ospedaliera universitaria senese. all the data used in this study were anonymized. figure 2. the β-turn peptide structure exposing at position 7 the n-glucosylation recognizing specific antibodies in rett syndrome in a home-made elisa.32 22 f. real-fernández et al. materials solid‐phase elisas were performed using 96‐well plates nunc maxisorp f lat bottom (sigma‐aldrich, milan, italy). washing steps were performed using a microplate washer hydroflex (tecan, männedorf, switzerland). fetal bovine serum (fbs) was purchased from sigma-aldrich (milan, italy). secondary anti‐human igg and igm antibodies conjugated with alkaline phosphatase were purchased by sigma‐aldrich (milan, italy). p‐nitrophenyl phosphate was purchased from fluka (milan, italy). absorbance values were measured on a plate reader tecan sunrise purchased from tecan (tecan italia, milan, italy). electrocompetent er2566 e. coli cells were purchased from new england biolabs (ipswich, ma, usa). plasmid pet‐22 was purchased from novagen (madison, wi, usa). protein purification and refolding were performed using a chelating sepharose fast flow column on äktabasic chromatography system (ge healthcare, milan, italy). the far‐uv circular dichroism (cd) spectra were recorded by using a j‐810 jasco spectropolarimeter (jasco, easton, md). enzyme-linked immunosorbent assay (elisa) the protein fragment hmog(1–117) cdna was subcloned into the his‐tag expression vector pet‐22. recombinant hmog(1-117) was produced according to the protocol published by gori et al.37 recombinant hmog(1-117) was dissolved in coating buffer (12mm na2co3, 35mm nahco3, ph 9.6) to obtain a solution 10 µg/ml. then 100 µl of solution were dispensed in each well of 96 well maxisorp flat bottom plate, pinchbar design. plates were incubated a +4°c overnight. subsequently, plates were washed 3 times with washing buffer (0.9% nacl, 0.01% tween 20), and blocked 1 h at rt with 100 µl/well of fbs buffer (10% fbs in washing buffer). after fbs buffer removal, 100 µl/well of diluted sera sample (1:100 in fbs buffer) were dispensed in triplicates. plates were incubated at +4°c overnight, and then washed 3 times with washing buffer, 100 µl/well of secondary ab labeled with alkaline phosphatase diluted in fbs buffer (anti-h igg 1:8000 and anti-h igm 1:200) were dispensed and incubated 3 h at room temperature. plates were washed 3 times with washing buffer, then 100 µl/well of substrate solution (1mg/ml p-pnp in carbonate buffer containing 1mm mgcl2, ph 9.8) were dispensed. absorbance was read at 405 nm with a spectrophotometer. sera values were calculated as (mean absorbance of triplicate) – (mean absorbance of blank triplicate). statistical analysis data are expressed as mean values and elaborated using the statistical software graphpad prism version 6.01. d’agostino-parson test was employed as normality test. student t-test or mann-whitney unpaired t-test were used to compare continuous variables between groups. spearman correlation analysis was used to test any relationship between pairs of variables. differences were deemed statistically significant when p < 0.05 (twotailored test). results and discussion in order to study the antibody response against recombinant refolded h-mog in rtt, we tested 28 rtt patients, 48 non-rtt pdd, and 30 healthy controls by using a home-made sp-elisa. the recombinant hmog(1-117) was tested as an antigen evaluating igg and igm type antibodies separately. data distribution of igg antibody titers detected to hmog(1-117) in rtt, non-rtt pdd, and controls are plotted in figure 3. the overall data distribution were statistically analyzed using d’agostino-pearson test and results showed that none of the rtt, non-rtt pdd, or healthy controls group passed the normality test (alpha = 0.05). then, antibody titer differences between groups were evaluated separately using the mann-whitney u-test. results showed no discriminant differences between rtt and non-rtt pdd patients (p value = 0.6629, two-tailed), rtt and healthy controls (p value = 0.2583, two-tailed), figure 3. comparison between igg antibodies against the hmog(1-117) identified by sp-elisa in rtt (), non-rtt pdd patient sera (●), and healthy controls (○) respectively. mean group values and standard error of mean (sem) are represented. 23is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? or non-rtt pdd and healthy controls (p value = 0.6137, two-tailed). similar results were observed when igm-type antibodies were evaluated. data distribution of igm antibody values are plotted in figure 4. the overall data did not present a gaussian distribution (d’agostino-pearson omnibus normality test, alpha = 0.05). moreover, mannwithney test showed no significant statistic differences between groups (p value > 0.05, two-tailed) further evidencing no meaningful differences, thus allowing us to assume that mog as a possible antigen in rtt and/or non-rtt pdd is irrelevant. moreover, no relationship was found between igg and igm autoantibody levels (nonparametric spearman correlation, p values > 0.05). evidences of anti-mog antibody-associated diseases in children with acquired demyelinating syndromes, whose sera test were positive for anti-mog antibodies, have been described.38. as discussed in the introduction, the genetic mechanism underlying the rtt syndrome appear directly linked to a demyelinating process. on the other hand, despite previous studies reporting a connection between multiple sclerosis and rtt humoral responses, the role of anti-mog antibodies in these disorders cannot be clarified. the lack of a clear anti-mog antibody identification in rtt, herein observed, reminds the open controversy around anti-mog antibodies in the case of multiple sclerosis, as a kind of parallelism between these diseases. previously, our expertise in antibody detection using proteins37,39,40 or peptides41,42 prompted us to develop the so-called “chemical reverse approach” in which synthetic peptides were demonstrated to be more effective than native proteins.43 in fact, their principal advantage is the complete control of the synthetic molecules. mazzucco et al. showed that the n-glucosylation (n-glc) of the hmog peptide [asn31(n-glc)]hmog(30-50) allowed to detect antibodies in 40% of an unselected group of multiple sclerosis patients.44 after almost 20 years, we discovered that anti-n-glc antibodies from multiple sclerosis patients preferentially recognize adhesin of nontypeable haemophilus influenza hyperglucosylated on asparagine residus exposed on β-turns.39 therefore, it is clear that the folding issue is relevant in antibody recognition, and synthetic peptides can be designed to adopt specific conformations, e.g. β-turns.45,46 moreover, synthetic conformational peptides can be efficient tools as antigenic probes for serum antibody detection, because they can also include unique chemical modifications, such as asparagine n-glucosylation, on strategic positions in selected sequences. this strategy has been, up to now, to the best of our knowledge, the only winner in detecting antibodies in rtt patient sera.32,47 our findings offer a new insight into the mechanism underlying the rtt as they unveil the possible participation of the immune system in this pathology.48 moreover, our previous work contributes to elucidate that two disorders such as rtt and autism, seemingly contiguous as they share some behavioral symptoms, but are in fact different for their ruthlessness, life-span expectation, and, as we previously demonstrated, for different immune system derangement. in this context and in light of the results herein presented, the connection of anti-mog antibodies and rtt remains an uncertainty. in particular, the involvement of the correct folding, but also the lack of a mimicry effect reproducing n-glucosylation (and other molecules) as possible aberrant post-translational modifications on mog amino acids (involved in triggering immune responses), require to be deeply investigated. conclusions the screening of rtt patient sera, other relative non-rtt pervasive developmental disorders (non-rtt pdd) including mainly autism, and healthy controls group to evaluate anti-mog antibodies was uncertain. despite anti-mog antibody detection in multiple sclerosis and generally speaking in mog-igg–related diseases have improved substantially with cell-based assays, in which the molecules involved in antibody recognition are not fully chemically characterised. on the other hand our preliminary results are in agreement with the idea that the reproduction of post-translational modifications possibly involved in the immune response figure 4. data distribution of igm antibodies against hmog(1117) identified by sp-elisa in rtt (), non-rtt pdd patient sera (●), and healthy controls (○), respectively. mean group values and standard error of mean (sem) are represented. 24 f. real-fernández et al. could be a must for antibody identification, as it occurs in other diseases connected with rtt, such as multiple sclerosis. in particular, investigating glycan-peptide mimicry in the context of immune response is an emerging topic, pointing toward the multiple roles that unique glycans of bacterial origin may play. these novel preliminary results pave the way to further studies, already ongoing in our laboratories, focused on understanding the responsible agents triggering the immune response in 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frost, j. mol. neurosci., 2015, 57(2), 176-84. 36. h. tani, n. ishikawa, y. kobayashi, s. yamaoka, y. fujii, k. kaneko, t. takahashi, m. kobayashi, brain dev., 2018, 40(10), 943-946. 37. f. gori, b. mulinacci, l. massai, c. avolio, m. caragnano, e. peroni, s. lori, m. chelli, a.m. papini, p. rovero, f. lolli, j. neuroimmunol., 2011, 233(1-2), 216-220. 38. y. hacohen, t. rossor, k. mankad, w. chong, a. lux, e. wassmer, m. lim, f. barkhof, o. ciccarelli, c. hemingway, developmental medicine & child development, 2018, 60(4), 417-423. 39. m.t.c. walvoort, c. testa, r. eilam, r. aharoni, f. nuti, g. rossi, f. real-fernandez, r. lanzillo, v. brescia morra, f. lolli, p. rovero, b. imperiali, a.m. papini, scientific reports, 2016, 6, 39430. 40. f. real-fernández, r. cimaz, g. rossi, g. simonini, t. giani, i. pagnini, a.m. papini, p. rovero, anal. bioanal. chem., 2015, 407(24), 7477-7485. 41. f. nuti, a. gallo, f. real-fernandez, m. crulli, c. rentier, f. piarulli, e. peroni, g. rossi, p. traldi, p. rovero, a. lapolla, a.m. papini, archives of biochemistry and biophysics, 2018, 659, 66-74. 42. m. di pisa, s. pascarella, m. scrima, g. sabatino, f. real fernández, m. chelli, d. renzi, a. calabrò, a.m. d’ursi, a.m. papini, p. rovero, j. med. chem., 2015, 58(3), 1390-1399. 43. a.m. papini, j. pept. sci., 2009, 15(10), 621-628. 44. s. mazzucco, s. matà, m. vergelli, r. fioresi, e. nardi, b. mazzanti, m. chelli, f. lolli, m. ginanneschi, f. pinto, l. massacesi, a.m. papini, bioorg. med. chem. lett., 1999, 9(2), 167-172. 45. a. carotenuto, a.m. d’ursi, b. mulinacci, i. paolini, f. lolli, a.m. papini, e. novellino, p. rovero, j. med. chem., 2006, 49(17), 5072-5079. 46. a. carotenuto, m.c. alcaro, m.r. saviello, e. peroni, f. nuti, a.m. papini, e. novellino, p. rovero, j. med. chem., 2008, 51(17), 5304-5309. 47. f. real fernández, m. di pisa, g. rossi, n. auberger, o. lequin, m. larregola, a. benchohra, c. mansuy, g. chassaing, f. lolli, j. hayek, s. lavielle, p. rovero, j.m. mallet, a.m. papini, biopolymers (pept sci)., 2015, 104(5), 560-576. 48. c. de felice, s. leoncini, c. signorini, a. cortelazzo, p. rovero, t. durand, l. ciccoli, a.m. papini, j. hayek, autoimmunity reviews, 2016, 15, 411-416. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 3(2): 59-64, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-636 citation: w. isaacson (2019) leonardo da vinci – the scientist. substantia 3(2): 59-64. doi: 10.13128/substantia-636 copyright: from leonardo da vinci by walter isaacson. copyright © 2017 by walter isaacson. reprinted by permission of simon & schuster, inc. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article leonardo da vinci – the scientist walter isaacson e-mail: isaacson@tulane.edu abstract. to celebrate the 500th anniversary of leonardo’s death we gladly republish, with permission, one chapter from walter isaacson’s book “leonardo da vinci” by simon & schuster. leonardo was born as a natural child on april 15, 1452 in anchiano, a handful of houses near vinci, close to florence. he died on may 2, 1519, in the grandiose castle of clos lucé near amboise, not far from tours in the middle of france. a free spirit, a true master in interand multisciplinarity, indifferent to taboos and scientific dogmas, one of the fathers of what we call the “scientific method”. obsessed by experience and observation, eager devourer of the first scientific printed books, he understood and practiced the correct balance between experiments and theories. in particular, on the role of experience and mathematics he wrote in the “treatise on painting”: “nissuna umana investigazione si pò dimandare vera scienzia s’essa non passa per le matematiche dimostrazioni, e se tu dirai che le scienzie, che principiano e finiscono nella mente, abbiano verità, questo non si concede, ma si niega, per molte ragioni, e prima, che in tali discorsi mentali non accade esperienzia, sanza la quale nulla dà di sé certezza.” (no human investigation can be termed true science if it is not capable of mathematical demonstration. if you say that the sciences which begin and end in the mind are true, i do not agree, but deny it for many reasons, and foremost among these the fact that the test of experiment is absent from these exercises of the mind, and without these there is no assurance of certainty). keywords. leonardo, scientific method, epistemology, empirism. teaching himself leonardo da vinci liked to boast that, because he was not formally educated, he had to learn from his own experiences instead. it was around 1490 when he wrote his screed about being “a man without letters” and a “disciple of experience,” with its swipe against those who would cite ancient wisdom rather than make observations on their own. “though i have no power to quote from authors as they have,” he proclaimed almost proudly, “i shall rely on a far more worthy thing—on experience.”1  throughout his life, he would repeat this claim to prefer experience over received scholarship. “he who has access to the fountain does not go to the water-jar,” he wrote.2  this made him different from the archetypal renaissance man, who embraced the rebirth of wisdom that came from rediscovered works of classical antiquity. the education that leonardo was soaking up in milan, however, began to soften his disdain for handed-down wisdom. we can see a turning point 60 walter isaacson in the early 1490s, when he undertook to teach himself latin, the language not only of the ancients but also of serious scholars of his era. he copied page after page of latin words and conjugations from textbooks of his time, including one that was used  by ludovico sforza’s young son. it appears not to have been an enjoyable exercise; in the middle of one notebook page where he copied 130 words, he drew his nutcracker man scowling and grimacing more than usual (figure 49). nor did he ever master latin. for the most part his notebooks are filled with notes and transcriptions from works available in italian. in that regard, leonardo was born at a fortunate moment. in 1452 johannes gutenberg began selling bibles from his new printing press, just when the development of rag processing was making paper more readily available. by the time leonardo became an apprentice in florence, gutenberg’s technology had crossed the alps into italy. alberti marveled in 1466 about “the german inventor who has made it possible, by certain pressings down of characters, to have more than two hundred volumes written out in a hundred days from the original, with the labor of no more then three men.” a goldsmith from gutenberg’s hometown of mainz named johannes de spira (or speyer) moved to venice and started italy’s first major commercial publishing house in 1469; it printed many of the classics, starting with cicero’s letters and pliny’s encyclopedic  natural history, which leonardo bought. by 1471 there were printing shops also in milan, florence, naples, bologna, ferrara, padua, and genoa. venice became the center of europe’s publishing industry, and by the time leonardo visited in 1500, there were close to a hundred printing houses there, and two million volumes had come off their presses.3  leonardo thus was able to become the first major european thinker to acquire a serious knowledge of science without being formally schooled in latin or greek. his notebooks are filled with lists of books he acquired and passages he copied. in the late 1480s he itemized five books he owned: the pliny, a latin grammar book, a text on minerals and precious stones, an arithmetic text, and a humorous epic poem, luigi pulci’s morgante, about the adventures of a knight and the giant he converted to christianity, which was often performed at the medici court. by 1492 leonardo had close to forty volumes. a testament to his universal interests, they included books on military machinery, agriculture, music, surgery, health, aristotelian science, arabian physics, palmistry, and the lives of famous philosophers, as well as the poetry of ovid and petrarch, the fables of aesop, some collections of bawdy doggerels and burlesques, and a fourteenth-century operetta from which he drew part of his bestiary. by 1504 he would be able to list seventy more books, including forty works of science, close to fifty of poetry and literature, ten on art and architecture, eight on religion, and three on math.4 he also recorded at various times the books that he hoped to borrow or find. “maestro stefano caponi, a physician, lives at the piscina, and has euclid,” he noted. “the heirs of maestro giovanni ghiringallo have the works of pelacano.” “vespucci will give me a book of geometry.” and on a to-do list: “an algebra, which the marliani have, written by their father. a book, treating of milan and its churches, which is to be had at the last stationers on the way to corduso.” once he discovered the university of pavia, near milan, he used it as a resource: “try to get vitolone, which is in the library at pavia and deals with mathematics.” on the same to-do list: “a grandson of gian angelo’s, the painter, has a book on water which was his father’s. get the friar di brera to show you  de ponderibus.” his appetite for soaking up information from books was voracious and wide-ranging. in addition, he liked to pick people’s brains. he was constantly peppering acquaintances with the type of figure 49. trying to learn latin, with a grimace. 61leonardo da vinci – the scientist questions we should all learn to pose more often. “ask benedetto portinari how they walk on ice in flanders,” reads one memorable and vivid entry on a to-do list. over the years there were scores of others: “ask maestro antonio how mortars are positioned on bastions by day or night. find a master of hydraulics and get him to tell you how to repair a lock, canal and mill in the lombard manner. ask maestro giovannino how the tower of ferrara is walled without loopholes.”5 thus leonardo became a disciple of both experience and received wisdom. more important, he came to see that the progress of science came from a dialogue between the two. that in turn helped him realize that knowledge also came from a related dialogue: that between experiment and theory. connecting experiment to theory leonardo’s devotion to firsthand experience went deeper than just being prickly about his lack of received wisdom. it also caused him, at least early on, to minimize the role of theory. a natural observer and experimenter, he was neither wired nor trained to wrestle with abstract concepts. he preferred to induce from experiments rather than deduce from theoretical principles. “my intention is to consult experience first, and then with reasoning show why such experience is bound to operate in such a way,” he wrote. in other words, he would try to look at facts and from them figure out the patterns and natural forces that caused those things to happen. “although nature begins with the cause and ends with the experience, we must follow the opposite course, namely begin with the experience, and by means of it investigate the cause.”6 as with so many things, this empirical approach put him ahead of his time. scholastic theologians of the middle ages had fused aristotle’s science with christianity to create an authorized creed that left little room for skeptical inquiry or experimentation. even the humanists of the early renaissance preferred to repeat the wisdom of classical texts rather than test it. leonardo broke with this tradition by basing his science primarily on observations, then discerning patterns, and then testing their validity through more observations and experiments. dozens of times in his notebook he wrote some variation of the phrase “this can be proved by experiment” and then proceeded to describe a real-world demonstration of his thinking. foreshadowing what would become the scientific method, he even prescribed how experiments must be repeated and varied to assure their validity: “before you make a general rule of this case, test it two or three times and observe whether the tests produce the same effects.”7 he was aided by his ingenuity, which enabled him to devise all sorts of contraptions and clever methods for exploring a phenomenon. for example, when he was studying the human heart around 1510, he came up with the hypothesis that blood swirled into eddies when it was pumped from the heart to the aorta, and that was what caused the valves to close properly; he then devised a glass device that he could use to confirm his theory with an experiment (see chapter 27). visualization and drawing became an important component of this process. not comfortable wrestling with theory, he preferred dealing with knowledge that he could observe and draw. but leonardo did not remain merely a disciple of experiments. his notebooks show that he evolved. when he began absorbing knowledge from books in the 1490s, it helped him realize the importance of being guided not only by experiential evidence but also by theoretical frameworks. more important, he came to understand that the two approaches were complementary, working hand in hand. “we can see in leonardo a dramatic attempt to appraise properly the mutual relation of theory to experiment,” wrote the twentieth-century physicist leopold infeld.8 his proposals for the milan cathedral tiburio show this evolution.  to understand how to treat an aging cathedral with structural flaws, he wrote, architects need to understand “the nature of weight and the propensities of force.” in other words, they need to understand physics theories. but they also need to test theoretical principles against what actually works in practice. “i shall endeavor,” he promised the cathedral administrators, “to satisfy you partly with theory and partly with practice, sometimes showing effects from causes, sometimes affirming principles with experiments.” he also pledged, despite his early aversion to received wisdom, to “make use, as is convenient, of the authority of the ancient architects.” in other words, he was advocating our modern method of combining theory, experiment, and handed-down knowledge—and constantly testing them against each other.9 his study of perspective likewise showed him the importance of joining experience with theories. he observed the way objects appear smaller as they get more distant. but he also used geometry to develop rules for the relationship between size and distance. when it came time to describe the laws of perspective in his notebooks, he wrote that he would do so “sometimes by deduction of the effects from the causes, and sometimes arguing the causes from the effects.”10 62 walter isaacson he even came to be dismissive of experimenters who relied on practice without any knowledge of the underlying theories. “those who are in love with practice without theoretical knowledge are like the sailor who goes onto a ship without rudder or compass and who never can be certain whither he is going,” he wrote in 1510. “practice must always be founded on sound theory.”11 as a result, leonardo became one of the major western thinkers, more than a century before galileo, to pursue in a persistent hands-on fashion the dialogue between experiment and theory that would lead to the modern scientific revolution. aristotle had laid the foundations, in ancient greece, for the method of partnering inductions and deductions: using observations to formulate general principles, then using these principles to predict outcomes. while europe was mired in its dark years of medieval superstition, the work of combining theory and experiment was advanced primarily in the islamic world. muslim scientists often also worked as scientific instrument makers, which made them experts at measurements and applying  theories. the arab physicist ibn al-haytham, known as alhazen, wrote a seminal text on optics in 1021 that combined observations and experiments to develop a theory of how human vision works, then devised further experiments to test the theory. his ideas and methods became a foundation for the work of alberti and leonardo four centuries later. meanwhile, aristotle’s science was being revived in europe during the thirteenth century by scholars such as robert grosseteste and roger bacon. the empirical method used by bacon emphasized a cycle: observations should lead to a hypothesis, which should then be tested by precise experiments, which would then be used to refine the original hypothesis. bacon also recorded and reported his experiments in precise detail so that others could independently replicate and verify them. leonardo had the eye and temperament and curiosity to become an exemplar of this scientific method. “galileo, born 112 years after leonardo, is usually credited with being the first to develop this kind of rigorous empirical approach and is often hailed as the father of modern science,” the historian fritjof capra wrote. “there can be no doubt that this honor would have been bestowed on leonardo da vinci had he published his scientific writings during his lifetime, or had his notebooks been widely studied soon after his death.”12 that goes a step too far, i think. leonardo did not invent the scientific method, nor did aristotle or alhazen or galileo or any bacon. but his uncanny abilities to engage in the dialogue between experience and theory made him a prime example of how acute observations, fanatic curiosity, experimental testing, a willingness to question dogma, and the ability to discern patterns across disciplines can lead to great leaps in human understanding. patterns and analogies in lieu of possessing abstract mathematical tools to extract theoretical laws from nature, the way copernicus and galileo and newton later did, leonardo relied on a more rudimentary method: he was able to see patterns in nature, and he theorized by making analogies. with his keen observational skills across multiple disciplines,  he discerned recurring themes. as the philosopher michel foucault noted, the “protoscience” of leonardo’s era was based on similarities and analogies.13 because of his intuitive feel for the unity of nature, his mind and eye and pen darted across disciplines, sensing connections. “this constant search for basic, rhyming, organic form meant that when he looked at a heart blossoming into its network of veins he saw, and sketched alongside it, a seed germinating into shoots,” adam gopnik wrote. “studying the curls on a beautiful woman’s head he thought in terms of the swirling motion of a turbulent flow of water.”14  his drawing of a fetus in a womb hints at the similarity to a seed in a shell. when he was inventing musical instruments, he made an analogy between how the larynx works and how a glissando recorder could perform similarly. when he was competing to design the tower for milan’s cathedral, he made a connection between architects and doctors that reflected what would become the most fundamental analogy in his art and science: that between our physical world and our human anatomy. when he dissected a limb and drew its muscles and sinews, it led him to also sketch ropes and levers. we saw an example of this pattern-based analysis on the “theme sheet,” where he made the analogy between a branching tree and the arteries in a human, one that he applied also to rivers and their tributaries. “all the branches of a tree at every stage of its height when put together are equal in thickness to the trunk below them,” he wrote elsewhere. “all the branches of a river at every stage of its course, if they are of equal rapidity, are equal to the body of the main stream.”15 this conclusion is still known as “da vinci’s rule,” and it has proven true in situations where the branches are not very large: the sum of the cross-sectional area of all branches above a branching point is equal to the cross-sectional area of the trunk or the branch immediately below the branching point.16 63leonardo da vinci – the scientist another analogy he made was comparing the way that light, sound, magnetism, and the percussion reverberations caused by a hammer blow all disseminate in a radiating pattern, often in waves. in one of his notebooks he made a column of small drawings showing how each force field spreads. he even illustrated what happened  when each type of wave hits a small hole in the wall; prefiguring the studies done by dutch physicist christiaan huygens almost two centuries later, he showed the diffraction that occurs as the waves go through the aperture.17  wave mechanics were for him merely a passing curiosity, but even in this his brilliance is breathtaking. the connections that leonardo made across disciplines served as guides for his inquiries. the analogy between water eddies and air turbulence, for example, provided a framework for studying the flight of birds. “to arrive at knowledge of the motions of birds in the air,” he wrote, “it is first necessary to acquire knowledge of the winds, which we will prove by the motions of water.”18  but the patterns he discerned were more than just useful study guides. he regarded them as revelations of essential truths, manifestations of the beautiful unity of nature. curiosity and observation in addition to his instinct for discerning patterns across disciplines, leonardo honed two other traits that aided his scientific pursuits: an omnivorous curiosity, which bordered on the fanatical, and an acute power of observation, which was eerily intense. like much with leonardo, these were interconnected. any person who puts “describe the tongue of the woodpecker” on his todo list is overendowed with the combination of curiosity and acuity. his curiosity, like that of einstein, often was about phenomena that most people over the age of ten no longer puzzle about: why is the sky blue? how are clouds formed? why can our eyes see only in a straight line? what is yawning? einstein said he marveled about questions others found mundane because he was slow in learning to talk as a child. for leonardo, this talent may have been connected to growing up with a love of nature while not being overly schooled in received wisdom. other topics of his curiosity that he listed in his notebooks are more ambitious and require an instinct for observational investigation. “which nerve causes the eye to move so that the motion of one eye moves the other?” “describe the beginning of a human when it is in the womb.”19and along with the woodpecker, he lists “the jaw  of the crocodile” and “the placenta of the calf ” as things he wants to describe. these inquiries entail a lot of work.20 his curiosity was aided by the sharpness of his eye, which focused on things that the rest of us glance over. one night he saw lightning flash behind some buildings, and for that instant they looked smaller, so he launched a series of experiments and controlled observations to verify that objects look smaller when surrounded by light and look larger in the mist or dark.21  when he looked at things with one eye closed, he noticed that they appeared less round than when seen with both eyes, so he went on to explore the reasons why.22 kenneth clark referred to leonardo’s “inhumanly sharp eye.” it’s a nice phrase, but misleading. leonardo was human. the acuteness of his observational skill was not some superpower he possessed. instead, it was a product of his own effort. that’s important, because it means that we can, if we wish, not just marvel at him but try to learn from him by pushing ourselves to look at things more curiously and intensely. in his notebook, he described his method—almost like a trick—for closely observing a scene or object: look carefully and separately at each detail. he compared it to looking at the page of a book, which is meaningless when taken in as a whole and instead needs to be looked at word by word. deep observation must be done in steps: “if you wish to have a sound knowledge of the forms of objects, begin with the details of them, and do not go on to the second step until you have the first well fixed in memory.”23 another gambit he recommended for “giving your eye good practice” at observations was to play this game with friends: one person draws a line on a wall, and the others stand a distance away and try to cut a blade of straw to the exact length of the line. “he who has come nearest with his measure to the length of the pattern is the winner.”24 leonardo’s eye was especially sharp when it came to observing motion. “the dragonfly flies with four wings, and when those in front are raised those behind are lowered,” he found. imagine the effort it took to watch a dragonfly carefully enough to notice this. in his notebook he recorded that the best place to observe dragonflies was by the  moat surrounding the sforza castle.25  let’s pause to marvel at leonardo walking out in the evening, no doubt dandily dressed, standing at the edge of a moat, intensely watching the motions of each of the four wings of a dragonfly. his keenness at observing motion helped him overcome the difficulty of capturing it in a painting. there is a paradox, which goes back to zeno in the fifth cen64 walter isaacson tury  bc, involving the apparent contradiction of an object being in motion yet also being at a precise place at a given instant. leonardo wrestled with the concept of depicting an arrested instant that contains both the past and the future of that moment. he compared an arrested instant of motion to the concept of a single geometrical point. the point has no length or width. yet if it moves, it creates a line. “the point has no dimensions; the line is the transit of a point.” using his method of theorizing by analogy, he wrote, “the instant does not have time; and time is made from the movement of the instant.”26 guided by this analogy, leonardo in his art sought to freeze-frame an event while also showing it in motion. “in rivers, the water that you touch is the last of what has passed, and the first of that which comes,” he observed. “so with time present.” he came back to this theme repeatedly in his notebooks. “observe the light,” he instructed. “blink your eye and look at it again. that which you see was not there at first, and that which was there is no more.”27 leonardo’s skill at observing motion was translated by the flicks of his brush into his art. in addition, while working at the sforza court, he began channeling his fascination with motion into scientific and engineering studies, most notably his investigations into the flight of birds and machines for the flight of man. references 1. codex atl., 119v/327v; notebooks/j. p. richter, 10–11; notebooks/irma richter, 4. in his commentaries, carlo pedretti (1:110) dates this page to circa 1490. 2. codex atl., 196b/596b; notebooks/j. p. richter, 490. 3. brian richardson,  printing, writers and readers in renaissance italy  (cambridge, 1999), 3; lotte hellinga, “the introduction of printing in italy,” unpublished ms., university of manchester library, undated. 4. a fuller description can be found in nicholl, 209, and kemp marvellous, 240. 5. notebooks/j. p. richter, 1488, 1501, 1452, 1496, 1448. vitolone is a text on optics by a polish scientist. 6. paris ms. e, 55r; notebooks/irma richter, 8; james ackerman, “science and art in the work of leonardo,” in o’malley, 205. 7. paris ms. a, 47r; capra science, 156, 162. 8. for more, see leopold infeld, “leonardo da vinci and the fundamental laws of science,”  science & society 17.1 (winter 1953), 26–41. 9. codex atl., 730r; leonardo on painting, 256. 10. codex atl., 200a/594a; notebooks/j. p. richter, 13. 11. paris ms. g, 8a; codex urb., 39v; notebooks/j. p. richter, 19; pedretti commentary, 114. 12. capra learning, 5. 13. james s. ackerman, “leonardo da vinci: art in science,” daedalus 127.1 (winter 1998), 207. 14. gopnik, “renaissance man.” 15. paris ms. i, 12b; notebooks/j. p. richter, 394. 16. ryoko minamino and masakai tateno, “tree branching: leonardo da vinci’s rule versus biomechanical models,” plos one 9.4 (april, 2014). 17. codex atl., 126r-a; winternitz, “leonardo and music,” 116. 18. paris ms. e, 54r; capra learning, 277. 19. windsor, rcin 919059; notebooks/j. p. richter, 805. 20. windsor, rcin 919070; notebooks/j. p. richter, 818– 19. 21. codex atl., 124a; notebooks/j. p. richter, 246. 22. paris ms. h, 1a; notebooks/j. p. richter, 232. 23. codex ash., 1:7b; notebooks/j. p. richter, 491. 24. codex ash., 1:9a; notebooks/j. p. richter, 507. 25. codex atl., 377v/1051v; notebooks/irma richter, 98; stefan klein, leonardo’s legacy(da capo, 2010), 26. 26. codex arundel, 176r. 27. paris ms. b, 1:176r, 131r; codex triv., 34v, 49v, codex arundel, 190v; notebooks/irma richter, 62–63; nuland,  leonardo da vinci, 47; keele  elements, 106. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 3(1): 101-111, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-69 citation: f. barzagli, f. mani (2019) the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming?. substantia 3(1): 101-111. doi: 10.13128/substantia-69 copyright: © 2019 f. barzagli, f. mani. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 1 university of florence, department of chemistry, via della lastruccia 3, 50019 sesto fiorentino, italy 2 iccom cnr, via madonna del piano 10, 50019 sesto fiorentino, italy e-mail: fabrizio.mani@iccom.cnr.it abstract. some frozen bodies have been recently discovered in the alp glaciers because the global warming is forcing the ice to retreat. many years have passed since the first perception of a strong link between the temperature of the earth and the amount of some gases in the atmosphere, the so called greenhouse gases. today there is a general consensus among the governments, the scientists and industrial organizations of most countries in recognizing the relationship between the increase of the atmospheric co2 concentration resulting from over a century of combustion of fossil fuels and the observed global warming. the development of technologies to reduce the anthropogenic emissions should not be further delayed, in accordance with the paris agreement that recommended keeping the global mean temperature well below 2 °c above pre-industrial levels to reduce the risks and impacts of climate change. this paper gives an overview of the different greenhouse gases, their emissions by economic sectors and the international treaties that require the most developed countries to pursue the objective of reducing their greenhouse gas emissions. amongst the different actions directed towards a low-carbon economy, the chemical capture of co2 from large stationary emission points is the most efficient and widespread option. additionally, new technologies are currently exploited to capture co2 directly from air and to convert co2 into fuels and valuable chemicals. keywords. global warming, climate changes, greenhouse gas emissions, co2 capture, co2 utilization. the global warming and the policies for its mitigation it is very likely the relationship between the earth’s temperature, climate and the concentration of some gases, the so called greenhouse gases (ghgs), in the atmosphere. as a matter of fact, the greenhouse effect made our planet habitable with an average temperature of 18 °c, otherwise it would be – 19 °c. 102 francesco barzagli, fabrizio mani if we look back to hundreds of thousands years ago, cooler glacial and warmer interglacial cycles occurred with periods of about 100,000 years (figure 1). they are related to the variation of the amount of solar radiation with time, caused by the precession of the equinoxes (the rotation of the earth’s direction axis), the variation of the obliquity of the earth’s axis with respect to the perpendicular to the plane of the orbit around the sun, and the variation of the eccentricity of the orbit that varies the earth-sun distance. it must be noted that the variation of co2 concentration over time was a consequence of the variation of the temperature: the increasing temperature released more dissolved co2 from the oceans and permafrost, thus increasing the greenhouse effect that accelerated the global warming. the opposite effect occurred when the temperature decreased. the last glacial period ended about 21,000 years ago, and currently we are in an interglacial period of very low increasing earth’s temperature that has been accelerated in the last century, most likely by the increasing ghg emissions from human activities. the anthropogenic ghg emissions, predominantly carbon dioxide, add to the “natural” greenhouse effect and could result in earth’s temperature rising and subsequent climate change. the “greenhouse effect” and the global warming have a long history, that started two centuries ago. the famous french mathematician and natural philosopher jean-baptiste fourier (auxerre, 1768 – paris, 1830), suggested in the late 1820 that the atmosphere limits the heat loss from the earth’s surface, that is warmer than it would be in the absence of this effect. in 1860 john tyndall (leighlinbridge, 1820 – haslemere (uk), 1893), an irish scientist, measured the absorptive power of some gases and discovered that water vapour and “carbonic acid” (carbon dioxide) absorb the re-emitted heat from the earth’s surface that cools overnight. he realised that climate changes could be related to the concentration of these gases. svante arrhenius (vik, 1859 – stockholm, 1927), a swedish physicist and chemist, nobel laureate for chemistry in 1903, in 1896 calculated that 50% increase of co2 concentration in the atmosphere would take thousands of years and would increase the earth’s temperature of 2.5-3 °c. arrhenius concluded that the world population would benefit in the future from a warmer climate that would prevent new glacial ages, thus affording more land for harvesting. contrary to the arrhenius’ belief, the 50% of co2 concentration has increased in the last two centuries, because of the fossil fuel combustion to sustain the continuously increasing demand of energy of the industrial revolution and the economic growth of the population that, additionally, rose from about 1 billion in 1800 to today 7.6 billion. now, there is a general consensus among the governments, the scientists, and industrial organisations of most countries about the correlation (95-100% probability) between the ghg emissions in the atmosphere originating from the human activities, the rise of the earth’s temperature and the climate change (figure 2).3-5 it has become a worldwide priority to reduce the anthropogenic ghg emissions, particularly those of co2, the main component of ghgs, together with the techniques for the adaptation to climate change. afterwards the first stations at south pole and mauna loa, hawaii, in 1950 began measuring the co2 concentration in the atmosphere, accurate data were available. in 1988 the intergovernmental panel on climate change (ipcc) was established by the world meteorological organization (wmo) and the united nations environmental programme (unep) to provide “policyfigure 1. correlation between co2 concentration1 in the atmosphere and earth’s temperature2 over the last 800,000 years. temperature change is the difference from the average of the last 1000 years. figure 2. correlation between the change in the mean annual temperature records and the co2 concentration. temperature data from nasa/giss;3 co2 concentration data from mauna loa, hawaii,4 and from ice cores from law dome, antarctica.5 103the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature makers with regular assessments of the scientific basis of climate change, its impacts and future risks, and options for adaptation and mitigation”. until now ipcc has released f ive assessment reports,6,7 and the sixth will be completed in 2021. the fifth assessment report (ipcc ar5)8 is referred to 2014 and is based on the work of 831 worldwide experts on physics, engineering, chemistry, meteorology, oceanography, ecology, economics. the scenarios provided on the ghg emissions by human activities and global warming are indisputable. the co2 concentration in the atmosphere, largely the main component of ghgs, increased from 280 ppm (0,028 % v/v) of the pre-industrial level (the beginning of the industrial society is conventionally fixed to 1750) to today 410 ppm (0,041%; april 2017). in the same time the earth’s temperature increased approximately of 1.0÷1.2 °c, most of which in the last century. before 1750 the mean temperature, even if with ± 0.3 °c variations, and ghg concentration remained roughly constant for hundreds of years. carbon dioxide emissions from fossil fuel combustion and industrial processes account for about 76% of the current total ghg emissions. the percentage of the other ghgs is reported in table 1 as co2-equivalent (co2eq), that takes into account for the relative amount of emissions and for the global warming potential (gwp) relative to co2.9 gwp100 measures the warming effect of a mass of a ghg relative to that of the same mass of co2, over a period of 100 years. the lifetime of each ghg in the atmosphere, and consequently its gwp, is different to each other, because of the different reactivity with the other components of the atmosphere and with solar radiation. about 75% of overall anthropogenic co2 emissions between 1750 and 2010 occurred in the last 60 years, because of the unrestrainable growth of the population (from 2.5 billion in 1950 to 7.6 billion in 2018), the energy intensive lifestyle of the population and the economic activities of the developed countries, and the socioeconomic growth of rapidly developing countries (currently, china, india, brazil), that require more and more energy production. total anthropogenic ghg emissions increased over 1970 to 2012 of 91% from 24 to 47 gtonne co2eq/y, the highest in human history. also the rate of warming of the atmosphere and ocean since 1950 is the greatest ever recorded.10 the kyoto protocol (december 1997) is an international treaty that commits the 39 most industrialised countries to tackle the global warming by reducing their ghg emissions in the atmosphere to a level that “would prevent dangerous anthropogenic interference with the climate system”. the six greenhouse gases taken into consideration by the kyoto protocol were carbon dioxide (co2), methane (ch4), dinitrogen oxide (n2o), sulfur hexafluoride (sf6), hydrofluorocarbons (hfcs) and perfluorocarbons (pfcs) (table 1). the treaty was signed and ratified by 187 countries and entered into effect on 2005, after being ratified by at least 55 of the most industrialised countries which accounted in total for at least 55% of the total co2 emissions for 1990 (“55%” clause). usa and australia did not ratify the treaty; china, india and brazil had no targets of reduction. by 2012 the signatory countries should have fulfilled the cut of ghg emissions of 5.2% below the 1990 level (–8% for european union); the reduction target 2013-2020 should be –18%. european union met the objective of kyoto protocol by 2011. in the 21st paris climate conference (cop21, 2015), an agreement was signed by 195 countries and entered in force in 2016. for the first time the countries signatories agree to carry out actions to limit the increase of the earth’s temperature in the range 1.5 2 °c above preindustrial levels; the increase of temperature from today should be comprised between 0.65 °c and 1.15 °c. each country is committed to provides the ghg inventories every five years, starting from 2023. however, it must be pointed out that the paris protocol is not a legally binding treaty, and, additionally, a country that did not accomplish its reduction target may purchase carbon credits (ghg certificates) from other countries that have no reduction obligation or are below their reduction target. in 2017 donald trump declared he is going to withdraw us from the paris agreement, which was previously signed by the former us president barack obama. to keep the temperature increase below 2 °c relative to pre-industrial level, the co2 concentration in the atmosphere by 2100 should be about 450 ppm, compared to current 410 ppm. the fulfilment of that objective relies on some strategies, namely reducing fossil fuel table 1. contribution of each gas to global ghg emissions, relative to co2, based on the amount of gas emitted and on the relative global warming potential (gwp100). gwp100 emissions (co2eq) co2 1 76% ch4 21 16% n2o 310 6% hfc/pfca 650 ÷ 11,700 2%b sf6 23,900 a hydrofluorocarbons (hfcs) and perfluorocarbons (pfcs); b summed fluorides. 104 francesco barzagli, fabrizio mani combustion increasingly substituted by renewable energy sources, improving the efficiency of energy production and use, enhancing the co2 capture from large-point sources, the so called carbon capture and sequestration (ccs) technology. without mitigation scenarios, by 2100 the co2 concentration in the atmosphere is expected to increase up to 750 ppm and the earth’s surface temperature between 3.7 to 4.8 °c. obviously, the mitigation objectives cannot be an obstacle to the increasing food production and to the socio-economic development of the world population that is expected to grow to at least 9 billion over the next 35 years. from the data reported in table 1 it is clear that the greatest contribution to the overall ghg effect comes from co2 emissions, mainly originating from fossil fuel combustion in power plants, transportation and building heating. livestock farming, agricultural and other land use, waste management, account for most of nonco2 (ch4 and n2o) ghg emissions. due to their sparse point sources, most of the non-co2 emissions cannot be abated. consequently, the strategies aimed at reducing the overall ghg emissions should be focused on the abatement and capture of co2 emissions from the energy sectors (fossil fuel power generation without ccs technology should phase out by 2100),8 industry and transport. in summary, most of the sectors of the human activities must be redirected towards a sustainable low– carbon economy. replacing coal and oil by less carbon containing fuels in all of the sectors of energy production, are feasible objectives. for instance, an immediate great contribution to the co2 emission abatement from combustion (between 11% and 25%) should be gained by replacing carbon rich fossil fuels with natural gas (ch4). the global ghg emissions by economic sector are reported in table 2. low carbon electricity must play a crucial role in accelerating the global transformation to a low-carbon society, by substantially increasing the use of renewable technologies: photovoltaic cells, wind farm, solar energy, will continue to grow and to become cheaper and more competitive compared to fossil fuel combustion. however, it must be pointed out that wind and solar are intermittent energy sources, and their transformation and storage in the form of chemical energy would be a feasible solution. nuclear energy also cannot be omitted, even though in europe its contribution is decreasing; however, contrary to popular belief and mass media information, 59 new nuclear reactors are under construction around the world. in europe, the production of electricity by renewable sources (wind, solar, biomass) should increase from the current 32% to 80% by 2050. afforestation, reduced deforestation and bioenergy production are natural sinks of co2. to date, the decarbonisation of energy generation occurs at a greater rate than in industry, building and transport sectors. as worldwide transportation sector accounts for about 20% of co2 emissions from fossil fuel combustion, it is expected a substantially reduction of the co2 emissions attained from technological innovations that include more efficient thermal engines, cleaner fuels (natural gas, biofuels produced by biomass and regenerated fuels), light materials and electric propulsion systems. hybrid, plug-in-hybrid and full electric vehicles (powered by improved batteries or fuel cells) should eventually replace those equipped with thermal engines. by 2025, it is expected that the electric cars equipped with more efficient batteries will have cruising range over 600 km and substantial reduction of charge time. sustainable biofuels should replace kerosene in aviation and diesel fuel in heavy duty trucks. the building conditioning should reduce their co2 emissions by about 90% by 2050: this objective can be achieved by the new zero-energy buildings, and by refurbishing as much as possible the yet existing buildings, in particular the commercial and tertiary ones. the industrial sector, especially the cement and steel production, could reduce their ghg emissions (mostly co2) by about 80% with more energy efficient processes and increased recycling of the wastes and by-products. also, ccs technology should be applied to reduce co2 emissions of the industrial sector. the agricultural sector is expected to have a less impact in the ghg reduction with a non-co2 ghg emission (ch4 and n2o) reduced by 45-50%, thanks to an improved land and fertiliser use, improved livestock farming, and bio-gas recovery from organic manure. moreover, improved agricultural and forestry activities can increase co2 sink and can provide feedstock for energy and industry. it must be considered that the biosphere (land and oceans) takes part to the global cycle of co2 through photosynthesis of green plants and phytoplankton, that represent a natural 50% sink of the global anthropogenic emissions of co2. table 2. the global ghg emissions percentage by economic sector.a power plants 38% agriculture and forestry 22% transport 20% buildings 10%b industry 10%b a there is poor agreement amongst different sources on the share of individual sector: the data are adapted from references 8 and 11; b doesn’t comprise the consumption of electricity. 105the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature it is hard to believe that hydrogen could be a substitute of fossil fuels in a short-term (hydrogen economy), even if it could have a crucial role in the conversion of co2 into liquid fuels. hydrogen is currently produced by fossil fuels (mostly from methane), because its production from water electrolysis is not cost-effective. finally, an appreciable contribution to the mitigation scenarios could be given by a less energy consuming lifestyle of the population of the most developed countries, for instance less mobility demand, less energy use in households, choice of longer-lasting products, less disposable items, reduction in food wastes; moreover, it would be highly beneficial recycling wastes into industrial new products (italy is a european leader in this field). noticeable, thanks to the policies of low-carbon technologies, yet worldwide adopted mostly for energy production, the global emissions of co2 remained stable to 35.8 gton co2/year in the last three years (2014-2016). on the contrary, the ghg emissions increased in 2017 because of the growing industrial emissions that weren’t compensated by the increased energy production by renewables and by the reduction of coal use. benefiting from low-carbon energy sources and energetic efficiency, european union has set up the ambitious objective of the following reductions compared to 1990, to be completed before 2020 (before 2030 in parenthesis):11 1) 20% (40%) reduction of ghg emissions; 2) 20% (27%) of the overall energy from renewable sources; 3) 20% (27%) of the increase of energetic efficiency. currently the 26% reduction of co2 emissions has been attained in italy. by 2050 the reductions of ghgs in the 28 countries of the european union should be: co2 – 63%; ch4 – 60%; n2o – 26%. nevertheless, it must be pointed out that europe accounts for only 9.6% of the worldwide co2 emissions (compared to 14.0% of us and 29.2% of china; 2016 data),10 and once these objectives were reached, they would not sufficient for the 2 °c target. last but not least scenarios are the technologies of co2 capture from large point sources (the co2 concentration in the exhaust gases may be comprised between 5% and 40% v/v), such as fossil fuelled power plants and some industrial processes, and the safe co2 storage underground (ccs technology). notwithstanding its low concentration (0,04% v/v), co2 can be also captured directly from air (dac technology). contrary to the co2 storage, in the carbon capture and utilization option (ccu technology), pure co2 could be used as a feedstock for producing chemicals and fuels. technologies of co2 separation from gas mixtures the co2 separation from gas mixtures is a technology applied at industrial scale in hydrogen and ammonia production, natural gas processing and sweetening. these methodologies can be also applied to large fixedpoint sources, such as cement and steel production, and to post combustion gases from fossil fuelled power plants, the main sources of ghg emissions (table 2). chemical capture of co2 by a liquid alkaline solution (the absorbent) is recognized as the most efficient technology for dilute co2 (low partial pressure) removal from a gas mixture. different technologies for co2 capture have been also proposed, based on physical methods, cryogenic and membrane separation processes, biological fixation, but none of them went into application to large scale separation of co2 from exhaust gases because of the low efficiency or high costs. in this section, an overview of the chemical capture of co2 with possible application to power plants is presented.12,13 combustion of fossil fuels with air produces exhaust gases containing 4-15% (v/v) co2, n2 (from air), with residual o2, water vapour, and variable amount of sulfur and nitrogen oxides as well as particulate matter. the co2 percentage depends on the carbon content of the fossil fuel and the technology employed: the lowest value refers to a gas turbine combined cycle, where the combustion is accomplished with a large excess of air. a typical coal-fired power plant of 1000 mw can emit about 3·106 m3/h of exhaust gases containing 15% (v/v) of co2.14 the storage underground of that huge amount of combustion gases is not a feasible option, because of the high compression costs and of the very large geologic reservoirs where the gas mixture should be stored. on the other hand, the storage in the deep sea is not safe, and would increase the water acidity which is harmful for sea life. therefore, it is firstly necessary to remove co2 from the gas mixture, afterwards the nearly pure co2 is compressed and injected underground (carbon capture and storage, ccs technology). an accurate geological investigation must be performed to select the site of co2 storage, that should reduce as most as possible leakage in time of sequestered co2 from the reservoirs.15 the employed technologies for the chemical capture of co2 are substantially similar to each other and differ, at most, in the liquid absorbents. to be a cost-effective process and to avoid millions of tons of wastes per year (the carbonated absorbent), the co2-loaded absorbent 106 francesco barzagli, fabrizio mani must be regenerated and recycled: the reactions of co2 with the absorbent must be reversible. the equipment for co2 capture comprises the stainless-steel absorber (the scrubber) and desorber (the stripper) units connected to each other through a heat exchanger (figure 3). the absorber and the desorber are packed columns that maximize the gas-liquid exchange surface, thereby enhancing the reaction rate. the absorbent circulates continuously between the two devices in a continuous cyclic process. the gas stream (12-15 % co2 v/v) is injected to the absorber (kept at about 40-50 °c) and the carbonated solution exiting from the absorber is preheated by the cross-heat exchanger and sent to the desorber where it is heated to 110-130 °c (at pressure of 1-2 bar) by steam. the regenerated solution is cooled and then it is circulated back to the absorber and reused for further co2 capture. finally, the nearly pure co2 released from the top of the stripper can be compressed at 100-200 bar and transported to the storage site by a pipeline. the size of the equipment to be fitted in a power plant is proportional to the flow rate of the exhaust gas i.e. to the amount of co2 to be captured. the height/ diameter of the packed columns may be 15 m/7 m for the absorber and 10 m/4.5 m for the desorber; the plants have a capacity of co2 capture in the range of 3-4·106 tonne/year. most of the absorbents for co2 removal from gas mixtures are based on aqueous solutions of primary and secondary alkanolamines;12-17 a few examples are: mea (monoethanolamine) 2-aminoethanol nh2 ho dea (diethanolamine) 2,2’-iminodiethanol h n ho oh amp (aminomethylpropanol) 2-amino-2-methyl-1-propanol nh2 ho the hydroxyl functionality of the amines provides their sufficient solubility in water and substantially lowers their vapour pressure, to reduce as much as possible the amine loss by evaporation. in the continuous search of more efficient absorbents, blends of amines and nonaqueous absorbents have been also investigated.18-21 the concentration of the aqueous absorbents is usually limited to 30% (wt/wt), to reduce corrosion of the equipment and amine loss by heating, yet pursuing the target of 90% (v/v) of co2 removal from the gas stream. the main reactions of co2 with aqueous primary and secondary alkanolamines are: amh + co2 + h2o ⇄ hco3– + amh2+ (1) 2amh + co2 ⇄ amco2– + amh2+ (2) where amh denotes the free amine; amco2– and amh2+ indicate, respectively, the amine carbamate and the protonated amine. equation (2) doesn’t apply to tertiary amines that are unable to form carbamate, as well as to amines featuring steric hindrance around the amine functionality (amp) because the carbamate is less stable than bicarbonate in aqueous solution. the forward reactions (1) and (2) are exothermic and the reverse endothermic reactions account for co2 release and amine regeneration in the desorber. whatever the technolog y and absorbent may be used, the overall process of co2 separation from gas mixtures is energy intensive, therefore the co2 capture from a fossil fuelled power plants reduces the output electric power by 20% up to 40%, depending on the process configuration and fuel used; the cost of co2 capture from a power plant can be as high as 50-60 $/tonne co2. as a result, more fuel is consumed (additional 15-45%), more co2 is emitted that must be captured, for a given output of electric power.22-26 the main operating cost of any process of co2 removal is the heat for absorbent regeneration, namely to reverse the exothermic absorption reactions (1) and (2). additional energy is required to pump the absorbent within the entire apparatus and for final co2 compression. moreover, the thermal and oxidative degradation of the alkanolamines may be another serious concern in the ccs technology.27 figure 3. a simplified flow sheet for the co2 removal process 107the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature compared to organic absorbents, very few inorganic solvents have been investigated, mainly aqueous na2co3, k2co3 and nh3. aqueous alkali carbonates do not suffer of thermal degradation and loss of the absorbent, have low regeneration energy and high absorption capacity (mass co2/ mass absorbent), but have low rate of reaction with co2.28 co32– + co2 + h2o ⇄ 2hco3– (3) absorbents based on aqueous nh3 display fast absorption rate, significantly lower regeneration energy and thermal and oxidative stability compared to alkanolamines, but entail a major concern related to its high volatility.29-31 the reactions of aqueous ammonia with co2 are: nh3 + co2 + h2o ⇄ hco3– + nh4+ (4) nh3 + hco3– ⇄ co32– + nh4+ (5) in the absence of water, ammonium carbamate is the sole reaction product 2nh3 + co2 ⇄ nh2co2– + nh4+ (6) with the purpose of substantially reducing the energy penalty of absorbent regeneration, new absorbents based on “ionic liquids” and “demixing solvents” have been recently developed. both methodologies avoid the heat wasted to bring the diluent to the desorption temperature (sensible heat), a significant share of the overall desorption energy; it must be pointed out that water account for 70 wt% of the aqueous absorbents. additional cost saving and advantages come from the reduced size of the equipment and from the negligibly vapour pressure and high thermal stability of ionic liquids. ionic liquids are organic salts in the liquid phase at room temperature (rtils): as an example of a common ionic liquid, the chemical structure of 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]pf6), a common ionic liquid is reported. n n p f f f f f f one-component rtils containing an amine functionality or mixtures of rtils and alkanolamines have been exploited for the co2 capture.32-34 because those absorbents are liquid before and after the co2 capture, no added diluent is necessary. to overcome the intractable viscosity of most of the carbonated absorbents based on rtils, commercially available and inexpensive secondary amines (2-(butylamino)ethanol, for example) have been recently formulated35,36 that reversibly react with co2 at room temperature and pressure to form liquid carbonated species without any aqueous or organic diluent. demixing solvents are based on two liquid-liquid phase separation. upon co2 capture, some aqueous or non-aqueous amines split into two separate, immiscible, liquid phases (figure 4) which separate by virtue of their different density.37,38 only the lower phase that contains the carbamate and the protonated amine must be thermally regenerated, thus avoiding to heat the diluent in the upper phase. direct co2 capture from the atmosphere the objective of zero-emission energy should be fulfilled by 2100 in most of the developed countries. meanwhile, the lifetime of co2 in the atmosphere and the inertia of the climate change, strongly suggest to reduce figure 4. two liquid phase recovered from co2 capture: the lower phase is the carbonated absorbent and the upper phase is predominantly the diluent with a small amount of the amine carbamate. 108 francesco barzagli, fabrizio mani the co2 concentration in the atmosphere. moreover, the direct co2 capture from air (dac technology) is the only method to contrast the dispersed emissions from transport, heating systems of buildings and biomass burning, that cannot be captured at their sparse sources. a comprehensive overview of dac is provided by the american physical society report (june 2011).39 the dac method is at the early stage of investigation and no proposed process is today suitable for large scale application because of the low efficiency and high costs. because of the very low concentration of co2 in the air (0,04% v/v), large air-absorbent contactors are necessary equipped with many fans to blow air to the absorber (figure 5). the absorbents so far used are concentrated aqueous solutions of naoh or koh (2–3 mol dm–3) which capture co2 as soluble na2co3 or k2co3; the efficiency of co2 capture is usually no more than 50%.40 to be a feasible process, the hydroxide regeneration is accomplished with lime 2na+ + co32– + ca(oh)2 → caco3 + 2na+ + 2oh– (7) once separated from the solution, calcium carbonate is calcinated at 900-1000 °c to restore quicklime (cao) and to release co2 caco3 → cao + co2 (8) the entire energy requirement of the process has been estimated 17 gj/tonne co2 captured (4.7·106 kwh/ tonne co2 captured) and about half is due to the calcium carbonate calcination.41 the production of the same amount of energy (thermal and electric) from coal combustion, releases in the atmosphere 1.89 ton of co2: more co2 is emitted than captured! the ch4 combustion produces less co2 but it doesn’t compensate the investment, maintenance and overall operational costs. to make the dac technology attractive, it is mandatory to produce the energy to run the process (thermal and electrical) with photovoltaic cells and solar heat concentration. benefiting of the advantage of the dac technology that can be placed everywhere, areas with higher solar radiation should be preferred. moreover, the aqueous naoh or koh solutions must be replaced by new absorbents that require less regeneration energy, yet maintaining sustainable efficiency. if that method will be successfully implemented at a pilot-scale, co2 will be captured from air by using the solar radiation, as green plants are used to do. from co2 to valuable products at present, the carbon capture and utilisation (ccu) technologies are non-profit options, because of their high costs. notwithstanding, the ccu technology is more and more studied, because it has the potential of converting co2 into value-added chemicals and synthetic fuels, combined with the mitigation of co2 emissions, yet at a low extent.42-48 in other words, the energy depleted co2 is captured and converted into reusable chemical energy, contrary to the co2 storage underground of ccs technology. it must be pointed out that ccs technology can store underground billions of tonnes co2 per year (about six million per year from a single 1000 mw power plant), whereas ccu relies on different products that overall could capture millions of tonnes of co2 per year. the very high stability of co2 (δg° = –395 kj mol–1) is a great advantage in the energy production from the combustion of carbon containing fuels [equation (9), for example], but has an adverse effect on its reactivity. for instance, the reverse of reaction (9) is thermodynamically disfavoured, whereas the reduction of co2 with hydrogen, [reaction (10)], features a severe kinetic obstacle; much energy together with catalysts therefore are necessary to convert co2 into useful chemicals. ch4 + 2o2 → co2 + 2h2o(g) (9) δh° = –803 kj mol–1 δg° = –801 kj mol–1 co2 + 3h2 → ch3oh + h2o (10) δh° = –131 kj mol–1 δg° = –9 kj mol–1 europe is leader in the study of the ccu technology, in particular germany, thanks to its long-lasting traditional leadership in the chemical industry. the first company that has demonstrated (2015) the feasibility of the production of a liquid fuel from co2, h2o and renewable energy is based in dresden. figure 5. proposed design to capture 1 million tonnes of co2 per year. photo-illustration: courtesy of carbon engineering ltd. 109the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature without any doubt, the most challenging option of ccu is the conversion of co2 into liquid fuels (power to liquid technology, ptl), to reduce the dependence from the fossil fuels and to address the progressive decarbonisation of the fuels for the transportation sector (an example of the so called circular economy). the most promising ptl technology is the methanol production,49 obtained by reacting co2 with hydrogen [equation (10)]. to increase its rate, the reaction is accomplished at 200 °c with copper-based catalysts; notwithstanding, the yield of reaction is no more than 40%, based on today technologies. the cost, mainly due to the cost of electricity, is estimated to be about 600-700 euro/tonne ch3oh, which is not competitive with the standard production of methanol from methane, and with the methane itself as a fuel. to be sustainable, the reaction (10) must be accomplished with solar and wind energy, so that intermittent and fluctuating energy is stored as disposable chemical energy of methanol. methanol, directly or in blends, can be used as fuel for thermal engines in transportation, or converted into gasoline (methanol to gasoline, mtg, process) or into dimethyl ether, a possible substitute of propane, a liquefied petroleum gas (lpg). liquified dme has been also proposed as an alternative fuel to diesel for compression ignition engines. combustion of dme eliminates particulate and greatly reduces nitrogen oxides from exhaust emissions, compared to conventional diesel fuel, but at the expense of about half energy density.50 biofuels as alternative to the fossil fuels are currently produced at industrial scale (millions of tonnes every year), mainly in brazil and usa. gasoline blended with 25% up to 85% of ethanol is delivered in usa, and ten million of vehicles in brazil are fuelled by 100% ethanol.51 all the efforts to imitate the photosynthesis of the green plants that converts sunlight into chemical energy are failed because the energy costs to produce useful chemicals from artificial photosynthesis by far overcome the energy output of the combustion of those artificial fuels. consequently, it is much more advantageous to allow the nature make most of the work. based on that strategy, ethanol is produced in brazil from sugarcane, whereas corn is the main feedstock in usa. biodiesel as alternative fuel for diesel engines is produced with the alkaly-catalyzed transesterification process which converts vegetal oils into methyl or ethyl esters, featuring a reduced viscosity compared to the natural sources.52 the production of biofuels points out some problems.51 the cost of the raw material (planting, irrigation, fertilization, harvesting and transportation) accounts for 60% to 75% of the cost of biodiesel producing. if the life cycle assessment of the process is taken into account, the biofuels are still not a viable alternative to fossil fuels, in the absence of the government support. as a final consideration, it should be a better option to use farmland for food production instead of crop-based biofuels. in the search of nonedible sources of biofuels, any form of biomass can be converted into a liquid fuel by means of a thermochemical process, but at unsustainable costs. in that contest, algae-based biodiesel has emerged as a promising option, because it doesn’t entail a reduction of food production and features a substantially higher photosynthetic efficiency compared to land crops.53,54 using co2 for the manufacture of plastics and speciality chemicals is a further option to store and re-use co2. however, the estimated worldwide production of such products is about 180 million tonnes every year, that corresponds to less than 1% of the anthropogenic co2 emissions. compared to the production of fuels, the production of chemicals doesn’t have an appreciable impact on the reduction of co2 emissions. taking the advantage of the thermodynamically favoured and fast acid-base reactions between co2 and nh3, it has been recently developed an innovative process that integrates the co2 capture with the production of urea, the most worldwide used nitrogen fertilizer, more than 108 tonne/year. the co2 capture (15% v/v in air) in water-ethanol produces solid mixtures of ammonium bicarbonate and carbamate [reactions (4), (6)]. by heating the solid mixtures at 165 °c in a closed vessel without any external pressure, both ammonium carbamate, and bicarbonate are converted into urea.55,56 nh2co2nh4 ⇄ nh2conh2 + h2o (11) 2nh4hco3 ⇄ nh2conh2 + co2 + 3h2o (12) the industrial production of urea is carried out with nh3 and purified co2 in the gas phase at high temperature (180 –230 °c) and pressure (150 – 250 bar). pure co2 is obtained by the conventional aqueous amine scrubbing and thermal stripping. the advantage of process based on the solid ammonium salts compared to the industrial process, is the potential energy saving because both the co2 purification step with aqueous amine scrubbing and the high pressure working are avoided, yet with efficiency (about 47% with respect to nh3) and reaction time (60 min at most) comparable with the industrial process. as a final consideration, 60 million tonnes of co2 are employed in different commercial sectors every year, and are currently extracted from natural sources under110 francesco barzagli, fabrizio mani ground. a cheap capture technology from exhaust gases yet recovering high purity co2, could replace the current co2 production that is re-emitted in the atmosphere and the end of its utilization cycle. conclusions the increased greenhouse effect originating from human activities is most likely responsible of the increase of earth’s temperature in the last century, and possibly of the climate change. the climate change has, and will have to a greater extent in the future, adverse impacts on the society development and world economy, because of the increasing extreme weather events such as storms, floods, drought and heat waves. the frequency of snowfall and rain is reduced in the recent years, but they are heavier. the objective of mitigation of climate change cannot be further delayed, and many possible actions have been proposed to reduce the ghg anthropogenic emissions. as most of the ghg emissions is due to combustion of fossil fuels, the reduction of dependence from fossil fuels would provide further benefits to the economy of most countries, whereas the improved air quality will have noticeable beneficial effects on human health. the world economy will be more and more dependent from solar and wind energy; this form of energy is intermittent, and its storage as chemical energy (renewable fuels) and chemicals (fertilizer, plastic) by using the 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separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 4(2): 125-137, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-851 citation: a.v. kessenikh (2020) estonian scientist in ussr (memories and reflections about endel lippmaa, 19302015). substantia 4(2): 125-137. doi: 10.13128/substantia-851 received: feb 01, 2020 revised: apr 14, 2020 just accepted online: apr 21, 2020 published: sep 12, 2020 copyright: © 2020 a.v. kessenikh. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh leading researcher of s.i.vavilov institute ras for history of science and technology 125315, moscow, baltiiskaya, 14, russia e-mail: kessen32@mail.ru;kessen@ihst.ru; orcid id 0000-0001-8727-4642 abstract. endel lippmaa estonian physicist and chemist was one of the pioneers in the development and application of nmr method (1950s-1970s). he had to work in conditions when estonia was part of the ussr as the estonian ssr and, nevertheless, the development of science in the republic was not interrupted. he later became an academician and vice-president of the academy of sciences of the estonian ssr. the important role of lippmaa in the development of nuclear magnetic resonance and other areas of chemical physics in estonia, the ussr, and around the world is considered. the article also contains the reminiscences considering personal contacts with lippmaa of the famous russian chemist yu.a. ustynyuk. in 1994 lippmaa was awarded the ampere prize for original research in high-resolution nmr of solid-state. perhaps in more favorable conditions, in contact with other eminent scientists who worked abroad, he would have achieved even greater results, but such contacts were during a long time difficult or impossible for him. keywords: endel lippmaa, estonia, soviet period, proton magnetic resonance, carbon-13 nmr, nmr high resolution in solid, ion cyclotron mass spectrometry. figure 1. endel lippmaa (photo 1970-s. author archive). http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia mailto:kessen32@mail.ru mailto:kessen@ihst.ru 126 alexandr vladimirovich kessenikh historical background (based on materials available on the internet) scientific and educational institutions in the history of estonia estonia became a battleground for centuries where denmark, germany, russia, sweden and poland fought their many wars over controlling the important geographical position of the country as a gateway between east and west. the «russian era» from the 1720s to the first world war, it was a time when german elites prevailed and even had some autonomy in the baltic countries. however, in those same years, the formation and consolidation of the estonian nation, its culture and language took place. there were also tendencies in russification of estonia. the impact of this was that many of the baltic german legal institutions were either abolished or had to do their work in russian – a good example of this is the university of tartu. it was founded under the name of academia gustaviana in 1632 , shortly before the king’s gustavus adolphus death on 6 november in the battle of lützen (1632), during the thirty years’ war (1618–1648). the university of tartu moved to tallinn in 1656, and in 1665, it closed down. the university was reopened by the baltic germans in estonia in april 1802. the language of instruction at dorpat (russian – “derpt”) was german from 1802 to 1893. during that time, dorpat had a dual nature in that it belonged both to the set of german-language and russian universities. tartu was a multicultural crossroads with strong representation of russians, germans and estonians. orthodox, lutherans and jews, scientists and humanists, all were quite active at the city’s university. since estonia became independent in 1918, the university of tartu has been an estonian-language institution since 1919. the university was named ostland-universität in dorpat during the german occupation of estonia in 1941–1944 and tartu state university (estonian: tartu riiklik ülikool) in 1940–1941 and 1944–1989, during the soviet rule, although estonian remained the principal language of instruction, some courses were taught in russian, with several russian curricula. before estonia independes young people from estonia had received their specialist education in st. petersburg, germany or riga. opportunities had to be sought for engineering-minded people to acquire an estonianbased education which was adapted to local conditions and needs; estonia was in the process of establishing itself as an independent country. on 17 september 1918, the estonian engineering society opened an estonian-based engineering school named special engineering courses. that date has been recognised as the founding date of tallinn university of technology. programmes were offered in mechanical, electrical, civil and hydraulic engineering, shipbuilding and architecture. in 1919, the school became the private tallinn college of engineering, which in 1920 was declared a state institution. teachers’ efforts to develop an estonian terminology for science and technology proved fruitful and the first engineering books were published. in 1923, the first engineering graduation theses were defended in estonia. in the same year, a state laboratory of materials testing opened for research work. by the 15 september 1936 act of the head of state, the school was granted university status, and named tallinn technical institute. the institute had two faculties: civil and mechanical engineering and chemistry and mining. in 1938, the name tallinn technical university (tallinna tehnikaülikool, ttü in estonian) was effective. in 1940 the faculty of economics, in 1958 the faculty of power engineering and in 1965 the faculty of control engineering were founded. the estonian academy of sciences was established in 1938. when soviet troops entered estonia the academy was dissolved on july 17, 1940. in june 1945 it was reestablished as the academy of sciences of the estonian ssr (estonian: eesti nsv teaduste akadeemia). in soviet times, it consisted of a central library and four divisions containing 15 research institutes as well as other scientific societies and museums. in april 1989, shortly before estonian independence, the academy regained its original name of estonian academy of sciences. the estonian scientific community was least affected by the repressions carried out by the soviet authorities and directed against country’s leading politicians, military officers, and many small private owners. remarks on the history of estonia in the soviet period after stalin’s death in 1955 the tv centre was built in tallinn; it began tv broadcasts on 29 june of that year. one positive aspect of the post-stalin era in estonia was the regranting of permission in the late 1950s for citizens to make contact with foreign countries. ties were reactivated with finland, and in the 1960s, a ferry connection was opened from tallinn to helsinki and estonians began watching finnish television. this electronic “window on the west” afforded estonians more information on current affairs and more access to western culture and thought than any other group in the soviet union. this heightened media environment was important in preparing estonians for their vanguard role in extending perestroika. see for example [1]. 127estonian scientist in ussr the tallinn song festival grounds, the venue for the song festivals, were built in 1960. communist party membership vastly expanded its social base to include more ethnic estonians. by the mid-1960s, the percentage of ethnic estonian membership stabilized near 50%. on the eve of perestroika the ecp claimed about 100,000 members; less than half were ethnic estonians and they totalled less than 7% of the country’s population. only after the khrushchev thaw period of 1956 did healthcare networks start to stabilise. due to natural development, science and technology advanced and popular welfare increased. all demographic indicators improved; birth rates increased, mortality decreased. healthcare became freely available to everybody during the soviet era. from the history of the scientific dynasty of lippmaa the ancestors of endel lippmaa during the reign of the german elites in baltic (during the eleventh and beginning of the twentieth centuries) bore the name “lippmann”. an outstanding scientist, botanist and chromatographer born at riga in 1904, endel’s father theodor lippmaa was registered under this name, but changed this name to consonant estonian after moving to the territory of independent estonia. unfortunately, the father of endel lippmaa tragically died on january 27, 1943 in tartu as a result of the bombing of the city by soviet aircraft. endel lippmaa left two sons jaak and mickey, who continued the scientific dynasty. introduction in the very beginning of the 1960-s among soviet physicists and chemists formulated a task to equip chemists with new instruments suitable for studying nuclear magnetic resonance spectra (nmr). european and american colleagues have already solved this problem (at the technical level of that time) by the efforts of the american company varian, with which some fairly weak european firms and japanese jeol competed. already in those years on the so-called «world level», it was impossible to imagine the identification of a new chemical compound without nmr spectra (most often 1h, sometimes 19f, 31p, 11b, etc.). however, in the ussr, nmr spectrometers were exotic, often useless for chemists due to their technical characteristics. they were manufactured and debugged in separate laboratories with rather outdated electromechanical workshops. the estonian engineer and scientist endel lippmaa who graduated in 1953 from the tallinn polytechnic institute and worked there, decided to devote his scientific activity to nmr. but as early as 1956, he became a candidate of technical sciences, having defended a thesis in the field of chromatography (the undoubted influence of the works of his father t. lippmaa). endel lippmaa’s activities for a considerable time were closely connected with the functioning of the entire soviet scientific community, especially the part of it that was engaged in the technique and application of magnetic resonance. subsequently, lippmaa contributed to the development of ioncyclotron resonance mass spectrometry (icr ms) first nmr spectrometer in estonia. the beginning after five years of painstaking work in 1962, e. lippmaa joined a cohort of nmr radiospectroscopists. he published a series of works on the construction of a high-resolution pmr spectrometer (proton magnetic resonance spectrometer) in the works of the tallinn polytechnic institute (tpi) [2,5]. the table shown in fig. 2 was apparently photocopied from the work of lippmaa [3], which was then kept in the «literature in the languages of the peoples of the ussr» hall of the russian state library preserved from soviet times. although the article was published in russian (annotations in english and estonian), estonian journals were supposed to be in the above named hall. the notes were on the text of the copy we received, supplemented by the author of the cited article by hand. for the first time this photocopy with notes was published in our book [6, p. 579]. we clarified the notes and allow ourselves to bring a table with the old and our necessary new additions. figure 2. a photocopy of the table from the lippmaa article that compares the characteristics of the instrument manufactured in his laboratory and the characteristics of the instruments of his predecessors. 128 alexandr vladimirovich kessenikh from the experience of cooperation with a specialist in the development of semi-industrial nmr spectrometers a.n. lyubimov and acquaintance with his attempts to “embed” his development at the plant [7] we know that the fatal limit of 1.5·10-7 is easily overcome with adequate heat treatment of the pole pieces of a magnet (annealing in a hydrogen atmosphere as an example), which is inaccessible, as a rule, for laboratory developers. we clarified the notes [6] and allow ourselves to bring a table with the old and our necessary new additions (see table 1). among the staff of lippmaa, as a true leader, you can identify assistants (a.sügis, abira olivsson), associate (v. sinevee) and followers (t. pehk, m. mägi). lippmaa went his own way, he studied all the available data from the experience of his predecessors, immediately chose an electromagnet, and not a permanent magnet. he himself checked the magnetic susceptibility of materials for manufacturing the details of the nmr sensor [4], applied the method of stabilization of resonance conditions along one of the lines in the nmr spectrum. moreover, as it became clear later, for this team the creation of a high-resolution nmr spectrometer for protons was only a necessary intermediate step. at the same time, lippmaa was not going to create a model of the nmr spectrometer that soviet industry could produce. his aim at the first stage was to create his own laboratory of chemical nmr radiospectroscopy. sector of physics at the institute of cybernetics in the early 1960’s. (at the end of 1961), lippmaa and his team became employees of the new academic institute of cybernetics (academy of sciences of estonia). institutes with such a name were created in several academies of sciences of the union republics of the ussr, for example, also in georgia, but this does not mean that they were engaged there only cybernetics. creation of a new institute affected availability of new equipment. in particular, the lippmaa’s laboratory in a fantastic way received a japanese (jeol) magnet providing the resolution necessary for proton resonance, and a finnish storage device (the simplest computer). the research sector of new institute, which was headed by endel teodorovich, had the name “sector of physics”. and, because already at the first stage of work at this institute in the laboratory (sector) lippmaa began to master the application to the programming of experiment and accumulation of experimental data on digital computing devices, this could justify the appearance of such a subdivision in the institute of cybernetics. the institute received a new building in the very center of tallinn, comfortable and decorated in a slightly abstract style, reminiscent of the design style of some of moscow and novosibirsk institutes. the institute was headed by a relatively young (specialist in the field of mechanics, born in 1918, academician of the academy of sciences of the estonian ssr) niil alimäe. the support of the undoubtedly talented and promising endel lippmaa, who graduated from the estonian higher educational institution (tpi) after the war and there defended his thesis, points to the continuity of the development of science in estonia for three periods: pre-soviet, soviet and post-soviet. in the new institute, the lippmaa laboratory intensively mastered the methods of the double protonproton nmr and took the first steps in the development table 1. resolution of some nmr spectrometers of own design. no year of edition constructors reference resolution by oh * resolution by – ch3 1 1956 arnold ph.r. 10.2.136 1.3·10– 8 1.3·10– 8 *** 2 1957 primas h.p.a. 30.515 2.5·10– 8 2.1·10–8 *** 3 1961 vladimirsky p.t.e 6.с.459. – 9.7·10–8 **** 4 1961 bystrov, dekabrun et al. see p.t.e 1961. n1. с. 122 1.3·10– 7 1.7·10– 7 5 1961 samitov see p.t.e. 1961. № 5. с. 100 1.8·10– 7 2.3·10– 7 6 1962 lippmaa et al. [2, 4] 1.5·10– 7 1.7·10– 7 additions are in italics. * the relative line width of the hydroxyl group of acidified ethyl alcohol at half-height; ** the relative width of the center line of the triplet of the methyl group of acidified ethyl alcohol at half-height; *** one line of doublet. the line widths are measured from published spectra; **** without sample rotation usually applied in nmr. abbreviations: ph.r. – physical review; h.p.a. – helvetica physica acta; p.t.e. – russian journal “pribory i tekhnika ersperimenta” (“instruments and experimental technique”). 129estonian scientist in ussr of the rare isotopes 13c and 15n nmr. a series of publications in these fields appeared in 1965 1969 in the proceedings of the estonian academy of sciences [8–23]. some of these publications were in english and one of them (together with v. sinivee) is in estonian [14], which demonstrated the availability of scientific terminology in the new field of knowledge in this language. for example, «tuuma magnetilises toplet-resonantsis» is «nuclear magnetic double resonance».. one of the founders of carbon 13c nmr spectroscopy since 1965, the most authoritative specialists in organic chemistry and the heads of the general and technical chemistry division of the academy of sciences of the ussr began to cooperate with lippmaa for a simple reason: the tools of the lippmaa’s laboratory in the 1960s made it possible to carry out experiments «unattainable even for remarkable imported instruments, which were acquired for the moscow institutes» (e. lipmaa, speech at the first all-union symposium on nmr, tallinn, 1967). endel lippmaa in the 1960s received an opportunity to contact chemists from the german democratic republic, finland and sweden, he established strong ties with soviet chemists. his laboratory was one of the three in the world that laid the foundation for 13c carbon spectroscopy. he became the third creator (after lauterbur [24] and holm [25]) of the experimental base for nmr spectroscopy of a rare carbon isotope. in 1970, three fundamental studies of the carbon-13 nmr of several classes of organic compounds were published by lippmaa in an international scientific journal jointly with chemists of the various countries [26–28] (and earlier works [13, 16, 23]). in this, he somewhat overtook even the firm of the varian brothers, leading the implementation of nmr in chemistry. outstanding expert in the nmr area the authority of lipmaa was extremely high both in the circles of soviet physicists (the council of radio spectroscopy of the ussr academy of sciences, the symposium on nmr and nqr in 1967, the administration of all-union schools on magnetic resonance) and soviet chemists (reports at the general meeting of the department of general and technical chemistry in 1967 and in the presidium of the academy of sciences of the ussr in 1972, cooperation with academicians and their closest associates in the study of chemical structures, regular consultations with colleagues from the chemical faculty of lomonosov moscow state university). in 1967, at a general meeting of the general and technical chemistry division of the ussr academy of sciences, lippmaa demonstrated the capabilities of double proton nmr resonance and nmr of carbon, and nitrogen isotopes to study the structure of chemical compounds. in the same year, lippmaa met soviet nmr specialists at the joint symposium on nuclear magnetic resonance in tallinn, and they had the opportunity to get acquainted with the original equipment created in his laboratory. in 1969 endel lippmaa defended his thesis for the degree of doctor of physical and mathematical sciences, specializing in «chemical physics» in the alma mater of soviet chemical physics – the institute of chemical physics of the ussr academy of sciences, the topic – the overhauser nuclear effect and the structure of organic compounds. reviewers (official opponents) were well-known theorist g.v. skrotsky, creator of one of the first pmr spectrometer in the ussr l.l. dekabrun, and highly reputable doctor of chemical sciences, yu.n. sheinker. a review from a scientific organization was sent by s.a. altshuler’s department from kazan university. lippmaa becomes corresponding member (1972), and academician (1975) of the academy of sciences of the estonian ssr, specializing in «chemical physics». in 1980, endel lippmaa founded the institute of chemical and biological physics (now the institute of chemical physics and biophysics of the estonian academy of sciences). in 1977-1982 he was the academician-secretary of the department of physical, mathematical and technical sciences of the academy of sciences of the estonian ssr. he was a recognized expert and official reviewer of several dissertations of soviet specialists in the field of magnetic resonance. lippmaa always had clear goals, strategic (to overcome everything and become an expert in a certain field – to start – in the field of nmr application in chemistry) and at each stage – a new tactical goal (create a spectrometer for pmr; master the methods of double resonance, make an essential contribution to the nmr spectroscopy of rare isotopes, master method of highresolution nmr in a solids). however, more ambitious plans were not alien to him. the first deviation from the “general line” (chemical and analytical nmr), were two papers [29, 30] devoted to a very interesting effect the polarization of nuclear spins 13c in chemical reaction products in liquids with the intermediate formation of a pair of free radicals (chemically induced dynamic polarization of nuclei, cpn or cindp). in 1972, the international conference on cindp even took place in tallinn. endel lippmaa had however left this direction. the interests of lippmaa always went beyond the practice and theory of purely applied nmr and cov130 alexandr vladimirovich kessenikh ered a wide range of problems of chemical and biological physics, as well as physics and chemistry in general. in 1984, on an ion-cyclotron resonance equipment with a field strength of 4.7 t lippmaa and his colleagues performed an experiment to measure the mass difference between tritium and helium-3 ions. see about it below in a special section. the scientific authority of lipmaa in international scientific circles was recognized in 1969 by him inclusion in the editorial board of the newly created journal organic magnetic resonance. subsequently, he led such events as the international congress on molecular spectroscopy (1973), the congress ampere (1978), the viii all-union school on magnetic resonance (1983). in 1978 the first in the ussr congress ampere was held in tallinn. lippmaa was the head of the local organizing committees for the above-mentioned events, and on behalf of all soviet science he welcomed foreign guests and apologized that he could not welcome guests as fluently in french, as he welcomed them in estonian, russian, german and english. high resolution nmr of solid state in the 1970–1990’s lippmaa with his disciples (m.alla, e.kundla, a.samoson, t.saluvere and others) became classics in the field of high resolution nmr in solids [31–33]. they developed methods for observing nmr of silicon-29, aluminum-27 and others nuclides in powders and polymers. the most important work in this direction was published in 1977 in jetp letters at 1977 [31] (see photocopy of abstracts of english translation of soviet jetp letters on fig.3). in his report at a joint session of the branches of the academy of sciences of the ussr and the academy of sciences of the essr [34], lippmaa reported on the first results of research in this area. experiment [31] was rather complicated (actually was a prototype of a distinct variant of two-dimensional spectroscopy) and included both sample rotation (at an angle of arccos(1/√3) to the direction of a polarizing magnetic field), which eliminated the dipole interactions broadening the spectral line of nmr, and strictly periodic (during each revolution) switching on the radio frequency resonant pulses, inverted 13c magnetic moments (hartman-hahn sequence type series of resonant π-pulses [35]). the signals obtained after the usual fourier transform in this case had the form of damped oscillations and again underwent the fourier transform. the oscillation period was clearly determined by inner anisotropic interactions that were not fully eliminated by rotating the sample (so-called anisotropic part of chemical shift). another problem arose in the study by nmr of 27al nuclei with spin 5/2 and electric quadrupole moment. quadrupole broadening as well as dipole broadening in the first approximation of perturbation theory could be eliminated by rotation at the same angle to the direction of the polarizing magnetic field as the dipole broadening, since the correction of the first approximation at the value of the electric quadrupole interaction (eqi) is proportional to the expression: νq (1–3cos2θ1), where νq is the frequency of the nuclear quadrupole resonance of the nucleus under consideration in the absence of a magnetic field, θ1 is the angle between the directions of the main axis of the eqi tensor and the magnetic field. however, if eqi is not too small compared to the nmr frequency (larmor frequency νl), the broadening will be determined in the second approximation of perturbation theory by an expression proportional to (νq2/ νl) cos2θ•(1cos2θ). if, nevertheless, eqi is not so large that it was necessary to take into account the following approximations of perturbation theory, proportional to (νq ( n + 1) / νln), then a second rotation is suggested around the axis perpendicular to the field direction (cos2θ2 = 0) or directed along the field (1cos2θ3) = 0. one of the successful representatives of the lippmaa school a. samoson together with the outstanding american scientist a. pines in 1988 developed a device for an nmr sensor with two rotors [33] that ensured the elimination of eqi broadening via elimination of both the first and second order, what is important for research in solid nmr of nuclei such as 14n, 27al , etc. with moderate eqi values (the nqr frequency is much less than the larmor frequency if magnetic field is strong enough). in the late 1970s and in the 1980s, the lippmaa’s figure 3. a photocopy of the abstract of the article in the letters of jetp [31] devoted to the determination of the anisotropic chemical shift 13c in the nmr spectrum of hexamethylbenzene. 131estonian scientist in ussr laboratory developed cooperation with the chemists of the gdr (g. engelhardt, (berlin, adlerhof ) and others, see, for example [36]) and of the czechoslovakia (jan shraml and others, see for example, [37]). their joint work was devoted mainly to chemical radiospectroscopy of 29si nmr, primarily in solid silicates and in molecules containing trimethylsilyl groups. separate articles were published in the journal of the american chemical society, a significant number of publications with czech chemists were published in english in the czechoslovak journal and some works were published with german chemists in gdr. in 1980, endel lippmaa together with g.v. skrotsky edited a russian-language translation of the monographs haeberlen and mehring combined in one edition [38, 39]. the subject of this publication [40] («high resolution nmr in a solid state») has found only limited application among soviet specialists. the endel lippmaa’s successful researches in this area, was awarded the ampere’s diploma and prize in 1994. the most recent meeting between endel lippmaa and his soviet colleagues took place in 1988 in the village of viitna between tallinn and kohtla-jarve. it was the second joint school for the application of nmr in chemistry and petrochemistry gave a lecture on high-resolution nmr in solids. it was an extremely informative and understandable lecture for specialists. after the school, its participants visited the laboratory of lippmaa in tallinn and got acquainted with the new equipment. lippmaa’s work in the field of ion cyclotron mass spectrometry let us dwell on the work of lippmaa and his colleagues on high-precision measurements of the nuclide mass differences. the first attempts to master for this purpose a new method of ion-cyclotron resonance mass spectroscopy (icr ms) were undertaken by lippmaa in 1980. the method is based on the action of the lorentz force in a magnetic field and resonant transitions from one closed orbit of motion to another under the action of an alternating electric field. the resonance frequency of the icr ωi in this case is equal to: ωi=hqi/mi, where h is the magnetic field strength, qi, mi is the charge and mass of the ion i. the icr method with the fourier transform [41] has developed in 1974. lippmaa immediately understood: the method is appropriate for implementation on a kind of modification of the nmr spectrometers with the fourier transform. in 1984, using an icr ms equipment with a field strength of 4.7 t (magnetic and computer system of a pmr spectrometer at 200 mhz could be a base for an icr spectrometer) created with the support of company bruker, lippmaa and his colleagues performed an experiment to determine the mass difference of tritium 3h+ and helium-3 3he+ ions (3he nucleus is the product of β-decay of the tritium nucleus). this result (estimate of the upper mass limit of the neutrino (antineutrino ν̃e) mν, equal to 18588 ± 3ev [42, 43]) is still cited in the world literature (at least 45 citations in the wos database), although the model chosen for the evaluation was inappropriate. this episode in the scientific life of the lippmaa’s laboratory was overshadowed by the fact that with the help of the same company (bruker spectrospin), researchers from the institute of chemical physics of the academy of sciences of the ussr published the same results two months earlier [44]. however, the links go mainly to the article by lippmaa et al. in journal phys. rev letters [43]. in recent publications about the neutrino mass estimation, the interest in which was fueled by some cosmological hypotheses and the results of the mission of the spacecraft of the european space agency plank (2009 2013), for example [45], mentioned another model for estimating the upper limit mν. this is the mass difference in the pair of nuclides 187w → 187re + e– + ν̃e, which turned out to be equal to 2555 ev, that is, about an order of magnitude less. based on some theoretical models of neutrino physics and data from other experimental methods, it is now believed that the neutrino mass is still many times smaller. results of the soviet period a result of twenty-eight years of successful work of lippmaa in the field of chemistry and physics is very fruitful .some data about lippmaa collaboration with soviet specialists see too in application (memoires of yu. a. ustynyuk [46], with links to [47– 50] and our comments) . with the collapse of the ussr and the return of estonia’s independence, lippmaa’s scientific career was far from over, although he had to share his time and energy between political and scientific activity. the beginning of his political activities was initiated by the so-called «phosphate war», the struggle against the deployment of phosphate rock in northeastern estonia. the direction of his further political activities was the 132 alexandr vladimirovich kessenikh restoration of estonia’s independence. when endel lippmaa passed away, most of his obituaries (for example in [1]) began with a mention of his role in finding copies of the secret protocols to the soviet-german pact of 1939. i would like to give an excerpt from the memoirs of astronomer jaan einasto, lippmaa’s successor as academic secretary of the physical sciences division of the academy of sciences of estonia [51]: «i would especially like to emphasize the contribution of endel lippmaa to the restoration of estonian independence. among the scientists, he was undoubtedly the most active fighter on the front line for the cause of estonia. and he achieved success: he managed to succeed in the phosphate war (struggle to stop the development of phosphate rock in estonia), and then, being a deputy of the supreme council, managed to squeeze opponents and make moscow recognize the existence of <a secret protocol to> the molotov-ribbentrop pact». further scientific researches of lippmaa and his disciples in the late 1980s, in the 1990s and after 2000 were devoted to the study of solids by nmr and molecular spectroscopy. some of his works even before 1990 were devoted to the study of the structures of high-temperature superconductors by magnetic resonance methods. lippmaa also collaborated with the european cern center in programs cms (compact muon solenoid) and totem (total cross section, elastic scattering and diffraction dissociation measurement at the large hadron collaider). a certain intermediate result of twenty-eight years of successful work of lippmaa in the soviet period should be summed up. firstly, lippmaa created a national estonian scientific school in the field of chemical nmr spectroscopy. it was one of the strongest scientific schools in this field in the former ussr. let us note that the some other scientific schools enjoyed much more substantial material and organizational support by the scientific leadership of the ussr. secondly, endel lippmaa became involuntarily one of the leading experts in the nmr in the ussr. this imposed certain duties on him, with which, however, he coped without much difficulty, thanks to his outstanding erudition and organizational skills. what he resolutely avoided was everything connected with the problem of industrial production of nmr equipment in ussr, he was cooperating with german-swiss company bruker instead. thirdly, lippmaa and his school received a number of scientific results of the world level. first of all, these are pioneering studies of 13c and 15n nmr spectroscopy of a number classes of organic compounds and original research and development in the field of high-resolution nmr spectroscopy in solids. lippmaa was awarded for the achievements in this field of spectroscopy by the ampere price, and one of the employees of lippmaa ago samoson with his inventions was involved in the work of the instrument-making firm bruker. a group of researchers in the field of ion-cyclotron resonance mass spectrometry (icr ms) also appeared in the new institute of chemical and biological physics of the academy of sciences of the essr. and for the soviet specialists in nmr, the most important result of their long years of cooperation with lippmaa was the possibility of sharing scientific knowledge with foreign colleagues. thanks to the high authority of endel lippmaa in the scientific world and his very loyal attitude to soviet colleagues, they had access to important international events that lippmaa supervised, and to placing his publications in an international scientific journal, to whose editorial board he was a member. in [52], in the spirit of the tallinn city jargon, this opportunity was called «lühike jalg to europe». «lühike jalg» literally means «short leg» in estonian, that is, the shortest path (meaning the path from the center of tallinn to the upper part of the city). in addition to the soviet chemists with lippmaa, as we mentioned above, the chemists of the gdr and czechoslovakia cooperated with him fruitfully. in 1994, in the midst of the «evil nineties» of russia, the ampere congress was held in kazan, dedicated to the half-century anniversary of the discovery of the epr by e.k. zavoisky. for reasons we can only guess, endel lippmaa refused to come to this congress, saying that he does not want to apply for a russian visa. the star of this second in the territory of the former ussr congress ampere was richard ernst (swiss), a recent (1991) nobel laureate in chemistry for the use of pulsed one-dimensional and multidimensional nmr spectra. the nmr technique was moving forward and double resonance methods, so successfully mastered by lippmaa, were replaced by two-dimensional spectroscopy methods. analyzing his results and the history of their achievement, it can be noted that endel lippmaa, in part of nmr, was not a «discoverer of new paths», but undoubtedly was an outstanding pioneer of these paths. and it was very relevant in the xx century, the century of «big science». the study, dedicated to one of the prominent «founders» of the nmr pathway in chemistry, j. roberts (usa) [53], contained the statement: «during the 1960s, organic chemistry underwent a dramatic transformation as a result of the introduction of high-tech tools. in this process, nuclear magnetic 133estonian scientist in ussr resonance (nmr) has become an important analytical method in organic chemistry.» in a sense, endel lippmaa could claim in the scientific community of ussr chemists the same role that j. roberts, j. schoolery and similar researchers played in the united states. of course, he recognized too the merits of vf bystrov and others in solving this important task in the ussr. in addition, lippmaa, in contrast to the above-mentioned scientists, did not stop in his work on analytical applications of nmr in solutions and picked up a high-resolution nmr development initiative in a solid state, and contributed to ion-cyclotron mass spectrometry. endel lippmaa possessed all the necessary qualities for this role: engineering intuition, excellent knowledge of physics and chemistry, the sheer charisma of the leader. his fantastic working capacity and ability to manage his time caused surprise and admiration. but there was one more, extremely necessary quality: «the feeling of the possible». it is the talent of the born politician. this sense of the possible was needed just under the conditions of the «wonderland» (of the soviet reality and the complicated situation of estonia in the soviet system), as well as the rapid development of nmr technology abroad with the lagging of soviet technology in this area. at the same time, his interests extended far beyond the chemical applications and development of nmr technology. in more favorable conditions, lippmaa’s contribution to world science could be more meaningful. undoubtedly, he was not satisfied with the conditions in which his scientific creativity developed. perhaps in contact with other eminent scientists who worked in the same area of science abroad, he would have achieved even greater results, but such contacts were almost impossible for him. doesn’t the ustynyuk’s (see application.) comparison between the erudition and the efficiency of lippmaa and the nobel laureate r. hoffmann speak about this? however, (note in parentheses), the comparison of these two outstanding scientists is not quite legitimate. this is evidenced by the difference in their second specialties. lippmaa is a famous politician, and hoffmann is a brilliant writer and poet. acknowledgements the author is grateful to yu.a. ustynyuk for permission to publish his memories (see application.) and for many valuable comments on the content of the article. thanks to v.v. ptushenko, who found out, at the request of the author, the composition of opponents of lippmaa’s doctoral dissertation and provided significant assistance in choosing the place of publication, as well as in editing the article. i thank especially s.v. semenov (kurchatov institute) for his analysis of the role of lippmaa’s work on ion-cyclotron resonance in neutrino physics. author is grateful to ga kessenikh (freelance teacher of mathematical methods in economics at moscow state university), which completed a preliminary editing of the translation of the article from russian into english. application. from personal memories of professional collaboration with e.t. lippmaa the author was lucky to have among his closest colleagues yuri alexandrovich ustynyuk (see about him [46]) direct student of a.n. nesmeyanov, an outstanding specialist in the field of organoelemental chemistry and high resolution nmr, who headed for a long time (1968–2012) interdepartmental nmr laboratory on chemical faculty of lomonosov moscow state university. yuri alexandrovich was closely associated by work and scientific interests with e.t. lippmaa. author in 1974 attended the defense of the doctoral dissertation yu.a. ustynyuk «structure and intramolecular rearrangements of cyclopentadienyl compounds of the ivb group», where lippmaa was one of the official opponents. therefore, it was decided to turn to yuri alexandrovich with a request: to evaluate the text and the content of the proposed publication. with the permission of yu.a. ustynyuk we give here his memories, sent to the author by e-mail. friendly criticism and additions to the initial outline of our article, which accompanied the mentioned memories, we, were possible, clarified and fully considered when finalizing the article. our comments and additions in the text below are in italics. yuri alexandrovich wrote about the following: i have read everything carefully. you see, i had a very special and very complicated relationship with endel. they began after he opposed my dissertation in 1974. of course, he gave an excellent review, having understood more than two other opponents in his work (academician oa reutov in chemistry and adolf bolotin (quantum calculation specialist)). but at the same time, when i met him at the station, lippmaa handed me a notebook on 24 pages, written in small handwriting, which contained comments and criticism on mistakes, inaccuracies, stylistic errors. i have never heard such a deep, comprehensive analysis. it turned out that lippmaa brilliantly knew chemistry, catalysis, quantum 134 alexandr vladimirovich kessenikh chemistry, and all spectroscopy. after defending my dissertation, for about a month i carefully studied everything that he wrote and sent him letters with explanations. he answered very carefully, and in controversial cases, gave a bunch of references to literature. in general, this correspondence has greatly changed my view of who a serious scientist is, how he should work. i accepted the first invitation of lippmaa to oppose a dissertation to someone from his team with great joy. of course, i tried not to lose face and thoroughly worked the text. i also brought 8 pages of comments. at first there was a defense, and then a coffee seminar after that, i was accepted in this company as my own, opposed several doctoral works, including in 1983 the work of tönnis pehk «nmr spectroscopy of 13c isomeric aliphatic and carbocyclic compounds». almost every year i received invitations to seminars in tallinn at the very end of february (they were on fridays), after which i then with the whole team on saturday and sunday skied in their camp, sat in a sauna. in turn, endel, when he was in moscow, usually visited us at the faculty for half a day. after lunch, different people gathered around him and threw questions at him. these visits caused great interest among people from other laboratories. they wrote to him, and on arrival he allotted time to many. i have been a constant witness to these conversations. endel with the professor of physical chemistry spoke as an equal to him, but more erudite scientist. he acted as a mentor with specialists in catalysis, offering his own solutions to problems. when one of the biochemists came, endel gave a brilliant lecture on the structure and mechanisms of action of proteolytic enzymes. one of his visits to us was interrupted by a docent from the department of organic catalysis, who considered him/herself an important specialist in zeolites. as it is known, endel made a series of brilliant works on the structures of zeolites using silicon and aluminum nmr in a solid [47–49]. one docent with great aplomb began to state the opinion on the mechanism of catalysis on zeolites, relying, it seems, on the ideas of the beginning of the 1930s. a terrible situation for me! and i just cannot stop it. finally, it was said: «well, now you understand how they work?» i thought that now endel would berate his opponent completely. however, he smiled gently and, with a touch of regret, said: «yes, now very many people think so.» i think that in the article about his work it would be necessary to describe in more detail how important were his results obtained by the nmr method for solving chemical and physical problems that were then in the spotlight. then it becomes clear what he actually did. in the 70s, the latest issues of foreign scientific journals in natural sciences could only be found in the lenin library and in the scientific hall of the library of foreign literature, where they were in the public domain. so i always went there on sundays. once, having arrived there at 10.30 with a desire to look through the latest jacs issues, i did not find them on the shelf. i noticed, endel was sitting, who has taken all 10 issues. of course, he greeted me in a friendly way, i sat down next to him and began to look through the issues that he had already processed. apparently, he mastered speed reading techniques in english. i barely managed to look through one issue, but he in the same time three. at the same time, he was very quickly writing something in a notebook in fine, even handwriting. by two o’clock in the afternoon all jacs’s he worked. i got up three times and rested for 5 minutes. he sat without straightening. his notebook ended, and he asked me for a couple more sheets of note paper. at three afternoon we had a snack in a cafe opposite to broth pies, and he quickly rushed off somewhere. yury konstantinovich grishin in our laboratory did several works on nmr of mercury-199. in tallinn, he reported these works a couple of times at a seminar. already in 1992 much later than the declaration of independence of estonia, endel gave a response from the “third organization” to grishin’s doctoral thesis «nuclear magnetic resonance of mercury-199. the nature of magnetic parameters and applications in the study of the structure and dynamics of organo-mercury compounds». as always, his review was the most informative. as you correctly write, one of the first 60 mhz nmr spectrometers in estonia was created on the basis of a japanese magnet with an induction of 2.35 t. this magnet went to tallinn because the jeol device purchased by the msu chemical faculty did not have enough funds allocated to moscow state university, and the techsnabexport manager deleted the magnet from the msu application (he believed they will do the magnet themselves) and did a favor by them to the new institute cybernetics in tallinn, the application of which in other conditions would hardly have been implemented. and in our basement turned out to be useless electronics. it stood there for 10 years, and then i gave it to endel for some symbolic amount. it was useful to him in creating the ion-cyclotron resonance spectrometer, with which he made experiments to estimate the neutrino mass. this part of lippmaa’s activity was not at all reflected in your text. in all my life i have met only two people of such tremendous capacity for work, such a deep, comprehensive erudition. the first endel, the second roald hoffman, winner of the nobel prize in chemistry (in 1981 for the generalized quantum theory of molecular and atomic col135estonian scientist in ussr lisions), see about him [50], with whom i worked closely for several years. of course, it is difficult to compare hoffman (a brilliant theorist who collaborated with many outstanding scientists such as william nunn lipscomb, robert burns woodward and others) and endel lippmaa, a brilliant and very erudite organizer of independent engineering and experimental research. however, i would like endel to be recognized not only as a specialist in nmr, but as a brilliant versatile scientist. he was a surprisingly charming modest man with a soft sense of humor, but at the same time with iron principles. references 1. the telegraph. telegraph news. 16.08.2015 https:// www.telegraph.co.uk/news/obituaries/11801251/ endel-lippmaa-physicist-obituary.html 2. lippmaa e., syugis a. sravnenie spinovykh stabilizatorov magnitnogo polya yamr-spektrometrov vysokoy razreshayushchey sily. trudy tallinnskogo politekhnicheskogo in-ta, ser.a. sbornik statey po khimii i khimicheskoy tekhnologii .viii. – proceedings of the tallinn university of technology. series a. collection of articles on chemistry and chemical technology .viii) . 1962 . vyp. 195. s. 59–64. (russian). [comparison of spin stabilizers of the magnetic field of high-resolution nmr spectrometers]. 3. lippmaa e., yadernyy magnitno-rezonansnyy spektrometr vysokoy razreshayushchey sily so spinovoy stabilizatsiey. ibidem: 1962 . vyp. 195. s. 65–78. (russian). [high-resolution nuclear magnetic resonance spectrometer with spin stabilization.] 4. lippmaa e., o magnitnykh svoystvakh materialov, primenyaemykh v yamr spektroskopii . ibidem: 1962 . vyp. 195. s. 79–82. (russian). [on the magnetic properties of materials used in nmr spectroscopy]. 5. lippmaa e., syugis a. yadernyy magnitno-rezonansnyy spektrometr vysokoy razreshayushchey sily s elektromagnitom. ibidem: 1962 . vyp. 195. s. 83–100. (russian). [high resolution nuclear magnetic resonance spectrometer with electromagnet]. 6. nauchnoe soobshchestvo fizikov sssr. 1950–1960-e i drugie gody. vypusk 2. sanktpeterburg. izdatelstvo rkhga. 2007.751 s. (russian). [scientific community of physicists of the ussr. 1950–1960s and other years. issue 2. saint petersburg. publishing house rhga. 2007.751 p.]. 7. kessenikh a.v. (publikatsiya). iz istorii khimicheskoy radiospektroskopii yamr v sovetskom soyuze. (vospominaniya, dokumenty, materialy). voprosy istorii estestvoznaniya i tekhniki 2014. № 1. s. 119– 141. (russian). [(publication). from the history of chemical radio spectroscopy nmr in the soviet union. (memoirs, documents, materials)] 8. lippmaa e. o primenenii dvoynogo rezonansa pri issledovanii spektrov yamr eesti nsv teaduste akad. toimetised fuus.-matem. – proceedings of the estonian academy of sciences. series physics and mathematics 1965. vol. 14. № 1. p. 125–128. (russian). [on the use of double resonance in the study of nmr spectra]. 9. lippmaa e., syugis a. issledovanie spin-generatora na bokovoy polose s fazovo-sinkhronizovannoy chastotoy modulyatsii . ibidem: 1965. vol.14, № 1. p. 129– 132. (russian). [the study of the spin-generator on the sideband with phase-synchronized modulation frequency]. 10. sinivee v., lippmaa e. weak perturbing radio frequency field effects in nuclear magnetic double resonance i. ibidem: 1965. vol.14, № 2. p. 258–265. 11. lippmaa e., puskar yu.,alla m.,syugis a. primenenie dvoynogo yadernogo magnitnogo rezonansa so slafigure 4. yuri alexandrovich ustynyuk. from an article in the “bulletin of moscow state university” (2017). [46] https://www.telegraph.co.uk/news/obituaries/11801251/endel-lippmaa-physicist-obituary.html https://www.telegraph.co.uk/news/obituaries/11801251/endel-lippmaa-physicist-obituary.html https://www.telegraph.co.uk/news/obituaries/11801251/endel-lippmaa-physicist-obituary.html 136 alexandr vladimirovich kessenikh bym vozmushchayushchim polem («tikling») dlya ustanovleniya vzaimnogo raspolozheniya urovney energii spin-sistemy ibidem: 1965. vol. 14, № 2. p. 306–307. (russian). [the use of double nuclear magnetic resonance with a weak perturbing field (“tickling”) to establish the relative position of the energy levels of the spin system]. 12. lippmaa e., puskar yu., alla m. issledovanie yadernogo effekta overkhauzera metodom dvoynogo mezhyadernogo magnitnogo rezonansa («indor»), ibidem: 1965. vol. 14, № 3. p. 487–489. (russian). [nuclear magnetic resonance carbon-13. i.]. 13. lippmaa e., olivson a., past ya. yadernyy magnitnyy rezonans ugleroda-13. i. ibidem:1965. vol. 14, № 3. p. 473–485. (russian). [nuclear magnetic resonance carbon-13. i.]. 14. sinivee v., lippmaa e. nõrga raadiosagedusliku hãirevãlja efektid tuuma magnetilises toplet-resonantsis. ii. ibidem: vol. 14, № 4. p. 564–568. (estonian). [weak perturbing radio frequency field effects in nuclear magnetic double resonance. ii]. 15. lippmaa e., past ya., puskar yu., alla m., syugis a. impulsnyy metod issledovaniya spektrov yadernogo magnitnogo dvoynogo rezonansa vysokogo razresheniya. ibidem: 1966. vol. 15, no 1. p. 51–57. (russian). [pulse method for studying high-resolution nuclear magnetic double resonance spectra.]. 16. lippmaa e., past ya., olivson a., saluvere t. yadernyy magnitnyy rezonans ugleroda-13. ii. ibidem: 1966. vol. 15, no 1. p. 58–63. (russian). [nuclear magnetic resonance carbon-13. ii.]. 17 .sinivee v., lippmaa e. weak perturbing radio-frequency field effects in nuclear magnetic double resonance iii. ibidem: 1966. vol. 15, no 1. p. 64–75. 18. lippmaa e., alla m., mezhmolekulyarnyy dvoynoy rezonans i effekt overkhauzera v zhidkostyakh. ibidem: 1966. vol. 15, № 3. p. 473–476. (russian). [intermolecular double resonance and the overhauser effect in liquids]. 19. lippmaa e., rang s., eyzen o., puskar yu. yamr spektroskopiya uglevodorodov. i. ibidem: 1966. vol. 15, № 4, p. 615–620. (russian). [nmr spectroscopy of hydrocarbons. i]. 20. lippmaa e., alla m. modulation transfer in nuclear magnetic double resonance of nitrogen compounds. ibidem:1966. vol. 15, № 4. p. 620–623. 21. lippmaa e., pehk t., past j. carbon-13 double resonance absorption spectra of strained molecules. ibidem: 1967. vol. 16, p. 345–356. 22. lippmaa e., alla m.,syugis a. vnutrimolekulyarnyy i mezhmolekulyarnyy effekty overkhauzera v aromaticheskikh soedineniyakh s tretichnoy butilnoy gruppoy. ibidem: 1967. vol. 16, № 3.p. 385–389. (russian). [intramolecular and intermolecular effects of overhauser in aromatic compounds with a tertiary butyl group]. 23. olivson a., lippmaa e., past j. spin-lattice relaxation times of carbon-13 nuclei in organic compounds. ibidem: 1967. vol. 16, № 3.p. 390–392. 24. lauterbur p.c. 13c nuclear magnetic resonance spectra. j. chem.phys. 1957. vol. 26, no 1. p. 217–218. 25. holm c.h. observation of chemical shielding and spin coupling of 13c nuclei in various chemical compounds by nuclear magnetic resonance. j. chem.phys. 1957. vol. 26, no 3. p. 707–708. 26. lippmaa e., pehk t, andersson k., rappe c. carbon-13 chemical shifts of a, b-unsaturated acids. org. magn. reson. 1970. p. 109–121. 27. rosenberger h., pettig m., pehk t., lippmaa e. kernresonanzunterversuchungen am 1,10-phenantrolin und seinen komplexbildungen – iv: 13c resonanzen des freien und protonierten 1, 10 phenanthrolins. org. magn. reson. 1970. p. 329–336. 28. lippmaa e., pehk t., paasivirta j., belikova n., plate a. carbon-13 chemical shifts of bycyclic compounds. org. magn. reson. 1970. p. 581–604. 29. lippmaa e., pekhk t., buchachenko a.l., rykov s.v. chemically induced dynamic nuclear polyarization of 13c nuclei in the thermal decomposition of organic peroxides. chemical physics letters 1970. vol. 5. no 8. s. 521–635. 30. lippmaa e., saluvere t., pehk t., olivson a. chemical polarization of 13c and 15n nuclei in the thermal decomposition of diazoaminobenzene (1,3-diphenyltriazene). org. mag. reson. 1973. vol. 5. p. 429–436. 31. alla m.a., kundla e.i., lippmaa e. t. selektivnoe opredelenie anizotropnykh magnitnykh vzaimodeystviy iz spektrov yamr vysokogo razresheniya poroshkoobraznykh obraztsov. pisma zhetf 1978. t. 27, vyp. 4. s. 208–211. (russian). [selective determination of anisotropic magnetic interactions from high-resolution nmr spectra of powder samples. letters of jetp 1978. vol. 27, no. 4. p. 194–197]. 32. lippmaa e., samoson a., mägi m. high-resolution 27al nmr of aluminosilicates. j. am. chem. soc., 1986. vol. 108. p. 1730–1735. 33. samoson a., pines a. double rotor for solid-state nmr. rev. sci. instrum., 1989. vol. 60, no 10. p. 3239–3241. 34. lippmaa e.t. magnitnyy rezonans redkikh yader vysokogo razresheniya v tverdykh telakh. (nauchnaya sessiya otdeleniya obshchey fiziki i astronomii an sssr i otdeleniya fiziko-matematicheskikh i tekhnicheskikh nauk an essr. tallinn – tartu, 20–23 aprelya 1976). uspekhi fizicheskikh nauk 1976. 137estonian scientist in ussr t.120, vyp. 3 (11). s. 512–514. (russian). [lippmaa e.t. high-resolution magnetic resonance of rare nuclei in solids. (scientific session of the division of general physics and astronomy of the ussr academy of sciences and the division of physical-mathematical and technical sciences of the academy of sciences of the 10essr. tallinn tartu, april 20–23, 1976) sov. phys. usp. 19. 965–967 (1976)] 35. hartman s.r., hahn e.l. nuclear double resonance in rotating frame. phys. rev. 1962. vol. 128, no 5. p. 2042–2053. 36. lippmaa e., maegi m., samoson a., engelhard g., grimmer a.r. structural studies of silicates by solidstate high resolution silicon-29 nmr. j. am. chem. soc. 1980. vol. 102 no. 15, p. 4889–4893. 37.jaan past, jüri puskar, jan schraml and endel lippmaa assignment techniques for 29si nmr spectra of pertrimethylsilylated products. 29si satellites in 13c nmr spectra measured with selective 29si decoupling. czechoslovak chemical communications 1985, vol. 50, issue 9, p. 2060–2064. 38. haeberlen u. high resolution nmr in solids. selective averaging. n.y. san francisco. london: academic press. 1976. (advances in magnetic resonance ed. by j.s. waugh). 39. mehring m. high resolution nmr spectroscopy in solids. berlin. heidelberg. new york: springer – verlag. 1976. (nmr basic principles and progress. eds. p. diehl, e. fluck, r. kosfeld). 40. kheberlen u., mering m. yamr vysokogo razresheniya v tverdykh telakh (per. s angl. pod red. e.t. lippmaa i g.v. skrotskogo) m.: mir. 1980. 504 с. [highresolution nmr in solids (translated from english under the editorship of e.t. lippmaa and g.v. skrotsky) m.: mir. 1980. 504 s. (russian translation).]. 41.comisarovm.v., marshall a.g. fourie transform ion cyclotron resonance spectroscopy. chem.phys. letters 1974. vol. 25, no2. p. 282–283. 42. lippmaa e.t. pikver r.y., surmaa e.r., past ya.o., puskar yu. kh., koppel i.a.,tammika.a. ob izmerenii raznosti mass ionov geliya-3 i tritiya metodom iontsiklotronnogo rezonansa vysokogo razresheniya. pisma zhetf, 1984.t.39, vyp. 11. s. 529–531. (russian). [measurement of the mass difference between helium-3 and tritium ions using high-resolution ion-cyclotron resonance. jetp lett., 1984.vol.39, no. 11. p. 646–649]. 43. lippmaa e., pikver r., suurmaa e., past j., puskar j., koppel i., tammik a. precise h-3 – he-3 mass difference for neutrino mass determination. phys. rev. letters 1985. vol. 54. no 4. p. 285–288. 44. nikolaev ye.n., neronov yu.i., gorshkov m.v., talroze v.l. ispolzovanie ionnogo tsiklotronnogo rezonansa dlya opredeleniya raznosti mass tritiya i geliya-3 pisma v zhetf. t. 39, vyp. 9. s. 441–443. (russian). [the use of ion cyclotron resonance to determine the mass difference between tritium and helium-3. jetp letters. vol. 39, no. 9. 531–534]. 45. formaggio j.a. direct neutrino mass measurements after plank. physics of the dark universe. 2014. vol. 4. p. 75–80. 46. yuri alexandrovich ustynyuk (on the occasion of the 80th birthday) vestnik moskovskogo universiteta. seriya 2. khimiya. 2016. t. 57, № 3 . s. 127. (russian). [moscow university bulletin. series 2. chemistry.] 47. lippmaa e., maegi m., samoson a.,tarmak m., engelhard g. investigation of the structure of zeolites by solid-state high-resolution silicon-29 nmr spectroscopy. j. am. chem. soc. 1981. vol. 103, no 17. p. 4992–4996. 48.engelhard g., löhse u., patzelova v.,mägi m.,lippmaa e. high resolution 29si n.m.r. of dealuminated y-zeolites. the dependence of the extent of dealumination on the degree of ammonium exchange and the temperature and water vapour pressure of the thermochemical treatment. zeolites. vol. 3, issue 3. p. 233– 238. 49. engelhard g., löhse u., lippmaa e., tarmak m. 29si-nmr-untersuchungen zur verteilung der siliciumund aluminumatome im alumosilicatgitter von zeolithen mit faujasit-struktur. zeitschrift für anorganische chemie b. 482, h. 11. s. 49–64. 50. https://www.nobelprize.org/prizes/chemistry/1981/ hoffmann/biographical/. 51. jan einaste. the tale of dark matter (translation in russian from estonian by vlad pustynskii). www. astronet.ru/db/msg/1233291/text.html. 52. kessenikh av., our «lühike jalg» to europe (a remembrance of the estonian physicist and chemist endel lippmaa). ampere bulletin 2015. t. 64, no. 1/2 (258 / 259). p. 9–10. 53. reinhardt c. a lead user of instruments in science. john d. roberts and the adaptation of nuclear magnetic resonance to organic chemistry. 1955–1975. isis. 2006. vol. 97. no 2. p. 205–236. https://www.nobelprize.org/prizes/chemistry/1981/hoffmann/biographical/ https://www.nobelprize.org/prizes/chemistry/1981/hoffmann/biographical/ http://www.astronet.ru/db/msg/1233291/text.html http://www.astronet.ru/db/msg/1233291/text.html substantia an international journal of the history of chemistry vol. 4, n. 2 2020 firenze university press some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy, ph.d., j.d. …and all the world a dream: memory outlining the mysterious temperature-dependency of crystallization of water, a.k.a. the mpemba effect evangelina uskoković1, theo uskoković1, victoria wu1,2, vuk uskoković1,3,* the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries aleksander sztejnberg communicating science: a modern event antonio di meo substantia. an international journal of the history of chemistry 5(1): 99-117, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-963 citation: siderer y. (2021) udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors. substantia 5(1) : 99-117. doi: 10.36253/substantia-963 received: jun 08, 2020 revised: sep 06, 2020 just accepted online: sep 14, 2020 published: mar 01, 2021 copyright: © 2021 siderer y. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors yona siderer edelstein center for the history and philosophy of science, technology and medicine, the hebrew university of jerusalem e-mail: sideryon@netvision.net.il abstract. this work presents chemistry studies of the japanese scholar udagawa youan (1798-1846), specifically, his pioneering book seimi kaiso, introduction to chemistry, and includes a short biography of youan. the first aim of this work is to present youan’s contribution to western chemistry in japan. youan studied many western books and listed their authors. the new terms he invented for chemistry in japanese influenced the development of chemistry writing and application in japan. the seven books of seimi kaiso that were published during 1837-1847 and republished with annotation in japanese in 1975 are discussed in this article. the impact of youan’ terminology on the history of chemistry writing in the nineteenth and twentieth centuries is discussed. the conditions of knowledge transfer among japanese and western scholars were very different. youan had severe difficulties facing the strict attitude of the tokugawa authorities toward studying and distributing knowledge coming from foreign countries. the later development of japanese chemistry language and studies is also described. keywords: japan, udagawa youan, seimi kaiso – introduction to chemistry, western sources of science, dutch studies in japan, japanese chemistry terminology. 1. udagawa youan (1798-1846) – scholar of dutch studies udagawa youan– a multi-talented nineteenth century scholar udagawa youan (1798-1846) was a scholar of many talents who touched very many topics during his lifetime.1 youan was a medical doctor of tsuyama town in okayama prefecture, translated and investigated plants in edo japan, studied modern chemistry and many other topics like musical instruments, geography, history of holland and playing cards; he wrote an early article on coffee and more. youan studied foreign languages, first dutch, to some level german, even latin and greek russian, and copied a list of arabic letters. it is told that in 1822 he stayed on a british ship for three nights in order to learn english. he saw maps of the world from which he could study names of european and other countries.2 http://www.fupress.com/substantia http://www.fupress.com/substantia 100 yona siderer in his youth, youan studied chinese classics in the house of his teacher and adoptive father udagawa genshin. an official translation office of the tokugawa regime, bansho wage goyo was established in 1811; youan joined the translation office in 1826. youan collaborated there in dutch translation with his adoptive father, his teacher baba sajuro, otsuki gentaku who was one of the founders of dutch studies and other japanese scholars. they translated parts of chomel encyclopedia, from which youan learnt about western botany.3 youan’s good knowledge of chinese classics and good knowledge of dutch language that he acquired due to years of translating books on plants, botany, medical drugs, and other topics, helped him understanding and coining suitable terms in japanese for the new discipline, chemistry: names of the chemical elements, compounds, and chemical processes. youan’s innovation of scientific language remains in use today. 2. seimi kaiso – introduction to chemistry – youan’s book and its current research youan’s main book on chemistry seimi kaiso will be dealt with in the following chapters. before this book he wrote several other, shorter books on various chemical topics translated from the scientific books imported to japan. a thorough survey in archives was carried out by j. mac lean searching the years 1712 – 1854. he studied the records of the dutch factory in japan, and from the colonial records, both preserved in the rijksarchief (state archive) in the hague, the netherlands. mac lean listed the year that a ship arrived, its name, its captain’s name, the scientific instruments and books that were imported; the names of those who ordered those items are also listed.4 udagawa youan might have had access to some of those books and instruments, especially those delivered to the official translation office whose member he was since 1826. a partial list of u. youan’s early chemistry books includes: metal chemistry, introduction to chemistry characters sound, dyeing chemistry, earth chemistry number 1, chemistry of light, element earth (non-metal) chemistry, consideration of western measures, note on western mineral springs, introduction to chemistry sequel potassium nitrate theory, theory on hot springs experiments in several provinces.5 description of seimi kaiso udagawa youan’s seimi kaiso is considered the first extensive book on chemistry in japan. it includes seven books; each divided into three volumes and numbered chapters. six books are considered inner books that are the main text; the seventh book is called an external or appendix book. all together it has more than 1100 pages, published between 1837 to 1847. the print is in kanji and katakana. the books are bound by ribbon with several stiches along the back of the book. the pages are folded and numbered on their margin. fig. 2 presents a full set of seven books in an original book case at the edelstein collection of the national library of israel (nli) in jerusalem. supposedly, it was bought by dr. sidney edelstein from a books shop in new york. the first page of the first book is presented in figure 3. the upper line, written from right to left, shows the year of printing, corresponding to 1837. on the upper right side is written “udagawa youan translator.” seimi kaiso 舎密 開宗 are the four large letters in the middle of the figure. seimi 舎密 meaning “chemistry” follows the sound of the dutch word chemie. the word for chemistry was changed to kagaku 化学 meaning “the study of change” after the chinese term.6 there is a written warning against forgery on the left lower first page of each book.7 in seimi kaiso youan dealt with topics such as chemical affinity, solution, caloric, alkali, salts, phosphoric acid, ammonia, oxidation and reductions of metals, glass, constituents of plants and more. youan studied the ingredients of water in hot springs in japan and figure 1. scholar udagawa youan. 101udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors described chemical ingredients of hot springs in foreign countries. udagawa youan cited fifty-eight elements, five of them were found to be mistakes, among those are caloric and light.8 the chemistry studies that youan started continued after him, some of the chemistry terms that he coined are still in use, see below, chapter 4. in 1975 youan’s seimi kaiso was rewritten in modern japanese, including translators’ comments. seimi kaiso is based on about 24 chemistry books from europe of late eighteenth and early nineteenth centuries. the revised text is written in kanji, hiragana, and katakana, the last one is used for foreign names of places, people and chemicals. this volume, seimi kaiso research holds 570 pages, in a hard black cloth cover, a paper cover and a book case. the book is opened from right to left, as are the original seimi kaiso books. editor and preface writer is tanaka minoru. each page shows the original book on its upper part and its currently rewritten text below it, (figures 4 and 5). it contains index of foreign names, index of japanese materials, photos of several of youan’s apparatus drawings and copies of relevant books’ covers. it also contains conversion tables of units of length and volume (p. 542) and weight (p. 543).9 the main seimi kaiso research book (hence skr) is followed by a second book, written by tanaka minoru, sakaguchi masao, dōke tatsumasa and kikuchi toshihiko, with articles on udagawa youan, his life, work and his diary. this book of articles will be referred to as seimi kaiso articles (hence ska).10 western books that youan studied japanese and dutch scholars tried to find out the original books from which youan received his knowledge. in the introduction to seimi kaiso youan wrote the names of the authors of the books he studied from and his translation of the title of the book, in japanese. in figure 4 a circle ⃝ marks the beginning of a book or author’s name. japanese scholars searched the books left by youan and tried to match his japanese writing with the dutch books found in his house, or in the house of other scholars of dutch studies. tsukahara togo observed that “youan must have been able to use those manuscripts because he occupied one of the most privileged position in the rangaku society as the member of the udagawa family and also through his official function in the translation bureau, he was supposed to have wide access to the dutch sources. in holland, the identification of the original works of seimi kaiso was attempted in 1858 by j. j. hoffmann (18051878), the first professor of japanese studies in leiden that started in 1855, and later by serrurier (1846-1901), curator of museum of ethnology in leiden.” their work relied on deciphering the phonetical transcription of the author’s name and the modified western book title.12 figure 2. seimi kaiso set of 7 books at sidney edelstein collection of the history of science, the national library of israel (nli) in jerusalem. photo: y. siderer. figure 3. seimi kaiso first page of the first book. photo: y. schley. 102 yona siderer the list of western books and their authors following is the list of authors as they appear in the original first book of seimi kaiso (fig. 4), hence shortened sk.13 the list presents the following authors names. kasteleyn, p. j. (1746-1794), blumenbach, j. f. (17521840), plenck, j. j. (1735–1807), lavoisier, a. l. (17431794), ypey, adolph (1749-1822), niewenhuis, g., bernvald, william van (1747-1826), hagen, k. g. (1749–1829), guiton de morveau l. b. (1737-1816), trommsdorff, j.b. (1770-1837), ségur o. (1779-1818)  , houte, h. j. (17891821), isfording, j. j. (1776-1841), hijmans, h. s., stratingh, e. (1804-1876), reinwardt, c. g. c. (1773-1854), dutch pharmacopeaia 1826, richerand, a. (1779-1840), catz smallenburg, f. van, water, j. a. van de (18001832(?)), rees, w. van (1752-?). detailed descriptions of authors’ names, their book or books and western book source are presented in appendix 1, including: author’s name in english. book’s title in english, japanese book’s name in kanji, japanese name in english letters, japanese book title in english. dutch book title. book title in its original language in case there is one; further details and explanations. youan wrote a shortened name for the authors he cited, in which the first syllable of the author’s name is written before the book’s title. in some of the citations youan mentions studying the book he had, in order to study another chemist whose book he did not have. these include citation of his european contemporary scientists e.g., berzelius (17791848), davy (1778-1829), dulong (1785-1838), gay-lussac (1778-1850) and others. so actually he studied more than the books listed above and from those he chose which text and authors to cite. scholars cited by youan from books not present in seimi kaiso list, include (not inclusive, there are more than 160 names of authors): wedgewood josiah, empedocles, cavendish henry, gaubius hieronymus d., gadolin johann, kirwan richard, gmelin leopold, glauber johann r., klaproth martin h., gay-lussac joseph l., figure 4. names of western authors and books in udagawa youan’s seimi kaiso book 1 vol. 1 p. 7.11 photo: y. schley. 103udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors scheele carl w., chaptal jean a.c., stahl george e., seignette pierre, saussure horace b. de, thales, davy humphry, döbereiner johann w., dulong pierre l., thomson thomas, hatchett charles, buffon georges l.l., faraday michael, black joseph, priestley joseph, fourcroy antoine f. de, proust joseph l., bergman torbern o., berzelius jöns j., berthollet claude l., boyle robert, hoffmann friedrich, beaumé antoine, homberg wilhelm, ure alexander, richter jeremias b., linné carl, rinman sven, lemery nicolas, rosello hieronymus.14 we see the wide investment of youan’s chemistry study from books from the west, from original books in dutch, and from books translated into dutch from french, german, latin, and swedish. most of the books were written in the late eighteenth or early nineteenth century, so youan studied books that were about forty to ten years old in time of many new discoveries in chemistry. this could have led to his difficulty in understanding texts that were not clear or erroneous, or better understood in the west later. the chemistry studies that youan started continued after him, some of the chemistry terms that he coined are still in use, see below, chapter 4. in seimi kaiso youan dealt with topics such as chemical affinity, solution, saturation, heat element, caloric. gas, oxygen, nitrogen, atmosphere, hydrogen, water. alkali, ammonia, acid, carbon. youan addressed salts, sulfur and nitric acid. in the third book he addressed acids like phosphoric acid, boric acid, fluoric acid, and some metal compounds like barite, strontia and zirconia. metals like gold, silver, iron, mercury, copper, lead, tin, zinc, bismuth, antimony, mangan, cobalt, nickel, and others were discussed. organic acids like oxalic acid, citric acid, gallic acid, apple acid, tartaric acid, benzoic acid were studied. youan wrote about soap, oils, resin, camphor, fiber, pigments and wax. in the last, external book, he wrote about analysis of mineral water, vegetable pigments, classification of springs and artificial preparation of mineral water.15 tanaka minoru devoted articles to youan’s perception of chemistry in seimi kaiso and discussed youan’s misunderstanding and mistranslation.16 the question why youan did not include the discussion about “atom” deserves further study. 3. examples of youan’s translations from western sources four examples of youan’s studies are presented: 1. henry-youan: water chemical ingredients analysis. 2. galvani column. 3. nitrogen oxides compounds. 4. hot springs abroad and in japan. william henry (1774-1836) text on water analysis and udagawa youan’s translation examination of mineral water by re-agents henry: water is never presented by nature in a state of complete purity. even when collected as it descends in a form of rain, chemical tests detect in it a minute proportion of foreign ingredients. and when it had been absorbed by the earth, had traversed its different strata, and is returned to us by springs, it is found to have acquired various impregnations. the readiest method of judging the contents of natural waters is by applying what are termed tests or re-agents, i.e. substances which on being added to a water, exhibit, by the phenomena they figure 5. upper part: seimi kaiso external book vol. 1, ch. 2 on mineral spring. lower part: seimi kaiso research p. 474. the first lines of the text on water impurities are dealt with in chapter 3 below. photo: y. schley. 104 yona siderer produce, the nature of saline or other ingredients.17 youan’s translation, in the external, seventh book first volume, chapter 1-2 on mineral spring: water is not a pure thing. in a popular way, it can be said that water is pure, but, by using a reagent it can be seen that it is not pure. from under the sky water goes down to the earth and penetrates. then [coming out] from the earth a spring is formed, in it a part of mineral matter, naturally consisting of not a small amount of impurities.18 it is clear that youan follows henry in this section, even though it is a translation from ypey’s dutch translation of trommsdorff ’s german translation of william henry’s english text. mr. volta column (see figure 6) youan describes the finding in 1791 by galvani “by chance how electric power is generated and explained this fact to encourage junior. volta (alessandro) in the city made a column like a tower to generate electricity by piling up many metal plates whose form (is) oval.” youan gave a detailed description and drawing of its construction:19 volta’s column is an unusual device of modern invention. the following is the construction: zinc (or tin) is casted into the oval form whose size is that of dardel (the diameter is about one sun) and a little thicker than the dardel.20 next, silver (or copper) is used to make the same size of oval and moreover felt (or thick paper) is used to make the size of oval. then three kinds of 30 to 50 plates are piled up in order to make a column. the first is silver plate, the second is zinc and the last is felt dipped in condensed salty water and squeezed after it. piling 20 to 30 sets, the last top plate is zinc plate [in the original paper’s misprint stated that the last is silver plate]. on the bottom silver plate a strip of tin or lead is pierced which works as a contact to outside. if a tester touches the strip with his finger soaked in condensed salty water and another finger touches the top plate of zinc, he will get a shock in both arms. this shock strength is dependent upon the number of piled plates. (according to one theory, when the silver plate is used, salt water is effective, while for the copper plate, ammonium chloride solution is effective). youan added comment to his text: the pole of the power generated from the silver plate is named cathode (negatief, ontkennende pool), and the power pole from zinc is named anode (positief, stellige pool). these two poles are different from each other as follows. 〇 anode is signed as +. the taste on tongue is alkali; it changes the color of akana solution to red.21 nitrogen oxides compounds in the following text youan tells about cavendish’s discovery by citing smallenburg’s book. youan invented terms for the degrees of oxidation in japanese. chemical combination of nitrogen and oxygen forms nitric acid. nitric acid is formed from the combination of nitrogen and oxygen. into nitrogen gas oxygen gas is mixed, electric spark is passed through, and nitric acid is formed. …according to “smallenburg’s chemistry,” in 1784, an englishman, cavendish, mentioned nitric acid composition for the first time. …according to several french and dutch scholars, in nitrogen and oxygen compounds there are four grades.22 foreign spas in youan’s seimi kaiso youan mentioned five springs in bohemia, these include: bernard spring – there is a big building – it is called hospital; mill spring, since 1711. temp. 138 degrees fahrenheit [ca. 59° celsius].” youan mentioned the spring’s therapeutic effect. “new spring since 1748. temp. 145 deg. fahrenheit. it is attributed medical curative effects; hot spring since 1725. temp. 165 deg. fahrenheit. attributed medical benefits; telesia spring nearby. temp. 135 deg. fahrenheit: ‘many women patients are bathing.’ the above 5 springs compositions is about the same, including: 硫酸ソーダ: na 2so4 sodium sulfate 24-46 figure 6. youan’s volta pile sketch and explanation. sk book 1, vol. 3 figure 7. photo: y. schley. 105udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors grain; 塩酸ソーダ: nacl sodium chloride 5-6 grain; 炭酸 ソーダ: na2co3 sodium carbonate 10-15 grain; 炭酸カル キ: caco3 containing cao calcium carbonate – lime 1-4 grain; 酸化鉄: mainly fe2o3 iron oxide 0.02 grain; 炭酸 ガス: co2 carbon dioxide gas ∼ 5-30 cm3; 硫酸苦土泉: mgso4.23 1 grain ~ 0.02 gram. hot springs contain magnesium sulfate and iron oxide. the taste is bitter. bitter taste comes from calcium and magnesium sulfate and the color from iron oxide. analysis of chemical ingredients of hot springs in japan japan is famous for its abundance of hot springs and the tradition of hot springs bathing. udagawa youan studied the chemistry of the water in hot springs. a thorough study of udagawa youan research on chemical ingredients in hot spring was published by osawa masumi (1932). osawa studied von siebold’s books and bürger research on mineral contents of hot springs in japan.24 some of von siebold chemical collections are stored in the museum of ethnology in leiden (museum volkenkunde). the reagents used by youan are stored at waseda university archive. according to osawa, “chemical analysis of mineral spring water was first carried out by p.f. von siebold (1796-1866) and h. bürger (1806 -1858), medical officers of the dutch east india company (voc) in nagasaki, for several samples from kyushu, southwest japan in 1820s.” when they went to edo (now tokyo) in 1826, they met udagawa youan (1798-1846), at nagasakiya inn located in hongokucho, edo city several times during the 3rd day of march to the 12th day of april (lunar calendar).25 they probably discussed mineral springs among other topics like japanese plants. a lot of chemical reagents and equipment were carried to japan when siebold came to nagasaki in 1823. siebold and bürger probably brought them to edo. then, from 1828, udagawa started his chemical study of mineral springs from a wide area of japan.”26 osawa cites a summary of minerals found by youan in suwa, shinshu (today nagano prefecture) in 1829 (bunsei 11) as written in a draft kept at osaka takeda science foundation library. for example: ｽﾜ ﾌーﾙｼ ｭ゙ｰﾙ zwavelzuur, 硫酸 ryuusan, sulphuric acid.27 4. coining chemistry vocabulary and the development of chemistry language in japan youan’s terms, their original dutch and their survival table 1 is composed of three contributions: sakaguchi masao listed 58 japanese terms, as they were used in 1975, and he put in parentheses youan’s terms. sakaguchi’s japanese list was followed by a list of the same terms in dutch (1). the list in japanese was previously published by tanaka m. in 1964 (2).28 english translation is added by the current author (3). it shows udagawa youan inventions of various terms for chemistry tools and processes. for most of the words youan combined two characters that should transfer the meaning of the dutch term into japanese. some words like no. 48 cork and no. 51 retort were written by youan in kanji as ateji, phonetic pronunciation. several of the terms that were formed by two kanji combination were preserved and are still used today, e.g., 結晶 crystal. others have been changed, either by one, e.g. 燃焼 combustion or both kanji letters, e.g., 融 点 melting point. it may be said that youan understood the meaning of the terms that he was translating and chose the appropriate kanji for them. those new terms added to their practical use in chemical processing since the nineteenth century until today. for example: entry no. 40: 飽和 houwa, saturation, is formed by 飽 tired of, satiate, and 和 that has several meanings: harmony, japanese style, peace, japan. the same term 飽和 is used today for saturated fatty acid, as in 飽和 脂肪酸 houwa shibousan. thus, contemporary scientists find it appropriate to use youan’s kanji combination for the dutch term verzadiging, saturation. another example, no. 41: dutch: opheffing 昇華 shouka, meaning sublimation: 昇rise up 華 has several meanings: splendor, flower, gorgeous. this term is used today for transfer of matter directly from solid to gas. it is also used for sublimation in psychology.29 in his chapter on “youan the linguistic,” takahashi terukazu (1944) showed several kanji letters combinations that youan chose in order to use phonetically. e.g., an 諳安, ba 抜婆、ta 太. 30 he used them for no. 51 in the table, 列篤爾多レトルト for retort; for writing the western names shown in fig. 4, e.g. 布廉吉 フレンキ佛 如 plenck; and for writing names of foreign countries, e.g. 波尓杜瓦尓 ポルトガル for portugal. other terms have a combination of katakana and kanji, like litmus paper ラッカムース紙. the pronunciation of no. 48 cork コルク and no. 49 beaker ビーカー in today’s reading is somewhat different than youan’s, possibly due to change in pronunciation during the years.31 the birth of the term 元素 genso, element. in 1834 youan published his book shokugaku keigen 植学啓原 (introduction to physical science. principle of botany). in its third, last volume, he addressed plant biochemistry; it became a textbook for natural sciences. in shokugaku keigen third volume there is the following exposition for the first time: air, water, oil, salt. he used the 106 yona siderer table 1. current and youan’s chemistry terms, dutch terms he studied and their english translation. dutch (1) recent japanese (1,2) udagawa youan (1) english(3) 1 wet 法則 法則 law 2 eigenschap 性質 禀性 property 3 ontbinding 溶解、分解 分離 dissolution, separation 4 scheikundige probeermiddelen (reagentia) 化学者 試みの手段 (試薬) 試薬 chemisttesting means (reagents) 5 droogeweg 乾式法 燥道の法 dry way method 6 onbewerktuigde ligchamen 無機物 無機性体 inorganic substance 7 bewerktuigde ligchamen 有機物 機性体 organic substance 8 verbranding 燃焼 熱焼 combusion 9 bestanddeel 成分 成分 component 10 volumen uitgebreidheid 容積 示量 容積 volume extensiveness 11 gewigt 重量 秤量 weight 12 eigendommelijke zwaarte 比重 異類重 specific gravity 13 gaz ガス 瓦斯 gas 14 damp 蒸気 蒸気 vapor 15 vaste lichaamen 固体 凝体 solid 16 vloeibaare lichaamen 液体 流体 liquid 17 drukking 圧力 圧力 pressure 18 temperatuur 温度 温度 temperature 19 kooking opbruisching 沸騰 ドレッシング 沸騰　 boiling dressing 20 het punt van kooking 沸点 沸度 boiling point 21 meltpunt 融点 熔度 melting point 22 uitzetting 膨張 廓張 expansion 23 vermeerdering van warmte 発熱 熱起 　 fever 24 luchtledige 真空 無気　 vacuum 25 electriek, electriiteit 電気 越列気　エレキ electric, electricity 26 stellige (positief ) pool 陽極 積極　 anode (positive) pole 27 ontkennende (negatief ) pool 陰極 消極 cathode (negative) pole 28 kooken 煮沸 煮沸　 boiling 29 vervliegen 揮発 揮散　 volatilization 30 uitdamping 蒸発 蒸散 evaporation 31 droogheid, uitdroogen 乾 涸 乾固　 dry up 32 overhauling 蒸溜 蒸餾 distillation 33 drooge overhauling 乾 溜 乾餾　 dry distillation 34 schudding 振盪 振蘯　 shock 35 beweging 攪拌 攪擾　 stir 36 kristal 結晶 結晶 crystal 37 vervloeien in de lucht 潮解 潮解 deliquescence 38 oplossing 溶液 溶液 solution 39 filtreeren 濾過 濾過　 filtration 40 verzadiging 飽和 飽和 saturation 41 opheffing 昇華 昇華　 sublimation 42 nederplofsel benzinkzel 沈降 沈殿 澱　 sedimentation precipitation 43 toestel 装置 装置　 device 44 lakmoespapier リトルマス紙 勒法母斯ラッカマース紙 litmus paper 107udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors character so -素 for several elements: oxygen, zuurstof is sanso 酸素; nitrogen, stikstof is chisso 窒素; hydrogen, waterstof is suiso 水素; carbon, koolstof is tanso 炭素. genso 元素 is translated from grondstof. 元 grond meaning basis, 素 is equivalent to 物質 busshitsu, substance, matter, stof in dutch.32 youan used those terms for the first time in his botany book in 1834. however, other japanese dutch scholars have used the ending term [~質] shitsu, meaning substance, matter. aochi rinso 青地林宗 in his book kikai kanran, overall view of the atmosphere, of 1827; takano choei 高野長英 in his book 西説医原枢 要seisetsu igen suoyou, western explanation of the theory of physiology, published in 1832; and hoashi banri 青地林宗 in 窮理通 kyuuritsuu, generalities of physics, (ca. 1836).33 a comparison of the various kanji characters choices is shown in table 2. several other terms with different kanji were used by scholars. for example, caloric: onshitsu 温質 matter of warmth. youan: danso 煖素. for nitrogen, youan tried two different kanji combinations: 殺素 lethal element and chisso 窒素 that is the term used to this day.34 sugawara kunika studied misaki shosuke (18471873) translation of fresenius. misaki, used terms coined by youan, but no citation of youan is shown.35 those words like 硫酸, 硝酸 for zwavelzuur or salpeterzuur should be from youan. but, those words like 能溶薬, 硫化炭精, or 造塩質属 for enkelvoudige oplossingsmiddelen, zwavelkoolstof, or haloiden, are probably not from youan.36 further evolution of chemistry language in japan tsukahara togo in the introduction to his ph.d. dissertation pointed out the influence of seimi kaiso on writing new chemistry books in japan immediately after its publication and even fifty years later. that was in spite of the developments in chemistry in the world during those years, the second half of the nineteenth century. tsukahara mentioned that in the curriculum of kaiseijo, a governmental institute for western learning founded in 1866, seimi kaiso was designated as a textbook for chemistry. tsukahara observed that “…it is dutch (1) recent japanese (1,2) udagawa youan (1) english(3) 45 curumapapier クルクム紙 姜黄紙 turmeric paper 46 smelt-kroes 坩堝 坩堝　 crucible 47 blaaspijp 吹管 吹管 blowpipe 48 kurk コルク 鳩爾古 キュルく cork 49 bekerglas ビーカー 玻黎ベーケル beaker 50 flesschen フラスコ フラスコ flask 51 retort kromhals レトルト 列篤爾多レトルト retort 52 glaspijp ガラス管 玻黎筥 glass tube 53 schaal 目盛 度目どめ scale 54 kraan 蛇口 回銓 かいせん tap 55 luchtledige klok 真空計 排気鍾はいきしょう vacuum clock 56 eudiometer 水「ガス」電量計 欧実阿墨多爾 ユーヂオメートル eudiometer 57 thermometer 温度計 験温器　 thermometer 58 calorimeter 熱量計 験熱器　カロリメートル　 calorimeter table 2. choices of kanji for element by udagawa youan and other scholars. udagawa youan 宇田川榕庵 hoashi banri 帆足万里 takano choei 高野長英 aochi rinso 青地林宗 元素 genso element 原質 造質/原質 原質 酸素 sanso oxygen 酸質 酸質 酸質 窒素 suffocating elementnitrogen 殺素 lethal element 塞質 窒質 suffocating matter 窒気 suffocating gas 水素 suiso hydrogen 水質 水質 水質 炭素 tanso carbon 炭質 炭質 煤質 table 1. (continued). 108 yona siderer righteous to assume that seimi kaiso paved the way for the introduction of western chemistry in japan, which was a prerequisite and indispensable condition for the development of chemical industry.” he assured that “the creation of a new vocabulary was by all means the most essential part of the introduction of western science in japan.”37 kaji masanori (1956-2016) mentioned those who followed youan’s chemistry book seimi kaiso. among those was kawamoto kōmin 川本幸民 (1810-1871), a teacher of chemistry at the bansho shirabesho, school of western learning, who translated a number of chemistry textbooks, such as kagakushi shinsho, a new book of chemistry. in that book kawamoto wrote for the first time concepts that were not in seimi kaiso like: genshi 原子 atom, bunshi 分子 molecule. in addition, topics like tampaku 蛋白 protein, budoutou ブドウ糖, grapes sugar, glucose, nyouso 尿素 urea, and the like are seen in kagakushi shinsho for the first time. kawamoto wrote a text book on dalton’s atomic theory.38 the topic of the vocabulary and teaching language of chemistry remains relevant in japan. first generation of japanese chemistry teachers after 1868 meiji restoration studied in europe and taught chemistry in english (or german?). as kikuchi yoshiyuki described “sakurai [jōji] gave at least some of his lectures in english. his lectures on chemical philosophy in 1882-1883 at tokyo university were in english… however…, teaching in japanese became the norm by 1884 throughout tokyo university and its preparatory schools as the number of foreign teachers decreased.”39 5. european knowledge exchange vs. japanese isolation many connections and extensive knowledge transfer existed between scholars in europe: by personal correspondence, by scholars visiting scholars in other countries and by circulations of scientific journals. this is in comparison with the japanese who were secluded from most of the world with almost no possibility to exchange knowledge with others out of japan, except china, and restricted conditions for exchanging knowledge within japan. the political situation in japan, the strict observance and surveillance of the citizens by the bakufu authorities, including watching scholars of dutch studies, should be taken into consideration. e.g., watching the books that were allowed to enter the country and to be studied, and forbidding transfer of knowledge to lower rank people.40 moreover, as goodman explained “…some orthodox cunfucianists held to their belief that the westerners would make use of christianity to invade japan. to the extent that all western scholarship was considered as a tool of the religion of christ, the work of the rangakusha was subjected to the oppressive scrutiny.”41 fear of the persecution of scholars of dutch studies was also expressed by fukuzawa yukichi (1835-1901) in his autobiography. it is cited by blacker from his memories that “had it been safe to do so he would certainly have taken western learning beyond the stage of scientific techniques and advocated it as a weapon against bullying feudal officials as well as against bullying foreigners.”42 interestingly, fukuzawa told about running chemistry experiments with other students during his studies in the tekijuku school in osaka, directed by ogata kōan, a physician of western medicine, in 1854-1855.43 fukuzawa decided to start learning english after he realized that his investment in studying dutch was not useful when he wanted to speak and understand the american sailors of commodore perry’s ships. in europe at the same time, a wide and intensive exchange of knowledge existed in the seventieth through the nineteenth centuries between scholars; by correspondence, reading and translating articles, as well as personal visits, e.g., berzelius visit in france in summer 1818,44 berzelius visit with davy in london in 1812 and their correspondence 1808-1813, as well as berzelius correspondence with wöhler, berthollet, mulder, mitcherlich and many others.45 william henry in “the elements of experimental of chemistry”, in his examples and discussion in the chapter on analyzing water he mentioned dr. wollaston, mr. watt and berzelius.46 french, english, german, swedish and italian scientists were exchanging scientific knowledge, discussing information, arguing about their philosophical ideas and the interpretation of the results of experiments. in contrast, japanese scholars were isolated from the western world and could hardly get any information from europe. in 1826 and until 1830 youan received some help from von siebold and bürger in botany, plant drawings, and hot spring water analysis. but von siebold was not in japan while youan wrote seimi kaiso since 1836. in his letter to his friend and disciple ito keisuke (1803-1901) youan complained that he could not meet foreigners in edo and could not get chemistry books from them.47 two events show youan defending himself from the ruling authorities. after what is called the siebold incident in 1829, the work of the translation office was stopped by the bakufu authority. on march 25, 1829, udagawa genshin, youan and other members of the translation office wrote a letter to the authorities, saying 109udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors that they did not have any connection with that affair and asking to let the office continue its important translation work.48 we learn about a second event concerning youan under such a prevailing socio-political, anti-western spirit and anti-christianity atmosphere. takahashi terukazu raised a question – “was youan christian?” and presented a document that was written in order to remove suspicions against youan who was involved in studies of western books. the document dated 1834 is preserved in waseda university library, shows a declaration by the head priest of a buddhist temple in asakusa, edo, concerning udagawa youan belonging to his buddhist temple, and that youan did not become a follower of christ yasu (jesus).the priest declaration states that youan’s writing room was named 菩薩楼 bosatsurou, bodhisattva room, after a buddhist scripture, the heart sutra 般 若心経 hannyashingyou. youan attached the phrases from the heart sutra on the wall of his writing room.49 udagawa youan did not know much about christianity, he studied western science without leaving his religious faith. concerning youan’s religion, goodman concluded that “… despite all his remarkable credentials as a rangakusha, youan was, like his father and otsuki gentaku before him, a committed confucian scholar, devoted first and foremost to the classical chinese intellectual heritage of japan.”50 in light of the continuing surveillance the achievements of udagawa youan, and indeed his colleagues, are even more impressive. 6. further chemistry studies from the west concerning the japanese dutch scholars, tsukahara observed that “it is an over simplification to say that the japanese have only copied western sciences and exploited its practical parts. philosophical discussions and practical demand were interrelated; they were interwoven into a new pattern of theory and practice, slightly different from that of the west. likewise, it would also be a distortion to suppose that this interaction involved nothing more than the relationship between “pure” and “applied” sciences. scientific theory and technical practice were merged in rangaku. this tradition was a remarkable feature of science in japan.”51 by the middle of the 1850s the japanese had both skillful capacity for craft production and basic scientific knowledge translated and adapted from the west. a change of attitude started after the arrival of commodore perry from america by the “black ships” in 1853 and again in 1854. one of its results was the opening of several japanese ports to foreign ships. in 1868 the meiji restoration rejected the long feudal rule of tokugawa and brought the emperor back into power. confronted with the american ships, cannons and other demonstration, the japanese realized that they are not as advanced as they have believed, actually lagging behind the western knowledge for large ships building, for the constructions of railroads and trains and manufacturing weapon like cannons. this realization was concluded in the decision to learn technology from the west, while keeping the japanese spirit. nevertheless, the educator fukuzawa yukichi explained that studying just the surface of technology is not enough if one wants to be able to further develop things by oneself. in order to make progress in chemistry science and technology the japanese invited foreign teachers to come and teach in japan. late 1860s to early 1870s, two foreign chemistry teachers were the american william griffis (1843-1928) and the dutch konraad wolter gratama (1831-1888). early publication of chemistry textbooks in japan since the 1870s included the translation of the chemistry lectures by american william griffis (1843-1928) in fukui. in a letter to philadelphia to his sister margaret clark griffis on june 25th 1871 he wrote: “in chemistry, i have carried out two classes through oxygen, nitrogen, hydrogen, sulfur, chlorine and carbon and their compounds.” these lessons were translated by his students into japanese and circulated among them. in a letter of july 15th 1871 he asked his sister to send him a copy of roscoe’s chemistry, latest american edition. teaching chemistry from roscoe’s book was later spread in japan.52 roscoe’s book was published in the same year, so griffis could teach from an advanced chemistry book of his time 53. japanese students in the laboratory of henry enfield  roscoe  (1833-1915)  in manchester translated his 1866 chemistry book into japanese. ichikawa seizaburo’s (alas morisaburo) translation “chemistry entry book for elementary school” was published by the ministry of education 1873. griffis moved to tokyo after eight months in fukui. his students in tokyo became the first generation of meiji chemists. another translation was of the chemistry course taught by the dutch konraad wolter gratama (18311888) in seimikyoku, the chemistry school in osaka specifically built according to his design. it was built for instructing technicians, methods to separate metals from the ores excavated in mines that included copper, silver and gold. gratama used reagents, analytical tools and reference books that he brought with him by ship in nearly two hundred crates to nagasaki in 1866. gratama chemistry lectures were translated into japanese by misaki shosuke 三崎肅輔 (1847-1873) into seimikyoku kaiko 110 yona siderer no setsu, chemistry theory course, 1869. the translated books were further circulated and studied in japan.54 in the conclusion of his article kaji observed: “the discovery of the periodic law between 1869 and 1871 and its dissemination in the 1880s coincided with the institutionalization of chemistry in japan. this factor helped make the appreciation of the periodic system as a basis for chemistry in japan easier. most of the first generation of japanese chemistry professors accepted the periodic law as one of the recent developments in chemistry in europe without much doubt.55 the department of chemistry was founded in the governmental institute for western learning, kaiseijo, in 1866. it became a department of chemistry of tokyo university in 1877. for the role of foreign chemistry teachers at tokyo university see for example kikuchi yoshiyuki’s book.56 the chemical society of japan (csj) was founded in 1878 “by approximately twenty motivated and enthusiastic young scholars wishing to advance research in chemistry.”57 they formed a committee to assemble chemistry dictionary, it worked for more than ten years.58 the first english-japanese chemistry dictionary that was the result of the work of the (tokyo) chemical society of japan was published in 1891. it presents in abc order chemical names, experimental tools, processes etc., and contains japanese terms in kanji, katakana, and their combinations. it reflects the development of chemical theory and the change of the dominant foreign language from dutch to english.59 detailed description of the current japanese rules of naming chemistry compounds can be found in the japanese-english chemical dictionary edited by markus gewehr, 2007.60 summary this work presents udagawa youan pioneering studies of chemistry from western books. he studied botany first and then chemistry and wrote several books before writing his larger book seimi kaiso, introduction to chemistry. he translated chemistry from western scientific books in dutch that are presented in this study. for the translation youan coined new terms in japanese. he could choose appropriate chinese-japanese characters to transfer the meaning of words from dutch to japanese, trying to shift the new terms from memories of the prevailing confucian view of the world. the difficulty in moving from the eastern philosophical thought to the western is partly discussed. the confucian traditional priesthood objection to introduction of foreign ideas contributed to obstacles faced by youan and other rangakusha. another difficulty pointed at was the objection of the ruling bakufu to wide spread of western knowledge. still, udagawa youan’s successful pioneering of chemistry translation and terminology can be considered as a milestone in japanese modernization. chemistry studies and practice continued after youan, using some of the vocabulary he invented. teaching materials of foreign teachers in japan, mentioned above are griffis and gratama, were translated into japanese. roscoe’s book was also translated by his chemistry students in england. following meiji restoration there was further progress in scientific studies, and the establishment of tokyo university and other national universities led to the creation of a successful japanese academy and a prosperous chemical industry. acknowledgements this research started as a grant recipient from japan foundation that let me spend six months at tokyo institute of technology, at the unit of prof. kaji masanori. he introduced me to the name of udagawa youan, and continued guiding me until the very day of his hospitalization on 12 july 2016, just before his untimely death. he is very much missed. my research continued during one year fellowship as a visiting scholar at nichibunken, international research center for japanese studies in kyoto, april 2009-march 2010. the devoted instruction of prof. frederik cryns enabled me to continue the research after returning to my country and our discussions during annual short visits to japan. i thank the scholars who helped me in various steps of this work for their advice and information: prof. sato shin, my first chemistry teacher in japan, prof. dōke tatsumasa, prof. azuma toru, prof. furukawa yasu, prof. ochiai hirofumi, prof. osawa masumi, mr. uchida masao, prof. ohmichi naoto, prof. kato nobushige, dr. yakup bektas, dr. karl grandin, prof. shimon vega, dr. jochanan de graaf, and dr. neomy soffer. colleagues of the japanese society for the history of chemistry in japan are deeply acknowledged. my gratitude is extended to the librarians at nichibunken and to ms. chaya meier herr at the edelstein collection for the history of science at the national library of israel in jerusalem. notes 1. t. dōke, 1973 p. 99. siderer, 2017, p. 224. 2. dōke, 1973 p. 105; takahashi 2002 p. 172. youan had access to maps of the world, at least one, a 111udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors map called “shinsensokaizenzu 新鐫総界全図”new engraved whole world map”, 1809 (ref. stored in the waseda university library, call mark is “bunko 08 c0995 (文庫08 c0995); takahashi terukazu p. 172. takahashi mentioned the map drawn by the italian mateo richi in china, great map of ten thousand countries, in the beginning of 17th century and its revised map by takahashi kageyasu’s shinteibankokuzu 新訂万国図 shinteibankokuzu new revision of ten thousand countries 1810, that youan received. 3. chomel encyclopedia. 4. mac lean 1974, p. 9. 5. t. shiba 2010; t. azuma, 2013; t. azuma 2017; y. siderer 2017. 6. k. sugawara, 1987 p. 29. in japanese (j), english abstract. 7. on seimi kaiso first page of each book there is a warning against forgery: “our shop was opened outside the asakusa castle gate, at the east of kikayamachi-asa(?), and it possesses all the books written by master udagawa, over a span of three generation, which our shop assembled entirely, made books and published. all our favorite wise customers! we recommend you surely to confirm the seal authenticity of each volume of the books. if there is a seal, the book is authenticated. if there is a fake seal, such book is a pirate edition. sincerely yours, owner of this bookstore, seireikaku.” thanks to prof. ohmichi naoto for this translation. 8. sk book 1, preface; skr p. 11. 9. tanaka minoru 田中実 ed., the authors of the modern revision and comments on youan’s seimi kaiso are: books 1, 2,3 and 7: hayashi yoshishige 林良重; book 4: kurokui seiji 黒杭清治; book 5: kusuyama kazuo 楠山和雄; book 6: kanazawa shouji 金沢昭 二． 10. m. tanaka, m. sakaguchi, t. dōke, t. kikuchi 1975. 11. copies of old prints of seimi kaiso books nos. 1-6 this author received with thanks from prof. osawa masumi. 12. tsukahara, 1993, hoffmann p. 319 and serrurier p. 325. 13. the list follows researches on: seimi kaiso rewritten 1975 shortened skr; sakaguchi masao article in ska 1975; tsukahara togo 1993; azuma toru 20062020; osawa masumi since 2006; miyashita saburo 1997, and references cited in those articles. 14. skr index pp. 568-540. 15. tsukahara, 1993, p. 148. 16. m. tanaka, 1975, in ska p. 104. 17. henry, epitome of chemistry, 1808, p. 413. 18. sk external book, vol. 1 ch. 2; skr p. 474. 19. sk book drawing on last pages, figure 7; skr p. 78. 20. currency name: a daalder is a silver coin which was first minted around 1500 in joachimsthal (tyrol), hence the name ‘joachimstaler’ which later became ‘taler’ or ‘daalder’. 21. sk book 1, vol. 2, ch. 50, mr. volta column; skr pp. 54. thanks to prof. s. sato for the translation. 22. sk book 2 ch. 101; skr, 1975, p. 118, comment 10 p. 161 on nitrogen oxide compounds. 23. seimi kaiso external book vol. 3; skr pp. 519-520. 24. osawa in onsen 2018 winter issue. 25. thanks to prof. kato nobushige for the dates of siebold in edo. e-mail dated 1.10.2019. 26. osawa, 2009, p. 84. 27. osawa, in onsen 2019 spring issue, p. 35. 28. sakaguchi ska 1975, p.57; tanaka 1964. 29. denshi jisho 22.5.2020. sped terra shogakukan professional english dictionary 2004, p. 1623. 30. takahashi, 2002, p. 174. 31. tsujimura, 2007 on language variation. p. 422. frellesvig bjarke, 2011. 32. after takahashi 2002, p. 157 33. goodman, 2014 (2000), authors’ names and books: takano choei p. 202, hoashi banri p. 113, aochi rinso 153. 34. shimao, 1972, p. 317, p. 319. 35. sugawara, 1984. 36. uchida, email correspondence 15.8.2020. 37. tsukahara, 1993, p. 1. 38. kaji, 2015, p. 286; encyclopedic dictionary 2017, p. 168 (j); invitation to chemistry history 2019 p. 242 (j). 39. y. kikuchi, 2013, p. 134; appendix p. 175 and reference cited there. 40. marie-christine skuncke, 2014, p. 110. 41. goodman, 2014, p. 199. 42. blacker, 1969, p. 25. 43. the autobiography of yukichi fukuzawa 1901, p. 90. 44. carl gustaf bernhard, avec berzelius en france parmi ses genies et ses volcans eteints. pergamon press 1985 (french 1989). 45. jaqueline reynolds and charles tanford, science, nature’s robots: a history of proteins 2003. 46. william henry. 1808, p. 415. 47. dōke, 1973, p. 109; dōke, ska 1975, p. 84. 48. goodman, 2014, p. 187. 49. takahashi, 2002, p. 140. 50. goodman, 2014, p. 139; f. cryns, personal discussion. 51. tsukahara, 1993, p. 3. kaji, 2015, p. 284, p. 286. kikuchi, 2013. pp. 97-100. 52. y. siderer. presentation at the 21st international society for the philosophy of chemistry (ispc) conference, 5 july paris 2017. submitted 2017. 112 yona siderer 53. kurahara, 1995, p. 1. 54. misaki, 1869; shihara and mcabee, 1988 p. , sugawara, 1984, p. 20. uchida et al. 1990?, p. 247. 55. kaji, 2015, p. 299. 56. kikuchi 2013, ch.2, p. 27. kaji, 2015, p. 289. furukawa 2019. 57. common knowledge. the chemical society of japan, president kobayashi yoshimitsu 2019. 58. takata seiji, 1995, (j). 59. m. uchida, 2014, personal communication. 60. japanese-english chemical dictionary: including a guide to japanese patents and scientific literature, markus gewehr (editor). isbn: 978-3-527-312931 november 2007. 61. tsukahara, 1993, p. 268, c1. 62. azuma. kagakushi, the journal of the japanese society for the history of chemistry 2006, vol. 33, no. 3, 129 (1). 63. sk book 6, vol. 16, ch. 266; skr p. 407; sk book 6 vol. 17 ch. 279; skr p. 442. 64. sk book 3 vol. 7 ch. 144; skr, 1975, p. 187. 65. tsukahara 1993, c.2 p. 268 and c.9 p. 272. 66. sk book 2, vol. 4, ch. 84, skr p. 103. 67. sk book 3, vol. 9, ch. 167; skr p. 220. see tsukahara c.9. p.272 for further discussion. 68. after 元素の秘密がわかる本, gakken publishing 2015, p. 158. 69. tsukahara, 1993, p. 268. 70. tsukahara, 1993, c.5, p. 270. 71. lavoisier, 1789, french p. 200. dutch 1800 p. 198. 72. miyashita, 1997 no. 7, p. 74. 73. skr p.13. sk first book preface p. 5. 74. azuma, in kagakushi journal 2013, vol. 40, no. 4 p. 189 (19). kagakushi journal 2014, vol. 41, no. 1 p. 1 (1). 75. sk preface p. 7; skr 1975, p. 14. 76. ska, 1975, p. 24. tsukahara, 1993, p. 280. mac lean 1974, p. 45, p. 50. 77. sk book 1, vol. 1 p. 7; skr, 1975, p. 14; tsukahara, 1993, p. 272. 78. tsukahara, 1993, p. 273; sakaguchi, ska, 1975, p. 25; sk external book vol. 1 ch.10; skr, 1975, p. 486. 79. sk book 1, vol. 1, p.7; skr, 1975, p. 14; tsukahara, 1993, p. 274. 80. sk book 1 vol. 1 p. 7; skr, 1975, p. 14 and others; tsukahara, 1993, p. 274; sakaguchi, ska, 1975, p. 25. 81. sakaguchi, 1975, in 科学史研究 kagakushi kenkyuu ii, 14, p. 67 (j), english abstract. 82. sk book 1 vol 1, p. 7; skr 1975, p. 14. 83. sk preface following p. 7; sk book 1 vol. 1 ch. 13; skr 1975, preface p. 15, p. 24; tsukahara 1993, p. 277. 84. tsukahara 1993, p. 278; sk book 3 vol. 7 ch. 144; skr, 1975, p. 187. 85. sk book 4 vol. 11. ch. 185; skr, 1975, p. 278; tsukahara 1993, p. 278. 86. miyashita 1997, no. 159, p. 94. 87. sk book 1 vol. 1 ch. 18; skr, 1975, p. 28; tsukahara 1993, p. 279. sakaguchi 1970 p. 185. 88. sk book 2, vol. 4, ch. 74; skr, 1975, p. 94. 89. sk book 2, vol. 4, ch. 79; skr, 1975, p. 97. 90. tsukahara, 1993, p. 281, c.21. 91. sk book 1, vol. 3. ch. 51; skr, 1975, p. 58. 92. sk book 5, vol. 14, ch. 235; skr, 1975, p. 352. 93. mac lean 1974, p. 42 and p. 48. 94. sk book 1, vol. 3 ch. 58 on kali and soda; skr, 1975, p. 64. 95. azuma, in kagakushi kenkyuu vol. 44, no. 3, 2017, p. 117 (5) and 126 (14). 96. tsukahara, 1993, ch. vii p. 147. 97. sk book 1, vol. 3, 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(j), english abstract. m. sakaguchi, in kagaku kenkyu, 1970, no. 96, p. 185. e. shimao, the reception of lavoisier’s chemistry in japan. isis vol. 63, p. 309, 1972. i. shihara and m. mcabee, ce&en, western chemistry comes to japan, a historical account, 31 october 1988, p. 26. 114 yona siderer shiba tetsuo, chemistry and industry 化学と工業 vol. 63-7 july 2010 (j). y. siderer, foundations of chemistry, udagawa youan’s (1798–1846) translation of light and heat reactions in his book kouso seimika, 2017 vol. 19(3) pp. 224-240. y. siderer, the life of udagawa youan and his natural science translation; his translation of light and heat reactions in  kouso seimika. perspectives on chemical biography in the 21st century, edited by isabel malaquias and peter j.t. morris, cambridge scholars publishing 2019. p. 207. marie-christine skuncke, carl peter thunberg botanist and physician. swedish collegium for advanced study 2014. sugawara kunika, a historical study of the use of the term kagaku for chemistry in japan, in kagakushi 化 学史研究 1987 p. 29. (j) english abstract. takata seiji, 高田誠二． 維新の科学精神『米欧回覧実 記』の見た産業技術 scientific spirit of meiji restoration written as seen in industry and technology world (in) [a true account of the ambassador  extraordinary & plenipotentiary’s journey of observation through the united states of america and europe]. 朝日選書 547 朝日新聞社. (j). asahi shimbun publisher 1995. m. tanaka, m. sakaguchi, t. dōke, t. kikuchi, seimi kaiso kenkyu, seimi kaiso research. kodansha, tokyo, 1975 (j). tanaka minoru, seimi kaiso ni okeru yoan no kagaku ninshiki 舎密開宗における榕菴の化学認識 in udagawa youan seimi kaiso fukkoku togendai koyaku ・ chuu 宇田川榕菴舎密開宗復刻と 現代語訳・ 注” udagawa youan seimi kaiso republishing, (its) recent language and explanatory notes” kodansha publishing house, tokyo, 1975 (j), pp. 99–114. m. tanaka, “part 2 chemistry” chapter 6  seimi kaiso  section  3, in yuji shibata ed.  meiji-zen butsuri kagaku shi, history of physical and chemical science before meiji era, p. 281, p. 321, 1964. t. takahashi, siebold and udagawa youan, edo dutch studies friendship account, heibonsha, tokyo, japan (j). 高橋輝和: siebold to udagawa youan edo rangaku kouyuuki シーボルトと 宇田川榕菴 江戸蘭学 交遊記 東京: 平凡社. 2002. t. tsukahara, affinity and shinwa ryoku, introduction of western chemical concepts in early nineteenth-century japan. ph.d. thesis. university of leiden, holland, j.c. gieben publishers, amsterdam 1993. tsujimura natsuko, an introduction to japanese linguistics, blackwell publishing 2007. p. 422. uchida takane, oki hisaya, sakan fujio, isa kimio, and nakata ryuji, william elliot griffis’ lecture notes on chemistry, in foreign employees in nineteenth century japan. (e.r. beauchamp and akira iriye eds.), boulder san francisco and london. west view press 1990. p. 247 udagawa youan, seimi kaiso. in edo: suharaya ihachi 1837-1847, in japanese. appendix 1. ⃝ kasteleyn, p. j., descriptive and practical pharmaceutical, economic and physical chemistry 1788. 『葛氏舎密』 ka shi seimi, mr. ka chemistry. youan used 葛氏 mr. ka as name abbreviation when he cited kasteleyn. beschouwende en werkende pharmaceutische, oeconomische, en natuurkundige chemie, tweede 2dln, amsterdam, 1788. this book was cited fourteen times in seimi kaiso, concerning the preparation of chemical reagents, but not theoretical issues. kasteleyn (1746-1794) represented a group of chemists in the netherlands at the end of the eighteenth century that was partly against the new doctrine of lavoisier.61 youan favored lavoisier, but used more of henry’s more practical descriptions. azuma toru (1953) thoroughly studies udagawa youan’s chemistry translation by searching articles stored at kyō-u archive of takeda science foundation in osaka and at waseda university library in tokyo. azuma showed three journals that were edited by kasteleyn, from which youan translated chemistry in several of his books. those books included metal chemistry, udagawa chemistry book, dyeing chemistry, plant chemistry and seimi kaiso – introduction to chemistry.62 in seimi kaiso youan mentioned kasteleyn concerning sugar acid, oil extract and oxalic acid.64 oxalic acid is mentioned also in an earlier book of youan, in a citation from hijmans.64 2. ⃝ blumenbach, j. f., the basic of physics of the human being. 『貌氏人身窮理篇』 bushi jinshin kyurihen mr. bu basics of the human being groendbeginselen der natuurkunde van den mensch. translated by g. j. wolff, 1791. blumenbach (1752-1840) was one of the founders of comparative anatomy. however, no direct influence on seimi kaiso can be seen.65 in the dutch book the chapters include the human body, liquids in the human body, blood, muscles, respiration and more. ⃝ “three little studies”. questions and answers on pharmacy. 『三有小學』 sanyuu kogaku. this book is written under the 9th bullet on sk p. 7, unknown publication 115udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors year. (figure 5). handboek der natuurlijk historie of natuurgeschiedenis. 1802. the topic of sulfur, its two forms of crystals, e.g. sulfur flowers crystals,66 and the topic of barium sulfate were written by youan.67 interestingly, barium was written by youan as 重土, whereas it is written today using katakana バリウム. it was explained that since barium element is heavier (than the second group in the periodic table), it was called barys from greek language. so youan used 重い, the kanji for “heavy” to name the barium element.68 3. ⃝ plenck, j. j.,physical and chemical description about the liquid in the human body. 『布氏明液論』 fu shi mei ekiron 1791. mr. fu treatise on clear liquid. natuur-en scheikundige verhandeling over de vochten des menschlijken ligchaams1791.69 ⃝ second book by plenck (sk 5th bullet in fig. 5): handbook of chemistry 1803. 『舎密備要』 seimi biyou grondbeginselen der scheikunde, of oversicht over alle de vakken der scheikunde, uithet lat. vert. door j.s. swaan, amsterdam, elwe en werlingshoff 1803. original book was published in latin in viena in 1800, titled elementa chymiae.70 4. ⃝ lavoisier, a. l., elements of chemistry, in a new systematic order, containing all the modern discoveries, english translation by r. kerr, 1790. 『舎密原本』 seimi genpon. a principle book for chemistry. grondbeginselen der scheikunde. utrecht, 1800. original french: traité élémentaire de chemie, présenté dans an ordre nouveau et d’aprés les découvertes modernes, paris 1789 lavoisier, a. l. (1743-1794).71 miyashita mentions three drafts by youan of the 2nd parts of grondbeginselen that are kept at takeda chemical industries that is kyō-u library of takeda science foundation since 1978.72 5. ⃝ see plenck no. 3. 6. ⃝ ypey, adolph, 『依氏廣義』 i shi kougi mr. i broad sense 1804. systematisch handboek der beschouwende en werkdadige scheikunde. amsterdam, 1804-1812. chemie voor beginnende liefhebbers of aanleiding 1803. william henry’s chemistry book – epitome of chemistry was translated into dutch by a. ypey. referred to as cbl for w. henry dutch translation: chemie, voor beginnende liefhebbers, uit het engelsch, van j.b. trommsdorff verm. uitg door a. ypey, amsterdam, 1803. ypey’s dutch translation was used by youan while writing seimi kaiso. in seimi kaiso preface p. 5 (skr p. 13) youan explained the use of books by henry, trommsdorff and its ypey’s translations. youan stated that he mentioned names of only three men but he does not ignore achievements of others.73 this was the most cited work in seimi kaiso for theoretical as well as practical topics. azuma studied three books in dutch by ypey that youan used. those are:74 · systematisch handboek der beschouwende en werkdadige scheikunde, 5dln, amsterdam, 1804-1812, in 9 vols. shortened name: shs · verbeteringen en bijvoegsels tot het systematisch handboek der werkdaadige scheikunde, 3dln, amsterdam, 1808-1810 · bladwijzer der voornaamste zaken, voorkomende in het systematisch handboek der werkdaadige scheikunde, amsterdam, 1812 azuma showed ten unpublished manuscripts that youan studied thru ypey’s books on chemistry; compared youan’s citing shs, and pointed at the places in youan’s texts corresponding to the places in ypey’s shs. 7. ⃝ niewenhuis, g., questions and answers on pharmacy. 『合薬問答』 gouyaku mondou. printing date unknown. questions and answers on pharmacy.75 bullet no. 19: ⃝ general dictionary on art and science for the intellectuals in collaboration with dutch scientists. 『紐氏韻府』 nishi inpu mr. ni’s dictionary. 1825. algemeen woordenboek van kunst en wetenschappen voor den beschaafden stand onder medewerking van een aantal vaderlandsche geleerden bijeenverzameld. several copies arrived to japan by the dutch ships during 1832 – 1849. sakaguchi attributed the dictionary to egbert buys, tsukahara discussed other translations and attribution of the dictionary and suggested that youan used niewenhuis’ dictionary and possibly acquired one.76 8. ⃝ bernvald, william. van, medical treatment by electricity 1785. 『越列機療法』 ereki ryoho.1785. electricity treatment. over de geneeskundige electriciteit, amsterdam 1785-1789.77 9. ⃝ bullet 9 is included in blumenbach no. 2. 10. ⃝ hagen, k. g., pharmacy teaching. 『薬舗指南』 yakuho shinan. pharmacy teaching. leerboek der apotheker-kunst. amsterdam, 1807.78 116 yona siderer it is cited three times in seimi kaiso, concerning procedures to make ink and tincture. 11. ⃝ guiton de morveau, l. b., the method of purifying atmosphère 1811. 『大気修繕法』 taiki shuuzenhou. verhandelingen over de middelen om der lucht te zuiveren, en de besmetting te voorkomen leyden, 1802. french origin: traité des moyens de désinfectant l’air 1801.79 12. ⃝ trommsdorff, j.b., experimental finding in chemistry 1815. 『合薬舎密』 gouyaku seimi. medicine chemistry. leerboek der artseneimengkundige, proefondervindelijke scheikunde, naar de derde veel verbeterde uitage uit het hoogduitsche. amsterdam, translated by n.c. meppen 1815. original german title: systematische handbuch der pharmacie für angehende aerzte und apotheker, erfurt, 1792. 2nd. ed. 1811. most frequently cited work in seimi kaiso. more than 34 times referred to, including theoretical and applied parts.80 trommsdorff, j. b. (1770-1837) was also the translator into german of epitome of chemistry (eoc) by william henry. (see ypey no. 6). 13. ⃝ ségur, o.,the sea of letters on chemistry. 『舎密翰海』 seimi kankai. 1817. the sea of letters on chemistry. brieven over de grondbeginselen der scheikunde: gewezen leerling bij de polytechnische school, rotterdam, 1811. original french: lettres élémentaires sur la chimie 1803. sakaguchi masao noticed in udagawa youan’s list of sources for seimi kaiso, the title seimi kankai by octave ségur. sakaguchi identified that it is a translation of octave ségur’s book, written after lessons taught by professors berthollet, fourcroy, chaptal, guiton de morveau, etc. udagawa youan studied its dutch translation translated by m.j. reinhout, a medicine researcher from leiden, holland. in ségur’s book, following four chapters with an introduction and explanation about chemistry, the total of thirty two chapters describe topics of crystals of potassium carbonate, ammonium chloride, phosphorus, potassium phosphate, alum, silica, glass, black patina of silver, iron, mucus, rubber and more.81 14. ⃝ houte, h. j., medicine treaty 1817. 『福烏多薬論』 houto yakuron. medicine treaty by houte handleiding tot de materies medica, 1817. except for youan’s first list, there is not another citation of this book in seimi kaiso.82 15 ⃝ isfording, j. j., physical handbook for students of medicine. 『理学初歩』 rigaku shoho.basics of physical science natuurkundig handboek voor leerlingen in de heel en geneeskunde. amsterdam, translated by g.j. van epen 1826. german original: naturlehre für angehende aertze und wundärtze, als einleitung in das studium der heilkunde. wien 1814. tsukahara mentions several translations for this book, but there is only one citation in seimi kaiso, in a chapter about heat element, youan adds a note about light element 光素 kouso, that he also called photogeniumu and further describes the topics of calorique, photon and color.83 16. ⃝ hijmans, h. s., outline of general chemistry 『舎密崖略』 seimi gairyaku outline of general chemistry 1820. ontwerp van eene algemeene scheikunde. dordrecht, 1820. chapter 187 is a discussion on chemical combination of chloride of lime and acids. specifically, about the affinity between oxalic acid and lime, and boric acid and lime. tsukahara discusses another book by hijmans on chemical affinity for which youan wrote a separate manuscript.84 17. ⃝ stratingh, e., chemical study of cinchonine and quinine. 『幾那鹽說』 kina ensetsu. kina salt theory. scheikundige verhandeling over de cinchonine en quinine bevattende eene opgaaf van derzelver verschillende bereidingen, eigenschappen, verbindingen en geneeskundige vermogens,  groningen 1822.85 an autograph copy kept in waseda university library; it is a translation of chapters 1-9 on separation of quinine and 1-4 on its nature.86 18. ⃝ reinwardt, c. g. c., treatise on the measurement of the heights of mountains. 『測山説』 sokuzan setsu. mountain measuring theory. voorlezingen over de hoogte en vedere natuurlijke gesteldheid van eenige bergen in de preanger regentschappen, wit verhand. batavia. t.w.ix deel, 1822. comment 10 p. 82 in skr cites an article by sakaguchi 1970 on youan’s special interest in the method of the boiling point of liquids at different heights. in seimi kaiso youan presents exemples of five foreign mountains, boiling temperature on those mountains and their heights given in english and in japanese units.87 19. ⃝ niewenhuis, see no. 7. 20. ⃝ dutch pharmacopeaia 1826. 『和蘭局方』 waran (oranda) kyokuhou. dutch pharamcopeia. 117udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors nederlandsche apotheek ‘s-gravenhage (the hague) 1826. this work is cited 15 times in seimi kaiso, about manufacturing and properties of substances that are mainly used in pharmacy. e. g., property of potassium carbonate,88 and its manufacturing.89 21. ⃝ richerand, a., new basics of the physics of human physiology 1826. 『利氏身窮理篇』 rishi sinkyurihen. mr. richerand’s study of the physical laws of the human body. nieuwe grondbeginselen der natuurkunde van den mensch. amsterdam, 1826. french origin: nouveaux elements de physiologie, paris 1801, dutch translation by a. van erpecum, 1821 and 1826.90 in chapter 51 on “water containing vapor, vapor containing water”, youan comments saying that “according to richerand, in water, there is a kind of gas, inner water is used in animal breathing, and the sense of hearing is affected. if you put fish in a bell exhausted of air, the fish dies. also, insert into glass bottle, hermetically seal its mouth, the same thing happens”.91 youan also cites richerand’s book on human physiology in a chapter on bismuth and other metals.92 22. ⃝ catz smallenburg, f. van, chemistry study book. 『蘇氏舎密』 su shi seimi, mr. su’s chemistry. leerboek der scheikunde. leiden, 1827-1829. there are forty eight citations of catz smallenburg (1781-1848) in seimi kaiso. youan could have acquired there the most advanced chemical ideas such as berzelius’ electro-dualism. catz smallenburg cited many authors, including davy, bergman, gmelin, döbereriner, meinecke and others (1833 leyden edition). mac lean mentions catz smallenburg chemistry book presence in deshima in 1837, it was brought on the ship de twee cornelissen.93 the book was found in udagawa house old possessions. humphry davy (1778-1829) is cited 15 times. davy is cited concerning his use of the powerful volta column and the isolation of kalium. (see rees no. 24 below).94 azuma found in kyō-u library unpublished manuscripts by youan. azuma suggested that youan was exploring the possibility of publishing a chemical book titled kaibutsu engen-ko 開物淵原稿, based on the content of smallenburg’s chemical book.95 according to tsukahara, youan cites the work mainly from its practical and experimental parts; not advanced scientific theories but a more reflection of popular issues by a pragmatic chemist whose theoretical discussions were rather superficial.96 interestingly, in the next section on kalium, “that is also called potassium”, youan cites together the books by ypey 『広義』, smallenburg 『蘇氏舎密』 and niewenhuis 『紐氏韻府』.97 one may imagine youan sits and those three books are opened in front of him, perhaps more than those three only. the text reflects youan’s professional approach to his study. 23. ⃝ water, j. a. van de, mr. water’s pharmacy 1829 『窊多児氏薬論』 watarushi yakuron. mr. wataru’s pharmacy 1829. beknopt doch zoo veel mogelijk volledig handboek voor de leer der geneesmiddelen(materiamedica). amsterdam, 1829. topics cited in seimi kaiso from water’s book include: phosphoric acid,98 magnesium carbonate,99 potash and ammonia,100 barium hydrochlorate,101 and iodine.102 24. ⃝ rees, w. van, a report on galvani. 1803. 『ガルヴァニ 紀事』 gar ubani kiji ga lva ni account. verzameling van stukken, als bijdragen tot het galvanismus, zoo in opzicht tot dezelfs geneeals natuurkundige werkingen, 2 dln (1st en 1803, 2nd en 1805), arnhem, moelman. 103 end of udagawa youan’s list. substantia an international journal of the history of chemistry vol. 5, n. 1 2021 firenze university press giving credit where it’s due – the complicated practice of scientific authorship seth c. rasmussen history of research on antisense oligonucleotide analogs jack s. cohen chemistry, cyclophosphamide, cancer chemotherapy, and serendipity: sixty years on gerald zon thermodynamics of life marc henry darwin and inequality enrico bonatti loren eiseley’s substitution bart kahr new insight into the “fortuitous error” that led to the 2000 nobel prize in chemistry udagawa youan (1798-1846), pioneer of chemistry studies in japan from western sources and his successors yona siderer capillary electrophores is and its basic principles in historical retrospect 1. the early decades of the “long nineteenth century”: the voltaic pile, and the discovery of electrolysis, electrophoresis and electroosmosis ernst kenndler1,*, marek minárik2,3 the eminent russian – german chemist –friedrich konrad beilstein (1838-1906) in the literature between the 19th and 21st centuries aleksander sztejnberg review of what is a chemical element? by eric scerri and elena ghibaudi, eds. oxford: oxford university press, 2020 helge kragh substantia. an international journal of the history of chemistry 1(1): 7-24, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-6 citation: b.w. ninham (2017) the biological/physical sciences divide, and the age of unreason. substantia 1(1): 7-24. doi: 10.13128/substantia-6 copyright: © 2017 b.w. ninham.this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declares no competing interests. feature article the biological/physical sciences divide, and the age of unreason barry w. ninham department of applied mathematics, research school of physical sciences and engineering, australian national university, canberra act 2600, australia e-mail: barry.ninham@anu.edu.au abstract. d’arcy thompson in on growth and form tells us that the early founders of the cell theory of biology, and the physiologists believed that progress in their sciences depended critically on our knowledge of molecular forces. the hubris of a new science that followed the application of x-rays and other techniques to the structure of proteins, the focus on dna, transport in neurophysiology and ion pumps is understandable. in that progress, the environment, molecular forces and lipids played no role. structure and form took a giant, unifying step forward in the recognition of a key role for hyperbolic (non euclidean, bicontinuous) geometries, from the self assembly of lipids, surfactants and proteins; to nanostructure in inorganic and solid state chemistry generally. but the complementary concepts of function and growth that depend on molecular forces remained poor cousins. the reasons are becoming clear. changes in the foundations of colloid and physical science took place over the last 70 years since the theory of deryaguin, landau, verwey and overbeek took center stage. a number of related advances occurred. the first is in the conceptualisation and quantification, and understanding of recognition built into lifshitz theory, its many body, temperature and frequecy dependencies. the second lay in the quantification of hofmeister (specific ion) effects. these, due to dispersion and related hydration forces,  had been inaccessible to classical theories of electrolytes and molecular forces. this defect rendered theory impotent for prediction. the third has to do with the startling recognition that dissolved atmospheric gas, at a molecular level has qualitative effects which have been ignored. also ion specific, the effects are ubiquitous and range over enzyme activities to protein structure, catalysis and emulsion stability – “hydrophobic interactions” apparently disappear when gas is removed. the fourth is a new “nonhofmeister” universal ion specificity that occurs for bubble bubble interactions. inhomogeneity in temperature between bubbles and solvent can be used to catalyse high temperature reactions at low temperatures. these so far inexplicable effects open up other new technologies unimagined., in e.g., desalination, water purification and sterilisation and others. in other words the classical theories of physical chemistry that inform our intuition had become rigid and inhibiting to progress. application of fundamentally wrong theories of molecular forces based on electrostatic forces to many areas of biology like has produced an unhappy muddle. an account is given of these complexities that are missing from classical theories of physical chemistry. essentially although the greeks told us that the elements were water, earth, fire and air, we forgot the last two. 8 barry w. ninham when we include them, a different intuition and a new vistas emerge. the paper is complemented by two other relevant manuscripts: one is published in colloids and surfaces science b: biointerfaces 2017, vol. 152, 326-338. two sides of the coin. part 1. lipid and surfactant self-assembly revisited. the second has appeared in current opinion in colloid & interface science 2016, vol. 27, 25-32, surface forces: changing concepts and complexity with dissolved gas, bubbles, salt and heat. keywords. progress of sciences, molecular forces, surface forces, specific ion effects, bubble-bubble interactions, dissolved gas. 1. introduction this essay has a precedent in and pays homage to the magnificent book mathematics: the loss of certainty by morris kline.1 kline relates the calamities that have befallen mathematics. the realisation that the foundations were insecure, and did not as we thought, represent absolute truth led to a widening gap between mathematics and science. they are both poorer for it. mathematics, once the queen of the sciences, and science are hardly on speaking terms. our essay mirrors kline and explores a similar calamity that has befallen physical chemistry. that subject is the enabling discipline that underpins subjects as diverse as chemical engineering to soil science to molecular biology and physiology . the discipline of chemistry, whose name, from khemia, the black soil of egypt that gave it life, is the most venerable of the tribes of the physical sciences. it has failed to contribute to biology as it ought to have done. the reasons lie deep. we will show that the foundations were flawed. and that when they are repaired, a wall of non communication between biological and physical sciences begins to come down. 2. john w. draper and celebration of the enlightenment in the heyday of the age of reason in the 19th century there was an unlimited confidence in reductionism. let us hear from the american polymath and professor of chemistry at new york university, j.w. draper in the peroration to his encyclopaedic history of the intellectual development of europe published in 1876 by harper brothers.2 here is his peroration: in such things are manifested the essential differences between the age of faith and the age of reason. in the former, if life was enjoyed in calmness, it was enjoyed in stagnation, in unproductiveness and in a worthless way. but how different is the latter! everything is in movement. so many are the changes we witness even in the course of a very brief period, that no one, though of the largest intellect, or in the most favourable position, can predict the future of only a few years hence. we see that ideas which yesterday served us as a guide, die today and will be replaced by others, we know not what, tomorrow. in this scientfic advancement, among the triumphs of which we are living, all the nations of europe have been engaged. some, with a venial pride, claim for themselves the glory of having taken the lead. but perhaps each of them, if it might designate the country alas not yet a nation that should occupy the succeeding post of honour, would inscribe italy on its ballot. it was in italy that columbus was born; in venice, destined one day to be restored to italy, newspapers were first issued. it was in italy that the laws of the descent of bodies to the earth and of the equilibrium of fluids were first determined by galileo. in the cathedral of pisa that illustrious philosopher watched the swinging of the chandelier, and observing its vibrations, large and small, were made in equal times, left the house of god, his prayers unsaid, but the pendulum clock invented. to the venetian senators he first showed the satellites of jupiter, the crescent form of venus, and, in the garden of cardinal bandini, the spots upon the sun. it was in italy that sanctorio invented the thermometer; that torricelli constructed the barometer and demonstrated the pressure of air. it was there that castelli laid the foundations of hydraulics and discovered the laws of the flowing of water. there too, the first christian astronomical observatory was established, and there stancari counted the number of vibrations of a string emitting musical notes. there grimaldi discovered the diffraction of light, and the florentine academicians showed that dark heat may be reflected by mirrors across space. in our own times melloni furnished the means of proving that it may be polarised. the first philosophical societies were the italian; the first botanical garden was established at pisa; the first classification of plants given by caesalpinus. the first geological museum was founded at verona; the first who cultivated the study of fossil remains were leonardo da vinci and fracasta. the growth of chemical discoveries of this century were made by instruments which bear the names of galvani and volta. why need to speak of science alone? who will dispute with that illustrious people the palm of music and painting, of statuary and architecture? the dark cloud which for a thousand years has hung over that beautiful peninsular is fringed with irradiations of light. there is no a department if human knowledge from which italy has not extracted glory, no art she has not adorned. 9the biological/physical sciences divide, and the age of unreason draper’s book was written first in 1859 before italy became a nation; when the industrial revolution was coming into its apogee. it was reissued in 1876 america was still young and had recovered its confidence. hubris abounded in the emerging empires. it was as if, quoth general smuts, statesman of the british empire: “mankind has struck its tents and is on the march” . we can forgive draper’s naivete on an apparently boundless future driven by science and too easy dismissal of the age of faith. if we imagined that the core of what he says still rings true today, we face a rude shock. in the 19th century it was possible for one man to understand all science. the meetings of the british association for the advancement of science of the 19th century were attended and followed with much interest by the press and “gentlemen”, products of greater public schools who knew latin and greek. huxley argued with bishop wilberforce in defense of darwin. they followed burton and speke’s dispute over priority on the sources of the nile. they waited on the translation of the rosetta stone and layard’s and the french and german archeologists in nineveh, were excited by adams and le verrier’s prediction and observation of neptune in 1846. they were excited by the fossil record. they rejoiced with queen victoria when stanley greeted the lost hero missionary in darkest africa with: dr. livingston i presume. they rejoiced with the expansion of the railroads and even more when kitchener avenged general gordon with the systematic massacre of the mahdi’s large part of army with the new machine guns in khartoum. it has changed now. there is now fragmentation into a multitude of disciplines. each is surrounded by firewalls, and there is litle intercommunication. hubris now attends modern science, biology, and quantum mechanics. mindless replacement of thought by computers is our century’s equivalent of the age of faith. to computers are imputed all wisdom just like the church in the worst of prereformation times. this is a reflection of the tides of fashion or a gestalt, the periodic emergence and dominance of which we are hardly aware. just a time when science seems dominant, triumphant even, the new age of reason has disappeared, again. a new age of unreason is upon us. 3. d’arcy thompson’s plea it is exactly 100 years since d’arcy thompson (18601948) published his book on growth and form.3 he told us that the early founders of the cell theory of biology and the physiologists emphasised that progress in their disciplines had to wait on advances in our understanding of molecular forces and what even then we called colloid science. immanuel kant (1724-1804) had much the same to say, reported d’arcy. he said “of the chemistry of his day and age that it was a science but not a science – eine wissenschaft aber nicht wissenschaft, for that the criterion of a true science lay in its relation to on mathematics”.3 curiously, an aside, d’arcy could not bring himself to mention the great german chemists of the preceeding century on the track of what he pleaded for, fredrik w. ostwald (1853-1932) who mentored the first four nobel prizes in chemistry men like wöhler who synthesised urea to break down the myth of a special life force for biomolecules and friedrich august kekulé von stradonitz (1829-1896). perhaps this was because britain was at war with germany. the same recurs. witness the furious prejudice attached to “polywater” in felix franks’ book polywater and the russians during the cold war.4 lest our thesis be misinterpreted as an unfair attack on orthodoxy, let us remark that the claim that “the science is settled” raises a red alert. it is unique to the science of climate change only. there is no other science for which that claim is made by its acolytes. indeed if it were, the “science” would be dead and uninteresting. let us go through some of them. astronomy: at an international meeting in kyoto in 2016 the astronomers/cosmologists agreed that they have no idea of how to find dark matter or what it is, after 30 years of looking. (they are missing 98% of the mass of the universe necessary to explain the too rapid motion of spiral arms of galaxies). this is a bit of a problem to practitioners who can nontheless tell us the age of the universe with great precison. solar physics: we have no idea of the source of solar magnetic field nor of the origin and genesis of sunspots.5 these dark spots on the sun’s surface are gigantic magnetic storms. they cause a solar wind of ionised particles that hit the poles of the earth and ionise the upper atmosphere. hence ozone. but the sunspots flucuate and have disappeared in the last few years as they have in the past, coinciding with major weather fluctuations. for that matter the standard solar model lacks conviction. quantum mechanics: considered possibly the greatest achievement of physics. it is still in a mess. particle physics: it seems in a worse mess. the story of the many species of neutrinos and the higgs giant boson cern is as credible to those of us not adepts as the book of genesis, but less useful. geology. remember how samuel w. carey in tasmania who pushed the theory of continental drift was exco10 barry w. ninham riated? the theory was only accepted in the 1960s. revolutionary theories of the formation of granite and oregenesis are in the wind with the new book of john elliston.6 biology of all kinds. these new sciences still very much in the process of big changes. the sex of crocodiles depends on the temperature. kangaroo sex depends on concerted work between 17 different chromosomes. hence epigenetics, a word that means imputing all wisdom to dna is too simplistic. the physico-chemical environment of dna is important too. as for the source of the energy that drives ubiquitous enzymatic action, most are content with the statement that energy flows downhill. agriculture: the practice of planting without ploughing, a previously unheard of idiocy for millenia, is now often de rigueur – we forgot about the soil microbes. mathematics: as already remarked, it never recovered from gödel’s theorem that showed 100 years ago too that there was no such thing as absolute proof. in a stunning example of delusions of claims of rationality, the mathematicians not only rejected divergent series, but also rejected the delta function and periodic delta functions and their other generalised function cousins until 1950. the rejection is of major significance and still uncomprehended. the fact that a periodic delta function is a sum of cosines is both intuitive and profound. it is equivalent to the two forms of euler’s product, to jacobi’s theta function transformations, and the riemann relation. the latter is also intuitive and its equivalence to the periodic delta function means geometry and arithmetic, shape and that we count, are two sides of the same coin. a finite version of the calculus can be derived from these which also gives analytic continuation automatically. the usual infinitesimal calculus is a special case. the schrödinger equation of quantum mechanics and the diffusion equation are satisfied by the jacobi theta functions, which give out the classical, fermi dirac and bose einstein statistics of statistical mechanics. the uncertainty principle is not necessary in the more physical finite calculus.7 archaeology. a bit closer to the bone: the old kingdom in egypt ground to a big full stop after pharoah pepi i about 4500 years ago. this was discovered only thirty years ago. it turned out that the blue nile stopped flooding for thirty years. egypt was completely destroyed. the middle kingdom remerged in bastardised form several hundred years later. and of course they found the same happened to the euphrates and tigris rivers in mesopotamia. we had no idea. and the climate scientists forget what herodotus (484-425 bc) and strabo (65 bc-23 ad) reminded us about the rapid changes that took place in central  asia. a much larger oxus river used to flow into the  caspian sea and spill over to the black sea before it changed course again to the  aral sea so explaining how alexander went so far so fast. and so it goes in all these sciences, the science is definitely not settled. and all are deficient. this is not bad. it means that the challenges make life more interesting. we can be comfortable, not threatened if physical chemistry has some problems. to these we now turn. 4. growth and form, structure and function, lock and key structure, form, lock imply visual images, geometry and shape of living things. growth, function, key imply forces, dynamics, more than visualisable streaming matter in hydrodynamic movement like the gel interior of an amoeba in chemotactic motion. forces also implies the aether, the fifth element of the greeks, mysterious, that cause molecules to signal and recognise each other and come together as a result. forces will be our central preoccupation. they depend on all 5 of the elements of the greeks: earth, water, fire, air, aether (or quintessence). we will take fire to mean temperature. the secrets of greek fire which kept the turks at bay and the roman empire alive for 1000 years has been revealed by marcus graecus: recipe for greek fire: (due to marcus graecus, 10th century, quoted by john julius norwich) “take pure sulphur, tartar, sarcocolla (persian gum), pitch, dissolved nitre, petroleum, (obtainable from surface deposits in mesopotamia and the caucasus) and pure resin; boil these together, then saturate tow with the result and set fire to it. the conflagration will spread, and can be extinguished only by wine, vinegar or sand.”8 further illumination on greek fire we leave to the to the erudition of professor partington.9 but first consider. 4.1 structure it is self evidently a matter of physics. from bone to dna, with the discovery of x-rays by wilhelm conrad röntgen (1845-1923) and their deployment in x-ray spectroscopy by the braggs, father and son around 1912, structure took off, culminating in the structure of haemoglobin by m. perutz to 2 å resolution. although always plagued by the inverse scattering problem, of which more later, biology and physics came together in a productive 11the biological/physical sciences divide, and the age of unreason synthesis. (after papering over a few problems! the fact that revisiting the original x-ray data of rosalind franklin showed 4 stranded not two stranded dna as interpreted by watson and crick was dismissed by wilkins. he shared their nobel prize. when confronted with this annoyance he said: “why reject a good theory because of an experiment!” (told to the author by sir ernest titterton who knew him)). and then post the 1960s it all went pear shaped. for soft matter like self assembled lipids and microemulsions and colloidal suspensions. light scattering, sophisticated low angle x-ray scattering, neutron scattering, became possible because of accessibility of more and bigger machines for rent in search of problems and off-the-shelf computer programs. the results have been catastrophic. the non uniqueness of the inverse scattering problem means that the interpretation of an experiment depends on a theory. for example, with light scattering the inference of the zeta potential of a colloidal particle assumes that the theory applies to all particles and for all electrolytes. the theory is wrong and the results meaningless. with lipid-water self assembled structures, for thirty years distinguished physicists like luzzatti insisted on interpreting data in terms of models involving alternating stacks of rods. this was opposed by larsson and colleagues who interpreted the data in terms of bicontinuous cubic phases (see figure 1 for an example). the geometries are non euclidean. invented 200 years ago by gauss, lobatchevsky, bolyai and riemann, they were first thought to be mathematical anomalies. not so. the realisation that such geometries are the rule rather than the exception in biological structures was revolutionary.10-13 here then is a classical illustration of stephen jay gould’s (1941-2002) maxim: “i have long believed that conceptual locks are far more important barrier to progress in science than factual lacks”.14 ironically, gould’s main academic research devoted to the geometry of snail shells, committed the same error. he analysed them in terms of euclidean geometries when they were in fact non euclidean shapes.15 for microemulsions, self assembled soft matter from water or brine, oils and surfactant, the story is much the same. powerful and expensive scattering data interpreted microstructure in terms of spheres, cyinders and bilayers because that was all the the computer algorithms allowed. or more often than not, they are random bicontinuous structures as that revealed by cryo-scanning electron microscopy in microemulsion system containing isooctane, water and ddab (didodecyl dimethylammonium bromide).16 a structure – depicted in figure 2 that was easily determinable by use of a conductivity meter.17 or by taking account of constraints on packing by geometric packing, and volume constraints.18 figure 1. bicontinuous cubic phases of phospholipids. the average or sum of normal curvatures is everywhere zero, the gaussian curvatures varies continuously. reproduced from ref. 12 with permission of the international union of crystallography. http://journals.iucr.org/ figure 2. the bicontinuous structure inferred by a conductivity meter 30 years before the cryo-sem micrographs. the conductivity meter is cheaper than an electron microscope. such structures were often interpreted as spheres or cylinders from techniques like neutron scattering. reprinted with permission from ref. 17. copyright 1986 american chemical society. 12 barry w. ninham 4.2 structure and simulation at a nobel symposium in 1986 devoted principally to simulation in biology the first speaker, a swiss german working in the pharmaceutical industry began with a slide that said “nmr”. what, said he, does this mean? not nuclear magnetic resonance. no, quoth this enthusiast. it means: “no more research”. he proceeded to explain. with modern computer power and with 30,000 molecular potentials for each possible group – ch3, –oh, -nh2 –cl, etc. (but note, no water molecules) he could simulate the structure of any required drug and enzyme. game, set and match. when asked how he would deal with the fact that his model (human) enzyme denatured at 37 degrees centigrade this genius replied. “no problems. we change the parameters!” and more, we still can not explain or simulate why ice floats on water. for more than 40 years this evident insanity has persisted, and does to this day. much larger programs are bought on nih grants to “predict” the “structure” of proteins for extravagant amounts of money, by biologists mainly, and cancer research grants. the molecular parameters used have no relation to real molecular interactions, and the key ingredient, water, is missing. when asked if they would please turn off all parameters except that for neon-neon interactions, to test if their program would decide if the ground state energy of solid neon was a face centered or body centered crystal at zero temperature there is no simpler problem for simulation they resolutely refuse. the acceptance by hapless biologist and chemists of such evident charlatism is difficult to comprehend, and arose from frustration and ignorance. 4.3 structure: the rise of computers and simulation the story of this deviant science due to misuse of and unquestioning reliance on computers has lessons for the future progression of the age of unreason. one side of this we have already discussed. the easy interpretation of scattering data for structure in self organised soft matter through automated computer programs was clearly a massive and helpful development. but the programs depended on the assigment of structure via euclidean geometry, restricted to spheres, cylinders and planes. fitting of data was always possible by allowing an arbitary parameter that covered “interactions”. the fact that these were impossibly unphysical was ignored. this can be forgiven. no one was aware that the real geometries of nature were non euclidean, an example of stephen j. gould’s conceptual locks as a barrier to progress in science.14 this was not a fault of the physical sciences. it was a consequence of ignorance on the art of the life scientists and of chemists. the more serious issue is how such massive assignment of resources could be devoted to mindless simulation of matter.19 by simulation we mean for example taking a collection of spherical atoms like argon that interact via hard core repulsion and a two body van der waals interaction. program a collection of these in a theoretical box and let them go buzzing around like a bunch of bees until they reach a state of equilibrium. do this all at different “temperatures” and so construct the whole phase diagram for argon and its thermodynamic properties. the ultimate aim is described by practitioners as the “vision thing”. this is a state of nirvana where all proteins, all states of assembly, micelles, vesicles, membranes can be simulated by big enough computers, and as the german said: nmr. 4.4 life from outer space in his elegant account on the debate between galileo and lodovico delle colombe on the question of why ice floats on water, remarked that “galileo, i will argue, had a scientific style marked by overconfidence. he tended to downplay the importance of obvious contradictory evidence that undermined his claims, and he did this by producing auxiliary hypotheses that sometimes verged on the extravagant. if we focus on this somewhat neglected aspect of his style, some interesting new questions emerge: to what extent did galileo depend on such auxiliary hypotheses?”.20 very much so it turns out, and so for all of us in ways we do well to recognise. his thesis on reliance on “auxiliary hypotheses” is, in our parlance, tampering with the truth in support of one’s own prejudice. here is a true story that is relevant to our thesis: a professor from california came to my research department on sabbatical leave with a piece of a chondoraceous meteorite. these are meteorites containing organic material. the particular meteorite was called the murchison meteorite after a small rural town in the state of victoria, australia where it arrived on a farm. the farmer sold it, illegally, to nasa. nasa divided it up amongst scientists interested in such objects. their question was since the meteorites contain organic material, could it be that the material contained life-forming molecules. life might then be considered to have arrived on earth from outer space. our expertise was in colloid and surface chemistry, 13the biological/physical sciences divide, and the age of unreason relevant to the investigation. a very beautiful honours student was assigned this as a research project. she extracted the organic material and tested it out on a langmuir trough, a simple apparatus used for examining surface active molecules like proteins, polymers and other molecules. indeed the pressure-area curves showed all the signatures of biological molecules. this caused great excitement, celebrated by the appearance on a world wide science tv show by the student. the american professor went home happy. the success of his next grant application was guaranteed. alas, after he left the student and her professor finally got hold of a surface infrared spectrometer from another lab and tested these life forming molecules. they had all the signature of a protein called bovine serum albumin. the conclusion was obvious: either there are cows flying around in space or the murchison meteorite arrived at the farm on a piece of cow dung. it was clearly genuinely bullshit. when i told this story to the nasa chief scientist after his invited lecture to a gordon conference, he laughed and said – “of course”. but the american congress like this kind of stuff. it was good for funding. 4.5 berthollet and water structure claude louis berthollet (1748-1822) was a famous french chemist who went down to egypt with napoleon’s 1795 expedition.21,22 he observed on dried salt beds of the retreating nile flood lakes shiny deposits of soda lime, sodium carbonate. (this key observation marks the beginning of physical chemistry). how could it be? everyone knows that with a solution of sodium carbonate and calcium chloride as the water evaporates calcium carbonate, limestone, is precipitated first with the sodium and chloride ions remaining in solution. the missing factor is temperature. with the midday sun above 60° c the water structure is different, and the reverse happens. in many dried up rivers in egypt natron sodium carbonate essential for the economy in mummy preservation is the dominate precipitate. whatever water “structure” means it depends on temperature. water, h2o, above 80-90° c, is not hydrogen bonded, at all whatever that means. above such a temperature it behaves exactly like hydrazine, n2h4. the thermodynamics are identical for both water and hydrazine except that hydrazine is explosive. in solutions of calcium carbonate aragonite is the preferred precipitate above 100° c, calcite that at lower temperatures. water structure changes not just with temperature, but also with background solutes. this can be seen in precipitating nanoparticles. with magnesium or calcium hydroxide particles the size can be varied from microns to zero at will by adding sugars or indifferent salts to change the ambient water structure. the role of atmospheric dissolved gas is another overlooked and ignored factor that determines these matters. it depends on temperature and background solutes. it is generally considered irrelevant because it is so low. this is absolutely not so, as we shall see below. 4.6 microfossils and siderite recent debates on the age of life forms and astrobiology occurred with the observation of “microfossils” in very ancient rocks. the microfosills are much smaller than the familiar fossils, too small to represent traces of early life. that conclusion received support from the extraordinary observations in crystallography of juanma garcia, stephen t. hyde and other collaborators on “microfossils”.13 they can be made in the lab with simple experiments. such inorganic structures probably result from precipitation under double diffusion gradients, and mimic precisely real fossils in form. i leave this challenging new old world to the reader to explore. relevant to these matters is the work of mccollom on the formation of meteorite hydrocarbons from thermal decomposition of siderite, feco3.23 thermal decomposition of siderite had been proposed as a source of magnetite in martian meteorites. laboratory experiments were conducted to evaluate the possibility that this process might also result in abiotic synthesis of organic compounds. siderite decomposition in the presence of water vapor at 300° c generated a variety of organic products dominated by alkylated and hydroxylated aromatic compounds. the results suggest that formation of magnetite by thermal decomposition of siderite on the precursor rock of the martian meteorite alh84001 would have been accompanied by formation of organic compounds and may represent a source of extraterrestrial organic matter in the meteorite and on mars. the results also suggest that thermal decomposition of siderite during metamorphism could account for some of the reduced carbon observed in metasedimentary rocks from the early earth.23 the important point hardly noticed is that the addition of water to the inorganic iron carbonate rock produced a huge range of complex organic products that occur in oil reservoirs. it had been thought that such “life” product molecules in oil reservoirs had to be the consequence of bacterial activity or forests. it had been postulated by t. gold in 1990’s and other model experiments done in 2004 confirmed that such processes can 14 barry w. ninham indeed be the source of semi infinite as yet untapped sources of natural gas and oil.24 the matter is completely open and of extreme interest. it is connected also to the present interest in “climate change”. 4.7 the business of water structure the several examples above have been chosen to illustrate something we will continue to emphasise. in the absence of solutes or interfaces we think of water and model it as a greek element in its own right. hydrogen bonding is a concept widely used. it derives from a calculation of interactions between two water molecules only. it is elusive and even as an effective quantity a la pople changes with temperature. attempts to model water structure cooperatively, imitating a kind of dynamic zeolite that go back to bernal seem to capture some of it.25 but dissolved atmospheric gas is missing. and that really matters. the tensile strength of water against cavitation is 200 times larger than for gas free water, a matter of profound economic importance for the shipping industry. even if we were to make a molecular model of pure water correctly, the reality is this business of gas, temperature and salts and other solutes, and of their interdependence. and of chirality. is water chiralic?26 and of magnetic and electric fields. and of jellyfish, last studied seriously by gortner27-29 in 1933. jellyfish exist with as little as 2% nonaqueous material. there are some very long range forces that might explain their existence.30 but nobody knows. and and and ... so much then for structure and form. let us see how we are placed with forces and function. 5. surface forces we have reviewed the state of surface and molecular forces in a number of recent papers, in particular ref. 31. the situation is evolving. by and large it has been mired in dogma and catastrophic. the entire foundations of the 150 year old venerable field of physical chemistry are flawed. the edifice built on those foundations, has necessarily been built on sand and continually patched up and papered over with more and more effective parameters. the intuition drawn from the theories was wrong and all predictability was lost. where theory failed, reconciliation was sought by invoking undefined and unquantifed words like hydration, hydrophobic, hydrophilic, hydrogen bonds. after a long time, there is at last a clearer path through the morass. at risk of repetition, but it is so complex that to put our thesis into context, and how to go forward we do so partially and briefly again. several missing factors influence real surface forces remarkably. so much that the classical theory is often useless to the real world. among these factors, we count dissolved atmospheric gas or other sparsely soluble solutes, bubble–bubble interactions. moreover, inhomogeneity in temperature between bubbles and solvent can be exploited to catalyse endothermic reactions at low temperatures. further, the additivity of electrostatic and dispersion forces assumed in the classical theory of forces is wrong. it also ignores ion specificity (hofmeister effects) due to dispersion forces acting on ions. we will explain below the complications that we are missing from classical theories of surface forces. some are explained, most not. once revealed however, fortunately these phenomena can be exploited for a range of novel technologies as we shall see. 5.1 the classical picture of molecular and surface forces: limitations and insights the van der waals interaction potential between two atoms behaves as v(r) ~ 1/r6, where r is the distance between the centre of the atoms. this was known to newton. the potential of interaction between two planar surfaces at separation l follows by pairwise addition. it varies as 1/l2. newton tried to quantify this force, but gave up, with the comment (art. 31 of the principia): surface combinations were owing. unlike gravity, surface forces vanish rapidly over very short distances and depend critically on the material properties. and, as for contamination, it will always be with us. for the opposing electrical double layer forces between two charged surfaces in a continuum electrolyte, the repulsive forces decrease exponentially with distance; asymptotically, v(l) ~ exp(-κl) where κ-1 is the electrolyte debye length. the pre-factor depends on assumed boundary conditions, constant potential or constant charge. these conditions were relaxed with the extension to allow charge regulation.32 this was a great conceptual advance. the degree of ionisation of surface charges – and therefore surfaces forces – recognises, and changes in its response to the proximity of, and signalling from, another body. these few short lines underlie the dlvo (deryaguin, landau, verwey, overbeek) theory of colloidal particle interactions. the theory has been a core belief to physi15the biological/physical sciences divide, and the age of unreason cal chemists for 50 years. it still is so in spite the fact the theory has severe limitations, already acknowledged by both deryaguin and overbeek. these have to do with the assumption that a liquid between interacting bodies keeps its bulk properties up to a molecular distance from an idealised surface. further, apart from the contamination problem, most surfaces are not molecularly smooth or chemically homogeneous and pure. in addition solvent molecules may interact directly with the surface, for example through hydrophilic or hydrophobic effects in the case of water. specific ion effects are also ignored. and more, the theory has other amplified problems when the background electrolyte concentration increases, where only very short range surface forces emerge and these other factors can dominate. especially in the real world. the dlvo ansatz supposes that van der waals and electrostatic forces are additive. sadly they are not.33,34 note that this key ansatz is wrong even for a continuum solvent approximation, and wrong for free energies of transfer (born energies), interfacial tension, activities of electrolytes and particle interactions. it is deficient in two crucial respects even within the constraints of its own assumptions. the additivity of forces ansatz is wrong. which implies that the theory can not handle specific ion effects crucial in biology. it is wrong for any problem involving interpretation of experiments on electrolytes at interfaces, zeta potentials, electrochemistry, ph, buffers, ion binding to proteins or lipids, conduction of the nervous impulse and ion transport. the statement is heretical but remains true. even the iupac committee on ph warns us about the problems of ph and its meaning. and as for buffers, every biologist knows one does not mess with any protocol that accidentally works! 5.2 first steps beyond dlvo theory: complexities with double layer and oscillatory forces a not insignificant aside is that the standard equation to calculate the debye length for symmetric electrolytes is not valid for asymmetric electrolytes. it has a much more complex form. direct force measurements for 12:1, 8:1 electrolytes (cytochrome c) and insulin 5:1 and 3:1 give precise agreement with theory.35,36 at small distances, i.e. several molecular sizes, the electrostatic forces are dominated by oscillations. these are sometimes called depletion forces. they act to stabilise emulsions and other systems where e.g. proteins or micelles form part of a fluid that separates two interacting objects.37 this “molecular granularity” emerges in all liquids, from van der waals hard core fluids38-40 to micellar suspensions.37 the oscillations decay with separation and merge into the continuum theories after about 6 oscillations. 5.3 hydration: surface induced liquid structure the assumption that a liquid adjoining a surface has its own bulk properties up to contact (at molecular distance) breaks down for reasons other than molecular granularity. the profiles of surface induced liquid order can overlap and originate either repulsive or attractive “hydration” forces. (the terms surface dipole or hydrogen bond ordering are often used and cause much damage. the effects are cooperative not individual molecular properties) these forces dominate at small separation. for surfaces that are rough at the molecular level, e.g. phospholipid head groups in a bilayer, the oscillations are smoothed out and decay with an exponential form with a range of about a molecular diameter (0.3 nm). they dictate van der waals interactions up to say 3 nm separations. correlated fluctuations in the surface dipoles of the head groups can produce other forces. they can appear in force measurements as a hidden contribution that changes effective hydration decay lengths. thus, for example in the smaller ethanolamine polar head group such contribution is larger than in the bulkier phosphatidylcholine residue. the apparent hydration range is smaller for the former.41 maxwell was the first to calculate correctly hydration forces,42 followed by marcelja 100 years later.43,44 5.4 complexity in van der waals forces. lifshitz theory: emerging concepts of recognition lebedev, the discoverer of light radiation pressure, renovated d’arcy thompson’s criticism and wrote:45 ... of special interest and difficulty is the process which takes place in a physical body when many molecules interact simultaneously, the oscillations of the latter being interdependent owing to their proximity. if the solution of this problem ever becomes possible we shall be able to calculate in advance the values of the intermolecuar forces due to molecular inter-radiation, deduce the laws of their temperature dependence, solve the fundamental problem of molecular physics whether all the so-called ‘molecular forces’ are confined to the already known mechanical interaction of light radiation, to electromagnetic forces, or whether forces of hitherto unknown origin are involved. lifshitz with theory in 1955, and abrikossova and deryaguin with experiments in 1956, confirmed lebedev’s vision on molecular forces. the work was continued also by dzyaloshinski and pitaevski who developed – with lifshitz a theory of interactions between two planar dielectric surfaces separated by a liquid. again, 16 barry w. ninham the hydration was neglected, as the liquid in contact with the two surfaces was assumed to retain its bulk properties.45-47 under these premises, the theory was developed in the framework quantum field theory and was expected to provide the full solution of the problem. it comprised the temperature dependence of the intermolecular interactions, all many body interactions, and contributions from the entire electromagnetic spectrum. the major step was the acknowledgment that the measured dielectric susceptibilities of interacting bodies – that depend on the frequency – include implicitly all many body interactions.46,47 this topic is still an active field of basic research. however, the theory was difficult to test, until the work of ninham and parsegian on lipid-water systems.48,49 the theory was then extended to include different shapes, layered, conducting and magnetic bodies, and electrolytes.50 again, the crucial point for us here is the fact that the potential is given by all the contributions that derive from the electromagnetic spectrum. some of these terms are positive, some repulsive, depending on the specific interacting materials, i.e. depending on their dielectric properties. for a planar geometry, the frequency term f(ω) decreases exponentially as: f ω,l( )~− a ω( ) l2 exp − 2ωl cε iω( ) ⎡ ⎣ ⎢ ⎤ ⎦ ⎥ (1) where ω, l, c, and ε(iω) are the frequency, the distance between the two bodies, the velocity of light and the imaginary dielectric susceptibility of the medium at frequency ω, respectively. for simplicity i omit the expression of the pre-factor. the most important result of this model is that two bodies feel and recognise temperature dependent zero frequencies first. as they come closer and closer, then frequencies contribute in order of increasing energy: first the lower energy infrared components (with wavelenghts λ between 2 and 5 micron), followed by optical (λ ~ 400 nm), far ultraviolet (λ ~ 100 nm), until the two ojects come into atomic contact or hydration. this is precisely where chemistry takes over. alternatively, two objects sense each other’s “specific vibrations”, and respond appropriately. in some cases this specific interaction is very strong and extended in space. it is interesting to calculate the interaction potential for two thin parallel rods of a conducting material at a distance l, which is the case of dna strands: v l( ) ~1/ l for r<< κ-1 (2) v l( )~ l•ln l r ⎛ ⎝ ⎜ ⎞ ⎠ ⎟ 2⎡ ⎣ ⎢ ⎤ ⎦ ⎥ −1 for r >> κ-1 (3) where r is the radius of the rod and κ-1 is the debye length. the force is strictly non additive and basically infinitely long ranged. instead, two planar conducting surfaces interact with a short ranged potential.51 the problem becomes more intricate, as the temperature dependent contributions decrease with another factor that is related to the reciprocal of the debye length, i.e. as exp(-κl). the concept of recognition, that depends on the physico-chemical features of the materials and of the surrounding medium, was captivating. but the claims for generality went too far. in fact at the end the theory turned out to comprise an integration trick. the mystique of quantum field theory (qft) was exposed and the entire building collapsed to a semi-classical theory: it was shown to be nothing more than maxwell’s equations for the electromagnetic field with boundary conditions plus the planck hypothesis for quantisation of light.31,51 the equivalence of qft with a semi-classical theory brought about a deep extension of the theory. but the theory on molecular interactions is constructed at zero temperature, for example the casimir-polder and casimir interactions for “retarded” van der waals interactions. “retardation” refers to a reduction in the interactions because of the finite speed of light. the problem is that all this is quite wrong!52,53 in a similar way the discussion of resonance or retarded forster interactions involving excited stateground state interactions that are the basis for disputed quantum computing procedures are even more incorrect and with no physical correspondence.54 nonetheless the visions, as in the case of the dlvo theory, endure and cheer the boetians. furthermore, another overlooked development emerges if we try to relate casimir–lifshitz forces at finite temperature in a vacuum and particle physics. weak interactions (mesons) seem to merge naturally and quantitatively.55,56 we have mentioned these matters because however arcane that may appear, it is reassuring that the same errors underlie both physical chemistry and physics. 6. hofmeister phenomena and the inadequacy of dlvo theory hundred and fifty years have passed, since the pioneering work of franz hofmeister in prague at the end 17the biological/physical sciences divide, and the age of unreason of the 19th century, and physical chemistry is still unable to comprehend and predict specific ion effects. unless one introduces arbitrary parameters like postulated ion size. as in the debye-hückel theory, the size is adjustable and different for every solvent and temperature.57 the issue propagates and affects born energies, interfacial tensions, activities, ph, pkas, buffers, ion binding, viscosities and all other bulk or interfacial experimental parameters.58 hofmeister investigated the relative effectiveness of different salts in precipitating albumin in water and established the so-called “hofmeister series”:58 anions at fixed cation: citrate3> ch3coo> so42> f> cl> br> ications at fixed anion: n(ch3)4+ > nh4+ > cs+ > rb+ > k+ > na+ > li+ > ca2+ > mg2+ such series occur in chemistry, biology, biochemistry, geochemistry, practically everywhere. it is not universal but depends on substrate and probably dissolved gas.58 hofmeister’s original work is translated and re-published in ref. 59. two examples are illustrative of the problem. 6.1 measuring the ph if one measures the ph of 1:1 strong sodium electrolytes in buffered solutions with a glass electrode, the “ph” change in a phosphate buffer follows a hofmeister sequence. but if sodium is replaced by potassium salts the sequence reverses! and using a cacodylate buffer at the same stated ph as phosphate the sequence reverses from the phosphate case also.34,60 this and several other common measurements are inexplicable with classical theory, because it does not have room for specific ion effects. none of the measurements make any sense in classical theory. according to common knowledge and understanding the two buffers must give the same results, and these must not according to textbook theory depend on the nature of background electrolyte (hofmeister effects). though the measurements are performed in terms of that erroneous theory. if we ask what a ph measurement in the ocean means, it makes sense only if interpreted as alice in wonderland says: when i use a word, humpty dumpty said, in rather a scornful tone, it means just what i choose it to mean—neither more nor less.61 the same problem emerges in a plethora of different phenomena and measurements, like ion binding to proteins. 6.2 indirect forces and the activity of enzymes another stark example of the failure and inadequacy of theory is any explanation of the energy that drives enzyme action. the cutting by a restriction enzyme of linear dna44,62 is an essential tool of molecular biology. like the problem of ph, cutting efficiency makes no sense in terms of dna-enzyme forces predicted by dlvo. the energy required to cut segments on the dna chain seems to be indirect and subtle. it seems to be given by hydrophobic cavitation that originates free radicals. figure 3 shows the efficiency of enzyme (expressed as percentage of linear dna) as a function of the electrolyte concentrations for a set of sodium salts. similar results exist for cation sequences.44,62a as for our ph problem the phenomenon is remarkably ion specific. it depends on the buffer used to set the nominal ph value of 7.5. strikingly, the trend reverses when the phosphate buffer is replaced by cacodylate.44 the standard theories of forces  cannot explain the experiments. nor does it provide any hint  at the  source of the energy to carry out the enzymatic activity. specific ions, both cations and anions, and buffer anions compete to set hydration and inter-substrate and enzyme water structure that determine association. the enzyme dimerises, diffuses up and down the linear dna chain to find the right palandromic sequence (figure 4).62b there follows hydrophobic cavitation, a cooperative harnessing of all the weak van de waals forces that creates free radicals. these then cut the dna at precise palandromic sequence. whether the cavitation phenomenon depends on dissolved gas is unknown. that this mechanism is likely can be seen if a free radial scavenger is added to the mix. it stops the enzyme dead. the gap between physical theories and real molecular biology is evident. but, importantly this example shows there is  a way through what seems to be a bewilderingly inexplicable mess. 6.3 more on hofmeister effects: unpleasant facts and pleasant consequences as i mentioned, specific ion effects emerge dramatically in a myriad of other phenomena, e.g., in the formation of self-assembled micelles, vesicles and microemulsions from surfactants. interestingly here we observed that forces with different coions and counterions and forces between interfaces can change very remarkably.34,58,63,64 the dlvo theory unsuccessfully tries to explain such variability by importing extra non predictive parameters like ion size. these are often absurd. the ansatz of 18 barry w. ninham dlvo theory that supports the entire fabric of the discipline is flawed. in fact physics does not allow to add electrostatic forces, treated in non-linear theory, to van der waals forces treated in a linear theory. the problem is not simply a matter of approximation, the entire theory has to be rewritten. the bad consequences are that most measurements like ph and ion binding that are based on the classical theory are of unsure meaning. on one hand this is unpleasant and disappointing and is therefore almost universally ignored. on the other hand, a great effect is that the few who do not try to hide or neglect the problems are in a good position to use forces due to specific ion effects. deryaguin and overbeek both were well aware of the limitations of their theory of interactions of colloids, of specific ion effects and that it failed above a concentration of 50 mm. the best advice of the iupac committee on ph is to avoid electrolyte concentrations above at most 100 mm. and anything more complicated: forget it. for a detailed account of the present state of affairs and opinion on hofmeister effects see a recent current opinion in colloid & interface science special issue63 and a recent paper of leontidis.64 the physical chemistry of electrolytes, and electrochemistry, got stuck in a frustrating swamp, a parameter-rich hiatus for a century. more recently the recognition that we lack the quantification and inclusion by ab initio quantum mechanics of ion size, hydration and dispersion forces was understood and at least partially accepted. some promising advances on born self energies, interfacial tensions, ion activities and the vexed problem of the air-water interface potential. average ionic activities of twenty one monovalent electrolytes can be actually predicted with just three universal parameters. whether these advances can be extended to asymmetric, and mixed electrolytes and include temperature is still an open question.65-69 figure 4. cartoon of the problem of restriction enzymes. the enzyme cuts a dna strand at a specific sequence of nucleotides. the star represents the enzyme active site. adapted from ref. 62b with permission of springer. figure 3. enzyme cutting efficiency versus the concentration of the electrolyte at ph 7.5, for a set of different 1:1 sodium salts. the buffer used was phosphate (a) or cacodylate (b). reprinted from ref. 44, copyright 2016, with permission from elsevier. 19the biological/physical sciences divide, and the age of unreason 7. hydrophobic forces and dissolved gas however, the challenge generated by the flaws in the foundations of the theory and the disregard of hofmeister effects is a minor concern.44 long ranged hydrophobic forces between interfaces have been measured and reported in several papers. but the mystery that surrounds this kind of forces remains: when the dissolved atmospheric gas is removed from the sample these forces disappear. although tricky, this fact offers a possible hint to clarify thr mechanism: surfaceinduced water structure can extend only a six molecular diameters or so. the perturbation lowers the density of a thin film compared with bulk water. this causes a density lowering in the gap between the interfaces and generates the force due to the difference between the pressure inside the gap and outside. the range should be about 3 nm, i.e. 6 water molecules. dissolved gas molecules play the same role that defects do in a solid. they disturb the tensile strength of a thin film of water between the two surfaces. the fluctuations or defects that result in the lowering of the liquid film density are carried from the surfaces from one gas molecule to another and percolate across the gap. ions can either oppose or promote these complex fluctuations in the interfacial liquid density. further discussion on the mechanisms of hydrophobic forces can be found in the literature.70-73 yaminski pioneered studies on hydrophobic forces along with — and independently of pashley and kitchener. he actually had read and understood gibbs’ work, famous for its obscurity. “hydrophobic” forces exist, extend across long distances and depend on interacting surfaces and dissolved gas, no matter which microscopic mechanisms control them. unfortunately they cannot be easily simulated. they are not explained or predicted by classical theory, but must be part in any picture of self-assembly and interactions in biologically relevant systems. an outstanding, surprising and graphic demonstration of surface forces arises when a mixture of a hydrocarbon and water is almost completely de-gassed.74 some years ago it was reported that cavitation occurs when two hydrophobic surfaces immersed in water were pulled apart. this means that the removal of dissolved gases may facilitate ‘oil mixing with water’ because dissolved gases promote cavitation. this idea has now been well established. the degassed oil-water dispersion remains stable for several hours, whereas a regular mixture (with dissolved gas in) phase separates very rapidly. if dissolved gases significantly affect hydrophobic interactions then direct surface force measurements should be able to detect and quantify such effects. these have been reported, although the topic is fraught with contraddictory results. in the future it will be interesting to check the effect of dissolved gases on coalescing a single oil droplet, an experiment that has not yet been performed. dissolved gas and other poorly soluble solutes must propagate the attractive force between two hydrophobic surfaces to a much longer distance than should be predicted from merely a solvent molecular ordering perturbation, which in water can extend a few nanometers. by comparison, hydrophobic attractions have been reported out to about 90 nm. the gas problem poses more than just a dilemna. the solubility of a gas in water depends also on salt nature and concentration. so far this evidence has been simply ignored. as descartes might have said “i breathe, therefore i am”. fish philosophers would have a similar view. and they are certainly correct. 8. bubble-bubble interactions: a case of non hofmeister ion specificity an even more perplexing problem is the phenomenon of bubble-bubble coalescence in electrolytes. it is hard to think of a simpler and relaxing experiment – contemplate the ocean. in fresh water bubbles coalesce (look at a water fall). instead the ocean is foamy, and this is not a consequence of pollution or of the presence of organic matter. the effects of salts on inhibiting bubblefigure 5. scheme of the apparatus for producing bubbles and measuring their optical density. the gas is admitted from the bottom, passes through the frit and bubbles through the liquid contained in the chromatographic column. from the top more solvent or a salt solution can be added. courtesy of vincent s. j. craig. 20 barry w. ninham bubble coalescence has been well studied for more than 30 years.75-79 but there is still no explanation at all. the background (and more references) is described in ref. 44. this is the experiment: air or another gas are passed through a frit to a column filled with salt solutions. figure 5 illustrates the very simple apparatus. the bubbles collide as they rise in the column and fuse. the column remains clear. as the salt concentration increases, in a sharply defined range the bubbles no longer fuse and the column becomes opaque. it is filled with a mass of fine bubbles. the effect is the same for a whole range of all salts (see figure 6) and scales with the debye length of the electrolyte 1:1, 2:1, 1:2, 3:1, etc. the phenomenon occurs for one class of ion pairs. for another class no effect occurs the bubbles continue to fuse at all concentrations! this is inexplicable within the framework of a classical physical chemistry theory of forces between bubbles (dlvo). in fact dlvo predicts a bubble coalescence enhancement with added salt because (i) it should screen out any electrical double layer repulsion between negatively charged bubbles and (ii) should increase the surface tension — favouring bubble coalescence. the situation is further, and greatly complicated, by the fact that some salts inhibit coalescence and some do not. and similar effects occur in polar non-aqueous organic solvents too, like methanol, propylene carbonate, formamide and dimethylsulfoxide. “explanations” of hofmeister effects re-appear every decade, but they are specious and wrong.44 they reflect the religious fervour in which the dlvo theory is clung to. these results are as profound as they are simple and inexplicable. temperature, gas type, adsorbed ion hydration and film viscosity and other candidates have all been ruled out of contention and appear not to influence the observations and their ion pair dependence. the same kind of specifc bubble-bubble interaction inhibition occurs for different isomers of sugars or mixtures of sugars. a related puzzle is that of the sign of the air-water interface. is h3o+ or ohthe more favoured species? bubbles are negatively charged. it is a simple question. see ref. 44 for the latest state of play. 8.1. contingency in evolution an interesting speculation is suggested by the bubble bubble salt inhibition phenomenon. in the ediacaran extinction, 570 million years bp, multicelled animals all died. in the burgess shales extinctions, 530 million years bp there were considered to be at least 24 highly successful phyla. that figure may have been reduced by now due to better classification. but only 4 phyla surface to become us. only 4 survived including us. in the permian extinction, 230 million years bp 95% of all species disappeared. these extinctions coincide with known co2 cycles and consequent ice ages. there followed precipitation and removal of salt from isolated oceanic regions. after the ice ages and melting of the ice, there would follow a reduction of salinity below 0.175 m, as for example in the baltic ocean. the present ocean is about 0.4 m, while all animals including us have permian ocean salt concentration 0.175 m. massive extinction of phytoplankton would follow the end of the ice age. it is possible the extinctions occurred as every species would have died of the bends, due to bubble-bubble fusion! 9. wishing reason of the ocean jan morris in the third of her exquisite volumes on the british empire, farewell the trumpets began with the fin de siècle celebration of queen victoria’s diamond jubilee of 1897. she said:80 figure 6. the gas bubbles diffuse through water (left) and through a 0.3 m nacl solution. in the salt solution the bubbles coalescence is remarkably reduced. courtesy of vincent s. j. craig. 21the biological/physical sciences divide, and the age of unreason if to the queen herself all the myriad peoples of the empire really did seem one, to the outsider their unity seemed less than apparent. part of the purpose of the jubilee jamboree was to give the empire a new sense of cohesion. but it was like wishing reason upon the ocean, so enormous was the span of that association, and so unimaginable its contrasts and contradictions. physical chemistry is a bit like that. like the empire it made a muddled progress during the same period. and like the empire it was like wishing reason upon the ocean. literally! as morris said of the empire that had reached its nadir. suddenly it was time to go, like the whisking away of an opera set on a revolving stage. and maybe too for our venerable discipline of physical chemistry. it ought to be supporting the rambunctious new tribes of the biologists still confident in the first flush of success in a new science, but is not. in our essay, we have seen that what we considered dependable, and the ritual experiments we practiced and their paraphenalia to give us reassurance were false gods. think of non euclidean and random bicontinuous geometries that are taking center stage, of erroneous force laws, of hofmeister specific effects, of the astonishing pervasive role of dissolved gas and hydrophobic interactions, and of the equally astonishing phenomenon of bubble-bubble interactions. so, is nothing sacred? probably not. at least now though we can recognise the value of stephen j. gould’s aphorism on conceptual locks14 and practice the first steps towards a damascene insight and conversion. there are difficulties that can be identified. a major one is that the biologists have been seduced into paying lip service to false gods which are now deeply imbedded into their dogmas. perhaps that can be overcome as the rewards for service have been few. we began with morris kline. in his peroration on the plight of mathematics he said:1 it behooves us therefore to learn why, despite its uncertain foundations and despite the conflicting theories of mathematics, mathematics has proved to be so incredibly successful. for the physical sciences in biology and medicine the question is reversed. why is it that we have been so incredibly unsuccessful? the reasons seem clear enough. time to rebuild the temple. heresy, but necessary. from that vantage point we return to john w. draper and his enthusiastic boundless confidenee in the age of reason.2 it parallels the confidence of the mathematicians at the world congress in paris in 1900. hilbert the acknowedged best of the brightest announced 21 propositions that remained to be proved before the edifice of mathenatics was consistent. the edifice fell to the ground almost immediately after. is draper’s confidence justified? not in the age of reason which led us via kantian certainty to a sterile cul de sac. when the physicists have a theory that allows neutrinos en masse to penetrate 100 light years of solid lead before a few are detected, reason has to go. 10. the ocean fights back curiously, we can hope that draper’s confidence will be justfied in the new age of unreason. and here is why. we have identified substantial deficiencies in theory, and in consequence, in measurements that depend on those theories. suppose those difficulties are resolved — the matter is more complex still. dissolved gas, cavitation and bubbles, specific ion effects, and temperature, are all components of the ancient greek view of the elements: earth, air, water and fire. we have been missing air and fire and light, which we have hardly touched on. we have described some of the astonishing phenomena that attend admitting gas as one of our elements. we have no theory. if we now do include temperature by allowing hot bubbles through a sinter to our electrolyte bubble column marvellous things happen that we never dreamed of. some are described in refs. 44 and 81. technologies have emerged that allow high temperature aqueous solution reactions to be done at low temperature. the hot bubble surfaces are amazingly reactive. desalination can be done without membranes very much more cheaply than the best conventional methods. viruses and drug molecules are killed so that the use of recycled water becomes possible. removal of heavy metals like arsenic, lead and mercury becomes easy. carbon dioxide gas bubbles are extraordinarily reactive even at room temperature. and more that experiment reveals, that we can use, and we have not the faintest idea of why they work. these new breakthroughs are pioneered by r.m. pashley. watch this space. finally in homage to morris kline we repeat his translation of some aphorisms of xenophanes (6th century bc) that seem to be apposite: the gods have not revealed all things from the beginning. but men seek and so find out better in time. let us suppose these things are like the truth. but surely no man knows or will ever know the truth about the gods and all i speak of. for even if he happens to tell the perfect truth, he does not know it, but appearance is fashioned over everything. there are rapid strides being made to improve and remedy present theories. and what is encouraging is that 22 barry w. ninham when the chemistry is done correctly, when the conceptual locks are removed, more often than not the emerging theories do actually work, predictively. acknowledgments i have worked on the topics of this paper since 1968 when i began an exciting collaboration with v. adrian parsegian. since then i have had the luxury and privilege of working with very many colleagues and students. i am indebted to them all. i owe a special debt to pierandrea lo nostro, stephen hyde, adrian parsegian, and richard pashley. references 1. m. kline, mathematics: the loss of certainty, oxford university press, 1960. 2. j.w. draper, history of the intellectual development of europe, harper brothers, new york, 1864. 3. d’arcy w. thompson, on growth and form, cambridge university press, 1917, 1942, 1969. 4. f. franks, polywater, the mit press, 1981. 5. o.k. manuel, b.w. ninham, s.e. friberg, j. fusion energ. 2003, 21, 193. 6. j. elliston, the origin of rocks and mineral deposits, connor court publ., ballarat, 2017. 7. b. hughes, b w ninham, physica a 2016, 443, 495. see the book of james lighthill and the papers of m.j. berry cited 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yaminsky, b.w. ninham, langmuir 1996, 12, 4969. 71. v.v. yaminsky, b.w. ninham, langmuir 1993, 9, 3618. 72. v.v. yaminsky, b.w. ninham , adv. coll. interface sci. 1999, 83, 227. 73. v.v. yaminsky, s. ohnishi, b.w. ninham, in handbook of surfaces and interfaces of materials, vol. 4., chapter 3, pp. 131-227. academic press, cambridge, 2001. 74. r.m. pashley, j. phys. chem. b 2003, 107, 1714. 75. b.w. ninham, adv. coll. interface sci. 1982, 16, 3. 76. v.s.j. craig, b.w. ninham, r.m. pashley, nature 1993, 364, 317. 77. v.s.j. craig, b.w. ninham, r.m. pashley, j. phys. chem. 1993, 97, 10192. 78. c.l. henry, v.s.j. craig, langmuir 2008, 24, 7979. 79. g. liu, y. hou, g. zhang, v.s.j. craig, langmuir 2009, 25, 10495. 80. j. morris, farewell the trumpets, vol. 111 of the pax britannica trilogy, penguin, london, 1979. 81. a. garrido, r.m. pashley, b.w. ninham, colloids surf. b biointerfaces 2016, 151, 1. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments substantia. an international journal of the history of chemistry 2(2): 81-91, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-63 citation: a.m. papini (2018) from morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller. substantia 2(2): 81-91. doi: 10.13128/substantia-63 copyright: © 2018 a.m. papini. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article from morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller anna maria papini interdepartmental laboratory of peptide and protein chemistry and biology, department of chemistry “ugo schiff ”, university of florence, via della lastruccia 13, i-50019 sesto fiorentino (italy) email: annamaria.papini@unifi.it abstract. opium was known since the neolithic era and in 5th century wild papaver use was reported to induce sleep and relieving pain. first active component isolated from opium was morphine, the paradigm of a natural product discovered 150 years before isolation of endogenous opioid ligands, brain pentapeptide enkephalins. since then many endorphin peptides and their mode of action were discovered. native endorphins were characterized thanks to the synthetic antagonist naloxone. keywords. opium, morphine, peptides, peptidomimetics, analgesics. morphine: a paradigmatic example of a natural product mimicking endogenous molecules the story of morphine (figure 1) and its analogues is a paradigmatic example of the classical pathway to drug development undertaken by those researchers starting from a natural compound. in particular the phases of development and optimisation of morphine-like drugs are exemplified as follows: 1. recognition of the pharmacological activity of a plant 2. extraction and identification of the active ingredient 3. studies on synthesis (partial and total) 4. structure-activity relationship studies (through synthetic analogues) 5. development of analogues as drugs to optimize activity and decrease side effects 6. receptor theories; ‘rational’ synthesis of analogues/structure-based design morphine was isolated for the first time from the opium poppy by friedrich wilhelm adam sertürner (figure 2). in a letter to the editor of the journal der pharmacie für ärzte und apotheker (vol. 13, 1805), he reported on the isolation of a substance from opium with alkaline character. in 1806, sertürner moved to einbeck, ger82 anna maria papini many where he was assistant to the tenant of the magistrate’s pharmacy. in 1809, he became pharmacist and, since the tenant was already 75 years old, he intended to take charge of the pharmacy. however, he was not successful. during the invasion of napoleon bonaparte’s troops into germany, french legislation became the law of the land in those parts, which fell under french government and sertürner was allowed to open a second pharmacy. therefore sertürner continued his research work on morphine in einbeck and published the results in two papers. in one of these (1817), he reported his observations on the use of a drug in humans that he called for the first time “morphine”, name with a clear mythological reference. the french chemist gay-lussac was interested in sertürner’s publication and ordered a french translation, which earned sertürner the scientific breakthrough of morphine. he is recognized the pioneer in alkaloid research, and for that he received a doctor degree from the university of jena in 1817 when he published the isolation of pure morphine from opium after at least thirteen years of research and a nearly disastrous trial on himself and three teenagers, leading to pain in the region of the stomach, exhaustion, and severe narcosis that came close to fainting as described in details by sertürner.1-4 historical background the poppy and possibly its bioactivity was known since the neolithic era, since seeds were found in tombs dating to 4200 bc. it was certainly cultivated in mesopotamia, persia, india and china and widely used as sleeping or sedative remedies, but also used in religious and spiritual rituals. the five-volume de materia medica written by pedanius dioscorides, remained in use from the 1st to the 16th centuries, described opium and the wide range of its uses. in the 5th century pseudo-apuleius refers to the use of wild poppy papaver agreste for inducing sleep and relieving pain. the persian abu bakr muhammad ibn zakariyya al-razi (865-925 ad; 251-313 ah) also known as rhazes because of the place where he was born and died, i.e., rayy, near teheran. he studied medicine in baghdad and became one of the greatest physicians of the medieval period, writing over 200 works; half of them on medicine, but others on topics that included philosophy, theology, mathematics, astronomy and alchemy.5 he made use of opium in anesthesia and in “in the absence of a physician” (a home medical manual directed toward ordinary citizens for self-treatment), he recommended the use of opium for treatment of melancholy. all the leading physicians of baghdad used opium that was considered particularly effective for diseases of the intestines and of the eyes, but it also featured in a number of remedies to treat gout and painful joints. al-razi gave recipes for gout and the joints based on ointments that were applied to the painful areas with a damp piece of paper or cloth to keep the medication moist. a good paste that al-razi described contained equal parts of opium and liquid storax (liquidambar orientalis).6 the renowned andulasian opthamologic surgeon abu al-qasim alzahrawi (“abulcasis”, 936–1013 ad) relied on opium as a surgical anaesthetics and wrote a treatise, al-tasrif, that influenced medical thought well into the 16th century. in 1527 the swiss physician, alchemist and astrologer philippus aureolus theophrastus bombastus von hohenheim (1493-1541) who called himself paracelsus, introduced to western medicine laudanum or opium tincture returning from arabia with a famous sword, figure 1. structures of the bioactive (-)-morphine and of the inactive (+)-morphine. (r) (s) (s) (s) (r) o ohho h h n (+)-morphine (s) (r) (r) (r) (s) o ohho h h n (-)-morphine h figure 2. friedrich wilhelm adam sertürner (1783-1841) who isolated the substance from opium with alkaline character that he called “morphine”, a name with a clear mythological reference: the greek god of dreams morpheus. 83from morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller within the ball of which he kept “stones of immortality” composed of opium thebaicum, citrus juice, and “quintessence of gold”. the name laudanum was invented by paracelsus from the latin “laudare” or was a corrupted form of ladanum (from the persian ladan), a resinous juice or gum obtained from various kinds of the cistus shrub (by m. ray, editor of encyclopaedia britannica, 2017). the term is used now to describe the alcoholic tincture of opium, a 10% solution of opium powder dissolved in high-proof distilled spirits. it was used as an analgesic substance and paracelsus understood that opium was more soluble in alcohol and reported the first evidence of dependence. laudanum was a major part of the pharmacopeia into the 20th century. it was a common drug of abuse during the victorian era. paracelsus considered himself an alchemist and his ideas were not always well accepted by the medical community. however he was the first to introduce chemistry into medicine in the 16th century. most of his work was published only after his death (figure 3) and peder sorensen in 1571 in “idea medicinæ philosophicae” started emphasizing paracelsus’s pioneering work in chemical medicine.7 laudanum became the basis of many popular patented medicines of the 19th century (figure 4). the english physician thomas dover (1660-1742) was the first to market in england a powder, the dover’s powder, a preparation of opium and ipecacuanha, the later was added for its emetic properties to limit its use.8 its recreational use was therefore widespread, godfrey’s cordial was sold freely,9 and opium was freely imported from india, like tea or tobacco. in the 17th century in china the use of smoking opium was widely spread, also because of the prohibition of tobacco (1644); consumption was very high and opium was imported from india via canton by english and american merchants. the blockade of the importation by chinese authorities caused the opium war (18391842). interestingly in 1841, the us president william henry harrison was treated with laudanum.10 moreover, in the american civil war, the union army used 2.8 million ounces of opium tincture and powder and about 500,000 opium pills.11 figure 3. cover of the labyrinthus medicorum errantium by d. theophrasti paracelsi. figure 4. label of laudanum bottle prepared by chas. hooper & sons, chemists and druggists, london. 84 anna maria papini opioids and opiates opium is the latex or rubber obtained by etching the immature capsules of papaver somniferum (figure 5). it contains various alkaloids with analgesic action, of which the most relevant one is morphine. the term opiate (widely used until the 1980s) describes any natural or synthetic agent derived from morphine. in 1833 macfarlane prepared morphine on a commercial scale,12 and in 1853 injectable morphine comes into use during the american civil war.13 noteworthy is that in 1898, bayer registered diamorphine (diacetylmorphine) the name of heroin in germany as an antitussive (cough suppressing) drug.14 the harrison narcotics act, which was passed in 1914 and took effect in 1915 marked the beginning of federal narcotics control in usa. this act aimed to control each phase of production and distribution of opium, morphine, heroin and any new derivatives that could have similar biological activity. the first drug prohibition federal law in usa was the smoking opium exclusion act. it passed in 1909 and prohibited the importation of opium prepared for smoking in the united states.15 from morphine to codeine and to semisynthetic analogues via thebaine morphine structures morphine is an opium phenantrenic alkaloid with 5 stereogenic centers (*), and therefore with the theoretical possibility of presenting 25 = 32 stereoisomers. practically, geometric restrictions limit the possibilities to 16 stereoisomers. the natural bioactive enantiomer is (-)-morphine (5r, 6s, 9r, 13s, 14r) (fig. 1). isomorphine is the epimer in which the absolute configuration at c-6 is r (hydroxyl in position b). the synthetic enantiomer of (-)-morphine, the (+)-morphine (fig. 1) has about 10,000 times less affinity than the natural (-)-morphine and possesses no functional efficacy when tested at concentrations up to 100 fold the effective dose of natural morphine. in 1925 robinson and gulland determined for the first time its structure16 and only more than 25 years later, i.e. in 1952, gates performed its first chemical synthesis.17 it took additional 20 years to univocally determine morphine x-ray structure.18 in 1832 codeine (figure 6) was isolated from opium and characterized by pierre-jean robiquet, a french pharmacist who discovered other important natural substances such as asparagine, amygdaline in bitter almonds, caffeine, etc.19 he reported that he was commissioned by the “société de pharmacie” to examine the procedure to extract morphine that was proposed by william gregory (1803-1838) in edinburgh and that during his routine work he discovered codeine as a powder crystallized after evaporation of the mother liquor left after treatment with koh and washing with water. therefore, for the first time he discovered that morphine was not the only active ingredient in opium. he named the new ingredient codeine and m. kunckel demonstrated its strong action on the spinal cord and that it did not paralyze the back parts as morphine did.20 thebaine (figure 7) is a minor constituent of opium similar to morphine and codeine but with a weak analgesic action. its significance comes essentially from its industrial use as the starting material to produce semisynthetic drugs such as codeine but also the opiate antagonist naloxone (see below). codeine is none other than methyl-morphine. codeine itself is oxidized into codeinone, and the methyl ether of the enol form of codeinone is thebaine. figure 5. papaver somniferum. 85from morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller it was not until 1927 that a compound identified as the dimethyl ether of morphine was finally isolated from the mixture of the products of hydrogenation of opium.22 to conclude this enumeration of the most striking chemical interrelations between morphine, codeine and thebaine, it should be recalled that, as knorr demonstrated in 1909,23 treatment with acids transforms thebaine into codeinone. in 1874 heroin was prepared as first example of a semi-synthetic opioid by the english chemist and physicist, c.r.a. wright, at st. mary’s hospital medical school in london.24 wright synthesized heroin (diacetylmorphine) after mixing and simmering morphine with acetic anhydride (figure 8). heroin displayed 5-fold the analgesic activity of morphine. first tests of heroin were conducted on dogs and rabbits showed severe side-effects and c. r. a. wright stopped the experiments. however, in 1897 heroin was rediscovered by felix hoffmann at the bayer pharmaceutical company in elberfeld (germany) acetylating morphine with the objective of producing codeine. therefore heroin, the same compound discovered by wright was not patentable. before the extreme addictiveness of heroin was recognized, from 1898 to 1910 heroin was marketed by bayer as a non-addictive morphine substitute and cough medicine for children,25 to prepare patients for anesthesia, and to control certain mental disorders (figure 9). a range of synthetic opioids such as methadone (1937), pethidine (1939), fentanyl (late 1950s), and derivatives thereof have been introduced, and were targeted for certain specialized applications. o orho h h n h 1 2 3 4 5 6 7 8 910 11 12 13 14 15 16 figure 6. r = h: morphine; r = ch3: codeine. adapted from ref. 21. o och3 n och3 h3c h figure 7. thebaine or paramorphine (0.3%) weak analgesic action. adapted from ref. 21. figure 8. heroin. adapted from ref. 21. figure 9. advertisement for bayer heroin: the sedative for coughs. figure 10. structure-activity relationship: modifications in the morphine structure and analgesic effect. morphine = 100 as a reference. 86 anna maria papini morphine pharmacological profile morphine is the most studied molecule of natural origin in the last two hundred years, with the aim of discovering a central analgesic orally active molecule, free of side effects and not addictive. the main effects of morphine are: analgesia, euphoria and dysphoria (psychological distress), sedation, respiratory depression (the first cause of death due to morphine overdose), depression of cough reflexes, nausea and vomit, physical and psychological dependence, miosis (constriction of the pupil), constipation (reduction of intestinal motility), spasms of the biliary tract, stimuli and difficulties in urination, stimulation of histamine release with consequent vasodilation, bronchial constriction, redness and itching, effects on the endocrine system (decreased libido, impotence, amenorrhea) and immunosuppression. morphine can be administered orally (the analgesic potency is reduced to about 5-30% of that obtained by parenteral administration); subcutaneously and intramuscolarly absorption is effective with the inconvenience of tissue irritation; intravenous administration via slow infusion is preferred for better analgesic coverage and reduction in the risk of overdose. the antalgic therapy uses drugs belonging to different classes: non-steroidal anti-inf lammatory drugs (nsaids), opioids (morphine-like) and local anesthetics. local anesthetics (e.g. lidocaine) clearly have a mechanism of action external to the central nervous system (cns), as they affect transient pharmacological blockade of nerve conduction from peripheral receptor sites. the assumptions underlying the historical distinction between nsaids, endowed with peripheral activity, and opioids, active at the cns, no longer seem to be justified. in fact, the central effects of some nsaids have been demonstrated, as well as the existence of peripheral opioid receptors. from agonist to antagonist activity: on the way to the discovery of endorphins and opioid receptors observing the relationship between structure and analgesic activity not only in different opium components but also in the semi-synthetic analogues derived from morphine (fig. 9), it is reasonable to think that a natural plant originated product such as morphine could be further optimized for interaction with a mammalian opiate receptor (for a long time unknown) for which it is not the natural ligand. interestingly on june 4, 1970 the use of narcotic antagonists in the treatment of heroin addiction was debated in a symposium sponsored by the national institute of mental health and the department of psychiatry, new york medical college. many molecules were tested and cyclazocine apperared to be the most promising one (figure 11). cyclazocine was found to be a clinically effective and protracted opiate antagonist whose effect lasted for at least 24h. in addition it exhibited unpleasant initial side-effects including dizziness, headaches and hallucinations that were disproportionately intensified as the dose was increased and reappeared when it was discontinued. it was concluded by the review of the clinical data that an ideal antagonist would be one exhibiting antagonistic efficacy for weeks or months, without agonistic activity.26 efforts to avoid these side-effects led clinicians to the use of the first “pure” antagonist: naloxone (figure 12). originally synthesized in the private laboratory of mozes judah lewenstein and subsequently developed by endo laboratories, garden city, naloxone has no pharmacological properties of its own but it abolishes or prevents the hallucinations, euphoria, respiratory depression, nausea, convulsions and other effects produced by narcotics. it can also abolish these effects when they are produced by other antagonists. naloxone is synthesized from thebaine, which explains its high cost.27 naloxone is a specific opiate antagonist that has no residual agonist activity. it is a competitive antagonist at the different receptors: μ, δ, and k opioid receptors above described. it was introduced in 1973 and is used to inhibit the effect of narcotics on the cns (see below). figure 11. cyclazocine. x o oh n r h oh figure 12. morphine agonist oximorphone and antagonist naloxone. oximorphone (x = co, r = ch3) agonist. naloxone (x = co, r = ch2-ch=ch2) antagonist used in opiates overdose. 87from morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller narcan, an injectable form of naloxone is currently used to fight the opioid epidemic and substance abuse to reverse drug overdose and addiction.28 from morphine antagonist naloxone to endogenous opioid peptides: the discovery of endorphins after the advent of the pioneering work of robert b. merrifield,29 who introduced the solid-phase synthesis of peptides, the easiest pathway to develop drugs acting at peptidergic receptors is based on characterization of endogenous bioactive peptides that can be synthesized and subsequently structurally stabilized to increase in vivo half-life, limiting rapid metabolism and excretion and fine tuning their biological properties. however, this general trend was not observed in the case of morphine, since evidences of the existence of endogenous substances with morphine-like activity (endorphins) were obtained only in the 70’s, after decades of use of morphine and its derivatives for both recreation and therapeutic applications, extensively described above. of particular significance was the observation that naloxone was able to antagonize the analgesia induced by electrical stimulation of specific areas of the brain (gray periaqueductal area). the emerging hypothesis suggests that under stress conditions (electrical stimuli), the release of endogenous substances with an activity profile similar to that of morphine is activated. this is the paradigmatic example that exogenous natural products are able to mimic the activity of endogenous molecules. in 1975, hans w. kosterlitz and his former student john hughes discovered enkephalins, natural ligands for opiate receptors that were characterized as the pentapeptides h–ty r–gly–gly–phe–met–oh and h– tyr–gly–gly–phe–leu–oh (figure 13). the structure was elucidated by the determination of the amino acid sequence of natural enkephalins by the dansyl–edman procedure and mass spectrometry and followed by synthesis and demonstrating the complete chemical and biological equivalence of the natural and synthetic peptides. these morphine-like peptides that can be antagonized by opiate antagonists, such as naloxone, are naturally occurring substances in the brain, which affect how we feel pleasure and help fight pain.30 independently solomon h. snyder identified the same two peptides in bovine brain.31-33 kosterlitz, hughes and snyder shared the prestigious albert lasker prize in 1978 for this research that paved the way for the development of new kinds of nonaddictive analgesic. interestingly, only one single c-terminal amino acid residue is the difference between [met5]enkephalin and [leu5]enkephalin. both peptides induce in vivo a deep analgesia in rat (completely antagonized by naloxone), but the activity is short-lived, because of a fast degradation by blood and cerebral peptidases. [met5]enkephalin has about 30% of the morphine potency and is about 3-fold more potent than [leu5]enkephalin. the n-terminal tyrosine residue was found to be the main pharmacophoric determinant of opioid peptides, a structural feature shared also by morphine and analogues (figure 13). in fact, this portion is strictly maintained by all the brain opioid peptides discovered subsequently (figure 14). the brain opioid peptides discovered in the ‘70s led to the implementation of a new nomenclature. in fact, the endogenous peptides were initially considered not related to morphine from a structural point of view, but their pharmacological actions are similar to those of morphine, as they are ligands of the same receptors. the term opioid has over the years been used to indicate a substance that is pharmacologically similar to opium or to morphine, both of an endogenous nature and of a synthetic or semi-synthetic nature. enkephalins figure 13. similarities of the pharmacophoric feature in bold of morphine (a) and [met5]enkephalin (b). figure 14. endogenous opioid peptides: endorphins.34 [leu5]enkephalin tyr-gly-gly-phe-leu [met5]enkephalin tyr-gly-gly-phe-met dinorphin a(1-17) tyr-gly-gly-phe-leu-arg-arg-ile-argpro-lys-leu-lys-trp-asp-asn-gln dinorphin b(1-8) tyr-gly-gly-phe-leu-arg-arg-ile dinorphin (1-13) tyr-gly-gly-phe-leu-arg-arg-gln-phelys-val-val-thr α-neoendorphin tyr-gly-gly-phe-leu-arg-lys-tyr-prolys β-neoendorphin tyr-gly-gly-phe-leu-arg-lys-tyr-pro βh-endorphin tyr-gly-gly-phe-met-thr-ser-glu-lysser-gln-thr-pro-leu-val-thr-leuphelys-asn-ala-ile-ile-lys-asn-ala-tyrlys-lys-gly-gln 88 anna maria papini and other brain peptides discovered later are collectively known as endorphins (figure 13). endorphins are among the brain chemicals known as neurotransmitters, which are molecules inducing electrical signals from one neuron to the subsequent within the nervous system. at least 20 types of endorphins have been discovered in humans. endorphins can be found in the pituitary gland, in other parts of the brain, or distributed throughout the nervous system. stress and pain are the two most common factors leading to the release of endorphins. endorphins bind and interact with the opiate receptors in the brain leading to nociception, a perception of analegesia. as such they act similarly to drugs such as morphine and codeine. in contrast to the opiate drugs, however, activation of the opiate receptors by the body’s endorphins does not lead to addiction or tolerance. the characterization of opioid receptors identification in the 70’s of endorphins and in particular enkephalins, as the endogenous substances with morphine-like activity enabled the search and characterization of the opioid receptors. therefore it was possible to classify the opioid receptors into three types, called μ, δ, κ.35 the genes of these receptors were cloned and the relative transcripts showed similarities of more than 60% of the nucleotide sequence. all opioid receptors belong to the superfamily of g protein coupled receptors (gpcr), whose α-subunits are of the gi/0 type. using these transductional couplings, opioid receptors control the activity of effectors such as adenylate cyclase (inhibition) and some ion channels (ca2+ and k+). μ opioid receptors the μ receptors are the most widespread and abundant and mediate most of the opioid analgesic effects. morphine and naloxone have a weak μ selectivity. however, μ opioid receptors are located also outside the cns, in numerous intramural nerve plexes (gastrointestinal tract, biliary tract, urogenital pathways, circulatory and respiratory systems). accordingly, it was not possible to confirm the elegant hypothesis, that a single opioid receptor subtype could be the unique mediator of “pure” analgesic activity. based on this hypothesis, a selective agonist of this receptor subtype would be the “perfect” analgesic, devoid of side-effects, induced by activation of different receptor subtypes by non-selective compounds. in fact, several attempts to develop such a selective agonist by modification of morphine failed, simply because each receptor subtype mediates many different biological effects. κ opioid receptors the hypothesis that suggested their existence was advanced by martin,36 and was based on the different effects produced by morphine and some structurallyrelated analogues (for example, ketociclazocine). they have been so named to highlight the ketonic nature of the compounds that activate them selectively (in particular ekc, ethyl ketociclazocine). they play an important role in receiving and processing the primary afferent pain information. in the brain they integrate the ascending pain information and inhibit the painful sensations that descend to the spinal cord. also located in the limbic system and in the cerebral cortex, they are involved in affective and emotional states and in the awareness of analgesia. function of receptor κ. they exert a modulation role of the processes of: analgesia, diuresis, hypothermia, neuroendocrine secretions, feeding (activation of k receptors causes an increase in appetite, inhibited by nor-bni, a selective k antagonist. κ-agonists. in various animal models, the κ-agonists cause sedation at lower concentrations t han t he μ-agonists. the increase in diuresis, induced in a characteristic way by the κ-agonists, is consequent to the inhibition of the release of vp from the neurohypophysis. the withdrawal symptoms from κ-agonists are different and less severe than those that occur with agonists μ. a further advantage of their use is linked to the absence of respiratory depression and constipation. a disadvantage, found when κ-agonists are administered, is the occurrence of dysphoric and psychotomimetic effects in humans. this is due to a lack of selectivity, as many of these substances also interact with δ-receptors. the use of κ-agonists with arylacetamide structure induces neuro-protection from cerebral ischemic damages. the endogenous ligands of the κ-receptor belong to the dynorphin and neoendorphin families. the first peptide to be isolated from the pig’s pituitary gland was dinorphin – (1-13) in 1979;37 in 1982 the dynorphin-(1-17) was isolated,38 and the neoendorphin was first isolated in 1979 from the porcine hypothalamus but an incorrect sequence was assigned.39 the sequence was then assigned corrected in 1981 by the same research group.40-41 89from morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller δ opioid receptors the distribution of δ opioid receptors (studied by autoradiographic techniques with tritiated and iodinated radioligands) at the cns level is pre-eminent in the more evolutionary younger cerebral structures (olfactory bulb, caudate nucleus, neopallio, putamen), while it is relatively poor in midbrain and in the medulla oblongata. following the observation of their almost total absence, for example in reptiles and birds, this receptor subtype would have developed fully later than the other opioid receptors. function of δ receptor. δ opioid receptors play a role in regulating the processes of analgesia, motor coordination, intestinal motility, smell, respiration, cognitive function, emotional state. opioid-receptor-like in addition to the three classic opioid receptors (μ, δ, κ), a new opioid receptor named opioid-receptorlike (orl) was discovered in 1994.42 it is also coupled to g proteins and has a high sequence homology (> 60%) compared to μ, δ, κ. however, the typical opioid ligands (peptides and non-peptides) do not bind to orl. it is present in all brain regions and in the spinal cord. it is located in the intestine, in the vas deferens, in the liver and in the spleen. it was not found in skeletal muscles, in the esophagus, in the kidneys and in the adrenal glands. an endogenous agonist characterized to be an eptadecapeptide structure (see comparison with dinorphin a) called orphanin-fq (ofq) or nociceptin (nc) has been identified. ofq (or nc) is generated by pro-orphanin-fq (or pro-nociceptin). the pharmacological profile of nc has not yet been fully defined, but nc has analgesic activity. ofq: phe-gly-gly-phe-thr-gly-ala-arg-lys-serala-arg-lys-leu-ala-asn-gln dina: tyr-gly-gly-phe-leu-arg-arg-ile-arg-prolys-leu-lys-trp-asp-asn-gln synapsis and endorphins release as depitected in the general scheme reported in figure 15, pro-opioid proteins are synthesized in the cell nucleus (1) and are transported by microtubular system (2) to the nerve terminal. (3) the active endogenous opioids (e) are released from the pro-opioid proteins by the “process” proteins that are specific proteinases, (4) they are transported and stored in the presynaptic vesicles, and (5) are released when the presynaptic neurons are excited. (6) endogenous opioid peptides bind to the postsynaptic receptor, activating the inhibitory g protein (gi) that induces inactivation of adenylyl cyclase, inhibiting release of camp and (7) influence the influx of potassium ions through the cell membrane. the overall effect is hyperpolarization of postsynaptic neuron and inhibition of cell excitation. (8) exogenous opioids (op) such as morphine bind to the opioid receptors and simulate the action of (e). (9) opioid antagonists such as naloxone (nx) bind to receptors and competitively inhibit the action of (e) and (op). (10) the action of (e) is interrupted by a membrane-bound peptidase, which hydrolyzes the peptide bond gly3-tyr4 in enkephalin and leads to its inactivation. toward the perfect painkiller: dual activity peptidomimetics pharmacological studies suggest that the δ-opioid receptor plays a key role in modulating some side effects associated with opioids including analgesic tolerance and physical dependence. in fact coadministration of δ-opioid receptor antagonist with morphine attenuate analgesic tolerance, physical dependence and drug-seeking behavior. accordingly recent studies aimed to develop molecules concomitantly acting as μ-opioid receptor agonist and δ-opioid receptor figure 15. general scheme of peptidergic synapses.43 figure 16. peptidomimetic lead compound concomitantly acting as μ-opioid receptor agonist and δ-opioid receptor antagonist.44 90 anna maria papini antagonist. in particular recently mosberg et al. reported a family of peptidomimetics (figure 16) producing longlasting and dose dependent antinociception in mice after peripheral administration.44 the bioavailable molecules recently described are promising leads in the search for future drug candidates endowed with dual activity as μ-receptor agonist/δreceptor antagonist. these novel peptidomimetics can represent the long sought painkillers. acknowledgments fulvio gualtieri, emeritus professor of medicinal chemistry, inspired this review that does not have the ambition to be exhaustive. moreover paolo rovero and mario chelli are gratefully acknowledged for fruitful discussion. references 1. f. sertürner, journal der pharmacie fuer aerzte und apotheker 1805, 13, 229-243. 2. f. sertürner, darstellung der reinen mohnsäure (opiumsäure) nebst einer chemischen untersuchung des opiums mit vorzüglicher hinsicht auf einendarin neu entdeckten stoff und die dahin gehörigen bemerkungen. journal der pharmacie fuer aerzte und apotheker 1806, 14, 47-93. 3. f. sertürner, ueber das morphium, eine neue salzfähige grundlage, und die mekonsäure, als hauptbestandtheile des opiums. annalen der physik 1817, 55, 56-89. 4. i. jurna, sertürner and morphine a historical vignette. schmerz 2003, 17, 280-283. 5. s. tibi, al-razi and islamic medicine in the 9th century. journal of the royal society of medicine 2006, 99, 206–207. 6. s. tibi, the medicinal use of opium in ninth-century baghdad, brill, leiden, 2005. 7. a. g. debus, paracelsus and the medical revolution of the renaissance: a 500th anniversary celebration, nih u.s. national library of medicine, bethesda, 2011. 8. d. n. phear, thomas dover 1662-1742; physician, privateering captain, and inventor of dover’s powder, journal of the history of medicine and allied sciences 1954, 9, 139-156. 9. t. e. jordan, the keys of paradise: godfrey’s cordial and children in victorian britain. journal of the royal society of health 1987, 107, 19-22. 10. j. mchugh, p. a. mackowiak, death in the white house: president william henry harrison’s atypical 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natural alkaloids. journal of the chemical society (london) 1874, 27, 10311043. 25. bayer heroin hydrochloride advertisement, american journal of physiology 1901, 7. 91from morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller 26. m. fink. narcotic antagonists in opiate dependence. science 1970, 169, 1005-1006. 27. th. h. maugh ii. narcotic antagonists: the search accelerates. science 1972, 177, 249-250. 28. m. salaun. the new york times, oct 26, 2017. 29. r. b. merrifield. solid phase peptide synthesis. i. the synthesis of a tetrapeptide. journal of the american chemical society 1963, 85, 2149–2154. 30. j. hughes, t. w. smith, h. w. kosterlitz, l. a. fothergill, b. a. morgan, h. r. morris. identification of two related pentapeptides from the brain with potent opiate agonist activity. nature 1975, 258, 577– 579. 31. r. simantov, s. h. snyder. rabi isolation and structure identification of a morphine-like peptide “enkephalin” in bovine 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of the united states of america 1979, 76, 6666-6670. 38. a. chavkin, i. f. james, a. goldstein. a. dynorphin is a specific endogenous ligand of the k opiate receptor. science 1982, 215, 413-415. 39. k. kangawa, h. matsuo, m. igarashi. biochemical and biophysical research communications 1979, 86, 153-160. 40. k. kangawa, n. minamino, m. chino, s. sakakibara, h. matsuo. biochemical and biophysical research communications 1981, 99, 871-878. 41. n. minamino, k. kangawa, m. chino, s. sakakibara, h. matsuo. biochemical and biophysical research communications 1981, 99, 864-870. 42. c. mollereau, m. parmentier, p. mailleux, j. l. butour, c. moisand, p. chalon, d. caput, g. vassart, j. c. meunier. orl1, a novel member of the opioid receptor family. cloning, functional expression and localization. febs letters 1994, 341, 33-38. 43. v. s. seybold. the role of peptides in central sensitization. in: sensory nerves, vol. 194 (eds.: b. j. canning, d. spina), handbook of experimental pharmacology book series, springer nature switzerland ag, basel, 2009, p. 451-491. 44. a. f. nastase, n. w. griggs, j. p. anand, t. j. fernandez, a. a. harland, t. j. trask, e. m. jutkiewicz, j. r. traynor, h. i. mosberg. synthesis and pharmacological evaluation of novel c-8 substituted tetrahydroquinolines as balanced-affinity mu/delta opioid ligands for the treatment of pain. acs chemical neuroscience 2018, 9, 1840-1848. substantia. an international journal of the history of chemistry 2(2): 73-80, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-61 citation: v. lusa, a. franza (2018) visualizing chemistry. the application of chemical imaging to address scientific challenges in space research. substantia 2(2): 73-80. doi: 10.13128/ substantia-61 copyright: © 2018 v. lusa, a. franza. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article visualizing chemistry. the application of chemical imaging to address scientific challenges in space research vincenzo lusa1, annarita franza*2 1 jd, pontificia università san bonaventura, via del serafico, 1 00142 rome (italy) 2 phd, dipartimento di scienze biomediche, sperimentali e cliniche “mario serio”, università di firenze, largo brambilla, 3 50134 florence (italy) e-mail: viclusa@libero.it; annarita.franza@gmail.com abstract. chemical imaging helps to answer difficult questions, especially when those questions occur in complex environments. for instance, forensic neuroradiology plays an important role in the courtroom to understand a defendant’s personality. but could this branch of science be essential in human exploration of space? even if no emergency has happened so far, nasa established a partnership in 2002 with the u.s. national institute of justice to promote the knowledge of investigative techniques in the case of a crime being committed on a space mission. based on forensic neuroradiology and behavioral genetics, this article presents a brand-new study protocol for creating security procedures designed to safeguard astronauts engaged in long-duration space travel. since 2009 in italy, some individuals have been prosecuted who, although convicted of murder, benefitted from reduced sentences through the verification of some genetic polymorphisms and computed axial tomography (cat), positron emission tomography (pet), and functional magnetic resonance imaging (fmri) results which showed brain malformations that may produce manifestations of violence. the protocol specifically uses chemical imaging and behavioral genetics to show how cerebellar anomalies and biological markers predictive of criminal behavior can trigger impulsive reactions in response to stress. this protocol may prove critical when space agencies are evaluating candidates for extra-orbital flights of long duration. keywords. chemical imaging, forensic radiology, nasa, behavioral genetics, space research. introduction in 1958, president eisenhower proposed creating a civilian space agency for the united states. after considerable congressional debate, the national aeronautics and space administration (nasa) began its operations on october 1, 1958. no one could ever have foreseen what would occur over the next 50 years as humans discovered that the sky was no longer a limit and it is now about to enter a new era of space exploration with a 365-day stay on the iss, the establishment of a lunar landing out74 vincenzo lusa, annarita franza post, and the future missions to mars and to a nearearth asteroid (nea).1,2 as missions to nea and mars are not just ordinary space flights, the analysis of physiological and psychological risk factors of past missions will not be relevant bases for predicting the risk factors astronauts may encounter during space flights.3 at the hawaii space exploration analog and simulation center, nasa concluded in 2016 a year-long study regarding the use on a shuttle of the forensic sciences utilized in examining crime scenes.4 in fact, the probability of criminal conduct in space is not so remote. for instance, astronauts have carried weapons into space since the soyuz flights in 1965.5 thus, forensic scientists are prepared to face the eventuality of assessing crime scenes and identifying evidence during space travel. so it is no coincidence that nasa established a partnership with the u.s. national institute of justice to implement investigative techniques for use in future crime scenes in space.6 over the last two decades, several studies have been published regarding the impact of long-duration space flight on the health of crewmembers.7 moreover, while the physiological effects of space flight are well documented,8 a paucity of knowledge exists on the potential behavioral and cognitive issues that can affect the astronaut’s psychophysical performance during flights. for instance, the neurobiological consequences of long-duration space flight and long-term exposure to microgravity can lead to alterations in cerebral morphology (e.g. the visual impairment and intracranial pressure syndrome) that are poorly understood.9.10 even if no emergency has happened so far, we need to think the unthinkable: how would we deal with a catastrophic scenario during a long-duration space flight? in this paper, we present a study protocol that aims at certain security procedures designed to safeguard astronauts engaged in long-duration space travels. the protocol is based both on chemical imaging, e.g. forensic neuroradiology, to evaluating the cerebral regions whose anomalies can lead to antisocial behaviors,11 and on behavioral genetics where it has been demonstrated how specific predictive biomarkers of criminal behavior can lead to an unpredictable response in very stressful situations.12 these evaluations can be crucial for space agencies at a time in which space tourism is going to become an achievable dream.13 materials and methods nasa’s human research program has identified 32 space-related health risks associated with space f light and has listed them in the human bioastronautics roadmap. the level of risk refers to three specific parameters: a 1-year tour of duty on the iss, a monthlong stay on the moon, and a 30-month mission to mars. health risk factors are then categorized into: (1) behavioral health and performance; (2) human health countermeasures (e.g., bone metabolism and physiology, nutrition, immunology, cardiac and pulmonary physiology); (3) space radiation; (4) space human factors and habitability; and (5) exploration medical capabilities. the risk factors have been rated as controlled, acceptable, unacceptable and insufficient data. the roadmap then highlights as unacceptable the risk of behavioral issues and psychiatric disorders.14 in 2007, nasa developed various health standards (i.e., crew health concept of operations and medical operations requirements) directed towards “a healthy and safe environment for crewmembers during all phases of space flight”.15 a review of all the nasa health standards is conducted every 5 years or any time new scientific data suggest that an update is needed. in addition to the standards described above, nasa has identified specific health criteria for crew selection including a medical screening and annual examinations reported in the astronaut candidate program and supported by the nasa aerospace medicine board.16 it is worth mentioning that health risk and stressor parameters may be different from mission to mission. concerning behavioral health and performance risks, nasa has identified three stressors associated with long-duration space flight: (1) adverse behavioral conditions and psychiatric disorders;17 (2) performance errors due to fatigue;18 and (3) performance decrements due to inadequate cooperation, coordination, communication, and psychological adaptation within a team gap.19 these criteria were identified by analyzing observational data and experimental studies in analogous settings, such as submarine,19,20 space simulations,21 mountain survival programs and polar expeditions.22 it is important to note that behavioral health problems may be underestimated due to the reluctance of crewmembers to report them.23,24 in 2000, a survey documented a 2.86 per person-year incidence of behavioral problems among the 508 astronauts engaged in space shuttle flights between 1981 and 1989.25 in 2009, observational information collected for 28.84 personyears described anxiety and irritability as the most common behavioral symptoms (0.832 cases per personyear).26 furthermore it was pointed out that behavioral health issues are frequent during long-term periods of isolation and confinement.27 a 2004 study reported a 5.2 percent probability of behavioral issues in aspiring 75visualizing chemistry. the application of chemical imaging to address scientific challenges in space research astronauts after extended stays in antarctica. among the most common risk factors of behavioral health problems are mission duration, circadian rhythm disorders and microgravity effects on human physiology, social isolation, cultural and organizational issues and personality traits.28 risk management procedures have focused on providing social and psychological support to crewmembers through ground control. however, even if these countermeasures have proved to be effective on the iss, it is unknown whether they could be useful during long-term space flights at greater distances from earth.2 cognitive and psychiatric tests are administered during both the astronaut enrollment procedures and the annual medical examinations.29 neurocognitive and behavioral genetic testing have also been developed, but they serve mainly to point out phenotypic and genotypic variations to manage sleep-wake disruptions during space missions.30 to date, few policies have been established for long-duration space flights. in analogous settings, the national science foundation’s division of polar programs require a psychiatric evaluation conducted by a civilian contractor of all aspiring astronauts engaged in winter-over duty at antarctica’s amundsenscott south pole and mcmurdo stations. limits have also been placed on the number of continuous seasons a candidate can stay at the same station.29 astronauts are then informed that ordinary social and personal problems can become clinically significant during periods of extended isolation and confinement. for instance, the mars society conducted a 4-month simulated mars exploration mission at the flashline mars arctic research station in 2007. analyzing the questionnaires that crewmembers completed on five different occasions during the simulation, scientists found an increase in stress factors as well as higher levels of excitement, loneliness and tiredness. these results thus prompt serious questions about psychological issues during missions to the outer solar system where a mission’s total duration is expected to last 10 years or more (e.g., interstellar travel to the oort cloud, a broad spherical shell of comet nuclei located 0.63-0.94 light years away from the sun).31 these kinds of human expeditions will cause astronauts to undergo psychological and interpersonal stressors that they have never before experienced, such as an unknown level of monotony and isolation, impossible real-time communication with the earth, which will even disappear from their view. such would be the case of missions to mars where a crew of six or seven people would be on a space flight lasting at least 2.5 years. for the very first time in human history, they would experience the “earth-out-of-view phenomenon”. gazing at the earth has been one of the major positive factors of being in space for astronauts. its absence could lead crewmembers to an increased sense of isolation, emotional instability, hypersensitivity, depressive reactions, and possibly psychiatric disorders.32 as has already been mentioned, many unknown health risks may influence long-duration space flight. in this regard, it is noteworthy to emphasize that chemical imaging can make a positive contribution to forensic space research. for instance, a recent clinical survey tested via fmri the neuronal functions of a 44-year-old male cosmonaut engaged in a long-duration space flight (169 days) on the russian segment of the iss. even if his physical state and performance showed no relevant anomalies, the f mri scans indicated abnormalities in the vestibular and motor-related cerebral regions.10 moreover, results from the mars105 study have shown a deterioration in the astronauts’ psychological state during a long period of confinement, which was accompanied by a decrease in brain cortical activity.33 again, in a study carried out using low-resolution brain electromagnetic tomography (loreta), neuropsychiatrists have demonstrated how the microgravity phases of parabolic flights induce changes in frontal lobe activity, a cerebral region that is involved in the regulation of emotional processing.34 despite what has been described above, the contribution of forensic neuroradiology and neurobiology to space research seems to be underestimated. therefore, increased focus on brain imaging and behavioral genetics can lead to the development of adequate countermeasures to safeguard astronauts involved in long-duration space missions brain imaging cognitive neurosciences have as a study subject an understanding of the mechanisms that are the basis of human aggressivity; they find their correspondence at an organic level and in particular cerebrally. the main objective of this branch of research is to investigate violent behavior in humans by studying certain cerebral areas using neuroimaging techniques, which constitute a major source of scientific acquisition in the neurocrime field. it follows that cognitive neurosciences, linked to the growing technological development in the field, are destined to evolve over the next few decades influencing such fields as psychiatry, forensic psychology, and criminal law in studying the mens rea.35 the development of multiple imaging techniques provides powerful tools to probe multiple aspects of brain anatomy. new technologies not only allow the study of structural features but also reveal brain con76 vincenzo lusa, annarita franza nectivity, neurotransmitter receptor profiles, and other important aspects of brain function. these sophisticated imaging systems are divided mainly into the following areas: eeg (electroencephalography); cat (computerized axial tomography) scan; functional magnetic resonance imaging (f mri); positron emission tomography (pet); single-photon emission computed tomography (spect); and magnetoencephalography (meg). in detail, eeg allows direct assessment of the brain’s electrophysiology by displaying the temporal and spatial pattern of the neuronal populations generating the underlying neuroelectric and neuromagnetic fields. given its temporal sensitivity, eeg is useful in the evaluation of dynamic cerebral functioning such as suspected seizures and unusual spells.36 cat scan is a computerized x-ray imaging technique where a motorized x-ray source rotates around the circular opening of a gantry, producing signals that are then processed by the machine’s computer to generate 2-d cross-sectional tomographic images (often called “slices”). the thickness of each slice usually ranges from 1-10 millimeters. when the number of desired slices is collected, image data is recorded in dicom format and images can be displayed separately or stacked together by the computer to produce high-resolution 3-d images (c.50μm).37 cat scan and magnetic resonance imaging (mri) have allowed for the first time the noninvasive evaluation of brain structure. in particular, f mri is a modern noninvasive imaging technique to measure and localize specific functions of the human brain without the application of radiation. indeed, fmri takes advantages of the differences in magnetic susceptibility between oxyhemoglobin and deoxyhemoglobin. when a task is performed, oxygenated blood in excess of the amount needed (luxury perfusion) is delivered to the active area. the difference in magnetic susceptibility between deoxyhemoglobin concentrations and oxyhemoglobin concentrations creates the signal in functional imaging. brain function is indirectly assessed with high spatial resolution via detection of local hemodynamic changes in capillaries and draining veins of the so-called functional areas, e.g. regions of the human brain that govern motor, sensory, language, or memory functions. thus, f mri not only offers a variety of novel options for research but also opens up a new diagnostic field of neuroradiology, by shifting paradigms from strictly morphological imaging to measurement and visualization of brain function.38 other frequently applied methods for the identification of functionally important brain structures are pet and spect, which detect changes of cerebral blood flow and glucose metabolism. most significantly, pet measures generally reflect the functional biochemistry and physiology of the brain. this is accomplished by injecting radioactive isotopes that have short half-lives. isotopes used frequently in pet research allow a variety of radiochemical approaches to ligand synthesis. of particular importance, isotopes of carbon and nitrogen may be directly incorporated, and 18f can be substituted for hydrogen or a hydroxyl substituent in many compounds without loss of bioactivity. blood flow indeed increases in areas of the brain that are in heavy use and a fair portion of the injected isotopes will end up in the active part of the brain. as the isotopes decay, a positron is released. this positron will collide with an electron and they will annihilate each other, sending two photons, or γ-rays, in opposite directions. these γ-rays are picked up by the pet scanner, which then determines where they came from the brain. tomographic techniques analogous to those utilized in cat scanning, are used to reconstruct the image from the rays. the resulting pet images are spatial maps of radioactivity distribution within tissue slices.39 spect is another nuclear imaging technique for imaging molecules, metabolisms, and biochemical functions of organs and cells, and like pet, the use of radioisotopes is required. as its name suggests, it involves the emission of a single γ-ray per nuclear disintegration, which is measured directly. numerous single γ-rays are detected by rotating gamma cameras to reconstruct an image of the origin of the γ-rays, which identifies the location of the radioisotope. before a test is performed, the patient is injected with a radiopharmaceutical that emits γ-rays and can be detected by the scanner. the most common radioisotopes used in spect are iodine-123, technetium-99m, xenon-133, thallium-201, and fluorine-18. spet scan is primarily used to measure the regional cerebral blood flow. one of its major advantages is that spect provides improved contrast between regions of different functions, and also give better spatial localisation and greater accessibility because it uses radioisotopes with longer half-lives.40 finally, meg is the measure of magnetic fields generated by the electrical activity of neurons. when neurons are activated synchronously they generate electric currents and thus magnetic fields, which are then recorded by meg outside the head. once generated, magnetic fields are relatively invulnerable to intervening variations in the media they traverse, so they are not distorted by the skull, grey and white matter, and cerebrospinal fluid. but these neuromagnetic signals are extremely small, about 10−15 t. thus, meg scanners require superconducting quantum interference device (squid) sensors. to detect and amplify the magnetic fields, the squid sensors are bathed in a large liquid helium cooling unit at about -270°c. a magnetically shielded room houses the equipment and mitigates interference.41 77visualizing chemistry. the application of chemical imaging to address scientific challenges in space research the brain areas that are relevant to the present study are the amygdala, hippocampus, thalamus, midbrain, and prefrontal cortex. the amygdala is involved in predatory and affective attacks. the thalamus connects the limbic emotional areas and cortical areas. when activated, the midbrain manages impulsive aggression due to emotions.42 the literature has found that reduced hippocampal function can be associated with high levels of psychopathy.43 the hippocampus also plays a primary role in fear conditioning and in emotional responses.44 the almond-shaped amygdala is also involved in the generation of emotions. an amygdala dysfunction leads to manifesting impulsive, even violent behaviors.45 for instance, a decrease in the amygdala’s volume equal to 18% can instead be the basis of sociopathic behaviors.46 as regards the midbrain, a disorder in the posterior cingulate cortex can trigger anger. in addition, it distorts the possibility of understanding how this behavior can influence others.47 the same applies to the anterior cingulate, the cerebellar anatomical region designated to inhibit automatic and instinctive behaviors and to regulate instinctive reactions.48,49 the most important evidence capable of translating into reality the literature attesting to the biological nature of the anti-social acts is found in the judicial practice of both italian and us criminal trials, where a reduced sentence was imposed on the basis of the confirmation of anatomical differences in the defendant’s brain as well as genetic anomalies that were capable of influencing the behavior of individuals, causing them to carry out heinous behaviors against their fellow humans. us criminal trials the use of bioscience in criminal cases dates back to the early 1980s when chemical imaging and behavioral genetic evidence began to enter us courtrooms. on march 30, 1981, john warnock hinckley jr. shot president ronald regan six times, also critically wounding police officer thomas delahanty, secret service agent timothy mccarthy, and reagan’s press secretary, james brady. when he was put on trial for his crimes, hinckley was found not guilty by reason of insanity and confined to st. elizabeth’s mental hospital in dc. he was released in september 2016. the hinckley case revolutionized the us criminal justice system introducing cat scans as a useful tool for proving mental incapacity. the psychiatric david bear explained to the jury that the defendant’s brain scans indicated that hinckley’s sulci were wider than average, a feature that he had noticed in patients suffering from schizophrenia. the cat scans bolstered bear’s diagnosis of mental insanity and the jury agreed that hinckley was mentally incapable of understanding the crimes he had committed.50 in 1991, while engaged in a heated argument, herbert weinstein strangled his wife barbara and then tried to cover the murder up by throwing her body from the window. before the trial began, and because he had no history of violent behavior, weinstein had an mri followed up with a pet scan. exams revealed an anomaly in weinstein’s prefrontal cortex and an arachnoid cyst growing in his left frontal lobe. these findings showed how the defendant was not able to control his aggressive behavior in a very stressful situation and thus he was found not criminally responsible due to mental defect.51 on october 18, 1992, johnny hoskins was arrested for having raped, beaten and strangled dorothy berger, an 80-year-old who lived in brevard county, florida. he was sentenced to death on april 4, 1994. seven months later, hoskins filed a direct appeal with the florida supreme court (fsc), claiming that the trial judge had improperly barred neurological testing. upon review, the fsc affirmed hoskins’s convictions, but remanded him to the state circuit court for a pet scan. results showed hoskins as having frontal lobe lesions and thus a lack of control of his inhibition restraints. consequently, the fsc vacated the death sentence.52 in march 2010, brian dugan was admitted to northwestern memorial hospital in chicago to have an f mri and a series of cognitive, attention and moral decision-making tests. in 1983, dugan had kidnapped, raped, and beaten to death 10-year-old jeanine nicarico. one year later, he raped a 27-year-old nurse and drowned her in a quarry. in 1985, he kidnapped, raped, and killed a 7-year-old girl. the neuroscientist kent kiehl who concluded that dugan’s brain suffered from an anomaly in his prefrontal cortex performed neurological testing. consequently, dugan was incapable of controlling his impulses, differentiating right from wrong, and understanding the consequences of his actions. kiehl’s report was used to mitigate death penalty charges against dugan.53 one recent study reported over 1585 cases between 2012 and 2015 in which neuroscience and behavioral genetics were reported in a judicial decision in the us criminal justice system. the data collected show an increasing use of neurological testing by the courts, with over 300 decisions in 2012 alone. neurobiological evidence has been introduced in 5-6% of all murder trials and the most common type of brain scanning is mri or cat, rather than fmri or spect. the study then highlights the use of neuropsychological testing and neuroimaging in pretrial proceedings as an improvement in the evaluation of subjective competency.54 78 vincenzo lusa, annarita franza italian criminal trials the bayout case in 2007, a forty-year-old algerian, bayout was involved in a quarrel in udine, which erupted into a fight as the defendant usually wore eye make-up for religious reasons and for having been insulted with racial slurs. this led to his stabbing to death the individual who had provoked him. sentenced to nine years in prison, the court of appeal made arrangements for a genetic test in which anomalies were detected in five of the genes linked to violent behavior, including a gene polymorphism (mao-a). the court of justice stated that being a carrier of the low-activity allele for the maoa gene (maoa-l) would make bayout more inclined to manifesting impulsive, aggressive behavior when provoked or socially excluded (from judgment no. 5-09/18/2009). namely, he was affected by a kind of “genetic vulnerability” and the presence in the defendant’s chromosomal inheritance of certain genes made him “particularly reactive in terms of aggressivity in stressful situations, and even more so if the individual had spent his childhood in a disadvantageous, family environment” (from sentence no. 5-09/18/2009). for these reasons, the trieste court of justice reduced the sentence by one-third (trieste (italy) court of assizes appeal no. 5 09/18/2009). the albertani case the judge for preliminary investigations at the como criminal court sentenced to twenty years in prison a young woman accused and found guilty of killing her forty-year-old sister. besides also strangling her mother to death, she had tried to destroy the corpse by burning it. simultaneous to the sentence being pronounced, a partial mental defect of the killer came to the judge’s attention because of the results of specific neuroscientific tests intended to ascertain whether the woman presented those alleles significantly associated “with an increased risk of impulsive, aggressive and violent behavior” (from judgment 05/05/2011 no. 536). during the trial, the judge established the presence, through biological testing, of some unfavorable alleles present in the defendant’s genetic inheritance, such as the lowactivity mao-a allele, scl6a4 (stin2 polymorphism) and comt (rs4680 polymorphism), with the sentence later essentially being reduced. high-resolution brainimaging techniques (voxel-based morphometry), were also used in the como case, which proved how it was possible to make a definite correlation between anomalies in certain sensitive areas of the brain and the young murderer’s antisocial actions, particularly, in the woman’s brain where abnormally dense gray matter was found in the anterior cingulate. as a matter of fact, the test showed that the volume of gray matter mentioned above, in the anterior cingulate gyrus, turned out to be different from that in a control group of ten healthy women. it is noted that the previously mentioned cerebellar anatomical region is intended to inhibit automatic and instinctive behaviors. moreover, in critical situations, it regulates aggressive reactions as well as mendacity (como (italy) court, judgment 05/05/2011 no. 536).55 results and discussion if we further examine the risks listed by nasa for the space voyages completed so far, it seems incontrovertible to state that all kinds of possible emergencies can indeed take place in space. some of these contingencies are known, while others are currently unknown. indeed, the high degree of stress to which the astronauts could find themselves subjected could promote the gradual development of uncontainable stress in individuals whose genetic makeup contains particular polymorphisms or structural abnormalities in the brain that could lead an antisocial behavior being manifested. the protocol presented here is based on forensic neuroradiology and will have to be implemented together with the psychological and aptitude tests that are usually used in astronaut selection. therefore it should consider, for maximum crew safety the genetic profile and brain anatomy of the candidates and in particular: 1) an examination of those brain structures involved in controlling aggressive impulses and possible anatomical malformations including the telencephalon and cerebral cortex on which the limbic system is present; 2) a study of some alleles that enable understanding the relationship between genetics and crime. in fact, the protocol should be based on examining those brain structures involved in controlling aggressive impulses and any anatomical defects inherent in the telencephalon in which the limbic system is present. examinations must also be performed on the hypothalamic-pituitary-adrenal axis, (involved in the control and adaptation to stress) as well as on the connections between the limbic system (the seat of emotions) and the prefrontal cortex (control over impulses including aggressive ones) by using chemical imaging such as functional neuroimaging techniques that study brain function based primarily on measuring blood flow (f mri), (spect), and glucose metabolism (pet) in different areas of the brain. voxel-based morphometry (vbm) shows anatomical connections in the brain as well as the density of gray matter composed of 79visualizing chemistry. the application of chemical imaging to address scientific challenges in space research neurons and of white matter that instead forms axons. using this technique, anomalous structures in the brain can be highlighted – something that proved valuable in the como court case discussed here. the protocol then focuses on examining some of the biomarkers genetically predictive of criminal behavior. for example, regarding the polymorphisms mentioned here, the aspiring astronaut will have to have evaluated and monitored the monoaminergic system to determine the presence of the shorter mao-a variant (on the x chromosome) in the polymorphic version of maoa-l as well as the catechol o-methyltransferase (comt) to confirm the val158met polymorphism in the comt. regarding the serotonergic system, the scl6a4 gene must be monitored as it is able to reduce aggressive behavior in humans that codes for the serotonin transporter (sert), a key modulator of serotonergic transmission. the possible detection of reduced serotonergic activity in the brain may result in increased impulsive and aggressive behaviors via the “s” polymorphism of the scl6a4 gene, whose existence involves a greater inability to adapt in unfavorable environmental conditions. the dopaminergic system will also be subject to careful study as, for example, the slc6a3 gene (dopamine transporter) has been linked to extremely violent impulsive-aggressive and antisocial behaviors in an individual whose slc6a3 gene is found to have the 10 allele. conclusions the ability to image the interior of the human body with techniques with chemical imaging has revolutionized medical diagnosis and treatment. clearly it appears evident that chemical 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69-83. 52. a.r. beech, a.j. carter, r.e. mann, p. rotshtein, the wiley blackwell handbook of forensic neuroscience, wiley-blackwell, new york, 2018. 53. m.j. saks, n.j. schweitzer, e. aharoni, k.a. kiehl, j empirical legal stud. 2014, doi 10.1111/jels.12036 54. n.a. farahany, j law biosci. 2016, doi 10.1093/jlb/ lsv059 55. l. de cataldo neurburger l., la prova scientifica nel processo penale, cedam, padova, 2003, pp. 317-34. substantia. an international journal of the history of chemistry 1(1): 37-41, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-9 citation: p.-g. de gennes (2017) the tribulations of the inventor. substantia 1(1): 37-41. doi: 10.13128/substantia-9 copyright: © 2017 p.-g. de gennes. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declares no competing interests. feature article the tribulations of the inventor pierre-gilles de gennes* keywords. progress of science, innovation, inventor. this is the translated transcription of a speech given in may 2005 in florence. my topic is innovation. the starting remark is that we are sick and tired of the innovation in the form of speeches, colloquia, prizes, etc. a great deal of people speak about it and, as usual, it does not result in anything concrete. however, we need innovation. if we look at the world as it is, we can say that we need innovation at two levels. there is, i would say, a selfish perspective, the perspective of a western country’s citizen who says: “we live in an incredible luxury in comparison to the third world. if we want to keep this situation of comfort, we have to be constantly in lead, we must have more patents to sell, and industries to create that are not those of today because these will be much better ruled for example in southeast asia. we must do something else”. there is this reducing point of view and then there is a more generous point of view which consists in saying: “actually, we are in front of this third world. if we want that this earth remains in the long term, we have to discover its own way of evolution, and this implies a considerable technical innovation.” thus one way or the other, we cannot escape it. but it is not so simple to do. i have to admit, contrary to what you just heard, that i am not at all an inventor. all that i can say is that i have been the advisor of a number of inventors at the industrial and academic level. and also i see some of the pupils of the école de physique et chimie coming up, at least we must try not to suffocate their enthusiasm, i would say. it is more or less the level of what we know to do. i should also tell you that there are heaps of epinal prints on invention and innovation that are completely off the track. the first maybe is bernard palissy, a little bit crazy inventor who burns his last chair to cook its ceramics, to make something extraordinary. this picture is very dangerous. it often goes with the idea that this inventor is also misunderstood. this situation is dangerous. being misunderstood does not mean to be a real creator. i could quote the most famous newspaper in france, dedicated for a considerable time to people who made only stupid things, but that became heroes by their condition of being misunderstood. thus, as for bernard palissy, this is distrust. there is another aspect that we still find in novels or things like that, which is the lightning revelation of the gentleman which suddenly has an idea that is going to submerge an entire domain. 38 pierre-gilles de gennes it certainly occurs in some cases. there is a funny case, it is the story, that takes place more or less in 1900, of a young hungarian who was walking in a park in budapest and who suddenly decided with his friend that he knew the way to build an electric engine that could work. at that time electric engines worked horribly badly. he drew with his cane (at that time, they still had sticks) in the sand of the park what will be the synchronous engine, the future engine, that will turn direct electricity used by edison into the alternating electricity in which we live. it is an illumination, it is true. there is a very small number of cases of this kind. a lightning revelation is not at all what we expect from a pioneer. and then, there is a third feature which concerns you more, a sort of creed of the current companies: in order to innovate, it is necessary and sufficient to follow the market, to know what your customers demand and to come out with the substantial answer to their request. this is absolutely insufficient. i can try to make two or three examples. a first example is the story of the liquid crystals watches, the liquid crystal display in general, but in particular for the watches. as this appeared, the industry of the watch was a swiss factory that worked magnificently, used to listen very well to its market, and developed market oriented quartz watches. however at the time the company did not see the upheaval that this type of display and the associate microprocessors represented. because of this error the swiss industry knew 10 or 15 years of dramatic slump. it came out finally with a nice restoring as in the case of swatch or things like that, but in any case it was a considerable strategic fault. thus, the market piloting in that case was completely dangerous. another example that fortunately affects you at a minor extent, is the one of a sir named hounsfield who worked in a disks company. the disks company used to make good bargains and had a certain investment policy in all-out research. he was persuaded that x-rays pictures could be taken to look at objects. he did that with what was at hand, that is a target, a rotating arm which was pulled by the engine of a vacuum cleaner and an x-ray tube. instead of taking one picture as we usually do to get an x-ray radiography as we say in medicine, he took hundred pictures by turning the arm. later, through a smart reconstruction, he got something that was much more informative. then he went to the doctors. for a decade the customers and the market kept answering: “no interest”. and then finally the device became a breakthrough and this object, that before was mounted on a vacuum cleaner, became what we call now a scanner, an object on which we are all dependent regrettably at one point or another during our life. we gladly crow on the invention of the laser, a little bit dangerous pride because if we look at the old reports, we notice that the laser would have been invented much earlier, probably 20 years earlier. there were the practical and theoretical tools to make it. so probably, it was made unknowingly. in certain arc discharges or things like that, there are strange phenomena that people did not look deeper into, but probably they were producing lasers without knowing it. if you like, the laser, but it is not the case for making a trumpet blow, is a discovery guided by the theory. good! that’s very good. but in many other cases, it is not at all the theory that created the economic activity and finally did a service. an example that i came across this morning is the glass. you know how the glass came out: some phoenician traders were transporting natron, that is sodium carbonate, and they arrived to a river in palestine, they made a stop by the river and set a fire to cook their chow. it was necessary to build a sort of oven to make the fire and the only thing handy they had there was no stone was blocks of natron. they made it on a beach in flint, on a sandy beach. and then suddenly they saw while cooking that something like a river of fire this is what pliny reports spread and that later, this cooled river became a transparent extraordinary material. this is how the glass appeared, but the glass developed through a sequence of fabulous technological inventions. the melting pots to avoid dirt inside, the ovens to blow it was necessary to let air in and also the blowing in another sense, i.e. the idea to have a pipe and inflate in a glass pocket to make a bowl, all this dates from syria-phoenicia-carthage, well before the christian era. it was a fabulous technological innovation and after that there have been other remarkable developments. there has been something like that at the time of a technology transfer to the west, towards cumae, at the end of the roman empire, and then towards murano and altare, in the middle of the middle ages. this technological transfer was not made without troubles because there was no more natron. the natron is found in the dead sea or places like that, but not in the west. we had no sodium carbonate, it was necessary to find something else. people eventually noticed that the ash of ferns, was a good starting point. it is not the same carbonate, it is potassium carbonate. this allowed to restore the industry in the west. it was not made without difficulties because the practical properties, the melting points, all the miscibility properties of potassium are not the same as those of sodium salts. but people of the year 1000 ad more or less knew how to make 39the tribulations of the inventor it because they were pushed by the invasions the invasions that cut the west from the east. then, here we are, the glass. yet, this glass that nowadays is an extraordinary technological tool: in the 19th century was used for lenses and optical instruments, in the 20th century for what we call the ice flow (the glass made on a molten metal that allows to make it very smooth) and recently the glass of the optical fibers which allow to communicate stupidities at a large scale, it is still the technology of the glass. this magnificent technology here is where i return to my original subject is made up of a material that we do not understand. we do not have a serious description of what we call the glassy state. franklin, you know franklin, great man, ambassador of the young republic of the united states in france, but also one of those who understood the electricity, he was curious about everything. franklin had what we regrettably have no more: a robust greek culture. he had read by the greeks that if we put some oil which is a kind of cleaner on the sea, the waves are calmed down. but this observation had remained at the level where greece was, that is, i would say in a pretty provocative way, at the level of the philosophers. we have a fact like that, but we do not learn anything real. franklin had the idea to learn something out of that. at that time he used to live in london, and he went to clapham common, near london. there was a puddle which some of you maybe saw if you are interested in cricket or things like that, there are still activities of this kind and he chose one pretty windy day, with small ripples at the surface of the puddle, very easy to see. he brought a small bottle of a cleaner of his time, probably an oleate or something like that, a by-product of oil. he poured on the puddle a teaspoon of this cleaner and it calmed the waves on a surface probably a little bigger than this room. there, he got a number. it was not simply a qualitative idea, he had a number. in fact, this number was extraordinarily precious as it represented one of the biggest stages, we can say, of the knowledge of matter. if he knew the volume it was one teaspoon and if he knew the surface over which this volume spread out let’s say the surface of this room -, dividing the volume by the surface he could find the height. in fact, he found the height of the molecules of surfactant, he found the size of molecules. exactly, it was an immense progress compared to the greek miracle. the greeks had conceived an idea of atoms and molecules for a difficulty in reasoning, because they did not know how to go to the infinitely small, they badly knew how to manipulate atoms and molecules. but because of a lack of mathematical ease, they figured out: “it has to stop”. by the way, small size objects, atoms, microlites and some others, but it is purely philosophical. since the experiment of franklin, his finding becomes a scientific fact because we do not say that there must be something, but we say that there is something and that it has this size. from this moment, slowly things are. but you will notice the simplicity of the methods one teaspoon, a small jar of oil and a puddle and one of the biggest discoveries of the conceptual history of the matter follows. there is a second example on the same line, due to a lady (i might be wrong, but maybe she was the first woman scientist in the western world). maybe i am wrong, but it is the first that i know personally, she was called agnes pockels. she lived in germany in the middle of the 19th century, fascinated by sciences, wanting to go to the university, but it was impossible for a woman. her brother went to the university and did nothing. but she tackled a problem that fascinated people at that time, which is what we call the surface tension of water. water does not like to lay bare, there is an energy associated with the surface. this energy by square centimeter is what we call the surface tension that we measure by pulling a drop of water by very fine devices and by seeing which strength is necessary to engage in order to convince the water to undress. but the measures that were made at that time gave totally conflicting results. sir x in naples and sir y in göttingen, etc., found absolutely different results. of course the good scientists used to say: “you did not clean your water, it must be dirty”. they said: “we did everything that current chemistry allows us to do, that is we distill, we crystallize the water and then we melt it again, etc.”. we eliminate the maximum of impurities, but no go, nothing. agnes understood that it was not the usual impurities that are in the water such as the common salt or things like that that made the tragedy, but that they were some very rare molecules of these cleaners that i just mentioned. how to get rid of these cleaners? certainly not by the classic methods because they are so few that those methods are useless, there is a much simpler method. she took her water, shook it strongly – this produces foam where there was a cleaner, an impurity and she skimmed this foam with a paddle about twenty times. once she made it in her kitchen, she obtained a perfectly reproducible water. she was the first to measure the surface tension of the water. very happily, it came out. lord rayleigh who was the big guru at that time in this field of science gave her a considerable publicity and she came out well. i will show this story to you. do not expect someone line marilyn monroe, she was an austere lady of the 19th century, but she was someone infinitely respectable in her working. 40 pierre-gilles de gennes there is another aspect, it is the tenacity. innovation is not exactly a job where you find something close by. the concours lépine that started in france in the 19th century is very dangerous, is not at all like that. innovation requires a long time, it is a long investment. it is important to underline this point because it is also an opinion that often escapes to the big companies’ shareholders. i am going to make an example which is a little bit older. we go back to 1891. at that time, ladies carried corsets and ankle boots. a very difficult problem is to manage how to tie all the sequential units of the corset or even more in certain hot occasions to untie the same stuff. judson in the united states is convinced that it would be necessary to find something better. his attitude at the beginning is to try to find a sort of key which opens all the locks at the same time. there was an absolutely horrible mechanical device with stalks in brass meant to open the corset along the lady’s back. obviously, this device did not work, but judson worked hard. in 1905 look at the timescale -, he found a partner called sundback. in two, it works better. finally, they came very gradually with this idea to have, instead of a stalk, a flexible join and they created, just before the great war, what we call nowadays the zipper, which is a very beautiful discovery. look at the timescale from 1891 till 1910 that was necessary for this thing. thus, the tenacity of these people is something extraordinarily respectable and we still need it. i often say that if an extraterrestrial came with the idea to observe a little what is going on on this small planet, he will note maybe with interest that we found as i said the transistor, the laser, etc., but i believe that he will also note that we found the zipper and maybe that we did not find a number of things which are under our nose. let us be humble. this experiment that requires a rather complex material that i am going to collect here, is about what we call the dewetting. i take here some water, h2o, that i am going to place on a sheet of polyethylene. polyethylene hates water. first i put a small drop, you will not see it very well, i try to add two or three. when it is quite small, it tries to minimize its surface to be exposed. the shape that has the smallest surface for a given volume is the sphere. thus, it is a spherical cap, it is a portion of sphere. if i force a little the nature, i put some more there, i face a difficulty which is due to the slope of my system. you see, what is made here is an object that is an interesting compromise. it is an object in which the capillarity and the surface forces want to retract this drop, to make it expose less surface, but there is its weight that goes the other way and that forces the drop to flatten. there is a compromise weight-capillarity analyzed by laplace in 1805 which leads to a thickness very well defined of the order of the millimeter. the object which is there, and that we usually call a puddle, is a very precise object of interface science. it is all good, but it is not enough to look at the nature in this way. we try to tease it a little more, that is we force the sheet of plastic to be wetter than what it likes. i will make it by means of this experimental device. i have some troubles with this story of the slope, but in any case you can see that the sheet gets by quite well. it retracts, there are dry regions which grow either from a small hole inside, or from edges or from defects. if you have a good eye and some faith, you will see that as long as it moves forward, it does it at a constant rate. this process, it is what we call dewetting. it is something that we meet in our everyday life, but that is also important in many industrial applications. these things were made at the institut curie by françoise brochard’s team. they sensed that it was going to be important, they did not very well figure out how, but they established the fundamental laws. obviously, it is not as simple as in the air. to prepare clean surfaces with no defect that may hamper the movement, etc., we need the chemical synthesis on surfaces, it means three years of work, or something like that. then, there is some hydrodynamics. it is very interdisciplinary, it is necessary to understand how it moves, etc. but finally, everything has been clarified and they had the very clear impression that it was going to serve, but they did not know so much where. it turned out to serve in several domains that have an interesting industrial impact. since it is late, i am only going to quote one that is described by what i call the british experiment. in the british experiment, these british wanted the rain. on the road there is more or less 1 mm maybe less, some micrometers of water. under the water there is the asphalt and there comes a car that drives at a british speed of the order of 50 km/h. if this car was really on a film of water like that, you would immediately lose control. it is absolutely necessary to recover a contact between the rubber of the tire and the asphalt. the rubber of the tire turns like this. it keeps the contact with the asphalt during the short moment that corresponds to the flattened part of the tire of your car, which is not very large. at this speed, it means that the tire remains only some milliseconds in contact with the asphalt. during these few milliseconds, the film of water has to strip out. this problem is not so that far from what i showed you in my superb experiment. in my magnificent experi41the tribulations of the inventor ment, there was some polyethylene, there was some plastic, some water and air. in this experiment, there is some asphalt that behaves precisely as the plastic, which hates the water, some water and the rubber. it is not the same problem, as rubber is very different from air, but it is a cousin of this problem. these people at the institut curie dedicated three generations of theses to understand these phenomena. now, we can say that they are relatively well understood and that we have an idea of what a car aquaplaning is. the industrial impact is not so much on the industry of the tire because many of the countermeasures that you can think of to facilitate this process would consist in carving the surface of the tire, like a lace on the surface of the tire. unfortunately, as you know, a tire wears out very fast and this lace would be very quickly removed. thus, many of the countermeasures designed for the tire are not good. on the other hand, the countermeasures about the road, some effective dewetting initiators on the road, are the most interesting for the future. thus in that respect, there are interesting hopes. i mention this to show you that this kind of very simple experiment remains valid even in the 21st century and that it is not of the past that i am talking about. if i come on the big perspectives it is necessary a little bit in a way i would say that what strikes me, is the fact that the inventors had several following cycles. there was an extraordinary time in the 19th century with people working alone such as edison, who really changed our world. and then, there was also another extraordinary time, that of the heavy industries. in the domains that i know it is very restrictive -, it is for example general eletric. general electric had a big pilot, langmuir, who was, let us say, the author of the flashlight as we know it today. the edison’ flashlight was made with a roasted fern had no mechanical stability and did not resist in time. whom shall i quote still? dupont. and carothers for the nylon, or bell labs and schockley for the transistor. thus, there was this superb time of the heavy industries that was an admirable superposition. but you should be aware that this time is about to go and that these heavy industries do not play anymore the same piloting role in the future as they did in the 20th century for a simple reason that your professors will explain to you better than i, what is the grip of the power by the shareholders of the big companies. at present, the shareholders have the power and these shareholders are not you and me, they are rather the pension funds of california or things like that, they are very demanding on the profitability in the short term, that is in three years. in other words, they accept to support all the projects of innovation that are very fast, within three years. they do not support anymore whatever is in a 10-year frame. a big part of what was made in all these examples that i mentioned there was exactly a research that lasted at least 10 years. thus under this point of view, the heavy industries are in a very difficult situation. you see in france the bosses of companies who are in troubles and try to defend a long-term corporate development plan, but who do not always succeed. some are kicked out, others are threatened, let us say. thus, there is a hole there. thank you for your attention. * pierre-gilles de gennes (1932 2007) was awarded the nobel prize for physics in 1991. translation by pierandrea lo nostro the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments 1 citation: v. balzani (2020) the universe, the light, the earth, the life: the reality is greater than w e are. substantia 4(1) suppl. 1: 957. doi: 10.13128/substantia-957 received: may 30, 2020 revised: jun 03, 2020 just accepted online: jun 05, 2020 published: jun 05, 2020 copyright: © 2020 v. balzani. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia feature article the universe, the light, the earth, the life: the reality is greater than we are vincenzo balzani “g. ciamician” department of chemistry, university of bologna, italy email: vincenzo.balzani@unibo.it abstract. the pandemic caused by covid-19 locked us at home for several weeks. some clever town councillors took this opportunity to offer their citizens cultural pills. in my little town i was asked to present a few short lectures on general scientific concepts. i tried to link together four entities of reality (universe, light, earth and life) showing that reality is much more complex than we think and much greater than us. e.g.: age of the universe vs age of human civilization (~1.3x1010 vs ~ 1x104 years), size of universe vs human size (~1x1025 m vs ~1 m), velocity of light vs velocity of sound (3x108 vs 3.5x102 m/s), number of stars in the sky (~ 1x1023), number of molecule in a drop of water (~ 3x1021), number of atoms in a human body (~ 1x1027). although we know reasonably well how universe, light, earth and life “work”, we are still surrounded by profound mysteries related to the why questions, i.e., the “questions of meaning”, that science cannot answer. such questions, e.g., why is there the universe? why is there life in this insignificant fragment of the universe called earth? why did the evolution of life lead to human? what's the meaning of my life? what is the meaning of the covid-19 pandemic? the answers to the these “questions of meaning”, that cannot be given by science, are discussed in the enciclic laudato si’ of pope francis in relation to the ecological and social crisis we are going through. keywords. universe, light, earth, life, reality, complexity, mysteries, unbelievable numbers, stars, atoms, time, energy, human, questions of meaning, talents, spiritual energy. premise during the pandemic caused by covid-19, i was asked by the cultural center of my town to present a series of short lectures of general interest for students as well as for citizens locked in their homes. i thought it was a good opportunity to recall some fundamental concepts on the universe, the light, the earth and the life, to show that the world is full of mysteries, that is, things that are not understood or that, if they are understood, are so strange as to seem incredible: incredibly large, incredibly small, incredibly organized, incredibly efficient. the reality is much, much greater than we are. substantia. an international journal of the history of chemistry 4(1) suppl. 1: 957, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-957 http://www/ http://www/ http://www.fupress.com/substantia vincenzo balzani 2 the universe let's start from the universe.1 what is the universe, which we sometimes call the world? has there always been? no. science tells us that the world was "born" 13.8 billion years ago. scientists are unable to say what was before. we are faced with a first mystery, we will see many others. according to some scientists, before there was nothing. other scientists think that there are not only one universe, ours, but that there are many: and to say that there are many, the word multiverses is used. but these are only hypotheses, in which science borders on the field of philosophy. the most accredited scientific hypothesis on the universe is that everything started with the so-called big bang, a big explosion (better: a great expansion) of a very small "thing" in which an incredible amount of energy was concentrated (figure 1). we do not know what was before this big bang, but we know, at least in broad terms, what happened after, that is, during the 13.8 billion years of "life" through which the universe came to us. at the beginning there was only a very small volume of incredibly concentrated energy at very high temperature; then, a great expansion in the space occurred and the universe cooled down. energy began to condense forming matter, matter aggregated to give galaxies, stars and all other celestial bodies, including our earth, which formed 4.5 billion years ago (when the universe already existed for 9 billion years). then life originated on earth about 3.5 billion years ago (how life originated, it is not known: another mystery), then the evolution of life led to human. our civilization is only 10,000 years old! what else do we know about the universe? as we can see with our eyes, there are many material objects: stars, planets, satellites, meteorites, and there are phenomena such as gravitational attraction, heat, and light: that is, there are matter and energy. according to scientists, in addition to matter that is seen and energy that manifests itself, there is also a large amount of matter that we do not see (the socalled dark matter) and there is energy that we do not perceive (dark energy). as we will see below, we know a lot about the universe, but a famous einstein phrase is enough to throw us back into the mystery:2 "the most incomprehensible thing about the universe is that it is understandable". but how do we see and understand how the universe is made? by means of the light. the light what is the light? we think we know it, but try to give a definition, to explain it to another person: it's difficult.3 in physics books one can find pages and pages about light, its many properties and characteristics; but when it comes to saying what light is, they just say that light is energy. at this point one thinks one has understood, but it is not so. yes, okay, light is energy, but what is energy? maybe we think we know, but we will see later that we don't even know what energy is. another mystery. the first thing to say about light is that it's a strange “thing”. in fact, light manifests itself in two different ways: as a wave, an electromagnetic wave (that is, a wave with electrical and magnetic properties), or as a set of granules, of energy particles called photons. a ray of light is a wave, but also a set of photons. the light is very strange indeed: it manifests itself with the wave aspect or the photonic aspect depending on how we study it, on what experiment we do! light is emitted from a source (e.g., sunlight) and travels until it encounters something that absorbs it, that uses it: for example, in our eye light causes a chemical reaction that sends a signal to the brain: and this allows us, in fact, to see. in science, the word light has a very broad meaning: by light science means not only what our eyes can see, more precisely defined visible light, but also other types of light, different in their content in energy, which our eyes cannot see. our eyes do not see photons that have very high energy, for example those of ultraviolet light or x-rays, nor do photons that have too low energy, such as those of infrared light or radio waves. often in science instead of light the term radiation is used, which includes all types of light, both that which our eyes can see and that which our eyes cannot see. stars emit radiation that is in part visible light, what we see, but they also emit many other types of radiation, x-rays, gamma rays, radio waves, etc., which our eyes do not see. but scientists have invented special equipment with which they can "see", that is analyze, radiation that our eyes do not see. by analyzing radiation, visible or non-visible, emitted by celestial bodies we can learn many things about the universe. the quality and quantity of light emitted by a source depend on the materials of which the source is made and the temperature at which it is located. therefore, by analyzing the light emitted by a star we can understand what material there is on that certain star and also what temperature that star has. the light has another oddity, another exceptional property: it comes out of the source and propagates at an figure 1. this image represents the evolution of the universe, starting with the big bang. the red arrow marks the flow of time. credit: nasa the universe, the light, the earth, the life: the reality is greater than we are 3 unimaginable speed: 300,000 km per second. to get an idea of what 300,000 km per second means, consider that the circumference of the earth is about 40,000 km. so a ray of light in a second travels around the earth seven times. there is nothing faster than light. for comparison, remember that the sound propagation speed is only 350 meters/sec. (1000 km/h). the distance between the moon and earth is 380,000 km: the light of the moon takes 1.3 sec to reach earth. the distance between the sun and earth is 146.6 million km: a jet plane would take 16 years to go from the sun to earth. the light takes 8.5 minutes. this number, 8.5 minutes, tells us another very important thing: when we see it, the sun is actually no longer there; it was there 8.5 minutes before. the distances in the universe are so great that it is not convenient to measure them in km. antares, one of the brightest stars, is away from us 10 million billion km: a 1 followed by 16 zeros, too large a number, too inconvenient to use. thus it was decided to take as a unit of distance measurement in the universe not the kilometer, but the light year, that is, the distance that light travels traveling for a year. the light year equals nearly 10 trillion km. expressed in light years, the distance between the earth and the antares star is 1000 light years. this means that by looking at antares, we actually see where antares was 1000 years ago! since its inception, the universe has expanded and continues to expand: it has not yet been understood what shape it has, and therefore what size. someone has calculated that if you imagine the universe as a sphere, but also on this point there are many discussions, it has a radius of one hundred thousand billion billion km, equal to 46 billion light years. how big the universe is! and it is expanding! certainly there are stars so far away that we have not yet seen because their light has not yet arrived! always thanks to the light, with simple trigonometric calculations we can measure the distances between us and the various stars and also understand the movements of the stars. stars are celestial bodies at very high temperatures that emit light. our sun is a star. stars are often surrounded by other celestial bodies which we call planets, which in turn may be surrounded by satellites. the earth is a planet of the sun, which is much larger than earth: it has a radius 109 times greater than that of the earth. the moon is a satellite of the earth, it has a radius 4 times smaller than that of the earth. planets and satellites do not emit light: they are bright because they partly absorb, but partly reflect the light emitted by their star. analyzing the reflected light we can get information on the chemical composition of the planet or of the satellite. and dark matter, what would it be? matter that does not emit any type of radiation and therefore we cannot see it in any way. but it can manifest itself through gravitational effects. and what about dark energy? it is light that cannot leave the star that emits it, light that is swallowed up, attracted by the great gravitational force of the star. this happens in the so-called black holes that emit light that cannot reach us. how many stars are there in the sky? have you ever tried to count them? the visible ones, that is those that emit light that our eyes can see, are about six thousand, but there are many other stars that are not bright enough to be seen without a telescope or that do not emit visible light, but other types of radiation (x-rays, gamma rays, radio waves etc.) that scientists are able to analyze with their equipment. in total, it is estimated that there are about one hundred thousand billion billion stars in the sky (a 1 followed by 23 zeros), a number so large that it is difficult to understand. to try to appreciate it, suppose we can see them all and start counting them, one per second: to count them all, it would take 3 million billion years. an impossible task for a human! the universe is not on a human scale. reality is much bigger than we are. in the bible there is a psalm, psalm 147, which says: “the lord appoints the number of the stars; he calls to them all by names”. then there is another psalm, psalm 115, which says "the heavens are the heavens of the lord; but he has given the earth to the sons of men”. here, we have to take care of the earth, not the universe. the earth, says pope francis in the encyclical laudato si’, is “our common home”.4 the earth the earth was formed 4.5 billion years ago, then 9 billion years after the "birth" of the universe, the big bang. the earth was formed by the aggregation of materials that have become detached from the sun. as a first approximation, the earth has a spherical shape, with a radius of 6,400 km (fig 2). but to understand well what earth is, our common home, we need to do other types of reasoning. in a famous photograph, taken by nasa astronaut william anders on december 24, 1968 during the apollo 8 mission, one can admire the extraordinary spectacle of the rising of the earth seen from the moon. contemplating the scene he was photographing, anders said,5 "we came all this way to explore the moon, and the most important thing is that we discovered the earth." looking at the earth from far away, we indeed realize what our real condition is: we are passengers of a spaceship that travels in the infinity of the universe. figure 2. one of the most famous photographs of earth, taken on december 7, 1972 by the apollo 17 crew from ~ 45,000 km away. credit: nasa vincenzo balzani 4 on this spaceship, we are many, almost eight billion and so different: white, black, yellow, rich and poor, good and bad. in another famous nasa photograph (figure 3), taken by the cassini orbiter spacecraft when it was near the rings of saturn, at a distance of 1.5 billion kilometers, the earth appears as a pale blue dot in the cosmic darkness. it looks like an insignificant fragment of matter that travels aimlessly in the infinity of the universe. there is no evidence that the earth is in a privileged position in the universe, there are no signs that suggest our particular importance, nothing that leads us to believe that we can receive help from others, no indication of places where possibly be able to emigrate. it is very interesting and also instructive to look at these two photos: they should be shown and commented in elementary, middle and high schools and, even more, in university courses that open up to political careers. if you meditate on these photos, you understand that the earth is indeed a spaceship,6,7 but it is a very special spaceship, very different from those we see in the movies: from the spaceship earth no one can leave, if not dying, and nobody can come from outside: to live on the spaceship earth you have to be born on it. not only that: it is a spaceship that can never "land" anywhere, can never dock at any port to refuel or unload waste. the resources we can count on are the materials that make up the ship and the sunlight. and if something doesn't work, if something "breaks" we have to get by on our own, without even going down. this is what we have been trying to do in recent months, since the covid-19 pandemic has developed on the spaceship earth (figure 4). the virus has killed tens of thousands of people in several countries and forced billions to shut themselves up in their houses. waiting for a vaccine, we hope to have taken control of the pandemic at least for the next few months. what is the origin of the covid-19? president trump claims that it has been released from a chinese research laboratory, by purpose or mistake, but scientists believe that the covid-19 pandemic, as well as previous ones, are caused by our mistakes in the relationship with nature:8-10 exaggerated use of resources, pollution, climate change, excessive occupation of the soil, growing loss of biodiversity, increase in the consumption of animal products, including wild food. originally, viruses only infected animals, particularly wild animals, but then make the jump from animal to humans, a well-known phenomenon called spillover. in a way, viruses are "refugees" from environmental destruction caused by the progressive occupation of human in all natural environments. a great scientist, edward wilson, has provocatively proposes to leave half the earth to nature if we want to live well on this planet.11 the most serious problems are caused by fossil fuels, coal, oil and natural gas, used to obtain energy. on earth, every second we burn 250 tons of coal, 1000 barrels of oil and 105,000 cubic meters of gas.12 every second! the use of fossil fuels causes the release into the atmosphere of huge quantities of carbon dioxide (1200 tons per second) and many polluting substances. the huge amount of carbon dioxide (co2), a colorless, invisible gas, wraps the planet like a blanket that allows the sun's rays to reach the ground, but prevents, in part, the heat generated from escaping towards the outer space. it is the so-called greenhouse effect: the planet heats up. this global warming,6,7 causes complex climate changes such as melting ice, rising sea levels, changes in the precipitation regime, extension of desert areas. the "breakdowns" caused by the climate change are already very evident and scientists warn that if measures are not rapidly implemented to reduce the consumption of fossil fuels to zero, the situation will get worse and faster and will have catastrophic results for the next generations. to avoid pollution and climate change we will have to use sunlight and the force of wind and rain as energy sources. all these problems, pollution, climate change, loss of biodiversity, the corona virus and many others, we have only us who are on this strange, small planet of the solar system, the earth. it should be noted that they are not intrinsic problems of the planet, they are our problems: problems that we have created, we who are the result of the strangest and most mysterious figure 3. photograph taken by the cassini orbiter spacecraft on september 15, 2006, at a distance of ~ 1.5 billion kilometers from earth. the dot to the upper left of saturn's rings, indicated by the arrow, is the earth. saturn was used to block the direct light from the sun, otherwise the earth could not have been imaged. inset: expanded image of the earth which shows a dim extension (the moon). credit: nasa. figure 4. the covid-19 pandemic the universe, the light, the earth, the life: the reality is greater than we are 5 thing of all those we have already seen, probably unique in the whole universe: the fact that on earth, about 3.5 billion years ago, life developed and then the evolution of life led to us! thinking about it, you have to be breathless: the earth, this insignificant fragment of a universe that includes one hundred thousand billion billion stars, the earth, this small fragment of matter seems to be the only place in which life has developed! the life what is life?13,14 we know it well, but if we were to explain what is life to someone, we would be in trouble. on the other hand, even scientists do not agree in saying what life is, nor are they able to "build" it in the laboratory. life is a "concept", an "entity", a "something" too complex, important and sublime to be "forced" into a definition. this also happens for other fundamental concepts. of the concept of time, saint augustine said: "if nobody asks me, i know; if i want to explain it to those who ask me, i don't know anymore”.15 also of the concept of energy, richard feynman said:16 "we must realize that in physics we don't know what energy is”. a scientist who has recently tried to define energy in a dictionary took 10 lines and then concluded as follows:17 "energy is something of a universal nature that appears in material and immaterial forms and that cannot be "reduced" to anything more elementary". yes, energy also appears in an immaterial form: human is not only made of matter, but also of something that we call spirit, an entity which is also difficult to define, but easy to clarify with an example. when my wife sees me fatigued and says “i am going to prepare you a tea”, she performs material actions (she warms up water, she pours it in a cup etc.), but she is guided by her loving me. she makes me a tea because she loves me. loving is a spiritual energy. so, what is life? what do we know? how does it work? we know that the earth and also all living beings that populate it are made up of atoms (c, o, n, fe, etc.) that join together to give rise to aggregates that we call molecules.18 the molecule that everyone knows, that of water, h2o, is made up of two hydrogen atoms linked to an oxygen atom. there are millions and millions of types of molecules. there are also very large ones such as hemoglobin which is composed of 9072 atoms: c2954h4516n780o806s12fe4. atoms and molecules are very small. the unit of measurement that we use in everyday life is the meter, but we have seen that in the universe we cannot measure distances in meters and not even in kilometers: it is better to use as a unit of measurement the light year, which is worth ten thousand billions of km. similarly, for very small things, we cannot use the meter as a unit of measurement. we must use the thousandth of a meter (millimeter) or the millionth of a meter (micron), or even the billionth of a meter, the nanometer (10-9 m). the dimensions of atoms and molecules are measured in nanometers. the water molecule, h2o, has a diameter of about 0.2 nm, two tenths of billionths of a meter. the molecules, therefore, are incredibly small. hard to believe, but it's true! scientists, just as they invented equipment to study the infinitely large universe, have invented other equipment to study very small things like atoms and molecules. to understand how small molecules are, an example will suffice: in a drop of water there are 1021 water molecules, that is, one thousand billion billion molecules. here is another incredible number! if we could and wanted to count, at the rate of one per second, the molecules that are in a drop of water would take 30,000 billion years. another example, even more incredible, is the following: in the body of a human there is a number of atoms ten thousand times greater than the one hundred thousand billion billion stars of the universe! and, which causes an even greater wonder, these billions of billions of atoms that make up a man's body are not piled up in bulk, but are extremely well ordered and connected to form molecules, which in turn are grouped together to form more and more complex systems. as complexity and organization increase, new properties emerge that make it possible to perform increasingly valuable functions: this leads to the simplest form of life, the cell of a bacterium, which is made up of thousands of billions of molecules and has dimensions of 200 nm (two hundred billionths of a meter). a further increase in complexity leads to the formation of larger and more complex cells that come together to give tissues, which in turn form organs that are capable of performing increasingly complex functions, up to that supreme organ which is the brain of the human.18 the mistery of life from the view point of science, the mystery of life does not lie, as once thought, in a not better defined "life force", but in a huge number of extremely complex chemical processes, incredibly organized and capable of such a rich diversified functionality to arouse our amazement and escape our reasoning. the more we know about life, the more wonder increases. edoardo boncinelli wrote:19 "every day, in every moment of our life, a real miracle occurs within us: the ability to learn, to remember, to make choices". george wald, a famous american scientist, spoke of the thread that connects the atom to human in these terms:20 “it is a very important part of our dignity that we can know and that through us matter can know itself. organized as they are within us, hydrogen, carbon, oxygen, nitrogen, water, having become "us", can begin to understand what they are and how they came to be". so we are shrouded in mystery. science speaks to us only of concrete, material things, not of spiritual ones. science gives us news on how the world works, but leaves open all the questions of meaning. why is there the universe? why is there light? why is there life in this insignificant fragment of the universe called earth? why did the evolution of life lead to man? what is the meaning of the presence on earth of man, the only thinking creature, subject in a world of objects, formed by a number of atoms ten thousand times larger than the hundred thousand billion billion stars of the universe? what's the meaning of my life? why can a virus, a vincenzo balzani 6 non-living 100 nanometer entity, attack and kill a human, a living entity made up of ten billion billion times more atoms? we are not the masters of the world. reality is much, much greater than we are. it is beyond our ability to understand it. science is useful for understanding how the world works and can help us solve problems, even if sometimes it is science itself that creates problems. in any case, science cannot make us omnipotent. the answers to the questions of meaning are not found in matter and science. we must look for them in the categories of the spirit, in philosophy and in religion. even pope francis, in the encyclical laudato si ’, asks questions of meaning:3 "what is the purpose of our life in this world? why are we here? what is the goal of our work and all our efforts? what need does the earth have of us?” the answer, says pope francis, lies in the dignity of man: “we need to see that what is at stake is our own dignity. leaving an inhabitable planet to future generations is, first and foremost, up to us. the issue is one which dramatically affects us, for it has to do with the ultimate meaning of our earthly sojourn”. therefore, we must “… protect our common home and bring the whole human family together to seek a sustainable and integral development, for we know that things can change”. human is free to choose between good and evil but “human beings, while capable of the worst, are also capable of rising above themselves, choosing again what is good, and making a new start. …… no system can completely suppress our openness to what is good, true and beautiful. … education in environmental responsibility can encourage ways of acting which directly and significantly affect the world around us; … such actions can restore our sense of self-esteem; they can enable us to live more fully and to feel that life on earth is worthwhile”.3 here then: perhaps the covid-19 pandemic is a providential reminder. we are asked to better protect the common home and all its inhabitants, to abandon wars, consumerism and inequalities and to take the path of peace and ecological and social sustainability. we are asked to learn how to make better use of all the talents that have been given to us and, in particular, our precious sources of spiritual energy: wisdom, creativity, responsibility, collaboration, friendship, sobriety and solidarity. we are asked to understand that on this spaceship earth which, as the psalm says, god “gave to the sons of men" and on which we are all born and we must all live to death, we are all brothers because we are loved children of that god much greater than us who, as the psalm says, “appoints the number of the stars and calls to them all by names”. references 1. hawking, s. (2018) “brief answers to the big questions”, john murray publisher, london 2. einstein, a. (1936) “physics and reality” in ideas and opinions, trans. sonja bargmann (new york: bonanza, 1954), p. 292 3. feynman, r.p. (1998) “qed: the strange theory of light and matter” princeton university 4. holy father francis (2015) “on care for our common home”, laudato si’, vatican press. 5. space quotations, http://www.spacequotations.com/earth.html 6. armaroli, n., balzani, v. (2011) “energy for a sustainable world. from the oil age to a sun powered future”, wiley-vch, weinheim 7. armaroli, n., balzani, v., serpone, n. (2013) “powering planet earth”, wiley-vch, weinheim 8. evans, t., et al. (2020) “links between ecological integrity, emerging infectious diseases originating from wildlife, and other aspects of human health an overview of the literature” doi: 10.13140/rg.2.2.34736.51205 9. https://www.climateforesight.eu/ 10. balzani, v. (2020,) “a providential last warning.” substantia 4(1) suppl. 1: 907 11. wilson, e.o. (2017) “half-earth: our planet's fight for life”, new york time bestseller
 12. balzani, v. (2019) “saving the planet and the human society: renewable energy, circular economy, sobriety”, substantia, 3(2) suppl. 2: 9-15 13. schrodinger, e. (1967) “what is life? mind and matter” cambridge university press 14. regis, e. (2008) “what is life?”, brockman, new york 15. www.brainyquote.com/quotes/saint_augustine_108119 16. feynman, r.p. (2005) “six easy pieces: essentials of physics by its most brilliant teacher,” perseus books, new york 17. balzani, v. (2015) “energia, definizione d’autore”, vocabolario lo zingarelli, p. 791, zanichelli, bologna 18. balzani, v., venturi, m. (2012) “chemistry: reading and writing the book of nature”, royal society of chemistry, london 19. boncinelli, e. (2000) “il cervello, la mente e l’anima”, mondadori, milano 20. wald, g., quoted in ball, p. (2001) “life’s matrix: a biography of water”, university of california press. http://www.spacequotations.com/earth.html 10.13140/rg.2.2.34736.51205 https://www.climateforesight.eu/ http://www.brainyquote.com/quotes/saint_augustine_108119 substantia. an international journal of the history of chemistry 3(1) suppl.: 53-60, 2019 firenze university press www.fupress.com/substantia citation: i. ciabatti (2019) gold parting with nitric acid in gold-silver alloys. substantia 3(1) suppl.: 53-60. doi: 10.13128/substantia-606 copyright: © 2019 i. ciabatti. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-606 gold parting with nitric acid in gold-silver alloys iacopo ciabatti r&d manager, tca|precious metals refining, zona industriale castelluccio 11, capolona, arezzo e-mail: i.ciabatti@tcaspa.com abstract. this article is an overview of gold parting with nitric acid on a both industrial and laboratory scale, supported by more recently reported experimental and theoretical studies on the gold dealloying process for the fabrication of nanoporous gold material. keywords. parting, assay, gold refining, dealloying, nanoporosity. introduction metals have played a fundamental role in human history and were the basis for the development of ancient societies. precious metals and gold in particular have always been considered status symbols and a measure of power. in all likelihood gold was one of the first known metals due to its presence in native form as grains or nuggets [1]. as soon as gold was discovered, men recognized its extraordinary properties, such as malleability and incorruptibility, which differentiates it from all other metals. the earliest gold artefacts known to us were found in a pre-historic settlement in southern bulgaria and date back to 4500-4600 b.c. [2]. however, the metallurgical expertise required to purify gold did not develop until the second millennium b.c. most gold in its natural state is a gold-silver alloy (electrum) containing other base metals as impurities [3]. in the latter case, purification was historically achieved via cupellation, although this metallurgical treatment was originally conceived as an extractive process of the silver contained in lead ores, and only later it also became a refining and assay process of alloy gold metals [4]. however, the separation of gold and silver, generally referred to as gold parting, cannot be done via cupellation. the oldest gold parting process involved salt cementation and the first evidence of this dates back to the 6th century bc in sardis, lidia [5]. in this process, silver metal was converted into its chloride salt by alternating thin sheets of gold alloy with layers of a mixture of sodium chloride, brick-dust, vitriol, alum, and other materials which were then heated together in a sealed pot. the main drawback of the cementation process is a tangible loss of material, though a high-grade gold purity can be 54 iacopo ciabatti achieved. with the discovery of the nitric acid synthesis, cementation soon became obsolete. alchemists were pioneers of this approach as they recognized that this new product was ideal for the purification of gold in silverand copper-gold alloys. nitric acid could be made by distilling saltpeter with a specific sulfate salt, the choice of which historically fostered the dissemination of a variety of terms [6]. for example, the term spiritus nitri was used when nitric acid was made from saltpeter and alum, while it was called aqua fortis when made from saltpeter and vitriol (such as iron sulfate, known as green vitriol) according to the follow reaction: 2kno3 + feso4∙7h2o → 2hno3 + feo + k2so4 + 6h2o (1) the first mention of nitric acid is in the writings of pseudo-geber, who described its obtaining from calcining a mixture of saltpeter, alum and blue vitriol (copper sulfate) [7]. however, nitric acid preparation was no simple matter and it is likely that only small amounts of this compound were originally available, thus allowing for only limited-scale treatment. nitric acid concentration and purity were the main challenges throughout the middle ages and the renaissance. indeed, hydrochloric acid was often present because saltpeter contamination with potassium chloride and this made nitric acid unsuitable for gold parting. prior to gold parting, small quantities of pure silver were added to the acid solution as a sacrificial reagent to precipitate chlorides. after geber, more detailed descriptions of gold parting with nitric acid appear in the writings of vannoccio biringuccio [8], georgius agricola [9] and lazarus ercker [10]. in the nineteenth century, the large-scale nitric acid production using the birkeland–eyde, and thereafter the ostwald process, via nitrogen and ammonia oxidation respectively, allowed extensive use in gold refining on a commercial scale. in the modern period, gold parting with nitric acid has been largely replaced by other treatments such as chlorination using the miller process [11]. nonetheless, nitric acid is still used today in the parting stage on the laboratory scale after cupellation assay. parting with nitric acid in gold assay and refining gold parting consists of a selective corrosion process, also known as leaching or dealloying, which is based on the “incorruptibility” of gold to nitric acid. as a result, in the case of silver-gold alloys with a suitable composition, silver is oxidized and transfers into the solution as silver nitrate. if an alloy contains also other metals, these elements can either be solubilized like silver (e.g. copper) or behave in the same way as gold (e.g. iridium). in addition to these two borderline cases, other metals can be partially dissolved (e.g. palladium) or lead to the formation of insoluble compounds (e.g. tin). on a laboratory scale parting occurs after cupellation, which consists in an oxidative fusion in which samples are melted with lead in a cupel at 1050°c [12, 13]. atmospheric oxygen reacts with lead to form litharge (lead oxide), which catalyzes the oxidation of the other base metals present in the sample as alloys. magnesite cupel absorbs the metal oxides, leaving only precious metals in the cupel as small doré bead made up of noble metals, generally silver and gold and pgms (platinum group metals). this alloy usually contains insufficient quantities of silver to be oxidized by nitric acid. when parting is used as assay, selective dissolution of silver is quantitative and the residual gold compacts enough to be weighed after annealing without powdering on handling. for this purpose, the first operation is designed to make suitable au-ag alloys, which consist in three parts of silver and one of gold, hence the term “inquartation process”. at this point, the common procedure is to melt bead with pure silver to generate a suitable alloy. after the inquartation process (figure 1a) and prior to the parting process, bead is hammered (figure 1b), annealed, rolled to a thin strip (figure 1c), annealed for a second time (figure 1d) and rolled up to a shape like ionic order column volute (figure 2). the hammering and rolling stages serve to increase the surface area for the subsequent silver dissolution with nitric acid, while annealing is designed to relieve residual stress. moreover, a second rolling stage must be carried out to allow the wettability of the whole surface, thus avoiding the occlusion of impurities as oxides obtained from the previous cupellation process. in this regard, the ionic volute is probably better than the cornet shape (figure 2), as battaini et al. pointed out [14], on the basis of the greater distance between the internal metal walls. the parting process takes place in two stages by keeping the sample in boiling nitric acid inside a kjeldahl flask, which has a long neck. the first treatment makes use of a 5.6 m nitric acid aqueous solution (22°bè) and the second one of a 9.4 m nitric acid aqueous solution (32°bè). the stoichiometry of pure silver and copper reactions with nitric acid have been the subject of a great deal of enquiries and, in particular for the latter metal, the attribution of the correct reaction coefficient sets is discussed in several articles reported in the literature [15]. the oxidation of silver by nitric acid takes place mainly according with the following parallel reactions [16]: 55gold parting with nitric acid in gold-silver alloys 4hno3 + 3ag → 3agno3 + no + 2h2o (2) 2hno3 + ag → agno3 + no2 + h2o (3) as reported by martinez at al. [17], it is possible to determine the contribution of each reaction by titration of the unreacted nitric acid moles in relation to the moles of silver dissolved. in the case of high concentrated acid (5.3 m) the reaction (3) dominates, on the contrary when the concentration is low (2.5 m), nitric oxide is the main nitrogen product, according to the reaction (2). similar behavior has been also observed for au-ag alloys, suggesting that, during parting stage, reaction (3) represents the main contribute for silver oxidation. in the case of large-scale refining, a correct balance between a suitable separation gold-silver alloy and the rate of dissolution should be considered. indeed, gold parting is not necessarily quantitative. in all likelihood, this compromise is the main reason for the different silver content values recommended by scholars which ranges from 60 to 80% [12, 18, 19]. in the case of the laboratory scales discussed above, beads obtained after fire assay are rolled in order to increase the surface area. the same strategy can be used on an industrial scale. the operations involved are similar: first of all, the material is heated to a dull red and chilled in cold water to anneal it. then it is rolled and the thin foils thus formed are twisted into what figure 1. characteristic gold parting steps on a laboratory scale. after the inquartation stage (a), the precious metal bead is hammered (b), rolled (c) and annealed (d). the parting process occurs inside a kjeldahl flask (e), keeping the rolled specimen in a boiling acid solution (f ). figure 2. cornet (top) and volute shapes (bottom) in the same rolled cupellation bead. 56 iacopo ciabatti are called cornets to prevent them from lying flat in the reactor. the second and more common approach is granulation. after melting, the molten alloy is poured into cold water with a thin stream moving the crucible in a circular motion or bobbling air in the water. the grains are small shell shaped (figure 3). the parting process takes place in two stages involving nitric acid solutions with different concentration. the solution is often heated only at the beginning because silver dissolution is exothermic. generally, the nitric acid concentration is lower in the first process than in the second, but this is not a rule and the formulation changes from company to company [19]. a small amount of silver is removed by the second nitric acid treatment and this solution may be used once again in a subsequent parting treatment. when the reaction is finished or the acid is exhausted, hot water is added to have more solution for the decantation of residual gold, avoiding the precipitation of silver nitrate. in contrast with the laboratory scale, the firmness of the residual gold is not necessary even if it involves different types of reactors and filters. this is due to the fact that gold content varies from a minimum of 1%1 to a maximum of 35%, close to the value used in assay. concerning the reactor, parting is normally carried out in steel vessels including roto-barrels (tumbler machines) or tanks, which are equipped with a rotating basket. the right choice between the two model plants is dictated by the physical form of the final gold prod1 note that in this case the separation of the two metals using electrorefining should be taken into account. this approach is cheaper and the final product is pure metal silver (99.95% or more). the impure gold is recovered as sludge and after melting it can be parted with nitric acid. uct. indeed, when the gold content in the bullion is low and/or there is a quantitative presence of other base and precious metals, the formation of impure and gluey gold powder requires the use of a rotating basket which is suspended in the tank. this arrangement enables the powder to be continuously separated from the grain and avoids the passivation of the latter. particle size is related to gold concentration in the alloy, the presence of other metals and reaction conditions. if gold content is less than 1% the dealloying process can lead to the formation of undesirable gold colloids which are difficult to separate2. generally, gold powder is separated using a filter press. by contrast, when parting is carried out after an inquartation process, the bullion conserves some of its firmness and a roto-barrel can be used for the reaction (figure 3). this reactor consists of a cylinder tilted to about 20-30 degrees which rotates by means of a motor. in such cases, solid-liquid separation is simpler and industrial büchner funnels are commonly used. parting pure au-ag alloy alone is rare and the quantitative presence of other metals is common, however only traces of base metals such as tin3 and antimony should be present for a satisfactory refining [19]. after filtration, parted gold is washed with hot water and finally melted, obtaining bullion ranging from 994 to 999 fine. moreover, silver is recovered from the spent nitric acid solution as insoluble chloride salt or by means of cementation with a more electropositive metal (e.g. iron). alternatively, gold parting can be carried out with sulfuric acid. on a laboratory scale this is suitable when the specimen is a silver-rich alloy. from an industrial point of view, sulfuric acid is a cheaper reagent than nitric acid, which incidentally it also has the drawback of generating toxic pollutants such as nitric oxide (no) and nitrogen dioxide (no2) according to reactions (2) and (3). nitric oxide reacts instantly4 and almost quantitatively with atmospheric oxygen to produce nitrogen dioxide [20]. conversely, the kinetics of the nitrogen dioxide adsorption are relatively slow and large scrubbers are required to provide minimum residence times for complete removal. the scrubbing of nitrogen dioxide with water results in the production of nitric acid and nitric oxide as the following reaction shows: 2 this problem can be overcome by treating the sol with activated carbon. 3 tin is oxidized by nitric acid to gluey insoluble sn(iv) oxide which passives the grains, hindering their further dissolution. 4 in the gas phase, this oxidative reaction is second-order in no because a transient dimer (no2) is produced which subsequently collides with oxygen molecules. because the reaction is second-order, the concentration of no seriously influences the rate of oxidation. in this case, the high concentration of no ensures fast oxidation. figure 3. effect of the silver dissolution by nitric acid on the goldsilver alloy grains. 57gold parting with nitric acid in gold-silver alloys 3no2 + h2o → 2hno3 + no (4) the reaction is exothermic and thus the liquid circulated over the scrubbing equipment may be cooled to increase absorption efficiency. the nitric oxide generated undergoes oxidation by atmospheric oxygen to produce new nitrogen dioxide. as a consequence of this tandem reaction, where the product of one process generates the starting material for another, large scrubbers are required to provide minimum residence times for the nox removal in order to fit into legal emission limits. significant residual nox content in the exit gas stream is typically abated by absorption into an alkaline solution in a second tower. moreover, from an industrial point of view, dilute nitric acid has little or no value and, in practical terms, represents a waste treatment problem5. to reduce the volume of the towers, either air or oxygen may be introduced into the gas or liquid phases to improve nitric oxide oxidation rates. formally, the generation of nox by metal dissolution with nitric acid may be overcome by moving the oxidation of nitrogen oxide from the gas phase to the reaction solution. this goal can be achieved using hydrogen peroxide, according to the follow overall reaction [20, 21]: 2ag + 2hno3 + h2o2 → 2agno3 + 2h2o (5) another approach is the reduction of nox with soluble ammonium nitrate [22]. in this case, the incipient formation of nox in solution reacts with the ammonium nitrate release of nitrogen gas according to the follow reactions: 2no + 3nh4no3 → 3n2 + 2hno3 + 5h2o (6) 2no2 + nh4no3 → n2 + 2hno3 + 5h2o (7) gold parting: a microscopic enquiry gold parting with nitric acid in gold-silver alloy has been the subject of several studies supported by theoretical and experimental data. martinez et al. [17] systematically studied the effect of silver-gold alloy composition on silver dissolution using a 6.56 m nitric acid solution at 80°c for 48 hours. their experiments showed that such alloys become completely resistant to nitric acid oxidation when the gold content is greater than 40% by weight. this value is the so-called part limit above which the dealloying process is quantitative. the various 5 the dilute nitric acid recovered by this process may be returned to the process. basically, it is used as “water dose” for the other parting treatments. thresholds reported in the literature are due to different reaction conditions such as lower temperatures or lower nitric acid concentration. however, from a practical point of view, the relationship between the dissolution rate and the composition of the alloy should be taken into account. in particular, in the case of the inquartation process, when the gold content is 25% by weight, the dealloying process is slow as compared to that of other silver-rich alloys [17, 23]. during the dealloying process, in the first instance, a static model in which silver ions may exit the alloy lattice only through the holes previously generated by the dissolution of more superficial silver atoms without invoking any type of atomic rearrangement might be assumed. on the basis of this consideration, after the first selective dissolution of silver on the surface, the progress of the reaction depends on composition and alloy metal lattice. the exclusive presence of face centered cubic lattices for any metal au-ag composition alloys, partly due to almost identical radii, makes the model easier to describe and analyze. each atoms in the lattice displays a coordination number of 12 and the probability that a gold displays n homometallic contacts can be calculated using statistic equations [17]. trends in these probabilities against silver-gold alloy composition are reported in figure 4. in particular, for au25%-ag alloys, gold atoms come principally into configure 4. probability (pn) for a gold atom to display n homometallic contacts against the percentage of weight silver in gold-silver alloys. pn functions are calculated using the same statistic expression used by martinez at al. [17]. note: the absence of a mirror plane across 50% of the silver is due to the different weights of the two precious metals. 58 iacopo ciabatti tact with one or two other gold atoms, although the presence of gold with three and zero au-au contact is not negligible. thus, with this composition, the random alloy lattice excludes the presence of suitable preformed gold networks as required by a static model in order to justify the lack of powdering. moreover, without any type of atom surface diffusion, it might be expected that dissolution would stop after about 4-5 metal monolayers have been dissolved, making the separation of the two metals non-quantitative. this is in contrast to experimental values [17] which show quantitative dealloying characterized by a faster dissolution rate than those observed in the case of pure silver (99%). thus, a simple static process in which silver is removed by means of nitric acid, which leaves only gold atoms inside the bulk alloy, is not sufficient to describe exactly what happens. from a macroscopic point of view this is corroborated by volume contraction and an unexpected product color obtained after the dealloying process. indeed, after the parting and subsequent annealing stages, the au25%-ag alloy shows characteristic shrinkage, with memory of form, that is particularly visible in the case of laboratory scale assays. moreover, after the dealloying stage, including when parting is quantitative, gold color is not the characteristic bulk phase yellow but generally brown. in order to give a qualitative idea of this phenomenon, parting and annealing stages starting from an au25%-ag alloy specimen with a tca logo shape are shown in figure 5. dealloying occurred in two stages using 22° and 32° bè boiling nitric acid for 30 minutes respectively. after parting, these fragile specimens were slowly dried in the oven at 105°c (figure 5b) and finally put into a furnace at 1050°c (figure 5c). battaini et al. [14] described the changes in shape and color during the parting stage with an extensive study by means of scanning electron microscopy, which revealed the nanoporosity architecture obtained after the parting stage. the nanoevolution of porosity during dealloying is well known, and over the last two decades it has received great attention from the scientific community [24-27]. indeed, the porous gold materials obtained by selective dissolution of silver present numerous potential applications as functional materials on the basis of their chemical stability and unique surface chemistry6. as a result, fabrication of newly performed 6 whilst several other methods have been developed to fabricate porous gold materials such as sintering, templating and additive manufacturing, the dealloying approach has attracted remarkable interest on the basis of its simplicity and reproducibility [25]. in addition to chemical gold-silver dealloying, the subject of this work, the selective oxidation of silver may be carried out by electrochemical and liquid metal dealloying. tailor-made porous gold materials, and their related characterizations, have favored an understanding which moves in the direction of a clearer vision of what happens in gold parting. however, whilst the first detailed look by forty at the porosity formed by dealloying processes using electron microcopy dates back to 1979 [28], the mechanisms involved in the gold nanoreorganization were studied only two decades later. according to erlebacher’s studies [29-32], during silver dissolution, gold is freed to move along the surface, reorganizing into a three-dimensional network, which generates nanoporosity. the dissolution of silver primarily involves atoms from surface defects, e.g. terraces or steps, which are more reactive [30]. this leads to the creation of terrace vacancies that then grow sideways into vacancy clusters as lateral near neighbors are subsequently dissolved. as a consequence of silver oxidation, unsaturated gold atoms, which are thermodynamically unstable, move from lowto high-concentration areas leading to the formation of two-dimensional figure 5. effect of gold parting (b) and annealing treatments (c) on an au25%-ag alloy specimen (a) with tca logo shape. 59gold parting with nitric acid in gold-silver alloys gold clusters. as dealloying proceeds, new gold-silver layers are exposed to nitric acid solution around the base of the gold islands previously formed in the top layers after dissolution and surface reorganization. the threedimensional development of such gold islands results in gold covered hills with base perimeters that grow in diameter as dealloying proceeds. this increased surface area requires more gold atoms compared to the gold adatom generated, leading to undercutting and bifurcation of ligaments. the result of this process is a continuous porous structure with gold-rich surface ligaments. the large surface area to volume ratio of these ligaments leads to metastable nanoporous structures. thus, the length scale of porosity tends to increase over time and, as the atoms move from smaller to larger ligaments, residual silver atoms are exposed and dissolved. thus, from a kinetic point of view, the dealloying process can be viewed as a competition between three processes: (i) silver dissolution; (ii) surface diffusion of gold and (iii) mass transport of the dissolved silver ions and the nitric acid through the cavity between the gold nanomounds. the rate-limiting step of nanoporosity evolution is the dissolution of silver from surface defects which is nearly ten orders of magnitude slower than the two other processes. as a result, the dealloying front advances at a constant rate, as shown for a first time by martinez et al. [17] who employed electron microscopy for kinetics studies of an au25%-ag alloy. recently, similar conclusions were reached by chen-wiegart et al. [33], who studied the dealloying front in an au30%-ag alloy by means of transmission x-ray microscopy. after dealloying, the final gold nanosponge is isotropic and characterized by ligament spacing in the order of 10 nm and surface areas greater than 8 m2/g [34]. it has been found that the length scale of the porosity inversely increases with the dealloying front velocity. thus, factors that can be related to the dealloying rate such as acid concentration [23], alloy composition [35] and temperature [36] affect the evolution of nanoporosity. the dealloying process is controlled by the diffusion of gold atoms on the alloy surface, which is strongly dependent on the reaction temperatures [37]. low dealloying temperatures significantly reduce the interfacial diffusivity of gold atoms and the overall result is an ultrafine nanoporous structure. obviously, the presence of other metals in the alloy, in addition to silver and gold, may play an active role during the gold nanoevolution but no systematic studies have been reported. gold evolution during the dealloying process at nanometric scale justifies the preserving memory of larger size structures such as specimen form (figure 5a-b). moreover, the nanoporous structure explains the brown color on the basis of the interaction between light and gold by surface plasmon resonance [38-39]. as previously observed, the high surface area makes the gold sponge thermally unstable. in the annealing stage, higher temperatures increase the surface diffusion of gold atoms leading to thermal coarsening. this process is exothermic in accordance with reduction in the energy of the system moving from high to lower surface material. with the annealing process the nanoporous structures disappear, resulting in a typically yellow gold bulk color. generally, at 500°c the nanoporous structure is almost completely destroyed [14], although in the case of assays specimens are heated to 1050°c for practical reasons. conclusions gold parting with nitric acid substantially contributed to historical knowledge acquisition relating to the development of building furnaces, chemical glassware and synthesis of inorganic acids. with the development of large-scale industrial production of nitric acid, the use of the latter in the parting stage grew, with a peak in the first half of the 20th century. however, more recently, the high cost of nitric acid and the requirement for large nox scrubbers have vetoed its extensive use in largescale industrial refining. as a result, other treatments are now used to refine low-grade gold bullion, such as the miller process due to its technological development. however, nitric acid is still used at the parting stage on the laboratory scale after cupellation assay. over the last two decades, the experimental and theoretical studies reported in the literature of dealloying process have allowed the mechanism involved in the formation of nanoporous gold material to be understood. in conclusion, from a historical point of view, gold parting development occurred as the result of human experience without real scientific understanding of the treatment taking place. recent academic research on the dealloying process represents a bridge to the understanding of the same phenomenon that occurs during the parting stage in the case of gold refining. acknowledgments i would really like to express my thanks to all members of tca ownership, doctor marco fontani (university of firenze) and professor carla martini (university of bologna) for the encouragement to carry out this work. finally, i thank my closest colleagues francesco donati and alessio tommasini for the technical support of this article. 60 iacopo ciabatti bibliography [1] l. aitchison, a history of metals, ii vols. macdonald & evans, london, 1960. 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[39] a.i. maaroof, a. gentle, g.b. smith, m.b. cortie, j. phys. d. 2007, 40, 5675-5682. substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press the arezzo seminar on precious metals iacopo ciabatti1, marco fontani2, carla martini3 apprentices and masters the transmission of ancient goldsmith techniques alessandro pacini the authenticity of the false daniela ferro electrodeposition and innovative characterization of precious metal alloys for the galvanic and jewel industry massimo innocenti, walter giurlani, maurizio passaponti, antonio de luca, emanuele salvietti gold and silver: perfection of metals in medieval and early modern alchemy ferdinando abbri “antichi strumenti orafi” of the garuti collection – the virtual exhibition francesca frasca1, adelmo garuti2, gian lorenzo calzoni3 do monetary systems rediscover precious metals in the era of ‘bitcoins’? roberto santi gold parting with nitric acid in gold-silver alloys iacopo ciabatti hi-tech waste as “urban mines” of precious metals: new sustainable recovery methods angela serpe substantia. an international journal of the history of chemistry 5(2): 129-152, 2021 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.36253/substantia-1191 citation: larraz r. (2021) a brief history of oil refining. substantia 5(2): 129-152. doi: 10.36253/substantia-1191 received: jan 17, 2021 revised: may 04, 2021 just accepted online: may 06, 2021 published: sep 10, 2021 copyright: © 2021 larraz r. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles a brief history of oil refining rafael larraz cepsa r&d, madrid, spain e-mail: rafael.larraz@cepsa.com abstract. since its beginnings in the mid-nineteenth century, oil refining technology has evolved in a continuous process of adaptation to the demands of society, in matters as vital as the supply of energy, lighting, transportation or new materials to improve the quality of life. in that time, this has been one of the greatest examples of how the technological innovation of an industry contributes to the welfare and development of society. the objective of this manuscript is to describe the history of these technological advances and the causes that motivated them. keywords: technology history, oil refining, catalysis, chemical engineering, process design. introduction since its beginnings in the mid-nineteenth century, oil refining technology has evolved in a continuous process of adaptation to the demands of society, in matters as vital as the supply of energy, lighting, transportation and producing chemicals to improve the quality of life. in that time, this has been one of the greatest examples of how the technological innovation of an industry contributes to the welfare and development of society.1 the objective of this manuscript is to describe the history of these technological advances and the causes that motivated them. the magnitude of the achievements obtained by the refining industry far exceed the available space, which is why in this manuscript the detailed technical description of the processes has been sacrificed and attempts have been made to expose the causes that have motivated the successive technological advances, establishing a common thread, such as the evolution of the refinery configuration over time.2, 3 chemical engineering and oil refining the purpose of a refinery is to transform crude oil into more valuable products that meet the demands of the market, both in quantity and quality, respecting safety and environmental regulations. since the production of crude oil began in 1850, the market for petroleum products has been changhttp://www.fupress.com/substantia http://www.fupress.com/substantia 130 rafael larraz ing continuously and drastically in some cases, forcing the refineries to modify their configurations to meet this demand. refineries have also adapted to the growing diversity of crude oils with different compositions. the evolution of the refineries has been deeply linked to the advances of engineering and vice versa. in the refinery ś process units, term coined by p.h. groggins in 1928, we can find all the examples of the unit operations as defined by arthur d. little in 1912. the concept of unit operations in chemical engineering is very much related to the development of refining technology. in 1910, the most important chemical industry in the world was in germany, where synthetic dye companies such as the ig farbenindustrie ag or the haber-bosch process for the manufacture of ammonia, were milestones in the chemical industry. however, the design of these plants was based on the product to be obtained and their equipment was designed specifically without benefiting from the exchange of experience with the manufacturing technology of other products. on the other hand, chemical engineering, founded by warren k. lewis from the massachusetts institute of technology (mit), is based on identifying and grouping common processes or unit operations. based on this classification, a process unit is designed by choosing several unit operations seeking the highest efficiency, performance and economy. the developments in each of the unit operations are shared between the different technologies and these evolved rapidly benefiting from the common experience. some authors have cited the use of unit operations in the american chemical industry as one of the causes of their worldwide leadership until the 1970s. in the sequel, we will describe the main milestones that have guided the evolution of the petrochemical industry and the refinery configuration evolution.5 the pioneers of the industry in the early days of the industry, fuel was the main use of crude oil, even though it had been found that the combustion of crude oil, as an energy source in oil wells, produced toxic fumes and gases that prevented its use. then, crude oil started to be processed in oil refineries that evolved, as shown in figures 1 and 6, from discontinuous distillation in foundry vessels that had kerosene as their major product to the highly complex refineries that we have today, which produce a multitude of different fuels and petrochemical products from a variety of different crudes. samuel m. kier was the first person to distill oil. by 1845 in southwestern pennsylvania, he verified the presence of oil in the salt production facility he owned, when drilling wells to obtain salt water, a liquid with a strong odor mixed with brine appeared. in general, this was considered an inconvenience in the production process and was usually burned or poured into nearby waterways. kier was an innovative entrepreneur and decided to use oil as fuel for the lamps that illuminated brine wells at night, despite the smoke and its bad smell. this figure 1. refinery configuration evolution in 1915, 1920 and 1930. reproduced from u.s. petroleum refining: meeting requirements for cleaner fuels and refineries. appendix c. history and fundamentals of refining operations, national petroleum council, 1993. 131a brief history of oil refining allowed him to use the already expensive whale oil available at the time for other applications. he even bottled it and sold it for 50 cents as a medicine, establishing a commercial network for its distribution. in 1849, kier shared oil samples with james c. booth, a chemist in philadelphia, and both agreed that it could be used as fuel for lighting lamps, but that it could be greatly improved if refined so that its combustion did not produce fumes and odors. in 1850, kier began to experience different distillation processes and was the pioneer of this use of oil, by obtaining a product called “carbon oil” that allowed lighting in oil lamps with little smoke and odors. kier partnered with john t. kirpatrick and tested the first oil distillation in pittsburgh, pennsylvania.6 in 1846, semyonov and alekseev had already produced oil in the baku oil fields (azerbaijan), then in 1859, edwin l. drake began producing oil near titusville, pennsylvania and the market was flooded by oil production. the first refineries were built in europe, in 1854 ignacy lukasiewicz built a primitive crude oil refinery near jasło in southern poland, distilling kerosene from a tar sand available in the region. the first large refinery was started in 1856 near ploiești (romania), one of the best-known and oldest oil fields in europe and bucharest was the first city in the world to be lit with kerosene lamps in 1857. also in 1859, a kerosene refinery was built on pirallahi island (azerbaijan), distilling the so-called “kir” produced in the baku oil fields near the caspian sea and in 1860 already 58 refineries were built in pennsylvania. there are currently about 700 refineries in the world that can process close to 100 million barrels of oil per day.7, 8 in 1860, due to indiscriminate whaling and the near extinction of these species, the use of whale oil as fuel for lighting had become expensive. the price of whale oil was $ 1.77 per gallon and almost doubled that of crude oil, which was sold at $ 0.90 per gallon. this fact, together with the invention and improvement of the kerosene lamp in 1857 by michael dietz, further strengthened the supremacy of kerosene for lighting.9 in the refineries, crude oil was distilled to produce kerosene that was used for lighting lamps. the advantage of kerosene in this case was that it did not emit smoke when burned due to the paraffinic nature of pennsylvania crude. the heaviest parts were used as lubricants for steam engines, which were ubiquitous at that time. the lighter distillation fractions such as naphtha, propane and butane were considered to be a residue and were burned in flares since their high vapor pressure and low flash point prevented their safe storage.10 the installation was operated in a discontinuous mode and the oil was loaded in a vessel where it was heated with gas or other crude product. this heating generated a residue inside the container and other equipment that required cleaning from time to time. the dephlagmator tower was the precursor of the distillation towers and separated the generated vapors that were sent to a separator where the gaseous fraction and the final kerosene product were separated. this product was redistilled to control its flash point and thus allowed its safe use in the lamps reducing the generation of smoke. the heavy fraction or tar was re-distilled under vacuum, obtaining a lubricating oil and greases in addition to waxes and paraffin for candle making. at this time, and as means for transportation were needed, both the oil and the products produced began to be transported in barrels and a standard measure that still survives emerged. a barrel of oil had 42 gallons, about 159 liters. the measure was imported from england, where a law issued by edward iv in 1482, established 42 gallons as the standard capacity for herring barrels and to prevent scams in the fish trade. in 1866, seven years after the discovery of the first well by colonel drake, the pennsylvanian producers confirmed this measure as the norm in the oil business. the discontinuous distillation system was limited in terms of capacity. as the size of the vessel increased, the ratio between the heat transfer surface and the volume of oil decreased, and therefore, it was not profitable to increase the process capacity more than a given volume of oil. a long contact time between the oil and a hot surface led to oil decomposition and the deposition of a layer of coke, which further limited direct heat transfer. it was also quite risky to subject large quantities of oil to direct heating. the maneuvers of loading the oil and emptying the residue, in addition to the cleaning of the systems, required a lot of time and effort making the entire process very inefficient. as the demand for kerosene grew, two distillation units began to be used, one for the first separation and the second to refine the quality of the kerosene, paving the road for continuous distillation.11 in 1880, continuous distillation was introduced, the process consisted of several vessels connected to each other and heated separately at growing temperature levels. the vessels were installed so that the oil flowed by gravity from the first to the last. the product was subjected to successive distillations, the operation was adjusted by means of the “look box” through which the distilled product could be seen and depending on its color the operating conditions were adjusted to improve the separation by distillation of light and heavy naphtha and kerosene. in the last vessel the temperature was successively increased causing oil cracking to obtain more 132 rafael larraz kerosene. the residue from the last vessel was used to obtain lubricants or fuel oil. one of the drawbacks during the combustion of kerosene related to the variability of the distillation quality, was the emission of noxious odors and gases due to the presence of sulfur compounds in kerosene and gasoline. in 1885, herman frasch discovered that copper or lead oxides reacted with the sulfur compounds of petroleum and could be regenerated and reused, thus eliminating the problem of odors and producing sulfur. this technology started the oil treatment industry to eliminate oil contaminants.12 in 1900, the partial condensation was introduced, which allowed a better separation of the products. a partial condenser or dyke tower was installed between the vessel and the water-cooled condenser. the lower part of the tower was filled with stones and insulated with bricks to facilitate the condensation of heavier compounds that were subsequently sent back to the distillation vessel. the light part passed to another section where it condensed in air-cooled tubes to obtain a head product. the rest of the stream continued towards the water-cooled condenser. vacuum distillation was developed to solve the need to separate less volatile products, such as lubricating oils without degrading their properties due to high temperatures. the boiling point of the heaviest cut obtained by atmospheric distillation is limited by the temperature and residence time at which it begins to decompose thermally modifying the quality of the cut. around 1910, some of those limitations were solved when a continuous distillation process was developed by grouping several connected containers, where the products were flowing from one to another subjected to increasing temperatures to obtain a stepped vaporization of the different cuts. heat exchange systems with cold feed oil and stirring systems were introduced that improved the process efficiency. instead of condensers, fractionation columns were installed with internal liquid-vapor exchange systems, which, although rudimentary, improved the quality of the fractionation. to eliminate the direct heating system of a vessel and improve the capacity and efficiency of the system, it was necessary to find a system with a high surface to volume ratio, which could be heated throughout its entire surface. this would allow faster heating while having smaller volumes of crude oil so that they could flow rapidly through the heating zone and minimize coke formation by increasing heat transfer. in 1910, milo j. trumble introduced a distillation process that met these requirements and is shown in figure 2. the oil was pumped through a pipe into a furnace and the furnace outlet was directed to a tower – the evaporator – where vaporized and liquid products flowed over a series of screens. the vapors were collected in a central pipe and the hot residue transferred its heat to the cold load in a heat exchanger. in the initial design, the vapors were condensed in a single stream, later the system was modified to obtain three or more fractions. the first plant was installed in santa fe, california in 1911.13 the advantages of the trumble process meant lower operating costs due to a large increase in the energy efficiency of the process; in addition, the installation cost was also lower compared to existing systems. furthermore, the design allowed the construction of higher capacity plants. in 1925, the initial design of the condensers was replaced by tray towers, which simplified and improved the process leading to the present distillation unit designs. the separation between the furnace and the distillation tower was the fundamental innovation to achieve efficient distillation units. the internal combustion engine and its fuels the demand for oil remained stable during the second half of the 19th century. in 1878 and thanks to the invention of the electric light bulb by thomas edison, the demand for lighting kerosene began to decline, although it remained in many places far from cities or in services such as rail transport. in 1893, rudolf diesel developed the diesel engine, and in 1889 gottlieb daimler, wilhelm maybach and, independently, karl benz developed figure 2. continuous distillation trumble process. reproduced from v. alderson, quarterly of the colorado school of mines 1924, 19 (3), 5-7. 133a brief history of oil refining the internal combustion engine that has been the transportation paradigm since then. in 1901, ransom e. olds began the production of affordable price cars under the oldsmobile brand. henry ford built his first gasoline vehicle in 1896 and founded the ford motor company in 1903. in 1908, he started selling the t model for $ 950 and he revolutionized the world transport and also the oil industry. in fact, the demand did not stop growing until the arab oil embargo of the 70 ś. beetween 1907 and 1917, 15 million ford model t vehicles were sold in the us, and the price dropped to $280 thanks to the reduction in the assembly line costs. this technological innovation drastically changed the oil refining industry.14 in the first refineries, the most demanded products were kerosene and light distillates. gasoline was a byproduct until the beginning of the 20th century, when the development of the combustion and automobile engines caused a large increase in the demand for automotive gasoline and other refinery products such as asphalt, lubricants and fuel oil. although the history of the asphalt dates back to the time of the babylonians, paving tests with naturally obtained asphalts were made in the nineteenth century. it was in 1870 when belgian chemist edmund j. desmedt paved the avenue of pennsylvania in washington dc with a mixture of asphalt. then, in a short time the first patents for asphalt road blends were filed. in 1901, the warren brothers built the first modern asphalt factory in massachusetts. as a result of the success of the car industry, by 1908 all the roads necessary for the circulation of cars were paved with asphalt, thus adding another product of great demand to the oil industry. these technological advances doubled the demand for asphalt every decade from 1880 until the oil crisis in 1973. another important milestone was the change from coal to fuel oil as marine fuel. in 1911, winston churchill was appointed first lord of the admiralty and with the collaboration of admiral john fisher decided to change the fuel of british navy ships from coal to fuel oil, the heaviest and most abundant fraction of oil. this fact was justified by the easier handling due to its liquid state and the greater calorific value of the fuel, which allowed the boats navigate faster. at the time, it was a hotly debated decision because britain produced large quantities of coal and also due to the complicated logistics of the world’s fuel oil supply, but given its technical advantages, fuel oil was quickly adopted as the preferred marine fuel.15 the conversion increase the rise of transport vehicles based on internal combustion engines created a new challenge for the oil industry. at the beginning of the 20th century, the proportion of products obtained by distillation did not match the market demand. the automobile industry and later on the aviation industry improved their engine designs to increase power, which led to the need for higher quality fuels able to maintain higher compression ratios in the engines. the introduction of the internal combustion engine and the decrease in vehicle prices increased the demand for oil and especially for gasoline, compared to the traditional kerosene market. improving the distillation of oil was not enough to meet the demand and in response, the refining industry developed conversion processes to obtain more gasoline and reduce the proportion of heavy products while improving its quality. adjusting to market demand and producing higher quality fuel and products have been the factors that have guided many of the innovations in oil refining technology, some of these process development dates are shown in table 1. indeed, a key conversion process to meet the demand of gasoline has been oil cracking, first thermal and later catalytic. there are already references in 1850 and since 1860 to using thermal cracking of hydrocarbons for the production of kerosene. initially, thermal cracking was carried out at atmospheric pressure at which the kerosene yield was high. the process consisted basically on heating a vessel with oil until all the kerosene had been produced and the overhead product had a dark color. at that point, the distillation was stopped and the heating of the vessel was maintained to favor the thermal cracking reactions that produced lighter products of lower molecular weight. after a certain operation time that was empirically fixed, distillation was resumed by extracting cracked light products. this practice increased the kerosene yield, but did not produce gasoline in large quantities. in 1889, two english chemists, j. dewar and b. redwood, registered a patent on cracking carried out at pressures greater than atmospheric. when the pressure was raised, the selectivity of the process changed and much more gasoline than kerosene was produced. in pressure cracking, the oil was heated to about 425 °c in specially reinforced vessels to operate at pressures of about 7 kg/cm2 for 24 hours. then, the distillation of the cracked product began and low molecular weight compounds were obtained. those compounds were treated with sulfuric acid to remove the gums and residues formed by the generation of olefins and diolefins and then redistilled to produce gasoline and a residual fuel oil.16 the first process that innovated the technology to increase the conversion of the refineries, was the thermal cracking patented in 1912 by william burton and rob134 rafael larraz ert humphreys. the burton-humphreys process doubled the gasoline production of a refinery and prevented fuel shortages during world war i. w.m. burton, who was responsible for one of the standard oil company refineries, had the idea of cracking only the fraction called diesel instead of the whole oil fraction with boiling points higher than kerosene. depending on the crude oil treated, diesel constitutes 30 to 50% of the total volume. this change together with improvements in the design of the cracking installation made by r.m. humphreys in 1910, allowed the first thermal cracking unit in indiana standard to be successfully launched in 1913.17 the burton process operated discontinuously at a temperature of 425 °c and 5 to 7 kg/cm2, the cracking vessel had to be stopped every day and the residue was cleaned out. the process was successful but from 1914 to 1922 a series of continuous cracking technologies were developed that significantly improved the process. in these technologies the diesel was pumped and heated to the operating temperature, it was maintained under these conditions and then the cracked products were sent to a distillation unit where they were separated into gases, gasoline, diesel and a residue often known as tar. gasoline from thermal cracking had a higher octane number so it worked much better in combustion engines than the gasoline produced by direct distillation. in 1914, jesse dubbs and j. ogden armor founded the national hydrocarbon company, which would later be the universal oil products (uop). the uop would grow to be the largest technology licensor for petroleum table 1. oil refining process timeline. process target process type 1862 atmospheric distillation kerosene production separation 1870 vaccum distillation lubricants (original) cracking feedstock (1930’s) separation 1913 thermal cracking gasoline production thermal cracking 1916 sweetening sulphur and odor removal chemical treatment 1930 thermal reforming gasoline ron improvement reforming 1932 hidrogenation sulphur removal catalytic treatment 1932 coking gasoline production cracking 1933 solvent extraction lube viscosity index improvement extraction 1935 dewaxing cloud point improvement extraction and crystalization 1935 polimerization high ron gasoline production reforming 1937 catalytic cracking high ron gasoline production cracking 1939 visbreaking fuel oil viscosity reduction thermal cracking 1940 alkylation high ron gasoline production reforming 1940 isomerization feedstock to alkylation reforming 1942 fluid catalytic cracking high ron gasoline production cracking 1950 deasphalting lube quality improvement extraction 1952 catalytic reforming high ron gasoline production reforming 1954 hydrodesulfuration sulphur removal catalytic treatment 1956 mercaptan oxidation mercaptan removal or sweetening chemical treatment 1957 catalytic isomerization high ron gasoline production reforming 1960 hidrocracking light distillates production cracking 1974 catalytic dewaxing cloud point improvement cracking 1975 residue hidrocracking residue yield reduction cracking 1990 gasification residue removal cracking 2000 fcc naphtha hydrotreatment sulphur removal with no ron loss catalytic treatment 2000 gasoil hydrotreatment sulphur removal below 10 ppm catalytic treatment 2005 petrochemical fcc increase propylene yield cracking 2008 biofuels renewable fuels from vegetable oils catalytic treatment, reforming 2012 tight oil tight oil refining metal removal and additives 2014 reside slurry hidrocracking residue removal cracking, nonocatalysis 2020 “crude to chemicals” petrochemical refineries cracking, refining 135a brief history of oil refining refining and petrochemicals. in 1919, uop commercialized the dubbs process, which solved some of the technical problems of the burton-humphreys process. the dubbs process generated fewer coke deposits, treated heavier crudes and had longer operating cycles. the dubbs process developed by the uop, meant an advance in thermal cracking technology and its use was competitively extended until the forties. in this case, the feedstock was crude oil with the light fractions removed. the feedstock was preheated with the reaction products, sent to an oven and from there to a reaction chamber. the biggest advance of the dubbs process was to recirculate the cracked stream from the fractionation section to the reaction section; this allowed a finer control of the reaction and stabilized the process.18,19 the “tube and tank ” process introduced a significant advance by adding the concept of the cracking reactor. in this process, diesel preheated by heat exchange with the reaction products, was pumped into a furnace where cracking was carried out. the outlet was sent to a reaction chamber (soaker), where it was kept at the temperature and reaction pressure for a certain time until the cracking reactions were completed. the reaction products then entered a low pressure separator where all the products were vaporized except for the residue. the vapors left the separator at the top and were distilled to obtain gases, gasoline and gas-oil. the residue from the bottom of the separator was extracted for use as asphalt or fuel oil. with the exception of a lower operating temperature, the “tube and tank” process can be considered a precursor to the current delayed coking units.20 in 1919, the uop sued the standard oil company for the thermal cracking patent since they considered that dubbs had preference over the burton process. dubbs filed a patent in 1909 on the manufacture of asphalts that included the production of gasoline through an operation similar to thermal cracking. this lawsuit, which ended in 1931 with an adverse result for the uop, placed the company in a difficult situation and gave rise to a company model of great importance for refining technology. in this way, a licensing company, whose maximum exponent was the uop itself, had its own research, development and engineering resources to market processes that were sold to those refining companies who did not have r&d departments and were, therefore, at a disadvantage with large companies such as standard oil that had their own technologies. hiram halle, president of the uop, created this concept, that has become popular within other companies such as scientific design, axens, haldor topsoe, kbr, etc . the license to operate a process allows a company to acquire the design of a plant and its catalyst. the company builds the plant according to the design of the licensor who collaborates during the engineering and supervises the construction and commissioning until compliance with guarantees of capacity and quality. apart from the income due to the purchase of the design, catalyst and license, the licensor charges annual fees or royalties depending on the capacity processed by the plant, which allows to continue investigating to improve the process. the licensor also benefits from the experience acquired during the installation of the new plants to improve the technology. the refinery, in turn, benefits from the installation of competitive technologies that allow it to remain profitable without having to wait for the development of the process or incurring research and development expenses.21,22 the search for gasoline the manufacturers of internal combustion engines complained to the refineries that the quality of the gasoline was not uniform and the engines had disparate performances depending on the origin of the distilled oil. better gasolines allowed the engines to go at more revolutions by providing more power without affecting the integrity of the engine. poor quality gasoline, on the other hand, produced a knock on the engine that affected its performance and could cause mechanical damages. the ability of gasoline to avoid engine knocks is expressed as its octane number on a numerical scale. the scale is based on pure chemicals, ranging from n-heptane with an octane number of 0 to isooctane with a value of 100. this scale was proposed by graham edgar of the ethyl corporation in 1926. a high octane gasoline burns slowly in the engine piston producing a regular movement of the engine. on the other hand, the low octane gasoline burns quickly, generating sudden increases in pressure on the piston that generate the engine knocking and can damage the engine.23 a similar parameter is defined in diesel engines, the cetane number, developed in 1930 by the cooperative fuel research (cfr). the cetane number measures the time between fuel injection and the beginning of its combustion. in this case, unlike gasoline engines, the more paraffinic the diesel, the better the cetane number is because the ignition delay in the engine is smaller. in 1919, charles f. kettering and thomas midgley from general motors began studying the phenomenon of knocking and in 1921, they discovered that a mixture of tetraethyl lead and gasoline attenuated this phenomenon. in a few years the process of synthesis of tetraethyl 136 rafael larraz lead (tel) was industrialized and refineries could manufacture gasoline with a constant octane number from naphtha of different crude oils. the tel additive added 5 to 7 octane numbers to gasoline, but its toxicity made it very difficult to handle in the refineries. afterwards, its harmful effects on humans were discovered when lead compounds were emitted in the exhausted gases.24 between 1920 and 1930, gasoline demand growth confirmed the trend of converting heavy residue and distillates into high quality gasoline. another advance was the consolidation of vacuum distillation as a second stage after atmospheric distillation. it has been indicated that the heavy distillation cut consisted of hydrocarbons that did not vaporize at atmospheric pressure. subjecting this cut to vacuum distillation allows an additional amount of distillate, known as vacuum diesel, to be vaporized and sent directly to the thermal cracking units, increasing the refinery’s gasoline yield. also in the thirties, the thermal reforming of naphtha was introduced, a seeking an increase in the octane number. in this process the naphtha was subjected to cracking reactions in a reactor after heating in a furnace. the process had a low selectivity and added little performance to high octane gasoline, for these reasons, its use was limited. the solution for further increasing the yield and quality of the gasoline was achieved by means of catalysis. it can be said that the introduction of catalysis in the refining industries opened a new era in this industry. catalysts allowed to improve yields without the necessity of introducing major modifications in the original design. as we have seen, the reaction mechanism of thermal cracking is not very selective towards the desired products and generates a large amount of gases rich in unsaturated hydrocarbons or olefins, which are generally burned to provide the necessary energy in the cracking process. olefins are very reactive compounds and can be combined to form heavier and more useful cuts. the processes of polymerization and alkylation were developed in the thirties to valorize this very rich olefin stream converting it into high octane gasoline. in 1935, the pure oil and philips company developed a thermal polymerization process, although its low yields doomed it to be quickly surpassed by catalyst-based processes. in 1930, the russian chemist v.n. ipatieff from uop, investigating in the riverside laboratory (illinois), introduced the first important catalytic process in refining technology. the catalytic polymerization, shown in figure 3, employed a catalyst based on phosphoric acid supported on alumina. light olefins reacted with each other giving rise to heavy olefins of longer chain length and whose boiling points allowed their use in the formulation of high octane gasolines. the efficiency of the process was improved by separating the light olefins in a gas recovery plant for processing in the polymerization unit. this unit increased the value of the gaseous stream produced during cracking and thermal reforming and was included in the schemes of the refineries of the thirties. since the ipatieff ’s discovery, the polymerization has played an important role in the refinery until the development of olefin alkylation.25, 26 the alkylation of olefins produced either by thermal or catalytic cracking had been a developing field since the thirties. it was mainly used in the alkylation of isobutane and butene or propylene to produce branched paraffins of seven or eight carbon atoms with high octane number. the alkylation of paraffins was discovered by v.n. ipatieff in 1935. in the search for gasoline with a high octane number, a consortium of refining companies anglo-iranian (future bp), humble (future exxon), shell, standard oil and texaco developed the alkylation process of butene and isobutane to produce high octane gasoline by means of a strongly acid catalyst. this process was commercialized in 1938 at the humble refinery in baytown, texas. the catalyst used for this reaction was sulfuric acid. the alkylation produced large quantities of aviation gasoline that was particularly important during world war ii. in 1940, phillips petroleum (future phillips 66) developed alkylation with hydrofluoric acid, which produced better reaction yields. the alkylation process combines light olefins, mainly butenes, with paraffinic isobutane, to produce a high octane gasoline. this reaction needs, as we have seen, an acid catalyst, hydrofluoric or sulfuric acid, under conditions that maximize the performance and quality of the product. the resulting alkylate has an figure 3. first polymerization unit in curaĉao refinery circa 1939. reproduced from acs catalysis 2018, 8, 8531-8539. 137a brief history of oil refining excellent octane number, as well as a low vapor pressure and does not contain sulfur, olefins or aromatics, all this makes it the ideal component for formulating gasoline.27 research and development in alkylation technology has been aimed at eliminating the use of sulfuric or hydrofluoric acids as catalysts. for a long time, solid catalysts have been sought to replace them and recently, the alkyclean process of lummus and neste oil has been commercialized, with a zeolitic catalyst from abermarle. another option has been to use ionic liquids instead of acids, as in the chevron and uop isoalky process.28 the catalytic cracking until 1925, high-boiling petroleum molecules reacted with low-boiling molecules subjected to thermal cracking reactions, mainly through the processes developed by dubbs and burton-humphreys. in 1930, approximately half of the gasoline produced in the world came from thermal cracking processes, the average octane number was 70 versus values between 50 and 60 for direct distillation gasoline. the thermal cracking gasoline was mixed with polymerization or thermal reforming gasoline to produce a base gasoline of octane number 65, which required tetraethyl lead (tel) for increasing the octane number to 70 and 80 for regular and premium gasoline, respectively. the compression ratio demanded by the engines of the increasingly powerful cars created by the industry needed something else and by 1936, a new process opened the way to obtain high octane gasoline. in 1915, the mcaffe catalytic cracking, process used aluminum trichloride as a catalyst, and operated in a discontinuous mode due to the deposition of sludge formed by hydrocarbons and aluminum chloride residues. between 1912 and 1926, gurwitsch and herbst described the activity of certain activated clays, but it took until 1936 when the french chemist, eugene houdry presented a process where the problems of catalyst deactivation, regeneration and stability were solved, in combination with an effective process design. looking for better quality gasoline, he studied the chemistry of hydrocarbons and the synthesis of branched chains of paraffins and olefins that gave gasoline a higher octane number. houdry designed a cyclic reaction-regeneration system with activated clays and fixed-bed reactors that maintained the energy balance of the cracking unit and allowed for continuous operation, greatly facilitating the commercialization of the process. the cyclic operation of these fixed-bed cracking units used the heat of regeneration to obtain high cracking temperatures in the reactors and became a reality when the houdry process corporation together with the socony vacuum oil company and the sun oil company, built the first industrial units for both companies between 1936 and 1938. the catalyst was loaded in a series of parallel tubes which were kept in a bed of molten salts. the houdry process was very successful and in world war ii it is considered that 90% of the aviation gasoline used, with an octane number of 100, contained products obtained in houdry units. the war increased the needs for aviation gasoline and accelerated the diffusion of the new process. between 1938 and 1950 many units were built and despite subsequent developments, some of the units were still operative in 1960.29,30 again, world war ii and the demand of large quantities of high octane aviation gasoline was an incentive for the oil industry in the search for technological improvements in refining processes. the industry, especially at the allied side that had access to large quantities of oil, dedicated its best talents and means to respond to the war needs. processes such as alkylation, isomerization, toluene production for explosives and, finally, the greatest innovation among the conversion processes of heavy oil fractions, catalytic cracking in fluidized bed, came out from research work at companies and academia. the production of fuels by catalytic cracking required large investments to install the reactors where the reactions occurred, as well as the associated product separation equipment. in addition, the houdry company charged very expensive licenses for the use of its technology. then, some companies decided to study other technological processes. this group known as catalytic research associates was formed by standard oil of new jersey (exxon), mg, kellog, standard oil company of indiana (amoco), anglo-iranian oil company (bp), royal dutch shell, texaco and universal oil products (uop).31 in an attempt to improve the process and especially to avoid the discontinuous operation of the cracking reactors, designs were created in which the catalyst moved continuously from the reactor through a purge zone to the regenerator, and from there once regenerated it returned to the reactor again. this was achieved in the so-called mobilized bed operation, which was introduced by socony-vacuum oil company in 1942. the pellet-shaped or extruded catalyst moved by gravity from the reaction zone to the regeneration zone and then was raised from the bottom of the regenerator to the reactor inlet by means of a bucket system. at the beginning of the fifties, this design was improved by replacing the elevator with a pipe where the catalyst circulated mobilized by a high speed gas. the designs were marketed by the socony vacuum oil company under 138 rafael larraz the name of “thermofor catalytic cracking” (tcc), and by the houdry process corporation under the name of “houdry flow”. these units have operated satisfactorily for many years but disappeared due to their limitations in the heat balance that prevented building units of more than 20,000 barrels per day. in 1942, the catalytic research associates consortium, under the leadership of the standard oil of new jersey introduced the first fluid bed cracking unit, “fluid bed catalytic cracking” (fcc). a key fact of this technological milestone was the suggestion by warren k. lewis and edwin r. gillian from the mit that a low velocity gas could fluidize the powder catalyst making it behave like a liquid. subsequent tests confirmed this hypothesis and a pilot plant was built that began operating in 1940, from there, the model i of the fluid catalytic cracking unit was launched in may 1942, being the first fcc unit in the world.32 the fcc represents one of the paramount developments in oil refining technology and was based on the idea coming from the academia that the catalyst could behave like a fluid. for this, the catalyst was in the form of very fine particles with sizes smaller than 70 microns and kept in suspension by a stream of reacting vaporized hydrocarbons. in this way, the catalyst crossed the reactor and was collected in cyclones, while reacted hydrocarbons went to the fractionation section. the deactivated catalyst passed from the cyclones of the reactor to the bottom of the regenerator and was fluidized by an air stream that produced coke combustion. then, once its activity was recovered, it travelled back to the reactor, on a closed loop, as shown in figure 4. this revolutionary idea changed the refining industry and gave the industry a high conversion cracking process with an unbeatable energy balance, as the heat generated was recovered in the process. over the years, improvements have been added to this design, such as the reduction of the contact time between the catalyst and the feedstock jointly introduced into a tubular reactor or riser, where the reaction occurs in a high turbulence regime. the design of the fcc could be easily scaled due to the good control of the reaction temperature provided by the heat exchange between the catalyst and the charge. this fluidized bed reactor design has been used in other processes with exothermic or endothermic reactions. the fcc converts heavy distillates into high octane gasoline, gases with a high olefin content and distillates known as light cycle oil (lco) and heavy cycle oil (hco), finally producing a residue known as slurry. with a proper design and in the right operating conditions, the fcc’s performance in terms of produced gasoline and distillates can be 75-80% by volume of the unit feedstock. the stream of light olefin-rich gases could be sent to the polymerization or alkylation units, already described, to produce high octane gasoline. the fcc and alkylation processes are of great importance in the manufacture of gasoline. the gasoline yield of both processes, that is, fcc gasoline and alkylate obtained from fcc light olefins, exceeds 90% of the fcc feedstock volume.33 as we have seen, isobutane is consumed in the alkylation process, therefore, the process of isomerization of butanes can be included in the refinery scheme to supplement the natural content of isobutane in the crude. in 1930, v.n. ipatieff discovered that the butane molecules present in gasoline could be transformed into isobutane using an aluminum trichloride catalyst. in those years, this did not raise much interest because the isobutane content of gasoline was limited by its high volatility. but the need for high octane aviation gasoline revived interest in this process and large quantities were produced during the war to feed the alkylation units that supplied the allied air forces. later in the fifties and sixties, coinciding with the development of the catalytic reforming and the demand for high octane streams, the light gasoline composed of pentanes and hexanes with low octane was identified as a potential feedstock for the isomerization process and alumina-supported platinum catalysts were developed to increase the octane number from 60 to 90. in the 1980s, the possibility of using zeolites to isomerize light naphtha was investigated; in that vein, the mordenite-supported platinum catalysts were shown to be excellent for isomerization. after the emergence of the fcc, thermal cracking processes were progressively abandoned due to their lower yields and selectivity to gasoline and distillates, and thermal cracking technology evolved towards an increase in cracking severity and the use of vacuum residue as feedstock. this process, known as delayed figure 4. fcc reactor and fractionation scheme. 139a brief history of oil refining coking or coker, was introduced in 1929 by indiana standard oil, based on the facilities of a tube and tank unit in whithing (indiana). in the coker the feedstock is heated and maintained at high temperature until the long chain hydrocarbon molecules are cracked into light hydrocarbons and also decomposed to a carbonaceous residue known as coke. periodically the reactors, typically from two to six, or coke drums are filled with this coke and must be switched off to eliminate the accumulated coke, in a reaction-decoking cycle of the reactors. the products of the coker are light olefins, as well as naphtha and diesel with low quality that must be hydrotreated prior to marketing. the coke that is extracted from the reactors, depending on its quality, is used as fuel or other uses such as the manufacture of anodes.34 the zeolites as changes in the mechanical design of the fcc were introduced, the catalyst itself saw great improvements. the original catalysts were acidic clays of the montmorillonite type. with them, good yields were obtained of high-octane gasoline. these clays were progressively replaced by synthetic amorphous silica-alumina catalysts, which were more stable under regeneration conditions and gave a good product distribution. gasoline yields increased from 20% in thermal cracking to 40% with silica-alumina catalysts. in 1945, after three years of operation, the importance of the shape of the catalyst, its pore distribution and also the improvement of its attrition resistance produced by operating cycles in fluidized regime were clearly identified. also, modifying the silica/alumina ratio, usually at 65/35, allowed better product yields. in 1952, the silica/magnesium catalysts were introduced with increases in gasoline yield but a worsening of octane, their bad behavior in regeneration prevented their commercial success. an important revolution in the technology of catalytic cracking was the synthesis and catalytic use of zeolites. this constitutes one of the innovations with the highest impact on refining technology.35 crystalline silica-alumina zeolite compounds have been known for more than 150 years and are present in nature. they had been used in ion exchange applications, but their catalytic properties were discovered in the late 1950s. the zeolites can be synthesized by modulating their acid character and pore size. it can be said that the synthesis of zeolites allows to design an appropriate catalyst for each reaction. the first attempts to use the zeolites in catalytic cracking failed, and for a long time it was thought that their regular and uniform pore structure was inferior to the pore distribution of amorphous materials and given that the reactions occur inside the pores of the catalyst, zeolites were not useful for this purpose. in the mid-1950s, the union carbide corporation commercialized the first synthetic zeolite of the faujasite x and y type. initially, they were used as adsorbents although soon later were used as catalysts.36 in 1960, rabo’s work, once again, drew attention to the use of zeolites as catalysts for the isomerization reaction, but it was plank and rosinsky at the soconymobil corporation who stabilized the x and y zeolites so that they could withstand the temperature and the presence of steam in the reaction-regeneration cycles of catalytic cracking, without losing their crystalline character. this catalyst had greater activity and selectivity than the amorphous silica-alumina catalysts of the time. although they were initially used in the thermofor (tcc) process at the end of 1961, zeolites were quickly applied to the fcc. the high selectivity of these catalysts reduced the amount of feed oil required to produce gasoline. in fact, between 1964 and 1970, the rate of installation of fcc units was reduced by one million barrels per day, thanks to the good yields of the new catalyst that allowed to supply the gasoline market without the need of adding more fcc capacity. extrapolated to savings in crude oil to be distilled in the refinery, this meant about $ 200 m per year with oil prices prior to the 1973 crisis. as in the dubbs process, there was a lawsuit over the priority in the patents of the catalyst that lasted ten years and ended giving plank and rosinsky the rights of his patent over several oil companies.37 following the introduction of the zeolite-based fcc catalyst, a number of improvements increased its stability and selectivity. in 1977, mobil oil launched a new generation of catalysts that included a combustion promoter that contained less than 50 ppm of platinum on alumina. this allowed the regeneration of the catalyst to very low levels of coke at lower regeneration temperatures and also the conversion of carbon monoxide generated in the regeneration to carbon dioxide, reducing emissions and improving the heat balance. in 1974, mobil oil introduced a new zeolite, figure 5, called zsm-5 (zeolite socony mobil), with applications in many processes such as the fcc (where it increased the production of propylene and butenes) catalytic reforming, catalytic removal of waxes in lubricating oils, isomerization of xylenes and disproportionation of toluene, etc. the description of the huge development of zeolites since the zsm-5 discovery onwards, exceeds the scope of this manuscript, but we can say that zeolites are present in virtually all refining processes and have con140 rafael larraz tributed to the present and future development of the refineries. 38, 39 catalytic reforming and hydrotreatment after world war ii, the availability of fcc and alkylate gasoline meant that low octane naphtha produced by distillation had no place in the formulation of high octane gasoline. in the late forties, the development of a new process that constitutes an important technological innovation in the oil refining industry took place. this process known as catalytic reforming had a precedent in the thermal reforming of naphtha developed in the thirties, but as in thermal cracking, the reaction mechanism was not very productive towards high octane gasoline and gave low yields. catalytic reforming converts low octane naphtha into high octane gasoline, also known as reformate or reformed gasoline. the catalytic reforming of naphtha improves the octane number by catalyzing reactions like isomerization of paraffins to branched paraffins, dehydrocyclization of paraffins to aromatics, dehydrogenation of naphthenes to aromatics and hydrocracking of some paraffins. the reformate product is rich in aromatic hydrocarbons such as benzene, toluene and xylenes. over time, this formed the foundation for the aromatic-based petrochemicals associated with oil refineries. during world war ii, the catalytic reforming was used to produce toluene from methylcyclohexane, as a raw material for explosives and aviation gasoline. in 1947, standard oil of indiana, launched a fluid bed catalytic reforming unit. unfortunately, an explosion destroyed the unit and delayed this development by thirty years highlighting the difficulty of operating with hydrogen at high pressures. in 1950, there was a sharp advance in reforming technology when uop introduced platforming, based on a bifunctional catalyst of platinum on acid alumina developed by vladimir haensel, a disciple of ipatieff. other similar developments such as catforming of the atlantic reforming company or houdryforming from the houdry process corporation were marketed, but the success of the platforming process was overwhelming, as the platinum content needed was as low as 0.3% by weight. the catalyst employed gamma-alumina whose acidity was maintained by adding small amounts of hydrochloric acid to the unit charge. the operating conditions were between 25-40 k/cm2 pressure and 430-510ºc temperature. the operating cycles lasted between six and twelve months and the activity was maintained by gradually increasing the reaction temperature. after the operating cycle, the unit was stopped and the catalyst was replaced by a fresh one. the discarded catalyst was sent to disposal after being subjected to a platinum recovery process. very soon it was learned how to regenerate the catalyst in the unit itself through oxidation and activation of the catalyst loaded into the reactors. 40, 41, 42 a fundamental advantage of the reformer unit for the refinery was that during the reforming of naphtha, hydrogen was produced and could be used for hydrotreatments or hydrocracking reactions. in fact, the catalytic reforming process provided a high percentage of the hydrogen demand of the refinery. the bifunctional character of the reforming catalysts, where the reforming reactions occur in the active centers of platinum and alumina, was described in 1953 by mills, heinemann, milliken and oblad. in 1953, it was discovered that etaalumina was more stable and active than the catalyst based on alumina. in 1954, standard oil of indiana introduced the ultraforming process, and in 1956 esso introduced the powerforming process. these processes operated at lower pressures and favored aromatization reactions producing reformate with more aromatics and better octane numbers. the reforming reactions are mainly endothermic and therefore the best design is to alternate unit reactors and furnaces to get conditions as close as possible to an isothermal profile. generally, three reactors are installed, in the first two the endothermic dehydrogenation reactions occur, while in the third reactor the slightly exothermic hydrocracking and hydrogenation reactions take place. to favor a low pressure drop in the reaction system, the reforming reactors have a radial flow with a specific design that is part of the technology. figure 5. zsm-5 zeolite. adapted from chemical society review 2015, 44, 7342-7370 published by the royal society of chemistry. 141a brief history of oil refining in 1967, there was a great technological advance with the introduction of bimetallic catalysts. chevron developed the rheniforming process whose catalyst was platinum-rhenium on alumina, and this combination gave great stability to the catalyst by prolonging the cycle length and increasing the resistance to poisons such as sulfur. in 1975, exxon developed a catalyst from iridium and platinum allowing a stable operation at low pressures. in 1970, larry stines from uop developed another important milestone in this technology, the continuous catalytic reforming process, licensed as “continous catalytic regeneration” (ccr), which eliminated the need to stop the operation of the unit to regenerate the catalyst.43, 44, 45 the catalytic reforming platinum catalyst is rapidly deactivated in the presence of poisons such as sulfur, which may be present in the unit feedstock. sulfur is part of all crude oils in greater or lesser proportions and, as the use of catalytic reforming was expanded by industry, it became necessary to develop a technology to remove sulfur and other contaminants from the unit’s feed. the hydrotreatment process dates back to 1869 when berthelot studied the hydrogenation of coal to liquid hydrocarbons. following the research work of sabatier (1897), ipatieff in 1900, and bergius in 1910, the first coal hydrogenation plant was installed in leuna in 1927. in 1940, the i.g. faberindustrie successfully employed tungsten and molybdenum sulphide catalysts on alumina. in the first half of the twentieth century and during the war, germany was the leader of the hydrogenation technology. due to the shortage of oil, germany was forced to produce hydrocarbons from coal in this way, and in 1944, 3.5 million tons where produced through this process. in the us, the first plant was installed in 1928 in baton rouge belonging to the standard oil company of louisiana, other companies such as humble oil and shell installed plants in the forties, but their use was limited by the lack of hydrogen availability in the refineries. in the fifties the introduction of catalytic reforming provided abundant and cheap hydrogen and hydrotreatment units were installed for treating naphtha and other oil cuts. the hydrotreatment process used the hydrogen generated by the catalytic reforming unit and a cobalt and molybdenum sulfide catalyst was used to remove sulfur, nitrogen and other poisons from the reforming catalyst. the hydrotreatment process was also used to remove these contaminants from the distillates produced in the refinery. the hydrotreatment acquired more and more relevance in the configuration of the refineries from 1970s onwards.46 as a complement to the hydrotreatment of refinery cuts and to improve the quality of lpg and light gasoline and kerosene, the chemical treatment processes of these streams or sweetening were improved, based on the oxidation reactions of mercaptans with chemical substances such as sodium plumbite or the use of liquid phase catalysts based on iron chelates, like in the merox process of uop.47 the manufacture of lubricating oils also experienced a great boom with the popularization of the automobile industry. the necessary technology is very specific and is not usual in refineries that produce fuels. the lubricant manufacturing process requires the use of crude oils from the middle east whose vacuum distillates generate a highly paraffinic stream. the aromatic components are then removed by the furfural extraction process and heavy paraffins are also removed by solvent extraction, such as the methyl ethyl ketone (mek) process, to improve their cold properties. after the development of appropriate catalysts, paraffins can also be removed catalytically in dewaxing reactors. also, asphaltenes are removed from the heavy distillation cut by propane extraction. the lubricating oil is then subjected to a treatment to remove olefins and diolefins by passing through activated clay reactors or by severe hydrotreatment. waxes obtained from solvent dewaxing undergo a residual oil removal before commercialization. the hydrocracking in the late fifties and early sixties, the emergence of turbojet engines in commercial aviation led to an increase in the consumption of kerosene as aviation fuel. the demand for kerosene had declined since the days of the kerosene lamp, when it was the star product of the refinery, but jet fuel demand turned kerosene again into a key product of the refinery. the turbine manufacturers demanded from the industry that, for security reasons, aviation kerosene came exclusively from the crude distillation. with the development of the hydrocracking process in 1960, the industry had a technology that produced excellent aviation fuel. the hydrocracking, like hydrotreatment, was developed mainly in germany from 1910 until the end of the war. between 1925 and 1930, the i.g. faberindustrie in collaboration with the standard oil of new jersey developed the high pressure hydrocracking of heavy to light cuts. in 1960, chevron research co., unocal in collaboration with esso and uop launched several processes that popularized the technology.48 hydrocracking is a very versatile process that can use heav y vacuum distillates as feedstock to obtain lpgs, light naphtha, naphtha, aviation kerosene, diesel 142 rafael larraz and an unconverted residue with excellent properties for manufacturing lubricants. the process also removes all contaminants such as sulfur, nitrogen and oxygenated compounds, thus, the quality of the products meet in many cases the specification of the commercial product. hydrocracking reactions occur in the presence of hydrogen with a silica-alumina catalyst or zeolites at very high pressures. a disadvantage is the high cost of the process due to the need to use equipment with a high pressure and temperature design; on the other hand, hydrogen consumption raises the operating costs over other conversion processes such as fcc. the oil refining technology experienced dramatic technological improvements from 1940 to 1970, mainly due to wwii and the post-war economic boom, many of them are shown in figure 6. the continuous incorporation of new technologies to the configuration of a refinery improved the availability and quality of petroleum cuts, but increased their blending complexity in order to meet the quality specifications and the economic optimum. linear programming had been introduced during the war to optimize many problems of manufacturing military supplies. in 1948, george b. dantzig discovered the simplex method that facilitates the resolution of large systems of linear equations subject to restraints and from there, linear programming spread throughout in the industry as a way to optimize refinery operations. linear programming requires a large number of equations to find how to supply the refinery markets with the crude available, taking into account the yields and qualities produced by the refinery. whereas its initial use required great simplifications, the increasing power of computers gradually provided the basis for the economic management of any refinery.49 the petrochemistry in 1907, a belgian chemist, leo hendrik baekeland, synthesized the first plastic from phenol and formaldehyde, bakelite. years later, a pioneer in polymer research, wallace h. carothers confirmed the work of hermann staudinger, and took the company e.i. du pont de nemours to market the first synthetic rubber, neoprene, in 1932 and the first synthetic textile fiber, nylon, in 1939. 50, 51 but it was not until there was a high availability of raw materials that petrochemicals developed fully. once again, thermal cracking was the origin of a basic technology for petrochemicals. the steam cracker or cracker originated when c.p. dubbs introduced steam into its cracking process and verified that there was a decrease in coke formation because the steam decreased the partial pressure of the hydrocarbon molecules and therefore, the coke formation reactions; in addition, the production of olefins increased dramatically. in the 1920s, union carbide and standard oil of new jersey were the figure 6. refinery configuration evolution in 1940, 1950 and 1970. reproduced from  u.s. petroleum refining: meeting requirements for cleaner fuels and refineries. appendix c. history and fundamentals of refining operations, national petroleum council, 1993. 143a brief history of oil refining first companies to develop crackers for the production of ethylene and propylene. the cracker is currently the foundation of the chemical industry and produces three of the most demanded molecules such as: ethylene, propylene and butadiene. the cracker is versatile as several different feedstocks, i.e. lpgs, naphtha, natural gas or diesel can be used to produce other light olefins and aromatics such as benzene and toluene employed in the petrochemical industry. the lack of some raw materials during world war ii, such as rubber, whose production areas were occupied by imperial japan, promoted governmental efforts to obtain rubber substitutes from petroleum, such as butadiene53. the post-war economic development raised the demand for petrochemicals such as polyethylene, polypropylene, pet, phenol and synthetic detergents. in the refinery, and in order to separate the aromatic compounds in the reformed naphtha, aromatic extraction units with solvents such as sulfur dioxide or glycols followed by separation processes of benzene, toluene and xylenes began to be installed. the pioneer of the aromatic extraction technology was the romanian lazar edeleanu who in 1907, developed a sulfur dioxide extraction process to improve the quality of kerosene, eliminating the aromatics that produced lamp fumes from burning. in 1912, the royal dutch shell began studying the process and in 1916 it was marketed in europe. the american company evaluated its installation at the martinez refinery in california in 1915, but different problems were found and the process was not in service until 1927. the technology was extended to other companies such as california standard oil, associated oil and the union oil in those years. in 1928, shell and tidewater began using the edeleanu process to extract aromatics from the lubricant bases, improving their quality. 52, 53 at the end of the 1950s, improvements in the design and reliability of the alkylation units with sulfuric or hydrofluoric acid led to the progressive abandonment of the catalytic polymerization units as a way to convert light olefins into high octane gasoline. the polymerization found its place in the petrochemical industry where the development of catalysts by ziegler and natta, founded the polymer industry from ethylene and propylene. in 1951, while trying to convert propylene into gasoline, j. paul hogan and robert l. banks of philips petroleum obtained polypropylene and a short time later polyethylene was also obtained. 54 since 1960, the petrochemical industry developed in the fifties, experienced great success; especially the production of light olefins for plastics. the demand for figure 7. aromatic extraction plant. 144 rafael larraz ethylene tripled in those years. in the refineries, the aromatic extraction from reformed naphtha benefited from the synthesis of new solvents such as sulfolane synthesized by shell or morfilane by uhde, these new solvents increased the stability and safety of the process. the aromatic production plants became more complex thanks to the development of zeolitic catalysts and molecular sieves that increased the selectivity to produce preferably the para-xylene isomer, a raw material in the production of plastics; as well as the conversion of toluene, with lower commercial demand, into xylene and benzene through disproportionation or dealkylation reactions, figure 7. the integration of the refinery and one or several petrochemical plants is an incentive for the growth of large industrial complexes, with both, operational and process synergies between the refinery and the petrochemical plant, figure 8. typical examples of integration are the production of phenol, cumene and acetone by the hock process, using benzene from catalytic reforming and propylene from fcc and the manufacture of linear alkyl benzene (lab) as a detergent base material, again by the alkylation of benzene with paraffins extracted from the kerosene cut, uop-cepsa process. another example is the production of purified terephthalic acid (pta) from para-xylene from the aromatic complex of the refinery, a process developed by the scientific design company; the reaction of pta with ethylene glycol produces polyethylene terephthalate (pet), a raw material for plastic or fiber bottle manufacturing. 55 the large increase in propylene demand in the 21st century has changed the role of fcc and in some parts of the world such as asia and the middle east, propylene has replaced gasoline as the main product. the technology involved alters the catalyst to include a larger proportion of zsm-5 and also changes the design of the reactor internals to modify the contact time. in some cases, the designs add a second riser reactor where cracked naphtha is processed obtaining propylene yields of 30-40 % compared to yields less than 10% in a conventional fcc. the petrochemical complex based on fcc complements the aromatic plant in the production of petrochemical products in the modern refinery. the oil crisis during the oil crisis caused by the yom kippur war in 1973 and the fall of the shah in iran in 1979 due to figure 8. refinery-petrochemical integration. 145a brief history of oil refining the ayatollah’s revolution, the price of crude oil rose from 2 to 12 dollars per barrel. thereafter, opec maintained the price of crude oil at high values with the consequent impact on the profit margin of the oil refineries. the response of the refining industry to this important change affected two aspects of the technology. oil refining is a technology that requires high energy consumption, the processes described so far require high temperatures and pressures, as well as the transfer of large volumes of liquids, and those are high energy demanding processes. on average, and depending on its configuration, a refinery consumes 5% of the processed crude oil to supply the necessary energy for the process. the oil crisis led the technology to focus on efficiency and energy recovery in the refinery, affecting both, existing processes and new projects with very demanding energy consumption objectives. the main modifications to the technology involved the installation of heat exchangers, heat recovery from waste streams like the heat from the furnace stacks, or the generation of steam with process streams and the cogeneration of electricity from waste gases. all steam and electricity utility systems were also analyzed to optimize energy use. finally, new tools were developed to design energy recovery systems such as the “pinch” analysis developed by linnhoff and vredeveld at the end of the seventies, looking for the optimal way to exchange process streams from the point of view of energy recovery. 56 the rise in crude oil price revived the technologies for conversion of heavy oil cuts to light cuts, and many refineries incorporated fcc units and to a lesser extent hydrocracking so that less oil was necessary to achieve the same amount of high value-added products. this trend also revived the technologies for the conversion of the so-called bottom of the barrel or vacuum residue; among them we have cited the delayed coker as the heir of thermal cracking, which allowed 70% conversions to light products and a coke that was used as fuel in cement plants or to manufacture electrolysis anodes. also, a modality of soft thermal cracking known as viscorreduction or visbreaker was developed with conversions that dropped to 20%, but a fuel oil with commercial viscosity was obtained. this unit was oriented to the production of marine fuels with viscosities of 180 or 360 cst and its advantage was that it eliminated the need to mix the vacuum fuel oil with light products to decrease its viscosity and density, with the consequent savings in distillates that could be directed to formulate other more valuable products. the energy crisis also triggered the emergence of the vacuum residue hydrocracking technology, in this case the conversion of the residue occurred in the presence of hydrogen on a catalyst at high pressures and temperatures. the reactor type ranged from fixed bed to ebullated or fluidized bed, giving rise to different processes. units were installed in the eighties and nineties but the high cost and the need for hydrogen favored the delayed coker technology. the environment in the 1970s, concerns about the impact of hydrocarbons on human hea lt h and t he env ironment increased greatly. this trend continues today, largely leading the evolution of refining technology. in summary, regulations with an impact on refining technology began with the elimination of tetraethyl lead (tel) as an improver of the octane number of gasoline. the main regulations with an impact on refining technology can be summarized as follows: • the changes in fuel quality specifications eliminating the contaminant content, • the regulations related to emissions from refinery effluents, • the introduction of biofuels • and finally the decarbonization of oil refining, which will surely have a strong impact in the future of the industry. in 1974, a period began that lasted until the 1990s in which the tel was eliminated from the gasoline formulation as an octane improver. there was a great concern about the composition of vehicle effluents. the installation of a combustor with a platinum catalyst, which converts both nitrogen compounds and the remaining hydrocarbons into inert molecules solved this problem; for that purpose no poisons were allowed in the car effluents that could damage the platinum catalyst. lead is a permanent poison for platinum catalysts, therefore, its removal was necessary, apart from the harmful nature of lead compounds for humans. this fact increased the importance of catalytic reforming in refineries, making reformate the main contribution of octane to gasoline formulations. the gasoline components produced in other process units such as fcc, alkylation, hydrocracking and polymerization have a relatively constant octane number. the product of catalytic reforming has octane numbers from 80 to more than 100. unfortunately, as the severity of the operation increases to raise the octane number, the gasoline yield decreases. the normal performance in reforming can vary from 70 to 90% in feed volume, depending on whether the octane is high or low. in the eighties, the process of etherification of four or five carbon olefins from the fcc unit with methanol was developed as an alternative to tel to produce 146 rafael larraz methyl tert-butyl ether (mtbe) or tert-amyl ether (tame). these ethers have a high octane number and good properties as a gasoline component and their use extended from 1980 onwards. in the 1990s, the regulations regarding oxygenated compounds in gasoline were updated. subsequently, mtbe was replaced by ethyltert-butyl ether (etbe) due to various aquifer contamination episodes with mtbe caused by its high water solubility. in those years, the direct injection of ethanol into gasoline also began, although there are limitations in several quality specifications that advise against exceeding 10% in ethanol content. 57 the next environmental impulse came from the 1990s and continues today, fuel specifications hardened the limit values of pollutants in the benefit of human health and the environment. in a very general way, this affected especially the sulfur content in fuels and limited the content of aromatic and unsaturated compounds. additionally, the density of fuels was limited in order to obtain lighter products with less complex and harmful combustion products. in europe, the auto oil program was the framework for the development of these new specifications in which the automobile industry, the refining industry and the european commission were represented. the evolution of the euro specifications resulting from this analysis, strongly increased the regulatory pressure that oil refining technology had to solve. the impact of the new specifications on the manufacturing technology of automotive fuels covered several complex aspects.58 the limitation of sulfur forced the industry to rethink the use of fcc naphtha in gasoline, the fcc naphtha sulfur content depends directly on the fcc feedstock. the first option is to hydrotreat the fcc feedstock. since the sulfur specification virtually eliminates this compound, hydrotreatment is often not sufficient. the injection of additives based on magnesium oxides that react with sulfur and remove it from reaction products has also become popular. the most widespread solution has been the hydrotreatment of fcc naphtha, this process was a technological advance after an indepth study of the distribution of sulfur compounds and olefins in fcc products. compounds that give a high octane number to fcc naphtha are olefins and aromatics and hydrotreatment reactions in the presence of hydrogen tend to saturate those compounds, thus removing their aromatic and unsaturated character and reducing the desired octane number. refining technology elegantly solved this problem by discovering that the light fraction of the fcc unit contained the highest proportion of the compounds that contribute to the octane number and the heavy part contained the sulfur compounds. various technologies were developed by separating both parts of the naphtha and selectively hydrotreating the heaviest part with catalysts that desulfurized keeping the high octane compounds intact to a large extent. the technologies designed by exxonmobil, uop and especially axens solved this challenge and nowadays fcc gasoline is still the main component of gasoline. 59 the next major challenge for gasoline was the limitation of aromatic content and especially of benzene in its formulation. aromatic compounds have a high octane number and high density, which favors compliance with the vapor pressure of gasoline. the greatest contribution of aromatics to gasoline is made through reformed gasoline, refiners had to limit this component in the formulation and increase the contribution of fcc naphtha, oxygenated ethers and gasoline from alkylation. an added problem was to eliminate benzene from reformed naphtha, also in this case there was a technological analysis of how benzene was formed during catalytic reforming and two strategies were designed for its elimination. one strategy was the elimination of the so-called proto-benzenes or compounds that give rise to benzene during the reforming reactions and which were removed by distillation of the light part of the charge to the catalytic reforming. the other option was to eliminate the benzene present in the reformate by distillation. the limitation in aromatics and benzene was not a major problem in complex refineries, but in those without an fcc unit, it was a serious problem since its formulation was based on reformed naphtha, and they were forced to buy fcc naphtha to make their gasoline formulations, seriously compromising their future. the other major automotive fuel, diesel, was also deeply affected by the new specifications. in this case, the technology focused on the removal of sulfur by hydrotreatment. although diesel was desulfurized since the seventies, the almost total elimination of sulfur was an important technological challenge. firstly, the different sulfur compounds present in the diesel were identified and it was determined that depending on the position of the sulfur atom in the hydrocarbon molecule, its elimination could be more or less difficult. this implied that it was relatively easy to remove compounds with accessible sulfur atoms, but it was very difficult when sulfur atoms were in a position that hindered their access to the catalyst. dimethyl dibenzothiophenes are an example of molecules resistant to hydrotreatment for this reason. this fact induced two important technological advances, a great development of cobalt-molybdenum and nickel-molybdenum catalysts supported on alumina, improved with advances on the understand147a brief history of oil refining ing of the desulfurization reaction mechanisms, and the design of suitable reactors to carry out this process. catalyst manufacturers like abermarle, uop, haldor topsoe, axens, etc., made an important effort to put these catalysts on the market in a few years. 60 it is worth discussing in more detail the design of the hydrotreatment reactors for sulfur removal. during the diesel hydrodesulfurization reaction, liquid diesel, partially vaporized and hydrogen in the gas phase are present in the reactor, therefore, the flow in the reactor is mixed in the so-called “trickle-bed” reactor system. this is a problem since one requirement for efficient reaction on the catalyst is that the reactants are well mixed facilitating their access to the catalyst surface. since 2000, there was a technological change in the design of the hydrodesulphurization reactor internals. using tools such as computerized flow design (cfd), the designs of the gas-liquid distributors were improved to obtain reactors of increasing diameter and, therefore, units of greater capacity. today we can find mixed flow reactors of six meters in diameter when in the nineties three meters was an insurmountable limit. 61 as we have seen, the refineries have been forced to hydrotreat most of their products prior to their marketing. the question then became what to do with all the sulfur compounds that are removed from gasoline and distillates, and indeed, this is another technological and environmental challenge that the industry has had to solve. hydrodesulfurization reactions remove sulfur from the oil cuts in the form of hydrogen sulfide, this compound is incorporated into the refinery gas system that channels all the gaseous streams produced in the different refining processes and that are used as fuel in the furnaces of the process units. prior to environmental regulations, these sulfur compounds were oxidized to sulfur dioxide during combustion, and were emitted from refinery furnace stacks. european and american emission regulations began to regulate refinery emissions in the 1980s. the technology solved this new challenge by installing sulfur absorption units with ethanolamine-based compounds, which react quickly with hydrogen sulfide. ethanolamine captures hydrogen sulfide and in an absorption-regeneration cycle produces a stream of light sulfur-free hydrocarbons that are sent as fuel to the furnaces of the refinery and a so-called acid gas with a 95% content of hydrogen sulfide that is sent to the sulfur recovery units for conversion into solid or liquid sulfur that is marketed. this transformation is carried out in claus units, based on the reaction discovered by friedrich claus in 1883 and modified by ig farbenindustrie ag in 1937. the claus process partially oxidizes hydrogen sulfide to sulfur dioxide that reacts with the remaining hydrogen sulfide to produce elemental sulfur. sulfur recovery in a refinery exceeds 99.5% in this way, and can reach 99.9% through the waste or tail gas treatment unit, prior to its emission. 62 the next fuel subjected to quality specifications, marine fuel oil, is still an issue for refiners. marine fuel oil or bunker moves the engines of ships and is formulated with heavy distillates and vacuum residue. the international maritime organization (imo) regulated a maximum sulfur content in marine fuels of 0.5% after 2020. marine fuel is typically formulated with heavy cuts, which cannot undergo further valorization in the refinery process units. there are many refineries that use delayed coking units to convert all their heavy residue into naphtha and distillates. the less complex refineries or those serving the bunker markets employ their production of vacuum residue and heavy distillates for this purpose. an advantage of bunkering production used to be that marine fuel, whose sulfur specification was 3.5% by weight prior 2020, was a sink for much of the sulfur entering the refinery, this is not possible after 2020. alternatives to meet the sulfur content of marine fuels, include the installation of scrubbers with seawater that remove sulfur dioxide from the effluent of ship’s engines. another option is to change the fuel for products with lower sulfur content, such as natural gas, since it is possible to adapt the engines to these other fuels. a final option for the refineries is to produce marine fuels similar to the current ones but with a sulfur content less than 0.5%. the price of marine fuel has historically been below the price of crude oil and this raised doubts about the price of this new low sulfur fuel, and whether the necessary investments in hydrotreatment processes of vacuum residue and distillates involved in its formulation were justified, considering a solution similar to that of gasoline and diesel. many refineries rely on distilling low sulfur crude, whose residue allows a marine fuel to be obtained that meets the sulfur specification. from the technological point of view, there are processes for the conversion of the residue into more profitable products such as delayed coker or solvent deasphalting, but they do not produce fuel oil and would force the refinery to leave the bunker market. other technologies such as residue hydrocracking obtain conversions to gasoline and distillates in the vicinity of 70% and allow the refinery to formulate low sulfur fuels by desulfurization of the vacuum residue. residue hydrocracking technology (rhc) has undergone a breakthrough in recent years since its inception in the 1980s, and recently eni, clg and uop have introduced the “slurry” technology with a very small particle size catalyst that allows conversions of up to 148 rafael larraz 90%, practically eliminating the residue from the refinery. the evolution of the markets after the new specification of sulfur for marine fuels, will consolidate the best option for refineries in terms of conversion of the bottom of the barrel.63 the biofuels the third area where environmental requirements have had an impact on the configuration of the refineries is biofuels. these constitute renewable energy and are defined as fuels suitable for use in internal combustion engines that have been produced from biomass obtained through biological processes, and in general they consist on a mixture of organic compounds with a high oxygen content. their use is justified by the hypothesis that the carbon content of biomass comes from the photosynthesis process and eventually turns back into the atmosphere as a result of burning and carbon dioxide emissions, making the net carbon balance neutral. this last statement is subject to debate, and there is extensive bibliography discussing the net result of the carbon balance. the biofuels consumed in the world are primarily ethanol, an alcohol produced by the fermentation of agricultural crops or lignocellulosic materials; biodiesel, a methyl ester resulting from the esterification of vegetable oils, such as palm oil, and methanol; and finally hydrotreated vegetable oil (hvo), which is manufactured by removing the oxygen present in vegetable oils by reactions in the presence of hydrogen. biofuels are under great debate due to the effects that their production in large quantities has had on the food price, with which they share raw materials such as corn, wheat, palm oil, etc.; and also to due to changes in land use, either by varying the original yield of agricultural lands for cultivation or by dedicating areas of high biodiversity to the cultivation of biofuels. the last two phenomena are known as indirect land use change (iluc) and have significantly conditioned european legislation. nowadays, those biofuels coming from edible raw materials are known as conventional biofuels, and those whose raw materials are residues, animal fats, non-edible vegetable oils and cellulosic materials, and have no effect on the change of agricultural land use, are termed advanced biofuels. the regulations have increased the content of biofuels and the specification will lead refineries to introduce 10% biofuel (measured as equivalent energy) in the formulations of automotive fuels. the refineries have been pioneers in the production of biofuels since the 90s, figure 9; they included bio-etbe (ethyltercbutil eter) into the gasoline blending. etbe is an oxygenated derivative of ethanol and butenes produced in the refinery. it is a good oxygenated component in the formulation of gasoline, thanks to its figure 9. biofuels production in refineries. 149a brief history of oil refining stability and high octane number. refiners also incorporate biodiesel frequently produced in facilities near the refinery into diesel formulation. biodiesel has some stability problems and its content is limited by the specification. refining technology has developed processes for the production of hydrotreated vegetable oil (hvo) by selective deoxygenation of the fatty acids in the vegetable oil that are converted into paraffins. this process has a high hydrogen consumption and requires expensive construction alloys given the corrosive nature of vegetable oils. eni, uop, haldor topsoe, neste and axens have commercialized units and the production of hvo is today a common process in the refinery. in countries like spain, where it is permitted by current legislation, it is common to co-process vegetable oil up to 5-7% by volume in existing hydrotreatment units. hvo has excellent properties as a diesel component. 64, 65 the manufacture of hvo has resulted in a specific refinery configuration that today has two examples at the eni refinery in porto marghera and la mede refinery owned by total. both are based on obsolete refineries without conversion capacity and whose economic viability was compromised. the refinery feedstocks are vegetable oils, animal fats, used cooking oils or recycled plastics; the hydrogen for the reactions involved can be provided by the existing catalytic reforming unit or by a hydrogen plant and the products obtained are separated and stored in the refinery facilities for distribution. the refinery produces renewable diesel or green diesel, renewable naphtha or green naphtha, lpgs and potentially aviation fuel. eni is considering converting the gela refinery in italy to this scheme. there are technologies to produce bio-kerosene for jet fuel, however, despite its use in test flights, the implicit safety concerns in air transport means that the introduction of aviation biofuels is not expected soon. 66 the future the refineries have been implementing advances and technological innovations such as those we have described to satisfy their markets and the specifications applicable to their products, figure 10. the choice of a refining technology is based on the specific circumstances of its operation and depends on the type of crude oil, the demand and quality of the products and economic factors such as the cost of crude oil and products, availability of services such as steam, water, electricity, etc., type and cost of catalysts and the cost of the necessary equipment for its operation. considering our current knowledge on the past and present of oil refining technology, it is worth asking whether the refinery will remain as a supplier of essential products for society or there are risks of the industry being overcome by new technological advances or even disappearing. if we look in the past and the successive energy transitions, we see, for example, that the oil industry began in 1859, but it took more than a century figure 10. complex refinery (cepsa gibraltar san roque) in 2021. reproduced with permission from cepsa. 150 rafael larraz for coal to cease to be the main source of energy. oil, in turn, represented 5% of energy consumption in 1840 and its growth was slow until 1900 when it represented 50% of the energy supply, sharing the leadership with fuels as exotic as whale oil. in general, history tells us that energy transitions are slow phenomena and also that usually the preceding energy sources do not disappear and remain in niches of consumption in considerable quantities, for example, around 1960, oil was the main source of energy surpassing coal, but since then, coal consumption has tripled despite being a secondary source of energy. 67 historically, the transitions from one energy source to another have been due to the emergence of new technologies, better prices and lower energy costs and often to policies looking for more secured supplies. nowadays, it is the climate change who is causing the transition from low-cost energy sources to energies whose costs are currently higher but seek to reduce the emission of greenhouse gases (ghg). the difference in costs is covered by different types of subsidies, incentives and regulations, until investments in research and development make those energies competitive. however, it should not be forgotten that the wealth growth in the world has always been associated with an efficient and cheap source of energy. petroleum refining technologies, as we have seen, have been responding to the environmental challenges that have been presented, but the last one we have mentioned, decarbonization, affects the very nature of its products that are made of carbon atoms. next we will make a brief analysis of where it is more feasible to replace petroleum products and which of them will be maintained over time. vehicles with an internal combustion engine can be replaced by electric vehicles, hydrogen, hybrids, natural gas, etc., car manufacturers have understood this trend and regardless of the legislation they are making large investments in developing electric vehicles. as in the past, the automobile industry can dictate the demand for fuels and contribute to a significant decrease in diesel and gasoline consumption. at the moment, advances that allow the commercialization of electric heavy transport vehicles or the replacement of aviation fuel seem less viable. therefore, the demand for diesel and especially aviation kerosene should be maintained for the next decade. marine fuels, as we have already described, have the alternative of natural gas that would have a significant bunker market share in the coming years. hydrogen also appears as a long term option for decarbonizated bunker fuels. the future of transport fuels is therefore a challenge, perhaps the most complicated one that the refining industry has to face. road paving is another market where the use of asphalt mixtures seems to be the most economically and technically viable alternative, and therefore, the demand for asphalt can be maintained over time. the future of lubricants, already threatened by synthetic lubricants, is associated with that of the internal combustion engine. if this disappears, a large part of the manufacture of lubricants will also disappear, although some demand will still exist for other lubrication applications such as oils for machines, greases, waxes, etc. an area where oil seems irreplaceable is petrochemicals, this market demands 12% of the crude oil production and maintains sustained annual growth, especially in areas such as asia where the standard of living is growing rapidly. the refineries have increased their integration with petrochemical plants starting with 5-10% of their products being petrochemicals to more than 20-30%. in recent years, chemical products based on renewable raw materials have been developed. although technically possible a disadvantage is the low production yield that makes large quantities of raw material necessary, and often leads to irrational demands on land availability and logistics. the recycling of plastics is also a booming trend. the high demand for petrochemical products is giving rise to a new refinery configuration known as “crude to chemicals”, which is a good example of what the future could be. in these refineries, existing technologies and new developments are combined to directly convert crude into petrochemical products with conversions that exceed 50%. we have examples of these refineries in saudi arabia and china where the direct conversion of crude oil is the technological challenge; in that vein, exxon at its jurong refinery, launched in 2014, a process of direct crude cracking. the number of refineries that might follow this production strategy is a concern due to the small size of the petrochemical market in comparison to the fuel market. 68, 69 conclusions presently, 85% of the world’s energy consumption is generated by fossil fuels. the task of reducing the energy contribution of oil, requires time and substantial investments. it will be the society who will determine where and when this energy transition will materialize. renewable energies should have the role of feasible energy alternatives without prejudice for the standard of living. finally, the refining industry is facing its most important challenge that must be solved thanks to new 151a brief history of oil refining feedstocks and products, new technologies and to innovative mentality and adaptation to demand, which has always characterized oil refining. acknowledgments the author would like to thank flor garcia mayoral from cepsa research center for their guidance and valuable advices about the text. the author also thanks to the anonymous referees for their insights and comments that significantly improved the manuscript. bibliography 1. j. l. enos in the rate and direction of inventive activity: economic and 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pp. 141-173. 67. v. smil, energy research & social science 2016, 22, 194–197. 68. https://ihsmarkit.com/research-analysis/crude-oil-tochemicals-cotc-major-disruptor.html, last accessed on 18/04/2021. 69. a. corma, e. corresa, y. mathieu, l. sauvanaud, s. al.bogami, m.s. al-ghrami, a. bourane, catalyst science and technology 2017, 7, 1-34. substantia an international journal of the history of chemistry vol. 5, n. 2 2021 firenze university press our short talks dante alighieri science communicator gian italo bischi spin temperature and dynamic nuclear polarization. from the history of researches (1949–1983) alexander kessenikh can non-recyclable plastic waste be made environmentally sustainable? luigi campanella1, giuseppe b. suffritti2 translations of roscoe’s chemistry books into japanese and hebrew historical, cultural and linguistic aspects yona siderer first steps: synthetic ammonia in the united states anthony s. travis the «d.i. mendeleev’s periodic system of the elements» mural 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history of chemistry 3(2) suppl. 3: 13-28, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-702 citation: e. b. van de kraats, j. s. muncan, r. n. tsenkova (2019) aquaphotomics origin, concept, applications and future perspectives. substantia 3(2) suppl. 3: 13-28. doi: 10.13128/ substantia-702 copyright: © 2019 e. b. van de kraats, j. s. muncan, r. n. tsenkova. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. aquaphotomics origin, concept, applications and future perspectives everine b. van de kraats1, jelena s. munćan2,3, roumiana n. tsenkova3,* 1 water research lab, heidelberg, germany 2 biomedical engineering, faculty of mechanical engineering, university of belgrade, serbia 3 biomeasurement technology laboratory, graduate school of agriculture science, kobe university, japan *corresponding author. e-mail: everine.van.de.kraats@gmail.com, jmuncan@people. kobe-u.ac.jp, rtsen@kobe-u.ac.jp abstract. aquaphotomics is a novel scientific discipline which has made rapid progress in just 14 years since its establishment in 2005. the main novelty of this field using spectroscopy is placing the focus on water, as a complex molecular matrix and an integral part of any aqueous system. water is sensitive to any change the system experiences – external or internal. as such, the molecular structure of water revealed through its interaction with light of all frequencies becomes a source of information about the state of the system, an integrative marker of system dynamics. this novel field shifts the paradigm of seeing water in a system as a passive, inert molecule to one which can build various structures with various functionalities, giving water an active role in biological and aqueous systems. owing to the high sensitivity of hydrogen bonds, the water molecules are incredibly adaptive to their surroundings, reshaping and adjusting in response to changes of the aqueous or biological systems, and this property in aquaphotomics is utilized as a key principle for various purposes of bio-measurements, bio-diagnostics and biomonitoring. this paper will present the origin and concept of aquaphotomics and will, through a series of examples of applications, illustrate many opportunities and directions opened for novel scientific and technological developments. keywords. aquaphotomics, spectroscopy, water, light, bio-measurements. 1. origin of the new science the concept of aquaphotomics grew during years of experience with nearinfrared (nir) spectroscopy and mammary gland disease in cows (mastitis). first realizations about the role of water determining the state of biological systems were made by roumiana tsenkova, professor of bio engineering at kobe university, japan, during her early works at hokkaido university while studying biological systems in-vivo with near infrared spectroscopy. in 1996, when roumiana tsenkova moved from hokkaido university to kobe university in japan with a five-year grant in animal husbandry, 14 everine b. van de kraats, jelena s. munćan, roumiana n. tsenkova further investigations started at kobe university and four other teams in japan. the findings of this project opened the avenue for investigating water molecular systems in the biological world. she discovered that the water molecular matrix of milk and body fluids changes with inflammation of the mammary gland (mastitis) in dairy cows. in 2001, the seed of aquaphotomics was planted with a paper where r. tsenkova and colleagues had applied nir spectroscopy to measure milk proteins of healthy and mastitic cows.1 they applied chemometrics and found that the two groups had different regression models for protein measurement and somatic cell count and that their average spectra differed in the area of water absorbance bands, which meant that the water structures, shaped by proteins and cells, changed with the disease. this was the first publication showing that water, acting as a biological/chemical matrix, can tell if a system is healthy or diseased. that was the time when the term water matrix started to be in use to denote water as a molecular network consisting of different water molecular structures that cause different behavior inside a system. during those years, aquaphotomics basic spectroscopic experiments on water were performed as well by adding molecules or changing temperature or humidity or measuring water repeatedly and observing how the water spectrum changed at certain specific wavelength ranges. one of the most spectacular observations from these early years was that the absorbance spectrum of water changed with consecutive measurements (in aquaphotomics called illumination perturbations). this result was first presented at the international nirs conference in the year 2000 in korea. reactions varied from “i knew somebody would do it” and being interested to explore further, to “if this is true i will quit my job” because in conventional physical chemistry it is expected that good instruments will acquire the same spectra repeatedly. the fact that light changes the water seemed extraordinary and the exploration into the water spectrum as a source of information continued. further investigations were performed on cells, plants, and animals. similar spectroscopic patterns, meaning similar absorbance bands changed when perturbations were introduced on other investigated systems. the realization emerged that the water absorbance bands (wabs) in the found patterns were related to the same wavelength ranges that were influenced in the basic water experiments performed earlier. these wavelength ranges were presented as water matrix coordinates (wamacs), a new term introduced to denote the ranges in the electromagnetic (em) spectrum where measured absorbance of biological and aqueous systems changed due to perturbations, providing information about particular water structures and water functionality.2 conventionally, only a few symmetric and asymmetric stretching vibration assignments of water molecules are known in the first overtone of water oh stretching vibrations for pure water systems.3 however, the experimentally found patterns presented 12 ranges, see figure 1 for a schematic depiction of those wavelength ranges (wamacs). it must be noted that these ranges are not completely fixed and new bands or extensions of the bands have been and will be found in further explorations with other systems and perturbations. it is tempting to try to assign the wamacs to particular water structures, as has been done in various aquaphotomics publications.2 in the nir range, for such endeavors the found bands in wavelengths (x nm) are multiplied by an integer o, representing the expected overtone of the fundamental band of water structures (usually o is two for the first overtone), and converted into wavenumbers (y cm-1) through the following formula: y  cm–1  = 10,000,000  /  (o∙x) nm (adapted from v = 1/λ) and subsequently searched in literature for known assignments. however, since water vibrational modes and water interand intra-molecular bonding is complex and one system of molecules will entertain numerous types of water vibrations and inter and intramolecular bonding, it is usual that overlapping and shifting occurs and more than one band will respond to a change in the water matrix. consequently, figure 1. schematic depiction of the water matrix coordinates (wamacs), which are the wavelength ranges where the spectral absorption changes most in bio-aqueous systems due to pertubations.4 ~ 15aquaphotomics – origin, concept, applications and future perspectives it is suggested not only to find assignments based on water molecular structures, but to work with the ‘activated’ water bands as ‘letters’ creating ‘words’ that can be assigned to a functionality per system–perturbation combination.5 ‘activated’ water bands are found through aquaphotomics analysis where the steps of the analysis, such as raw data inspection, conventional and chemometric analyses, provide certain quantitative outputs such as derivatives, subtracted spectra, regression vectors or loading vectors, discriminating power and others, which all unravel the water absorbance bands most affected by the perturbation of interest.6 the spectra of aqueous systems are very complex, and changes caused by any perturbation will usually be subtle, but nonetheless persistent and consistent. acquiring spectra under a certain perturbation without stabilizing the influence of other factors provides more spectral variations and therefore a robust model for water functionality related to examined perturbation. averaging towards the main perturbation and subtracting of the average spectra is the first source of information about the specific bands that relate to the highest absorbance variations induced by the perturbation of interest. from all the water absorbance bands discovered during the multiple steps of aquaphotomics analysis, common absorbance bands will emerge to reveal perturbation-induced light absorbance pattern at specific water absorbance bands. in this way, aquaphotomics analysis provides a link between the observed water absorbance bands and the water functionality in the respective system. experience and studying the patterns in this ‘vocabulary’ of all observed system-perturbation combinations can result in assignment of certain wamacs to water structural behavior, see the often seen ‘assignments’ based on r. tsenkova’s experimental data in table 1. water is such a common element that the same ‘bands’ can be found in spectra of crystals as well as liquids and other (bio) systems. in this way, the building of the aquaphotome, which consists of the water absorbance bands and water spectral patterns (wasps) related to specific states or dynamics of various systems, started.2 every system–perturbation combination has its unique aquaphotome, i.e. the spectral pattern produced by the respective system under the respective perturbation. aquaphotomes build up the aquaphotome database that contains all the respective wasps of various systems under various chemical, physical, mechanical, biological, etc. perturbations. to illustrate this, two entries in the aquaphotome database, for the wavelength range 1300-1600 nm, representing two system–perturbation combinations, in this case cow’s milk – degree of increasing mastitis and water – increasing temperature, are provided in table 22. finally, in 2005, r. tsenkova proposed the establishment of aquaphotomics2,9–11 as a new scientific discipline complementary to other “omics” disciplines, with the aim to study water in aqueous and biological systems, using light as a probe and a spectrum, which results from their interaction, as a source of information about the system. systematization of knowledge about water from the aquaphotomics research studies and experience in working with various aqueous and biological systems showed that water-light interaction over the entire em spectrum can significantly contribute to the field of water science and provide better understanding of water molecular systems, and most importantly that it leads to the development of new technologies and applications.2 table 1. the 12 wamacs, their corresponding wavelength ranges, and the general ‘assignments’ often seen in r. tsenkova’s experimental data. they are in good agreement with the respective published assigned bands in ir range. wamac wavelength range general ‘assignment’ c1 1336-1348 nm va po r lik e h2o asymmetric stretching vibration protonated water clusters c2 1360-1366 nm hydroxylated water clusters water solvation shell c3 1370-1379 nm h2o symmetrical stretching vibration and h2o asymmetric stretching vibration c4 1380-1388 nm water solvation shell hydrated superoxide clusters c5 1392-1412 nm s0: trapped and free water c6 1421-1430 nm water hydration c7 1432-1444 nm bu lk w at er h3o (hydronium) s1: water molecules with 1 hydrogen bond (dimer) c8 1448-1458 nm protein transfer mode in acidic aqueous solutions water solvation shell c9 1460-1464 nm s2: water molecules with 2 hydrogen bonds (trimer) c10 1472-1482 nm s3: water molecules with 3 hydrogen bonds (tetramer) h3o2 h5o2 c11 1492-1494 nm ic e lik e s4: water molecules with 4 hydrogen bonds (pentamer) c12 1506-1516 nm strongly bound water 16 everine b. van de kraats, jelena s. munćan, roumiana n. tsenkova 2. setting the stage 2.1. aquaphotomics: water – from passive to active component the early aquaphotomics works were based on nearinfrared spectroscopy. the analysis of water in this field was present since its inception,12–14 but at that time water was still not considered as a molecular network system or a biologically relevant matrix. in fact, for years, water has been described as the ‘greatest enemy’ of infrared (ir) and nir spectroscopy on account of its dominant absorption. this attitude was a result of, at that time general, dominant opinion in biological sciences that water is an inert, passive medium. living processes were described in terms of genes, dna, proteins, metabolites or other single biomolecules acting as entities isolated from water. research methods were focused on extracting information related to the structure of these biomolecules, and in the near infrared region dominant absorbance of water was seen as an obstacle to observing their absorbance bands. however, the field of water science has seen significant progress in the last decades which has changed the general opinion about water and its role in the living systems.15–19 today, we are witnessing a paradigm shift – water is recognized as an active solvent, adapting its structure to the solutes that it accommodates, and in biological systems, water is seen as a biomolecule in its own right with an active role in the dynamics of biomolecular processes.2,7,17 2.2. aquaphotomics: from a segmented to a global watermirror approach the main aim of the aquaphotomics field is to understand the role of the water molecular network in biological and aqueous systems by monitoring the interaction with light in the broadest sense, and investigating the whole em spectrum of those systems under various perturbations. the name of this discipline is composed of three words: aqua – water, photo – light, and omics-all about something.2 aquaphotomics presents the water spectral pattern as a multidimensional, integrative marker related directly to the respective system functionality. the foundation stone of aquaphotomics is a discovery that water in biological and aqueous systems works as a ‘mirror’ of the components and environment (matter and energy) and therefore its spectral pattern can be used to characterize the system as a whole. this is also called the water mirror approach (wama) (figure 2).2 water is an invaluable resource for human health, food security, sustainable development, and the environment. understanding the role of water in aqueous and biological systems is of crucial importance. historically, water properties have been extensively studied using a variety of methods from x-ray to thz spectroscopy. however, even if these techniques provide valuable information on water molecules, they generally focus on water as an isolated/separate chemical and physical subject only, in contrast to focusing on water as an interdependent connected active and ‘functional’ system, interrelated to its environment. there are no isolated systems in nature. likewise, from biological sciences point of view, up to recently, biologists have been focusing on pinpointing single biomolecules related to natural phenomena, without considering the contribution of all components of the system, and especially without considering water. however, the function of single biomolecules is highly related to their molecular structure, which in turn is inf luenced by all components of the system, therefore biomolecules are not to be seen as separate from surrounding components. moreover, their molecular structure is highly related to the creation of hydrogen bonds with the surrounding water molecules. therefore, in aquaphotomics, the water molecular structure of a bio-aqueous system is considered as a global ‘mirror’ reflecting the state, dynamics, behavior and ‘functionality’ of the respective system. table 2. example of two entries in the aquaphotome database in the nir region (1st overtone of water oh stretching vibrations, 1300-1600 nm) showing how development of mastitis influences the water matrix of milk and how increasing temperature influences the water matrix of ultrapure water. wamacs perturbation systemc1 c2 c3 c4 c5 c6 c7 c8 c9 c10 c11 c12 1416nm down 1436nm down degree of mastitis increasing cow’s milk7 1410nm up 1492nmdown temperature increasing (6-80 °c) ultra-pure water8 17aquaphotomics – origin, concept, applications and future perspectives 2.3. aquaphotomics: from single disciplinary to multidisciplinary approach water has been studied by different disciplines in many different ways and all of them use their own particular terminology. it is quite difficult to translate scientific findings from one area into another. aquaphotomics provides an opportunity to start building up a “water vocabulary”5 where the water vibrational frequencies, i.e. water absorbance bands (wabs) are the “letters”, and the water absorbance spectral patterns (wasps) are the “words” identifying different phenomena in order to translate findings of water between different disciplines. these letters and words create fingerprints that are stored in the aquaphotome database, per bio aqueous system and ‘perturbation’, which can be physical (temperature, humidity, pressure, electromagnetic radiation, and so on), biological (disease, certain enzymes, dna, and so on), or chemical (concentration of salts, and so on) (as presented in table 2). 2.4. aquaphotomics: from a reductionist to a global and integrative approach genomics, proteomics, metabolomics, and other “omics” disciplines have revolutionized life science. however, these disciplines study isolated elements, therefore reducing the system to its parts. systems biology and other functional “omics” disciplines integrate proteomics, transcriptomics and metabolomics information to provide a better understanding figure 2. water mirror approach: just like the surface of the lake reflects its surroundings, the water on a molecular level is behaving like a mirror – its spectrum reflecting all the molecular components and influences of surrounding energies. 18 everine b. van de kraats, jelena s. munćan, roumiana n. tsenkova of cellular biology, thereby taking a more integrative approach, but still integrating isolated elements. aquaphotomics is introduced as a global and integrative approach (figure 3). all elements investigated in other “omics” disciplines can also be investigated through measurements of the water that surrounds them, an ‘indirect’ type of measurements where water serves as a sensor and an amplifier.20 the status, dynamics, and functionality of an intact system can also be measured directly with aquaphotomics, without reducing the system to its parts, by e.g. measuring the skin, the leaf and so on. 2.5. aquaphotomics: from a static, destructive/invasive to a dynamic, non-destructive/non-invasive approach in “omics” disciplines such as genomics or proteomics, creating databases and further using them for understanding biological processes, requires isolation of individual elements (genes, proteins) one at a time, making such analyses extremely time-consuming and laborious. it requires the destruction of the analyzed object and thus provides only a single time-point (static) picture of the processes. considering the speed, plasticity and multifactor-dependence of biological processes it is clear that such static one-at-a-time approach should be complemented with more dynamic and real-time methods. the aspect of dynamics has been partly addressed by metabolomic profiling, where a snapshot of the physiology of the cell at a specific moment can be acquired. even though metabolomics and aquaphotomics are taking completely different approaches, they try to solve the same problem – to provide a systematic view of the processes with time-dependent information of their interconnections. in contrast to metabolomics, aquaphotomics does not destroy the sample with the measurement, therefore it can study the same object  fast, non-destructively, non-invasively and  continuously, thereby it is able to monitor ongoing processes dynamically. through an understanding of water–light interaction dynamics and its relation to biological functions, aquaphotomics brings together the knowledge acquired by other “omics” disciplines describing single elements of biological systems and upgrades it to a systemic, integrated level as water does in biological and aqueous systems. 2.6. aquaphotomics: relationship to conventional spectroscopy the aquaphotomics approach is complimentary to the conventional spectroscopy approaches, too. in most of the vis-nir-ir spectroscopy studies, the water absorption bands are considered as masking the real information. for example, in order to measure bio molecules like proteins and glucose, water is evaporated in order to “see” better the absorbance bands of glucose. in contrast, in aquaphotomics, the  water spectral pattern  is considered as  the main source of information. water is the matrix, the “envelope”, the “scaffold” of the system.21 figure 3. aquaphotomics encompasses all other “omics” disciplines, providing an integrative approach to studying aqueous and biological systems. 19aquaphotomics – origin, concept, applications and future perspectives in aquaphotomics, the ‘functionality’, the biological state, the biological reaction to a change (dynamics) of the bio-aqueous system is the key, instead of the presence of individual molecules. in most conventional spectroscopy studies, quantitative models are made for each separate component to be used to diagnose a system, where combining the models multiplies the errors thereby producing inaccurate results. in aquaphotomics, instead of looking for the individual components, the water spectral pattern is used as a global marker, and monitoring this marker can provide information about changes in the system. in aquaphotomics analysis, specific water molecular structures (presented as water spectral patterns) are related to the status, dynamics and ‘function’ of the bio aqueous systems studied, thereby building an aquaphotome – a database of water spectral patterns correlating water molecular structures to specific ‘perturbations’ (disease state, contamination state, reaction to light, change in temperature, and so on). the process of extracting information from water spectra in aquaphotomics requires a field-specific approach.6 3. applications aquaphotomics is well developed in the visible and near-infrared range of the spectrum. aquaphotomics is used for fundamental studies as well as many field applications, where various spectroscopic techniques and measurements setups and devices can be applied, such as transmission and transflection spectroscopy, using handheld devices or benchtop systems. the nir range is especially suitable, the perfect window for non-invasive measurements of aqueous systems and living biological systems, as nir light can penetrate deep (1-10 mm)22 into the aqueous systems, and does not get fully absorbed, making it possible to measure the transflectance spectrum of the light that comes back out of the bio-aqueous system after interacting with the water and other components of the system. in the next sections, a brief overview of the various areas of aquaphotomics applications will be given. 3.1. basic studies and solute measurements and analysis it is well established that different water species, for example, water dimers, trimers, hydration and solvation shells, contribute very specifically to the spectrum.23–25 the changes in water spectrum accurately and sensitively reflect the changes of water molecular species, hydrogen bonding and charges of the solvated and solvent molecules or clusters. big data sets of water spectra acquired under various perturbations reveal immense information about the water molecular system dynamics and the role of water in bio-aqueous systems (‘functionality’). one of the proof-of-concept studies showing that water behaves as a mirror on a molecular level had an objective of measuring concentrations of different salts ranging from 0.002 to 0.1 mol/l.26 salts were used to demonstrate the water mirror approach since they do not have absorption bands in the nir range, therefore any result would be entirely due to changes of water matrix in response to perturbations of salts at different concentrations. this was also the first work using nirs to examine the effect of salts in such low concentrations. in a multi-center study, with three different locations and three different spectrometer systems, it was demonstrated that the water mirror approach of aquaphotomics enabled predictions of concentrations with a limit of detection at 1000 ppm level, which indicates that under specified conditions, aquaphotomics approach improved the detection limit for nirs around five times.27 a recent paper on the essentials of aquaphotomics explains the details of the experimental methodology, chemometric tools aquaphotomics uses and how the information on changes of the water matrix in response to perturbation of interest can be extracted from the complex water spectra.6 this paper shows how simple tools, such as spectra subtraction can reveal that salts (potassium-chloride in the concentration range of 10-100 mm) do change the water molecular system and that change is reflected in the absorbance spectra of salt solutions (figure 4).6 figure 5 shows the aquagrams corresponding to those solutions. aquagrams are a visual representation of a wasp – this type of graphs displays the normalized absorbance values at the selected wabs. aquagrams are very convenient visual tools to explore the differences between different perturbation steps, or different groups of interest. using the same concept, other molecules – single or in mixtures, in minute concentrations were measured such as monoand di-saccharides.28 this was the first research confirming the applicability of nir spectroscopy for qualitative and quantitative analysis of mono and di-saccharides at millimolar concentrations with the detection limit of 0.1-1 mm. figure 6 shows the aquagrams for lactose in 0.02-100 mm concentration range depicting that higher concentrations of lactose increase strongly hydrogen-bonded water, i.e. act as structure makers, and decrease weakly hydrogen-bonded water. similar findings have been reported for proteins in solution,29 metals in solution,30 etc. 20 everine b. van de kraats, jelena s. munćan, roumiana n. tsenkova figure 4. difference absorbance spectra in the spectral range of 1300–1600 nm (oh first overtone) of pure water and aqueous solutions of potassium-chloride in the concentration range of 10–100 mm. the average spectrum of pure water was subtracted from the spectra of potassium-chloride solutions.6 figure 5. aquagrams of aqueous solutions of potassium-chloride in the concentration range of 10–100 mm in the spectral range of 1300– 1600 nm (oh first overtone).6 21aquaphotomics – origin, concept, applications and future perspectives contrary to the common understanding of overtone spectroscopy (100 to 1000 times lower absorbance than in the mid-ir range), it has been shown that even very small concentrations31 of the solutes could be measured with nir. the water-mirror approach provides measurements of solute concentrations previously thought impossible at ppm,30–32 even ppb levels under certain experimental conditions.30,33–35 apart from the concentration of analy tes, this approach also was successfully applied to the measurement of physical parameters of water systems, such as ph and acidity,36 and the effects of mechanical filtration on water.37 thus, aquaphotomics contributed to basic knowledge about water-light interaction under perturbations and showed potential for fundamental applications. 3.2 protein studies through work in the field of protein-water interactions, aquaphotomics provided insight into their dynamics and the significant role water plays in their functionality. one of the first studies analyzed prion protein isoforms38 – the proteins which are the cause of neurodegenerative diseases. one of the possible mechanisms of converting the protein into the misfolded form was thought to be binding of manganese (mn) instead of copper (cu). the aquaphotomics analysis of mn and cu prion isoforms in water solutions revealed that while binding of copper resulted in increased protein stability in water, the binding of manganese resulted in protein instability and the subsequent changes led to fibril formation. subsequently, another study investigated the formation of amyloid fibrils39 – another type of protein linked to neurodegenerative diseases. changes during fibrillation of insulin were monitored in 2050–2350 nm and 1300–1600 nm spectral regions, covering the bands related to protein and related to water absorption. the results showed that all the steps of conformational changes of the protein, confirmed by the results in 20502350 nm region were reflected also in the changes of the water molecular network in the 1300-1600 nm region (figure 7). these studies unquestionably demonstrated one fundamental fact – proteins and water act together – they figure 6. aquagrams of lactose solutions in 0.02–100 mm concentration range. the radial axes are the 12 water matrix coordinates (wamacs) and the dynamic changes for low to high lactose concentration from structure maker to structure breaker properties – the water spectral pattern (wasp) changes gradually and the dominance of highly hydrogen-bonded water structures increases with increasing lactose concentration. figure is adapted from original.28 22 everine b. van de kraats, jelena s. munćan, roumiana n. tsenkova are a system. proteins are not isolated entities in an inert medium, and all the complexity of their function in living systems can only be understood if the water is recognized as an active part of it. 3.3. water quality monitoring water monitoring is one of the most natural applications of aquaphotomics. since measurements of very small concentrations of solutes was proven to be achievable using salts as model systems,40 the next direction of research was concerned with detection of pesticides (alachlor and atrazine, concentration from 1.25 – 100 ppm) which were measured with high accuracy by applying aquaphotomics principles achieving the detection limit of 12.6 ppm for alachlor and 46.4 ppm for atrazine.40 a great step forward in water quality monitoring was made by moving on from the detection of individual contaminants to monitoring the water by utilizing the water spectral pattern as a holistic, integrative marker.41 the proposed concept has significant advantages – it allows cost-effective, reagent-free, continuous screening of water quality where even small disturbances are reflected in the water spectral pattern which serve as a signal for possible contamination, reducing the possible need for conventional solute analysis.41 the concept is radically novel, because it shifts the perspective of water quality defined by a set of physico-chemical and microbiological parameters to the definition of water quality as a water spectrum within some defined limits – i.e. the spectrum integrates the influence of all single markers into one integrative, holistic marker which can be easily monitored in real time. the applicability of the proposed concept was evaluated on different types of water solutions (acid, sugars, and salt served as model contaminants) as well as in real life groundwater system.41 in addition, the same principles of using the water spectrum as an integrated marker characteristic for each water was applied for discrimination of commercial mineral waters42 and for discrimination of water before and after filtering as mentioned earlier.37 3.4. food quality monitoring most fresh foods contain more than 70% water, while fresh fruits and vegetables can contain up to 95% water.43 thus the quality is deeply related to their water status. nir spectroscopy (780 – 2500 nm wavelength region of the electromagnetic spectrum) has been used as a nondestructive tool for food quality monitoring for a long time.44 it has been found that in many foods the nir signal is dominated by the absorbance of water and multivariate analysis of nir spectra frequently demonstrates that the water absorbance band, located around 1450 nm, is the main contributor to quality prediction.2 this confirms that water status is a key indicator of food quality. aquaphotomics has been applied to understanding the role of water in food quality, for instance in the detection of surface damage in mushrooms,45,46 quality monitoring of milk,47,48 detection of honey adulteration,49 monitoring of the cheese ripening,50 investigating sugars in dehydration of apples51 and apple sensory texture,52 influence of packaging materials on cheese and winter melon53 and many more.43 3.5. materials and nanomaterials studies aquaphotomics studies on water-material interaction hold great promise in understanding some of the figure 7. time dependency of water spectral changes along the fibril formation process depicted by aquagrams. (a) 6 to 10 min for nucleation. (b) 10 to 18 min for elongation. (c) 18 to 30 min for the equilibrium phase. the wasp is plotted every 1 min, starting from the 6th minute, and those at 6 min, 10, 18 min and 30 min are colored by blue, green, orange, and red, respectively, the rest are colored grey. figure adapted from original.44 23aquaphotomics – origin, concept, applications and future perspectives very complex properties that are of interest for many applications such as wettability or biocompatibility. recent aquaphotomics studies utilizing timeresolved ir spectroscopy are excellent examples of other regions in em spectra that contribute to our understanding of water-light interaction and the functionality of different water species in the biocompatibility of polymers.54–56 other studies revealed crucial importance of ratios of different water species that contribute to excellent wettability of titanium dioxide surfaces.57 more recent studies explored the state of water in hydrogel materials of soft contact lenses58,59 – something that was in the past exclusively done using destructive calorimetric methods, and now for the first time performed on lenses in hydrated conditions similar to physiological conditions – these studies revealed that the water spectral pattern holds information about degree of damage of polymer networks and of protein deposits on the surfaces of worn contact lenses. they show the potential of using aquaphotomics in the exploration of water and hydrophilic materials at the same time in a completely non-destructive manner.  other aquaphotomics studies showed how nanomaterials shape the water matrix. for example, studies showed that fullerene-based nanomaterials in very low concentrations act as water structuring elements.60–62 this finding may actually provide the explanation for the peculiar findings of their excellent antioxidant and radioprotective properties which far exceed theoretical calculations based solely on fullerene structure.63 similar to the findings on biomolecules and water interaction, nanomaterials, or materials in general should not be viewed as systems functioning in an isolated manner – they form a system when they interact with water, and this results in the functionality and the properties as we know them. 3.6. microbiology studies aquaphotomics made a significant contribution to the field of microbiology by not only providing a fast and nondestructive analysis, but by contributing to better understanding of the mechanism of action of some microorganisms.64–66 an example of such an application was in growth monitoring of probiotic, non-probiotic and moderate bacteria strains.65 the three groups could be classified according to their probiotic strength with high accuracy – and each bacteria strain influenced the water in a specific way producing unique spectral pattern (figure 8). the absorbance bands that contributed most to the classification were in the first overtone of water oh stretching vibrations (1300-1600 nm). aquagrams of the three groups are shown in figure 7, probiotic bacteria strains (in red) were characterized by a higher number of small protonated water clusters, free water molecules and water clusters with weak hydrogen bonds.65 the discovery that strong probiotic bacteria shape water by producing more free water and less hydrogen-bonded water species, i.e. they break water structures in a way comparable to an increase in temperature, provides novel insight on their mode of action in biological organisms. another study showed that even in the first overtone of the combination bands of water oh stretching vibrations (1100-1300 nm) the aquaphotomics approach allows successful, rapid selection of probiotic bacteria strains.64 it was shown that the differences in the water spectral pattern of different bacteria strains were related to the presence of extracellular metabolites, which have a different influence on water molecular structure.66 3.7. plant biology studies nir spectroscopy coupled with suitable discrimination analysis provides an opportunity to gain information on the health status of plants in real time and nondestructively, even allowing a biological specimen to remain alive for continuous  in vivo  monitoring during biotic stress such as a viral infection or abiotic stresses such as cold and drought. figure 8. aquagrams of culture media of groups of probiotic, moderate and non-probiotic strains. average values of normalized absorbance values of the water matrix coordinates for each group are plotted on each wavelength axis. figure adapted from original.65 24 everine b. van de kraats, jelena s. munćan, roumiana n. tsenkova aquaphotomics provided a methodology to follow the impact of a virus infection based on tracking changes in water absorbance spectral patterns of leaves in soybean plants during the progression of the disease.67 compared to currently used methods such as enzymelinked immunosorbent assay (elisa), polymerase chain reaction (pcr), and western blotting, aquaphotomics was unsurpassable in terms of cost-effectiveness, speed, and accuracy of detection of a viral infection. the diagnosis of soybean plants infected with soybean mosaic virus was done at the latent, symptomless stage of the disease based on the discovery of changes in the water solvation shell and weak ly hydrogen-bonded water which resulted from a cumulative effect of virus-induced changes in leaf tissues. tracking the cumulative effect of various, probably even unknown biomarkers of viral infection in leaves provided grounds for successful, early diagnosis based on aquaphotomics principles. similarly, different water spectral patterns were found in leaves of genetically modified soybean with different cold stress abilities.68  this research on discrimination of soybean cultivars with different cold resistance abilities has proven that resistance to cold can be characterized by different water absorbance patterns of the leaves of genetically modified soybean. again, different genetic modifications resulted in a multitude of bio-molecular events in response to cold stress, whose cumulative effect was detected as a specific water spectral pattern of leaves – i.e. the higher the cold resistance, the higher was the ability of cultivar to keep the water structure in less-hydrogen bonded state, providing a supply of “working water” in the conditions of decreased temperature. in another study, aquaphotomics was applied for exploration of the remarkable property of extreme desiccation tolerance i.e. the ability of some plants, called resurrection plants, to survive extremely long periods in the absence of water and then to quickly and fully recover upon rewatering.69 application of aquaphotomics to study one such plant haberlea rhodopensis during dehydration and rehydration processes, revealed that in comparison to its biological relative, but a non-resurrection plant species deinostigma eberhardtii, h. rhodopensis performs fine restructuring of water in its leaves, preparing itself for the dry period. in the dry state, this plant drastically diminished free water, and accumulated water molecular dimers and water molecules with 4 bonds (figure 9). the decrease of free water and increase of bonded water, together with regulation during drying which is directed at preservation of constant ratios of water species during rapid loss of water, was thought to be the underlying mechanism that allows preservation of tissues against the dehydration-induced damages and ultimately the survival in the dry state, as well as resurrection to its fully functional state upon rewatering. 3.8. bio-measurements, bio-diagnostics, and bio-monitoring as briefly mentioned in the introduction, aquaphotomics was founded as a novel discipline on the applications of nir spectroscopy for milk quality analysis and cow mastitis (mammary gland infection) diagnosis.1,33,47,70 these works showed that as the various milk components change during the different stages of infection, they influence the water matrix of milk differently, therefore water spectral patterns found by the aquaphotomics analysis are suitable as a biomarker for diagnosis of mastitis.71 furthermore, for blood, and urine, it was shown that water spectral patterns were able to function as a biomarker. the water spectral patterns of blood, milk, and urine of mastitic cows, revealed that the same water absorbance bands are activated in different body fluids in response to the presence of disease.33 not only the presence of disease can be detected using aquaphotomics principles, but also basic physifigure 9. dynamics of different water species (si = water molecules with i hydrogen bonds, sr = protonated water clusters) during dehydration and rehydration of haberlea rhodopensis and deinostigma eberhardtii. relative absorbance of water species in haberlea rhodopensis (a) and deinostigma eberhardtii (b) during desiccation and subsequent rehydration.69 25aquaphotomics – origin, concept, applications and future perspectives ological changes can be tracked. for example, the water spectral pattern of urine was used to detect the ovulation period in the giant panda,72,73 as well as in the bornean orangutan,74 and the water spectral pattern of milk was used to detect the ovulation period of dairy cows.75 the method proved to be able to detect hormonal changes in a very low  range (0.80 ng/ml to 127.88 n/ ml)73 more rapidly and therefore can be practically done more often than conventional analysis and without using reagents. aquaphotomics has also been applied in the human medical field, one of the earliest works utilized nir spectra (600-1100 nm) for detection of hiv-1 virus in plasma.76 the results yielded a good correlation with those obtained by the reference elisa method suggesting that this can be a rapid and accurate screening method for hiv-1 infection, and for other viral diseases too. feasibility of discriminating different organ tissues was shown in brain, liver, kidney and testes tissue of mice,77 and detection of concentrations cu, mn, fe in the same tissues was also reported.78 one of the groundbreaking works dealt with the detection of uv induced changes in dna based on the changes in the water spectral pattern of dna solutions.79 non-invasive identif ication and measurement of very low concentrations of 3d conformations of dna were possible, see figure 9. the formation of uv-induced cyclobutane pyrimidine dimers caused an increase of strongly hydrogen-bonded water, which has been found in previous studies to be typical for oxidative stress. apart from the effect of uv radiation, even the dose of irradiation could be measured indirectly by the changes induced in the water spectral pattern, i.e. in the strength of water covalent bonds and other changes in the water matrix. figure 10 shows the y-fit and regression vector for dna concentration. aquaphotomics was also proposed for in  vivo  monitoring of topical cream effects,61,62 and in recent international conferences, other applications e.g. in the field of therapy monitoring have been proposed, such as dialysis efficacy, which uses a similar approach to what was used for water quality monitoring. it is expected that new publications about more aquaphotomics applications will follow. the next step with great potential is to bring these aquaphotomics applications to the market. 4. considerations as water is highly influenced by its environment, depending on the required limit of detection for the application, environmental changes have to be taken into account. in previous work it has been recommended that parameters of the environment, such as temperature, pressure, humidity, should always be recorded to match every measured spectrum.6 sensitive applications for subtler changes in the water matrix may require monitoring of high and low frequency measurements, magnetic fields, co2 levels, background radiation, and other factors such as periodical changes in the year, related to moon phases or sun spot activity, to interpret water spectral changes. all these measurements and controls are needed in order to confirm that the water spectral pattern related to each of these environmental perturbations is different from the water spectral pattern found for the perturbation of interest. figure 10. nirs regression model for dna concentration. (a) y-fit for dna concentration of partial least squares regression (plsr) with pretreatment by mean centering, smoothing (21 points), orthogonal signal correction (osc) (one component), and active class validation. n = 32, number of applied latent variables = 2, rcal = 0.9978, sec = 0.3882, rval = 0.9860, secv = 1.5131. (b) regression vector of the plsr calibration model for dna concentration showing characteristic water peaks at the 1400–1500 nm spectral interval.79 26 everine b. van de kraats, jelena s. munćan, roumiana n. tsenkova when it comes to unknown possible influences, not only environmental but also related to drift of instrument and more, it has been recommended to scan pure water samples (as environmental control) at regular intervals during the experiments.6 in subsequent analysis the spectra of these pure water samples are used for correction, either by using emsc (extended multiplicative scatter correction) using the first loading of pca (principle component analysis) as an interferent spectrum,26 or by applying a closest spectrum subtraction technique,80 in order to remove environmental influences not concerning the perturbation of interest. it is not always possible to ‘remove’ an influence entirely, but knowing its spectral pattern will help separating it from the spectral pattern of the main perturbation. for that purpose, new data analysis methods have to be explored and developed. 5. future perspectives with the theoretical and technological advancements in spectroscopies in the entire em range the development of aquaphotomics based applications has become more feasible. analytical tools and data processing have improved significantly and the miniaturization of sensors on the technological side has opened up the potential for high accuracy field applications being more cost-effective at the same time.81 also, the mentioned advantages of being nondestructive, fast and capable of comprehensive system (real-time) monitoring and diagnosis provide great potential to complement conventional technology used to perform similar tasks. as discussed in this paper, aquaphotomics can be applied in many fields, such as agriculture (plants and animals), biotechnology, life science, medicine, industry, and basic science. further pilot studies in real-life settings, combined with market research and sensor design specific for each application will pave the way towards implementation of aquaphotomics in daily life. in our opinion, cross-disciplinary research can also benefit from aquaphotomics by considering water as the matrix of life. water is the bridge and provides a new common platform for science and technology,4 a common ‘mirror’ for all disciplines. for example, the fractality and coherence of liquid water, as predicted by quantum electrodynamics, have been shown through nir spectral analysis of the isosbestic behavior induced by temperature perturbation.82 applying the concept of aquaphotomics in this way opens up the potential for exploring systems on micro and macro level, from cells to space. in the future, the areas of biotechnology and life science, as well as basic science of water will benefit as aquaphotomics provides a complimentary way of exploring water – through its interaction with matter and energy in real time. these interactions can be observed in various systems, such as liquids, cells, whole organisms, space, using the available technology and its upcoming advancements. a new language around water spectral patterns per system and perturbation, such as being built with the aquaphotome database, will enable new discoveries and understanding of bio aqueous systems and the role that water plays. next steps, such as the further building of the aquaphotome database, will stimulate cross-disciplinary science and will help understand the role of water as a functional ‘biomolecule’ in the dynamics of life. 6. acknowledgements author j.m. gratefully acknowledges the financial support provided by japanese society for promotion of science (p17406).  references 1. r. tsenkova, s. atanassova, s. kawano, k. toyoda, j. anim. sci. 2001, 79, 2550. 2. r. tsenkova, j. near infrared spectrosc. 2009, 17, 303. 3. y. ozaki, in near-infrared spectroscopy: principles, instruments, applications, ed. by hw siesler, y. ozaki, s. kawata, hm 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l. corbetta, s. li, j. li, g. m. rossolini, l. m. fabbri, w . guangfa, y. qin tai. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all rel evant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. firenze university press www.fupress.com/substantia webinar stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes. this document is the direct transcription of a webinar organized by prof. l. corbetta of the university of florence on may 19th, 2020. scientific coordination: lorenzo corbetta associate professor of respiratory diseases university of florence scientific and website director of the european association for bronchology and interventional pulmonology (eabip) organizing secretary: consorzio futuro in ricerca via saragat 1 – corpo b – 1° piano | 44122 – ferrara cfr@unife.it translation coordination and editing: giorgia biagini, md info@covid19expertpanel.network webinar’s partecipants: prof. lorenzo corbetta university of florence prof. shiyue li first affiliated hospital of guangzhou medical university prof. jing li first affiliated hospital of guangzhou medical university prof. gian maria rossolini university of florence prof. leonardo m. fabbri university of modena & reggio emilia prof. wang guangfa peking university first hospital prof. yang qin tai third affiliated hospital of sun yet-sen university corresponding author: lorenzo.corbetta@unifi.it substantia. an international journal of the history of chemistry 4(1) suppl. 1: 967, 2020 issn 2532-3997 (online) | doi: 10.13128/substantia-967 http://www/ http://www/ http://www.fupress.com/substantia l. corbetta et al. 2 “stand on the same side” videoconferences https://www.covid19expertpanel.network “implementing a science-based lockdown exit strategy is essential to sustain containment of covid-19. china’s experience will be watched closely, as other countries start considering—and, in some cases, implementing—their own exit strategies” the lancet, volume 395, issue 10232, 18–24 april 2020, pages 1305-1314 this phrase expresses the purpose of this program called “stand on the same side against covid-19” that takes advantage of the new and rapid digital technologies to put together several experts worldwide. it’s a global space were many countries hit by sars-cov-2 can share only scientific information in order to face the pandemic. may, 19th 2020, china-europe videoconference “stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes” professor corbetta: good morning to our friends from europe and america, and good afternoon or good night to our chinese friends. welcome to the second webinar of the project stand on the same against covid-19, that was started from the friendship with our chinese colleagues to recommend, to take and to share with the chinese colleague the experience to implement a science-based lockdown exit strategy. this project comes from years of collaboration with our colleague from guangzhou and also other chinese universities. now we have an agreement between our university of florence and their university of guangzhou. the first webinar on preventing a second wave of covid19's outbreak was a big success of audience with 5,000 participants, and now is available the video recording and the transcription in the website of the project https://www.covid19expertpanel.network/. this is an ideal graphic of an estimated picture of the diagnosis for covid-19: https://jamanetwork.com/journals/jama/fullarticle/2765837. there are many, many questions that are open, and we will try to answer during this conference. thank you to all the speakers and all the participants, and in particular to professor shiyue li, thank you very much. now i give theword to my friend professor li, please professor shiyue li. professor shiyue li: thank you very much, professor corbetta. good morning, good afternoon to the european colleagues and good morning to the latin american colleagues, and good evening to the chinese colleagues. welcome to the webinar. in this meeting we are focused on the diagnosis, screening tools and pathway for the clinical and prevention purpose. the main purpose is that we are still on the same side against the covid-19: the chinese colleagues, european colleagues and the other colleagues. before the meeting, i would like to thank professor corbetta for organising it, doing a lot of things. also thanks to the pharmaceutical company to support this meeting. thank you so much. next, i would like to call this meeting's host, professor jing li from guangzhou institute of respiratory health. please, professor li. professor jing li: in this webmeeting between europe and china i'm so glad to introduce the first speaker, professor gian maria rossolini. he is the professor of microbiology and clinical microbiology at the department of experimental and clinical medicine of the university of florence, and he's also the president of the degree course in the healthcare of university of florence, and also the director of the microbiology and virology unit, and of the laboratory diagnostics of the surveys department, careggi university hospital. he's going to give us a talk on the topic of characteristics of covid-19 and laboratory diagnosis. now please, professor rossolini. professor rossolini: so, i would like first of all to thank professor corbetta for inviting me to join this webinar, and to share with you our experience so far with the diagnosis of covid-19 disease and condition and subsequent to infections. the purpose is just to present a brief overview of the diagnostic approaches that we are using and we have been using in our setting, in order to make some discussion according to different experiences. well, so we have started in this field since three months, more or less, so it's a very early diagnostic work flow. https://www.covid19expertpanel.network/ https://www.covid19expertpanel.network/ https://jamanetwork.com/journals/jama/fullarticle/2765837 stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes. 3 the issues that we now face for covid-19 microbiological diagnosis are first of all related with confirming the suspect cases in order to decide whether they have to go in the covid or not-covid pathways inside of the hospitals, or if they should be isolated. we have also had to confirm viral clearance after infection, which is important to release patients and to take out the isolation from procedures. then a very important issue, that i have seen it will be further discussed in other presentations in this webinar, is about the need for identification of infected subjects that are asymptomatic or that have unrelated disease but no covid symptoms. finally, there is another need with surveillance of the prevalence of infection, and with declaring a protection status after infection. this part is still under debate, so i will mostly focus on the first three issues during this brief presentation. just going through the confirmation of suspect cases and viral clearance, we have at least three different approaches. one is the molecular detection of viral rna, which is the most common, the reference approach that all laboratories are now going for. there is the possibility of molecular detection of viral proteins, which is something under investigation that could be potentially useful in some settings. finally there is viral isolation, which of course is something of value for reference and for studying the viral biology but is not really feasible in routine diagnostic practice. in fact, so far, at least in our experience, the golden standard for the confirmed suspect cases is represented by the molecular detection of viral rna using different molecular technologies. currently in our laboratory we have implemented a number of different detection systems. this is something unusual for a diagnostic laboratory, because normally in a diagnostic laboratory you have to focus on a single diagnostic system in order to simplify and streamline the workload. this has not been the case for covid, however. these are the different systems that we have in our laboratory. the reason for having such a redundancy is mostly due to the shortage of reagents, in one case and to the different turnaround times that different systems provides. we have different maxi batch systems that can evaluate a large number of specimens in a batch and which provides results in a turnaround time of around four hours. then we have some mini batch systems that are faster and can analyze around 10 specimens per time with a turnaround time of slightly more than one hour, or slightly more than two hours. finally, we have implemented two different ultra-fast systems that work with single cartridge and provide results in less than one hour. with the last system, which was very promising at the beginning, we however have not had a positive experience so far due to mostly false positive results, apparently false positive results. the last system, the isothermal amplification system, which provides results in 20 minutes, is currently in standby in our laboratory and other task laboratories due to these problems. so, quite a broad number of diagnostic systems for covid. this is the current scenario, in order to address the requests and cope with the shortage of diagnostic reagents for covid that we are experiencing due to the pandemic. an issue that i would like to mention in this case is that even with the single cartridge systems, that could be proposed in a point of care format we have experienced that it is very important to look at the amplification cause and to look at the results. so, in our experience it is not possible to locate these systems in the emergency room or in clinical wards unless there is a technician from the lab that looks at the occurrence and experienced it personally from the lab that used to judge them. this is an example of positive curve, which is quite clear. no problem. the reagents reported results as positive and with two targets, but this for instance is an example of a single target positive after the focus cycle, and the systems in this case reported it negative but the curve is convincing. so, we have reassessed it with another system and it was in fact positive even at low viral loads. this is an example of a false positive. a curve which is not really convincing, and in fact this was a false positive, and a system reported this result as a positive. so, a warning. always have a look at amplification curve. do not trust entirely only to the machine, which is at least in our experience important to care for. this picture has already been showed by professor corbetta. i wanted just to refer to this, which is an ideal and schematic representation of virological parameters in covid infections, just to mention that while pcr positivity tends to remain positive for weeks, in some cases, after clinical recovery. in late-stage it may be seen that positivity is present in lower respiratory tract specimens, rather than in nasopharyngeal swabs. so, we may have different results depending on the different specimens that we test. it's also still partially unclear if in this late stage the subject is still infecting or not. according to this picture https://academic.oup.com/cid/advance-article/doi/10.1093/ci d/ciaa449/5821311 virus isolation is only possible during the first days, but this result has been reported after investigation of, so far to my best https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa449/5821311 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa449/5821311 l. corbetta et al. 4 knowledge, only nine cases of patients. i think that this is still a grey zone and we have to understand if really in these circumstances the patient is infectious or not. virus is not routinely searched for and normally not detected in bloods, but there was this very interesting report that appeared recently on clinical infectious disease which correlated the presence of rnaemia with the severity of disease and even with the il-6 levels. so, this might be just an indicator and marker for the severity of disease. we normally do not routinely search virus in serum, but this is something that could be considered according to the experiences of this covid. another interesting perspective could be that of looking for viral proteins in nasopharyngeal swabs. there is a commercial system that has recently been proposed, which suggests that we could look for antigen, viral antigen, in nasopharyngeal swabs during the early phases of infections. the system is based on lateral flow immunoassay technology, so it provides results in a very short time frame of around 10 minutes. the susceptibility, the reported sensitivity was 84% in terms of comparison of pcr in symptomatic patients. this could be something of interest. we are planning clinical investigation on this, but we have no direct experience. what i would like to underscore, however, is that this system could be useful for mass screening and for screening of asymptomatic patients as well. very recently in the lancet a proposal just appeared for the uk exit strategy from the lockdown by using the type of screening, for mass screening for people. finally, a comment on the antibody response. there have been a number of papers studying the production of different classes of immunoglobulins against viral antigens after infection. i just picked up this one, which was quite recent, just to underscore a few issues: https://www.nature.com/articles/s41591-020-0897-1 for instance, antibodies can be detected quite early after the symptoms' onset. in these cases, both the igm and igg tend to appear at the same time. in some cases, there is an early appearance of igg, in other cases of igm, but the title of igg tends to be higher than that of igm and the positivity also tends to be higher. so, in our experience in fact that the igg were more reliable as a serological marker for infection than igm, probably because the systems that we currently use for igm are less reliable than for igg. this is at least our experience. so, serological testing, considering these results, could be useful and helpful in some cases for diagnosis of pcr-negative patients. these are not very common, but in our experience it may occur patients who present a picture that is suggestive of covid-19 infection but nasopharyngeal swabs repeated testing is negative, and the patient is not so ill that we can do bal testing. at least in two cases we have experienced positivity. this is an example of how serology could be even helpful for diagnosis in some cases. the other interest for serology, at least in our experience, is that of using serology for identification of asymptomatic infections. also the authors of this paper just suggest this as a possibility. in fact, for identification of asymptomatic infections, there are at least three different strategies that can considered. one is that of viral testing in swab or saliva, but this of course is unsuitable for universal screening, at least for now, because of the complexity of costs and of the shortage of reagents. in this case, of course, it should be performed a repeated testing at very short intervals considering that we have a picture of the current situation. the second strategy is that of looking for viral antigens. we have already mentioned this before. in this case, this system could be suitable for mass screening, for universal screening. again there is a need for repeated testing, and the question mark open in my opinion here is the sensitivity of the system. so, we have seen that the producer report for this test has sensitivity of 84% but in symptomatic patients. so, we have no information, to my best knowledge, of the sensitivity of this system on asymptomatic carriers. so, if any of you have some information i would be grateful to know some more information about this. the third strategy, which is the one that we have adopted in our setting, is just to screen for antibodies and then on seropositive subjects to confirm viral testing by molecular testing. this is suitable for universal screening. again, there is a need for a repeated testing at intervals that may depend on the local epidemiology. the problem is the serological window. in our experience, i will report just as an example, the results in our hospital. we have tested more than 5,000 asymptomatic healthcare workers with no history of contact with covid patients. of these, we have found around 5% of seropositivity for igg or igm, and of these we found that eventually 20, so 7% of the positive which are pcr-positive for viral rna and so could be classified as asymptomatic carriers. currently in our laboratory we are testing and using a number of different testing symptoms for serology. apart from the lateral flow rapid tests which works with viral lysates, there are some elisa tests that work in batches and some chemiluminescent assays. we are testing with a collection of serums from different types of specimens to compare, and we are making some experience about that. i would be happy to share our preliminary experiences with https://www.nature.com/articles/s41591-020-0897-1 stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes. 5 you if you wish. finally, just to finish, which are in my opinion the open issues in diagnostic microbiology for covid-19. one is that currently sustainability of molecular testing due to the global shortage of reagents. it has been really a big problem, i don't know if it's the same in your cities but at least in our country from the beginning of the pandemic until now, and even more with the reopening, there will be a shortage of these types of reagents. then there is to clear which is the relationship between viral shedding versus the infectivity. so, all those cases that are clinically recovered and that retain positivity for a single viral target, for instance the n. normally it's the n gene if the subject is infected or not. then there is the development of reliable molecular testing for viral quantification, because so far the systems that we have had are not quantitative, are qualitative. we can have some kind of judgement by cities, but of course this is not precise quantification of the viral load. then the nature and the threshold of protective antibodies still is a matter of debate. of course it would be very interesting to further know and gather information as soon as we have more knowledge about this. finally, something that we have to face is that covid patients unfortunately may have bacteria and fungal coinfections, and this is not uncommon as originally reported. we have to, of course, contextualise the analysis of these types of infections together with covid. i will stop here and will be happy to take your questions. thank you very much for your attention. professor jing li: the issue after all the speakers are finished their talks, and this is a very useful and practical talk on how to diagnose the virus, sars-cov-2 from the virus including rna detection, viral protein protection systems, and viral isolation. also including the serological testing for the antibody igg and igm measurement, and also their clinical implication. thank you, professor rossolini. very practical talk. then we move into the second one, professor leonardo fabbri. he's a professor of respiratory and internal medicine, university of modena and reggio emilia. also he is the eminent scholar of the respiratory and internal medicine of university of ferrara. he's going to give us the talk with the topic of the reality of restarting industrial activities after the lockdown. let's welcome professor fabbri. professor fabbri: good afternoon. thank you, doctor li and corbetta. thank you very much for this invitation to contribute to this interesting webinar. my name is leonardo fabbri. i am a clinician, but recently i have been asked to plan the screening of 1,200 employees of a company that stopped during the pandemic in italy. i will go with you through the process of restarting an industrial activity during (as it is called here) phase 2, it occurs when the pandemic peak is over and the hospital and doctors' emergency is terminated. it's what is going on in italy these days. it's not really terminated, but the situation is much improved and as a consequence both the national and the regional government approved the application to restart industrial activity with very meticulous, specific precautions, and obviously proposing a medical surveillance. the scope of phase 2 is to run business under specific conditions. you have limited industrial activity, you have limitation in transportation and travel. i won't go into the details, because i think you know this from the newspapers. there is a risk of a rebound pyramid, so that everybody is very careful in detecting this danger. due to the political organization of the country that is run by the national government and by the regional government, there is not heterogeneity of intervention. more importantly, we don't have epidemiological data, so we don't know the denominator of the infection. by not knowing that, we get into the issue that was touched by professor rossolini, that is the l. corbetta et al. 6 asymptomatic subject. the phase 2 transition period started last 4th of may, and every week we have a progressive release of restrictions. it's tightly monitored, this phase 2, and already we had three or four micro-epidemics. not in industrial settings, mainly in nursing homes or hospitals. with micro-epidemics they need to establish stricter conditions, but the end of the phase 2, the real end of the phase 2, while it has run for 31st july 2020, will obviously be only when we will have a vaccine and we will be able to work with the presence of sars-cov-2 without the risk of ending up in the emergency room. i list very quickly the current containment options that are logic. first, no worker with covid symptomatic or suspicious symptomatic or subjects at risk because of close contact with covid are admitted at work. that's before even starting. they have under their own legal responsibility to stay home and to be investigated by the local gp and the local authorities. when the workers get to work there is a temperature check, and daily or monthly they are given protection equipment, personal protection equipment, a surgical mask for those who can respect the social distance of 1m, and a more sophisticated protective mask for those who cannot respect the distance of 1m. all the internal gathering places are either closed or restricted, like canteen meetings, and a large part of the administrative work is done as home working obligatory and progressively, at least it's three days per week now. some people's it's four of five days. sanification, of course there are areas within the company where they are protected so whenever it happens that a worker claims symptoms at work can be confined and then transported safely to the local medical facilities. there are very tight limitations of contact with external contractors. the medical surveillance, there is a very meticulous, is planned with the so-called occupational doctor that here is called a “medico competente”, who is in charge. usually they have visit every year, but of course during this period these controls are intensified. the issue of the serologic test that will be the focus of my next part of the presentation, it's very much debated. it has been implemented. we have just started, but just to give you an example, the ferrari company that is in my town already started the serologic testing and including the pcr for those who are positive to the serologic testing. i'll show you some examples. there is a precise algorithm that i would like actually to discuss at the end, hopefully with your feedback, on what to do when you have a positive test. the serology will be performed every two weeks in the first two months, and then every three or four weeks depending on the outcome. the numbers presented in the previous presentation are very encouraging, because health personnel is positive in that kind of range, 5%, and only 5% of the 5%, only 20% is positive to the molecular testing. those numbers are reasonable during this period. there are two aspects of the prevention at work that have been very strongly emphasysed. first, there must be a specific programme for fragile workers, defined as workers of more than 55 and/or with multimorbidity or chronic diseases. just to give you an example, chronic leukaemia, lymphoma, people treated with immunosuppressants or transplanted people have to undergo a specific control. in order to answer the question of the epidemiology of covid-19 in italy, the tracing technology is under development. it will be developed at the national level, but it will be made available also at the company level. this is the algorithm that we plan. i hope you see the pointer. we start with the serologic test for everybody. we recently were asked to include the iga, even if i agree with the previous presentation that the data is really non-existent, particularly in our population. now, let me underline once again what these serologic tests are performing onto people who are asymptomatic. so, all the people are by definition asymptomatic. if they are negative, then they repeat the test every two weeks for two months and then every month. if they are positive, first they are removed from work safely right away. actually, we are trying to abolish this step by having the communication of the positive result directly to the worker via telephone or email so that he get the procedure to follow in case of positivity without getting into the workplace or without meeting the doctor in person. the subject will undergo pcr, nasopharingeal swab for pcr. if the pcr will be negative, then he will go back to work and to the regular screening serologic test. if the pcr is positive, then he will go into the quarantine and followed by the general practitioner, and he will be allowed to come back only when, you will see the criteria at the end but basically you have two pcr negative within 48 hours and asymptomatic for more than five days. when we get the positive pcr, we also remove the subject from the contact at work. we remove the subject again. we keep the subject far from work, but also we search for the close contact at work: if they hear the negative test they will keep going with the regular serologic test. if they are positive then we go to the pcr and removal from work as well. now, the diagnosis, i won't go through it, has been described very carefully in the previous. stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes. 7 particularly i like to think that there are some false negative pcr in patient, false negative, in patients that are in the virus. this is a danger. this has been reported a few days ago, the 14th of may. the proportion, of course, diminishes with time from onset of symptoms, but i think that the serologic test may complement the molecular test to make the diagnosis. the alternative is the serology and the rapid tests. i think that they are not reliable and they are not taking into consideration. there is some evidence that the igm actually occur further before the igg, so when we started to design this strategy we considered to have the igm as a presymptomatic, pre-viral infection in our early detection of viral infection. i'll show you the data: https://academic.oup.com/cid/advance-article/doi/10.1093/c id/ciaa344/5812996 there is not much evidence of that. eventually we agreed with the previous proposals that any of the three of the two, igm and igg, possibly the iga, we have to make experience positive will activate the cascade that brings to the molecular taste testing (ph 42.30). here is a study that reported the median duration of igm and iga. antibody detection, five days since symptoms start, whereas the igg was detected at 14. if you look at the same paper, you can see that there is very much overlap. i don't think we can distinguish the early phase depending on the type of antibody. the outline that also professor corbetta showed suggests that the antibodies may not only be helpful for the screening but also for the diagnosis of disease when the pcr become negative after the disease. let me underline, before i close, that the purpose of screening, of serology in these conditions, in industrial conditions, is just for screening. it's not for diagnosis. the purpose of this exercise is to identify people that potentially are carriers of the virus, to identify them and to obviously protect the individual but also to protect the subjects that are close contacts to prevent micro-epidemic. again, the time course of the antibodies, we have already said that. this is the algorithm that i would like you to comment on at the end and give me any suggestions, because we have 10 more days before we start and if you have suggestions or experience in this field i will be delighted to take them on board and adapt the protocol according to your suggestions. https://academic.oup.com/cid/advance-article/doi/10.1093/c id/ciaa179/5758073 now, this is the afebrile removal from work of the subject that i mentioned to you. he must be afebrile and for more than 48 hours, two negative tests, six days with no symptoms excluding other diagnosis, contacts. there is a meticulous cascade to prevent exposure at work. eventually, i underline the importance of education. the communication, that all the personnel has to be educated on the nature of the disease, on the risk. we are much more worried of the potential infections outside of the workplace, because in the workplace all the technology that prevents from getting the infection that you know, they are familiar, they are released by the government, are followed. the problem is when they are at home, where some relatives may be sick, and transportation. people are now encouraged to use private transportation, not public transportation, because the public transportation first is very limited and second is a unique opportunity to get in touch with people. with this i am finished, and i thank you very much for your attention and for the opportunity to present this plan. professor jing li: thank you, dr. fabbri, for your very fantastic talk on the importance of how to screen the asymptomatic people using the serologic test. also you point out the very significant differences between the screening test and diagnostic test, and also the last one, how to educate and also the communication between people. okay, thank you very much. professor corbetta: okay. it's a real pleasure to introduce professor li jing. professor li jing is professor of medicine and doctoral supervisor at the the first affiliated hospital of guangzhou medical university. she is the director of the department of allergy and clinical immunology, of the guangzhou institute, and specially appointed professor at the loma linda university in the united states, and a member of the european academy of allergology ers and csa (ph 48.03). the title of her presentation is longitude in hematologic and immunologic variations associated with the progression of covid-19 patients. please, professor li jing. professor jing li: yes. thank you very much for inviting me to give this very brief presentation on the study we just published. it's a very nice study, because we look at the longitude and we look at the hematology and immunology variation, and we make the association with the progression of the covid-19 patients. from the contact of the virus, some people develop symptoms because of the immune systems then they make some actions against the virus infection. they will develop some systems systemically and locally, especially the symptoms in respiratory system. when you're looking at the response of the immune system, we can come up with different outcomes. on one side, mild and moderate patients, they have some light or normal or balanced immune response. they will get the outcome of minor symptoms and minor damage, the patient get recovery from the disease. on the other side, some patients have an imbalance of their immune response. some of the turbulence happens. then they have the outcome of severe symptoms and multiple organ failure, and also tissue damage, then have fatality outcome. we point out that a little is known about how different lymphocytes subsets and the dynamic change in the immunohttps://academic.oup.com/cid/advancearticle/doi/10.1093/cid/ciaa344/5812996 https://academic.oup.com/cid/advancearticle/doi/10.1093/cid/ciaa344/5812996 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa179/5758073 https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa179/5758073 l. corbetta et al. 8 related biomarkers differ during different prognosis and outcome of covid-19 patients. the purpose of our study is to address the dynamic change of all these kinds of biomarkers during the time of the disease. (jing li, jaci in press) this is a retrospective study, including 548 covid-19 patients in-hospital, and also it is a cross-session and also a longitudinal study, and we compare all the immunology and haematology biomarkers. then we kind of get the association between these biomarkers, and the different severity and outcome of the patients. you can see we have majority of them, they are mild and moderate patients, and 155 patients with severe of the degree. also we have 48 patients with critical situations. now you can see actually from this different severity of patients, in mild/moderate patients we have very little of them they have fatal outcome. also in the very severe degree of the disease, like critical situation, we have some degree of survival. this is very interesting, that different mechanism on baseline that may be associated with the survive and non-survive outcome. then on the admission of the hospital, we can see the survivor and non-survivor, they have a very significant difference in terms of the haematology indexes like leukocytes and neutrophils. they have a very significant higher level in the non-survivor compared with the survivors. however, the lymphocytes, eosinophils and basophils have a very significant lower level in the non-survivor compared with the survivors. also you can see the other ratio indexes in terms of nlr and plr. we have a significant increase in this ratio in the non-survivors. so, just on the admission they have significant differences between the two outcome groups. in terms of the t cell subsets level, you can see the dramatic loss of cd4 and cd8, and also the t lymphocyte size in very severe and non-survivor patients. cd4 and cd8 ratio didn't change much among the disease survivor. however the cd4 over cd8 ratio increase in non-survivors indicates the greater loss of cd8 t cells might lead to the fatal outcome in our patients. regarding the other infectious related parameters, such as saa, crp, ferritin, and d-dimer, we can see some significant increase in the non-survivors when compared with the survivors on the admission of the hospital. also, il-6, the level of il-6 and pct also increases significantly in this group of patients as well. this is the longitudinal dynamic change of the haematology and immunology indexes, they show different patterns. the first pattern, you can see the eosinophils and the lymphocytes and the platelets. the empty group shows the survivor patients, and solid group represent the nonsurvivor. you can see a significant continual upward trend in the survivor patients, regardless of their severity, but the downward or on the very low level, or even continued to decrease in their levels in the non-survivor patients. pattern three, we have no clear patterns. there is no difference between survivor and non-survivor patients but in some of the parameters, like this group, there is a very large amount of the biomarkers, they maintain a significant lower level and show a slightly downward trend in the survivor. neutrophils to lymphocytes ratio are six and some other parameter related to the infectious also show these patterns. so, you can see different groups of the parameters, they show different trends in the level between the survivors and non-survivors. this is some more of the cell to cell and index interaction network. we can see on admission non-survivors and survivors. you can see interaction amount, haematology and immunology cells in both survivor and non-survivors. on the admission, the cell to cell interaction and the interaction between the indexes have a very strong relationship in the non-survivors and survivors, but with different patterns. indicate immunology profile associated with host antiviral defence vary in different studies. when we see the interaction in our patient at the end of the hospitalization, comparing the subsiding of the cell to cell interaction in the survivors you can see very light interaction between these indexes. our nonsurvivors still have a very strong interaction between cells and the indexes, and these suggest higher virus load plus inflammatory turbulence might contribute to the mortality of this group of patients. this is the principal component analysis for immunology cells and biomarkers, and you can see from the colour we can separate the patients between the survivors and non-survivors, and also on the admission and at the end of the hospitalization. the top three positives to contribute to index on admission are lymphocytes, cd4+ t cell and cda+ t cell. at the end of the hospital are the platelets, lymphocytes and eosinophils. top three negatively-contributing indices include crp, ferritin, and saa. this is very interesting to us. we have also done some predictive factor for the fatal outcome for the survival curve, and when you see different haematology and immunology parameters you can see the eosinophils count, platelet count, and the differences of the eosinophils count between the end hospitalisation. on admission there are also lymphocyte differences. you can see eosinophils difference and platelet differences and also other parameters' differences. if you have lower level, or the differences of these parameters getting higher, you have lower survival rate in this group of patients. we can see some of the parameters, they have negative contribution, and some of them they have positive contribution to the progression of our patients. the last one, we have a summary of this immunology and haematology indexes. on the admission of the hospitalization, we can see some of our patients, they demonstrate normal level of all these parameters. some of them they have significant increase in the neutrophils and and infectious parameters. also, some of our patients have very low level of lymphocytes, platelets, and eosinophils, even at the beginning of the disease when they are admitted to the hospital and we will monitor their change of this immunology and haematology parameter. if your level recovers to normal range, the ending is recovery and you will be discharged from the hospital, but if you keep higher for the eosinophils or the inflammatory parameters, then maybe you'll end up deceased. also, the lymphocytes, platelets and eosinophils, also if you have the very low level or keep in this very low level, maybe the outcome was not good. so, we have this conclusion of outer interaction among immunology and haematology indices indicate impaired immune response in the covid-19 patient. stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes. 9 restored lymphocytes, eosinophils and platelets could predict recovery. progressive increases in neutrophils and cytokine level were associated with mortality. i would like to thank the leaders of our study, professor nanshan zhong and shiyue li, and also, we would thank all the participant hospitals around our country. thank you very much. lorenzo corbetta: thank you very much, professor li jing. very interesting and this is a very important experience in case of future outbreaks to prevent and to recognise the severe patients. please. jing li: i will continue to host the later section and the next speaker, we'll come to the famous professor of bronchoscopy therapy, professor wang guangfa, and he is the national consultant committee of the public health, and member of the national committee of public health and sanitation in emergency, and also, he has a lot of titles in the national and international society of bronchoscopy, and he also works closely with a lot of chest physicians in the fighting of covid19 in china. he's going to give us a talk of the asymptomatic covid-19, a real risk. now, please, professor wang. guangfa wang: good afternoon, and good evening ladies and gentleman. it's my pleasure to join the webinar and to communicate with our european colleagues and to share with our experience on covid-19. so, i would like to talk about asymptomatic covid-19. is it a real challenge or a real risk? so, i have no disclosure about my presentation. so, covid19 occurred in china in early this year. so, in a very short time, it spread all over china, and even out of china. so, with restrective measures the containment of the disease succeeded. this is the epidemic curve of covid-19 in china. the most dominant measure is the lockdown of wuhan. after one week of the lockdown in wuhan, the epidemic curve changed and it went down. right now in china there are only a few local covid-19 patients. most are coming from abroad: we still are facing a high pressure from the importation of covid-19 cases. so, retrospectively, the success of covid-19 containment in china are visible. we adopted a different, very successful measures, including individual measures, case isolation and management, close contact quarantine, suspension of public gatherings, and mobility restrictions. so, right now, these measures are very, very successful. now, we are facing a new stage. so, everybody is talking about the restart of the economy and work and other social activities. so, for clinical practice in the management of covid-19, we emphasize the early detection, early reporting, early isolation and early treatment. this is also very successful in china, but we are facing a high pressure from the rebound of covid-19 because we have some cases from importation. so, another risk, i think, is asymptomatic covid-19 cases. so, here is a study from nanjing, china. they have reported 24 cases with asymptomatic infection: they are collected from the screening of close contacts. so, five cases developed symptoms during hospitalization. twelve showed a typical chest ct scan of covid-19. five showed a typical presentation as stripe shadowing in the lungs. only seven cases showed a normal ct scan and had no symptoms during hospitalization. so, for these cases, these seven cases, the median age is only fourteen. so, they are a young group. so, that is the report from nanjing. so, here is some report from south korea. so, they have retrospective analysis from over 200 covid-19 mild cases. about 20% were asymptomatic until admission. so, i think most of them were developed symptomatic. so, i don't think they are all symptomatic cases. similarly in the united states, in a nursing facility, so this facility experienced an outbreak of covid-19, 23 residents in the facility have a positive pcr. ten had symptoms on the date of testing, and thirteen were asymptomatic, but among the thirteen asymptomatic cases, ten ones had developed symptoms. so, that means only three were real asymptomatic cases. so, what is the instance of asymptomatic covid-19? different studies at different rates, but i think most of the studies include covid-19 patients during incubation period. so, most of the patients will develop the symptoms. so, i don't think it is real asymptomatic covid-19. so, we have retrospected our 30,000 covid-19 cases from out of wuhan in china. only twenty cases were real asymptomatic, because they are asymptomatic before and during hospitalization. so, it is not in the incubation period. the instance in terms of age was quite different. for younger cases 1.36%: his population have the highest asymptomatic covid19 cases. for older patients, the instance rate is very, very low. so, all the asymptomatic covid-19 cases do not have l. corbetta et al. 10 comorbidities, there is no death it seems that asymptomatic covid-19 cases will have a good prognosis. so, how about the transmissibility of covid-19? as we know, covid-19, the r0, the reproduction number is about three. that means one patient can produce three patients. so, it is higher than seasonal influenza. so, that means the transmissibility of covid-19 is higher than seasonal influenza. also, the generation interval is longer than influenza. so, it seems that the speed of transmission of covid-19 is almost similar to seasonal influenza. how about transmissibility of asymptomatic covid-19? so, there are only a few studies dealing with this issue. here a study from ningbo, china: this study is published in a chinese journal, so perhaps our foreign colleagues have not read the paper. so, this city has reported imported covid-19 cases, the total is 59. among them, 51 are symptomatic. only eight are asymptomatic. so, these imported cases produce totally 132 local secondary cases. so, among them, most of the secondary cases are caused by symptomatic patients. so, 126, but only 6 are infected by asymptomatic cases. here we can calculate the r0 for asymptomatic cases. so, 6/8. so, only less than one. if we just look at r0 asymptomatic cases it's not a problem, because for a transmissible disease, if r0 is less than one, the transmission of the disease will spontaneously stop, but we should not look at it as safe, because an asymptomatic case can produce symptomatic cases. the symptomatic case r0 is three. so, the risk or the challenge of asymptomatic cases is they can produce symptomatic cases and can cause a persistent community transmission of covid-19. that is real. so, it is very important to find an asymptomatic case, and also, the prognosis of asymptomatic cases is very good. there is no death. also, the transmissibility is very low, but as it can cause symptomatic cases, then symptomatic cases can arise a large epidemic of covid-19. so, maybe we will do our best to find asymptomatic cases. so, how do we find these cases? so, i think two strategies can be used. one is population screening, but for a community, for a city, or for a whole country the price is very, very expensive. i don't think it is acceptable by the government. another strategy is tracing among close contacts. so, when you find a symptomatic case, then you should try to find all the close contacts, and among the close contacts, you can screen the asymptomatic cases. so, i think that this strategy is rational and feasible. so, it can be accepted by the government. so, in summary to my slide, asymptomatic covid-19 cases can be seen frequently, but the definition may be different with different incidence. the incidence of real covid-19 is rare. it is not a popular phenotype. most of the asymptomatic cases are younger, and without comorbidities. so, the prognosis of asymptomatic cases is very good. the transmissibility of asymptomatic cases is lower, but can produce symptomatic cases. that is a big challenge for us. so, we should keep high alert on the risk of transmission caused by asymptomatic cases, and try to trace these cases among close contacts, so that is very important for, in the future, the containment of covid-19 in the world. thank you for your attention. so, thanks, doctor corbetta and doctor shiyue li and doctor jing li for inviting me to join the webinar. so, i think it is a good opportunity for us to communicate with each other and to learn from each other, and in the future we can find more opportunities to collaborate with each other. so, i think the world will benefit from our collaboration. thank you for your attention. jing li: very insightful talk on the thinking and pointing out some important points on the finding of prevention and tracing the asymptomatic patients with covid-19. very, very insightful talk. thank you, professor wang. now, we move to the last speaker, professor qintai yang. he's my good friend, and he is the associate dean of the third affiliated hospital of sun yat-sen university in china. he's also the director of the department of allergy at the third affiliated hospital of sun yat-sen university. also, the associate director of the department of otorhinolaryngology, head and neck surgery of the third affiliated hospital of the sun yat-sen university. he's going to give us a very interesting talk on what have we learned from big data analysis on covid-19 symptoms. now, please professor yang. qintai yang: okay. ladies and gentlemen, good afternoon and good evening. okay. i'm honoured to have the opportunity to speak at this meeting. the topic i'm is what have we learned from big data analysis on covid-19 symptoms? first of all, let me introduce a book called 'everybody lies'. everyone often lied to make themselves look better. they're real when faced with an internet search engine, because they're not admitting to people face to face at the time, and the search content in their accurate need. therefore, the search engine is also not a data truth serum . nowadays, the most popular search engine is mainly google outside of china. baidu in china. there are 854 million web users in china, more than 90% of them use the baidu search engine. as we know, searching online before visiting a doctor has become a habit of patient and their families in china. therefore, the search data of baidu will affect the real needs of the people. the amount of data it generates is large enough to be spread the trend. some studies indicate that the search volume of symptom key words was highly correlated with the symptom of patients. it could reflect a real trend of public demand. for example, use the google trends to analyze the flu trend accurately. for example, use the internet big data to stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes. 11 monitor new infectious diseases, such as ebola, and use the baidu index to analyse aids and flu in china. the baidu index is a data-sharing platform based on the baidu search data of users. google trends is the equivalent to baidu in china. it could provide search data for many key words. in our study, first of all, we determined the total of ten provinces of the total confirmed cases nationwide, also after february 20 and the tenth number of the daily newly confirmed and suspected cases through the data released by the china cdc. secondly, we searched key words in mandarin on the baidu index to obtain the search volume, as shown in the table from january 1 to february 20 each year from 2017 and 2020. geographically, in the ten provinces, different key words were combined. finally, the data from 2020 was compared with those of the previous three years. the data from hubei province was compared with the average of the other nine provinces. in our results, it showed that from january 1 to february 20, compared with the average of the other nine provinces, the people in hubei was more concerned about covid-19. the curve began to increase sharply on january 20, with the peak on january 23, and gradually fell back. on the other hand, compared with the average of the other nine provinces, hubei did not have a significant search volume for diseases such as copd, rhinitis, gastroenteritis and chd. moreover, the search volume of this disease in hubei province was even lower than those in the other nine provinces. from january 20 to february 20, compared with the average search volume in the previous three years, the average daily search volume in hubei province for symptoms increased significantly. the top symptom with the significantly increased search volume was cough, fever, diarrhoea, chest tightness and dyspnoea. look at this picture: figure a compared with the previous three years. it's a significant increase, and figure b compared with the average of the other nine provinces, it's significantly increased. interestingly, we found that the search volume increment of lower respiratory tract symptoms was significantly higher than upper respiratory symptoms in hubei. according to the baidu index increment, the symptom of organ infection of the sars-cov-2 includes the respiratory system, digestive system, circulatory system and locomotion system and nervous system and eyes. according to the spearman correlation analysis, the curve of newly confirmed and suspected cases was closely correlated to the curve of the baidu index. what's more, we constructed a distributed lag model to analyze the lag, the effect between baidu index and the number of confirmed and suspected cases. the result of figures: https://www.sciencedirect.com/science/article/pii/s20958811203 00639?via%3dihub doi: 10.1016/j.wjorl.2020.05.003 reproduced under cc by nc nd license https://www.sciencedirect.com/science/article/pii/s2095881120300639?via%3dihub https://www.sciencedirect.com/science/article/pii/s2095881120300639?via%3dihub https://doi.org/10.1016/j.wjorl.2020.05.003 http://creativecommons.org/licenses/by-nc-nd/4.0/ l. corbetta et al. 12 the distributed lag model, this indicated that in fact, people who searched for related symptoms on the internet may start to see the doctor, become suspected cases in two or three days later, and be confirmed in about three days later. it was confirmed by the national health commission that the national average time from the onset to confirmation was 4.95 days. so, conclusion, during the epidemic, the total search volume increment of the low respiratory system was higher than of the upper respiratory system the search volume of diarrhoea also increased significantly. it warned us to pay attention to not only the symptoms of the lower respiratory tract, but also the gastrointestinal system, especially diarrhoea in patients with covid-19. the internet search behaviour has a positive correlation with the number of newly confirmed and suspected cases, suggesting that big data has an important role in the early warning of infectious diseases. in short, the internet big data contributed to the recognition, monitoring, prevention and control of the new disease. the internet big data contributed to analyzing the symptom characteristics of covid-19. the internet big data contributed to predict and warning potential patients with covid-19. that's all. thank you for your attention. jing li: thank you, professor yang. your talk is very different from all of us, very interesting thinking on the big data from the internet. two of the very powerful engines, google and baidu in china and about the appearance of the symptoms, the type of the symptoms and the cases using the big data search. very, very interesting job. okay. thank you very much. then, i think i've finished with my job of hosting the scientific section then. i am passing the host to professor corbetta to host the discussion section. lorenzo corbetta: thank you very much for your work. there is one question for professor fabbri. the question is “should you consider testing the employee twice a week apart, since igg may take up to eight days to be detected?” leonardo fabbri: yes. in fact, we discussed the frequency of testing. the issue, once again, is the cost, because, you know, every time it's not only just the test itself, but you have to move the people and so on, but let me tell you that the data that professor rossolini presented earlier on the 5,500 health employees of careggi in florence that were tested and only 5% were positive, and of the 5%, only 20% were also pcr positive. i think that it gives you the perspective of a very limited number of asymptomatic, true positive patients. the last presentation also, the one before the last, actually showed that the number of asymptomatic positives is very limited, and what is also reassuring is that they are not actually very contagious. so, to make a long story short, i think that the compromise of fifteen days was a good compromise, because you can fall anywhere between zero and 30. so, it's a small risk the one that you take by just doing every fifteen days, because then, you repeat it every fifteen days, you know? the contacts or the infection can occur any time during that period. i think that is already very generous by the company to pay for this surveillance, because with all the uncertainties we have about the meaning of the antibodies, i think it's a lot of investment to put a regular programme of twice-a-month control. lorenzo corbetta: thank you very much. other comments about this topic, this question? if not, i have a question for professor li jing about the immunological topic. the question is, “is there any reactivity between antibodies for sars-cov2 and other corona viruses”? leonardo fabbri: if i may come in, this is leo fabbri speaking, yes, indeed because of the homology between sars-cov-2 and sars-cov, there is some cross-reactivity, but the number of sars-cov positive in china must be very small, minute. they have been exposed, you know, many, many years ago, and i don't think that is confirming, but the possibility is actually there. i have a question, if i may ask. professor guangfa, a question for you. i very much enjoyed your presentation, very useful, because i know how difficult it must have been for you to find out the asymptomatic positive people, because either you do a general population or it's difficult to find them. having said that, are you aware of any ongoing study in china where you have a large group of asymptomatic subjects that are regularly followed epidemiologically to see those who become positive to the antibodies and then to the virus, to see the natural history of the disease? are there any epidemiological study going on in china? guangfa wang: yes. so, as of now, there is a study, so focusing on asymptomatic cases led by doctor gao fu, the chairman of the chinese cdc. so, the study is just at the very beginning. it doesn't have any results yet, but i think in china we are facing some difficulty to collect enough cases, because only a few imported cases and also, recently, the various community outbreaks in a small city in the north of china. so, currently only 40 cases. so, perhaps in the future we can do some collaboration. if you want, i can talk with doctor gao fu, so thank you. leonardo fabbri: thank you. one question for professor li. i mean, i very much enjoyed your presentation showing the biomarker of survivals versus non survivals. from your experience, and from your review of the literature, two questions. one is if you had to select one biomarker that predicts the fast development of severity in a hospitalized stand on the same side against covid-19 diagnostic, screening tools and pathways for clinical and preventive purposes. 13 patient, you know, the clinical experience that we have is that we admit 100 patients and only ten for unknown reasons, within one day or two develop respiratory failure and they get into the icu. now, the question to you is any marker among those that you measure that you believe can predict this risk to identify before the respiratory failure the subjects who are going to develop the respiratory failure? jing li: yes. a very good question. if you want me to point out one i think that it's most important to predict the prognosis of the disease in terms of immunology parameters, i will give you the cytokine of il-6. leonardo fabbri: okay. thank you. jing li: it represents mostly the cytokine storm in the progression. it is a representative cytokine, but you need to have a dynamic measurement of these parameters to see whether they are continuing to increase, or they keep in the lower level. if they continue increasing, that is dangerous for the prognosis of the patient of the disease, a bad outcome. leonardo fabbri: thank you. finally, if i may, one question to professor qintai is you nicely showed that the upper respiratory symptoms were prevailing in the wuhan region. are you suggesting that covid-19 can be clinically distinguished from other viral infection of the respiratory tract by having predominant lower respiratory symptoms compared to upper respiratory symptoms? it clinically looks like that. i mean, when you have influenza, mostly you have upper airway abnormalities. when you have covid, you have lower airway, because you have a cough, but also dyspnoea. jing li: yes. professor yang, that means the difference of the symptoms when you compare covid-19 and other upper airway tract infections/disease, the symptoms are different that you collected from the big data from the internet. qintai yang: from the internet big data it's very difficult to tell, but flu symptoms and covid symptoms are difficult to tell apart, but we can do it from the internet. they're similar, the symptoms are similar. guangfa wang: can i have some questions? so, one to doctor yang, the other one to doctor li. so, the first question is to doctor yang. so, you did a very good study. so, big data can reveal a lot of details. so, maybe we can expect the trends of something. your study, can you say that from big data, we can prospect the early patterns of covid-19 or other contagious diseases? so, if your big data can have such a prospective alert, perhaps we should add big data analysis to our disease control system. so, that is the question to doctor yang. i will ask the next question later. so, please. qintai yang: thank you for your question. in the big data is a trend. i do think that big data can gradually influence our understanding of covid-19, but big data can help us under the covid-19 from the non-medical medicine. as we note, searching online before visiting a doctor has become a habit of the patient and their families in china. therefore, the search data of the baidu can show the real need of the people. the big data you generate is large enough to present a trend. so, we can predict it. it's a real situation, and really what we search. so, it will be enough to represent a trend, so that you can predict and face disease. so, i think so. guangfa wang: so, for my contact there are people, many, many people very nervous to the epidemic of covid-19. even there is no disease, infection, so he or she thought, 'i was infected by covid-19, and i will be dead.' so, they are searching a lot of help. so, including searching from baidu or google, but if nobody knows the epidemic of covid-19, so can the big data about search volume reflect the epidemic, or the early stage of an epidemic of a disease? qintai yang: yes. maybe your symptom is right. there are some limitations in our study from the big data. so, such a difference in the number of the internet use and difference in the age of the internet use. so, our study has a lot of limitations. guangfa wang: so, another question to doctor li jing. so, you did a very good job, and very good research. so, from your study, i observed that eosinophils count can predict the death of the patient. so, what is the explanation of the phenomenon? jing li: good question. very good question. yes, because when we wrote the article, we searched a lot of other literature about the virus infection, the effect of a virus infection on the haematologic change, especially on eosinophils. we explained that the decrease of the eosinophils may be the reaction or reflex of the body against the virus infection, the severe virus infection, or the attack or the high intensity of the body response of the attack, like if somebody experienced a very high tension work or high intensity of swimming training, or some severe virus infection. they express the decrease of eosinophils. yes. this is the general response of the immune system. yes, but the detailed mechanism on why the decreasing of eosinophils in such a scenario, i think we need to further study. yes. thank you. lorenzo corbetta: may i? a question for all of you. what is the role of ct scan for the identification of the patient with covid-19, especially patients with symptoms but negative swab. question for professor shiyue li, for example. shiyue li: okay. yes. i think based on clinical experience, i think, as we all know, that the sensitivity of the rna tests is just maybe 50%. so, the sensitivity is a little bit low, so, for a one-time test. so, i think also at the beginning of the outbreak of the covid-19 in china, there are some limitations of the rna test. ct scan is very convenient in the hospital. so, based on chinese doctors' experience, the sensitivity of the ct image is quite sensitive. it's more than, based on the literature, about 95%. it's more sensitive than the rna, but i don't think it's the golden standard now for the diagnosis. it should be combined with the rna test. i think combined, this ct scan and rna test, it's good for the clinical practice. this l. corbetta et al. 14 is my opinion. lorenzo corbetta: thank you. you performed many bronchoalveolar lavages and bronchoscopies? shiyue li: yes. you know, in terms of the sample, the nasal swab is a little bit better than the throat swab and sputum is better than the nasal swab. i saw a literature that a biopsy through the bronchoscopy is about 60% of the time, is it, yes, for the rna test. guangfa wang: my answer to the first question is that so i think a ct scan is more sensitive and very rapid. so, for screening or for the examination of covid-19 patients, but i think the specificity would be a problem. on recent weeks, we have at least two patients: the ct scan is very, very similar to covid-19, but there is no epidemiological history, pcr of novel coronavirus are negative several times. so, at last, this patient has got, like another one, other immunodisease. so, i think the diagnosis of covid-19 should not really only on ct scan. so, in china, as we have experienced a reasonable time; in that time, a lot of patients come out and the capacity for current virus tests is very limited. but they need the official diagnosis and confirmation. so, if they are confirmed, so several patients can stay in one room, but if they are not confirmed cases, only suspected cases, one patient, one room to avoid cross infection. so, at that time, in wuhan and hubei a new diagnosis criteria have been put out. that is, a clinically diagnosed case. so, that means the patient had epidemiological history and a positive ct scan. so, although the guideline emphasized the features of covid19, but on the first day of the application of the new criteria, so over 13,000 new cases appeared. so, then right now, we have a retrospective analysis to the clinically diagnosed cases. we observed the hospital-acquired infection is much higher, almost more than fifteen times higher than confirmed cases. so, i worried about, so these clinically diagnosed cases are not really covid-19. so, it may be other pneumonia. so, back when they were classified as covid-19 patients, they were staying with others in the one room. so, then cross infection happened. so, that is a problem. so, i think in the future, we should not emphasize the ct value on confirming the diagnosis of covid-19, but if you want to find suspected cases, so that is a good tool. why china selected ct, so for only one week they used these criteria? so, one reason is that we had many, many cases. the other reason is that the positive range of throat swabs is lower, very low. so, it has been recorded as 30% to 50% of confirmed cases. so, it is very low. so, we need a quality control. another issue about bronchoscopy and bronchial lavage. at the early stage of the wuhan covid-19 epidemic, we observed the lavage has highest possibility to reach of covid-19 than pcr, but when doing bronchoscopy, so we were risking a much higher risk for cross infection, especially for healthcare workers. in china, we do not encourage doctors to do bronchoalveolar lavage for the diagnosis, just for the diagnosis of covid-19. lorenzo corbetta: okay. thank you very much all. thank you and i invite you to the next webinar that will be held on may 29th on the clinical management of covid-19 and will be led by some chinese presenters, like bin cao, professor li jing again and italian professors, expert in immunology and in coagulation and an italian doctor who is working in london, very expert in intensive care. so, thank you very much for your presentation, and see you soon. see you on 29th may. thank you. substantia. an international journal of the history of chemistry 3(2): 11-17, 2019 firenze university press www.fupress.com/substantia citation: m. taseidifar, a.g. sanchis, r.m. pashley, b.w. ninham (2019) novel water treatment processes. substantia 3(2): 11-17. doi: 10.13128/substantia-631 copyright: © 2019 m. taseidifar, a.g. sanchis, r.m. pashley, b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-631 research article novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 1 school of science, unsw canberra, northcott drive, canberra, act 2610, australia 2 department of applied mathematics, research school of physical sciences and engineering, australian national university, canberra act 0200, australia *e-mail: r.pashley@adfa.edu.au abstract. the effect of a natural, biodegradable surfactant obtained using a novel and efficient chemical reaction between cysteine (a thiol-based amino acid) and an octanoyl (c8) compound, was investigated for its application to the ion flotation removal of low levels of different contaminant ions from aqueous solution. the synthesised amino acid-based single-chain surfactant shows a high water solubility and exhibits extensive foaming in a typical flotation chamber over a wide ph range. in a batch ion flotation process, this surfactant was able to remove 97‒99% of the 5ppm of strontium, lanthanum, arsenic and different heavy metal ion levels present in contaminated water, in a simple, single-stage physiochemical process. also, significant differences in ion binding selectivities could be used as the basis for the complete separation of some specific ions from mixed solutions, using the ion flotation process. recycled water is an invaluable resource but it often also contains inorganic and organic nutrients, and chemical and biological substances, such as enteric microbial pathogens, which are often not monitored. this is a key inhibition to its reuse. the application of a novel co2 bubble column sterilization process is presented here and compared with other commonly used processes. keywords. icp-ms, surfactant, ion flotation, heavy metals, cysteine, octanoyl chloride, water reuse, sterilization. 1. introduction the demand for developing new techniques to treat contaminated water containing hazardous ions, has grown significantly in recent years. some of these ions like strontium1 and lanthanum2 or heavy-metal ions like arsenic3, mercury4, cadmium5, chromium6, lead7 and copper8 can accumulate in the body and cause serious damage to health due to their high affinity for binding with proteins in biological cells9. some of these ions and their environmental effects are listed below. strontium (sr) from radioactive wastewater is considered to be one of the most dangerous radionuclides to public health because of its high transferability, large consumption, high solubility and easy bioaccumulation. radioactive strontium can be interchanged with calcium ions, which have major 12 m. taseidifar et al. functional activities to preserve bone and teeth as well as performing many essential enzymatic reactions in the body; therefore, this exchange can produce genetic damages to the living organisms and consequently can cause serious harm to the human health10. among different strontium isotopes, the long-lived unstable one, with a half-time of 28.9 years is 90sr which emits beta particles that can cause severe damage to seawater creatures. therefore, removing radioactive sr from water is of great importance since, especially, the fukushima daiichi accident (japan 2011), which led to disastrous seawater contamination by radioactive 90sr1. moreover, the fukushima event became a motivation for researchers to focus on removing the released contaminant toxic elements, such as caesium, from leached soil and polluted water. it was shown that caesium (cs+) can be removed from contaminated aqueous solutions by employing the flotation of copper-based prussian blue nanoparticle analogues as a ph-sensitive surfactant11. contamination of groundwater and natural water with heavy-metal ions, especially arsenic, is a worldwide problem. it has become a major challenge for scientists and policy makers13,14. in addition, groundwater contamination with heavy metal ions causes contamination of agricultural products, like rice, which has been reported in several countries including china, canada, the usa, and bangladesh15, and taiwan, mexico, argentina, mexico, poland, hungary, japan and india16, during recent years. in addition, heavy-metal ions contaminate drinking water even at low concentrations, and hence they can be taken up via human consumption, which can ultimately lead to the risk of cancer, in the bladder, lung and also skin17-19. to remove these ions in water treatment, adsorption can be used as a general process, especially when there is a strong affinity to bind hazardous ions in an efficient and simple alternative20. using natural adsorbers which are green and non-toxic to the health like l-cysteine have been shown to be very promising in the treatment of water contaminated with these ions21. cysteine, used as the polar head group of a surfactant, could provide selective and efficient ion capture in an ion flotation removal process, in one step. cysteine chelates with dissolved ions in aqueous solution, which can be effectively removed by rising bubbles into a foam on the surface of the aqueous solution. in this study, the natural amino acid, l-cysteine was reacted with octanoyl chloride to form a single chain n-octanoyl cysteine surfactant (denoted n-octanoylcys). our motivation was to use the surfactant for removal by selective ion flotation of low levels of strontium, lanthanum and other heavy-metal ions from drinking water. this was achieved by the use of this new surfactant with cysteine head-groups which adsorbs at the water-air interface of a bubble. rising bubbles within a flotation column can then offer a continuous supply of cysteine coated monolayers, where the surfactant and head-group will be relatively mobile, at room temperature. collisions between the dissolved ionic species and the cysteine coated rising bubbles might be useful for selective and efficient ion capture and removal at a level of more than 97% for most of the discussed ions, in a one-step, continuous water treatment process. in addition, the surfactant is readily decomposed into natural products; therefore, this offers an environmentally acceptable process. the world health organization (who) considers three reference pathogens in drinking water: for bacteria (campylobacter jejuni); for protozoans (cryptosporidium); and for viruses (rotavirus)22. who guidelines for drinking-water quality compare thermal inactivation rates for different types of bacteria and viruses in hot liquids, concluding that temperatures above 60°c effectively inactivate both viruses and bacteria. when the temperature range lies between 60°c and 65°c, bacterial inactivation occurs faster than viral inactivation. such studies show that, at a water temperature of 60°c, e.coli needs 300 seconds to reach a 1.5 log-unit reduction in viability; it takes 1800 seconds for viruses, such as enterovirus, echovirus 6, coxsackievirus b4 and coxsackievirus b5, to reach a 4 log-unit reduction (i.e. 99.99%)23. 1.1 common water-sterilisation technologies collivignarelli et al.24 found that uv irradiation and chemical treatments using chlorine, chlorine dioxide, peracetic acid or ozone were the most used technologies for wastewater disinfection. chlorine in the form of sodium hypochlorite, chloramines or chlorine gas is the most common disinfectant in water treatment, as it is cheap and relatively easy to handle25. the bactericidal power of chlorine lies in its ability to affect the chemical structure of the bacterial enzymes through complex mechanisms. hypochlorous acid and hydrochloric acid are produced when chlorine gas is added to water24: cl2 + h2o ⟷ hcl + hocl 13novel water treatment processes chlorine dioxide is a water-soluble bactericidal gas with high oxidizing power that affects protein synthesis and enzymes in bacteria. this gas is produced by the reaction26: 5naclo2 + 4hcl ⟶ 4clo2 + 5nacl + 2 h2o paracetic acid is able to inactivate bacteria through the destruction of their membranes and enzymes due to the generation of reactive hydroxyl radicals and active oxygen. it is used as a chlorination alternative and is produced from the reaction26: ch3cooh + h2o2 ⟷ ch3co3h + h2o ozone is a highly oxidizing agent produced by ozone generators when o2 is exposed to uv light or electric shocks. this produces individual oxygen atoms that combine with o2 generating o3. ozone affects the cell wall of the pathogens, inactivating them. it is a very unstable gas that dissociates as26: o3 ⟶ o2 + o water-disinfection uv lamps work in the spectrum 100-400 nm. there are four regions in the spectrum: uv (100-200 nm); uv-c (200-280 nm); uv-b (280-315 nm); and uv-a (315-400 nm). in water disinfection, uv-a and uv-c are the most effective; they are able to penetrate the pathogen membranes, inactivating them27. however, all these water-disinfection technologies have limitations. for example, chlorine and chlorine dioxide react with organic compounds and form reactive chlorinated organic compounds that are hazardous to humans. in addition, chlorine needs at least 30 minutes contact time and is not able to eliminate cryptosporidium. chlorine dioxide has high management costs and is very unstable. other disinfection methods such as ozone and uv irradiation are complex to operate and maintain. rotavirus can be resistant to uv treatments and its efficiency is affected by the dissolved organic and inorganics in the wastewater, as well as its colour and turbidity28. paracetic acid increases cod (chemical oxygen demand) and bod (biochemical oxygen demand) due to the formation of acetic acid24. therefore, a major challenge exists to develop new, energy-efficient technologies to address these problems. one such candidate is the newly developed hot-bubble column evaporator (hbce). this technique is able to inactivate pathogens for water reuse without the need for boiling and does not produce toxic side products. 2. materials and methods 2.1 ion flotation system the solution obtained, after taking one sample for detecting the initial concentration of ions by icp-ms (inductively coupled plasma mass spectrometry) analysis, from which removal rates will be calculated according to this, was then poured into a column (with 30cm height and 3cm diameter, as shown schematically in figure 1) while a 1l/min flow of air gas was passed through a glass sinter, pore size no. 2, using an air pump (hiblow hp40, philippines). two samples were taken after each of 30 and 60 minutes from around 2cm above the sinter, and the ion concentration of each sample was determined by icp-ms analysis. the upper-outlet foam was also collected in a waste container using an outlet tube. a schematic diagram of the laboratory batch ion flotation column setup is shown in figure 1. it should be noted that in this protocol the surfactant, unlike the ions, is not fully depleted from the column during 60mins of bubbling time. that is, the surfactant concentration was approximately halved in the column during the bubbling experiments. 2.2 hot bubble column evaporator the hbce process produces hot gas bubbles of 1-3 mm of diameter. the collision between these hot bubbles and the dispersed pathogens sterilizes the water29. at the same time, low solution temperatures (<50°c) are maintained, leading to good energy efficiency. the hbce figure 1. schematic diagram of the batch ion flotation apparatus. reproduced from [21]. 14 m. taseidifar et al. process requires less thermal energy than solution boiling because the heat capacity of the inlet hot dry air is much lower than that of water29. the hot, dry gas bubbles were produced continuously at the base of the bubble column using a glass sinter. the evaporation of water into the rising bubbles requires a substantial amount of latent heat and this produces only a modest temperature rise in the column solution. experiments have been carried out using hot inlet gases at up to 275°c. 3. results and discussion 3.1 ion flotation for heavy metal ion removal the experimental results obtained using the na+ form of the n-octanoyl cys surfactant in an ion flotation process for the separation of a range of heavy metal ion contaminants from water, as individual ions and in appropriate ion mixtures, is summarized in the following tables. these results indicate that, in mixed solutions, the favourable binding of strontium ions to the cysteine surfactant can depress the removal rate of calcium ions, and this effect may be related to the stronger hydration of the smaller calcium ion. table 3. flotation results for 100ml mixed ion solutions of 5mg/l lanthanum and iron (initially) using crystallised n-octanoyl-cys surfactant with dry air ion flotation, the batch process had an initial surfactant concentration, csurfactant=0.01m and ph=8. mix pollutant c (mg/l) after 30min removal (%) after 30min c (mg/l) after 60min removal (%) after 60min la 1.00 80 0.27 94.6 fe 4.78 4.4 4.6 8.0 the significant differences in selectivity found here for the la/fe mixture suggests that the ion flotation could be used to efficiently separate specific ion mixtures, possibly using multi-stage separation processes. table 4. a comparison of removal rates observed in a mixture of cadmium, chromium, copper, lead, lanthanum, magnesium, and iron ions (each initially at 5mg/l) using the ion flotation process with n-octanoyl-cys surfactant. the initial concentration of the surfactant was csurfactant=0.01m and the solution was maintained at ph=8. mix ions c (mg/l) after 30min removal (%) after 30min c (mg/l) after 60min removal (%) after 60min cd 4.4 12.0 2.8 43.8 cr 3.57 28.6 1.07 78.5 cu 1.53 69.4 0.82 83.6 pb 4.76 4.8 3.72 25.6 la 4.5 10.0 3.2 34.6 mg 4.8 4.0 4.2 16.3 fe 4.98 0.4 4.7 6.3 again, these results suggest that specific ion mixtures could be efficiently separated using multi-stage ion flotation processes. table 5. ion flotation results for 100ml solutions of 50mg/l (7.87 × 10-4 m) copper using crystallised n-octanoyl-cys surfactant with dry air flotation. the batch process had an initial surfactant concentration of 0.01m and ph=8. time (min) c (mg/l) removal (%) 15 9.712 80.6 30 3.903 92 45 0.6 98.8 table 1. batch ion flotation results using air bubbles with 100ml solutions of 5mg/l each with single solutions of strontium, selenium and calcium ions using crystallised n-octanoyl-cys surfactant. the batch process started with a surfactant concentration, csurfactant=0.01m and was maintained a ph=8. ion c (mg/l) after 30min removal (%) after 30min c (mg/l) after 60min removal (%) after 60min sr 0.03 99.4 0.009 99.8 ca 0.72 85.6 0.13 97.3 se 4.6 8 4.4 14 table 2. batch ion flotation results using air bubbles for 100ml solutions of 5mg/l calcium and strontium mixtures, using n-octanoyl-cys surfactant at an initial concentration, csurfactant=0.01m and ph=8. mix ions c (mg/l) after 30min removal (%) after 30min c (mg/l) after 60min removal (%) after 60min sr 2.14 57.2 0.13 97.4 ca 3.39 32.2 1.3 73.8 15novel water treatment processes table 6. a comparison of arsenic, cadmium, lead and nickel removal rates observed in the ion flotation process using n-octanoyl-cys surfactant. the batch process had an initial surfactant concentration of 0.01m and ph=8. ion species c (mg/l) at t0 c (mg/l) after 30min removal (%) after 30min c (mg/l) after 60min removal (%) after 60min arsenic 5.0 0.04 99.2% 0.03 99.4% cadmium 2.0 1.64 18% 1.55 22.2% lead 2.5 2.44 2.2% 2.25 9.8% nickel 3.5 3.83 2.9% 3.3 5.9% table 7. comparison of removal rates of au3+ and hg2+ in binary mixtures of heavy metal ions (each initially at 5mg/l) using the batch ion flotation process with n-octanoyl-cys surfactant at an initial concentration of csurfactant=0.01m and ph=8. ion c (mg/l) after 30min removal (%) after 30 min c (mg/l) after 60min removal (%) after 60 min au3+ 3.12 37.6 2.88 42.4 au3+ as (au3+ + hg2+) 3.20 36.0 3.13 37.4 hg2+ as (au3+ + hg2+) 3.88 22.4 3.50 30.0 au3+ as (au3+ + fe3+) 3.62 27.6 3.38 32.4 the removal rates observed for most individual ions were typically reduced in mixed ion solutions, even with an excess of surfactant at an initial concentration of 0.01m of (na+) n-octanoyl-cys surfactant, in the batch ion flotation process, summarized in the tables above. the results obtained for ca and sr ions alone and as a mixture are a good illustration of these effects. the consistent removal rates observed, suggests that there is strong selectivity of the n-octanoyl-cys surfactant toward arsenic, strontium, copper and chromium ions, compared with the other heavy metal ions. by comparison, there was very low removal rates observed for iron, selenium, gold and magnesium ions in these experiments. these relative selectivities could be developed further for use in specific ion separation processes. 3.2 hbce sterilization. comparison with other technologies in table 8, e.coli and ms2 virus inactivation rates using the hbce process are compared with different studies of the most common disinfection technologies. for both pathogen groups hbce and uv technologies presented the best inactivation results, with 3-log inactivation after 230 seconds and 3.5-log after 180 seconds, respectively when inactivating ms2 viruses and 2.3-log after 300 seconds for hbce and 3.8-log after 300 seconds for uv, when inactivating e.coli. ozone and chlorination sterilisation rates could be improved by increasing the dosage but at the concentrations used in these studies they present less or similar inactivation rates than the hbce process30 (table 8). the novel hbce technology could become a new disinfection technology candidate able to compete with the existing ones. the fact that the process can use heated co2 gas and the possibility of reusing exhaust gas from combustion processes makes the hbce process potentially more energy efficient. if pure co2 or combustion gas from gas generators is used, the only byproduct that the system will generate will be 1% of carbonic acid at ph 4.1. the lack of potentially hazardous side products gives this new process a substantial advantage over other common processes. table 8. summary of studies of inactivation of e.coli and ms2 virus with different technologies [30]. pathogen treatment log 10 reduction time (s) source escherichia coli thermal inactivation 60° c 1.5 log 300 who[22] 2.0 mg o3/l 1.3 log 300 de souza et al.[31] 2.0 mg cl2/l 2 log 300 de souza et al.[31] uv (0.78mw/cm2) at 295-400 nm. 3.8 log 300 mamane et al.[32] dpcd, co2 at 197 atm. and 34°c 1.25 log 300 richard et al.[33] bubble column, co2 at 200°c, 1 atm. 2.3 log 300 garrido sanchis a. et al [30] ms2 virus 0.1 mg o3/l 1.2 180 fang et al.[34] 1.0 mg h2o2/l 0.001 log 90 richard et al.[35] 30 mg cl2/l 1 log 300 tree et al.[36] uv (0.19mw/cm2) 3.5 log 180 fang et al.[34] bubble column, co2 at 205°c, 1 atm. 3 log 230 garrido sanchis a. et al [30] bubble column, air at 200°c, 1 atm. 0.17 log 300 a.g. sanchis et al.[37] 16 m. taseidifar et al. it is interesting to note from these results that hot co2 inlet gases are effective on both coliforms and waterborne viruses. by comparison, hot air is not as effective with viruses. previous studies have used high pressure co2 for water sterilization but the high density bubble column is effective even at atmospheric pressure. 4. conclusions ion flotation should be more widely considered for the treatment of contaminated waters containing hazardous ions, especially when environmentally acceptable surfactants are available, which can be efficiently used in this process. for example, the recrystallised na+ form of the n-octanoyl-cys surfactant was found to be successful in removing a range of low levels of hazardous ions from water using an ion flotation process. this process offers the potential for a simple industrial physiochemical process to treat waters contaminated with a wide range of hazardous, mostly heavy metal ions, to achieve removal rates at more than 97-99% of these ions from drinking water. this process needs further study to extend its application to the recovery of valuable ions, such as gold, to reduce the significant costs of current refining processes. the surfactant also showed high efficiency for the removal of relatively high concentrations of copper ions, which could be used as a promising alternative for the treatment of industrial and mining wastewater. the significant selectivity of this surfactant for some of the ions studied suggests that the ion flotation process could be used to completely separate some specific ion mixtures. in addition, the surfactant collected in the foam can be released from the ion and then re-used to improve recycling of the surfactant to help with the commercial development of this process with potentially wide applications in several countries where these hazardous ions are present in the drinking water. this surfactant also readily decomposes into products which are acceptable for human ingestion. water is a very valuable resource therefore its reuse is imperative, but if this water carries pathogens these usually have to be inactivated. the hbce process has proved its efficiency inactivating different types of pathogens in water by heating the gas, not the solution. the hbce process can be effectively used to inactivate viruses and bacteria in different solutions at modest temperatures of around 47°c, where normal water bath heating produces no effect. the inactivation is apparently caused by the collisions between viruses and the transient, rising hot bubbles. many industries, such as pig farms, landfill, bio-gas plants and coal power plants, emit large amounts of hot combustion gases. the potential use of these hot combustion gas bubbles in water-treatment processes to sterilize water offers an attractive new energy-efficient technology. this new technology would then be able to compete with other water-disinfection technologies, such as uv irradiation, ozonation, and even chlorination, due to its low operating costs and its energy efficiency and also because of its complete absence of potentially hazardous side products. 5. acknowledgement we thank the university of new south wales, along with the australian research council (arc grant number dp160100198). the authors would like to gratefully acknowledge ms rabeya akter for icp-ms analysis support within the mark wainwright analytical centre at the university of new south wales. the authors also thank dr fatemeh makavipour for her assistance with the arsenic flotation experiments. 6. references 1. t. nur, p. loganathan, j. kandasamy, s. vigneswaran, removal of strontium from aqueous solutions and synthetic seawater using resorcinol formaldehyde polycondensate resin, desalination 2017, 420, 283291. 2. c. deng, x. li, x. xue, r.m. pashley, the effects of low levels of trivalent ions on a standard strain of escherichia coli (atcc 11775) in aqueous solutions, microbiologyopen 2018, 7, e00574. 3. j.f. ferguson, j. gavis, a review of the arsenic cycle in natural waters, water res. 1972, 6, 1259-1274. 4. who, mercury in drinking-water, in: background document for development of who guidelines for drinking-water quality, 2005. 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sobsey, inactivation of hepatitis a virus and ms2 by ozone and ozone-hydrogen peroxide in buffered water. vol. 27, 1993, 371-378. 36. j.a. tree, m.r. adams and d.n. lees, chlorination of indicator bacteria and viruses in primary sewage effluent, applied and environmental microbiology, 2003, 69(4), 2038-2043. 37. a.g. sanchis, m. shahid, and r.m. pashley, improved virus inactivation using a hot bubble column evaporator (hbce), colloids surf b biointerfaces, 2018, 165, 293-302. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 2(2): 125-130, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-66 citation: l. colli, a. guarna (2018) the dextrorotatory sweet asparagine of arnaldo piutti: the original product is conserved in florence. substantia 2(2): 125-130. doi: 10.13128/substantia-66 copyright: © 2018 l. colli, a. guarna. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article the dextrorotatory sweet asparagine of arnaldo piutti: the original product is conserved in florence laura colli*, antonio guarna dipartimento di chimica “ugo schiff ” dell’università degli studi di firenze, via della lastruccia 3-13, polo scientifico e tecnologico, 50019 sesto fiorentino – firenze (italy) e-mail: laura.colli@unifi.it abstract. in 1886, pasteur presented a note on the work of the italian chemist arnaldo piutti concerning the difference between the two physical isomers (enantiomers) of asparagine. the octahedral crystal of asparagine appeared only as “levorotatory hemihedralism” but, in principle, should also exist as a dextrorotatory asparagine with a symmetric crystalline form. in 1886 arnaldo piutti isolated the dextrorotatory asparagines while he was working as an assistant of ugo schiff in florence. he obtained also another unexpected information, of which only pasteur immediately understood the importance: the dextrorotatory aspargine had a sweet taste. the dextrorotatory sweet asparagine of arnaldo piutti is conserved in the schiff collection of the department of chemistry “ugo schiff ” at the university of florence, and is the first compound where a relationship between the optical isomerism of a molecule and a different response of human receptors, in this case the taste, was observed. keywords. asparagine, chemical heritage, history of enantioselectivity. this research stems from a purely museological question. a few years ago, during the reordering of the products synthesized by ugo schiff (18341915) at that time conserved at the department of chemistry “ugo schiff ” of the university of florence, and now merged into the museum of natural history, a small bottle was found. it carried a “ugo schiff ” museum label, written by “our” german chemist, referring to: “asparagina destrogira dolce” (dextrorotatory sweet asparagine)1. after reading the work by joseph gal2-4 in 2008, antonio guarna (the scientific director of the museum project for historical chemical finds) immediately had the intuition that the product could contain the famous dextrorotatory sweet asparagine isolated by arnaldo piutti. the historical research that was conducted, within the chemical heritage project of the university of florence, proved him right. in this contribution we discuss some insights about the discoverer and how this discovery took place. 126 laura colli, antonio guarna “piutti’s asparagine”: was it an important discovery? the work of gal on the discovery of piutti reports in the conclusions, the following statements4: piutti was a highly original chemist who carried out notable investigations in a wide variety of research topics. his discovery of a difference in the taste of dand l-asparagine was a milestone first observation of enantioselectivity at a biological (human) receptor. the discovery was also the first observation of stereoselectivity of any kind in taste; the first finding of biological enantioselectivity in an organism higher than microorganisms; the first example of biological enantioselectivity in an effect other than enzyme action; and one of the two earliest reports of the preparation of a d-amino acid. the sample preserved in the schiff collection of the university of florence therefore has a considerable historical and scientific relevance. the discovery had a good resonance at the time of piutti. louis pasteur (1822-1895) himself showed a great interest in this research, and in 1886, at the french academy of sciences, commented on the work of the italian chemist with these words5: why this big difference in taste between these two asparagines? one might assume the existence of a very special isomerism, but i think otherwise […] if two dissymmetrical inverse bodies offer in their interaction with inactive bodies, physical and chemical properties that are very similar and almost identical, these dissymmetrical inverse bodies will give combinations of different absolute properties when they merge with asymmetric and optically active bodies. the active dissymmetrical bodies that will interact with the nervous system, leading to a sweet taste in one case and almost tasteless in another, won’t be anything else in my opinion than like the nervous matter itself, dissymmetrical, just like all the basic substances of life: albumin, fibrin, gelatin, etc. the scientific context of arnaldo piutti’s discovery at the end of the nineteenth century stereochemistry did not exist yet. in 1867 the german chemist friedrich august kekulé von stradonitz (1829-1896) proposed for the first time the tetrahedral structure of carbon. two years later the italian chemist and politician emanuele paternò (1847-1935) applied this hypothesis to saturated organic compounds6. on the relationship between structure and optical properties of a molecule, in 1874, jacobus henricus van’t hoff (1852-1911), a dutch chemist awarded with the nobel prize in 1901, proposed that compounds with asymmetric carbon may exist in two different forms corresponding to the two optical antipodes, which could be separated into two optically active compounds. van’t hoff ’s theory, considered too audacious and abstract, was almost rejected by the academic world. only when hermann emil fischer (18521919), a german chemist, almost contemporary of schiff, and nobel prize winner in 1902, in 1894 adduced evidence in favor of this thesis by synthesizing the levorotatory (not natural) antipode of glucose, the propositions of van‘t hoff became accepted by the academics, paving the way to modern stereochemistry7,8. arnaldo piutti biography arnaldo piutti was born on january 23, 1857 in udine. he graduated in 1875 at the technical institute of udine, in the physics-mathematics section and from there he moved to turin where he enrolled in the faculty of natural sciences9. in 1879 he brilliantly completed his studies under the guidance of ugo schiff (1834-1915), a german chemist that served as professor of chemistry in florence for fifty years and in his florentine laboratory discovered the bases and the schiff reaction10. piutti had the opportunity to meet schiff just in the two years when the german scientist was lecturing in turin. in fact, schiff moved from florence to turin in 1877, because of the disagreements he had with the management of the florentine royal institute of practical and advanced studies (regio istituto di studi pratici e di perfezionamento). he eventually returned to florence in 1879 after the promise of more funds for his laboratory11. after his graduation, piutti remained in turin as an assistant to angelo mosso and icilio guareschi, two important italian chemists of the time. in 1881 he joined ugo schiff in florence as assistant at the laboratory of general chemistry. in florence, piutti helped with the course of general chemistry and later in 1885 also of organic chemistry. in 1886 he received a degree in pharmacy, a professional pratice that was quite usual at that time. in this way he was able to apply for a position in pharmaceutical chemistry and in the same year he obtained a professorship at the university of sassari in sardinia9. in 1888 he moved from sassari to naples, where in 1890 he was appointed as full professor, with the maximum score6 (figure 1). he also won the position in general chemistry in padua, but he preferred to remain in naples where he could organize the new institute, following the example of schiff in the reorganization of the chemistry institute florence11. 127the dextrorotatory sweet asparagine of arnaldo piutti: the original product is conserved in florence piutti was a member and correspondent of numerous academies and scientific societies, including the prestigious accademia dei lincei. he held the office of dean of the faculty of science and of the school of pharmacy in naples for several years, he became vicerector and represented the minister of education at the international congresses of applied chemistry in 1896, 1890, 1900, 1903 and 1910. in naples he was for a long time appreciated director of the institute of pharmaceutical chemistry and toxicology and he personally followed with great commitment the construction of the new headquarters in san marcellino9. piutti’s scientific contributions are mainly focused on the study of aspartic acid, asparagines and their derivatives and on the optical rotation of organic compounds. his research ranged also in other fields of chemistry. he studied the toxicity of the combustion products of locomotives and he traced the presence of helium in a mineral of the vesuvian area, demonstrating the diffusion of this gas in solids. he patented the pirantina solubile piutti (soluble pirantina piutti), an antipyretic and analgesic9. despite having personally contributed to the construction of the new laboratories in san marcellino, he finally abandoned those in the place called “il salvatore” only when they were declared unfit. during that period, not being able to carry out experimental work, he devoted himself to theoretical studies on the spatial representation of chemical elements, arranging them in an alternative way to the mendeleev table9. he died in conegliano, near treviso, on october 19, 1928. isolation of asparagine asparagine is an α-amino acid (figure 2) that was identified for the first time by the french chemists louis nicolas vauquelin (1763-1829) and pierre jean robiquet (1780-1840) in 1815, in the asparagus sprouts. shortly afterwards joseph bienaimé caventou (1795-1877), another french chemist who pioneered the research in amino acids and plant alkaloids, and heinrich hlasivetz isolated asparagine from glycyrrhiza glabra (liquorice) and robinia pseudoacacia. later asparagine was found in many other plant species: in the roots of althea, in potatoes, in hop, in legumes sprouted in darkness and in sweet almonds12. to isolate the asparagine molecule, the juice squeezed from the plant was boiled until it formed an abundant coagulation of albumin. at this stage it was filtered, purified and crystallized, obtaining crystals that looked like “sugar candy”12,13. the isolated asparagine was an optically active molecule that caused a left-handed rotation of the polarization plane. in 1835 william hallowes miller (1801-1880) a british mineralogist and physicist, determined the crystallographic constants and measured its refractive indices. in 1848 pasteur identified a relationship between the crystalline form of the asparagine and the rotation of the polarization plane, arguing that in principle, a dextrorotatory asparagine with symmetrical crystalline form should exists, albeit the occurrence of the octahedral crystal of the asparagine only as “levorotatory hemihedralism”14. even karl friedrich rammelsburg, (1813-1899), a german mineralogist and chemist, in 1855 advanced the possibility of crystallization in the form of a left or right-handed tetrahedron15, but the isolation of the dextrorotatory asparagine was carried out only in 1886. figure 1. a portrait of arnaldo piutti in his laboratory at naples9. figure 2. the two forms of asparagine. 128 laura colli, antonio guarna the discovery of dextrorotatory “sweet” asparagine piutti guessed that the failure in identifying the dextrorotatory asparagine was presumably due to its low abundance in nature. in the factory of mr. galgano parenti, near siena, piutti prepared a large quantity of the product from sprouted vetch, a legume15. through fractional crystallization he observed the precipitation of two species of crystals: ordinary levorotatory asparagine, described at that time as “almost tasteless”, and dextrorotatory, which turned out to be “sweet”. thus the dextrorotatory asparagine could be detected and separated from the levorotatory form on the basis of its taste (figure 3). the two types of crystals were analyzed and found to be chemically identical, with the same refractive indices and same plane of optical axes. in the laboratory of physics headed by prof. roiti at the royal institute of practical and advanced studies in florence, piutti determined the optical rotation of the two species with a laurent polarimeter, measuring the following values: [α]d = -5.43 for the ordinary or levorotatory asparagine and [α]d = +5.41 for the dextrorotatory sweet asparagine15 . the dextrorotatory asparagine, whose existence was theoretically proposed by pasteur, was finally discovered. the synthesis of sweet asparagine after separating the dextrorotatory asparagine in 1886, piutti succeeded in setting up the synthesis in hislaboratory in 188716. the synthesis was carried out through the reduction of the oxime of oxaloacetate ether. piutti separated two monoethyl esters, written with the formulae: cooc2h5-ch-chnh2-cooh and cooc2h5-chnh2-ch2-cooh (according to the original notation). from the former derivative he obtained the amidate, and finally the two rotatory asparagines, identical to the natural products and called by piutti as a whole “β-asparagine”, with the formula: conh2-ch2chnh2-cooh (figure 4). this is of course a historical nomenclature, which does not comply with the common rules currently in use. from the second amidate he obtained the inactive “α-asparagine”, an isomeric form of the β-asparagines. thus, he came to the conclusion that he had obtained three asparagines. he did not know whether the inactive form, called “α-asparagine”, could be separated into two optically active asparagines. he successfully separated the β-asparagines and found that the compounds, like the natural products, differed in the rotation of the plane of polarization as well as in taste, in solubility and in density. piutti wrote: the synthetic asparagines, thus obtained, differ from each other, just like the natural ones. besides the different hemihedralism and the opposite rotatory power, even the taste, which in the levorotatory is insipid, while the dextrorotatory is “sweet”. furthermore “…as the rotatory asparagines have the same chemical composition, they are to be considered as physical isomers. piutti continued: this result […] also shows how the dextrorotatory asparagine, discovered by me in the vetch and now obtained by synthesis, is the physical isomer of the ordinary asparagine15. according to piutti “the second [amidate ] supplied the inactive species, chemically isomeric, and until today unknown” (inactive α-asparagine) that he specified with figure 3. the words of piutti about the first discover of sweet asparagine: “from the mother liquor from which the asparagine was crystallized, some crystals formed whose pronounced sweet taste i immediately caught”15. figure 4. nomenclature given by piutti to the “asparagines” he found: on the left the inactive asparagines that he called α-asparagine and the “mixture” of the two optically active asparagines, that he called β-asparagine (α-asparagine and β-asparagine are two racemic mixtures; piutti reported this observation, but was not able to confirm this assumption). on the right the products obtained by separation of the mixture of β-asparagine: the asparagine levorotatory, tasteless, and the dextrorotatory, with a sweet taste. 129the dextrorotatory sweet asparagine of arnaldo piutti: the original product is conserved in florence the formula: conh2-chnh2-ch2-cooh. he concluded by saying: i intend to complete the study of this asparagine [inactive α-asparagine] and to determine whether or not it is separable from the two rotatory asparagines of the same composition (such as the presence of an asymmetric c would suggest) when i will be able to prepare it in greater quantities. in 1890 piutti modified the preparation method 17. this time the asparagines were obtained from the silver salt of “acido γ-ossimmidosuccinico” in ether via solvent evaporation and filtration of the iodide excess. the result is an oil: “nitrilosuccinato dietilico”, a nitrogen derivative of diethyl succinate. the oil was treated with bromine in acetic acid solution yielding the compound c6h7n2o3br which is optically inactive. this compound was reduced in acetic acid solution with sodium amalgam. the mother liquor was left resting for a long time together with copper acetate; finally: with a fine sieve the [inactive] α-asparagine, reduced to powder by the loss of its crystallization water, is separated from the crystals of the rotatory β-asparagines, in their turn recognizable and separable by their taste or by their different hemihedralism17. in this way piutti understood that the formation of the rotatory asparagines is independent on the synthesis procedure. this observation also emphasizes the instability of the inactive asparagine for what he refereed to as “reasons of physical order”. however, his goal changed: he was prompted to isolate the inactive α-asparagine, and to separate it into the two rotatory forms. he wrote: the resolution of the inactive α-asparagine into two corresponding rotatory asparagines acquires therefore more interest now and i am confident of having the means to experiment later17. presence in nature of the sweet form in 1915 piutti made another important discovery: the two rotatory β-asparagines “coexist in the products of germinated lupins” 18. according to piutti, as the dextrorotatory sweet asparagine is mainly used by the plant itself, much more than its optical antipode, only a small quantity can be isolated. finally the dextrorotatory asparagine disappears with the process of germination18. the presence of dextrorotatory sweet asparagine was not due to racemization during the extraction from the plant, but according to piutti’s hypothesis, it was already present in the plant itself. the dextrorotatory sweet asparagine is the d-aminoacid: piutti demonstrated its presence in nature. during the years in which the theories of van ‘t hoff on optically active compounds were not yet easily accepted, piutti successfully identified the two enantiomers of asparagines. he demonstrated the correspondence between the crystallographic form and the optical properties of a chiral molecule and discovered a correlation between the different optical rotation of the molecule and the different response of the human receptors17. finally, a few years later, he observed the enantio-specific use of amino acids by plants 18. the existence of the two rotatory asparagines in lupins and their selective use in the plant and the observation that only one of the two enantiomers interacts with our receptors, giving the sweet taste, represented two major discoveries in biological chemistry. these results were of fundamental importance that, perhaps piutti (unlike pasteur) did not fully understand. the asparagine of piutti is conserved in the museum of natural history in florence the original sample of dextorotary sweet asparagine obtained by piutti in 1886 is conserved in the schiff collection of the university of florence. recently, the sample of dextrorotatory sweet asparagine has been included as a cultural asset to the scientific-technological heritage (“pst”, patrimonio scientifico e tecnologico), according to the italian ministry for cultural heritage and activities (ministero per i beni e le attività culturali). the information concerning this sample are available online through the sigecweb system of the central cataloging and documentation institute (iccd)19. the scientific and private correspondence of ugo schiff is also conserved at the “ugo schiff ” department of the university of florence, including the correspondence between schiff and piutti of those years. a study of these letters will elucidate how and why the sample of the asparagine of piutti remained in florence in his master’s laboratory. furthermore, it can shed light on piutti’s arguments related to his experimental work and whether he really understood or not the importance of those discoveries. acknowledgments the authors gratefully acknowledge the current head of the department of chemistry “ugo schiff ”, 130 laura colli, antonio guarna prof. andrea goti, the past directors and all the staff of the department, for the support to their research on the historical roots of the chemistry works carried out in florence. we thank dott.ssa mariagrazia costa for her constant and timely attention. we are also grateful to the museum of natural history for the aid to the chemical heritage project, in particular we thank prof. marco benvenuti, dott.ssa angela di ciommo and dott. ssa maria giulia maraviglia, prof. guido chelazzi and prof. giovanni pratesi. we acknowledge also fondazione cassa di risparmio di firenze for funding the chemical heritage project. references 1. a. guarna, l. colli, m. costa, in rendiconti della accademia nazionale delle scienze detta dei xl, serie v, vol. xxxiii, parte ii, tomo ii, 391-400, 2009. 2. j. gal, chirality, 2008, 20 (1), 5-19. 3. j. gal, chirality, 2008, 20 (10), 1072-84. 4. j. gal, chirality, 2012, 24 (12), 959–976. 5. l. pasteur, académie des sciences, 1886, comptes rendus hebdomadaires des séances de l’académie des sciences / publiés... par mm. les secrétaires perpétuels 6. g. montaudo, bollettino accademia gioenia di scienze naturali, 2000, catania, vol. 42 n. 371, 41-50 7. j. h. van’t hoff, la chimie dans l’espace, rotterdam, 1875. 8. j. i. solov’ev   jurij ivanovič,   l’  evoluzione del pensiero chimico dal ‘600 ai giorni nostri,  edizioni scientifiche e tecniche mondadori, milano 1976. 9. l. pescitelli, arnaldo piutti, napoli, tip. cimmaruta, della r. università, 1914 10. t.t. tidwell, angewandte chemie, 2008, volume 47, issue 6, 1016-1020 11. l. colli, l. dei, a. guarna, m. costa, in la palazzina dei servi a firenze. da residenza vescovile a sede universitari, a cura di cristina de benedictis, roberta roani, giuseppina carla romby, edifir edizioni firenze, 2014 12. l. cantoni appunti chimici sull’asparagina, milano, stab. della antica casa edit. dott. francesco vallardi, 1889 13. r. piria cimento, 1846, gennaio-febbraio 14. l. pasteur, annales de chimie et de physique, 1848, xxiv, 442. 15. a. piutti, gazzetta chimica italiana, 1886, xvi. 16. a. piutti, ricerche fatte nel laboratorio di chimica farmaceutica della r. università di sassari, 1887-88 17. a. piutti rend. della r. accademia delle scienze fisiche e matematiche di napoli, 1890, fasc. 3° 18. a. piutti estratti dalla r. accademia delle scienze fisiche e matematiche di napoli, 1915, allegato alla seduta del 4 dicembre, fasc. 11° e 12°. 19. http://www.iccd.beniculturali.it/index.php?it/118/ sistema-informativo-generale-del-catalogo-sigec. accessed on 13/07/2018. figure 5. the dextrorotatory sweet asparagine of piutti: on the left the compound in the original bottle with the original label handwritten by ugo schiff; on the right, a particular of the crystals of original asparagines contained in the bottle. this item is conserved in the schiff collection of “ugo schiff ” chemistry department at university of florence (class: collezione schiff, dco20). courtesy of the museum of natural history of the university of florence. substantia. an international journal of the history of chemistry 4(1): 71-81, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-647 citation: a. sztejnberg (2020) vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of the xx century. substantia 4(1): 71-81. doi: 10.13128/substantia-647 received: oct 02, 2019 revised: dec 20, 2019 just accepted online: dec 21, 2019 published: mar 11, 2020 copyright: © 2020 a. sztejnberg. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of the xx century aleksander sztejnberg professor emeritus, university of opole, oleska 48, 45-052 opole, poland e-mail: a.sztejnberg@uni.opole.pl abstract. vladimir nikolayevich ipatieff (1867–1952) was one of the most prominent chemists of the first half of the 20th century. he studied catalytic processes in organic chemistry. his discoveries include, among others, the explanation of the structure of isoprene, the method of obtaining butadiene from ethanol, dehydrogenation of alcohols to aldehydes and ketones, dehydration of alcohols to alkenes, including ethanol to ethylene, hydrogenation of benzene to cyclohexane, polymerization of ethylene in the presence of various catalysts. much of his experimental studies were carried out at high pressure in a rotating autoclave, the so-called “ipatieff bomb”. the purpose of this article was to familiarize readers with important events in the life of v. n. ipatieff and his research activities, in particular with selected results of his experimental studies. in addition, the statements by american and russian chemists about v. n. ipatieff and his research were presented. keywords. v. n. ipatieff, organic chemistry, catalysis and catalysts, russia, united states xx century. just as rays of the sun are distributed to all men, rich and poor, good and evil, so also scientific ideas, new discoveries, and inventions serve all humanity. v. n. ipatieff (1867-1952) [1] 72 aleksander sztejnberg the important events in the ipatieff’s life1 vladimir nikolayevich ipatieff (fig. 1) was called a man of the unusual fate, a brilliant experimenter and an outstanding organizer of industrial production. sixtyeight years have passed since his death, but in that time little has appeared in the literature about this outstanding man. his contribution to catalytic organic synthesis, as well as to major change in the chemical industry, is enormous. therefore, his name was forewer written in letters in gold in the history of chemistry. vladimir n. ipatieff was born in moscow on november 9 [according to the julian calendar (old style); nov. 21, by the gregorian calendar (new style), adopted in russia on february 1, 1918] 1867, the son of nikolay alekseevich ipatiev (1841-1891)2, an architect from an old and respectable merchant family, and anna dmitrievna ipatieva (née gliki) (1847-1880)3. at the age of 11, after two years of study at the fifth classical gymnasium, he continued his education at the third moscow military gymnasium. in 1884 he began studying at the 3rd alexandrovskaya military school in moscow. after two years, he transferred to the mikhaylovskaya artillery school in st. petersburg, which he graduated in 1887. for the next two years, he served in the artillery brigade in serpukhov, near moscow. to continue with his education, ipatieff successfully passed the entrance exams at the st. petersburg’s mikhaylovskaya artillery academy in august 1889. after three years of study, he graduated from the academy and became a tutor there. from september 1892, he began to give lectures on inorganic and theoretical chemistry. he also perfected his experimental skills in the organic chemistry in the chemical laboratory at the st. petersburg imperial university. lecturer of the organic chemistry, privat-docent, alexey evgrafovich favorsky (1860-1945) 1 presented facts from ipatieff ’s life were collected, basing on the following sources of information from 1905-2017 [2-14,16,17,19]. a brief description of the life and achievements of 38-year-old ipatieff was found in the encyclopedic dictionary, published in 1905 [2]. very useful turned out to be the book with his scientific biography published in russian in the early 1990s [3]. interesting information on his life and scientific activity was also found in scientific literature, both in russia [4-9] and the usa [10-13]. many descriptions of ipatieff ’s experimental studies were found in his authoritative book published in russian in 1936 [14]. this book was translated into english in 1937 [15]. a great source of information about the life of vladimir n. ipatieff was a two-volume book with his memories from the years 1867-1930, published in russian in new york in 1945 [16,17]. this book was published in english by stanford university press a year later [18]. in the ex-soviet union excerpts from this book were published in the journal khimiya i zhizn’ (chemistry and life) in 1989 [19]. 2 in 1890, he became seriously ill due to asthma and arteriosclerosis. a year later, he died at the age of 50 [16]. 3 she died of tuberculosis at the age of thirty-three [16]. offered him help and advice. in may 1895, after working for three years as tutor, he defended his dissertation in chemistry entitled deystviye broma na tretichnyye spirty i bromistogo vodoroda na atsetilenovyye i allennovyye uglevodorody v uksusnom rastvore (action of bromine on tertiary alcohols and the action of hydrogen bromide on acetylenic and allene hydrocarbons in an acetic solution) and was nominated a full-time lecturer of chemistry at the academy. a foreign internship in germany, which ipatieff began in 1896, was very important to shape him as a scientist. he worked there in the chemical laboratory of the academy of sciences in munich (das chemische laboratorium der akademie der wissenschaften zu münchen) with adolf von baeyer (1835-1917). in december 1896, baeyer and ipatieff published a paper, “ueber die caronsaüre”, in which the authors described their figure 1. vladimir nikolayevich ipatieff (1867-1952) (public domain, from reference 20]. the image was made in 1914. v. n. ipatieff is in the uniform of lieutenant general [13]. 73vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of the xx century study on the structure of the caronic acid (3,3-dimethylcyclopropane-1,2-dicarboxylic acid; c7h10o4) [21]. on march 1, 1897, he completed his an internship abroad. travelling from munich to paris, he stayed 2 days in strasbourg, where he attended a lecture of the german chemist-organic wilhelm rudolph fittig (1835-1910). in paris, he for three months worked in the laboratoire central des poudres et salpêtre (central laboratory of gun powder and saltpeter) with chemist paul vieille (1854-1934), discoverer of the smokeless gunpowder, and physicist emile sarrau (1837-1904). on the end of june 1897, on his way from paris to russia, he stayed in germany – first in frankfurt am main, where he visited factory manufacturing carbolic acid [phenol], next in ludwigshafen, where he visited factory producing dyes and soda. then, he reached russia via berlin. after a 3-week rest in moscow, he went to st. petersburg. in 1898, ipatieff submitted his professor’s dissertation to the academy, entitled allenovyye uglevodorody, reaktsiya khloristogo nitrozila i dvuoksi azota na organichaskiye soyedineniya, soderzhashchiye dvoynuyu svaz’, i sintez izoprena (allene hydrocarbons, the reaction of nitrosyl chloride and nitrogen dioxide on organic compounds with double bond, and the synthesis of isoprene) and paper under the title prigotovleniye i vzryvchatyye svoystva trinitrokrezola i trinitronaftalina (preparation and explosive properties of trinitro-cresol and trinitro-naphthalene). at the end of february 1899, after successful public defense of the dissertation, he was unanimously awared the title of professor of chemistry and explosives at the academy. in 1902, he was appointed professor ordinary at the academy. in the same year, physico-mathematical faculty at the st. petersburg imperial university invited ipatieff as the privat docent to lecture thermochemistry. since that time, he maintained constant contact with the university up to 1916. from 1906, he was given obligatory lectures of the general chemistry for physicists, mathematicians, and astronomers. in the thirds decade of march 1908, ipatieff defended his dissertation for the doctor of chemistry degree at the st. petersburg imperial university entitled kataliticheskiye reaktsii pri vysokikh temperaturakh i davleniyakh (catalytic reactions at high temperatures and pressures). v. n. ipatieff was elected the supervisor of the chemical laboratory at the st. petersburg’s mikhaylovskaya artillery academy in 1909. his helper was a fulltime lecturer, chemist nikolay mikhalovich vittorf (1869-1929). ipatieff ’s military career did not interfere with his scientific life. in 1910, he was promoted to the rank of major general of the russkoy imperatorskoy armii (russian imperial army). at the age of forty-seven in 1914, he had obtained the rank of lieutenant general. during world war i, from february 1915, ipatieff served as a head of the commission for preparation of explosives, which controlled almost the entire russian chemical industry until the end of the war, among others, the production of potassium nitrate, dinitronaphthalene, benzene, toluene, sulfuric acid, nitric acid, and picric acid from benzene. in 1916, he was named chairman of the chemical committee of the chief artillery administration, which was formed mainly due to the use of poison gas by the germans on the eastern front in may 1915. thanks to the activities of the chemical committee and included in its composition the commission for the preparation of asphyxiating gases, the production of liquid chlorine, phosgene, chloropicrin and sulfuryl chloride from liquid sulfur dioxide was started. after the october revolution in 1917, ipatieff began to cooperate with the bolsheviks. he was appointed chairman of both the chemical committee and the technical department of the military economic council of the people’s commissariat for military affairs. in june 1918, he was relieved from these positions. in the years 1921-1926, he served as chairman of the general chemical directorate of the supreme council of the national economy. at the beginning of 1927, he was relieved of all posts in state structures. he returned from moscow to leningrad [name of the city of st. petersburg in 1924-1991], where he founded and directed the institute of high pressures. on october 23-26, 1927, ipatieff took part in the jubilee celebrations organized in paris on the occasion of the 100th anniversary of the birth of the french chemist marcellin berthelot (1827-1907). the ceremony was attended by scientists from 60 countries around the world, including richard willstätter (1872-1942), who was honoured by the award of the nobel prize for chemistry in 1915, heinrich wieland (1877-1957), fritz haber (1868-1934), who was awarded the nobel prize for chemistry in 1918, wilhelm schlenk (1879-1943), and walther nernst (1864-1941), who was the winner of the 1920 nobel prize in chemistry. there he first met with 73-year-old paul sabatier, who received the nobel prize in chemistry in 1912. their meeting took place in a pleasant and friendly atmosphere. in 1929, the political situation in the soviet union worsened. the campaign against specialists has begun. many people were arrested in moscow and leningrad by the g.p.u. (state political administration), among them those, who worked with ipatieff for years. he, com74 aleksander sztejnberg ing back from the international engineering congress in tokyo, was agitated by the execution of five military engineers-technologists. all were his very smart students at the academy, who since the very beginning of the october revolution worked on the bringing factories manufacturing military equipment to work. moreover, physicochemist yevgenii ivanovich shpitalsky (1879-1931) was arrested. later, in 1945, ipatieff wrote in his memoirs: “my mood became especially alarming, because ye. i. was my great friend, knew all the details of my life and during an interrogation, purely incidentally, he could report some facts, that would allow to bring me to interrogation, and subsequently to be arrest” [17]. in early june 1930, ipatieff was appointed as one of the ten delegates to the international energy congress in belin called the second world power conference. he replaced one of the professors of electricity who was arrested. on june 12, 1930, he and his wife varvara dmitrievna (1869-1952) crossed the soviet union (ussr) border in negorloe4. their matured children – anna vladimirovna and son vladimir vladimirovich stayed in ussr5. the oldest of their two other sons, dimitri (1893-1914) was already dead. he was killed near vilnius during the world war i. their next son nicolay after the october revolution left russia with participants of the white movement called belogvardeytsi (white guardsmen) and has lived in belgium since 19196 [22]. ipatieff ’s half-brother chemist lev aleksandrovich chugaev7 (1873-1922) was already dead, and his younger brother, engineer nikolay nikolayevich ipatiev (1869-1938), from 1921 he stayed in prague (czechoslovakia, now the czech republic)8. at the berlin conference, which took place on june 16-26, 1930, vladimir n. ipatieff met many eminent 4 while wives were usually not allowed to travel abroad with their husbands, ipatieff received his wife’s passport in just three days, stating that he would be a delegate only if his spouse can accompany him because she needs treatment abroad. until they left russia, he didn’t tell his wife that he did not expect to return to the country [13]. 5 professor and doctor of science, vladimir vladimirovich ipatiev (1897-1955), like his father, was a chemist. he managed the laboratory of the leningrad scientific-research institute dealing in the processing of crude oil and the production of synthetic liquid fuel. he also lectured at the forestry academy and the leningrad state university [4]. 6 in 1935, nikolay [nicolas (d’) ipatieff ] died in africa testing a treatment he had invented for yellow fever. at that time, he worked in the belgian congo as the government inspector industry and commerce [22]. 7 the father of lev aleksandrovich was the teacher alexander fomich chugaev. his mother was ipatieff ’s mum, anna dmitrievna. vladimir n. ipatieff did find out that lev a. chugaev is his half-brother in 1907 [16]. 8 on july 17, 1918, in his house in yekaterinburg the bolsheviks killed tsar nicholas ii and his family [17]. chemists from different countries all over the world. one of them was an american chemist gustav egloff (18861955) from universal oil products company (uop) in chicago [12]. he told engloff that he interested in visiting uop laboratories in the usa. in september, 1930, he and his wife arrived in new york city, thanks to egloff ’s help in obtaining a visas from the american consul. after his visit to research laboratories of the uop in riverside (illinois), and talk with the president of uop – hiram j. halle (1867-1944), he agreed to take a post of the director of chemical research. as he was bound by a 3-year contract with german bayerische stickstoffwerke (bavarian nitrogen), he agreed with halle that 6 months he will stay in germany and remaining 6 months in the united states. then, ipatieffs returned to berlin. in may, 1931, both spouses came to the usa again. in addition to working as a research director at uop research laboratories, he also became a lecturer on catalysis in organic chemistry at northwestern university. the political situation in the ussr, after leaving the country by ipatieff, did not improve. in 1934, his close associate organic chemist grigory alekseevich razuvayev (1895–1989) was arrested. a former his student, a geochemist nikolay alexandrovich orlov (1895-1937) was also arrested. in january 1935, many well-known people from the party and government were convicted and soon shot, including lev borisovich kamenev (18831936) and grigory yevseyevich zinoviev (1883-1936), with whom he has previously collaborated. from the last month of the third quarter of 1936, correspondence was conducted between the permanent secretary of the academy of sciences of the u.s.s.r, academician nikolay petrovich gorbunov (1892–1938) and ipatieff about the need to return the scientist to the ussr. the translation of an excerpt of gorbunov’s letter of september 17, 1936, to ipatieff into english is as follows: “… for about six years now you have been outside the borders of the ussr and are not taking any part in the practical work of socialist construction. you are a citizen of the ussr, a major scientist, a full member of the academy of sciences, our country needs you. therefore, on behalf of the presidium of the academy of sciences, i ask for your direct, clear and frank answer to the following question do you consider yourself obligated to work fully for your homeland the soviet union, for to enhance his power and prosperity … . if you answer the question posed to you in the affirmative, then you should soon return to the ussr for scientific work. …” [9]. here is an excerpt from a ipatieff reply to gorbunov, translated from russian into english (letter of 1 december, 1936). “… i must say, firstly, that i 75vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of the xx century can in no way agree with the fact that i do not take any part in the scientific work that has taken place in the ussr over these six years. … it is enough to indicate that … i wrote a book, which, in addition to summarizing my old studies, contains very valuable new material that will be used to great advantage in the ussr. … in addition, i sent all my new studies to russian chemical journals at the same time as sending their translations to american journals. … it is undeniable that every scientist works not only for his country, but for all mankind. i love my homeland and, making new discoveries, i always thought and think now that all this belongs to her and she will be proud of my work. … i ask you to declare to the presidium of the academy of sciences that i’m not giving up my hope of coming to the ussr, but now the circumstances are such that i actually can’t do this. ...” [9]. on december 29, 1936, ipatieff was deprived the title of the member of the academy of science of the ussr. in its justification was written, among other, “refusing to return to work at the academy of science, decidedly preferring work in the foreign commercial company, v. n. ipatiev grossly violates the basic duty of every citizen of the soviet union – to work for the good of his homeland” [23]. ipatieff was expelled from the academy by sixty-three votes in favor, no one against, and six abstentions [24]. on january 3, 1937, presidium of the central executive committee ussr in the decision signed by mikhail ivanovich kalinin (1875-1946) and ivan alekseyevich akulov (1888-1939) decided to “deprive vladimir nikolayevich ipatiev of citizenship of the ussr, because he refused to fulfill his duty to his homeland and forbid to cross the borders of the soviet union” [25]9. vladimir n. ipatieff did not wait long for american citizenship. on march 11, 1937, he became united states citizen. his wife received such citizenship one month later. on the day of the 70th birthday of ipatieff, chicago section of the american chemical society (acs) organized ceremonious meeting, in which he gave the lecture entitled “catalysis chemistry of the future”. he in this occasion received greetings from the scientists of 30 countries all over the world, for instance german chemist friedrich bergius (1884-1949), american chemist-organic mozes gomberg (1866-1947) and estonian chemist gustav tammann (1861-1938). 9 ipatieff ’s daughter, anna vladimirovna (1894-1958) persistently fought for the restoration of the good name of her parents. in 1957, she turned to kliment efremovich voroshilov (1881–1969) for posthumous rehabilitation of her father. in 1990, citizenship and membership in the ussr academy of sciences was posthumously restored to vladimir n. ipatieff [4]. on december 18, 1939, ipatieff underwent a serious throat surgery, after which he spoke in a hoarse whisper. his doctor forbade him any public speech. however, this problem did not exist too long, and after a few months after surgery, he was again able to speak at meetings. particularly interesting were the celebrations that took place on november 14-20, 1942, on the occasion of ipatieff ’s 75th birthday, 50 years of his scientific activity and the golden anniversary (50 years of his marriage). in the organized ceremonious meetings, warm greetings he received from gustav egloff and representatives of the chemical institutions from various american states. greeting sent also american chemists: linus pauling (1901-1994), paul emmet (1900-1985), and kasimir fajans (1887-1975). between may 28 and june 6, 1951, ipatieff attended the third world petroleum congress in the hague (the netherlands). in july 1952, he celebrated the 60th anniversary of his wedding. there were no any meetings on the occasion of his 85th birthday because he categorically opposed their organization by northwestern university. he died a few month later, at 07:00, in saturday on november 29, 1952, and was buried in the saint vladimirs russian orthodox cementary in jackson, ocean county (new jersey). ten days later (on december 9) died his wife varvara dimitrievna. ipatieff’s research activities. description of selected results of experimental studies the list of ipatieff ’s published works includes 399 papers. there are the articles published in russia and the soviet union, among other in the journals zhurnal russkogo fiziko-khimicheskogo obshchestva (journal of the russian physical-chemical society) and doklady akademii nauk sssr (proceedings of the academy of sciences of the u.s.s.r), and many papers published in german, french and american journals [13,26]. ipatieff ’s first work was published in 1892 and concerned the chemical investigation of the structure of steel. in the following years, he focused his research in the field of organic chemistry. in two articles from 1897 he described his method of the synthesis of isoprene (2-methyl-1,3-butadiene) and as the first among chemists, correctly explained the diene nature of its structure [5,27,28]. information about isoprene synthesis by ipatieff appeared, among other, in the book written by thomas percy hilditch (1886-1965) – british chemist – in 1911 [29], and in 1913 in the book written by another british chemist benjamin dawson porritt (1884-1940) [30]. 76 aleksander sztejnberg the studies of catalytic processes in organic chemistry was started by ipatieff in 1901, independently and simultaneously with french chemist paul sabatier (18541941) [1,16]. he did a lot of safe laboratory experiments using a rotating autoclave, so-called “ipatieff bomb”, which he designed to conduct studies under pressure of several hundred atmospheres. such apparatuses, for the first time, were made in 1904 according to the drawings of ipatieff in a private mechanical workshop by the mechanic mal’mstrem (malmstrom), and then were made at a mechanical plant in st. petersburg, which belonged to richard langensiepen (1847-1920) [14]. v. n. ipatieff used various catalysts in his experimental studies. he and his co-workers carried out many different catalytic reactions, among others, the reactions of dehydrogenation, dehydration, hydrogenation, alkylation, destructive hydrogenation, condensation, destructive alkylation, polymerization, selective demethylation, and isomerization. the examples given below relate to experimental studies carried out in 1901-1951. based on studies of both dehydration and dehydrogenation of alcohols, carried out in high temperatures under ordinary pressure, ipatieff stated that depending on the material of the tube in which alcohol was decomposed, he received various products [31]. dehydration of ethanol to ethylene was his first experimental study carried out in the laboratory of the st. petersburg’s mikhaylovskaya artillery academy in 1901. in this study, he passed vapors of the ethanol through a graphite tube inserted into an iron tube at 600°c. confirmation of obtaining ethylene in this reaction was that the resulting gas reacted with bromine to form ethylene dibromide (1,2-dibromoethane) [14]. in another study, he passed vapors of the ethanol through a glass tube containing pieces of graphite mass also at 600°c, and the ethanol quickly decomposed into ethylene and water. propyl alcohol in the same way was dehydrated into propylene [32]. when the vapors of a primary aliphatic alcohol, for instance ethanol, passed through a platinum tube inserted into a wide iron tube, at 780°c the alcohol decomposed and the main reaction product was acetaldehyde [14]. he also found that secondary alcohols dehydrogenate in an iron tubes to ketones [33], and tertiary to olefins [14]. vladimir n. ipatieff discovered a new method for the conversion of ethanol to divinyl (1,3-butadiene), during which hydrogen was formed. when passing the vapors of this alcohol at high temperature and ordinary pressure over powdered aluminum as a catalyst, the following reaction take place: ch3 – ch2oh + ch3 – ch2oh = 2h2o + ch2 = ch – ch = ch2 + h2 [14,34]. using a rotating bomb, ipatieff studied the reduction of benzene by hydrogen under high pressure. he, working with 25 grams of benzene and 2 grams of black nickel oxide (nickel (iii) oxide) at 250°c under a hydrogen pressure of 180-186 atmospheres10(18.238500 to 18.846450 mpa), hydrogenated benzene to hexahydrobenzene (cyclohexane) for one and a half hours [14,35]. the hydrogenation of the citral (3,7-dimethylocta2,6-dienal) was carried out by ipatieff at 110°c in the presence of palladium. he found that under a hydrogen pressure of 110 atmospheres (11.145750 mpa), pure decanol (3,7-dimethyl-1-octanol) could be obtained in four hours [14]. the simultaneous used of nickel oxide and alumina, in another experimental study, allowed him to obtain isocamphane (c10h18) from borneol (c10h17oh) within 10-12 hours at 215-220°c under a hydrogen pressure of 110 atmospheres (11.145750 mpa). he also mixed 30 grams of camphor (c10h16o) with 3 grams of nickel oxide and 1.5 grams of alumina. the hydrogenation of camphor into isocamphane was achieved in 24 hours at 200°c under a hydrogen pressure [14]. for the first time, v. n. ipatieff and finish chemist o. rutala polymerized ethylene in the presence of dry zinc chloride as a catalyst at 275°c under pressure 70 atmospheres (7.092750 mpa). according to the gas product analysis, paraffins (61%), olefins (36%) and hydrogen (3%) were present. the results of study also showed that the liquid reaction product contained pentane and hexane, and some alkenes (hexylene, hepylene, octylene and nonylene) [14,36]. the study on the catalytic synthesis of methane from carbon and hydrogen ipatieff carried out in the presence of catalyst consisting of nickel and alumina at 500-519°c and under hydrogen pressure of 35 to 60 atmospheres (3.546375 to 6.079500 mpa) [14,37]. for hydrogenation of anethole (1-methoxy-4-(1prop-1-en-1-yl)benzene), ipatieff used nickel as a catalyst. this compound was reduced to dihydroanethole (1-methoxy-4-propylbenzene) at 95°c under a hydrogen pressure of 50 atmospheres (5.066250 mpa) within 4 hours [14,38]. for the first time v. n. ipatieff and his associates carried out alkylation of phenol in the presence of alumina. the phenol was heated with methyl alcohol and alumina in a ipatieff rotating bomb at 440°c. it was found that at a pressure of up to 200 atmospheres (20.265000 mpa), o-cresol (ch3c6h4oh) as a the main product of this reaction was obtained within 24 hours. neither m-cresol nor p-cresol was found in reaction products [14,39]. 10 in the article the conversions have been made from atmospheres to mpa as a derivated unit of si. 77vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of the xx century as the result of experimental study v. n. ipatieff and n. kljukvin were successful in solving the problem of destructive hydrogenation of naphthalene in a rotating autoclave. they, working with 3 grams of catalyst (50% nio, 50% al2o3) and 40-60 grams of naphthalene at 450-480° under a hydrogen pressure of 60 atmospheres (6.079500 mpa), succeeded in hydrogenating naphtalene in 25 hours. the main reaction product was hydrogen. small amounts of methane and carbon dioxide were also obtained [14,40]. vladimir n. ipatieff and his associates proposed a new method for obtaining xanthene (ch2[c6h4]2o) in a catalytic condensation reaction. this compound was obtained by heating o-cresol (ch3c6h4oh) and phenol (c6h5oh) in the presence of alumina as a catalyst at 440-450°c under the high pressure [14,41]. v. n. ipatief and v. i. komarewsky conducted research that enabled the destructive alkylation of benzene. they used 81.1 grams of benzene and 8 grams of aluminum chloride saturated with hydrogen chloride. the reaction proceeded in a rotating bomb at 125°c within 24 hours [14,42]. the main reaction products were ethylbenzene (c6h5c2h5) and diphenyl (c6h5c6h5). “the formation of these two compounds makes probable the following scheme of the reaction: (a) two parts of benzene combine to form [under the influence of aluminum chloride] diphenyl, liberating hydrogen; (b) a destructive hydrogenation of the benzene occurs during which benzene decomposes, and the decomposed fragments are hydrogenated to form ethylene; (c) ethylene alkylates the unchanged benzene to form ethylbenzene” [42]. for the first time polymerization of ethylene under pressure of 48.39 atmospheres (4.903325 mpa) at 330°c in the presence of 90% phosphoric acid as a catalyst was studied by v. n. ipatieff and herman pines (1902-1996). olefins, paraffins, naphthenes and aromatic hydrocarbons were found among the reaction products obtained within eight hours [43]. studies of the catalytic dehydrogenation of gaseous of paraffins in the presence chromium oxide on alumina as a highly selective catalyst at 500-750°c have been carried out by v. n. ipatieff and aristid v. grosse (1903-1985). it was found that the conversion of paraffins to the corresponding olefins proceeded with a yield of 90-95%. the ethane was converted into ethylene, the propane into propylene, and isobutane (2-methylpropane) into isobutylene (2-methylpropene). a mixture consisting of α-butylene (1-butene), cis-β-butylene (cis2-butene) and trans-β-butylene (trans-2-butene) was obtained from n-butane [44]. the research of v. n. ipatieff and robert l. burwell, jr. (1912-2003) has led to the preparation of various ethers. as a result of the passage of an equimolar mixture of benzyl alcohol and methanol over seventy five cubic centimeters of “solid phosphoric acid” in the form of pellets (5 x 7 mm) used as a catalyst at 350°c under pressure of 50 atmospheres (5.066250 mpa), benzyl methyl ether (methoxymethylbenzene) was obtained. they also showed that “solid phosphoric acid” catalyze at 336°c under pressure of 60 atmospheres (6.079500 mpa), the reaction between methanol and ethanol. the product of this reaction was ethyl methyl ether (methoxyethane) [45]. vladimir n. ipatieff with vladimir haensel (19142002) developed the catalytic method of selective demethylation. this method was used to obtain triptane (2,2,3-trimethylbutane), a hydrocarbon with antiknock properties. triptane began to be used as an aviation gasoline component. thanks to it, the performance of aircraft engine has improved significantly [46]. the results of experimental studies conducted by herman pines, william a. huntsman, and v. n. ipatieff showed that alkylation is accompanied by isomerization. for instance, by reacting of 1.2 mole of benzene (c6h6) with 0.1 mole of ethylcyclopropane (c3h5c2h5) in the presence of 0.5 mole hydrogen fluoride as a catalyst, at 0-5°c, were obtained the mixture which consisted of about 63% of 2-phenylpentane [ch3ch(c6h5)c3h7] and 37% of 3-phenylpentane [c2h5ch(c6h5)c2h5] [47]. they also showed that the product from the reaction 0.114 mole of 3-pentanol (ch3ch2chohch2ch3) with 1.0 mole of benzene and 1.0 mole of hydrogen fluoride in the same temperature consisted of 56% 2-phenylpentane and 44% 3-phenylpentane [48]. statements by american and russian chemists about vladimir n. ipatieff and his scientific research in 1942-2018, some chemists and historians of chemistry in both the united states and russia have spoken very positive about ipatieff and his scientific research. in their eyes, he was not only creator, excellent experimenter, and organizer, but also the great patriot. below, these statements are quoted. frank clifford whitmore (1887-1947), professor at the school of chemistry and physics of the pennsylvania state college said in 1942: “russia has produced three outstanding chemists among its many great ones. these are lomosoff, mendeleev, and ipatieff. ipatieff has had a far greater influence on world chemistry than his two famous countrymen. he is a chemist who was a pioneer 50 years ago and is still pioneering today” [11]. 78 aleksander sztejnberg ward v. evans (1880-1957), former chairman of the department of chemistry of northwestern university, on the ocassion of the ipatieff ’s eightieth birthday said in 1947: “ocasionally a great research worker is born. occasionally the world produces a great teacher. occasionally a great humanitarian appears in the race. very rarely, almost in defiance of the law of probability, are all these personalities embodied in a single individual. when to this unusual combination is added yet another, the gallantry to endure unheardof hardship and suffering and to rise above it with head unbowed and eyes bright, to carry out at 80 years some of the greatest researches of a lifetime, you have an idea of the man you meet in this russian scientist whom we now proudly claim as a fellow american—vladimir n. ipatieff ” [49]. jacob joseph bikerman (1898-1978), head of the adhesives laboratory of the massachusetts institute of technology (1956-1964) wrote: “if he were born in america instead of russia, he probably would become the president of a billiondollar corporation. he emigrated to the united states when he was about 60, learned english at this age, and showed (in the universal oil company) that he was more than a match for american-born rivals. … the first great success was achieved by ipatiev relatively late because he was trained to be an army officer and, as a chemist, was a self-made man. this success was in the field of heterogeneous catalysis. other scientists studied and utilized this technique at moderate temperatures and at the atmospheric pressure” [50]. in the 1991 book historian of chemistry vladimir ivanovich kuznetsov (1915-2005) wrote, that ipatieff was “the originator of the catalysis theory in the high temperatures and pressures, which became scientific basis of the industrial organic synthesis”, and also that during the world war i, he was “the organizer of the sulfuric acid and benzene industries in russia” [8]. the authors of the brochure commemorating the research carried out the “uop riverside research and development laboratory” wrote that ipatieff “was one of only three industrial chemists to receive the prestigious willard gibbs medal of the chicago section of the acs since the award’s inception in 1911. because he played a leading role in the development of uop’s polymerization, alkylation, and isomerization processes, ipatieff made a major contribution to the development of the high-octane aviation fuel that helped the allies win world war ii” [51]. in the 2017 publication andrey g. morachevskiy, professor of st. petersburg polytechnic university of peter the great wrote: “he laid the groundwork of the innovated heterogenic catalysis in the organic chemistry, he was an excellent experimenter and industrial production organizer. the general-liutenant, academician, he managed the whole military-chemical industry in russian in the difficult years of the world war i” [52]. herman pines, who was the “student, friend, and the executor of v. n. ipatieff ’s will” said in 1967: “you, russians, cannot even comprehend who vladimir ipatieff was. every hour of his life here, in the united states, every step in his research, he dedicated it all to russia. his limitless love for his motherland, which i have never seen in any of the emigrants, was the soil on which grew the outstanding results of his scientific work …” [53]. in 2018 publication christopher p. nicholas, principal scientist at honeywell uop wrote: “vladimir ipatieff contributed numerous concepts to catalysis including high pressure, dispersion of metals on supports, and the use of promoters. he also discovered many catalysts and reactions, several of which are still in use today, some 80 years later. his efforts continue to inspire the catalysis community in many ways, including through the ipatieff prize administered by the acs, processes offered by industry, and the teaching of students at northwestern university” [54]. conclusion vladimir nikolayevich ipatiff was one of the eminent chemist of the first half of the xx century. he played a huge role in the development of catalysis, first in russia and then in the united states. he was a pioneer in the study of catalytic reactions at high temperatures and pressures in organic chemistry. the results of his many experimental studies have been published in scientific journals in several countries around the world. he, as an inventor or co-inventor, acquired 174 u.s. patents. v. n. ipatieff became a corresponding member of the imperial st. petersburg academy of sciences on november 29, 1914. he was elected an academician on january 9, 1916. at that time only two chemists pavel (paul) ivanovich walden (1863-1957) and nikolay semenovich kurnakov (1860-1941) shared this distiction with him. vladimir n. ipatieff became member of the göttingen academy of sciences in 1922. in 1930, he was elected an honorary member of the deutsche chemische gesellschaft (german chemical society) [10]. the russian institute of science in belgrade (former yugoslavia) elected him an honorary member in 1938. on april 26, 1939, he became a member of the national academy of science of the united states of america. he was elect79vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of the xx century ed doctor honoris causa of the universities of munich (1927), of strasbourg (1928), of northwestern (1938), and of sofia (1939) [6,13]. on the american website medill reports chicago in the article entitled nu symposium of honors chemist vladimir nikolayevich ipatieff who helped win world war ii by lakshmi chandrasekaran [55] is an information about symposium devoted to ipatieff ’s 150th anniversary, which took place on september 7, 2017. it was organized by the center for catalysis and surface science (ccss) and the institute of sustainability and energy (isen) at northwestern university [56]. chandrasekaran’s article also contains the photograph of wolfgang sachtler (1924-2017), ccss director in 19851994, robert l. burwell, jr., and herman pines, standing in the front of a big, hanging on the wall on the second floor of the catalysis building, beautiful, color ipatieff ’s portrait. on his chest is visible the insignia of commander of the legion of honour (commandeur de la légion d’honneur). this is one of the highest honours of the french republic, which the french government awarded him in 1916 in recognition of all his work during world war i [10,57]. the russian physical-chemical society awarded ipatieff with the minor butlerov prize in 1896. the ivanov prize of the imperial st. petersburg academy of sciences was awarded to him in 1906; in 1920, the major butlerow prize, and in 1927, the lenin prize, granted by the soviet government for his work on catalysis and high pressure. in 1928, at the congress of industrial chemistry in strasbourg, he was honored the berthelot medal awarded by la société de chimie industrielle (the industrial chemistry society) in paris [10,13,17]. the high pressure and catalytic laboratory at the department of chemistry of northwestern university, estabilished in 1940, was named in honor of ipatieff [58]. in the same year, he was honored with the willard gibbs award, which is granted to the: ”eminent chemists, who through years of application and devotion, have brought to the world developments that enable everyone to live more comfortably and to understand this world better” [59]. in 1942, he was awarded with the honor scroll award “presented annually by the chicago chapter of the american institute of chemists for distinguished service to the science and profession of chemistry” [60]. the russian academy of sciences on the occasion of the 150th anniversary of ipatieff ‘s birth organized two exhibitions in 2017-2018. the first exhibition on-line organized by st. petersburg branch of the russian academy of sciences archive besides an information about the most important events in ipatieff ’s life contains photocopies of his and the members of his family personal documents [4]. the second exhibition contained his selected works, which were ranked, among other, in the following categories: general catalysis, alcohols dehydrogenation, alcohols degradation, hydrogenation, and general chemistry. moreover, chemistry handbook written by ipatieff in 1902-1909 were shown: kurs neorganicheskoy khimii (a course of inorganic chemistry, 1902), kurs organicheskoy khimii (a course of organic chemistry, 1903), rukovodstvo dlya prakticheskich zanyatiy po khimii (a guide for practical training in chemistry, 1905), and kratkiy kurs khimii (a short course in chemistry, 1909). photographic part of the exhibition is available in the web, still. it contains among other ipatieff ’s photographs made in various periods of his life and photocopies of the title pages of the books written by him [61]. the name of this remarkable russian-american chemist is loudly heard in the chemists milieu in both united states and russia. there are two awards associated with his name. first “ipatieff ’ prize”, is sponsored by the ipatieff trust fund. it is awarded by the american chemical society every three years, since 1947, for “the outstanding chemical experimental work in the field of catalysis or high pressure, carried out by an individual of any nationality, who is not over 40 years of age” [62]. second prize, premiya imeni v. n. ipat’yeva (the prize named after v. n. ipatiev) is awarded by the russian academy of sciences every three years, since 1994. russian chemists receive this award “for outstanding work in the field of technical chemistry” [63]. references 1. v. n. ipatieff, russian review. 1943, 2, 68. http:// dx.doi.org/10.2307/125254 2. i. e. andreevsky (ed.), entsiklopedicheskiy slovar’. dopolnitel’nyy tom 1а. gaagskaya konferentsiya – kochubey [encyclopedic dictionary. additional volume 1a. the hague conference – kochubey], f. a. brockhaus, i. a. efron, st. petersburg, 1905, 835 (in russian). retrieved from https://dlib.rsl.ru/ viewer/01003924175#?page=362 3. v. i. kuznetsov, a. m. maksimenko, vladimir nikolayevich ipat’yev (1867-1952), izdatel’stvo “nauka” [vladimir nikolayevich ipatiev (1867-1952), publishing house “science”], moskva, 1992 (in russian). 4. o. a. kirikova, a. s. maleshek, formula zhizni v. n. ipat’yeva: k 150-letiyu so dnya rozhdeniya uchenogo [the formula of life of v. n. ipatiev: to the 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http://www.ihst.ru/projects/sohist/document/chim36a.htm http://isaran.ru/?q=ru/person&guid=1857538a-1e46-06e1-5b8a-e300f7d39e11 http://isaran.ru/?q=ru/person&guid=1857538a-1e46-06e1-5b8a-e300f7d39e11 http://isaran.ru/?q=ru/person&guid=1857538a-1e46-06e1-5b8a-e300f7d39e11 https://dx.doi.org/10.1002/prac.18970550101 https://dx.doi.org/10.1002/prac.18970550102 https://dx.doi.org/10.1002/prac.18970550102 https://doi.org/10.1002/cber.19010340352 https://doi.org/10.1002/cber.190203501174 https://doi.org/10.1002/cber.190203501173 https://doi.org/10.1002/prac.19030670139 https://doi.org/10.1002/prac.19030670139 https://doi.org/10.1002/cber.19070400209 81vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of the xx century 36. w. ipatiew, o. rutala, ber. dtsch. chem. ges. 1913, 46, 1748. https://dx.doi.org/10.1002/cber.19130460278 37. wl. ipatiew, j. prakt. chem. 1913, 87, 479. https://doi. org/10.1002/prac.19130870131 38. wl. ipatjew, ber. dtsch. chem. ges. 1913, 46, 3589. https://doi.org/10.1002/cber.191304603142 39. v. ipatieff, n. orloff, g. rasuvaeff, bull. soc. chim. fr. 1925, 37, 1576. 40. w. ipatiew, n. kljukwin, ber. dtsch. chem. ges. 1925, 58, 1. https://doi.org/10.1002/cber.19250580103 41. w. ipatiew, n. orlow, a. petrow, ber. dtsch. chem. ges. 1927, 60, 130. https://doi.org/10.1002/ cber.19270600121 42. v. n. ipatieff, v. i. komarewsky, j. am. chem. soc. 1934, 56, 1926. https://doi.org/10.1021/ja01324a029 43. v. n. ipatieff, h. pines, ind. eng. chem. 1935, 27, 1364. http://doi.org/10.1021/ie50311a032 44. a.v. grosse, v. n. ipatieff, ind. eng. chem. 1940, 32, 268. https://doi.org/10.1021/ie50362a024 45. v. n. ipatieff, r. l. burwell jr., j. am. chem. soc. 1941, 63, 969. http://dx.doi.org/10.1021/ja01849a021 46. v. haensel, v. n. ipatieff, science, 1943, 98, 495. https://doi.org/10.1126/science.98.2553.495-a 47. h. pines, w. d. huntsman, v. n. ipatieff, j. am. chem. soc. 1951, 73, 4343. https://doi.org/10.1021/ ja01153a092 48. h. pines, w. d. huntsman, v. n. ipatieff, j. am. chem. soc. 1951, 73, 4483. https://doi.org/10.1021/ ja01153a532 49. ipatieff honored on 80th birthday, chem. eng. news archive. 1947, 25, 3720. https://doi.org/10.1021/cenv025n050.p3720 50. j. j. bikerman, ann. sci. 1971, 27, 202-203. https:// doi.org/10.1080/00033797100203727 51. riverside laboratory: uop, mccook, illinois: a national historic chemical landmark, 1995, p. 5. retrived from https://www.acs.org/content/dam/acsorg/education/whatischemistry/landmarks/uoplaboratory/uopriverside-laboratory-historical-resource.pdf 52. a. g. morachevskiy, zh. prikl. khim. 2017, 90, 393 (in russian). 53. v. b. fenelonov, science first hand, 2018, 1, 7. retrieved from https://scfh.ru/files/iblock/f1e/f1e0eb851341f023096ebc684368bbc7.pdf 54. c. p. nicholas, acs catal. 2018, 8, 8537. http:// dx.doi.org/10.1021/acscatal.8b02310 55. l. chandrasekaran, nu symposium honors chemist vladimir nikolayevich ipatieff who helped win world war ii. 2017. retrieved from http://news.medill. northwestern.edu/chicago/nu-symposium-honorschemist-vladimir-nikolayevich-ipatieff-who-helpedwin-world-war-ii/ 56. photos: ipatieff 150th anniversary celebration, 2017. retrieved from https://isen.northwestern.edu/photosipatieff-150th-anniversary-celebration 57. nagrady i premii (awards and prizes), 2017. retrieved from http://isaran.ru/?q=ru/person&guid=1857538a1e46-06e1-5b8a-e300f7d39e11 58. the ipatieff high pressure and catalytic laboratory of northwestern university, science, 1945, 102, 4. http://dx.doi.org/10.1126/science.102.2636.4 59. willard gibbs award, 2019. retrieved from https:// chicagoacs.org/willard_gibbs_award 60. schlesinger receives 1951 honor scroll award, chem. eng. news archive. 1951, 29, 4260. https://doi. org/10.1021/cen-v029n042.p4260 61. akademik vladimir nikolayevich ipat’yev (1867– 1952). knizhno-illyustrativnaya vystavka k 150-letiyu so dnya rozhdeniya [academician vladimir nikolayevich ipatiev (1867-1952). a book-illustrative exhibition for the 150th anniversary of his birth], 2018. retrieved from http://www.rasl.ru/science/17_ exhibitions/ipatiev_vn.php 62. ipatieff prize, 2018. retrieved from https://www. acs.org/content/acs/en/funding-and-awards/awards/ national/bytopic/ipatieff-prize.html 63. premiya imeni v. n. ipat’yeva [prize named after v. n. ipatiev], 2018. retrieved from http://www.ras.ru/ about/awards/awdlist.aspx?awdid=93 https://dx.doi.org/10.1002/cber.19130460278 https://doi.org/10.1002/prac.19130870131 https://doi.org/10.1002/prac.19130870131 https://doi.org/10.1002/cber.191304603142 https://doi.org/10.1002/cber.19250580103 https://doi.org/10.1002/cber.19270600121 https://doi.org/10.1002/cber.19270600121 https://doi.org/10.1021/ja01324a029 http://doi.org/10.1021/ie50311a032 https://doi.org/10.1021/ie50362a024 http://dx.doi.org/10.1021/ja01849a021 https://doi.org/10.1126/science.98.2553.495-a https://doi.org/10.1126/science.98.2553.495-a https://doi.org/10.1021/ja01153a092 https://doi.org/10.1021/ja01153a092 https://doi.org/10.1021/ja01153a532 https://doi.org/10.1021/ja01153a532 https://doi.org/10.1021/cen-v025n050.p3720 https://doi.org/10.1021/cen-v025n050.p3720 https://doi.org/10.1080/00033797100203727 https://doi.org/10.1080/00033797100203727 https://www.acs.org/content/dam/acsorg/education/whatischemistry/landmarks/uoplaboratory/uop-riverside-laboratory-historical-resource.pdf https://www.acs.org/content/dam/acsorg/education/whatischemistry/landmarks/uoplaboratory/uop-riverside-laboratory-historical-resource.pdf https://www.acs.org/content/dam/acsorg/education/whatischemistry/landmarks/uoplaboratory/uop-riverside-laboratory-historical-resource.pdf https://scfh.ru/files/iblock/f1e/f1e0eb851341f023096ebc684368bbc7.pdf https://scfh.ru/files/iblock/f1e/f1e0eb851341f023096ebc684368bbc7.pdf http://dx.doi.org/10.1021/acscatal.8b02310 http://dx.doi.org/10.1021/acscatal.8b02310 http://news.medill.northwestern.edu/chicago/nu-symposium-honors-chemist-vladimir-nikolayevich-ipatieff-who-helped-win-world-war-ii/ http://news.medill.northwestern.edu/chicago/nu-symposium-honors-chemist-vladimir-nikolayevich-ipatieff-who-helped-win-world-war-ii/ http://news.medill.northwestern.edu/chicago/nu-symposium-honors-chemist-vladimir-nikolayevich-ipatieff-who-helped-win-world-war-ii/ http://news.medill.northwestern.edu/chicago/nu-symposium-honors-chemist-vladimir-nikolayevich-ipatieff-who-helped-win-world-war-ii/ https://isen.northwestern.edu/photos-ipatieff-150th-anniversary-celebration https://isen.northwestern.edu/photos-ipatieff-150th-anniversary-celebration http://isaran.ru/?q=ru/person&guid=1857538a-1e46-06e1-5b8a-e300f7d39e11 http://isaran.ru/?q=ru/person&guid=1857538a-1e46-06e1-5b8a-e300f7d39e11 http://dx.doi.org/10.1126/science.102.2636.4 https://chicagoacs.org/willard_gibbs_award https://chicagoacs.org/willard_gibbs_award https://doi.org/10.1021/cen-v029n042.p4260 https://doi.org/10.1021/cen-v029n042.p4260 http://www.rasl.ru/science/17_exhibitions/ipatiev_vn.php http://www.rasl.ru/science/17_exhibitions/ipatiev_vn.php https://www.acs.org/content/acs/en/funding-and-awards/awards/national/bytopic/ipatieff-prize.html https://www.acs.org/content/acs/en/funding-and-awards/awards/national/bytopic/ipatieff-prize.html https://www.acs.org/content/acs/en/funding-and-awards/awards/national/bytopic/ipatieff-prize.html http://www.ras.ru/about/awards/awdlist.aspx?awdid=93 http://www.ras.ru/about/awards/awdlist.aspx?awdid=93 substantia an international journal of the history of chemistry vol. 4, n. 1 2020 firenze university press peer review – critical feedback or necessary evil? seth c. rasmussen particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 consciousness, information, electromagnetism and water marc henry leonardo and the florence canal. sheets 126-127 of the codex atlanticus filippo camerota the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí astatine – the elusive one keith kostecka vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of xx century aleksander sztejnberg substantia. an international journal of the history of chemistry 3(2) suppl. 2: 9-15, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-696 citation: v. balzani (2019) saving the planet and the human society: renewable energy, circular economy, sobriety. substantia 3(2) suppl. 2: 9-15. doi: 10.13128/substantia-696 copyright: © 2019 v. balzani. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. editorial saving the planet and the human society: renewable energy, circular economy, sobriety vincenzo balzani emeritus professor of chemistry, “g. ciamician” chemistry department, university of bologna, bologna, italy e-mail: vincenzo.balzani@unibo.it abstract. planet earth is a very special spaceship that cannot land or dock anywhere for being refueled or repaired. we can only rely on the limited resources available on the spaceship and the energy coming from the sun. the huge amounts of carbon dioxide produced by using fossil fuels in affluent countries has caused global warming, which is responsible for climate change. ecological degradation of the planet is accompanied by an increased social disparity. as pope francis warns, we are faced with a complex crisis which is both social and environmental. strategies for a solution demand an integrated approach to combating poverty and protecting nature. if we want to continue living on planet earth, we must achieve the goals of ecological and social sustainability by implementing three transitions: from fossil fuels to renewable energies, from a linear to a circular economy, and from consumerism to sobriety. science, but also consciousness, responsibility, compassion and care must be the roots of a new knowledge-based society. keywords. sustainability, energy, materials, environment, climate crisis, social crisis, economy, efficiency, sobriety. scientist are called to see what every one else has seen and think what no one else has thought before 1. living on spaceship earth the image taken by the cassini orbiter spacecraft on september 15, 2006, at a distance of 1.5 billion kilometers, shows the earth as a pale blue dot in the cosmic dark (figure 1). there is no evidence of being in a privileged position in the universe, no sign of our imagined self-importance. there is no hint that we can receive help from somewhere, no suggestion about places to which our species could migrate. like it or not, planet earth, the only place we can live on, is a kind of spaceship that travels in the infinity of the universe. it is a very special 10 vincenzo balzani spaceship, however, because it cannot land or dock anywhere for being refueled or repaired. any damage has to be fixed and any problem has to be solved by us passengers, without disembarking. we travel alone in the universe, and we can only rely on the energy coming from the sun and on the resources available in our spaceship.1 the first thing we passengers should be aware of is that the planet earth has “finite” dimensions. therefore, the resources we have are limited and the space for waste disposal is also limited. this is an undeniable reality, even though many economists and politicians seem to ignore it. the views from space have allowed us to observe the entire earth as a planet. in the earth-at-day images from the space, national boundaries are invisible and this may strengthen the consciousness of the collective human responsibility for the future of our planet. on the contrary, the earth-at-night images show boundaries: those between aff luent and poor areas. the passengers of spaceship earth travel, indeed, in very different “classes”. disparity is the most worrying feature of our society. the number of billionaires has almost doubled, with a new billionaire created every two days between 2017 and 2018. they have now more wealth than ever before while almost half of humanity have barely escaped extreme poverty, living on less than $5.50 a day.2 in his encyclical letter laudato si’ pope francis warns:3 “the pace of consumption, waste and environmental change has so stretched the planet’s capacity that our contemporary lifestyle, unsustainable as it is, can only precipitate catastrophes (paragraph 161). he adds: “we are faced not with two separate crises, one environmental and the other social, but rather with one complex crisis which is both social and environmental. strategies for a solution demand an integrated approach to combating poverty, restoring dignity to the excluded, and at the same time protecting nature” (paragraph 139). if we want to continue living on earth, we must achieve the goal of ecological and social sustainability by going through three transitions: from fossil fuels to renewable energies, from a linear to a circular economy, and from consumerism to sobriety. 2. from fossil fuels to renewable energies energy is the most important resource for humanity1. in the present anthropocene epoch4, as primary energy we use mainly fossil fuels, a non-renewable resource that in the long run is going to be exhausted. in 2018, every second in the world we have burned 250 tons of coal, 1140 barrels of oil and 105,200 cubic meters of gas,5 generating heat along with pollution and 1074 tons of carbon dioxide (co2). that the use of fossil fuels generates substances that are harmful to health has always been known, but it was only in the mid-1980s that another, more serious, problem emerged: the enormous amounts of co2 released into the atmosphere cause global warming (greenhouse effect) which is responsible for climate change.6 since 1992, several united nations sponsored conferences tried to tackle the problem of climate change without success. in 2014 the 5th ipcc (intergovernmental panel on climate change) assessment report showed that the influence of human activities on climate change is unequivocal and increasingly worrying: the earth warms up, glaciers melt, sea level rises, drought advances, extreme weather events are more and more frequent. in december 2015, after a long cycle of negotiations, the united nations organized a conference in paris, preceded by pope francis’ encyclical laudato si’ in which climate change and related problems had been addressed with great authority and concern3. at the paris conference, 196 national delegations approved an agreement based on the following points: (i) it is absolutely necesfigure 1. photograph taken by the cassini orbiter spacecraft on september 15, 2006, at a distance of 1.5 billion kilometers from earth. the dot to the upper left of saturn’s rings, indicated by the arrow, is the earth. saturn was used to block the direct light from the sun otherwise the earth could not have been imaged. 11saving the planet and the human society: renewable energy, circular economy, sobriety sary to reduce strongly, or better eliminate greenhouse gas emissions by 2050, to limit the increase in global average temperature to less than 2 ° c (possibly, less than 1.5 ° c) compared to the pre-industrial level; (ii) in tackling the problem of climate change, all countries must consider, respect and promote human rights; (iii) it is urgent that developed nations make financial and technological resources available to enable developing countries to reduce their greenhouse gas emissions. beyond the lack of concreteness of the commitments made, the paris agreement induced a strong cultural change. in spite of the withdrawal of the usa from the agreement, decided by president trump in august 2017, there is a broad scientific and political consensus that the transition from fossil fuels to renewable energies will stop climate change, avoid the premature death of many people, increase the number of jobs, bring economic benefits and even advantages from the social point of view because the poorest nations, those most affected by climate change, are the richest in renewable energies1. however, at the katowice conference in december 2018 it was verified that the energy transition proceeds too slowly and that the objectives of the paris agreement will not be achieved without a strong acceleration6. one of the most controversial problems about the transition concerns its costs/benefits, as thoroughly discussed with different opinions in two chapters of this issue.7,8 renewable primary energies of the sun, wind and water, that we should use to replace fossil fuels,1 not only do not produce co2 and pollution, but they have the advantage of generating electricity instead of heat (figure 2). electricity is the most valuable form of energy because it can be stored as chemical energy (batteries or hydrogen), used as such, or converted with high efficiency into mechanical energy (figure 3).9 thus, the economy based on renewable energy sources is not only cleaner but also much more efficient than the fossil fuel based economy. the energy transition from fossil fuels to renewable energy is proceeding. for example, at the end of 2018 the installed power was 505 gw and 591 gw for photovoltaic (pv) and wind energy, respectively.11 at present pv is less developed than wind energy, but pv increases at a much faster rate (25% a year) and in 2050 it will become the most important source of energy for mankind. pv is indeed an ideal source of energy: it converts sunlight into electricity with 20% efficiency (100 times more than natural photosynthesis!), it can be used everywhere, it is scalable, long lasting, cheap and reliable. for some top research in the field of conversion of solar energy into electric energy, see.12, 13 the unavoidable transition from fossil fuels to renewable energies, however, is hindered not only by commercial competition, but even more by obscure interests of various kinds: military, because fossil fuels, with their high energy intensity, are not only the object of wars, but also the most important resource for fighting; national, because many countries have abundant reserves of fossil fuels and do not intend leaving them underground; financial, because speculation does not care about the health of the planet; economic, because in many countries oil companies have become so powerful as to condition government policy (this is what happens in italy with eni). therefore, all the people who care about our “common house”3 should show a strong social and political commitment to accelerate the energy transition. figure 2. renewable primary energies generate electricity. figure 3. conversion of primary energy (fossil fuels or wind/solar energy) into electricity and mechanical energy (adapted from10). 12 vincenzo balzani 3. the materials problem since solar energy is abundant and can be converted with high efficiency, e.g. into electricity by pv modules, one could think that we are going towards an age of plentiful energy for every body. this however, is not true because to exploit solar energy we need to construct equipment, machines and devices (e.g., pv cells), and to make them we must use materials available on the earth. in the end, what we have on earth are the chemical elements of the periodic table. some elements are abundant, but others, including most of those needed for energy conversion, are scarce (figure 4). therefore bottlenecks for the production of energy for final use are not the number of photons arriving from the sun or the availability of wind, but the materials we need for converting such primary renewable energies into the final energies that we use every day. storage of the intermittent electricity generated by renewable energies is an important part of the problem. materials shortage affects several sectors of eu economy, in particular advanced technology.15 the european commission has compiled a list that contains 27 critical materials or classes of materials such as platinum group metals or rare earth elements. concern about criticity of some materials used for energy conversion and storage are based non only on shortage, but also on geographic, economic and political factors. for example, 95% of rare earth production comes from china and most of lithium, the basic component of the lithium ion batteries used in ict devices as well as electric vehicles, comes for australia and chile, and cobalt comes from a politically unstable country such as the democratic republic of congo.15 4. from linear to circular economy as already underlined, earth’s resources are limited and the space available for waste disposal is also limited. our current economic model however, the so called linear economy (figure 5), is based on the assumptions that resources are infinite and that infinite is also the space for waste disposal: thus, we extract resources, use them to make products that then we throw away creating enormous amounts of waste that we think we can eliminate. all this by using energy from fossil fuels, which figure 4. a “quantitative” periodic table [14]. figure 5. schematic representation of the transition from a linear to a circular economy (adapted from16). 13saving the planet and the human society: renewable energy, circular economy, sobriety cause well known problems, including climate change. such an economic model is clearly unsustainable. we have to move to another economic model, the circular economy (figure 5, right), which is based on the correct consideration that natural resources are limited. for this reason, raw materials must be used as little as possible (savings) and with high efficiency to fabricate things not only for use, but also for being repaired, reused, collected and recycled to provide new useful materials. the only energy on which we can trust are renewable energies directly or indirectly related to sunlight (figure 6). therefore, more research should be devoted to improve energy conversion efficiencies and to develop means that can counter the two intrinsic defects of sunlight, low density and intermittency. can our civilization develop by adopting a circular economy powered by the electrical, mechanical and thermal energies obtained by the conversion of the primary, renewable energies of sun, wind and water? perhaps not, if population continues to increase and everybody wishes to use more energy (and, in general, more resources), because of the bottleneck due to material limits (figure 6). therefore it could be wise to reduce our energy consumption, which poses a question: is it possible to live well using less energy and, more generally, less resources? 5. from consumerism to sobriety the availability of energy is important for reaching a decent standard of life.17,18 the average energy consumption of a united states citizen corresponds to about 7.0 toeq/year (toeq means tons of oil equivalent) or 9200 w, much more than the average energy consumption figure 6. a circular economy system powered by renewable energies. the bottleneck is the avalability of materials for energy conversion (adapted from16) 14 vincenzo balzani of a european citizen, about 3.2 toeq/year, or 4200 w. data concerning the analysis of a series of parameters describing the quality of life (e.g., human development index, infant mortality) suggest that, at the current levels of efficiency in energy conversion, a primary consumption of around 2.6 toeq/year per person (about 30003500 w) can guarantee a good quality of life.17,18 therefore, all we citizens of affluent countries could decrease our energy consumption without losing our wellbeing. the same reasoning can be extended to any other resource we consume. interestingly, swiss scientists have estimated that 2000 w (about 1,5 toeq/year per person) represents a sufficient amount of energy to live comfortably and the swiss government has thus proposed a law to decrease to 2000 w the energy consumption per person (presently around 4700 w) by 2050-2100.19 such a law, in the form of a referendum, has been approved on may 21 2017 by swiss citizens. thus, for people living in rich nations reducing energy consumption is indeed possible without compromising the quality of life, which is good news. a second question, however needs an answer: how can an affluent person reduce his/her energy consumption? scientist involved in the study of this problem say that there are two routes. one is acting on “things”, which means to increase the efficiency of all the devices and machines we use every day. for example, using more efficient cars, replacing f luorescent lamps with leds, increasing the thermal insulation of the house, etc. experience shows, however, that increasing the efficiency of “things” often does not lead to a reduction in energy consumption for several reasons,20 including the so called “rebound effect”).21 it may happen, indeed, that an increase in energy efficiency encourages a greater use of energy services. for example, when a person replaces an old car with a more efficient one (say a euro 4 with a euro 6) sometimes he is so proud to have bought a greener car that ends up using it more than the old one. the other way to reduce energy consumption is acting on “people” rather than on things. we must start from the concepts of sufficiency and sobriety and “kindly” solicit22 and, in extreme cases, oblige people, with laws and sanctions, to reduce unnecessary use of energyec services. to consume less, we have to “do less”: fewer trips, less speed, less light, less heating, etc. if, after having adopted the strategy of sobriety, what we use is more efficient, we will have a even greater saving: it is doing less (sobriety) with less (efficiency). what we have discussed above for energy also applies to any other type of resources. we need to change our lifestyle based on consumerism, that means produce-sell-buy-use-throw away regardless of the resource consumed, the real utility of the object made or service supplied, and the kind of waste generated. we need to enter a logic of sufficiency to attain ecological stability. we need to learn to say “enough”. 6. conclusion up until now we have taken from nature any kind of resources to increase our well-being. only a relatively small part of mankind, however, has made use of them, and it appears that there are insufficient natural resources to bring all people at the level of consumption of affluent countries. the claim for new goods and services is deeply entrenched in western culture, which sees growth and development as absolutes. indeed, in the western world, the pressure made by ceaseless advertisements quickly converts goods and services, originally considered luxuries, into necessities for everyone. we are persuaded to consume at a faster and faster rate, without any understanding of the consequences of that consumption. the most pessimistic among scientists think that at the end we will be forced by the degradation of the planet to chose sobriety. indeed, only a new set of ethics and policies, accompanied by decisive changes in attitudes and practices can prevent a destructive collapse of the planet. we should take the energy and climate crisis as an opportunity to move away from fossil fuels, to reduce disparities, increase international cooperation, and lead humanity to an innovative concept of prosperity. science, but also consciousness, responsibility, compassion and care must be the roots of a new knowledge-based society. bibliography 1. armaroli n., balzani v. (2011) “energy for a sustainable world. from the oil age to a sun powered future”, wiley-vch, weinheim 2. available online. 3. holy father francis (2015) “on care for our common home”, laudato si’, vatican press 4. 4. crutzen, p.j. (2002) “geology of mankind”, nature, 415, 23 5. bp statistical review of world energy 2019 6. for a more detailed and thorough discussion of climate change, see: fuzzi, s. “energy in a changing climate”, this issue, p. 17 7. fitzroy, f., “some simple economics of energy transition”, this issue, p. 57 https://www.ipcc.ch/site/assets/uploads/sites/2/2019/05/sr15_chapter4_low_res.pdf 15saving the planet and the human society: renewable energy, circular economy, sobriety 8. smil, v., “what we need to know about the pace of decarbonisation”, this issue, p. 71 9. armaroli n., balzani v. (2011), “towards an electricity-powered world”, energ. environ. sci., 4, 3193 10. balzani, v. (2018), “salvare il pianeta: energie rinnovabili, economia circolare, sobrietà, parte prima”, la chimica e l’industria newsletter, 5(7), 4-20 11. ren21 global status report 2019; available online. 12. michl, j. “singlet fission – toward more efficient solar cells”, this issue, p. 47 13. grätzel, m. “mesoscopic photosystems for the generation of electricity and fuels from sunlight”, this issue, p. 29 14. available online. 15. for a more detailed and thorough discussion of materials limitation, see armaroli, n. “battery electric vehicles: perspectives and challenges”, this issue, p. 77 16. balzani, v. (2018), “salvare il pianeta: energie rinnovabili, economia circolare, sobrietà, parte seconda”, la chimica e l’industria newsletter, 5(8), 4-28 17. available online. 18. available online. 19. available online. 20. shove, e. (2018), “what is wrong with efficiency?”, buildingresearch&information,46(7), 779; available online. 21. available online. 22. r.h. thaler, c.r. sustein: nudge: improving decisions about health, wealth, and happiness, yale university press, 2008. italian version: la spinta gentile, universale economica feltrinelli, 2009. http://www.ren21.net https://www.euchems.eu/euchems-periodic-table/ https://data.worldbank.org/indicator/eg.use.pcap.kg.oe hdr.undp.org/en/content/energising-human-development https://www.2000watt.swiss/english.html https://www.tandfonline.com/doi/full/10.1080/09613218.2017.1361746 https://www.tandfonline.com/doi/full/10.1080/09613218.2017.1361746 https://environment.yale.edu/gillingham/gillinghamrapsonwagner_rebound.pdf substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 3(1): 19-41, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-207 citation: h.-j. apell (2019) finding na,k-atpase ii from fluxes to ion movements. substantia 3(1): 19-41. doi: 10.13128/substantia-207 copyright: © 2019 h.-j. apell. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell dept. of biology, university of konstanz, universitätsstraße 10, 78464 konstanz, germany e-mail: h-j.apell@uni-konstanz.de abstract. after identification of the na,k-atpase as active ion transporter that maintains the na+ and k+ concentration gradient across the membrane of virtually all animal cells, a long history of mechanistic studies began in which enzyme activity and ion-transport were intensively investigated. a basis for detailed understanding was laid in the so-called post-albers pump cycle. developing new experimental techniques allowed the determination of different flux modes, the analysis of the kinetics of enzyme phosphorylation and dephosphorylation as well as of the transport of na+ and k+ ions across the membrane. the accumulation of results from transport studies allowed the proposal of the gated channel concept that turned out to be a successful approach to explain the transport-related experimental findings. eventually, it found its counterpart in the high-resolution structure of the ion pump. recently it turned out that simple mutations of the na,k-atpase are the cause of several diseases. keywords. ion transport, enzyme activity, flux modes, structure-function relation, electrogenicity, gated-channel concept, pump-related diseases. dedicated to the late prof. david c. gadsby (1947-2019), a brilliant physiologist and biophysicist i. development of a functional concept in the 1950s the need for active ion transport through membranes was recognized. a number of concepts of the molecular mechanism of active transport had been proposed and discussed before the identification of the na,k-atpase. during that time james f. danielli reviewed five possible mechanism that summarized the ideas.1 they were adaptations of the carrier mechanism, which at that time had already been introduced as concept for passive ion transport. to perform active transport contractile proteins were coupled to the carrier to enable appropriately directed substrate transport. a different approach was proposed in 1957 by peter mitchell. his idea was substrate binding in a transporter to specific sites that experience translocation across the membrane by a rocking mechanism.2 this proposal was published the same year as when jens p. skou identified the na,k-atpase as protein in crab nerve cell membranes.3 20 hans-jürgen apell ii. the post-albers cycle the consequence of skou's identification of the na,katpase and the fact that the ion pump could be selectively inhibited by ouabain (or other cardiac steroids) led directly to numerous target-oriented studies that provided a wealth of characteristical details.4 a first proposal of the pump mechanism was published in 1963 by r. wayne albers and colleagues.5 they discussed, as a possible pump mechanism of the “adenosine phosphatase” in the electrophorus electric organ na+-atpase, a transphosphorylation in which phosphates were transferred along a chain of sites for phosphorylation from the cytoplasmic to extracellular side. na+ transport was suggested to be a by-product of the oriented transphosphorylation by acting as counter ion to the phosphate. k+ transport might have been coupled with phosphate uptake. compilation of the continuously increasing experimental findings led robert l. post and amar k. sen in 1965 to a first guess of a reaction cycle with seven states.6 in 1967 it was followed by the presentation of a reaction cycle by albers and collaborators that described the enzymatic reactions, in which phosphorylation by atp required the presence of na+ and dephosphorylation required k+.7 the four steps of the cycle are shown in fig. 1a. in its e1 forms the enzyme had inwardly oriented cation sites of high na+ affinity. the e2 forms were characterized by outwardly oriented cation sites of high k+ affinity. while albers and collaborators focused their view on the enzyme activity of the ion pump, post et al. included five years later detailed information on the ion transport and presented the first pump cycle that assigned enzyme and transport activity together in a unified reaction cycle.8 his proposal accounted not only for the physiological na,k-atpase function but also for na-atpase activity observed under (two) unphysiological conditions (fig. 1b). this scheme, the so-called postalbers cycle, has become the prototypical reaction cycle of all p-type atpases studied so far. two basic features of the pump mechanism of the na,k-atpase are captured in this scheme: (1) the transport is performed in a consecutive (or “ping-pong”) mode, which means that at first one ion species is translocated in one direction, then, after an exchange of ions, the second species is conveyed in the opposite direction. since it was impossible to establish that na+ and k+ were bound to the ion pump at the same time, it was suggested that they bind alternatingly to the same spatial sites which exhibit different binding affinities when accessible from one or the other side of the membrane. (2) na+ transport is connected to enzyme phosphorylation by atp, k+ transport takes place when the enzyme runs through the dephosphorylation half cycle. two non-physiological pump modes, included in post’s proposal, were identified when the substrate conditions were modified appropriately: the first was observed when k+ was removed from the extracellular medium. nevertheless, a ouabain-sensitive but significantly reduced atpase activity was detected. this finding led to the suggestion of a atpase that is able to transport na+ out of the cell without a countertransport of k+, named “na-atpase”. the second modifigure 1. first representation of the pump cycle of the na,k-atpase. a: reaction cycle of the enzyme activity with the ion substrates needed to enable the respective reaction step, published in 1967 by albers and collaborators.7 b: reaction cycle with merged enzyme and transport functions, the so-called post-albers cycle, introduced 1972 by post and collaborators.8 the cycle marked in red represents the physiological mode. 21finding na,k-atpase ii from fluxes to ion movements fication of the pump mechanism was found when the atp concentration in the cell was reduced to values far below the physiological millimolar range. the dependence of the atpase activity on the atp concentration revealed the existence of two distinct binding affinities, “low affinity binding” in the range above 10 µm, and a high affinity binding in the 100 nm range. the low-affinity binding was associated with the rb+ (or k+) bound e2 conformation. binding of atp accelerated the transition from the e2 to the e1 conformation and deocclusion of the ion sites. but this process was not accompanied by phosphorylation of the enzyme.8 high affinity binding of atp occurred in the e1 conformation and the presence of na+.9 it was also shown that the atpconcentration dependence revealed both low and high affinity binding of the nucleotide in the presence of na+ and k+. in the absence of k+ only high-affinity binding was detected10 that took place in the na+ exporting half cycle, which was passed through in both pump modes. in the years after 1972 extensive series of kinetic studies were published by several authors, in which a whole range of research activities were covered, such as studies on conformation transitions, enzymatic and transport activities. based on these findings karlish and collaborators presented in 1978 an extended post-albers scheme (fig. 2a) which summarized all observed functional properties known at that time.11 in their pump cycle an additional fundamental characteristic of the transport process, ion occlusion, was included: in the e1 conformation the ion-binding sites were accessible from the cytoplasm, but after 3 na+ ions were bound, the enzyme became phosphorylated by atp, and simultaneously the access to the ion-binding sites was locked and the ions were trapped inside the protein. only thereafter the access of the ion sites to the extracellular side was unlocked, a process related to the conformation transition from e1 to e2, and the na+ ions were released. with respect to the k+-transporting half cycle a corresponding reaction sequence occurred: enzyme dephosphorylation caused occlusion of the k+-loaded ion sites, and release of the k+ ions to the cytoplasm only happened after deocclusion which was coupled to the conformation transition from e2 to e1. systematic and particularly time-resolved kinetic measurements led to a further extended post-albers scheme that allowed a successful simulation of those experiments.12 the pump scheme shown in fig. 2b is adapted from heyse et al. and includes all six known flux modes of the na,k-atpase (see below). in this reaction scheme those reaction steps which have been identified in experiments with rabbit-kidney na,k-atpase are labeled with rate constants. the rate constants were either directly measured, determined from experiments or calculated from theoretical constraints. the reaction cycle shown in red represents in clockwise direction the post-albers cycle under physiological conditions. the counterclockwise reaction sequence describes the performance of the na,k-atpase as atp synthase. figure 2: development of the post-albers cycle with enhanced complexity provoked by increasing experimental insights. a: inclusion of na+ and k+ occluded states, indicated by framing the ions in parentheses, (na) and (k). this scheme was adapted from karlish and collaborators.11 b: pump scheme composed of all reaction steps that were determined experimentally from rabbit kidney atpase until 1994, and which was used for successful numerical simulations of the experimental results.12 the cycles drawn in red represent the physiological pump mode. 22 hans-jürgen apell iii. flux modes under diverse specific substrate conditions at least six additional transport modes (“non-canonical f lux modes”) were detected besides the physiological transport mode in which 3 na+ were removed from the cytoplasm in exchange against 2 k+ taken up from the extracellular medium.13,14 these flux modes are: (1) pump reversal, which can be observed at high intracellular concentrations of k+, adp and inorganic phosphate, pi as well as low concentration of atp, high extracellular concentration of na+ and in the absence of k+.15,16 in this substrate condition the pump cycle is run through backwards and atp in synthesized. (2) isostoichiometric exchange of na+ across the cell membrane was found to have taken place in the absence of k+ and the presence of cytoplasmic adp. in this mode the na,k-atpase acted as na+ shuttle by which the na+-translocating half cycle was executed forward and backward. first, 3 na+ were transferred out of the cell under consumption of atp, then the 3 na+ were exchanged on the outside and transported back into the cell while atp was produced from adp and pi, i.e. no net consumption of atp took place in this mode.17 (3) isostoichiometric exchange of k+ operated also as shuttle service in which the k+-translocating half cycle was executed forward and backward. 2 k+ were bound extracellularly and transported into the cell via enzyme dephosphorylation and binding of atp. in the absence of intracellular na+ and the presence of pi the physiological process was reversed by k+ binding from the cytoplasmic side, release of the bound atp and enzyme phosphorylation by pi. atp was bound but not hydrolyzed.18 atp was required only to promote the e2/e1 conformation transition. (4) uncoupled na+ eff lux consuming atp could be measured when neither na+ nor k+ were present extracellularly.19,20 in this mode it was assumed for a long time that after external release of na+ the pump cycle was completed by a return from the e2-p to the e1 conformation with empty binding sites. not so long ago it was revealed, however, that this rather small flux (compared to the na+,k+ mode) was only apparently uncoupled, but a na+,h+ exchange in which protons were transported into the cell as k+ congeners much less effectively but with the standard stoichiometry of 3 na+/2 h+/atp.21 (5) na+ exchange consuming atp was detected in the absence of external k+ but in the presence of na+ on both sides of the membrane.22,23 this mode evolved from the uncoupled na+ eff lux with increasing external na+ concentration.14 an obvious mechanistic explanation for this flux mode was that the extracellular na+ acted as (less well fitting) congener of k+ with a stoichiometry of 3 na+/2 na+/atp.10 (6) finally, an uncoupled k+ eff lux from red blood cells was found in the absence of extracellular na+ and k+ that did not require the presence of atp.24 in the light of h+ acting as congener of k+ this flux mode may be explained also as shuttle mechanism exchanging k+ and h+ in homology to mode (3). this concept would avoid the necessity of an energetically less favorable return of the pump from state e2-p to e1 with empty ion-binding sites, as proposed in the originally published mechanism.24 iv. electrogenicity an important feature of the na,k-atpase (and of biological ion transporters in general) is the transfer of ions from one side of the membrane to the other, because ions are charged particles and well soluble in water but not in the membrane. a main task of the cell membrane is to exactly prevent unfacilitated permeation of ions between different compartments of the cell. therefore, structure and properties of biological membranes are optimized to reduce diffusion of ions through the membrane to a minimum. repulsive electrostatic interactions are the predominant reason for this effect.25 the charge of an ion is the origin of an electric field that influences the surrounding matter by attracting charges of opposite sign, repelling charges of the same sign, and reorienting electric dipoles. the energy needed to promote these responses in matter is provided by the kinetic energy of the moving ion. because of the long range of electrostatic interactions a considerable portion of the surrounding matter is involved, and the amount of energy needed is dependent on a property of the matter called polarizability. the higher the energy is to displace a charge or reorient a dipole and make way for ion movement, the less probable it is that an ion will be able to permeate through the matter. in fig. 3a a schematic representation of the energy profile of a lipid membrane is shown. the rise of the potential energy close to the water-membrane interface indicates the amount of energy needed to transfer the ion from the water into the hydrophobic and “apolar” core of the membrane formed by the fatty acids of the lipid molecules. this amount is large compared to the thermal energy of the ions. therefore, a common property 23finding na,k-atpase ii from fluxes to ion movements of all ion transporters in membranes has to be that they provide a pathway through the membrane that requires only a low amount of energy to be passed by an ion. this is accomplished by a pathway with a diameter that exceeds an ion-species dependent minimum and a lining of the pathway by molecules or parts of molecules such as amino-acid side chains that are easily polarizable (or “polar”). in fig. 3b the energy profile of an ideal ion channel without ion-binding sites is depicted. thus, the energy expenditure is low enough to allow an easy diffusion of ions along the pathway. that can be implemented, as one extreme, by a wide, water-filled corridor or, as the other extreme, by a narrow channel lined with polar groups. an example for the latter is the gramicidin channel with a diameter of 4 å in which carbonyl groups mimic the hydration shell which the passing monovalent cations have to leave behind for the most part at the entrance into the channel.26 numerous variations of channel shapes were found in between both extremes throughout the “channel kingdom”. in the case of ion pumps, a pathway must exist that allows ion movement at low energy cost, however, it may not be continuous between both sides of the membrane because that would create a counterproductive bypass for ions. a promising proposal, the gated channel concept, which will be discussed in the subsequent chapter, is outlined in one of its states in fig. 3c. here an ion-binding site, indicated by a dimple in the energy profile, is accessible from the left side. a discharge of the ion from its binding site to the right side of the membrane is prevented by a high energy barrier. the fact that a biological membrane consists primarily of a core of hydrophobic, apolar and insulating matter enclosed between conducting aqueous phases, allows the representation of a membrane as physical (plate) capacitor, which has in principle exactly this composition. since the layer between both conductive plates of a capacitor is named “dielectric”, the layer of the membrane formed by fatty acids is called membrane dielectric. it is characterized by a “dielectric constant”, ε, that is low in the case of apolar matter (e.g. lipids, ε = 3-4) and high in polar phases (water, ε = 80). it controls the membrane capacity, c = ε·a/d, where a is the membrane area and d its thickness. a fundamental consequence of this membrane property is that the transfer of an ion across the membrane is an “electrogenic” process. electrogenic transport is defined as the movement of electric charge through a medium with a low dielectric constant such as a biological membrane.27,28 electrogenic transport is characterized by two basic properties that were and are exploited constantly to study details of ion transport in the na,k-atpase and other ion transporters. the first impact of electrogenicity is that ion transport through the membrane dielectric produces an electric current and affects the electric membrane potential, vm (fig. 4). therefore, electrogenic ion pumps act as current generators, and charge movements can be detected as current signals with an external measuring device.27 the second impact is that the activity of an electrogenic transporter is affected by the membrane potential. when charges are moved inside the membrane in the course of voltage-dependent reaction steps, they move ‘uphill’ (as in fig. 4) or ‘downhill’ on the electric membrane potential, δφ. this generates an additional energy term for the process, δe = δq·δφ, which in turn modifies the rate constant of this reaction step and can be detected as altered kinetic behavior. in consequence, figure 3. schematic representation of potential energy profiles as detected by an ion along a pathway across a membrane in three different cases: (a) a simple lipid membrane, in which specific effects of the membrane-water interface are neglected, (b) an ideal ion channel without binding sites, and (c) an ion pump with an internal ion-binding site accessible from the left side and an energy barrier preventing propagation to the right-hand aqueous phase. 24 hans-jürgen apell the externally measured pump current becomes voltage dependent.29 when the electrogenicity of an ion pump is investigated one may find an overall electrogenic behavior as in the case of the na,k-atpase or the sarcoplasmic reticulum (sr) ca-atpase, when after a complete pump cycle net charge is transferred across the membrane. in the case of the h,k-atpase, two k+ are exchanged against two h+, therefore, no net charge is transferred after a pump cycle, the overall transport is electroneutral. but when the pump cycle is subdivided into single reaction steps, in some of these partial reactions charge is moved within the membrane dielectric, and these steps show electrogenic behavior.30 the experimental concept to confine the activity of the na,k-atpase to specific partial reactions by appropriate experimental conditions, has turned out to be a powerful approach to identify electrogenic reaction steps in the pump cycle and to analyze their kinetic behavior.12 v. the gated channel concept as indicated above, the initial ideas of the molecular mechanism of ion translocation across the membrane by ion pumps were influenced by the carrier concept1 or a rocking mechanism.2 in both cases ions bind in a first step to sites provided by the protein and then these sites, imbedding the ion in a cage, are moved through the membrane. already in 1957 clifford s. patlak introduced another mechanistic proposal on a more general level, the “gate type non-carrier mechanism”.31 he assumed that the transporter had a substrate-chelating moiety that was not physically displaced during pumping. initially, it was accessible only from one side of the membrane at a time (fig. 5a). then the transporter “closed” on the approachable side and “opened” subsequently on the opposite side, where the substrate was released. after the site is empty, the conformational arrangement is reversed and the transporter returned to its initial state. in 1979 peter läuger published an enhancement of this concept as “channel mechanism for electrogenic ion pumps”28 in which he assumed an ion channel traversing the membrane inside the transport protein with varying energy barriers that were able to separate the ion-binding site from the external aqueous phases. he applied this approach first to the light-driven proton pump bacteriorhodopsin. a few years later he introduced this concept to atpases (fig. 5b),32 and used it to provide a detailed microscopic model to analyze the current-voltage behavior of the na,k-atpase.27,33 in this concept the ion pump was represented by a channel which consisted of a sequence of shallow energy dimples and two barriers that were able to change their height when the pumps ran through its multiple conformational states (fig. 5b). those variable barriers correspond to the gates of the channel. there is a variety of designs possible to construct the ion pathway in the gated channel concept. the ion-binding sites can be arranged asymmetrically, i.e. close to one interface of the ion pump with the aqueous outside, or symmetrically buried deep inside the hydrophobic core of the protein. the implications would be the existence of one or two access channel, respectively, through which the ions have to move. for the sake of the gating mechanism, which is needed on either side of the binding sites, these must not be located on the protein’s surface. access channels may, however, differ in their shape. two principal cases have to be distinguished, a narrow, even ion-selective ion channel (or “ion well”) in contrast to a wide funnel (or “vestibule”) that is filled with water molecules and various ions. in case of a narrow channel, the ions moving through it may be partly stripped of their hydration shell and interact with the wall-forming amino-acid side chains. the diffusion of ions through this structure resembles the process taking place in a typical ion channel. an important feature in this case is that part of the transmembrane voltage drops along the length of the channel and this action would be electrogenic (see above).27 in the case of a wide open vestibule ion movement, it occurs more or less as free diffusion in a solution, and correspondingly, the electric conductance in this environment is high. this fact entails that figure 4. schematic representation of electrogenic transport. the red line indicates the course of the electric membrane potential, here in case of a homogeneous membrane dielectric. the difference of the electric potentials on both sides, φ1 – φ2, is the membrane potential vm. in cells it is always inside negative. according to basic principles of electrostatics, the movement of a charge, δq, from one side of a capacitor to the other alters the electric potential difference, δvm = cm·δq, proportionally to the membrane capacitance, cm. 25finding na,k-atpase ii from fluxes to ion movements electric-field strength is low in such a vestibule, and no (significant) drop of the transmembrane voltage occurs. correspondingly, both appearances were described in the literature as high-field and low-field access channels, respectively. based on the assumption that in the na,k-atpase the transported ions have to pass through access channels on either side of the ion-binding sites, the transfer of the ions from one aqueous phase to the other can be subdivided into at least four different reaction steps which are ion binding from one side, ion occlusion, deocclusion on the opposite side of the membrane, and ion release, as depicted in fig. 6 for the na+-translocating half cycle. for k+ transport a corresponding series of transport steps is valid. in principle, all partial reactions indicated in color in the simplified post-albers cycle (fig. 6a) may be accompanied by ion movements within (or through) the na,k-atpase. when, as in this case, a na+ ion is at the beginning in the cytoplasm, it resides at the electric potential, vm, of the cell. at the end of the transport process, it is located outside the cell, where the level of the electric potential is 0 (per definition). therefore, at each of the indicated reaction steps the ion may move through a fraction of the membrane potential, vm. in the cartoon of fig. 6b, these fractions of vm were indicated by the parameters α’, β’, β”, and α”. for each ion that traverses vm completely the condition, α’ + β’ + β” + α” = 1 must hold. these parameters were termed as “dielectric coefficients”.33 by determining their magnitude experimentally, important information can be achieved on the molecular mechanism of the ion transport. if the dielectric coefficient is zero, no charge is moved through the electric field within the membrane domain of the na,k-atpase. this has to be expected if the ion moves in a wide water-filled vestibule or if it is sterically fixed within the protein, e.g. in an immobile binding site. a high dielectric coefficient of a specific reaction step indicates a movement through a narrow channel. as will be shown later in detail, in case of the na,k-atpase the coefficients β’ and β” were zero (or not significantly different from zero) which means that during enzyme phosphorylation and ion occlusion as well as during the conformation transition and ion deocclusion the ions were not shifted within the ion pump, their binding sites were sterically immobile.34,35 vi. experimental approaches after the identification of the na,k-atpase the first functional study was restricted to monitoring of the figure 5. original mechanistic concepts in which the ion-binding sites are not displaced during the transport process rather than the protein structure that controls access to these sites. a: the first proposal was the so-called gate type non-carrier mechanism by c.s. patlak31 in which two different conformational states of the protein generate alternatingly access to immobile ion sites from either side of the membrane. (scheme adapted from ref. 31). b: the second proposal is a channel mechanism in which ions diffuse through a low-resistance access channel (or ‘ion well’) to a binding site inside the membrane domain of the transporter, which is framed by mobile barriers on either side that control access from the outside. here it is applied to the light-driven proton pump bacteriorhodopsin. in this representation the energy profiles of the access channels were omitted on both sides.(scheme adapted from ref. 32). 26 hans-jürgen apell enzymatic activity because open membrane preparations from crab nerve were used, which did not separate both aqueous compartments that are needed to detect ion transport.3 atpase activity was measured as amount of inorganic phosphate released per volume of “enzyme solution.” pi was determined by the colorimetric method introduced by fiske and subbarow in 1925,36 and in later years by variations derived therefrom.37,38 when post studied broken erythrocytes he calculated a specific enzyme activity “per mg dry weight”.39 after introduction of a method to isolate and purify active na,katpase from kidney medulla preparations by peter jørgensen in 1969,40 two methods were used to determine the amount of the enzyme in an assay, a micro-kjeldahl method that quantifies the nitrogen content in a solution,41 and the lowry method (1951)42 which became the standard method of protein determination in the years following. in 1978 a modified assay was introduced by markwell et al. that allowed protein determination also in membranes without prior solubilization of the membrane-bound proteins.43 an elegant method to determine the atpase activity was introduced by schwartz and collaborators in 1971.44 a coupled pyruvate kinase/ lactate dehydrogenase assay allowed ‘real time’ monitoring of atp consumption by the na,k-atpase (or other atpases) in buffers within a reasonable range around physiological conditions, which was and is widely used. post et al. published in 1965 a study with enzyme isolated from guinea-pig kidneys in which they used radioactive [γ-32p]atp as further technique to study enzyme phosphor ylation and dephosphor ylation.45 measuring bound and released radioactive pi for a long time became the ‘gold standard’ to investigate enzyme phosphorylation and dephosphorylation. a thorough and comprehensive review on enzymatic properties of the na,k-atpase was published by ian m. glynn in 1985.14 the first ion-transport studies of the na,k-atpase were performed with intact erythrocytes by post and jolly in 1957 who measured changes of na+ and k+ in the cells by flame photometry and determined a transport ratio of 2 k+/3 na+ for the strophanthin sensitive flux.46 this method, at that time was state of the art, but was improved about ten years later by garrahan and glynn who introduced the use of a radioactive sodium isotope, 24na, to measure na+ transport in red cells.20 in 1970 paul de weer applied tracer ions in experiments with squid giant axons. he measured 22na+ and 24na+ fluxes, determined rate constants and studied substrate dependencies,47 followed by the first direct measurement of the electrogenicity of the na,k-atpase in axons with figure 6. a: post-albers cycle of the na,k-atpase under physiological conditions. the na+-transporting half cycle is subdivided in four partial reactions, na+ binding (green), enzyme phosphorylation by atp, occlusion of 3 na+, and release of adp (blue), conformation transition, e1-p to p-e2, and deocclusion of the binding sites to the extracellular side (magenta), and release of the na+ ions (red). b: sequence of schematic energy profiles as detected by the ions during na+-transport in three consecutive conformations as indicated in the pump cycle (a). the height of the energy barriers is schematic. this representation shall indicate that the high barriers are virtually impregnable for the ions with their available (thermal) energy. the quantities α’, α”, β’, and β” are so-called dielectric coefficients that describe the fraction of the electric potential traversed by an ion in the respective reaction step (for details see text). 27finding na,k-atpase ii from fluxes to ion movements electrodes in 1973.48 rhoda blostein introduced in 1976 the use of inverted erythrocytes49 to combine [γ32p]atp phosphorylation studies with 22na and 42k fluxes in order to identify the sidedness as well as interaction of fluxes and enzymatic activities.50 important contributions could be provided also by the use of human resealed red cell ghosts.51-53 another chapter on transport studies with cells was opened by david gadsby in 1979 who used purkinje fibers from dog hearts and performed voltage clamp experiments with a microelectrode set-up.54 he determined strophanthidin sensitive outward currents through the membranes of these cells. a further development was the whole-cell patch clamp with isolated cells from guinea pig ventricles that allowed the determination of the current-voltage dependence to the na,k-atpase.55 in 1994 don hilgemann supplemented the set of electrophysiological techniques by the giant membrane patch method.56 applied to guinea pig myocytes he obtained in kinetic experiments, a time resolution of 4 µs, and analyzed external na+ binding. six years later electrophysiological equipment was even further developed so that high-speed voltage jump experiments could be performed with squid giant axons, and time-resolved na+ release in the p-e2 conformation was measured at a 3 µs time resolution.57 a different electrophysiological approach was introduced in 1988 by bob rakowski and cheryl paxson.58 they were able to measure the current-voltage dependence of the na,k-atpase in xenopus laevis oocytes in a membrane potential range between -120 mv and +60 mv by a conventional two-microelectrode voltage-clamp circuit. these cells were of interest in several ways: in the maturation state, in which they typically were used, they had low passive membrane conductance and a significantly reduced set of ion transporters compared to other cells. they were easy to investigate with electrophysiological techniques, and most of all, they were very suitable for heterologous expressions of na,k-atpase mutants.59 since then this technique has been used in numerous projects such as to study the interaction mechanism with ouabain59, the role of glycolysation60 or the properties of disease-inducing mutations.61 when transport activity is tracked by ion fluxes and overall electrogenicity in cellular systems, other ion transporters present in the membrane have to be accounted for. this is typically achieved by performing two identical experiments successively, once in the absence and once in the presence of a saturating concentration of a na,k-atpase-specific inhibitor, mostly ouabain. the difference of both recorded currents (or fluxes) is the contribution of the na,k-atpase. in 1974 a new approach was introduced when stanley goldin and siu tong reconstituted purified na,k-atpase from canine kidney in lipid vesicles.62 they demonstrated that it was possible to incorporate active ion pumps into the lipid membrane by a dialysis method, and at least a fraction of pumps was oriented in a way that they could be activated by externally added atp. active and passive fluxes could be monitored by the use of tracer ions, 22na+, 42k+, and 36cl-. at almost the same time, lowell e. hokin and collaborators published a study on purified shark enzyme reconstituted in vesicles. they showed that ouabain inhibited the pump activity only from inside the vesicles when atp was added on the outside and confirmed pump-mediated na-na exchange as it was found in erythrocytes.63 later on, beatrice anner and collaborators used reconstituted vesicles to measure 22na uptake and 86rb export (as congener of k+, more suitable because of its appropriately longer radioactive halflife time), and determined a transport ratio of approximately 3 na+ against 2 rb+.64 in 1980 elisabeth skriver and collaborators published an electron-microscopical study in which they reported vesicle diameters of 90 ± 20 nm with randomly oriented intramembranous particles which were assigned as na,k-atpase molecules.65 a few years later, bliss forbush introduced a rapid sampling technique of tracer f luxes across vesicle membranes that allowed a determination of rate constants in the order of below 10 ms.66 this approach was very successfully applied to analyze the kinetics of 86rb+ or 42k+ release from the occluded e2p conformation of the na,katpase in the presence of other substrates and inhibitors.67,68 in 1985, an alternative method to the use of radioactive substrates was introduced by apell and collaborators when the electrogenicity of the transport was exploited by a membrane-potential sensitive fluorescence dye, diic1(5), that was used together with valinomycin, to determine k+ fluxes out of the vesicles upon pump activation by addition of atp.69 two years later a further voltage sensitive fluorescence dye, oxonol vi, was introduced by apell and bersch which became a frequently used fluorescent probe to directly record the electrogenic pump activity of reconstituted na,k-atpase.70 the detection mechanism was analyzed and it was shown that this technique may be used to measure a significant part of the current-voltage curve of the reconstituted ion pumps in a single experiment.71 a potent tool to gain access to details of the transport kinetics of the na,k-atpase was provided by jack kaplan and collaborators in 1978 when they introduced “caged atp” that allowed triggering of the atpase activity by production of an atp-concentration jump.72 caged atp is a photolabile 2-nitrobenzyl derivative of atp that cannot be metabolized. by a short intensive uv flash in 28 hans-jürgen apell the nanoto microsecond time range photolysis is activated and atp released in millisecond time range.73 based on this concept of the synchronized activation of the na,k-atpase, peter läuger proposed an assay of adsorbing na,k-atpase-containing open “membrane fragments” onto an artificial lipid bilayer (blm), creating a capacitive coupling between both membranes and then trigger the pumping process by a uv-flash induced release of atp from its caged precursor in the buffer. thus current transients may be detected in an external current pickup system by electrodes on both sides of the blm. a first implication of this technique was published by klaus fendler and collaborators in 1985.74 they verified that current transients could be recorded by this method and information on the kinetics of the na+ translocation through the na,k-atpase may be determined from the current transients. two years later borlinghaus et al. provided a detailed mechanistic analysis of the compound membrane system and the current transients activated by the atp-concentration jumps.34,75,76 they showed that enzyme phosphorylation, ion occlusion and the conformation transition, e1-p to p-e2, were not electrogenic. the time resolution of this technique was, however, limited by the photochemistry of atp release with a ph-dependent limit of about 4 ms (at ph 7.2).73 to overcome the ph-dependent limitations a modified caged atp was introduced with a (ph-independent) atp release rate of >105 s-1, and it could be successfully applied to experiments with the na,k-atpase.77,78 since it turned out that in the pump cycle much faster reaction steps follow the rate-limiting conformation transition, a modified technique was developed that allowed the use of the compound membrane system to obtain kinetic parameters of those fast na+-moving reaction steps. in 1995, this charge-pulse technique was applied to measure the kinetics of na+ release in the e2p conformation and the rate constants in the submillisecond time range could be determined.35 further modifications of the compound membrane techniques were used to determine na+ binding and release on the cytoplasmic side by monitoring membrane-capacitance changes,79,80 and by correlation of capacity changes and rh421 fluorescence signals (see below).81 the problem of the fragility of the blm was circumvented by the introduction of so-called solid supported membranes onto which na,k-atpase containing membrane fragments were adsorbed. these very robust compound membranes allowed fast buffer exchange. the possibility to freely choose buffer compositions had the advantage that ion-concentration changes could be performed in both directions.82-84 since 1976, fluorescence techniques have been introduced to gain detailed information on the kinetics of conformation transitions in the na,k-atpase. steven karlish established several approaches with different collaborators. in stopped-flow experiments he used intrinsic tryptophan fluorescence to monitor and analyze the rate of the conformational transition e2(k) → e1na and its dependence on atp.85 formycin triphosphate, a fluorescent analog of atp, was used to detect binding and dissociation of the nucleotide at different states of the pump cycle and the substrate dependence of these reactions.11,86,87 while the enzymatic activities of the na,katpase were not or not significantly affected by these two techniques, a third assay, labeling the enzyme with fluorescein88 or with fluorescein isothiocyanate (fitc),89 confined the possibilities to investigate functional properties significantly. labeling of the enzyme with these fluorescent compounds occurred close or in the nucleotide binding site, therefore, atpase activity, phosphorylation by atp, and nucleotide binding were abolished, but phosphorylation from inorganic phosphate and k-phosphatase activity were only partially inactivated. advantage of these fluorescent labels was that they reported transitions between the e1 and e2 conformation.89-91 fitc-labeled enzymes showed high fluorescence levels in e1 and lower in e2. fitc was found to bind covalently to a specific lysine of the cytoplasmic domain related to atp binding, and was correspondingly affected by atp (if present).92 the molecular mechanism of the conformational sensitivity was that fluorescein is a ph sensitive dye and conformation transitions of the na,k-atpase include spatial rearrangements of the n domain with its nucleotide binding site, and thus minor local ph changes in the binding-site environment modulated the detected fluorescence (stürmer & apell, unpublished data). in 1982 a different fluorescein derivative, 5’-isothiocyanate f luorescein (5-iaf), was introduced by kapakos and steinberg.93 this dye bound covalently to cys457 on the cytoplasmic surface of the protein without inhibiting the enzyme activity.94 it was used to study conformational changes, especially, e2 ⇄ e1,95 as well as na+-binding and atp-induced partial reactions.12,96 another conformation-sensitive f luorescent dye was eosin, whose application was introduced by skou and esmann in 1981.97 they demonstrated that eosin bound reversibly to the na,k-atpase, with low affinity in the presence of k+ and showed the same fluorescence emission as the free form in solution. in the presence of na+ it bound with high affinity and exhibited enhanced fluorescence. its competition with atp indicated that it bound to the atp site. eosin was used to monitor changes of enzyme conformations in the presence of a wide variety of substrate conditions.97-99 29finding na,k-atpase ii from fluxes to ion movements in the 1980s electrochromic styryl dyes100 were introduced to gain further access to details of the iontransport mechanism of the na,k-atpase. originally these dyes were used to detect changes of the membrane potential of nerve cells in brain tissue.101 the extremely hydrophobic compounds insert into the lipid phase of membranes, parallel to the fatty acids with their polar head facing the interface to the water phase. because of an electrochromic effect their fluorescence properties change with the electric field in the hydrophobic part of the membrane. due to this mechanism the response time upon changes of electric field was µs or faster. in 1988 klodos and forbush applied the dye rh160 to na,k-atpase containing membrane fragments and detected fluorescence changes upon addition of various substrates, although no transmembrane voltage was able to build up across the open membrane fragments.102 they could not discriminate whether the detected response was caused by changes of local electric fields or due to interaction between dye and protein. the läuger lab started in 1989 comparable studies with the dye rh421. they provided evidence that local electric fields induced by ions within the membrane domain of the na,k-atpase were the predominant cause of the observed fluorescence changes and presented a detection mechanism that correlated ion movement into and out of the membrane domain of the ion pump with the fluorescence changes.103,104 the advantage of an easy application of styryl dyes with ion pumps in membrane fragments led to a frequent use of this technique by several groups.105-110 it allowed the investigation of electrogenic and rate-limiting reaction steps around the post-albers cycle. the initial limitation that this technique required membrane fragments with a high density of ion pumps was conquered by its adaption to single na,k-atpase complexes solubilized in lipid/detergent micelles. this allowed an extension of its use even to recombinant na,k-atpase expressed in yeast which could be solubilized only as single enzyme molecules and not be isolated in form of purified membrane fragments.111 vii. enzyme function as mentioned above, atp hydrolysis was the very feature to identify the enzyme.3 it was found that na+, k+, and mg2+ were essential cofactors to control the enzyme activity and assumed that it was involved in the active extrusion of na+ from the cell. 3 three years later, in 1960, an adp-atp exchange was detected with 32p-labeled adp, which was phosphorylated by an enzyme that was phosphorylated beforehand. the (β-32p) labeled atp was formed although no adenylate kinase was present.112 since 1962 it was known that the γ-phosphate of atp forms an acid-stable phosphoenzyme.113 in 1963 it was shown by the use of 32p-labeled atp that the enzyme is phosphorylated in the presence of na+, and dephosphorylated subsequently by addition of k+, the latter reaction was inhibited by the presence of ouabain.114 in 1965, it was demonstrated that an acyl phosphate was formed by 32p-labeled atp.115,116 at the same time ‘e1p’ and ‘e2p’ were discussed as different conformations with respect to dephosphorylation,7,117,118 as well as their decomposition by k+,45,115,119 or adp. 120,121 in 1967 garrahan and glyn reported for the first time a backward running enzyme by formation of atp from adp and inorganic phosphate.15 three years later it was shown that the mgatp complex was the effective compound needed for enzyme activity,122 although free atp could bind and subsequent addition of mg2+ was able to start the reaction.9 in 1972 it was found that atp accelerated at high concentrations (> 400 µm) the conformation transition e2k → e1k in a non-phosphorylating fashion.8 in 1973 it could be shown that an aspartyl side chain was phosphorylated by atp.123,124 it lasted until 1985, when the first amino-acid sequence became available, that the phosphorylated aspartate was identified in the large cytoplasmic loop between the fourth and fifth transmembrane helix.125 this aspartate formed together with the next three amino acids a characteristic motif, asp-lys-thr-gly, that turned out to be invariant in the phosphorylation site of all p-type atpases.126 the striking obser vation that the phosphor ylated enzyme could be dephosphorylated by adp or k+ attracted a lot of interest and was considered to be a useful property to gain more insight into the molecular mechanism of the enzymatic machinery. the first concept to describe the enzymatic behavior was that of a two-pool model of the phosphorylated enzyme, e1~p and e2p. the first pool was filled upon binding of cytoplasmic na+ and phosphorylation from atp. enzyme in this pool had the na+ ions occluded127,128 and could be dephosphorylated by adp (“adp-sensitive ep”). this pool was discharged by spontaneous conformation transition into the second pool, in which the ion-binding sites were extracellularly accessible. therefore, na+ was released, and subsequently the enzyme could be dephosphorylated upon addition of k+ (“k-sensitive ep”). the experimentally observed bi-phasic time course of the dephosphorylation of both pools and its dependence of the na+ concentration could, however, not be explained by this simple model.129 in particular, experiments showing that the amount of enzyme dephosphorylat30 hans-jürgen apell ed by either adp or k+ together was larger than 100% made the two-pool model obsolete. the consequence was the introduction of an extended concept, a three-pool model that included an additional pool intercalated between e1~p and e2p.130 the additional pool was thought to be drained via both dephosphorylation modes, by k+ and adp. extensive experiments and discussion of na+, k+ and adp dependences as well as the sizes of the proposed three pools under various substrate conditions led to different concepts according to whether the pool ‘in the middle’ might “effectively be both adpand k-sensitive”131 or might be “not sensitive to both adp and k+ but has to be converted to ea~p, the first pool, which is e1-p.”132 when in retrospect the concept of enzyme dephosphorylation is revisited in terms of the detailed postalbers pump cycle available nowadays, the (linear) sequence of phosphorylated states of the na,k-atpase consists of (derived from fig. 2b): na3e1atp adp ⎯ →⎯⎯← ⎯⎯⎯ na3( )e1~p ! p-e2na3 ! ...! p-e2 ! ... ! p-e2k2 pi⎯ →⎯← ⎯⎯ e2 k2( ) only the (boxed) first and last state in the respective reaction sequence may be dephosphorylated directly. all states in between are inert to dephosphorylation. they are e2-p states in which the ion-binding sites are accessible from the extracellular side of the membrane and are able to bind or release ions and are occupied by 1 to 3 na+, by 1 k+ or no ion. the occupancy of these states rapidly achieves a steady state distribution in a diffusion controlled manner, depending on the current ion concentrations in the extracellular medium. the low na+ affinity of the ion-binding sites in the p-e2 conformation and high affinity for k+ leads under physiological conditions preferentially to dephosphorylation upon binding of a second k+, p-e2k2 → e2(k2) + pi. only at high na+ concentrations and very low (or no) k+ a considerable amount of enzyme will undergo the (backward) conformation transition, p-e2 na3 → (na3)e1~p, and the resulting state can be dephosphorylated in the presence of adp, (na3)e1~p + adp → na3e1atp.53,133 this approach to a mechanistic description makes the introduction of pools of phosphorylated states unnecessary to explain the various dephosphorylation experiments. in 1965 post and sen showed that it was possible to produce a k+ influx into cells in the absence of atp but in the presence of mg2+ and inorganic phosphate6 which indicated binding of pi to the unphosphorylated enzyme, a reaction step later called ‘backdoor phosphorylation’. only two years later glynn and garrahan demonstrated that the thermodynamic requirement that the enzyme runs backwards could be fulfilled experimentally under appropriate substrate condition.15 in the presence of k+, mg2+ and pi, addition of ouabain induced rapid backdoor phosphorylation.134 in the absence of ouabain less steady-state phosphorylation was obtained because of k+ promoted dephosphorylation.135 the identical proteolytic digestion pattern obtained from the pi-induced and atpinduced phosphoenzyme was understood as strong indication that both phosphoenzymes were the same.136,137 another interesting question was the nucleotide specificity of the enzyme. in 1968 matsui and schwartz studied the effect of nucleotides other than atp, namely ctp, itp, gtp, utp.138 subsequently, their dissociation constants were determined.9 after the method was introduced to reconstitute enzyme functionally in lipid vesicles, active transport of na+ and k+ energized by ctp (almost as effective as atp) und utp (relatively ineffective) was reported.63 from the na+ transport with various nucleotides and two synthetic atp analogs a correlation was found between the proton-accepting properties of the nucleotides and their ability to provide active transport.139 considerable attention was paid to the role of mg2+ for the enzyme activity after it was noticed from the very beginning that this ion was indispensable for function.13,112 detailed studies revealed that the mgatp complex was the activating substrate of the na,katpase.122,140 this is not really surprising since physicochemical investigations yielded equilibrium dissociation constant of the mgatp complex in a ph-dependent manner between 1.5 µm (ph 8) and 10 µm (ph 6)141, while the free mg2+ concentration in cells typically is in the order of 200 µm142. this implies that under physiological conditions more than 95% of total atp is present as mg complex. free mg2+ was reported to bind to a low-affinity site where it caused inhibition of the enzyme activity.143 it was shown that mg2+ is released from the enzyme only after its dephosphorylation in the e2 conformation.144 therefore, it could be considered to be a product inhibitor when high mg2+ concentrations in the buffer impeded dissociation from its site and thus affected the e2 → e1 transition.145 this concept was confirmed by forbush67,68 and complemented by the proposal that only one site for mg2+ per enzyme was required for both phosphorylation by atp and enzyme inhibition by stabilizing the e2 conformation. binding of atp at the lowaffinity site in e2 promoted mg2+ release and the site was reoccupied only after enzyme phosphorylation in e1 by mgatp. in 2000, a conserved segment in the p domain of the α subunit was identified in which asp710 contributed to the coordination of mg2+.146 another tool to enlarge the insight into enzyme functions were various inhibitors that allowed the arrest 31finding na,k-atpase ii from fluxes to ion movements of the na,k-atpase in defined states or a restriction of possible reaction sequences to specific parts of the pump cycle. a review presenting a comprehensive survey was published by glynn in 1985.14 the most important group of inhibitors is that of cardiac steroids. compounds in which a sugar is attached to the steroid are so-called cardiac glycosides (cgs), of which the most prominent is ouabain. although it was clear that cgs interact with the extracellular side of the na,k-atpase, the molecular mechanism of inhibition was unknown until the 1990s. with the progress of molecular-biological methods mutagenesis of numerous (and ‘suspect’) amino acids was performed and the effect of the mutations and their resistance against different cgs was investigated to identify the binding site of the inhibitor.147,148 crucial amino acids were found in transmembrane and extracellular domains. at the same time, in 1996, functional studies revealed that k+ accelerated enzyme dephosphorylation and thus antagonized ouabain binding. in the presence of high concentrations of ouabain (in the mm range), however, ouabain was able to bind even when 2 rb+ (as congeners of k+) were bound, e2rb2, and the inhibitor stabilized this state.149 major progress in mechanistic understanding was made when detailed structural information became available. in 2009, a first crystal structure of na,k-atpase at 2.8 å resolution was published with a low-affinity bound ouabain in a state analogous to p-e2k2.150 ouabain was deeply inserted into the transmembrane domain with the lactone ring close to both k+ ions bound to their sites. most of the mutagenesis data, obtained with high-affinity bound ouabain, could be explained by this arrangement, which suggested that the cg binding site should be essentially the same in both conditions. two and then four years later structures with high-affinity bound ouabain became available with a resolution of 4.6 å and 3.4 å.151,152 these structures made visible that ouabain was bound to a site in the α subunit formed by transmembrane segments m1 to m6 and thus blocked the ion pathway from the extracellular side to the ion-binding sites. in the structure with the higher resolution it was found that a mg2+ ion was present in the cation transport site ii when ouabain was bound with high-affinity. comparison of the position of ouabain in the lowand high-affinity bound state showed that both were indeed mostly not significantly different. prominent was only a difference in the location of the lactone ring of the inhibitor in the mg2+-bound and k+-occluded condition. altogether, functional and structural findings allowed a consistent explanation of the inhibition mechanism by preventing the conformation transition from e2 to e1 while clogging the extracellular access channel of the na,k-atpase. the well-known antagonistic effect of k+ on ouabain (or any other cardiac glycoside) binding could be attributed to k+-induced low-affinity ouabain binding.152 when the effect of cgs was studied with enzyme from many animals, typical binding affinities of the na,k-atpase were found in the range of µm.153 such a high affinity raised the question of why the enzyme should have evolved such a specific binding site for an exogenous compound and whether there were endogenous inhibitors aimed at this site. john m. hamlyn and collaborators reported in 1982 the existence of a circulating inhibitor of the na,k-atpase,154 in 1991 they identified a ouabain-like factor,155 in 1999 it was confirmed that it was ouabain,156 and in 2000 wilhelm schoner introduced ouabain as new steroid hormone.157 in a recent review the story of discovery, advances and controversies of endogenous ouabain was published.158 ouabain also plays a role as a signal messenger. regulatory effects of the na,k-atpase inhibition by ouabain were initially assigned to changes in intracellular na+ and k+ concentrations.159 from research in cardiac hypertrophy crucial information was collected over a couple of years and it was established that ouabain stimulated myocyte growth and protein synthesis, comprised the induction of a number of early response proto-oncogenes and activated transcription factors already at low, nontoxic concentrations. finally, experimental observations were published that ouabain binding activated signaling cascades.160 the ouabain-stimulated signal transduction was mediated by the na,k-atpase but was apparently independent of ion transport function.161 the signaling function of na/k-atpase controlled by cgs has been gradually appreciated over the last 20 years as can be followed in several reviews.161-164 another potent inhibitor of the na,k-atpase (and all other p-type atpases) is orthovanadate, vo43-. it was identified 1977 by lewis c. cantley and collaborators as a potent inhibitor of the sodium pump with a ki of 40 nm. inhibition was reversed to 100% by millimolar additions of norepinephrine. vanadate was initially found as contamination in commercial “sigma grade” atp, isolated from horse muscle. from its tetrahedral structure it was concluded that it may bind to “a phosphate site”.165 from their study of interaction with the na,k-atpase cantley concluded that “the unusually high affinity for vanadate is due to its ability to form trigonal bipyramidal structure analogous to the transition state for phosphate hydrolysis.”166 mg2+ was required as cofactor for inhibition. its inhibitory action can be attributed to its high-affinity binding to the phosphate binding site, a condition in which it stabilizes the e2 conformation of the enzyme. 32 hans-jürgen apell one further inhibitor should be mentioned in the framework of this presentation, oligomycin, which was found to inhibit the mitochondrial atp synthase. it is an antibiotic originally isolated from streptomyces. in 1962, first reports were published that this macrolide also inhibited the na,k-atpase.167,168 it was demonstrated that oligomycin is a potent inhibitor, however, it did not inhibit the enzyme completely, e.g. adp-atp exchange was unaffected. eventually, all experimental findings were explained by the mechanistic concept that oligomycin blocked the conformation transition e1-p → p-e2.14,169 this was supported by findings that the inhibitor shifted the equilibrium from a na+-deoccluded form to a na+-occluded form,128 and stabilized na+ occlusion but not k+ occlusion.170 in 2013 a structure of the na,katpase complex with 3 na+ and an oligomycin molecule was published at a resolution of 2.8 å.171 therein the inhibitor was bound close to helix 1’ on the cytoplasmic side adjacent to the membrane surface. viii. transport function as can be seen from figure 2, ion transport is a complex process even when restricted to the pump cycle under physiological conditions. by means of experimental studies at least ten reaction steps were identified that form the complete pump cycle and embrace the interplay of enzyme and transport functions (fig. 2a). in the following, the focus will be set on molecular processes investigated in experimental studies to enlighten the transport mechanism of both ion species across the membrane. (an earlier review was published in 2004.172) to discuss the transport function of the na,k-atpase in detail, the pump cycle will be divided into four partial reactions: (1) cytoplasmic ion exchange, (2) access transfer from the cytoplasmic to the extracellular side, (3) extracellular ion exchange, and (4) access transfer from the extracellular to the cytoplasmic side. (1) k2e1·atp ⇄ e1·atp ⇄ na3e1·atp the cytoplasmic ion exchange occurs in the e1 conformation of the na,k-atpase. under physiological conditions, in which the cytoplasmic k+ concentration is high, na+ low, and the binding affinity for k+ is higher than for na+, a significant fraction of the enzyme is found in the k2e1·atp state.173 consequently, under steady-state conditions only a small fraction of the na,katpase populates na3e1·atp, the state which is the one capable of being phosphorylated. despite this unfavorable displacement of the occupation of the states in this reaction sequence, the pump is obviously able to perform its task of extruding na+ from the cytoplasm. this fact has to be assigned to the finding that the exchange of ions between binding sites and aqueous bulk phase is fast (and for the most part diffusion controlled) compared to the subsequent phosphorylation step so that a quasi-equilibrium distribution between the differently occupied states may be assumed. therefore, the drain of the na3e1·atp state by the phosphorylation step is instantaneously compensated. it is known, however, that the na,k-atpase runs way below their kinetically possible maximum turnover due to this limiting condition. when initial studies of ion binding and release in the e1 conformation were performed, it was observed that k+ release and binding of the first two na+ ions were not electrogenic.174,175 this observation was interpreted as indication that both binding sites were negatively charged and located close to the cytoplasmic surface in a wide, water filled vestibule. this electroneutrality turned out to be, however, only an apparent effect176. in the e1 conformation, the affinity of both binding sites for protons is so high that at physiological ph and in the absence of na+ and k+ the sites are mostly protonated. therefore, binding of both k+ ions and of the first two na+ ions in titration experiments was effectively an electroneutral exchange against bound protons. at unphysiologically high ph, the electrogenicity of k+ and na+ binding became very well visible in titration experiments when beginning with a cation-free electrolyte176. while k+ and the first two na+ ions compete for the same sites in the pump, binding of the third na+ occurs to an exclusively na+-specific site in the e1 state. this process was found to be electrogenic and the dielectric coefficient was shown to be in the order of 0.25.12,35,83,177 it was demonstrated that electrogenic binding of the third na+ could be detected by styryl dye rh421 and simultaneously by a directly measured charge movement with identical results.81 that means that na+ traverses 25% of the electric-potential drop across membrane to reach its binding site from the cytoplasm. (which does not necessarily imply that the spatial distance is also 25 % of the membrane thickness.27) a study of cytoplasmic na+ binding and detailed analysis of the binding affinities revealed that the third na+ binds to a site with a higher affinity for na+ than the second site.173 such an observation could be explained by the assumption that the third binding site became available only after the first two sites were already occupied by na+. a possible mechanism was a conformational rearrangement in the transmembrane helices of the membrane domain upon binding of the second na+ which then assembled the third na+ site or opened access to it. furthermore, bind33finding na,k-atpase ii from fluxes to ion movements ing of the third na+ was monitored also with a fluorescence change of the conformation-sensitive label fitc, which was linked to a highly conserved lysine in the nucleotide-binding site at the cytoplasmic n domain.175 the accordance of results from the fitc and rh421 experiments was a strong indication that binding of the third na+ and conformational rearrangement at the cytoplasmic n domain of the protein were concurrent events. in the composition of a mechanistic concept it may be concluded that binding of only the third sodium triggers a rearrangement of the cytoplasmic n domain with an appropriately bound mgatp, and thus arms the protein to make way for enzyme phosphorylation at the specific aspartate in the cytoplasmic p domain. such a mechanism would also be in agreement with the finding that binding of the third na+ needed significantly higher activation energy (63.4 kj/mol) than binding of the first two na+.178 an activation energy of such a high magnitude points as well to a conformational rearrangement related to binding/release of the third na+. an alternative proposal was suggested by kanai et al., based on their structure of the na,k-atpase in an e1 conformation with 3 na+ occluded.171 their concept was that the first na+ is bound to the na+-specific site iii followed by occupation of sites i (in the middle) and ii (outermost). they assumed from their crystal structure, which represented a na+-occluded phosphorylated intermediate, that there is just one access pathway to all three sites and the “innermost” site iii can be reached only through (empty) sites i and ii. if so, a possible reconciliation with the results from functional studies could be a single-file push-on mechanism in which sites i and ii are occupied first, but with the arrival of a third na+ both ions in sites i and ii are moved forward into sites iii and i to make way for binding of the third ion into site ii. to clarify the actual mechanism a crystal structure of the pump in the antecedent, non-occluded (and preferably only partly occupied) state would be very helpful. (2) na3e1·atp ⇄ (na3)e1-p ⇄ p-e2na3 when all three ion sites are occupied by na+ and mgatp is bound to the nucleotide binding site, the pump is able to perform auto-phosphorylation associated with a simultaneous occlusion of the ions. during this reaction step no charge movements were detected.34 this observation indicated that the three ions in their binding sites are not displaced (at least not perpendicular to the membrane plane). this behavior is in agreement with the observation that the ion-binding sites of the closely related sr ca-atpase also are not significantly relocated throughout the complete pump cycle as can be established by comparison of the crystal structures obtained in numerous different states of the pump.179 in the absence of oligomycin the gained occluded state, (na3)e1-p, is transient and followed by a spontaneous transition to the p-e2 conformation with deoccluded ion binding sites. this step is the rate-limiting process in the na+-translocating half cycle,12,35,57,78 with a rate constant of about 22 s-1 at 20 °c, and has the highest activation energy of all reactions of the pump cycle. with purified membrane preparations from rabbit kidney a value in the order of 115 kj/mol was determined.180 the conformation transition showed only a minor dielectric coefficient (0 – 0.1),35,57 and it could not be determined whether this was caused by ion movements or (more probably) movements of charged side chains in the helices of the membrane domain which underwent considerable reorientations during the transition. besides unclasping the access channel between binding sites and extracellular aqueous phase, another major functional consequence of the transition was the reduction of the binding affinity for na+ by a factor of about 500.12 this dramatic change was caused by minor movements of transmembrane helices which in turn modified the coordinating interactions between amino-acid sidechains and the na+ ions. (3) p-e2na3 ⇄ p-e2 ⇄ p-e2k2 the extracellular sodium release is the best investigated partial reaction of the na,k-atpase pump cycle.12,35,56,57,181-183 release of the three na+ occurred sequentially and with different kinetic and electrogenic properties, which allowed an assignment to the respective reaction steps. the first na+ released had the highest dielectric coefficient of the whole pump cycle. the ion traversed 65 – 70 % of the electric potential in the membrane, and its release process had the lowest rate constant of the three ions in the order of 1000 s-1 at 20 °c.35,57,183 the activation energy of this partial reaction was found to be about 80 kj/mol.184 dissociation of ions from a binding site and diffusion through a narrow pore-like structure typically would have activation energies below 20 kj/mol. the observed high activation energy was, therefore, an indication of a conformational rearrangement of the participating membrane domain. the commonly accepted release mechanism is an initial rate-limiting deocclusion process for the first ion as associated consequence of the conformation transition from e1-p to p-e2. the high dielectric coefficient of the first na+ released has to be explained by an ion 34 hans-jürgen apell migration through a narrow access channel. thereafter, another conformational relaxation was required before the second and third na+ ion exited the membrane domain, since the electrogenicity of these reaction steps was found to be just 10 – 20 % even though the distance between the ion binding sites was small. because it is expected that the binding sites are not (significantly) dislocated during this partial reaction, a rearrangement of the α helices in the protein’s membrane domain has to take place in a way that they form a wide access structure being filled with water molecules, as was proposed.35,185,186 such a vestibule would remodel the dielectric shape of the protein so that the bound ions would be able to reach the polar aqueous phase within a short “dielectric” distance of < 20 %.35,57 the existence of such a structural rearrangement was supported by the high activation energy of 70 kj/mol that was determined for this partial reaction.57 the subsequent release of the second na+ was found to be fast with a rate constant in the order of 10,000 s-1.57 thereafter, the release of the last na+ occurred with a similarly low dielectric coefficient, and with a rate so fast (≥ 106 s-1)57 that it could not be resolved with the experimental techniques available. in the resulting p-e2 state the ion-binding sites had a significantly lower binding affinity for protons than in the e1 conformation176 and were virtually empty at low na+ concentrations and in the absence of k+. the following k+ binding and transport into the cell have been studied extensively.12,187-191 sequential binding of k+ (or its congener rb+) was resolved and a mechanism described as “flickering gate model” was introduced which implied that the first k+ is slowly bound (or released) while the second k+ bound was able to exchange fast with the aqueous phase187. the equilibrium dissociation constants for the first and second k+ differed by a factor of 5 to 6 at a level in the sub-millimolar range. besides k+, congeneric monovalent cations were also able to be transported, such as rb+, cs+, tl+, nh4+, h+ or even na+. quaternary organic amines, which are large monovalent cations of different size, were used to probe the extracellular access channel and, in addition, they could be used as inhibitors of the na,katpase.186,192-195 (4) p-e2k2 ⇄ atp·e2(k2) ⇄ k2e1·atp while k+ binding (or release) on either side of the membrane was electrogenic, occlusion, conformation transition and deocclusion on the opposite side of the membrane were electrically silent.104,196,197 release of k+ to the cytoplasmic aqueous phase was actually a k+/na+ exchange or a k+/h+ exchange in the absence of na+ (see above), and therefore, also only apparently electroneutral.176 when the second k+ ion was embedded in its binding site in the p-e2 state, a spontaneous conformational rearrangement occurred that caused ion occlusion and dephosphorylation of the enzyme, resulting in state e2(k2).187 the available experimental evidence indicated that dephosphorylation and occlusion go hand in hand. in 1988, the rate constant could only be estimated, and forbush reported that it has to be much larger than 100 s-1.198 a few years later fits to kinetic data led to values of >103 s-1 (all at room temperature).12 for the reverse reaction, the backdoor phosphorylation, rate constants of > 105 m-1s-1 were determined.68,199 under physiological conditions, the dephosphorylated e2(k2) state was only transient. from there, the pump cycle could advance in two different ways, depending on the atp concentration present (fig. 2). at physiological atp concentrations (“high atp”), low-affinity binding of the nucleotide occurred,8 and the resulting state, atp·e2(k2), underwent an accelerated transition to the e1 conformation, k2e1·atp. rate constants of about 60 s-1 were obtained for this reaction step at saturating [atp] and room temperature.200,201 nevertheless, this reaction step was rate-limiting in the k+-transporting half cycle. in analogy to the e1/e2 transition, it was linked up with a deocclusion of the ion sites, then accessible from the cytoplasmic side. in the presence of low atp (< 100 nm), the occluded e2(k2) state was able also to perform a transition to the e1 conformation, e2(k2) → k2e1, with a dramatically lower rate constant of < 0.3 s-1 at room temperature.67,201 the rate constant of the reverse step was much larger (290 s-1)89 so that in the absence of atp and presence of k+ the equilibrium of both conformational states was strongly shifted to the e2 conformation when two ions occluded. summarizing all these findings, the pump mechanism can be represented schematically by the cartoon shown in figure 7. it is based on the gated channel concept, in which the ion sites are embedded deep inside the membrane domain of the na,k-atpase. the ion sites are accessible only from one side at the same time. the observation that electrogenic ion movements were found only in one of both access channels at the same time may be interpreted as indication that the respective other channel is completely blocked. only reaction steps in which ions are taken up from the aqueous phase or released from their binding sites to the outside of the protein are electrogenic and produce a detectable electric signal. ion movements in the access channels are diffusion controlled, which leads to the consequence that under physiological conditions the exchange of both 35finding na,k-atpase ii from fluxes to ion movements k+ against (the first) two na+ and correspondingly the reverse reaction occur so fast that the respective electric current contributions cancel each other. therefore, it was assumed for some time that k+ transport by the na,katpase was electroneutral until experiments were performed under k+-limiting conditions.176,188,191 in the open p-e2 conformation two different conformational arrangements of the access were found. initially after the transition from e1 a narrow channel with high electrogenicity was formed, and after the release of the first na+ a wide water-filled funnel developed and induced low electrogenicity. in the e1 conformation, no such significant changes were found. the question whether the third na+ that binds to the na+-specific site, enters through an access different from that of the first two na+ or both k+ ions could not be answered so far. ix. transmembrane channel formation the gated channel concept received convincing experimental support when the molecular mechanism of the interaction of palytoxin with the na,k-atpase was investigated. palytoxin is a lethal marine toxin extracted from polyps of the genus palythoa.202 it was found that addition of palytoxin to mammalian cells caused the occurrence of rather nonselective cation channels with a single-channel conductance of about 10 ps.203,204 scrutinizing the membranes led to the discovery that those ion channels were formed by the na,k-atpase.205-208 an important step forward was obtained when artigas and gadsby used outside-out or inside-out excised membrane patches to detect the effect of palytoxin on the level of single na,k-atpase molecules.209,210 they recorded typical single-channel events upon addition of palytoxin with conductance of 7-10 ps210 (fig. 8), and proposed that palytoxin modified in the p-e2 conformation the gate between the cytoplasm and the ion-binding sites, when the access channel to the extracellular side was already open. thus a continuous pathway was established that formed a relatively non-selective cation channel. at a low palytoxin concentration, when only one or a few na,kfigure 7. schematic representation of the functional behavior of the na,k-atpase membrane domain (the cytoplasmic domain is omitted for clarity) in characteristic states of the pump cycle. the ion binding sites are located almost in the center of the membrane domain and are accessible from the cytoplasm in the e1 conformation and from the extracellular aqueous phase in p-e2. the open states in both conformations are separated by occluded states in which no ions may move within the access channels. in the p-e2 conformation the initially narrow access channel widens up after release of the first na+. the pink fractions of the cycle indicate electrogenic (ion uptake and release), the green ones represent electroneutral processes (phosphorylation/dephosphorylation, conformation transition). while in the p-e2 conformation the ion-binding sites may be empty, in the e1 conformation the binding sites are occupied by protons in the absence of other monovalent cations (due to the high affinity for protons in e1) as insinuated by the inset. figure 8. schematically represented palytoxin (ptx) induced ionchannel behaviour of the na,k-atpase. a. in the presence of na+ and mg·atp and 25 pm ptx for a few seconds typical opening and closing of a single cation-selective channel were observed. b. after washout of ptx no longer channel events could be recorded and ion-pump activity was restored. c. upon prolonged exposure to 25 pm ptx more and more na,k-atpase molecules were transformed into ion channels. d. in the presence of high concentrations of ouabain channel activity was completely suppressed. figure adapted from artigas & gadsby209. 36 hans-jürgen apell atpase molecules were modified, a characteristic toggling between conducting and non-conducting states of the channel could be observed (fig. 8). therefore, it was concluded that the effect of palytoxin is reversible. in addition, when the toxin was washed out, the channel activity ceased. the fast reversibility of the open-channel formation suggested that no major conformational reorganization or even denaturation of the protein occurred but a simultaneously open condition of both occlusion gates was induced.209 this concept was supported by the fact that common blockers of the access channels were able to clog the continuous ion pathway on both sides of the na,k-atpase.211 by mutation of more than sixty amino acids in transmembrane helices tm1 to tm6, those could be identified by which the conductance of the ion channel could be affected, and a comparison with the crystal structure of the na,k-atpase allowed the proposal of the channel’s shape and position.212,213 x. coupling of enzyme and transport activityies one of the major unresolved issues of the function of the na,k-atpase is the mechanism of energy conversion by the na,k-atpase (or any other p-type atpase). from basic thermodynamic principles it is known that hydrolysis of atp in the presence of known concentrations of atp, adp and pi provides under physiological conditions a gibbs free energy in the order of -55 kj/mol.27 this energy is transferred to the ion pump by a chemical reaction, the phosphorylation of the specific aspartate in the p domain. terrell l. hill showed that energy transduction in molecular machines does not occur in a single reaction step of the reaction cycle (here: the pump cycle of the na,k-atpase) but is distributed over the whole cycle.214,215 therefore, to analyze the energetics of the na,k-atpase, it has to be determined to what extent single reaction steps contribute to the storage and consumption of the system’s free energy in terms of changes of the so-called “basic free energy levels”.27,180 it was found that there was indeed no single “power stroke” reaction step in the pump cycle. under physiological conditions many steps were even close to thermodynamic equilibrium such as the na+ binding and release steps. extracellular k+ binding and atp binding in the e2(k2) state were distinct “down-hill” steps in which energy was dissipated, where in contrast, release of both k+ to the cytoplasm were the most prominent energy consuming steps. the overall energy consumption during a pump cycle could be calculated from the definition of the electrochemical potential gradients of na+ and k+ across the membrane using the known concentrations of both ion species on either side of the membrane, and the electrical membrane potential.27 at typical values of mammalian cells it was calculated that about 80 % of the energy provided by atp hydrolysis was utilized in ion transport.180 compared to macroscopic machines such a yield is impressive. while it is possible to calculate basic free energy levels, these numbers do not provide insight into the molecular processes of how energy is transferred from the initial “high energy phosphate” in state (na3)e1-p to other moieties of the protein with the result that ions are eventually transferred from one side of the membrane to the other, a vectorial process. it can be assumed that the provided energy is distributed over the protein by rearrangements of amino-acid side chains in response to the coordination of the high-energy phosphate, thus creating changes in spatial alignments, mechanical tension and torque of helices, modified electrostatic interaction and dipole movements. such transiently enhanced potential energy is buffered in various subdomains of the protein structure. subsequently, it may drive a meticulously concerted sequence of relaxation processes that perform ion pumping by promoting specific reactions such as ion binding, occlusion and release to the opposite side of the membrane. so far the whole process did not, however, advance from the level of hand-waving arguments. perhaps, additional structural details with atomic resolution of closely neighboring states of the pump cycle will produce fuel for thoughts, or an inspiring idea may be triggered by revisiting the available wealth of experimental data. here, but not only here, an exciting terra incognita in the world of the na,k-atpase is waiting for exploration. xi. pump-related diseases a final chapter shall reveal and summarize how the knowledge on the location of single amino acids and their role in the functional context provided understanding of specific diseases. small mutations on the molecular level of the na,k-atpase were found to significantly affect pump functions with far-reaching organismic impact. as in the case of ion-channel induced pathology, it was found also for the na,k-atpase that errors in the genetic code may provoke malfunctions of the ion pump that lead to phenotypes of explicit diseases. from early studies of the na,k-atpase it has been known already that cardiac glycosides inhibit this enzyme.216 because these compounds were applied to treat congestive heart failure and cardiac arrhythmias, 37finding na,k-atpase ii from fluxes to ion movements it stood to reason that improper regulation of the na,katpase activity may correlate with various clinical conditions. until the year 2000, the focus has been commonly set onto investigations with alteration of endogenous or xenobiotic factors. the cause of several diverging diseases such as cardiovascular, neurological, metabolic or renal disorders were traced back to a dysfunction in salt and water homeostasis of cells that is controlled by the na,k-atpase.217 in 2004, a specific mutation in the α2 isoform of the na,k-atpase was found to cause familial hemiplegic migraine,218 and in the years that followed, further mutations were discovered to provoke various forms of migraine.219 more recently it has been reported that mutations in the neuron-specific na,k-atpase α3 subunit are linked to rapid-onset dystonia parkinsonism220 and that a mutated α3 subunit may play a role in the neurodegeneration of alzheimer patients.221 a further disease, primary aldosteronism, was also attributed – among other causes – to malfunction of the na,k-atpase. modifications of pump activity caused secondary hypertension by overproduction of aldosterone, which is initiated by single mutations of the α1 isoform of the na,k-atpase in adenomas within the zona glomerulosa of the adrenal cortex. each of at least five single mutations in the α1 subunit has been found to induce overproduction of aldosterone.222-224 very recently, it was reported that the capos (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) syndrome is caused by the single mutation, e818k, of the α3-isoform of na,k-atpase.225 mutations in the gene atp1a1, which encodes the α1 subunit of the na,k-atpase, were identified as a cause of autosomal-dominant charcot-marietooth type 2 disease. a missense change was found that induced loss-of-function defects, resulting in peripheral motor and sensory neuropathies.226 a missense mutation of the α2 subunit of the na,k-atpase was found in a patient with hypokalemic periodic paralysis and cns symptoms.227 an informative review on structure and function of the na,k-atpase isoforms in health and 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isom, r. barro-soria, k. w. chung, s. s. scherer, h. p. larsson, n. g. laing, b. o. choi, p. seeman, m. e. shy, l. santoro, s. zuchner; am. j. hum. genet., 2018, 102, 505. 227. castaneda m.s., e. zanoteli, r. s. scalco, v. scaramuzzi, c. marques, v, r. u. conti, a. m. s. da silva, b. o’callaghan, r. phadke, e. bugiardini, r. sud, s. mccall, m. g. hanna, h. poulsen, r. mannikko, e. matthews; brain, 2018, 141, 3308. 228. m. v. clausen, f. hilbers, h. poulsen; front physiol, 2017, 8, 371. substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 3(2) suppl. 5: 79-90, 2019 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-740 citation: h. kragh (2019) controversial elements: priority disputes and the discovery of chemical elements. substantia 3(2) suppl. 5: 79-90. doi: 10.13128/substantia-740 copyright: © 2019 h. kragh. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. controversial elements: priority disputes and the discovery of chemical elements helge kragh niels bohr institute, university of copenhagen, blegdamsvej 17, copenhagen, denmark. e-mail: helge.kragh@nbi.ku.dk abstract. there are only a limited number of chemical elements and to be credited with the discovery of a new one is therefore considered of great importance. adding to the honour and fame is that traditionally the discoverer has the right to name the element in question. for these and other reasons, element discoveries are often followed by controversies regarding priority. while some of these are contemporary with the discovery process, others occur much later and are attempts to rewrite history. but what is a scientific discovery, more precisely, and why does it sometimes become controversial? from a scientific point of view, does it really matter who is recognised for the discovery of a new element? these are some of the questions considered in the paper, together with a few concrete cases from the history of chemistry. as shown by the recent disputes concerning the discoveries of synthetic elements at the end of the periodic system, modern priority disputes differ in some ways from the disputes of the past. on the other hand, there are also significant similarities. keywords.discovery, chemical elements, controversy, priority, periodic system. 1. introduction the subject of this paper is priority controversies related to the discoveries of chemical elements. in order to discuss the subject rationally it will be useful to introduce and clarify the meaning of two key terms, namely “discovery” and “priority controversy,” in a general way that does not necessarily relate to the chemists’ elements. these are concepts that are often taken for granted, but scientists, philosophers and historians actually use them with different meanings, such as will be discussed in the following two sections. nor is the meaning of “element” self-evident as it has changed through different phases of history to be explicated in section 4, where a historical classification of element discoveries is suggested. in the last sections i look at aspects of three discovery cases from different periods and with different characteristics. the chosen cases are aluminium from the pre-mendeleev era, lutetium from the early twentieth century, and nobelium from the transuranic age. 80 helge kragh 2. what is a scientific discovery? much of the discussion about scientific discoveries can be traced back to different conceptions of what constitutes a discovery.1 it is generally assumed that a scientist (or a group of scientists) has discovered x if he or she has convincingly established that x exists or is the case. x may be an object, a phenomenon, or a significant relation between empirical data. in the latter case it may consist of a structural organisation of data, where all or some of the data may be known in advance. an example from the history of chemistry is the dulong-petit law of 1819 correlating the specific heats of elements and their atomic weights. another and more important example is mendeleev’s periodic system fifty years later. although mendeleev’s system did not originally rely on new discoveries of objects and their properties, he discovered the system in the constructive sense that he organised known data into a new conceptual framework. it may seem obvious that only objects which really exist can be discovered. when we say that william ramsay and lord rayleigh discovered argon in 1894, it implies that argon really exists as a component of the atmosphere. as the philosopher peter achinstein has argued, truth and discovery go together: “discovering something requires the existence of what is discovered. you cannot discover what doesn’t exist.”2 of course, one can claim to have discovered a non-existing object, and the claim may even be broadly accepted for a period of time, but in that case the claim does not count as a proper discovery. although achinstein’s view may seem to be common sense, from a historical perspective it is problematic to reserve the category of discovery for what is presently accepted as true. from this perspective one may legitimately speak of the discovery of non-existing objects or phenomena, namely if the discovery claim received wide recognition at the time it was announced. phlogiston does not exist and yet the substance was believed to exist for half a century or so. it makes sense to say that georg e. stahl discovered phlogiston in about 1720 and also that joseph black discovered the heat substance called caloric in the 1730s. these non-existing entities were discovered and later de-discovered. there is another reason why achinstein’s claim is problematic, namely that it seems to presuppose that objects exist in nature prior to their discovery. but there are objects, such as the artificially produced superheavy elements, that only come into existence with their discovery. the so far heaviest known element, oganesson with atomic number 118, was not discovered because it existed. it exists because it was discovered. a chemical element is not a specific and localisable object of the same kind as, say, a planet. the chemist cannot point to a piece of sodium and claim that “this is sodium” in the same sense as the astronomer can point to a planet and claim that “this is neptune.” on the other hand, to say that something is or contains the element sodium involves the concept of an element, just like the identification of neptune as a planet involves the concept of a planet. the discovery of a new element is thus to demonstrate convincingly the elemental nature of some substance, which is a conceptual discovery, and also to find this substance in nature – or perhaps to synthesize it in the laboratory. the latter is an empirical discovery. for something to be a discovery it is normally assumed that it must be a novelty, and for this reason it cannot be made twice at different times. on the other hand, there are many examples in the history of science of so-called rediscoveries, a concept which typically refers to insights that originally attracted very little attention and at a later time were unknowingly duplicated.3 the rediscovery will almost always be in a different form than the original discovery. an example from the history of chemistry is provided by the discovery of vanadium, which was first isolated by andrés manuel del río in 1801 and rediscovered by nils g. sefström thirty years later.4 if a discovery is little known and exerts almost no impact on the scientific community, the rediscovery is more effective than the one with which the discovery is often associated. the useful concept of the “effective discovery of an element” was introduced by the danish chemist edmond rancke-madsen, who referred to the cases of hydrogen (henry cavendish, 1766), oxygen (joseph priestley, 1775) and chlorine (carl w. scheele, 1774) as examples.5 according to rancke-madsen, for a scientist to be the effective discoverer of an element, he (or she) must have observed the existence of a new substance “which is different from earlier described substances, and this new substance is recognized by him or later by scientists as being elemental” (emphasis added). moreover, the discovery of the new substance must have been announced publicly and attracted attention among contemporary scientists. notice that according to this view, the effective discoverer does not need to have recognised the substance as an element; what matters is only that it was granted this status by later scientists and that this is still its status today. the notion of an effective discovery underlines that a discovery cannot be a private matter or limited to just a few persons. not only must the discovery claim be publicly available, it must also be known and accepted 81priority disputes and the discovery of chemical elements by at least a substantial part of the relevant scientific community. it must be communicated, usually in a journal article although it can also be in the form of a wellpublicized lecture or a press conference. the swedish chemist and historian of chemistry jan trofast offers the following definition of the discovery of a chemical element: a discovery is established when the scientist has shown new properties of the new element in form of e.g. a number of salts and clearly and unambiguously shown that it is a new element. … further the time of discovery is said to be when the first publication (could be in the form of a letter to a colleague) is available and not when the first observation is made or when the first suspicion was aroused in the laboratory.6 however, to include a private letter under the label “publication” is too wide an interpretation of the term. communication by letter does not secure dissemination to the scientific community but at most to a few members of it. only in exceptional cases, namely if the letter is copied or its content otherwise circulated to a large number of scientists, can this form of communication be of a public or semi-public nature. the scientist who makes an observation of something new, but reports it only in his diary or in a letter, has not made a discovery and that even though he may have recognised the novelty and significance of what he has observed. according to alan gross, “there is no such thing as a private discovery… a scientific discovery, then, is the public attribution of novelty to a claim regarded by a relevant scientific community as possible and as the consequence of following appropriate methods.”7 consider the case of plutonium which was identified in nuclear reactions by glenn seaborg and his team in late 1940 (pu-238) and early 1941 (pu-239). as a result of the unusual political circumstances of world war ii the discovery paper submitted on 7 march 1941 to physical review, only appeared in print five years later.8 although plutonium thus became publicly discovered only in 1946, it is customary and reasonable to date the discovery to the year 1941. incidentally, in this case there was no priority controversy as the discovery was unanimously assigned to seaborg and his collaborators. according to the individualist or “heroic” model of discovery widely favoured by scientists and journalists, one can identify the moment a discovery occurred and also the individual who should be credited. however, historical studies demonstrate that in many cases this is not possible and, generally, that the model is inadequate. rather than focusing on the discovery itself some historians and sociologists of science argue that what matters is not so much the discovery’s intellectual history as its social history. how and why does a discovery claim become accepted as a bona fide discovery by the scientific community? according to this view discoveries are retrospective judgments which are socially defined and constructed. they are labels attributed post hoc to some discovery claims but not to others. as one author puts it, “discoveries do not simply ‘occur’ or ‘happen’ naturalistically, but are socially defined and recognized productions.”9 while the importance of the social history is beyond doubt in discovery studies, it does not follow that it offers a sufficient account of discoveries and their receptions. moreover, the social analysis is not incompatible with a more traditional, intellectual analysis. the two approaches are supplementary and none of them is sufficient alone. discoveries are often thought to be purely empirical, meaning that the first observation of an object or phenomenon x constitutes the discovery of x. however, philosophers have long pointed out that this is too simplistic a view and that a discovery involves an active mental process as it relies on theoretical preconditions. a scientist may observe or perceive x without identifying it as x. or to put it differently, there is a crucial difference between “seeing that” and “seeing as.”10 for example, in experiments with iron and dilute strong acids robert boyle and other seventeenth-century chemists observed an “air” without recognising it to be new or elemental. they observed what became known as hydrogen, but they did not discover hydrogen. this view is contrary to the one of rancke-madsen as cited above. the idea that discoveries involve changes in the theoretical or conceptual framework was a leading theme in thomas kuhn’s influential essay dating from 1962. using the discovery history of oxygen as a lead example kuhn argued that “observation and conceptualization, fact and assimilation of fact to theory, are inseparably linked in the discovery of scientific novelty.”11 moreover, he distinguished between two classes of discovery, namely those which could be predicted from accepted theory in advance and those which could not. kuhn found the second class – “discovery by accident” – to be more interesting, as this kind of discovery would typically force scientists to organise known data into a new conceptual framework. as a result an existing paradigm might be challenged and give rise to a revolutionary phase in science. with respect to discoveries of the first class, such as the elements predicted or anticipated from the periodic system, kuhn wrote that “there have been few priority debates … and only paucity of data can prevent the 82 helge kragh historian from ascribing them to a particular time and place.” however, this is definitely a misconception. after the acceptance of the periodic system the frequency of priority controversies did not diminish nor did they become less serious. on the contrary, conflicts of this kind rather increased in number and intensity. 3. controversies over priority in his history and present state of electricity dating from 1767, priestley suggested that “mistakes, misapprehensions, and altercations” should have no place in the annals of science. according to him, all the disputes which have no way contributed to the discovery of truth, i would gladly consign to eternal oblivion. did it depend upon me, it should never be known to posterity, that there had ever been any such thing as envy, jealousy, or cavilling among the admirers of my favourite study.12 yet it is all too clear that controversies of various kinds do play an important and often fruitful role in science and have always done so. they are sometimes instrumental in defining the disciplinary boundaries related to a new subfield, such as exemplified by the emergence of physical chemistry in the late nineteenth century.13 as robert merton pointed out in a pioneering paper of 1957, not only are controversies abundant they also contribute – contrary to what priestley thought – to scientific progress.14 to be involved in a scientific controversy whether as a winner or loser, may cause a loss in reputation, but this is not generally the case. priority controversies, in particular, may have the effect of increasing the competitive pressure and forcing the participants to study the subject in question more extensively and in greater depth than if the controversy had not existed. this kind of controversy goes far back in time, certainly to the age of galileo if not earlier. one reason why the assignment of credit is important is that it helps in understanding the historical dynamics in the discovery process. assigning the wrong credit for a discovery may distort the picture of how and why the discovery occurred. there is no generally accepted definition of a scientific controversy, but it is useful to distinguish the concept from other forms of communicative disagreement, such as debate, discussion, polemics and dispute.15 first, for a disagreement to qualify as a scientific controversy, evidently it should centre on a scientific issue and involve scientists as key participants. while some controversies are “pure,” meaning that they are concerned almost exclusively with scientific questions, others are “mixed.” the latter category refers to cases where political, environmental and ethical concerns enter significantly, such as the use of flame retardant chemicals.16 whether belonging to one class or the other, typically a controversy is of some duration, it is expressed in public, and it takes place by means of arguments and counterarguments. contrary to what is the case in a debate or discussion, the parties involved in a controversy must be committed to one of the opposing views. being more than a quarrel between two individual scientists a controversy involves the relevant scientific community, and it is only if the community considers the disagreement worth taking seriously that it will develop into a proper controversy. in some if not all cases major parts of the scientific community will be engaged on both sides of the disagreement, although often disproportionally. there are different kinds of controversies. following a proposal of ernan mcmullin, one may distinguish between controversies of fact, of theory, and of principle.17 in the present context dealing with element discoveries the first category is the most important. here scientists disagree on whether a claimed entity or property actually exists. does the substance claimed to be a new chemical element really have the status of an element? the two other categories relate to different theoretical views and methodological principles, respectively. the three categories are not mutually exclusive and may in some cases appear together, such as was the case with the much-discussed discovery history of oxygen.18 disputes over priority mostly concern either factual or theoretical disagreements as in the discovery of objects or theories. they may also be about names which, in the case of new elements, have often provoked controversy if of a different kind. the accepted name of an element may directly or indirectly refer to the discoverer and thus suggest which scientist is to be credited with the discovery. consider a scientist x who proposes the name a for a new element he claims to have found, while scientist y independently finds what he names b and believes is the same element. in this case a dispute about the name reflects a controversy about discovery (see section 6). naming controversies have been common for the transuranic elements and in particular for those named after a scientist. the most controversial of the names was the one of element 106, seaborgium, but there were others as well.19 as controversies appear in different forms, so they terminate in different ways. a controversy may be resolved, meaning that the two parties come to agree, by 83priority disputes and the discovery of chemical elements means of scientific arguments, that one of the competing claims is after all superior to the other. the irish chemist richard kirwan had for long defended the phlogiston theory and criticized lavoisier’s oxygen alternative, but in 1792 he gave in. “i lay down my arms and abandon the cause of phlogiston,” he wrote.20 a controversy may also terminate by withering away, perhaps by lack of interest or simply because the protagonists of one of the competing views disappear from the scene. finally historians and sociologists speak about termination by closure if political or other non-scientific factors force the controversy to end. in most cases priority controversies take place simultaneously with the discovery claims and involve the competing scientists as the main contenders. but in other cases they emerge retrospectively many years after the contenders have passed away and the case apparently was closed. it may be that new data or historical sources come to the light of day, or that scientists re-examine the case and argue that x rather than y should be credited with the discovery. as we shall see below, the discoveries of aluminium and lutetium are examples. another and more recently discussed case concerns element 75, rhenium, which is credited work by ida tacke (later noddack), walter noddack and otto berg in 1925. however, many years earlier the japanese chemist masataka ogawa believed to have found evidence for the element, which he called nipponium. by 1925 nipponium was long forgotten, but as late as 2004 it was argued that ogawa had indeed discovered the element.21 to the extent that one can speak of a priority conflict in this rather unconvincing attempt of rehabilitation, it was constructed much post festum (see also section 4). 4. an overview of element discoveries it is generally agreed that phosphorus is the first element with a known discovery history and discoverer. the earlier elements known to ancient cultures, such as sulphur, gold, silver and tin, were not discovered in any real sense (figure 1). when the hamburg merchant and alchemist hennig brand in or about 1669 produced a white, waxy and luminous substance by distilling male urine and heating the remaining paste, he serendipitously discovered phosphorus in the form p4 (figure 2).22 but he did not, strictly speaking, discover the chemical element phosphorus as neither he nor his contemporaries conceived the substance as an elementary body. nor did brand communicate his discovery publicly, in the form of a publication. only in 1678 did the german chemist johann kunckel publish an account of the new substance and how to prepare it. still a century after brand’s discovery phosphorus was thought to be a composite body, namely “a kind of sulphur composed of a particular acid united with phlogiston … [and which] resembles vitriolic sulphur also in this point that its phlogiston may be burnt, even with rapidity, without any decomposition of its acid.”23 figure 1. discoveries of chemical elements since 1650. source: https://commons.wikimedia.org/wiki/file:known-elements-1650-present.png figure 2. detail from joseph wright of derby’s painting of 1771 showing an alchemist discovering phosphorus. source: https:// resobscura.blogspot.com/2017/06/urine-phosphorus-and-philosophers-stone.html 84 helge kragh although brand’s work of 1669 does not live up to current philosophical, non-anachronistic ideas of what constitute an element discovery, somehow it seems artificial to deprive him of the credit of having discovered phosphorus. there was at the time a kind of priority controversy even though it did not concern phosphorus as an element but only as a new and exciting substance. within a decade or two brand faded into obscurity, his priority defended only by leibniz. by the turn of the century priority had effectively been conferred to either kunckel or his compatriot johan daniel krafft. the point is that according to the early chemists phosphorus was not elemental. a concept of chemical elements roughly similar to the modern one only arose in the 1780s, perhaps first stated by the german chemist johann gmelin.24 more famously and in greater detail it was stated by antoine lavoisier in his seminal treatise traité élementaire de chimie published in 1789. according to lavoisier, phosphorus was an element or “simple substance,” meaning that it could not be decomposed – or had not yet been decomposed – into still simpler bodies (figure 3). the later history of element discoveries may conveniently be classified in four chronological phases, the first of which is associated with john dalton’s atomic theory. the immediate importance of dalton’s new system of chemical philosophy was not so much the atomic hypo thesis as the idea to associate the relative weights of atoms with a measurable quantity, the atomic weight. as far as the concept of element was concerned, dalton followed lavoisier’s operational formula: “by elementary principles or simple bodies we mean such as have not been decomposed, but are found to enter into combination with other bodies.”25 with jöns jacob berzelius’ staunch support of dalton’s theory the establishment of still more precise atomic weights became a matter of prime concern. in 1826 berzelius published his final table of atomic weights. to him and many of his contemporaries the identification of new elements relied on determinations of their atomic weights. often credited as the discoverer of five new elements (cerium, selenium, silicon, zirconium, and thorium), berzelius was eminently successful and his successes depended to a large extent on his analytical skills in determining the elements’ atomic weights.26 dmitri mendeleev’s classification of elements in 1869, which i take to be the beginning of phase two, rested crucially on the postulate that an element was defined by its atomic weight. in his faraday lecture of 1889 the russian chemist pointed out that before the periodic system “there was no special reason to expect the discovery of new elements.” it was only the gaps in the sequence of atomic weights as organised in the periodic system that “enabled us to perceive undiscovered elements at a distance which formerly was inaccessible to chemical vision, and long ere they were discovered.”27 with the acceptance of the periodic system or table it came to define the possibility of new elements: if x has no place in the table, it cannot possibly be an element. the dogma was challenged with the discovery of argon and helium in the 1890s, but in this case order was reinstated by adding a new group of inert gases to the system. despite the authority of mendeleev’s system, or the corresponding one of lothar meyer, chemists continued to suggest new elements. they sometimes hid them in the poorly understood group of rare earths and at other times they were just unconcerned with whether they fitted into the system or not. random examples are nebulium, etherion and carolinium.28 characteristically these discovery claims were rarely taken seriously. figure 3. lavoisier’s table of “simple substances” in his traité élémentaire de chimie from 1789. 85priority disputes and the discovery of chemical elements in the third phase, starting with the introduction of isotopy and the atomic number z in about 1913 it turned out that the atomic weight was not after all the defining property of an element.29 yet the periodic system survived the redefinition of an element and the change of the elements’ ordinal number from the atomic weight to the atomic number. the latter quantity, as given by the charge of the atomic nucleus, could be measured by means of the method of x-ray spectroscopy pioneered by henry moseley. however, it took until 1923 before the new definition of an element was sanctioned by iupac, the international union of pure and applied chemistry. whereas the periodic system did not originally restrict the number of possible elements, with the introduction of the atomic number the existence of elements lighter than hydrogen was ruled out. what had formerly been possible, if unlikely, now became impossible. on the other hand, the new understanding of the periodic system did not preclude new elements heavier than uranium. in principle there might be any number of them. the fourth and last phase in the history of element discoveries may be said to have started in 1937 with the manufacture and hence discovery of the first artificial element, soon to be followed by many transuranic elements. technetium, the approved name of element 43, was discovered by the physicist emilio segré and the mineralogist carlo perrier by analysing a molybdenum target irradiated with deuterons and neutrons. there had earlier been several unconfirmed claims of having detected element 43 in nature, noticeably by the noddacktacke-berg team which in 1925 claimed to have found small amounts of the element. this evolved into a priority controversy between “masurium” and technetium which much later was re-opened by scientists in favour of the masurium claim.30 the much delayed attempts to change the discovery history of element 43 were ignored by iupac and the large majority of chemists. 5. the third-most common element given that aluminium makes up 8.1% of the earth’s crust, it is remarkable that its discovery dates back less than 150 years. in the case of element 13 there was no major priority controversy, but there are other features in the history of the element that makes it instructive from a discovery perspective.31 it is generally agreed that the german chemist andreas sigismund marggraf was the first to realise, in 1754, that there is a separate “earth” (alumina) in alum different from the one in limestone.32 the still unknown earth appeared as “argile” in lavoisier’s table of 1789, with the author suggesting that it might be a metallic element saturated with oxygen. attempts to isolate the metal in alumina made by humphry davy and later by berzelius failed, although berzelius was able to determine its atomic weight to 27.4. the element was known to exist and davy had even coined a name for it, alumium or what later became aluminium, but it had not yet been discovered. the main steps in the element’s discovery process are well known and need only to be briefly recapitulated. in early 1825 h. c. ørsted, the discoverer of electromagnetism, reported to the royal danish academy of science a new method in which he transformed alumina (al2o3) to anhydrous aluminium chloride and subsequently reduced it by means of potassium amalgam (figure 4). the result was what ørsted described as “a lump of metal resembling tin in colour and lustre.”33 the brief danish report was abstracted in schweigger’s journal für physik und chemie and poggendorff ’s annalen der physik und chemie, and in 1827 it appeared in a german translation in berzelius’ jahresbericht über die fortschritte der physischen wissenschaften.34 nonetheless, it failed to attract interest. ørsted, who did not find the method and the new element to be very important, never returned to the subject. in september 1827 young friedrich wöhler visited ørsted, who told him about the metal and encouraged him to take a closer look at it. back in germany wöhler was unable to confirm that ørsted’s method yielded aluminium, but by using pure potassium as the reducing agent he produced the metal in the form of a grey powder. wöhler came to believe that what ørsted had thought was a lump of aluminium was instead a kind of alloy of aluminium and potassium. in his discovery paper of 1827 wöhler gave full credit to ørsted for his discovery of aluminium chloride, carefully pointing out that he had no intention to exploit ørsted’s pioneering work of 1825 or being disfigure 4. the first step in ørsted’s isolation of aluminium, the synthesis of alcl3. in modern nomenclature the process is al2 o3+3c +3cl2→3co+2alcl3. reproduced from a danish textbook of 1853 (h. westergård, uorganisk kemi). 86 helge kragh loyal. he mentioned that the danish scientist “has indirectly encouraged me to try to attain to further results myself.” ørsted seems not to have cared about priority, and there was no rivalry between him and wöhler. in 1845 wöhler was able to obtain aluminium in a compact metallic if still impure form and to determine, for the first time, the metal’s principal properties. if ørsted’s work of 1825 was the first birth of aluminium, and wöhler’s of 1827 and 1845 marked the second birth, the third birth dates from 1854 when henri saintclaire deville found a new method to produce the metal in pure form. it was only with deville’s work that aluminium became a useful metal and not a mere chemical curiosity. deville never claimed to have discovered aluminium, an honour he fully ascribed to wöhler, and yet in france he was widely and in part for national reasons considered the true discoverer.35 as to ørsted’s role in the discovery process, deville simply ignored it. in his influential book de l’aluminium from 1859, the first comprehensive work on the history and use of the new metal, there is no mention of ørsted. for most of a century wöhler was recognised as the one and only discoverer of aluminium, whereas ørsted’s earlier synthesis was generally considered to be wrong or incomplete, perhaps an anticipation of aluminium but not an isolation of the metal. however, on the occasion of the centenary of the discovery of electromagnetism danish chemists reconsidered ørsted ’s method and reconstructed the old experiments to establish whether or not aluminium had been obtained back in 1825. the result of this attempt to rewrite history was that in all likelihood ørsted had isolated impure aluminium two years before wöhler, a conclusion in which there clearly was an element of national pride. it is about time, wrote the distinguished chemist niels bjerrum, “to reinstate ørsted as the first who obtained aluminium.”36 contrary to the earlier mentioned case of element 75 (section 3), in this case the attempt of rehabilitation succeeded to some extent. according to harry holmes, an american chemist, “it is now in order for the world to atone for the injustice by giving the dane credit for the discovery.”37 not all chemists and historians agree, but today it is not uncommon to name ørsted as the discoverer of aluminium or to share the credit between him and wöhler. so, when was aluminium discovered and to whom should priority be allocated? as indicated in section 2, the question is misguided as it presupposes an answer in terms of a definite year and a definite discoverer. a summary of the discovery process may provide the only appropriate answer: in 1754 marggraf recognised a special “earth” in alum which subsequently became known as an element and prepared by ørsted in 1825 in an impure form; two years later wöhler produced aluminium as metallic powder and in 1845 he determined its density and some other properties; finally, in 1854 deville created pure aluminium and laid the base for its industrial use. 6. lutetium, a controversial element contrary to the case of aluminium, the discovery of the rare earth element 71, lutetium, involved a series of convoluted priority controversies concerning scientific as well as external issues. although disputes about fact entered the controversy, it was basically about priority. for a long time the number of rare earths and their position in the periodic system was a matter of confusion and dispute, a situation which was only settled in the mid1920s. the uncertainty resulted in several premature or wrong discovery claims of which “celtium” as a candidate for element 72 has received much attention by historians of science. as it turned out in 1923, element 72 (hafnium) is not a rare earth but a homologue to titanium and zirconium.38 the case of element 71 is closely connected with the celtium-hafnium controversy but started earlier, at a time when a chemical element was still defined by its atomic weight. the controversy over this element took place in two separate phases, originally around 1908 and with a second round in 1923. it provides one more example of how later research may throw new light on the history of the discovery of elements. the ytterbium earth isolated by jean c. g. marignac in 1878 was generally accepted as a chemical element for more than two decades, but in 1907 two chemists, georges urbain in france and carl auer von welsbach in austria, independently concluded that ytterbium contained a hitherto unknown element. urbain reported his finding to the paris academy of science on 4 november 1907, whereas auer presented his full report to the vienna academy six weeks later (but had stated his claim in preliminary communications of 1905 and 1906; figure 5). while urbain named the new element lutecium (lu), and proposed neo-ytterbium (ny) for the more dominant element corresponding to marignac’s ytterbium, auer suggested the names cassiopeium (cp) and aldebaranium (ad). both chemists claimed priority and immediately engaged in a heated controversy.39 for example, at one stage auer accused his french rival of foul play, to which urbain indignantly responded: “[auer] goes as far as accusing me of simply plagiarizing him. … it is disgraceful of mr. auer v. welsbach to 87priority disputes and the discovery of chemical elements make such accusations against his colleagues.”40 without going into further details, in 1909 the international committee on atomic weights decided in favour of urbain’s priority, primarily because he was the first to publish an atomic weight for what now became lutecium and since 1949, lutetium. several years later auer unexpectedly got a second chance. in the wake of the celtium-hafnium dispute scientists at niels bohr’s institute in copenhagen investigated anew auer’s cassiopeium by means of optical spectroscopy and compared the result with urbain’s spectrum of celtium from 1911. from this they concluded not only that celtium anno 1911 was nothing but element 71, but also that urbain’s original sample of lutetium contained much less of the element than auer’s cassiopeium. consequently the copenhagen scientists initiated a campaign to reinstate the austrian chemist as the discoverer of element 71. the campaign succeeded in so far that the german atomic weight commission gave full credit to auer in 1923, but iupac maintained the name lutetium, or rather lutecium, and urbain’s priority. contrary to what is often stated in the chemical literature, urbain’s claim of having discovered lutetium in 1907 rested on a somewhat shaky foundation. element 71 was undoubtedly discovered this year, but it might be just as reasonable to credit auer with the discovery and relegate urbain as an independent co-discoverer. the international committee’s decision to honour urbain was based on incomplete information and an interpretation of available data favourable to urbain’s claim.41 a contributing reason may have been that in 1909 urbain served as chairman of the international committee, the other members being wilhelm ostwald, frank w. clarke and thomas thorpe. finally, the american chemist charles james is sometimes mentioned as an independent discoverer or co-discoverer of lutetium, but since james did not publish his discovery and never pushed his own claim, this is unjustified.42 he could have discovered the element, but did not. 7. nobelium, element 102 the manufacture of many of the transuranic elements, and especially those with atomic numbers between 100 and 113, has given rise to controversies regarding identification, name and priority. a noteworthy example is element 102, nobelium, which was first claimed discovered in 1957 but only received official recognition by iupac 35 years later.43 the controversy, which was primarily concerned with whether priority belonged to teams of american or russian scientists, has certain features in common with the earlier controversy over element 72. as the latter controversy was coloured by the international political climate in the early 1920s, so the controversy over element 102 included external factors reflecting the political atmosphere of the cold war era. but it started with a third group of contenders, namely an international team working at the nobel institute of physics in stockholm and consisting of four swedes, two britons and one american. in 1957 the team announced that it had detected element 102 by bombarding a sample of curium (z = 96) with ions of carbon-13. as regards the name of the element the stockholm scientists suggested to call it nobelium in honour of alfred figure 5. carl auer von welsbach. source: https://commons.wikimedia.org/wiki/file:carl_auer_von_welsbach_1910.jpg 88 helge kragh nobel. the discovery claim created much attention in swedish and british news media, not least because it was the first transuranic element discovered in europe. at the time nuclear syntheses of heavy elements was a monopoly of two research groups, one associated with the university of california at berkeley, and the other with the dubna nuclear research facility in russia. none of the groups accepted the news from stockholm and they were unable to reproduce the claimed results. even though the swedish-led discovery claim turned out to be unfounded, this was only the beginning of a much longer priority controversy involving american and russian scientists as competitors. the discovery story of nobelium has been called “the most convoluted and misunderstood of all [the discovery stories of ] the transfermiums.”44 in short, the berkeley team led by albert ghiorso first claimed to have produced the element in 1958, but the dubna team vehemently denied the claim and argued that, “element 102 was discovered at dubna in studies carried out during 1963-1966. those papers contain unambiguous and complete evidence for the synthesis of its nuclei.”45 ghiorso and his collaborators (including the nobel laureate glenn seaborg) responded by criticizing the russian results and maintaining the validity of their own work. somewhat strangely, element 102 is still named nobelium and thus refers to a discovery claim that was known to be wrong or at least highly insufficient. although neither the americans nor the russians accepted the claim, none of them suggested a different name. nobelium had quickly entered textbooks and periodic tables, and in 1961 iupac approved the name and symbol without evaluating the validity of the stockholm experiments. for a while the russians used the name “joliotium,” a reference to the french nuclear physicist frédéric joliot (or joliot-curie), but the name never caught on.46 it is not irrelevant to mention that joliot was a devoted communist and staunch supporter of the soviet union. to take care of the many priority disputes iupac and iupap (international union of pure and applied physics) established in 1985 a joint transfermium working group (twg) consisting of nuclear physicists and chemists. after a review of all relevant papers on element 102, in a report of 1992 the twg concluded in favour of the dubna team whereas it found that the berkeley experiments did not qualify as a discovery. the decision caused strong reactions from the americans who not only charged that the twg panel was incompetent but also that it was biased in favour of the dubna claim. but iupac accepted the twg report, meaning that the russian nuclear physicist georgii flerov (or georgy flyorov) and his team were approved as discoverers of element 102 (figure 6). this was not quite the end of it, though, for ghiorso and seaborg restated their case in “an appeal to the historians of science to reread the cited literature and perhaps, belatedly, to reassign credit.” if they could not get full credit they would accept “in the spirit of glasnost” to share it with the russians.47 but the appeal was ineffective. the controversy terminated by a mixture of resolution and closure. the twg panel was acutely aware that an assignment of priority for having discovered an element cannot be separated from a definition of what constitutes a discovery. the chosen and agreed-upon definition was simply that the discovery of a chemical element is an experiment which convincingly demonstrates “the existence of a nuclide with an atomic number z not identified before.” the twg panel further reflected on the historical importance of element discoveries: the centuries-old history of the definition and discovery of chemical elements has a deep scientific and general fascination. … the problem is open although of final scope, unlike the number of continents upon the surface of the earth where we know with certainty that none still awaits discovery. these considerations give to the discovery of new elements an importance, an allure and a romance that does not attach to the discovery of, say, a new comet or a new beetle where many more such discoveries are to be anticipated in the future.48 the twg comment related to the synthetic elements produced at the end of the twentieth century, but it could as well have been written by chemists at the time of mendeleev. figure 6. russian stamp of 2013 dedicated to g. flerov after whom element 114, flerovium, is named. flerov was also head of the research team credited with the discovery of nobelium. source: https://commons.wikimedia.org/wiki/file:rusmarka-1660.jpg 89priority disputes and the discovery of chemical elements 8. conclusion although there are today formal criteria for the discovery of a new element, and for assigning priority to the discovery, these are not applicable to many discoveries in the past. the relevant criteria depend on the historical period and so do the accepted rules for priority. it seems hardly possible to come up with a fixed definition of element discovery which makes sense over the approximately 250 years during which chemists have searched for new elements. the search has often given rise to priority controversies, a phenomenon one can find throughout history and independent of whether or not the discovery was guided by theoretical expectations. to understand these and other controversies related to the discovery of new elements, one needs to adopt the norms and rules of the period in question and not those of a later time. in this essay i have also pointed out that accepted discovery histories may retrospectively be questioned and revised. at least in principle it is possible that a future list of element discoveries will differ significantly from the one accepted today. references 1. t. nickles, phil. sci. 1985, 52, 177-206; j. schickore, 2018, https://plato.stanford.edu/archives/sum2018/ entries/scientific-discovery/ 2. p. achinstein in histories of the electron: the birth of microphysics (eds.: j. z. buchwald, a. warwick), mit press, cambridge, ma, 2001, pp. 403-424. 3. r. c. olby in new trends in the history of science (eds.: r. visser, h. bos, l. c. palm, h. snelders), rodopi, amsterdam, 1989, pp. 197-208. 4. l. r. caswell, bull. hist. chem. 2003, 28 (1), 35-41. 5. e. rancke-madsen, centaurus 1975, 19, 299-313. 6. j. trofast, jac. berzelius: the discovery of cerium, selenium, silicon, zirconium and thorium, ligatum, lund, 2016, p. 17. 7. a. g. gross, science in context 1998, 11, 161-179. 8. j. w. kennedy, g. t. seaborg, e. segré, a. c. wahl, phys. rev. 1946, 70, 555. 9. a. brannigan, the social basis of scientific discoveries, cambridge university press, cambridge, 1981, p. 77; ref. 7 (gross); s. schaffer, soc. stud. sci. 1986, 16, 387-420. 10. n. russell hanson, patterns of discovery: an inquiry into the conceptual foundations of science, cambridge university press, cambridge, 1958. 11. t. s. kuhn, science 1962, 136, 760-764; t. s. kuhn, the structure of scientific revolutions, university of chicago press, chicago, 1970, pp. 52-65. see j. a. berson, chemical discovery and the logicians’ program, wiley-vch, weinheim, 2003, p. 113 for an illustration of kuhn’s model in organic structural chemistry. 12. j. priestley, the history and present state of electricity, dodsley, johnson and cadell, london, 1775, p.vii. 13. k. gavroglu in scientific controversies: philosophical and historical perspectives (eds.: p. machamer, m. pera, a. baltas), oxford university press, oxford, 2000, pp. 177-198. 14. r. k. merton, am. sociol. rev., 1957, 22, 635-659, reprinted in r. k. merton, the sociology of science: theoretical and empirical investigations, university of chicago press, chicago, 1973, pp. 286-324. part of this section relies on material in h. kragh, brit. j. hist. sci. 1997, 30, 203-219. 15. m. dascal, science in context 1998, 11, 147-154. different forms of scientific controversies are comprehensively analysed in scientific controversies: case studies in the resolution and closure of disputes in science and technology (eds.: h. t. engelhardt, a. l. caplan), cambridge university press, cambridge, 1987, and in ref. 13 (machamer, pera, baltas). 16. a. cordner, toxic safety: flame retardants, chemical controversies, and environmental health, columbia university press, new york, 2016. 17. e. mcmullin in ref. 15 (engelhardt, caplan) pp. 49-92. 18. t. sukopp in knowledge communities in europe (eds.: b. schweitzer, t. sukopp), springer, wiesbaden, 2018, pp. 15-47. 19. g. rayner-canham, z. zheng, found. chem. 2008, 10, 13-18; h. kragh, from transuranic to superheavy elements, springer, berlin, 2018, pp. 70-73. 20. quoted in ref. 17 (mcmullin), p. 68. 21. e. scerri, a tale of seven elements, oxford university press, new york, 2013, pp. 109-114. see also m. fontani, m. costa, m. v. orna, the lost elements: the periodic table’s shadow side, oxford university press, new york, 2015, pp. 219-222. 22. j. r. partington, science progress 1936, 30, 402-412; m. e. weeks, h. m. leicester, discovery of the elements, journal of chemical education, easton, pa, 1968, pp. 110-135; j. emsley, the shocking history of phosphorus, pan books, london, 2001. 23. p. j. maquer, a dictionary of chemistry, t. cadell, london, 1771, vol. 2, p. 531. 24. see f. a. paneth, brit. j. phil. sci. 1962, 13, 1-14, 145160. 25. j. dalton, a new system of chemical philosophy, part ii, r. bickerstaff, manchester, 1810, p. 221. 90 helge kragh 26. ref. 6 (trofast). 27. d. i. mendeleev, j. chem. soc. 1889, 55, 634-656. 28. many other examples are given in ref. 21 (fontani, costa, orna) and in j. druce, science progress in the twentieth century (1919-1933), 1927, 21, no. 83, 479-491. 29. h. kragh, stud. hist. phil. mod. phys. 2000, 31, 435450. 30. for details on element 43, see ref. 21 (scerri), pp. 116-143. 31. j. w. richards, aluminium, henry c. baird, philadelphia 1896, pp. 1-38; ref. 22 (weeks, leicester), pp. 555-589. 32. ref. 22 (weeks, leicester), p. 560. 33. english translation in ref. 31 (richards), p. 246, which mistakenly refers to ørsted’s original paper as “a paper in 1824 in a swedish periodical.” richards apparently thought that ørsted – whom he misspells “oerstedt” – was “a swedish chemist” (p. 6). on ørsted and aluminium, see d. c. christensen, hans christian ørsted: reading nature’s mind, oxford university press, oxford, 2013, pp. 424-430. 34. j. berzelius, jahresbericht 1827, 6, 118-120. 35. ref. 22 (weeks, leicester), p. 574, refers to ”certain trouble makers” who tried to convince deville that he “ought to claim for himself the honor of discovering the metal.” 36. n. bjerrum, zs. angew. chem. 1926, 39, 316-317. 37. h. n. holmes, scientific monthly 1936, 42, 236-239. 38. h. kragh, centaurus 1980, 23, 275-301; p. thyssen, k. binnemans in handbook on the physics and chemistry of rare earths, vol. 41 (ed.: k. a. gschneider), academic press, burlington, 2011, pp. 1-94. 39. for the controversies between auer and urbain, see h. kragh in episodes from the history of rare earth elements (ed.: c. h. evans), kluwer academic, dordrecht, 1996, pp. 67-90, and ref. 21 (fontani, costa, orna), pp. 213-216, 233-235. another, still valuable resource is j. f. spencer, the metals of the rare earths, longmans, green and co., london, 1919. references to the original sources can be found in these works. 40. quoted in ref. 39 (kragh), p. 74. 41. see ref. 39 for details and references. 42. see ref. 22 (weeks, leicester), pp. 693-695. 43. this section relies on ref. 19 (kragh), pp. 37-42, which contains further information and references. see also j. emsley, nature’s building blocks, oxford university press, oxford, 2011, pp. 367-372. 44. p. j. karol in the periodic table: into the 21st century (eds.: d. h. ouvray, r. b. king), research studies press, baldock, uk, 2004, pp. 235-262. a “transfermium” is an element beyond fermium, meaning z > 100. 45. g. n. flerov, i. zvara, e. d. donets, g. m. ter-akopian, v. a. shchegolev, v. l. mikheev, radiochim. acta 1992, 56, 111-124. 46. joliotium (jl) was also suggested for elements 103 and 105, and in the latter case recommended by iupac in 1994 until the name changed to dubnium (db) three years later. see ref. 21 (fontani, costa, orna), pp. 385-388. 47. a. ghiorso, g. t. seaborg, radiochim. acta 1992, 56, 125-126. 48. a. h. wapstra, pure appl. chem. 1991, 63, 879-886. substantia an international journal of the history of chemistry vol. 3, n. 2 suppl. 5 2019 firenze university press setting the table: a retrospective and prospective of the periodic table of the elements. mary virginia orna1, marco fontani2 the development of the periodic table and its consequences john emsley the periodic table and its iconicity: an essay juergen heinrich maar1, alexander maar2 discovering elements in a scandinavian context: berzelius’s lärbok i kemien and the order of the chemical substances ferdinando abbri mendeleev’s “family:” the actinides mary virginia orna1, marco fontani2 controversial elements: priority disputes and the discovery of chemical elements helge kragh carl auer von welsbach (1858-1929) a famous austrian chemist whose services have been forgotten for modern physics gerd löffler a book collector’s view of the periodic table: key documents before mendeleev’s contributions of 1869 gregory s. girolami a brief history of early silica glass: impact on science and society seth c. rasmussen mendeleev at home1 mary virginia orna substantia. an international journal of the history of chemistry 3(2) suppl. 1: 99-110, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-612 citation: p. c. dastoor, w. j. belcher (2019) how the west was won? a history of organic photovoltaics. substantia 3(2) suppl. 1: 99-110. doi: 10.13128/substantia-612 copyright: © 2019 p. c. dastoor and w. j. belcher. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. how the west was won? a history of organic photovoltaics paul c. dastoor, warwick j. belcher centre for organic electronics, university of newcastle, university drive, callaghan nsw 2308, australia e-mail: paul.dastoor@newcastle.edu.au abstract. the history of organic photovoltaics has been characterised by the complex interplay between fundamental research, large scale manufacture and commercialization activities. in addition, the field is highly interdisciplinary; ranging across physics, chemistry and engineering. this environment has resulted in a frontier character to the field, with researchers constantly expanding into new areas and confronting new challenges as the area has developed. this article seeks to chart the developments in organic photovoltaic research, with emphasis on the last two decades, to provide some historical context to current status of the field. keywords. photovoltaics, conjugated polymers, renewable energy, flexible electronics, roll-to-roll printing, bulk heterojunction. come forth into the light of things, let nature be your teacher. —william wordsworth we have dominated and overruled nature, and from now on the earth is ours, a kitchen garden until we learn to make our own chlorophyll and float it out in the sun inside plastic membranes. —lewis thomas 1. go west young man (setting the scene) the interaction of light with matter has framed existence since the earth was first formed some 4.5 billion years ago, with the key step in abiogenesis being the synthesis of complex organic molecules occurring via photochemical processes. ultimately, the creation of the biosphere via photosynthesis and the consequent development of our entire ecosystem has, of course, been driven by light-matter interactions. more recently, the expansion of human 100 paul c. dastoor, warwick j. belcher100 paul c. dastoor, warwick j. belcher civilization has been enabled by the energy resources contained within fossil fuel sources; representing the historically stored effects of ancient photochemical processes. the direct generation of electrical energy from light is a much more recent phenomenon. photoelectrochemical effects were first reported in 1839, with the french physicist alexandre edmond becquerel (1820–1891) observing the photovoltaic (pv) effect via an electrode in a conductive solution exposed to light.1, 2 in 1876 william grylls adams (1836–1915) and his student, richard evans day, observed the photovoltaic effect in solidified selenium, and published a paper; ‘the action of light on selenium’ in the proceedings of the royal society.3 in 1883 the american inventor charles fritts (1850–1903) developed the first selenium wafer based solar cells. these cells, which were typically around 2 x 2.5 inches in size, had a power conversion efficiency of around 1% and employed an extremely thin layer of gold as a transparent electrode.4 the history of the modern silicon solar cell (figure 1) is much more recent. on april 25, 1954, bell labs announced the invention of the first practical silicon solar cell. shortly afterwards, they were shown at the national academy of science meeting. these cells had about 6% efficiency. the new york times forecast that solar cells may eventually lead to “the beginning of a new era, leading eventually to the realization of one of mankind’s most cherished dreams – the harnessing of the almost limitless energy of the sun for the uses of civilization.”5 since then there has been an enormous development of silicon (and other inorganic) solar cell, technologies. early work determined that the maximum theoretical efficiency of a single junction cell is 33.16%, the shockley-queisser limit6, and maximum values of 27% have been reached for single junction crystalline si cells7, with four junction cell efficiencies of 39% achieved.8 perhaps surprisingly, the history of photoelectrical processes in organic molecules is almost as long as that of inorganic materials. the photoconductivity of anthracene was first studied by the italian physical chemist alfredo pochettino (1876–1953) at sassari, italy in 1906 9 and later by max volmer (1885–1965) at leipzig in 1913.10 in 1958 the nobel laureate melvin calvin (1911–1997) and his student david kearns worked with magnesium phthalocyanines (mgpc), measuring a photovoltage of 200 mv.11 this early work suggested that a photovoltaic effect could be observed if a sandwich cell consisting of a low work function metal, an organic layer and a high work function metal (or conducting glass) is illuminated. throughout the 1960s and onwards many organic dyes and biomolecules were discovered to exhibit photoconductivity and a photovoltaic effect, however it was not until the mid-1970’s that this phenomenon would be utilized to generate electrical currents. 2. riding the range (the first devices) the first true organic photovoltaic (opv) devices were developed in the 1970’s and incorporated small organic molecules with porphyrins being a natural place to start given their fundamental role in photosynthesis. in 1975 ching w. tang (b. 1947) and andreas c. albrecht (1927–2002) at cornell university showed that chlorophyll-a (chl-a) from green spinach (figure 2) could be sandwiched between metal electrodes and under optimal conditions (cr/chl-a/al) had a power conversion efficiency (pce) of 0.01%; orders of magnitude better than other organic devices at the time (which had efficiencies of around 10-6 %) and arguably the first working example of an organic solar cell.12 in 1978 larry r. faulkner (b. 1944) and his student fu-ren opvfan (b. 1946) demonstrated the generation of short circuit photocurrent in zinc and free base phthalocyanines (znpc and pc, respectively) when sandwiched between an ohmic contact (au) and a blocking contact (al or in).13 in 1979 geoffrey chamberlain and peter cooney of shell research ltd observed similar effects in al/cupc/au cells.14 in 1983 chamberlain published “organic solar cells: a review” proclaiming that “remarkable progress p+ nec ev + incident photon figure 1. schematic of modern silicon solar cell. light absorbed in intrinsic region and creates free electron-hole pairs. the built-in electric field separates charges with holes migrating to the p-doped region and electrons migrating to the n-doped region; resulting in a tilting of the conduction (ec) and valence (ev) energy bands in the material. 101how the west was won? 101how the west was won? a history of organic photovoltaics has been made in recent years in improving the sunlight efficiency from about 0.001 % in the early 1970s to about 1% recently” and describing the range of porphyrin, phthalocyanines and other small molecules which had been been observed to produce photovoltaic effects.15 interestingly, even in these early days of organic photovoltaic research chamberlain noted that “it is generally accepted, however, that cell efficiencies must be as high as possible and at least 5% to offset area-related costs arising from encapsulation materials, support structures etc.”; beginning an efficiency-based bias which has haunted the opv field ever since. in 1986, ching tang was able to show (by fabricating a bilayer device with copper phthalocyanine and a perylene tetracarboxylic derivative) that the interfacial region was responsible for the generation of photocharges and therefore, for determining the devices photovoltaic properties. exciton dissociation is known to be efficient at interfaces between materials with different electron affinities and ionization potentials, where the electron is accepted by the material with larger electron affinity and the hole by the material with lower ionization potential. a significant advantage of this device architecture over the prevalent single material devices was that charge generation was no longer dependent on the electric field but rather the work functions of the two layer materials. a pce of ~1% was achieved.16 the process of photosynthesis (the conversion of solar energy into chemical energy) involves two protein complexes, photosystem i (psi) and photosystem ii (psii), that drive photoinduced electron separation. interestingly, and despite decades of research, by 2017 the best solid-state solar cell device based on photosystem i (psi) still has a pce of only 0.069%.17 however, in 2018 shengnan duan fabricated devices by combining chl-a as the psi simulator (electron acceptor) with chl-d as the psii simulator (electron donor) in an indium tin oxide (ito)/zno/chl-a/(chl-ds)/moo3/ ag structure which mimicked the pathway of photoinduced electron transport from photosystem ii (psii) to photosystem i (psi) in nature (figure 4).18 the optimized devices had a pce of 1.30%, much higher than devices based on psi alone. figure 2. structure of chlorophyll-a (chl-a). glass cupc pv ag interfacial region ito figure 3. schematic of tang’s bilayer device using copper phthalocyanine (cupc) and a perylene tetracarboxylic derivative (pv). figure 4. schematic of indium tin oxide (ito)/zno/chl-a/(chlds)/moo3/ag devices mimicked the pathway of photoinduced electron transport from photosystem ii (psii) to photosystem i (psi) in nature. reprinted with permission from 18. copyright (2018) american chemical society. 102 paul c. dastoor, warwick j. belcher102 paul c. dastoor, warwick j. belcher by comparison, the history of conjugated and conducting polymers also dates back to the early 19th century.19 beginning in 1834, various forms of oxidized polyaniline were produced by friedlieb ferdinand runge (1794 –1867) via the oxidation of aniline, although the structure of these materials was not determined until 1920.20 in 1963 an important breakthrough in the field occurred when donald eric weiss (1924–2008) and coworkers at csir, australia identified iodine doped derivatives of polypyrrole (figure 5) with resistivities down to 0.1 ω.cm.21-23 until this time, other than conductive charge transfer complexes, organic molecules were still considered insulating materials. however, publishing in the australian journal of chemistry, the initial results were not widely recognized or known. nevertheless, a new class of compounds was born and gradually additional reports of conducting polymers encompassing new examples of oxidized polyacetylenes,24 polyanilines, 25-28 and polypyrroles29 surfaced. finally, in 1977 alan j. heeger (b. 1936), alan g. macdiarmid (1927–2007) and hideki shirakawa (b. 1936) reported highly conductive, doped polyacetylene.30 following their award of the 2000 nobel prize in chemistry for “the discovery and development of conductive polymers”, this developing field became widely recognized and conducting polymer research exploded. 2.1 single layer junctions – the earliest polymer opvs interest in conjugated polymers as photovoltaic materials really commenced in 1994 when heeger and co-authors fabricated photodiodes of poly[2-methoxy5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (meh-ppv; figure 5) between indium tin oxide and calcium electrodes. the open circuit voltage (voc) and short circuit current (isc) under 20 mw/cm2 were 1.05 v and 1.1 µa/ cm2, respectively, and the sensitivity and the quantum yield at 10 v were 5×10 ma/w and 1.4% el/ph (electrons per photon).31 schottky cell devices fabricated from other conjugated polymers at the time (such as polyacetylene32 and poly(alkylthiophenes)33) showed similar (low) efficiency photovoltaic behavior. in 1996 lewis j. rothberg (b. 1956) and coworkers, working on ppv diode devices35,36, showed that a significant issue associated with simple single material organic diodes and solar cells is that exciton dissociation must occur at the dye/polymer electrode interface since the built in electric field imposed by the electrode materials is insufficient to drive charge separation. this limitation severely restricts the charge generation efficiency of the device and increases the likelihood of recombination of separated charges. in 1996 richard friend (b. 1953), andrew holmes (b. 1943) and co-workers produced bilayer meh-ppv/c60 opv figure 5. chemical structures of some common conducting polymers. 103how the west was won? 103how the west was won? a history of organic photovoltaics devices. they showed that excitons generated in the meh-ppv layer had a diffusion length of 7±1 nm and that photocurrent was only generated by excitons formed within this distance of the meh-ppv-fullerene interface. devices with a pce of ~1.5% were achieved.37 2.2 bulk heterojunctions – altering the paradigm of polymer opvs however, one of the most significant advances in polymer opv research occurred in 1995 when richard friend, andrew holmes and co-workers applied the principles observed by ching tang in 1986 to produce highly efficient photodiodes from interpenetrating networks of meh-ppv and poly(2,5,2 ,́5´-tetrahexyloxy7,8 -́dicyano-p-phenylene vinylene (cn-ppv; figure 5). phase separation of the two materials led to the spatially distributed interfaces necessary for efficient charge photogeneration, as well as the connected domains required to collect both the electrons and holes.39 coincidentally, also in 1995, fred wudl (b. 1941) and co-workers overcame a major barrier to the use of fullerenes in opv devices by reporting the synthesis of a range of soluble methanofullerene derivatives suitable for solution deposition of active layers.40 previous work by alan heeger, fred wudl and co-workers in 1992 had demonstrated picosecond charge transfer from photo-excited conducting polymers (meh-ppv) to fullerene (c60).38 alan heeger, fred wudl and co-workers then combined these ideas, taking advantage of the near perfect charge transfer between conducting polymers and fullerene by blending meh-ppv with one of these methanofullerenes (phenyl-c61-butyric acid methyl ester or pcbm; figure 6) together in an opv device active layer with a 1:4 ratio. the resultant bicontinuous network (or bulk heterojunction; bhj) resulted in devices with a pce of 2.9%, more than two orders of magnitude higher than devices of meh-ppv alone.41 subsequently, n. serdar sariciftci (b. 1961), jan c. hummelen and coworkers showed that control of blend morphology in mdmo-ppv:pcbm devices was critical to optimized device performance.42 interestingly, the authors proposed that the pce of 2.5 % achieved in these devices “approaches what is needed for the practical use of these devices for harvesting energy from sunlight”. indeed, the bhj active layer morphology has remained the basis for the majority of opv devices to this day. 2.3 the focus on metrics – the millstone around the neck of opvs from the first days of opv there has been an arguably disproportionate focus on pce as the key metric for device performance. from 1993, martin green (b. 1948) has published regular (biannual) sets of solar cell and module efficiency tables summarizing the highest independently confirmed results for different technologies in progress in photovoltaics. as well as keeping researchers informed of the state-of-the-art in the field, a stated aim of these tables is “the encouragement of researchers to seek independent confirmation of research results and the further simulation of intercomparison of measurements between designated cell test centres”.43 unfortunately, despite the importance of this topic and the clear necessity for rigorous characterization of devices in the field, independent confirmation of device performance (and in particular pce) is still not comfigure 6a. chemical structure of phenyl-c61-butyric acid methyl ester (pcbm). exciton bound e – h pair free carriers ground state figure 6b. schematic of bulk heterojunction (bhj) structure and charge generation process in opv devices. an incident photon generates a coupled electron-hole pair (exciton) which diffuses to a donor (polymer) – acceptor (fullerene) interface to form a bound electron-hole pair. this bound state can then either recombine or separate into free charge carriers to generate a photocurrent. 104 paul c. dastoor, warwick j. belcher104 paul c. dastoor, warwick j. belcher monplace. whilst the highest performing devices are routinely tested by certified laboratories, such as the national renewable energy laboratory (nrel), logistics and expense prohibit the vast majority of devices in published reports from being tested outside of the reporting laboratory. this situation has led to some controversy in the field. in 2007 rene janssen (b. 1959) published a rebuttal of a paper by wong et al. (july 2007 issue of nature materials) that presented a new platinum metallopolyyne donor polymer (p1) with a bandgap of 1.85 ev that provided a photovoltaic power-conversion efficiency, η, of up to 4.93% in combination with a c60 fullerene derivative (pcbm) as acceptor. this high efficiency represented an important step towards the development of more efficient plastic solar cells. rene janssen argued, however, that the optical properties of the new polymer presented in the paper were incompatible with the published high efficiency and that — based on the optical data — the efficiency was unlikely to exceed 2%.44 in response, in 2008 the journal solar energy materials and solar cells resorted to using an editorial to provide a guide on how efficiency data should be reported, especially whenever power conversion efficiencies require external quantum efficiencies (eqe) values above 50% over a large range of wavelengths or when reported power conversion efficiencies exceed 2.5%. in particular they stated that “extra care should be taken in submitted manuscripts to document the measurement’s quality, relevance and independent verification”.45 in 2011, the international summit on opv stability (isos) published a series of generally agreed test conditions and practices to allow ready comparison between laboratories and to help improve the reliability of reported values.46 in 2012 henry snaith (b. 1978) published “the perils of solar cell efficiency measurements”, a critique on the use of pce for characterising opv devices.” he pointed out that pce as a performance metric has become so influential and has such a high level of perceived importance that it is now widely used as a key parameter for assessing the value or worth of an entire solar technolog y, particularly for new and emerging solar technologies, which must constantly justify their existence. furthermore, in the specific field of opv, ignorance and negligence are frequently causing solar cells to be mischaracterized, and invalid efficiency results have been reported in a number of journals.47 unfortunately, little has changed since this time. independent certification of “record” devices is now essentially mandatory for publication, but routine certification of published device performance is not commonplace. in light of the import which is placed upon opv device efficiency by researchers and reviewers this oversight is a major problem and poses a significant barrier to the transfer of knowledge between practitioners. 3. the taming of the old west (the new millennium and the maturing of the field) in 2002, pavel schilinsky (b. 1974) reported the characterization of new poly(3-hexylthiophene):methanofullerene [6,6]-phenyl c61 butyric acid methyl ester (p3ht:pcbm) solar cells, with a pce of 2.8% and began a fascination with this material system which dominated the opv research scene for a decade, and has continued to this day.48 the appeal of the p3ht:pcbm system is not hard to see. even the initial schilinsky publication highlighted the excellent interpenetrating “bulk heterojunction” phase morphology, ideal for efficient photovoltaic performance. monochromatic (550 nm, the absorption maximum) external quantum efficiencies of up to 76% and internal quantum efficiencies of close to unity were reported and recombination of photoinduced carriers was negligible when operated in the photovoltaic mode. as a polymer, p3ht was easy to synthesize at large scale,49-54 considerably more soluble and oxidatively stable than the ppvbased polymers which had been studied previously55 and p3ht’s semi-crystalline nature meant that thermal56, 57 and solvent-annealing58 of the blended active layer could be readily used to optimize donor and acceptor domain sizes and crystallinity. consequently, p3ht:pcbm solar cells became the “best seller in polymer photovoltaic research” with guillaume wantz (b. 1977) and co-workers reviewing 579 papers published between 2002 and 2010 alone. the pce of the p3ht:pcbm solar cells reported in these publications is moderate at best, with a wide range of reported values averaging around 3% and approaching 5% at best.59 nonetheless, p3ht remains a key model polymer for research in organic solar cells. however, as pointed out by darren lipomi (b. 1983) and co-workers, p3ht is structurally and morphologically very different from the majority of new generation polymers in osc research. consequently, the validity and value of transferring design and processing knowledge from the p3ht material system must be questioned.60 ultimately, however, the relatively poor overlap between the absorption of p3ht and the sun’s irradiance spectrum prohibits significantly higher pces and this mismatch has driven the development of polymers with lower bandgaps which better match the suns irradiation.61 105how the west was won? 105how the west was won? a history of organic photovoltaics 3.1 lower band gap materials in polymer:fullerene solar cells the primary light absorbing component is the polymer, since most fullerenes do not absorb strongly in the visible and near-ir, where terrestrial solar intensity is at its greatest. indeed, paul dastoor (b. 1968) and coworkers have shown that pcbm contributes only ~13% of the photocurrent in a p3ht: pcbm device under am 1.5 illumination.62 consequently, over the last decade or so, attention has been focused at tuning and reducing the optical bandgap, eg, of the polymer to increase device light absorption.63 the bandgap which determines light absorption in a conjugated polymer is a result of overlap and delocalization of π-orbitals along the polymer backbone. increasing the planarity of this backbone maximizes the p-orbital overlap and extends the π-delocalization, lowering the bandgap. a range of both structural and electronic methods have been employed to alter polymer planarity and/ or π-delocalization.64 structurally, fused ring systems (either fully aromatic or using bridging atoms) and the use of steric peripheral groups on the backbone are both routinely used to enhance polymer planarity. increasing the quinoidal nature of linked ring systems breaks aromaticity (and thus electron confinement to the ring), which allows more extensive delocalization. this last effect is particularly prevalent in polythiophene polymers, in part explaining their success in the opv field. planarity of the polymer backbone is not the whole story however. p3ht itself can form ordered microcrystalline domains in which the polymer backbone is highly planar,65 but has a wide bandgap of ~1.8 ev (which means it has a maximum solar photon absorption of ~ 46 %).66 the optical bandgap can be further reduced by alternating electron rich (donor, d) and electron poor (acceptor, a) subunits along the polymer backbone. the resulting molecular orbital mixing and intermolecular charge transfer between the d and a moieties produces a new set of hybrid molecular orbitals with a bandgap that can be lower than either of the subunits alone. in addition, it has been proposed that alternation of the donor and accepting components increases the double bond character between the units, which could enhance planarity and further decrease the bandgap.67 in 2006 paul blom (b. 1965) and co-workers presented model calculations for the potential for polymer: fullerene solar cells. they predicted that lowering the band gap of the polymer would result in devices exceeding 6% and that, ultimately, with optimized level tuning, band gap, and balanced mobilities polymeric: fullerene solar cells could reach power conversion efficiencies approaching 11%.68 the first truly low bandgap polymer, poly(isothianaphthene) was reported by reported by fred wudl in 1984, with a bandgap of ~1.0 ev,69 but initially the synthesis of suitable, soluble low band gap materials proved difficult.70 however, in 2002 christoph brabec (b. 1966) et al. reported ~1% efficient devices from the recently synthesized poly(n-dodecyl-2,5,-bis(2’-thenyl)pyrrole-alt-2,1,3-benzeothiadiazole) (ptptb) with pcbm. ptptb consists of alternating electron-rich n-dodecyl-2,5,-bis(2’-thenyl)pyrrole (tpt) and electron deficient 2,1,3-benzeothiadiazole (b) units and is the first example of the use of a molecularly engineered lower bandgap material in opv devices. the electrochemical bandgap of the polymer was determined to be 1.77 ev, placing just within the range of low bandgap materials as defined by the authors (eg <1.8ev) but higher than the official definition as set in the handbook of conducting polymers. (eg <1.5ev).71 since these humble beginnings, a wide range of donor-acceptor low band gap polymers have been synthesized from a growing catalogue of donor and acceptor building blocks. in 2011 mitsubishi chemical announced the first certified single junction organic solar cell with a pce of >10%.72 the device was certified at nrel, but no detail information on either the active layer composition or the device structure was given. the first device to reach the η > 10% milestone published in a full peer review journal, was a polymer tandem solar cell with a pce of 10.6% reported by yang yang (b. 1958) and coworkers in 2013.73 the d-a polymer used was poly[(5,5-bis(3,7dimethyloctyl)5h-dithieno[3,2-b:2’,3’-d]pyran-2,7-diyl)-alt-(5,6-difluoro-2,1,3-benzothiadiazole-4,7-diyl)] (pdtp-dfbt) with a reported bandgap of 1.38 ev, in conjunction with pc71bm. a single-junction device was also reported with a spectral response that extended to 900 nm and which had a pce of 7.9%. since then, progress in opv development has been rapid, especially in terms of electrode interfacial layers, new active layers (ternary systems), and the synthesis of new low bandgap polymers. the current certified efficiency record for a single junction organic solar cell lies at 11.2 ± 0.3% by toshiba.8, 74 3.2 understanding the fundamental physics it was realized early on that the physical behavior of semiconducting polymers is dominated by their relatively low dielectric constant compared with that for inorganic semiconductors (εp3ht~3 vs εsi~11). thus, there is much less screening in organic devices and so tightly bound 106 paul c. dastoor, warwick j. belcher106 paul c. dastoor, warwick j. belcher frenkel excitons are formed upon light absorption rather than free electron-hole pairs. as a consequence, the energy levels in organic are localized and thus a band transport picture no longer holds. instead exciton (and charge transport) occurs via a hopping mechanism. finally, the picture for organic solar cells is further complicated by the fact that charge separation occurs via an intermediate charge-transfer state at the heterojunction. the realization of these key differences has driven a re-evaluation of classical p-n junction theory and the development of new formalisms in understanding how organic solar cells work. early work on different electrode materials suggested that voc depended on work function difference between electrodes. however, work by christoph brabec on different acceptors in 2001 showed that changing the nature of the acceptor played a much bigger role than changing the work function. it was argued that fermi level pinning through charged interface states between the nµative metal electrode and the fullerene reduction potential caused the insensitivity to work function.80 two possible origins for voc are either the homolumo cross gap (voc1) or the electrode work function difference (voc2). in 2003, work by blom’s group showed that in the presence of non-ohmic contacts then voc could depend strongly on work function difference.81 a key driver for device design is to try to increase the voc to increase the power conversion efficiencies of opvs. however, even when the homo-lumo gap dominates we never observe voc equal to the calculated gap potential. in 2006, scharber developed an empirical set of rules for determining the voc of a bhj device with pcbm as the acceptor; arguing that there was always a general 0.3v loss in voc. for more than 26 different material combinations, no influence of the contact work function on the voc is observed. the 0.3v loss was postulated to be due to the dark current characteristics (~0.2v) and the field driven nature of the charge separation process (~0.1v) since the the open-circuit voltage depends on the slope of the field-driven current around the built-in voltage (vbi). in around 2008–2009 it was realized that electronic coupling at donor‐acceptor interfaces, or in donor‐ acceptor blends, leads to the formation of an intermolecular charge‐transfer complex that simultaneously influences the photogeneration of mobile charge carriers and the dark current due to thermal generation.84-86 later work (2010) argued that for bilayers, there are relatively “flat” donor-acceptor (d/a) and metal-organic (m/o) interfaces. there is a large distance between d/a and m/o interfaces and a large barrier resulting in a low electric field at the m/o interface and fermi-level pinning. as such, unipolar transport dominates at interfaces and there is little effect of electrodes upon voc. for bhj devices, however, intimate contact between d/a regions produces large field at m/o interface. in addition, it is possible to obtain an ambipolar carrier distribution at the electrodes. both effects lower the barrier at the m/o interface and photogenerated carriers can no longer ‘pin’ electrode fermi level.82 so, the question remains – does the homo-lumo cross gap or the electrode work function determine voc. the answer is that both can affect the open circuit voltage. in the case of non-ohmic (blocking) contacts then we see that the voc is dominated by the electrode work function. however, for ohmic contacts we see that electrons can flow into the m/o interface producing accumulated charges and leading to band bending and fermi-level pinning. the device structure also affects the voc since the distance of the d/a interface can affect the electric fields at the m/o interface. large distances result in unipolar charge distributions at the m/o interface (and little dependency of voc on work function) whereas for ambipolar distributions the opposite is true. in polymer-fullerene systems (and building from earlier work in organic light emitting diodes (oleds) and dye-sensitized solar cells), charge recombination was identified as a major loss mechanism; whether geminate (electron hole–pair recombines while still bound) and non-geminate (electron hole–pair recombines after charges have been separated). it is widely understood that non-geminate recombination in the blended bulk phase dominates in bhj devices.87-90 4. of ranchers, fences and range wars (initial attempts to upscale and commercialize) attempts to commercialise the technology has featured early in the history of organic photovoltaics with numerous start-up companies founded, growing, merging, being acquired or going bankrupt. moreover, the commercialization space has encompassed companies focused on materials and devices. however, given the commercially sensitive nature of establishing start-up companies, publications in the area are few and piecing together the history of opv commercialization is challenging. 4.1 the early promise one of the earliest companies in this space was quantum solar energy linz (qsel), founded in 1997 on the back of advances made at the linz institute for 107how the west was won? 107how the west was won? a history of organic photovoltaics organic solar cells (lios) under the leadership of n. serdar sariciftci. in 2001, konarka technologies, inc. was founded in 2001 as a spin-off from the university of massachusetts, lowell. named after the konark sun temple in india and co-founded by, amongst others, the nobel laureate alan heeger, the company initially decided to work on both solid-state polymer-fullerene solar cells and liquid dye-sensitized solar cells (dsscs). in 2003, konarka acquired qsel, in a move that was described at the time as designed to “make the company the worldwide leader in organic photovoltaics”. meanwhile, again in the us, plextronics was founded in 2002 in pittsburgh as a spin-off company from carnegie mellon university primarily as a materials supply company based on the ability to synthesise regioregular p3ht developed by richard mccullough (b. 1959). the business was aimed at supplying the anticipated market for conductive inks and process technologies with the advent of organic solar cells and organic lightemitting diode lighting. in the early days, plextronics was extremely successful, highlighted as one of pittsburgh’s fastest growing companies in 2008 and raising over $40 m in equity capital. on the west coast of the usa, solarmer energy was founded in california in 2006. the company licensed opv technology developed by yang yang at the university of california, los angeles and new semiconducting material technology developed at the university of chicago. solarmer established a facility in el monte, california and initially worked on developing opv with a goal to demonstrate commercial grade devices and indeed its devices held the record for opv efficiency in 2009 and 2010. however, it rapidly focused on supplying advanced organic materials to the research community. a little later, in the uk, ossila was founded in 2009 by david lidzey (b. 1967) and james kingsley at the university of sheffield. the focus of the company was on the supply of materials and equipment for organic electronics research. meanwhile, in cambridge, the company eight19 was founded in 2010 to commercialise organic solar cell technology developed by richard friend at the cavendish laboratory of the university of cambridge. the company was named after the time taken for light to travel to the earth from the sun and raised over $7 million from the carbon trust and rhodia to develop plastic organic solar cells. 4.2 the crash after nearly a decade of research and development, it became increasingly clear that the pathway to commercial scale opv was challenging and unlikely to be realized in the short term. the inability to deliver on its initial promises resulted in a number of these initial start-up companies filing for bankruptcy and closing down. probably the most dramatic was in may 2012, when konarka filed for chapter 7 bankruptcy protection and laid off its approximately 80-member staff. this event sent shockwaves through the opv community and was the subject of much discussion at opv conferences around the world. this event was followed by plextronics filing for chapter 11 bankruptcy in january 2014. 4.3 rising from the ashes the assets and rights of konarka’s german operations (konarka technologies gmbh) were acquired by belectric, a germany-based solar developer, financier, and construction firm in late 2012, who established belectric opv gmbh with the aim of manufacturing bespoke opv devices for the building integrated pv, automotive and consumer electronics markets. their approach was to overcome the short lifetime of opv’s by creating thin plastic laminates that could be readily integrated into a range of products. commencing with consumer products (such as opv based garden ornaments) by 2016, belectric opv had already showcased installations such as the german pavilion at the world expo in milan in 2015. in 2017, belectric opv was renamed opvius developing a range of opv products based on small opv modules encased in polycarbonate laminates. in march 2014, solvay sa, an international chemical group headquartered in brussels, completed the acquisition plextronics inc. to bolster its oled electronic display technology and launch a new development platform with a strong asian foothold. in 2016, and after 6 years of technological partnership with the major names of the global chemical industry and an investment of €40 million, the french company armor launched industrial production of a new generation of photovoltaic material, designed and manufactured in france. called asca©, it is a opv material based on combining the expertise of a number of different partners: cea-ines france (devices and durability testing), cnrs-ims france (materials and devices), cambrios advanced materials usa (silver nanowires), merck germany (photoactive polymers and interface materials), lcpo france (organic polymers), amcor france (films and encapsulation), and adhex france (technical adhesives). in may 2019, opvius and armor announced the decision to merge opvius development, integration and marketing activities for flexible organic photovoltaic films with those of armor. their stated common 108 paul c. dastoor, warwick j. belcher108 paul c. dastoor, warwick j. belcher objective was “to pool know-how in order to become the global benchmark company in flexible organic photovoltaic technology.” in parallel with these commercialization activities there has been significant research effort undertaken in developing the scale-up technologies needed to mass manufacture opv devices. primarily based around rollto-roll (r2r) printing91, one of the earliest pioneers of large scale manufacturing was frederik krebs who was originally based at the riso national laboratory, denmark and subsequently went on to found infinitypv, with a focus on providing materials and tools to the research community. 5. high noon (the verdict) devices with pces in excess of 15 % are now possible, far in excess of the 5 % efficiency threshold proposed by chamberlain 1983, so why is opv not a commercially viable technology? the last decade of research and commercialization attempts have highlighted that the successful commercialisation of opvs is governed by three key parameters: device efficiency, lifetime and cost (figure 7). as identified in this review, the opv research community has primarily been focussed on improving device efficiency with device lifetime becoming increasingly recognised as an important research topic. however, reducing the cost of opv materials has thus far had much less attention, yet is an equally important scientific challenge that is crucial to the future development of opv. indeed, it is the high cost of materials that is currently holding back scientific research at the large scale, and it is increasingly recognised that advances in the cost and scalability of organic photovoltaic (opv) active materials are urgently required for the rapid industrial development of printed solar technologies.92 more recent work has highlighted the development of low cost materials for opv manufacture93 and the importance of understanding how the cost of materials and upscaling material manufacture impacts upon the viability of opv as an energy generating technology94. however, one explanation for the fact that opv has yet to become a viable commercial prodict is that r2r equipment is very costly to acquire, and as a consequence reports of large scale r2r processing are limited to very few research groups95. looking to the future, it is clear that opv is in the process of emerging from the classic “valley of death” commercialization phase with a number of restructured and consolidated companies developing large scale opv products. interestingly, those companies that have focused on supplying materials and tools to the research community appear to be those that have survived the “opv crash” most successfully. further development of the field requires the community to focus less on delivering ever higher efficiency opv devices but rather to 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www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-633 citation: h. geurdes (2019) hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules. substantia 3(2): 27-36. doi: 10.13128/substantia-633 copyright: © 2019 h. geurdes. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes gds kvk64522202 cvdlinstraat 164 2593nn den haag netherlands1 e-mail: han.geurdes@gmail.com abstract. in the history of the debate about the completeness of quantum theory, schrödinger and einstein exchanged letters concerning the fact hat, according to schrödinger, quantized classical mechanics in the form of the schrödinger equation cannot be einstein separable. in the present paper the question is raised if, next to wave-particle duality and quantum tunneling, a schrödinger wave function can transform itself such that it no longer ”feels” the (non-relativistic instantaneous and omnipresent) coulomb attraction of opposite charges. looking at the separability debate between einstein and schrödinger this appears to be a, strange but, meaningful ques tion. should such transformation be possible then we can conclude that the particles described by a schrödinger equation would be coulomb separable. this is contrary to what schrödinger said. translating the mathematics to chemistry, we will look at a mesoscopic inter-molecular description of the behavior of charged radical molecules. firstly, given a restricted experimental geometry set-up such as described in the paper. secondly, given that the intra-molecular wave function of a charged radical molecule does not prevent the mescoscopic inter-molecular wave function to be described in the present paper. then it is found that a transformation of mesoscopic inter-molecular wave functions is possible that entails a kind of ”immunization” for coulomb interaction. the author acknowledges that immunization is a medical term. he has not a better term at this moment. in the appendix of the present paper, an experiment is proposed where micelle based molecules are turned into opposite charged radical molecules and are separated in the special geometry of the experiment. the generation of the opposite charged radicals can be performed with light. the method is borrowed from spin-chemistry. the separation is with ”dipole radiation”. the method is borrowed from positronium separation. after the mathematical proof, we ask the question what kind of chemical transformation is possible to mimic the mathematical transformation of the wave function provided here in the paper. the theory given here is that the coulomb immunity can be approximated through the geometry of the oligomerization of charged radical molecules. keywords. coulomb interaction, einstein-schrödinger discussion, unexpected separability, charged radicals, spin-chemistry.1 1 the author would like to thank two anonymous referees for their comment. 28 han geurdes 1. introduction in the philosophy of physics there is every now and then some debate about the exact meaning of einstein’s seminal criticism [1] on the completeness of the quantum theory. 1.1 philosophy of physics and chemistry einstein’s idea of entanglement was to let two particles a and b have a brief interaction and then to separate them [2] and [3]. the wave function is writtenas ψa,b. einstein reformulated his criticism, which still contained the heisenberg uncertainty in [1], into the following. if the wave fuction of a, denoted by ψa, can be manipulated by observer oa, then, the wave function to be observed by the distant ob and denoted with ψb is not uniquely attached to b. this is einstein’s inseparability criticism. don howard [2] argues that, because of e.g. bose statistics, already far before the publication of the epr paper, einstein had his doubts about the separability of quantum particles. in later developments bohm [4] replaced the brief interaction between a and b with the singlet spin state to entangle spins of particles a and b. bohm’s paradigmatic particle was para positronium. bohm’s work gave rise to bell his formula and the inequality derived there of [5]. the present author has shown a critical flaw in bell’s work [6]. this flaw is in fact a reference to concrete mathematical incompleteness: the gödel incompleteness phenonmenon, as quoted by [8], in concrete mathematics. non inequality research supported the idea that bell inequalities are perhaps not the only way to establish that, in nature, the quantum mechanical non-relativistic analogue of classical mechanics is effectively at work. a non-quantum mechanics falls short to explain the outcome of the experiment. historically, one of the earliest proofs thereof is by kocher and commins [12]. the study of kocher and commins is an example of a photon correlation experiment without the need for a bell correlation formula based inequality. recently, nordén [14] discussed the question how wrong einstein was after all. the mathematical incompleteness of bell’s inequalities in [6] and [7] questions ≈ 40 years of experimental research into non-locality. it will not receive a warm welcome in certain quarters of research. it does, however,not invalidate quantum mechanics as a statistical theory. the latter view on quantum mechanics was einstein’s conception [2]. in a sense, nordén [15] supports this idea with an explanation that comes close to a hanbury-brown twiss view of spin-spin correlation. it must, in addition, be noted also that wenneström [16] advances criticism on the conclusions of bell inequality experiments. he based his criticism on the physics of measurement instruments. a famous experiment that deserves mentioning here is aspect’s [18]. to continue, it must be noted that in his letter to schrödinger, einstein was interested in the physics of a brief interaction followed by a spatial separation. this means a transformation of the joint wave function ψ(xa, xb) into a product of two separate wave functions ψa(xa) ψb(xb) for distant particles a and b. a. furthermore, einstein was displeased with the epr paper [3, page 175]: “[…] die hauptsache ist sozusagen durch gelehrsamkeit verschüttet […]”2. in my humble opinion this was not because of a more or less artisitic need for simplicity. the epr paper formulated something close to, but definitely not identical with, einstein’s inseparability criticism [2]. in an earlier letter to schrödinger, einstein writes down after correction [2], a schrödinger equation for entangled particles in the sense discussed here. the conversation between the two giants of physics continues with schrödinger noting that with the non-relativistic quantum analogue of classical mechanics, separability cannot be conceived [3, page 177]. one can with a more modern view imagine virtual photons carrying the coulomb interaction between two opposite charged particles. because the absence of relativity, the schrödinger equation with coulomb potential function is, apparently according to schrödinger, unfit to describe the separability that einstein was looking for. end of story according to schrödinger [3, page 177]. perhaps that the inseparability notion expressed by einstein in his exchange of letters with schrödinger, does not meet the modern standard requirements of entanglement. however the principles, namely brief interaction between a and b leading to a joint wave function ψab and subsequently spatial separation of a and b into separate ψa and ψb, are the same. in this present paper we will look at the “end of story” argument of schrödinger. einstein directed his arrows of criticism to the unexpected inseparability in non-relativistic quantum theory. let us accept the words of schrödinger for the quantum analogue of classical mechanics. but what about unexpected separability in non-relativistic quantum theory? what would that tell us about the quantum analogue of classical mechanics. 2 the main point is burried under erudition. 29hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules 1.2 possible realization in chemistry before entering into the mathematics of this question we first may note that this question is most likely not pure philosophy. it is possible to design a real experiment with e.g. charged molecular radicals and perform separation within the boundaries of distances where coulomb potentials can be felt. this means, we can employ the kind of schrödinger equation that einstein considered. however, now we look for unexpected separability. we look for disentangling, perhaps better: coulomb immunity, transformation in the realm where an inevitable “entangling” coulomb potential function rules. the matter of separeability and therefore disentanglement because of temperature [19] will be discussed later. in order to find the properly charged radicals we can look at e.g. the interesting field of spin-chemistry and make use of their experimental techniques [10]. let us look at figure 1.2. the use of nearly equal mass radicals make sense when we want to approximate a kind of chemical/molecular onium-type of “atom” on the meso scale where quantum theory is still valid. the schrödinger equation can be similar to the one which approximates the positronium [9]. in figure 1.2 the two radicals are presented. the (ideal) molecular mass with mc= 12, mn= 14, mh= 1, is for n-methyl carbazole, mc13h11n = mnmcz = 181. for tetra cyano benzene we have mc10h2n4 =mtcnb = 178.the two charged molecular radicals come close to a meso scale type of “onium” atom approach that can also be found with e.g. positronium but then for electron and positron. of course electron and positron are particles with equal mass but also each carrying far less mass. nevertheless we believe that the radical molecules hamiltonian show some formal equality with the positronium one and therefore the following picture isjustified. let us suppose a number of plus nmcz and min tcnb that can, at a certain stage of the separation in the experiment, see appendix a.1, be described with a positronium akin schrödinger equation. we note here that, for clarity, we are dealing with a hydrogenic-like mesoscopic inter-molecular hamiltonian. in a paper of tanimoto and fujiwara, [10, page 440] we learn about a charged radicals generating reaction for n-ethyl carbazole necz and tetra cyano benzene tcnb. this is what we want to accomplish for (mnmcz = 181) nmcz and (mtcnb = 178) tcnb. the method is to capture necz and tcnb in a micelle. upon 308-nm laser excitation, the excited triplet state of necz undergoes an electron transfer reaction with tcnb [10]. the generation of the radicals is performed with the use of photons denoted by nν. from [10] we also learn that nmcz will most likely be less effectively turned into a radical than necz. because we are looking for 1-1 coulomb interactions this does not seem to be a big problem. in our case we capture nmcz and tcnb (figure 1.2) in micelles and use light to generate theradicals. the generation of charged molecular radicals in micelles, is presented below the right hand side of this equation serves as the entangled pair (better: pairs) in a micelle. the spinchemistry literature shows that this step is possible. a subsequent step is the separation of nmcz•⊕ and tcnb•⊖. this can be done by e.g. ”destroying” the micelle confinement and simultaneously separate nmcz•⊕ and tcnb•⊖ with e.g. dipole radiation. the latter separation method can be compared to the way e.g. wigner described the separation of entangled electron and positron from positronium [11]. hence, the dots denote the spatial separation. we claim that einstein’s treatment of the schrödinger equation can be applied to nmcz•⊕ and tcnb•⊖ generated in the micelle. what is needed is that, perhaps for a short moment in time upon generation of the radicals, nmcz•⊕ and tcnb•⊖ are in a state where a joint wave function exists. let us call this the “onium” state. most likely, similar to spin-chemistry, there will be a loss of free nmcz•⊕ and tcnb•⊖ through chemical reaction. moreover, the number of “onium” typed but afterwards free nmcz•⊕ and tcnb•⊖ must not be too small compared to the nmcz•⊕ and tcnb•⊖ that never were in the “onium” state. to be clear, upon the start of the separation of nmcz•⊕ and tcnb•⊖ the joint “onium” wave function exists. then we have a einstein-schrödiger hamiltonian. figure 1. left, n-methyl carbazole radical r denotes n•⊕–ch3 abbreviated as nmcz•⊕ and right tetra cyano benzene radical with r’ denoting c ≡ n•⊖, abbreviated as tcnb•⊖. in fact, the position of ⊕ in the nmcz radical and ⊖ in the tcnb radical isunknown. 30 han geurdes shortly afterwards, the separation of the two wave functions is accomplished according to appendix a.1. in relation to that we may note that spin-chemistry experiments [10] do show that separate molecular radicals can be in the spin singlet state. so in case of spinspin entanglement, if this state occurs sufficiently long enough between two charged radical molecules in a micelle, a comparable “onium” is possible. we claim that therefore our “onium” without explicit consideration of the spin, living in the micelle state and described by the compound schrödinger equation [2, page 26], is not just sheer fantasy. in fact our description here is independent of spin entanglement. we are dealing here with an inspection of einstein separability on a molecular scale in a coulomb field without by necessity spin entanglement. this will be made clear in the next section. initially there is a jumble of a number of nmcz and tcnb radical molecules. for a clear picture on intra molecular and inter molecular wave functions we introduce the following. when the separation sets in via dipole radiation, there is a more ordered situation that can be described by the equation. we assume here a number, k, of tcnb particles that form a kind of minus k charged virtual particle. the corresponding k plus charged nmcz molecules give a virtual positive charged particle. virtual particles occur in quantum statistical mechanics and can be described by a schrödinger equation. quantum quasi-particles see: [17, e.g. page 32 & appendix a]. 2. hamiltonian in a non-relativistic quantum analogue of classical mechanics let us start with the, normalized in form, stationary schrödinger equation for the coulomb bound state of two particles. the structure in a sense resembles a positronium [9] and coincide with [3, page 26]. in the lowest non-relativistic approximation the binding energy is determined by the instantaneous electrostatic interaction, similar to the hydrogen atom but then for, for instance, 1 ≡ nmcz•⊕ and 2 ≡ tcnb•⊖. the reduced molecular mass m = m1m2/(m1 + m2) is close to 179.49/2, e.g. m ≈ mnmcz/2 in e.g. kg, the reduced mass is m ≈ 1.4987×10−25 kg. in si units, n ≈ 1.055×10−34 j.s and e ≈ 1.602 ×10−19 coulomb. (1) in this equation , with, x1 = (x1,1, x1,2, x1,3). similarly for , with, x2 = (x2,1, x2,2, x2,3). furthermore, and and e the unit of charge. ε1,2is 2m/n2 times the energy eigenvalue [9, page 182] if n is not in units giving n is unity. to our mind, the generated plus and minus charged particle participate in a meso-scale hamiltonian. this hamiltonian corresponds to the schrödinger equation that einstein and schrödinger were discussing in their friendly exchange of letters. this corresponds to the positronium form but it is a multiparticle equation where k plus and k minus particles form virtual particles. k must not be too large because of the o(m2) approximation. we note that this kind of virtual particles we have in mind are clusters of real particles. this is not the same thing as e.g. the phonon virtualparticle. 2.1 unexpected independence here we ask can there be a transformation of the approximate schrödinger equation such that, despite the presence and validity of the coulomb force, we have mutual independence between distant particles? of course temperature effects are here crucial to the question [19]. in the experiment (see the description appendix a.1) we have a number of subsequent stages. each stage is described by a stationary schrodinger equation. this is what is intended by a steps-in-time change. first we have the situation where interacting particles are in a micelle. then, secondly, the initial separation sets in. here ξ = (x1,2 + x2,1)/2 is, momentarily, a constant despite changes in respectively, x1,1 and x2,1. this can be accomplished when e.g. x1,1 → x1,1 + ∆x and x2,1 → x2,1 − ∆x. in the third next stage in time, we freeze x1,1 and let y = x1,2 and z = x1,3 vary on the particle 1 side. on the particle 2 side we let x2,1 increase. the ξ in that stage or moment of time is no longer a constant because x1,1 is ”freezed”. the mathematics below makes things clear about the arrangement of the experiment for “free” but within coulombrange nmcz•⊕ and tcnb•⊖ radical pairs. the cluster of virtual particles, k nmcz•⊕ together with k tcnb•⊖, mimic the ψa and ψb of the einstein schrödinger debate. in order to study this we first look at the coulomb potential function itself. now suppose that there is a ξ ∈ r and the (x1,1−x21,)2 dominate the such that . if we then subsequently arrange it such that x1,1 > ξ and x2,1 < ξ we approximate with a 0 < β using ≈ 2−β−1{(x1,1 − ξ)−β + (ξ − x2,1)−β} (2) 31hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules if we take e.g. ξ = (x1,1 + x2,1)/2, then ≈ (x1,1 − x2,1)−β. this amounts to an approximation of the coulomb potential in the “amount of space and time” where a coulomb potential rightfully may be employed. we have (3) let us define . if we then accept that at a certain point in time the stationary schrödinger equation (1) for a product wave function ψ(x1, x2) = ψ1(x1)ψ2(x2) can be writtenas (4) the a and b indices are replaced with indices 1 and 3. this equation (4) can be split into two equations given below. the step-in-time development of the experiment appendix a.1, allows us to momentarily take ξ is constanε x1,1 → x1,1 + ∆x and x2,1 → x2,1 − ∆x. both the x·,1 coordinates change but ξ does not. the idea is to separate the particles with the use of “dipole radiation” such as described by wigner [11, around equation (46) of wigner’s lecture]. this appears in principle to be possible with the charged radicals nmcz•⊕ and tcnb•⊖. see appendix a.1. hence, (5) and (6) with, ε1,2= ε1 + ε2. it is supposed that the two separate equations describe the situation in a stationary form just after the separation split. then one may imagine that in experiment it is possible to restrict the stationary de scription of particle one with wave function ψ1(x1) to the directions x1,2 = y and x1,3 = z. the y and z notation are introduced for ease of the presentation ofcomputation. if we then introduce the transformation of ψ1with (7) the question can be asked if it is possible to find a transformation (7) such that ϕ1does not depend on ξ. the symmetric propagation where x1,1 → x1,1 + ∆x and x2,1 → x2,1 − ∆x and the x·,1 coordinates change but ξ does not, is broken in that step in time of the experiment (appendix a.1). in turn ξ depends on the x2,1 coordinate of particle 2. it is assumed that the value of ξ with fixed x1,1 can vary with x2,1. of course, in experiment one can fix x1,1 without fixing x2,1. inaddition ξ can vary because nobody knows exactly where we are allowed to start talking about two separate particles / particle groups. at the “split” the ξ is approximatedly fixed when looking at e.g. x1,1 for the equation of particle 1. similar case for particle 2. but when the stationary equations for particle 1 and 2 evolve for later steps in time, ξvaries. given equation (5) we then may have (8) with x = (x, y, z) = (x1,1, x1,2, x1,3) and x = x1,1 fixed. for ease of notaton denote grad2,3 for the gradient . therefore, div2,3 grad2,3 = . this is the nabla squuared in two dimensional (y, z) space. obviously we also have, (9) 2.2 transformation let us first look at the term d in (8). subsequently observe div2,3 grad2,3 ϕ1 = div2,3 grad2,3 .hence, (10) therefore the first term in the differential equation (8) transforms like d div2,3 grad2,3 ψ1 = (11) div2,3 grad2,3 ϕ1 − ψ1 div2,3 grad2,3 χ − 2 grad2,3 ψ1·grad2,3 χ the second term contains a ξ. we have 32 han geurdes (12) or, the second term can be written down as, (13) for completeness, note the definition of ϕ1provided in (7) and used in (13). the third term of (9) is a simple transformation dε1ψ1=ε1ϕ1 (14) if we then add equations (11), (13) and (14) we are back at (9) and note that (15) provided (16) if we observe the previous equation (16), then by construction, ϕ1(x|ξ) i s a solution to (8) operator equationas is ψ1(x|ξ). 2.3 a transformation that allows ϕ1independent ofξ we start with the assumption that the experiment is such that, after the split. remembering, div2,3 grad2,3 = (17) let us assume an o(m2) approximation theory for m from γ in the potential function and take ψ1(x,y,z|ξ) = g(y,z) (x−ξ)β+1 (18) as an aside please note that this wave function is intended as the intermolecular one for the k ensemble of radical molecules denoted with the index 1 in the experiment with the other cluster consisting of k molecules denoted with index 2. the equation (17) results into (div2,3 grad2,3 g) (x−ξ)β+1 + γg(x−ξ) + ε1g(x−ξ)β+1 = 0 (19) or (div2,3 grad2,3 g) (x−ξ)β + γg + ε1g (x−ξ)β = 0 (20) now because we approximate in o(m2) it is possible to e.g. have g(y, z) = mh(y, z) and so, γg = o(m2). the possibility to have a function with only g = g(y, z) is there with acknowledged and this is what is needed to have a ϕ1 that, according to our aim, does not in o(m2) approximation depend on ξ. the equation (20) then turns into div2,3 grad2,3 g(y,z) + ε1g(y,z) = 0 (21) in o(m2). subsequently we can have a look at ψ1(x,y,z|ξ)=g(y,z)(x−ξ)β+1 (22) the first of the equations obeys the schrödinger equation (19) and holds a g = g(y, z) which is independent of ξ. the second of the equations in (22) is not trivial even though we can multiply nominator and denominator with g(y, z) to, obviously,obtain it is a part of d transformation and combines with the ψ1, for convenience again given in the first of (22), to form a ϕ1 as (23) hence, ϕ1= g(y, z) f (y, z) and ϕ1is, clearly, independent of ξ. for completeness, and 33hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules χ(x|ξ) ψ1 (x|ξ) = g(y,z) f (y,z) + g(y,z) (β+1) (x−ξ)β 3. discussion and conclusion 3.1 verification we need to verify if the condition in (16) is fulfilled in a way that warrants ϕ1independence of ξ. if (22) is substituted in (16) we find, remembering, grad2,3 = and x, ξ constant for grad2,3 g div2,3 grad2,3 ( f + (β + 1) (x − ξ)β + (24) 2 grad2,3 (g)·grad2,3 ( f + (β + 1)(x −ξ)β − βγg = 0 therefore, g div2,3 grad2,3 ( f ) + 2 grad2,3 (g)·grad2,3 ( f ) − βγg = 0 (25) with,grad2,3= and, x−ξ = (x1,1−x2,1)/2.for x = x1,1 fixed, grad2,3 ((β + 1) (x − ξ)β) = (0,0) (26) we also note that it is assumed γg = o(m2). moreover we note that (25) allows the conclusion that f = f(y,z) is indeed possible. this implies that ϕ1 = ϕ1(y,z) is a solution of (15) despite the presence of the potential in that equation. please also observe that ϕ1(y, z) = g(y, z)f (y, z) which need not be o(m2). in addition, γg(y, z) is o(m2) but that does also not imply that ψ1, defined in (22), is small of o(m2) for all cases as well. this so because of the occurence of the (x − ξ)β+1 as a factor in ψ1. when x1,1 − x2,1is large, the potential in (15) decreases. but some wave function descriptions of the same particle, like ψ1, still “feel” the effect while others ϕ1 = dψ1 may become “immune” to it. observe that the d transformation can transform ψ(x|ξ), which is ξ dependent, into ϕ(x), which is ξ independent. both functions in (8) and (15) are a solution to (27) here, ψ1 ∈ {ψ1(x|ξ), dψ1(x|ξ),…}. as an aside we note that also in 2 instead of 3 spatial dimensions, anyons do not obey the fermion/boson spin statistics [13]. let us look at the potential and combine this with the wave function ψ1(x,y,z|ξ) = g(y,z)(x−ξ)β+1. we note that γg(y,z) is o(m ). this, however, does not make by necessity (5), (27) and the transformation ϕ1(y,z) = dψ1(x,y,z|ξ) = f(y,z)g(y,z), trivial. for instance, εj, with j = 1,2, is 2m/n2 times the energy eigenvalue. 3.2 schrödinger’s end of story a “relatively” large |x1,1−x2,1|, with fixed x1,1, maintains the influence of the x2,1 coordinate of the second particle on the ψ1 function. this must be true despite the 1/(x1,1 − x2,1) form of the potential function in the hamiltonian. it allows also a transformation to ϕ1 = dψ1which is order o(m2) independent of ξ. suppose that we in our analysis remain in the distances where schrödinger implicitly talked about in his letter to einstein. the ξ represents the influence, via the coulomb force, of the coordinate of the second entangled charged molecular radical(s) on the wave function of the first. apparently, quantum mechanics allows a transformation of a wave funcion where the inevitable coulombic interaction (a prehistoric entanglement start equation [3]), according to schrödinger’s end of story, is “immunized”. the use of charged molecular radicals makes the description with theschrödinger equation more open to experimen: appendix a.1. note that the charged radicals are particles with wave functions of their own. the latter intra-molecular wave functions are likely related to the posibility of the inter-molecular wave function in the here discussed schrödinger equation. nevertheless, a description of the role of the particle in the experimental environment is aimed for, not the intrinsic molecular wave function. we are looking at a meso-scale, but still quantum, behavior. the mathematics of the schrödinger equation implies that one can transform away the coulombic influence of the second particle on the first. we can also ask the question what it means when not a single “onium” pair can be found. e.g. what does it mean for radical chemistry, when this transformation cannot be accomplished. a possible explanation for the effect can be a transformation or decoherence to classical levels. but then again coulomb interaction is basic. can temperature effects disallow all kinds of “non temperature based” mathematics to be realised in the real world. from [19] we may learn that asymptotic behavior of atom-atom interaction at sufficiently large separation, which is perhaps needed in our present case, are profoundly influenced by excitations in the radiation field. this has the effect that the initial quantum interaction goes over to its classical analogue. on the other hand, working with molecular radicals perhaps lowers the thermal noise that 34 han geurdes could as well spoil the physical realization of the “non temperature based” mathematics [20]. it is also noted that other forces [19] of the order 1/ might play a role as well in the physics of a possible experiment with photon generated micelle based charged radicals. in any case, the transformation ϕ1 = dψ1 appears to open a new chapter in the schrödinger-einstein story. one may, firstly, wonder what einstein would have thought of a description of a particle or small group of particles that can transform itself in such a way that it does not “feel” the coulomb force anymore. note that both particle groups are supposed to be in a distance towards each other where coulomb forces reign. the question may linger if in classical domain the coulomb force at the distance in the experiment will persist. secondly, the author believes he is halfway a criticism of the inseparability of the quantum analogue of classical mechanics and a genuine possible discovery in the physical organic chemistry of charged radicals. perhaps that the ”mechanism” in appendix a.2 and appendix a.3 allow applications e.g. in synthesis of molecules or the biochemistry of radical molecules[21]. here we tally the conditions for a phenomenon in physical organic chemistry. they are presented in the form of questions. • is it possible to create onium for most of the nmcz•⊕ and tcnb•⊖ in the micelle? the situation is described in appendix a.1. • is it possible to separate nmcz•⊕ and tcnb•⊖ and to stop one radical group along the x axis but still allow movement along y and z, while the other charged radical group is separated along the x axis in the opposite direction? again we refer to appendixa.1. • is it possible to, initially, orderly x-axis separate nmcz•⊕ and tcnb•⊖ with x1,1→x1,1 + ∆x and x2,1→x2,1−∆x ? • is it possible to bring (a number of ) either nmcz•⊕ and tcnb•⊖, considered mesoscopic, in a state wave function that can be represented with ψ1(x,y,z|ξ) = g(y,z)(x−ξ)β+1? – what is the influence of the intrinsic wave function on the possibility to arrive at mesoscopic ψ1? – what does it mean when it is impossible to bring the – or even any – charged radical molecules in mesoscopic ψ1. is this state function, based on schrödinger equations, unphysical? • is it possible to find a physical equivalent for d = +χ(x|ξ) so that the “coulomb immunity” mesoscopic state wave function actually can be determined? we refer here to appendix a.2 and appendix a.3. if these points can be met in an experiment then, looking at appendix a.1, there is a circle c in a plane parallel to the yoz plane of the experiment where the ϕ1 form of the first radical can move more freely because of “immunity” for the attraction of the second opposite charged particle. the condition must apply that the 1/|x1,1−x2,1| approximation of the coulomb 1/r1,2 is valid for given x and (y, z) ∈ c. we claim for this experiment that c for the nmcz or tcnb radical in ϕ1 = dψ1is larger, but still with 1/|x1,1−x2,1|≈1/r1,2, than for the nmcz or tcnb radical with ψ1. it is assumed that either tcnb or nmcz can play the part with a wave function ψ1. references [1] a. einstein, b. podolsky and n. rosen, can quantum-mechanical description of physical reality be considered complete?, phys. rev., 1935, 47, 777. [2] d. howard, nicht sein kann was nicht sein darf, or, the prehistory of epr, 1909-1935, in: sixty-two years of uncertainty, ed. a. miller, plenum, 1990. [3] d. howard, einstein on locality and separability, stud. hist. phil.sci., 1985, 16, 171-201. [4] d. bohm, quantum theory, pp 611-634, prenticehall, englewood cliffs, 1951. [5] j.s. bell, on the einstein podolsky rosen paradox, physics, 1964, 1, 195. [6] h. geurdes, k. nagata, t. nakamura and a. farouk, a note on the possibility of incomplete theory, arxiv1704.00005v3, 2017. [7] h. geurdes, a probability loophole in the chsh, results in physics, 2014, 4, 81-82. [8] h. friedman, “…the proper development of the gödel incompleteness phenomenon…”, https://m. youtube.com/watch?v=cygnqsfca80, uploaded u gent, 2013. [9] g. källén, quantum electrodynamics, george allen & unwin ltd. london, springer, 1972. [10] y. tanimoto and y. fujiwara, effects of high magnetic fields on photo-chemical reactions, chap 10 in: handbook of photochemistry and photobiology, ed h.s. nalwa, vol 1, american scientific publishers, 2003. [11] e.p. wigner, interpretation of quantum mechanics, lecture physics department of princeton university during 1976, as revised for publication, 1981, qc, 1983, princeton university press. [12] c.a. kocher and e.d. commins, polarization correlation of photons emitted in an atomic cascade, phys. rev. lett., 1967, 18, 575-577. [13] f.wilczek,new kinds of quantum statistics, 35hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules arxiv0812.5097v3, 2009. [14] b. nordén, quantum entanglement facts and fiction-how wrong was einstein after all?, quart. revs. biophys., 2016, 49, 1-13, doi:10.1017/ s0033583516000111. [15] b. nordén, entangled photons from single atoms and molecules, chem. phys., 2015, 507, 28-33. [16] h. wennerström and p.o. westlund, a quantum description of the stern-gerlach experiment, entropy, 2017, 19, 186-189, doi 10.3390/e119050186m. [17] r.d. mattuck, a guide to feynman diagrams in the many-body problem, dover edition, 1992; mcgraw hill 1976. [18] a. aspect, p. grangier and g. roger, experimental realization of einstein-podolsky-rosen-bohm gedankenexperiment, phys. rev. lett., 1982, 49, 91-92. [19] h. wennerström, j. daicic and b.w. ninham, temperature dependence of atom-atom interactions, phys. rev. a., 1999, 60, 2581-2585. [20] b.nordén, personal communication, 2019. [21] c.t. rodgers and p.j. hore, chemical magnetoreception in birds: the radical pair mechanism, pnas, 2009, 106, 353-360. appendix a picture of a possible experiment and a tentative reaction path geometry in fig a1 below a possible experiment is depicted. we assume that intra-molecular wave functions do not resist mesoscopic inter-molecular coulomb immunity. this immunity transformation is presently unknown. in this appendix we look at a transformation via a synthesis of a 1,3,5 triazine ring with substituents (fig a2) and suggest (fig a3) that next to internalpi-bon dstorageof theadditiona lelectron,geometr yof themolec ule allows external compensations with e.g. a n→n⊕ bond (fig 3a). one of the participating ns comes from the 1,3,5 triazine. the other one from a nearby cyanide group in tcnb. this could be a step towards the claimed immunisation. the whole scheme in fig 1 fig 3 is theoretical. nevertheless the mathematics of the schrödinger equation presented in the paper suggests that this hiding of charge in the geometry of a molecular structure is perhaps an interesting possibility in physical organic chemistry. in this sense we tried to provide the chemical equivalent of figure appendix a.1. set-up of the experiment described in the main body of paper. the charged radical molecules are generated by light in a micelle. subsequently they are separated and a transformation of the mesoscopic inter-molecular wave function such that the nmcz(+) and the tcnb(-) are immune to each others coulomb field at a mesoscopic scale. micelle containing tcnb and nmca 36 han geurdes in the paper. we remind the reader, perhaps superfluous, that the chemical transformation equivalent to the wave function d transformation, is speculative. the reader please forgive the author also for yet another (nutty ?) observation.please note that the synthesis structure in appendix a.2 below is a rather flat, pi-bond, system of atoms connected to each other. perhaps this geometry neatly reflects the yoz plane restricted freedom in the wave function represented in the mathematics and holds a chemical expression of (a.1) such as suggested in appendix a.3. figure appendix a.2. possible reaction path on the tcnb side of the experiment (fig a1). the r residual is depicted on the left hand upper side of the figure and is presented to provide details. the reaction is among three tcnb radicals. we think this reaction is theoretically possible. cn is the cyanide group. for ease of drawing we omitted the (-) charge in the r of the lower row right hand product. figure appendix a.3. possible formation of n→n coordinate bond with cn group and (the lone electron pair) on the n from the triple n ring. a coordinate bond on a lone pair of n generates a plus on the n of the triple n ring. one can compare this to the formation of the plusion nh⊕4 or e.g. (ch3)2n⊕ = o. in addition to the internal pi-bond storage of the additional electric charge, a plus charge can be formed with a coordinate bond. perhaps that such a geometric hiding of the charge will contribute to what is claimed in the paper to be a immunization of coulomb interaction between nmcz and tcnb. the three joined tcnb molecules are triple negatively charged. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 3(2): 37-54, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-634 citation: m. henry, j.-p. gerbaulet (2019) a scientific rationale for consciousness. substantia 3(2): 37-54. doi: 10.13128/substantia-634 copyright: © 2019 pr. m. henry, j.-p. gerbaulet. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article a scientific rationale for consciousness marc henry1,*, jean-pierre gerbaulet2,* 1 université de strasbourg, umr 7140, 4 rue blaise pascal, 67000 strasbourg 2 n-light endowment fund, 30 rue de cronstadt, 75015 paris e-mail: henry@unistra.fr; jpg@n-light.org abstract. consciousness is a concept that can be easily experimented but not easily defined. we show that the same observation applies to information, entropy and even energy. the best we can do is thus to generate and present “identity-cards” of these notions by listing their observable attributes with the help of mathematics, logics, information theory and thermodynamics. from a top-down approach starting from a view of reality based on a universal information field, emerges a ternary logical structure of consciousness that further generates, through meaning, a dualistic space-time continuum populated with an infinite number of “things”. the validity of our logical structure is backed by quotations from topmost scientists and by various mappings such as famous previous models used in philosophy and science. implications in neurosciences are also briefly discussed. keywords. consciousness, meaning, information, activity, matter, neurosciences. introduction in a previous paper, a thought experiment arrived to the conclusion that consciousness has anteriority over energy and matter.1 such a statement should not be a surprise for eastern civilizations but seems to be in conflict with the materialism prevailing in western civilizations, due to the development of science since galileo’s first attempts to replace qualitative philosophical statements by observations and quantitative argumentation. this is illustrated in the first of two lectures held by galileo galilei at the accademia fiorentina in 1588 in order to solve a literary controversy concerning the interpretation of dante’s inferno.2 in these lessons galileo took the opportunity to show how mathematics could support a model suggested by the architect antonio manetti and demonstrate that the model proposed by alessandro vellutello had parts that would have collapsed under their own weight. shortly after he delivered his inferno lectures, he also published a discourse on bodies in water, which refuted the aristotelian explanation of why objects float in water.3 galileo’s works thus paved the way to the intensive use of science and mathematics for giving rational explanations of natural phenomena. as evidenced by his work on the structure of dante’s inferno, quantitative consid38 marc henry, jean-pierre gerbaulet erations are of considerable help for settling between several philosophical controversies. accordingly, the playwright eugen berthold friedrich brecht has put the following words in galileo’s mouth: “one of the main reasons why the sciences are so poor is that they imagine they are so rich. it isn’t their job to throw open the door to infinite wisdom, but to put a limit to infinite error. make your notes”.4 figure 1 shows an illustration of the current scientific paradigm initiated by galileo, in which every phenomenon is assumed to occur in a 4d spacetime continuum called minkowski’s space referred to as m4 space hereafter. a widespread view is that it exists a pyramidal hierarchy for scientific knowledge that is based on eight fundamental disciplines: mathematics, physics, quantum mechanics, general relativity, electromagnetism, thermodynamics, chemistry and biology. in a previous paper, it has been advocated that such a pyramidal structure originating in the positivist thinking of the french philosopher auguste comte should be rejected and that a much better approach is to use group theory for revealing the fundamental links between these autonomous disciplines.5,6 fitting consciousness in such a materialistic frame is generally perceived as a “hard problem”,7 while fitting free will of living beings may be referred to as the “hard question”,8 domains where qualitative arguments predominate over falsifiable quantitative statements. the aim of this paper is then to show what science has to say about consciousness, independently of philosophical descriptions characterized by a total lack of consensus among thinkers. we were motivated in our approach by some remarks made by topmost scientists about the role played by consciousness in our universe. first, the importance of consciousness is obvious in quantum theory where the finite value of the quantum of action imposes that the observer always has an influence over what is observed. it is timely here to quote werner heisenberg, the father of matrix mechanics: “i think that modern physics has definitely decided in favor of plato. in fact these smallest units of matter are not physical objects in the ordinary sense; they are forms, ideas which can be expressed unambiguously only in mathematical language (...). god is a mathematician”.9 one may also quote his enemy brother, erwin schrödinger, the father of wave mechanics: “as a matter of fact, i think that the material universe and consciousness are made out of the same stuff... but although i think that life may be the result of an accident, i do not think that of consciousness. consciousness cannot be accounted in physical terms. for consciousness is absolutely fundamental. it cannot be accounted for in terms of anything else”.10 two weeks later, the same journalist asked to their common mentor, max planck, this crucial question: “do you think that consciousness can be explained in terms of matter and its laws? ”. planck’s reply was: ”no, i regard consciousness as fundamental. i regard matter as derivative from consciousness. we cannot get behind consciousness. everything that we talk about, everything that we regard as existing, postulates consciousness”.11 moving from physics to mathematics, it is worth quoting eugene wigner, the father of group theory applied in physics: “when the province of physical theory was extended to encompass microscopic phenomena, through the creation of quantum mechanics, the concept of consciousness came to the fore again: it was not possible to formulate the laws of quantum mechanics in a fully consistent way without reference to the consciousness. all that quantum mechanics purports to provide are probability connections between subsequent impressions (also called “apperceptions”) of the consciousness, and even though the dividing line between the observer, whose consciousness is being affected, and the observed physical object can be shifted towards the one or the other to a considerable degree, it cannot be eliminated. it may be premature to believe that the present philosophy of quantum mechanics will remain a permanent feature of future figure 1. a picturing of the current materialistic paradigm in western science. reality is manifested in a 4d-continuum (x,y,z,ic·t) called minkowski’s space, having inaccessible zones out of a light cone associated to a given observer. on the left, a schematic hierarchy for scientific disciplines shown here as the progression: mathematics (mt) → physics (ph) → quantum mechanics (qm) → electromagnetism (em) → thermodynamics (th) → chemistry (ch) → biology (bl). general relativity (gr, not illustrated here) is represented as a separate branch owing to the considerable difficulties met for merging this science with quantum mechanics. 39a scientific rationale for consciousness physical theories; it will remain remarkable, in whatever way our future concepts may develop, that the very study of the external world led to the conclusion that the content of the consciousness is an ultimate reality”.12 it should thus be obvious that putting consciousness at the source of any reality is definitively not the prerogative of an eastern way of thinking. this means that science, the western way of thinking, has also something to say on this subject. it would thus be very nice if both ways of thinking could lead to the same conclusion. this was demonstrated in a previous paper using a thought experiment and showing that consciousness cannot be the result of neural activity.1 here, we plan to develop the same idea using science’s language. we will show that concepts of consciousness, analogic information with meaning, digital information lacking meaning and information activity may be defined out of any spacetime framework. consequently, information necessarily preexists any other concept such as entropy, energy or matter that could be viewed as a mere mapping from a virtual information field towards the observable m4 space-time framework. to keep the paper at a reasonable length, the problem of the physical nature of the information field will not be discussed here but treated in a third paper.13 consequently, we will present here only a static version of consciousness based largely on thermodynamics. the scientific reason for such a choice is that thermodynamics aspects are universal and do not depends on mechanisms or physical implementation of the system. this is not true for dynamical aspects that are strongly implementation-dependent with mechanisms that are highly dependent on the physical structures used for storing and processing information. our methodology is inspired by david bohm’s model, addressing how the unfolding of an implicate order results in manifest order and structure as a result of the activity of a super-implicate order, which generates various levels of organization, structure, and meaning. according to bohm, one finds at the root of capacities such as awareness, attention and understanding a preconscious “undivided state of flowing movement” – the actual and immediate activity of the holomovement. the nature of this movement can be discerned in a number of common experiences, such as listening to music. in such a model any transformation of consciousness must be a transformation of meaning, suggesting that everything, including ourselves, is a generalized kind of meaning.14 quoting bohm himself about such an approach: “as in the discussion of reason, it was shown how one level of thought will organize the next level. this can go on to produce a structure that may develop indefinitely with relatively closed loops of many kinds. this implies that consciousness is organized through a generative order whose totality is in many ways similar to the totality of the generative and implicate order that organizes matter. it is now possible to look into the question of how consciousness and matter are related. one possibility is to regard them as two generative and implicate orders, like separate but parallel streams that interrelate in some way. another possibility is that basically there is only one order, whose ground includes the holomovement and may go beyond. this order will unfold into the two orders of matter and mind, which depending on the context will have some kind of relative interdependence of function. yet at a deeper level they are actually inseparable and interwoven, just as in the computer game the player and the screen are united by participation in common loops. in this view, mind and matter are two aspects of one whole and no more separable than are form and content”.15 finally, the scientist that has most investigated a consistent connection between physics and psychology is beyond any doubts ernst mach: “if psychical life is to be harmonized at all with the theories of physics, we are obliged, i reasoned, to conceive atoms as feeling (ensouled). the various dynamic phenomena of the atoms would then represent the physical processes, whilst the internal states connected therewith would be the phenomena of psychic life. if we accept in faith and seriousness the atomistic speculations of the physicists and of the early psychologists on the unity of the soul, i still see no other way of arriving at a tenable monistic conception.”16 from such a survey of what have been said about consciousness by some greatest men in science, it should be clear that the consciousness-brain relationship should be understood as a unity and not as a duality between spirit and matter. a formal proof of the validity of such a statement has been given previously.1 now, it seems that time is ripe to go one step further and analyze at the light of the knowledge accumulated over the xxth century and over the first fifth of the xxist century how such a monist view fits into modern science. our philosophical position will thus be that it is possible to map brain activity onto computability with the immediate implication that consciousness should be external to the brain/brains for reasons listed below. we agree that postulating non-biology based brain/mind activity, is seriously disputable and we do not pretend to solve conclusively a debate that has agitated mankind during millenaries. our aim is rather to allow the reader interested in the phenomenon of consciousness to deepen his own thoughts about the ontologic questioning: “what is”, by providing a safe scientific guideline to the complex bottom-up approach of reality, and a hint of the simple and powerful top-down avenue to the same. 40 marc henry, jean-pierre gerbaulet a logical approach to consciousness as stated by david bohm, one of the most striking attributes of consciousness is its ability to make order emerge from chaos. consequently, logics should be at the very root of consciousness. it has been proven in 1913 by the american mathematician henry maurice sheffer (1882-1964) that the boolean algebra could be derived from the use of a single binary nand logical operator (alternative denial) represented by the so-called sheffer stroke (↑).17 this remarkable property has the consequence that nand gates are now crucial components of today’s computers, for instance, through the use of flash memories. accordingly, as all logical operations of binary logic may be encoded with just a single logical connector, high-performance computing processors may be readily developed. this immediately suggests basing consciousness on nand operations. accordingly, let p and q be two propositions that can be either true or false. the alternative denial operation is then defined as being such that v(p↑q) = 1 in all cases except when v(p) = v(q) = 1, in which case v(p↑q) = 0. consequently, if p stands for a proposition such as “i am”, three primitive concepts immediately emerge: negation: ¬p = p↑p that could be interpreted as “i am not” tautology: ⊤ = (¬p↑p) = p↑p↑p meaning “i am who i am” contradiction: ⊥ = ¬⊤ = ⊤↑⊤ = p↑p↑p↑p↑p↑p or “i am who i am not”. our claim is that we are facing the very basis of any kind of consciousness, in other words, its “identity card”. accordingly, the negation operation allows defining what is outside, the tautology what is inside, while the contradiction allows for the existence of incompleteness, that is to say the inevitable existence of undecidable propositions in any kind of coherent computing system using numbers.18 the other attributes of consciousness then logically follow as soon as the sheffer stroke is applied to at least two different propositions p and q. it is for instance possible to introduce the concept of causality through the use of an implication operator: implication: (p ⇒ q) = p↑(p↑q) setting p = q, one recovers the tautology under a new form (p ⇒ p) that could be translated as “if me, then me”. in fact, causality allows defining the existence of “time” seen as a never-ending succession of causes (p) and effects (q). irreversibility is very easily introduced at such a level, by the mere fact that the truth table of the proposition (p ⇒ q) is different from the truth table of the reverse proposition (q ⇒ p). the implication allows also introducing the concept of “inhibition”, another crucial attribute of consciousness: inhibition: (p ⊣ q) = (p ⇒ q)↑(p ⇒ q) = [p↑(p↑q)]↑[p↑(p↑q)] it is worth noticing that implication and inhibition are dual concepts, as it is possible to write: (p ⇒ q) = (p ⊣ q)↑(p ⊣ q). both operations refer to the same conditional statement “if … then …” and differ by the output: “go outside” for implication and “go inside” for inhibition. the existence of an active and expansive mode of action, or “yang” mode using implication, as well as the existence of a complementary passive or contractive mode, or “yin” mode using inhibition typical of eastern philosophies, is thus logically deduced. from a neuronal standpoint, this implies the existence of two modes of autonomy: sympathetic or active, as well as parasympathetic or inhibitive. alternation between awake state (active consciousness) and sleepy state (passive consciousness) is also described using this logical implication. the former explains the existence in the brain of a default mode network (dcn) associated to introspection, self-referencing, emotional regulation and mind wandering, all anti-correlated to the latter, a task control network (tcn) associated to top-down regulation of sensorimotor processing in control of oriented attention.19 it has thus been proved that shutting down the dcn was positively correlated with behavioral performance (implication), while reinforcing it interferes with task control, leading to degraded behavioral performance (inhibition). another attribute of consciousness is its ability to discriminate things. this is possible through the use of two other logical operators: equivalence: (p ⇔ q) = [(p↑p)↑(q↑q)↑(p↑q)] incompatibility: (p ⊕ q) = (p↑p)↑(q↑q)↑(p↑q)↑(p↑ p)↑(q↑q)↑(p↑q) translated into words, this gives “if me then you and if you then me” for equivalence the very basis for affinity or attraction and “if me then not you and if you then not me”, the basis for repulsion. such operations explain the structuration of groups of conscious beings into clans, parties, societies, religions, etc. finally, consciousness has also the ability to unite things (synthesis) according to a conjunction mode (p ∧ q) = (p↑q)↑(p↑q) translating as “me and you” or to 41a scientific rationale for consciousness separate things (analysis) through a disjunction mode (q∨p) = (p↑p)↑(q↑q) translating as “me or you”. consequently, through synthesis conscious beings interact for sharing something independently of any kind of affinity, while through analysis, they gather for increasing diversity and wealth. these last two modes form the basis of any culture whether scientific, artistic or philosophic. it is obviously quite amazing that all these fundamental attributes of consciousness derive from the existence of a single logical operation corresponding to the “alternative denial”. from a symbolic viewpoint, such a denial has been represented many times under the symbol of the ouroboros, i.e. a dragon biting its tail, which clearly suggested by its circular shape, an exterior (negation), an interior (tautology) and an incompleteness (contradiction), owing to the self-referencing of the symbol where the beginning also corresponds to the end (figure 2). to conclude, this section on formal logics, it is worth noticing that consciousness may a priori proceed according to three different types of logics, depending on the meaning given to contradiction. the first logical mode is based on the allowance for the “reductio ab absurdum” proof, in which one deduces from a contradiction (¬p ⇒ ⊥) that p or ¬¬p are true statements (elimination of the double negation). here we have the rational and coherent thinking mode typical of classical physics, based on boolean algebra.20 the second logical mode rejects “reductio ab absurdum” proofs, by stating that contradictions are perfectly allowed, but that starting from a contradiction which is false by nature, one may deduce any kind of true propositions (⊥ ⇒ p explosion’s principle). here we have the typical thinking mode of quantum physics stating that quantum objects may have contradictory descriptions such a wave/particle duality for instance. mathematically speaking, this corresponds to intuitionistic logic characterized by the use of multi-valued heyting algebra.21 using intuitionistic logic, it may be shown that the double negation has an autonomous status that cannot be assimilated to an affirmation. on the other hand, it is always true that ¬¬¬p = ¬p. the explosion principle typical of heyting algebra has physical consequences such as the existence of a big bang for inert matter explaining the observed diversity for matter. at a psychical level, the intuitionistic logic may clearly be associated to the unconscious mind, explaining why dreams are so difficult to interpret using the boolean conscious active mode. the third logical mode corresponds to minimal logic that simply gives no special treatment to the contradiction.22 it follows that using minimal logic, there is no difference between the formula ⊥ and any other kind of formula f. this means that it is here possible to associate contradiction at any formula f, the negation becoming p ⇒ f. this is obviously the most amazing mode where nothing can be denied, as everything is true by essence. it is also the “anything goes” apothegm of the philosopher paul feyerabend.23 here one may speak of oneness, i.e. the feeling of the deep unity of the universe. this is also the kind of logic depicted by the ouroboros (figure 2). meaning, information, communication, language the above formulation leads to an identity card of consciousness, which is a mapping of its basic logical attributes. this is the only safe attitude when facing a concept that cannot be defined in an absolute manner. by experimenting consciousness, we meet the above attributes and by trying to go beyond that, we perform an act of faith that is out the scope of a scientific figure 2. the mythical ouroboros or snake biting its tail. left : representation from a greek manuscript, codex parisinus graecus 2327, fol. 196, written in 1478 by theodoros pelecanos. top right: representation from another greek manuscript entitled chrysopoeia of cleopatra from codex marcianius graecus 299 (venice), written probably during the 11th century. inside the ouroboros, a text stating “hen to pan” translating as “all in one”. bottom right: zen’s ensō (japanese world meaning “circle”) is a circle that is handdrawn in one or two uninhibited brushstrokes to express a moment when the mind is free to let the body create. 42 marc henry, jean-pierre gerbaulet approach. moreover, as it is consciousness that gives the three possible meanings to contradiction, it should come first, before the two other concepts that are “meaning” and ‘information”. accordingly, with logical thinking, we are at the very root of scientific knowledge corresponding to plato’s world of abstract ideas. the logical attributes of consciousness introduced above apply to any kind of proposition. meaning is then the way chosen by consciousness for treating contradiction along 3 fundamental modes (rejection, acceptation or detachment). however, in order to make the connection with our observable physical world, we cannot stay at such an abstract level and we see in the information concept an obvious “fuel”. the idea is then to state that when consciousness meets information, a meaning emerges through application of its three modes and nine ways of reasoning. the notion of meaning may then be applied either internally for introspection (dcn mode of the brain) or externally to act and communicate (tcn mode). figure 3 shows an illustration of our viewpoint. as demonstrated by the palo alto school of thinking, it is absolutely impossible to “not communicate”.24 any silence or omission always carries a deep meaning suggesting that meaning is hierarchically superior to information. now, “to communicate” means exchanging information through a language that may be digital or analogic. information is thus not a primary attribute of consciousness, but always a secondary attribute of it that can be non-reflexive (digital mode, tcn) or reflexive (analog mode, dcn). consequently, upon any information exchange, it is mandatory to consider two levels of language: the objectoriented language dealing with raw information, and a meta-language taking as object the language itself, thus dealing with more abstract structures. if the object-oriented language is perfectly suited for digital communication at a bit-level, it is however devoid of any meaning. consequently, the role of the meta-language is to give meaning to the object-oriented language, thus placing analog communication above the digital one. such a viewpoint is also in agreement with gödel’s incompleteness theorems18 stating that languages able to close on their selves contain unavoidable contradictions (and if they don’t, they contain undecidable issues). in order to decide of the truth of an object-oriented language l, it is thus mandatory to go at an upper ml (meta-language) level to find the resources needed for referring to all the expressions of l. in other words, the truth for l is located in ml and not in l. similarly, the truth for ml will be located a still upper level mml and so on without ever ending. this shows that a language cannot contain an adequate true predicate for itself and truth cannot be defined at this level: it should be defined using a superior language. it then transpires that any communication has always two aspects: the content (raw information) and the relation (meaning or interpreted information). as it is the relation that organizes the content, it follows that such a relation can only be a meta-communication. it should also be realized that, in any communication, the emitter may have more information at its disposal than the receiver, even it the receiver thinks that he has exactly the same amount of information (or vice-versa). it is then very dangerous to think that another party holds the same amount of information as oneself and will draw the same conclusions from a given communication. the trouble with the analogic language is that a large amount of the elements constituting the morphology and the syntax of the digital language is missing and that it is the role of the translator to re-insert the missing elements. consequently, upon translation of an analogic material into a digital one, it is mandatory to introduce the logical truth functions that are absent in the analogic communication mode. this is particularly true at the level of negation, which does not exist at all in minimal logic, heavily used in analogic communication modes. any exchange of communication can thus be identified as symmetric or complementary depending on the fact that one considers similarities or differences. figure 3. a pictorial representation of a conscious being (me), represented here as a body and a mind living in a material world, and using its consciousness to give meaning (?) to information represented by a pen and a book. consciousness has been symbolized on the head of the conscious being by the mantra “om”, the cosmic sound of atman, identical in essence with brahman, the self, the only reality (in hinduism). 43a scientific rationale for consciousness moreover, in any cognitive act, a clear distinction should be made between the fact of perceiving (raw information or object-oriented digital language) and the fact of understanding what has been perceived (information carrying meaning or analogic meta-language). this allows defining the meaning as information within a context. alternatively, one may say that «  a bit of information is definable as a difference, which makes a difference  ».25 these two kinds of information may be easily confounded in the common language, despite the fact that raw and interpreted information do not act at the same level of communication. information activity up to now consciousness appears as a primordial entity embedded in a kind of non-dual universal field filled with a “substance” named information, and has the ability to give meaning to the information stored in such a field through three logical modes and nine logical tools. upon information exchange two levels of communication have been identified: digital language or analogic meta-language. the next step is then trying to define what could be an “object” in a world holding only information. our postulate is that consciousness, focusing on a certain amount of information measured in bits, isolates within the non-dual field what we will call an “information pool”. obviously, such an information pool would be first characterized by a certain number of binary digits (bits), the storing medium being the “stuff “ evoked by e. schrödinger in a 1931 interview and from which the illusion of matter could be created.10 as consciousness is able to give meaning to a given information pool, it directly follows that some pools will be perceived by consciousness as holding highly meaningful groups of bits that could be used for building an “identity card” for the pool. obviously, such highly meaningful bits will be eagerly kept within the pool and not transferred towards another pool, because such a transfer would cause an identity loss. accordingly, the notion of “ego” is clearly introduced and identified. consequently, besides the information content, one should also introduce an information availability measuring the strength of each ego. being a conscious information pool, each ego may exchange information with another ego that could hold less-meaningful bits, in which case the information availability will be high. at an upper level, ego may accept transferring its meaningful bits towards the universal information field, undergoing a dissolution process. the notion of information availability thus introduces a fundamental “duality” within the non-dual information field. for instance, one may consider an information pool having low information availability. this basically means that the identity of such an information pool should be preserved during information exchanges. in such a case, one may speak of a static “volumetric” information pool. alternatively, one may come across an information pool having high information availability. this means that we encounter in such a case a dynamic “radiating” information pool having no “volume” owing to the ease of transferring information. such dynamic information transfers allow introducing the concept of “time” in order to characterize the “speed” of any information transfer and the associated bandwidth. a space-time frame filled with matter and radiation thus emerges as a direct consequence of consciousness giving meaning to various pools of the information field. as consciousness has three modes of logical inference, we may identify three ways of perceiving space and time (figure 4) giving rise to three modes of apprehension of reality: by computing with numbers (wakefulness), by using symbols loaded with meaning (awareness) or by trying not to understand or describe by just living here and now (mindfulness). on such a ground, it is possible to introduce a new concept, information activity, defined as the product of information content by information availability and characterizing the overall intensity of information transfers between information pools. furthermore, this leads to a distinction between emitters that send information and receivers that accept information. but in order to behave as a potential information sender, the emitter has figure 4. in our approach space and time are creation of consciousness and should be perceived along three different modalities according to the status given to the contradiction. the digital time is useful for a rational comprehension with the brain, the analog time for intuitive comprehension with the heart and the timeless time for immediate comprehension with the gut. 44 marc henry, jean-pierre gerbaulet to handle both the emitted information and the context, the context being here defined as the amount of information not transmitted and kept by the emitter. this means that an emitter has a consciousness allowing it to discriminate between the information that should be emitted and the context that should not be emitted. it then logically follows that emitters should have necessarily higher information contents than receivers and that information should flow from pools having higher information contents towards pools having lower information content. moreover, if it happens that two pools of information have the same information content, there is neither emitter nor receiver and one may then be allowed to define a new single pool of information by adding the information contents of these two pools. in other words, information pools are thus doomed to always increase in size and should never decrease, leading to the logical conclusion that information content behave as the concept called entropy in thermodynamics. such an identification of the information content with entropy is then in full accordance with the shannon/von neumann definition of entropy26, giving further confidence in this interpretation. consequently, we meet here thermodynamics, a science sharing with consciousness the ability to deal with information at a meta-language level and with energy and matter at an object-oriented level. staying at an information level, one may say that entropy measures the amount of digital information available on one hand,26 while, on the other hand, complexity or thermodynamic depth27 corresponds to the amount of information rejected at an analogic level. alternatively, one may speak of digital information and analogic exformation that is treated by consciousness to define a context not transmitted during the communication.28 it then becomes possible to reconcile the two conflicting interpretations of entropy. at a digital level of object-oriented language, one finds the shannon-von neumann thermodynamic entropy, while at the analogic level of the metalanguage, one meets the cybernetics negentropy of wiener/schrödinger.29 a fundamental error is here to think that it is possible to obtain the meaning (cybernetics negentropy) by merely changing the sign of the amount of information (thermodynamics entropy). it should also be clear that assimilating entropy to disorder and negentropy to order, as done in most thermodynamics textbooks, should be completely avoided. this is because there is no order or disorder at a digital level, such notions belonging to the analogic realm of consciousness observing things. at a digital level, information corresponds to what is unexpected, and there are more unexpected things in a disordered situation than in an ordered one.28 moreover, it follows from gödel’s incompleteness theorems that it is impossible to know if there is order or disorder at a digital level. order and disorder are thus clearly subjective notions located at the level of the digital meta-language and, as such, they have nothing to do with thermodynamics. it follows that discriminating between pools of information according to their information contents allows distinguishing between potential emitters having high information contents and receivers having low information contents. however, it should be clear that, at this level, nothing is “observable”. in other words, we are moving in a virtual world where everything is perceived as made of information. here, it is worth quoting the great physicist john archibald wheeler: “i think my life in physics is divided into three periods ... i thought at first that everything was made of particles .... in my second period everything was made of fields ... in this third, my impression is that everything is made of information”.30 figure 5 shows a translation of wheeler’s statement. it is also worth noticing that david bohm has also introduced in 1985 the notion of activity of meaning, a nonmechanical reality associated to enfoldment and unfoldment and quite close to the information activity concept discussed here.14 the next step is then to introduce fundamental coupling constants, the role of which is to set a limit between what can be observed (matter) and what cannot be observed (information, entropy and energy). entropy and temperature the first constant has the role of giving physical meaning to the abstract notions of information content, information availability and information activity. as shown in figure 6, there is an identity in logical structure between communication and measurements in figure 5. the three fundamental modes of perception of consciousness gives rise to the three basic models of reality: viewed as information at a primordial source level, viewed as fields during propagation and viewed as particles upon manifestation as matter. 45a scientific rationale for consciousness quantum physics.31 this suggests generalizing the entropy concept used in statistical thermodynamics to the information theory. accordingly, the mathematician john von neumann when asked by claude shannon to suggest a name for his newly discovered uncertainty function lucidly stated: “you should call it entropy, for two reasons. in the first place your uncertainty function has been used in statistical mechanics under that name, so it already has a name. in the second place, and more important, no one really knows what entropy really is, so in a debate you will always have the advantage”.32 it thus should be no surprise that a great confusion exists in science about the definition of entropy that merely reflects the great difficulty of defining consciousness. such difficulties in definitions stem from the fact that entropy or consciousness cannot be defined explicitly as they are both primary concepts. however, in the spirit of what has been done for introducing consciousness, the best way to introduce entropy to a material world is to describe its fundamental attributes.33 replacing the unobservable “information pool” by its visible counterpart, the “body” or the “soma” in bohm’s language,14 it appears that entropy is a “stuff ” that can be transferred, poured out, cumulated or distributed among bodies. each body contains more or less entropy depending on its information content, the entropy of the whole system being equal to the sum of the entropies of its parts. rubbing, grinding, heating or performing a chemical reaction, are examples of processes able to generate entropy. entropy also has the property of being unable to cross thermally insulated walls, meaning that if it can be created, it is doomed to increase and never decrease in any isolated system. when entropy is poured into a body, this body becomes warmer, meaning that a body without entropy is absolutely cold. any entropy increase also causes changes in volume, in shape, changes the state of aggregation as well as electric or magnetic properties. finally, it is rather easy to measure the amount of entropy in a body: for example, the volume loss of ice while melting is directly proportional to the amount of entropy added. it follows from such an analogy that our first coupling constant should be an entropy. now, knowing that entropy s measures also the information content, it comes that temperature t is readily assimilated to information availability, while information activity takes the figure of energy w through a fundamental relationship: w = kb·t measured with a physical unit named “joule” (symbol j). such a unit is well adapted to the human body characterized by an average resting metabolic rate of 3611 j·kg-1·h-1,34 corresponding to an average power of 105 watts (1w = 1 j·s-1). a more convenient energy scale for discussing elementary phenomena in the visible universe is the zepto-joule (symbol zj), with 1 zj = 10-21 joules. on such a scale, the universal entropy constant takes the value kb = 0.0138 zj·k-1 also known as boltzmann’s constant in memory of the austrian physicist ludwig boltzmann, the father of statistical thermodynamics. such a “quantum of entropy” allows discriminating between a non-observable world involving entropy changes such that s < kb and the visible universe where s ≥ kb. action and frequency now, let us consider the situation where information sent by an emitter is captured by a receiver and then re-emitted without any loss towards the sender, restoring the initial situation. as the final state is the same than the initial one, the process may occur a second time and so on without interruption, leading to the concept of “vibration” characterized by the number of cycles performed per unit of time, i.e. by a frequency f. it should be obvious that activity and frequency have to be related in some way through a second universal coupling constant relating this aspect of the information world to the physical world. such a coupling constant h is well known in physics under the name of “quantum of action” with a new relationship: w = kb·t = h·f where h is planck’s constant, with h = 663 zj·fs, (1 femto-second (fs) = 10-15 s). as for the quantum of entropy, the quantum of action l allows discriminating between a nonobservable world involving action changes such that l < h and the visible universe where l ≥ h. it is worth noticing that the fact that physical action l is quantified is a mere consequence of the quantification of information in bits. in other words, quantum physics, one of the most fundamental theories of modern science, emerges quite naturally from informafigure 6. similarity in logical structure between information theory and quantum theory meaning that information content for the mind should correspond to entropy for the body. adapted from j. rothstein (1951).31 46 marc henry, jean-pierre gerbaulet tion theory.35 with such a link in hand, movement in the information world becomes what is called “kinetic energy” in the physical world, whereas structural information has his physical counterpart named “potential energy”. the first law of thermodynamics stating that the total energy should always be conserved stems from the fact that, once created, information can never be destroyed. thus, at the scale of the whole universe, information exchanges are necessarily without losses.36 alternatively, planck ’s constant can also be interpreted as the multiplicative scale factor setting the scale of classical zero-point radiation appearing in classical electromagnetic theory, as relativistic classical electron theory with classical electromagnetic zero-point radiation gives many results in agreement with quantum theory.36 consequently, the identification made here would remain valid even if quantum mechanics was finally proved to be fundamentally wrong. such an uncertainty in the validity of quantum theory stems from its well-recognized incompatibility with general relativity, another most important physical theory, as both theories diverge on the evaluation of vacuum energy density by more than 120 orders of magnitude!!!5, 37. light, matter and electromagnetism it should also be obvious that the distinction between static spatial-like information and dynamic time-like information cannot be a fundamental one as it is consciousness that gives meaning and identity to the various pools of bits. consequently, a third universal constant should exist, intimately associating space with time. the basic postulate of equivalence between space and time stemming from the theory of relativity is thus logically introduced. by this definition, the third universal constant should be a speed c = 299 792 458 meters per second (m·s-1) giving an upper limit for the transfer of information between information pools. the fact that such a constant should not be infinite is here directly related to the fact that it belongs to the realm of the physical world where pools of information always have a finite number of bits. it then follows that two kinds of entities should exist in a physical universe: those able to propagate with the maximum allowed speed c, known as “photons”, and those propagating at speeds v < c, known as “matter”. in the second case, one may assign to a material object with an energy w, an inertial coefficient m or “mass”, linked to it by m = w/c2. as for the quantum of entropy or the quantum of action, the speed of light c allows discriminating between a non-observable world involving speeds v such that v > c and the visible universe (light cones) where v ≤ c (see figure 1). at this stage we have in hand a possible justification for the observation of a physical universe where energy, the physical counterpart of information activity, could manifest itself through three kinds of variables (temperature, frequency and mass) corresponding to various kinds of information availability, linked through a fundamental equivalence relationship: w = kb·t = h·f = m·c2. however, such a picture applies to an observable universe having movement occurring in a single direction through translation. in order to be able to perform rotations, a 2d-spatial frame is required, requiring introduction of a fourth universal coupling constant e being a quantum of electrical charge with a physical unit named coulomb (symbol c) and such that e = 0,106 atto-coulombs (symbol ac), with 1 ac = 10-18 c. associated to this new aspect of information activity, one should have a new variable measuring static information availability corresponding to the so-called electrical potential u (si unit volt v or energy per coulomb) and leading to another fundamental equivalence relationship: w = kb ·t = h·f = m·c2 = e·u. here, the reason for the quantification of electrical charge is that it is a fourth possible manifestation of the same stuff named information that is naturally quantified in bits. as for the quantum of entropy, the quantum of action or the speed of light, the quantum of charge e, allows discriminating between a non-observable world involving charges q such that q < e and the visible universe where q ≥ e. finally, one may combine translations with rotations to allow for spiral movements, requiring a fifth coupling constant related to the existence of magnetism. however, as electricity is linked to static rotations and magnetism to dynamic screw rotations, this new dynamic aspect of information availability µ0 = 4π·10-7 h·m-1 corresponds to a magnetic inductance (si unit henry h or v·s2·c-1) per unit length. this leads to yet another fundamental equivalence relationship: w = kb·t = h·f = m·c2 = e·u = (µ0·e·c)·i involving an electric current i = dq/dt, measuring the rate of variation in electric charge q with time t. introduction of a magnetic permeability for empty space 47a scientific rationale for consciousness means that such a medium should be considered as a “substance” having an electric permittivity ε0 = 1/(µ0·c2) corresponding to a capacitance (si-unit farad f or c·v-1) per unit length. what is energy? according to the present formulation, energy should be considered as the manifestation of information activity in m4 space-time. as information activity is driven by consciousness through the meaning, energy and entropy should be considered as an attribute of a manifested consciousness. however, it is worth noticing that in the material m4 world, energy is indeed a mongrel concept. this fuzzy nature of the energy concept was well perceived by the french mathematician henri poincaré: “in every particular case we clearly see what energy is, and we can give it at least a provisory definition; but it is impossible to find a general definition of it. if we wish to enunciate the principle in all its generality and apply it to the universe, we see it vanish, so to speak, and nothing is left but this – there is something which remains constant“.39 translated in our language, this means that energy as an attribute of consciousness may exist under an infinite number of different forms. as energy is the shadow of information activity and as information activity was defined as the product of information content by information availability, we have in hand a universal “recipe” for talking about energy in a manifest world. each form of energy should then be considered as a product of a “coordinate” measuring the amount of something (a “thing” being, for consciousness, a pool of information with interesting conserved properties) by an associated “propensity” ruling spontaneous or natural transfers of such things between different parts of a thermodynamic system. let us briefly demonstrate that all forms of energy known in m4 comply with such a universal recipe. a first coordinate could measure for instance the entropy content s of a body with an associated propensity corresponding to its temperature t, their product dw = t·ds being called “thermal energy”. the propensity is identified by stating that spontaneous evolution always occurs when entropy flows from a part with a high temperature towards another colder part, the reverse evolution needing another external form of energy. at thermal equilibrium, all temperatures have to be equalized to the same value, meaning that parts at similar temperatures do not exchange entropy anymore. a second coordinate would measure the weight of a body, that is to say the product of its mass m by a characteristic constant acceleration g = g·m/r 2 provided by another bigger mass m of size r where g = 66.7384 pj·kg-2·m is newton’s gravitational constant. to this coordinate, one may associate a propensity corresponding to altitude h, their product dw = d(m·g)×h being called “gravitational energy”. stating that spontaneous evolution always occurs when a part at high altitude moves towards a lower altitude identifies the propensity. at gravitational equilibrium, all altitudes have to be equalized to the same value meaning that parts at the same altitude do not move anymore. the reverse evolution consisting on moving from a low altitude towards a higher one cannot be spontaneous, needing the mobilization of another form of energy. a third coordinate would measure the amount of momentum p of a body, that is to say the product of its mass m by its speed v (p = m·v) associated to a propensity corresponding to its speed, their product dw = v·dp being called “kinetic energy”. the propensity is identified by stating that spontaneous evolution always occurs when a part of high speed changes towards a state of low speed, the reverse evolution needing another external form of energy. at kinetic equilibrium, all speeds have to be equalized to the same value, meaning no more exchange of momentum between parts moving at the same speeds. a fourth coordinate would measure the amount of space (volume v) occupied by a body associated to a propensity corresponding to the pressure p inside the body, their product dw = -p·dv being called “mechanical energy”. the propensity is identified by stating that spontaneous evolution always occurs when a part of high pressure changes towards a state of low pressure, the reverse evolution requiring another external form of energy. at mechanical equilibrium, all pressures have to be equalized to the same value, meaning no more volume variations for parts having the same pressures. a fifth coordinate would measure the amount of electrical charge q at the surface of a body associated to a propensity corresponding to the electrical potential u, their product dw = -u·dq being called “electrical energy”. the propensity is identified by stating that spontaneous evolution always occurs when a part of high electrical potential changes towards a state of lower electrical potential, the reverse evolution requiring another external form of energy. at electrical equilibrium, all potentials have to be equalized to the same value, meaning no more exchange of charge between parts at the same potential. a sixth coordinate would measure the amount of electric flux v·d (where d stands for electric flux density measured in c·m-2) within a given volume v asso48 marc henry, jean-pierre gerbaulet ciated to a propensity corresponding to the electric field e, their product dw = e·d(v·d) being called “dielectric energy”. the propensity is identified by stating that spontaneous evolution always occurs when a region where the electrical field is high changes towards a state of lower electrical field, the reverse evolution requiring another external form of energy. at equilibrium, electrical field should be the same everywhere in the volume meaning no more exchange of electric polarization between different spatial regions. a seventh coordinate would measure the amount of magnetic flux v·b (where b stands for the magnetic flux density measured in wb·m-2) within a given volume v associated to a propensity corresponding to the magnetic field h, their product dw = h·d(v·b) being called “magnetic energy”. the propensity is identified by stating that spontaneous evolution always occurs when a region of high magnetic field changes towards a state of lower magnetic field, the reverse evolution requiring another external form of energy. at magnetic equilibrium, magnetic field should be the same everywhere in the volume, meaning no more exchange of magnetization between different spatial regions. an eighth coordinate would measure the amount of matter n within a given volume v associated to a propensity corresponding to the chemical potential µ, their product dw = µ·dn being called “chemical energy”. the propensity is identified by stating that spontaneous evolution always occurs when a region of high chemical potential changes towards a state of lower chemical potential, the reverse evolution requiring another external form of energy. at chemical equilibrium, chemical potentials should be the same everywhere in the volume, meaning no more exchange of matter between different spatial regions. as shown above and as stated by poincaré, if the energy concept can be easily defined in a particular situation as the product of an energy coordinate by an energy propensity associated to such a coordinate, it is impossible to give it a definition covering all possible situations. the only thing that could be said about energy without going into details is that “it exists something that remains constant during any evolution”. obviously, such a general definition corresponds more to a postulate than to a scientific statement derived from empirical evidence. our scheme nicely relates this postulate to the existence of consciousness. this suggests that energy could also be rigorously introduced in psychology and spirituality. for instance, sigmund freud was the first one to formulate a scientific theory of psychological facts by introducing the idea of the existence of a new form of energy called “mental energy”. accordingly, it was rather easy to introduce a coordinate measuring the amount of thoughts n coming from the “id” with an associated propensity that freud called “libido” acting as a kind of chemical potential that could be related for instance to glucose consumption within the brain40 or to the amplitude of the 0.1 hz component of heart rate variability.41 within such a framework of thinking, knowledge of a total metabolic energy m could be divided by boltzmann’s constant kb to retrieve a “psychic temperature” ψ = m/kb as well as an associated mental energy dw = ψ·dn. it is worth noticing that such an energetic approach of mental activity has been criticized and rather linked to a degree of controllability with mental fatigue associated to a lack of desire and not to a lack of energy.42 here, it seems better to identify “desire” with information activity defined as explained above as the product of information content by information availability. the same holds for qi or prana that would better be viewed as information activity rather than “spiritual energy”. again, such misuse of the term energy directly stems from the intrinsic vagueness of the concept. the vagueness of the energy concept is also well illustrated by the fact that one may also consider only two kinds of energy: a first one describing the ability to change position of a body (kinetic energy) and a second one describing the ability to change the relative disposition of its constituting parts (potential energy). by contrast, entropy has a single meaning: measuring the information content in the world of consciousness and as the spreading of energy over all the accessible degrees of freedom in m4. the reason for the existence of the second law is then to distinguish between reproducible experiments in m4 and non-reproducible ones that are “virtual”.43 accordingly, during mental activity, everything is possible, and the fact that an event is reproducible or not does not matter anymore. the fact that self-organized structures and diversity in m4 stem from a flux of entropy44 may also be logically related to an information flux in the information field of consciousness. finally, it is worth noticing that it is possible to avoid speaking about energy and entropy as two different entities in thermodynamics. it is the “free energy” concept or ”chemical potential” defined as the total energy corrected of any entropy variation at a given temperature.45 the trouble here is that the expression “free energy” may also be interpreted as the energy contained in the physical vacuum, i.e. as “zero point energy”.37 a much better way is then to associate to each substance an “activity” variable, noted “a”, with the value a = 1 when the system contains only this substance (pure state) and the value a = 0 when the substance is com49a scientific rationale for consciousness pletely missing in the system. intermediate values (0 < a < 1) will thus describe any kind of mixture containing a given substance in variable amounts. using such an “activity” concept avoids facing the troublesome energy/entropy duality, with just a single rule stating that exchanges of energy, entropy or matter always occur from spatial regions having a high activity, towards spatial regions having a low activity. this is a much satisfying alternative way of stating that energy should always be conserved (first law) and that entropy should always increase (second law). it then appears that the activity concept is not only a convenient way of giving a direction to any kind of evolution, but that thanks to its unified nature, it could also be considered as a more fundamental concept than energy or entropy considered separately. this is why activity has been put at the forefront and energy/entropy in the back in our previous paper.1 discussion in this paper we have proposed associating the concept of consciousness to the operation of a single alternative denial logical operator (↑) acting on pools filled with information and giving meaning to them. using the computer metaphor, pools with meaning then correspond to software, while pools devoid of meaning correspond to raw data. the ensemble of all information pools forms an information field that we may call “supra-consciousness”. at this level of minimal logic, there is no special treatment for the contradiction (⊥ = p↑p↑p↑p↑p↑p) that cannot be considered as the negation of a tautology (⊤ = ¬p↑p). at a second level of intuitionistic logic (meta-consciousness), contradiction is viewed as the mother of any kind of truth (⊥ ⇒ p), the negation having the property that ¬¬¬p = ¬p. at a third level of boolean logic (rational consciousness), contradiction is used by consciousness to infer that something is true (if ¬p ⇒ ⊥ then ¬¬p ⇒ ¬⊥ = ⊤). such a ternary approach of consciousness is by no means new and has already been explored by ernst mach by considering that nature consists of the elements given by the senses.16 in other words, mach was convinced that what we usually call sensations are the true elements elements in the sense that no further resolution has yet been made of them of the world. then, the primitive man first takes out of them certain complexes of these elements that present themselves with a certain stability and are most important to him. consequently, every physical concept is nothing but a certain definite connection of the sensory elements denoted by symbol a, b, c..., and every physical fact rests therefore on such a connection. these elements are the simplest building stones of the physical world that we have yet been able to reach. in our approach such complexes of elements may be mapped with the notion of “information pool”. in his analysis, mach was indeed obliged to introduce three kinds of complexes noted abc (i.e. ¬p = p↑p = things out of the body), klm (⊤ = (¬p↑p) = p↑p↑p = the body) and αβγ for anything else (⊥ = ¬⊤ = ⊤↑⊤ = p↑p↑p↑p↑p↑p = the spirit). with these three complexes, one may for instance derive the existence of conscious i (ego) as (klm + αβγ) facing an external world (abc) made of things. but this is not the only possibility as one may have a pure spirit as αβγ facing a material world (abc + klm). a third combination could also be a material body (klm) facing a spirit impregnating all things (abc + αβγ = god). finally, one could also envision a non-dual and non-local consciousness (abc + klm + αβγ = atman). but, if mach has derived such a scheme from its scientific empirical expefigure 7. eight common forms of energy in the observable m4 space. in each case, energy corresponds to the product of a coordinate measuring an amount (highlighted in blue) by an associated propensity (highlighted in red) taking at equilibrium the same value everywhere in the system. other forms of energy not represented here may also exists such as for instance interfacial energy dw = γ·da where a is the coordinate measuring the amount of area and γ a propensity called surface tension. one may also cite elastic energy, dw = x·d(k·x) where k·x is the coordinate measuring the amount of tension and x the propensity corresponding to a length. in fact it exists an infinite number of energy forms according to the meaning given by consciousness to the manifestation of information activity. one may thus even define a psychic energy, dw = ψ·dn, where n is the coordinate measuring the amount of thoughts and ψ the associated propensity that could correspond to the intensity of desire for instance. 50 marc henry, jean-pierre gerbaulet rience, we get the same result from the mathematical structure of logics based on propositions about the world linked into complexes through the sheffer’s stroke (↑). it was also deduced that space and time also have a triple interpretation (digital, analogic and both attributes) as well as physical reality (particles, fields and information). the fact that the time sensation is intimately associated to consciousness has already been analyzed in details by ernst mach16, and before him by saint augustine (time was a feature of consciousness named animus) and plotinus (time is generated by the soul or psyche while eternity is the quality of the spirit or nous).46 the evolution towards a ternary aspect of time was perceived in the middle ages by meister eckart by adding the notion of nu ̂as, the intersection of time and eternity. eckart was thus talking of the nu ̂ (=now) in which time dissolves into eternity, a concept also identified by sufi masters as ibn al-waqt i.e. “son of the moment”, free from the chains of past and future. the fact that time is a feature of the activity of consciousness was also well perceived in hinduism (ksana) and buddhism (u-ji). however different these spiritual ways may be, they all require three actions: focusing on the interior (internal analog time), body exercise to strengthen the will (external digital time) and some kind of regulation of breath (timeless time). we have also introduced the concept of information activity in relation with the physical notions of entropy and energy with a fundamental relationship: w = kb·t = h·f = m·c2 = e·u = (µ0·e·c)·i. on the other hand ernst mach has clearly identified five basic elements for sensations: time-sensation related to consciousness, colorsensation and space-sensation related to the sight/touch pair, tone-sensation related to the ear/voice pair and matter-sensation related to the taste/smell pair.16 following our approach an immediate mapping emerges: color/ temperature (t) through wien’s displacement law, tone/ frequency (f ) through the existence of music, matter/ mass (m) through the notions of atoms and molecules. such a mapping leaves space-sensation mapped to the existence of static charges (electricity) and time-sensation mapped to the existence of moving charges (magnetism). moreover, as movement needs specification of an inertial referential frame, a complete equivalence between electric and magnetic field and thus of space with time is expected. this is in agreement with the basic postulate of special relativity. this could be a quite convincing argument in favor of putting a single concept (information) at the source of mach’s five elemental-sensations associated to a physical world. but one may also make a mapping with the five platonic solids of antiquity: tetrahedron (fire/color-sensation), octahedron (air/tone-sensation), cube (earth/matter-sensation), icosahedron (water/space-sensation) and dodecahedron (ether/time-sensation). in such a symbolic language, the space/time equivalence could be mapped to the mathematical duality existing between dodecahedron and icosahedron. as cube and octahedron are also dual geometries, this also suggests another equivalence between tone (frequency) and matter (mass) in full agreement with quantum field theories based upon the equivalence h·f = m·c2. finally, the fact that the tetrahedron is its own dual could be mapped to the well-known fact that colors may be generated either by addition (unequal rgb-triples) or by subtraction (dual unequal cmj-triples), the white-sensation (light) being produced by equal rgb-triples and the black-sensation (darkness) by equal cmj-triples. noticing that the wood grows from the earth and that the metal drops as meteorites from the sky (ether), we also have a mapping connection with the five chinese elements. obviously, one could argue that such mappings are just coincidences occurring by chance. such a position would in fact be the only reasonable conclusion in a bottom-up approach where the “big” is explained by the properties of the “small” holding the ultimate truth. however, in the top-down approach used here, where it is the big that is the ultimate reality that could be fragmented in a infinite number of ways into an infinite number of small illusory entities, these mapping based on mathematical ideas are just the glint of the profound unity and coherence of the information field holding supra-consciousness. going to neurosciences, it is satisfying to see that three kinds of consciousness states have also been identified: c0-consciousness for unconscious processing, c1-consciousness for having an information in the mind calling for an action on the outer world and c2-consciousness for introspection or meta-cognition.47 a possible mapping would be to associate supra-consciousness (detachment from contradiction) to unconscious information monitoring c0, meta-consciousness (acceptation of contradiction) to introspective c2-consciousness and rational consciousness (reject of contradiction) to extrovert c1-consciousness. it is worth noting that three levels of consciousness (type i primary, type ii oriented outwards and type iii oriented inwards) was also developed by jean-françois houssais48 or by philippe guillemant (anima, me and self ).49 referring to block’s concepts of a-consciousness (availability of information for use) and p-consciousness (perception of information),50 it should be clear that here a fundamental ingredient is missing, explaining the considerable difficulties met by such a reduction from three modes to only two modes.51 51a scientific rationale for consciousness taking such a triple structure of consciousness for real then leads to the unavoidable conclusion that the current m4 framework is too narrow and should be enlarged by adding at least two dimensions to it. the need for such an enlargement from m4 to a v6 space, where the letter ‘v’ stands for verity or virtual, is already obvious in physics where general relativity is not compatible with quantum physics and is strongly suggested by the conformal invariance of maxwell’s equations.5 this point will be fully developed in a third paper13. another important point that has not been addressed here is the physical nature of the information field. speaking of information without referring to the kind of memory used for storage is obviously not a tenable position from a scientific viewpoint.52 taking for granted the metaphor of the computer, we know that memory is a crucial component for information processing. here, we have proposed to link consciousness to an information field without referring to the kind of memory used for computing. in an annex to this paper, we have recapitulated the main technologies currently used for building memory devices for artificial intelligence design. in biology, we find neurons that can fire (spike of action potential or bit 1) or not (no spike or bit 0). these all-or-nothing pulses are the basic language of the brain supporting a brain-computer metaphor. even, if there are good reasons for criticizing such a metaphor53, all the standard arguments about why the brain might not be a computer are nevertheless rather weak nowadays.54 viewing consciousness as a “secretion” of neural activity, the problem appears to be awfully complex and unsolvable owing to gödel’s incompleteness theorems18 stating that all consistent formal systems, that concern themselves with numbers, contain formulas about those very systems that are undecidable within the systems themselves. as self-reference is key for deriving meaning from elements that in themselves do not have meaning such as strings of bits, symbols, neuronal firing, etc., we are forced, in order to keep coherence, to kick consciousness out of neurons and brain activity as proposed here. it thus emerges in the brain a blind spot, something present but unable to be represented from within the system, which could be called the conscious “self ”.55 but, in contrast with vukadinovic austere conclusion viewing consciousness as a nothingness having no independent existence apart from the brain, we argue that such a necessary blind spot is the door by which supra-consciousness enters the brain.) last but not least, our approach is closely related to eastern traditions emphasizing that consciousness is the ultimate reality and that matter is just “maya” or illusion. amazingly, such a nature consciousness was clearly perceived by the great mathematician henri poincaré, in a paper written in 1906 and added to french editions of his book “science and hypotheses”: “one of the most surprising discoveries that physicists have announced in the last few years is that matter does not exist”.56 recognition of this basic fact is also the reason why defining consciousness is generally perceived as a hard problem.7 as quoted by the cognitive neuroscientist marcel kinsbourne: “what makes any problem hard is that something false but attractive stands in its way”.8 here the thing that is fundamentally wrong but nevertheless quite attractive is obviously the fact that matter and spacetime exists by itself. conclusion to conclude, it should be recognized that from a scientific viewpoint based on the mathematical structure of logics that at least three levels of consciousness have to be distinguished in any discussion about such a concept that can be experimented : a rational consciousness giving an autonomous status to the logical operation of negation, to which no contradiction is possible since a double negation is equivalent to an assertion. rational consciousness finds itself associated to digital information, objectoriented languages at the level of communication, or to thermodynamic entropy in the physical world. a meta-consciousness that admits the existence of contradiction, which allows for double negation to acquire an autonomous status different from the one of the assertion. meta-consciousness is linked to analogic information, to meta-languages carrying meaning in communication, or to cybernetic entropy, also named negentropy, that we can relate to the existence of living systems. a supra-consciousness that does not attribute any specific status to contradiction, which amounts to making the operations of negation and implication equivalent. supra-consciousness, for its part, transcends digital/analogic duality of information, for, at this level, only positive assertions linked by nonlocal causality chains exist. the existence of supra-consciousness is usually ignored in neurosciences but was anticipated by topmost scientists: max planck (theory of quanta), werner heisenberg (matrix mechanics), erwin schrödinger (wave mechanics), eugene wigner (group theory), john a. wheeler (cosmology), henri poincaré (theory of chaos), david bohm (aharonov-bohm effect), albert einstein (theory of relativity) and ernst mach (theory of sensations). we have given here scientific arguments for 52 marc henry, jean-pierre gerbaulet the necessity of using a top-down approach where consciousness generates space/time/matter/energy concepts from an universal stuff named information instead of the usual bottom-up scenario where space/time/matter/ energy secretes consciousness as an emergent property of complex systems. it should be clear that our approach does not claim to be a kind of universal and transcendental truth that cannot be falsifiable by doing experiments. as shown in a third paper,13 it is perfectly possible within the proposed framework to formulate falsifiable assertions after considerations of dynamical aspects of information processing. to do this, we will have to introduce physical mechanisms allowing computing quantitative data that may be checked against welldesigned experiments. it is our hope that the argumentation developed here will be of some help for performing well-designed experiments about the phenomenon of consciousness in a very next future. references 1. j.-p. gerbaulet, m. henry, 2019, substantia, 3(1), 113-118. 2. galileo galilei, mss filza riniccini 21, insertion 19, bibl. naz. cent. di firenze, 1588, pp. 1-29. reprinted in le opere di galileo galilei vol. 9, firenze, 1899, pp. 31-57. 3. galileo galilei (1612), apresso cosimo 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brain, epoché 2018, issue #14. 56. h. poincaré, science and hypothesis: the complete text, chap. 14, bloomsbury academic, london, 2018, p. 163. annex here we describe for readers not familiar with technological aspects of information processing, the main techniques used to build artificial or natural memory devices. in the physical m4 world, information is read or written on a material substrate that could be polycarbonate covered by aluminum for optical disks, a ferromagnetic material for tapes or hard-disks, silicon for memory chips, or a metal-oxide semiconductor for flash memories. in all cases, one have to encode a succession of bits that can be zero (0) or one (1). for optical compact disks, one uses lasers of different wavelengths: λ = 780 nm for cd, λ = 650 nm for dvd and λ = 450 nm for bluray to read and write bits. upon writing, the laser beam etches bumps (called pits) into the plastic surface, a bump representing the number 0 or leave a flat unburned area on the disc, called a land, representing the number 1 forming a continuous spiral of about 3–5 billion pits. the burned polycarbonate is then coated with an aluminum layer that reflects light. upon reading, the laser flashes up onto the shiny side of the cd, with the lands reflecting the laser light straight back (bit 1), while the pits scattering it (no reflection or bit 0). for recordable compact disk (cd-r), there is a layer of dye between the protective polycarbonate and the ref lective aluminum. for writing information, a high-power is used able to heat the disc in order making a tiny black spot on it. upon reading, the laser light is completely absorbed by black spots (bit 0) while hitting unburned areas the laser light reflects straight back (bit 1). such technologies cannot be used to manufacture rewritable compact disks (cd-rw). instead of having a layer of dye, a cd-rw has a layer of metallic alloy aginsbte that can be crystalline and transparent to light (bit 1) or amorphous and opaque blocking light (bit 0). when a laser hits this material, tiny little areas can be changed back and forth between the crystalline and amorphous forms, allowing reading and writing information at will. ferromagnetic materials used in magnetic tapes, magnetic hard drives, and magnetic random access memory can also be used for information storage because they magnetic state can switched between two states using a magnetic field that is generated by electric currents. here, a conductive layer forms a program/erase line for altering the logic value stored in the device. a bit one or a bit zero can be stored in the ferromagnetic region depending upon a direction and a magnitude of current flow through the conductive layer. by contrast memory chips use mosfet transistors made of silicon to store information that is basically a three-terminal device with terminals named as source, gate, and drain. gate voltage controls the flow of current between source and drain. if gate voltage exceeds a particular threshold voltage, a current flows (bit 1) while below if gate voltage is below the threshold; there is no current (bit 0). the drawback is that as soon as the power is turned off, all the transistors revert to their original states—and the memory loses all the information it has stored. to overcome this problem, flash transistors have 54 marc henry, jean-pierre gerbaulet been developed having a second gate (control gate) above the first one (floating gate). oxide layers through which current cannot normally pass separate the two gates. in this state, the transistor is switched off storing a bit zero. but upon application of a positive voltage between the drain and control gate, electrons get pulled in a rush from source to drain. a few also manage to wriggle through the oxide layer by a process called tunneling and get stuck on the floating gate storing a bit one. the electrons will stay there indefinitely, even when the positive voltages are removed and whether there is power supplied to the circuit or not. putting a negative voltage between the drain and the control gate repels the electrons back the way they came, clearing the floating gate and making the transistor store a zero again. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 4(1): 7-22, 2020 firenze university press www.fupress.com/substantia citation: p thyssen, a. ceulemans (2020) particular symmetries: group theory of the periodic system. substantia 4(1): 7-22. doi: 10.13128/substantia-671 received: oct 15, 2019 revised: dec 19, 2019 just accepted online: dec 21, 2019 published: mar 11, 2020 copyright: © 2020 p thyssen, a. ceulemans. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 2532-3997 (online) | doi: 10.13128/substantia-671 research article particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 1 institute of philosophy, ku leuven, kardinaal mercierplein 2, b-3000 leuven, belgium 2 department of chemistry, ku leuven, celestijnenlaan 200f, b-3001 heverlee, belgium *corresponding author: pieter.thyssen@kuleuven.be abstract. to this day, a hundred and fifty years after mendeleev’s discovery, the overal structure of the periodic system remains unaccounted for in quantum-mechanical terms. given this dire situation, a handful of scientists in the 1970s embarked on a quest for the symmetries that lie hidden in the periodic table. their goal was to explain the table’s structure in group-theoretical terms. we argue that this symmetry program required an important paradigm shift in the understanding of the nature of chemical elements. the idea, in essence, consisted of treating the chemical elements, not as particles, but as states of a superparticle. we show that the inspiration for this came from elementary particle physics, and in particular from heisenberg’s suggestion to treat the proton and neutron as different states of the nucleon.we provide a careful study of heisenberg’s last paper on the nature of elementary particles, and explain why the democritean picture of matter no longer applied in modern physics and a platonic symmetry-based picture was called for instead. we show how heisenberg’s platonic philosophy came to dominate the field of elementary particle physics, and how it found its culmination point in gell-mann’s classification of the hadrons in the eightfold way. we argue that it was the success of heisenberg’s approach in elementary particle physics that sparked the group-theoretical approach to the periodic table. we explain how it was applied to the set of chemical elements via a critical examination of the work of the russian mathematician abram ilyich fet  the turkish-american physicist asim orhan barut, before giving some final reflections. keywords. periodic system, group theory, symmetry, elementary particle approach, period doubling, madelung rule. at the heart of chemistry lies the periodic system of chemical elements. since mendeleev’s discovery in 1869 — 150 years ago — the periodic system has figured as the undisputed cornerstone of modern chemistry. no lecture theatre or scientific laboratory is complete without a copy of the periodic table adorning its walls. from time to time, a new chemical element is added to the taxonomic chart. but its overall structure has remained the same ever since it was developed in the 1860s. “such has been the scientific and cultural impact of dmitri mendeleev’s periodic table of the elements that many people assume it is essentially complete”, writes eric scerri in a recent nature 8 pieter thyssen, arnout ceulemans special on the periodic system.1 in reality, however, mendeleev’s iconic chart has remained something of a mystery till the present day. when examining the overall structure of the standard periodic table, two defining features stand out: (1) the organisation of the elements in s-, p-, dand f-blocks which reflects the particular filling order of the orbitals for many-electron systems, and (2) the so-called period doubling — the fact that all periods occur in pairs of equal length, except for the first period. despite the quantum revolution in the 1920s, both of these characteristic features remain in need of explanation. quantum chemistry can predict the states of every individual element, but it has great difficulties in treating the periodic system as a whole. as a result, chemists commonly use the so-called madelung rule to rationalize the orbital filling order and to predict the onset of the s-, p-, dand f-blocks in the periodic table. as a welcome extra, the period doubling emerges as a natural consequence of the madelung rule. but the madelung rule has never been derived from first principles and remains a purely empirical (or lexicographic) rule — a useful mnemonic without quantum mechanical underpinning. in 1969, a century after mendeleev’s discovery, the swedish physicist per-olov löwdin (1916–2000) noted how remarkable it was that “the simple [madelung] rule has not yet been derived from first principles”.2 the quest for an ab initio derivation of the madelung rule came to be known as the löwdin challenge. allen and knight called it the “oldest and largest standing problem in quantum chemistry”.3 many claims to a successful derivation have been published, but all have been dismissed. as a result, the madelung rule has witnessed several critical attempts to bury it once and for all.4 but each time, it has found proponents who have called it back from the grave, and for good reason. the madelung rule, after all, successfully describes the overall architecture of the periodic system. it is this aspect of the madelung rule, in particular, that endows it with explanatory power. it is this aspect also that drew the attention of a 1 scerri (2019). 2 löwdin (1969, 332). 3 allen & knight (2002, 83). 4 for some recent criticisms, see wang & schwarz (2009), schwarz & wang (2010), schwarz & rich (2010) and schwarz (2010). however, as described in thyssen & ceulemans (2017), one really should consider the orbital correlation diagram between two lexicographic orderings: the hydrogenic order and the madelung order. both are limiting cases, with the actual systems lying in between. be that as it may, there is no doubt that the actual ground state configurations of the elements are much closer to the madelung rule than to the hydrogenic rule. handful of group theoreticians in the 1970s, whose work will be the focus of this essay. as so often happens in the history of science, the insight to study the periodic system from a group-theoretical perspective cropped up almost simultaneously at several places in europe and north-america around 1970. the pioneers included the turkish-american physicist asim orhan barut (1926–1994) in boulder (colorado), octavio novaro (1939–2018) in mexico city (mexico), valentin n. ostrovsky (1945–2006) in saintpetersburg (ussr), and abram ilyich fet (1924–2007) in novosibirsk (ussr), each with their respective co-workers.5 in their quest for the symmetries that lie hidden in the periodic system, each of these teams worked independently. their hope was that symmetry might provide a key to the system’s secrets. since no quantum mechanical derivation of the madelung rule was known, an important target of their research became the group-theoretical derivation of the madelung rule. if successful, this project also held the promise of explaining the period doubling in a group-theoretical, rather than quantum mechanical, way. in this essay, we explore some of the attempts to explain the periodic system in group-theoretical terms.6 our focus will be on the contributions by abram ilyich fet and asim orhan barut. we will not discuss the work of octavio novaro and valentin ostrovsky. the reason for this is quite simple. although each team had the same goal in mind — viz. the derivation of the madelung rule and the period doubling — their approaches differed significantly. novaro and ostrovsky took a traditional atomic physics approach, whereas fet and barut adopted an elementary particle approach. let us briefly explain both approaches. historically, when simple quantum systems were studied, such as the hydrogen atom or the harmonic oscillator, the hamiltonians of those systems were exactly known, and their symmetries under various transformations could be directly studied.7 since most of these systems belong to the domain of atomic physics, this was called the atomic physics approach.8 both ostrovsky 5 some key publications are barut (1972a), barut (1972b), novaro & wolf (1971), novaro & berrondo (1972), novaro (1973), novaro (1989), novaro (2006), ostrovsky (2004), ostrovsky (2006), byakov et al. (1976), fet (2010), and fet (2016). for more recent additions to this literature, see kibler (1989) and thyssen & ceulemans (2017). 6 a detailed account of the symmetry groups involved and the current status of the group-theoretical approach is presented in the recent book by thyssen & ceulemans (2017). 7 the hamiltonian of a system corresponds to the sum of the kinetic and potential energies for all the particles in the system, and thereby provides a detailed description of that system. 8 the distinction between the atomic physics approach and the elemen9particular symmetries: group theory of the periodic system (together with demkov) and novaro (together with berrondo) followed this approach when they attempted to construct a hamiltonian for the periodic system.9 coming up with such a hamiltonian, however, proved extremely difficult. this was due, in part, to the fact that no ab initio derivation of the madelung rule existed. both fet and barut therefore felt the need for another approach. they found their inspiration in the recent developments in elementary particle physics, and in particular in the work of the german physicist werner karl heisenberg (1901–1976) and american physicist murray gell-mann (1929–2019). their approach was therefore called the elementary particle approach. the aim of our essay is threefold. first and foremost, to show that the elementary particle approach required an important paradigm shift in the understanding of the nature of chemical elements. as we will demonstrate, the idea, in essence, consisted of treating the chemical elements, not as particles (as in the atomic physics approach), but as states of a superparticle. second, our essay retraces the origin of this paradigm shift via the developments in elementary particle physics in the 1960s and the work of heisenberg, all the way back to plato (428–348 bc). it was heisenberg’s deep respect for plato, after all, that led him to propose treating the proton and neutron, not as elementary particles, but as different states of the nucleon. third, our essay aims to highlight the inevitable tension that the symmetry program created between the formal mathematical treatment and the under-lying physical reality. this becomes particularly clear when comparing the work of fet and barut. outline our essay is structured as follows. in section 1, we briefly introduce the two main characters of our paper: abram ilyich fet and asim orhan barut. in section 2, we provide a careful study of heisenberg’s last paper on the nature of elementary particles. what might feel like a long detour, will turn out crucial to understand the approaches by fet and barut. we explain why according to heisenberg the traditional democritean picture of matter no longer applied to modern physics, and why a platonic symmetry-based picture of matter was called for instead. according to this picture, the elementary particles are only material realizations of certain ‘particular’ symmetries. indeed, according to heisenberg, it tary particle approach was first made by ostrovsky (2006). 9 a typical example is the attempt by ostrovsky and demkov to develop a hamiltonian based on maxwell’s fish eye potential. see demkov & ostrovsky (1972) and also ceulemans & thyssen (2018). was not the particles, but their ‘particular’ symmetries that were truly fundamental. in section 3, we explain what heisenberg precisely meant by this philosophical claim via a brief study of isospin. we also show how heisenberg’s platonic philosophy came to dominate the field of elementary particle physics, and how it found its culmination point in gellmann’s classification of the hadrons in the eightfold way. in section 4, we return to the periodic system. we demonstrate that it was the success of heisenberg’s approach in elementary particle physics that sparked the grouptheoretical approach to the periodic system. in section 5, we show that the history of this approach was marked by the continuous tension between the attraction to beautiful mathematical structures, and the need to keep contact with physical reality. we illustrate this via a critical examination of the work of fet, in comparison to the work of barut. 1. biographical prelude abram ilyich fet abram ilyich fet was a russian mathematician and philosopher. according to his wife, ludmila p. petrovafet, and his colleague rem g. khlebopros, fet “belonged to a particular ‘species of human’ that is becoming extinct today”.10 while he mainly worked in mathematics and physics, he also explored biology, chemistry, economics, history, sociology, psychology, literature, music and the arts. as a dissident of the soviet regime, he got dismissed twice from research institutes. in the years of unemployment, he nevertheless continued to do science on his own, living from casual translations. his interest in the periodic table came through his collaboration in the early 1970s with the acclaimed soviet physicist yuri borisovich rumer (1901–1985). rumer was convinced of the importance of symmetry groups for the natural sciences in general. he studied the symmetries of the genetic code with the help of b. g. konopel’chenko, and the symmetries of elementary particles with fet. the latter work culminated in the publication of a monograph on the theory of unitary symmetry groups.11 having studied the symmetries of biology and physics, rumer and fet decided to embark on a “non-traditional” project, as rumer later phrased it in a letter to the academician m. a. leontovich (1903–1981) in 1973. they would study the symmetries of the periodic sys10 gladky et al. (2015, 283). 11 see rumer & fet (1970). 10 pieter thyssen, arnout ceulemans tem of chemical elements. inspired by gell-mann’s work in elementary particle physics, they decided to apply the same elementary particle approach to the periodic table. their first paper appeared in 1971 in the journal teoreticheskaya i matematicheskaya fizika.12 numerous papers and conference proceedings followed in the ensuing decade as fet continued to develop their initial ideas. in 1984, fet wrote a monograph, entitled symmetry of the chemical elements, which presented a summary of his work on the periodic system. however, his book was only published by the novosibirsk academy in 2010, more than a quarter of a century later, and three years after fet’s passing. in the foreword to fet’s book,  khlebopros explains that fet’s work was edited in 1984 by the siberian publishing department nauka. everything was ready for publishing. even the cover had been approved by the arts council. but all of a sudden the book was withdrawn from publication, and the type matter was decomposed. the reason for this became clear a little later: on 8 october 1986, fet was dismissed from work “due to noncompliance with the position held based on the performance evaluation.” fet, in other words, lacked publications; he did not live to see his reputation vindicated.13 according to the author’s widow, though, fet was fired for reasons which were entirely political and had no relation to science.14 khlebopros suggested that it had to do with fet’s personality: “a talented mathematician and physicist, a very well-educated and intelligent person with a sense of dignity and independence, he was, of course, envied and hated by ungifted science bureaucrats”.15 recently, an english translation of fet’s monograph was published by de gruyter.16 asim orhan barut born in malatya (turkey) in 1926, asim orhan barut studied at the eidgenössische technische hochschule (eth) in zurich (switzerland), where he obtained his under-graduate diploma in 1949 and his phd in 1952.17 after postdoctoral work in theoretical physics at the university of chicago from 1953 to 1954, barut served as an assistant professor at reed college from 1954 to 1955 and at syracuse university from 1956 to 1961. in 1962, barut became a faculty member at the university of colorado (boulder), where he served for 32 12 rumer & fet (1971). 13 see fet (2010). 14 private communication with ludmila p. petrova, january 4, 2011. 15 see fet (2010). 16 fet (2016). 17 scully (1998). years until his untimely death in 1994 at the age of 68. like fet, barut had broad interests which ranged from physics to politics, philosophy and religion.18 but his true love was mathematical physics, and in particular group theory. barut published more than 500 scientific papers, and authored 6 books.19 he was also a devoted teacher and sought-after speaker — “his teaching style was blackboard and chalk” — and he travelled the globe to teach and speak at numerous summer schools and workshops.20 in 1971, barut was the visiting erskine fellow at the university of canterbury in christchurch (new zealand), where he also attended the rutherford centennial symposium on the structure of matter. his stay in new zealand gave rise to two important publications in connection with our topic — the symmetry of the periodic system. the first one was a small booklet which contained the notes of his lectures as erskine fellow on “dynamical groups and generalized symmetries in quantum theory”. the second one was his contribution to the proceedings of the rutherford centennial symposium on the “group structure of the periodic system”.21 there are important similarities but also crucial differences in the works of fet and barut. as we already mentioned in the introduction, both fet and barut were greatly inspired by heisenberg’s and gellmann’s achievements in elementary particle physics, and both wondered to what extent the elementary particle approach could be applied to the periodic system. the key to this approach, as we will argue, was a radical revision of the nature of the chemical elements. fet and barut were forced to treat the element, not as composite particles, but as states of a superparticle. in order to fully grasp the need for this paradigm shift, we will have to consider the works of heisenberg and gell-mann. this will be done in sections 2 and 3. we will turn to the contributions of fet and barut in sections 4 and 5. it is also here that the differences between both will begin to shine through. fet occupied a position at the mathematical end of the spectrum, whereas barut’s position was more balanced between mathematics and physics. 2. heisenberg’s platonic philosophy heisenberg’s last paper was published posthumously.22 it was devoted to the nature of elementary parti18 dowling (1998). 19 on top of that, he also co-edited another 25 books. 20 scully (1998). 21 see barut (1972a) and barut (1972b). 22 heisenberg passed away on 1 february 1976; his paper appeared in 11particular symmetries: group theory of the periodic system cles. the question “what is an elementary particle?” had haunted heisenberg for most of his scientific career. according to heisenberg, “certain erroneous developments in particle theory […] are caused by a misconception by some physicists that it is possible to avoid philosophical arguments altogether.” “starting with poor philosophy”, heisenberg continued, “they pose the wrong questions.” as we intend to show in this section, heisenberg had come to the conviction that the traditional democritean picture of matter no longer applied, and that it had to be replaced by a platonic one.23 the idea that “in the beginning was the particle”, in other words, had to be replaced by “in the beginning was symmetry”.24 in the beginning was the particle for over 2500 years, scientists and philosophers have pondered what would happen if one continued to divide matter into ever smaller constituents. would this process go on ad infinitum or would one reach a point where no further division was possible? is matter continuous or discrete? different (reductionist) answers were offered by different pre-socratic philosophers. the material monists (thales, anaximander and anaximenes) thought that matter was composed of a single material substance. the material pluralist empedocles, on the other hand, claimed that all matter was composed of four roots: fire, air, earth and water.25 it was plato who first referred to these roots as στοιχειον (stoicheion or elements) in his major cosmological dialogue timaeus, and who associated the four classical elements with the platonic solids. however, according to heisenberg, the best-known answer to the above questions was given by the prethe march edition of the journal physics today. see heisenberg (1976a). it was based on a translation of his opening lecture to the german physical society’s spring meeting, given on 5 march 1975. the original version of his talk was published in the february 1976 issue of naturwissenschaften. see heisenberg (1976b). 23 the materialistic interpretation of democritus’ atomic theory is due to aristotle. democritus himself thought of the atoms as immaterial entities, in full agreement with plato’s ideas. in that sense, heisenberg’s conviction to replace particles with symmetry principles was not in reaction to a democritean picture of matter, but rather to the aristotelian view of atomic theory. however, since our aim is historical (rather than philosophical) accuracy, we will keep with heisenberg’s terminology when representing his ideas on the nature of elementary particles. 24 heisenberg (1976a), quotations on p. 32. 25 aristotle later added a fifth element to this list of earthly and corruptible elements. the aether or quintessence (quinta essentia) was a heavenly substance and formed the constituent of all the stars and planets in the universe. socratic philosopher democritus.26 democritus (like his teacher leucippus) was a materialist who postulated that all matter was ultimately composed of atoms — small, (physically) indivisible, immutable and indestructible units of matter. indeed, the greek word ατομον (atomon) literally means “indivisible” or “uncuttable”. the philosophical atoms of democritus were too small for us to see, and came in a variety of shapes and sizes. they were infinite in number and in constant motion, colliding with each other in an otherwise empty vacuum (or void).27 plato’s pluralistic doctrine was very different from democritus’ atomistic doctrine, and despite plato’s influence at the time, it was democritus who emerged victoriously in the long run. in heisenberg’s opinion, “the strongest influence on the physics and chemistry of the last century undoubtedly came from the atomism of democritos”.28 bertrand russell, in his history of western philosophy, concurred that the atomistic doctrine of leucippus and democritus “was remarkably like that of modern science”.29 indeed, in the 18th-century, john dalton (1766–1844) proposed that each chemical element is composed of a unique type of atom with characteristic atomic weight.30 like the philosophical atoms of democritus, dalton’s chemical atoms could not be created, nor divided into smaller constituents or destroyed during chemical processes.31 the growing particle zoo for nearly one century, the chemical atoms were thought to be the smallest possible units of matter. however, with the discovery of the electron by sir joseph john thomson (1856–1940) in 1897, it became apparent that dalton’s atoms were not elementary after all. after the discoveries of the proton in 1917 and the neutron in 1932, the rutherford–bohr model of the atom was proposed with a central atomic nucleus of positively charged protons (p+) and neutral neutrons (n0), surrounded by a cloud of negatively charged electrons (e-). despite their revolutionary character, these discoveries did not put into question the atomism of democritus. on the contrary, “the electron, the proton and pos26 heisenberg (1976a). 27 the atomistic doctrine of democritus was further refined by epicurus and popularised by the roman poet lucretius in the first-century bc in his poem de rerum natura (the nature of things). see lucretius (2007). 28 heisenberg (1976a, 37). 29 russell (1946, 84). 30 dalton (1808). 31 chalmers (2009). 12 pieter thyssen, arnout ceulemans sibly the neutron could, it seemed, be considered as the genuine atoms, the indivisible building blocks, of matter”, dixit heisenberg.32 the idea thus originated that all matter is ultimately composed of three fundamental particles: protons, neutrons and electrons. since they seemed immutable, and their number was therefore fixed, physicists called them elementary particles. the elementary particles of modern physics became the modern analogue of the philosophical atoms of democritus. this sparse ontology came to an abrupt end in 1947 with the discovery of pions by cecil powell (1903–1969) in cosmic ray experiments. the pions (π+, π0 and π-), moreover, were observed to disintegrate into yet another class of particles, muons (μ+, μ0 and μ-). for example: π+ → μ+ + ν the situation only worsened with the construction of particle accelerators. by accelerating particles to tremendous velocities, and forcing them into head-on-collisions, a plethora of new particles were discovered in the 1950s. among these were the kaons (k+, k-, k0 and k̄0), the lambda particle (λ0), the sigma particles (σ+, σ0 and σ-, as well as σ*+, σ*0 and σ*-), the xi particles (ξ0, ξ-, ξ*0 and ξ*-) and the delta particles (δ++, δ+, δ0 and δ-). in the early 1940s, the universe was a simple place, composed of only three fundamental particles. by the early 1960s, the universe had turned unfathomably complicated, with over 30 “fundamental” particles. the parsimonious ontology of the 1940s, in other words, had given way to a baroque ontology in the 1960s, in seeming contradiction with occam’s well-known razor. as we shall see, an entirely new way of looking at the elementary particles was needed before order could be restored in the growing particle zoo. the loss of elementarity for heisenberg, the discovery of the particle zoo was ample evidence that the materialistic picture no longer applied in modern physics. “in the physics of elementary particles of our time,” wrote heisenberg, “good physics has sometimes been unconsciously spoiled by poor philosophy” — referring to the atomistic doctrine of democritus.33 the problem according to heisenberg was not that physicists were now forced to take these 30 odd particles as elementary. on the contrary, the problem was 32 heisenberg (1976a, 37). 33 heisenberg (1976a, 37). that their elementary nature was called into question by recent experimental findings. for example, when an electron (e-) and a positron (e+) collide at low energy, they annihilate, producing two gamma-ray photons (γ): e+ e+ → γ + γ the reverse reaction, electron-positron creation, also occurs. here, a high energy photon is converted into an electron-positron pair: γ → e+ e+ clearly then, electrons and positrons are not immutable. they can be created and annihilated. “they are not “elementary” in the original meaning of the word”, wrote heisenberg.34 another example of the breakdown of the materialistic picture is provided by radioactive βdecay, such as the decay of carbon-14 into nitrogen-14. in order to change the parent nuclide 614c into the daughter nuclide 7 14n (a process known as nuclear transmutation), a neutron must be converted into a proton. due to the conservation of electric charge and lepton number, this must be accompanied by the emission of an electron and an electron antineutrino (ν̄e): 6 14c → 714n + e+ ν̄e generalising, βdecay always involves the transmutation of a neutron into a proton: n0 → p+ + e+ ν̄e the reverse process is observed in β+ decay (or positron emission), with a proton turning into a neutron: p+ → n0 + e+ + νe clearly then, protons and neutrons are not immutable. they can be transmuted into one another. no particle is more elementary than the other one. what these, and other empirical findings, showed according to heisenberg, was that the question “what do these particles consist of?” had become meaningless. after all, from the point of view of βdecay, one might (naively) consider the neutron to be a compound particle, consisting of a proton, an electron and an electron antineutrino. but from the point of view of β+ decay, it is 34 heisenberg (1976a, 32). 13particular symmetries: group theory of the periodic system not the neutron, but the proton that is compound, consisting of a neutron, a positron and an electron neutrino. “experimentally, the concept of “dividing” had lost its meaning”, blurted heisenberg. in heisenberg’s opinion, this fading of the distinction between elementary particles and compound particles was probably “the most important experimental result of the last fifty years”.35 plato and that sort of thing since the materialistic picture of matter no longer applied in modern physics, a paradigm shift was called for. according to heisenberg, “if we wish to compare the results of present-day particle physics with any of the old philosophies, the philosophy of plato appears to be the most adequate”.36 heisenberg had a deep love and appreciation for plato. according to david peat, “his scientific attitudes reflect a debt to philosophy and in particular his respect for plato.” heisenberg concurred that “my mind was formed by studying philosophy, plato and that sort of thing”.37 heisenberg’s father, august heisenberg (1869–1930), was a scholar of ancient greek philology and modern greek literature; he became a professor of philology at the university of munich in 1910 when heisenberg was nine years old. in 1911, the young heisenberg entered the maximilians-gymnasium. at that time, it was still common practice to place more emphasis upon classical greek and latin than on the sciences and mathematics. all of this contributed to heisenberg’s classical-humanistic education. in his teenage years, as a result of the political turmoil in munich after the first world war,38 the young heisenberg became part of the cavalry rifle command no.  11. their headquarters were located in the theological training college, opposite the university. heisenberg often retired to the roof of the college with a greek school edition of plato’s dialogues. “there, lying in the wide gutter, and warmed by the rays of the early morning sun,” heisenberg later recalled, “i could pursue my studies in peace.” it was there, in the spring of 1919, that heisenberg first read plato’s cosmological treatise, the timaeus.39 35 heisenberg (1976a), quotations on p. 33. 36 heisenberg (1976a, 38). 37 see peat (1996, 3) and heisenberg (1996, 6). 38 specifically, the rise and fall of the bavarian soviet republic in munich during the german revolution of 1918–1919. 39 heisenberg (1971, 8). platonic solids in the timaeus plato believed the universe had been created out of chaos by a demiurge using the four elements — fire, air, earth, and water — as basic building blocks.40 plato associated each of these elements with one of the five platonic solids. the element fire was thus identified with the pointy tetrahedron; air with the smooth octahedron; earth with the bulky and weighty cube; and water with the fluid and nearly spherical icosahedron (figure 1).41 empedocles, who first introduced the four elements, believed the elements could be mixed in various proportions but were themselves immutable and indestructible. what makes plato’s “theory of everything” so exciting is that the elements are no longer elementary. each regular polyhedron, after all, is constructed from regular polygons. the tetrahedron, octahedron and icosahedron are built from (respectively 4, 8 and 20) equilateral triangles; the cube (or hexahedron) is built from 6 squares. the elements can therefore be broken down into triangles and squares and recombined to create new elements.42 for example, two particles of fire can be broken down into 8 equilateral triangles and recombined to form one particle of air: fire + fire → air 4 4 8 likewise, a particle of water, consisting of 20 triangles, can transmute into five particles of fire, or two particles of air and one of fire: 40 see plato (1976). 41 the fifth platonic solid, the dodecahedron, was used for the universe as a whole. aristotle later conjectured that it represented the aether which made up the celestial heavens. 42 plato (1976, 1259). 1. 2. 3. 4. 5. figure 1. the platonic solids: 1.  tetrahedron; 2.  octahedron; 3.  cube (or hexahedron); 4. dodecahedron; and 5. icosahedron. 14 pieter thyssen, arnout ceulemans water → 5×fire 20 (5×4) notice though that since earth is made up from squares, it cannot be transmuted into any of the other elements. these elemental transmutations resemble the ones described above for elementary particles. in the beginning was symmetry to heisenberg, “the whole thing seemed to be wild speculation []. it saddened me to find a philosopher of plato’s critical acumen succumbing to such fancies.” yet one aspect of plato’s account captured his imagination. “i was enthralled by the idea that the smallest particles of matter must reduce to some mathematical form,” wrote heisenberg. in his opinion, “the elementary particles in plato’s timaeus are finally not substance but mathematical forms”.43 what is more, these mathematical forms — triangles and squares, and the platonic solids they make up — are highly symmetrical. what is fundamental, in other words, are not the material particles themselves, but the mathematical symmetries underlying them. this platonic way of thinking moreover seemed applicable to modern physics. according to heisenberg, “our elementary particles are comparable to the regular bodies of plato’s timaeus”.44 as heisenberg explained: so far we had always believed in the doctrine of democritus, which can be summarised by: “in the beginning was the particle.” we had assumed that visible matter was composed of smaller units, and that, if only we divided these long enough, we should arrive at the smallest units, which democritus had called “atoms” and which modern physicists called “elementary particles.” but perhaps this entire approach has been mistaken. perhaps there was no such thing as an indivisible particle. [] in the beginning was symmetry!45 according to heisenberg, it was not the elementary particles, but the symmetries that lie beyond them, that are truly fundamental. the elementary particles are but material realizations of these underlying symmetries.46 one eloquent model of such ‘particular symmetries’ will be presented in the next section. 43 heisenberg (1971), quotations on p. 8. 44 heisenberg (1971, 241). 45 heisenberg (1971, 133). 46 see also peat (1987). 3. the symmetry of elementary particles in order to make heisenberg’s position more concrete, we will briefly look at the example of isospin. after all, the concept of isospin was introduced in 1932 by heisenberg himself, soon after the discovery of the neutron by sir james chadwick (1891–1974) that same year. protons and neutrons are sometimes called nucleonic particles because they are the components of atomic nuclei. despite their difference in electric charge, the proton and neutron are nearly identical in all other respects. both are fermions, and both have almost the same mass.47 heisenberg was baffled by this consanguinity, and intent on uncovering the reason for it. when two or more particles have the same mass (or energy), they are said to be degenerate. degeneracies are a tell-tale sign that there is a symmetry lurking in the background. symmetry is all about the interplay between change and permanence; it is about the quest for permanence in a world of constant flux. more precisely, an object is said to be symmetric when there is a transformation (change) that leaves certain aspects of the object fixed (permanence). rotating a ball around its centre, for example, leaves its overall appearance unchanged. hence, the ball is said to be spherically symmetric. the same applies to the nucleonic particles. if someone were to exchange a proton for a neutron — as we saw happens during β decay — it would be practically impossible to tell, given their similarity in mass. indeed, the strong interaction force cannot, as a matter of fact, distinguish protons from neutrons.48 in view of all this, heisenberg suggested treating the proton and neutron, not as two distinct elementary particles, but as two possible states of one and the same particle, which he called the nucleon. heisenberg did not have to look far to find an equivalent quantum system that also appears in two possible states. since the so-called stern–gerlach experiment, it was known that the electron has a spin, which can adopt two states, commonly denoted as spin up |↑⟩ and spin down |↓⟩.49 in the same way, heisenberg proposed the nucleon has an isospin, which can adopt two states, denoted as |p+⟩ and |n0⟩. both spin and isospin are characterised by the same symmetry group: the special unitary group of degree 2, or su(2) group. the su(2) group is an example of a 47 to be specific, mp+ = 938.272046 mev/c2, and mn0 = 939.565378 mev/c2. fermions are particles that obey fermi–dirac statistics, as opposed to bosons which obey bose–einstein statistics. 48 it is only the (weaker) electromagnetic force that makes the distinction on the basis of their difference in charge. 49 gerlach & stern (1922). 15particular symmetries: group theory of the periodic system lie group, named after the norwegian mathematician sophus lie (1842–1899).50 let us only note here that the fundamental representation of su(2) is a doublet. the spin up and spin down states of the electron form an su(2) spin doublet; the proton and neutron form an su(2) isospin doublet. it is here that heisenberg crossed the conceptual line between particles and states. on the one side are two nucleonic particles that are clearly related to each other as they have nearly the same mass. on the other side are the two degenerate states of a spin system that is described by the su(2) group. the connection consists in associating the two nucleons (particles) with the two components (states) of the su(2) doublet. this was perhaps the first time that such a connection was made. it predates the discovery by gell-mann (and others) of the su(3) symmetry of hadronic matter — to be discussed in the next section — by more than three decades. above all, it offers support to heisenberg’s conviction that symmetries are more fundamental than particles. with the help of heisenberg’s isospin, all elementary particles can be assigned into isospin multiplets. the pions π+, π0 and π-, for instance, are assigned to an isospin triplet, as are the sigma particles σ+, σ0 and σ-. the delta particles δ++, δ+, δ0 and δform an isospin quartet; the xi particles ξand ξ0 constitute an isospin doublet, and the lambda particle λ0 an isospin singlet. from the su(2) symmetry point of view, particles within a multiplet are identical. just as the spherical symmetry of a ball allows one to rotate one orientation into another, the su(2) symmetry allows one to transform the particles of an isospin multiplet into one another. the eightfold way the american physicist murray gell-mann (1929– 2019) took heisenberg’s idea a step further in the 1950s and 1960s. for reasons which are beyond the scope of this article, gell-mann introduced a new quantum number, which went by the name of strangeness, and was denoted s. the proton and neutron, for example, were assigned strangeness s = 0; the sigma and lambda particles s = -1, and the xi particles s = -2. gell-mann subsequently ordered the particles on the basis of their isospin component t3 and strangeness s. this process is illustrated in figure 2 for the baryons 50 a full account of the su(2) group (and the others to follow) is given in thyssen & ceulemans (2017). n0, p+, σ-, σ0, σ+, λ0, ξand ξ0.51 the result is an octet of particles, with six particles at the corners of a regular hexagon, and two more particles at the centre. inspired by the eightfold path of buddhism, gell-mann named his classification scheme the eightfold way.52 particles along the same horizontal line in figure 2 form the familiar isospin multiplets. on the upper line, we have the proton-neutron doublet; on the lower line the xi doublet, and on the middle line the sigma triplet superposed with the lambda singlet. gell-mann realised that the eightfold way pointed at a hidden symmetry. just as the isospin multiplets are representations of the su(2) group, the baryon octet is a representation of the larger su(3) group. indeed, from the su(3) symmetry point of view, the baryons are no longer treated as distinct particles. instead, they are taken to be the states of a superparticle. this implies that the members of the baryon octet can be transformed into one another. as a result, the strong force cannot distinguish them. the interchange of one baryon for another goes unnoticed in strong interactions. broken symmetry from the su(2) point of view, the proton and neutron are identical; they appear as two faces of the same nucleonic coin. hence, in order to tell them apart, the su(2) symmetry has to be broken. this is done by imposing the quantisation of the charge operator, which 51 the name “baryon” refers to the greek word βαρύς for “heavy”. 52 see gell-mann & ne’eman (2000). +1 -1 t3 y +½ -½ +1-1 +½-½s = -1 s = 0 s = -2 q = -1 q = 0 q = +1 p+n0 σ0σ +σ ξξ0 0λ figure 2. the baryon octet. 16 pieter thyssen, arnout ceulemans breaks the su(2) symmetry to the u(1) symmetry. it is only at that point that the proton and neutron regain their identities, and that one can meaningfully distinguish them. the same principle applies to gell-mann’s eightfold way. from the su(3) point of view, all baryons are identical. hence, in order to tell them apart, the su(3) symmetry has to be broken. as a first step, the su(3) symmetry can be broken to the su(2) symmetry. the su(3) octet is then split into the familiar su(2) submultiplets: the nucleon doublet, sigma triplet, lambda singlet and xi doublet (indicated by the horizontal lines in figure 2). from that point onwards, particles from different isospin multiplets can no longer be transmuted into one another; they are no longer identical. this series of symmetry breakings is typically represented by a chain of subgroups: su(3) ⊃ su(2) ⊃ u(1) the importance of symmetry breaking cannot be overstated. as the world unfolds, and the phenomena take place, the initial ideal symmetries break down, and only remnants remain, as with plato’s ideals. according to most physicists today, it is the breaking of symmetry that makes the world an interesting and variegated place to live in. as the french physicist pierre curie appropriately said: “c’est la dissymétrie qui crée le phénomène”.53 with the eightfold way, the zoo of particles was finally classified, and order was restored to the world of elementary particles. most importantly, when gellmann drew up his classification schemes, some seats remained unoccupied, hinting at the existence of as yet undiscovered particles. like mendeleev a century earlier, gell-mann predicted the existence of the eta meson (η0) and the omega baryon (ω-), which were discovered soon afterwards. such was the predictive force of symmetry. “i was playing around with the particles. [mendeleev] was playing around with the elements,” said gell-mann in 1997.54 “it was natural to make a comparison between them, although i think mendeleev’s work was much more important.” gell-mann was ultimately awarded the nobel prize in 1969, a century after mendeleev’s development of the periodic table. the key to these revolutionary developments in elementary particle physics was the move from materialism to idealism. as heisenberg explained, symmetries are ontologically prior to particles. symmetries represent the 53 curie (1894, 127). 54 quoted from an interview between gell-mann and the former editorin-chief of science news, tom siegfried on september 16, 1997 in santa fe, new mexico. see also siegfried (2002). fundamental level of reality, whereas particles only constitute a secondary level of reality. the elementary particles, after all, only emerge from these symmetries by a series of symmetry breaking steps, and therefore have a derivative status. 4. the symmetry of chemical elements it did not take long before the same group-theoretical approach was applied to the zoo of chemical elements. the situation with the periodic system in the 1970s, after all, resembled the one in elementary particle physics in the 1950s. as we explained in sections 2 and 3, when the zoo of elementary particles was discovered, their internal dynamics were still shrouded in mist.55 the exact hamiltonian for these hadronic systems was not known, and another approach was called for. instead of inferring the symmetry group of the system from the behaviour of the hamiltonian under various operations, the symmetry group was simply postulated on the basis of the known empirical data and phenomenology of particle reactions. that is, instead of adopting an atomic physics approach, heisenberg and fet opted for a phenomenological elementary particle approach. the goal of fet and barut was to apply the same phenomenological approach to the periodic system. after all, despite the developments in quantum mechanics and computational chemistry, the internal dynamics of many-electron systems was also still shrouded in mist. both fet and barut therefore took the structure of the periodic system as empirical input and looked for a particular symmetry group that could explain this data.56 not surprisingly, the key to their approach was once again the move from democritus to plato, which required a radical revision of the nature of chemical elements, as we now intend to explain. the nature of chemical elements heisenberg did not treat the proton and neutron as distinct particles, but as distinct states of one superparticle: the nucleon.57 in a similar vein, fet and barut did not treat the chemical elements as distinct elements, but as distinct states of a superparticle, which was later named the baruton in honour of barut for his contri55 quantum chromodynamics was only developed in the 1970s. 56 to be specific, the empirical data consisted of the various period lengths which were assumed to be the dimensions of the various multiplets of the symmetry group. 57 gell-mann similarly treated the baryons, not as distinct particles, but as distinct states of some baryonic matter. 17particular symmetries: group theory of the periodic system butions to the symmetries of the periodic system.58 the chemical elements, in other words, were no longer treated as concrete, physical particles with an internal substructure. the structural conception of the atom was thus excluded from the consideration of these group theoreticians. this had at least two crucial advantages. first, by treating the chemical elements as states of a single quantum system, the periodic system was being studied as a whole. contrast this with the atomic physics approach, where each element was treated as a separate quantum system. second, by stripping the atoms from their physical content, the link with quantum mechanics was entirely lost. what remained, was an abstract ‘group-theoretical’ atom, a structureless non-composite entity, without internal dynamics. fet and colleagues, for example, emphasised that their approach was “not a theory of electronic shells”.59 as a result, there was no mention of electronic configurations, orbitals or quantum numbers. by ignoring the internal substructure of the elements, fet and barut could thus circumvent the traditional quantum mechanical challenges, such as the löwdin challenge referred to in the introduction. yet another advantage of the elementary particle approach can be mentioned. heisenberg and gell-mann did not know of the possible substructure of the elementary particles when they studied their symmetries. yet, the eightfold way did pave the way towards the discovery of quarks, the constituents of all elementary particles.60 both fet and barut wondered whether a group-theoretical study of the periodic system might similarly pave the way to a deeper understanding of the substructure of the elements and new insights in the internal (quantum) dynamics of many-electron systems. fet was well aware of these advantages, and mentioned them on more than one occasion. interestingly, he also referred to the work of barut and novaro and made an important remark about the difference with his own work: these authors, in his opinion, considered “the symmetry developed as a symmetry of the electron shells only, not distinguishing it from the bohr model”.61 in contrast, in his own perspective the atom system was considered as 58 wulfman (1978). 59 byakov et al. (1976, 3). 60 it is telling that heisenberg, as a true platonist, remained extremely skeptical about the possible existence of quarks, as this seemed to herald back the democritean materialism. for him, the quark hypothesis was perhaps useful as a mathematical tool, but it certainly did not provide a picture of reality. “even if quarks should be found (and i do not believe that they will be),” said heisenberg, “they will not be more elementary than other particles, since a quark could be considered as consisting of two quarks and one anti-quark, and so on.” quoted from peat (1987). 61 fet (2010, 154). a whole.62 later on, he repeated this claim by stressing the novelty of his approach in the most explicit terms: we’ d like to point out again the most important distinct feature of the theory suggested: while the bohr model considers one element as a separate quantum system (and the atomic number is included in the theory as a parameter, so the number of quantum systems is the same as the number of elements), our model considers the atoms of all possible elements as the states of a unified quantum system, linkable to each other by symmetry group action.63 despite these claims, it is difficult to maintain that there is a fundamental difference with the perspective in barut’s work, who explicitly asked in his rutherford lecture: “are there (global) quantum numbers which would characterize the elements as different ‘states’ of a single system? all elements would then constitute a single ‘multiplet’.” barut then expressed the atomic numbers, not as parameters, but as functions of these quantum numbers.64 the symmetry group of the periodic system having thus introduced the baruton, whose states are the chemical elements, the primary challenge for fet and barut was to find the symmetry of the baruton (just like heisenberg had identified the su(2) group as the symmetry of the nucleon, and gell-mann the su(3) group as the symmetry of the eightfold way). the principal key turned out to be the hydrogen atom. the symmetries of the hydrogen atom were wellknown. fock had shown that the hydrogen atom possesses rotational symmetry not only in three dimensions but also in four. this rotational symmetry was described by the special orthogonal group in 4 dimensions, also known as the fock group or so(4) group. as a result, all the hydrogen orbitals of fixed were grouped in so(4) multiplets of dimension n2.65 the ultimate goal, however, was to treat the entire set of hydrogen orbitals, regardless of their principal quantum number n, as a single symmetric object. this called for a so-called covering group which would contain the so(4) group as a subgroup. the orbitals would then form a single infinite-dimensional multiplet of this covering group. it was only in the sixties of the previous century that this goal was achieved. one of the first proposals came 62 see also kibler (2018). 63 fet (2010, 155). 64 see barut (1972a), quotation on p. 84. 65 see fock (1935). 18 pieter thyssen, arnout ceulemans from barut in 1964. he found an extension of the fock group, known as so(4,1), which was able to pack all the discrete states of hydrogen into one infinite-dimensional multiplet.66 within a year, two young doctoral students (classmates and childhood friends) in moscow, ilya a.  malkin and vladimir ivanovich man’ko (°1940), took this idea a bit further and extended the group to so(4,2).67 the so(4,2) group  describes the  conformal  or scaling transformations of  spacetime.  in a later development barut and haugen  considered a further extension  to scale trans-formations of mass and charge.68 this yields a theoretical framework that incorporates the maxwell equations, and ultimately the photon. the so(4,2) group is thereby enlarged to the  inhomogeneous  conformal group io(4,2) with 21 parameters. however  the physical significance  of these conformal generators remains a recurrent matter of debate.69 all of these groups are called conformal symmetries. from the so(4,2) symmetry point of view, any hydrogen orbital can be transformed into any other orbital. but the so(4,2) group also provided an excellent starting point for the group-theoretical study of the periodic system. since the chemical elements could be labelled by the same set of four quantum numbers as were used to describe the hydrogen orbitals, the so(4,2) group served as an ideal candidate to describe the symmetry of the baruton. both fet and barut recognised the conformal symmetry of hydrogen as the master equation from which to start. from the so(4,2) symmetry point of view, all chemical elements are identical. the so(4,2) group, in other words, can transmute any chemical element into any other. it can be compared with the philosophers’ stone, although the transformations induced by the conformal group are of course not physical but merely mathematical. in order to distinguish the chemical elements, the so(4,2) symmetry has to be broken. it is only by shattering the so(4,2) group that the elements regain their identities. the next challenge therefore was to find a proper symmetry breaking that would explain the ordering of the elements in the periodic system. it is here that the real differences between the treatments of fet and barut became clear as both proposed a different symmetry breaking chain. as we will explain in the next section, fet’s approach occupied a position at the mathematical end of the spectrum, whereas barut’s approach retained the link with physics and chemistry to a larger extent. 66 barut et al. (1965). 67 malkin & man’ko (1966). 68 barut & haugen (1972). 69 jaekel & reynaud (1998). 5. the madelung rule and period doubling we evaluate fet’s proposal, as it was described in his monograph on the symmetry of the chemical elements.70 several introductory chapters of fet’s book are devoted to the construction of the conformal so(4,2) group for the hydrogen system. in chapter 4, fet devoted an extensive discussion to the concept of isospin. fet had a special interest in representing this example, since later on the su(2) group would have to come to his rescue, when he was struggling with the period doubling in the periodic table. of importance at present are chapter 5 and 6. in chapter 5, fet exposed his views on the symmetry of the periodic table. in chapter 6, he confronted his views with chemical evidence. in chapter 5, fet first explained the conformal symmetry and then also introduced the madelung rule as an observation of the basic regularity in the periodic table. both fet and barut agreed that the madelung rule offered the most concise explanation of the periodicity. following this rule, one could regroup the elements of the periodic table in subsets, with the same n and l, and insert these in an (n,l) matrix. the madelung rule traces a zigzag path through this matrix, which guided both barut and fet. in doing so, they observed a distinctive feature of the periodic table, namely that it seems to consist of two separate twin tables. this is the wellknown period doubling. the difference between both is the parity of n + l. but here, the treatments of fet and barut diverged. barut solved the riddle of the period doubling by considering a symmetry breaking from so(4,2) to so(3,2). he had studied this group chain earlier with bohm in a study on hadronic matter and found that the mother representation of so(4,2) splits into two identical representations of so(3,2).71 note that there are no quantum characteristics that discriminate these two subgroup representations. as far as so(3,2) is concerned, they have the same symmetry. they are distinguished in odd and even according to the parity of n + l, but we do not have a symmetry operator in the model to determine this parity. here appears a critical turning point in fet’s work, which characterises the author as a mathematician of one piece, not willing to compromise on a matter of principle. fet reminded the reader that the l quantum number is not really a quantum number, in the sense that it does not correspond to an eigenvalue of 70 our present analysis of fet’s book is based on a personal copy, which was given to us by fet’s widow. the manuscript was translated for us by jewgienij liszczuk., see fet (2016). 71 barut & bohm (1970). 19particular symmetries: group theory of the periodic system an operator of the enveloping algebra. it only serves for the development of the square of the total angular momentum which is given as l(l + 1), and so this value is always even. in the eyes of fet, the unavoidable consequence was that the n + l sum of the madelung rule had no group sense. no compromise was possible: “that is why from the view of the elements group description, the n + l number should not be included in the ‘lexicographic rule’ formulation. therefore we should replace the madelung indexing by another one, which would also logically describe the properties of the elements, but which would be free from this disadvantageous feature”.72 fet concluded that there are thus two separate periodic tables, each of which follows a hydrogen sequence and must thus be described as so(4,2), but with n and l redefined. for the odd sequence, instead of the quantum number v, he defined a pseudo principal quantum number as: ν = 1/2 (n + l + 1) the odd sequences are then mapped onto the new as follows: 1s → 1s 2p 3s → 2p 2s 3d 4p 5s → 3d 3p 3s 4f 5d 6p 7s → 4f 4d 4p 4s hence this sequence has become a perfect so(4,2) representation again. likewise, for the even sequence, one has to apply ν = 1/2 (n + l) which will turn the even sequence in an equivalent system: 2s → 1s 3p 4s → 2p 2s 4d 5p 6s → 3d 3p 3s 5f 6d 7p 8s → 4f 4d 4p 4s these two tables are like heisenberg’s nucleonic matter, forming the states of a spin-like doublet. the resulting symmetry group is the combination of both symmetries. in mathematical terms, this corresponds to the product of an so(4,2) like group and an isospin-like group: su(2) ⊗ so(4,2). 72 fet (2010, 177). in light of barut’s alternative, fet’s proposal appears artificial. it is true that there is no proper operator for l in the so(4,2) group, but the symmetry breaking from so(4,2) to so(3,2) generates exactly the doubling that is observed. indeed, in this process only operators which either preserve n + l or change n + l by two units are possible. so this group preserves the parity of the sum and is thus the perfect rationale for the existence of an odd and an even half of the periodic table. this is a valuable insight which we owe to barut. fet was aware of barut’s rutherford lecture, but he missed the point of the argument.73 the crucial point of the doubling is not the individual value of l, nor n, but only the parity of their sum. and clearly, this is the property that is conserved in so(3,2). later in the chapter, fet also took into account the spin quantum number of the electron, which allowed all orbitals to be occupied by two electrons. so this was a further doubling, requiring an extra su(2) group. however, this group was not an artificial construct but simply the true spinor characteristic. t treatment which then followed, however, was quite remarkable again, since fet combined the spin quantum number 1/2 with the angular momentum l, thus dividing the 4l + 2 elements of every manifold into two submanifolds with respectively 2l and 2l + 2 elements. in physical terms, this means that every manifold (except for l = 0) is divided into two spin-orbit levels: a lower one with j = l 1/2, and an upper one with j = l + 1/2. this is at odds with the quantum mechanical description of the elements, which certainly indicates that for the lighter elements spin-orbit coupling is not ruling the ground state terms. the chemical data chapter 6 displayed chemical data to strengthen fet’s case. he took as an example the ionisation potential of the main group elements from boron to neon. according to fet’s claim, this graph should consist of two different trends: one corresponding to the spinorbit doublet {b, c}, and another one for the spin-orbit quartet {n, o, f, ne}. the data were plotted in a way to emphasise the existence of two separate parts, with a dashed border line in between.74 nonetheless, this way of drawing the graph was unable to hide that no distinction of the kind is at stake. indeed, there is a linear increase from boron to nitrogen; the break does not occur between carbon and nitrogen, but between nitrogen and oxygen. the reason for this is 73 see barut (1972a). 74 see fet (2010, 194). 20 pieter thyssen, arnout ceulemans perfectly clear. it is due to electronic repulsion: in nitrogen, the 2p shell is half-occupied, with three electrons nicely distributed in space, at a maximal distance of each other. in oxygen, the nuclear charge increases so all 2p valence electrons are expected to feel an increased charge, and it would be more difficult to ionise them. on the other hand, one cannot avoid occupying one of the 2p orbitals twice. these two electrons are doomed to occupy the same region in space and to repel each other more strongly. this effect more than offsets the increase in the attraction of the nucleus, and thus the ionisation potential drops. similar discrepancies between fet’s claims and the actual data can be found in other properties, such as the dissociation energies of the diatomics.75 as the number of electrons increases, multiple bonding becomes possible, and the strength of the diatomic bond increases accordingly in an uninterrupted linear correlation from boron to nitrogen. the highest stability is reached for dinitrogen n2 since it realises a triple bond, based on the sp-hybridization. the bonding in o2 and f2 is smaller due to the occupation of antibonding orbitals and finally vanishes for neon. 75 fet (2010, 199). perhaps fet as a mathematician was less susceptible to such chemical explanations. nevertheless, the graphical representations of his claims were highly misleading. 6. the limits of symmetry when heisenberg proposed to consider the proton and neutron as the two sides of the same isospin coin, a paradigm shift was set into motion. the materialistic interpretation of the world consisting of particles gave way to a new understanding which views the particles as representations of symmetry groups. heisenberg depicted this as the confrontation between the atomism of democritus versus the idealism of plato. symmetries, not particles, were taken to be fundamental. they represented the deepest ontological level, whereas the particles only had a derivative status. “in the beginning was symmetry”, exclaimed heisenberg on more than one occasion.76 the culmination of heisenberg’s symmetry program was attained when gell-mann introduced the eightfold way, which provided a classification of all hadronic matter, and which led to the successful prediction of two new elementary particles. to some extent, the ability of a system to make successful predictions echoes mendeleev’s belief in the periodic law that enabled him to make detailed predictions for certain unknown elements (such as gallium, germanium and scandium). it is thus no surprise that the symmetry program was also applied to the periodic system, even though such attempts were relatively scarce. the success of the symmetry program did not stay confined to the hermetic circles of elementary particle physics, but as this contribution has illuminated, it inspired new perspectives on the periodicity of mendeleev’s table as a hallmark of an as yet unidentified underlying symmetry group. here as well, the key to the symmetry program was the move from materialism to idealism. the chemical elements were no longer treated as particles, but as states of a superparticle, the baruton, whose symmetry was described by the conformal group so(4,2). from the perspective of this group, the chemical elements had lost their identities, and merely functioned as different states of a single quantum system. it was only by a controlled breaking of the so(4,2) symmetry that the elements regained their chemical and physical identities. as we noted, several groups started the group-theoretical study of the periodic system almost simultaneously in the early seventies of the previous century. in this account we devoted particular attention to the 76 heisenberg (1976a), quotations on p. 32. figure 3. first ionization potentials. [figure adapted from fet, 2010, 194] 21particular symmetries: group theory of the periodic system contributions by fet and barut, both of whom adopted the elementary particle approach of heisenberg and gell-mann. in comparing the work of fet and barut, we also illustrated the tension between a formal mathematical treatment and an underlying physical. fet approached the problem from a rigorous mathematical point of view. the result was a formal scheme that accommodates the chemical elements, but on the other hand did not advance our knowledge of the structure of the periodic table, nor reflected the actual chemical and physical properties of the elements. in that sense, barut approached the problem from a much more physical and chemical point of view. as heisenberg already warned in his last paper, for a theory to be not only successful but also useful, it should not restrict itself to a description of phenomena but also offer an understanding. there is the danger to get lost in the mathematical details of a theory by focusing too much on its structural aspects, and to ‘loose touch’ this way with physical reality. it is not always easy to find the right balance between mathematics and physics. while the formal system, set up by fet, perhaps fell short of achieving this balance, other contributions opened a much more promising perspective. here we mention especially the legacy of asim barut who explained the group-theoretical origin of the period doubling from a much more physical and chemical point of view. the original line of thinking in the work of the late ostrovsky is also worth mentioning, although ostrovsky adopted an atomic physics approach.77 recently, the introduction of non-linear lie algebras has provided a synthesis of the key elements of both (atomic physics and elementary particle) approaches. this has expanded the study of the periodic system into a different realm, where its intriguing structure might finally reveal its secrets. 78 references glimpsing reality: ideas in physics and the link to biology. 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(1978). dynamical groups in atomic and molecular physics. in: recent advances in group theory and their application to spectroscopy. edited by j. c. donini. new york: plenum press. substantia an international journal of the history of chemistry vol. 4, n. 1 2020 firenze university press peer review – critical feedback or necessary evil? seth c. rasmussen particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 consciousness, information, electromagnetism and water marc henry leonardo and the florence canal. sheets 126-127 of the codex atlanticus filippo camerota the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí astatine – the elusive one keith kostecka vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of xx century aleksander sztejnberg substantia. an international journal of the history of chemistry 3(2): 65-72, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-637 citation: b.w. ninham (2019) b. v. derjaguin and j. theo. g. overbeek. their times, and ours. substantia 3(2): 65-72. doi: 10.13128/substantia-637 copyright: © 2019 b.w. ninham. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham department of applied mathematics, research school of physical sciences and engineering, australian national university, act 0200, australia e-mail: barry.ninham@anu.edu.au abstract. this year is the 25th anniversary of boris vladimirovich derjaguin’s death. the author was priviledged to know derjaguin and theo. overbeek quite well. these two giants of colloid science oversaw the evolution of the subject from a qualitative backwater to center stage in the now rapidly developing enabling discipline of modern physical chemistry. this is a personal account of events in their times. keywords. derjaguin, overbeek, dlvo, colloid science, polywater, cold fusion. the schools of derjaguin (1902-1994) and overbeek (1911-2007) dominated colloid and surface science completely for over 50 years. they did so deservedly because, to quote overbeek in his (1948) book: the science of colloids appears to be entering upon a new stage, which is less empirical, and where the experimental study of better defined objects will be guided rather by qualitative“rules”or“working hypotheses”. the theory of the stability of lyophobic colloids, as developed in this book, may serve as an example of this development” [3].1 over the following half century and more, its acolytes and disciples clung to the core foundations because for the first time there was a firm mathematical scaffolding on which to build. dlvo theory provided the backbone of colloid science since 1948 when theo overbeek published his thesis on the theory of the stability of lyophobic colloids with his supervisor verwey. germany had taken over philips industries when it occupied the netherlands. verwey protected overbeek who worked on his thesis. at night, overbeek, who had three young daughters, worked for the resistence arranging for jews to escape. had he been caught it would have meant instant death. not an ideal research environment. it took he and annie his wife 30 years before they could face going across the border to germany. i went there with them to the border. independently, derjaguin and landau published what is essentially the dlvo theory in russian in 1941. their paper is distinguished by the vitriol * a more detailed history of derjaguin’s work can be found in the introductory paper of his collected works published by this author at derjaguin’s request [1,2] 66 barry w. ninham and contempt with which they put down and dismiss an earlier 1937 attempt by sam levine from manchester. landau’s diatribe is worth reading, a marvel of undeserved arrogant contempt from the great man landau! it can be found in translation [1] or landau’s collected works. levine’s sin was to replace a non linear charging process in the theoretical development of double layer electrostatic forces by a linear one. it is ironic that in 1961 when dzyalshinski, lifshtz and pitaevski developed their quantum field theory of electromagnetic interactions between colloidal particles they made the same mistake. the whole impressive edifice then collapsed to semi classical theory [4]. (the implications of this error are prodigious and unrealised still, both for physical chemistry and physics generally). in 1952 overbeek and derjaguin met at a faraday conference in britain, and their interchanges are all recorded in the discussions of the faraday society record of the meeting. no punches were pulled overbeek always being a gentleman, and derjaguin definitely not. it was about priority and while in principle the russians might have the better of it, a manuscript in russian in moscow during the war was not readily accessible. the two never got on. derjaguin liked cowboy movies, and others that, shall we say, are less cultural, at least on his visit to canberra many years later to the author’s lab. the polywater business this almost certainly costed overbeek and derjaguin their expected nobel prize. around 1967-1968 derjaguin seized on some work of a junior worker called nikolai  fedyakin who discovered a new form of water he called polywater. derjaguin, anxious for a nobel prize, published it in nature. this was against the advice of a number of colleagues. in particular an eminent russian academician, an infrared spectroscopist, advised against publication, as did v. sobelev. n. churaev with it. (i know this from my friend vadim ogarev who was rumored to be nominal head (kgb) of derjaguin’s lab. vadim was actually a very good scientist, and his father twice order of lenin, invented the soviet u235 separation technology. everyone knew everyone on those days, much as in the usa on the manhattan project. it was at the height of the cold war. the whole polywater thing went viral. the author heard boris talk about it at nih (national institutes of health, bethesda, maryland, us) in 1969. like a precursor of climate change the earth might be consumed when all the world turned to sticky polywater! eminent american quantum chemists “proved” that the sceptics were wrong; polywater, like climate change, existed. brian pethica, pragmatic british scientist, who knew about thermodynamics, proved the contrary [5,6]. derjaguin withdrew. the americans had a lot of egg on their faces and derjaguin was never forgiven. kurt vonnegut’s ‘ice-nine’ in his ‘cat’s cradle’ novel was based on the polywater “discovery” [7]. felix franks who edited 12 large volumes on water, wrote a racy book called “polywater” about it in 1981 while on sabbatical in the author’s lab [8]. it is somewhat biased, written during the cold war. felix worked as british spy in germany in the war and hated russian communists. pethica took him to task in a review well worth reading [9]. the americans did something more ridiculous than polywater at the same time, when president nixon launched his war on cancer [10]. this was a new model for science reflected in today’s fashion for computer simulation. the idea was that a billion dollars would be contracted to entrepreneurs who would set up labs run by technicians (black, underpaid) who would inject mice with all the conceivable chemicals in the world to see if they cured cancer. brilliant. simple. an unanticipated difficulty was that the entrepreneurs underpaid their resentful technicians who injected the mice at random and, in sympathy, allowed them to escape. the main frame computer to process the data was literally rusting when adrian parsegian and i who were at nih at the time went to see the program manager. shades of the present fashion for simulation. some years later, derjaguin invited the author to participate in moscow in one of his biannual surface forces conferences. i faxed back – no e-mail then to say that the man he really needed was jacob israelachvili from my lab. jacob had done the first direct measurements of surface forces beween molecularly smooth mica sheets, with tabor in cambridge, before coming to australia [11-13]. at the time he and richard pashley had pioneered surface measurements between surfaces in liquids. derjaguin faxed back that regrettably while there were was accomodation for me, every hotel room in moscow was competely booked out. naturally i withdrew. it did not help that russia and israel had no diplomatic relations. and i was informed what was going by a friend, scientific attaché in moscow at the time. derjaguin had a gun at his head as it were. but jacob israelachvili, not one to mince words, went to war writing outrageous letters to the royal soci67b. v. derjaguin* and j. theo. g. overbeek. their times, and ours ety and others protesting this (soviet ) discrimination against israel (himself). it is again ironic that practically all direct surface forces measurements, dating back to the famous work of israelachvili and tabor are wrong, due to incorrect theory, incorrect use of theory, multiplicity of parameters and so on. we shall have more to say on this below (the first experiment in the west with an accuracy of 2 å, subsequently could not be fitted to lifshitz theory of surface forces until was realised the radii of the two crossed glass cylinders used – one or two centimeters, and measured with a schoolchild’s drawing compass had an error of 100%) [11]. cold fusion derjaguin committed another sin, with the discovery by he and his coworkers of the phenomenon of cold nuclear fusion. this controversial observation takes place when deuterium containing ionic solids are put under mechanical loading, and was published after a great deal of careful work 3 years before the competing claims of nuclear fusion [14-16], lately widely dismissed, of some americans, by a different method. derjaguins discovery was derided but may not be so silly. when a hard crystalline material cracks, the crack can be 2000 å long and a tenth of an å wide. electrons ripped off in the high energy grinding process are a confined instantaneously high temperature plasma. who knows? this was explained to me by derjaguin when i visited him at one time in moscow on my way to sweden. he instructed me that i should tell sture forsen, chair of the nobel prize committee in chemistry, that he, sture, should give derjaguin a nobel prize for this. i did not have the heart to tell him that in the previous year i had chaired a committee that reviewed research in physical chemistry in sweden. and that in a light hearted concluding paragraph i had said that“the committee formed the distinct impression that very shortly the entire surface of sweden would be covered in close packed array by nmr machines. and unless they were fitted with solar collectors no good would come of it.” this gentle hint at over emphasis on nuclear magnetic resonance research went down like a lead balloon with my friend forsen. molecular forces in retrospect at this point we can look back at the long period of “dlvo dominance” and see where it has taken us. we will then look at the implications of the polywater business. newton in a letter to his friend bishop bentley had this to say about forces: “that gravity should be innate, inherent and essential to matter, so that one body may act upon another at a distance through a vacuum without the mediation of anything else, by and through which their action and force may be conveyed from one to another, is to me so great an absurdity, that i believe no man who has in philosophical matters a competent faculty of thinking can ever fall into it. gravity must be caused by an agent acting constantly according to certain laws; but whether this agent be material or immaterial, i have left to the consideration of my readers.” action at a distance a-la-gravity, or via electromagnetic forces transmitted by a virtual field through space remains a mystery disguised by equations. we have no such trouble understanding “hydration” forces. (neighboring molecules, squashed tight push against each other). newton tried to measure molecular (surface) forces but gave up saying “surface combinations were owing” i.e. contamination. the work of the russian school under derjaguin and of the dutch led by overbeek brought it all into sight again culminating with the simultaneous dramatic publication of the lifshitz theory and its extension by dzyaloshinski, lifshitz and pitaevski and the first direct measurements of forces between molecularly smooth (mica) surfaces by israelachvili and tabor [11-13,17]. the triumphs are trumpeted and now imitated by armies of people practising force measurements with afm machines, an innovation that came from our group at the anu in canberra [18]. the limitations of both theory and experiment are now apparent. they have been reviewed extensively elsewhere [19]. indeed if anyone claims agreement with dlvo theory, his measurements are wrong. the foundations of the theory, are deeply flawed even of continuum solvent theory. they include ph, pkas, interfacial tensions, activities, interparticle interactions, zeta potentials, etc. since the theory with condensed media is wrong, the measurements that claim agreement must also be incorrect except for a gallant few. people took both the theory of overbeek and derjaguin outside their own claimed domain of validity. anomalous water and polywater as already remarked “polywater “ burst upon the scene in1969. 68 barry w. ninham very long range water structure, if we like bulk “hydration”, a new form of water, anomalous water, is invoked with monotonous regularity whenever phenomena occur that are not explained by existing theory. the classical exemplar, exhibit one, is a jellyfish. the concept has long history going back to thomas young who used the concept of a liquid having bulk properties right up to a molecular distance from an interface. (that is an assumption of dlvo theory as spelt out by hamaker in his thesis and a student of de boer). (jellyfish have a longer history, more than 700 million years to the edicara era. anomalous water is a matter of supreme existence to them) young’s 1805 theory of interfacial tension was taken over by laplace, dressed in fancy equations that young went to great pains to avoid, and incorporated into volume 6 of his mécanique céleste [20]. (laplace ignored contact angles !) poisson, in 1831 disputed the assumption and introduced the idea that a surface had to induce a change – hydration, a decay in order in near surface liquid molecules. the debate was settled in favour of young–laplace by ockham’s razor. poisson’s case was not helped by a mistake in a factor or 2 in his analysis. the story is outlined superbly in two magnificent articles by the rev. challis of trinity college cambridge (newton’s college). these much neglected reports to the british association of 1834 and 1836, on forces and hydrodynamics in colloid science – for which subject he coined the term “mathematical physics, for this the highest department of science” — deserve to be recognised. in the 1834 paper he suggested that measurement of molecular forces could be accomplished by using the new work of fresnel on diffraction of light, as indeed it was by israelachvili, winterton and tabor 150 years later [12]. george peacock, professor of mathematics at cambridge and young’s biographer, furiously accused laplace of plagiarism perfidious french ! and there the matter lay until the great 1876 article of james clerk maxwell on capillary action in the 9th edition of encyclopeadia britannica, updated by lord rayleigh in the 11th edition. note to editors – j. c. maxwell, a scotsman, a clade of humanity famous for its impecunity, preferred publication there as they paid very well.the paper is also in his collected works . maxwell resolved the issue decisively in favour of poisson. and deduced the range of the exponentially decaying hydration forces – about 3 å. this anticipated a similar advance of stjepan marcelja exactly 100 years later [21]. in no sense was this “hydration water” polywater. at the same time, 1876, hofmeister was doing his seminal work on specfic ion effects and pondering if they were due to surface (adsorption of ions) or due to effects of some very long range water structure. so if we like polywater, anomalous water was always in the air, and for jellyfish in the sea. following the advances in spectroscopic chemical analysis techniques which clearly demonstrated that ‘polywater’ produced in fine glass capillaries was actually a silicate based solution, r. m. pashley, a beginning phd student of kitchener’s [22] further proposed that thin ‘polywater’ films produced on condensation on silica based glass plates often gave adsorption isotherms which could be accurately described by raoult’s law. that is, the vapour pressure reduction could be caused by solutes created during the adsorption process, corresponding to about a monolayer of dissolved material from the glass surface. even michael faraday considered water films condensed on glass to conduct electricity due to dissolved solutes. pashley presented this work in stockholm in 1978, and explained faraday’s isotherms. boris derjaguin commented that this may indeed be the proper explanation. pashley was also the first to measure and interpret long range hydrophobic forces.2 2 for the measurement and theory of van der waals-lifshtz forces see also [23] where the film heght was studied vs film thickmess of liquid helium on vertical crystal of cleaved calcium fluoride can reasonably claim priority see also [24]. this is the preferred story in some quarters. the dutch, sparnay et al. tried to measure the van der waals forces between glass spheres, dutch industry having centuries of experience in grinding smooth lenses. alas, the asperities on the glass surfaces were too large, larger than 60 å, so the experiments were doomed. derjaguin had the advantage of them. his step father was the great russian physicist p. n. lebedev, the discoverer of light radiation pressure and a friend of j. clerk maxwell, got derjaguin his start in research at age 17 in a biophyics institute. (deryaguin was a school mate in moscow of george kistokowski, who emigrated to the u.s.a and became president of m.i.t. they met up again during the cold war). lebedev in 1894 quoted in ref. 25 had written this amazingly prescient paragraph that clearly inspired derjaguin: “... of special interest and difficulty is the process which takes place in a physical body when many molecules interact simultaneously, the oscillations of the latter being interdependent owing to their proximity. if the solution of this problem ever becomes possible we shall be able to calculate in advance the values of the intermolecuar forces due to molecular inter-radiation, deduce the laws of their temperature dependence, solve the fundamental problem of molecular physics whether all the so-called ‘molecular forces’ are confined to the already known mechanical interaction of light radiation, to electromagnetic forces, or whether forces of hitherto unknown origin are involved.” lifshitz with theory in 1955, and abrikossova and derjaguin with experiments in 1956, confirmed lebedev’s vision on molecular forces. the work was continued also by dzyaloshinski and pitaevski who developed – with lifshitz a theory of interactions between two planar dielectric surfaces separated by a liquid. hydration was neglected, as the liquid in contact with the two surfaces was assumed to retain its bulk properties [25-27]. the theory used measured bulk dielectric properties as a function of frequency and so avoided the impossible donkey work of pairwise summation or simulation of molecular forces. brilliant! 69b. v. derjaguin* and j. theo. g. overbeek. their times, and ours the russians measured the forces between conducting cylinders at large distance, the “retarded” classical regime and so can claim priority. but credit for the first measurements of non retarded van der waals forces goes to isrealachvili, winterton and tabor in cambridge in 1969 [12]. winterton quit to become an anglican priest in yorkshire. (rabinovich and derjaguin almost caught up). the story is intersting and deserves retelling. the inhibition to direct measurement going back to newton was asperities on surfaces as well as contamination. tabor, a reader at cambridge worked under a professor bowden, a tasmanian who was interested in friction. they transferred to melbourne, australia, to work on radar as part of the world war 2 effort. their job was to work on electrical condensers that use molecularly smooth mica. so tabor conceived the idea of using sheets of this mica glued onto glass cylinders at right angles (the same geometry as a sphere on a flat surface to do the job.) and after the war back at cambridge set to it. distance was measured by the interferometric method suggested by the rev. challis in 1834. the forces showed up as deviations of spring on which one cylinder was suspended. and so a large industry was born. the technique therefore made the journey from australia, back to cambridge and then back to my department in canberra with isrealachvili whence his departure to san diego 12 years later rebadged it as an american invention! tabor also invented the term “tribophysics” for the subject of lubrication. note on the discovery of long range hydrophobic interaction. the long range hydrophobic interaction between similar surfaces was first measured and reported by israelachvili and pashley in 1982 [38,39] based on their experiments using the surface forces apparatus (sfa), which was developed by israelachvili. two symmetrical, cleaved and smooth mica surfaces were coated with a hydrophobic surfactant monolayer and the forces between them was measured in various aqueous electrolyte solutions. comparing these measured forces with the expected van der waals attractive forces, indicated that there was an additional attractive force an order of magnitude larger than any van der waals force out to many tens of nm., which was identified as a ‘long range hydrophobic attraction’. since then, these attractive forces have been measured at separations up to several hundred nms. the origin of these forces has generated much debate, with the likelihood that their unexpectedly long range is probably related to dissolved gas cavitation created between the hydrophobic surfaces, evidence for which was also observed in the original studies [40]. in fact there are not one but many “hydrophobic” interactions that have different mechanisms [31-33]. there may be some dispute about who measured what first when and where. priority may go to our colleague v. v. yaminski then in moscow or to pashley or both. yaminski, no longer with us, has the distinction of being the only person ever to have read and understood j. willard gibb’s collected works. the works are so turgid that anyone else who claims to have read them is a liar. a consequence is that yaminski, given a choice between choosing to describe a phenomenon in 50 words or 200 invariably chose 10,000, so honouring his hero and obscuring his works completely. some hydrophobic interactions involve cavitation, an important and completely ignored driver of enzymatic interactions [41]. some involve nanobubbles at interfaces. some involve surfactants, and electrostatics, some polymer bridging. nearly all involve dissolved gas [33]. the most striking are the observations that emulsions become more stable when gas is removed. hydrophobic proteins disperse when gas is removed. certainly hydrophobic interactions generally disappear when gas is removed. two other explicit examples are reported in refs. 42 and 43. more theoretical and experimental results are found in refs. 44-51. a more recent publication (after 20 years study) is that of kekicheff [52]. the sustained work on water structure near hydrophobic and hydrophilic surfaces, with and without salts by novel laser optical spectroscopic techniques is now likely to move center stage as we move to incorporate the new dimension provided by dissolved gas. the denouement derjaguin’s polywater was due further to contamination from human skin. the dismissal of polywater, to this day, was very shortsighted. jellyfish do exist, and their “anomalous” water structure is probably due to cooperative very long ranged fluctuation forces between the extremely dilute conducting polymers that permeate the carapace of the creatures. the same is true for the curious anomalous exclusion zone of nafion, a fuel cell polymer [28], and for the remarkable sustained work on colloid stability of latex spheres of norio ise [29]. and for the endothelial surface layer on veins and arteries in physiology [30]. these matters are made more complex by this realisation that dissolved atmospheric gas, and its self organised state in nanobubbles everywhere present is responsible for most of what we label “hydrophobic” interactions, and is truly a hidden variable. anomalous water is not necessary. the greeks told us so with their four elements: fire (energy), water, earth and air but we ignored them. the fourth element, air, is universally ignored. its presence and the major effects of dissolved gas are missing from classical theory and open up whole new dimensions. refs. 30-33 allow us to see how we can look forward to bridging biology and physical chemistry. ref. 30 and the papers on novel water technologies in an upcoming special issue of this journal are examples computer simulation is impotent to handle this realisation. descartes might well have said i breathe: therefore i am instead of i think: therefore i am. there is more. even without the extra dimension and hidden variable provided by dissolved gas we have moved far from the simpler world of dlvo. by that statement we include all of physical, colloid and electrochemistry. for the intuition derived from on the classical theory assumes a fundamental ansatz –that electrostatic, double layer and dispersion (quantum mechanical) forces can be dealt with separately. they can not, and the fundamental ansatz is wrong, violating two physical principles, the gibbs adsorption isotherm and the gauge condition on the electromagnetic field [34,35]. once electrostatic and dispersion forces are treated consistently however [31,33], much that was mysterious and handled by fitting parameters falls into place systematically; hofmeister, specific ion effects and hydration for example. the situation means however that the meaning and interpretation and intuition that we are familar with 70 barry w. ninham needs reworking , for ph, pkas, buffers, interfacial tensions, intermolecular forces, zeta potentials, hofmeister effects, hydration. to put matter in perspective, recall a lovely quotation [36]: “over a hundred years ago, in the heyday of belief in self-sufficient progress, paul valéry insisted emphatically on the fact that civilisations are mortal. fifteen hundred years before, st. augustine echoed the same thought when in a simple sermon (and not in the famous work which contains one of the few philosophies of history that the west has produced), he summed up the true functions of earthly civilisation in a single illuminating phrase: ‘an architect builds a durable house with the aid of a temporary scaffolding.’ civilisations are the impressive, complicated and bewildering scaffolding, machinamenta temporalia (sermo 362.7). the edifice that arises above it is, he maintains, the eternal city of god”. we can interchange the word civilisations with scientific theories. the beliefs of one era evolve into others that are very far removed. it is therefore not usually possible to value scientific contributions for at least 50 years after their appearance. but the new theories depend on the earlier foundations. we have moved very far from where dlvo began and developed. finally then, for theo. overbeek and boris derjaguin, and their followers. we honour them still. because like the ancient egyptians they stood steadfast to that which they once believed to be valid. and by so doing they have laid us all under an obligation. we have work to do. postscript the author was priviledged to be a friend of both overbeek and of derjaguin. he was honoured by the award of the overbeek gold medal of the european colloid and interface society in 2014 [37]. he was one 5 lecturers at overbeek ’s 85th birthday celebrations, the others being dutch. he has the rebinder medal of the ussr academy of science. he experienced the many sad inhibitions to research on eastern colleagues during the cold war. his most celebrated contribution to the cold war was when the russians launched the sputnik in 1957. the announcement on public radio by the australian broadcasting commission occasioned the immediate formation of the st. george’s college astronomical society (university of western australia) whose presidency he assumed. the secretary, one david muschamp a philosopher was delegated to report a sighting by the society of the sputnik traversing the clear night sky of the city of perth. the announcement and publication of this “first” ever satellite sighting was received by the citizenry with acclamation. sadly, a first example of fake news, you could see the thing, a gold coated sphere 15 cm diameter, traversing the perth evening skies. the st. georges college astronomical society, overwhelmed with its successes never met again. figure 1. b. derjaguin in his laboratory. 71b. v. derjaguin* and j. theo. g. overbeek. their times, and ours references 1. b. w. ninham. b. v. derjaguin and his contributions. in: selected works of b.v. derjaguin. progr. surface sci. 1992, 40(1-4), xv-xx. 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langmuir 1993, 9(12), 3618-3624. 52. p. kékicheff. adv. coll. interface sci. 2019, 270, 191215. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 3(2) suppl. 2: 69-73, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-700 citation: v. smil (2019) what we need to know about the pace of decarbonization. substantia 3(2) suppl. 2: 69-73. doi: 10.13128/substantia-700 copyright: © 2019 v. smil. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. what we need to know about the pace of decarbonization vaclav smil university of manitoba, canada e-mail: vaclav.smil@umanitoba.ca abstract. proper recognition of energetic, engineering and economic realities means that the decarbonization of global energy supply will be much more difficult and it will take much longer than is often assumed by uncritical proponents of “green” solutions. energy transitions have been among the key defining processes of human evolution (smil 2017a). the first (millennia-long) transition was from the reliance on traditional biofuels (wood, charcoal, crop residues) and animate prime movers (human and animal muscles) to increasingly common reliance on inanimate energy converters (water wheels, wind mills) and on better harnessed draft animals for fieldwork and in transportation. transition to fossil fuels (burned to produce heat, thermal electricity and kinetic energy) began in england already during the 16th century but it took off in europe and north america only after 1800, and in most of asia only after 1950. this transition has been accompanied by increasing reliance on primary electricity (dominated by thermal electricity since the 1880s, with nuclear generation contributing since the late 1950s). post-1800 transition from traditional biofuels to fossil fuels has resulted in gradual relative decarbonization but in enormous growth in absolute emissions of co2. relative decarbonization is best traced by the rising h:c (hydrogen to carbon) ratios of major fuels: they rise from no more than 0.5 for wood and 1.0 for coal to 1.8 for the lightest refined fuels (gasoline and kerosene) and, obviously, to 4.0 for methane (ch4), the dominant constituent of natural gas (smil 2017b). the reverse order applies to co2 emissions per unit of energy: combustion of natural gas produces less than 60 kilograms of co2 per gigajoule (kg co2/gj) while the rates for liquid hydrocarbons are between 70-75. as the global energy transition progressed, coal consumption overtook the burning of traditional biofuels and it was, in turn, overtaken by the combined mass of hydrocarbons (crude oils and natural gases) and rising share of primary electricity has further reduced the average carbon intensity of the world’s primary energy supply. the global mean declined from nearly 28 kilograms of carbon per gigajoule (kg c/gj) in 1900 to about 25 kg c/gj 70 vaclav smil in 1950 and then to less than 20 kg c/gj by 2015. but this relative decline has been accompanied by an almost uninterrupted growth of absolute co2 emissions. combustion of fossil fuels contributed just 8 million tonnes of carbon (mt c) in 1800 (for co2 multiply these totals by 3.667), 534 mt c in 1900, 6.77 gt in 2000 and 9.14 billion tonnes (gt) c in 2018 (boden et al. 2017; iea 2019). these emissions have been the principal reason for the rising atmospheric concentration of co2, from 285 parts per million (ppm) in 1850 to 369.6 ppm in the year 2000 and to 408.5 ppm in 2018 (nasa 2019a; noaa 2019). in turn, these rising concentrations have been the principal reason for gradual increase of average tropospheric temperature that has, so far, amounted to about 0.80 c (nasa 2019b) but that would, in the absence of any remedial actions, surpass 20 c or even 30 c in a matter of decades and result in rapid anthropogenic global warming (ipcc 2014). past transitions were driven by a variety of factors ranging from the need for higher unit power (even small water wheels were more powerful than an ox or a horse) and better conversion efficiency (windmills can lift irrigation water much more efficiently than people) to more affordable supply (heating coal was far cheaper than charcoal) and reduced environmental impacts (natural gas is a much cleaner fuel than coal). in contrast to previous energy transitions the unfolding quest for decarbonization is not primarily driven by resource shortages or technical imperatives (most of the existing conversions are highly efficient and also very reliable). today’s quest for decarbonization has one dominant goal: limiting the extent of global warming. the goal is to establish a new global energy system devoid of any combustion of carbon-containing fuels or the world with netzero carbon emissions where a limited amount of fossil fuel combustion would be negated by the removal and sequestration of the gas from the atmosphere resulting in no additional carbon releases. how have we done so far? concerns about anthropogenic global warming (a phenomenon whose basic cause has been appreciated since the late 19th century) began to receive wider public attention during the 1980s, and the first united nations framework convention on climate change was signed in 1992 (unfccc 1992). it was followed by the kyoto protocol of 1997 and its latest global endeavor was the 2015 paris agreement that included nationally determined contributions designed “to combat climate change and to accelerate and intensify the actions and investments needed for a sustainable low carbon future” (uncc 2019). numerous meetings and assorted pledges aside, what has actually taken place since 1992? the most important fact is that during those decades of rising concerns about global warming the world has been running into fossil carbon, not moving away from it. since 1992 absolute emissions of co2 from fossil fuel combustion have declined significantly (by nearly 20%) in the eu28 and have grown only marginally (in each case by about 5%) in the us and japan (boden et al. 2017) but these accomplishments have not set the world on the road to decarbonization as emissions have nearly tripled in asia, largely because the chinese combustion of fossil fuels has almost quadrupled (boden et al. 2017; pbl 2018). as a result, global emissions of co2 increased by more than 60% since 1992, setting yet another record in 2018. historians of energy transitions are not surprised by this development, as history shows that neither the dominant sources of primary energy nor the common energy converters can be displaced rapidly and completely in short periods of time. the high degree of the global dependence on fossil carbon and the enormous scale of the fuel-dominated global energy system mean that the unfolding energy transition will inevitably follow the progress of all previous large-scale primary energy shifts and that it will be a gradual, prolonged affair (smil 2017a). in 1800 traditional biomass fuels (wood, charcoal, crop residues, dung) supplied all but a tiny share of the world’s primary energy, a century later their share was about 50%, and at the beginning of the 21st century they still accounted for nearly 10%. this means that even after more than two centuries the world has not completed the shift from traditional biofuels to modern sources of primary energy. coal’s share of global primary energy supply has been in retreat for generations as the reliance on hydrocarbons has grown – but the fuel still supplies nearly 30% of the total requirement. that is still more than natural gas (whose commercial extraction began about 150 years ago but whose share of total supply has been growing slower than expected) and in absolute terms its output is more than eight times larger than it was in 1900 when the fuel dominated the global energy supply. and while most economies began to reduce their reliance on crude oil in the aftermath of opec’s two rounds of large price increases during the 1970s, the fuel remains the dominant source of the world’s primary energy, supplying nearly 40% of the total. the unfolding transition toward non-carbon energies has to take place on unprecedented scales. annual extraction of fossil fuels now includes about 7.7 gt of coal, 4,4 gt of crude oil and 3.7 trillion cubic meters of natural gas, altogether an equivalent of nearly 9 gt of crude oil or about 370 ej (bp 2018). this grand total is 71what we need to know about the pace of decarbonization the flux that matters: unlike all other previous shifts in primary energy use, the unfolding decarbonization can achieve its goal – eventual elimination of fossil carbon – only when it succeeds on the global scale. substantial decline of carbon emissions, even an instant decarbonization of energy supply in a major advanced economy, makes little difference as long as the greenhouse gas emissions from other sources and from other countries keep on rising. even after some three decades since the beginning of high-level global warming concerns the unfolding transition is still in its earliest stage and even the relative shift has been, so far, minor. when the shares of primary energy are calculated by excluding traditional biofuels and by converting all non-thermal primary electricity by using its energy equivalent (1 wh=3,600 j), fossil fuels supplied 91.3% of the world’s primary energy in 1990 and by 2017 their share was still 90.4%. as with many phenomena in early stages of expansion, the combined growth of contributions made by new renewables (wind and solar electricity generation and modern biofuels) has been rapid: in the year 2000 they supplied only about 0.2% of the global primary energy supply, their share reached 1.3% by 2010 and 2.2% by 2017 – but that was still well behind the contributions made by either hydro and nuclear generation. of course, the shares of new renewables are significantly higher for electricity generation because this sector has been the main focus of the unfolding drive for decarbonization. photovoltaic cells and wind turbines generated a mere 0.2% of the world’s electricity in the year 2000, the share reached 4.5% in 2015 and nearly 7% in 2018 (bp 2018). but even if the decarbonization of global electricity generation were to proceed at an unprecedented pace, only the availability of affordable, massive-scale electricity storage would make it possible to envisage a reliable system that could rely solely on intermittent renewable energies of solar radiation and wind. even securing just three days-worth of storage for a megacity of more than 10 million people that would be cut off from its intermittent renewable sources (a common occurrence during the monsoonal season in asia with heavily overcast skies and high winds) would be prohibitively expensive by using today’s commercial batteries. setting aside exaggerated media claims, a technological breakthrough meeting that requirement appears unlikely in the near future as pumped hydro storage (originally introduced during the 1890s) remains today the only way to store electricity at gigawatt scale. and even major advances toward large-scale electricity storage would not be enough to bring about rapid decarbonization of the global energy supply as electricity generation accounts for no more than 20% of total final energy consumption, and as decarbonizing transportation, heating, agriculture and industrial production is considerably more difficult than installing new intermittent capacities, connecting them with major load centers and securing the required back-up supply. electrification of passenger cars is in its earliest stage, with 5.4 million electric vehicles on the road by the end of 2018, still less than 0.2% of all vehicles registered worldwide (insideeves 2019). more than a century after they were first seen as the best road transportation choice, electric cars are finally ascendant, but even under the best circumstances it will take many decades to accomplish the transition from internal combustion engines. the international energy agency sees 160-200 million electric vehicles by 2030, bp expects 320 million by 2040 and my best forecast (based on a polynomial regression) is for 360 million in 2040 (iea 2018; bp 2019). but by that time there might be about 2 billion vehicles on the road globally (compared to about 1.25 billion today), and hence even 400 million electric cars would be just 20% of the total. forecasting the future adoption of hydrogen-fueled vehicles is even more uncertain, but it is hard to see how even the most likely combined progression of electric and hydrogen cars would completely eliminate internal combustion engines before 2040, or even soon after. given the energy density of today’s best commercial batteries, the electrification of trucking, shipping and flying is even more challenging. the key to understanding the fundamental difficulty is to compare the energy densities of the best li-ion batteries with the energy density of diesel fuels used in trucking and shipping. today’s widely deployed li-on batteries have an energy density of up to 260 wh/kg, and it is foreseen that they could reach up to 500 wh/kg in the future (j.p.morgan 2019). in contrast, diesel fuel used in land and marine transport and aviation kerosene have, respectively, energy densities of 12,600 wh/kg and 12,800 wh/kg), which means that today’s dominant liquid transportation fuels are nearly 50 times as energy dense as our best commercial batteries and this gap is not to be closed anytime soon. shipping and flying present particularly insurmountable challenges as only high energy density fuels can power massive container ships carrying more than 20,000 steel units on their long intercontinental routes (smil 2019) and high-capacity commercial airliners. while air conditioning is powered by electricity, seasonal heating in cold parts of eurasia and north america now relies overwhelmingly on natural gas delivered by large-diameter trunk lines and dense networks of 72 vaclav smil small-diameter distribution lines serving more than half a billion customers. obviously, replacing this fuel supply and abandoning this extensive infrastructure will not be achieved over a single generation. and even more intractable challenges come with the decarbonization of industries producing what i have called the four pillars of modern civilization: ammonia, cement, steel and plastics (j.p. morgan 2019). mass-scale production of these materials (annual outputs are now close to 200 mt for ammonia, about 4.5 gt for cement, 1.6 gt for steel ad about 300 mt for all kinds of plastics) now depends on large-scale inputs of fossil fuels, both for process heat and as feedstocks. without haber-bosch synthesis of ammonia (with natural gas as the dominant feedstock and fuel), nearly half of today’s humanity would not be alive as even the most assiduous recycling of all available organic matter could not supply enough nitrogen to feed nearly 8 billion people. cement and steel are the two irreplaceable infrastructural components. cement is produced in kilns heated by low-quality fossil fuels, two-thirds of all steel are made in basic oxygen furnaces from pig iron that is smelted in blast furnaces with the aid of about one billion tonnes of coke, augmented by natural gas (smil 2016). and gaseous and liquid hydrocarbons are the dominant feedstocks (and fuel) for synthesizing a wide variety of plastics. all of these processes have one important characteristic in common: there is no available non-carbon alternatives that could be readily deployed on mass commercial scales. there are some interesting innovations, and entirely new pathways might be possible – ranging from new catalyses for ammonia synthesis (ashida et al. 2019) to hydrogen-based steelmaking (green 2018) – but none of these innovations has been deployed even as pilot plant experiments and, once again, it is obvious that scaling up those processes that may eventually prove acceptable in order to reach annual outputs of hundreds of millions, even billions, of tonnes is a task that would take generations to accomplish. yet another important factor to consider are the enormous energy, food and material needs of emerging economies. china’s post-1990 surge in demand for these inputs indicates the extent of future needs. china’s population of 1.39 billion people will be soon surpassed by india – whose per capita energy use is only about a quarter of the chinese level (bp 2018) – and between 2015 and 2050 1.3 billion people will be added in africa where per capita use is generally well below the indian level. much like china has done by more than quadrupling its fossil energy use since 1990, these populous modernizing countries or regions will use any available source of energy to raise their standard of living and to build their essential infrastructures. not surprisingly, india’s total primary energy consumption is forecasted to increase nearly five-fold between 2012 and 2047 according to a recent study by the national institution for transforming india (niti aayog), and coal is expected to remain its dominant fuel (thambi et al. 2018). in conclusion, the verdict – based on the history of past energy transitions, on the unprecedented scales of the unfolding shift, on the limits of alternative pathways, and on the enormous and immediate energy needs of billions of people in low-income countries – is clear. designing hypothetical roadmaps outlining complete elimination of fossil carbon from the global energy supply by 2050 (jacobson et al. 2017) is nothing but an exercise in wishful thinking that ignores fundamental physical realities. and it is no less unrealistic to propose legislation claiming that such a shift can be accomplished in the us by 2030 (ocasio-cortez 2019). such claims are simply too extreme to be defended as aspirational. the complete decarbonization of the global energy supply will be an extremely challenging undertaking of an unprecedented scale and complexity that will not be accomplished – even in the case of sustained, dedicated and extraordinarily costly commitment – in a matter of few decades. references ashida, y. et al. 2019. molybdenum-catalysed ammonia production with samarium diiodide and alcohols or water. nature 568:536-540. boden, t. et al. 2017. global co2 emissions from fossilfuel burning, cement manufacture, and gas flaring: 1751-2014. oak ridge, tn: ornl. bp (british petroleum). 2018. bp statistical review of world energy. london: bp. bp. 2019. bp energy outlook. london: bp. green, e. 2018. the use of hydrogen in the iron and steel industry; available online. iea (international energy agency). 2018. global ev outlook 2018. paris: iea. iea. 2019. global energy & co2 status report. paris: iea. insideevs. 2019. ev sales scorecard; available online. ipcc (intergovernmental panel on climate change). 2014. ar5 synthesis report: climate change 2014. geneva: ipcc. jacobson, m.z. et al. 2017. 100% clean and renewable wind, water, and sunlight (wws) all sector ener https://www.energy.gov/sites/prod/files/2018/08/f54/fcto-h2-scale-kickoff-2018-19-green.pdf https://insideevs.com/news/344006/monthly-plug-in-report-card-archive/ 73what we need to know about the pace of decarbonization gy roadmaps for 139 countries of the world. joule doi:10.1016/j.joule.2017.07.00 j.p. morgan. 2019. mountains and molehills: achievements and distractions on the road to decarbonization. new york: j.p. morgan. nasa (national aeronautics and space administration). 2019a. global mean co2 mixing ratios (ppm): observations; available online. nasa. 2019b. world of change: global temperatures; available online. noaa (national oceanic and atmospheric administration). 2019. trends in atmospheric carbon dioxide; available online. ocasio-cortez, a. 2019. resolution recognizing the duty of the federal government to create a green new deal. washington, dc: the us house of representatives. pbl (netherlands environmental assessment agency). 2018. trends in global co2 and total greenhouse gas emissions: 2018 report; available online. smil, v. 2016. still the iron age: iron and steel in the modern world. amsterdam: elsevier. smil, v. 2017a. energy transitions: global and national perspectives. santa barbara, ca: praeger. smil, v. 2017b. energy and civilization: a history. cambridge, ma: the mit press. smil, v. 2019. electric container ships are a hard sail. ieee spectrum march 2019:2. thambi, s. et al. 2018. india’s energy and emissions outlook: results from india energy model. new delhi: niti aayog; available online. uncc (united nations climate convention)/ 2019. what is the paris agreement?; available online. unfcc (united nations convention framework convention on climate change). 1992. united nations convention framework convention on climate change; available online. https://data.giss.nasa.gov/modelforce/ghgases/fig1a.ext.txt https://data.giss.nasa.gov/modelforce/ghgases/fig1a.ext.txt https://www.esrl.noaa.gov/gmd/ccgg/trends/data.html https://www.pbl.nl/en/publications/trends-in-global-co2-and-total greenhouse-gas-emissions-2018-report http://www.niti.gov.in/writereaddata/files/document_publication/india’s-energy-and-emissions-outlook.pdf https://unfccc.int/process-and-meetings/the-paris-agreement/what-is-the-paris-agreement https://unfccc.int/files/essential_background/background_publications_htmlpdf/application/pdf/conveng.pdf substantia an international journal of the history of chemistry vol. 3, n. 1 suppl. 2019 firenze university press substantia. an international journal of the history of chemistry 4(1): 51-61, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-620 citation: p. grapí (2020) the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination. substantia 4(1): 51-61. doi: 10.13128/substantia-620 received: sep 11, 2019 revised: jan 09, 2020 just accepted online: jan 10, 2020 published: mar 11, 2020 copyright: © 2020 p. grapí. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical articles the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí societat catalana de química e-mail: pgrapi@gmail.com abstract. dalton’s chemical atomism was inspired by his physical fascination with gases and developed through his chemical investigation. in regard to the latter, dalton’s very first chemical experiments on nitrogen oxides enabled him to identify the first verifiable case of multiple proportions of combination, as well as playing a significant role in the process of establishing the basis for the reinvention of the nitrous gas eudiometer. nevertheless, the eudiometrical background of dalton’s trials on the oxides of nitrogen is yet to be elucidated. his interest in the nitrous gas test was in principle concerned with the justification of his statement on the multiple combining proportions, rather than with the improvement of the test as a eudiometrical method for verifying the oxygen content in common air. on the whole, after passing through dalton’s hands, the nitrous gas test was returned to eudiometrists as a simpler type of the eudiometrical test than those performed with the latest nitrous gas eudiometers. in 1809, in line with dalton’s suggestions, gay-lussac was eventually able to deliver a reshaped version of the nitrous gas eudiometer. keywords. nitrous gas test, dalton, eudiometry, proportions of combination, gaylussac. an overview of the nitrous gas test in a landmark paper, observations on different kind of airs, read in 1772 but published in the following year, joseph priestley (1733-1804) proposed a nitrous air (nitrogen monoxide) test to replace the use of mice and birds for checking the goodness (i.e. the respirability) of an air sample.1 for this test, priestley was indebted to stephen hales’ (1677–1761) work statical essays of 1738.2 nevertheless, the chemical phenomenon underpinning the test had already been observed by john mayow (1640-1679) in 1674, and described by hales himself in his previous work vegetable staticks of 1727.3 the purpose of this development was not only to achieve a greater precision, but also to remove the inconvenience of maintaining a stock of mice in the appropriate conditions.4 this nitrous air test relied on the contraction in volume that an air sample underwent when mixed with nitrous air.5 52 pere grapí the goodness of air was considered to be inversely proportional to the content of phlogiston. priestley was of the opinion that nitrous air appeared to consist of the nitrous acid vapour combined with an excess of phlogiston. on mixing nitrous and common air, this nitrous acid vapour disengaged from the phlogiston, which united with the acid principle of the common air, while a fixed air that it contained was precipitated out, and the water in which the mixture was made absorbed the acid of the nitrous air. these two latter phenomena caused the contraction in volume of the air mixture.6 indeed, during the last quarter of the eighteenth century, doubts began to be cast on the simple nature of atmospheric air, and the idea that only a part of the common air was breathable started to gain acceptance. then, in parallel with the hygienist approach to atmospheric air, a more analytical and quantitative methodology to determine the composition of common air was adopted, mainly in regard to the uncertainty about its proportion of respirable or vital air; that is, our oxygen. priestley presented the experimental device he conceived for conducting the nitrous air test in the first and second volumes of his work experiments and observations on different kinds of air (1774-1775, 1776).7 this experimental device was very simple. it consisted of collecting the common air measures by means of a number of vials of proportional capacities (figure 1: f, f, f ), and a cylindrical tube (g) on which all these measures were engraved in order to indicate where to mix the common and nitrous air. this experimental device was to become a source of inspiration for investigators such as marsilio landriani (1751-1815), felice fontana (1730-1805) and, in particular, jan ingenhousz (1730-1799). priestley did not christen his experimental device with any particular name, and it was landriani who in 1775 coined the term “eudiometer” for his own instrumentalist version of the nitrous air test (figure 2).8 hereafter i will refer to this test as the “nitrous gas test”. from 1778 onwards, the nitrous gas eudiometers had to coexist with different kinds of eudiometers. as experimental devices, all eudiometers were based on the fact that the respirable part of atmospheric air could be extracted from an air sample by the action of a particular substance. these absorbent substances could be solid materials (phosphorus, iron filings with sulphur and potassium sulphide), aqueous solutions (iron sulphate the relevant reactions taking place in the nitrous air test carried out over water are equilibrium processes that do not occur independently. they are outlined in the following chemical equations: 2 no (g) + 2 o2 (g) = 2 no2 (g) relatively slow and proceeds essentially to completion within minutes. 2 no2 (g) = n2o4 (g) rapidly achieve equilibrium. no (g) + no2 (g) = 2 n2o3 (g) rapidly achieve equilibrium. n2o4 (g) + h2o (l) = hno3 (aq) + hno2 (aq) fast and irreversible. n2o3 (g) + h2o (l) = 2 hno2 (aq) fast and irreversible. additionally, oxygen dissolved in the water can play a role. figure 1. priestley’s glass vials used for eudiometrical measurements. from joseph priestley, experiments and observations of different kinds of air (london, 1776), plate i 53the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination impregnated with nitrous gas and alkaline or calcium sulphides) and gaseous substances such as nitrous gas (nitrogen monoxide) and hydrogen, this latter being the basis of volta’s eudiometer (figure 3).9 the existence of these competing eudiometers and the difficulties surrounding the procedural standardisation of the nitrous gas eudiometer eclipsed its utility.10 nevertheless, the nitrous gas test was far from being dismissed and would mutate into a new version at the beginning of the nineteenth century. after this overview of the nitrous gas test, it is time to examine john dalton’s involvement in this eudiometrical test. john dalton (1766-1844). laying the foundations for the reconversion of the nitrous gas test the first public description of dalton’s experiments on nitrogen oxides appeared in his paper experimental enquiry into the proportions of the several gases or elastic fluids constituting the atmosphere, read on november 12th, 1802, at the literary and philosophical society of manchester, and which remained unpublished until 1805. dalton’s account of his experiments is commonly regarded as the confirmation of his understanding of multiple proportions in the nitrogen oxides. unfortunately, dalton’s notebook, together with many of his papers held in manchester, were destroyed as the result of an air raid in 1940 during the second world war. the only surviving references to the notebook are to be found in the work by roscoe and harden, a new view of the origin of dalton’s atomic theory. in a discussion of dalton’s experimental results on nitrogen oxides, these authors state that the interesting question was not how dalton managed to obtain them, but when he obtained them.11 the chronology of these experiments undoubtedly constitutes a crucial part of the origin and development of dalton’s widely studied chemical atomic theory.12 even so, a knowledge of how these experimental results were obtained would enable both they and the origin of the atomic theory to be placed in their instrumental and procedural context. dalton gave an account of the first clear instance of multiple proportions of combination in the first section of his 1805 paper. this section, entitled of the weight of the oxygenous and azotic atmospheres, was devoted to assessing different eudiometrical procedures in relation to the composition of common air. although dalton had had the opportunity, prior publication, to revise the draft of this paper, which he read in 1802, the eudiometrical context of his early experiments on the oxides of nitrogen nevertheless remained unclear.13 notwithstanding, there is no doubt that in the published and debatable version of his 1805 paper, dalton wished to frame these experiments in a eudiometrical context. a beginner in chemistry and eudiometry in order to gain an understanding of dalton’s knowledge in the field of eudiometry, it would first be worthwhile to become acquainted with the extent of his training in chemistry before 1805. during his stay in kendall (1781-1793), his post as an assistant teacher at a boarding school provided him with access to the vast library of his tutor and friend, the natural philosofigure 2. landriani’s eudiometer. from marsilio landriani, ricerche fisiche intorno alla salubrità dell’aria (milano, 1775), plate 1. 54 pere grapí pher john gough (1757-1825), as well as to the impressive library at the school, where he became familiar with boyle’s and boerhaave’s works. in 1793, he moved to manchester to teach mathematics and natural philosophy at the new college, but soon found himself obliged to teach chemistry as well. while in manchester he entered a more challenging scientific world than the one he had known in kendall, and in 1794 went on to become an elected member of the manchester literary and philosophical society, of which he became secretary in 1800 and president in 1817. dalton’s involvement in the activities of this society and his close friendship with william henry (1774-1836) considerably extended his scientific knowledge and experience. it was in manchester, in early 1796, where dalton received his first formal education in chemistry thanks to a series of thirty chemical lectures given by thomas garnet (1776-1802), who was to become a professor at the royal institution in london. after these lectures he felt confident enough in his expertise in chemistry to agree to give some six lectures on chemistry the following summer in kendall. in 1800, he resigned his teaching position and opened his own mathematical academy, where he offered tuition in mathematics, experimental philosophy and chemistry. in march 1803, he informed his brother that in his leisure time he had been very busily engaged in his chemical and philosophical enquiries.14 it would not be presumptuous to say that prior to 1805 dalton had had access to the foremost chemistry books and scientific journals, first, in kendall, in gough’s private library, and then in manchester in the extensive chetham’s library as well as in the society’s library, not to mention his own private library.15 there exists no published trace of dalton’s involvement in eudiometrical tests before the publication of his 1805 paper on the proportions of the several atmospheric gases. nevertheless, it seems that dalton was well acquainted with the current eudiometrical methods after attending the chemical lectures in 1796. thus, in the sequel to a paper on the constitution of the atmosphere, published in 1837, dalton affirmed that he had been engaged in the investigation of the proportions of oxygen and nitrogen in mixtures of both gases for more than forty years.16 the eudiometrical context of dalton’s law of multiple proportions dalton began the first section of this 1805 paper by listing the five eudiometrical tests widely used at that time: nitrous gas, alkaline or calcium sulphides, hydrogen ignition, green sulphate or chloride of iron impregnated with nitrous gas, and phosphorous fast combustion. he then made it clear that he regarded the finding that atmospheric air contained 21% oxygen as an accepted fact, explaining past discrepancies as a misunderstanding of the nature of the different tests and of the circumstances influencing them. figure 3. (left) a view of the lower part of a copy of the volta-type eudiometer. (right) modern replica of spallanzani’s phosphorus eudiometer exhibited at the centro studi lazzaro spallanzani. courtesy of tempio voltiano, musei civici di como, comune di como and of centro studi lazzaro spallanzani, scandiano, photography by the author. 55the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination it was nothing unusual for dalton to focus his attention in the nitrous gas test, given his work on meteorology and mixed gases. while he acknowledged the discredit attaching to the nitrous gas test, he valued it for being not only the most elegant and expeditious of all the existing eudiometrical tests, but also as accurate as any other when properly conducted. it appears that dalton had not been fully aware that the reliability of the test depended on skilful trained experimenters to conduct it. his intimate friend william henry had discarded it because the sources of error inherent in the employment of the test had caused him to mistrust the results obtained thereby. henry’s reference to humboldt’s researches on the nitrous gas published in the annales de chimie may have influenced dalton’s experimental design and textual presentation of his enquiries into the combination of nitrous gas with atmospheric oxygen. humboldt’s researches proved useful for demonstrating that the test should be performed over water instead of mercury, as well as the influence on the experimental outcomes of the size of the eudiometrical recipient and the order in which gases were added to it.17 dalton began his conclusions by criticising the nitrous gas test in four comments mainly regarding some material and procedural aspects of the test already addressed by humboldt in his paper:18 i shall, on this occasion, animadvert upon it [the nitrous gas test] in his first comment, dalton pointed out the need of using nitrous gas that was virtually free of azotic gas (nitrogen), with less than 2-3% at most, and nitrous oxide (dinitrogen monoxide). the remaining comments were devoted to summarising his experiments in the form of two eudiometrical trials. the first trial consisted of adding 100 measures of common air to 36 of nitrous gas (no in dalton’s terms) in a tube 3 1/10 inches wide and 5 inches long. after waiting for a few minutes, the whole mixture was reduced to 79 or 80 measures, without exhibiting signs of either oxygen or nitrous gas. in the second trial, 100 measures of common air were added to 72 of nitrous gas (twice as many in the first trial) in a wide vessel over water so as to form a thin stratum of air.19 after an immediate momentary shaking, as before, a residue of 79 or 80 measures of pure azotic gas was found. finally, if fewer than 72 measures of nitrous gas had been used, there would have been a residue containing oxygen, but if more, then some residual nitrous gas would have been found. at this point, all the foregoing findings led dalton to state what has been regarded as a key step in the development of his atomistic reasoning; the discovery of multiple combining proportions:20 the elements of oxygen may combine with a certain portion of nitrous gas, or with twice that portion, but with no intermediate quantity in order to account for the diversity of the results obtained with the nitrous gas test, dalton suggested that nitric acid (no2 in dalton’s terms) had been formed in the first trial, and in the second nitrous acid (n2o3 in dalton’s terms).21 however, since both acids could be formed at the same time, one part of the oxygen went to one of nitrous gas, while another part of oxygen went to two others of nitrous gas.22 therefore, the quantity of nitrous gas absorbed had to be variable across a range of 36 to 72 parts for 100 parts of common air. regarding the size of the tube used, he concluded that the wider the tube the quicker the test could be completed, and the more the mixture was exposed to water the greater was the quantity of nitrous acid and the lesser of nitric acid yielded. sometime between october and november, 1803, dalton carried out a series of experiments on the oxides of nitrogen that he reported in the two trials in his paper of 1805. according to dalton’s notebook, nitrous gas and common air should be suddenly mixed in the second trial.23 in earlier trials, dalton had calculated the corresponding nitrous gas–oxygen ratio. actually, this ratio was nothing but the proportion between nitrous gas and oxygen at the point of saturation. as far as eudiometrical purposes were concerned, dalton recommended attempting to form either nitric acid (first trial) or nitrous acid (second trial) entirely alone rather than a mixture of both. however, he decided on the first experiment because it appeared to be the most easily and accurately performed. to this end, he recommended the use of a narrow tube, but wide enough to allow nitrous gas to be absorbed by water without the need for any shaking.24 the test was executed by providing a little more nitrous gas to the oxygen gas than was sufficient to form nitric acid. as soon as the diminution in volume appeared to be complete, the gaseous residue was transferred to another tube. 7/19 of the loss was due to oxygen.25 this was necessary to prevent the nitric acid, formed and combined with water, from absorbing the remainder of the nitrous gas to form nitrous acid. on october 21st, 1803, nearly a year after the reading of the 1802 paper, dalton read a paper at the literary and philosophical society of manchester on the absorp56 pere grapí tion of gases by water and another liquids, which also remained unpublished until 1805 in the memoirs of the society. by that date, therefore, dalton had already arrived at the conclusion that the rapid mixture of oxygen and nitrous gas over a broad surface of water occasioned a greater diminution in volume than otherwise.26 from 1806 onwards, more details emerged about the development of dalton’s nitrous test thanks to the new editions of william henry’s work an epitome of chemistry. a personal communication to henry provides the conclusions of dalton’s study regarding the influence of the size of the tube and the manner in which the gases were mixed on determining the proportion of oxygen in an air sample. if pure nitrous gas was admitted to pure oxygen gas in a narrow tube so that the oxygen gas was uppermost, the two gases united very nearly in the proportion 1.7 [first trial]. if, on the other hand, the nitrous was the upper gas, a much smaller quantity of it disappeared [1 oxygen/1.24 nitrous gas]. if nitrous gas was admitted to pure oxygen gas in a wide vessel over water, the whole effect took place immediately and one measure of oxygen united with 3.4 of nitrous gas [second trial]. to render this rule more intelligible, dalton gave as an example the case of 100 measures of common air that were delivered to 100 measures of a mixture of nitrous gas with an equal proportion of azotic or hydrogen gas, which after standing for a few minutes in the eudiometer were found to give 144 measures. when this loss of 56 was divided by 2.7, it gave a measure of almost 21 for the oxygen gas present in 100 measures of common air.27 when analysing atmospheric air samples, it was scarcely necessary to dilute the nitrous gas with any other gas prior to its use. the recommendation was to wait for a certain period of time 10 minutes, for instance before noting the diminution in volume, without the need to transfer the residue to another vessel. if the gas sample under examination contained much more oxygen than in atmospheric air, then it was appropriate to dilute the nitrous gas with an equal volume of hydrogen, in which case the narrower the tube the more accurate would be the result. as regards the experimental equipment, two graduated tubes with funnel-shaped extremities (figure 4: 1 and 2) were employed, each from 3 to 4 tenths of an inch in diameter and 8 or 9 inches long.28 by 1806, henry had changed his mind about the employment of nitrous gas for determining the purity of air. he came to prefer dalton’s method to all the others because of its facility, quickness and accuracy, at least for gaseous mixtures of a very similar standard to the atmosphere. notwithstanding this constraint, the method was valued because it could be applied to determining the proportion of oxygen in some gaseous mixtures to which other eudiometrical tests were not applicable, such as mixtures of hydrocarbons and oxygen gases. the application of nitrous gas to eudiometrical purposes would still admit of further accuracy when used by gaylussac.29 gay-lussac’s study on the oxides of nitrogen. reshaping the nitrous gas eudiometer the combinations of nitrous gas with oxygen constituted one of the issues in chemistry about which little agreement existed at the beginning of the nineteenth century. on march 13th, 1809, gay-lussac read the mémoire sur la vapeur nitreuse et sur le gaz nitreux considére comme moyen eudiométrique at the institut de france, where he reported on his research work, the aim of which was not only to establish the theory of the formation of nitrous and nitric acids using nitrous gas and oxygen, but also the transformation of the nitrous gas eudiometer into an instrument of accuracy. joseph-louis gay-lussac (1778-1850) had been appointed to the post of demonstrator (répétiteur) at the école polytechnique in september 1804. he had attended the chemistry lectures given at this same institution by antoine-françois fourcroy (1735-1809) and louisfigure 4. apparatus that belonged to dalton.29 1, 2. glass funnels with long graduated stems closed at the ends used by dalton as eudiometrical tubes. 3. graduated bell jar with bent tube attached for collecting and measuring gases. 4. graduated bell jar with brass cap and stopcock for measuring gases. 5. conical glass vessel containing mercury. 6. a fragment of hope’s eudiometer. from memoirs and proceedings of the manchester literary & philosophical society, 1904, vol. 48 (no. 22), plate 2. 57the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination nicolas vauquelin (1763-1829) in the first year, by jeanantoine chaptal (1756-1832) in the second year, and by louis-bernard guyton de morveau (1737-1816) and claude-louis berthollet (1748-1822) in the final year. all were luminaries of french chemistry in the late eighteenth century. gay-lussac had the good fortune to be recruited for the arcueil group by berthollet, who eventually became the supervisor of his scientific career. his volumetric approach to matter, i.e. his concern with gases, volatile liquids and volumes rather than condensed matter and weights, was largely due to the influence of berthollet and pierre-simon laplace (1749-1827), the patrons of the arcueil group.30 in his landmark paper of 1808 on the law of combining volumes of gases, gay-lussac had ascertained that the nitrous gas (nitrogen monoxide) was composed of equal parts in volume of oxygen and nitrogen.31 in other words, 100 parts of oxygen and 100 of nitrogen produced 200 parts of nitrous gas without any diminution in volume. he also recalled that nitric acid (dinitrogen pentoxide) was composed of 100 parts of nitrogen and 200 of oxygen. nitric acid could therefore be regarded as composed of 100 parts of oxygen and 200 of nitrous gas, because the latter contained as much oxygen as nitrogen without any diminution in volume. he also found that 100 parts of nitrogen required 50 parts of oxygen to form nitrous oxide (dinitrogen monoxide). to obtain the nitric or the nitrous (nitrogen dioxide) acids by combining nitrous gas with oxygen was not simply a matter of first introducing one gas and then the other, but of which gas predominated in the mixture. when oxygen and nitrous gas were mixed in the appropriate ratios, the absorption of the vapour formed thereby was prompt and complete. thus, by using a narrow tube, nitric acid containing 100 parts of oxygen and 200 of nitrous gas was obtained. however, when both gases were mixed in a slightly larger tube, absorption did not vary significantly, providing that no shaking took place, because water would dissolve the nitrous gas. in this case, the acid obtained was nitrous acid gas. on the other hand, if either of the two gases predominated to excess, the nitrous gas was prevented from coming into contact with the water and dissolving easily. thus, with an excessive amount of oxygen, nitric acid was produced, while on the other hand an excessive amount of nitrous gas produced nitrous acid.32 despite the discrepancy between gay-lussac’s results and dalton’s on the composition of the oxides of nitrogen,33 he did not refrain from stating his conclusions on the influence of the size of the tube in which the gases combined a key factor in the design of his eudiometrical device. gay-lussac’s volumetric approach to matter was not the only inf luence of his mentor berthollet, whose experience with procedures in large scale chemical productions was probably decisive for his view that chemical phenomena were to a large extent conditioned by their surrounding circumstances. from this perspective, the fact that gay-lussac gave so much importance to the size of the reaction tube and its effect on the outcome of the combination of gases may be better understood. since the aim of eudiometrical analysis was to remove all the oxygen in an air sample, an excess of nitrous gas was needed in order to obtain a volume reduction four times larger than the volume of oxygen in the sample. thus, possible errors corresponded to only a quarter of the oxygen, and since it was not possible to err by four degrees, the oxygen content in a gas mixture could be estimated by much less than one-hundredth. the only precautions to be taken were to avoid shaking the mixture and to ensure that nitrous gas was always predominant without too much excess, since the more it was absorbed the less it would be mixed. even in this case, however, error would never reach a hundredth part of oxygen. in addition to these precautions, two sources of error also had to be taken into account. first of all, if the gases were mixed in a very narrow tube, nitrous acid would scarcely be absorbed by water because of the lack of contact, which would necessitate shaking, in which case nitrous gas would also be absorbed. it was for this reason that by mixing 100 parts of common air with 100 parts of nitrous gas very variable absorptions were obtained. secondly, the question of whether to introduce the nitrous gas into the tube before or after the air sample was also important, because if it was introduced first, both nitrous and nitric acids might be formed. to avoid these two shortcomings gay-lussac conducted a nitrous gas test that employed an apparatus very similar to that used by humboldt for assessing carbonic acid in a gas mixture or for analysing common air by means of nitrous gas and chlorine.34 this test was performed in the following manner (figure 5):35 the sample of the air to be analysed was collected in the measure (n), equivalent to 100 parts of the tube (k) graduated in 300 parts. the air sample was then introduced into this tube (k) with the copper funnel (m) coupled to the ferrule (hi) of the tube. the number of parts of the air sample contained in the tube was noted. afterwards, the air sample was transferred to a wide glass vessel (a) with a flat bottom, containing about 250 parts and closed by a copper component (bfgc). this component consisted of a slightly funnelled part (bc), a funnel (fg) and a sleeve (de) abraded with emery so that the ferrule (hi) of the tube (k) fitted exactly. the nitrous gas was measured in 58 pere grapí the same way and rapidly mixed with the air sample by coupling the tube to the sleeve (de) without agitating. a red vapour appeared immediately and then disappeared very quickly. after half a minute, or one minute at most, absorption could be regarded as complete. the device was then turned upside down and the residual gas ascended in the tube. after that, the tube (k) was removed from the vessel (a) to restore the pressure equilibrium and the residue was assessed. the total absorption divided by 4 gave the quantity of oxygen. gay-lussac reported having performed many varied analyses, always finding a perfect agreement among them. in 1818, william henry still regarded gay-lussac’s application of nitrous gas to eudiometrical purposes as an accurate procedure, provided certain precautions suggested by his theoretical views of the constitution of nitrogen oxides were taken into account.36 final remarks the sources of dalton’s criticisms of the nitrous gas test were very precise: the influence of the size of the eudiometrical vessel and the shaking of the gas mixture in its volume reduction. he opted for the use of a narrow tube that allowed nitrous gas to be absorbed by water without shaking in an attempt to obtain nitric instead of nitrous acid. nevertheless, he was aware that a greater reduction in volume was obtained if the test was performed over a broad surface of water. his assumptions about these two factors were in principle concerned with the justification of his statement on the multiple combining proportions, rather than with the improvement of the nitrous gas test, and he was in fact obliged to conduct the test in vessels of different sizes and with variable procedures until he obtained the results he was aiming for. from 1806 onwards, dalton contributed material as well procedural improvements to the nitrous gas test employed as a eudiometrical method. thus, in addition to recommending the use of narrow tubes, he emphasised the advantage of adding the nitrous gas once the oxygen gas was already in the tube and not the other way around. arguably, the nitrous gas test that in the hands of dalton had evolved from a eudiometrical method to an iconic case of multiple combining proportions was returned to eudiometrists in a simpler and more trustworthy version of the eudiometrical test than those performed with the latest nitrous air eudiometers. in a certain sense, it was as if priestley’s conception of the nitrous air test, characterised by simplicity of materials, apparatus and experimental procedures, had won out in the end. dalton’s investigations on the nitrous gas test engendered further developments in 1809 at the hands of gaylussac, who had already begun his research work on eudiometry some years earlier. he did not agree with dalton’s experimental results on the proportions of combination of nitrous gas with oxygen, mainly because these proportions did not match his law of combining volumes. however, this discrepancy proved to be no obstacle to gay-lussac’s acceptance of dalton’s conclusion on the influence of the size of eudiometrical recipients on the experimental outcomes. his own researches on the oxides of nitrogen, together with dalton’s recommendations on the size of the recipients, guided him in the reshaping of the nitrous gas eudiometer that culminated in a more definitive version of this type of instrument. figure 5. gay-lussac’s nitrous gas eudiometer. from mémoires de physique et de chimie de la société d’arcueil, 1809, vol. 2, plate 2. 59the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination acknowlegment the author wishes to acknowledge the vernon press for its permission to reproduce a number of excerpts from the author’s book (see note 9). references and notes 1. j. priestley, philos. trans. r. soc. london. 1772, 62, 147, pp. 211, 214. 2. s. hales, statical essays containing vegetable staticks, w. and j. innys & t. woodward, london, 1738, 2 vols, vol.1, p. 224, vol. 2, pp. 280-284. 3. j. mayow, tractus quinque medico-physici. quorum primus agit de sal-nitro et spiritu nitroaereo, theatro sheldoniano, oxon, 1674, (english translation: 1907, edimburgh: the alembic club reprint, no. 17.), pp. 162-163. s. hales, vegetable staticks: or, an account of some statical experiments on the sap in vegetables, w. and j. innys; t. woodward, london, 1727, p. 125. 4. the expression ‘mouse-free route’ encapsulates the meaning of this replacement. t.h. levere in instruments and experimentation in the history of chemistry (eds.: l.h. holmes, t.h. levere), the mit press, cambridge, ma and london, 2000, 105, p. 110. 5. upon contact of no with atmospheric oxygen, a brownish gas [no2] forms immediately and the color dissipates within a few minutes as no2 dimerises to n2o4 and completely and irreversibly dissolves in water, giving a mixture of hno3 and hno2. simultaneously, no and no2 react to form n2o3, which also dissolves in water to give additional hno2. consequently, a contraction in volume of the gas mixture is observed. in stoichiometric ideal conditions the global process would be: 6 no (g) + 2 o2 (g) + 3 h2o (l) = 5 hno2 (aq) + hno3 (aq). therefore, the only residual gas with a common air sample in such conditions would be nitrogen. m. c. usselman, d.g. leaist, k. d. watson, chemphyschem, 2008, 9, 106, p. 107. 6. j. priestley, experiments and observations relating to various branches of natural philosophy, with a continuation of the observations on air, j. johnson, birmingham, 1779, p. 69. chemists believed that phlogiston was an intangible fluid released in combustion that was impossible to handle. atmospheric air was believed to consist basically of a mixture of phlogisticated or mephitic air (later called nitrogen) and dephlogisticated or vital air (later called oxygen). with regard to animal respiration, the prevailing belief was that expired air conveyed the phlogiston released from the lungs during breathing and evacuated it from the body. phlogisticated air (i.e. saturated with phlogiston) was consequently unable to absorb more phlogiston and would not be appropriate for breathing; that is, it would be unhealthy or mephitic air. on the other hand, dephlogisticated air was deprived of more than its normal allocation of phlogiston, and therefore was more wholesome. in other words, the healthier an air the less phlogiston it contained. 7. j. priestley, 1775, experiments and observations of different kinds of air, j. johnson, london, 1775, pp. 20-21, 110-112. 8. this term is derived from two greek words. the first part of the term (εὔδιος) means “clear or mild weather”, but also with the implication of good air, because (διος) stemming from zeus can mean “weather” or “air”. the second part of the term (μέτρο) means “measure”. m. landriani, ricerche fisiche intorno alla salubrità dell’aria, s.n., milano, 1775, pp. 3, 6. 9. to explore and comprehend how eudiometers work, the materials used in making them and the reagents employed in each eudiometrical test, all with special attention paid to the experimental procedures involved over the course of the test, constitute the main aims of the author’s book. p. grapí, inspiring air. a history of air-related science, vernon press, wilmington, de, 2019. to understand eudiometers, it is essential to stress the interplay between the instruments themselves and their contextual environment and, in this sense, it is equally indispensable to emphasise that eudiometers took on a life of their own in many different contexts; human and animal health, quantification, gas analysis, chemical theory, medical therapeutics, plant and animal physiology, atmospheric composition, chemical compound composition, gas lighting, chemical revolution, experimental demonstration and the chemical industry. 10. progress in the nitrous air test and eudiometer was mainly reflected in their use in research experiments and in the search to obtain a standard test procedure in order to arrive at a reliable test. the reliability of the test depended on many intrinsic and extrinsic factors, which were not always easy to define and control. however, the factors that proved to have the most significant effect were: the establishment of the test endpoint; the determination of the saturation ratio of nitrous and dephlogisticated air (oxygen); the dosing of the air samples; the time spent on particular operations; the water source used, and the 60 pere grapí quality of the nitrous air as a reagent. standardising the nitrous air test to make it more reliable involved working out an operating protocol that demanded skilful experimenters with the appropriate training. the issue was not that skilful experimenters such as ingenhousz were able to execute that protocol successfully, but rather that novices in eudiometry would also be capable of performing it. 11. h. e. roscoe, a. harden, a new view of the origin of dalton’s atomic theory. a contribution to chemical history, macmillan and co, london and new york, 1896, p. 33. 12. a. j. rocke, chemical atomism in the nineteenth century. from dalton to cannizzaro, ohio university press, columbus, oh, 1984, pp. 27-33. 13. a. j. rocke, social research. 2005, 72, 1, 125, pp. 136-137. 14. w. c. h. henry, memoirs of the life and scientific researches of john dalton, the cavendish society, london, 1854, p. 47. a. thackray, john dalton. critical assessments of his life and science, harvard university press, cambridge, ma, 1972, pp. 48-51, 64-66. 15. r. w. a. oliver, m. carrier, the library of john dalton, titus wilson & son, kendal, 2006, pp. 9-14, 28-30. 16. j. dalton, philos. trans. r. soc. london. 1837, 127, 347, p. 348. 17. w. henry, an epitome of chemistry, j. johnson, london, 1803, p. 74. 18. j. dalton, memoirs of the literary and philosophical society of manchester. 1805a, 2nd series, 1, 244, p. 249. a. f. humboldt, ann. chim. 1798, 28, 123, pp. 151-171, 177-180. 19. dalton gave no details of the size of this wide vessel. 20. a. j. rocke, 1984, 45, note 28. see note 12. 21. at that time, nitrous acid was not known to be a distinct and less oxygenated acid, but rather regarded as a mixture of nitric acid and nitrous gas. h. davy, researches chemical and philosophical, chiefly concerning nitrous oxide, j. johnson, london, biggs and cottle, bristol, 1880, p. 31. the collected works of sir humphry davy, (ed.: john davy), smit, elder and co. cornhill, london, 1836-1840, 9 vols, vol. 3, p. 22. 22. the first trial yielded the most oxygenated nitric acid [o + no = no2, in dalton’s terms], while the second yielded the least oxygenated nitrous acid [o + 2 no = n2o3, in dalton’s terms]. the latter reaction took place rapidly in the thin gas stratum of the wide vessel, but slow enough in the narrow tube to enable nitric acid to be the sole product (usselman et al., 107. see note 5). 23. h. e. roscoe, a. harden, 1896, p. 35. see note 11. 24. j. dalton, 1805a, pp. 247-251. see note 18. 25. the 136 [100 +36] parts of the mixture gave a residue of 79 parts in the first trial (assuming 21% of oxygen in common air). therefore, the loss was 57 [136-79] and 7/19 [21/57] of the diminution was oxygen. 26. j. dalton, memoirs of the literary and philosophical society of manchester. 1805b, 2nd series, 1, 271, pp. 274-275, note. in this way, nitrous acid was formed, whereas when water was not present nitric acid was obtained, which required just half the quantity of nitrous gas. the replications of dalton’s experiments reported in his 1805 paper proved that in the narrow tube conditions (first trial) the greatest diminution in volume occurred at a ratio of 1.7, as dalton reported. nevertheless, the contraction in volume reported at a ratio of 3.4 (second trial) was significantly different from the replicated value. all in all, it is necessary to recognize that the influence of dissolved oxygen in water could make the second trial results plausible. the lack of published details on the exact size of the reaction recipients rendered a meaningful replication of the second trial impossible. (usselman et al., 2008, pp. 108-109. see note 5) 27. w. henry, an epitome of chemistry, collins and perkins, new york, ny, 1808 (first american from the fourth english edition of 1806), pp. 153-154. 28. these tubes were of the same width but of shorter length than the one described by dalton in 1805. 29. in 1904, the council of the manchester literary and philosophical society resolved that photographs of the apparatus belonging to dalton should be taken for reproduction in the papers of the manchester literary & philosophical society. 30. m. crosland, gay-lussac, scientist and bourgeois, cambridge university press, cambridge, 1978, pp. 28-31. 31. j. l. gay-lussac, mémoires de physique et de chimie de la société d’arcueil, mad. ve. bernard, paris, 1809a, 3 vols, vol. 2, pp. 206-234, 215-216, 218. 32. j. l. gay-lussac, 1809b, mémoires de physique et de chimie de la société d’arcueil, mad. ve. bernard, paris, 1809b, 3 vols, vol. 2, 235, pp. 236-239. the study of the oxides of nitrogen was a complex field of research for early nineteenth century chemistry. gay-lussac successfully re-examined his conclusions on this issue in 1816, after dalton’s and davy’s criticisms (ann. chim. phys. 1816, 1, 394). 33. gay-lussac’s results on the composition of the oxides of nitrogen did not agree with those published by dalton in 1805. according to dalton, 21 parts of oxy61the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination gen could unite with 36 of nitrous gas or with twice 36, i.e. 72 parts. in other words, 100 parts of oxygen united with 171.4 or 342.8 parts of nitrous gas. in gay-lussac’s opinion, these results were inaccurate because the first ratio of nitrous gas was too small and the second was too large, in addition to which the two gases did not combine in simple ratios. it should be remembered that gay-lussac’s law of combining volumes established that gases combined in very simple ratios, and that the volume reduction they underwent on combination also had a simple ratio to their volume, or at least to the volume of one of them. (gay-lussac, 1809b, p. 244. see note 32) 34. ibid. pp. 246-247. 35. ibid, pp. 249-251. 36. w. henry, the elements of experimental chemistry, baldwin, cradock and joy and r. hunter, london, 1818, 2 vols; vol. 1, pp. 393-394. substantia an international journal of the history of chemistry vol. 4, n. 1 2020 firenze university press peer review – critical feedback or necessary evil? seth c. rasmussen particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 consciousness, information, electromagnetism and water marc henry leonardo and the florence canal. sheets 126-127 of the codex atlanticus filippo camerota the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí astatine – the elusive one keith kostecka vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of xx century aleksander sztejnberg substantia. an international journal of the history of chemistry 3(2): 73-96, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-638 citation: p.r. salvi, v. schettino (2019) sadi carnot’s réflexions and the foundation of thermodynamics. substantia 3(2): 73-96. doi: 10.13128/ substantia-638 copyright: © 2019 p.r. salvi, v. schettino. this is an open access, peer-reviewed article published by firenze university press (http://www. fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino dipartimento di chimica “ugo schiff ”, università di firenze via della lastruccia 3, 50019 sesto fiorentino (fi), italy abstract. the purpose of this article is to present a short review of sadi carnot work on heat engines and on the role his adherence to the caloric theory may have had. the essential points developed in the réflexions are reviewed as forerunners of the science of thermodynamics. the antecedents that may have inspired the brilliant scientific insights of carnot are reviewed together with the reception of the carnot principles in the engineering and in the scientific community until the formulation of the two principles of modern thermodynamics. 1. introduction in several cases new important scientific theories have been outlined starting from models or interpretative schemes that later developments have shown groundless or partially incorrect. the limits of the starting bases were overcome by the intuition or the imagination of the scientists. an example of this twisted way in the advancement of science is the discovery of the periodic system of the elements by dmitrij ivanovich mendeleev (1834-1907). in a meeting of the newly founded russian chemical society (held on march 6, 1869) mendeleev presented his periodic table of the elements, later published in the journal of the society [1] and in a german edition [2] and included in mendeleev’s treatise principles of chemistry (1868-1870). mendeleev arranged the 63 known elements in order of increasing atomic weight and the table showed the periodic recurrence of their physical and chemical properties, identifying group of elements with similar properties. the really innovative aspect of the table was in its heuristic power. in fact, in his ordering mendeleev was forced to leave empty places corresponding to unknown chemical elements whose physical and chemical properties were predicted by mendeleev. these unknown elements were actually discovered a few years later [3] and their properties were found to be in good agreement with mendeleev predictions. almost simultaneously a similar periodic table, including only 28 elements, was published by lothar meyer [4]. today we know that the ordering of the elements in the periodic table is based on the atomic number and that the chemical and physical properties of the elements depend on the electronic structure of the atom. nevertheless, the general idea of mendeleev’s periodic table has remained unchanged 74 pier remigio salvi, vincenzo schettino surpassing, almost unscathed, the revolution of quantum mechanics apart from the adaptations required to accommodate the numerous new elements discovered. sadi carnot’s contribution to the foundation of thermodynamics can be analyzed along the same lines. in a historical period in which the first and second principle of thermodynamics and the equivalence between heat and work had not yet been established nicolas léonard sadi carnot (1796-1832), in his famous booklet réflexions sur la puissance motrice du feu et sur les machines propres à développer cette puissance [5], published in 1824, (fig. 1), was able to arrive at a substantial definition of the second principle, starting from the assumption of the caloric theory which attributed a character of materiality to heat. even though, in addition to the erroneous nature of the current heat theory, various aspects of gas properties, such as the pressure-volume relationship along adiabatic transformations or the specific heats of gases, were not completely defined at the time on the basis of available experiments and theories, carnot, starting from the study of the general characteristics of the thermal engines and the conditions for optimizing their performances, succeeded in defining general principles that would open the way to the establishment of thermodynamics as an autonomous science . the work of carnot and his réflexions have been the subject of extensive and detailed studies (as it will be reported and discussed in the following) regarding, on the one hand, the original type of scientific reasoning underlying his conclusions and on the other the previous scientific knowledge and the later developments in thermodynamics. the aim of this work is to present a review of carnot’s contribution to thermodynamics and the various possible interpretations of his work. after a brief biographical profile of sadi carnot and an overview of the theories of heat, the essential points of the réflexions will be revisited and subsequently examined with reference to possible scientific backgrounds and to the subsequent reception of the réflexions in the scientific and engineering community. 2. brief biography of sadi carnot to better frame the work of carnot in its historical context a brief biographical profile may be appropriate. the first information we have on sadi carnot can be found in the note of one of his fellow students of the école polytechnique, and probably his friend, michel chasles [6] and in the obituaries of claude-pierre robelin [7] and of adolphe gondinet [8], this latter reported by pietro redondi [9]. more substantial biographical information has been reported later by paolo ballada count of saint-robert, a piedmontese engineer interested in thermal machines and industrialization processes [10], based on a letter from the grandson adolphe of sadi carnot [11]. a similar but more informative letter dated 1878 from the brother hippolyte carnot has been reported by r.h. thurston [12]. on the biography of carnot, birembaut has returned with new documentation [13] noticing various inaccuracies in his brother’s story. sadi carnot (fig. 2) was born in paris, june 1st, 1796. his father, lazare carnot (1753-1823), was a leading political figure during and after the french revolution, deserving the name of organizer of victory due to the military successes during the revolutionary period. he was also a great mathematician and physicist and a cultivated poet and in honor of the persian poet sadi of figure 1. front page of the original work of carnot. 75sadi carnot’s réflexions and the foundation of thermodynamics shiraz he gave the name to his first son. the mother was a gifted pianist. carnot had a very reserved character but, whenever necessary, he was able to show great energy and decision. this results already from an anecdote of his childhood as reported by the brother hippolyte [12]. his father often brought sadi with him. on one occasion, when napoleon bonaparte enjoyed throwing rocks in the water to splash a group of ladies, including madame bonaparte, who were on a boat, the little sadi did not hesitate to turn to the first consul decisively: beast of a first consul, will you stop tormenting those ladies? the great tension of the moment vanished when napoleon, followed by everyone present, burst into laughter. sadi carnot, after being initially instructed directly by his father lazare [14], at age 16 was enrolled at the polytechnic school having as professors, among others, poisson, thenard, arago, petit and dulong [15]. after graduation he was admitted in 1814 in the artillery and engineering application school of metz as a cadet sub-lieutenant. he entered the military career in april 1817 with typical duties like inspecting fortifications, proposing and reporting on engineering plans. in 1818 he applied successfully for a position in a newly formed engineering corps at the army headquarters in paris. this allowed him to attend courses of mathematical sciences, natural history, industrial art and political economy held in the college of france and sorbonne. he had also the opportunity, as it will be discussed in the following, to make acquaintance with clément at the conservatory of arts and crafts. in 1821 he visited his father in exile at magdebourg. back in paris and after completing various tasks as a military engineer he resigned as captain of the military engineering and developed a more direct interest in heat engines which led, in the following years, to publication of the réflexions. in 1831 he resumed the study on the properties of gaseous substances encouraged by the appearance of two memoirs on the subject by dulong. unfortunately, in the same year he took scarlet-fever and fell seriously ill. sadi carnot died at age 36 in paris by a violent attack of cholera on august 24, 1832. 3. caloric versus mechanistic theory of heat the type of reasoning used by carnot in the réflexions was based on the acceptance, albeit with significant distinctions, of the caloric theory. the theory of heat, with its evolution and oscillation between a materialistic and mechanistic view, has been discussed in great detail in many texts [16-19] and in many articles in scientific journals [20-23]. in this section only some points of this long history will be recalled to highlight how, even if the caloric theory was dominant in france at the time of carnot, the two aspects of the heat theory tended to overlap in general and sometimes even in the same author, as it was indeed the case for carnot. intuitively, the concept of heat is linked to that of fire. fire was assumed as the prime element in the philosophy of heraclitus, to explain the continuous becoming of natural phenomena, and had then become one of the four constitutive elements of empedocles’ philosophy. the fire instinctively arouses the idea of the motion of elementary particles emitted by the bodies and capable of producing the physical sensation of heat. from this point of view, it is remarkable that in the title of his réflexions carnot refers to fire: la puissance motrice du feu, a diction that in english translations will become the motive power of heat. redondi [10] attached a particular significance to the use by carnot of the word feu instead of chaleur as an attempt to give to the term a wider generality. the concept of heat has remained scientifically undefined for a very long time because of a lack of experimental tools to measure and quantitatively define figure 2. sadi carnot at the age of 17. 76 pier remigio salvi, vincenzo schettino heat and make a clear distinction between heat and temperature. these shortcomings were overcome by thermometry and calorimetry. confining the attention to chemistry, hermann boerhaave (1668-1738), a physician and chemist, introduced in the chemical laboratory a thermometer, built by daniel gabriel fahrenheit (16861736), allowing to go beyond the sensory abilities in the control and understanding of heat [24]. for boerhaave heat, or fire as he called it, was a subtle and imponderable fluid that interacted with matter to give rise to all that concerned heat [25]. however, the materialistic vision of boerhaave had a dynamic character: the particles of heat were constantly moving and the increase in heat produced an increase in the movement of the particles. further progress in the study of heat was made with joseph black (1728-1799) who highlighted the conceptual difference between temperature and heat and invented the calorimeter to measure the amount of heat that develops in a chemical reaction [26]. an important discovery of black was the observation that in the process of melting or boiling a substance absorbed heat without changing temperature arriving at the distinction between latent heat and free (or sensible) heat. black also established that the specific heat differs for various substances. it is remarkable to note that james watt (17361819), the instrument maker who perfected newcomen’s steam engine, was a student of black. black was a follower of the phlogiston theory that had been developed by johann joachim becher (16351682) and his pupil georg ernst stahl (1660-1734). according to becher [27] there were three elements, the terra fluida (or mercurial), the terra pinguis (or fat or combustible) and the terra lapidea (or vitrifiable). the combustible earth produced oils and fuels. stahl [28] developed the master’s ideas and called the combustible earth phlogiston. the phlogiston was volatile and tended to rise upwards. according to the theory, the metals were rich in phlogiston which was liberated during the calcination and their transformation into calxes (oxides). the process was reversible and by burning the oxides with coal the metal was regenerated with the reabsorption of the phlogiston. the phlogiston theory spread among chemists because of its ability to explain the phenomena of combustion, despite considerable inconsistencies. for example, since metals during calcination increase in weight, it was necessary to hypothesize that the phlogiston had a negative weight. despite this, the phlogiston theory held up until antoine laurent lavoisier (1743-1794) correctly interpreted the phenomena of combustion as reactions of substances with oxygen, the dephlogisticated air discovered by joseph priestley (17331804) and carl wilhelm scheele (1742-1786) [29]. in discussing his new theory of chemistry and the critique of the phlogiston theory [30] lavoisier was unable to abandon the theory of caloric although he still considered the caloric as one of the chemical elements. the caloric theory still survived for its extraordinary ability to explain many physical or chemical phenomena in a simple way. for example, pierre simon laplace (1749-1817), a staunch supporter of this theory [31], on the basis on the theory of caloric was able to calculate the velocity of sound in gases. it is, however, remarkable that lavoisier and laplace in a joint article [32,33] adopt the caloric theory but, preliminarily, express severe doubts about the same theory with respect to a theory based on atomic movements. in the renaissance, with resumption of atomism, a more convinced connection of heat with the movement of the microscopic particles constituting matter gradually makes its way. francis bacon (1561-1626) adopts the atomistic philosophy of democritus and in the novum organum [34] explicitly expresses himself on the nature of heat: from the instances taken collectively, as well as singly, the nature whose limit is heat appears to be motion. this is chiefly exhibited in flame, which is in constant motion, and in warm or boiling liquids, which are likewise in constant motion… the very essence of heat, or the substantial self of heat, is motion and nothing else.1 also galileo galilei (1564-1642) did not disdain the atomistic theory of the constitution of matter and in the saggiatore [35] he writes about heat: …i incline very much to believe that [...] those materials that produce and make us feel the heat, which we call with general name of fire, they are a multitude of little bodies, in such a way figured out, moved with so much speed, which, meeting our body, penetrate it with their subtlety, and that their touch, made in their passage through our substance and felt by us, generates the effect that we call hot.2 these conceptions, and similar ones we can find, for example, in robert boyle and isaac newton, must be considered intuitions rather than scientific theories. a progress in this direction will take place with dan1 [30], book 2, aphorism xx. 2 original sentence in [35], section 48, which in italian reads: … inclino assai a credere che […] quelle materie che in noi producono e fanno sentire il caldo, le quali noi chiamiamo con nome generale fuoco, siano una moltitudine di corpicelli minimi, in tal modo figurati, mossi con tanta e tanta velocità; li quali, incontrando il nostro corpo, lo penetrino con la loro somma sottilità, e che il lor toccamento, fatto nel lor passaggio per la nostra sostanza e sentito da noi, sia l’affezzione che noi chiamiamo caldo. 77sadi carnot’s réflexions and the foundation of thermodynamics iel bernoulli (1700-1782) and the publication in 1738 of hydrodynamica [36] a treatise on the dynamics of fluids which, in chapter x, proposes a kinetic model of a gas, consisting of spherical particles in rectilinear motion. for the interest of the present paper, the model assumes that heat increases the velocity υ of the particles and that both the pressure of the gas and its temperature are proportional to υ2, that is to the kinetic energy. even if the work of bernoulli did not immediately undergo the resonance that deserved, it constituted an anticipation of the kinetic theory of gases that would take place only a century after its publication. from an experimental point of view, doubts about the theory of the caloric had been advanced in 1798 by benjamin thomson (1753-1814), count of rumford, who, witnessing the reaming of the cannon barrels in the munich arsenal, observed that large (apparently inexhaustible) quantities of heat developed in the process both in the cannon and in the boring shavings [37] without changes in the properties (and in particular of the specific heat) of the cannon or shavings. similarly, in 1799 humphry davy (1778-1829) reported that the fusion of ice occurred by simply making friction between two blocks of ice at a temperature lower than the melting point [38]. later, in 1842, julius robert mayer (1814-1878) showed that the water temperature could be increased by one degree by simple mechanical stirring [39]. although these experiments were not able to undermine the caloric theory, a preliminary form of kinetic theory continued to affirm its uncertain presence thank to work by john herapath (1790-1868) and john james waterston (1811-1883), with considerable hostility in the scientific community. the seminal work of bernoulli saw a definitive flowering with the work of james prescott joule (1818-1889) [40] and rudolf clausius (1822-1888) [41] and with the complete elaboration in statistical terms by james clerk maxwell (1831-1879) [42,43] and ludwig boltzmann (1844-1906) [44,45]. 4. the thermodynamics of carnot the réflexions sur la puissance motrice du feu et sur le machines propres à développer cette puissance were initially printed in 1824 by bachelier in paris [5]; this edition can be easily accessed online. a second french edition was published in 1872 [46] and can be accessed in the annales scientiques de l’école normale supérieure at the site www.numdam.org/item/asens_1872. among the english versions we already mentioned the translation edited by r.h. thurston in 1897 [12]. an english critical edition by r. fox [47], containing also the surviving manuscripts including the recherche d’une formule propre à représenter la puissance motrice de la vapeur d’eau, first published by gabbey and herivel [48], has been published in 1986. other notable english translations have been edited by mendoza [49] and magie [50]. the réflexions begin by extolling the contribution of steam engines to the progress and wealth of england and the further advantages that could be foreseen for the development of civilization if technical improvements were able to increase their efficiency. however, carnot realizes that their theory [of steam engines] is very little understood, and the attempts to improve them are still directed almost by chance.3 and remarks that the phenomenon of the production of motion by heat has not been considered from a sufficiently general point of view.4 hence, the declared purpose of the work is of a theoretical nature, i.e., the identification of the principles and laws that regulate the phenomenon. the extraordinary nature of the réflexions lies in the critical discussion of general principles without being anchored to a corresponding mathematical formulation so that the conclusions lend themselves to be framed in the scheme of the subsequent theory of thermodynamics. 4.1 the steam engine after establishing the issues to be analyzed, namely: a) if the motive power of heat is limited; b) if the improvement of the steam engine can go beyond a certain limit; c) if there is an agent more efficient than water vapor, carnot initially focuses the attention on the steam engine, schematically represented in fig. 3. the water vaporizes in the boiler and the steam is admitted in the cylinder, thus causing the piston to move, and then, by further expansion cools back to water at the condenser temperature. the first general statement rules out the possibility of a thermal engine, like the one depicted in fig. 4a, in which heat from a single source is transformed in motive power. for the production of motive power two heat reservoirs at different temperatures are necessary: 3 [12], p. 42. 4 [12], p. 43. 78 pier remigio salvi, vincenzo schettino the production of heat alone is not sufficient to give birth to the impelling power: it is necessary that there should also be cold; without it, the heat would be useless. and in fact, if we should find about us only bodies as hot as our furnaces, how can we condense steam? what should we do with it if once produced? we should not presume that we might discharge it into the atmosphere, as is done in some engines; the atmosphere would not receive it. it does receive it under the actual condition of things, only because it fulfils the office of a vast condenser, because it is at a lower temperature; otherwise it would soon become fully charged, or rather would be already saturated.5 the heat flow from the furnace at high temperature th to the condenser at lower temperature tc would not be by itself effective in producing motive power unless the heat transfer occurs through the mediation of an agent, the steam in the present case, able to expand under the action of heat. the temperature difference 5 [12], p. 46-47. between the two reservoirs plays the role of a potential energy difference like the height in the waterfall: according to established principles at the present time, we can compare with sufficient accuracy the motive power of heat to that of a waterfall. each has a maximum that we cannot exceed, whatever may be, on the one hand, the machine which is acted upon by the water, and whatever, on the other hand, the substance acted upon by the heat. the motive power of a waterfall depends on its height and on the quantity of the liquid; the motive power of heat of heat depends also on the quantity of caloric used, and on what may be termed, on what in fact we will call, the height of its fall, * that is to say, the difference of temperature of the bodies between which the exchange of caloric is made. in the waterfall the motive power is exactly proportional to the difference of level between the higher and lower reservoirs. in the fall of caloric the motive power undoubtedly increases with the difference of temperature between the warm and the cold bodies; but we do not know whether it is proportional to this difference.6 in transmitting the caloric from the hot to the cold reservoir the volume of the steam changes and this generates the motion of the piston in the cylinder. besides steam, any substance that expands due to heat could be employed as an agent in the cyclic operation. in the context of the caloric theory as an indestructible fluid, the heat engine would work according to the scheme of fig. 4c [51], while the correct thermodynamic functioning is that of fig.4b. after establishing these general criteria, carnot moves on to the examination of the steam engine, iden6 [12], p. 60-61. figure 3. schematic representation of the steam engine. figure 4. (a) a heat engine with a single heat source; (b) a heat engine operating between two reservoirs at th and tc temperatures; (c) the steam engine according to the caloric theory of heat. in the three schemes q is the heat expended, -q the heat absorbed by the reservoir and -w the work done by the engine. 79sadi carnot’s réflexions and the foundation of thermodynamics tifying three successive phases described in detail in the recherche [48]: a) steam generation in the boiler absorbing heat from the high temperature source at th and expansion into the cylinder equipped with a movable piston by the opening of the upper valve; b) further steam expansion and piston motion with upper and lower valves closed; c) steam condensation at the refrigerant temperature tc after the opening of the lower valve and return of the piston to the initial position. it can be seen that, from the beginning, carnot includes the adiabatic expansion (process b) according to the expansive principle of watt introduced explicitly by clément [52,53]. supposing that the steam engine works without dispersion of heat and the conditions for maximum power output are satisfied, the mode of operation of the steam engine can be reversed. calling the hot and cold reservoirs a and b, respectively, the direct and inverse operation of the steam engine can be compared: in the first the caloric is transferred from a to b and motive power is produced, in the second the caloric flows from b to a and motive power is expended. it is evident that acting on the same quantity of vapor and with no loss of caloric or motive power, the a → b and b → a amounts of caloric are equal as well as the direct and inverse motive powers, apart from the sign, so that the overall balance is zero. alternating the two processes in opposite directions in an indefinite number of operations neither motive power is produced nor caloric is transferred. if a different process were available producing more motive power than that produced by the steam engine, all other conditions being equal, it would be possible to couple this process with the steam engine, to return at the initial conditions and to divert a portion of the motive power at the end of the reversed process. the net result would be creation of motive power from nothing. this is perpetual motion, contrary to the laws of mechanics and as such inadmissible. the conclusion is: the maximum of the motive power resulting from the employment of steam is also the maximum of motive power realizable by any means whatever.7 carnot realizes that the proposition should be considered only as an approximation8 and that a more rigorous demonstration is necessary. an important point is that the described process of the steam engine is not reversible since the agent at the end of the process has not recovered the initial state, which is a basic requirement 7 [12], p. 55. 8 [12], p. 56. for the comparison of the performances of engines with different agents. the closure of the cycle cannot be simply obtained by the direct contact of the cold liquid with the high temperature reservoir since this direct contact between bodies at different temperatures will cause a loss of motive power and the reverse process would be impossible. this problem is circumvented when the temperature difference between a and b is indefinitely small since in such a case the heat necessary to raise the cold liquid to the initial temperature is also negligibly small compared to the caloric producing power. in the more general case of a finite temperature difference one may imagine that a series of other reservoirs, c, d, e, …… could be inserted between a and b with infinitely small spacing between two adjacent reservoirs such that the caloric transfer from a to b occurs through intermediate steps each developing maximum motive power. 4.2 the carnot cycle the analysis continues to arrive at a more exhaustive demonstration of the general principle derived from the study of the steam engine which carnot himself defined as approximate. to this end carnot proposes an ideal thermal engine, the famous carnot engine, which works in a perfectly cyclical manner and which uses a permanent gas, air, as an agent. this choice corresponded to a need felt in the environment of thermal engines to use an agent other than water that could be used at higher pressures and, hopefully, with fuel savings [16]. the starting experimental observation is that expansion causes a temperature fall, and compression a temperature rise, which can be compensated by absorption and release of caloric, respectively. the series of operations can be described with reference to the reproduction of the original carnot drawing shown in fig. 5a: i) the gas, initially enclosed in the abcd volume (with cd the actual position of the piston), is in contact with the wall of the cylinder which freely transmits the caloric from furnace a. the gas is thus taken at the temperature th of the furnace. ii) the piston gradually moves isothermally up to the position ef. iii) the furnace is removed and the gas is fully isolated from external bodies. the piston moves from position ef to gh. during this adiabatic expansion the gas temperature decreases until it reaches the temperature of the condenser b. iv) the gas is now placed in contact with the condenser b and isothermally compressed until the piston moves back from the position gh to cd recovering the initial volume but at the condenser temperature. 80 pier remigio salvi, vincenzo schettino v) the condenser b is removed. an adiabatic compression of the gas is carried out until the temperature rises to reach again the temperature of the furnace a. the piston moves from cd to ik. vi) the gas is now placed in contact with the furnace a and the piston goes from ik to ef. the cycle is successively repeated along the steps iii, iv, v, vi. for the sake of clarity in fig. 5b the usual representation of the carnot cycle on a p-v diagram is shown. problems connected with the correct closure of the cycle in the p-v diagram have been discussed by klein [54], kuhn [55], la mer [56,57] and tansjo [58]. useful motive power is obtained since the elastic force (i.e., pressure) of the gas in the isothermal expansion is greater than in the isothermal compression so that the power produced in the first operation exceeds that consumed for compression: the quantity of motive power produced by the movements of dilatation is more considerable than that consumed to produce the movements of compression.9 by a line of similar reasoning as employed to show the impossibility to produce motive power greater than that by a reversible steam engine, the general conclusion, known as carnot’s principle, is reached the motive power of heat is independent of the agents employed to realize it; its quantity is fixed solely by the temperatures of the bodies between which is effected, finally, the transfer of the caloric.10 9 [12], p. 65. 10 [12], p. 68. the next basic question concerns the dependence of the motive power on the temperature of the two reservoirs and, in particular, whether a difference of motive power should be expected for a fall of caloric from 100oc to 50oc and from 50oc to 0oc. to this purpose, carnot considers two air engines working between 100oc and (100 – h)oc and 1oc and (1 – h)oc, respectively, with h extremely small. the motive power results from that supplied by the air in the v1→v2 expansion minus that expended in the opposite compression and is the same for the two engines. carnot easily comes to this conclusion, valid also within the later thermodynamic theory, in a long note ([12], p. 98). for the comparison between q100, the heat necessary to keep air at 100oc during the expansion, and q1, the equivalent quantity at 1oc, carnot considers two different paths from the starting point, 1oc and v1, to the final point, 100oc and v2. one is performed by heating at v1 up to 100oc and then expanding isothermally to v2, the other by the reverse combination, i.e., expanding isothermally at 1oc to v2 and then heating at v2 up to 100oc. according to the caloric axiom the two amounts of heat are independent on the path and therefore qv1 + q100 = q1 +qv2 where qv1 and qv2 are heats to increase the air temperature from 1oc to 100oc at the two different volumes v1 and v2, respectively. it was incorrectly established from measurements reported in previous years by delaroche and bérard on several gases that their specific heats depend on density, decreasing with increasing density [59]. carnot acknowledges the result by saying that “the capacity of gases for heat changes with their volume” ([12], p. 78), increasing as the volume increases. since qv2 > qv1,it follows that the quantity of heat due to a change of volume of a gas is greater as the temperature is higher11 and as a consequence the fall of caloric produces more motive power at inferior than at superior temperatures12 because the amounts of heat are different (q100 > q1), while the motive power is the same for the two engines. the conclusion happens to be correct, as everybody of us knows looking at the efficiency of thermal engines reported in all thermodynamic textbooks, but, as 11 [12], p. 96. 12 [12], p. 97. figure 5. (a) the carnot cycle as shown in the original drawing; (b) the usual representation of the carnot cycle for a gas on the p-v diagram. points a and 4 correspond to the initial volume and to completion of the isothermal compression. 81sadi carnot’s réflexions and the foundation of thermodynamics already noted [16], the justification rests on the false assumption of the caloric conservation and on the misleading volume dependence of the specific heat of gases [59]. as to the latter point, it is correct to say that a word of caution about the experimental observations by delaroche and bérard in favor of this dependence was advanced also by carnot and an invitation to further investigate about the law relating the motive power and temperature was clearly expressed in the réflexions. in retrospect, the q100 > q1inequality holds not because qv2 > qv1 but because the heat absorbed in an isothermal expansion is equal to the work performed (for an elastic fluid behaving as an ideal gas) and the latter depends linearly on temperature. the second problem analyzed is concerned with the evaluation of the motive power developed by the same amount of heat absorbed by agents such as air, steam or alcohol vapor at the same or at different temperatures. here we mention only the case of steam. to this purpose the cycle of fig. 5a is simplified to include only the two isothermal steps, expansion abcd → abef and compression abef → abcd, joined by two cooling/warming steps at constant volume. starting with 1 kg of water, with specific volume ≈ 10-3m3kg-1, and expanding, abcd → abef, under atmospheric pressure at 100oc, it was well known that the vaporization leads to a volume increase ≈ 1700 times the initial value, resulting in an increment ∆v ≈ vsteam= 1.7 m3kg-1. the reverse process, the compression abef → abcd, is assumed to occur in the cycle at 99oc at a slightly smaller pressure inducing steam condensation to water and volume decrement 1.7 m3kg-1. the motive power is ∆v times the difference ∆p of the water vapor pressure at 100oc and 99oc, which according to data available to carnot amounts to 26 mmhg or 0.36 m.w. (meter of water, 760 mmhg = 10.4 m.w.)13. the product ∆v·∆p is 1.7 m3kg-1· 0.36 m.w. = 0.611 units the hot source delivers heat to the cycle since (a) at constant volume the temperature of the water must increase from 99oc to 100oc and (b) at 100oc the expansion step must absorb heat in order to be isothermal. the first contribution is much smaller than the second and is 13 data on vapor pressure of water at discrete values of temperature from 0°c to 100°c were already known [60]. assuming that steam obeys the ideal gas law in the form p = c(267 + t)/v [p(mmhg), t(°c), v(liters) and c = 3.52 solving for c with v(steam) = 1700 liters at 100°c and 760 mmhg ] carnot found v(steam) at these temperatures and then fitted the calculated values to a known function of t(°c) in the range 0-100°c . the vapor pressure at the desired t(°c) was obtained applying the gas law equation and solving for p. for instance, p results 734 mmhg at 99°c [61]. neglected by carnot in the calculation of the total heat. being experimentally known that 550 units of heat, i.e., 550 kcal, are necessary to vaporize 1 kg of water under atmospheric pressure, the conclusion is, through the simple proportion 550/0.611 =1000/x, thus 1000 units of heat transported from one body kept at 100 degrees to another kept at 99 degrees will produce, acting upon vapor of water, 1.112 units of motive power14 next, the steam engine working between 1oc and 0oc is considered. carnot was able to estimate15 ∆p = 0.358 mmhg and ∆v = 174 m3kg-1 following the computational procedure described in footnote 13. the heat of vaporization of 1 kg water at 1oc is determined under the vapor tension at that temperature, p(1oc)=5.418 mmhg. according to carnot, this is the same heat necessary to raise under atmospheric pressure the water temperature from 1oc to 100oc and then to vaporize completely water. the total heat delivered by the hot source to the engine at 1oc (and transmitted to the cold source at 0oc) is therefore (100 + 550) kcal·kg-1= 650 kcal·kg-1. it is easily found after convenient unit conversion of the ∆p∆v product from m3kg-1mmhg to m3kg1m.w. that 1000 units of heat will produce 1.290 units of motive power. the soundness of this last number is obviously related to the estimate of the vaporization heat at 1oc but the strength of carnot physical insight is shown by the comparison with the actual value: the enthalpies of vaporization at 100oc and 1oc are [61] 549.5 kcal·kg1and 597 kcal·kg-1, respectively, so that the 650 kcal· kg-1 value differs from the last one only by ≈1/11. 4.3 carnot and the caloric theory in a note of the réflexions carnot explicitly states that a basic principle of his scientific reasoning is the assumption of the theory of caloric as an imponderable and indestructible fluid that, in a modern diction, is a function of state: we tacitly assume in our demonstration that when a body has experienced any changes, and when after a certain number of transformations it returns to precisely its original state, that is, to that state considered in respect to density, to temperature, to mode of aggregation – let us suppose, i say, that this body is found to contain the same quantity of heat that it contained at first, or else that the quantities of heat absorbed or set free in these different 14 [12], p.104. 15 full details about the carnot calculations on this as well as on all the others heat engines considered may be found in ref. 61. 82 pier remigio salvi, vincenzo schettino transformations are exactly compensated. this fact has never been called into question.16 however, in the conclusion of the same note, carnot explicitly expresses profound doubts about the same theory: for the rest, we may say in passing, the main principles on which the theory of heat rests require the most careful examination. many experimental facts appear almost inexplicable in the present state of the theory.17 in a subsequent step of the réflexions, after calculating the motive power generated when 1000 units of caloric experience a thermal fall of 1°c in air, steam and alcohol engines, to demonstrate its independence from the agent, carnot is again openly critical of the caloric theory: the fundamental law that we propose to confirm seems to us to require, however, in order to be placed beyond doubt, new verifications. it is based upon the theory of heat as it is understood today, and it should be said that this foundation does not appear to be of unquestionable solidity.18 therefore, while adopting the caloric theory, it is apparent that the theory does not appear to be well founded to carnot [62]. for instance, with reference to the principles of the caloric theory he explicitly states that: these theories furnish no means of comparing the quantities of heat liberated or absorbed by elastic fluids which change in volume at different temperatures.19 and in another passage he writes: we do not know what laws it [the caloric] follows relative to the variations of volume: it is possible that its quantity changes ….. with its temperature.20 the extraordinary character of the réflexions lies in the fact that, while officially adopting the caloric theory, carnot is able to reach general conclusions that go beyond the starting hypothesis. this circumstance may well be highlighted by the closing mechanism of the thermodynamic cycle adopted by carnot [54-58]. the set of six transformations that activate the ideal engine starts from point a in figure 5b and the achievement of 16 [12], p. 67. 17 [12], p. 67. 18 [12], p. 107. 19 12], p. 84 20 [12], p. 62. point 4, at the end of the isothermal compression and from which the adiabatic compression starts, is defined exclusively in terms of volume, without any reference to the heat exchanged. on the contrary, in the clapeyron discussion [54,63] the cycle starts at point 1 of the p-v diagram and the end of the isothermal compression 3-4 is defined when the heat transferred to the condenser equals that absorbed during the expansion at high temperature, with explicit reference to the theory of caloric. a certain ambiguity in the adhesion of carnot to the caloric theory was already noted by clausius [64]. in fact, after reporting the experimental tests showing that heat could not be considered as an indestructible fluid, he writes: these circumstances, of which carnot was also well aware, and the importance of which he expressly admitted, pressingly demand a comparison between heat and work, to be undertaken with reference to the divergent assumption that the production of work is not only due to an alteration in the distribution of heat, but to an actual consumption thereof; and inversely, by the consumption of work heat may be produced.21 after further discussing experiments in favor of the dynamic theory of heat, clausius defines the carnot’s principle that “no heat is lost” only as an additional statement in his logical reasoning not affecting the conclusions drawn: on a nearer view of the case, we find that the new theory is opposed, not to the real fundamental principle of carnot, but to the addition “no heat is lost;” for it is quite possible that in the production of work both may take place at the same time; a certain portion of heat may be consumed, and a further portion transmitted from a warm body to a cold one; and both portions may stand in a certain definite relation to the quantity of work produced. this will be made plainer as we proceed; and it will be moreover shown, that the inferences to be drawn from both assumptions may not only exist together, but that they mutually support each other.22 however, callendar [20] notes that carnot’s statement concerning a perfectly reversible cyclical process was actually misquoted by clausius when he reports that carnot expressly states that no heat is lost in the process, that the quantity (transmitted from the fireplace to the condenser) remains unchanged23 21 [64], p. 2. 22 [64], p. 4. 23 the original carnot statement: les quantités de chaleur absorbées ou degagées dans les diverses transformations sont exactement compensées, is 83sadi carnot’s réflexions and the foundation of thermodynamics according to callendar [20] the bad interpretation of clausius to identify “compensated” with “equal” may have been induced by the work of clapeyron [63]. callendar’s conclusion is that the principles that carnot reaches with regard to reversible processes are independent of the caloric theory. considerations of this type can be applied to the description of carnot’s work by maxwell [65]. maxwell starts the cycle from the point 2 in the p-v diagram with an adiabatic compression up to the temperature of the cold source, again without reference to the heat exchanged. apart from the unpublished manuscript reported in ref. 48, carnot did not publish anything else on the theory of heat and thermal engines after the réflexions and some considerations or speculations have been advanced as an explanation [16,47]. it is possible that the increasing dissatisfaction with the caloric theory caused in carnot some embarrassment when discussing with influential figures of the scientific milieu, which did not support the idea of destroying the fundamental axioms of the theory inherited from the founding fathers, lavoisier and laplace [30-33]. a second concern was perhaps bound to the assessment of the validity of the réflexions and to some uncertainty about the parts of the work which could be saved after the collapse of the old theory. although most of carnot’s ideas overcame untouched tens of years, it was necessary to wait the experimental results of joule and the theoretical considerations of kelvin and clausius to reach the final objective, a giant effort for a single man. it has been observed [47] that in the remaining years of his life carnot was probably disappointed and frustrated not being able to reconcile the published work with the ideas, freshly growing in his mind, tightly relating heat and work. a sad conclusion has been drawn that these years had elements of tragedy more than of triumph for carnot, contrary to what we are inclined to think on the basis of his anticipation of the future laws of thermodynamics. the doubts of carnot on the theory of caloric are expressed more explicitly in his scientific notes which are more or less contemporary to the réflexions [12,47,49]. with reference to the radiant heat, which is clearly associated to motion, carnot poses the problem: could a motion (that of radiant heat) produce matter (caloric)? undoubtedly no; it can only produce motion. heat is then the result of motion.24 translated as: the quantities of heat lost and gained in the various processes cancel one another out, by fox [47] and as: the quantities of heat absorbed or set free in these different transformations are exactly compensated , by thurston [12]. 24 [49], p. 63, selection from the posthumous manuscripts of carnot. from a more general point of view carnot position is as follows: is heat the result of a vibratory motion? if this is so, quantity of heat is simply quantity of motive power. as long as motive power is used to produce vibratory movements, the quantity of heat must be unchangeable; which seems to follow from experiments in calorimeters; but when it passes in movements of sensible extent, the quantity of heat can no longer remain constant.25 4.4 the physics of gases the physics of gases presented in the réflexions has been critically reviewed and discussed [47] (see notes 42, 46, 53, 61 and 63 of the commentary). the sharp insight into the matter, despite the carnot’s adherence to the conservation of caloric as a fundamental axiom of the theory, is shown by the following examples. considering a cycle where the two isothermal operations occur at temperatures differing only slightly, the adiabatic contributions to the total motive power may be legitimately ignored with respect to those from the isothermal operations. if different gases are used in the cycle, ensuring that they go exactly through the same states of pressure and volume, the same motive power will be obtained since the gases obey the same law. by the carnot principle this means that the caloric absorbed at higher and released at the slightly lower temperature is the same whichever the gas used. the proposition follows: when a gas passes without change of temperature from one definite volume and pressure to another volume and another pressure equally definite, the quantity of caloric absorbed or relinquished is always the same, whatever may be the nature of the gas chosen as the subject of the experiment.26 in modern terms, the same follows from the first principle, ∆u = q + w, and the fact that the internal energy u of an ideal gas depends only on temperature. in an isothermal process ∆u = 0 and q = -w. the statement follows since all ideal gases perform exactly the same amount of work in the same reversible isothermal process. proceeding further, for one mole of an ideal gas expanding isothermally from va to vb the heat absorbed from the surroundings is given by rt ln(vb/va). carnot expresses the same result with the proposition when a gas varies in volume without change of temperature, the quantities of heat absorbed or liberated by the 25 [49], p. 67, selection from the posthumous manuscripts of carnot. 26 [12], p. 72. 84 pier remigio salvi, vincenzo schettino gas are in arithmetical progression, if the increments or the decrements of volume are found to be in geometrical progression.27 and represents the volume dependence in analytical form by the equation s = a + b log v28 as a second result, it was known at his time that by adiabatic compression the temperature of the atmospheric air rises by 1oc when the volume v reduces to v – (1/116) v while, on the other hand, the isobaric heating of air by 1oc increases the volume to [v + (1/267) v]. the amount of heat absorbed in the last process is cp, the specific heat of air at constant pressure, since ∆t = 1oc. the final state of the isobaric process may be reached alternatively through a second trajectory which involves first the adiabatic compression by 1oc and then the isothermal expansion to the final volume. due to the conservation axiom the amount of heat remains cp but now is entirely expended in the isothermal process, being the compression adiabatic. a second point along the isotherm curve may be certainly reached at constant volume heating air by 1oc and increasing pressure from p to [p + (1/267) p] and in this case the heat absorption is equal to cv, the specific heat of air at constant volume. going again through the second trajectory but stopping now along the isotherm at a volume equal to the initial volume, the heat absorbed in this portion of isotherm expansion is cv. as the variations are small with respect to the original volumes the amount of heat may be reasonably taken as proportional to these variations and therefore cp/cv= (1/116 + 1/267)/(1/116) = 1.43, not far from the value measured by gay-lussac and welter, 1.3748, reported elsewhere [31]. it should be noted that the argument is valid also in later thermodynamics and made explicit by the expression cp/cv= 1 – (∂v/∂t) p/(∂v/∂t)ad [47]. in addition, taken cp as unity, cv ≈ 0.7. the difference, 0.3, represents the amount of heat due to the increase of volume when air is heated by 1oc at constant pressure. since this increase of volume is the same for all gases, also the heat absorbed, cp– cv, is the same whichever the gas. provided that the gases are at the same pressure and temperature it follows that the difference between specific heat under constant pressure and specific heat under constant volume is the same for all gases.29 27 [12], p. 81. 28 [12], p. 90. 29 [12], p. 76. 4.5 the mechanical equivalent of heat as already noted, in the unpublished notes carnot clearly refuses the caloric theory to such an extent to identify heat as a form of work (or energy): heat is simply motive power, or rather motion which has changed its form. it is a movement among the particles of bodies. wherever there is destruction of motive power there is at the same time production of heat in quantity exactly proportional to the quantity of motive power destroyed. reciprocally, wherever there is destruction of heat, there is production of motive power.30 and goes as far as to propose a numerical estimate of the mechanical equivalent of heat: according to some ideas which i have formed on the theory of heat, the production of a unit of motive power necessitates the destruction of 2.70 units of heat.31 the reported value (which rigorously is the thermal equivalent of work), once the appropriate conversion factor is inserted, is equivalent to a mechanical factor of 3.7 joule/cal, quite close to the actual value, 4.184 joule/cal. the theoretical justification of this number was however not advanced and successively various reconstructions have been attempted [47,49]. one possible procedure, suggested by décombe [66] and cited in ref. [49], is particularly simple and makes use of the only data present in the réflexions. it has been seen in the previous section that (cp– cv) is the difference between the quantities of heat expended for 1oc increase under constant pressure and volume, respectively, and that this difference fully accounts for the increase of volume in the first case. this difference results to be 0.3 if cp is taken as unit heat. since cp of air is 0.267 that of water ([12], p. 100), the heat (cp– cv) absorbed by the air for a 1oc increase under constant pressure is 0.267·0.3 = 0.081 cal. on the other hand, work is performed by the air due to heat absorption. starting with 1 kg of air, the volume at 0oc and 1 atm, 0.77 m3([12], p. 99), increases by 1/267 for a temperature increase of 1oc at the constant pressure of 1 atm. the work is 1·0.77·103/267 ℓ atm = 2.88 ℓ atm. with the conversion factor from ℓ atm to tonne meter (the unit of work to which carnot refers [66]) the result is 0.03 tonne-meter. since the heat and work estimates are relative to 1 kg of air, it follows that a work of 1 tonne-meter is performed when air absorbs 0.081/0.03 = 2.7 kcal of heat. 30 [49], p. 67, selection from the posthumous manuscripts of carnot. 31 [49], p. 68, selection from the posthumous manuscripts of carnot. 85sadi carnot’s réflexions and the foundation of thermodynamics 5. scientific antecedents of sadi carnot for a historical overview of the work of scientific innovators, it is important to identify the background that may have inspired or facilitated their discoveries. the problem, from a general point of view, can be framed by paraphrasing the famous line of john donne that no man is an island, entire of itself. indeed, isaac newton, the most famous of the innovators of science, said of himself that he had seen farther because he was travelling on the shoulders of giants. in this perspective it seems unlikely that sadi carnot was a solitary innovator as claimed, for example, by cimbleris [67]. considering the topic of the work of carnot, the thermal engines, any antecedent must be sought primarily in the world of technical and engineering literature [52,68-72]. moreover, the formation of carnot at the école polytechnique and, above all, at the école de metz was mainly of a technical nature, although, as described by taton [15], considerable attention was also paid to a formation of a scientific character. the importance of the formation process of sadi carnot for his subsequent scientific work has been discussed by payen [73] and by taton [15]. it is easy to assume that sadi had a more exquisitely scientific preparation also in the initial phase of his formation under the guidance of his father lazare. a possible scientific influence of his father on sadi was already taken into consideration in the memory of saint-robert [11] in 1868 drawing attention to the analogy between the fall of water in hydraulic machines [74,75] and the transfer of heat between the heat source and a refrigerant. this connection has since been discussed in detail by various authors [14,23,76-79]. according to gillispie [76] and gillispie and pisano [77] the réflexions by sadi would have been inspired or would even be a continuation of the work of the father lazare on mechanics and on hydraulic engines [74,75]. the authors reach this conclusion through the discussion of available documents as well as with a complex treatment that involves an epistemological and semantic analysis of the writing of sadi carnot [78]. the elements deriving from the father lazare [75] would be, in particular, the idea of a cyclic character in the functioning of ideal engines and of the reversibility of the involved processes, the need to avoid improper dispersion of the work by friction and, correspondingly, of heat by direct contact, the denial of the possibility of a perpetual motion, the extension of the physical principles of operation of particular engines to general cases and the discursive nature of the arguments. in fact, in the réflexions an analysis or mathematical deduction of the principles enunciated by carnot is found only in a long note [79]. it is now clear that, since mechanics was one of sadi carnot’s scientific interests, he certainly had to know his father’s work. in fact, the clearest correspondence between the réflexions and the work of lazare carnot is found in the explicit analogy between the fall of water from a certain height in hydraulic engines and the transfer of heat between a high temperature source and a low temperature sink in thermal engines. the analogy has been discussed in some detail by muller [14] as the real scientific inheritance of sadi carnot from the father. apart from this, the conclusions of gillispie and pisano [77] appear absolutely plausible but in many cases they seem to be based mostly on circumstantial evidence. for example, when it is recalled that sadi subjected some points of the réf lexions to his brother hippolyte to check their readability for non-experts [12] the authors conclude in a dubitative or presumptive way: the brothers could scarcely have failed to talk then of their father’s science32. in this regard, it should be noted that lazare carnot is never quoted or mentioned in the réflexions, a strange circumstance in the normal scientific practice. gillispie and pisano [77] take this circumstance as a possible evidence that perhaps the réflexions were actually the work of lazare carnot, which would then have been simply completed by the son who would have considered it useless to quote his father, the true author of the work. the possible influence on the thought of carnot by nicolas clément and charles bernard desormes, but above all the first, is based on more certain documentary elements. in the first instance, we find three quotations of clément and desormes in the réflexions. the first is related to an experiment, confirming previous poisson data, on the gas temperature during compression33. the second concerns the experimentally established law (in english known as the watt law) which states that the saturated water vapor, with the same weight, always contains the same amount of caloric whatever the temperature at which it is formed34. in modern terms this law is equivalent to say that the enthalpy of saturated steam is conserved at all temperatures [49] and implies that the vapor, adiabatically expanded or compressed, maintains the initial saturation state. the third quotation, the most important from our point of view, is in reference to adiabatic expansion and occurs when carnot states that for better performance of a steam engine not only is an initial high pressure important but also, subse32 [77], p. 78. 33 [12], p. 73. 34 [12], p. 92. 86 pier remigio salvi, vincenzo schettino quently, progressively decreasing pressures35. in a note, carnot acknowledges that the related clément’s law is indeed fundamental in the steam machine theory and he has come to the knowledge of the unpublished article of clément by the author’s kindness. with the help of this law, and of the one mentioned above, it is possible to calculate the work in an adiabatic expansion or compression of the saturated vapor. in absence of a caloric flow between vapor and surroundings the heat content is constant and the pressure and temperature of the vapor change in such a way to maintain the saturation conditions. the two parameters may thus be related following well known saturation tables such as those of dalton. then, the volume is found assuming the vapor obeys the boyle and gaylussac laws. once the correspondence between pressure and volume is established at each temperature the strategy to calculate the adiabatic work is straightforward. the note in question clearly indicates a relationship of frequentation and, perhaps, of friendship between carnot and clément. in fact, even in the biographical note of the brother hippolyte [12] we find that carnot was familiar with clément. the possible debt of carnot to clément has been discussed in detail by fox [52] and associated with the idea of the expansive principle, first conceived by watt and then developed by clément. the principle concerns the advantages that can be obtained in the efficiency of the steam engine allowing to continue the expansion after the initial supply of steam. while watt considered this further expansive phase to be substantially isothermic, clément, departing from the commonly accepted view, clearly defines it as adiabatic. it comes to this conclusion on the basis of a thought experiment in which a vapor bubble is introduced to the bottom of a cylinder, generating mechanical work measured by the water that flows from the top of the cylinder. the bubble continues to rise in the cylinder, expanding and letting other water to flow out of the cylinder corresponding to additional motive power. a similar but more detailed analysis of the relationship between carnot and clément is reported by lervig [53]. in particular, lervig reports on the participation of carnot to at least some lessons of the clément’s course on industrial chemistry at the conservatoire des arts et métiers. this results from the set of notes to the course written in the years 1824-28 by a certain j.m. baudot (partially reported by lervig) which clearly show that carnot was well acquainted with clément and his scientific work (and in particular with the aforementioned clément’s law and with the phases of expansion [détente] 35 [12], p. 115. and compression in the steam engine). in these notes the lecture of january 20, 1825 is reported where clément says that carnot, one in the audience of the course, has dealt with the principles of thermal engines [53] … mais un des auditeurs de ce cours, m. carnot, off.erdu génie, ancien élève de l’école polytechnique, a eu le courage et l’ heureuse idée d’aborder cette intéressante question dans un ouvrage fort remarquable qu’ il vient de publier sous le titre de réflexions sur la puissance du feu.36 in the note of march 8, 1827 carnot is further mentioned by clément as distinguished mathematician la formule algébrique n’est ici que comme sujet d’exercice pour ceux qui voudront l’employer … elle lui a été donnée, dit-il, par un mathématicien distingué.37 lervig, more explicitly than fox, advances the hypothesis that in fact it was carnot that influenced clément at various points, as in the numerical examples contained in the notes taken by the mathematician l.b. francoeur attending as a student the 1823-24 course (also these reported in part in ref. 53). the remarkable conclusion of the lervig analysis is relative to the condensation phase of the steam engine and states that it was an idea entirely due to carnot that in the evaluation of the total work the (negative) contribution of the isothermal work of compression must be taken into account. this conclusion is supported by an in-depth study of the francoeur notes and by the accurate reconstruction of calculations present in the long abstract of the clément and desormes lost memoir describing the theory of the steam engines. also, no hint about the condensation term is found in the notes taken by baudot in the successive years [53]. in a simpler and more direct way the search for antecedents of carnot can be conducted on the basis of the cites in the réflexions. gouzevitch [69] discussed the influence prony and betancourt (mentioned in réflexions) may have had on carnot for the emphasis these authors have put both on the need for a theoretical treatment of the thermal engines and on the necessary presence of a hot source and a low temperature sink [69]. 6. the reception of carnot’s ideas carnot’s réflexions had a very limited initial fortune for various reasons. carnot, like many at the time, 36 [53], p. 185. 37 [53], p. 188. 87sadi carnot’s réflexions and the foundation of thermodynamics was an amateur scientist not introduced into the important circuits of scientific communication. moreover, already in his presentation in the front page of the book he defined himself simply, with an understatement, an ancien élève de l’école polytechnique. the book was presented by pierre simon girard, a well-known engineer, at a meeting of the académie des sciences on 14 june 1824 to the presence of many important scientists but only in oral form and therefore the book was not published in the mémoires of the academy, which would have guaranteed the necessary publicity. this was not afforded either by a subsequent written presentation by girard himself in the revue enciclopédique [80]. in an obituary of 1832 robelin [7] attributed in part the scarce diffusion of the work to the difficult style of carnot: unfortunately, this writing ….. could be accessed by only few readers, and lacked the degree of utility it entailed.38 actually, the réf lexions were published at the expenses of carnot in a very limited number of copies so that later, in 1845, william thomson (lord kelvin) found it impossible to find a copy despite his research at all booksellers in paris [81] i went to every book-shop i could think of, asking for the puissance motrice du feu, by carnot. ‘caino? je ne connais pas cet auteur’ … ‘ah! ca-rrrnot! oui, voici son ouvrage’, producing a volume on some social question by hippolyte carnot [sadi’s brother]; but the puissance motrice du feu was quite unknown.39 and he was initially acquainted with carnot’s work only through emile clapeyron [82] having never met with the original work, it is only through a paper by m. clapeyron, on the same subject, published in the journal de l’école polytechnique, vol. xiv. 1834, and translated in the first volume of taylor’s scientific memoirs, that the author has become acquainted with carnot’s theory.40 in the next ten years after publication the book had a footnote citation in a treatise by jean victor poncelet [83] where the analogy was made between the properties of gases and those of the caloric intended as a gas-like material. apart the biographical note prepared by his brother [12], sadi was scarcely referenced also in books on the carnot family and in other contexts. in a two-volume 38 [7], authors’ translation of the french obituary. 39 [81], p. 458. 40 [82], p.100. biography of the father [84], hippolyte barely alluded to the sadi’s work. the family history by maurice dreyfous [85] reported primarily on lazare, hippolyte and sadi, hippolyte’s son, which was the fourth president of the third republic, murdered in 1894 by the italian anarchist sante ieronimo caserio. françois arago, secretary for life of the academy of sciences, mathematician, physicist and politician wrote a historical note on steam engines [86] with the purpose of denying the thesis that the steam engine was entirely an english invention and emphasized the role of denis papin while completely ignoring sadi’s contribution. as regards the success of the réflexions, it is of course necessary to consider the dual nature of carnot’s work defined by redondi [9] as “un défi théorique à la pratique” (a challenge of theory to practice) and to look at its reception both in the engineering environment and application and to its impact as a moment of foundation of the science of thermodynamics. the first aspect has been considered in detail by redondi [9,87]. on the basis of a new documentation, reported as a group of annexes accompanying his work, redondi brought to attention numerous explicit references to carnot, also as explicit quotations of the réflexions, in works by engineers and technicians, even though there is no evidence of practical applications of carnot’s principles. in particular, redondi mentions an essai sur le machines à feu (1835) by m. boucherot, an emploi de l’air comme moteur and a machine à air à effet alternative (1838) both by f. bresson. these are all projects submitted to the académie des sciences. these, and other technological projects mentioned by redondi, have the common purpose of proposing the air at high pressures as an agent of thermal engines and therefore constitute a logical reference to the ideal air engine of the réflexions. of particular interest may be the air engine proposed by boucherot, the pyraéromoteur, a new variant of the pyreolophore proposed by the niepce brothers in 1800, an antecedent of the internal combustion engine, mentioned by carnot in the refléxions. of course, clapeyron, the first true communicator of carnot’s ideas, was also an engineer but his interest in the réflexions was not really technical. but this is another story [88-93] that is discussed in the ref. [47], p. 110-111. 6.1 the clapeyron contribution to the diffusion of the carnot theory it was in 1834 that a detailed exposition of the réflexions appeared in the journal de l’école polytechnique by clapeyron [63]. in the mémoire sur la puissance motrice du feu the verbal analysis of carnot, sometimes 88 pier remigio salvi, vincenzo schettino cumbersome, was substituted by the symbolism of the calculus and use was made of the indicator diagram of watt, since then the familiar p-v diagram, to discuss the carnot cycle. as the law relating pressure and volume in an adiabatic process was unknown to clapeyron, the analysis was restricted to cycles with very small temperature difference between isotherms. making reference to fig. 5(b) clapeyron assumes that the two isotherms, 1 → 2 and 3 → 4, are closely approaching each other at temperatures t + dt and t (degrees centigrade), respectively, and that the gas is allowed to expand, 1 → 2, and to compress, 3 → 4, by the volume increment/decrement dv. due to the infinitesimal variations the two isotherms, 1 → 2 and 3 → 4, as well as the two adiabats joining them, 2 → 3 and 4 → 1, are essentially parallel segments and the area of the minute 1234 parallelogram is the “quantity of action” [63], i.e., the work performed due to the absorption of heat dq during the 1 → 2 isotherm. as a fervent calorist clapeyron points out that successive states which the same weight of gas experiences are characterized by the volume, the pressure, the temperature, and the absolute quantity of caloric which it contains: two of these four quantities being known, the other two become known as a consequence of the former41 thus, the differential dq may be defined as a function of p and v and the ratio between the “quantity of action” and dq, which represents the maximum work for a unity of heat falling from t + dt to t, is determined by the expression rdt/[v(dq/dv) – p(dq/dp)] where (dq/dv) and (dq/dp) are partial derivatives, the first at constant pressure and the second at constant volume. the constant r comes from the combination of the boyle-mariotte and gay-lussac laws for a given weight of an elastic fluid pv/(267 +t) = p0v0/(267 + t0) = r where p, v, t and p0, v0 and t0 are two different sets of values of pressure, volume and temperature and 1/267 is the (then) measured reduction/magnification factor of volume (1/273.15, actual value) for 1oc lowering/ increasing at constant pressure. through mathematical analysis the q equation, q = r(b – c ln p) with b and c unknown functions, is determined and, more important, the above defined ratio is found to be equal to dt/c. the carnot principle says that c must depend only on tem41 [63] middle sect. ii. perature and not on the specific nature of the substance working in the cycle. the function b may in addition vary from gas to gas [63]. it follows that (1/c), called later the carnot coefficient by kelvin for its importance in the theory of heat and denoted by µ, is the maximum work due to a unit heat descending 1oc. in another passage of the mémoire, taking in consideration the saturated vapor as working substance, clapeyron was able to derive the now famous “clapeyron equation”, a most remarkable fact in absence of the second law and the entropy concept. he observes that the maximum work performed with a unit input of heat when a liquid is vaporized in a cycle with infinitely close isotherms cannot be different from that obtained by any other substance between the same temperature limits, which was already shown to be dt/c. the following equation is obtained k = (1 – δ/ρ)·(dp/dt)c where k is the latent caloric contained in the unit volume of vapor and δ and ρ are the vapor and liquid densities. the comparison with the clapeyron equation appearing in all textbooks of thermodynamics suggests that c coincides with the absolute temperature, a quantity not yet defined at that time. clapeyron not only recovered the carnot réflexions from obscurity but also introduced the point of true weakness of the theory, hinting at the possibility of vis viva (i.e., kinetic energy) destruction for the special case of direct contact of two bodies at different temperatures caloric passing from one body to another maintained at a lower temperature may cause the production of a certain quantity of mechanical action; there is a loss of vis viva whenever bodies of different temperature come into contact42 the mémoire was translated into english in 1837 and into german in 1843, thus making the carnot theory available for further analysis and development. as a mining engineer, clapeyron was engaged in railroad engineering construction in france and abroad. later clapeyron was professor in the école des ponts et chaussées from 1844 to 1859 but alluded scarcely to the mémoire in his courses and only briefly in 1847 in the scientific biography supporting his election to the academy of sciences [70]. 42 [63], end sect. ii. 89sadi carnot’s réflexions and the foundation of thermodynamics 6.2 the joule kelvin controversy and the approach to the second principle a full recognition of the ideas contained in the carnot réflexions was granted only by the two founders of the second principle, lord kelvin and rudolf clausius. it it is worthwhile to first refer shortly to the point of view of lord kelvin’s brother, james thomson, about the carnot’s theory since it heavily influenced kelvin’s ideas in the following years. according to james [94], heat and work are proportional to one another in the sense that a given quantity of heat produces a given quantity of work and vice versa but the two entities cannot interconvert. it may help to go back to the waterfall analogy: as the fall from upper to lower height produces work with no loss of water, so the transfer of heat from high to low temperature produces work with heat conservation. this view was a source of strong debate, the two main actors being joule, who in a series of experiments [95] in the years 1843-1844 had conclusively shown that work is converted into heat at a fixed ratio, and lord kelvin. indeed, the defective point in the clapeyron report on the carnot theory was caught with penetrating criticism by joule i conceive that this theory, however ingenious, is opposed to the recognized principles of philosophy, because it leads to the conclusion that vis viva may be destroyed by an improper disposition of the apparatus. thus mr. clapeyron draws the inference that “the temperature of the fire being from 1000oc to 2000oc higher than that of the boiler, there is an enormous loss of vis viva in the passage of the heat from the furnace into the boiler” ([63], sect. viii). believing that the power to destroy belongs to the creator alone, i entirely coincide with roget and faraday in the opinion that any theory which, when carried out, demands the annihilation of force, is necessarily erroneous43 the joule’s idea about the steam engine, substantially coincident with the modern interpretation, was clearly expressed the steam expanding in the cylinder loses heat in quantity exactly proportional to the mechanical force which it communicates by means of the piston and on condensation of the steam the heat thus converted into power is not given back.44 and led necessarily to the dramatic confutation of heat conservation, the basic principle of the caloric theory: the theory here advanced demands that the heat given out in the condenser shall be less than that communicated 43 [95], p. 188. 44 [95], p. 189. to the boiler from the furnace, in exact proportion to the equivalent of mechanical power developed.45 these considerations represent a turning point in the science of thermodynamics: the conversion of heat into work is apparently incompatible with the transmission of heat associated with the production of work. kelvin knows joule’s results but the first reaction is of opposition [82] in the present state of science no operation is known by which heat can be absorbed, without either elevating the temperature of matter, or becoming latent and producing some alteration in the physical condition of the body into which it is absorbed; and the conversion of heat (or caloric) into mechanical effect is probably impossible, certainly undiscovered.46 adding in the footnote that joule has reported … some very remarkable discoveries which he has made with reference to the generation of heat by the friction of fluids in motion … seeming to indicate an actual conversion of mechanical effect into caloric. no experiment however is adduced in which the converse operation is exhibited; but it must be confessed that as yet much is involved in mistery with reference to these fundamental questions of natural philosophy.47 successively, kelvin had a more cautious approach to joule’s conclusions trying, in a long note of [96], to answer the core question about thermal engines; what happens when heat flows by conduction from the hot to the cold body or in other words when the thermal engine has zero mechanical effect? when thermal agency is thus spent in conducting heat through a solid what becomes of the mechanical ef fect which it might produce? nothing can be lost in the operations of nature – no energy can be destroyed. what effect is then produced in place of the mechanical effect which is lost ? a perfect theory of heat imperatively demands an answer to this question; yet no answer can be given in the present state of science. it might appear that the difficulty would be entirely avoided by abandoning carnot’s fundamental axiom; a view which is strongly urged by mr. joule. if we do so, however, we meet with innumerable other difficulties, insuperable without further experimental investigation, and an entire reconstruction of the theory of heat from its foundation.”48 45 [95], p. 189. 46 [82], p. 102. 47 [82], p. 102. 48 [96], note 7. 90 pier remigio salvi, vincenzo schettino as it is evident from these considerations, kelvin maintained an open mind on the issue. on one hand he did not venture in the complete rejection of the carnot’s theory for the above mentioned difficulties to adequately replace the caloric theory; on the other he brought to completion three major achievements, the calculation of the maximum work in the cycle as a function of the temperature [96], the successful proposal for the absolute scale of temperature [82] and the discovery of the pressure dependence of the water freezing point [97,98], all of them representing brilliant results coming from the application of carnot’s theory. the key work [96]: account of carnot theory of the motive power of heat: with numerical results derived from regnault experiments on steam, already in title indicates that the author not only reviews the original study but also provides a strong basis for the theory using the data on latent heat of vaporization and pressure of saturated vapors collected by the great experimentalist victor regnault. two expressions are obtained for the mechanical effect due to “the transference of heat from one body to another at a lower temperature” ([96], paragraph 11) in an engine operating with steam or air. by the carnot principle the maximum work m is the same in the two cases. if h units of heat are allowed to fall from the body a at temperature t + τ to b at t, the result is, in the kelvin notation, m = (1 – σ) (dp/dt)(1/k)hτ = e[p0v0/(vdq/dv)]hτ where the hτ coefficient is denoted by µ and has the usual meaning of maximum work for a unit heat transmitted from a to b with 1oc gap (measured by an air thermometer). thus, µ is given by µ = (1 – σ) (dp/dt)(1/k) = e[p0v0/(vdq/dv)] where the left expression is appropriate for the saturated steam (with σ the ratio of steam and water densities, k the latent heat of water vaporization per unit volume) and the right expression for air. using regnault data for (a) the pressure p of saturated steam in the range 0oc 230oc and (b) the latent heat of vaporization per unit weight in the same temperature range; and assuming that the density of the vapor follows the law of ordinary gases up to 100oc and beyond may be estimated from pressure data, µ was found from 0oc to 230oc. the coefficient steadily diminishes increasing the temperature, consistently with the few scattered points obtained by clapeyron using boiling water, sulphuric ether, alcohol and turpentine [63]. kelvin was fully aware of the great generalization embodied in this calculation but, at the same time, he worried about its physical basis, emphasizing the request of experimental confirmation in paragraph 30 some conclusions drawn by carnot from his general reasoning were noticed; according to which it appears, that if the value of µ for any temperature is known, certain information may be derived with reference to the saturated vapor of any liquid whatever, and, with reference to any gaseous mass, without the necessity of experimenting upon the specific medium considered. nothing in the whole range of natural philosophy is more remarkable than the establishment of general laws by such a process of reasoning. we have seen, however, that doubt may exist with reference to the truth of the axiom on which the entire theory is founded, and it therefore becomes more than a matter of mere curiosity to put the inferences deduced from it to the test of experience.49 the second important point is concerned with a fundamental quantity like temperature which is expected to be defined in a general way rather than looking at specific properties of a substance, so as to make its definition independent of any kind of material [82]. on the basis of the carnot theory the mechanical effect due to the transmission of heat from a hot to a cold body does not depend on the nature of the working medium but only on the temperatures of the two bodies. further, the maximum work done by a unit heat falling 1oc is given by µ. from µ data on steam and few others on different substances [96], µ is found to decrease as the temperature, measured by the air thermometer, increases. the kelvin proposal was that µ, rather than other physical properties, must be used to fix the temperature scale. the central point of the proposal is that a degree is defined by the amount of maximum work done by a unit heat falling down this degree, irrespective of the temperature value. this is equivalent to say that µ becomes constant through the whole temperature range. in kelvin’s own words: in m. clapeyron paper various experimental data, confessedly very imperfect, are brought forward, and the amounts of mechanical effect due to a unit of heat descending a degree of the air-thermometer, in various parts of the scale, are calculated from them, according to carnot’s expressions. the results so obtained indicate very decidedly, that what we may with much propriety call the value of a degree (estimated by the mechanical effect to be obtained from the descent of a unit of heat through it) of the airthermometer depends on the part of the scale in which it is taken, being less for high than for low temperatures. the characteristic property of the scale which i now propose is that all degrees have the same value; that is, that a unit of 49 [96], paragraph 41. 91sadi carnot’s réflexions and the foundation of thermodynamics heat descending from a body a at temperature to of this scale, to a body b at the temperature (t−1)o, would give out the same mechanical effect, whatever be the number t. this may justly be termed an absolute scale, since its characteristic is quite independent of the physical properties of any specific substance.50 finally, a curious question was raised by kelvin, possibly representing a fatal argument to endanger carnot’s theory. it is known that water ices at 0oc under atmospheric pressure with volume expansion. in this process the latent heat is released while in the opposite process, i.e., melting under the same conditions of temperature and pressure, an equal amount of heat is absorbed with volume contraction. therefore, at least in principle, it may be thought of an ice engine in which heat does not flow from a hot to a cold body but between bodies at the same temperature, i.e. 0oc, with the result that “mechanical work would be given out without any corresponding expenditure” ([97] p.156). it was the brother james, who succeeded in showing that under pressure the melting point of water is lowered allowing kelvin to escape from this impasse [97]. thus, for an ice engine properly operated, it is necessary to run with the cold body at a temperature lower than 0oc otherwise the freezing process stops when freezing water starts to exert a pressure. the theoretical estimate of the temperature lowering with pressure was proposed considering a cyclic ice engine, analogous to the steam engine, which was working with the following steps: 1) isothermal (and isobaric) compression of ice at 0oc and 1 atm until one cubic foot of water is obtained from ice, absorbing heat from a reservoir (“an indefinite lake of water at 0oc”) ([97], p. 160); 2) adiabatic compression of the water/ice mixture to pressure pa(pounds/squarefoot) above that of the atmosphere. at the end of the process the temperature of the mixture is −t(oc); 3) isothermal (and isobaric) expansion causing the complete freezing of water and the heat release to a reservoir at − t(oc) (“a second indefinitely large lake at −t(oc)”) ([97], p.160). according to the caloric theory, of which james thomson was a follower, “continue the motion till all the heat has been given out to the second lake at −t(oc), which was taken in during process 1 from the first lake at 0oc” ([97], p. 160); 4) adiabatic expansion to the original values of temperature and pressure to close the cycle. it should be noted that james thomson predicted the temperature lowering with two independent strategies and not making recourse to the laws of thermody50 [82], p. 104. namics. in the first the work is calculated considering the area enclosed by the cycle in the p-v diagram, i.e., pa·(vice– vwater); in the second, being known to james the thermal units q to melt one cubic foot of ice and the value of µ at 0oc, the same work was calculated as the product q·µ·t. the final expression is [97] t = 0.0075n where t (degrees centigrade) is the lowering of the water freezing point with respect to 0oc and n is the pressure (atmospheres) above one atmosphere. the theoretical estimate was confirmed by the experimental measurements performed by kelvin [98]. it may be concluded that the validity of the carnot theory was supported also by the discovery of an unsuspected new physical effect and the admiration of kelvin for this result was expressed by words which go beyond the brotherhood relation in this very remarkable speculation, an entirely novel physical phenomenon was predicted in anticipation of any direct experiments on the subject; and the actual observation of the phenomenon was pointed out as a highly interesting object for experimental research.51 6.3 the second principle of thermodynamics: the final statements given the circumstances, it may be conjectured that a critical revision of the carnot theory was not a primary objective for kelvin. it was clausius in a historical paper [64] that conclusively solved the problem of the joule – carnot antinomy at the expenses of the principle of heat conservation. while kelvin sees insurmountable difficulties if the caloric theory is abandoned, clausius in a quite illuminating passage of the paper states: i believe, nevertheless, that we ought not to suffer ourselves to be daunted by these difficulties; but that, on the contrary, we must look steadfastly into this theory which calls heat a motion, as in this way alone can we arrive at the means of establishing it or refuting it. besides this, i do not imagine that the difficulties are so great as thomson considers them to be; for although a certain alteration in our way of regarding the subject is necessary, still i find that this is in no case contradicted by proved facts. it is not even requisite to cast the theory of carnot overboard; a thing difficult to be resolved upon, inasmuch as experience to a certain extent has shown a surprising coincidence therewith.52 51 [98] p. 165. 52 [64], p. 3. 92 pier remigio salvi, vincenzo schettino the option by means of which joule’s conversion of heat to work and carnot transmission of heat from a hot to a cold body are reconciled is rejection of heat conservation. however, a question remains: how can the carnot principle still be valid if the caloric theory is “cast overboard”? according to clausius, the production of work in a thermal engine is due to the transmission of heat from a warm body a to a cold body b with heat consumption. following carnot, the maximum work is obtained if the two bodies never come in contact each with the other (in our terms, if the cycle is reversible). reversing the engine, i.e., by consumption of the maximum work, heat is transferred from b to a. alternating the direct and reverse cycles the work production (direct) and consumption (reverse) are equal. the same may be repeated for the heat consumption and production. the two bodies go back to the initial conditions and no total work is done. let us now consider two different working substances k and k’ with the former producing a larger amount of maximum motive power. equivalently, we may assume that if the two substances develop the same amount of work, k’ transfers from a to b a larger amount of heat, qb’, than k, qb. operating the engine with k and k’ in the direct and reverse cycle, respectively, works are cancelled but b will transfer in the reverse operation more heat to a than received in the direct operation. in conclusion, an amount of heat qb’-qb is passed from a body at low temperature to a body at high temperature without any other change hence by repeating both these alternating processes, without the expenditure of force or other alteration whatever, any quantity of heat might be transmitted from a cold body to a warm one; and this contradicts the general deportment of heat, which everywhere exhibits the tendency to annul differences of temperature, and therefore to pass from a warmer body to a colder one.53 this constitutes the first historical statement of the second principle of thermodynamics. as a consequence, the carnot principle is justified even if the principle of heat conservation does not hold anymore. with its elimination, other concepts such as “latent heat” and “total heat of a body” must be dismissed or critically revised. the “latent heat” of vaporization, for instance, had in the old theory the meaning of caloric fluid surrounding the particles of vapor as if a composite particle was formed. according to clausius heat actually disappears and is converted into the expansion work from liquid to vapor 53 [64], p.103. … we can form a notion as to the light in which latent heat must be regarded. referring again to the last example [the liquid – vapor transition] we distinguish in the quantity of heat imparted to the water during the change the sensible and the latent heat. only the former of these, however, must we regard as present in the produced steam; the second is, not only as it name imports, hidden from our perception, but has actually no existence; during the alteration it has been converted into work.54 as to the “total heat of a body”, i.e., the sum of the sensible and latent heat, this property is dependent, according to the caloric theory, on the parameters which characterize the state of the body. it follows that, going from one state to another and then back to the original, the total heat is zero. on the contrary, clausius argues that during the cyclical transformation work may be done or absorbed by the body and the total work may not be necessarily equal to zero, as it is indicated by the occurrence of volume change in the body. this work must correspond to a well defined amount of heat, on the basis of the joule principle of equivalence. clausius summarized the theory of heat by means of the two principles [64, 99]: 1) in all cases where work is produced by heat, a quantity of heat proportional to the work done is consumed; and inversely, by the expenditure of a like quantity of work, the same amount of heat may be produced.55 2) heat cannot by itself pass from a colder to a warmer body.56 kelvin acknowledged the dynamical theory of heat one year later [100]. from his point of view the two basic propositions are 1) when equal quantities of mechanical effect are produced by any means whatever from purely thermal sources, or lost in purely thermal effects, equal quantities of heat are put out of existence or are generated.57 2) it is impossible, by means of inanimate material agency, to derive mechanical effect from any portion of matter by cooling it below the temperature of the coldest of the surrounding objects.58 the first proposition is essentially the joule principle of equivalence, as it is in the clausius statement. as to the second, it is a fair acknowledgment to declare clausius’ priority: 54 [64], p. 5. 55 [64], p. 4. 56 [99], p. 45. 57 [100], p. 178. 58 [100], p. 181. 93sadi carnot’s réflexions and the foundation of thermodynamics it is with no wish to claim priority that i make these statements, as the merit of first establishing the proposition upon correct principles is entirely due to clausius.59 at the same time it is a point of honor to say i may be allowed to add, that i have given the demonstration exactly as it occurred to me before i knew that clausius has either enunciated or demonstrated the proposition.60 and to note that the two formulations of the second principle are different only in the form, either of them being a consequence of the other. the crucial argument of the kelvin second proposition is that heat absorbed cannot be integrally converted to work performed in a cyclic process. suppose that a thermal engine is operating between temperatures t1 and t2, being t1 > t2, and both higher than the temperature t0 of the coldest of the surrounding bodies, for the sake of clarity the environment. the amount of heat delivered to the body at t2 is wasted unless it acts as input heat in a second thermal engine operating between t2 and t3, being t2 > t3 and both still higher than t0. it is a result of the kelvin enunciation that this step-by-step conversion of heat to work may proceed until the temperature of the environment is reached and that the work produced is q1 + q0, where q0 is the (negative) amount of heat delivered to the environment. as the proposition may be of no immediate comprehension, it was exemplified by a note “if this axiom be denied for all temperatures, it would have to be admitted that a self-acting machine might be set to work and produce mechanical effect by cooling the sea or earth, with no limit but the total loss of heat from the earth and sea or, in reality, from the whole material world”.61 probably, kelvin was motivated to reformulate the principles of clausius to express his own ideas in his own way on the issue. in the second place the enunciation contains the kelvin answer to the difficult question concerning the sort of the mechanical effect which does not appear when the two bodies are put in direct thermal contact. the work is “ irrecoverably lost to man, and therefore wasted although not annihilated”.62 7. conclusions a question that has frequently been debated in the history of science and technology is whether science has 59 [100], p. 181. 60 [100], p. 181. 61 [100], p. 181. 62 [100], p. 189. been the driving force behind technological development or whether, on the contrary, the development of technologies has been the stimulus for new scientific knowledge. even if the question, posed in this way, appears too schematic, it has aroused the interest of many scientists and historians of science. a case in point is the statement by lawrence joseph henderson (18781942), reported by charles coulston gillispie [101] that: science owes more to steam engine than steam engine owes to science.63 on the other side, hermann von helmholtz is more cautious on the immediate or direct transfer of scientific findings to technology [102]: whoever in the pursuit of science seeks after immediate practical utility may rest assured that he seeks in vain.64 but ludwig boltzmann [103], and others as well [104], seem more convinced of the primacy of science: there is nothing more practical of a good theory. in such a hypothetical dispute carnot and his réflexions place themselves in an intermediate and more balanced position. in fact, as we have already discussed, even if carnot’s initial inspiration is derived from the consideration of technology and the practice of steam engines, an object that is so eminently technological, its line of reasoning is anchored on a logical and principle level. so much so that, even with long induction times, the work of carnot has influenced and oriented the definition of the principles of thermodynamics rather than an immediate improvement of the thermal machines. the truly extraordinary aspect of the work of carnot is that, although starting from a theory of heat that already known results and subsequent experiments would have proved wrong, has led to the identification of extremely fruitful principles for the elaboration of the theory of thermodynamics. acknowledgment the authors wish to thank dr. cristina gellini for figure drawings and suggestions. 63 [101], p. 357. 64 [102], p. 93. 94 pier remigio salvi, vincenzo schettino references 1. d. i. mendeleev, on the relation of the properties to the atomic weights of the elements, russian chemical society 1 (1869) 60-77. 2. d. i. mendeleev, ueber die beziehungen der eigenschaften zu den atomgewichten der elemente, zeitschrift für chemie 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treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 4(2): 15-57, 2020 firenze university press www.fupress.com/substantia issn 2532-3997 (online) | doi: 10.13128/substantia-894 citation: m.a. murphy (2020) early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s. substantia 4(2): 15-57. doi: 10.13128/ substantia-894 received: apr 03, 2020 revised: may 15, 2020 just accepted online: may 30, 2020 published: sep 12, 2020 copyright: © 2020 m.a. murphy. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy uvlaw patents llc, 171 china creek rd., blowing rock north carolina 28605, usa e-mail: uvlawpatents@gmail.com abstract. many literature articles and/or conventional histories of “green chemistry” describe its start as being a result of actions at the us environmental protection agency (“epa”) and/or in academia during the 1990’s. but many examples of environmentally friendly real-world chemical processes were invented, developed and commercialized in the oil refining, commodity chemical, and consumer product industries starting about the time of world war ii. those efforts dramatically accelerated and evolved into explicitly environmentally oriented “pollution prevention” efforts during the 1970’s and 1980’s. a un conference in november 1976 brought together over 150 attendees from industry, academia, and governmental and non-governmental organizations from 30 countries to address environmental issues related to preventing pollution caused by the chemically-related industries. seventy-nine papers published in 1978 from the conference proceedings (titled “non-waste technology and production”) addressed a wide variety of technical, economic, environmental, and policy issues and approaches, and documented many examples of already commercialized environmentally friendly chemically based processes. on a parallel track, in 1975 the 3m corporation initiated a major corporate-wide program called “pollution prevention pays (“3p”) that commercialized thousands of environmentally oriented real-world processes and/ or inventions, in many countries, and simultaneously saved 3m large sums of money. similar “pollution prevention” approaches were emulated and elaborated by many chemically based corporations in many countries during the 1980s. the “green chemistry” terminology adopted by the epa and academia in the 1990’s evolved from the “pollution prevention” approaches, programs, and commercialized inventions that had occurred long before the 1990s. keywords: green chemistry, green engineering, history, non-waste technology, pollution prevention, economic commission for europe (ece), 3m corporation, 3m3p, environmental protection agency, american chemical society. http://www.fupress.com/substantia http://www.fupress.com/substantia http://www.fupress.com/substantia mailto:uvlawpatents@gmail.com 16 mark a. murphy if i have seen further it is by standing on the shoulders of giants. isaac newton in 16751 1. the origins of green chemistry? according to the u.s. epa’s website in 2012, 2 “green chemistry consists of chemicals and chemical processes designed to reduce or eliminate negative environmental impacts. the use and production of these chemicals may involve reduced waste products, non-toxic components, and improved efficiency. green chemistry is a highly effective approach to pollution prevention because it applies innovative scientific solutions to real-world environmental situations” (bolding added). there is much justifiable emphasis in this epa definition on “use and production,” “pollution prevention,” and on the application of “innovative scientific solutions to real world environmental situations.” it seems obvious from this definition, and from common sense, that green chemistry (and green chemists and green engineers) should address themselves (though perhaps not exclusively) to “real-world” situations and considerations. over the last twenty years, conventional histories of “green chemistry” (see for example linthorst (2010, ref 54)) and/or many academic and/or educationally ori1 newton’s statement in his letter to robert hooke in 1675 apparently echoes earlier similar sentiments going back (at least) to bernard of chartres in the 12th century. see https://en.wikipedia.org/wiki/standing_on_the_shoulders_of_giants. the visual abstract shows a portrait of newton painted in 1689 by godfrey kneller (and copied from a wikilpedia article about newton), and a photograph of the 2011 presidential green chemistry challenge award trophies, taken from an august 4, 2011 chemical & enginering news article by stephen k. ritter, and used herein with permission of the american chemical society. 2 the quotation was first accessed by the author on the epa website, http://www.epa.gov/greenchemistry/pubs/about gc.html in 2012, but is no longer available there. a very similar and earlier passage was recited by the epa’s 2002 green chemistry program fact sheet stored at the national service center for environmental publications at https://nepis. epa.gov/exe/zypurl.cgi?dockey=p1004h5e.txt ented papers3 have often repeated a “narrative”4 about the origins of green chemistry, describing it as arising in the early 1990s from concepts and actions by the us government and environmental protection agency (epa), and/or from research and publications from the academic world. green chemistry (and engineering) has subsequently blossomed into an avalanche of research, with multitudes of specialized academic journals and scientific conferences devoted to the new field, all over the world (see for example anastas and beach, (2009, ref 12), figure 1). nevertheless, professor martyn poliakoff (one of the earliest academic champions of green chemistry) recently noted that “although most people agree that the epa gave birth to green chemistry, there is much less certainty about its conception”, (poliakoff 2013, ref 63). as will be seen below, the words “pollution prevention” described a set of real-world concepts and commercialized inventions that long preceded and was the evolutionary precursor of the “green chemistry” terminology that was coined at the u.s. epa and then became recognized as an “academic field” in the 1990s and afterwards. there can be no doubt that the “green chemistry” terminology, narratives, and “movement,” that became popular in academia in the 1990s, and at least some of the inventions afterwards, were aided and/or accelerated by the activities of the us government, the epa, the acs, and academia. but this author (who conceived in 1984 one of the earliest and well-known industrial examples of green chemistry the bhc ibuprofen process) recently argued that the complex evolutionary origins of “green chemistry” began long before the 1990s and provided several examples from the commodity chemicals industry that traced their origins to shortly after world war ii, see murphy (2018, ref 59). 3 to see a few of many literature examples of this “narrative” about the origins of “green chemistry”, consider anastas (1994, ref 2); anastas and williamson (1996, ref 6); anastas and williamson (1998, ref 7); anastas and warner (1998, ref 8); cann and connely (2000, ref 19); anastas, bartlett, kirchhoff, and williamson (2000, ref 9); hjeresen, anastas, ware and kirchhoff (2001, ref 38); the “green chemistry program fact sheet, chemistry designed for the environment” (2002, ref 34); poliakoff, fitzpatrick, farren, and anastas (2002, ref 63); warner (2004, ref 85); woodhouse and breyman (2005, ref 87); anastas and beach (2007, ref 11); anastas and beach (2009, ref 12); gurney and stafford (2009, ref 36); laber-warren, e.l., scientific american (2010, ref 51); anastas and eghbali (2010, ref 13); anastas, p.t. (2011, ref 4); sanderson (2011, ref 73); anastas, p.t. (2012, ref 5);wolfe, j., forbes (2012, ref 88); lynch (2015, ref 56); lynch, w.t., (2015, ref 57); “history of green chemistry, origins of green chemistry” (2017, ref 42); howard grenville et al., (2017, ref 41); török and dransfield (2018, ref 81); and the thomas history of green chemistry and processes (2019, ref 80). 4 see below a discussion of nassim nicholas taleb’s criticism of “the narrative fallacy” and its relevance to “green chemistry,” in section 10. https://en.wikipedia.org/wiki/standing_on_the_shoulders_of_giants https://en.wikipedia.org/wiki/standing_on_the_shoulders_of_giants http://www.epa.gov/greenchemistry/pubs/about https://nepis.epa.gov/exe/zypurl.cgi?dockey=p1004h5e.txt https://nepis.epa.gov/exe/zypurl.cgi?dockey=p1004h5e.txt 17early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s this article will describe and provide many more examples of individual, corporate, governmental, and/ or collaborative international actions that grew into many examples of the real-world industrial commercial practice of “non-waste technology” and “pollution prevention” decades earlier than the 1990s, beginning after world war ii and especially during the 1970’s and 1980s. those early but currently largely unrecognized examples of “non-waste technology” and “pollution prevention” will be the focus of this article. 2. conventional histories of green chemistry a widely cited histor y of “green chemistr y” (linthorst 2010, ref 54) divides the history of green chemistry into three periods based on a graph (see linhorst’s figure 1) of the number of academic publications over time using several specific alternative terminologies; i.e. “clean chemistry”, “green chemistry”, “benign chemistry,” “sustainable chemistry,” and “environmental chemistry.” linthorst’s first period, wherein the mention of any one those terms was infrequent in the academic literature, was described as having “no formal starting point” and ending in 1993. a purported “second period” from 1993-1998, “when there is a marginal increase in the use of the specific term green chemistry” in the academic literature, was then asserted to have been followed by a third period of expansion from 1998 till 2008, “because a huge linear growth has taken place,” especially in the use of the specific term “green chemistry”. examining linthorst’s discussion more closely, linthorst’s very short discussion of his “first period” brief ly mentions rachal carson’s 1962 book “silent spring”, then mentions the creation of the us environmental protection agency in 1970 (during the nixon administration), when the “us epa adopted a command and control policy in the execution of environmental regulations” (bolding added). linthorst’s account then skips forward to the mid 1980’s, asserting that “a shift in paradigm occurred in the oecd (organization for economic co-operation and development) countries. during the 1985 meeting of the environment ministers of the oecd countries, the focus was on three themes: economic development and the environment, pollution prevention and control and environmental information and national reviews.” shortly thereafter linthorst mentions that “internationally, the idea of command and control policy (often referred to as end-of-pipeline control) shifted towards an approach of pollution prevention.” linthorst’s account then shifts back toward the u.s. government, stating: “a shift in paradigm of the us epa policy also started in the 1980s. pollution prevention instead of end-ofpipeline control had to become the option of first choice, as was confirmed by the us epa officers david stephan and john atcheson in their “the epa’s approach to pollution prevention” (stephan and atcheson 1989)… us epa and the chemical industry, cooperating in developing new processes more and more, mainly based this paradigm shift on a shared financial interest and modification of old processes, based on the pollution prevention principle (stephan and atcheson 1989). as a consequence, in 1988 the office of pollution prevention and toxics was established within the us epa, even before the concept was politically formalized in 1990…. in 1990, us congress passed the ‘‘pollution prevention act of 1990’’ under the administration of president george h.w. bush (pollution prevention act 1990). this occurred in a bad economic period that also featured serious environmental problems…. this emphasized the environmental and economic urge to adopt the policy of pollution prevention.” (bolding added) the linthorst account then describes the us 1990 act, outlining “that there was a shared interest of government (e.g. us epa) and chemical industry to cooperate and meet environmental and economic goals”… and “included the establishment of an annual award program to recognize a company or companies which operate outstanding or innovative source reduction programs.’’ “one of these was ‘‘alternative synthetic design for pollution prevention’’ developed within the office of pollution prevention and toxics” (anastas 1994, ref 2). in the remainder of linthorst’s account, the adoption and use of the particular term “green chemistry” appeared to be the major factor in the explosive growth and popularity of an academic/governmental green chemistry “network,” and a resulting avalanche of “green chemistry” academic publications. a 2011 chemical & engineering news article titled “twenty years of green chemistry,” (see anastas 2011, ref 4) displayed a graph similar to the linthorst graph, of the frequency of “scientific papers” using the term “green chemistry” in their titles, over time, and asserted that the beginnings of “twenty years of green chemistry” occurred about 1991. many, many academic publications have subsequently repeated that narrative (see for example the references in footnote 3), which will be called the “1990s green chemistry narrative” in this paper. conspicuously absent (in this author’s opinion) from lindhorst and/or anastas accounts (and from many subsequent academic “green chemistry” publications, 18 mark a. murphy some of which are cited herein) was any recognition of or significant discussion of the many, many much earlier environmentally friendly commercialized inventions and other real-world efforts at “pollution prevention” in the oil refining, commodity chemical, and consumer products industries, decades earlier. as we shall see below, the “1990s epa narrative” about the origins of green chemistry, was and is highly incomplete and oversimplified, and even deceptive. similarly, the american chemical society’s brief current website account of the history of green chemistry5 briefly mentions, with respect to the 1960s, the environmental movement, rachael carson, and the 1969 us national environmental policy act (nepa). with respect to the 1970s, the acs account briefly mentions the establishment of the us environmental protection agency (epa) in 1970, and “a series of regulatory laws…such as the safe drinking water act”. it also briefly noted “the discovery and publicity surrounding the love canal… scandalized the chemical industry.” regarding the 1980s, acs’s history stated (at least since 2012 and until very recently), “until the 1980s, the chemical industry and the epa were focused mainly on pollution clean-up and obvious toxins, but a major paradigm shift began to occur among chemists.  scientists, who came of age during the decades of growing environmental awareness, began to research avenues of preventing pollution in the first place. leaders in the industry and in government began international conversations addressing the problems and looking for preventative solutions.” (bolding added) recently, the acs website slightly revised its history by adding the following two paragraphs. “the organization for economic co-operation and development (oecd), an international body of over 30 industrialized countries, held meetings through the 1980s addressing environmental concerns. they made a series of international recommendations which focused on a cooperative change in existing chemical processes and pollution prevention. the office of pollution prevention and toxics was established within the epa in 1988 to facilitate these environmental goals.” as we shall see below, even these recent corrections to the “1990s epa narrative” remain highly incomplete, and even deceptive. this author originally conceived, in 1984, one of 5 see https://www.acs.org/content/acs/en/greenchemistry/what-is-greenchemistry/history-of-green-chemistry.html . the most widely recognized early industrial examples of “green chemistry”, the bhc ibuprofen process. the technical details of the bhc ibuprofen process were first published in a european patent publication in 1988 and issued as a us patent in 1991 (elango, murphy, smith, davenport, mott, zey and moss 1991, ref 28). the bhc ibuprofen process was commercialized at bishop texas in 1992. the bhc ibuprofen process invention won chemical engineering magazine’s 1993 “kirkpatrick award” and one of the very first presidential green chemistry awards in 1997. but multiple 3d party academic and/or popular publications told and/or repeated inaccurate narratives about that bhc ibuprofen process invention. in 2018 this author published an open access article (see murphy 2018, ref 59) that described the real-world history of that bhc ibuprofen process invention, from an inventor’s perspective. that paper documented some of the decades-long evolution of industrial methods for making acetic acid and its derivatives (and other related commercial syngas-based chemistries such as olefin hydroformylation) that were the main technical inspirations for and/or precursors of the bhc ibuprofen invention. that paper also described many economic / human / cultural factors and/or motivations (including the “quality movement” of the 1980s and its focus on waste avoidance) that drove those early industrial “green” inventions. those acetic acid and/or bhc ibuprofen process invention stories will not be retold in this article. but a similar complex combination of technical, economic, human / cultural roots, factors, and motivations also contributed to the many other early examples of industrial “pollution prevention” that were in actual commercial practice long before the 1990s. the remainder of this article will document and focus on the individual motivations, actions, and/or voluntary collaborative activities of a large international collection of industrial and academic chemists, engineers, economists, managers, corporations, and international governments, starting after world war ii, and accelerating during the 1950’s, 1960s, 1970s and 1980s. those actions and collaborations resulted in the invention, development, and commercialization of many examples of the “non-waste technologies” and “pollution prevention” long before the adoption of the “green chemistry” terminology that became popular during and after the 1990s. 3. environmentally favorable evolutionary processes in the early oil refining industry the evolutionary pathway that led toward “green chemistry” appears to have had its origins in the oil https://www.acs.org/content/acs/en/greenchemistry/what-is-green-chemistry/history-of-green-chemistry.html https://www.acs.org/content/acs/en/greenchemistry/what-is-green-chemistry/history-of-green-chemistry.html 19early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s refining industry boom that began at about the time of world war ii. this author is not genuinely expert, either technically or historically, regarding the details of the technical developments in and/or the evolution of the oil and/or oil refining industry. but a simple inspection of readily available literature sources6 revealed that multiple environmentally positive major process modifications and/or improvements which produced positive real-world environmental benefits began to evolve in the oil refining industry from about the time of world war ii. some examples from that history that illustrate the evolution of increasingly environmentally friendly oil refining processes will be briefly reproduced/ outlined in this section. the first oil well was drilled by colonel edwin drake in titusville pennsylvania in 1859. prior to world war i, oil refining was typically carried out by very simple atmospheric pressure distillations of crude oil, with the primary goal of producing kerosene for heating and lighting. a large proportion of the light and heavy residues from those simple distillations were often dumped, burned, and/or or evaporated into the atmosphere. in 1912 amoco introduced a thermal cracking process at a refinery near chicago that converted some of the heavy residues to lighter gasoline-like fractions. then more modern fractional distillations came into practice in the 1920s (after world war i), and “increased the efficiency of separating crude oil into its constituents by 25%.” after world war i, the use of automobiles and airplanes increased very rapidly, creating a growing demand for gasolines. the gasolines produced by distillation had low octane numbers however, limiting the compression ratios of the engines and therefore their power and fuel efficiency. in 1921, chemists at general motors discovered that adding small amounts of alkyl lead compounds to gasoline significantly increased the octane numbers, but the resulting environmental problems were ignored and weren’t actually addressed until the 1970’s (lead also fouled the expensive noble metal catalysts in the new catalytic converters for automobile exhaust gases). in 1936 eugene hoody introduced a fixed bed catalytic cracking unit that doubled the volume of gasoline produced from the lower value heav y residues7. the heavy residues were mixed at very high temperatures with solid alumina-containing clays that caused the heavy molecules to crack into lighter and more valuable 6 the early (pre-1970) history of oil refining recounted herein is based on leffler’s 2008 book (ref 48) titled “oil refining” and/or from wikipedia articles on “oil refinery” (see https://en.wikipedia.org/wiki/oil_ refinery) and “gasoline” (see https://en.wikipedia.org/wiki/gasoline). 7 see leffler (2008), chapter 8. organic molecules. esso introduced a much-improved f luidized bed catalytic cracker into its baton rouge refinery in 1942. later (in the 1970s and later) the natural clay catalysts originally used were replaced with synthetic zeolite catalysts that were more selective for producing products in the desired gasoline ranges. use of such catalytic cracking processes in oil refineries greatly increased the availability and decreased the price of ethylene and propylene. jira remarked (jira 2009, ref 45) that the increasing availability and lower price of ethylene was a major motivation for his 1956 coinvention of the wacker process for the aqueous air oxidation of ethylene to acetaldehyde, which may have been the first major industrial process that was both highly atom economical and genuinely environmentally friendly (see jira 2009, german patentcraft 1 049 845 filed january 04, 1957 and published february 05, 1959. also see murphy (2018, ref 59) for a short discussion of the chemistry and environmental friendliness of the wacker process). new catalytic “alkylation” processes entered service in u.s. refineries about 1940. alkylation is a class of reactions in which volatile alkenes (such as propylene or butenes) are condensed with branched alkanes (often isobutane) in the presence of strong acids (initially and typically hf or sulfuric acid) to produce higher branched alkanes (typically iso-heptane and iso-octane) with high octane numbers.8 the products of alkylation units and processes are also typically low in alkenes and/or aromatics that don’t burn as cleanly as the desired branched alkanes. the hf catalyst was more easily and efficiently recycled than the sulfuric acid catalyst, but because of hf’s volatility, corrosive properties, and toxicity it represents a significant safety risk at the plant site.9 as the decades passed, many refineries began to replace hf with h2so4 for safety reasons, as exemplified by us patent no. 5,284,990 to peterson and scott. in 1949, the first catalytic reforming process was started up at the old dutch refining company of muskegon michigan. catalytic reformers convert napthas (from the initial distillations and which contain large amounts of normal alkanes and napthenes) into isoalkanes, and aromatics, which dramatically increased octane numbers.10 the by-product hydrogen liberated from the reforming processes is used elsewhere in the 8 see leffler (2008), chapter 9, and https://en.wikipedia.org/wiki/alkylation_unit. 9 a 380 page hydrogen flouride safety study, and final report to congress under section 1112(n)(6) of the clean air act was generated in 1993, after a refinery accident occurred in 1987. a copy of that report is available at http://www.documentcloud.org/documents/70516-epahydrogen-fluoride-study.html . 10 see leffler (2008) chapter 10. https://en.wikipedia.org/wiki/oil_refinery https://en.wikipedia.org/wiki/oil_refinery https://en.wikipedia.org/wiki/gasoline https://en.wikipedia.org/wiki/alkylation_unit https://en.wikipedia.org/wiki/alkylation_unit http://www.documentcloud.org/documents/70516-epa-hydrogen-fluoride-study.html http://www.documentcloud.org/documents/70516-epa-hydrogen-fluoride-study.html 20 mark a. murphy refineries, especially in hydrocrackers. the reforming catalysts typically contain platinum on heterogeneous supports (and sometimes other metals and promotors such as chlorine). the reforming catalysts were originally used in fixed-bed designs, but later fluidized bed catalyst designs improved performance and decreased the downtime needed to regenerate fouled catalysts. catalytic hydrocracking11 was introduced during the 1950s and continued to further develop later. hydrogen and heavy distillation fractions such as diesels, kerosene’s, heavy gas oils, etc. are heated to high temperatures and pressures in the presence of catalysts (typically comprising cobalt, molybdenum, nickel, sulfur, and supports such as aluminas) to produce lighter napthenes, paraffins, and other gasoline-range components. hydrocracking also breaks up the rings of heavy aromatics to produce branched alkanes (such as isobutane) of higher value. hydrocracking also removes sulfur and nitrogen hetero atoms from the heteroaromatics in the feeds. olefin metathesis is sometimes used in commercial refineries for upgrading low molecular weight olefins produced by cracking processes to higher molecular weight and octane number components for gasoline blending.12 the olefin metathesis reaction was serendipitously discovered in 1956 by h.s. eleuterio of the du pont petrochemicals department (see eleuterio 1991, ref 29). eleuterio was investigating the then novel zieglernata polymerization of olefins such as ethylene and propylene (see ziegler 1955 ref 89). eleuterio detected the unexpected formation of ethylene and 1and 2-butenes from propylene over molybdena containing catalysts (as illustrated below) and investigated the unexpected reaction further. eleuterio recognized some of the potential scope and value of the olefin metathesis reaction at the time, 11 see leffler (2008) chapter 11. 12 see for example https://en.wikipedia.org/wiki/olefin_metathesis. and suspected the likely involvement of “carbene-type intermediates”, but “although the chemistry was recognized as novel, with much up-side theoretical and synthetic potential, a decision was made to terminate the work by writing a summary research report along with appropriate patent notes.” one of eleuterio’s proposals for a patent, to claim a process for upgrading propylene to butene, “was rejected by the section manager with the comment that “du pont was not in the oil business”. another eleuterio patent proposal directed to polymeric compositions prepared by metathesis of cyclic olefins was filed in 1957, and granted as a german patent 1 072 811 in 1960, and u.s. patent no. 3,074,918 in 1963. patenting or publication of eleuterio’s discoveries relevant to the polypropylene metathesis reaction “was set aside because some of the results were considered relevant to pending polymer and copolymer patent applications.” a major round of patent litigations relating to the polyolefin compositions and methods resulted between du pont, standard oil of indiana, phillips petroleum, hercules, and montecatini. the patent litigations did not get settled for decades, and “further complicated an already complex information generation and transfer process, inhibiting the ripening of time for many ideas…” yves chauvin started his career in the french petrochemical industry in the mid-1950s and apparently encountered olefin metathesis reactions there. in 1960 chauvin moved to the public institut français du pétrole, and in 1971 chauvin publicly proposed a mechanism for olefin metathesis involving metal carbene complexes13 that is now widely accepted. subsequent developments led to many new olefin metathesis applications in both industry and synthetic organic chemistry (see for example delaude (2005, ref 24)), and eventually led to a “green” nobel prize (along with robert h. grubbs and richard r. schrock for later developments) in 2005.14,15 when lead additives were banned from gasolines during the 1970s, a need for new secondary refining processes that could efficiently produce increased volumes of high-octane non-leaded gasolines became acute. a tremendous amount of r&d effort. over dec13 jean-louis hérisson, p.; chauvin, y. (1971). “catalyse de transformation des oléfines par les complexes du tungstène. ii. télomérisation des oléfines cycliques en présence d’oléfines acycliques”.  die makromolekulare chemie  (in french).  141  (1): 161–176.  doi:10.1002/ macp.1971.021410112. 14 grandin, k.; ed. (2005).  “yves chauvin biography”.  les prix nobel. the nobel foundation. available at https://www.nobelprize.org/prizes/ chemistry/2005/chauvin/facts/ 15 see https://www.treehugger.com/sustainable-product-design/nobelprize-in-green-chemistry.html . https://en.wikipedia.org/wiki/olefin_metathesis https://www.nobelprize.org/prizes/chemistry/2005/chauvin/facts/ https://www.nobelprize.org/prizes/chemistry/2005/chauvin/facts/ https://www.treehugger.com/sustainable-product-design/nobel-prize-in-green-chemistry.html https://www.treehugger.com/sustainable-product-design/nobel-prize-in-green-chemistry.html 21early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s ades, was poured into developing new synthetic zeolite catalysts for a wide variety of refinery applications.16 the improvements in the catalysts typically increased the efficiency of conversion of the raw materials into salable products, and decreased the amount of waste to be disposed of, both of which improved the economic results. decreased waste production and waste disposal costs became increasingly important in view of the antipollution statutes that were passed in many countries in the 1960s and 1970s. appreciation for the altruistic environmental benefits of lower waste production, as well as addressing the concerns of the governments and the customers also grew over time. as leffler noted in 2008, “most of the technological change in the last 20 years has been driven by environmental concerns, causing refiners to tweak existing processes, especially with the introduction of new and improved catalysts.” an unexpected invention that arose from the zeolite catalyst work in the 1960s and 1970s and the oil shortages of the 1970s was the now well-known mobil methanol to gasoline processes. several patents issued for various embodiments of such processes.17 as already summarized in many places (including murphy 2018) methanol can be prepared very efficiently and atom economically on industrial scale from methane, or less efficiently from coal. in the mobil process, in a first catalytic stage methanol is dehydrated to form a mixture of water, methanol, and dimethyl ether, then the stream is passed over a zeolite catalyst to form olefins, which further condense to form paraffins, napthenes, and methylated aromatics. the size selective zeolite catalyst limits the product range to about c11. the process was piloted in 1979 and commercialized in new zealand in 1985 at a scale of 14,500 barrels per day. a second-generation process was piloted in china in 2009 at a scale of 2,500 barrels per day, and agreements for additional larger scale units are in place.18 by the time robert sheldon (a european chemical industry veteran who moved to academics in 1991) published his seminal 1992 chemistry & industry paper (sheldon, 1992, ref 74) that first publicly defined the “e-factor”, sheldon estimated that the oil refining indus16 see for example rabo, j.a. (ed.), “zeolite chemistry and catalysis”, 1976, acs monograph 171, american chemical society (ref 67), which contains thirteen papers predominantly from industrial authors, seven of which address synthesis, characterization, and properties of then new zeolites, and six papers relating to the catalytic properties of new zeolites. 17 see for example u.s. patent no. 3,931,349 issued january 6, 1976 to kuo and assigned to mobil oil corporation, and several other related u.s. patents recited therein and assigned to mobil. 18 see https://www.exxonmobilchemical.com/en/catalysts-and-technology-licensing/synthetic-fuels try (where the use of catalysis was common) was producing only about 0.1 kg of waste per kilogram of useful products, as compared to estimates of 5-50 kg/kg in the fine chemical industry segment, and 25->100 kg/ kg in the pharmaceutical industry segments (where use of traditional synthetic organic chemistry techniques were dominant). clearly the evolutionary progress in the oil refining industry, over decades, had come a very long way toward environmentally friendly processes by 1992. much of that progress was achieved by improving catalysts, and sheldon argued that catalysis had initially developed as an industrial discipline largely separate from traditional synthetic organic chemistry, only to have the separate fields start to merge as the field of organometallic chemistry developed in the 1960s and 1970s. the oil and gas industry was also actively addressing process safety issues long before “green chemistry” became fashionable in academia in the 1990s. on october 16-18, 1991, the national petroleum refiners association held a meeting denver that included a question and answer session with a panel of experts. the session was reported in the oil & gas journal (1992, ref 62) in an article entitled “refiners discuss hf alkylation process and issues”. one audience question was “what progress is being made on developing a solid catalyst for the alkylation of light olefins and isobutane?” a panel expert named mcclung answered “i cannot be terribly encouraging on this subject. what progress is being made is published in patents, which i review just about monthly….i know that it is the “holy grail” of the petroleum industry to find this kind of process, and there is a lot of work being done. i think mobil is your most reliable source for progress”. another expert, michael humbach from uop stated “we concur with what has been said. we have a fairly intense r&d effort going on right now in this area. what we are finding is that indeed it is going to take a breakthrough, not only in catalyst technology, but also in process technology.” the oil ref ining industr y’s “grail quest” has required 20-25 additional years, but the needed breakthroughs have finally come. in september 2016, honeywell uop announced19 that after 5 years of small-scale testing, it initiated conversion of the alkylation unit of its salt lake city refinery to use of an isoalkyl™ technology which uses an ionic liquid as an alkylation catalyst. honeywell uop licensed that ionic liquid technology from chevron, and the technology appears to be related to u.s. patent no. 7,495,144 by inventor salch elomari. a parallel breakthrough in refinery alkylation chemistry appears to have come from albemarle 19 see https://www.hydrocarbonprocessing.com/news/2016/09/honeywell-uop-introduces-ionic-liquids-alkylation-technology https://www.exxonmobilchemical.com/en/catalysts-and-technology-licensing/synthetic-fuels https://www.exxonmobilchemical.com/en/catalysts-and-technology-licensing/synthetic-fuels https://www.hydrocarbonprocessing.com/news/2016/09/honeywell-uop-introduces-ionic-liquids-alkylation-technology https://www.hydrocarbonprocessing.com/news/2016/09/honeywell-uop-introduces-ionic-liquids-alkylation-technology 22 mark a. murphy of the netherlands. in june 2007, albemarle corporation announced the development of a breakthrough zeolite-based solid acid catalyst for refinery alkylation processes.20 that process appears to be related to related to u.s. patent application initially filed in january 2007 and eventually issued in 2012 as u.s. patent no. 8,163,969, to four netherlands inventors; van brockhoven, harte, klaver, and nieman. the invention won one of the 2016 presidential green chemistry awards21 in november 2017 albemarle and its corporate partner cb&i were awarded chemical engineering magazine’s biannual “kirkpatrick chemical engineering achievement award” for the zeolite-based alkylation process.22 overall, the oil refining industry clearly has, since world war ii and continuing to present time, consistently made and is continuing to make significant strides, both economically and environmentally. since world war ii, some of the commodity chemicals companies also made comparable strides to invent, develop, and commercialize many examples of clean and highly atom efficient processes for making non-toxic commodity chemical products for real world customers, often via the use of catalytic processes. examples include the air oxidation of ethylene to ethylene oxide, wacker and methanol carbonylation processes for producing acetic acid (and then onward to polyvinyl acetate and polyvinyl alcohol, major commodity polymers that are biodegradable). rhodium catalyzed olefin hydroformylation has also developed into highly efficient and atom economical processes for making commodity aldehydes, alcohols, carboxylic acids and esters. some of those developments preceded and partially inspired the bhc ibuprofen process invention that won chemical engineering magazine’s kirkpatrick award in 1993, and one of the very first presidential green chemistry awards in 1997. some of the history of those early “green” developments in the commodity chemical industry was recounted in this author’s prior paper, see murphy (2018, ref 59). 4. non-waste technology and production this section will describe and summarize excerpts from a 1978, 681page book,23 that documents some of 20 see for example https://www.biospace.com/article/releases/albemarlecorporation-and-partners-develop-breakthrough-catalyst-for-refineryolefin-alkylation-process-/ 21 see https://www.epa.gov/greenchemistry/presidential-green-chemistry-challenge-2016-greener-synthetic-pathways-award 22 see https://www.chemengonline.com/cbi-and-albemarle-win-the44th-kirkpatrick-chemical-engineering-achievement-award/ 23 the selected quotations in this section of this article are reprinted from “non-waste technology and production” copyright (1978, ref the earliest international efforts to improve the environmental performance of the chemically related industries. the book, titled “non-waste technology and production” (1978, ref 61), was published by the united nations and/or its economic commission for europe. the book contains papers based on a november 1976 un/ ece seminar. the book has an “introduction,” a list of “conclusions and recommendations,” then a compilation of seventy-six individual papers and two inaugural addresses. a listing of the individual titles, authors, nationalities, and affiliations of the individual papers and inaugural addresses presented at the 1976 conference is listed in appendix i of this paper. according to the 1978 book, the un’s economic commission for europe, after “many years of activity by the ece in various environmental fields” had established a body of senior advisers in 1971. in 1973 the senior advisers “decided to include, among other subjects, the principles and creation of non-waste production systems in their work programme.” in geneva in 1974 the senior advisers defined non-waste technology as “the practical application of knowledge, methods and means so as, within the needs of man, to provide the most rational use of natural resources and energy and to protect the environment. non-waste technology, it was stressed, should be seen as a long-term strategy, as a philosophy of the evaluation of the environmental complex.” the senior advisors decided to hold a seminar, which “was held in paris from 29 november to 4 december 1976. more than 150 representatives of thirty countries and nine international inter-governmental and non-governmental organizations took part.” the “conclusions and recommendations” section of the resulting “non-waste technology and production” book stated the following: “the question today is whether technology can solve the environmental problems which technology has helped to cause. there is widespread belief that this question can be answered positively… awareness of negative side effects of modern technology has, in recent years brought about new economic and legislative measures which are fostering new industrial attitudes and approaches. attention has been mainly focused on problems connected with treatment of wastes at the end of the production line, once the product (and its consequent wastes) has been produced. but more and more frequently it is being asked whether it would not be economically and socially less costly to minimize all along 61), with permission from elsevier, current owner of the copyrights originally held by the original publisher permagon press on behalf of the united nations. https://www.biospace.com/article/releases/albemarle-corporation-and-partners-develop-breakthrough-catalyst-for-refinery-olefin-alkylation-process-/ https://www.biospace.com/article/releases/albemarle-corporation-and-partners-develop-breakthrough-catalyst-for-refinery-olefin-alkylation-process-/ https://www.biospace.com/article/releases/albemarle-corporation-and-partners-develop-breakthrough-catalyst-for-refinery-olefin-alkylation-process-/ https://www.epa.gov/greenchemistry/presidential-green-chemistry-challenge-2016-greener-synthetic-pathways-award https://www.epa.gov/greenchemistry/presidential-green-chemistry-challenge-2016-greener-synthetic-pathways-award https://www.chemengonline.com/cbi-and-albemarle-win-the-44th-kirkpatrick-chemical-engineering-achievement-award/ https://www.chemengonline.com/cbi-and-albemarle-win-the-44th-kirkpatrick-chemical-engineering-achievement-award/ 23early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s the line the creation of wastes that need to be treated – from the extraction of raw materials to the end of life final consumer goods. the essence of non-waste technology is in the answer to this question… an examination of the papers submitted on this topic has made it clear that there are many different points of view as to how to promote non-waste technology and to what degree it should be promoted. even though the range of ideas was very wide, the need for a technology that reduces or avoids waste was universally recognized. thus, even though the various countries demonstrated their unique problems, they all supported the promotion of non-waste technology and agreed on the possibility of discussion of the common themes.” in a section relating to “concepts and principals of non-waste technology,” m.g. royston, an economist at the centre d’etudes industrielles of geneva switzerland (whom we shall see later became a leader in the economic analysis / legal aspects of non-waste technologies), contributed a paper entitled “eco-productivity: a positive approach to non-waste technology”. some comments from mr. royston’s paper (ref 71) are reproduced below: “pollution is waste. waste today leads to shortages tomorrow, “waste not want not” is a motto as true now as it was for all those generations before the brief flowering and decaying of the affluent/effluent society. the very sustainability of dignified life on this planet earth must depend on re-establishment of a non-waste society, a non-waste economy, a non-waste technology, and above all a nonwaste value system.” “in a finite world, the one resource which is unlimited is the human spirit and the love, sense of purpose, and quest for knowledge that flows from it. indeed, the one resource in this world which grows is this resultant knowledge and from which human understanding, human wisdom and, hopefully, human institutions and technology spring. thus, one key to the new ‘product-not-waste society’ is the liberation of the human spirit, the encouragement of new scientific research and the application of the new insights to develop the new systems which meet human needs without creating waste.” royston commented multiple times in his paper about the many prior european efforts by both governments and corporations to deal with waste and environmental issues, writing: “in the public sphere, in europe again, it has been common practice for many years to burn garbage in specially designed plants in order to generate electricity, such plants exist in geneva, zurich, munich, stuttgart, paris and many other cities and can provide around 15 per cent of a city’s need in power. also in this area, a number of power plants in europe have for many years used their waste heat to supply hot water and space heating for houses and apartment blocks. the lack of development of these processes in the u.s. is almost entirely due to much lower energy costs in the u.s. compared with europe. since the oil crisis however,24 american engineers and city authorities have made up for this lack of interest.” royston then commented on possible waste-savings and anti-waste approaches that could be undertaken in the energy, organic chemicals, inorganic chemicals, non-metallic minerals, and metallic minerals industries, and efforts that could be taken to economically and even profitably undertaken to reduce pollution of the air, land, and water. in the book ’s section about relating to topic iib, “the industrial experience,” the following comments were made: “numerous discussion papers received for this topic provide information on many industrial applications of this technology. it was noted that different methods could be used to eliminate or significantly reduce wastes: (a) by improv ing existing technologies: recycling, increasing yields, development of recovery processes, and waste transformation; (b) by creating new techniques or by radically modifying existing techniques, in order to obtain production processes which produce less wastes and noxious pollutants. it is clear that the research work necessary to promote non-waste technology has not attained a desirable level. countries must develop multi-disciplined research in order to improve non-waste technology for all branches of industry. the economic aspects of the rational utilization of raw materials and energy must be tackled simultaneously.” in a subsequent comment, it was observed that: “the introduction of non-waste technology in industry cannot be accomplished without the active participation of everyone concerned. it is therefore necessary that educational institutions (particularly for technical staff ) take practical measures to ensure that their courses take into account the impact on the environment of the technologies which are being taught and that the ideas relative to non-waste technology are propagated. moreover, it is necessary that, in the course of their education, young people are familiarized with environmental problems, such 24 this footnote is not part of royston’s original paper. some younger readers may not recall that after the arab-israeli war of 1973, opec embargoed oil shipments to the us and some european countries, causing years of severe oil and gas shortages, skyrocketing oil prices, and economic damage and inflation in those embargoed countries. 24 mark a. murphy as the use of natural resources, protection of the countryside, etc.” in the book section about topic iic, “case studies” the following comments were made regarding the iron and steel industry: “it was recognized that the iron and steel industry is one of the most polluting sectors with respect to water and air pollution. in addition, it is an important source of solid waste. nevertheless, efforts already undertaken in all countries have permitted large reductions in the emission of these pollutants.” the following comments were made regarding the pulp and paper industry: “the traditional technologies to transform wood and vegetable fibres into pulp and paper generate various kinds of waste: … for ten years, great progress has been made to reduce this waste by: – trying to utilize the whole tree; – using closed circuits in pulp and paper production; – utilization of oxygen instead of chlorine as a bleaching agent; – systems of recovery of wood fibres in paper production. these objectives can only be attained through considerable research and development efforts and by continued association of the paper industry with the mechanical and chemical industries.” the following comments were made regarding the packaging industry: “the non-waste technology of a package type must be examined in all its aspects before definitive conclusions may be drawn. these aspects include the stages of design, production, distribution, transport, consumption, recycling and waste management and environmental impact.” the following comments were made regarding topic iii, “cost-benefit aspects of non-waste technology: “all nations have limited budgets for environmental expenditure. benefit/cost analysis, along with other evaluation methods, can be used to help select those non-waste technologies that should be given high priority, and thereby assist in making the environment as clean as possible.” somewhat later there was a comment that: “there is an additional matter that must be understood. there are sometimes several ways of reducing pollution. the benefits of each method may exceed their respective costs. but the appropriate method is to select the approach which can achieve the objective in the lowest-cost manner, in order to honor the true spirit of non-waste technology.” yet another subsequent comment was that “over a period of time, it is likely that waste treatment will become increasingly costly and that non-waste technology will become less costly. this reality must start to be included in present decisions.” in the “recommendations” section the following comment was made: “it is recommended that the senior advisers on environmental problems envisage wide consideration of the problems of non-waste technology in the chemical and petro-chemical industries and possibilities for the creation of energo-technological complexes with no harmful discharges into the environment.” but the “non-waste technology and production” seminar/book didn’t just produce abstract ideas and/ or strategies for the future. it also documented multiple real-world examples of “non-waste technology and production” that had already been implemented in realworld commercial production! some relevant examples and comments from the sections on “national experience and policy” and “industrial experience” will briefly reproduced below. in the “national experience and policy” section of the book, a.j. mcintyre (rapporteur) summarized multiple papers from national representatives of many of the attending nations (whose details will not be reproduced here). mcintyre made the following comments: austria – “the list of non-waste developments in austria is extensive and impressive.” belgium – “the government’s interest in f inancing research and development and the response of industry has been very productive indeed.” “the motivation for these programmes is a mix of raw material saving, energy saving, and pollution abatement.” canada – “…canada has some evident interest in nonwaste technology. the balancing that goes on between social, economic, and political processes is seen to have resulted in some relevant policy and in certain tangible developments.” “the tangible results are most clearly seen in the can-wel project and in the reeve-rapson process.” federal republic of germany – “the level of state activity in the federal republic of germany is both advanced and extensive.” france – “this paper focuses on the term “clean technologies” which refers to those technologies that reduce or evade waste or pollution.” the netherlands – “this country seems to have considerable interest in non-waste technology and is actively involved in developing approaches that are expected to promote and encourage industry to innovate in socially acceptable ways.” the united states – “increasing concern about availability of raw materials is increasing the pace of development of non-waste technology in the us.” 25early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s the united kingdom – “here we are warned that the real aspirations of society are expressed in economic terms and that if this is not recognized we run the risk of being, or appearing to be, idealistic… we must be realistic in order to be effective.” a next major section of the book related to specific papers and examples of “the industrial experience.” a few of the major papers will be briefly reviewed below. seppo hä rk k i, of outoku mpu o y, fin la nd, described an energy saving and pollution preventing method of smelting copper ore that had been in commercial operation since 1949. conventional processes had used large amounts of electricity to provide the heat required for smelting copper ore. the outokumpu process air oxidized the ore, and heat from the oxidation of iron and sulfur in the ore provided most of the heat required for smelting the copper. furthermore, the sulfur oxides that would have been air pollutants were converted to salable sulfuric acid. professor lászló marko of the veszprém university of chemical engineering, hungary was a wellknown academic chemist in the field of organometallic chemistry at the time. professor markó wrote about the importance of catalysts in increasing the selectivity of chemical reactions and thereby increasing yields and reducing waste in the organic chemical industry. markó addressed the resulting important problem of how to recycle or reactivate the metal-containing catalysts, and methods for recovering potentially toxic metals from the heterogeneous catalysts including the recovery of nickel from spent raney nickel. the later part of markó’s paper discussed the importance of the then new field relating to the use of homogeneous metal complexes containing optically active ligands as catalysts for organic reactions, to produce optically active products that are highly relevant to biological/pharmaceutical applications. although not explicitly mentioned, this discussion was clearly related to the then new discoveries of asymmetric hydrogenations of olefins by william s. knowles of monsanto, who pioneered that field. knowles work at monsanto resulted in a commercial synthesis of l-dopa and eventually resulted in a nobel prize in 2002. dr joseph ling, vice president for environmental engineering and pollution control at 3m corporation gave an important talk about 3m’s already established and extensive experience (since 1974 or before) in nonwaste technologies, entitled “developing conservationoriented technology for industrial pollution control.” some quotations from ling’s 1978 paper are reproduced below: “successful application of a resource conservation-oriented pollution-control technology program throughout a single transnational company has been especially encouraging. it also indicates that on a large scale involving many countries, the rate of industrial conversion to this technology may depend largely on the amount of practical support given by governments.” “legislative requirements or the short-term deadlines of recent environmental legislation, particularly in the united states, have forced industry to use removal technology, which is not always the most environmentally efficient method.” “within industry, the primary objective in management of pollution-control activities is achievement of the highest degree of pollution reduction with the lowest use of human, material and financial resources. non-waste technology programs appear to be the best means of meeting this objective in many cases.” while describing some specifics of 3m’s experiences with its internal program, ling commented that: “one extensive non-waste technology program recently was implemented by the 3m company, a large diversified transnational manufacturing company based in the united states. the firm, with nearly 80,000 employees in more than 40 countries, stresses new and improved products. manufacture of these products often produces pollutioncontrol problems that require special solutions. initial results of the 3m program are particularly encouraging because they demonstrate the superiority of this new pollution-control approach over removal technology. the program was aimed at applying conservation-oriented technolog y to the company’s facilities around the world. it began with the strong support of top management, which was considered essential for successful implementation throughout the firm.” “appropriate prevention methods include: 1. product reformulation. 2. process modification. 3. equipment redesign. 4. recovery of waste materials for reuse. in 9 months the program was introduced in fifteen countries. in the united states, non-waste technology projects eliminated 70,000 tons of air pollutants and more than 500 million gallons of wastewater per year. in addition, the program saved an estimated $10 million in actual or deferred costs associated with pollution control, including energy and raw materials as well as retained product sales.” dr. ling also briefly described three example projects from the 3m program: “the company developed a new cotton herbicide chemical. the original process emitted a toxic substance and one that caused a strong odor. it also introduced 12 26 mark a. murphy pounds of pollutants per pound of product. using nonwaste technology, the laboratory then developed a new process that eliminated the toxic substance and the odor. it also reduced other pollutants to only 2 pounds of waste per pound of product. in addition, manufacturing costs were significantly reduced. another case involved control and recovery of hydrocarbon solvents, which can contribute to photochemical smog when released into the atmosphere. the firm developed and built a unique inert gas drying process. it features a large oven that operates as a closed system. this prevents hydrocarbon emissions and allows recovery of most of the valuable solvents. in a third case, a mercury free catalyst was developed for a resin product to prevent a mercury problem. this made the product more environmentally acceptable and prevented a substantial loss in sales.” lastly, dr. ling introduced a concept that “in a sense, many pollutants can be considered misplaced resources… but it took knowledge (technology) to turn these former pollutants into resources.” dr. ling then restated the concept into an “equation” form that was often quoted (and put into practice) later: “pollutants (waste materials) + knowledge (technology) = potential resources” in retrospect, it is obvious from the “non-waste technology and production” seminar/book, that during the 1970s (and even well before) many people and organizations in many countries were actively conceiving, reducing to practice, and commercializing “green” chemical processes and downstream chemically-based products that were intended to be both environmentally and economically efficient. a variety of scientists and engineers (industrial and/or academic), economists, and national and international governmental authorities were already voluntarily collaborating to achieve such goals long before the 1990s. 5. 3m’s “pollution prevention pays” (“3p”) program 3m’s corporate “pollution prevention pays” program (“3p”), already mentioned above in connection with the 1976 “non-waste technology and production” seminar and 1978 book, formally began in 1975. a pioneer in those 3m efforts was dr. joseph t. ling who was the 3m vice president for environmental engineering and pollution control. dr. ling was elected to the national academy of engineering in 1976, and many of the facts recited in this section were sourced from a memorial tribute to dr. ling published by the national academies after dr. ling’s death in 2006 (see joseph t. ling (2008, ref 50). an on-line version is available at https://www. nap.edu/read/12473/chapter/31. dr. ling was born in china in 1919, educated as an engineer, and left china in 1948 to obtain a ph.d. in sanitary engineering from the university of minnesota. ling worked briefly at general mills, then returned briefly to china before returning to the us in 1960 to become 3m’s first professionally trained environmental engineer. dr. ling moved 3m away from pollution control (treatment) approaches and toward pollution prevention and/ or natural resource conservation approaches that could simultaneously improve efficiency, production yields, and economics. ling wrote a new environmental policy for 3m that was adopted by its board of directors in 1975. “joe realized that government and public awareness was essential to regulatory and legislative acceptance of this new approach, so he ‘went public’ with the idea in 1976,” at the ece non-waste technology and production seminar described above. “he stressed the need for cooperation among industry, government, academia, and the general public, because ‘the environmental issue is emotional … the decision is political … but the solution must be technical.’” this author conducted a 2018 telephone interview with one recently retired 3m employee, keith miller, an engineer who had just ended a 37-year career at 3m as a “sustainability strategic advisor”. the telephone interview was a follow-on to a 2015 “exit interview” published at greenbiz (see https://www.greenbiz.com/article/ exit-interview-keith-miller-3m). miller recalled that after graduation as a chemical engineer from the university of minnesota he began his first job at 3m in 1974. miller said his first major project assignment was to a convert a process for making an adhesive tape product from a solvent-based adhesive application process to a hot-melt process. miller recalled that he collaborated with 3m chemists to identify suitable hot-melt formulations and develop practical methods for economically and reliably applying the adhesive to produce a good quality adhesive tape product that was acceptable/desirable to the customers. miller recalled that he was involved in environmental projects using similar multi-disciplinary teams and approaches throughout his career. when asked, miller also recalled being trained, in the 1980s, in deming style “total quality management (“tqm”) methods.25 miller recalled finding the “quali25 see murphy (2018) for more description of deming’s “quality” approaches, philosophy, and techniques and their relevance to the conception and invention of the bhc ibuprofen process in the mid-1980s. https://www.nap.edu/read/12473/chapter/31 https://www.nap.edu/read/12473/chapter/31 https://www.greenbiz.com/article/exit-interview-keith-miller-3m https://www.greenbiz.com/article/exit-interview-keith-miller-3m 27early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s ty” training useful and “compatible” with 3m’s operating methods and approaches, which were being applied to thousands of different products. when asked, miller did not recall much patenting activity, believing that most of the company’s intellectual property, for its many products, was primarily protected by trade secret ip strategies, rather than patents.26 most of all, miller seemed very appreciative of the strong support the 3p program and approaches had received from 3m management, over decades. that support was highly economically and environmentally productive. the national academy memorial tribute to dr. ling (in 2008) remarked that “after 30 years, the 3p program is still a key strategy in 3m’s environmental management plan. from 1975 to 2005, with some 8,500 pollution prevention activities and programs in 23 countries, the company was able to keep from producing an estimated 2.2 billion pounds of pollutants while saving nearly $1 billion.” subsequent to the 1976 ece seminar, several countries including england, france, and germany, adopted the pollution prevention strategy as national policy. “in 1977, the environmental protection agency (epa) and u.s. department of commerce conducted a series of industry/government seminars on pollution prevention.” dr ling and other 3m speakers spoke at many of those seminars and 3m published multiple subsequent papers describing its 3p program. examples of the papers include susag (1982, ref 76), zoss and koenigsberger (1984, ref 92), koenigsberger (1986, ref 47), susag (1987, ref 77), zosel (1990, ref 90), and zosel (1994, ref 91). those papers were united by their description of the general approaches 3m employed over many years, directed to many types of its chemically based consumer products, by working with many people at most levels throughout their international organizations, using many kinds of processes, in many countries. the papers consistently emphasized the importance of the high level of support for those activities received from 3m management. the national academy noted that “by 1988, 34 states had established pollution prevention programs.” 6. the importance of economics in pollution prevention by the time of the un/ece “non-waste technology and production” seminar in 1976, many individu26 this author has done some cursory searching for patents (in the us or abroad) that issued to 3m during the 1970s and 1980s, and found surprisingly few patents, and no patents of clear relevance to green chemistry. als and organizations had recognized the high economic costs and industrial resistance that had been produced by the “command and control” / “end of the tailpipe” approaches mandated by many environmental statutes of the early 1970s, especially in the united states. the importance of the economic issues was crystalized and summarized by professor michael g. royston of the center of education in international management in geneva. professor royston’s paper at the 1976 conference has already been described, but his analysis further crystalized in his 197-page book, “pollution prevention pays” (royston 1979, ref 71). royston’s book adopted its title (with permission) from 3m and/or dr. joe ling, and ling wrote the foreword to royston’s book. ling’s foreword commented that “most environmental laws, regulations, and technologies have been devoted to cleaning up pollution, with little or no attention paid to prevention…. government, industry, and the public are beginning to become aware of the shortcomings of conventional pollution controls, not to mention their cost.” ling then added that “the conservation approach…. means eliminating the causes of pollution before spending money and resources to clean up afterwards. it also means learning to create valuable resources from pollution…” ling further commented that “the concept is embodied in pollution prevention pays, which speaks to the proposition that it is environmentally, technically, and economically superior to eliminate the sources of pollution before clean-up problems are created.” royston’s book stated (on page 9) that its purpose was to demonstrate: “that environmental protection is economically justified both from the point of view of the community and at the national and regional level; that the resources required for development or even the maintenance of the status quo can be damaged by pollution; that the damage is likely to cost the community more than it would have to spend to prevent the damage from occurring at all; and finally the positive contribution environmental protection policies make to the development of enterprises – both public and private.” royston was critical of both socialist and capitalist traditional economic approaches, asserting that both had actually produced increasing concentration of decisionmaking power in fewer and fewer hands, and an underlying economic justification that “was typically cartesian in its scope, completely linear in its approach…” royston further commented that “in both these centralized systems the vital link between man and his envi28 mark a. murphy ronment is broken… for the central planner or the wall street banker alike, the environment is a free resource to be fed into the economic development system… both of them are remote from the environmental results of their decisions and from the people who suffer from those results.” royston asserted that “the modern manager has a responsibility not only to the company which he manages, but also to the society in which his country functions.” royston continued (on page 43) that “gone are the simplistic notions of maximizing production or maximizing profit. in their place is the reality of multiple objectives, often defined in terms of “profit (or productive surplus), growth (quantitative or qualitative), survival, and human and social responsibilities” in his chapter 7 entitled “non-waste technology” (pages 87-113), royston described many examples from many countries where chemically-related industrial companies, had already (as of 1979) begun using “pollution prevention” or “non-waste technology” strategies to simultaneously reduce or eliminate pollution while simultaneously saving money, energy, reduce waste and/ or make positive profits. examples included 3m at multiple locations, union carbide at a ferro-alloy plant in west virginia, dow chemical at midland michigan, dow corning at hemlock michigan, a u.s. goldkist poultry plant, kamchai iamsuri rice millers in thailand, several scottish whiskey distilleries, an ahlstrom pulp and paper plant in varkaus finland, a great lakes paper plant, a westvaco paper plant, a french dying process, a georgia pacific plant in bellingham washington that produced 190 proof ethanol, a shell canada refinery process for utilizing refinery sludge, a mobil oil refinery in england wherein waste heat from the refinery was used to grow hothouse tomatoes, and many, many more. an “index of non-waste technology” at the end of royston’s book documented 215 such already existing “non-waste technology” projects in many countries. part iii of royston’s book, “why technocrats fail” addressed the reasons for the failures of the “command and control” legal/regulatory approaches to pollution control. legally inspired “command and control” approaches were common, especially in the us, in the 1970s. he stated (chapter 8, page 117) “what we have seen so far is that pollution control as a whole and particularly its costs form an extremely complex issue, involving as it does values, social aspirations, and the total system in which individuals and institutions are embedded….given the complex nature of the problem of pollution control, one would not expect solutions to it to be unitary.” later in the same paragraph, royston states “such a solution requires a system view of products, wastes, and natural resources so that even a pollutant is seen to be a potential raw material. as was shown in chapter 2 this systems view includes links and feedback loops from the outputs of the development process to the inputs…. given this complex problem, one might ask whether government legislation reflects anywhere the intricacy of this highly sensitive system with its particularly effective negative feed-back loops? unfortunately, the answer is, except in one or two notable instances that it does not.” royston then went on to analyze in some depth the failures of “command and control” legally-based approaches based on the political/legal imposition of abstract “legal standards” that ignore the great importance and effects of the real-world complexity and evolution, and the failure to take local circumstances into account.27 royston stated (page 121) that “the difference between the centralized legalistic tradition based on standards and a more decentralized pragmatic approach based on case-by-case examination typifies the extremes which are to be found. in between there is a whole series of systems based on regional administrations, which enable individual states, provinces, or regions to set their own standards within the overall frame law. given what has been said so far in this book, it might be supposed that national governments faced with the complex problem of pollution control would respond by trying to match pollution standards to local environmental conditions, by integrating pollution within the environmental system and by matching technology to economic factors. but that is not the case.” in chapter 9, royston argued that “the benefits of pollution control are considerable,” and provided many examples. in part iv, chapter 10, royston argued for an “integrated approach.” “the most effective, harmonious, and economical approach to pollution prevention is one which works through the whole environmental system, using an integrated systems approach,” that addressed “technological, economic, physical, cultural, social, and political aspects”. first, royston asserted that “from the technological point of view the solution to the environmental problem lies in the application of non-waste technology to pollution problems. non-waste technology is a subsystem which integrates inputs and outputs, resources, product and waste.” royston then turned the economic aspects of a systems approach, saying “the prerequisites of a successful strategy are…the inter27 this author has long planned and hopes to soon begin writing a series of legally oriented articles and/or books about “dr. murphy’s corollary: law is mostly a bunch of linear approximations of a non-linear world” 29early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s nalization of all environmental damage caused by any party in the economics of a particular operation, and … the provision of economic incentives to encourage the clean-up of the environment and to create the economic benefits which result from a clean-up operation.” in his chapter 11, royston detailed “action programmes for the community, for government, and for industry,” whose details will be bypassed in this paper. 7. the widening commercialization of pollution prevention strategies during the 1980s subsequent to publication the un/ece book in 1978, and the publication of pollution prevention pays in 1979, several of 3m’s representatives, professor royston, and others engaged in a sustained campaign of writing and speaking about pollution prevention strategies. in 1980 royston published an article in the harvard business review (royston 1980, ref 72). the article cited many examples from europe and the us wherein corporations were already commercializing “pollution prevention” strategies, and as a result simultaneously attaining profits and growth. royston (and 3m representatives) spoke at more international and regional technical conferences on pollution prevention strategies. a book of papers from a 1982 regional conference in winston-salem north carolina (huisingh and bailey, 1982, ref 44) contained contributions from many corporations that were already implementing pollution prevention strategies in their real-world businesses. a listing of authors and titles from those papers is attached in appendix ii. articles about pollution prevention strategies also began to appear in the mainstream consumer press. on january 4, 1981, william greider, an assistant managing editor at the washington post, published an article titled “the rise of corporate environmentalism” (greider 1981, ref 35). the article described royston’s book, and commented about other “environmentalists who do not usually get much fanfare. i am thinking, for instance, of boeing, exxon, dow chemical, minnesota mining, caterpillar tractor, shell, british petroleum, krupp, and phillips, to name a few.” the article described existing projects at hercules powder, goldkist poultry, haynes dye and finishing, and noted that corporations were discovering that “complying with federal standards on pollution produced a startling result for them. it increased their profits.” a 1984 new york times article entitled “the recycling of chemical waste” (marcus 1984, ref 58) described successful projects to recycle chemical wastes at several companies, including allied corporation, du pont, monsanto, 3m, and dow chemical. but the article noted the tremendous variety of the problems being addressed and remarked that “decades will be needed to approach this goal.” the article quoted an arthur d. little consultant as saying, “we end up with many examples – successes in smaller and smaller packages – that are not transferable to other wastes.” bob bonchek, a director of environmental affairs at du pont, remarked that “each technique requires great imagination and persistence, and none is a panacea.” by the 1980s, at least some major segments of the chemical industries were considering waste/pollution issues as a routine part of their business, research, and/or culture. this author’ recent article titled “early industrial roots of green chemistry…” recounted the genuine28 and previously untold story of how the bhc ibuprofen process began and was developed and commercialized (starting in 1984) (see murphy 2018). this author recalled that “one thing i was told very soon after my arrival at celanese, in no uncertain terms, by several veterans, was that any project or process that i proposed to work on that generated significant quantities of waste products, especially inorganic salts, would have a very large strike against it. that strong internal prejudice against processes that produced significant amounts of wastes was already very much a part of celanese culture the day i arrived there in january 1983.” independent industrial efforts were going on internationally. for example, the “responsible care®” initiatives in the canadian chemical industry were formalized in 1985, though the roots went significantly earlier (see belanger et. al., 2009, ref 15, and a wikipedia article on “responsible care”). responsible care® “is now a global, voluntary initiative developed autonomously by the chemical industry for the chemical industry. it runs in 67 countries whose combined chemical industries account for nearly 90% of global chemical production. 96 of the 100 largest chemical producers in the world have adopted responsible care.” similar current initiatives are being carried out by the american chemistry council (2018, ref 1). as noted in the national academy’s tribute to joe ling, “by 1988, 34 states had established pollution prevention programs, and epa had published a national 28 a continuing series of highly incomplete (to the point of being almost false) narratives have long propagated in the academic literature about the origins of and motivations behind the bhc ibuprofen process invention, which won one of chemical engineering magazine’s kirkpatrick awards in 1993 and one of the first presidential green chemistry awards, in 1997. (see murphy 2018). 30 mark a. murphy policy and established the office of pollution prevention. in 1989, the american institute for pollution prevention was founded, sponsored by epa, with joe [ling] as its chairman. in 1990, congress passed the pollution prevention act, requiring that pollution prevention be considered the first phase of any environmental enhancement program.” and there had been even earlier efforts in the u.s. federal government. in september of 1986 the u.s. congress’s office of technology assessment published a long document entitled serious reduction of hazardous waste: for pollution prevention and industrial efficiency (u.s. office of technology assessment 1986, ref 83). participants in the preparation of the report included many representatives of major corporations, smaller corporations, major environmental groups, academia, ota and epa staff, and multiple state-based agencies involved in pollution control efforts. the foreword to the report noted the prior superfund clean-up efforts, but then stated “now congress is turning its attentions to preventing hazardous waste problems by cutting down on the generation of hazardous waste at its source through innovative engineering and management… but while everyone agrees in a philosophical sense that waste reduction is good, there is confusion about definitions and methods.” the report then went on to try to address such definitional and methodological issues and noted that “over 99 percent of federal and state environmental spending is devoted to controlling pollution after waste is generated. less than 1 percent is spent to reduce the generation of waste” and estimated that it costs 10 to 100 times more money to clean up toxic waste contamination than it would have cost to prevent the original releases into the environment. related activities had also progressed in europe. acs’s histor y of green chemistr y29 was recently amended to note that “the organization for economic co-operation and development (oecd), an international body of over 30 industrialized countries, held meetings through the 1980s addressing environmental concerns. they made a series of international recommendations which focused on a co-operative change in existing chemical processes and pollution prevention.” in 1983 the united nations founded a “world commission for environment and development” to prepare a report about long-term sustainable and environmentally friendly economic development, and in 1987 issued the “brundtland report”, see brundtland (1987, ref 18). similarly, linthorst (2010) noted that “during the 1985 meeting of the environment ministers of the 29 see https://www.acs.org/content/acs/en/greenchemistry/what-isgreen-chemistry/history-of-green-chemistry.html oecd countries, the focus was on three themes: economic development and the environment, pollution prevention and control, and environmental information and national reviews. between this meeting and 1990 several (oecd council acts) decisions, decisionsrecommendations and recommendations were formulated,” and referenced a comprehensive history of the oecd and environmental issues by long (2000, ref 55). the epa’s office of pollution prevention and toxics (oppt) was established in 1988 to pursue “pollution prevention” approaches. in 1989, stephan and atcheson of the epa (stephan, atcheson, 1989, ref 75) wrote about “the epa’s approach to pollution prevention.” they stated “the recent focus on pollution prevention as the ‘first choice’ for environmental protection by the environmental protection agency is very real, and it involves a true, operative, non-adversarial approach by the agency, perhaps a first for the epa in its 18-year history… it has become apparent to the congress that even strongly enforced end-of-the-tailpipe and top-of-the-stack discharge and vigorously regulated hazardous waste disposal alone will not solve all the environmental problems in the united states.” another early leader at the epa was dr. joseph breen, who was a chemist and manager at the epa for 20 years and played a major role in creating the “design for the environment,” and “green chemistry” programs at epa. after retirement from the epa in 1997, breen helped found and was the first director of the green chemistry institute that was founded in 1997, as an independent non-profit organization. breen passed in 1999, but the green chemistry institute continued and later joined the american chemical society in 2001. the industrial efforts were also getting more attention in the popular press. in march 1988 the journal of commerce ran an article by craig dunlop (dunlop 1988, ref 25) that reported that in 1986 dow implemented a formal program called “waste reduction always pays,” and reported waste reduction successes at its dalton georgia and freeport texas plants. at the dalton latex plant, workers installed scrubbers for gas emissions that recovered latex starting materials and cut “emissions by 90% while generating sufficient raw material to pay for the recovery process.” at freeport, a byproduct from the production of anti-freeze and airplane de-icer was being used as a feedstock to produce dry-cleaning fluid in louisiana, california, and west germany. a dow spokesman named delcambre was quoted as saying that “the industry’s mind-set is changing and waste reduction is becoming a top priority with virtually every u.s. chemical company.” a 1990 article in the baltimore evening sun (ferrier 1990, ref 30) reported that dows wrap program had reduced air emissions by 44% and https://www.acs.org/content/acs/en/greenchemistry/what-is-green-chemistry/history-of-green-chemistry.html https://www.acs.org/content/acs/en/greenchemistry/what-is-green-chemistry/history-of-green-chemistry.html 31early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s hazardous wastes by 25% and been awarded a 1989 gold medal award for international corporate environmental achievement by the world environmental center. the article also reported that that dow had spent $47 million on 47 projects in two years, and that the average payback period for a “wrap investment is only eight months.” similar early “green chemical” advances were also occurring at many smaller companies, though those efforts and results tended to get less or no publicity. one example was the development of copper-based wood preservatives used to pressure treat wood by chemical specialties inc. (csi – now viance). the csi “acq” (ammoniacal copper quarternary) wood preservatives replaced much of the prior uses of chromated copper arsenate wood preservatives and won a presidential green chemistry challenge award (in the designing greener chemicals category) in 2002. the story goes much earlier however and illustrates the inherently interdisciplinary nature of green chemical research, especially at small companies. the acq story was told to this author in a 2018 personal interview with dr. kevin archer, originally with csi, which later became viance. csi had an established business making and selling chromated copper arsenate wood preservatives, but regulatory pressures to remove the chromium and arsenic from wood preservatives began in the 1970s, especially in europe. the discovery work on the acq wood preservatives was done by david finlay and neil richardson of domtar inc. of canada (both now deceased, see u.s. patent no. 4,929,454 first filed feb 05, 1981, pct patent publication wo 82/03817, and richardson (1991, ref 70)). the patents and some early phase demonstration compositions were licensed to csi for commercial development in north america. alan richardson had begun his career as a professor of plant pathology at the university of canterbury in new zealand, and dr. kevin archer had received a ph.d. under richardson there, for studies of wood decay. both men had personal interests in making more environmentally friendly wood preservatives. preston moved briefly to michigan tech in the us, then to csi. in june of 1988 archer followed richardson to csi and both became involved in the several years of product development/testing required to develop the domtar lab compositions into viable and customer-acceptable commercial products. after conducting a series of three-year field tests, in 1992 csi introduced its first commercial product, which used ammonia as the amine part of the wood treating compositions, along with copper oxide and quarternary ammonium chloride salts. the new copper compositions cost four times as much as the prior chromated copper arsenate compositions and gave the treated wood a smell and blue color that customers disliked. sales were initially slow due to the high cost and color / smell issues, but regulatory pressures continued to build. in 1995 csi brought out a new version of the acq preservatives that replaced ammonia with ethanolamine and had a better smell and more desirable green color. but problems were also being encountered related to chloride corrosion of metal pieces in the wood (caused by the quarternary ammonium chloride salts). those problems were overcome by modifying the compositions to employ quarternary ammonium carbonates. significant commercial success finally resulted about 2002. preston and archer (both biologists by training) prepared the applications for the presidential green chemistry awards, but the 2002 presidential green chemistry award said nothing about the history of the development of the invention, or it’s inventors or developers. 8. the early 1990s – interest broadens in the late 1980s and early 1990s, interest in the ongoing “pollution prevention” approaches began to grow rapidly in the u.s. government and in academia. the pollution prevention act of 1990 was signed by president george herbert walker bush in october 1990. the history of the legal / statutory / regulatory development of the provisions of the pollution prevention act, and similar amendments to the clean air act, the clean water act, the emergency planning and community right to know act, the resource conservation and recovery act (rcra) and toxic substances control act (tsca) were reviewed by walzer and maynard in march 1993 (walzer 1993, ref 84). in 1991, professor barry m. trost of stanford university published an article in science entitled “the atom economy – a search for synthetic efficiency) (trost 1991, ref 82). trost was later awarded a presidential green chemistry award in 1997, for ‘‘the development of the concept of atom economy.’’ but the acs/ epa’s published commentary to prof. trost’s presidential green chemistry award also noted “when prof. trost’s first paper on atom economy appeared in the literature, the idea generally was not accepted by either academia or industry. many in industry, however, were practicing this concept without enunciating it.” (bolding added) in 1991, epa’s office of pollution prevention and toxics launched a model research grants program called “alternative synthetic pathways for pollution prevention”. it has also been reported in the literature (see sanderson 32 mark a. murphy 2011, ref 73) that in 1991 dr. paul anastas (who had been out of graduate school and employed at epa for just two years) coined the term “green chemistry”. also in 1991, two veterans of academia and/or the u.s. congress’s office of technology assessment, and non-governmental “pollution prevention” projects, published a book entitled “prosperity without pollution – the prevention strategy for industry and consumers” (hirschhorn and oldenburg 1991, ref 39). they argued that government should not be counted on, and was often part of environmental problems, because it often focused most of the country’s political and financial resources on new programs and mandatory “end-of-the-tailpipe” approaches, rather than endorse spending money on maintenance and preventative solutions. they argued that industry should take individual responsibility and focus on preventing, rather than cleaning up waste. in october 1991 the epa’s oppt issued a major report (pollution prevention 1991, ref 65. 197 pages plus appendices) that reported in considerable detail the status of pollution prevention efforts at a wide variety of entities of the u.s. federal government, the states, universities, and localities. on-going programs were detailed for a wide variety of corporate entities. in 1992, breen and dellarco of epa edited volume 508 of the acs symposium series entitled “pollution prevention in industrial processes; the role of process analytical chemistry”. the book documented and highlighted the already on-going industrial efforts to use analytical chemistry in the prevention of pollution that were the precursors of one of the later “principals of green chemistry,” i.e. “real time analysis for pollution control” (see discussion below). but the first paper of the book (also authored by breen and dellarco) had a more general theme and was entitled “pollution prevention – the new environmental ethic” (breen and dellarco 1992, ref 16). the abstract stated: “prosperity without pollution has become the fundamental environmental theme of the 1990s. or at least, the consideration of how we will achieve this economic and environmental imperative. the new paradigm pollution prevention will serve as the keystone of federal, state and local environmental policy. support for the new approach the new ethic is broad based and includes environmentalists, industrialists, lawmakers, academicians, government regulators and policy-makers, and the general public. the challenge is to switch from two decades of environmental policy based on pollution controls and government mandated regulations, to a future environmental policy based on pollution prevention, source reduction, recycling, and waste minimization. it will require a new social compact amongst environmental, industrial, and regulatory interests. the roles and contributions of the chemical engineer, synthetic organic and inorganic chemist, and the process analytical chemist will be integral to the full articulation and implementation of the new vision.” the 1992 breen article then went on to describe the considerable progress toward pollution prevention that had already been achieved by various trade associations, individual companies, state and local programs, and federal agencies. in reviewing company-based pollution prevention programs, breen and dellarco remarked in 1992 that: “some companies have programs which they are willing to share with the public and other companies whose efforts are considered internal and proprietary. the more accessible programs are usually with large multi-facility companies. they are engaged in a wide range of operations, from specialty chemicals to high technology electronics. some programs are well established with formal names and acronyms. others are newer and more informal. the earliest dates back to 1975, with some following in the early and mid-1980s and others initiated in the 1990s.” a few paragraphs later breen and dellarco remarked: “a major change in industrial perspective on the way business is to be done has taken place. most programs and activities are voluntary. the programs initiated by industry on pollution prevention are important because they raise expectations for future progress. if the successes are real and include financial gains, there is a legitimate expectation other firms will follow the leaders into this new era of environmental protection.” regarding status in academia, breen and dellarco remarked that “pollution prevention interests and coursework are newcomers to the campuses of the united states. historically, few faculty members had developed the relevant background to make it an important element in the environmental, chemical engineering or business curricula,” but commented that the level of interest was increasing. the article noted however that the american institute of chemical engineers (aiche) “aggressively encourages industry sponsorship of university research.” the article characterized the efforts of the american chemical society at that time as “modest,” and commented that “clearly contributions are needed from the synthetic organic and inorganic chemists to build more environmentally friendly molecules molecules designed for the environment, while still fulfilling their intended function and use.” also, in 1992, freeman, harten, springer, randall, curran, and stone of the pollution prevention research branch of epa in cincinnati ohio published a 49-page 33early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s paper in the journal of the air and waste management association (freeman et. al., 1992, ref 33) entitled “industrial waste prevention: a critical review.” the paper was initially begun as a critical review of the papers, articles, reports and books relating to “pollution prevention” from the prior four years. but the authors stopped collecting new papers “at 472 such sources, recognizing that our first conclusion was that there has been an awful lot written on the subject the last few years.” the first issue addressed in the freeman paper was terminology, noting that while “pollution prevention” was popular in the u.s. and in use at the epa, its table 1 also listed 35 other alternative terminologies that were being used in various places. the paper then addressed many benefits of pollution prevention techniques (which were being abbreviated as “p2”), including economic and cost advantages. the paper then went on to describe very many p2 activities that were already ongoing in 1992, including activities at several major u.s. federal agencies, legislative activities, epa, the office of technology assessment, the department of defense, the department of energy, and the post office. freeman et. al. also described many activities that were then ongoing at state and local agencies, noting that “before 1985 there was only one state law which dealt with any aspect of pollution prevention. six years later there are almost 50 laws dealing with some aspect of pollution prevention,” and that “as of april 1, 1991, over half of the states have passed pollution prevention laws.” they also documented a good deal of such activity going on internationally, and much already on-going activity in “industrial p2 programs.” as of 1991 epa had documented “the p2 programs for 24 major companies whose program, goals, and accomplishments are company-wide,” specifically mentioning already functioning programs at chevron, dow, general dynamics, ibm, and monsanto. the article then documented ongoing efforts by the chemical manufacturers association and its responsible care program. in a 1992 article entitled “pollution prevention methods in the surface coating industry” (randall (1992, ref 68), paul m. randall of epa’s risk reduction engineering laboratory in cincinnati reviewed then on-going efforts aimed at pollution prevention in the paints and coatings industry. randall remarked that “in response to the environmental and economic crisis, the surface coating industry is re-examining the production, application, and disposal of paints to reduce vocs to meet environmental regulations and for coating manufacturers to optimize processes to reduce costs and increase profits.” randall then went on to discuss many aspects of those efforts. obviously, by 1992, many organizations and people from many disciplines and many countries (especially industrial chemists and engineers) were already working on and had already made very significant real-world progress in “pollution prevention.” interest in the environmental / chemical waste issues also began to increase in the academic chemistry fields. in december 1992, professor roger sheldon, a long-time veteran of the european chemical industry who had moved to academics in 1991, published his seminal paper “organic synthesis – past, present, and future” in the industry trade journal chemistry & industry. sheldon’s article reviewed the history and evolution of organic chemistry and its problems with waste generation. sheldon also reviewed the largely separate industrial progress and evolution on the waste issues toward better “e-factors,” via the use of catalysis. professor sheldon identified (sheldon, 1992, ref 74, page 904) an industry segmentation of the ecological performance of the existing industrial processes: “the seriousness of the problem is readily appreciated by considering the amount of waste produced per kilogramme of product – the ‘e factor’ in various segments of the chemical industry (see table 1).” in 1991, few in academia had recognized that environmental performance in the oil refining and commodity chemicals industry segments (where catalysis had been in common use) was so dramatically better than in the fine chemical and pharmaceutical industries (where the use of traditional synthetic organic chemistry was dominant and use of catalysis was uncommon). sheldon exemplified the progress on the waste generation in the commodity chemical industry with a discussion of the modern and highly atom economical industrial commercial synthesis of ethylene oxide by catalytic air oxidation of ethylene, the industrial synthesis of acetic acid by methanol carbonylation (that had been invented at monsanto in 196630) and “light at the end of the tunnel” 30 see paulik, f.e., hershman, a, know, w.r. , and roth, j.f., u.s. patent 3,769,329 issued october 30, 1973, assigned to monsanto. murphy table 1. the e factor. industry segment product tonnage kg byproduct / kg product oil refining 106-108 ca. 0.1 bulk chemicals 104-106 <1 5 fine chemicals 102-104 5 >50 pharmaceuticals 10-103 25 >100 (from sheldon, 1992). 34 mark a. murphy bhc ibuprofen process31 which was commercialized at bishop texas in 1992, and had a very low e-factor for a fine chemical / pharmaceutical process. in january 1993 the clinton administration was inaugurated in the u.s. and the epa, nsf, and counsel for chemical research cooperated to initiate a special research grant program titled “environmentally benign chemical synthesis and processing program” (see anastas 1994, ref 2, page 18). in november 1994 acs published volume 577 of its symposium series (see anastas 1994) entitled “benign by design – alternative synthetic design for pollution prevention.” the book consisted of papers from a symposium sponsored by the acs division of environmental chemistry at the 206th acs national meeting in chicago in august 1993. chapter 1 of the book, authored by p.t. anastas of epa’s oppt, began with a brief description of the prior “pollution prevention” efforts, and mentioned in passing dow’s wrap program and 3m’s “3p” program, but it didn’t describe them any further or provide useful citations to those programs. the only other industrial inventions or programs included in the book were two papers from monsanto and one from dupont. the anastas (1994) article did describe the passage of the u.s. pollution prevention act of 1990 and noted that the statute mandated that epa “pursue pollution prevention in all its environmental protection initiatives.” somewhat later anastas characterized “early approaches to pollution prevention” as “housekeeping solutions” and/or “low-hanging fruit.” anastas then went on to describe some ideas about how synthetic organic chemists should go about designing environmentally friendly new molecules and/or new chemical processes. it made no mention of or reference to sheldon’s 1992 chemistry & industry article, or the history and/or technologies it described. the anastas (1994) article did not use the term “green chemistry”. an early public use of the term “green chemistry” occurred at the 208th acs national meeting in august 1994. papers from a symposium (organized by joseph breen and allan ford and sponsored by the acs division of environmental chemistry) were published in volume 626 of the acs symposium series, in 1996 (ref 6). the book was titled “green chemistry – designing for the environment,” and contained seventeen article / chapters authored by a variety of scientists from u.s. and foreign governments, industry, and academia from (2018) details several more commercial examples from the commodity chemicals industry that had nearly perfect e-factors. 31 see elango, v., murphy, m.a., smith, b.l., davenport k.g., mott, g.n., zey, e.g., moss, g.l.: ‘‘method for producing ibuprofen,’’ us patent 4,981,995, granted january 1, 1991, and murphy (2018). several countries. its preface said it described “the current research efforts and recent results of leaders in the field of green chemical syntheses and processes.” chapter 1 of that 1996 book, titled “green chemistry: an overview,” authored by anastas and williamson, began in its abstract with the statements that “green chemistry is an approach to the synthesis, processing, and use of chemicals that reduces risks to humans and the environment. many innovative chemistries have developed over the past several years that are effective, efficient, and more environmentally benign.” the first sentences of the article’s text stated that “over the past few years, the chemistry community has been mobilized to develop new chemistries that are less hazardous to human health and the environment. this new approach has received extensive attention (1-16) and goes by many names including green chemistry, environmentally benign chemistry, clean chemistry, atom economy and benign by design chemistry.” a bit later the article noted “simply stated, green chemistry is the use of chemistry techniques and methodologies that reduce or eliminate the use or generation of feedstocks, products, by-products, solvents, reagents, etc., that are hazardous to human health or the environment.” that definition was certainly broad and certainly encompassed many of the 20 prior years of “pollution prevention” efforts by others. the article then briefly described some of the prior “pollution prevention” efforts and the u.s. pollution prevention act of 1990. then the article commented that “there is no doubt that over the past 20 years, the chemistry community, and in particular, the chemical industry, has made extensive efforts to reduce the risk associated with the manufacture and use of various chemicals.” but then the article commented that “many different ways to accomplish pollution prevention have been demonstrated and include engineering solutions, inventory control and ‘housekeeping’ changes. approaches such as these are necessary and have been successful in preventing pollution, but they also are not green chemistry.” the authors seemed to be implying that “engineering solutions” weren’t “green chemistry,” a very questionable proposition given that the many prior “engineering solutions” had been developed and implemented in industry as solutions to “chemical” problems. the statement also seemed to ignore the large number of genuinely “chemical” pollution prevention inventions and/or solutions that had been invented, developed, and commercialized by industrial chemists over the prior 20 years, typically using multi-disciplinary approaches that integrated the chemistry and engineering together to produce the desired prevention of pollution. 35early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s the article then went on to discuss a handful of techniques, goals, and concepts of “green chemistry”, along with multiple examples of each of those techniques, goals, and concepts that that had already been explored by a variety of international academic, governmental, and/or industrial researchers. those techniques, goals, and concepts (which appear to have been precursors of the “principals of green chemistry” formally announced later in 1998) included “alternative feedstocks and starting materials,” “alternative synthetic transformations and alternative reagents,” “alternative reaction conditions,” “alternative products and target molecules,” “atom economy,” and “catalysis.” examples from each of these categories were cited from a variety of prior academic and industrial researchers and/ or reports in academic journals and even from several patents. this author remains unclear as to how the allegedly new “green chemistry” was or is different than the many prior research and/or “pollution prevention” efforts that had gone before, other than using a new terminology. in 1995-1996 the epa/acs “presidential green chemistry challenge awards” were created and generated a great deal of publicity, in academia and elsewhere. as epa / nsf grant money flowed into academia, academic interest in “green chemistry” started to increase dramatically. for example, in an august 1996 chemical and engineering news article (breslow 1996, ref 17), acs president ronald breslow described “the greening of chemistry,” and recounted that “several events make it clear that the chemical community, including our major chemical companies, has decided that we can and must be environmentally benign.” breslow described a visit to eastman chemical’s plant in kingsport tennessee where chemicals were already being manufactured cleanly from coal.32 breslow mentioned the efforts of the responsible care program of the chemical manufacturer’s association. breslow also described participating in a ceremony for the first presidential green chemistry challenge awards, and a first gordon conference on “environmentally benign organic synthesis.” breslow concluded that “although some thoughtful chemists have been concerned with these matters for a while, 1996 saw important firsts: the first green chemistry challenge awards and the first gordon conference devoted to this topic. there is no turning back.” in 1997 joseph breen retired from the epa and cofounded (with anastas) the non-profit green chemistry 32 see murphy (2018) and the original references cited therein for a brief discussion of the details of the chemistry of eastman chemical’s then new commercial (in 1983) and perfectly atom-economical process for producing acetic anhydride via catalytic carbonylation. institute that later (in 2000) merged into the american chemical society. tragically, joseph breen died in 1999 of pancreatic cancer. in 1998, anastas and warner’s now famous book, “green chemistry: theory and practice” (ref 8) was published, with 10 chapters. this author will now comment on some of those chapters, which began with some bits of history, then proceeded to abstractly describe at some length a variety of theories about “green chemistry,” and then finally arrived at “practice” and/or examples in chapter 9. introductory chapter 1 briefly addressed some bits of the early history of the chemical industry and its historical problems with waste generation, dumping, and pollution, as well as the rise of the environmental movement and its negative reactions to the pollution. chapter 1 then briefly mentions the “command and control” regulatory approach of many of the environmental statutes of the 1970s. chapter 1 briefly mentioned the u.s. pollution prevention act of 1990, but says almost nothing about similar activities in the rest of the world, or the many “non-waste technology” and “pollution prevention” efforts that had preceded the u.s. 1990 act. it did however remark on page 8 that “green chemistry 6,7,8 which is discussed throughout this book, is a particular type of pollution prevention.” on page 9 the article remarked that “historically, synthetic chemists, those who design new chemicals and their manufacturing processes, have not been particularly environmentally conscious.” while that statement may have reasonably described the history of academic synthetic organic chemistry, as seen above it was not a complete description of the work of the many industrial chemists in the oil refining, commodity chemical, and consumer products and some other chemically based industries in the twenty years preceding the book. chapter 2 of the anastas / warner 1998 book began by redefining “green chemistry” as compared to the prior anastas publications. the first sentence of chapter 2 did remark that “green chemistry environmentally benign chemical synthesis, alternative synthetic pathways for pollution prevention, benign by design; these phrases all essentially describe the same concept.” this author agrees with that statement, and that “green chemistry” clearly was and still is “a particular type of pollution prevention.” as described above, many examples of chemically oriented “pollution prevention” products and processes had been invented, developed, and commercialized in industry for more than twenty years before 1998. this author disagrees with the second sentence of chapter 2; “green chemistry is the utilization of a set 36 mark a. murphy of principles…” the prior anastas 1996 definition had stated that “green chemistry is the use of chemistry techniques and methodologies that reduce or eliminate the use or generation of [things] that are hazardous to human health or the environment.” many such “techniques and methodologies” had been in regular and repeated use for twenty prior years, but their many (mostly) industrial users didn’t consider those already well-known techniques to be new and abstract “principals.”33 chapter 3 of the 1998 anastas / warner book, titled “tools of green chemistry” abstractly expounded on six such “principals”, i.e., “alternative feedstocks / starting materials,” “alternative reagents,” “alternative solvents,” “alternative product / target molecules,” “process analytical chemistry,” and “alternative catalysts.” as seen above and below, chemists had been inventing, developing, and commercially using these “alternative tools” for decades, but only one of them, the frequent prior uses of catalysis in industry, was explicitly acknowledged in the book. chapter 4, described at abstract length the twelve now famous “principals of green chemistry,” but did not discuss examples or cite the work of the many prior industrial inventors. the following chapters 5-8 were written in similar abstract, theoretical, “professorial” styles. only in chapter 9 did the book reach or discuss anything resembling “practice.” a few specific examples of the prior work of others were described, but only publications from academic journals, or from the epa / oppt were cited. there were no citations at all to patents or chemical trade journals. 9. the “1990s green chemistry” narrative develops during the clinton administration, the events at the epa described above became the source of what this article terms “the 1990’s green chemistry narrative,” namely that “green chemistry was conceived and developed at the epa in the 1990s”. that “1990s green chemistry narrative” has since been repeated many, many times in the academic literature and taught as fact to at least hundreds of thousands of students. this section will examine the origins, development, and validity of that narrative. that “1990’s green chemistry narrative” was clearly stated in anastas and beach’s 2009 paper entitled 33 this author (and many of his colleagues) were some of those many prior “users” at the time. “changing the course of chemistry” (see anastas and beach 2009, ref 12). the book was published just as anastas was moving from yale back to the epa. the anastas / beach paper from the book was titled “changing the course of chemistry” and was mainly focused on changing the way chemistry is taught at universities. however, on page three a single paragraph / section of the 2009 article was entitled “introduction of green chemistry as a field.” that paragraph is reproduced below. “the idea of green chemistry was initially developed as a response to the pollution prevention act of 1990, which declared that u.s. national policy should eliminate pollution by improved design (including cost-effective changes in products, processes, use of raw materials, and recycling) instead of treatment and disposal. although the u.s. environmental protection agency (epa) is known as a regulatory agency, it moved away from the “command and control” or “end of pipe” approach in implementing what would eventually be called its “green chemistry” program. by 1991, the epa office of pollution prevention and toxics had launched a research grant program encouraging redesign of existing chemical products and processes to reduce impacts on human health and the environment. the epa in partnership with the u.s. national science foundation (nsf) then proceeded to fund basic research in green chemistry in the early 1990s. the introduction of the annual presidential green chemistry challenge awards in 1996 drew attention to both academic and industrial green chemistry success stories. the awards program and the technologies it highlights are now a cornerstone of the green chemistry educational curriculum. the mid-to-late 1990s saw an increase in the number of international meetings devoted to green chemistry, such as the gordon research conferences on green chemistry, and green chemistry networks developed in the united states, the united kingdom, spain, and italy. the 12 principles of green chemistry were published in 1998, providing the new field with a clear set of guidelines for further development (1). in 1999, the royal society of chemistry launched its journal green chemistry. in the last 10 years, national networks have proliferated, special issues devoted to green chemistry have appeared in major journals, and green chemistry concepts have continued to gain traction. a clear sign of this was provided by the citation for the 2005 nobel prize for chemistry awarded to chauvin, grubbs, and schrock, which commended their work as “a great step forward for green chemistry” (5).” (bolding added) the substance of that paragraph has been repeated and/or cited in the academic / educational literature, and popular press an enormous number of times in the last ten years. but there is a major problem with this paragraph, and especially its first sentence, i.e. “the idea 37early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s of green chemistry was initially developed as a response to the pollution prevention act of 1990…” it is arguably (though not literally) true that the words “green chemistry” were first used in the current context at the epa.34 it is also arguably true that the developments, “principals,” and new terminology that were adopted by the epa in the 1990s were at least an important factor in the beginnings of “green chemistry,” provided one defines “green chemistry” as an “academic field.” but if “green chemistry” is defined as the invention, development, and commercialization of practical real-world scientific solutions to real-world chemical / environmental /economic problems, green chemistry” was not invented or “developed” at the epa, or in academia. as we have seen above, many environmentally conscious compositions, and processes were purposefully conceived, invented, developed, and commercialized by many industrial inventors, in many countries, long before the 1990s. “green chemistry” (as a real-world r&d activity) was actually an evolutionary product of (and/or re-naming) of the broader set of “pollution prevention” concepts that had been used, developed and commercialized by many industrial inventors and companies as early as the mid-1970s.35 those on-going “pollution prevention” concepts were adopted, and intentionally supported and encouraged by the epa’s office of pollution prevention and toxics in the late 1980s. the new “green chemistry” terminology and “principals” were only popularized well after the clinton administration came to office in january 1993. the anastas / warner book, and it’s twelve “principals of green chemistry” have since been very widely praised in the governmental, academic, and educational literature for many years, see for example the references cited footnote 3. praise for the twelve “design principals of green chemistry” can also be currently found in multitudes of other prominent websites and public press documents, including the current website of the american chemical society36 which references the anastas / warner book, and comments that the list of twelve principals “outlines an early conception of what would make a greener chemical, process, or product.” anastas has been described many times in the popular press as “the 34 the words “green chemistry” were first literally used in a slightly different context by clive cathcart in a 1990 chemistry and industry article about environmental issues in the irish chemical industry, see cathcart 1990, ref 20). 35 a little noticed sentence in anastas and warner 2009, in section 1.2.5, is that “green chemistry, which is discussed throughout this book, is a particular type of pollution prevention.” 36 see https://www.acs.org/content/acs/en/greenchemistry/principles/12principles-of-green-chemistry.html father of green chemistry,” see for example the website of the american association for the advancement of science (limpinen 2010, ref 53), scientific american (kay 2012, ref 46, and laber-warren 2010, ref 51) and forbes magazine (wolfe 2012, ref 88). praise for anastas and warner’s 1998 book was not universal at the time however, and significant early criticism was leveled from a credible industrial perspective. in june 2000, trevor laird, the editor of the acs journal organic process research & development reviewed the paperback edition of anastas & warner’s book (see laird, 2000, ref 52). laird criticized the book in the following two paragraphs: “the objective appears to be to introduce green chemistry concepts to chemists or chemistry students, to try to influence the way they practice chemistry. the theory and principals expounded in the text are sound enough, and few chemists would disagree with the aim to reduce pollution by appropriate design of chemicals and particularly by the appropriate design of chemicals and particularly by the design of environmentally friendly processes. the “practice” section of the book is woefully inadequate however, reflecting the author’s lack of experience of industrial chemistry in the real world. for example, there is no real discussion of the importance for green chemistry of introducing convergence into a synthetic sequence to reduce the overall weight of starting materials, reagents, solvents etc., to produce a kilogram of end product.” this author agrees with laird that at the time “few chemists would disagree with the aim to reduce pollution by appropriate design of chemicals and particularly by the appropriate design of chemicals and particularly by the design of environmentally friendly processes.” as shown above, many industrial chemists and engineers in many companies and in many countries had been consciously and actively inventing, developing and commercializing environmentally friendly and commercially viable processes for decades prior to the 1990s. laird then criticized the view of the book that “solvents are always bad,” and mentioned the problems that can be generated by use of water as a solvent. laird then further commented as follows: “there is a naivety in the book that indicates that the authors are unaware of how industry has changed in the past few years. this is reflected in the reference list, there are 39 references, and 10 of these refer to papers in a publication from the office of pollution prevention and toxics. these references are mostly to u.s. based research and do not reflect work done in europe by, for example, the groups at york or delft, or to important work being carried out in industry (e.g. hoechst) which has been pubhttps://www.acs.org/content/acs/en/greenchemistry/principles/12-principles-of-green-chemistry.html https://www.acs.org/content/acs/en/greenchemistry/principles/12-principles-of-green-chemistry.html 38 mark a. murphy lished in the last year… this is an opportunity missed … and cannot be recommended.” the outokumpu copper smelting process mentioned above and commercialized in finland in 1949 was an example of early european efforts to invent and commercialize environmentally friendly chemical processes. the catalytic air oxidation of ethylene to ethylene oxide was invented in france in the 1930s and subsequently commercialized all over the world. another such example was the wacker process for oxidizing ethylene to acetaldehyde (as a step in a process for making acetic acid and eventually vinyl acetate) that was invented in germany in 1956 and first published in patent form in 1959. even if the objective was not expressly environmental at the time (see jira 2009, ref 45), the wacker process was perfectly atom economical in theory, extremely efficient in practice, and was carried out in water solvent in the presence of catalysts in 1956! as we have seen, many other such environmentally friendly inventions and processes appeared in the oil refining, commodity chemicals, and consumer products segments of international chemical industries throughout the 1970s and 1980s. furthermore, none of the twelve “principals of green chemistry” were actually new as of the early 1990s, and they were already in regular commercial use. 1. pollution prevention – prevention of waste / pollution was the explicit name and objective of the “pollution prevention” concepts and work that began at 3m and in europe in the mid-1970’s and spread widely during the 1980s. moreover, the first presidential green chemistry award, in 1996, to dow chemical company for the use of carbon dioxide to replace ozone depleting chlorofluorocarbons as blowing agents in polystyrene foam sheet manufacturing, was based on u.s. patent no. 5,250,577 to gary c. welsh (an engineer!). that patent application was filed august 2, 1989, before the passage of the pollution prevention act of 1990, and almost seven years before the first presidential green chemistry award. 2. atom economy earlier known good efficiency resulting in low waste production, many examples of excellent “atom economy” had been achieved by use of catalysis in the oil refining industry (as described above) and in the commodity chemicals industries (see sheldon (1992) and murphy (2018). notable examples were the highly atom economical air oxidation of ethylene to ethylene oxide over a heterogeneous silver catalyst by lefort (see u.s. patent no. 1,998,878 issued in april 1935 based on an original french patent application filed march 22, 1932) and the wacker air oxidation of ethylene to acetaldehyde using a homogeneous pd / cu / hcl catalyst in water solvent in germany in 1957 (see jira 2009, ref 45). the bhc ibuprofen process that was first published as a patent publication in 1988 was a highly atom economical three-step catalytic process for making a bulk pharmaceutical that replaced an original six-step process with many waste producing steps and poor atom economy with three highly atom economical catalytic steps whose only byproduct was acetic acid. 3. less hazardous chemical synthesis – as described above, as of 1991, replacement of hf as a catalyst for oil refinery alkylation reactions had long been a “holy grail” of research in the oil refinery industry. u.s. patent 5,284,990 to j.r. peterson and j.b. scott, assigned to stratco inc., filed july 16, 1992, describes an example of such safety-oriented industrial research, i.e. a method for converting a commercial refinery alkylation unit from hf to h2so4 as a catalyst in order to increase process safety. 4. designing safer chemicals – it had been routine practice in the pharmaceutical industry for decades prior to the 1990s to design and test pharmaceutical target molecules for low toxicity and increased safety. safety was also routinely considered in other parts of the industry whenever new products and processes were introduced. 3m, and the paints and coatings, and consumer products industry segments were routinely involved in many such successful efforts. 5. safer solvents – many industrial processes and products over decades have utilized the safest of solvents, water. the wacker process invented in the 1950s (for air oxidizing ethylene to make acetaldehyde) used water as a solvent, see jiri 2009 and eckert (2012, ref 26). furthermore, there were many successful adaptations of existing processes for applying adhesives in aqueous solution to substrates in in the 1970s and 1980s at companies like 3m. successful switches toward water as a solvent for paints and coatings occurred at many companies in the 1980s. 6. design for energy efficiency – design for energy efficiency was a very common engineering approach in the chemical industry for decades before the 1990’s. the installation of co-generation units to reclaim low grade waste heat from chemical plants / refineries was common during the 1980s. many processes in the oil and commodity chemicals industry were intentionally solvent-less, to avoid the energy 39early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s and equipment costs associated with separating desired products from solvents and/or recycling the solvents (usually by distillation). many catalytic processes were carried out in the vapor phase over heterogeneous catalysts and avoided the use or recycle of liquid organic solvents altogether. some homogeneous processes in the commodity chemical industry used the product as “solvent”, and thus avoided the energy (and economic) penalties associated with use of solvents. examples include methanol carbonylation to make acetic acid, and olefin hydroformylation to make aldehydes, both of which processes date back to the 1970s, see murphy 2018. 7. use of renewable feedstocks – many chemical products were made from renewable resources before world war ii (natural rubber and cellulose acetate37 for example) but were later supplanted after world war ii by alternative products that could be produced much more economically (and sometimes with lower waste and energy usage) via petrochemical processes. nevertheless, the oil and commodity chemicals companies regularly conducted research projects to evaluate whether natural feedstocks could potentially compete. to cite one example known to this author, at the time of the invention of the bhc ibuprofen process (19841986), celanese had a small biotech research group in their corpus christi texas laboratories evaluating bio-tech processes for making commodity products such as acetic acid and 1,4-butanediol. those efforts proved futile however (primarily because of the non-competitive costs of isolating those compounds from dilute aqueous solutions). the biotechnologists involved were spun out of celanese and into a startup company “celgene,” which has since developed into a major pharmaceutical company. 8. reduce derivatives – use of protecting groups and/ or derivatives has been very uncommon in the oil refining, commodity chemical, and consumer products industries at any point in time, because doing so is both expensive and un-desirable. use of protecting groups is a creature of traditional poorly specific organic synthetic methods and/or multi-step pharmaceutical synthesis, and even then, is (as a matter of common sense) used only when necessary. 9. catalysis – heterogeneous catalysis was invented, developed and extensively used in very many com37 cellulose acetate was first synthesized in 1865 and was first commercialized about 1910 by camile and henri dreyfus, for producing motion picture films and for coating fabrics used to make aircraft wings and fusilages in those times. see https://en.wikipedia.org/wiki/cellulose_acetate mercial applications in the oil refining and commodity chemical industries after world war ii. as more selective homogeneous catalysts were invented (mostly in industry in the 1960s-1980s), their commercial use also became common in the commodity chemical industry. major examples include the wacker process for air oxidation of ethylene to acetaldehyde, olefin hydroformylation to produce aldehydes, methanol carbonylation to produce acetic acid, methyl acetate carbonylation to produce acetic anhydride, and the knowles/monsanto’s asymmetric synthesis of l-dopa via asymmetric hydrogenation.38 10. design for degradation – most organic small / soluble molecules are biodegradable to some degree, but many petrochemically derived polymers (such as polyethylene, polypropylene, polystyrene, nylons, polyesters, etc.) are not adequately biodegradable. nevertheless, other petrochemically based biodegradable polymers had been in widespread commercial use for many decades, such as polyacrylic acids, polyacetals, derivatized celluloses, poly-vinyl acetate, and poly-vinyl alcohol. moreover, beginning in the 1980s, there were many efforts to develop chemical depolymerizations of some of the non-bio-degradable polymers back to their recyclable monomers, such as polyesters, nylons, and polystyrene. 11. pollution prevention – (originally termed “analytical methodologies need to be further developed to allow for real-time, in-process monitoring and control prior to the formation of hazardous substances”). real-time monitoring and control of chemical processes had been used in industry for decades prior to the 1990s. the use of such process monitoring for pollution prevention was the principal focus of breen and delarco’s 1992 acs symposium series volume 508. papers from monsanto (ford et, al. 1992 ref 32), 3m (eldridge et. al., 1992, ref 27), du pont (fleming et. al. 1992, ref 31), dow chemical (henslee et. al. 1992, ref 37), amoco (baughman 1992, ref 14) and microsensor systems inc. (wohltgen et. al. 1992, ref 86) all described various problems and solutions for on-line analysis and control of real-world chemical processes in connection 38 see “profile of william s. knowles, proceedings of the national academy of sciences, november 22, 2005, 102 (47) 16913-16915; https://doi. org/10.1073/pnas.0507546102 . it is worth noting that one of knowles early projects at monsanto was a chemical synthesis of vanillin, which was superseded commercially after lignin was identified as a source of vanillin, which was a precursor in the catalytic asymmetric synthesis of l-dopa. see also u.s. patent no. 4,005,127 to knowles, w.s., sabacky, m.j., and vineyard, b.d., assigned to monsanto company, first filed march 08, 1971 and granted january 25, 1977. https://en.wikipedia.org/wiki/cellulose_acetate https://en.wikipedia.org/wiki/cellulose_acetate https://doi.org/10.1073/pnas.0507546102 https://doi.org/10.1073/pnas.0507546102 40 mark a. murphy with pollution prevention efforts. furthermore, several additional papers were published by academic authors from the center for process analytical chemistry at the university of washington, which had been established in 1984 as a consortium of over 46 corporate sponsors and four federal agency and national laboratories sponsors, to address multidisciplinary challenges in process analysis and control through fundamental and directed academic research (see http://www.apl.washington.edu/project/project.php?id=cpac). clearly, process analysis and control research for pollution prevention was well established long before the 1990s. 12. safer chemistry for accident prevention – as already described, by the early 1990s, replacement of hf for alkylation catalysis had already been a “holy grail” of refinery research for many years, and a switch from hf to h2so4 had already begun in some commercial refineries. furthermore, many industrial scientists and engineers had previously utilized various combinations of those already well known “principals” to make environmentally friendly real-world processes. the commercialized bhc ibuprofen process directly exemplified six of the twelve “principals of green chemistry” (i.e. prevention of waste rather than treatment or cleanup, atom economy, minimization of solvents, energy efficiency, avoidance of protecting groups, and catalysis). two more of the “principals of green chemistry” had been utilized by the inventors of ibuprofen as a prescription drug at boots, (i.e. designing safer chemicals and designing for degradation). two of the twelve “principals of green chemistry”, (i.e. use of renewable feedstocks and real time analysis for pollution prevention) were of little relevance to that particular problem. this author’s conception of a generic synthetic scheme for “profen” drugs (more specifically including ibuprofen) in 1984 was later developed by an interdisciplinary team and commercialized in 1992. sheldon (in 1992) speculated (without having communicated with this author or his team-mates) that that the bhc process had been the result of a “catalytic retrosynthetic analysis.” he was very close to right, see murphy 2018. at the time of conception in 1984 this author viewed the bhc process idea(s) (generated via a retrosynthetic analysis using catalytic reactions) as a set of promising potential outcomes that could result from a combination of known techniques selected from a much larger set of known techniques and/or “tools” well known to both industrial and academic chemists and engineers at the time. at the time of conception that generic set of ideas seemed to have the potential to give good “quality” (i.e. unexpectedly good potential outcomes), but it was more than a little uncertain and unpredictable at the time of conception. fortunately the choices narrowed rapidly as a wide variety of facts and information were gathered and then (successful) experimentation and development began and progressed. empirical facts and information provided most of the “guidance”, not any “principal” that may have been unconsciously involved earlier. viewed now retroactively, should “catalytic retrosynthetic analysis” now be declared to be another new green chemical “principal”? this “chemist turned law yer” could easily and honestly argue many sides of such questions now, but certainly didn’t consider such questions at the time, or for years afterwards. this author also agrees with laird’s comments (in 2000) that “the ‘practice’ section of the book is woefully inadequate however, reflecting the author’s lack of experience of industrial chemistry in the real world,” and “there is a naivety in the book that indicates that the authors are unaware of how industry has changed in the past few years.” there is also a similar naivety in the anastas / beach statement in 2009 that the twelve “principals” provided “the new field with a clear set of guidelines for further development.” if the “new field” is defined to be academic research designed to produce academic papers, and/or for teaching purposes, then perhaps the “guidance” provided by the “principals” have had value, a question this author will leave to academics. in academic chemistry, the primary customers are other academic chemists. but if the “field” of “green chemistry” is the realworld conception, invention, development, and commercialization of new real-world products and processes to address the real-world needs of people and ecological problems, then the “principals” were and still are woefully narrow, theoretical, and inadequate. the “principals” had little or nothing to say about the vast and inherently inter-disciplinary nature of real-world industrial chemical processes, and the economic, business, and customer facets of real-world chemical research, or the tremendous relevance and importance of engineering, biolog y, competitor technolog y, economics and business positions, customer preferences, and/or or the legal/regulatory issues. few of those multi-disciplinary issues were addressed by the twelve “principals” but must be addressed to bring a new and/or improved chemical product or process to the real-world markets. the attendees of the 1976 ece seminar understood that! furthermore, experienced and competent industrial chemists and engineers are typically employed and paid to be predominantly focused on products and processes http://www.apl.washington.edu/project/project.php?id=cpac http://www.apl.washington.edu/project/project.php?id=cpac 41early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s that are relevant to that company’s business interests, not to pursue abstract “principals”. a real-world industrial chemist ultimately has a wide variety of customers to satisfy, including chemical, engineering, and/or biological peers, business managers, regulators, and ultimately customers who will voluntarily buy and pay for the product, which certainly encourages consideration of many broader perspectives when planning r&d work. that product / process focus provides far more real world “guidance” to an industrial chemist than any of the twelve abstract “principals”! one of the keys to this author’s 1984 conception of the bhc ibuprofen process was an unexpected encounter with prof. john stille’s comment at a conference that identified ibuprofen as a potentially commercially viable product molecule. as this author commented regarding the initiation of experimental work for the bhc ibuprofen process, “it is important to note that in a real-world industrial laboratory, as compared to an academic setting, even this exploratory work would very likely not have been supported at all without an identifiable commercial target and/or objective.” see murphy 2018. this author also seconds another of laird’s complaints about the anastas and warner book, that the “naivety” “is reflected in the reference list.” indeed! the anastas and warner book all but ignored the large amount of work (some of which is documented above) that had already been carried out internationally, and especially in industry. while the anastas / warner book, chapter 9 (“examples of green chemistry”), refers to multiple academic authors, it doesn’t mention the names any industrial inventors, or reference their original publications in trade journals and/ or patents. the anastas / warner book only rarely mentions even the names of companies from the very few industrial examples it did cite. from a more current perspective, close examination of the published summaries of the epa / acs’s presidential green chemistry awards, from their beginning in 1996 up to the present time, shows that while the names of academic principal investigators always get acknowledged in the award descriptions, none of the names of industrial inventors, or their “publications” are ever disclosed or referenced. it is very hard to understand or justify this rather glaring omission, especially since many at the epa (breen and freeman et. al.) and at acs (such as breslow) had been very clearly aware of the many “pollution prevention” efforts and inventions that had occurred in worldwide industry in the decades prior to the 1990s. from an even broader and more current perspective, examination of the over 25 years of international academic literature related to “green chemistry” shows that while the citation of academic authors in academic “green chemical” journals is frequent, it is rare that the names of industrial inventors, or their publications (such as in patents or trade journals) get a mention, let alone a proper reference. this author could cite many examples, but instead challenges the readers to investigate this point on their own and make up their own minds. how can this widespread failure of academic or governmental “green” authors to cite the work, patents, and names of much earlier real-world industrial “green” inventors possibly be explained, much less justified?? one last point. linthorst (2010) and anastas (2012) presented graphs of the frequency of use of the term “green chemistry” over time to justify the contention that “green chemistry” began in the 1990s. those graphs would have looked very differently if the term “pollution prevention” had been included among the search terms used. since epa’s office of pollution prevention and toxics included the words “pollution prevention” in its very name, it is not easy to understand why those words were not included in the search terms used! 10. the “1990s green chemistry” narrative – a “soviet-harvard illusion” the contention that “green chemistry originated in the 1990s at the epa” is an example of an oversimplified and/or deceptive “narrative.” wall street trader turned philosopher nassim nicholas taleb has recently had much to say against reliance on such narratives, in a series of widely acclaimed and best-selling books, the best known of which are “the black swan – the impact of the highly improbable” (taleb 2007, 2010, ref 78) and “antifragile – things that gain from disorder” (taleb 2012, ref 79). a major theme of taleb’s books is how we, especially if we consider ourselves “experts”, focus too much on the things we do know, and often deceive ourselves and others into ignoring the very many things we don’t and can’t know, and the extremely important role of those unexpected and unpredictable events in human, economic and even scientific affairs. in chapter 6 of “the black swan”, taleb discussed one of the ways by which we deceive ourselves, “the narrative fallacy.” taleb explains that “we like stories, we like to summarize, and we like to simplify, i.e., to reduce the dimension of matters… the fallacy is associated with our vulnerability to overinterpretation and our predilection for compact stories over raw truths. it severely distorts our mental representation of the world; it is particularly acute when it comes to the rare event.”39 39 it is disheartening to realize that such “narratives” seem to be the heart and soul of our politics. 42 mark a. murphy the “1990s green chemistry” account of the beginnings of “green chemistry” is just such a narrative. the popularization of “green chemistry” in the u.s. government and in academia during the late 1990s and afterwards was certainly inspired by the actions at epa. but how to account for or justify the obvious and continuing academic / governmental blindness toward acknowledging the existence and importance of very many long prior real-world “green” activities in industry and/or in many other countries? application of a bit of “legal” thinking on such matters seems natural to this chemist / lawyer. unconscious blindness and/or honest ignorance about industrial work and realities can be understandable and forgivable in complex and unpredictable r&d situations. but knowing and/or willful refusal to either consider or cite industrial work or workers seems very troubling. taleb has described a possible explanation; “the soviet-harvard illusion – (lecturing birds on flying and believing that the lecture is the cause of the flying).” see taleb 2012, chapter 13. taleb also severely criticizes “top-down” central planning approaches (exemplified by the former soviet union, and which regularly originate in academia) wherein self-described “experts” rely far too much on highly incomplete knowledge and fallible human logic, and studiously ignore the role and importance of complex, unexpected, and unpredictable events. ta leb explains that the “soviet-har vard illusion” originates from a “class of causal illusions called epiphenomena.”40 expanding his bird metaphor, taleb writes that: “think of the following event: a collection of hieratic persons (from harvard or some such place) lecture birds on how to fly…. the bird flies. wonderful confirmation! they rush to the department of ornithology to write books, articles, and reports stating that the bird has obeyed them, an impeccable causal inference. the harvard department of ornithology is now indispensable for bird flying. it will get government research funds for its contribution… it also happens that birds write no such papers and books… so we never get their side of the story. meanwhile, the priests keep broadcasting theirs to the new generation of humans who are completely unaware of the conditions of the pre-harvard lecturing days…. nobody has any incentive to look at the number of birds that fly without such help from the great scientific establishment.” “so the illusion grows and grows, with government funding, tax dollars, and swelling (and self-feeding) bureaucracies in washington all devoted to helping birds fly better.” 40 see the wikipedia article “epiphenomenon” at https://en.wikipedia. org/wiki/epiphenomenon talab’s bird metaphor was a parody of some unfortunately general behaviors in governments and academia. but taleb’s bird parody very well describes the “1990s green chemistry narrative.” industrial chemical birds had been flying, in many shades of green, all over the world, at least as early as the mid-1970s. they published a few generic descriptions of their ideas, motivations, and philosophy scattered over a variety of multi-disciplinary venues. but they did not publish much about the technical details of their methods and inventions in the peer-reviewed academic journals that academic chemists typically read. as a result, the real-world accomplishments of those early industrial green birds were, and often continue to be ignored by many in the u.s. government and academics. when epa and its office of pollution prevention and toxics was founded in the late 1980s and began to encourage the already on-going industrial “pollution prevention” efforts, the progress continued and even accelerated. when the clinton administration’s epa changed the “pollution prevention” terminology to “green chemistry,” and government grant money began f lowing towards academia, the “academic field” of green chemistry and the “1990s green chemistry narrative” were quickly created. in short order the epa and too many “green chemistry” academics began to publish academic papers and then lecture both industry and new generations of university students about the “principals of green chemistry” they theorized had caused the “green chemistry” progress. the government funding, tax dollars, bureaucracies, and lectures have indeed swollen ever since.41 taleb has an alter-ego for the “soviet-harvard illusion” which he terms “naive rationalism” which is “thinking that the reasons for things are, by default, accessible to university buildings.”42 taleb contends that “naive rationalism” overestimates the necessity and importance of academic knowledge in human affairs, which remain highly unpredictable. taleb also accuses many academics and government officials of dramatically over-emphasizing the importance of academic theory in both scientific / technical research and in the resulting economic outcomes, by habitually thinking in terms the “bacon linear model” of r&d: academia → applied science and technology → practice taleb asserts there have been relatively few realworld examples of the “bacon linear model.” the devel41 see anastas 2012 ref 5, “fundamental changes to epa’s research enterprise: the path forward” 42 see taleb 2012 ref 78, glossary. https://en.wikipedia.org/wiki/epiphenomenon https://en.wikipedia.org/wiki/epiphenomenon 43early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s opment of atomic energy and/or nuclear weapons based on einstein’s relativity theories is however one well known example. there have also certainly been other important inventions that originated in academia, especially in academic biotechnology (such as the discovery of dna, the polymerase chain reaction, crispr, and immunology) that have gone on to spawn very important downstream applications and real-world practice. but taleb accuses many academics and government officials of largely ignoring and/or denigrating the uncodifiable, complex, iterative, intuitive, and experiencebased type of interdisciplinary knowledge and research that he asserts comes from “random tinkering.” but taleb’s “random tinkering” isn’t completely random. he illustrates “random tinkering” with the example of a real-world treasure hunter for shipwrecks, who conducts a high-risk but high-reward business. the treasure hunter uses the incomplete knowledge he has to assign grids to be searched by estimated probability of success and the probability of a high payoff. the treasure hunter then searches each high probability grid completely before moving on to another lower probability grid. such a strategy uses available prior (but incomplete) knowledge, but also considers the importance of uncertainty and unpredictability. such “random tinkering” strategies avoid searches with low probability of success and payoffs and focuses its effort in areas of high estimated probabilities of success and high potential payoffs (or at least clear relevance to existing businesses). surely readers can recognize that such a “random tinkering” approach can be highly relevant to both academic and real-world industrial r&d, and green chemistry as well! as louis pasteur once said, “chance favors the prepared mind.” taleb asserts that a great deal of real-world r&d and/or change / evolution in commercial / economic practice occurs via very complex, iterative, evolutionary processes similar to those represented by the schematics below: random tinkering (anti-fragile) → heuristics (technology) → practice and apprenticeship →… random tinkering (anti-fragile) → heuristics (technology) → practice and apprenticeship →… many variations of such complex evolutionary processes typically go on in parallel, individually addressing different local problems, products, or processes or subprocesses, but there is also some communication between the many scientists and engineers carrying out those semi-independent parallel r&d processes. formal educations and academic / scientific theories certainly play a significant role in these sorts of complex real-world iterative and evolutionary processes, but many other factors are also involved and often introduce not very predictable outcomes that can nevertheless be very important, technically, environmentally, and economically. what emerges as a holistic outcome from the interactions of many such complex parallel iterative and evolutionary processes and sub-processes is certainly non-linear, somewhat unpredictable, and potentially “chaotic”. the entire concept of causation becomes murky in view of the unpredictability of the holistic final outcomes produced by such vastly complex evolutionary processes.43 while the “academic field ” of green chemistry may have originated in the 1990s and/or from the abstract “principals of green chemistry” that were published in 1998, taleb’s “random tinkering” model of scientific / technical r&d is much more consistent with the much earlier evolution of real-world industrial green chemical inventions documented above, and much of the industrial r&d work that continues to this day. this author contends that real-world industrial “green chemistry” emerged as a holistic final outcome from an extremely varied and complex set of parallel evolutionary “random tinkering” sub-processes that began about the time of world war ii, and that evolutionary process accelerated in the 1970s (see also murphy 2018, murphy 2020). that overall evolutionary process was the product of very complex interactions of very many internal and external events, carried out by many human investigators from multiple disciplines and countries, who were individually driven by many different goals, motivations, influences and input factors, including customer / societal needs and desires, economics, the environment, the legal / statutory / regulatory pressures, as well as the constantly evolving state of the underlying sciences of chemistry, biology, and engineering, over decades. many of the resulting individual inventions were also the direct product of individual human creativity, thought, and logic, as aided by intercommunications between the investigators, as well as the constraints of the laws of nature, local circumstances, and elements of chance. soviet-harvard illusions and lectures could never even hope to reasonably account for or predict such vastly complex phenomena and evolutionary developments. there was a fairly recent challenge to epa’s claims for credit for the environmental outcomes produced by 43 see chamberlin (2009, ref 21), holland (2014, ref 40), and dennett (2017, ref 23). see also murphy (2018) and murphy (2020, ref 60) for thoughts about how w.edwards deming’s “pdca circles,” which are based on the scientific method, can be continuously iterated to incorporate both reductionist and holistic ideas and perspectives, to solve real-world problems. 44 mark a. murphy “green chemistry”.44 up to 2015, epa had been including in its internal epa performance metrics tracking system the credit for the international pollution savings reported by the winners of the presidential green chemistry challenge awards. the epa’s inspector general successfully challenged the epa claims to credit for those pollution reductions, on the primarily legalistic grounds that the pollution reductions reported by the award winners were “unverified” and therefore were not “transparent”45 and therefore should not be included in epa’s internal credits. but in its initial 2015 report46 the inspector general had also noted that it is “inappropriate for the epa to take credit for the results of activities performed by predominantly non-epa parties.” that causation-related objection seems even more valid given that many of the industrial pollution prevention evolutionary processes and results began long before the epa activities and programs had even begun. but as a counterpoint, the 2015 inspector general’s report also noted that the epa’s presidential green chemistry awards program’s budget for fiscal 2015 was “between $80,000 and $90,000,” but had “lacked presidential support” during a number of the prior years, though that support was finally renewed by the white house office of science and technology policy in july 2015. it is nevertheless disheartening to recognize that the epa’s inspector general had expended so much time, money, and bureaucracy in the name of “investigating” an obviously beneficial but also very small epa expenditure of $80,000-$90,000 a year, for public recognition of new green inventions (and some of the inventors) provided by the presidential green chemistry awards program, regardless of whether or not the epa actually caused the inventions being recognized. such seems to be the state of the underlying legal / bureaucratic culture at the epa… yet the “1990s green chemistry narrative” has widely propagated though much of the peer-reviewed scientific literature, university classrooms, and even the popular press over the past 20 years, see the references of footnote 3 for only a few of many examples. the “1990s green chemistry narrative” has also penetrated the academic social sciences (“science and 44 see the u.s. epa’s office of the inspector general’s report, 18-p-0222 dated july 20, 2018 entitled “epa completed oig recommendations for the presidential green chemistry challenge awards program lacks controls over use of unverified results”, available at https://www.epa. gov/office-inspector-general/report-epas-presidential-green-chemistrychallenge-awards-program-lacks 45 see the section below discussing the nature and importance of trade secrets in modern industrial practice. 46 epa inspector general’s report #15-p-0279, september 15, 2015, see https://www.epa.gov/sites/production/files/2015-09/ documents/20150915-15-p-0279.pdf technology studies”) and the business schools and their academic literature. see for example woodhouse and breyman (2005, ref 87) and howard-grenville et. al. (2017, ref 41). the howard-grenville paper was authored by three professors of business administration from major universities and two university chemistry education instructors. that administrative science quarterly paper was entitled “if chemist’s don’t do it, who is going to? occupational change and the emergence of green chemistry.” the abstract begins as follows; “we investigate the emergence and growth of “green chemistry” – an effort by chemists to encourage other chemists to reduce the health, safety, and environmental impacts of chemical products and processes – to explore how occupational members, absent external triggers for change, influence how their peers do their work.” (bolding added) not one of the authors has done any green chemical research. in the body of the article, the authors asserted that “green chemistry emerged in the 1990s when a small group of chemists began advocating new practices that would enable chemists in academia and industry to reduce the environmental, health, and safety impacts of their work”. the article also stated that “green chemistry… emerged as a grassroots effort by chemists to influence their peers to alter their work in accordance with the 12 principals of green chemistry listed in table 1.” these statements were a clear re-statement of the core of the “1990s green chemistry narrative”. the authors had begun by searching “peer-reviewed research publications that reported the science of green chemistry… with 10 keywords selected by chemists on our author team.” they identified 6,394 scientific publications that included the term “green chemistry” and/ or employed at least one of the “principals.” there is no mention of any search of chemical industry trade journals, or patents, at any point in time. as a result, howard-grenville et. al, like so many other academics before them, remained unaware of the real-world “pollution prevention” industrial efforts that had preceded the 1990’s by decades. if the authors had also searched patents, chemical trade journals, or even the consumer press, or included the key words “pollution prevention” in their search strategies, virtually all their conclusions would have needed to be dramatically different. they would have encountered the many technical, legal, economic, and cultural “external triggers for change” that did in fact drive the development of “pollution prevention,” and then later “green chemistry,” in worldwide industry. after their initial review of the academic literature, the authors informally interviewed 36 individual https://www.epa.gov/office-inspector-general/report-epas-presidential-green-chemistry-challenge-awards-program-lacks https://www.epa.gov/office-inspector-general/report-epas-presidential-green-chemistry-challenge-awards-program-lacks https://www.epa.gov/office-inspector-general/report-epas-presidential-green-chemistry-challenge-awards-program-lacks https://www.epa.gov/sites/production/files/2015-09/documents/20150915-15-p-0279.pdf https://www.epa.gov/sites/production/files/2015-09/documents/20150915-15-p-0279.pdf 45early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s but unidentified green chemists “recruited from professional networks of the chemists of our author team, who knew green chemistry advocates.” they noted that “our sampling approach was theoretical rather than representative.” this author was immediately reminded of eleuterio’s quotation of sherlock holmes (see eleuterio 1991 ref 29), who fictionally cautioned that “it is a capital mistake, my dear watson, to theorize before one has data. insensibly one begins to twist facts to suit theories instead of theories to suit the facts.” there were very long “naïvely rationalistic” discussions / interpretations of the interviews and interviewees that essentially presumed the reasons for the “emergence” of green chemistry was a strong function of three mental / occupational “frames” that the “green chemistry advocates” had presumably used during the “emergence” of green chemistry. they discussed a “normalizing frame” wherein “advocates presented green chemistry as consistent with mainstream chemistry, associating it with core norms around discovery, design, and optimization.” they discussed a “moralizing frame” that “presented green chemistry as an ethical imperative…emphasizing chemist’s opportunity to deliver social benefits.” lastly the authors described a “pragmatizing frame” “presenting green chemistry as a tool that could help chemists gain leverage on problems they encountered in their work.” there were discussions of conflicts between the “occupational frames” of the “green chemists.” none of that discussion contemplated the possibility that “green chemistry” had actually existed in the real-world long before any of the twelve “principals of green chemistry” were published, or any of the “green chemistry advocates” interviewed had become either green chemists or “advocates”. the authors did note that “green chemistry advocates still lament that many of their peers fail to align with the change effort” of the moralists, seemingly unaware how long environmental consciousness has been a standard part of industrial culture and practice in some industrial segments for so long. other than multiple references to the “12 principals of green chemistry” as motivation and/or “guidance” for the way that green chemists allegedly “think,” and then lecture their peers as to what to think, the article doesn’t contain a word about what chemists and engineers actually do in their green chemical technical work, or how they decide what to do. there were telling comments on the perspectives of some of the academic green chemists interviewed. there was a comment from an academic and alleged “early advocate” of green chemistry that the “core content of chemistry curricula is “what [a chemist] learned from their professor and they are passing on to their students”. another explained “this was something that could be taught in a chemistry class.” there was very little description of industrial perspectives on or about green chemistry, or the extremely complex experience / practice-based types of knowledge that come from industrial r&d and/or industrial inventors, or that industrial scientists and industrial engineers often use. there was however a telling comment from an unidentified industrial chemist who commented “there is an elitism particularly among the academic community. [chemists say] ‘we do basic research…we don’t do applied stuff,’ [and] green chemistry i guess is for those folks who can’t come up with better ideas.” there was no recognition of or mention of the many “external triggers for change” that drove the early real-world industrial evolution of green chemistry documented above. in this author’s experience in the 30+ years since becoming an inventor of one of the earlier commonly recognized “green chemical” inventions, and later a practicing chemical patent attorney, virtually everyone in industry has for decades now recognized that “greener is better.” almost everyone in in modern industry is motivated at one level or another to at least contemplate “greener” processes. but not nearly enough people (including many modern “green chemists”) really know what to do. virtue signaling about identity and good intent and/or motivations is a very poor substitute for knowing how to figure out what to do. this author’s prior papers passed along some of w. edward deming’s ideas about how to figure out what to do. educating students about how to think, or about ecological issues is a good thing. lecturing professional “peers” about what to think is quite another thing. from this author’s perspective, the paper of howard-granville et. al. (and too many academic green chemistry papers as well) is filled with a veritable bonfire of soviet – harvard illusions, delusions, lectures, and vanities, not to mention naïve rationalism. it is terrifying to think that such obvious orwellian group-think is not only propagating as dogma amongst many chemists, university faculties, and new chemistry students, but is likely even being lectured and propagated as fact and “inspiration” to new mba’s who will soon be making major decisions for the corporations of the world. 11. the importance of trade secrets and “unread” patents to green chemistry taleb’s books focus on unknown, unexpected and unpredictable events in our lives and society, and our 46 mark a. murphy tendency to ignore and/or underestimate their importance. as he notes in his prologue, “black swan logic makes what you don’t know far more relevant than what you do know.” taleb mentions a friend and writer (umberto eco) who maintains a large personal library, containing many “unread books,” which he places very high value on, because they represent to him the many things he does not know that can cause many phenomena, expected or unexpected. taleb asserts that “a library should contain as much of what you do not know as your financial means … allow you to put there.” self-styled “green chemists” in government and academia would do well to more thoroughly consider what they don’t know, especially about what goes on in real-world industry. far too many academic and governmental green chemists don’t know or understand much about real-world processes, products, and r&d, and their complexity and unexpected facets, in part because they don’t appreciate the importance of industrial trade secrets, and they don’t often read patents. many of the interdisciplinary technical and economic / business details of real-world industrial processes for making real-world products are very important to the final desired outcomes but are often withheld from public knowledge because information about them is held in the form of trade secrets. trade secrets “comprise formulas, practices, processes, designs, instruments, patterns, or compilations of information that have inherent economic value because they are not generally known or readily ascertainable by others, and which the owner takes reasonable measures to keep secret.”47 unlike patents, trade secret protections can last (at least in theory) as long as the information is kept secret. 3m was an early example of the use of trade secrets in a green chemical context. in the 1970s and 1980s 3m repeatedly publicly announced their intent to improve both their environmental and economic performance by means of generically described “pollution prevention” strategies. but 3m kept most of the hard-earned technical chemical and engineering details regarding their many consumer products and production processes secret, in order to maintain their advantage over their competitors. in this author’s 20+ years of experience as a chemical / pharmaceutical intellectual property attorney, most industrial companies behave similarly, and maintain most of the details of the engineering, production, customer, and economic aspects of their businesses as trade secrets. 47 see the wikipedia article “trade secret” at the link below for a good introductory discussion of trade secrets and trade secret law, and further references.” see https://en.wikipedia.org/wiki/trade_secret . many academics ignore the real-world importance of trade secrets, but their real-world value has recently become clearer in view of massive trade secret theft by malign foreign companies and countries. trade secret law was traditionally state-based law in the united states, but the economic espionage act of 1996 created potential u.s. federal criminal penalties for trade secret theft, and the defend trade secrets act of 2016 created a right for us companies to sue in u.s. federal courts for trade secret theft.48 real-world industrial inventors almost always sign confidentiality agreements and sign away their ownership rights to the future inventions they will make on the day they begin employment. scientific publications from industrial scientists and engineers are not often permitted by the businesses, and industrial inventors they are only rarely allowed to publish their work, theories, and inventions in academic peer-reviewed journals. when industrial inventors are permitted by their employers to publish technical details about their inventions, they almost always publish it first in the form of a patent application. in this author’s opinion academic green chemists would do very well to start reading patents. good “lay” introductions to patents and patent law can be found in several articles at wikipedia. patents, which can be granted in most countries in the world, give inventors of new and non-obvious inventions a legal right to prevent others from commercially using that patented invention for a limited time (usually 20 years), in return for publicly disclosing some technical details about the new inventions. in most countries of the world, a patent application must be filed before the technical details of the invention are published anywhere else, or the inventions or its products are offered for sale, or else the potential legal rights are forfeited (though the u.s. has a short and narrow exception). patents were explicitly contemplated in the u.s. constitution, and are codified in title 35 of the united state code. most of the text of a patent application document is legally rather than technically oriented, one reason most technical academics don’t understand or like to read patents. most of the text in the patent specifications has the predominant legal purpose of establishing (on paper) words that can be used in or in support of the patent’s claims, which are intended to define legally enforceable boundaries for legal patent rights, rather than to describe the scientific / technical heart of the inventions. patent applications are custom legal documents drafted by people having both legal and technical 48 see https://en.wikipedia.org/wiki/defend_trade_secrets_act https://en.wikipedia.org/wiki/trade_secret https://en.wikipedia.org/wiki/defend_trade_secrets_act 47early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s backgrounds, and are very expensive to draft, prosecute, and enforce against competitors. because of the considerable expense involved, few companies and/or inventors draft and prosecute patent applications unless they envision a very significant economic or strategic benefit from obtaining the legal patent rights. but there are also some legally required empirical scientific / technical disclosures in patent applications. the patent specification must describe the claimed inventions in enough detail to allow one of ordinary skill in the relevant technical arts to make and use the inventions. importantly, the patent examples are typically empirical / factual descriptions of the procedures followed and empirical results of actual experiments conducted and/or products made. in the u.s. the patent application must also disclose the best mode for practicing the invention known to the inventor at the time of filing the application (which is usually early in the r&d process). once a patent application has been filed in the u.s. (and/or in most foreign countries) the patent application is published as a patent publication 18 months later, then subsequently examined by patent examiners who decide if legal rights and boundaries to the claimed inventions are to be granted. chemical patents only rarely disclose scientific theories about how or why the chemistry works, which is one reason academic chemists often dislike reading patents. disclosure of scientific theories (which are of course mental states, not verifiable facts) is not legally required in a patent application and disclosing such theories could easily damage the inventors / patent owners and their legal and economic interests. including “theories” (or “principals”) in a patent could provide a patent examiner a “roadmap” for locating other prior publications disclosing similar theories, and then combine those 3d party theories as justification to reject the claims as obvious. theories could similarly provide a roadmap for a competitor to argue during litigation that the claims to the inventions were invalid for obviousness. competitors could also use a patentee’s theories to inspire and predict new competitor inventions. as a result, a competent patent attorney typically avoids including “theories” in a patent application, preferring to hold their inventor’s theories as trade secrets. very often, the attorneys will strongly argue against disclosing such theories, even in a later published scientific publication, for some of the same reasons. accordingly, publications by industrial inventors in academic journals are typically discouraged by the attorneys and/or business managers, for legal / business reasons. but academics should read patents because they are a good source of empirical information about new industrial inventions that the inventors and their business managers believe may have both technical and economic value. the academics can then potentially formulate, test, and publish scientific theories about those new inventions, something the industrial inventors are only rarely allowed to do. olefin metathesis appears to have been such a case. olefin metathesis was discovered serendipitously by eleuterio at du pont in 1956, by what appears to have been a “random tinkering” sort of process. some of eleuterio’s discoveries were patented, but others were held as trade secrets (see eleuterio 1991). chauvin, who was working in the french oil industry encountered the olefin metathesis reaction there and moved to a public institute in 1960. the olefin metathesis chemistry evolved rapidly and produced many practical applications in both the oil and later in the pharmaceutical industries. in 1971 chauvin publicly proposed a (now generally accepted) mechanism for the olefin metathesis reaction. chauvin was awarded a nobel prize in 2005 (along with robert h. grubbs and richard r. schrock for later developments). however, a question (and injustice) remains. if chauvin’s publication of a mechanistic theory about olefin metathesis was deserving of a nobel prize, why is it either just or fair that the actual discoverer / inventor’s name (eleuterio) is rarely if ever mentioned alongside those of chauvin, grubbs, and schrock?? eleuterio was philosophic about such things. he quoted francis crick as saying “i enjoyed every minute of it, the downs as well as the ups…the important thing is to be there when the picture is painted.” eleuterio also commented that “historians continue to wonder whether science drives technology or is it the other way around? in my judgement, a more relevant key question is how do the key variables which are involved in doing science and technology contribute to a synergistic relationship between scientific discovery and technological innovation?” despite any injustices, the many academics that became involved in further developing olefin metathesis (and other catalytic chemistries that were first discovered in industry) have certainly benefited from the industrial discoveries, most of which are first published in patent publication form. practicing industrial chemists can also benefit from interactions with academic chemists.49 voluntary interactions and collaborations 49 consider professor john stille’s unknowing contribution to this author’s thought process that identified ibuprofen as a potential viable commercial product target, which then led to the conception of the new carbonylation chemistry that was the most important of several keys that led to the invention and development of the bhc ibuprofen process, see murphy (2018). 48 mark a. murphy between industrial and academic chemists and engineers, and their multi-disciplinary teammates are highly desirable and deserve to be encouraged, but there is very little justification for soviet-harvard style lectures toward other professional researchers. lastly, even a few hours training in intellectual property law would tremendously benefit both academics and graduate students in the academic sciences and engineering, and greatly facilitate positive academic / industrial communications and interactions. in this author’s experience it is often possible to find ip / patent attorneys (that typically have both legal and technical backgrounds) who are willing to teach intellectual property short courses “pro-bono.” 12. the real-world origins of “green chemistry” “green chemistry” has been very often described in the academic literature as having begun in the 1990’s as a result of concepts and action at the u.s. epa, and/or in academia. if “green chemistry” is defined as an “academic field” designed to produce academic papers, and lectures for students, then that “1990s green chemistry narrative” description of the origins of green chemistry has some validity. but if “green chemistry” is defined to be “chemicals and chemical processes designed to reduce or eliminate negative environmental impacts,” then the real-world origins of green chemistry began decades earlier, mostly in industry. beginning about the time of world war ii the petrochemical industries began to grow rapidly, in terms of both product volume, value, and the variety of products produced, in response to increasing consumer demands. new processes for producing those new products proliferated. more than a few of those new products and processes were toxic, wasteful, and polluting, and did not consider long-term issues such as biodegradability. there were multiple major oil and chemical / toxic spills and/ or intentional dumps of toxic wastes. by some companies and some people. but some of the new products and processes were non-toxic, non-polluting, and/or biodegradable. but the massive volume of both the products and the wastes in the oil and commodity chemical businesses assured quick recognition of the very practical question of what to do with the wastes. that soon led to the recognition that it was far better to reduce or not make the wastes than to expend money to dispose of them. many in the oil refining and commodity petrochemical industries soon began to work toward improving the efficiency and lowering the generation and/or release of waste products, even if their motivations were initially and predominantly economic rather than altruistically ecological. but those improvements in efficiency and reductions in waste did benefit the environment. in the 1960s the negative effects of the wastes and pollution from the increasingly large and diverse chemical industry became increasingly apparent as both the industries and the environmental movement grew. in the early 1970s many countries around the world began to enact environmental statutes intended to curb the pollution, but many of those statutes (particularly in the united states) were based on legally inspired “command and control” approaches. the “command and control” approaches forced companies to begin to address environmental issues, but also legally dictated end-of-thetailpipe “solutions.” the technical limits and negative economic effects of those “end-of-the-tailpipe solutions” rapidly became apparent. many researchers in many places and many realworld industries quickly began to recognize that preventing pollution and waste, rather than cleaning it up after the fact, offered a much superior approach, technically, economically, environmentally, and politically, even though the specific mixture of motivations probably varied tremendously among the individual cases and people, as well as with time. many real-world “pollution prevention” projects began to crop up at various places around the world. those inherently interdisciplinary concepts and efforts appear to have first coalesced into an organized “pollution prevention pays” program at the 3m corporation in 1975, led by dr. joseph ling (an engineer). thousands of real-world international projects were initiated at 3m over the following years that both reduced pollution and saved/made the 3m company money at the same time. furthermore, professor michael g. royston from geneva was an early leader in the analysis of the very complex economic / social / governmental issues that underlay the new “pollution prevention” strategy. the november 1976 un/ece “non-waste technology and production” conference in paris, and the subsequent 1978 book, seems to have been a turning point that coalesced and broadened interest in the “pollution prevention” strategies, which soon began to evolve and spread into many companies and industries around the world, throughout the 1980s. once industry discovered that it could actually increase profits by preventing rather than cleaning up pollution, the pollution prevention concepts quietly went “viral” in industry, even though relatively few academics were paying attention. the practical technical details of the real-world inventions, 49early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s development, and commercialization of specific examples of the general pollution prevention concepts varied tremendously, depending on the details of the products, processes, and local technical and economic/business details, as well as the particular people and companies involved. in the late 1980s the oecd and the u.s. epa began to actively encourage the already on-going pollution prevention industrial approaches. the epa’s office of pollution prevention and toxics (oppt) was formed, and was led by many epa professionals including stepan, atcheson, and breen, a chemist. the oppt and other government agencies aided in the more general push for passage of the u.s. pollution prevention act of 1990, and new voluntary / cooperative industry / government approaches during the administration of george herbert walker bush. when the clinton administration was inaugurated in january 1993, some of epa’s programs were expanded and eventually renamed “green chemistry”. the new research grants and presidential green chemistry awards accelerated the growth / popularity of “green chemistry” in both industry and academia. but “green chemistry” (at least as a real-world phenomenon) was not “created” or “developed” at the us epa, or in academia. real-world “green chemistry” emerged from multitudes of complex evolutionary subprocesses and many earlier roots in many places, and from a vast set of interactions between internal and/or external forces, events, people, and/or motivations.50 green chem ist r y had ma ny fat hers a nd mothers,51 and grandfathers and grandmothers as well, from many types of technical and business backgrounds. hopefully the academic green chemistry literature, and university lectures to students, will soon begin to recognize the existence of and significance of those early contributions, both practical / scientific and theoretical / philosophical, from those many early fathers and mothers of green chemistry. to echo the perspective of joe ling, “the environmental issue is emotional … the decision is political … but the solution must be technical.” in this author’s opinion aspiring green scientists and engineers would do well to remain cognizant of the emotional and political issues but focus much of their unique technical skills and attention toward “innovative scientific solutions to real-world environmental situations”, as did the many 50 see murphy 2018, and murphy 2020. 51 the reference list below uses the normal convention of only citing the initials of the cited authors, without regard for sex, race, or nationality. actual inspection of those references reveals that many females from many countries were authors and contributors to those cited references, and therefore are metaphoric “mothers” of green chemistry. real-world fathers and mothers of green chemistry. hopefully more current and future green chemists, green engineers, and their team-mates from other disciplines will also recall and appreciate newton’s comment that “if i have seen further, it is by standing on the shoulders of giants.” mark a. murphy ph.d., j.d. is a retired industrial chemist and mostly-retired “solo” patent attorney, writing “pro-bono.” he thanks his many prior colleagues from science, engineering, and law, and the authors of the references cited herein, and his wife mary bertini bickers (a woman of many very unusual talents in her own right) for her many forms of support. he would particularly like to thank richard t. nall, a friend and engineer, for bringing the writings of nassim nicholas taleb to the author’s attention. the opinions stated in this article are solely those of the author and were not induced or financially supported in any way by any other person, business, or legal entity. references 1. american chemistry council 2018, “the science behind sustainability”, available at 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problems on the principals and creation of non-waste technology and production, held in paris on 29 november -4 december 1976 https://www.sciencedirect.com/book/9780080235974/pollution-prevention-pays https://www.sciencedirect.com/book/9780080235974/pollution-prevention-pays https://www.sciencedirect.com/book/9780080235974/pollution-prevention-pays https://p2infohouse.org/ref/30/29510.pdf https://www.amazon.com/black-swan-improbable-robustness-fragility/dp/081297381x/ref=tmm_pap_swatch_0?_encoding=utf8&qid=&sr= https://www.amazon.com/black-swan-improbable-robustness-fragility/dp/081297381x/ref=tmm_pap_swatch_0?_encoding=utf8&qid=&sr= https://www.amazon.com/black-swan-improbable-robustness-fragility/dp/081297381x/ref=tmm_pap_swatch_0?_encoding=utf8&qid=&sr= https://www.amazon.com/black-swan-improbable-robustness-fragility/dp/081297381x/ref=tmm_pap_swatch_0?_encoding=utf8&qid=&sr= https://www.thomasnet.com/articles/chemicals/green-chemistry-history/ https://www.thomasnet.com/articles/chemicals/green-chemistry-history/ http://doi.org/10.1016/b978-0-12-809270-5.00001-7 https://inis.iaea.org/search/search.aspx?orig_q=rn:24059230 https://inis.iaea.org/search/search.aspx?orig_q=rn:24059230 https://www.forbes.com/sites/joshwolfe/2012/02/02/the-father-of-green-chemistry/#6e6f1249f0cf https://www.forbes.com/sites/joshwolfe/2012/02/02/the-father-of-green-chemistry/#6e6f1249f0cf https://www.forbes.com/sites/joshwolfe/2012/02/02/the-father-of-green-chemistry/#6e6f1249f0cf https://p2infohouse.org/ref/25/24969.pdf https://p2infohouse.org/ref/25/24969.pdf https://p2infohouse.org/ref/02/01123/0112301.pdf https://p2infohouse.org/ref/02/01123/0112301.pdf 54 mark a. murphy part i – concepts and principals of non-waste technology introductory report, by v. v. kafarov (rapporteur, ussr academy of sciences, mendeleev institute of chemical technology) “main results of the symposium of the cmea countries on the theoretical, technical and economic aspects of low-waste and non-waste technology, by the organizational committee of the cmea symposium” “a broader definition of non-waste technology”, by hussein saleh, environment canada “new, ways of developing chemical and related procedures free of wastes or low in wastes in hungary, by tibor blickle and micklov machace, research institute for technical chemistry of the hungarian academy of sciences “eco-productivity: a positive approach to non-waste technology”, by m. g. royston, centre d’ etudes industrielles, geneva switzerland “concepts and principles of non-waste technology”, by j. d. schmitt-teqqe, federal republic of germany part ii – state of non-waste technologynational experience and policy “introductory report” by a. j. mcintyre (rapporteur, environment canada) “state of non-waste technology in the netherlands: national experience and policy” by a. w. f. van alphen, ministry of health and environmental production, netherlands “non-waste technology: comments on the canadian scene” by a. j. mcintyre, environment canada “austrian national report on non-waste technology” by rudolf kauders and udo ousko-oberhoffer, vienna austria “some aspects of production without waste of mineral raw materials in poland” by stephan gustkowitz, committee of science and technology, poland “non-waste technology: united kingdom experience and policy” by r. berry, department of industry, london united kingdom “french policies in pollution free technology” by p. chassande, minestere de la qualite de la vie, france “experience and policy with regard to non-waste technology in hungary” by a. takats and j. francia hungarian national council for environmental protection, budapest hungary “report from the swedish government” by the ministry of agriculture, sweden “production sans dechets en belgique” by i. van vaerenberg, prime minister’s office, bruxelles belgium “non-waste technology in finland” by jali m. ruuskanen and matti vehkalahti, finnish national fund for research and development, helsinki finland ”state of non-waste technology: united states experience and policy” by david berg and c. lembit kusik, environmental protection agency, washington d.c., usa “experience and policies in the field of non-waste technology in the federal republic of germany” by j. orlich, federal republic of germany experience et politique de la yougoslavie” by the government of yugoslavia part iii – industrial experience “introductory report” by d. moyen (rapporteur, institut national de la recherche sur le securite, paris france) “introductory report” by laszlo marko (rapporteur, professor of organic chemistry, university of chemical engineering, veszprem hungary) “introductory report”, by m. f. torocheshnikov (rapporteur, medeleev institute of chemical technology, moskow, ussr) “protein recovery from liquid potato wastes”, by m. huchette, establissements roquette lestreme france “profitable industrial uses for whey” by f. bertrand, minstere de l’agriculture, antony france “dyeing in a solvent medium: stx process” by m. laurent, france “how and why we chose integral recycling” by b. marechal, tour rousselle-nobel, france “recovery of the iron contained in pickling solutions and waste ore etching solutions, in the form of magnetite” by d. lefort, centre de recherches de pont-a-moussun, france “waste exchanges: improved management for a new type of growth” by j. c. deloy, editor-in-chief, “nuisances et environment”, paris france “metals in the organic chemical industry: problems and aids for non-waste technologies” by laszlo marko, professor of organic chemistry, university of chemical engineering, veszprem hungary “the use of natural zeolites in the chemical industry” by denee kallo, head of dept. for hydrocarbon catalysis, central research institute for chemistry, academy of sciences, budapest hungary “the utilization of brown coals other than for energy production” , by v. cziglina, l. dszida and z. meleg, collieries of tatabanya, hungary “non-waste technology in belgium” by a. g. buekene, professor, vrije universiteit, warsaw, poland 55early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s “outokumpu flash smelting method” by seppo harrkki, helsinki finland “methods of conserving raw material and energy and protecting the environment in chemical and electro chemical plating plants” by bengt westerholm, metal finishing machines, lahti finland “experience in designing a complex scheme for refining and reuse of waste waters and creation of a drainagefree scheme of water supply and sewerage in an industrial enterprise” by v.n. yevstratov and m.i. kievsky, ministry of chemical industry, moscow ussr “a review of non-waste technology problems in some major production branches” by p. grau, institute of chemical technology, prague, czeckoslavakia “developing conservation-oriented technology for industrial pollution control” by joseph t. ling, 3m corporation, minneapolis minnnesota, usa “the nordic organization for waste exchange” k.e. kulander, l-g. lindfors and e. lohrden, sveriges industriforbund, stockholm sweden “program considerations and experiences in optimizing industrial materials flow and utilization for a non-waste technology” by jerome f. collins, division of industrial energy conservation, us energy research and development adminstration, washington d.c. usa “no waste salt, no decontamination: a new step in the salt bath technology” by b. finnern, degussa, federal republic of germany “the design of non-waste technologies taking the example lignite transformation complex in the german democratic republic” by w. kluge, institute of energetics, leipzig, german democratic republic case studies from the iron and steel industry, pulp and paper industry, packaging and tyre industry “the iron and steel industry: pollution control and recycling” by y. hellot, ministere d l’industre et de la recherche, paris, france “the outlook for progress and technological methods in a paper industry confronted with environmental problems” by p. monzie, centre technique du papier, grenoble cedex, france “non-waste production of bleached kraft pulp” by w. howard rapson and douglas w. reeve, university of toronto, canada “reduction de 1a charge de pollution de l’eau provenant d’une usine de pate au sulfate blanchie” by p. lieben, environmental directorate, paris, france “displacement bleaching” by johan gullichsen, archippainen, gullichasen and co., helsinki finland “biological method for purifying kraft pulp mill condensates” by ilpo vettenranta, enso-gutzeit osakeyhtio, paper division, imatra finland “packaging alternatives for wine” by w. p. fornerod, istitute tno for packaging research, delft, netherlands “the recovery of glass in switzerland” by yves maystre, environmental canada, ottowa canada “the status of non-waste technology in the united states steel industry” by arthur: h. purcell, director of research, t.i.p. inc., washington d.c. “the status of non-waste technology in the united states packaging industry” by w. david conn, university of california at los angeles, usa “non-waste technology: the case of tyres in the united states” by haynes c. goddard, environmental research center, environmental protection agency, university of cincinnati, usa “two examples of low emission technologies in the pulp and paper industry” by e. jochem, fraunhoffergesellschaft, karlsruhe, federal republic of germany “treatment and preparation of dusts and sludges in the steel industry” by m. haucke and w. theobald, eisenhutten dusseldorf, federal republic of germany “the application of material-saving and low-waste technologies in the metal container industry with special reference to drawn and wall-ironed beverage cans” by walter sprenger, schalbach-lubecha gmbh, braunschweig, federal republic of germany “disposal of ironworks waste” by rudolf roth, mannesmann ag huttenwerk, duisburg, federal republic of germany “the heye-epb process, a low-waste technology” by vollmarhallensleben, prime ministers office, scientific policy planning, bruxelles belgium part iv cost/benefit aspects of non-waste technology “introductory report” by charles j. cicchetti (rapporteur, university of wisconsinmadison, usa) “cost-benefit considerations in waste-free production methods” by j. picard, agence financiere de bassin moire-bretagne, cedex, france “the introduction of non-waste technological processes in the hungarian silicate industry” by -jozsef talaber, central research and designing institute for silicate industry, budapest, hungary “economic aspects of non-waste management” by c. cala and j. wieckowski, ministry of science, education, and technology, warsaw poland 56 mark a. murphy part v ways and means of implementing non-waste technology “introductory report” by m. schubert(rapporteur, techniche universitate, dresden, german democratic republic) “the role of design education in non-waste technology” by h. h. van den kroonenberg, twente university of technology, enschede, netherlands “a survey of the location, disposal and prospective uses of the major industrial by-products and waste materials” by w. gutt, department of the environment, building research establishment, watford uk. “statutory and financial provisions for the establishment of manufacturing methods free of waste products” by r. huissoud, conseil national du patronat francais, paris, france “applications of material flow analysis in resource management” by david w. nunn, chr michelsen institute, bergen norway “an overview of solid waste product charges” by fred lee smith, jr., environmental protection agency, washington d.c., usa “administrative ways and means of implementing nonwaste technology” by martin neddens, rat von sachverstandigen fur umweltfragen, wiesbaden, federal republic of germany “non-waste technologies: ways and means of implementation” by robert reid, energy and environmental analysis inc., arlington virginia, usa part vi methodological and strategic aspects of nonwaste technology “introductory report” by jean-franqois saglio (rapporteur, directeur de la prevention des pollutions et nuisances, seine, france) “general aspects of the development of chemical production systems in regions with a complicated state of environment” by a. zygankov and v. senin, state committee for science and technology, moskow, ussr “perspectives for the development of non-waste technological processes in various branches of industry” by b. laskorin, a. zygankov, b. gromov and v. senin, state committee for science and technology, moskow, ussr. “a method of assessing non-waste technology and production” by thomas veach long ii and s. ellie, resource analysis group, university of chicago, usa “non-waste technology and the materials flow in an economy: facts and perspectives” by m. fischer, institut fur systemtechnik und innovationsforschung, federal republic of germany annex – inaugural addresses vincent ansquer, minister for the quality of life, france james stanovnik, executive secretary, united nations economic commission for europe appendix ii titles and authors of papers published in “making pollution prevention pay, ecology with economy as policy” edited by donald huisingh and vicki bailey © permagon press 1982 papers presented at a symposium held in winston-salem north carolina, usa, may 26-27 1982 preface – don huisingh and vicki bailey, north carolina board of science and technology introduction “making pollution prevention pay” dr. m. g. royston, international management institute, geneva “pollution prevention pays: the 3m corporate experience” russell h. susag, phd., p.e. director of 3m environmental operations, st. paul, minnesota usa “in every dark cloud…” dan meyer, manager, environmental control department, dow corning corporation, midland, michigan, usa “disposal cost reductions from ciba geigy corporation’s cost improvement program” john a. stone, ph.d., manager, industrial health agricultural division, ciba-geigy corporation, greensboro, n. c., usa “polyvinyl alchohol recovery by ultrafiltration” h. c. (nick) ince, j. p. stevens & company, greenville, south carolina, usa “opportunities for clean technology in north carolina” dr. m. g. royston, international management institute, geneva switzerland “implications and procedures for waste elimination of hazardous wastes” dr. michael r. overcash, professor, chemical engineering department, professor, biological and agricultural engineering department, north carolina state university, raleigh, north carolina, usa “chemical recycling: making it work, making it pay” dr. paul palmer, chemsearch/zero waste systems, inc., emeryville, california, usa 57early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s “waste exchanges: an informational tool for linking waste generators with users” elizabeth w. dorn, piedmont waste exchange, urban institute, university of north carolina– charlotte, usa, and m. timothy mcadams, pacific environmental services, inc., durham, north carolina, usa “process design to minimize pollution case studies” donald d. easson, division manager, process and environmental engineering, daniel international corporation, greenville, south carolina, usa “a systems approach to waste management” james c. dickerman, radian corporation, durham, north carolina “waste reduction – concept to reality” a. brent brower, p.e., environmental design manager, j. e. sirrine company, research triangle park, north carolina, usa “positive incentives for pollution control in north carolina” dr. carlisle ford runge, public policy analysis program, department of political science, university of north carolina, chapel hill, n.c., usa “economic and environmental health through education and cooperation among industry, government, and citizens” claud “buck” o’shields, chairman, governor’s waste management board, north carolina, usa substantia an international journal of the history of chemistry vol. 4, n. 2 2020 firenze university press some thoughts written on ‘juneteenth’ of 2020, the day commemorating the end of slavery in the united states, june 19, 1865, at the end of our civil war richard g. weiss entropy as the driving force of pathogenesis: an attempt of classification of the diseases based on the laws of physics laurent schwartz1,*, anne devin2, frédéric bouillaud3, marc henry4 early industrial roots of green chemistry ii. international “pollution prevention” efforts during the 1970’s and 1980’s mark a. murphy, ph.d., j.d. …and all the world a dream: memory outlining the mysterious temperature-dependency of crystallization of water, a.k.a. the mpemba effect evangelina uskoković1, theo uskoković1, victoria wu1,2, vuk uskoković1,3,* the strange case of professor promezio: a cold case in the chemistry museum marina alloisio, andrea basso*, maria maddalena carnasciali, marco grotti*, silvia vicini estonian scientist in ussr (memories and reflections about endel lippmaa, 1930-2015) alexandr vladimirovich kessenikh the eminent french chemist claude-louis berthollet (1748-1822) in the literature between the 19th and 21th centuries aleksander sztejnberg communicating science: a modern event antonio di meo substantia. an international journal of the history of chemistry 3(2): 55-58, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-635 citation: i. klugman, a. melnikov, d.f. parsons (2019) derjaguin’s water ii: a surface hydration phenomenon. substantia 3(2): 55-58. doi: 10.13128/substantia-635 copyright: © 2019 i. klugman, a. melnikov, d.f. parsons. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. feature article derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 1 department of mathematics, university of haifa, israel 2 department of chemistry and physics, cshee, murdoch university, australia e-mail: anna.melnikov@gmail.com; d.parsons@murdoch.edu.au abstract. b.v. derjaguin’s promotion of anomalous water ii (polywater) in the early 1970s was an embarrassing point in the career of an illustrious chemist, and quickly repudiated by derjaguin himself. water ii does not exist as a bulk liquid. and yet a theoretical model of the hydration of ions developed by i. klugman, consistent with electrolyte properties such as equivalent conductivity, diffusion coefficient, and viscosity, found a density of water molecules in the hydration shell of ions to be 1.4 g/ cm3, close to the density of water ii reported by derjaguin and churaev. given derjaguin and churaev’s use of adsorption in fine capillaries, klugman postulates that their anomalous experiments can be understood as measuring the hydration layer of adsorbed water rather than bulk water. derjaguin’s last publication in 1994 on violation of archimedes’ law during adsorption may be intended to hint at this conclusion. perhaps derjaguin’s involvement with water ii can, in the end, be celebrated not as a study of bulk liquid but as a study of adsorption phenomena and hydration. keywords. derjaguin, water ii, polywater, water, water anomalies, electrolyte, adsorption, archimedes’ law. allow me to introduce myself: i am ilya klugman, born 1924, engineer by profession, now retired. i met b.v. derjaguin personally at the end of the 1960s, when i presented a talk at his seminar series on the theme of my doctoral dissertation concerning the dielectric properties of crude oil emulsions. my presentation was successful and received a positive reaction from b.v. derjaguin. a series of my papers were published in kolloidn. zh. 1–7, of which b.v. derjaguin was the chief editor. strange then, at that time i knew nothing of derjaguin’s work on the topic of water ii, or polywater as it came to be known in the west. in the 1980s i moved to israel, where i worked intensively as an engineer for more than 11 years. entering into retirement, i decided to return back to my own work which had been interrupted by the move. i knew that the theory of electrolytes, leaning on the work of debye-hückel, was far from complete. my first efforts building a new approach for electrolyte theory were published in the journal elektrokimiya 8–15. i developed a hydration model of electrolytes, with only two ion parameters drawn from first and second 56 ilya klugman, anna melnikov, drew f. parsons hydration shells, that enabled various electrolyte properties to be determined. but once i had finished developing the first variant of this theory, the editorial office of the journal elektrokimiya changed, and my articles started to meet rejection. discovering that the volume of water molecules changes on entering into the hydration shell of an ion, i proposed that this must be driven by denser packing, a result of their attraction towards the ion. we know that a water molecule at 25°c occupies a volume of v=30å3, while at the same time the intrinsic volume of the water molecule itself equals vw=11.25å3. it follows that a water molecule in water occupies a volume more than three times in excess of its intrinsic volume. in order to characterise the density of the molecule in the hydration shell, i introduced a “density coefficient” kp equal to the ratio of the intrinsic volume vw of a water molecule, to the volume v that it occupies in the hydration shell, kp = vw/v. calculations indicated that for all monovalent ions investigated, the ratio was a uniform kp = 0.535. this result seemed incorrect to me, since i supposed that as the ion radius falls, the strength of attraction of water molecules towards the ion must increase, in which case the packing coefficient kp would increase. at this time i happened to read a popular book by i. asimov16 , written during the period when a great amount of attention was being given to “anomalous” water, water with a density of 1.4 g/cm3, boiling point 250°c, freezing point -40°c and a linear coefficient of expansion across the entire temperature range. the packing coefficient i had calculated, kp = 0.535, corresponds to a water density of 1.422 g/cm3, essentially equal to the density of anomalous water. if water transforms into the anomalous modified phase upon forming the hydration shell around an ion, then it follows naturally that the packing coefficient will be constant. it was necessary to develop my interpretation based the foundation of these works. let us be clear: the anomalous bulk phase liquid, called water ii by derjaguin17, does not exist. but when molecules of ordinary water with its well known parameters (let us label it w1) cross into the hydration shell of an ion, a consequence of the interactions between them, they transform into molecules with the properties measured by derjaguin and churaev18,19 (we shall label this water as w2). it follows that, even if water ii does not exist as an independent liquid phase, the molecules of this type of water exist in any body of water around ions and other particles where adsorption takes place. under conditions where w1 water contains only a negligible amount of w2-type molecules, their presence will not be detectable. but when the number of w2 molecules becomes comparable to the number of w1 molecules, the properties of w2 molecules will start to become evident. the effect can be observed in electrolytes, where not only does the density increase with concentration, but also the boiling point rises and the freezing point falls. following these concepts, i applied my electrolyte model using the density 1.4 g/cm3 of anomalous water as measured by derjaguin and churaev. the correctness of my proposed electrolyte model was confirmed by the result that, with the help of two parameters: the radius of a hydrated ion, characterising the first hydration shell, and the thickness of the buffering layer (an exclusion zone around the ion) driven by the second hydration shell, it was able to determine to an accuracy of 4% such electrolyte properties as equivalent conductivity λ, diffusion coefficient d, and viscosity η. in order to compute the equivalent conductivity λ, i used the formula of stokes taking the radius of hydrated ion instead of the intrinsic ion radius, and added an amendment for the decreased viscosity caused by secondary hydration. in the computation of the diffusion coefficient d i took into account that the same ions participate in diffusion as well as in equivalent conductivity and the only difference is that in the diffusion coefficient the ions move in the same direction with the same velocity and in the equivalent conductivity they move in different directions with different velocities. in the computation of viscosity the increase of viscosity caused by hydrated ions is obtained by einstein’s formula and decrease of viscosity caused by the second hydration is defined by the thickness of the buffering layer. a chief argument of derjaguin’s opponents was the absence of anomalous water in nature (indeed, derjaguin himself agreed that this was a significant argument). derjaguin had extracted w2 molecules via a process of adsorption in very fine capillaries. with multistage distillation in specialised equipment it was possible for samples to be extracted with nearly equal quantities of w2 and w1. because of the difference in molecular densities, 1.4/1.0, and the long separation path, they were able to separate w2 molecules and measure their parameters. for this reason it is possible to assert that derjaguin did indeed measure properties of the group of w2 molecules. calculation using my electrolyte model confirmed that the density of water molecules in the hydration shell was equal to 1.4 g/cm3, i.e. w1 water molecules transformed to w2 molecules upon crossing into the hydration shell under the influence of the field of an ion. additional proof of this fact can be found in the change of other electrolyte properties in the presence of w2 molecules, the elevation of the boiling point and depression of freezing point. moreover, the proposed 57derjaguin’s water ii: a surface hydration phenomenon electrolyte model allows the freezing point of an electrolyte solution to be predicted. according to literature data the freezing point of nacl solution at 2.9%w/w concentration falls to -1.8°c, while the electrolyte model predicts -1.7°c. in a letter written to the chief editor of colloid journal seeking to publish my study, i wrote that after the scandal of water ii it is necessary to show courage to return to the theme once again. i suggested that, if my conclusions hold up to peer review, it would be an honour to publish a manuscript rehabilitating the work of derjaguin and his group, given that the first paper on the topic of water ii was published in that journal. however, i received a reply from the chief editor proposing instead that, since derjaguin had recanted from water ii, my manuscript served more as opposition against derjaguin. i was therefore encouraged upon reading a foreword written by barry ninham prefacing a collection of derjaguin’s works20, in which he showed that in many scientific debates derjaguin was in the end proven correct, and even in the story of water ii there remains an array of unanswered questions. i think that it is possible to demonstrate the significance of the results obtained by derjaguin’s group and remove the label of “the biggest mistake of scientists in the 20th century” from their work. could it be i am mistaken? i then became acquainted with the last paper of derjaguin in kolloidn. zh.21 (in english, published in colloid and surfaces a22) on the violation of archimedes’ law during adsorption. keeping in mind that the derjaguin group obtained water ii by adsorption in capillaries, it is possible to deduce that the chief aim of this paper, although not stated so directly, was to show that during adsorption water molecules with new properties are found, i.e. molecules of water ii, and that this process changes water so significantly that even archimedes’ law is violated. the same process occurs in hydration. from derjaguin’s article, i understood that a parameter which i had used to define volume, could in the context of the violation of archimedes’ law be called the coefficient of violation of archimedes’ law. i wrote a manuscript on how it can be used to define hydration properties and parameters of a model i proposed for 1:1 electrolytes. so as not to antagonise the established scientific community, in the manuscript i did not speak about molecules of water ii, but rather introduced the concept described above of the density coefficient kp of water molecules in the hydration shell, and showed that with kp=0.526, corresponding to the density of water in the hydration shell, 1.4 g/cm3, the proposed model allows the calculation of equivalent electrical conductivity of an electrolyte at infinite dilution. i published the manuscript in problems in applied physics, published by saratov university23. in two following papers 24,25 i showed that this model also permits to determine the dielectric constant, and to construct a basis for a hydration model of electrolytes. in this way there are now a few publications, one based on experimental data21,22 and the other based on theoretical considerations23–25, which confirm that during adsorption or hydration the properties of a water molecule change significantly. the concept of a surface hydration layer, or surface induced water ordering, is not unknown to the scientific community. it is known in gouy-stern theory as the helmholtz layer and is crucial for understanding the capacitance of surfaces26. devanathan and tilak estimated27 the dielectric constant of the surface hydration layer 0.37 nm thick at electrode surfaces to fall from 78 (bulk water) to 7.2. as for the existence of w2 in nature, although it cannot exist as a bulk liquid, nevertheless it does exist. my conjecture is that plants use capillaries and charged particles in order to transform molecules of w1 into w2 and this can explain why some plants are capable to survive the extreme heat of deserts and extreme winter cold without drying or freezing. these publications, it seems to me, must ease the process of rehabilitating the work of the derjaguin group, all the more given that derjaguin himself continued to study the question of water ii, arising during adsorption. when i told my wife (z. bykova) about derjaguin’s final paper, she expressively called it the “final will and testament of derjaguin”. i would like to express my admiration for the beautiful experiments of derjaguin and churaev. as b. ninham wrote,20 “derjaguin was, and remains controversial, and in the controversies that occasionally best him, usually is right in the end.” acknowledgements this letter is a personal reflection of ilya klugman on his experience with b.v. derjaguin and the anomalous water ii, related in russian to drew parsons, communicated by his daughter anna melnikov, and translated into english by drew parsons. i (i.k.) would like to express my deep gratitude to drew parsons for the correspondence and translation of the letter. bibliography 1. i. klugman, kolloidn. zh., 1966, 28, 42. 58 ilya klugman, anna melnikov, drew f. parsons 2. z.y. bykova, i.y. klugman, kolloidn. zh., 1969, 31, 17. 3. i.y. klugman, kolloidn. zh., 1974, 36, 966. 4. z.y. bykova, i.y. klugman, kolloidn. zh., 1975, 37, 100. 5. z.y. bykova, i.y. klugman, kolloidn. zh., 1975, 37, 206. 6. i.y. klugman, kolloidn. zh., 1975, 37, 353. 7. z.y. bykova, i.y. klugman, kolloidn. zh., 1978, 40, 513. 8. i. klugman, elektrokimiya, 1992, 28, 985. 9. i. klugman, elektrokimiya, 1996, 32, 324. 10. i. klugman, elektrokimiya, 1997, 33, 337. 11. i. klugman, elektrokimiya, 1997, 33, 1216. 12. i. klugman, elektrokimiya, 1998, 34, 1097. 13. i. klugman, elektrokimiya, 1999, 35, 79. 14. i. klugman, elektrokimiya, 1999, 35, 87. 15. i. klugman, elektrokimiya, 2002, 38, 415. 16. i. asimov, asimov’s guide to science. basic books, 1972. 17. b. v derjaguin, scientific american, 1970, 223, 52. 18. b. v. derjaguin, n. v. churaev, new properties of liquids: superdense water (water ii). nauka, 1971. 19. b. v. derjaguin, z.m. zorin, y.i. rabinovich, n. v. churaev, journal of colloid and interface science, 1974, 46, 437. 20. b.w. ninham, progress in surface science, 1992, 40, xv. 21. b. v. deryaguin, kolloidn. zh., 1994, 56, 45. 22. b. v. derjaguin, colloids and surfaces a: physicochemical and engineering aspects, 1993, 81, 289. 23. i.y. klugman, problems in applied physics, 2017, 24, 62. 24. i.y. klugman, problems in applied physics, 2018, 25, 71. 25. i.y. klugman, problems in applied physics, 2018, 25, 75. 26. j. lyklema, substantia, 2017, 1, 75. 27. m.a. v devanathan, b.v.k.s.r.a. tilak, chemical reviews (washington, dc, united states), 1965, 65, 635. substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 3(2) suppl. 2: 27-43, 2019 firenze university press www.fupress.com/substantia citation: m. grätzel, j. v. milic (2019) the advent of molecular photovoltaics and hybrid perovskite solar cells. substantia 3(2) suppl. 2: 27-43. doi: 10.13128/substantia-697 copyright: © 2019 m. grätzel, j. v. milic. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. issn 1827-9643 (online) | doi: 10.13128/substantia-697 the advent of molecular photovoltaics and hybrid perovskite solar cells michael grätzel*, jovana v. milić école polytechnique fédérale de lausanne, switzerland e-mail: michael.graetzel@epfl.ch, jovana.milic@epfl.ch abstract. over the past decade, we witnessed a remarkable development of a new generation of photovoltaic technologies, in particular dye-sensitized and perovskite solar cells. these systems have demonstrated potential to provide solutions for a more sustainable future in energy conversion. both of these technologies, however, still encounter a number of challenges that stimulate further research. while dye-sensitized solar cells would benefit from an effective transfer from solution-based to a solid-state technology, hybrid perovskite solar cells suffer from long-term operational instability that need to be addressed. in this perspective article, we provide an overview of the recent advancements along with the perspectives for future developments. keywords. molecular photovoltaics, dye-sensitized solar cells, perovskite solar cells, molecular modulation, layered hybrid perovskites. 1. introduction the increasing energy demands of our modern society and their impact on the environment call for novel solutions towards renewable energy conversion. one of the most auspicious technologies to meet these demands and prevent the devastating pollution caused by the combustion of fossil fuels are based on solar energy conversion.1,2 nature has long served as an inspiration in the ongoing quest for highly efficient light-harvesting technologies, stimulating research efforts towards sustainable energy. in natural photosynthesis, the control of molecular functions is often achieved through the role of supramolecular chemistry,3,4 which involves fine-tuning of noncovalent interactions.5-7 such an approach inspired the development of a number of artificial molecular systems that convert external energy inputs into chemical energy.5-7 in addition, natural photosynthesis has inspired the development of technologies for light-to-electrical energy conversion, in particular dye-sensitized solar cells (dsscs).8-12 in natural photosynthesis, the absorption of light triggers a sequential photoinduced electron transfer that contributes to the chemiosmotic gradient required to convert the electromagnetic stimuli into chemical energy that fuels the bioprocesses (figure 1a).3,4 instead, in dsscs an electrical potential gradient is generated via the photoinduced interfacial electron transfer from a molecular dye to a mesoscopic oxide, from where 28 michael grätzel, jovana v. milić it is extracted via a transparent contact to the external electric circuit. the complete cycle of converting light to electricity involves four key steps (figure 1b): (1)  photoexcitation of the light absorber (dye); (2)  electron injection from the dye into the electron transport layer, commonly a mesoscopic tio2 or thin film transporting the charge carriers via the front contact into the external circuit; (3)  dye  regeneration by the redox shuttle that acts as an electron donor; and finally (4)  shuttle regeneration at the counter electrode in the final step that closes the electric circuit.10-12 an effective solar-to-electric energy conversion requires alignment of the energy levels and favorable interaction of the participating species.10-12 in a conventional dssc, the redox mediator that “shuttles” electrons from the counter electrode to the photo-anode is dissolved in a liquid electrolyte. while this ascertains intimate contact with the sensitizer in the mesoporous film, it also poses limitations for industrial applications, thereby stimulating the development of solvent-free systems and solid-state technologies.13-15 therefore, the development of dsscs using solvent-free ionic liquid electrolytes or solid-state hole conductors is of great interest.13-15 the advent of mesoscopic solar cells presented a new paradigm in photovoltaic technology as the electron and hole-conducting materials form a three-dimensional junction, in contrast to the conventional planar p-n junctions. the prototype of this new photovoltaic family is the dye-sensitized solar cell (dssc), also named the “grätzel cell”, which employs dye molecules, pigments or semiconductor quantum dots to sensitize a nanocrystalline wide bandgap semiconductor films. the landmark paper published in 1991 had a substantial impact being cited approximately 21’000 times until now.8 according to an analysis by nature in 2014, this publication ranks by number of citations amongst the top 100 papers of all time published across all domains of science. this revolutionary approach has allowed very high efficiencies to be reached in a photovoltaic conversion process that separated, for the first time, light harvesting and charge carrier transport, mimicking successfully the primary process in natural photosynthesis. ten years ago, the dssc research became the cradle for the birth of a new closely related technology employing highly effective light absorbers known as hybrid organic-inorganic perovskites, which is referred to as perovskite solar cells (pscs; figure 2).16-18 pscs have emerged as the most promising thin-film, solution-processable, low-cost photovoltaic technology with extraordinary solar-to-electric power conversion efficiencies (pces) that have recently reached 25.2%, already surpassing the performance of the current market leader, polycrystalline silicon (figure 2).16,19-23 unlike silicon, which is a material based on a covalent structural framework (figure 2a),24 hybrid perovskites are ionic crystals based on organic and inorganic components featuring mixed electronicionic conduction (figure 2b).19-26 these materials can be described by the amx3 formula, which is composed of a monovalent cation a (commonly methylammonium (ma) ch3nh3+, formamidinium (fa) ch(nh2)2+, guanidinium (gua) c(nh2)3+, and cs+), a divalent metal m (pb2+, sn2+), and a halide anion x (cl–, br–, i–).19-26 pscs currently showing the highest performances are pb-based comprising a mixture of different cations and halides.22-26 despite their remarkable performance, however, the instability of pscs against environmental factors, as well as under operational conditions, remains an issue that has to be addressed before practical applications become feasible (figure 3).27-30 this particularly refers to the sensitivity against oxygen and water, as well as heat and light stress (figure 3a,c). furthermore, significant effort is necessary to unravel the structure-property relationships and provide guidance for advanced material design for perovskites to reach a leading position in today’s photovoltaics.18,22 figure 1. schematic representation of the sequential electron transfer in (a) natural photosynthesis and (b)  conventional dye-sensitized solar cells (pioneered by grätzel at al.8) inspired by natural photosynthesis. ps = photosystem; adp = adenosine diphosphate; atp = adenosine triphosphate; nadp = nicotinamide adenine dinucleotide phosphate; nadph = reduced nadp; q = quinone; pq = plastoquinone; pc = plastocyanin; p680 and p700 = chlorophyll pigments (p) of psii and psi, respectively, that best absorb light at either 680 nm or 700 nm, as indicated; fd = ferredoxin; fnr = ferredoxin nadp reductase; cb = conduction band; lumo = lowest occupied molecular orbital; homo = highest occupied molecular orbital; red = reduced; ox = oxidized. 29the advent of molecular photovoltaics and hybrid perovskite solar cells in contrast to three-dimensional (3d) perovskites, their layered two-dimensional (2d) analogues have demonstrated promising environmental stability.31-35 these materials are often described by the general s2an–1mnx3n+1 formula. here, species s (typically cmh2m+1nh3+) and a (typically ma, fa, or their mixtures) are organic cations, m is a divalent metal cation (pb2+, sn2+), x is a halide ion (br–, i–), and the value n represents the number of layers of [mx6]4– octahedra in the hybrid perovskite phase. the structure consists of layers of perovskite slabs separated by the organic ammonium cation spacers (figure 4).35 the spacer cation defines the properties of the layered 2d perovskites and consequently, the corresponding optoelectronic device performance.36 the most commonly used spacers feature hydrophobic alkyl chains, such as n-buthylammonium (ba) or phenylethylammonium (pea), which are essential to increasing the resilience of the material against the environmental factors. this contribution to the stability, however, comes at the expense of the solar-to-electric power conversion efficiency, which requires further advancement of these materials and the corresponding devices.31 2. recent advancements of dye-sensitized solar cells the inception of dye sensitized solar cells (dssc) about 30 years ago by the grätzel group provoked a revolution in photovoltaics.8 he is credited with moving the figure 2. structural representation of solar cell materials and the evolution of their performance. (a) schematic representation of the structure of silicon (upper; figure adapted from ref.24) and hybrid perovskites (lower) with the chemical formula amx3. (b) evolution of the photovoltaic performance of pscs since 2009 (blue) in comparison to polycrystalline silicon (22.3% efficiency) and the theoretical limit (red), with the corresponding number of publications on hybrid perovskite solar cells (based on the scopus analysis for the term “perovskite solar cell” on september 23, 2019). in 2019 the efficiency of pscs has reached 25.2%.16 a representative photo of a perovskite solar cell is shown in the inset (photo credit to the researchers at ntu singapore). figure 3. aging of typical triple cation double halide perovskite solar cells. (a)  evolution of solar-to-electric power conversion efficiency under operational stability conditions upon continuous irradiation by maximum power point (mpp) tracking. adapted with permission from ref.30 (b) cross-sectional scanning electron microscopy (sem) image of a typical psc highlighting its architecture and (c) time of flight secondary ion mass spectroscopy elemental depth profiling image showing the concentration of au species across the device, indicative of ion migration under operational conditions at elevated temperatures. adapted with permission from ref.30 copyright 2016 american chemical society. 30 michael grätzel, jovana v. milić solar cell field beyond the principle of light absorption via diodes to the molecular level, exploiting the sensitization of wide bandgap semiconductor oxides by the dye molecules, pigments or semiconductor nanocrystals for light energy harvesting. the key to this success was the introduction of a new paradigm in photovoltaics. instead of using the conventional planar p-n junction cell architecture, a 3d scaffold of semiconducting oxide nanoparticles was introduced in order to collect the electrons injected into the conduction band by the monolayer of adsorbed sensitizer molecules. the stacking of the nanoparticles produced a mesoscopic film with very high internal surface area, which enabled efficient light harvesting by the sensitizer. by contrast, on a flat surface, a self-assembled monolayer of molecular dye produces a very week photo-response, since the light absorption cross-section of a molecule is several orders of magnitude smaller than the area it occupies. introducing a 3d mesoporous semiconducting oxide film as electron selective contact to support the sensitizer overcame this fundamental problem. as a result of its large internal surface area, the film achieves very efficient light harvesting even at monolayer surface coverage by dyes or semiconductor quantum dots. this, nevertheless, left the challenge to find a way to collect the electrons injected by the sensitizer into the nanoparticle network before they recombine with the positive charges left behind on the sensitizer. this task appeared to be particularly arduous in view of the fact that the charge carrier collection was not assisted by an electric field of the type present in a conventional planar p-n junction device. judicious molecular engineering of sensitizers enabled to address this challenge and to realize chromophores that would sustain the light-induced charge separation across the interface for long enough time to collect the photo-injected carriers before they were recaptured by the dye or by the oxidized form of the redox mediator. this development was supported by computational analysis, which provided precious help in the conception, design and synthesis of the best performing sensitizers.37-41 examples of some of the structures of the molecules that have emerged as some of the most powerful dssc sensitizers and redox shuttles are shown in figure 5. due to their outstanding stability and broad visible light absorption, the bis-thiocyanato ruthenium bipyridyl complexes became the sensitizer of choice and are currently produced on the multi-kilogram scale for use in commercial products. the scaleup in production has lowered their prize by a factor of 100, from initially over 1000 us$/g to 10 us$/g, rendering dsscs competitive with conventional systems. today, we witness the emergence of organic and semiconductor quantum dots as sensitizers, which show superior light-harvesting properties to the ruthenium dyes. in-depth theoretical and experimental studies elucidated the fundamental features of the dynamics of interfacial electron transfer and charge carrier recombination within and at the surface of the semiconductor oxide nanocrystals. laser photolysis in conjunction with time-resolved spectroscopy at the femtosecond time domain showed that judicious design of the sensitizer molecule allows to control the rate of the interfacial electron transfer reactions. for state-of-the-art sensitizers, the electron injection in the conduction band of tio2 scaffold occurs on the femtosecond to picosecond timescale, while the charge carrier recombination takes milliseconds or even seconds. this is sufficiently long to allow for near-quantitative collection of the photo-generated charge carriers as electric current. these molecular systems can generate photocurrents that were about 10’000times larger than those obtained with planar architectures, converting over 90% of the incoming photons into the electric current within the absorption wavelength range of the sensitizer. the very efficient conversion of sunlight with molecular chromophores renders the dsscs the first photovoltaic technology to mimic the light reaction in natural photosynthesis. this presents one of the most exciting developments in the generation of renewable energy from solar power. a further advancement of dsscs was made through the molecular engineering of a new donor-acceptor porphyrin sensitizer, coded yd2, achieving an efficiency record of 12.4 % when employed with a cobalt complex as redox shuttle (figure 5).42 due to its beautiful green colour and its high efficiency, this sensitizer is presently upscaled for powering dssc-based glazing (figure 6). an example is the green sound protection barrier installed on the highway between bern and zurich that produces over 1000 kwh/year of electricity (figure 6). further computation-assisted molecular engineering of this type of donor-acceptor porphyrins allowed realizing panchromatic light harvesting across the whole visible spectrum, increasing the pce to 13%.43 figure 4. structural representation of layered two-dimensional perovskites. schematic of (a) s2an–1pbni3n+1 (ruddlesden-popper, rp), (b) san–1pbni3n+1 (dion jacobson, dj) formulations with different number of inorganic layers (n). blue octahedra illustrate the {pbi64– } units, light blue spheres the a cations, whereas the cyan and green rods correspond to the organic spacers (s, s’). 31the advent of molecular photovoltaics and hybrid perovskite solar cells ionic liquids played a crucial role as non-volatile, solvent-free redox electrolytes, enabling the practical deployment of dsscs. new hydrophobic ionic liquids were developed displaying low viscosity, which have found widespread applications and are now produced commercially.44 substantial advances in performance were achieved by introducing eutectic mixtures of imidazolium iodide salts as redox active ionic liquids, where the charge transport is accelerated by a groothus-type exchange mechanism.45 the breakthroughs made in this area have dramatically increased the stability of dsscs under prolonged light soaking and heat stress, fostering their practical development for outside deployment. several companies are now manufacturing ionic liquid based on dsscs on a commercial scale. solid-state dye sensitized solar cells are the main focus of current research efforts. taking the inspiration from the work of c. tang on organic light-emitfigure 5. structures of dye molecules (red) and redox shuttles (blue) commonly employed in dsscs. their roles are schematically illustrated in figure 1b. r represents various alkyl/alkoxy substituents while x = scn. figure 6. examples for dssc-based photovoltaic glazing. left: dssc panels produced by the company solaronix (www.solaronix.ch) mounted at the façade of the swiss high-tech convention centre in lausanne, switzerland. right: the first energy-producing noise-barrier based on the dssc panels developed by the swiss company h.glass is installed on the highway between bern and zurich in switzerland. 32 michael grätzel, jovana v. milić ting diodes, grätzel et al. replaced the liquid electrolyte by solid organic hole conductors. specifically, his group introduced the triarylamine derivative, namely 2,2’,7,7’-tetra k is(n,n-di-pmet hox y phenyla mine)9,9-spirobifluorene (spiro-meotad), as a hole-transporting material, which is now widely applied.46 starting from low efficiencies below 1%, the pce of solid-state dsscs reaches presently over 11% using a solid-state cu(ii)/cu(i) redox system for hole conduction. the advantage of employing a solid-state hole conductor is that it is non-volatile, showing faster charge carrier transport, while chemically less aggressive than a redox electrolyte. hence, further research on solid-state dsscs is presently being actively pursued. this development served as a springboard for the recent stunning rise of perovskite solar cells using the mesoscopic architecture of solid-state dssc and hole conductors based on the spiro-meotad family. dsscs based on cu complexes as redox shuttles have taken the lead in electric power generation from ambient lighting.47 ambient light-harvesting systems are of great practical interest, as they can serve as electric power sources for portable electronics and can render the operation of a great variety of devices for wireless sensor networks (wsn) or iot (internet of things) autonomous. a new dssc embodiment has recently been shown to achieve high power conversion efficiencies (pce) under ambient light conditions (figure 7a,b). the photosystem combines two judiciously designed sensitizers coded d35 and xy1 (figure 7c), with the copper complex cu(ii/i)(tmby) as redox shuttle (tmby = 4,4’,6,6’tetramethyl-2,2’-bipyridine; figure 7d), which quantitatively regenerates both dyes at a very low driving force, resulting in open circuit photovoltages (voc) up to 1.1 v (figure 7e). the electric power production at 1000 lux exceeded the pce of gaas under similar conditions, highlighting the potential of this technology. 3. recent advancements of hybrid perovskite solar cells since the first demonstration of the hybrid perovskite solar cell in 2009 by miyasaka et al., the performance of this technology has rapidly evolved from figure 7. example of a cu-based dye-sensitized solar cell. (a) schematic representation of the device architecture and (b) energy alignment of the device components, with the structure of the corresponding (c)  dyes and (d) redox shuttle, as well as the (e) current-voltage characteristic at different light intensities. adapted from ref.47 with permission. tmby = 4,4’,6,6’-tetramethyl-2,2’-bipyridine; pedot = poly(3,4ethylenedioxythiophene); fto = fluorine-doped tin oxide. 33the advent of molecular photovoltaics and hybrid perovskite solar cells pce of 3.8% to over 25% in just a decade, which has been unprecedented in photovoltaics (figure 2b).16,18,23,48 while this progress has been remarkable, pscs continue to face obstacles to their application, which are mainly related to their instability against moisture and oxygen, as well as light and heat stress under operational conditions.48,49 in addition, the progress in hybrid perovskite research has been primarily driven by the device performance, while the underlying degradation mechanisms and structure-property relationships remain poorly understood, which prevents rational material design required for further advancement.48,49 to overcome these challenges, a number of strategies emerged over the past years with promising future prospects. amongst these, three strategies related to the material design are particularly important (figure 8), namely (1) compositional engineering, (2) employing a variety of modulators to the perovskite composition to alter their properties50,51 as well as (3) layered two-dimensional perovskites and their heterostructures.52,53 this progress was accompanied by the development of the analytical tools based on solid-state nuclear magnetic resonance (nmr) spectroscopy to unravel the structural properties at the atomic level and guide rational material design.54-59 compositional engineering played a pivotal role in advancing pscs since the properties of hybrid organic-inorganic halide perovskite materials are strongly dependent on their composition. this progress was facilitated by several major advancements. following the first attempts to employ hybrid perovskite materials based on methylammonium (ma) cation,60 eperon et. al.61 introduced the formamidinium (fa) to reduce the band gap from 1.53  ev to 1.48  ev and consequently increase the theoretical performance limit. however, the performance of fa-based compositions were lower than that of ma-based ones, since the perovskite-type fapbi3 polymorph (α-fapbi3) is not thermodynamically stable at temperatures below 150 °c and it transforms into the yellow polymorph (δ-fapbi3) under ambient conditions.62 phase stability of the mixed fa/ma compositions were improved by gradually substituting ma with fa cations,19 and the utility of fa-based systems was further stimulated by their enhanced stability at elevated temperatures.63,64 this approach of mixing cations in hybrid perovskites was advanced further by introducing 15% mapbbr3 in fapbi3 to reach pces above 18%.65 furthermore, cs+ was introduced into the composition to define the commonly employed triple cation cs0.05m a0.17fa0.83pb(i0.83br0.17)3 perovskite formulation, which provided a more reproducible and stable composition for pscs reaching pce beyond 21%,25 and later on beyond 22% by reducing the bromide concentration.17 further progress in achieving the efficiencies that exceed 23% was reached through interfacial engineering66 and by figure 8. gradual evolution of hybrid perovskite materials. schematic representation of development through compositional engineering and molecular modulation to the layered hybrid perovskite materials. 34 michael grätzel, jovana v. milić employing either molecular modulation or layered twodimensional hybrid perovskite heterostructures.67 molecular modulation refers to utilising organic molecules within the hybrid perovskite composition with the aim of addressing a specific function at the molecular level.51 three functional areas are particularly relevant for molecular modulation (figure 9a), namely morphology alteration,68-70 passivation of defects that figure 9. molecular modulation case. (a) overview of effects of molecular modulation on hybrid perovskite solar cells: morphology alteration, defect passivation, and stability enhancement. adopted with permission from ref.51 (b) example of molecular modulators n (purple), s (grey), and sn (purple-grey) with a schematic representation of the interaction of sn with pb2+ ions (grey sphere) and the hybrid perovskite (fapbi3). (c) j-v curves of the modulated champion device recorded in reverse (black; from voc to jsc) and forward (red; from jsc to voc) scanning directions under am 1.5g solar radiation. (d) evolution of power conversion efficiency of devices over time upon continuous light illumination at 65 °c and maximum power point tracking under argon (upper) and ambient air (lower) conditions. adapted from ref.76 35the advent of molecular photovoltaics and hybrid perovskite solar cells might act as recombination centers,71-73 and stabilization of the perovskite structure against the environmental factors as well as by suppression of the internal ion migration.74,75 milic and grätzel et al. have shown that addressing these functional areas requires strategies that are based on purposefully tuning a variety of noncovalent interactions that can be employed to alter the morphology, passivate the defects, as well as selfassemble layers for either encapsulation or suppressing the detrimental ion migration.51 for instance, a bifunctional modulator, 3-(5-mercapto-1h-tetrazol-1-yl)benzenaminium iodide (sn), was developed comprising of the anilinium core (n; purple in figure 9b) that act as a hydrogen-bond-donating group for interaction with the surface of the hybrid perovskite and a thiol-tetrazolium unit (s; grey in figure 9b) to coordinate the pb2+ cations that can act as recombination centres.76 these functional groups are used as part of a hydrophobic aromatic scaffold introduced with the objective of enhancing the tolerance to environmental factors. as a result, adding the modulator to the perovskite precursor solution and treating the surface of the thin films provided a beneficial effect on the optoelectronic properties. this was evidenced in photovoltaic devices of conventional mesoscopic au/spiro-ometad/perovskite/mesoporous-tio2/compact-tio2/fluorine-doped tin oxide (fto) architecture, which were measured under conditions of standard am 1.5g illumination at light intensity of 100 mw cm–2 (figure 9c–d). the devices demonstrated an improvement of the photovoltaic performance as compared to the pristine (control) samples, including an increase of the short circuit current density (jsc), opencircuit voltage (voc), fill factor (ff), and the pce (figure 9 c–da). the jsc improvements are ascribed to the higher electronic quality of the films and effective charge collection, whereas increased voc stems from the suppression of charge carrier recombination upon defect passivation.51 this resulted in pces exceeding 20% pce, with jsc of 24 ma cm–2, voc 1.15 v, and ff up to 0.75 (figure 9c) for double cation single halide perovskite-based devices. moreover, the exceptional performance was accompanied by a long-term stability upon continuous illumination at elevated degradation conditions between 55–60 °c in either argon atmosphere or humid ambient air (figure 9d).76 this enhancement in stability and performance upon modulation corroborates the suppression of morphological changes upon aging, as well as passivation of defects, in addition to an increase in hydrophobicity that was evidenced by contact angle measurements.76 such effects of the modulation on the properties of hybrid perovskites are not limited to this modulator or a single perovskite composition.51 the atomic-level interactions responsible for this function can be analysed by solid-state nmr spectroscopy, which sets the basis for advanced molecular design. solid state nmr spectroscopy is a powerful technique that provides atomic-level information about the microstructure of the material. it has been successfully employed to scrutinize the incorporation of the variety of organic and inorganic cations into the hybrid perovskite structure.54-57 in particular, the comparison of 13c, 14n, and 15n magic angle spinning (mas) nmr spectra of neat mechanochemical α-fapbi3 and bulk mixtures with sub-stoichiometric amounts of modulators provide unique structural insights.54-58 this involves identifying the interaction between the modulator and the hybrid perovskite, assessing whether it involves incorporation of the modulator insight the a cation site, as well as whether the interaction induces any changes in the perovskite crystallographic properties (figure 10). the interaction between the modulator and the perovskite can be evidenced by the appearance of new nmr resonances in the mixtures prepared mechanochemically.51,76 for instance, a comparison between the 13c nmr spectra of the sn-modulated α-fapbi3 perovskite (figure 10a) and the neat modulator (figure 10b) reveals a set of additional carbon environments, which can be associated with the sn interacting with the perovskite. the chemical shifts can also provide more information about the interaction and scrutinize the propensity of the modulator to incorporate into the corresponding a cation sites. in this regard, the 13c and 15n nmr spectra of the neat and sn-modulated α-fapbi3 material reveals similar 13c and 15n resonances (figure 10c,d and figure 10e,f ), which suggests that sn does not incorporate into the perovskite lattice. however, a small (0.2  ppm) in the nmr spectra upon modulation evidences structural differences between the two materials, which points at the interaction taking place on the surface of the hybrid perovskite instead. such interaction can result in the changes in the crystallographic properties of the hybrid perovskite, which can be uniquely probed by 14n  nmr spectroscopy. this is due to the dependence of the breadth of the residual 14n spinning sideband (ssb) manifolds on the reorientation of fa inside the cuboctahedral cavity that is related to the symmetry of cation reorientation. specifically, narrower 14n ssb manifolds correspond to higher symmetry that is closer to cubic.54 the 14n mas nmr spectra of neat (figure 10g,i) and modulated α-fapbi3 (figure 10h,j) show a sbb pattern that becomes narrower in the modulated material. this means that the modulation of α-fapbi3 phase increases its crystallographic symmetry, 36 michael grätzel, jovana v. milić rendering it closer to cubic. moreover, the peak features the same shift in both samples, which supports the conclusion that the change is not caused by incorporation of the modulator into the a cation site but rather a result of a surface interaction.51,76 similarly, the interaction of the modulators with the potential defects, such as pbi2, can be probed, which can serve to unravel the likelihood of defect passivation. this role of molecular modulators in directing the structure of hybrid perovskites and passivating some of the defects was found to benefit the device performance and stability even for the substoichiometric amounts of the modulator. such molecular-level engineering assessed by solidstate nmr spectroscopy sets the stage for more elaborate material design with further enhanced stability, such as in the layered hybrid perovskites. layered hybrid perovskites fully incorporate the organic component within the layers of hybrid perovskite slabs. following the pioneering work of mitzi et al.77 a number of layered perovskite materials were developed over the past years. while these systems can stabilize the perovskite structure, particularly against the detrimental effect of humidity, the performances of the resulting solar cells remain inferior to those of their 3d analogues. this can be attributed to the charge transport inhibition by the organic cations that act as insulating layers, since the inorganic domains mainly contribute to the electronic charge transport.52,53 moreover, they feature a larger exciton binding energy that results in the decrease of the performance that is often related to the short circuit current losses owing to inefficient exciton dissociation.35 this can be circumvented by tuning the organic cation groups35 or by employing hot-casting fabrication techniques.31 a  unique advantage of tunability of the properties based on the molecular design of organic spacer cations permits to rely on hydrophobic chains and van der waals interactions between the adjacent layers to contribute to the stability, without compromising the crystallinity of the material.[32] commonly employed organic cations, such as the ba or pea, which form ruddlesden-popper perovskite phases, feature long alkyl chains that jeopardize the crystallinity of the materials.35,36 further engineering of the noncovalent interactions within the spacer layer has the propensity to boost the performances of this category of perovskites and the supramolecular strategies are underutilized in this context. in order to demonstrate the potential for exploiting the van der walls interactions of the spacer layer, for instance, a2fan–1pbni3n+1 (n = 1–4) compositions based on the (adamantan-1-yl)methanammonium (a) as a spacer were developed (figure 11). adamantane is a well-known building block in supramolecular chemistry that features ordered self-assembled structures based on van der waals interactions.78-83 in addition, the high symmetry and dynamics of functional adamantane systems is known to be used in plastic crystals and molecular machines.84 the utility of these systems was probed in the a2fan–1pbni3n+1 formulations based on thermally stable fa-based perovskite compositions by using stoichiometries with different numbers of layers (n = 1 – 4) separated by the spacer. the unique property of layered 2d perovskites is that they behave as natural quantum wells that feature a gradual decrease in the bandgap (eg) with an increase in the number (n) of inorganic layers, figure 10. probing molecular modulation at the atomic level by solid-state nmr spectroscopy. (a−b)  identifying interactions via 13c cross-polarization (cp) solid-state magic angle spinning (mas) nmr spectra at 11.7 t, 105  k, 10 khz mas of a) neat mechanochemical α-fapbi3 with 4 mol% sn and b) neat sn. blue circles showcase the new environments that are associated with the interaction of the modulator. (c–f ) minor changes in the chemical shift (0.2 ppm) highlighted by the blue arrows of the 13c cp and 15n cp solid-state mas nmr spectra at 11.7 t, 105  k, 10  khz mas of neat mechanochemical c,d) α-fapbi3 and e,f ) α-fapbi3 with 4 mol% sn suggest that the interaction takes place on the surface of the hybrid perovskite as opposed to by a-cation incorporation. (g–j) changes in the crystal structure of fapbi3 revealed by 14n solid-state mas nmr spectra at 11.7 t, 298 k and g,h) 3 khz and i,j) 20 khz mas of bulk mechanochemical g) α-fapbi3 and h) α-fapbi3 with 4 mol% sn implied by narrowing of the sbb manifold (grey arrows). panels i,j) shows the views of the center band. adapted from ref.51,76 37the advent of molecular photovoltaics and hybrid perovskite solar cells figure 11. hybrid layered perovskite ruddlesden-popper case. (a) uv-vis absorption spectra spectra of three different a2fan–1pbni3n+1 formulations (n = 1, 2, and 3). a = (adamantan-1-yl)methanammonium. (b) xrd  patterns on glass substrates for thin films based on the a2fan–1pbni3n+1 perovskite compositions (n  =  1, 2, and 3). the indices of the corresponding planes are based on the ruddlesden-popper systems with comparable inorganic phases ({pbi4} for n  =  1, {pb2i7} for n = 2, and {pb3i10} for n = 3).31 (c) 13c  cp  solid-state mas nmr spectra at 21.1 t, 100  k, 12 khz mas in the spectral area of the spacer (between 20 and 60  ppm) of neat ai and mechanochemical a2fan– 1pbni3n+1 (n = 1, 2, 3, →∞) powders. the n→∞ system contains a 3d α-fapbi3 perovskite powder modulated with 3 mol% ai. (d) 14n solid-state mas nmr spectra at 21.1 t, 298  k, 5  khz of neat α-fapbi3 and a2fan–1pbni3n+1 (n = 2, 3, →∞). cp = cross-polarization; mas = magic angle spinning. (e) left: schematic of the a2fa2pb3i10 composition. the arrows indicate the proximity between the fa cations and the backbone of the spacer, which provides a correlation observed by spin diffusion (sd) experiments. right:  1h-1h sd solid state mas nmr spectra at 21.1 t, 298 k, 20 khz mas of mechanochemical a2fa2pb3i10 using mixing times of 3 μs (red) and 23 ms (blue). the formulations are defined by the stoichiometry of the precursors and they include mixtures of phases for n > 2 compositions. the region inside a rectangle is magnified to highlight the low intensity cross-peaks. the black arrows show the cross-peaks that evidence atomic-level interaction between fa and a. adapted from ref.87 with permission. 38 michael grätzel, jovana v. milić from n = 1 (a2pbi4) to n = ∞ (α-fapbi3).31-35 in addition, as a result of high exciton binding energies, their uvvis absorption spectra typically show excitonic features that gradually disappear with an increase in the number of layers.85 the uv-vis absorption spectra of a2fan– 1pbni3n+1 (figure 11a) show strong exciton absorption signals and a gradual red shift of the absorption with an increase in the number of layers (figure 11a), which is suggestive of the formation of the layered structure. the excitonic absorption peaks are well defined for the n = 1–2 compositions, whereas multiple signals occur for n > 2 compositions, suggesting a mixture of different phases within a single predominant phase (figure 11a), which is typical for layered hybrid perovskite films. there is evidence that this feature can be beneficial for the electron transfer processes of interest to optoelectronic applications.85-86 with analogy to the modulated perovskite systems, the atomic-level microstructure of layered 2d perovskite materials can also be assessed by solid-state nmr spectroscopy. to probe the interaction between the spacers and α-fapbi3, 13c and 15n mas nmr spectra at 100 k are particularly insightful.54-59 the analysis requires comparing the neat spacer, the 2d perovskite compositions (n = 1, 2, and 3), and the 3d phase modified with sub-stoichiometric (e.g. 3  mol%) amount of the spacer (n →∞; figure 11c–d).51,76 the 13c nmr spectra of the (adamantan-1-yl)methanammonium spacer reveals clear differences between neat iodide salt of the spacer, layered 2d compositions, and the modified α-fapbi3 phase (figure 11c).87 the peaks shift and they are broadened compared to the signals of neat ai, which is in accordance with the existence of the spacer in a new chemical environment, interacting with the [pbi6]4slabs, as it would be the case in a layered structure. with the increasing of the n value, the 13c resonances gradually broaden, indicating structural disorder in the fa/ai phases. this is further reflected in the 14n mas spectra (figure 11d) of both a2fan–1pbni3n+1 and modulated α-fapbi3 (n→∞) compositions. unlike effective modulators shown previously, 14n nmr spectra of layered 2d systems show only subtle narrowing of the ssb manifold compared to the 3d α-fapbi3 perovskite. in this case, however, for unambiguous evidence of the atomic-level contact between fa and spacer a, it is necessary to demonstrate their presence within the same microstructure at a distance on the order of 10 å. for  this purpose, twodimensional 1h-1h spin diffusion (sd) measurements are particularly relevant (figure 11e), as in this experiment magnetization exchange is allowed to occur during a longer mixing period, which results in a correlation between species that are within 1 nm distance.58,87 for instance, the sd spectrum of a2fa2pb3i10 is symmetric around the diagonal, with the diagonal signals corresponding to those shown directly on the two projections (figure 11e). after a mixing time of 23 ms, a series of off-diagonal peaks appear that evidence the atomic-level proximity between species. this interaction can be either intramolecular (e.g. backbone of spacer) or intermolecular (between the fa cation and the spacer). as the crosspeaks are present in the spectrum for each of the two fa environments (ch and nh2+), which is correlated to the chemical environments of the spacer (the backbone, -ch2and -nh3+), this unambiguously shows that the two cations exist in the same microscopic phase.87 the analysis of structural properties of such layered systems is complemented by x-ray diffraction (xrd), as the corresponding xrd patterns commonly reveal the presence of low-dimensional phases through the appearance of low angle reflections in the 2θ range below 10 °. diffractograms of a2fan–1pbni3n+1 films on microscopic glass slides show low angle reflections below 10°, typical for layered perovskite materials (figure 11b).31-33 while the n = 1 compositions show predominant low angle reflections around 6° associated with (002) reflections that are related to the parallel orientation with respect to the substrate, the n > 1 compositions show a lattice reflection at 2θ  °15 that can be ascribed to the (111) plane, indicative of the perpendicular orientation. this orientation is of particular interest to the photovoltaic performance, as it enables effective charge extraction through the inorganic slabs. the photovoltaic properties of the layered hybrid perovskite solar cells are therefore more effective for the higher compositional representatives (n > 1), which is also in accordance with their optical properties revealed by the uv-vis absorption spectra (figure 11a). moreover, it is apparent that n  ≥ 3 compositions feature an onset above 720  nm. this is indicative of the presence of additional 3d phases.85 despite the co-existing phases, the highest-performing devices based on a2fa2pb3i10 composition show a short circuit current density (jsc) of 14.3  ma cm-2, open circuit voltage (voc) of  1.08  v, and fill factor (ff) of 0.50, resulting in a pce of 7.8% in a reverse scan,87 which is superior to other fa-based lowdimensional systems.88 furthermore, the long-term stability under full sun illumination under inert conditions at ambient temperature show that >84% of the overall pce is maintained over more than 800 h of continuous operation at their maximum power point. moreover, storage in humid ambient air with a relative humidity of ~50% maintains >90% of the initial pce after 900  h. on the contrary, pristine 3d fapbi3 pscs lose more than 50% of their performance after <200 h,88 which empha39the advent of molecular photovoltaics and hybrid perovskite solar cells sizes the potential in the performance and stabilization of layered hybrid perovskite solar cells. in this regard, the most prominent application of layered 2d perovskites is stabilization of highly efficient 3d perovskite materials. 2d/3d perovskite heterostructures are presently the most successful category of hybrid perovskite materials that meet both the performance and the stability requirements. the challenge, however, remains to retain performances comparable to the 3d pscs with high operational stabilities in ambient air. further engineering of organic spacer layers provides a productive platform to ascertain this potential, such as by engineering π interactions, through exploiting hydrophobic fluoroarene moieties. there are several examples of fluorine-containing aromatic spacers in layered hybrid perovskites over the past years.77,89 for instance, a 2d fea2pbi4 perovskite layer employing perf luorophenylethylammonium (fea) as a f luoroarene cation was inserted between the 3d hybrid perovskite film and the hole-transporting material  (figure 12).90 as a result of this overlayer, 2d/3d pscs were shown to retain 90% of their efficiency figure 12. 2d/3d perovskite heterostructure case. (a) schematic representation of a layered 2d perovskite structure incorporating perfluoroethylammonium (fea) spacer layer with the contact angle measurements of the neat 3d perovskite (left) and the corresponding 2d/3d heterostructure based on the fea overlayer (right). (b) time-resolved photoluminescence decay traces recorded for the 3d and 2d/3d perovskite films. (c) j-v curves of a 3d psc and a 2d/3d psc with the maximum power point tracking shown in the inset. (d)  ambient atmosphere ageing results of the unsealed 3d and 2d/3d pscs with the relative humidity shown in the inset. adapted from ref.90 40 michael grätzel, jovana v. milić during operation for 1000  h in humid air under simulated sunlight, which is ascribed to high hydrophobicity of the system (figure 12a,d). moreover, the 2d layer was also shown to enhance interfacial charge-extraction, suppressing non-radiative carrier recombination (figure 12b) and resulting in pce  >22% (figure 12c).90 these remarkable properties exemplify the beneficial effect of fluoroarene moieties on the structure and morphology of layered perovskite materials, as well as their heterostructures. it can be argued that such systems affect the ionic migration within the active layers of the solar cell through various ion-π interactions, which requires further investigation to exploit these molecular design concepts in the future. such investigations, in conjunction with solid-state nmr spectroscopic analysis, could set the basis for fully exploiting the strategies of supramolecular chemistry that are effectively employed by natural systems to further advance molecular photovoltaics. in summary, while a number of challenges with the hybrid perovskites remain to be addressed, recent developments in molecular design and atomic-level investigation open perspectives for further advancements. this is particularly the case in the context of molecular modulation and the development of layered perovskite architectures, which promise to revolutionize the field of hybrid perovskite solar cells. 4. perspectives for advancing dsscs and pscs dye-sensitized and perovskite solar cells have been extensively developed over the past decade, providing sustainable solutions to present energy demands. dyesensitized solar cells were inspired by natural photosynthesis and they remain the most powerful technologies for harvesting ambient light to date. their performances are complemented by an aesthetic appeal, which stimulated the first commercial applications, leading to the current yearly production in the megawatt range. this development involved a number of stages driven by molecular engineering of a variety of dyes and redox shuttles, as well as solvent-free electrolytes based on ionic liquids, fostering industrial applications. meanwhile, their efficiency remains below the theoretical limit. it is therefore instrumental to focus on the development of solid-state dye-sensitized solar cell technologies. the basis for such systems has already been established over the past years by relying on cu-based redox shuttles and co-sensitization with organic donor-π-acceptor dye systems. to drive this progress further, unravelling and controlling the interactions in the solid state is essential. towards this goal, natural systems might be able to provide inspiration. this particularly refers to controlling the assembly of the dyes and redox shuttles by relying on the strategies of supramolecular chemistry, which could enable engineering side-chains of both dyes and redoxshuttles to fine-tune their contacts. this effort should be complemented by the assessment of the potential for utilizing tandem redox shuttles for directing the electrontransfer cascades. overall, in-depth investigation of the orientation and packing in conjunction with rational supramolecular design can pave the way for overcoming the current performance limitations of dye-sensitized solar cells on the other hand, as the performance of hybrid perovskite solar cells starts to approach theoretical limits, the research focus shifts towards resolving their stability limitations without compromising the performance. in this regard, two strategies have been particularly promising, namely the molecular modulation and the development of layered two-dimensional perovskite architectures, which was facilitated by the use of solidstate nmr spectroscopy to assess the interactions at the atomic level, setting the stage for advanced molecular design. further advancements to overcome the challenges can be addressed by relying on the concepts of supramolecular engineering to develop novel supramolecular modulators, as well as layered perovskite materials with superior properties. as structure-property relationships are unravelled at the atomic level, a new platform for rational molecular design emerges to control the underlying processes. here, fine-tuning the noncovalent interactions can play a major role in controlling the phase purity and orientation of layered hybrid perovskites, while facilitating the implementation of electroactive systems and controlling the ionic motion. in addition, manipulating the interactions between the perovskite and holeand electron-transporting materials could ensure maximizing the impact of pscs. these strategies can open the way to combining the functionality exploited in artificial supramolecular systems with solar energy conversion. we predict that this approach will 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open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article consciousness, information, electromagnetism and water marc henry university of strasbourg, umr 7140, 4 rue blaise pascal, 67000 strasbourg e-mail: henry@unistra.fr abstract. there are very few things that modern science does not yet understand. one of them is consciousness; another is water. our main idea is then that if consciousness and water remain mysteries for science, it may be because the apparently different problems they pose are in fact deeply entangled. shedding light on one of them may thus have the effect of clarifying the other. in this article we explore the idea that a mirror relationship may exist between an immaterial pair formed by consciousness and information on the one hand, and a quasi-material pair formed by electromagnetic radiations and water on the other hand. it is formally deduced through group theoretical arguments applied to maxwell’s equations, that the so-called material world is not a 4d space-time continuum (named m4 hereafter), but rather a 5d-space-time-scale hyper-surface (named c5 hereafter) embedded in a 6d-continuum of consciousness (named v6 hereafter), identified as the vacuum state of quantum physics (static background) or the ether of general relativity (dynamic background). the new fifth degree of freedom in c5 is associated with the ability of living beings to grow from small size to larger size by keeping invariant their identity at all scales. the sixth degree of freedom in v6 is associated with the possibility for living beings to behave either as virtual non-observable entities, or as non-virtual observable ones. in both cases, life is associated with the ability to manage the information stored in the quantum structure of the v6ether, or in the water shells surrounding all living cells in the c5hyper-surface. memory capacities and associated bandwidths can be quantitatively evaluated from the theory and compared to experimental observations, hereby comforting the proposed approach. it follows directly from this model that space, time and mass can be considered as creations of consciousness in the form of persistent fields of bits. this strongly supports eastern philosophical ways of thinking based on vacuity, the only non-dual material reality. for western minds, the model has the great advantage to address what life and consciousness could actually be, thanks to a mathematical framework unifying physics, chemistry and biology. keywords. consciousness, group theory, information, water. introduction in a previous paper, a thought experiment reached the conclusion that consciousness has anteriority over information, energy and matter.1 in other words, the fact that consciousness pre-exists neurons should be both a philosophical as well as a scientific evidence. in another paper, it was proposed 24 marc henry that at least three levels of consciousness can be identified: a local rationale consciousness (rc) rejecting contradiction and associated to digital information processing; a meta-consciousness (mc) admitting the existence of a contradiction and associated to analogic information processing; and a non-local supra-consciousness (sc) not assigning any specific status to contradiction, thus transcending the digital/analogic duality of information.2 the non-local sc unveiled by such a scientific approach has obvious resonances with philosophical concepts such as brahman in hinduism or tao in buddhism, and with the idea of “oneness” exemplified by the mythical “ouroboros” in certain religions, and by the möbius strip or the klein bottle in topology. establishing conceptual and logical links between consciousness and information has also the advantage to give an obvious and simple explanation to the occurrence of quantum physics in the visible universe. moreover, the three notions of particles, fields and information fit nicely with the three kinds of consciousness (digital, analogic and non-dual). now, a question having a crucial connection with the understanding of consciousness is: what happens after death? here, it is worth quoting james clerk maxwell, the father of electromagnetism, who said on his death bed: i cannot help thinking about the immediate circumstances which have brought a thing to pass, rather than about any ‘will’ setting them in motion. what is done by what is called myself is, i feel, done by something greater than myself in me (campbell & garnett 1882).3  we will explain below how a fundamental key to the role of consciousness is provided by maxwell’s set of 20 equations (today reduced to 4 equations involving vectors) unifying electricity, magnetism and optics.4 the mechanism of propagation of light in the universe will help us in finding how many physical dimensions are necessary to qualify the existence of living beings and conscious entities. having identified the dimensions of our universe, it remains to be shown how information can be read, written and transferred between material/ visible structures and immaterial/invisible entities. concerning the material medium able to store and propagate information, 2d-water layers are the most viable candidates. as for the immaterial storage medium of information, we will propose quantum vacuum (ether), the existence of which is supported by leading physical theories: quantum physics and general relativity. in order to be credible, our approach must be able to give estimates of the different bandwidths associated with conscious processes involving either a watery medium or the ether. maxwell’s equations our starting point is the fact that, in current physics, any law can be considered a consequence of the existence of a symmetry group. for instance, at the time of isaac newton, space and time were seen as separate absolute entities. then, three laws of motion were formulated to fully account for related mechanical observations. then, it was realized by mathematicians that newton’s laws were the consequence of the existence of a lie group named gal(3,1). in such a notation, gal stands for the beginning of galileo’s name, the first scientist to have formulated the law of inertia. the two numbers in brackets refer to the fact that movements occur in a space having three dimensions associated to one-dimensional time unrelated with space. such a lie group is characterized by ten infinitesimal generators: three spatial translations, three spatial rotations, three galilean boosts (uniform changes in speed) and one translation describing a 3d-universe with one additional time dimension unrelated with the three spatial ones. it was easy to show that galileo’s group gal(3,1) has three casimir invariants corresponding to the laws of conservation of mass (spatial translations), energy (temporal translations) and spin (rotations). the trouble was that such a group is not able to describe electromagnetic phenomena. in other words, the famous maxwell’s equations published in 1865 ruling electricity, magnetism and optics were not invariant through the symmetry operations of gal(3,1). but, in may 1905 the french mathematician henri poincaré (1854–1912), communicating with his dutch colleague h. a. lorentz (1853– 1928), realized that the coordinate transformations leaving invariant maxwell’s equations form another symmetry group, iso(3,1), an acronym for “inhomogeneous special orthogonal” group.5 in fact, poincaré’s iso(3,1) group has seven infinitesimal generators in common with gal(3,1): three spatial translations, three spatial rotations and one translation in time. the difference is the existence of three lorentz’s boosts mixing each of the three space-coordinates with the time coordinate. a direct consequence of such a welding of space with time is that poincaré’s group displays only two casimir invariants corresponding to the conservation of a single entity called mass-energy (translations in space and time) and another one named spin (rotations in space and time). in group-theory language, mass and energy now belong to the same irreducible representation of iso(3,1), whereas in gal(3,1) mass and energy were parts of different irreducible representations. another consequence of such a welding of space with time was that our observable universe should 25consciousness, information, electromagnetism and water be considered as 4d (4 = 3+1) space-time continuum as suggested by the german physicist hermann minkowski (1864–1909). the existence of such a 4d space-time entity supported by the mathematical structure of maxwell’s equations, was a major step to establish the full validity of the special relativity theory introduced by the joint efforts of henri poincaré and albert einstein (1879– 1955).7 according to relativistic physics, speaking of an event requires to locate it in m4, i.e. specify where it has occurred in space (x = left/right, y = front/back, z = up/ down) and in time (t = past/future). however, just after the introduction of m4 minkowski’s space, it was realized that maxwell’s equations were in fact invariant under a larger lie’s group, named the conformal group iso(4,2).8 here, in addition to the ten infinitesimal generators of iso(3,1), five new generators had to be considered, one corresponding to dilatation in space and time and the four others to conformal symmetries that preserve angles between two arbitrary directions. the main consequence of such an invariance was that the universe had better be considered as a 6d-continuum (6 = 4+2) with four space-like coordinates and two time-like coordinates. this meant that by specifying only four coordinates in m4 (x, y, z, t), some ambiguity remained. taking for granted the existence of these two extra dimensions, their physical meaning had to be established. a clue was given by the fact that a m4 continuum devoid of matter remains invariant after any change in scale ‘s’ (a new coordinate measuring the 4d-spacetime dilatation). this means that besides (x, y, z, t) coordinates, one should also specify a fifth coordinate (s) setting the scale at which an observation is made. such a fifth coordinate is crucial for living entities that could exist either as a single cell or as multicellular organisms. at each cell division, the living entity gets bigger in space and older in time, suggesting that such a fifth dimension describing the ability to change in size (small/big) at a given space-time location (x, y, z, t) has something to do with the existence of life. one may also understand why a second time dimension is needed, as it is a well-known fact that the time coordinate of special relativity has nothing to do with the time of biology. accordingly, within minkowski’s space-time m4, the time reversal symmetry operation is allowed and is used to explain the matter/antimatter duality. moreover, noether’s theorem clearly states that as soon as energy is conserved, the origin of time has no absolute meaning owing to the symmetry of translation in time. it is thus impossible to describe the events of birth and death, typical of living beings in m4, because a date of birth or death has an absolute character and meaning. however, moving to the conformal space c5, i.e. considering an hyper-surface in iso(4,2), where an event is characterized by five coordinates (x, y, z, i·c·t, s), the last coordinate (s) referring to a position in scale (small/ big), it is possible to speak of birth or death in an absolute sense. from a mathematical viewpoint, by combining the dilatation symmetry operation with translation and rotation symmetries, it was possible to build a quantum-mechanical proper time operator conjugated to mass.9 in a conformal space c5, it is thus meaningful to state that a given mass has appeared here (birthplace) at a precise time (birth date) and disappeared there (death place) at a posterior time (death date). it is worth noticing that if inert matter undergoes evolution in m4 while living matter undergoes birth, evolution and death in c5 through the fifth dimension s (small/big), we are still describing the observable universe at an object-oriented level. as the conformal iso(4,2) group operates in six dimensions, it is logical to assume that the sixth dimension is a dimension allowing us to decide if a given c5 hyper-surface is observable or not. the existence of such a larger embedding space v6 where supra-consciousness operates on a virtual information field is thus not only in line with the invariance of maxwell’s equations under the symmetry operations of the iso(4,2) lie group, but also allows observing the c5 object-oriented conformal hyper-surface using an upper level meta-language giving meaning to events, and where logical contradictions occurring in c5 are resolved. another crucial point is that the use of dilatation symmetry operators may also be related to the fact that a conscious being is free to operate changes of measurement units without alteration of the observed system.10 in such an enlarged conceptual physical frame, scale invariance would be a fundamental attribute of the v6 information field. this is in line with the fact that information is basically a series of bits taking value 0 and 1, and that the memory holding such an information can be of any size. accordingly, bits may be stored on a polycarbonate support using pits (bit 1) and lands (bit 0) at a 450-780 nm scale. however, the same information could also be written on ferromagnetic domains at a 0.1-1 mm scale. typical mosfet channel lengths were once a few micrometers in size, whereas modern integrated circuits are incorporating mosfets with channel lengths of tens of nanometers. in biology, information may be coded on dna at a nanometer scale or at a micrometer scale in neurons. one could also imagine encoding information on galaxies, one galaxy corresponding to bit 1 and no galaxy to bit 0. a crucial point is that it is the alternation of 0 and 1 that defines an entity and not the 26 marc henry physical size of the memory device necessary for holding strings of bits. another crucial point is that a string of bits is meaningless unless a starting point is given for reading the chain, together with a fixed step telling how many bits should be loaded in the register memory at each read or write event. for instance, using the same string of bits, different outputs are expected using 8-bit, 16-bit, 32-bit or 64-bit processors. the choice of the starting point and of the step used for reading/writing information from a support should obviously be a prerogative of consciousness. one could then easily understand why a single and unique information field is able to hold a huge number of conscious beings. the identity of a given conscious being would then correspond to a starting point in v6, while the level of consciousness would correspond to the size of the register. the bigger the number of bits manipulated simultaneously, the higher the complexity and the level of consciousness. the fact that the information field v6 is fundamentally scale-invariant is just another way of saying that space, time and matter do not exist by themselves, being just a construction of a supra-consciousness giving different meanings to various pools of information. this was clearly perceived by henri poincaré, in a paper written in 1906 and added to french editions of his book “science and hypotheses”: one of the most surprising discoveries that physicists have announced in the last few years is that matter does not exist. (poincaré 1906).11 gravitation, mass and quantity of matter as explained elsewhere,2 the m4 minkowski’s subspace created by the generators of the iso(3,1) lie-group has been characterized by a fundamental equation w = kb·t = h·f = m·c2 = e·u = (2h·α/e)·i, stating that inert matter may through thermal, vibrational, mechanical, electrical and magnetic interactions, with a set of universal constants kb = 0,0138 zj·k-1, h = 663 zj·fs, c = 299792458 m·s-1, e = 0.16 ac and α = 1/137. we now understand that the information field of consciousness corresponds to the v6 space created by the generators of the iso(4,2) lie-group. in v6, nothing is forbidden and everything is fundamentally true. the existence of “forbidden” events is here a consequence of the choice of a particular location in v6 (identity of the observer) allowing to observe a m4 space as a projection of a c5 hyper surface along a line joining a space-time point in m4 to the fixed point in v6 and crossing the c5 hyper surface at a point defining the age of a system since its birth as a physical entity. for instance it is impossible in m4 to travel at a speed higher than einstein’s constant c (relativity), impossible to perform an action smaller than planck ’s constant h/4π = ħ/2 (quantum physics), impossible to have an entropy below boltzmann’s constant kb (thermodynamics) and impossible to bear an electrical charge lesser than coulomb’s constant e (electromagnetism). such limitations arise as soon as a conscious entity in v6 have the experience of living on a particular c5 hypersurface at a given scale corresponding to the biological age and not to the “time” of m4 that is just a coordinate for ordering 3d-events. but, in contrast with m4 spacetime coordinates, the scale coordinate in c5 is a hidden one as direct observation tells us that only the vacuum can be stretched or compressed at any scale. as soon as masses are present, this scale invariance is broken, giving the feeling to live in a m4 reality involving invariance through translations and rotations, and where dilatations of the c5 reality are no longer present. this basically means that in contrast with translations and rotations that are global symmetries of m4, dilatation symmetries of c5 are only local, the full symmetry being recovered by introducing forces between masses, explaining the occurrence of gravitation. alternatively, one may also say that changes of space-time scales preserve the velocity of light. consequently, only photons are able to perceive the full c5 space-time symmetry, massive objects seeing a broken symmetry manifested by a clear distinction between inert and living systems. however, from the viewpoint of consciousness able to unfold in a much larger space v6, such a distinction is meaningless and everything should be considered “living” either as particles, molecules, cells, rocks, plants, animals or humans. this also explains the existence of a sixth coupling constant g = c2·ru/mu, related to newton’s gravitational constant, linking spatial extent of the universe ru to its mass content mu,12 taking the value g = 66.7384 pj·kg2·m. it then becomes possible to define a quantum of spatial area ap = ħ·g/c3 (where ħ = h/2π is dirac’s constant) and a quantum of time area tp2 = ap/c2. alternatively, one may also define a quantum of mass mp, such that mp2 = ħ·c/g, allowing distinguishing between observable elementary particles having a mass less than mp and non-observable elementary particles having a mass higher than mp. existence of newton’s constant g also defines a maximum power in nature p = c5/4g ≈ 9.1×1051 w reached at the surface of a black hole. finally, it follows that one should recognize the existence of two kinds of masses, a conformal nonobservable mass m00 displaying scale-invariance in conformal c5 space and linked to the phenomenon of gravi27consciousness, information, electromagnetism and water tation, and a relativistic rest mass m0 responsible for the existence of inertia in minkowski’s m4 space, breaking vacuum’s scale-invariance. it also follows that as mass should be considered an attribute of space-time, it cannot be used to measure the amount of matter. however, from observation we know that all matter is made of atoms with a characteristic universal scaling constant na = 6.022×1023 mol-1, named avogadro’s constant, relating the mass of atoms and the one of macroscopic bodies. the fact that this constant may be found through the study of unrelated physical phenomena (gas viscosity, brownian motions, critical opalescence, color of the sky, black-body spectrum, electricity, x-rays or radioactivity) is good evidence that information is propagating in the fifth dimension of our universe. accordingly, at a given scale (coordinate s = constant), one retrieves the standard wave function ψs(x,y,z,t) of quantum physics insuring coherence between the descriptions of a particle at several different points in space and time. from quantum physics, we know that squaring the amplitude of a matter wave ψs(x,y,z,t)·ψs*(x,y,z,t) measures the probability of observing a particle at a particular position (x,y,z) at a given time (t). going to another higher scale of the same object, one retrieves a bigger mass that should correspond to a bigger number of particles, as matter particles are not scale invariant. but, as we are in the same object, its identity should not change in c5. this suggests introducing a new scaling wave function ψ(x,y,z,t,s) taking its values not only in space (x,y,z) and in time (t) but also in the scale (s). now, by squaring the amplitude of such a scaling wave ψ(x,y,z,t,s)·ψ*(x,y,z,t,s) we should obtain the probability of observing the mass of a system at any scale of observation. using conveniently scaled quantum operators, it is then possible to write a generalized schrödinger’s equation whose solutions are waves propagating with time in the scale as well as in space.13 it then follows that the square of the ratio of the amplitudes of the faster couple of such scaling waves (first two harmonics), are related by a constant n = ¼exp(4π2/ln2) ≈ 1024, giving the right order of magnitude of avogadro’s constant. including other harmonics in the description changes a little bit the value, but not the exponent. elementary particles physicists may also wonder how the standard model for elementary particles, a well-established description of nature, fits in such a scheme. a possible answer is to go back again to maxwell’s equations that have allowed us to discover the existence of a fifth and a sixth dimension. in fact, it was shown about forty years ago that maxwell’s equations were invariant under the symmetry operations of the highly symmetric iso(4,2)⊗u(2)⊗u(2) group characterized by 6×5/2 + 22 + 22 = 23 generators.14 this symmetry escaped notice for a long time because the eight integral-differential generators of u(2)⊗u(2) are associated with symmetry operations of a non-geometric nature. they are much harder to visualize than operations of the lie algebra in the neighborhood of identity.15 the nature of these operators suggests again that it should exist a communication between all scales, from the smallest to the largest and vice versa, whence nonlocality and non-separability, which are abundantly confirmed by experiments. the fact that u(2)⊗u(2) has eight generators allows establishing a direct correspondence with the symmetry group su(3) that has also eight generators (the so-called “gluons”) and responsible for the existence of the “strong” interactions between quarks. focusing our attention to the u(2) sub-group which has only four generators, it is quite satisfying to find that such a group is isomorphous to the product su(2)⊗u(1). now, the su(2) group with its three generators (w+, wand z° intermediate bosons) is responsible for the “weak ” interaction involving leptons, while the u(1) group with only one generator (the photon γ) is responsible for the electromagnetic interaction. obviously, the introduction of these new internal degrees of freedom means additional coupling constants in addition to the seven external coupling constants (kb, h, c, e, α, g and na). the best way to introduce these new constants is to use dimensionless numbers in order to comply with the basic scale invariance of the universe. taking the mass of the electron me = 9.109×10-31 kg as a reference then leads to a new constant β = mp/ me = 1638 for the strong interaction between quarks (where mp is proton’s mass), γ = gf·me2 = 3×10-12 (where gf = 1.166×10-5 gev-2 = 3.67×1048 kg-2 is fermi’s constant) for the weak interaction ruling beta-decay and δ = g·me2/(αħ·c) = 2.4×10-43 for the gravitational interaction between masses. the above approach suggests that consciousness should be compliant with physicalism stating that information may be physically stored in the v6 space underpinned by the abstract structure of the iso(4,2) symmetry group. information would be the “substance” of such a space that could well be identified with the “ether” concept introduced by aristotle and used in the xixth century for explaining light propagation in a medium devoid of matter. it is worth noticing that in order to justify the negative result of the michelson-morley experiment, existence of such an ether was denied in 28 marc henry 1905 by albert einstein in his special relativity theory. however, the same einstein was finally obliged to accept its existence in an address given on 5 may 1920 at the university of leiden: recapitulating, we may say that according to the general theory of relativity space is endowed with physical qualities; in this sense, therefore, there exists an ether. according to the general theory of relativity space without ether is unthinkable; for in such space there not only would be no propagation of light, but also no possibility of existence for standards of space and time (measuring-rods and clocks), nor therefore any space-time intervals in the physical sense. but this ether may not be thought of as endowed with the quality characteristic of ponderable media, as consisting of parts which may be tracked through time. the idea of motion may not be applied to it”.16 these words by einstein exactly define the v6-space introduced above: a non-ponderable information field (embedding ponderable c5 hyper-surfaces) with no parts which may be tracked through time, a concept belonging to the realm of m4-subspace (reversible mechanical time) or c5-subspace (irreversible biological time). in other words, v6 should be viewed as an entity existing beyond space, time and matter and being the ultimate source of any kind of reality as it holds as strings of bits all the past, present and future events of our universe. the ether of general relativity is thus the physical substance of v6 onto which it is physically possible to write or read bits of information as on any kind of memory. the only difference is that, owing to the lack of motion, it is a non-volatile random access memory (nvram) that can be configured in an infinite number of ways. in other words everything is possible within the space v6, even unphysical things that are routinely visualized during the dreams as chimera, monsters or other absurdities for the conscious “i” undergoing evolution in a c5-subspace. v6-ether is also the repository of all mathematical ideas, all scientific theories, all work of art, all music pieces, all deities, i.e. the common source of inspiration for all people involved in art, science or spirituality. as time does not exist in v6, it is impossible to use bandwidth for measuring a state of consciousness. instead, one may consider that the v6 space is covered by a multitude of trails (like footsteps in the snow) made by each conscious being. all these trails are deeply interconnected, forming a unique motif that we may identify as a state of “oneness”. concerning the mechanism for reading or writing on such an ether, one may refer to quantum loop gravity stating that the ether may exist under two distinguishable states : looped (bit 1) or un-looped (bit 0).17 from the knowledge of the age of the universe tu = 4.3×1017 s and the quantum of length lp = ap½ = (ħ·g/ c3)½, it comes that the memory capacity of our c5-universe embedded in a v6-ether is currently about m = (c·tu/lp)4 = c10·tu4/(ħ·g)2 ≈ 10244 bits. alternatively, the ether of general relativity may be replaced by the vacuum of quantum theory. at the level of the information stored in v6 this does not matter. however, after projection in a c5-subspace, where energy matters, the two viewpoints do not agree. this stems from the fact that mass m scales with length l in general relativity (m/l = g/c2) while it scales with the inverse of a length (m·l = h·c) in quantum physics. as a planck ’s force may be defined as fp = mp·c2/lp = c4/g, it follows that vacufigure 1. pictorial representation of the chasm that has opened up in the western scientific description of nature after the advent of molecular biology. the physical sciences are on the southern and biological sciences are on the northern side of the deep divide. in the reductionist landscape of the physical sciences, a road of deterministic logic leads from the most fundamental particles of all, the quarks, through atoms and molecules to complicated chemicals found in living organisms and even in minds, without any gap. this misses the crucial fact that the northern proteins work while the southern ones do not. this strongly suggests that a top-down nondeterministic logic should coexist with the bottom-up logic guiding the road through the northern landscape. drawing by john grant watterson, reproduced with permission. see http://www.thewaterpixel.com/ for a downloadable e-book of the solution proposed by j.d. watterson for bridging the chasm. 29consciousness, information, electromagnetism and water um’s energy density may be expressed either as fp/l2 = mp·c2/lp3 = c7/ħ·g2 ≈ 5×10113 j·m-3 if l = lp (quantum physics), or as fp/ru2 = c4/g·ru2 ≈ 0.6 nj·m-3 if l = ru (general relativity). this huge divergence of more than 120 orders of magnitude is one of the most stunning problems in modern physics. what is life? our western scientific mode of thinking is based on a bottom-up approach of reality where big things are thought to arise after aggregation of much smaller components. atoms are thus made from elementary particles themselves built from quarks and leptons, molecules are aggregates of atoms, cells are aggregates of molecules, tissues are aggregates of cells, bodies are aggregates of tissues, kingdoms are aggregates of bodies while aggregates of kingdoms compose the living world. for the inert world, the dominant view is that solids, liquids and gases are made of atoms or molecules, aggregating into planets belonging to stellar systems, themselves forming galaxies, the clustering of such galaxies defining the observable universe. it thus remains a deep enigma about why molecules should be the bifurcating point between living and non-living things. figure 1 is a picturing by john grant watterson of this strange situation with a chasm separating an inert protein seen as an aggregate of atoms on the one hand, from a living protein being, an entity having a precise function in a cell, on the other hand. albert szent-györgyi who won the nobel prize in physiology or medicine in 1937 was also quite lucid about such an enigma: one of my difficulties with protein chemistry was that i could not imagine how such a protein molecule can ‘ live.’ even the most evolved protein structural formula looks ‘stupid,’ if i may say so.18 in what follows we propose to fill this chasm with water that would then be the material substance making the interface between living beings and the ether. such a statement directly leads to the conclusion that the conscious ‘me’ should somehow be related to water. the fact that a living cell is 99.1 mol% water19 and that the brain is the more hydrated organ of the body is well in line with such a proposal. first, in our scheme, the distinction between inert and living things lies in the ability of a given material system to explore the fifth dimension allowing changes in size through a metabolism allowing duplication as well as the sixth dimension by being able to treat information (consciousness). by contrast, an inert thing is limited in its evolution by the m4-subspace. such a restriction has the consequence of associating the conscious ‘i’ to the activity of neurons in the brain. the trouble with such a reductionist view is that it exists other organs in the human body having neurons. for instance it is possible to record electro-gastrograms (egg) or electro-enterograms (eeng) as well as magneto-gastrograms (mgg) or magneto-enterograms (meng) for characterizing the electrical activity of the stomach and the gut.20 it is thus now accepted that it exists an enteric nervous system (ens) acting as a second brain and able to perform many of its tasks in the absence of central nervous system (cns) control.21 similarly, there is good evidence that the human heart contains a complex intrinsic nervous system comprised of multiple ganglia (clusters of neurons) that network with each other.22 neuro-cardiology has thus firmly established that the heart is a sensory organ and an information encoding and processing center, with an extensive intrinsic nervous system that’s sufficiently sophisticated to qualify as a little brain.23 associating consciousness with electrical activity of neurons then leads to byzantine discussions about the relative roles of brain, gut and heart in the “secretion” of consciousness. in our hierarchical view, it follows that neurons being made of matter surely holds in m4 a form of local consciousness (the conscious ‘i’) embedded in a supraconsciousness that extends in v6 well beyond the brain, the heart or the gut. moreover, neurons acting at the level of object-oriented language obeying to classical logic should obviously constitute one channel of expression of consciousness. accordingly, at least another channel of expression should exist involving the whole body obeying to intuitionistic logic (meta-consciousness). finally, a third channel may also be identified involving the mind/ body combination in the v6 field and obeying to minimal logic where negation simply does not exist. water, water everywhere for species living on earth, there is good evidence that water in contact with membranes made of self-assembled lipids could play the role of a hard disk memory.24 accordingly, it has experimentally proved that it was possible to convert unobservable virtual photons filling the vacuum into real photons using a mirror undergoing relativistic motion (dynamical casimir effect).25 the existence of such an energy filling the vacuum is granted by quantum field theory through the existence of an operator n whose eigenvalues corresponds to the number of quanta having a pulsation ω = 30 marc henry ∆φ/∆t, where φ is the unobserved quantum phase angle related to the internal state of each quantum. it is then possible to show that the hamiltonian of such a quantum system may be written as h/ħω = n + ½, meaning the existence of a zero-point energy zpe = ½ħω when the field is in its ground-state (vacuum) characterized by an eigenvalue n = 0.19 moreover, owing to the noncommutation between the number of quanta operator n and the phase angle operator θ, [n,θ] = -i, an uncertainty relationship ∆n·∆φ ≥ ½ exists, responsible for the existence of quantum coherence at all scales and even at a macroscopic scale.26,27 for an assembly of n similar quanta, the total energy may thus be written w = n·ħω, meaning that an uncertainty ∆n translates into an energy uncertainty ∆w = ħω·∆n. as ω = ∆φ/∆t, it finally transpires that the inequality ∆n·∆φ ≥ ½ translates into ∆w·∆t ≥ ½ħ. in other words, it is possible in quantum field theory to violate the energy conservation principle for a short duration ∆t provided that ∆t < ħ/∆w. now the water molecule is a very small entity having a diameter close to 0.3 nanometers with a first excited level rather high in energy at about 1120 zj and an energy of ionization of 2022 zj. as low-energy excited levels correspond to o-h anti-bonding states, it seems preferable using non-bonding rydberg’s levels locates on the oxygen atom for performing virtual excitations using vacuum’s energy. a good rydberg-level corresponding to 5d orbitals on oxygen and able to give a coherence gap of the same order of magnitude than the h-bond strength energy is in fact located at an energy w = 1934 zj above the ground state of the water molecule.28 this corresponds to a wavelength of self-excitation λ(μm) = 198,645/∆e(zj), i.e. λ ≈ 0.1 µm = 100 nm. as ħ = 106 zj·fs, the lifetime of such a virtual excitation should be ∆t < 106/1937 fs ≈ 10-16 seconds. on the other hand, we know that the power radiated by an electron submitted to an acceleration a is given by larmor’s formula: p = f·v = ⅔α·ħ·(a/c)2, where α ≈ 1/137 is sommerfeld’s fine structure constant (larmor 1897).29 for an electron of mass me ≈ 10-30 kg having a speed v = a·τe, we may write that p = (me·a)·v = (me·a2)·τe = ⅔α·ħ·(a/c)2, leading to a characteristic relaxation time τe = ⅔α·ħ/(me·c2) ≈ 10-23 seconds as me·c2 ≈ 82 f j. this means that the virtual photon extracted from the vacuum and having a lifetime ∆t ≈ 10-16 s is available for exciting about 10-16/10-23 = 10 millions of water molecules before its return to the vacuum. as the excitation is delocalized over n ≈ 107 water molecules, it follows according to quantum field principles that coherent domains sharing the same phase angle could form with a maximum uncertainty on the common phase angle such that ∆φ ≈ 1/2∆n or ∆φ < 5·10-8 rad with ∆n ≈ 107. the size of such coherent domains is given by the wavelength of the photon extracted from the vacuum for excitation of the water molecule, while their stability is insured by the existence of a 2d interface.30 consider now a mammalian cell having a weight of about 1 ng.31 assuming a density of 1 g·cm-3 into a volume of 10-9 cm3, corresponding to a diameter d ≈ 12 µm and an area a ≈ π·d2 ≈ 500 µm2. a well-known fact is that a lipid bilayer covered by a hydration shell delimits such a cell. with an excitation of water molecules at λ ≈ 0.1 µm, it follows that the amount of coherence domains associated to an eukaryotic cell is about ndc = 2·a/λ2 ≈ 2×500/0.01 = 100,000. the factor two stems from the fact that there is a water shell facing the extracellular medium and another water shell facing the intracellular one. as the coherence gap responsible for the cohesion of a coherence domain has an energy δw ≈ 42 zj,28 it is rather easy for the cell to have regions where coherence is on (bit 1) and other regions where the mechanism responsible for coherence is turned off (bit 0). physically speaking an energy gap δw = 42 zj, corresponds to an associated wavelength λ(μm) = 198.645/42 ≈ 4.7 µm, falling in the infra-red region of the electromagnetic spectrum. the energy needed for changing the coherence state in aqueous domains is thus readily available and could be furnished by the sun/earth couple owing to an emission at 0.5 µm by the sun associated to a re-emission at about 10 µm by the earth after processing by the biosphere. such a picture is also in agreement with the observation on any hydrophilic surface of an exclusion zone (ez-water) allowing converting ir radiation into an electrical potential in order to perform work.32 in other words, the water layers around any cell behave as a soft hard-disk upon which information may be written, deleted or read by consciousness with the help of infrared radiation. as each coherence domain stores 1 bit of information and as 1 byte = 8 bits, the memory capacity of the water shells of a eukaryotic cell may be estimated as m(cell) = ndc/8 = 105/8 ≈ 10 kb. now, the number of cells in a human body is about 3.72·1013 cells,31 leading to a static memory capacity of at least m(membranes) = 3.72·1017 bytes or 372 pb, as one petabyte (pb) = 1015 bytes. another upper estimate of the watery storage capacity of a human body is to consider a reference value of 36 liters of water, an average value between male and female in adult (20-79) us white population (ellis 2000).33 an elementary calculation also shows that water forms in a cell a hydration shell around bio-polymers corresponding to at most four monolayers of water.19 the diameter of a water molecule being about 31consciousness, information, electromagnetism and water 0.3 nm, this corresponds to a thickness of about 1 nm. a coherence domain having an area of 100×100 = 104 nm2, then occupy a volume vdc = 104 nm3 leading to a volume of 8×104 nm3 per byte of information. as 1 l = 1024 nm3, the number of bytes that can be stored in 36 l of intracellular and extracellular water is 36×1024/8×104 = 450 eb as 1 exa-byte (eb) = 1018 bytes. the recent discovery of a fluid-filled space within and between tissues named “interstitium”34 is an obvious candidate for being the watery hard-disk of the human body able to hold such a big amount of information. besides cell membranes and the interstitium, one may also consider the human gut known to hold about 3.8×1013 prokaryotes.35 we also know that a prokaryotic cell has a diameter ten times smaller than the diameter of a eukaryotic cell, meaning an area 100 times smaller. consequently, the memory capacity of the hydration shell of a prokaryote could be estimated as m(prokaryote) = 2·a×10-2/8λ2 ≈ 5/0.04 = 125 bytes. the memory capacity of the human gut is then m(microbiote) = 3.8×125×1013 = 4.75 1015 bytes = 4.75 pb, i.e. about 1% of the memory capacity of the cell membranes. however, if one considers that there are about 5×1030 prokaryotes on earth (whitman & al. 1998),36 this corresponds to a total memory capacity of 6.25×1032 bytes. by comparison, for 7.7×109 human beings in 2019 (http://www.worldometers.info for an instantaneous counting), each carrying 4.50×1020 bytes in their bodies, the amount of information is only 4.5×7.7×1029 bytes = 3.5×1030 bytes. this means that humanity participates in the memory capacity of the earth through its biosphere at a modest level of about 1%. however, as far as consciousness is concerned, considering memory capacity alone m is not enough. as recently suggested, a good measure of consciousness should be bandwidth bw(t) = dm(t)/dt, i.e. the rate of variation of information content with time.37 a reasonable bandwidth for information processing by a human being is about 10 millions of bits per second (or 1 mb·s-1) coming essentially from the sense of vision (nørretranders 1991).38 as a century is about 3 billions of seconds, the information processed in his life by a human being is thus about 3.2×109×106 = 3.2·1015 bytes = 3.2 pb. this corresponds to only 1% of the memory capacity of the body membranes. however, assuming an external stimuli bandwidth of 100 gb·s-1 (higher value in figure 2), corresponding to the memorization of all events (even those ignored by the senses) experienced during a whole human life translates into a memory capacity of 32·1018 bytes = 32 eb, i.e. about 10% of what is available in the body water (450 eb). this means that a human body is able to record and store any kind of raw data without the need to process them with the help of the conscious ‘i’. consequently, consciousness is needed for giving meaning to such raw data memorized in our body and defining what is usually called the “context”.39 as shown in figure 2, during a communication the conscious “i” discards a large part of this context that is not transmitted (exformation).38 knowing that water is the information vector in the body it is now easy to compute a bandwidth for the body, as the average water turnover of a sedentary adult is 3256 ml per day or 37 µl·s-1 (leiper & al. 1996).40 with vcd = 104 nm3 and 1 µl = 1018 nm3, this translates into a bandwidth of bw(t) = 37×1018/8×104 = 460 tb·s-1. by comparison, this is of the same order of magnitude as the global internet traffic estimated for the year 2021 at 106 tb·s-1 (cisco 2017).41 however, a much larger bandwidth may be obtained by considering water movement inside the body, independently of external losses. here, we may use the fact that on the one hand blood is distributed to the cells through about 10 billions of capillaries having an internal diameter of dc = 3.5 µm and accumulating a total cross-section of ac = 6 m2 in homo sapiens.42 on the other hand, the largest artery of the heart is the aorta with an average diameter da = 30 mm43 (hager & al. 2002) associated to an average blood flow velocity va = 76 cm·s-1 (haugen & al. 2002).44 writing the equation of continuity for steady flow of a non-compressible fluid leads to ¼π·da2·va = ac·vc = 537 cm3·s-1 corresponding to a blood velocity in capillaries vc ≈ 90 µm·s-1 associated to a quite large bandwidth bw(t) = 537×1021/8×104 = 6.7 eb·s-1 (as 1 cm3 = 1021 nm3). it should be obvious that the most probable place where such information f luxes occur are cell membranes. this means that any cell membrane could be the host of local consciousness and that primitive intelfigure 2. consciousness, information processing with bandwidths and exformation (non-transmitted information or context). 32 marc henry ligence is expected in amoebae for instance, as observed experimentally with the plasmodium of the slime mold physarum polycephalum.45 it has also been demonstrated that this mold was also able to anticipate periodic events.46 as the permeability osmotic coefficient of a lipidic bilayer for water is about 100 µm·s-1,47 we may predict for an area a(prokaryote) = 5 µm2 a bandwidth bw(t) = 5×100×109/8×104 = 6.25×106 byte·s-1 = 6.25 mb·s-1. the total bandwidth for all the prokaryotes on earth is then estimated as bwtot(t) = 5×6.25×1036 ≈ 3.1×1037 bytes·s-1. by comparison, for the whole humanity we get bwtot(t) = 6.7×1018×7.7×109 ≈ 5.2×1028 bytes·s-1, showing that our contribution to the overall consciousness of the earth is only one part per billion (ppb). in fact, in view of these huge bandwidths, it should be obvious that we are speaking here of consciousness at an object-oriented level, that is largely “unconscious”. consequently, for the blood f lowing in our capillaries one may speak of personal unconscious or freud’s “id”,49 while for the water flowing across prokaryote membranes we are probably facing the collective unconscious.50 concerning consciousness at a meta-level, we are leaving the digital object-oriented mode for landing in an analogical mode associated with muscles movements (figure 2) or with electromagnetic signals emitted by the brain, the gut and the heart (figure 3). here, it is possible, using shannon’s theory, to retrieve an information content c(t) = -σpn(t)·ln pn(t) using a time-dependent probability function pn(t) extracted from the correlations functions of such signals observed in measurements at n points.37 then, the conscious “i” bandwidth could be computed as the time derivative of this information content d(t) = dc(t)/dt. unfortunately, such a technique has not yet been applied in practice, but from figure 2, it could be anticipated a very low bandwidth of a few tens of bits.38 however, focusing heavily on information content or bandwidth miss an essential point that is a direct consequence of our modeling. accordingly, we know from the invariance of maxwell’s equations under the symmetry operations of the mathematical group iso(4,2)⊗u(2)⊗u(2) that all electromagnetic reality should be embedded in a v6-ether. figure 4 pictures such m4-reality with its associated pyramidal hierarchy for scientific knowledge represented by eight disciplines.51 fitting consciousness in such a m4 restrictive frame is generally perceived as a “hard problem”,52 while fitting free will of living beings may be referred to as the “hard question”.53 by contrast, in our proposal (figure 5), there should be no hard problem or hard question linked to consciousness. here, each conscious being occupies a certain volume in v6 with highly significant bits that never change and other bits that can be reconfigured according to experiences made on a c5 hyper-surface at a given figure 3. overview of analogic electromagnetic signals emitted by the heart, the gut and the brain, three organs containing neurons. figure 4. a picturing of the current paradigm concerning the universe according to western science. reality is manifested in a 4d-continuum called minkowski’s space having inaccessible zones out of a light cone associated to each observer. on the left, a schematic hierarchy for physical sciences according to figure 1 represented here as the progression: mathematics (mt) → physics (ph) → quantum mechanics (qm) → electromagnetism (em) → thermodynamics (th) → chemistry (ch) → biology (bl). general relativity (gr) is represented as a separate branch owing to the considerable difficulties met for merging this science with quantum mechanics. 33consciousness, information, electromagnetism and water location (x-,y-,zcoordinates), at a given time (t-coordinate) and at a given scale in space and time (s-coordinate). using group theory language, reducing the reality to a c5–space means separating the iso(4,2) group having infinitesimal generators describing an external world, from the u(2)⊗u(2) group having finite generators and describing the internal world of elementary particles (strong and weak interaction). consequently, our approach is compliant with physicalism as well as dualism. as explained above, the s-coordinate in c5 is crucial for differentiating between living being and nonliving things. accordingly, a rock has an existence in space and time at a given scale, but it is lacking software in v6 allowing it to grow by itself. in other words, for inert matter, v6 space and its m4 subspace appears to be completely disconnected owing to a poor water content. this is in deep contrast with a seed that has also an existence in m4, but owns in v6 a little rom containing down-loadable instructions on how to grow in time, i.e. change in size, using matter and energy (metabolism). at birth, the necessary information stored in the ethereal substance of v6 is transferred as rom on dna and as ram onto the hydration shells of membranes and bio-polymers. at death, information is transferred to hydration shells of earth’s microbiote or of animals after being eaten by them. the same is true for animals, but here the rom in v6 can be updated using their metabolism during their life in c5. this explains why animals, in contrast with plants, have the ability to move in c5 in order to look for food. being animals, humans are also able to reconfigure their software in v6 through their metabolism, but they have the additional capability of doing that after focusing mentally their attention (through meditation for instance) towards a particular pool of bits in v6 in a state called “mindfulness”. figure 5. a schematic view for the proposed new paradigm suggested by the invariance of maxwell’s equations through symmetry operations of the so(4,2)⊗u(2)⊗u(2) group. same abbreviations as in figure 4. 34 marc henry this would mean that humans have the ability to access mentally to the internal world of matter spanned by the u(2)⊗u(2) symmetry, while animals are doomed to use only the iso(4,2) part of reality. as the generators of the u(2)⊗u(2) group are of integral-differential nature, coupling the macrocosm with microcosm at all scales, more work is needed to understand fully their role in nature. when exchanging information between the v6 space and the c5 hyper-surface, the conscious being has the feeling of being traversed by a pure energy that could be identified with the “prana” or “qi” of eastern civilizations and whose flux is oriented by information content perceived as entropy for a western mind. accordingly, moving in the scale can only be experimented as an energy as presence of matter breaks locally the iso(4,2) symmetry, reducing it to iso(3,1) with apparition of a force named gravitation needed to restore the full symmetry on a global scale. consequently, our modeling of consciousness is intimately linked with gravitation, as proposed in the orch-r model of consciousness.54 such a reduction from iso(4,2) symmetry in c5 to iso(3,1) symmetry in m4 may be identified with wave-function collapse in quantum physics. as quoted by the cognitive neuroscientist marcel kinsbourne: “what’s make any problem hard is that something false but attractive stands in its way”.53 here the thing that is false but attractive is obviously the fact that matter exists by itself. as quoted before, the fact that matter does not exist and is an illusion was lucidly perceived by great scientists such as henri poincaré, max planck, werner heisenberg, erwin schrödinger and john wheeler.2 in our approach, einstein calls for thinking at a higher level55 means replacing the group iso(3,1) by its father iso(4,2). obviously, eastern philosophies have not waited the discovery of group theory or quantum physics to reach the conclusion that matter was an illusion and that consciousness should be the ultimate reality. what is nice is that, as demonstrated here, western science based on powerful mathematical models reaches exactly the same conclusion. our approach is also fully compliant with the concept of reincarnation typical of hinduism, the karma being the trails left in v6 by conscious beings experimenting several forms of life in c5. it is also compliant with shamanism, v6 becoming the world of spirits and more generally with all altered states of consciousness where one has a direct access to the invisible v6-reality without the necessity of experimenting death, the “normal” door to the v6-ether. another consequence is that near-death experiences (nde) or out-of-body experiences (obe) should be considered real travels in v6 with the help of consciousness and not as unreal mental images generated by a brain short of oxygen. finally, our approach points to at least three different ways of healing. healing in m4 using material drugs, healing in c5 using the ability of water to store or transmit information or by using energy (electromagnetic fields for instance), and also healing in v6 using information manipulated in a state of pure consciousness for instance. conclusion time is now ripe for science to include the phenomenon of consciousness in a physical description of the universe. according to the proposed modeling, consciousness should be the unique “true” reality of the universe generating through specific strings of bits memorized in the physical ether (rom) and written of water shells (ram) material things. such a proposal is suggested by the structure of the iso(4,2)⊗u(2)⊗u(2) symmetry group leaving maxwell’s equations through translations, rotations, boosts, scaling and conformal transformations and has the great advantage of being fully compliant with an eastern more philosophical way of thinking. our proposal also explains why the most prominent component of any living entity should be water. another important point is that it is a quantitative modeling able computing memory sizes as well as bandwidths for information processing based on the universal constants of physics conjugated with quantitative data accumulated by molecular biology as well as physiology. consequently, it is a model that is easily falsifiable by making both physical and biological measurements, a prerequisite for being accepted as a scientific model of consciousness. a very satisfactory consequence of the model is that consciousness and life are primitive attributes of the physical universe. this leads to the conclusion that the line of demarcation between physics, chemistry and biology becomes very thin, not to say imaginary. basically, depending on the hydration state, we have a whole continuous spectrum of material things ranging from inert matter with a very low level of consciousness to living matter able to express consciousness with no limits. this works by going not only from unicellular to multicellular entities, but also from multicellular entities aggregating into species and civilizations. with such a model in hand, it is easy to understand that as soon as dehydration occurs, illnesses first and then death are doomed to occur. this is just because without water bits of information “evaporate” into the ether. however, the most important thing, is that such an information transfer from water to the ether if it alters the body made of matter does not alter conscious35consciousness, information, electromagnetism and water ness that has always been located from the beginning of space and time in the non-observable v6-information field and definitively not in the observable m4-volume or c5-hyper-surface. we thus sincerely do hope that such a modeling will stimulate a large amount of legitimate scientific research around the phenomenon of consciousness. as with any kind of modeling, the fact of being right or wrong does not matter. this is because if we are right, then we have a possibility of unifying physics, chemistry and biology. on the other hand, if future research in this field would lead to the conclusion that the model is wrong, this would mean that a better modeling have been found whose discovery would have not been possible without first thinking in the wrong way. the best evidence for the necessity for science of being wrong in order to improve itself is provided by newton’s beautiful unification that was in fact based on false ideas that were rectified after the discovery of maxwell’s equations ruling electromagnetic phenomena. similarly, the marvelous maxwell’s unification was itself based on false ideas that were 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2017, vol. 3, issue 1, https://inference-review.com/letter/onthe-madelung-rule 52. d. j. chalmers, journal of consciousness studies, 2018, 25, 6. 53. d. c. dennett, phil. trans. r. soc. b, 2018, 373, 20170342. 54]  s. hameroff, r. penrose, neuroquantology, 2003, 1, 10. 56. a. einstein, the new york times magazine, june, 23, 1946, p. 7 & 42-44. https://inference-review.com/letter/on-the-madelung-rule https://inference-review.com/letter/on-the-madelung-rule substantia an international journal of the history of chemistry vol. 4, n. 1 2020 firenze university press peer review – critical feedback or necessary evil? seth c. rasmussen particular symmetries: group theory of the periodic system pieter thyssen1,*, arnout ceulemans2 consciousness, information, electromagnetism and water marc henry leonardo and the florence canal. sheets 126-127 of the codex atlanticus filippo camerota the reinvention of the nitrous gas eudiometrical test in the context of dalton’s law on the multiple proportions of combination pere grapí astatine – the elusive one keith kostecka vladimir nikolayevich ipatieff (1867-1952) – the eminent russian-american chemist of the first half of xx century aleksander sztejnberg substantia. an international journal of the history of chemistry 3(1): 9-17, 2019 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-68 citation: g. inesi (2019) similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b. substantia 3(1): 9-17. doi: 10.13128/ substantia-68 copyright: © 2019 g. inesi. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. research article similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi california pacific medical center research institute, 32 southridge rd west, tiburon ca 94920, usa e-mail: giuseppeinesi@gmail.com abstract. ca2+ and cu2+ atpases are enzyme proteins that utilize atp for active transport of ca2+ or cu2+ across intracellular or cellular membranes.1-4 these enzymes are referred to as p-type atpases since they utilize atp through formation of a phosphorylated intermediate (e-p) whose phosphorylation potential affects orientation and affinity of bound cations by means of extended conformational changes. thereby specific cations are transported across membranes, forming transmembrane gradients in the case of ca2+, or accepting cu2+ from delivering proteins on one side of the membrane and releasing it to carrier proteins on the other side. binding of ca2+ or cu2+ is required for enzyme activation and utilization of atp by transfer of atp terminal phosphate to a conserved aspartate residue. the atpase protein is composed of a transmembrane region composed of helical segments and including the cation binding site (tmbs), and a cytosolic headpiece with three domains (a, n and p) containing the catalytic and phosphorylation site. the number of helical segments and the cytosolic headpieces present significant differences in the two enzymes. in addition, details of transmembrane cation extrusion are different. the ca2+ and cu2+ atpase sustain vital physiological functions, such as muscle contraction and relaxation, activation of several cellular enzymes, and elimination of excess cation concentrations. a historic review of studies on chemical and physiological mechanisms of the ca2+ and cu2+ atpase is presented. keywords. calcium atpase, copper atpase, cation active transport. the calcium transport atpase the ca2+atpase (serca) is a mammalian membrane bound protein sustaining ca2+ transport and involved in cell ca2+ signaling and homeostasis. it is made of a single polypeptide chain of 994 amino acid residues distributed in ten trans-membrane segments (m1 – m10) and a cytosolic headpiece including three distinct domains (a, n and p) that are directly involved in catalytic activity (fig 1).5 the n domain contains residues such (phe-487) interacting with the adenosine moiety of atp whereby the atp substrate is cross-linked to the p domain. 10 giuseppe inesi the p domain contains a residues (asp-351) undergoing phosphorylation to yield a phosphorylated intermediate (e-p), a residue (asp-703) coordinating mg2+, and other features characteristic of p-type atpases. the a domain contains the signature sequence 181tge that provides catalytic assistance for final hydrolytic cleavage of (e-p). cooperative and sequential binding of ca2+ involved in catalytic activation and transport (figs. 1 and 3) occurs on sites i and ii located within the trans-membrane region.6,7 ca2+atpases (serca1 and serca2) are associated with intracellular membranes of skeletal and cardiac muscle (sarcoplasmic reticulum: sr), and especially high concentrations with the skeletal muscle sr. therefore, isolation of vesicular fragments of skeletal sr yields concentrated and fairly pure protein, shown by very frequent particles corresponding to atpase protein visualized by electron microscopy (fig 2 left panel), and prominent atpase component visualized by electrophoresis (fig 2, right panel). this preparation is very convenient for functional and structural characterization of the atpase.8 in fact, it was demonstrated (8) with this preparation that, at equilibrium and in the absence of atp, serca binds two ca2+ per mole, with high cooperativity and high affinity (2.3 x 106 m-1) (fig. 3a) at neutral ph, although the affinity is lower at low ph and higher at higher ph.9 when atp is added to sr vesicles pre-incubated with ca2+ in rapid kinetic experiments (fig 3b), the bound ca2+ facing the outer medium disappears soon (becomes non available to isotopic exchange, i.e., occluded), indicating that the outer opening of the binding cavity closes to the outside medium as soon as a first reaction product with atp is formed. pi release and further ca2+ uptake then occur following a delay, indicating that trans-membrane ca2+ release and hydrolytic cleavage of ep occur after a slow step and, soon after that, further cycles contribute to steady state activity.10 based on these kinetic observations, a diagram is shown in fig. 4, where the basal enzyme is indicated as 2h+.e2. following 2ca2+ binding in exchange for 2h+, the active enzyme is referred to as e1.2ca+. following binding and utilization of atp, the resulting phosphoenzyme is indicated as adp.e1-p.2ca2+. upon release of adp, the free energy associated with this intermediate is utilized for a slow conformational change yielding transmembrane release of bound ca2+ in exchange for 2 h+, figure 1. aminoacid sequence and two dimensional folding model of the serca1 ca2+ atpase.5 see text for explanations. figure 2. purified vesicular fragments of sarcoplasmic reticulum membrane shown by negative staining on electron microscopy. on the right side, electrophoretic analysis demonstrates that the protein composition consists almost entirely of ca2+ atpase.8 figure 3a. ca2+ binding to sr atpase under equilibrium conditions, in the absence of atp. the stoichiometry of binding is 2 ca2+ per atpase, with a binding constant of 2.3 x 106 m-1, and high cooperativity.9 figure 3b. pre-steady state activity of sr vesicles started by addition of atp in the presence of ca2+. note that upon addition of atp a rapid burst of ep formation occurs and, at the same time, 2 ca2+ per atpase become occluded. steady state pi production and further ca2+ uptake then follow, with a ratio of 2 ca2+ per pi produced.10 11similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b followed by hydrolytic cleavage of pi and return to the basic 2h+.e2 state. the reaction scheme in fig. 4 outlines a specific exchange of 2 ca2+ for 2h+ in the 2h+.e2 state and 2h+ for 2 ca2+ in the e2-p.2ca+ state. clear evidence for this exchange was obtained with serca reconstituted in phospholipids vesicles that do not allow trans-membrane passive leak of charge which occurs in native sr membranes (except for transported ca2+). ca2+ and h+ concentrations and electrical potential were then measured with appropriate sensors (fig. 5). it was found that addition of atp was accompanied by ca2+ uptake and stoichiometric h+ extrusion, as well as formation of electrical potential.11 the important role of h+ at the ca2+ sites was also demonstrated in experiments with native membrane vesicles, as it was found that phosphorylation of atpase with pi can be obtained only at acid ph. this indicates that upon 2 h+ binding to e2 (in exchange for ca2+ if present) the resulting 2h+.e2 acquires a specific conformation and free energy to allow phosphorylation with pi, i.e. reversal of the e2-p.2ca2+ to 2h+.e2 step in the atpase reaction cycle.12 pioneering and highly informative crystallography by toyoshima et al. revealed detailed structural information on the molecular structure of the entire molecule.13 nucleotide and phosphorylation domains of the ca2+ atpase, relative to different stages of the enzyme cycle, are represented in fig 6.14 in the figure, the structure and conformational states of the ca2+ atpase in the presence and absence of ca2+, substrate and product analogs are represented, with reference to e1. 2ca2+, e1.amppcp, e-2.alf4.(tg), and e2.(tg).atp, where tg (thapsigargin, a highly specific and potent serca inhibitor) is used to stabilize e2.13, 15, 16, 17 color changes gradually from the n-terminus (blue) to the c-terminus (red). the two ca2+ (i and ii) bound to the high affinity transmembrane site are circled when present. the two bound ca2+ undergo vectorial release in e2.alf4.(tg), as the binding sites undergo a change in affinity and orientation. three key residues (e183 in the a domain, d351 and d703 in the p domain) are shown in ball-andstick. note the positional change of headpiece domains in the various conformations. note the nucleotide binding to the n domain, and variable relationship of the nucleotide phosphate chain (and mg2+) with the p and a domains. as described above, kinetic and structural information yields a detailed understanding of the ca2+ atpase catalytic and transport cycle as outlined in fig. 4. figure 4. diagram outlining the sequential reactions of a ca2+ atpase cycle at neutral ph. the cycle starts with the enzyme in basal conformation, with h+ bound at the specific ca2+ exchange site (2h.e2). upon h+ dissociation, 2ca2+ bind and the enzyme is activated (e1.2ca). atp then leads to formation of the high potential phosphorylated intermediate (adp.e1*p.2ca). following dissociation of adp, the phosphorylated intermediate uses its potential for a conformational change reducing affinity and orientation of bound calcium. 2 ca2+ are then dissociation in exchange for 2 h+. the residual phosphoenzyme then undergoes hydrolytic cleavage with release of pi, and returns to the basal conformation with h+ bound (2h.e2). the stoichiometry of h+ binding is 2 per e at neutral ph. at high ph, less or no h+ exchanges for ca2+. thereby ca2+ is not released before pi cleavage, and the enzyme undergoes an uncoupled cycle. figure 5. atp dependent ca 2+ uptake, h+ countertransport and development of transmembrane electrical potential in reconstituted serca proteoliposomes. the proteoliposomes were placed in a neutral ph medium, containing 100 mm k2so4, 50 microm cacl2, and color reagents for detection of ca2+, ph and electrochemical gradients. the reaction was started by the addition of 0.2 mm atp, and followed by differential absorption spectrometry.11 12 giuseppe inesi the copper transport atpase bacterial and mammalian copper atpases sustain active transport of copper by utilization of atp . the mammalian cu+ atpases include isoforms (atp7a and atp7b) that are involved in copper transfer from enterocytes to blood, copper export from the liver to the secretory pathways for incorporation into metalloproteins, and general copper homeostasis.18,19 genetic defects of atp7a and atp7b are related to human menkes and wilson diseases.20, 21, 22 cu2+ atpases present functional analogies to the ca2+ atpases, but specific differences as well. a comparison of serca and atp7b bidimentional folding models (fig. 7) shows that atp7b comprises eight (rather than ten) transmembrane segments that include the copper binding site (tmbs) for catalytic activation and transport, and a headpiece comprising the n, p and a domains with conserved catalytic motifs analogous to serca. a specific feature of atp7b (less prominent in atp7a, and absent in the bacterial copper atpase) is an amino-terminal extension (nmbd) with six copper binding sites in addition to those in the tmbd. an additional feature is the presence of serine residues (ser478, ser-481, ser1211, ser-1453 in atb7b) undergoing kinase assisted phosphorylation.23 the native abundance of copper atpase is quite low and, in order to accomplish biochemical experimentation, larger quantities were obtained by heterologous expression in insect or mammalian cells.24, 25 it was found that addition of atp to microsomes expressing heterologous atp7b yields two fractions of phosphorylfigure 6. sequence of conformational states of the calcium atpase in the presence (e1.2ca2+), following nucleotide (analog) substrate binding (e1.amppcp), following enzyme phosphorylation (alf4 analog) and ca2+ release (e2.alf4.tg) and in absence of ca2+ with bound atp (e2(tg).atp).14 figure 7. two-dimensional folding models of the ca2+ atpase (serca1) and cu+ atpase (atp7b) sequence. the diagram shows ten serca or eight atp7b transmembrane domains including the calcium or copper binding sites (tmbs) involved in enzyme activation and cation transport. the extra-membranous regions of both enzymes comprises a nucleotide binding domain (n), the p domain with several conserved residues (in yellow) including the aspartate (asp351 and asp1027) undergoing phopsphorylation to form the catalytic intermediate (ep), and the a domain with the tge conserved sequence involved in catalytic assistance of ep hydrolytic cleavage. the his1069 residue whose mutation is frequently found in the wilson disease is shown in the atp7b n domain. specific features of atp7b are the n-metal binding domain (nmbd) extension with six copper binding sites, and serine residues undergoing protein kinase assisted phosphorylation (ser478, ser 481, ser1211, ser1453).23 13similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b ated atpase protein, one acid labile corresponding to phosphoenzyme intermediate, and the other acid stable and dependent on kinase assisted phosphorylation. acid labile phosphoenzyme is faster, and is not observed following mutation of the conserved aspartate (s1024) at the catalytic site, or following mutation of the transmembrane copper binding site (tmbd). kinase assisted formation of alkali resistant phosphorylation is slower, involves ser478, s481, ser1121 and ser1453, and is not observed in the presence of protein kinase inhibitors. interestingly, it is not observed following mutation of the trans-membrane copper binding site (tmbd), indicating a dependence on enzyme activation (e2 to e1) transition. specific features of copper atpase following addition of atp are shown in fig 8, to demonstrate the difference in phosphorylation of aspartate and serines in the copper atpase. the time course of atp7b following addition of atp is shown in fig 8a, with total phosphoenzyme (black squares) including acid and alkaline resistant (dark squares, including aspartate phosphoenzyme intermediate and phospho-serines), acid resistant (dark circles, i.e. aspartate phosphoenzyme intermediate) and alkaline resistant (light squares, i.e. phosphorserines). it is shown in fig 8b that no alkaline resistant phospoenzyme (i.e. phospho-serines, light squares) is observed if protein kinase inhibitor is present, and in fig 8c no acid resistant aspartate phosphoenzyme (dark circles) is observed when d1027n atp7b is used. by comparison, it is shown in fig 8d that wt serca undergoes only acid stable aspartate phosphorylation, and no alkali resistant serine (light squares) phosphorylation, i.e. the acid stable accounts for total phosphorylation .25 an estimate of cu2+ transport following phoshorylation of atp7b with atp was obtained by comparing microsomes of cos-1 expressing ca2+ atpase (serca) or cu+ atpae (atp7b) absorbed on a solid supported membrane (ssm). the ssm consists of an alkanethiol monolayer covalently bound to a gold electrode via the sulfur atom and a phospholipids monolayer on top of it.26, 27, 28 the adsorbed protein is activated by addition of atp in the presence of a medium supporting atpase activity. related electrogenic events are recorded as current transients due to flow of electrons along the external circuit toward the electrode surface, as required to compensate for the potential difference across the vesicular membrane produced by displacement of positive charge upon vectorial translocation in the direction of the ssm electrode. when atp is added to the membrane bound atpase absorbed on the ssm in the presence of ca2+ or cu2+, a current transient is obtained due to vectorial translocation of bound ca2+ or cu2+ in the direction of the ssm electrode after phoshoenzyme formation by utilization of atp. in these experimental conditions, the electrogenic signal generated within the first enzyme cycle is observed.29 it is shown in fig 9a that in experiments with serca that the charge transfer observed at neutral ph is much reduced at acid ph. on the other hand, the charge transfer observed with atp7b is significantly slower, and is not changed by alkaline or acid ph (fig 9b). this difference is due to the lack of cu2+/h+ exchange in the cation binding and release sites of the copper atpase, as opposed to the requirement of ca2+/h+ exchange in the calcium atpase. a crystallographic view of the copper atpase protein and of the copper transport pathway across the membrane was obtained through lpcopa crystallization, trapped in the e2.pi, as compared with e2p state.31 the two states show the same conduit, appearing equivalent and open to the extracellular side, in contrast to the figure 8. phosphorylation of wt atp7b (a, b), atp7b d1027n mutant (c), and wt serca (d), in the absence (a, c and b) and in the presence of proteinase k inhibitor. microsomes obtained from cos-1 cells sustaining expression of the various atpases were incubated with 50 microm (gamma -32p)atp in a reaction mixture sustaining enzyme activiy at 30 oc, in the absence (a, c and d) or in the presence (b) of pkd inhibitor. electrophoresis was then performed at acid ph to measure total phosphoproteins (black squares), or alkali ph to eliminate alkali labile phosphoenzyme and assess alkali resistant serine phosphorylation (empty squares). the difference (given in in the absence (a, c and d) or in the presence (b) of pkd inhibitor. electrophoresis was then performed at acid ph to measure total phosphoproteins (black squares), or alkali ph to eliminate alkali labile phosphoenzyme and assess alkali resistant serine phosphorylation (solid black circles) corresponds to the phosphorylated aspartate enzyme intermediate.25 14 giuseppe inesi calcium atpase where the e2.pi state is occluded. in fig 10a the a, p and n domains are colored in yellow, blue and red, respectively. the black arrows mark the copper transport pathway. in fig 10b the e2p (pink) and e2.pi (green) states are compared, showing movements of the extracellular domains (arrows), while the transmembrane domain remains rigid in two states, in contrast to the calcium atpase where the e2.pi becomes occluded. fig 10c shows a close up of the extrusion pathway with the opening from the copper high affinity coordinating residues cys382, cys384, and met717 shown as a red surface, with crystallographic water molecule shown as red spheres. a diagrammatic comparison of the calcium and copper atpases is shown in fig 11, where the sequential conformational transitions of the catalytic and transport cycle are compared for calcium and copper atpases.30 we then see that the two calcium ions exit the atpase from the e2p state, and the ion exit pathway closes concomitantly to hydrolytic cleavage of pi and transition to the e2.pi state. on the other hand, the copper ions exit the atpase from the e2p state, but the exit pathway remains open in the e2.pi state, and closes only in the e2 state after release of pi. considering experimental results and modeling shown above, there seems to be a clear parallel between the difference in cation/proton exchange, and the conformational outcome in the exit pathways following cation release in the two atpases. it is apparent that the closure of the release pathway in the calcium atpase is due to h+ binding in exchange for ca2+, and a consequent conformational effect on the e2.pi state. the pathway closure in the copper atpase occurs only following release of pi and acquisition of the e2 conformation. a further distinctive feature of the copper atpase is the effect of phosphorylation of serine residues catalyzed by proteine kinase d.25 in experiments with microsomes of cos1 cells or hepatocytes expressing atp7b it was found that utilization of atp by atp7b includes autophosphorylation of an aspartyl residue serving as the specific catalytic intermediate, as well as phosphorylation of serine residues catalyzed by protein kinase d. it is shown in fig 12 a that atp7b (stained in green) interacts first with transgolgi network (blue) in perinuclear (nuclei red) location and, in the presence of cu2+, is transferred to intracellular trafficking vesicles. it is shown in fig12 b that the trafficking is not interfered with by mutation of the tmbd asp1027 (whose phosphorylation serves as phosphoenzyme intermediate). on the other hand, trafficking is interfered by ser478, 481, 1121 and 1453 mutations in the nmd (fig12c), by tmbs copper site mutation (fig 12d), and by mutation of the 6th nmbd copper site mutation (fig 12 e). this demonstrates that the nmd, absent in the calcium atpase, plays a determinant role in conformational adaptations required for functions of the copper atpase. figure 9. charge measurements measured with enzymes absorbed on solid supports member (ssm). a: current transients following addition of atp to serca in a reaction mixture including 10 microm free ca2+ and 100 mm kcl at ph 7.0 (solid line) or ph 7.8 (dotted lines). c: current transients after addition to atp on atp7b in a reaction mixture containing 5 microm cu+ and 100 mm kcl at ph 6.0 (solid line) or 7.8 (dotted line).28 figure 10. diagrammatic representation showing that crystal waters of the e2-bef3structure support the copper release pathway.30 15similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b physiological roles of ca2+ and cu+ atpases ca2+ is a specific activator of muscle fibrils. activation of contraction depends on ca2+ delivery and, in turn, and relaxation depends on reduction of ca2+ concentration in the cytoplasm of skeletal and cardiac muscle cells. at rest, the cytosolic concentration of ca2+ is much lower than in extracellular fluids and in the intracellular vesicles of sarcoplasmic reticulum. muscle activation occurs when plasma membrane electrical action potentials open passive ca2+ channels, allowing flux of ca2+ in the cytosol for activation of myofibrils. following the end of action potential, passive channels close, and cytosolic ca2+ is returned to extracellular fluids and to the sarcoplasmic reticulum interior through active transport by the ca2+ atpase. due to time limits and quantities of ca2+ available, passive fluxes and active transport across the sarcoplamic reticulum membrane are much prevalent over those across the outer plasma membrane. in the diagram on fig 13, a cardiac myocyte is shown with the ca2+ atpase (atp) inserted in the plasma membrane (sarcolemma) and the sarcoplasmic reticulum membrane, collecting ca2+ to induce relaxation, and to be then released upon membrane excitation to induce contraction upon binding to myofibrils.31 the inset shows the time course of an electrical action potential, ca2+ release, and occurrence of contraction. channels for passive diffusion of ca2+, and mitochondria are also shown. copper is a required metal for homeostasis of plants, bacteria and eukaryotic organisms, determining conformation and activity of many metalloproteins and enzyme such as cytochrome oxidase and superoxide dismutase. furthermore, due to possible reactivity with non-specific proteins and toxic effects, elaborate systems of absorption, concentration buffering, delivery of specific protein sites and elimination, require a complex system including small carriers, chaperones and active transporters. the p-type copper atpases provide and important system for acquisition, active transport, distribution and elimination of copper. a diagram of copper distribution in eukaryotfigure 11. diagrammatic comparison of the calcium and copper atpases, showing the sequential conformational transitions of the catalytic and transport cycle. the two transported calcium ions exit the atpase from the e2p state, and the ion exit pathway closes concomitantly to hydrolytic cleavage of pi and transition to the e2.pi state. on the other hand, the copper ions exit the atpase from the e2p state, but the exit pathway remains open in the e2.pi state, and closes only in the e2 state after release of pi.30 figure 12. intracellular distribution of atp7b in cos1 cells expressing wt enzyme (a), subjected to mutation at asp-1027 (b), ser-478, ser-481, ser-1121 and ser-1453 (c), at the transmembrane (tmbd) copper site (d), or at the sixth nmbd copper site (e). note the presence of cytosolic trafficking vesicles with wt enzyme (a), and even and even following asp-1027 mutation (b), but no trafficking following serine, nmbd or tmbd copper sites (c, d and e).25, 29 16 giuseppe inesi ic cells is given in fig. 14, where it is shown that copper is imported into the cells copper permeases (ctr1: oval cell membrane bound circles).32 incoming cu2+ does not remain free in the cytosol, but is rather bound to various chaperones delivering it to specific proteins and secretory pathway. the cu2+ atpase (ccc2 in the figure with the trans-golginetwork) binds cu2+ through the intervention of the atx1 chaperone, for delivery and transport across the cell membrane, or other destination depending on cell specificity. cu2+ delivery to the cytochrome c oxidase complex (cco) involves cox11, sco1 and cox 17 chaperones. nuclear encoded chaperone proteins are imported unfolded across the mitochondrial membrane by a translocase, and then acquired in the inner mitochondrial space following introduction of disulphide bonds with the intervention of specific coupled enzyme. in summary, it is evident that ca2+ and cu2+ atpases are indispensable components of physiological systems, and the chemistry of their catalytic and transport mechanism is linked to biological function. transport atpases are required to regulate the concentrations of ca2+ and cu2+ within cells and cellular compartments, utilizing the energy of atp to sustain appropriate concentrations across membranes. appropriate cation concentrations are required to activate specific enzymes in one direction, and to produce relaxation and avoid toxic consequences in the other direction. references 1. r.w. albers, ann. rev. biochem. 1967, 36, 727-756. 2. r.l. post, c. hegyvary, s. kume, j. bio. chem. 1972, 247, 6530. 3. l. de meis, a. vianna, ann. rev. biochem. 1979, 48, 275. 4. g. inesi, j. cell commun signal 2011, 5, 227. 5. d.h. maclennan, c.j. brandl, b. korczak, n.m. green, nature 1985, 316, 696. 6. d.m. clarke, t.w. loo, g. inesi, d.h. maclennan nature 1989, 339, 476. 7. j. p. anderssen , b. vilsen, febs letters 1995, 359: 101. 8. d. scales, g. inesi, biophys j. 1976, 16, 735. 9. g. inesi, m. kurzmack, c. coan, d. lewis, d., j. biol. chem. 1980, 255, 3025. 10. s. verjovski-almeida, m. kurzmack, g. inesi, biochemistry 1978, 17, 5006. 11. l. hao, j.l. rigaud, g. inesi, j. biol. chem. 1994, 269, 14268. 12. l. demeis, g. inesi, biochemistry 1985, 24, 922. 13. c. toyoshima, m. nakasako, h. nomura, h. ogawa. nature 2000, 405, 647. 14. g. inesi, d. lewis, h. ma, a. prasad, c. toyoshima, biochemistry 2006, 45, 13769. 15. c. toyoshima, t. mizutani, nature 2004, 430, 529. 16. c. olesen, t.l. sorensen, r.c. nielsen, j.v. moller, p. nissen, science 2004, 306, 2251. 17. a.l. jensen, t.l. sorensen, v. olesen, j.v. moller, p. nissen, the embo journal 2006, 25, 2305. 18. j.m. arguello, s.j. patel, j. quintana, matallomics 2016, 8, 906. figure 13. ca2+ transport in ventricular cardiac myocytes. atp: atpase. ncx: na+/ca2+ exchange, sr: sarcoplasmic reticulum. bers dm. cardiac exitation-contraction coupling.31 nature 2002; 415 :198-205 figure 14. diagram of copper eukaryoyic cellular distribution. see text for explanations.32 17similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b 19. s. lutsenko, n.l. barnes, m.y. bartee, o.y. dmitriev, physiol rev. 2007, 87, 1011. 20. c. vulpe, b. levinson, s. whitney, s. packman, j. gitschier, nat. genet 1993, 7, 13. 21. j.d. gitlin, gastroenterology. 2003, 125, 1868. 22. m. harada, med. electron. microsc. 2002, 35, 61. 23. r. pilankatta, d. lewis, c. m. adams, g. inesi, j. biol. chem. 2009, 284, 21207. 24. y.h. hung, m.j. layton, i. voskoboinik, j. f. mercer, j. camakaris, biochem j. 2007, 401: 569. 25. r pilankatta, d. lewis, g. inesi. j.biol chem 2011, 286, 7389. 26. j. pintschovius, k. fendler, e. bamberg, biophys. j. 1999, 76, 827. 27. f. tadini-buoninsegni, g. bartolommei, m.r. moncelli, r. guidelli, g. inesi, j. biol. chem. 2006, 281, 37720. 28. g. tadini-buoninsegni, g. bartolommei, m.r. moncelli, r. pilankatta, d. lewis, g. inesi, febs lett. 2010, 584, 4519. 29. d. lewis, r. pilankatta, g. inesi, g. bartolommei, m. r. moncelli, f. tadini-buoninsegni, j. biol. chem. 2012, 287, 32717. 30. m. andersson, d. mattle, o. sitsel, a.m. nielsen, s. h.white, p. nissen, p. gourdon, nat. struct. mol. biol. 2013, 21: 43-48. 31. m.d. bers, nature 2002, 415, 198. 32. n.j. robinson, d.r. winge, annual rev. biochem. 2010, 79, 537. substantia an international journal of the history of chemistry vol. 3, n. 1 march 2019 firenze university press i won a project! juan manuel garcía-ruiz similarities and contrasts in the structure and function of the calcium transporter atp2a1 and the copper transporter atp7b giuseppe inesi finding na,k-atpase ii from fluxes to ion movements hans-jürgen apell range separation: the divide between local structures and field theories david m. rogers hydration of silica and its role in the formation of quartz veins part 2 john elliston chuckles and wacky ideas carl safina the increased anthropogenic gas emissions in the atmosphere and the rising of the earth’s temperature: are there actions to mitigate the global warming? francesco barzagli1,2, fabrizio mani2 the ‘consciousness-brain’ relationship jean-pierre gerbaulet1, pr. marc henry2 dmitry i. mendeleev and his time dmitry pushcharovsky early contributions of crystallography to the atomic theory of matter giovanni ferraris bringing together academic and industrial chemistry: edmund ronalds’ contribution beverley f. ronalds substantia. an international journal of the history of chemistry 3(2): 97-103, 2019 firenze university press www.fupress.com/substantia issn 1827-9643 (online) | doi: 10.13128/substantia-639 citation: a. sztejnberg (2019) vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry. substantia 3(2): 97-103. doi: 10.13128/substantia-639 copyright: © 2019 a. sztejnberg. this is an open access, peer-reviewed article published by firenze university press (http://www.fupress.com/substantia) and distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article vladimir vasilyevich markovnikov (18381904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg professor emeritus, university of opole, oleska 48, 45-052 opole, poland e-mail: a.sztejnberg@uni.opole.pl abstract. this is a survey of the literature concerning the empiric rule developed by vladimir vasilyevich markovnikov in 1869 and its various, unauthentic versions, which are available in the organic chemistry textbooks published in the xx and xxi centuries. this survey is supplemented with: 1) information about markovnikov’s chemical research, 2) selected facts of his life. keywords. v.v. markovnikov, organic chemistry, markovnikov’s rule, unsaturated hydrocarbons, russia xix century. wording of the original markovnikov’s rule in 1869-1876, vladimir vasilyevich markovnikov (fig. 1) presented the formulation of his empiric rule in a few articles published in russia, germany and france. this rule, known in the chemical literature as markovnikov’s rule, appeared for the first time in the article entitled materialy po voprosu o vzaimnom vliyanii atomov v khimicheskikh soyedineniyakh (materials on the question of the mutual influence of atoms in chemical compounds) in the uchenyye zapiski imperatorskogo kazanskogo universiteta (scientific notes of the imperial kazan university), that was published in 1869. markovnikov wrote: «если к такому пропилену будет присоединяться галоидоводородная кислота, то является вопрос: который из углеродов более способен соединяться с галоидом и который с водородом? опыт показывает, что галоид присоединяется к наименее гидрогенизированному углероду, m.е. к mакому, который наиболее подвержен влиянию других углеродных паев» [1,2]. the translation of the russian text describing the original markovnikov’s rule is the following: “if a hydrohalic acid is added to such a propylene, then the question is: which carbon is more capable of combining with a halogen and which one with hydrogen? experience shows that the halide adds to the least hydrogenated carbon, that is, to the one most susceptible to the influence of other carbon units”. 98 aleksander sztejnberg in 1870, markovnikov published an article entitled ueber die abhängigkeit der verschiedenen vertretbarkeit des radicalwasserstoffs in den isomeren buttersäuren (on the dependence of the various acceptability of the hydrogen chloride in the isomeric butyric acids) in the journal justus liebigs annalen der chemie. at the end of this article he presented a german version of his rule as follows: „...wenn ein unsymmetrisch constituirter kohlenwasserstoff sich mit einer haloïdwasserstoffsäure verbindet, so addirt sich das haloïd an das weniger hydrogenisirte kohlenstoffatom, d. h. zu dem kohlenstoff, welcher sich mehr unter dem einflusse anderer kohlenstoffe befindet ” [4]. the translation of the german text is the following: “when a hydrocarbon with an unsymmetrical structure combines with a halogen hydracids, the halogen adds itself to the less hydrogenated carbon atom, i.e. the carbon which is more influenced by the presence of another carbon”. markovnikov in this article presented the equations of the addition of hydroiodic acid (hj) to: propylene (1), 2-methylpropene (2), 1-butene (3), alpha-amylene (1-pentene) (4) and reaction of the addition of hydrochloric acid (hcl) to 3-methyl-1-butene (5) as examples of the application of his rule. in these equations he showed the formulae of both substrates and products of these reactions in the form which was typical at that time. in this article semi-structural formulae were used to illustrate these reactions: ch3chch2 + hj = ch3ch(j)ch3; (1) (ch3)2cch2 + hj = (ch3)2c(j)ch3; (2) c2h5chch2 + hj = c2h5ch(j)ch3; (3) c2h5ch2chch2 + hj = c2h5ch2ch(j)ch3; (4) (ch3)2chchch2 + hcl = ch3)2chch(cl)ch3 [4]. (5) in 1875, markovnikov published his rule in french in the journal comptes rendus hebdomadaires de séances de l’academie de sciences: «en examinant la plupart des cas, suffisamment étudiés, de l’addition directe, je suis arrivé, il y a quelques années, à la conclusion suivante: lorsqu’ à un hydrocarbure non saturé, renfermant des atomes de carbone inégalement hydrogénés, s’ajoute un acide haloïdhydrique, l’ élément électronégatif se fixe sur le carbone le moins hydrogéné. … cette loi générale semble être adoptée aujourd’hui par la plupart des chimistes» [5]. the english translation of the french version is: “in examining most of the sufficiently studied cases of direct addition, a few years ago i came to the following conclusion: when to an unsaturated hydrocarbon, containing unequally hydrogenated carbon atoms, a halohydric acid is added, the electronegative element is fixed on the least hydrogenated carbon. ... this general law seems to be adopted today by most chemists”. french language version of the original markovnikov’s rule is very similar to the russian one, which was published by markovnikov in the article entitled o zakonakh obrazovaniya pryamykh soyedineniy nepredel’nymi organicheskimi chastitsami (on the laws of the formation of direct compounds by unsaturated organic particles) in the journal zhurnal russkogo khimicheskogo obshchestva in 1876. markovnikov wrote: «разбирая большинсво случаев прямого соединения углеводородов, я пришел несколько лет тому назад к заключению, что при соединении несимметрично построенных углеводородов с галоидоводородными к и с л о т а м и г а л о и д (эл е к т р о о т р и ц а т е л ьн ы й э л е м е н т) п р и с о е д и н я е т с я к н а и м е н е е гидрогенизированному углероду. … это положение применяется ныне, повидимом у, большинством химиков» [2,6]. summing up, one may say that in the cited versions of the original markovnikov’s rule in three languages (russian, german, and french) we are talking about “the addition of the halogen atom from halohydric acid to the less hydrogenated carbon atom of the unsymmetrical molecule of the unsaturated hydrocarbon”. figure 1. vladimir vasilyevich markovnikov (1838-1904) (public domain, from reference 3). 99vladimir vasilyevich markovnikov (1838-1904) david e. lewis, professor of chemistry at the wisconsin-eau claire university (u.s.a.) in his book entitled early russian chemists and their legacy (2012), referring to the article which markovnikov published in the comptes rendus hebdomadaires des séances de l’acdemie des sciences [5] stated that: “he [markovnikov] had established a solid experimental basis for his rule based on his studies of halohydrin formation and other additions to alkene hydrocarbons” [7]. references to the markovnikov’s original rule in the chemical literature analysis of the chemical literature from the years 1908 – 2019 shows that some authors referred to the original markovnikov’s rule in their publications. in 1908, british chemist alfred walter stewart (1888-1947), lecturer on the stereochemistry at the london university college in his book entitled recent advances in organic chemistry explained an application of this rule emphasized that in reaction of hydrobromic acid addition to 2-methylpropene “(ch3)2c=ch2” 2-bromo-2-methylpropane “(ch3)2cbr-ch3“ is produced and not 1-bromo-2-methylpropane “(ch3)2ch-ch2br” [8]. in 1922, the german chemist richard stoermer (1870-1940), professor of organic chemistry at the university in rostock formulated the original markovnikov’s rule and its use in examples of two addition reactions: hydrogen iodide to propylene and hydrogen bromide to 2-methylpropene: “bei der addition von halogenwasserstoff nimmt vorzugsweise das wasserstoffärmere kohlenstoffatom eines olefins das halogenatom auf (in the addition of hydrogen halide, preferably, the hydrogen-poor carbon atom of an olefin absorbs the halogen atom): ch2 : ch · ch3 + hj = ch3. chj . ch3; (ch3)2c : ch2 + hbr = (ch3)2cbr . ch3” [9]. some chemists referred to the german version of the markovnikov’s rule, for instance julius berend cohen (1859-1935), professor of organic chemistry at the university of leeds, in his book entitled organic chemistry for advanced students published in 1919 [10], gurnos jones from the university college of north staffordshire in england in his article published in the journal of chemical education in 1961 [11], robert c. kerber, professor at the department of chemistry at the state university of new york in the article published in the foundations of chemistry in 2002 [12] and peter hughes from the westminster school in london in his article published in the journal of chemical education in 2006 [13]. other authors, for instance the russian chemists irina p. beletskaya and valentine g. nenajdenko, professors at the department of chemistry at the lomonosov moscow state university, presented a translation of the russian version of markovnikov’s rule into english [14]. in the ex-soviet union, the organic chemist alfred feliksovich plate (1906-1984) wrote about the original markovnikov’s rule in the book entitled kniga dlya chteniya organicheskoy khimii. posobiiye dlya uchashchikhsya (a book for reading in organic chemistry. student handbook) in the chapter devoted to vladimir vasilyevich markovnikov. the book was edited by pranas florionovich buckus and published in 1975 [15]. the historian of chemistry yuri ivanovich soloviev (born in 1924) cited the rule in the book entitled istoriya khimii: razvitiye khimii s drevneyshikh vremen do kontsa xix v. (history of chemistry: the development of chemistry from ancient times to the end of the xix century) [16]. various unauthentic versions of markovnikov’s rule in the chemical literature the american chemist john tierney, professor of chemistry at the pennsylvania state university (u.s.a.), in his article entitled markownikoff’s rule: what did he say and when did he say it? published in the journal of chemical education thirty-one years ago, wrote that in 11 analyzed american organic chemistry textbooks, published between 1962 and 1987, he found three different versions of this rule [17]. version (a) goes as follows: “when a hydrogen halide adds to an unsymmetric alkene the addition occurs such that the halogen attaches itself to the carbon atom of the alkene bearing the least number of hydrogen atoms”. the consecutive version (b)1 is the following: “when a hydrogen halide adds to an unsymmetric alkene the addition occurs such that the halogen attaches itself to the carbon atom of the alkene bearing the greater number of carbon atoms”. the third version (c) was found by tierney in 7 textbooks. he thinks that its wording “though not incorrect, is only obtained by inference from the original statement written in german …”. the rule in version 1 author of this article found slightly different wording of (b) version of markovnikov’s rule in the book wrote by john mcmurry entitled fundamentals of organic chemistry: “in the addition of hx to an alkene, the h attaches to the carbon with fewer alkyl substituents and the x to the carbon with more alkyl substituents” [18]. 100 aleksander sztejnberg c goes as follows: “when a hydrogen halide adds to an unsymmetric alkene the addition occurs such that the hydrogen of the hydrogen halide attaches itself to the carbon atom of the alkene bearing the most number of hydrogens”. the chemist harold hart (born in 1922), professor at the michigan state university (u.s.a.), in the viii edition of his textbook entitled organic chemistry. a short course, published in 1991 presented the rule in the following version: when an unsymmetric reagent adds to unsymmetric alkene, the electropositive part of the reagent bonds to the carbon of the double bond that has the greater number of hydrogen atoms attached to it” [19]. in the footnote related to this rule hart stressed that “actually, markovnikov stated the rule a little differently” and also that the wording included in his textbook “is easier to remember and apply”. then he invite the readers to read the paper written by tierney [17] to obtain more information “on what he [markovnikov] actually said” [19]. an analysis of the available literature shows that the markovnikov’s rule in (c) version is present also in the american textbook of the organic chemistry published in the years 2012-2015 [20,21], as well as in the polish textbook [22], in the russian chemical literature [23,24] and the german book [25]. information about markovnikov’s chemical research the list of works published by v. v. markovnikov in 1860-1904 includes 318 papers. the majority of these are the articles presenting the results of his experimental works, published in zhurnal russkogo khimicheskogo obshchestva in russia, as well as in german and french journals. here his original articles devoted to the problems of the chemical structure of the organic compounds, chemistry of the petroleum, and alicyclic compounds [26,27] can be found. the results of the 43 experimental research conducted by vladimir v. markovnikov were published in german in the following journals: 1) justus liebigs annalen der chemie (14 articles in 1870-1904); 2) journal für praktische chemie (7 articles in 1892-1899); 3) berichte der deutschen chemischen gesellschaft (22 article in 18731902) [28,29]. a few markovnikov’s articles were published in french in comptes rendus hebdomadaires des séances de l’academie des sciences and bulletin de la société chimique de paris [2,26]. selected facts from v. v. markovnikov’s life2 v ladimir vasilyev ich markov nikov was born december 10 (22) 1838 in the village of chernoreche, near nizhny novogorod. after high school graduation at the aleksandrovskii institute in nizhny novogorod, he entered the imperial university of kazan in 1856. markovnikov was the first and most talented student of aleksandr mikhaylovich butlerov (1828-1886). being a third-year student, markovnikov started participating in the chemical laboratory activities and attended butlerov’s lectures. these experiences impressed him very much and defined his future career. in 1860, defended his kandidat dissertation entitled aldegidy i ikh otnosheniya k alkogolyam i ketonam (aldehydes and their relationship to alcohols and ketones). since november 11th 1860, markovnikov started working at the kazan imperial university as laboratory technician in the chemical laboratory, and later as assistant. in 1862, markovnikov was lecturer of inorganic and analytical chemistry at the university, because of butlerov’s illness. in 1863, he passed the master’s examination. two years later, he defended his master’s dissertation entitled ob izomerii organicheskikh soyedineniy (about the isomerism of organic compounds). then, he left russia and went to germany for a two-year komandirovka (official mission abroad). first, markovnikov moved to heidelberg and attended the lectures given by the chemist hermann kopp (1817-1892), the physicist gustav kirchoff (1824-1887), and chemist emil erlenmeyer (1825-1909). he worked in erlenmeyer’s laboratory. then, he moved to the university in berlin, where he carried out a research in adolf von baeyer’s (1835-1917) laboratory. finally, he left berlin and went to leipzig, where he settled down for a long period. at the leipzig university he attended the lectures of the chemist adolph wilhelm kolbe (1818-1884) and worked in his laboratory. in 1867, markovnikov’s komandirovka was prolonged for half a year. he spent this time visiting several western chemical industries. for the same reason he attended the world exhibition in paris in august 1867. once back in russia, markovnikov worked at kazan imperial university in 1867-1873. in 1868, he was one of the founders of the russian chemical society. in spring 1869, markovnikov defended his doctoral dissertation entitled materialy po voprosu o vzaimnom vliyanii atomov v khimicheskikh soyedineniyakh (materials on the question of the mutual influence of atoms in 2 presented facts from markovnikov’s life were collected, basing on the following publications [7, 14, 26, 29, 30, 31, 32]. 101vladimir vasilyevich markovnikov (1838-1904) chemical compounds). in may 1869, he was nominated extraordinary professor (associate professor). in march 1870, he was promoted to ordinary (full) professor. in 1871-1873, markovnikov worked at the imperial novorossiysk university in odessa as professor of chemistry; between 1873 and 1904, he was professor at the imperial moscow university. in 1901, markovnikov celebrated 40 years of his research and didactic work. in 1904, in the last days of markovnikov’s life the chemist ivan alexandrovich kablukov (1857-1942) wrote “on his return from petersburg on christmas he felt bad and doctors forbade him to leave home. on january 13, he was better and even expected to leave home, despite doctors’ prohibitions, to go to the chemical laboratory, but at six o’clock in the evening a stroke deprived him consciousness. v. v. markovnikov died on the 29th january [11 february]” [33]. conclusion in 1869, v. v. markovnikov designed one of the most known empirical rules in organic chemistry, named after him markovnikov’s rule. the original wording of this rule in russian, french, and german is the “addition of the halogen atom from the halidic acid to the least hydrogenated carbon atom of the unsymmetrical molecule of unsaturated hydrocarbon”. it is worth stressing that actually markovnikov’s rule with such a phrase (original markovnikov’s rule) appears only in some textbooks and organic chemistry books, published among other in u.s.a. and russia. a very widespread version in the chemical literature is the unoriginal version (c), called also markovnikov’s rule by the authors of organic chemistry textbooks and books and chemical dictionaries, despite the fact that its wording completely differs from the original. another field of interest, which brought markovnikov fame in the world of chemistry was his research of the caucasian petroleum. together with the chemist vladimir nikolayevich ogloblin, his laboratory assistant in the chemical laboratory at the imperial moscow university [34], markovnikov wrote an article entitled issledovaniye kavkazskoy nefti (study of the caucasian petroleum), which was published in the zhurnal russkogo khmicheskogo obshchestva in 1883 [35]. in this article, markovnikov and ogloblin described the properties of several organic compounds isolated from the petroleum, which they named “naphtens” [cycloalkanes]. these are the following: octonaphten [cyclooctane] (c8h16), nonaphten [cyclononane] (c9h18), decanaphten [cyclodecane] (c10h20), undecanaphten [cycloundecane] (c11h22), dodecanaphten [cyclododecane] (c12h24), tetradecanaphten [cyclotetradecane] (c14h28), and pentadecanaphten [cyclopentadecane] (c15h30). in 1895, markovnikov described hexanaphtene [cyclohexane] (c6h12), a new naphten isolated by him from the petroleum, in the article entitled ueber das vorkommen des hexanaphtens in kaukasicher naphta (on the occurrence of the hexanaphtens in caucasian naphtha) published in berichte der deutschen chemischen gesellschaft [36,37]. two years later, in the article entitled ueber einige neue bestandtheile der kaukasichen naphta (about some new constituents of the caucasian naphta), published by the same journal, he informed the readers about the isolation of pentamethylene [cyclopentane] (c5h10) from petroleum [38]. the russian literary historian eufrosina dvoichenko-markov (1901-1980) in her article entitled the american philosophical society and early russian-american relations, published in proceedings of the american philosophical society in 1950, wrote, quoting words uttered by the russian-american organic chemist vladimir nikolaevich ipatieff (1867-1952) that markovnikov’s name “has become known to almost every american chemist working in the petroleum industry” [39,40]. on february 15, 1901, the american philosophical society at philadelphia elected markovnikov its member in recognition of his merits. on may 30, 1901, markovnikov sent to the secretary of this society ̶ arthur w. goodspeed (1860-1943) ̶ a letter of thanks for his election: “sir, i beg you to transmit my profound thanks to the american philosophical society at philadelphia for the honor, which was done me by the election as a member of that society. accept the distinguished salutations of your obedient servant vl. morcownikoff ” [40]. on may 8, 1901, markovnikov became also a member of the american academy of arts and sciences [41]. references 1. v.v. markovnikov, uchen. zap. kazan. univ. 1869, 5, 1 (prilozheniye)(in russian). 2. v.v. markovnikov, izbrannyie trudy [selected works]. 1955. (in russian). retrieved from http://books.eheritage.ru/book/10086056 3. portrait du chimiste vladimir vasilevich markovnikov [portrait of chemist vladimir vasilyevich markovnikov], public domain. 1905. retrieved from wikimedia commons website: https://commons.wikimedia.org/wiki/file:vladimirmarkovnikov.jpg 4. w. markownikoff, justus liebigs ann. chem. 1870, 153, 256. doi 10.1002/jlac.18701530204 102 aleksander sztejnberg 5. v. markovnikoff, compt. rend. acad. sci. 1875, 81, 668. retrieved from https://fr.wikisource. org/wiki/livre:comptes_rendus_hebdomadaires_ des_s%c3%a9ances_de_l%e2%80%99acad%c3% a9mie_des_sciences,_tome_081,_1875.djvu 6. v.v. markovnikov, zh. russ. khim. o-va. 1876, 8, 16 (in russian). 7. d.e. lewis, early russian organic chemists and their legacy, springer, heidelberg, new york, dordrecht, london, 2012, p. 73. 8. a.w. steward, recent advances in organic chemistry, longmans, green, and co, london, new york, bombay, calcutta, 1908, p. 105. 9. r. stoermer in methoden der organischen chemie. zweiter band [methods of organic chemistry. second volume] (ed.: j. houben), georg thieme verlag, leipzig, 1922, p. 768. 10. j.b. cohen, organic chemistry for advances students. part i. reactions (2nd ed.). edward arnold, london, 1919, p. 114. 11. g. jones, j. chem. educ. 1961, 38, 297. doi 10.1021/ ed038p297 12. r.c. kerber, found. chem. 2002, 4, 62. doi 10.1023/a:1014479921278 13. p. hughes, j. chem. educ. 2006, 83, 1152. doi 10.1021/ed083p1152 14. i.p. beletskaya, v.g. nenajdenko, angew. chem. int. ed. 2019, 58, 4778. doi 10.1002/ange.201810035 15. a.f. plate in kniga dlya chteniya po organicheskoy khimii. posobiiye dlya uchashchikhsya [a book for reading in organic chemistry. student handbook] (ed.: p. f. buckus), izdatel’stvo «prosveshcheniye», moskva, 1975, p. 62 (in russian). 16. yu. i. soloviev, istoriya khimii: razvitiye khimii s drevneyshikh vremen do kontsa xix v. posobiye dlya uchiteley (2-ye izd.) [history of chemistry: the development of chemistry from ancient times to the end of the xix century. a handbook for teachers (2nd ed.)], izdatel’stvo «prosveshcheniye», moskva, 1983, p. 209 (in russian). 17. j. tierney, j. chem. educ. 1988, 65, 1053. doi 10.1021/ed065p1053 18. j. mcmurry, fundamentals of organic chemistry (7th ed.), brooks/cole cengage learning, belmont, 2011, p. 114. 19. h. hart, organic chemistry. a short course (8th ed.), houghton mifflin company, boston, london, melbourne, 1991, p. 84. 20. w.h. brown, c.s. foote, b.l. iverson, e.v. anslyn, organic chemistry (6th ed.). brooks/cole cengage learning, belmont, 2012, p. 218. 21. r.j. ouellette, j.d. rawn, organic chemistry study guide. key concepts, problems, and solutions, 2015, p. 85. https://doi.org/10.1016/b978-0-12-8018897.00006-6 22. s. tołłoczko, chemia organiczna. wydanie vii. [organic chemistr y (7th ed.)], państwowe wydawnictwo naukowe, warszawa, 1954, p. 194 (in polish). 23. v.l. guretskaya, organicheskaya khimiya. izdaniye vtoroye [organic chemistry (2nd ed.]. izdatel’stvo «vysshaya shkola», moskva, 1983, p. 51 (in russian). 24. i.l. knunyants, khimicheskiy entsiklopedicheskiy slovar’ [chemical encyclopaedic dictionary], «sovetskaya entsiklopediya», moskva, 1983, p. 313 (in russian). 25. w. uhl, a. kyriatsoulis, namen-und schlagwortreaktionen in der organischen chemie [name and key reactions in organic chemistry], springer fachmedien wiesbaden gmbh, wiesbaden, 1984, p. 107. 26. g.v. bykov in v.v. markovnikov, izbrannyye trudy [selected works], 1955, pp. 835–889 (in russian). retrieved from http://books.e-heritage.ru/ book/10086056 27. i.a. kablukov, zh. russ. fiz.-khim. o-va. chast’ khimicheskaya, 1905, 37, 247 (in russian). retrieved from http://books.e-heritage.ru/book/10087807 28. wiley online library, 2018a. retrieved from wiley online library website: https://onlinelibrary.wiley. com/action/dosearch?contribauthorstored=markow nikoff%2c+w& 29. wiley online library, 2018b. retrieved from wiley online library website: https://onlinelibrary.wiley. com/action/dosearch?target=default&contribauthor stored=markownikoff,%20wl 30. a.e. arbuzov in lyudi russkoy nauki: ocherki o vydayushchikhsya deyatelyakh yestestvoznaniya i tekhniki, tom 1 (ed.: i. v. kuznetsov), gosudarstvennoiye izdatel’stvo tekhniko-teoreticheskoy literatury, moskva – leningrad, 1948, pp. 313-321 (in russian). 31. h.m. leicester, j. chem. educ. 1941, 18, 53. doi 10.1021/ed018p53 32. a.f. plate, g. v. bykov in izbrannyie trudy [selected works] (v.v. markovnikov), 1955, pp. 719– 777. retrieved from http://books.e-heritage.ru/ book/10086056 33. pamyati vladimira vasil’yevicha markovnikova [in memory of vladimir vasilyevich markovnikov], 1905, 52 (in russian). retrieved from http://books.eheritage.ru/book/10070378 34. f.a. brokgauz, entsiklopedicheskiy slovar’. т. 21а. neshvill’ – opatskiy [f. a. brockhaus, encyclopedic dictionary. vol. 21a. nashville opatsky], 1897, 691 (in russian). retrieved from https://dlib.rsl.ru/ 103vladimir vasilyevich markovnikov (1838-1904) viewer/01003924218#?page=242 35. v.v. markovnikov, zh. russ. khim. o-va. 1883, 15, 237–268; 307–354 (in russian). 36. w. markownikoff, ber. dtsch. chem. ges. 1895, 28, 577. https://dx.doi.org/10.1002/cber.189502801140 37. r.a. wischin, die naphthene (cyklische polymethylene des erdöls) und ihre stellung zu anderen hydrürten cyklischen kohlenwasserstoffen [the naphthenes (cyklic polymethylene of petroleum) and their position to other hydrogenated cyclic hydrocarbons]. druck und verlag von freidrich vieweg und sohn, braunschweig, 1901, p. 47. 38. w. markownikoff, ber. dtsch. chem. ges. 1897, 30, 974. https://doi.org/10.1002/cber.189703001189 39. v.n. ipatieff, russ. rev. 1943, 2, 70. doi 10.2307/125254 40. e. dvoichenko-markov, proc. amer. philos. soc. 1950, 94, 580. retrieved from http://www.jstor.org/stable/3143595 41. e. dvoichenko-markov, proc. amer. philos. soc. 1965, 109, 53. retrieved from http://www.jstor.org/stable/985778 substantia an international journal of the history of chemistry vol. 3, n. 2 september 2019 firenze university press chemical industry and sustainability vittorio maglia novel water treatment processes mojtaba taseidifar1, adrian g. sanchis1, richard m. pashley1,*, barry w. ninham2 is aberrant n-glucosylation relevant to recognise anti-mog antibodies in rett syndrome? feliciana real-fernández1,2, giulia pacini2, francesca nuti1, giulia conciarelli2, claudio de felice3, joussef hayek4, paolo rovero2, anna maria papini1,* hydrogen-like quantum hamiltonians & einstein separability in the case of charged radical molecules han geurdes a scientific rationale for consciousness pr. marc henry1,*, jean-pierre gerbaulet2,* derjaguin’s water ii: a surface hydration phenomenon ilya klugman, anna melnikov1, drew f. parsons2 leonardo da vinci – the scientist walter isaacson b. v. derjaguin* and j. theo. g. overbeek. their times, and ours barry w. ninham sadi carnot’s réflexions and the foundation of thermodynamics pier remigio salvi, vincenzo schettino vladimir vasilyevich markovnikov (1838-1904) – the eminent russian chemist, author of one of the best known empiric rule in organic chemistry aleksander sztejnberg substantia. an international journal of the history of chemistry 1(1): 55-59, 2017 firenze university press www.fupress.com/substantia doi: 10.13128/substantia-8 citation: l. dei (2017) i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place. substantia 1(1): 55-59. doi: 10.13128/substantia-8 copyright: © 2017 l. dei.this is an open access, peer-reviewed article published by firenze university press ( h t t p : / / w w w. f u p r e s s . c o m / s u b s t a n tia) and distribuited under distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author declares no competing interests. historical article i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei università degli studi di firenze, piazza san marco 4, firenze, italy e-mail: luigi.dei@unifi.it keywords. primo levi, holocaust, dynamite, literature. the periodic table1 by primo levi has been designed by the royal institution of great britain “the best science book ever written”.2 indeed, in this book there is a perfect mixture of science, allegory, chemistry, life, memory, history and human experience. the book is built as a collection of chapters or stories each entitled with an element of the very periodic table by mendeleev: in total 21 elements each recalling a life experience of the author, the chemist and writer primo levi, an author famous in the world as one of the most important witnesses of the shoah. primo levi was born in turin on july 31st, 1919 to two jewish families of provence (france) and spanish origins. immediately we discover in his childhood, adolescence, and youth a first paradox of the fate: he could not attend with constancy the primary school due to the very precarious conditions of his health, the same health that in the future will reveal fundamental for his survival in the lager. from 1934 primo attended the high school liceo classico “massimo d’azeglio” in turin where got his baccalaureate in 1937: second paradox of the fate, he didn’t succeed in passing the exam of italian literature – he had to pass a supplementary exam – the subject that made him famous in all the world. in the same years he started to attend the chemistry faculty at the university of turin. in 1938 the italian government under the fascist tyranny of mussolini promulgated the “racial laws” imitating the german anti-semitism actions. these laws prohibited the university studies to young people of “jewish race”, but allowed them to conclude their studies if they already attended university courses at the coming into force of them. therefore, primo levi succeeded in graduating in chemistry in 1941 discussing a thesis on the walden inversion with the grade 100/100 cum laude.3 in the following two years he worked as chemist in an asbestos quarry close to turin to extract nickel from the waste of asbestos production and then he moved to milan to work in a swiss drug factory. during this period he wrote two little tales – nickel and chromium – that successfully will go to constitute two chapters of the book the periodic table. in 1943 he joined a resistance fighting brigade against the nazi-fascists in valle d’aosta, but in december 1943 the fascist militia arrested him and he was imprisoned in a transit concentra56 luigi dei tion camp at fossoli close to modena. on february 22nd, 1944 levi, together with other 650 jewish prisoners, was crowded in a supply train and taken to auschwitz lager (buna-monowitz) where he remained until january 27th, 1945 when he was liberated by the russian army together with only 20 of the 650 calamity companions. at auschwitz he was registered with the number 174517 which is now carved on the gravestone that remembers him at the jewish camp of the monumental cemetery in turin. since he was a chemist and knew reasonably well german, due to his chemical studies at the university, towards the end of 1944 he was recruited to work as a chemist in a factory close to the camp, called buna, which produced synthetic rubber. during this last period, together with a friend working with him, alberto dalla volta, succeeded in earning a living selling flints for cigarette-lighters, that they succeeded in preparing in the chemical laboratory from some cerium-iron little rods used to ignite the flame of the oxyacetylene torches. this real story originated the chapter cerium of the same book the periodic table. some days before the liberation of the camp by the russians he fell ill by scarlet fever and therefore he was abandoned in the sickroom called ka-be (from the german krankenbau, camp sickroom) by the germans in fight. his friend alberto had already contracted this disease and due to the immunity memory didn’t fall ill and was compelled to follow the germans in fight: “alberto didn’t return and no trace remains of him.” the homeward journey was long and turbulent and ended after nine months in october 1945: it will be narrated in the book the truce published in italian in 1963.4,5 the experience of the concentration camp profoundly shocked him physically and psychologically. after recovering the health he started to work in a paint company – and this paint company named duco will be at the centre of this contribution since it had been in the past a nobel dynamite factory– and during this period he met lucia morpurgo who then became his wife. during this period he devoted feverishly himself to the writing of a book that was witnessing of his experience at auschwitz and that will be entitled if this is a man.6 an important role in reinforcing the idea to write his memories of the terrible experience in the lager is attributable to the date with his future wife as he declared some years later stating that she succeeded in allowing him to pass from the painful perspective of a convalescent to that described by himself in the periodic table: “a work by a chemist who weighs and divides, measures and judges on the basis of firm evidences, and strives to answer the whys and wherefores”. in 1947 he published this book with the little publisher de silva – the great publishing house einaudi refused the book – without any success: of the 2,500 copies only 1,500 were sold and mostly in turin. at the beginning of 1950s he was engaged by the siva company which produced paints: after some years he became director and remained there until retirement in 1975. for more than ten years levi did not write any book and dedicated himself completely to chemistry. in 1956 levi participated in turin to an important exhibition on the lager deportation where he had great success as witness and he started to attend many meetings in the schools where he received sincere sympathy from the audience. einaudi decided to print if this is a man and this time the success was amazing: immediately the book was translated in english and german under the supervision of the author. encouraged by the success of if this is a man, in 1962 levi started to write the truce, where he narrated his turbulent return to turin after the liberation of the camp. the book was published in 1963 and soon gained an important prize, the premio campiello. in the following literary production he was inspired by his experiences as a chemist, by the observation of nature, and by the impact of science and technology on the daily life. the most representative book of this inspiration was the periodic table, translated in many languages and defined by the royal institution of great britain the greatest book for the popularisation of science in the world. on april 11th, 1987 he died falling down from his home stairwell. this episode gave rise to the suspect he took his own life. apart from the very famous books above mentioned, if this is a man and the truce, two of the most impressive witnesses of the shoah, the rest of the literary work by primo levi is strictly linked to his way of reading the reality as a chemist. in the periodic table, as stated at the beginning, autobiographic episodes and fiction tales are associated to single chemical elements, each constituting a chapter of this book. saul bellow declared: “the book it figure 1. primo levi writing an article. by courtesy of lisa and renzo levi. 57i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place is necessary to read next. after a few pages i immersed myself gladly and gratefully. there is nothing superfluous here, everything this book contains is essential. it is wonderfully pure, and beautifully translated … i was deeply impressed”. maybe the story of the paint factory called duco where primo levi had the first employ after the second world war and his terrible experience in the lager is not well known to many people and this is the reason why i decided to write this contribution remembering alfred nobel work and life. using an expression coined by levi – “stealing others’ trade” – i, chemist as levi, would like to narrate the story of the nobel dynamite factory in avigliana close to turin that became a remembrance place, retracing a chapter of the periodic table, chromium, seemingly so distant from nobel and really strictly connected and married into. in 1872, when the law on the abolition of the government monopoly on the explosives fabrication was promulgated, the nobel dinamite anonymous society in hamburg decided to found close to avigliana near turin a dynamite factory that was called in italian the dinamitificio nobel and therefore the dynamite industry was born in that place in that time. the site was selected for security and safety reasons that were necessary for the type of manufacture. now in the avigliana territory, in the lower part of the susa valley, we can find the monumental remains of the most important explosives factory ever created in the 20th century.7 the complex, that represents one of the most significant and interesting examples of architectural industry at the beginning of the 20th century, hosted for more than ninety years (from 1872 until 1965) the most important explosives factory in europe. it was built by the initiative of a group of five bankers from paris and of the alfred nobel society in hamburg. this society chose this site probably due to two reasons: the important location on the communication axis with northern europe and the proximity to the railway lines and, maybe mainly, because of the alternation in the territory of flat regions and hill zones that allowed protection of the built-up area from the deflagrations that could be caused by the activity of such industry. in 1908 the nobel society purchased other grounds in the surroundings from the carvotto family to produce new types of explosive powders. in 1925 figure 2. verso and recto of a photo portrait of a worker engaged in the test of the gunpowder. by courtesy of ermis gamba.8 58 luigi dei from the small department of the first-born plant called valloya, thanks to a patent of the american dupont, the little factory of paints duco got underway; this complex then merged into the big national group montecatini constituted in the frame of the great italian chemical research lead by the future 1963 nobel prize winner, giulio natta. during the world war ii the area was subjected to bombing and war actions by the resistance fighters. the successive crisis of the military orders and the changing of the urban planning requirements caused the progressive decay of the industrial complex until the stoppage in 1965: now the remains host a museum. a part of the nobel dynamite factory was destined to host, since 1925, a factory of paint, « … a large factory on the shores of a lake, the same on which i had learned the rudiments of the varnish-making trade during the years 1946-1947. » in this factory primo levi had his first employ as chemist after the end of the darkness of our continent. in january 1946 all europe was trying to rebuild new life in peace with strong difficulty: meat and coal rationed, no cars in the streets, but hope and freedom warmed up the people. the period was very difficult even for the chemist primo levi: indeed, he felt something different from the others when he started to work close the factory that had produced so many weapons, the nobel dynamite factory in avigliana. these were his feelings: « the things i had seen and suffered were burning inside me; i felt closer to the dead than the living, and felt guilty at a being a man, because men had built auschwitz and auschwitz had gulped down millions of human beings, and many of my friends, and a woman who was dear to my heart. it seemed to me that i would be purified if i told its story, and i felt like coleridge’s ancient mariner, who waylays on the street the wedding guests going to the feast, inflicting on them the story of his misfortune . » the nobel factory was the place where the survival primo tried to build his new life: indeed he would never succeed in building a new life. his life ever remained sharply splitted in two: before auschwitz and after auschwitz. nevertheless, in that paints factory day by day he started to live again, to reborn. but at the same time this rebirth was accompanied by the reconstruction of the memory, the remembrance of what he had seen and for which he started to build his role of witness. this rebirth is extraordinarily expressed and condensed in his literary art in the tale chromium: « i, unoccupied as a chemist and in a state of utter alienation (but then it wasn’t called that), was writing in a haphazard fashion page after page of the memories which were poisoning me, and my colleagues watched me stealthily as a harmless nut. the book grew under my hands, almost spontaneously, without plan or system, as intricate and crowded as an anthill. » the book that levi was talking about is the very famous if this is a man. therefore, the duco paints factory just in the same environment of the nobel dynamite factory is the place where primo levi wrote, in a wonderful manner as described above, one of the most marvellous book of the world literature. primo levi started to work as a chemist and in the meantime to become one of the most famous writer in the world. the nobel factory witnessed the metamorphosis of a man who had become not-a-man, and that gradually was becoming again a man. now we know that this second man was no longer like the first one and maybe after many years matured in his mind the thought to draw a close to his days as man / not-a-man / man / no-longer-a-man by returning to nothingness. however, the destiny had decided that this reconstruction of a man from a prisoner had to occur there and that love had to have a beautiful role … « now it happened that the next day the destiny reserved for me a different and unique gift: the encounter with a woman, young and made of flesh and blood, warm against my side through our overcoats, gay in the humid mist of the avenues, patient, wise, and sure as we were walking down streets still bordered with ruins. in a few hours we knew that we belonged to each other, not for one meeting but for life, as in fact has been the case. in a few hours i felt reborn and replete with new powers, washed clean and cured of a long sickness, finally ready to enter life with joy and vigour; equally cured was suddenly the world around me, and exorcized the name and the face of the woman who had gone down into the lower depths with me and had not returned. my very writing became a different adventure, no longer the dolorous itinerary of a convalescent, no longer a begging for compassion and friendly faces, but a lucid building, which now was not longer solitary; the work of a chemist who weighs and divides, measures and judges on the basis of assured proofs, and strives to answer questions . » the absolute original style of writing was germinating in that place: literature that draws ideas, reasoning, and narrating “contraptions” from chemistry and that has made this character of the world literature a kind of unicum. the way of remembering the dreadful experience of the holocaust with an aseptic method that vivisects the events like the scientist analyses the matter and its transformation. this metamorphosis is perfectly explained by the very author in the same tale: « alongside the liberating relief of the veteran who tells his story, i now felt in the writing a complex, intense, and new 59i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place pleasure, similar to that i felt as a student when penetrating the solemn order of differential calculus. it was exalting to search and find, or create, the right word, that is, commensurate, concise, and strong; to dredge up events from my memory and describe them with the greatest rigor and the least clutter. paradoxically, my baggage of atrocious memories became a wealth, a seed; it seemed to me that, by writing, i was growing like a plant. » i believe that now is clear why i decided to entitle this contribution “i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place”. in a certain sense dynamite, chromium, chemistry, the job of the chemist are all strictly connected with matter, but the way to treat chemistry treats matter can be exactly the same people deal with human events: this is the strong primo levi’s lesson. the quintessence of this concept is well articulated in the last quotation i would like to add from the tale chromium by the periodic table: « it is the spirit that dominates matter, is that no so? was it not this that they hammered into my head in the fascist and gentile liceo? i threw myself into the work with the same intensity that, at not so distant a period, we had attacked a rock wall; and the adversary was still the same, the not-i, the button molder – a character in ibsen’s peer gynt – the hyle: stupid matter, slothfully hostile as human stupidity is hostile, and like it strong because of its obtuse passivity. our trade is to conduct and win this interminable battle; a livered paint is much more rebellious, more refractory to your will than a lion in its mad pounce; but let’s admit it, it’s also less dangerous. » we can say that the properties of the elements often reflect the properties of life itself: volatile, inert, lustrous, precious, poisonous, brittle, explosive … i believe alfred nobel would have appreciated so much the work by primo levi. in conclusion, the story i tried to narrate thanks to the beautiful help of levi’s writing can be considered the third and last paradox of primo levi’s life: the nobel dynamite factory, emblem and symbol in some way of the atrocity of the war due to the product of its activity (the explosives) hosted the “saved” – opposed to the “drowned” – primo levi and made him to feel the sensation he condensed in the sentence “i felt reborn”. acknowledgments the author would like to express sincere and deep gratitude to primo levi’s daughter and son, lisa and renzo, for the kind gift of the photo of their father. the quotations from the periodic table are drawn from the translation by raymond rosenthal first published in the usa by shocken books inc., 1984, first published in great britain by michael joseph 1985, and finally by penguin books 2000. references 1. p. levi, the periodic table, penguin books ltd., london, 2000. 2. http://www.rigb.org/, last accessed on jan 04, 2017. 3. h t t p : / / w w w. c h e m i s t r y. u n i t o . i t / d o / h o m e . p l / viewmobile?doc=history.html, last accessed on jan 04, 2017. 4. p. levi, the truce, the bodley head, london, 1965. 5. http://www.wollheim-memorial.de/en/der_roman_ la_tregua_von_primo_levi_1963#_edn1, last accessed on jan 04, 2017. 6. p. levi, if this is a man, orion press, 1959. 7. http://www.provincia.torino.gov.it/culturamateriale/english/tempo_industria/dinamitificio_nobel_ avigliana_en.pdf, last accessed on jan 04, 2017. 8. https://acomearchivista.com/2015/09/09/al-lavoronel-dinamitificio-nobel-di-avigliana/#more-229, last accessed on jan 24, 2017. the biological/physical sciences divide, and the age of unreason barry w. ninham developments of nmr from molecules to human behaviour and beyond c.l. khetrapal1* and k.v. ramanathan2 the tribulations of the inventor pierre-gilles de gennes* modelling polymers as compressible elastic spheres in couette flow donglin xie and dave e. dunstan* from water to the stars: a reinterpretation of galileo’s style* louis caruana sj i felt reborn (primo levi): from the nobel dynamite factory to a remembrance place luigi dei new astronomical observations: joseph weber’s contribution to gravitational waves and neutrinos detection stefano gottardo isaac newton and alchemy vincenzo schettino science is not a totally transparent structure: ştefania mărăcineanu and the presumed discovery of artificial radioactivity marco fontani1*, mary virginia orna2, mariagrazia costa1 and sabine vater1,3 manifesto of the journal acknowledgments substantia. an international journal of the history of chemistry 2(2): 93-118, 2018 firenze university press www.fupress.com/substantia issn 1827-9635 (print) | issn 1827-9643 (online) | doi: 10.13128/substantia-64 citation: e. kenndler, n.m. maier (2018) gas chromatography and analysis of binding media of museum objects: a historical perspective. substantia 2(2): 93-118. doi: 10.13128/substantia-64 copyright: © 2018 e. kenndler, n.m. maier. this is an open access, peerreviewed article published by firenze university press (http://www.fupress. com/substantia) and distribuited under the terms of the creative commons attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. data availability statement: all relevant data are within the paper and its supporting information files. competing interests: the author(s) declare(s) no conflict of interest. historical article gas chromatography and analysis of binding media of museum objects: a historical perspective ernst kenndler1, norbert m. maier2 1 institute for analytical chemistry, faculty of chemistry, university of vienna, a 1090 vienna, austria. corresponding author 2 department of chemistry, a.i. virtasen aukio 1 (p.o. box 55), fi-00014 university of helsinki, finland e-mail: ernst.kenndler@univie.ac.at; norbert.maier@helsinki.fi abstract. this contribution covers the major historic milestones of the evolution of gas chromatography (gc) from its beginnings to its current status as one of the most powerful analytical separation techniques, and demonstrates simultaneously how this technique has enabled and continuously improved the analysis of organic binding media in objects of cultural heritage. after an introduction into the basics of chromatography, the development of gc is traced from its emergence in the late 1800s as a mere preparative technique through a period of relative stagnation into the mid of the 20th century. then, the 1950s are covered by highlighting the major advances in theory and technology within this decade, all of which contributed to firmly consolidate the status of gc as a modern analytical separation technique. from there the maturing of gc is followed through the 1960s up to the present days, a period being marked by the transition from packed to capillary columns; the essential adaptation of injection and detection devices; the replacement of glass by fused silica as column material; major progresses in stationary phase chemistry; and, finally, the advent of the hyphenation of gc with mass spectrometric detection devices. throughout this survey, examples of applications of contemporary gc techniques to binding media analysis are discussed to provide an illustrative historic record of the continuous improvements achieved. the account will be closed with critical reflections on gc’s current relevance to and future role in the analysis of binding media in objects of cultural heritage.  keywords. natural organic binding media, gas chromatography, history, cultural heritage, museum objects. 1. introduction knowledge of both the genuine techniques and materials employed in the creation of objects of cultural heritage are of crucial importance for their scientific and artistic analysis. objects of cultural heritage (for which we shall use in the following the term “museum objects”) can consist of nearly innumerably inorganic and organic materials. nowadays, the reliable identification of the chemical nature and source of these materials is of eminent importance to guide the development of object-appro94 ernst kenndler, norbert m. maier priate conservation and restoration techniques. in addition, knowledge on the constituting materials in museum objects may provide a host of other important scientific insights, such as a historic record of the social and economic conditions at the time the respective objects were fabricated, and information on the contemporary status of craftsmanship, and intercultural exchange and technology transfer. elucidation of the geographic provenience of materials integrated in museum objects may also help to trace both ancient trade relationships and trade routes. and most importantly, a detailed profile of the constituting materials in museum objects may provide valuable evidence concerning the period of production and geographic origin, and thus for reliable establishment of authenticity of a given object of cultural heritage. the present contribution will focus on one class of these materials, viz. natural organic binding media (in the following termed binding media or binders).[1, 2] the determination of these materials in museum objects has a long tradition, and many analytical approaches have been applied to this purpose. these methods range from visual examination over microchemical tests to the current state-of-the-art spectrometric and separation methods, such as liquid and gas chromatography, often used in conjunction with powerful mass-sensitive detection devices. gas chromatography (gc), probably the most frequently employed analytical technique for the identification of binding media in museum objects, will be the central subject of this contribution. specifically, the intent of this account is twofold: our first objective is to provide an overview on the historical development of gc from its humble beginnings to its current mature status, and to pay credit to those scientists who through their ingenious contributions have advanced gc to one of the most powerful of the current analytical separation techniques. in addition, and as our second goal, we wish to demonstrate how the continuous technological advances achieved in gc methodology over the last five decades have made possible addressing the formidable challenges associated with binding media analysis in museum objects. before advancing to the discussion of the historic milestones in the synergistic evolution of gc methodology and concurrent improvements in binding media analysis, we find it beneficial to provide a brief section clarifying some fundamental terminology and aspects of chromatography. 2. methodology of chromatography a chromatographic system consists of two immiscible phases. under operational conditions, one phase (the stationary phase; either a solid or a liquid) is kept immobile whereas the second phase (the mobile phase; either a gas or a liquid) is forced to flow continuously through the separation system. after introduction of the sample into the system, the contained analytes are distributed between the mobile and the stationary phase according to their relative affinities, leading to their physical separation. chromatographic methods can be categorized by several criteria, e.g. (1) according to the geometry of the system; (2) the physical state of the phases and the operative interphase distribution mechanisms; and (3) by the mode of sample introduction. concerning geometry, a chromatographic system may exhibit a (quasi-)two-dimensional format, such as in thin layer and paper chromatography; however, we will not discuss these methods in the following. in contrast, in column chromatography, the stationary phase is situated within a tube, generally referred to as column, through which the flow of the mobile phase is directed. with regard to the physical state of the phases, chromatographic methods are classified either as gas chromatography (gc) or as liquid chromatography (lc), depending on the state of the mobile phase. gc and lc may further be categorized based on the physical state of the employed stationary phase as gas solid (gsc) and gas liquid (glc), and as liquid liquid (llc) and liquid solid (lsc) chromatography. note that in the present contribution the method is termed partition chromatography in case that the analytes are distributed between a liquid or a gaseous mobile phase, respectively, and a liquid stationary phase; distribution is based on absorption in the two phases. in adsorption chromatography, in contrast, the stationary phase is a solid surface (e.g. as in ion exchange chromatography). the mode of sample introduction may involve either the injection of a sample amount being small relative to the volume of the system, or, alternatively the continuous introduction of sample solution. for the former mode the elution mode the sample is introduced as a narrow plug at the inlet of the column into the flowing mobile phase. during the transport of the sample through the column, the contained analytes are separated into individual sample zones with the mobile phase in between. it should be mentioned that for almost all analytical applications, elution mode chromatography is employed, and the term chromatography (that will be often used in the present contribution) is currently a common synonym of elution mode column partition chromatography. in the latter mode the frontal analysis mode the sample is either continuously fed as the mobile phase 95gas chromatography and analysis of binding media of museum objects: a historical perspective into the column, or may be continuously introduced dissolved in the mobile phase. in this mode only the first eluting zone contains pure analyte, with the subsequently emerging zones containing mixture of analytes, the composition of which being determined by the relative affinity of the analytes towards the stationary phase. this mode of chromatography is normally not used for analytical, but rather for preparative purposes. it shall be mentioned that other modes of chromatography do exist, such as displacement chromatography or chromathermography, but these are irrelevant for the current topic and therefore are not further discussed here. elution mode glc is currently the sole gas chromatographic method employed for the analysis of binding media in museum objects. historically, glc has emerged from a number of precursor techniques, which will be outlined in some detail in the following account on the invention and evolution of chromatographic techniques relevant to binding media analysis. however, prior to these discussions, a brief overview of the most important classes of organic compounds used as binding media shall be given. 3. natural organic binding media in objects of the cultural heritage remarkably, despite the fact that nature provides a sheer unlimited repertoire of organic compounds, only a few classes have been applied as binding media in museum objects. in accordance with their chemical nature, binding media encountered in art objects can be categorized into six classes (see e.g. refs. [2, 3]), viz. waxes, resins, oils and fats, animal glues, plant gums, and bituminous material. representative compounds for each of these classes are depicted in figure 1. the main constituents of natural waxes are long chain n-alkanes (and of beeswax also esters of long-chain fatty acids and alcohols, and smaller amounts of free fatty acids). waxes are found in museum objects amongst others as varnishes and coatings, or as matrix components of wax models, and have been widely used in antiquity as binders for pigments in encaustic painting. natural resins are products secreted from woody plants, mainly consisting of complex mixtures of diterpenoids or triterpenoids (compounds with either 20 or 30 c-atoms in their molecules), preferentially of cyclic structures; these compounds often contain c=c double bonds, and bear hydroxy and carboxylic groups. it is worth noting that a given plant produces either diterpenoid or triterpenoid resins, but not both. in museum objects, resins have been generally employed as varnishes, for coatings, additives, and consolidants. chemically, oils and fats are triglycerides of longchain fatty acids. drying oils, employed as binders of the pigments for oil paintings in western art, contain a high proportion of unsaturated fatty acids. the commonly used linseed oil mainly consists of the c18 fatty acids oleic (c18:1), linoleic (c18:2) and linolenic (c18:3) acids (the suffix 18:2 denotes the presence of two c=c double bonds in a fatty acid containing 18 c-atoms). linoleic and linolenic acids possess isolated double bonds, in contrast to eleostearic acid, a c18:3 acid with three conjugated c=c double bonds, a main constituent of tung oil, which was applied in some objects as substitute for linseed oil in the first half of the 20th century.[4, 5] the drying process is a radical-induced oxidative polymerization of the unsaturated fatty acids, leading to the formation of a three-dimensional cross-linked network. this process is accompanied by cleavage of the double bond and formation of short chain c7, c8, c9 dicarboxylic acids, which are generally detectable in aged dried oil. egg, casein and collagens are the main animal glues used; they are proteins and consist of peptide chains containing essentially all of the twenty natural amino acids. however, the amino acid hydroxyproline is a specific constituent of collagens, formed by post translafigure 1. representative constituents of natural organic binding media. (i) waxes: triacontanyl palmitate (in bees wax). (ii) diterpenoic resins: larixyl acetate (in venetian turpentine). (iii) drying oils: linolenic acid (9,12,15 octadecatrienoic acid (in linseed oil). (iv) animal glues: hydroxyproline (in collagens). (v) plant gums: glucuronic acid (in gum arabic). (vi) bituminous materials: hopane in asphaltenes. 96 ernst kenndler, norbert m. maier tional modification of proline, and is a unique marker of this type of glue. egg was widely used as a binder of pigments in tempera painting, the dominating painting technique used prior to the invention of oil painting in western art in the early 15th century. plant gums are polysaccharides, composed of a range of monosaccharides and uronic acids (typically glucuronic and galacturonic acids). frequently employed plant gums in binding media are gum arabic, gum tragacanth and cherry gum. occasionally, starch has also been applied. bituminous material is a very complex mixture of high molecular mass compounds, and is a generic term for two classes of substances, amongst bitumen and asphalt are natural materials, and tars and pitches are technical products. pitches are directly resulting from pyrolysis of wood or resin, while tars represent the products of a subsequent distillation. however, these compounds are rarely encountered as binders in museum objects, and will not be treated here in more detail. readers interested in an in-depth treatise on organic binding media and coatings are directed to ref. [2]. as an essential prerequisite, gc analysis requires the analytes of interest (except for pyrolysis gc, see below) to be sufficiently volatile and thermally stable to avoid decomposition at the typically employed elevated temperatures. therefore, gc is not directly applicable to the majority of the common binding media. however, this limitation can be conveniently overcome by chemical transformation of these materials into more volatile compounds, e.g. by de-polymerization via acid-catalyzed hydrolysis and appropriate derivatization of the emerging low-molecular mass constituents. 4. a brief review of the general principles and the terminology of chromatography two main parameters determine the separability of analytes in chromatography, namely the retention factor1 and the plate number2. the former parameter reflects the velocity by which a given analyte zone moves through the column, while the latter is a measure of the continuous broadening the zone underlies upon migration through the chromatographic system. certainly, a combined knowledge of the properties of the chromatographic system and the analytes, and their interactions 1 we prefer to use the more explicatory term retention factor rather than mass distribution ratio, as proposed by iupac, or capacity factor, the more common term in older literature. 2 initially, in the classical literature of zone dispersion (see chapters 4.2. and 5.5) the term plate number is named “number of theoretical plates”. is key for an informed selection of favorable operational variables and parameters. while we wish to restrain from a detailed treatment of chromatographic theory, we consider it beneficial to familiarize interested readers with some fundamental relationships. we hope these will aid the understanding of crucial milestones that marked the development of gc from its beginning as a preparative technique to its present status as one of the most powerful methods for trace analysis. 4.1 zone migration: retention time, retention factor and separation selectivity the migration velocity, ui, of a given analyte, i, through a chromatographic column with the mobile phase flow velocity, v, is determined by the analyte ś degree of distribution between the stationary (denoted by subscript s) and mobile phase (denoted by subscript m). in the steady state, the fraction of the analyte in the mobile phase is equal to the ratio of mole number ni,m to the total mole number (ni,m+ni,s) being ni,m/(ni,m+ni,s), which can be also expressed as 1/[1+(ni,s/ni,m)]; the ratio ni,s/ni,m is the mass distribution coefficient. in partition chromatography like glc, the respective mole numbers are equal to n =c.v, the product of corresponding concentrations, c, and volumes, v. the analyte concentration ratio3 between stationary and mobile phase is the partition coefficient, ki=ci,s/ci,m, and the ratio of the volumes of stationary and mobile phase is named phase ratio, q=vs/vm. combining these expression allows formulation of the fraction of the analyte in the mobile phase by ni,m/(ni,m+ni,s)=1/(1+kiq)=1/(1+ ki) (1) we define ki, the retention factor, as ki=kiq; it is identical with the mass distribution coefficient, and is one of the most important parameters for the description of any chromatographic process. since the fraction 1/(1+ki) of the analyte in the mobile phase (see equation 1) migrates with velocity v, and assuming that the rate of the mass exchange of the analyte between the two phases by distribution is fast, it follows that the entire analyte zone moves through the column with velocity ui, which can be expressed as given in equation 2a by 3 note that in partition chromatography the concentrations in both phases are defined by moles per volume. in adsorption chromatography, in contrast, the concentration of the analyte at the stationary solid surface with area a is given by moles per area [mol/a]. in this case the distribution coefficient k is not dimensionless, but has the dimension of a length. 97gas chromatography and analysis of binding media of museum objects: a historical perspective a) ui = v 1+ ki( )= v 1+ kiq( ) b) tri = l ui = l v( ) 1+ ki( )= tr0 1+ ki( ) c) ki = tri −tr0( ) tr0 (2) from equation 2a it can be concluded that in glc the migration velocity, ui, of analyte, i, depends on three parameters, namely (i) on the mobile phase flow velocity v, and (ii) on the phase ratio q=vs/vm, with both of these parameters being equal, i.e. unspecific, for all analytes; and (iii) on the partition coefficient, ki. this partition coefficient is an analyte-specific quantity, reflecting the distinct interactions a given analyte undergoes with the stationary and mobile phase, respectively. differences in k, or more specifically in the retention factors k are mandatory to achieve analyte separation. the degree of separation depends on the ratio of the retention factors, the so-called selectivity coefficient rji=kj/ki (with kj≥ki), which is a measure for the separation selectivity of the system for a given pair of analytes, i and j. for column chromatography, t he retention or residence time, tri, is the time the analy te needs to migrate with its velocity ui through the column with length, l; it is given by equation 2b. the void or dead time, tro is the time the mobile phase requires to flow through the column over length, l. experimentally, retention times are measured at the maximum of corresponding ana ly te concentration prof iles (usua lly gaussian) upon elution from the columns. note that the retention time tri of the analy te depends on the same parameters as the migration velocity, viz. on the unspecific mobile phase velocity (and the column length), and on the analyte-specific retention factor, ki again emphasizing the importance of this parameter. the retention factor ki can simply be calculated from the measured retention time tri and the dead time tro according to equation 2c. 4.2 zone broadening: plate height, plate number and separation efficiency it is important to recognize that different migration velocities of a pair of analytes in the chromatographic column are an essential but not a sufficient criterion for their successful separation. this is caused by the fact that the migrating analytes are continuously diluted by the mobile phase, i.e. they become dispersed within a larger volume and, as a consequence, their zones become broader; thus, neighboring zones of a given pair of analytes might overlap even if they possess different retention factors. under the premise that the chromatographic column is operated at constant temperature and the sample is introduced as an (infinitely) narrow plug into the column, the recorded concentration distribution of the analyte forms the typical gaussian curve (usually referred to as a peak) due to various dispersion processes. the width of the peak is expressed by its standard deviation, σ. during migration, the peak variance, σ x 2 in the length scale increases directly proportional to the migration distance, x, according to σ x 2 = h x the proportionally factor, h, is a characteristic parameter for the dispersion property of the chromatographic column, i.e. for its efficiency. for historical reasons, h is referred to as height equivalent of a theoretical plate, or (theoretical) plate height and has the dimension of a length. note that the efficiency of a column must not be confused with its ability to separate compounds, efficiency (expressed by a figure) is a property that is strictly related to zone broadening. in column chromatographic practice, however, the zone width is not measured in the length domain at a certain time (as it is done in planar chromatography). rather, all components are permitted to traverse the entire column length l and are registered at the outlet of the column as a function of time. for convenience, the resulting peak widths are measured in the time domain, e.g. by the time-based standard deviation, σt,i. both standard deviations, σt,i and σx,i (since at x=l, σx,i can be written as σl,i), are related to the migration velocity, ui, which is l/tr,i by σ l,i = h l b) σ t ,i 2 = tr,i 2 × h l (3) the ratio l/h=n is referred to as the number of (theoretical) plates or (theoretical) plate number, n, and is a measure for the efficiency of a given column with length l and plate height, h. the plate number, n, can be conveniently calculated from the time-based peak width and the corresponding retention time according to equation 4a as a) n = tr,i 2 σ t ,i 2 b) σ t ,i = tr,i n (4) from the rearranged equation 4b it can be seen that σt,i increases directly proportional to the retention time tr,i (the causes for this increase will be discussed in more detail in chapters 5.5 and 7). 98 ernst kenndler, norbert m. maier 4.3 the chromatographic resolution: the quantity for the degree of separation as outlined above, the separation of a given pair of analytes, i and j, is governed by two processes, namely zone migration and dispersion. certainly, there is a need for a quantity that expresses the degree of separation in a well-defined fashion considering the combined effect of these processes. this quantity is the chromatographic resolution, rj,i. it is obvious that for successful separation of a pair of analytes their retention times must differ (which means that the selectivity coefficient rji must be larger than unity). it is, however, not meaningful to measure this difference (tr,j–tr,i) in absolute time units, because at a given retention time difference narrow peaks may be well resolved, while broad peaks may still strongly overlap. therefore (tr,j–tr,i) is related to the width of the two peaks, given by their time-based standard deviations, σt,i and σt,j. according to iupac, the degree of separation, the chromatographic resolution, is defined for this pair of analytes by rj ,i = tr ,j −tr ,i( ) 2σ t ,i + 2σ t ,j (5) the resolution as defined in equation 5 is a dimensionless number; baseline separation of two peaks (of equal size) is obtained when the resolution has a value equal to or larger than 1.5. however, equation 5 is not very practical when resolution needs to be expressed as a function of variations in experimental parameters. transforming this relationship considering equations 2b and 4b provides a practically more useful expression for the chromatographic resolution being a function of retention factors and plate number 4 by rji = 1 4 kj − ki( ) ki ki 1+ ki( ) n = 1 4 rji −1( ) ki1+ ki( ) n (6) from equation 6 it is evident that the achievable chromatographic resolution is impacted by three terms (we chose to ignore the factor ¼): the middle term, the retention or retardation term, plays a minor role; it is relevant only to analytes with very small retention 4 variation of the experimental conditions is needed only for a pair of closely migrating analyte, i.e. for analytes with very similar retention. in this case kj≈ki and nj≈ni=n however, note that even if the difference (kj–ki) is close to zero, the ratio rji can be significantly larger than unit. (e.g., very volatile compounds in thin film capillaries, see below). (ii) the third term, the efficiency term, contains the plate number, expressing the effect of peak broadening on resolution. since separation depends on the square root of n, realizing a twofold improvement in resolution requires a fourfold increase in plate number. practically, on the one hand, this could be achieved by employing a fourfold longer column, yet improvements in resolution would come at the prize of a fourfold increase in analysis time. on the other hand, efficiency can be enhanced by using columns with lower plate heights; this approach became feasible through the invention of open tubular capillary columns (see chapter 7). very significant improvements in resolution can be realized by changing separation selectivity, which is represented in the first term of equation 6 by the selectivity coefficient, rji. evidently, any variation in stationary phase and/or the operation conditions that results even in a minute increase of rji will produce pronounced changes in resolution. 5. a short history of gas chromatography decades before gas liquid chromatography was invented, separations were already carried out by liquid chromatography. the invention of liquid chromatography is attributed to m. s. tswett, yet there were several earlier studies by other scientists applying essentially liquid solid chromatographic techniques in the frontal analysis mode for preparative purposes; e.g. in 1893, l. reed separated salts by applying their solution onto a tube filled with kaolin as adsorbent[6]; and d.t. day published first investigations with lsc in 1897 aiming at the separation of colored constituents characteristic for oils from different sources.[7] 5.1 the invention of chromatography: liquid solid chromatography in his first publication from 1903 tswett, a russian botanist, described the successful separation of plant pigments.[8] in his experiments, he applied a chlorophyll extract in ligroin (i.e. petroleum ether) at the top of a vertically arranged cylindrical glass tube (see figure 2) filled with particles of a solid material with adsorptive abilities, and continued applying fresh ligroin. tswett observed the formation of separated colored rings, which migrated through the tube and broadened during their migration. tswett coined for this separation technique the term “chromatographic method“, first mentioned in 1906in 99gas chromatography and analysis of binding media of museum objects: a historical perspective two publications in a german journal.[9, 10] interestingly, the name of this method persisted until nowadays (although it is a misnomer, as analytes processed by modern chromatography are not necessarily colored). after a dormant period, tswett ś ideas were revisited in 1931 by the biochemist r. kuhn and his coworkers, who successfully used lsc to accomplish the separation of carotins and xantophylls.[11-14] in 1937, three decades after tswett’s reports on the chromatographic method, the first monograph dedicated to chromatography was published.[15] however, due to the limited scope of compound classes that could be addressed, the use of lsc remained somewhat limited in the scientific community. the ultimate breakthrough of liquid chromatography as a powerful separation technique came with the recognition that replacing solid by (solid-supported) liquid stationary phases allowed for an enormous extension and significant improvements of selectivity profiles. certainly, this notion marked the birth of modern liquid liquid partition chromatography (llc). 5.2 liquid liquid chromatography the innovative concept of liquid liquid partition chromatography was published by martin and synge in 1941, including a model to express the efficiency of a column[16]; in the same journal issue the separation of n-acetylated amino acids in a column with water as liquid stationary phase (absorbed in silica gel) and chloroform with 0.5 to 1.0% n-butanol as mobile phase was described.[17] in appreciation of their pioneering work, j.p. martin and r.l.m. synge were jointly awarded the nobel prize in chemistry 1952 “… for their invention of partition chromatography”. chromatography employing liquid stationary phases allowed exploiting a much greater variety of solute interactions for tuning selectivity than lsc, and ultimately promoted llc to one of the most important contemporar y ana ly tica l separation methods. the practical utility of llc was further potentiated by reducing the particle sizes of the packed bed down to the micrometer range and thus producing columns providing vastly enhanced column efficiencies. from this effort, high performance liquid chromatography (hplc) emerged, a chromatographic technique that from a general viewpoint is superior to gc for two reasons: one crucial limitation of gc is that its applicability is restricted to the relatively low number of sufficiently volatile and thermostable compounds, requirements that are certainly irrelevant to llc. the second aspect that favors llc over glc is that in the latter technique selectivity emerges through interaction with the liquid stationary phase only, as the mobile phase is an inert gas. in contrast, in llc, the mobile liquid phase offers an additional and highly versatile tool for varying separation selectivity via specific solvent-solute interactions. taken together, these advantages enormously widen the general separation ability of llc as compared to glc, and explain the outstanding success of hplc in modern analytical sciences. 5.3 early gc: gas solid chromatography even at times predating tswett ś introduction of lsc, the adsorption of gases or liquids on solid surfaces was actively investigated, with the first reports emerging at the beginning of the 19th century. in the early 20th century research was primarily devoted to the adsorption of gases on solid sorbents pursuing preparative applications. specific areas of interest were, e.g. the purification or recovery of constituents of vapors, or the improvement of the effectivity of gas masks. essentially all of these investigations were carried out by frontal analysis mode.[18-20] in 1930s p. schuftan introduced separation techniques for which he coined the general term “adsorption analysis”, and which may well have been the first successful demonstration of gas solid chromatography for analytical purposes, but still at a micro-preparative scale. he applied this method for gas analysis in the technical area, and separated and quantified gases such as low-boiling hydrocarbons, carbon monoxide and hydrogen. figure 2. tswett’s device with four packed chromatographic glass columns. drawing (1.): three columns filled with adsorbents for the separation of plant pigments. the columns had an inner diameter of 2-3 mm, and a length of 2-3 cm. drawing (5.): separated zones of 5 colored plant pigments (chlorophylls and xanthophylls) in a chromatographic packed column. from ref. [9] with permission. 100 ernst kenndler, norbert m. maier in early 1930s, tswett’s introduction of elution mode lsc returned from oblivion and was gradually adopted for gsc.[14] g. hesse et al. described gsc separation using a carrier gas as mobile phase rather than the sample mixture as in frontal analysis. remarkably, in 1943 the first separation by gas liquid chromatography appears to have been carried out by g. damköhler and h. theile.[21] specifically, they achieved separations of methanol from ethanol, and benzene from cyclohexane, employing tubes filled with grained fired clay as solid support and glycerol as stationary liquid phase (it should be mentioned that their primary intention for the addition of glycerol was to deactivate the solid surface) and hydrogen or nitrogen as mobile phase. unfortunately, their contribution, after having been published in a less renowned journal, did not find any resonance in the scientific community. in addition, as both authors were staff scientists employed at an institution 5 devoted to support the german war effort, their interest may have been redirected to issues more pressing than further research into this method. the decisive step towards establishing gsc as a useful microscale separation technique was taken by e. cremer and her coworkers, who constructed the first fully operational analytical gas chromatograph operating in elution mode, including a sufficiently sensitive homemade thermal conductivity cell as a detector. interestingly, cremer described the results in a manuscript that was accepted for publication in 1944, but which failed to appear in print due to the chaotic conditions at the end of world war ii. cremer’s results were published years later, between 1949 and 1952[22-24], and even then they remained largely ignored. anyhow, the application range of gsc was found to be rather limited, though a.v. kiselev et al.[25] and others invested considerable efforts in modifying the adsorbents to enhance the variety of available interactions towards the volatile analytes. nevertheless, it turned out that even with these modifications the application range of solid stationary phases remained restricted; and mainly suitable for the separation of low-polarity compounds. before closing the present section, we would like to refer readers interested in the historic development of gc to a recent review[26], covering most of the early achievements up of the 1950s. specifically, this article also gives due credit to a range of exceptional scientists from the former ussr for their contributions on this topic. 5 at the “institut für motorenforschung der luftfahrtforschungsanstalt hermann göring”. 5.4 the innovation: gas liquid chromatography a curiosity in the history of partition gc is the first traceable separation apparently based on gas liquid chromatography and described as early as in 1512, in the period between the late middle ages and the early modern age, by hieronymus brunschwig (ca. 1450 ca. 1512), in his book “liber de arte distillandi de compositis. das buch der waren kunst zu distilieren die composita”[27] (the title page of this book is shown in figure 3). brunschwig, a german surgeon and botanist, describes a procedure in which the vapor from a mixture of alcohol and water was forced through a sponge moistened with olive oil, and was leading to the recovery of a small quantity of pure alcohol. expressed in modern terminology, this technique represents a separation process based on frontal glc, with the oil acting as a liquid stationary phase, the sponge as a porous supporting material, and the alcohol vapor as mobile phase.[28, 29] figure 3. title page of the book liber de arte distillandi de compositis. das buch der waren kunst zu distilieren die composita by hieronymus brunschwig, published in 1512, describing a kind of gas liquid chromatography.[27] 101gas chromatography and analysis of binding media of museum objects: a historical perspective however, we will now return to the advancement of gas chromatography as a branch of modern separation science. in the early 1950s james and martin adopted the concept of liquid liquid chromatography (introduced by martin and synge in 1941[16, 17]) to gas chromatography by replacing the solid surface by a liquid as stationary phase, which switched the originally adsorption to partition-based interaction mechanism. in their publications from 1952, james and martin both suggested a comprehensive theory for gas liquid partition chromatography based on the plate concept (see below), and demonstrated experimentally the separation of volatile acids and bases.[30, 31] detection and quantitation were carried out by titration of the eluted analytes with an automatic recording burette. one of their first published separation by glc[30], that of short-chain carboxylic acids on a column packed with solid-supported poly(phenylmethyldimethylsiloxa ne) (with 10% w/w stearic acid added) as stationary and nitrogen as mobile phase at 137°c column temperature is shown in figure 4. note that all eight acids are completely resolved. arguably, this invention of partition gas chromatography by using a liquid as stationary phase was the foundation for all further developments in the field, ultimately making glc to one of the most useful analytical separation methods currently available. 5.4.1 separation selectivity in gas liquid chromatography in practical glc, the vaporized analyte is distributed between the stationary liquid and the mobile gaseous phase with a partition coefficient, ki, which is inversely proportional to the vapor pressure, pi 0, of the analyte as pure compound at the given temperature, and to the activity coefficient, γ i 0, of the analyte at infinite dilution in the liquid phase. i.e. ki = prop 1 pi 0 γ i 0( ). we do not give here the derivation of the partition coefficient, but just mention that it can be conveniently obtained by considering henry’s law for non-ideal binary liquid mixtures and dalton’s law of ideal gases (see textbooks about gc). as in gas liquid chromatography the selectivity coefficient, rji is expressed by rji = kj ki = k j ki = pi 0 pj 0 γ i 0 γ j 0 (7) and as rji must be larger than unity, it follows from equation 7 that a given pair of analytes can be readily separated if their products of p0 and γ0 differ. for chemically very similar analytes with about equal γ0 this can be achieved if the vapor pressures, pi 0 and pj 0 of the pure compounds differ at the operational column temperature. however, more relevant for the variation of separation selectivity is the ratio of the activity coefficients γ i 0 γ j 0( ) because it reflects the specific intermolecular interactions between the analytes and the liquid stationary phase.[32, 33] thus, by proper selection of stationary phases liquids from a broad range of chemically distinct compounds, the activity coefficients of given pair of analytes can be conveniently adjusted so as to achieve the level of selectivity required for a given separation. 5.4.2 isothermal and temperature-programmed mode in glc, the isothermal elution mode (in which the column is held at constant temperature) is suitable for the separation of sample constituents which possess retention factors within a reasonably narrow range. at a given constant column temperature, the vapor pressures, and the activity coefficients of the sample components, and therefore their retention factors, all remain essentially constant during the chromatographic run. consequently, the selection of an appropriate operational column temperature enables the adjustment of the elution of the analytes of interest to an acceptably narrow retention time window. however, isothermal conditions are not favorable for the separation of samples composed of analytes with largely differing retention factors. for such mixtures, at a low column temperature the early eluting analytes can be satisfactorily resolved, while those possessing very large retention factors will elute at unacceptably long retention times. moreover, the longer the retention time figure 4. separation of short-chain carboxylic acids by gas liquid chromatography demonstrated in the seminal paper by james and martin in 1952 introducing partition gas chromatography.[30] separations were carried out in a packed column in the isothermal mode. curve a, experimental results; curve b, derivative of experimental curve. for details see supplementary information and ref. [30]. from ref. [30] with permission. 102 ernst kenndler, norbert m. maier the broader the peaks become (see chapter 4.2), and the late-eluting wide peaks might even disappear within the noise of the baseline of the chromatogram. selection of a high temperature, on the other hand, would be an efficient means to adjust the retention characteristics of the late eluting compounds appropriately, yet with the drawback that under these conditions the early eluting compounds would be poorly retained and can thus emerge from the column unresolved (see the middle term of the resolution equation, equation 6). certainly, isothermal gc is not a beneficial method for the analysis of mixtures with such complex compositions. this general elution problem is valid for all chromatographic techniques, i.e. gc and lc. for glc this fundamental issue can be conveniently addressed by exploiting the strong temperature dependence of the distribution coefficient and the retention factor, respectively. pioneering investigations of the chromatographic behavior of compounds in adsorption columns in presence of longitudinal temperature gradients were carried out by turkeltaub, zhukhovitskii, et al.[34, 35]. the authors coined for this separation method the term chromathermography. in glc, the vapor pressure of the pure compound increases exponentia lly w it h increasing temperature (according to the clausius-clapeyron equation), and accordingly ki and ki decrease exponentially with increasing temperature. exploiting these facts, in 1958 s. dal nogare et al.[36, 37] introduced a method to run samples consisting of components with large differences in volatility by varying the column temperature, t, as function of time, t, i.e. by applying a certain gradient dt/dt to the entire column. when employing this temperature programming technique, the initial low-temperature conditions are adapted to ensure appropriate retention of the early eluting analytes, while the final high temperature conditions are chosen to enable complete elution of the late eluting sample components. between these limits, the retention factors of the analytes are continuously decreases by the action of the well-defined t-gradient, with the consequence that the observed retention times are significant shorter than those seen under isothermal conditions. apart from reducing the time of analysis, temperature programming also causes a pronounced compressing of the analyte zones into very sharp peaks. [38, 39] 5.5 glc with packed bed columns: low efficiency and needs for selectivity early analytical gc columns were fabricated from metal or glass tubes with inner diameters of several millimeters and few meters in length. they were packed with porous solid particles (initially e.g. granules of firebrick, later kieselgur, i.e. purified diatomaceous earth), which were impregnated with the stationary liquid prior to use. the early versions of supporting material were later replaced by well-defined commercially produced homogeneous synthetic particles. packed bed columns (also referred to as packed columns) could easily be prepared, which favored their general acceptance. as already mentioned, the separability of analytes is impaired by a number of processes caused by the inevitably broadening of the initially narrow sample zone, processes that determine the column efficiency. in the first theoretical approach to describe band broadening, formulated by the plate theory, the column is considered as being composed of a series of interconnected cells or “plates” containing the mobile and the stationary phase. upon migrating through the chromatographic column, the analyte is assumed to distribute between these two phases within each plate element with equilibrium being reached.[40] the mobile phase with the fraction of solute at equilibrium concentration is then transferred to the next plate downstream, where the same process takes place again. it is important to recognize that the plate theory assumes that at each distribution step equilibrium conditions are achieved. this requirement is certainly not fulfilled as during the chromatographic process in the column the fraction of the solute in the mobile phase is continuously transported by the mobile phase while the fraction in the stationary phase permanently lags behind. equilibrium would only be achieved under the condition of infinitely fast inter-phase mass transfer, which is an unrealistic proposition. this means that analyte distribution actually occurs under nonequilibrium conditions[41, 42], and therefore the kinetics of the mass exchange will additionally contribute to the “height equivalent of a theoretical plate” (hetp; the terminology is adopted from the plate theory). logically, this particular contribution will become the more pronounced the higher the migration velocity of the zone is. in contrast, at sufficiently low migration velocity the inter-phase mass exchange will approach equilibrium conditions. this additional contribution to zone dispersion is taken into account in the rate theory, which specifically accounts for the effects of finite inter-phase mass transfer kinetics. the rate theory for packed columns, considering the plate height, h, as function of the velocity, v, of the mobile phase, was formulated by van deemter, zuiderweg and klinkenberg [43] (for elution chromatography and for isothermal conditions), expanding the theories described by lapidus and admunson[44], and by e. 103gas chromatography and analysis of binding media of museum objects: a historical perspective glueckauf[42]. in its simplified form, h=f(v), is expressed by the three-term function h=a+b/v+c.v (8) for glc with packed columns term a reflects the contribution to peak broadening caused by eddy dispersion due to the heterogeneous particle-size distribution of the packing, term b describes the contribution of longitudinal diffusion and of the different path lengths of the flow lines around the particles, term c accounts for the kinetics of the mass transfer of the solute molecules between the phases. note that this equation contains objective quantities like retention factor, particle diameter, diffusion coefficients, but also several empirical factors, i.e. those characterizing packing geometry and tortuosity. for more complex conditions the rate theory was refined by j.c. giddings.[39, 45] according to the van deemter equation (equation 8) h decreases hyperbolically with increasing v considering term b/v, while it increases linearly with v with regard to term c.v (term a is independent of the velocity). the resulting h vs. v curve, given by the sum of the individual curves, exhibits a minimum plate height, hi,min, at a distinct, singular flow velocity; i.e. at this flow velocity the column will produce maximum efficiency for a given analyte (note that hi,min depends on the retention factor, and therefore the different analytes have different values of hi,min even under identical conditions). in their seminal contribution, van deemter et al. put their theory on test by measuring h=f(v) curves for a number of analytes and columns, and the results obtained for n-butane and i-butane are shown in figure 5.[43] the h vs. v curves show shapes that are in accordance with theory, i.e. curves exhibiting a minimum at a singular carrier gas velocity, and distinct hi,min for the individual analytes. as a consequence of their inherently low efficiency packed columns produce relative broad peaks, which can easily be rationalized using the general expression for the plate number n=l/h. obviously, one reason for the low plate number is the considerably large value of h generally observed for packed columns. the second reason is the relatively short column length (of about a few meters), which is a practical limitation dictated by the need to keep the inlet pressure of the carrier gas workably low. plate numbers are therefore rarely higher than a few thousands. given this limitation in efficiency, considerable research was devoted to improving separation performance of packed column glc through optimization of selectivity.[32, 33] this goal was met by employing a large number of the stationary liquids with a wide range of polarity, an effort that led to the development of several hundred commercially available stationary phases with optimized yet rather narrow selectivity profiles. 5.5.1 analyte identification by gc: retention or kováts index in the early days of glc, rather unspecific detection systems (instruments coupled with mass-sensitive detection devices were yet to come) were employed, rendering the identification of an unknown analyte, y, challenging. to address these issues, concepts were developed that allowed identification of unknowns based on their chromatographic behavior by comparing the retention characteristics with those of known reference compounds listed in the literature. the most obvious choice of parameter for this purpose, their retention time, is not sufficiently robust, as it depends on a number of instrumental variables, such as the mobile phase flow velocity, the length of the column, the phase ratio, and the temperature. the retention factor, ky of the unknown analyte, y, being independent of flow velocity and column length, is a better choice, yet is still a function of the phase ratio. however, the variation of the retention factors with different phase ratios can be accounted for by resorting to relative retention factors, i.e. retention factors that are calibrated using a set of reference compounds. for glc, e. kováts[46] proposed the homologue series of straight-chained alkanes as suitable reference compounds, and defined the so-called retention (or figure 5. plate height, h, in dependence on the mobile phase velocity, taken from the original publication of van deemter, zuiderweg and klinkenberg from 1956. measurements were carried out with a packed bed column under isothermal conditions. for details see supplementary information and ref. [43]. from ref. [43] with permission. 104 ernst kenndler, norbert m. maier kováts) indices, ir,n, for all stationary phases (and at all temperatures) as exactly the hundredfold of the number of their c-atoms: ir,n=100.n; normal undecane, e.g. has an index of 1100. an analyte, y, which elutes between two homologue straight-chained alkanes with carbon numbers of n and (n+1) is considered to behave like a hypothetical alkane with c-number ny, a fractional number between n and (n+1). this hypothetical number ny can be calculated from ky, given the linear dependence of logkn on n of the reference alkanes (this relationship is strictly valid under isothermal conditions only); the analyte-specific kováts or retention index results therefore ir,y=100.ny. retention indices depend on the stationary liquid only and thus enable the identification of unknown analytes by comparing experimentally measured values with those documented in the literature (huge collection of ir values for many compounds and stationary phases have been compiled over the years and were readily available in the literature and databases). identification of unknown compounds is considerably facilitated by comparison of indices measured on several different stationary phases. if no reference indices are available, the difference of retention indices, δir p/ap = ir p − ir ap, measured on a polar (p) and an apolar (ap) phase can be exploited to gain information about the type of the functional groups present in the analyte. it should be mentioned that this concept was successfully applied to the analysis of binding media of the paste layer of a shell-inlaid ceremonial shield from the solomon islands.[47] the object originates from the 1st half of the 19th century, and is housed in the weltmuseum (the former museum of ethnology) in vienna, austria. in the course of the investigation of the composition of paste layer two sample constituents were detected by gc, but compound identification by ms was hampered by observation of essentially identical mass spectra (at least with ms instrumentation available at the time the study was carried out). however, these two analytes could be identified as two isomeric octadecatrienoic acids by means of their δir p/ap. 5.5.2 polarity of stationary phases: rohrschneider-mcreynolds index polarity is a term employed to describe the chromatographic retention characteristics of a stationary phase. initially used rather intuitively, l. rohrschneider[48] and later w.o. mcreynolds[49] introduced a concept to codify the polarity by a number. this concept is based on the retention index differences, δir p/sq = ir p − ir sq, of certain selected reference compounds on a given stationary phase, p , relative to that of a highly apolar stationary phase, with the latter being squalane (sq), a branched c30 alkane. initially five reference compounds (benzene, ethanol, ethyl methyl ketone, nitromethane, and pyridine) were selected by rohrschneider (the set was later extended to ten reference compounds by mcreynolds) to represent characteristic types of interaction with the liquid phase (i.e., london dispersion, π– π electron, electron attracting and dipole-dipole interactions, h bonding capability). the δir p/sq values represent measures for individual intermolecular forces of these reference compounds with the stationary liquid, and are expressed for practical applications as constants x ', y ',z ',u',s '. under the assumption that the retention behavior of a stationary phase is a manifestation of its intermolecular interaction forces, the sum of the constants, σ = x '+ y '+ z '+u'+ s ' generally known as the rohrschneider-mcreynolds index, σ is a specific measure for the polarity of a given stationary liquid. this index can be used to rank the stationary phases according to their polarity; e.g., σ is zero for squalane, 229 for relatively apolar poly(dimethylsiloxane), and 3682 for highly polar poly(cyanopropylphenylsiloxane). in practice, these indices are particularly helpful for the assessment of the similarity of the polarity for stationary phases from different commercial sources. moreover, the rohrschneider-mcreynolds index and constants can be used to guide the selection of appropriate stationary phases for the separation of given analytes 6. 6. the inclusion of gas liquid chromatography with packed columns to the analysis of binding media from about 1965 the potential of gc for the analysis of binding media of museum objects was started to be recognized, although this technique was not directly applicable to a number of substance classes of present interest. plant gums (polysaccharides) or animal glues (protein) would rather decompose than evaporate at high temperature, but appropriate procedures for their transformation into gc-conform modifications were developed or adapted from the literature. however, some problems specific to the analysis of museum object still 6 such selections are often guided by the well-known rule-of-thumb “similia similibus solvuntur” concept, which may be understood as the three-word essence of the rohrschneider’s polarity classification. it appears to have been formulated in analogy to the principle “similia similibus curantur”, attributed to paracelsus, and “similia similibus curentur”, a motto of homoeopathy (for the source of the solubility rule see j.h. hildebrand, r.l. scott, the solubility of nonelectrolytes, acs monograph no. 17, reinhold publ. corp., 1950). 105gas chromatography and analysis of binding media of museum objects: a historical perspective have to be overcome, such as the very limited sample amounts available, the complexity of mixtures of several classes of binders often encountered in a single sample, occasionally together with products stemming from degradation and decomposition processes, the large excess of organic and/or inorganic matrix compounds and the presence of contaminants. much research was devoted to address these issues over the second half of the 1960s.[5053] especially j.s. mills and r. white carried out a number of systematic investigations concerning gc analysis of the different binding media[51, 54-59], and published later a comprehensive account on this topic.[2] first gc analyses of binding media were conducted with packed columns. an example for a chromatogram obtained under isothermal conditions for resinous material present in wax models is shown in figure 6, top panel. it is worth mentioning in this context that the results of modern analytical efforts can be supported as described in detail in johann melchior cröker’s book “der wohl anführende mahler …” which appeared in 1743. in the part attached to this volume entitled “diesem ist noch beygefüget ein kunst-cabinet rarer und geheim gehaltener erfindungen,...” cröker disclosed detailed recipes (“…rare and secret inventions,…”) concerning the fabrication of colored wax and recommended addition of venetian turpentine or, in some cases, cyprian turpentine. the chromatograms shown in figure 6b, top panel, were obtained from an anatomic wax model dating from the 18th century, and in figure 6c, top panel, from a wax model known as “christ rejected by the jews”, created ca. 1579 by giovanni bologna. peaks were attributed to resin acids (actually their methyl ester; the binding media were subjected to methylation prior to analysis to improve volatility) based on comparison with reference diterpenoic resins. note that the detection of larixyl acetate points to the presence of venetian turpentine as additive to the wax. the same resin was detected by capillary gc in samples taken from an anatomic wax model belonging to the collection of the history of medicine in vienna, austria, created in 1786 in the workshops of the famous anatomists f. fontana (in pisa) and p. mascagni (in florence).[60] certainly, the peaks of the chromatograms depicted in figure 6b and 6c (both top panel) are relatively broad, a feature which is characteristic for packed column gc, and their widths increase significantly with increasing retention time, inherent to isothermal conditions. as pointed out previously, elution at constant column temperature leads to unsatisfactory long times of gc analysis for samples consisting of components differing widely concerning volatility. natural waxes are good examples for such mixtures; e.g. beeswax, which mainly consists of straight-chained hydrocarbons with 21 to 33 carbon atoms, and long chain esters with triacontanyl palmitate (containing 46 carbon atoms, see also figure 1) being the most abundant one. it is obvious that for samples with such a composition application of temperafigure 6. comparison of packed column gc in isothermal with t-programmed mode. top panel: isothermal gc of resinous material in (b) an 18th century anatomic wax model; (c) the wax model “christ rejected by the jews” by giovanni bologna, ca. 1579[58] (chromatographic conditions as in ref. [54]). peak at 23.5 min, dehydroabietate; 37.5 min, larixyl acetate. for details see supplementary information and ref. [58]. from ref. [58] with permission. bottom panel: t-programmed gc. samples: waxes from (a) a surface coating of a 15th century intarsia work; contains bees wax, small proportion of ceresin wax; (b) 18th century italian wax sketch; contains a mixture of ozokerite with traces of bees wax (esters marked b). for details see supplementary information and ref. [59]. from ref. [59] with permission. 106 ernst kenndler, norbert m. maier ture programmed gc provides the combined advantages of reduced analysis time and narrow peak shapes. the benefits of temperature programmed gc are evident in chromatograms given in figure 6a and 6b (both bottom panel), both of which were obtained on a packed column[59]. the chromatogram in figure 6a (bottom panel), was obtained from a sample taken from a surface coating of an intarsia work dating from the 15th century, with beeswax being the main constituent. the chromatogram in figure 6b (bottom panel) represents the compound profile of a sample taken from an italian wax sketch dating from the 18th century, providing evidence for the presence of ozokerite, a naturally occurring wax consisting mainly of long-chain n-alkanes. 7. the breakthrough to high efficiency: capillary columns the transition of packed bed to capillary gc, an event that marks undoubtedly a major milestone in the evolution of gc, is closely connected with the name of marcel j.e. golay. golay was a swiss electrical engineer and mathematician; after having joined bell laboratories, he worked at the u.s. signal corps engineering laboratories for 25 years before affiliating with a leading instrument company aiming to develop a multiple slit ir spectrometer. remarkably, while golay had no previous involvement in chromatography[61], stimulated by the discussion of colleagues engaged in gc, he took interest in the mathematics describing the dispersion processes in the packed columns. through a critical analysis of the basic assumption of the underlying theory, golay concluded that the irregular pathways the analytes have to negotiate upon their passage through the particle beds are the main source of low efficiency of packed columns. golay suggested that this deleterious effect may be avoidable by employing straight parallel open tubes (with a thin film of the stationary liquid phase coating their inner wall) rather than a packed bed giving rise to meandering channels. within few months, he succeeded in working out a theory of chromatographic dispersion in open tubular columns, and suggested to test his theoretical predictions by experiment. in addition, to facilitate this efforts, he constructed a low-volume thermal conductivity detector better suited for the capillary column 7 he used (12 ft in length, with 0.055 inner diameter (i.d.), i.e. 366 cm x 1.37 mm) than the contemporary large-volume devices. one of the first chromatograms 7 nowadays these columns are generally named capillary columns, although golay preferred the term open tubular columns, because narrow tubes capillaries could in principle also be packed with particles. golay obtained with capillary columns is shown in figure 7, providing compelling proof that his predictions concerning the improvements in separation efficiencies were consistent with the physical realities. golay disclosed his theory and the supporting experimental results in 1958[62-64], and thus sparked a revolution in terms of further developments in gas chromatography. his results were successfully reproduced and confirmed by other leaders in the field, e.g., by d.h. desty et al.[65, 66] and by r.p.w. scott[67], and capillary columns went on to quickly replace packed bed columns essentially for all but preparative applications. given the impact golay ś contributions made on the state-of the-art in gc, it appears justified to review some important aspects of his mathematical description of the dispersion phenomena in capillary columns. for an open tube of cylindrical geometry with a film of liquid deposited at its inner surface and with a gas flow velocity, v, golay established the following equation for the dependence of hi=f(v) hi = 2dm,i v + 1+6ki +11ki 2( ) 1+ ki( ) 2 r2 24dm,i v + 2 3 ki 1+ ki( ) 2 ds 2 ds,i v (9) this equation can be expressed in a simplified form as hi = b v + cm +cs( )v = b v +c v (10) the first term, b/v=2dm,i/v in equation 9 stands for the contribution to peak broadening caused by longitudinal diffusion of the analytes in the mobile phase (dm,i is the diffusion coefficient of analyte, i, in the mobile phase). the middle term in equation 9 (cm in equation 10) expresses the combined contributions of the parabolic flow profile in the cylindrical tube (with inner radius, figure 7. m. golay´s one of the first chromatograms with a capillary column measured in 1956, separating a mixture of isomeric pentanes. column: 366 cm length, 1.37 mm i.d.; stationary phase (coating the inner capillary wall), polyethyleneglycol; isothermal at room temperature. detection with miniaturized thermal conductivity detector. for details see supplementary information and ref. [61]. from ref. [61] with permission. 107gas chromatography and analysis of binding media of museum objects: a historical perspective r) and the diffusion in radial direction which is part of the mass exchange in the mobile phase. its contribution is weighted by the factor which is solely ki-dependent. the contribution of the kinetics of mass exchange from the stationary phase is expressed by the third term in equation 9 (cs in equation 10); it depends on the film thickness ds on the diffusion coefficient in the liquid phase, ds,i, and on ki. for columns with very thin films this term plays a less pronounced role. the simplified form of the golay equation (see equation 10) resembles that of the van deemter equation for packed columns, with the exception that it lacks term a (simply because the column contains no packing) and the c-term does not feature any empirical parameters. compared with packed columns, golay`s approach predicts higher plate numbers for open tubular columns for two reasons: i) the attainable plate heights h are lower, and ii) the absence of a packing results in lower flow resistance and therefore much longer open tubes can be employed than is possible with densely packed columns. consequently, the plate number n=l/h is larger. since open tubular columns can be operated with lengths of up to 100 m, their plate numbers can reach several hundred thousands, being larger by nearly two orders of magnitude as compared to the plate number achievable with packed columns. from the discussions given above it can be concluded that the mobile phase velocity is an important parameter for adjusting the efficiency of a column in practice. it shall be mentioned that, since gases are viscous and compressible media, the flow velocity is not constant but is a function of the radial and of the axial position in the column. however, the fact of the different axial flow velocity will not be further discussed here, as under the usual operation conditions it is a factor of minor significance. if being of interest, pressure-dependent velocities can be calculated and accounted for by appropriate correction factors as described by james and martin[31] or retrieved from the literature. 7.1 the improvement of the capillary material 7.1.1 metal and glass capillaries the early capillary columns were fabricated from metal, such as copper, nickel, alumina or, preferentially, from steel, or from synthetic organic polymers, and different methods to implement the stationary phase were developed. however, metal columns suffered from some disadvantages, e.g. considerable activity and the unevenness of the inner surface, giving rise to band distortion and loss of separation efficiency. therefore, metal capillary columns were rapidly abandoned in favor of glass capillaries after d.h. desty et al.[68] had succeeded in the development of a device to draw reliable capillaries from a molding blank. in the currently most common column type the capillary wall is directly coated with a thin film of liquid. however, initially, with glass capillaries the direct coating approach was met with difficulty due to the low wettability of the solid surface (especially for apolar liquids) and its undesirable adsorptive properties. adsorption at the glass surface, caused by the presence of higher-charged cations, led to a severe distortion of the peaks with a distinct tailing, resulting from nonlinear adsorption isotherms of the solutes interacting with the liquid-solid interface. adsorption-triggered tailing occurred especially in the case of polar analytes containing donor/acceptor functionalities. a typical example of adsorption-induced peak distortion on a non-deactivated glass surface reported by schomburg et al.[69] is given in figure 8. note that in this particular case, symmetrical peak shapes were obtained after deactivation of the glass surface. to improve the quality of glass surfaces, special treatments were necessary prior to conducting the coating procedure. thus, wettability was enhanced by increasing the roughness of the surface by acidic etching, e.g. using dry gaseous hcl or hf.[70] for the deactivation of the surface a number of other procedures were advanced, e.g. the deposition of polymer layers, or the exhaustive silylation of surface silanol groups. figure 8. gc with glass capillary without surface deactivation prior to coating with polyethyleneglycol. analytes 1-9: alkylamines. figure taken from ref. [69] with permission and modified. 108 ernst kenndler, norbert m. maier in figure 9, left panel, one of the first applications of glass capillary columns in the area of binding media analysis is shown, namely for the separation of fatty acids (converted into their methyl esters prior to analysis) from a sample of drying oils. the glass capillary was coated with a polar stationary phase and gc was carried out in the isothermal mode. all relevant analytes are separated. yet, the peak widths are generally broad, and the analytes migrate over a relatively wide retention time window of about 10 min. in contrast, in figure 9, right panel, a temperatureprogrammed analysis of the same group of analytes is shown, originating from the paste layer of a ceremonial shield collected mid-19th century at the solomon islands (mentioned in chapter 5.5.1)[47], demonstrating the inherent advantages of this elution mode. specifically, here the fatty acid profile (also as methyl esters) elutes within a retention time window of about 4 min, with all compounds emerging as narrow peaks (note that in this case the relatively long overall run time was chosen deliberately to accommodate for potentially other unknown components in the sample). even though glass capillary columns found widely use in gc due to their high efficiency, some problematic properties remained. one of these but not the most relevant was their poor mechanical stability, which complicated their handling and installation, especially in context with the coupling to mass spectrometers. however, much more problematic was the fact that the coated glass surfaces, despite of careful surface pretreatment, often retained a certain level of active adsorptive sites. in efforts to address these issues, rather sophisticated protocols were developed for deactivation, coating and stabilization of the stationary phases, involving the cross-linking between polymer chains of the liquid stationary phase to obtain immobilized phases, and the figure 9. left panel: early gc with a glass capillary (isothermal mode) for binding media analysis (drying oil). samples: fatty acids (as methyl esters). numbering of acids: 1, palmitic (16:0); 2, suberic; 3, azelaic; 4, stearic (18:0); 5, oleic (18:1); 6, linoleic (18:2); 7, linolenic (18:3). for details see supplementary information and ref. [71]. from ref. [71] with permission. right panel: t-programmed capillary gc. sample: fatty acids (as methyl esters, after hydrolysis of the sample). sample taken from the paste layer of a ceremonial shield from the solomon islands (collected mid-19th century). time in min. for numbering of analytes see legend of left panel. for details see supplementary information and ref. [47]. from ref. [47] with permission. 109gas chromatography and analysis of binding media of museum objects: a historical perspective covalent anchoring of stationary phases onto the capillary surface to create bonded phases. major contributions in the field of the stationary phase chemistry in context with glass (and in the next generation of fused silica) capillary columns[61] are connected with the names of l. blomberg[72], k. grob[73], m.l. lee[74], s.r. lipsky[75], c. madani[76], v. pretorius[77], p. sandra[78] and g. schomburg[79]. 7.1.2 fused silica capillaries in the course of their pursuit of more suitable glass materials for capillary gc applications, r. dandeneau and r.h. zerenner discovered that fused silica proved the most inert material.[80] after their initial demonstration of the superiority of fused silica over glass capillaries for gc applications, this material was intensely investigated and further popularized by s.r. lipsky et al.[75] and others. at his time, the technology for the fabrication of synthetic fused silica was already well established in the field of fiber optics, and could be readily adapted for the production of capillaries with little additional effort. industrially, fused silica is produced by hydrolysis of sicl4 in the gas phase and subsequent melting of the resulting high purity sio2. the emerging material contains about 0.1 ppm metal oxides as impurities only, as opposed to naturally occurring quartz, for which the content of metal ions is typically higher by two orders of magnitude. due to this high purity, stationary phases coated or immobilized in fused silica capillaries were much more stable thermally, and showed much reduced adsorptivity for polar analytes as compared to other capillary materials. furthermore, residual activity due to silanol groups could effectively be suppressed using silylation procedures established in the past for glass surfaces. most procedures originally developed for the fabrication of immobilized and bonded phases in glass capillaries (see above) could be directly adopted to the fused silica material. bonded phases, in many cases polysiloxanes derivatives, possess a number of advantages. due to their attachment at the surface, they are resistant to extraction with organic solvents, and thus do not become detached upon direct injection of samples dissolved in polar solvents and even in water. furthermore, these columns show, yet at high operating temperatures, negligible bleeding (i.e. less release of lower molecular mass constituents of the stationary phase at elevated temperature). also, they exhibit chemically excellent long term stability, and maintain over extended periods of use their chromatographic performance in terms of retention and efficiency. given these advantages fused silica capillary columns completely replaced glass-based columns for most but some specialty application (e.g. for chiral separations) for which glass capillaries are still the preferred material. especially designed stationary phases featuring remarkable thermostability allow analysis of high molecular compounds. a typical application of high temperature gc is shown in figure 10, for profiling lipids contained in a sherd recovered from an early medieval ditch.[81] in this particular case, gc analysis was conducted in a temperature-programmed fashion with an upper temperature of 350°c, using a fused silica capillary containing a bonded apolar stationary phase. analytes were intact mono-, diand triglycerides, which were directly subjected to analysis without any prior hydrolysis/derivatization (note that other sample constituents featuring free carboxylic and hydroxyl groups were silylated prior to analysis). 7.2 the development of sample injectors required for capillary columns the plate heights expressed by the van deemter equation for packed columns and the golay equation for capillary columns account only for zone broadening processes occurring within the chromatographic columns. in other words, it is assumed that the length of the injected sample plug and therefore the standard deviation of the input function approach zero. in pracfigure 10. high-temperature gc. analysis of intact fatty acid mono-, diand triglycerides. samples extracted from a sherd recovered from an early medieval ditch. alumina cladded fused silica capillary column, immobilized stationary phase, end temperature 350°c. for details see text, supplementary information and ref. [81]. from ref. [81] with permission. 110 ernst kenndler, norbert m. maier tice, however, the injected zone has a finite length and consequently contributes to the final peak width. if, e.g., the injected plug is rectangular sized with length δ its variance is σ inj 2 =δ 2 12 in the length domain). the standard deviation of the final peak is then, according to the general additivity of variances, equal to σ inj 2 +σ col 2 with σ col 2 being the variance caused by the dispersion processes within the chromatographic column.[82] zone dispersion contributions from sources outside of the separation column, such as the injected plug and the detector volume, are generally referred to as extra-column effects, and inevitably impact the experimentally observable peak width. however, the impact of these generally unfavorably extra-column contributions on the overall performance is quite different in severity for packed and capillary columns, respectively. when using packed columns, samples are generally introduced by an injector which consists of an evaporation chamber, a heated cylindrical glass or quartz tube with about one ml volume. the injector is coupled with an external gas supply which provides a continuous flow of the mobile phase carrier gas. at the outlet of the injector the packed column is mounted, and the inlet of the injector is typically sealed by a silicon rubber septum. the solid or liquid sample is dissolved in a highly volatile solvent, and is injected through the septum by a syringe into the evaporation chamber and where it is flash-vaporized. here the vapor is homogeneously mixed with the gas phase before it flows into the packed column. typically, the injected volumes of the liquid sample solutions are in the microliter range, being volumes that can conveniently be handled by precision syringes. these volumes cause a considerable large injected zone of vapor at the column inlet, and typically contain a relatively large amount of sample. as pointed out earlier, this zone contributes to the width of the final peak in addition to the dispersion produced within the column, however, due to the inherently low efficiency of packed column, the extra-column contributions associated with sample introduction remain rather negligible relative to the significant in-column dispersion. in addition, mass overloading of the packed column by the relatively large amount of analyte does usually not occur due to the large volume of the stationary phase available in the column (more currently due to the large phase ratio). while the described type of injection device is well suitable for sample introduction into packed columns, it is incompatible with the requirements of capillary columns. firstly, a large input sample zone would dominate in-column peak broadening and thus obscure the high efficiency of the capillary column. secondly, introduction of a large amount of analytes would certainly mass-overload the column as result of its small phase ratio (the inner diameter of the capillary is about 200300 micrometer, the thickness of the stationary liquid is only in the micrometer range or lower) and thus give rise to severely leading peak profiles. therefore, the only way to preserve the inherently high efficiency of capillary column consists in introducing suitably small sample amounts in terms of mass and volume. however, as liquid volumes smaller than about 0.1 microliters are hard to handle by syringes, capillary column generated the need for especially designed sample introduction devices, e.g. allowing for a partial injection of the sample vapor after being mixed with the carrier gas. this was achieved by engineering injectors that split the gas flow between an additional outlet and the column. typically, the outlet consisted of a restrictor which enabled adjusting the desired split ratio between column and the vent. in practice, split ratios (vent to column) were selected between several 10:1 and few 100:1. in this way, extra-column peak broadening and sample overload of the capillary column can be avoided. this simple split-injector design, developed in the 1960s, and still in use nowadays, has some inherent disadvantages, e.g. the marked loss of analyte (via the vent) and the consequent loss of sensitivity of the analytical method. to address these limitations, other, more sophisticated injector types were developed, e.g. the splitless (see e.g. ref. [83]), the programmed temperature vaporizing (ptv)[84] and the on-column injectors. however, these developments will not be described here. in this context it must be pointed out that with the advent of the capillary column also new sensitivity requirements for the detecting systems arose. for packed columns initially the thermal conductivity detector was commonly in use and yet effective. its relatively large volume translates technically into low sensitivity, but given the large injected sample typically processed in packed column gc provided satisfactory signal strength. however, the typical sample amounts eluting from capillary gc are much smaller, and would produce a low if any signal with the traditional detection systems. it was therefore a fortunate coincidence, that golay ś introduction of capillary gc was synchronized with the first detailed technical description of the highly sensitive flame ionization detector (fid)[85], which could easily be miniaturized to meet the new demands. this detector responds to ch-groups and is, by the way, thus perfectly suitable for organic compounds of the binding media. 111gas chromatography and analysis of binding media of museum objects: a historical perspective 8. pyrolysis gas chromatography as mentioned previously, certain classes of non-volatile compounds can be addressed by gc analysis after being degraded into smaller volatile fragments through chemically well-controlled reactions (e.g. for proteins and polysaccharides through acid hydrolysis). however, this conventional approach is inapplicable to materials for which no suitable degradation reactions exist (e.g. high molecular mass condensed hydrocarbons, the main constituents of bituminous materials). for these non-volatiles, pyrolysis gc offers an attractive option for direct analysis. this technique is carried out with gc instruments in which the injector system has been modified into a pyrolysis chamber.[86, 87] after being loaded into the pyrolysis cell, the sample is heated there to high temperatures at which the contained analytes are thermally decomposed and the formed products are transferred by the mobile phase stream into the column. around 1959 early devices for pyrolysis gc were reported, one consisting of a metal loop, which replaced a gas sample loop at the inlet of the packed column.[87] to accomplish thermal sample decomposition, the loop was heated in a bath of wood’s alloy, while the temperature achieved by this heat source was measured by a thermocouple connected to a pyrometer. this design showed in principle all necessary functional features of modern pyrolysis gc, but it lacked provisions for the accurate adjustment of the instrumental parameters, which are essential for the reproducible sample decomposition and subsequent chromatographic analysis. parameters crucial to reliable analysis by pyrolysis gc are a well-defined and constant pyrolysis temperature, a precisely controlled heating rate, and a defined duration of the pyrolysis. a gas chromatogram obtained with the pyrolysis gc prototype device mentioned above for a synthetic polymer (applying 500°c for 30 sec in a helium atmosphere) is shown in figure 11, left panel. first instrumental improvements of the pyrolysis process were obtained by loading the sample onto an electrically heated metal wire or into a spiral[86, 88], with the temperature being calibrated by the melting points of suitable reference compounds. alternatively, other devices for accurate temperature adjustment were using ferromagnetic metals which, upon placement into a high frequency inductor coil, were heated exactly to the curie point and maintained a constant temperature by self-stabilization. modern commercial instruments regulate and control all crucial operational parameters fully electronically. equipped with platinum filaments, state-of-the-art pyrolizers can be operated at temperature up to 1400°c (which can be kept constant with an accuracy of 1°c), with flash pyrolysis heating rates up to 1000°c/s, and can be programmed to execute in highly reproducible fashion sophisticated user-defined pyrolysis protocols. upon thermally cracking the sample under welldefined conditions, the resulting pattern of chromatographic peaks allows conclusions to be drawn about the kind of the sample by comparison with reference materials and the identification of marker peaks. coupling ms detection devices to the gc column provides the possibility to gain detailed structural information. a striking advantages of pyrolysis gc over more conventional approaches is that samples can directly be analyzed figure 11. introduction and development of pyrolysis gc. left panel: early pyrolysis gc with packed column published in 1959. sample: polymethylmetacrylate. packed column, isothermal 100°c; pyrolysis at 500°c for 30 sec in he atmosphere. peak annotation: a, air; b, methanol; c, ethanol; e, methyl acrylate; g, methyl methacrylate. for details, see text and ref. [87]. from ref. [87] with permission. right panel: pyrolysis capillary gc recorded using a state-of-the-art instrument in 2005. t-programmed mode. detection: tic of ms. sample from a painting in “oleoresin” technique. peak annotation: 23, hop-22(29)-en-3-ol; 24, β-amyrin; 25, α-amyrin; all as tms esters. for other peaks see ref. [89]. for details see supplementary information and ref. [89]. from ref. [89] with permission. 112 ernst kenndler, norbert m. maier without any time-consuming pretreatment steps, such as dissolution, hydrolysis, derivatization, etc. moreover, simultaneous derivatization without elaborate pretreatment can be carried out in situ by admixing suitable derivatization reagents to the sample in the pyrolysis chamber. the improvement of pyrolysis gc instrumentation becomes obvious upon comparing the chromatograms in figure 11, left panel vs. right panel.[89] for the latter chromatogram the sample was taken from a painting executed in “oleoresin” technique by the mexican artist carmen lopez, and for which the pyrolysis was carried out using an in situ silylation protocol. as the resulting chromatogram is rather shown for comparison, only the peaks of three sample constituents are assigned, i.e. those of the pentacyclic c30h50o triterpenols hop22(29)-en-3-ol, and αand β-amyren. the results are indicative for a special resin, mexican copal, as a constituent of the painting medium. as useful as pyrolysis gc has proven for the analysis of binding media, we wish to place here a word of caution. despite of the maturity of the method, reproducibility of the results remains an issue, especially when different experimental conditions are applied, and instrumentation supplied from different vendors is used. moreover, it has been pointed out that the quantitation of specific analytes with pyrolysis gc might be less reliable than that carried out with conventional chromatographic methods. readers interested in a more in-depth treatise of the contributions of pyrolysis gc to binding media in objects of cultural heritage are directed to ref. [90]. 9. column switching, heart cutting, twodimensional gc when being challenged with highly complex samples, not all compounds of interest may be successfully separated with gc employing a single column. rather, a number of analyte zones may co-migrate and form overlapping peaks with the consequence that reliable identification and quantitation remain elusive. in this case, application of a column with a different chromatographic retention characteristic might resolve some critical pairs, but still may fail to separate other compounds of interest. a solution to this problem is to combine two columns of low chromatographic similarity in series, via a switching valve interface as introduced by d.r. deans[91]. this method, referred to as heart cutting or column switching, enables the transfer of a certain fraction of eluate from the first column (1) onto the second column (2), both being equipped with separate detectors. in column (2) this fraction is chromatographed simultaneously with the sample components remaining at column (1). given that the columns have been selected appropriately in term of complementary selectivity, successful separation (and detection) of the initially unresolved peaks may be achieved. certainly, column switching is not limited to only one unresolved peak pair, but may be repeatedly applied to many peak clusters in the same chromatogram. in case that the set of employed columns possess completely different chromatographic properties (i.e. are “orthogonal”), they are considered to represent different chromatographic dimensions and the method is named two-dimensional gc. this terminus is taken from twodimensional gel electrophoresis and thin layer chromatography. the similarity of the chromatographic properties of the stationary phases (and thus the “dimensionality” of the two combined columns) may be established quantitatively using chemometric methodologies[92, 93], and to some extent by comparison of their rohrschneider-mcreynolds indices for the polarity. to the best of our knowledge, column switching approaches have not yet been applied to the analysis of binding media, although it should have a high potential, especially for the separation of the components in very complex mixtures of different binders in the same sample. 10. on-line coupling gc-ms technically, coupling a gas chromatograph with a mass spectrometer is a nearly ideal combination of two powerful analytical techniques, because in both methods the analytes are present in the gaseous phase, albeit at pressures that differ by about 8 orders of magnitude. first attempts to realize this attractive option of an online combination of gc with ms were carried out with packed columns, but were complicated by the large volume of the gc gas flow, which, unsurprisingly, compromised the high vacuum conditions required for ms operation. solutions to this problem were sought by the design of innovative interfaces to harmonize the mutual flow requirements of the gc and ms module[94-98], respectively, by jet-type or by membrane separators, or by direct open coupling as described in ref. [99]. with the latter interface packed columns with inner diameters of up to 4 mm were successfully coupled with a double focusing ms (see e.g. ref. [100]), though some losses in sensitivity and an impairment of the detection limit of the gc-ms method were resulting. for analyses of binding media, application of packed column gc-ms coupling emerged in the 1970s, and a 113gas chromatography and analysis of binding media of museum objects: a historical perspective chromatogram documenting one of these early efforts is shown in figure 12. this study was reported in 1977 and aimed at identifying plant gums and gallic acid as possible constituents of an ink sample of a european manuscript on parchment from the 16th century.[101] prior to analysis, the ink sample was hydrolyzed and the emerging products subsequently silylated. a packed column of 2 mm i.d. was connected to the ms with a single-stage jet-type separator. the chromatograms were reconstructed by summing up the ion current of each scan. in trace (a) the total ion current (tic) is recorded, and arabinose, galactose and glucose are identified. being isobaric, the epimers of glucopyranose could not be differentiated by their mass spectra, but plausibly identified based on their chromatographic retention order. the extracted dual ion monitoring trace depicted in trace (b) with two m/e values specific for silylated gallic acid allowed its reliable identification. based on these results, the authors concluded that the investigated manuscript was written using ferro-gallic ink containing gum arabic as a binder. the mismatch between the gas flow volumes at the outlet of the packed gc columns and the inlet into the ms could largely be avoided by the use of capillary columns. due to the lower gas volume emerging from the capillary, the column outlet could directly be coupled via a heated transfer line to the ms without impairing its vacuum, enabling the introduction of the entire flow volume into the ion source of the ms. moreover, for routine analyses the sector ms instruments were replaced by the less expensive quadrupole mass spectrometers with their much faster scan rate, and with their very user-friendly operability. evidently, the combined benefits of a high level of technical maturity, and the ready availability at reasonable costs have made gc-quadrupole ms the most popular analytical method in laboratories devoted to the investigation of organic materials in museum objects. in figure 13 the result of directly coupled capillary gc-quadrupole ms for the analysis of a polysaccharide sample is shown[102], processed after hydrolysis and silylation. the sample was taken from the pluviale, known as the cope of the virgin mary, a liturgical vestment of the order of the golden fleece, housed in the imperial and ecclesiastical treasury in vienna, austria (see figure 13). it was fabricated between 1425 and 1440 in burgundy and most likely designed by the master of flémalle (highly probably identified with robert campin, c. 1375 1444). the vestment has been executed using two embroidery techniques, viz. in needle painting and in or nué, a lazur embroidery technique. the figure 12. one of the first on-line gc-ms for binding media analysis: computer reconstructed plots of (a) tic of a 16th century ink hydrolysate; (b) mass chromatogram at m/e 458 plus 443 specific for gallic acid (all analytes as tms derivatives). packed column, t-program; ms scan speed 1 set/decade in cyclic mode, period 4 s. peak numbering: peaks 1, 3, 5, 7, 8: furanose and pyranose epimers of arabinose and galactose, resp.; peaks 10 and 11, αand β-glucopyranose, resp.; peak 18, gallic acid. for details see supplementary information and ref. [101]. from ref. [101] with permission. figure 13. gc-ms of the polysaccharide fraction from a sample of the cope of the virgin mary (15th century). the cope measures 330 cm in width and 164 cm in length. peaks: αand β-glucopyranose. (tms derivatives after hydrolysis and concomitant group-separation by an ion exchanger from the proteinaceous fractions). insert: gc-ms of barley starch; same procedure as the for sample of the cope. time in min. peaks recorded from tic. for details see text, supplementary information and ref. [102]. from ref. [102] with permission. bottom and left picture: long shot and detail of the cope of the virgin mary. photographic images by courtesy of khm-museumsverband, vienna, austria. 114 ernst kenndler, norbert m. maier cope measures 330 cm in width and 164 cm in length. the background structure of the cope consists of several layers of textile materials stitched together. originally, these textiles may have been partially conglutinated, as small white round-shaped scales of about one square millimeter in size were found between the layers, probably applied as a gluing agent. for restoration and conservation purposes, it was of interest to identify the kind of this gluing material. for plausibility reasons, an analytic strategy capable of differentiate between animal and plant glues was chosen for this project. prior to gc-ms analysis, a mild hydrolysis protocol suited for a potentially present mixture of proteinaceous and polysaccharide binders was employed, using a cation exchange resin in the h+-form as a hydrolysis reagent.[103] importantly, this particular procedure provides additional benefits as it permits the separation of the protein hydrolysate from polysaccharide-based materials and prevents these classes of compounds from undergoing condensation reaction with each other. after the group-specific separation of the two binder classes, hydrolysis of the polysaccharide fraction was completed, and both hydrolysate solutions were subjected to appropriate silylation protocols. gc-ms analysis of the amino acid fraction did not provide any products consistent with amino acids, thus the presence of proteinaceous binder could be safely ruled out. however, in gc-ms analysis of the derivatized saccharide fraction two main peaks were detected, both of which were identified by ms being epimeric glucopyranoses; yet efforts towards unambiguous stereochemical assignment of the individual epimers proved difficult due to their almost identical mass spectra. however, as the α-epimer has a smaller retention factor than the β-epimer, the two peaks could be reliably assigned (see also ref. [101]). given the fact that no other saccharides were detected, the unknown material employed as a gluing material in the vestment was positively identified as starch (see insert in fig. 13). subsequently, this conclusion was independently confirmed by consistent results obtained by analyzing the other possible polysaccharides as reference samples under identical conditions. it should be pointed out that advanced protocols for group-specific isolation of lipids, animal and plant glues, waxes and resins prior to gc-ms analysis are described in refs. [104, 105]. these procedures involve mainly liquidsolid, solid phase, separation sorbent-tip, and clean-up by ion exchange extraction steps, respectively. historically, only a limited number of investigation of organic matter in museum objects with gc-ms were published before the turn of the millennium, but the acceptance of this technique as an enabling tool for the analysis of organic matter in museum objects has significantly increased over the last two decades. this is manifested by the growing number of groups being active in the field as well as the ever-increasing number of papers published on the topic. the objects investigated range from archeological finds and artifacts from antiquity[106, 107] (see figure 14, top panel) over those from middle ages[108] (figure 14, bottom panel) up to contemporary art works. as an addendum we mention that the gc-ms protocols developed for the determination of proteinaceous binders are exceptionally capable of distinguishing between classes of parent proteins, i.e. egg, casein or collagen, but unsuitable for identifying the species of the animal from which this protein originates. this question can be addressed using bioanalytical methods, originally developed for clinical diagnostics, such as enzyme linked immunosorbent assay (elisa) or by modern proteomics protocols. elisa methodology is based on selecfigure 14. gc-ms of binding media in objects from antiquity and renaissance. top panel: tic chromatogram of sample of embalming materials in egyptian skulls (neutral fraction from extraction). sample from the archaeological collection, natural history museum, florence, italy. according analytes as tms-derivatives. column, fused silica capillary; t-program, ms: single quadrupole. for details see supplementary information and ref. [107]. from ref. [107] with permission. bottom panel: capillary gc-ms of amino acid fraction of egg tempera sample from polyptych “annunciation and saints” (ca. 1385), giovanni del biondo (ca. 1356–1398), galleria dell’accademia, florence, italy; sample pretreatment and experimental conditions see ref. [104]. taken from ref. [108] and modified. 115gas chromatography and analysis of binding media of museum objects: a historical perspective tive binding of the protein of interest to a target-specific antibody. proteomics protocols, recently adapted to binding media studies[109], involve the enzymatic digestion of the protein sample of interest using appropriate hydrolytic enzymes (typically trypsin), separation and identification of the formed peptides via lc-ms techniques, and finally matching of the observed peptides with appropriate databases for identification of the original protein(s). the suitability of elisa and proteomics protocols for the species-specific identification of proteins in the binding media has been recently demonstrated for egypt-romano portraits dating to 180-200 a.d., for which cow hides could be established as protein source. [110] elisa and proteomics assay were also employed, together with a number of spectrometric techniques, for the identification of the proteinaceous material found in late medieval mortars, and their merits and limitations were critically discussed.[111] a study into the proteinaceous binders present in the giant buddha statues of bāmiyān in afghanistan (largely demolished in 2011) was carried out using a combination of gc-ms and proteomics techniques. in this case, egg tempera was found in the original paint layer, while cow and goat milk was detected in historical overpaintings.[112] certainly, elisa and proteomics protocols are useful to complement the knowledge accessible with established gc-ms methods, allowing identification of species-specific sources of proteinaceous binders. currently, however, these methods are rarely applied. reasons for this reluctance may be the need for specialized instrumentation and the high level of expertise required; and the question whether or not the high costs associated with these techniques are justifiable by additional scientific information potentially gained. to round off the discussion about the role of gc-ms in binding media studies, we wish to reflect on a very particular coupling technique evaluated at the end of the 1980s by one of the authors (e.k.). in co-operation with a major instrument vendor, the opportunity arose to test an innovative gc-ftir-ms prototype. in this configuration, a low-volume ir cell was directly connected to the outlet of the capillary column, allowing the nondestructive detection of gc effluents prior to transfer to the quadrupole ms. this gc-ftir-ms combination was successfully used for the identification of some nonresinous compounds detected in the chromatograms of samples of anatomic wax models from the 18th century. [60] however, there may have been little general interest in gc-ftir-ms at this time, as the instrument never made it to the market. thus, our scientific exploits may well have been the first and the last application of gcftir-ms to the analysis of organic binding media in museum objects. 11. conclusions the development of gc has been a long journey, which started in the late 1800s with the pursuit of methods for preparative gas separation and ultimately led to the establishment of one of the most versatile and sensitive modern analytical separation techniques. it needs to be emphasized that the evolvement of gc was made possible through the ingenious contributions of many outstanding scientists both in the fields of theory and applied research. important historic milestones in the development of gc are numerous; these involve i) the early efforts to adapt known adsorption liquid solid chromatographic concepts to gas solid separations; ii) the subsequent transition from solid adsorptive stationary phase to solid-supported liquid stationary phases, dramatically expanding the scope of interactions forces for tuning separation selectivity; iii) the establishment of a thorough understanding of the parameters that control retention and dispersion in chromatographic columns, and the theoretical understanding of how these contributions impact the overall achievable separation performance; iv) the following theory-guided transition from packed columns to open tubular capillary columns, obviating the performance-degrading particle beds and allowing for tremendous improvements in separation efficiency by using vastly enhanced column lengths; v) and the parallel occurring improvements in chromatographic materials and instrumentation, such as inert column materials, thermally highly stable stationary phases, improved injection systems and highly sensitive detectors, and, finally, vi) the optimized coupling of gc with mass spectrometric detection devices. the potential of gc for the analysis of binding media has been recognized as early as in the mid-1960s, and has found ever-increasing appreciation as the technology approached maturity. state-of-the-art gc instruments offer the benefits of low sample requirements, high sensitivity and separation selectivity, and straightforward analyte identification when coupled with mass spectrometric detection devices. special gc techniques, such as pyrolysis gc, can be employed to provide valuable insights into the compositions of samples difficult to characterize by other techniques, such as high molecular mass compounds and polymers. given these advantages, gc is currently appreciated as a standard tool in the field, and routinely employed for the characterization of all important media classes. 116 ernst kenndler, norbert m. maier other techniques are increasingly added to the repertoire of analytical tools employed binding media analysis; especially worth mentioning are dedicated raman and ir spectrometric techniques, which offer the benefit of being fully conservative. also, new chromatographic methods, in particular those involving lcms proteomics methodology, are finding recognition as tools for characterization of protein-based binding media to identify not only the class but also the speciesspecific source. for the same purpose, also bioanalytical approaches based on immunoaffinity binding, such as elisa are employed. while the advent of these new methods will certainly enhance the information accessible through binding media analysis, it is unlikely that they will replace gc as the prime enabling technique. gc, while being a micro-destructive analytical method, is uniquely suited for binding media analysis with regard to its low sample requirements, the broad scope of materials that can be analyzed, its inherently high sensitivity, and its perfect compatibility with mass spectrometric devices. also, there is a uniquely rich body of expertise and experience with gc in binding media analysis that has been compiled over five decades, which facilitates the interpretation of results, and is invaluable for guiding the design and execution of new studies. future progress in the field of gc-based binding media analysis may involve improvements in detection sensitivity by new generations of mass spectrometric devices, which is anticipated to further reduce sample amount requirements. also, future binding media analysis may potentially profit from the implementation of the emerging comprehensive two-dimensional gc technology using stationary phases with different retention characteristics, resulting in enhanced information outputs to better justify the use of precious and unique sample materials. arguably, gc will remain a technique of central importance in the field of binding media analytics in cultural heritage research and preservation. acknowledgements the authors gratefully acknowledge khm-museumsverband, vienna, austria, for the kind permission to use the photographic material of the cope of the virgin mary. competing interests the authors declare no competing interests. references 1. r. mazzeo, analytical chemistry for cultural heritage, 1st ed., springer, switzerland, 2017. 2. j. s. mills, r. white, the organic chemistry of museum objects, 2nd ed., butterworth-heinemann, oxford, 2000. 3. m. doerner, malmaterial und seine verwendung im bilde, 23rd ed., christophorus freiburg, 2010. 4. a. schönemann, m. eisbein, a. unger, m. dell`mour, w. frenzel, e. kenndler, stud. conserv. 2008, 53, 118. 5. a. schönemann, w. frenzel, a. unger, e. kenndler, stud. conserv. 2006, 51, 99. 6. l. reed, proc. amer. chem. soc. 1883, 9, 123. 7. d. t. day, proc. amer. phil. soc. 1897, 36, 112. 8. m. s. tswett, trudy varhavskago obshchestva estevoispytatelei otd. bio.l (t.r warsawsk obst. jestesv. otd. biol.); 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